key: cord-293170-ir2y6sfz authors: lal, tusharindra; sircar, mrinal title: covid-19 patients: when and whom to ventilate? date: 2020-08-19 journal: acute crit care doi: 10.4266/acc.2020.00451 sha: doc_id: 293170 cord_uid: ir2y6sfz nan | pissn 2586-6052 | eissn acute and critical care dear editor: the coronavirus disease-19 (covid-19) pandemic has severely strained intensive care unit (icu) resources worldwide. it is estimated that a country like india with a population of 1.3 billion, has one doctor for every 1,457 individuals, 1.7 nurses per 1,000 people, approximately 1.9 million hospital beds, 95 thousand icu beds, and 48 thousand ventilators. as the cases of severe acute respiratory syndrome (sars) increase rapidly, finding icu beds, ventilators, intensivists, and critical care nurses remains a big challenge. the need for mechanical ventilation in covid-19 patients, however, remains a subject of debate. a chinese study reported that invasive ventilation was required in only 2.3% of 1,099 covid-19 positive patients [1] . in contrast, noninvasive ventilation (niv), including bilevel positive airway pressure and continuous positive airway pressure, is being advocated for early/mild disease [1] . patients needing mechanical ventilation were sicker and had a higher mortality rate, as compared to those receiving niv. additionally, the pao2/fio2 ratio was worse among nonsurvivors [2] . a metaanalysis that included 1,084 patients from eight selected studies showed that high-flow nasal cannula (hfnc) treatment could reduce the rate of endotracheal intubation and icu mortality [3] . a more recent review concluded that hfnc and niv should be reserved for patients with mild acute respiratory distress syndrome until further data are available [4]. although aerosolization risk exists for both hfnc (up to 62 cm around the face) and niv (within 92 cm distance), the former has been recommended by surviving sepsis guidelines [5,6]. niv must be delivered with a well-fitted full-face non-vented mask, delivered in negative pressure (or single) rooms, and by adding a viral filter between the mask and the expiratory leak or tubing. besides face masks, niv may also be provided by nasal pillows (aerosolization risk up to 33 cm distance) and helmet masks (aerosolization risk up to zero to 27 cm distance) [5]. potentially, hfnc and niv have the advantage of being provided even outside the icu and can be managed by trained paramedical staff which conserves icu resources for more severe patients [7] . further, recent research has shown an emerging role for awake prone hfnc and niv [8]. awake prone positioning improves the mismatch between ventilationperfusion and opens the atelectatic lungs by promoting adequate sputum drainage. many patients will immediately improve their oxygenation while others show signs of exhaustion or excessive respiratory effort. high tidal volumes (breathing spontaneously or on hfnc/ niv), may expose diseased lungs to swings of trans-pulmonary pressures and may lead to patient self-inflicted lung injury. any undue delay in switching to invasive ventilation may worsen outcomes [9]. a recent study has shown that maximal level of interleukin-6 (il-6), followed by c-reactive protein (crp) level, was highly predictive of the need for mechanical ventilation suggesting the possibility of using il-6 or crp level to guide escalation of treat-ment in patients with covid-19-related hyperinflammatory syndrome [10] . with medical facilities severely stretched out, especially in resource-limited regions like india and other developing nations with large population clusters, selective use of hfnc or niv may reduce the need for ventilated icu beds while achieving desired clinical results. the decision to switch from hfnc/ niv to invasive ventilation could be a tricky one with several factors and co-morbidities to be taken into account. however, in the absence of randomized controlled trials (rcts) and lack of clear guidelines, the clinical judgment of physicians and the availability of necessary resources in their respective hospitals will largely determine the ventilation techniques employed. large rcts or well-designed observational studies are needed to define stratification of covid-19 patients for the best choice of initial respiratory support keeping in mind the resources available and the judicious and timely use of invasive ventilation. intubation and ventilation amid the covid-19 outbreak: wuhan's experience no potential conflict of interest relevant to this article was reported. key: cord-336690-ajmuaw10 authors: mcenery, tom; gough, ciara; costello, richard w title: covid-19: respiratory support outside the intensive care unit date: 2020-04-09 journal: lancet respir med doi: 10.1016/s2213-2600(20)30176-4 sha: doc_id: 336690 cord_uid: ajmuaw10 nan the optimal mode of respiratory support for individuals with severe coronavirus disease 2019 (covid-19) before invasive mechanical ventilation (imv) is currently a subject of much debate. recently published guidelines 1 and a comment 2 differ substantially to other guidelines in this regard, with some advocating high flow nasal cannulae (hfnc) over non-invasive ventilation (niv), 1,2 or vice versa (nhs guidance). this debate is understandable given the paucity of data and need for rapid generation of guidance, but it is a cause of confusion among respiratory physicians. much of the data guiding practice in this area derive from the critical care setting. in acute respiratory distress syndrome (ards), early intubation was associated with survival benefit when pao 2 /fio 2 ratio was <150 when compared with niv. 3 some covid-19 guidelines have therefore suggested niv as a bridging therapy only, before transfer to the intensive care unit (icu) and imv. however, up to 50% of patients with covid-19 admitted to the icu did not subsequently require imv. 4 given the considerable resource limitations imposed by the current unprecedented viral pandemic, it is important to ascertain whether selected patients can be safely managed outside of the icu. to our knowledge, there have been no randomised control trials in the use of either hfnc or niv in coronavirus-related pneumonia. it has been reported that use of niv during the middle eastern respiratory syndrome outbreak was associated with a 92% risk of requiring imv, thus suggesting futility. 5 this study was based in the icu, however, and patients enrolled had a median pao 2 /fio 2 ratio of 110 (iqr 62-160), indicating a degree of severity that likely warranted initial management with imv. conversely, data from only one study 6 on the severe acute respiratory syndrome (sars) outbreak suggest that niv can successfully avoid intubation. hfnc has received much interest since the florali trial. 7 acute hypoxaemic respiratory failure (ahrf) in this study was largely secondary to community or hospital-acquired pneumonia. though the primary outcome of intubation at day 28 was negative, hfnc reduced requirement for intubation in a subgroup of patients with pao 2 /fio 2 ratio <200 and was associated with a reduction in mortality when compared with niv or regular oxygen face mask. the niv group of this study involved niv use for an average of only 8 h per day, however, and a relatively high target tidal volume of 7-10 ml/kg. florali also utilised a flow rate of 50 l/min with hfnc. to ameliorate potential aerosol generation, a flow limit of 30 l/min in covid-19 has been proposed. the level of positive end-expiratory pressure (peep) supplied is consequently reduced. notably, with regards to aerosol generation and risk to health-care workers, intubation poses a greater risk than niv and a risk with hfnc has not been established. 8 concern regarding ward oxygen flow rates and hospital oxygen reserves is probably the most important cause for hesitancy over advocating hfnc (irish thoracic society guidelines). a major benefit of peep is that it might allow for down-titration of fio 2 , mitigating against over-consumption of hospital oxygen supply and avoiding hyperoxiarelated lung injury. anecdotal reports and our own experience of covid-19-related lung injury suggests a good response to application of peep, perhaps related to recruitment of atelectasis and reduced work of breathing. peep of 10 cm h 2 o or higher can shift the lung to the point on the pressure-volume curve with the highest slope (high compliance). 9 haemodynamic instability appears to be a relatively infrequent feature of these patients, and thus higher peep (ie, expiratory positive airway pressure) than traditionally applied with niv is likely to be tolerated well. benefits of bi-level positive airway pressure over continuous positive airway pressure in this setting have not been established conclusively. regardless of mode, the key factor in improving oxygenation is mean airway pressure (paw). addition of pressure support has the advantage of compensating for resistance present in the tubing and in further reducing work of breathing. 10 it is prudent to follow ardsnet guidelines in maintaining tidal volume of ≤6 ml/kg through low pressure support (driving pressure), relatively high peep, and the lowest fio 2 feasible. to mitigate against nosocomial aerosol transmission, it is critical that niv circuits are modified to include a filter at the exhalation port or vent. the debate about the optimal mode of respiratory support before imv in ahrf has not been settled, much less in the setting of coronavirus, and it is important treatment for severe acute respiratory distress syndrome from covid-19 non-invasive ventilation of patients with acute respiratory distress syndrome. insights from the lung safe study intubation and ventilation amid the covid-19 outbreak: wuhan's experience non-invasive ventilation in critically ill patients with the middle east respiratory syndrome effectiveness of non-invasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure transmission of severe acute respiratory syndrome during intubation and mechanical ventilation physiologic effects of non-invasive ventilation during acute lung injury inspiratory work with and without continuous positive airway pressure in patients with acute respiratory failure clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china key: cord-016042-iyuca9lv authors: keymel, stefanie; steiner, stephan title: noninvasive mechanical ventilation guidelines and standard protocols for noninvasive mechanical ventilation in patients with high-risk infections date: 2013-05-29 journal: noninvasive ventilation in high-risk infections and mass casualty events doi: 10.1007/978-3-7091-1496-4_40 sha: doc_id: 16042 cord_uid: iyuca9lv noninvasive ventilation (niv) is associated with lower rates of endotracheal intubation and decreased mortality in patients with acute respiratory failure. therefore, niv should be preferred to invasive ventilation whenever possible [1]. in clinical settings, most of the patients were treated by niv because of pulmonary edema or exacerbated chronic obstructive lung disease (copd) [2]. with endemic and high-risk infection, most of the critically ill patients develop acute lung injury (ali) and/or acute respiratory distress syndrome (ards). furthermore, niv, an “aerosol-producing factor” might be regarded as a high-risk procedure for medical staff [3]. as a result of the growing importance of niv in emergency and intensive care medicine, several guidelines on this topic were published during the last decade. the following overview summarizes the recommendations on niv in patients with ali and ards, which are known to complicate high-risk infections. in 2001, an international expert group concluded that niv may substitute for invasive ventilatory support in patients with hypoxemic respiratory failure due to pneumonia. the authors noted that there were only three randomized studies comparing niv with invasive ventilation and that they had different endpoints and results [ 2 ] . a year later, the british thoracic society (bts) published guidelines on the use of niv in patients with acute respiratory failure (arf). they did not consider the treatment of ali due to respiratory infection. conversely, at this time severe hypoxemia was regarded as a contraindication for niv [ 4 ] . certainly, there was no link to high-risk infection at that time. the canadian critical care trials group made no recommendations about the use of niv in ards patients or those with severe community-acquired pneumonia (cap) in 2011 [ 5 ] . in summary, compared to niv for exacerbated copd (hypercapnic respiratory failure), cardiogenic lung edema, or postextubation failure, the data regarding the use of niv in patients with hypoxemic arf are less clear [ 1 ] . tables 40.1 and 40.2 summarize common accepted indications and contraindications for niv. niv might be considered in patients with tachypnea and a respiratory rate >24 breaths/min, a poor alveolar gas exchange level as indicated by pao 2 / fio 2 < 200 mmhg, and/or severe dyspnea accompanied by the use of accessory respiratory muscles [ 6 ] . beyond this, niv may be undertaken as a therapeutic trial with a view to tracheal intubation if it fails or as a ceiling of treatment in patients who are not candidates for intubation [ 4 ] . it should be emphasized that intubation there is a broad agreement that niv should be conducted in the intensive care unit (icu), where immediate expertise is available to enable a rapid transition to invasive ventilation if needed [ 1 , 8 , 9 ] . noninvasive ventilation is defi ned as ventilator assistance to the lungs without an artifi cial airway. there are various devices, including negative-pressure ventilators (e.g., the so-called tank ventilator, or "iron lung"), several masks, and helmets. because of limited practicability, tank ventilators do not play a major role in modern intensive care medicine. selection of the optimal interface-which connects the ventilator to the nose, mouth, or both-is an essential part of niv. air leakage, discomfort, or claustrophobia might result in patient intolerance. in the acute care setting, nasal, oronasal, or full-face masks are primarily used [ 1 , 4 , 5 ] . there are few randomized controlled trials comparing the use of an oronasal mask with a nasal mask. nevertheless, the oronasal mask has been better tolerated than nasal mask or full-face mask [ 1 , 10 ] . because there is a lack of evidence regarding which interface is best, some guidelines do not give recommendations about the use of interfaces [ 5 ] . others favor the use of a full-face mask for the fi rst 24 h, switching to a nose mask if preferred by the patient [ 4 , 11 ] . in general, masks and exhalation valves that are licensed as reusable by the manufacturer require high-level disinfection. they should be disassembled in their parts and then undergo an automatic process using washer, disinfector, and dryer. attaching a bacterial fi lter to the ventilator's output can minimize respirator contamination [ 4 ] . as an alternative, using single-use material could reduce the risk of infection. noninvasive ventilation can be performed using pressure support ventilation, proportional assist ventilation, or volume-controlled ventilation [ 1 , 2 ] . schönhofer et al. [ 1 ] recommended the use of positive-pressure ventilation with inspiratory pressure support and positive end-expiratory pressure (peep). as patients with arf are often agitated and have pronounced respiratory drive, ventilation triggered by the patient's own respiratory efforts is benefi cial compared to controlled, timebased ventilation. when there is not suffi cient spontaneous inspiratory effort or it is inadequate to trigger the ventilator, pressure-controlled ventilation could be used [ 1 , 2 ] . other guidelines do not emphasize a mode of ventilation on the strength of insuffi cient evidence [ 5 ] . similar to invasive ventilation, ventilator settings should be adjusted to provide the lowest inspiratory pressures or volumes needed to improve oxygenation and patient comfort, which can be estimated by the decrease in the respiratory rate and respiratory muscle unloading [ 2 ] . because most of the critical ill patients with sars or h1n1 virus infection develop ards and ali, a lung-protective ventilatory strategy and fl uid restriction are essential. the most important parameters during the clinical course are paco 2 (arterial partial pressure of carbon dioxide), ph, respiratory rate, dyspnea, and alertness. the aforementioned parameters have to show a trend toward improvement during the fi rst 2 h of niv [ 1 ] . the niv failure rate in patients with hypoxic respiratory failure is estimated to be 30 % (cap) to 50 % (ards) [ 7 , 9 , 12 ] . failure occurs early or after a few days [ 1 ] . it should be noted that niv failure is associated with a worse outcome, which might be a consequence of a delayed response to the niv failure because of inadequate monitoring or delayed defi nitive care [ 13 ] . other predictors of failure are the duration of niv, oxygenation index, and the simplifi ed acute physiology score ii at admission, and, as expected, the length of icu stay [ 7 ] . other authors found a high apache score, copious respiratory secretions, poor nutritional status, and confusion or impaired consciousness to be associated with niv failure [ 2 ] . there are specifi c problems concerning the use of niv in patients with endemic and high-risk infections. first, there are no controlled trials on this topic. therefore, recommendations are largely based on supposition [ 3 ] . it is of concern that niv, as an "aerosol-producing procedure," possibly increases the risk of caregiver exposure or of exposure to other patients, which would be disastrous in case of a pandemic. therefore, organizations such as the world health organization [ 14 ] and the uk national health services agency [ 15 ] published guidelines that treat niv as a high-risk procedure. nevertheless, there are no controlled data comparing particle dispersion between individuals undergoing niv and those who are not. furthermore, it should be kept in mind that endotracheal intubation also is at risk of transmitting disease. in an experimental model, hui and coworkers [ 16 ] found that fl ow from a noninvasive ventilator may increase occupational risk. as this risk may be mediated by air leaks, fi tting the mask properly is essential. full-face masks and helmets might be superior to nasal masks. also, niv must be managed under strict isolation measures with adequate protection (e.g., n-95 mask) of the health care workers who attend to the patients. as far as possible, infected patients should be isolated in rooms with negative pressure. although most of the guidelines do not recommended use of niv, it has become part of the standard treatment protocol for sars [ 17 ] . han et al. [ 18 ] demonstrated that niv was not only effective in avoiding intubation and invasive ventilation, it effectively reduced the icu length of stay. no infection was detected in 155 health care workers, and their serology tests for coronavirus were negative. • current guidelines do not recommend niv for the treatment of hypoxemic respiratory failure in endemic and pandemic infections (e.g., sars or h1n1). however, the level of evidence is low. • noninvasive ventilation appears to be a reasonable option in carefully selected cases, which should be treated under optimal conditions with awareness of niv failure and might be regarded as a high risk procedure for medical staff. clinical practice guidelines: non invasive ventilation as treatment of acute ventilation international consensus conference in intensive care medicine: noninvasive positive pressure ventilation in acute respiratory failure should noninvasive ventilation be considered a high-risk procedure during an epidemic? british thoracic society standards of care committee. non-invasive ventilation in acute respiratory failure clinical practice guidelines for the use of nonivasive positive-pressure ventilation and nonivasive continuous positive airway pressure in the acute care setting noninvasive mechanical ventilation predictors of failure of noninvasive ventilation in patients with severe community-acquired pneumonia non-invasive mechanical ventilation in acute respiratory failure bts guidelines for the management of community acquired pneumonia in adults: update interface strategy during non invasive pressure ventilation for hypercapnic acute respiratory failure non-invasive ventilation in chronic obstructive pulmonary disease: management of acute type 2 respiratory failure predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study best practices for noninvasive ventilation infection prevention and control of epidemic-and pandemic-prone acute respiratory diseases in health care infl uenza: clinical management guidelines for adults and children. guidance department of health, uk guidelines noninvasive positive pressure ventilation an experimental model to assess air and particle dispersion effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome noninvasive positive pressure ventilation treatment for acute respiratory failure in sars key: cord-330704-4piesfxu authors: avdeev, sergey n.; yaroshetskiy, andrey i.; tsareva, natalia a.; merzhoeva, zamira m.; trushenko, natalia v.; nekludova, galina v.; chikina, svetlana yu title: noninvasive ventilation for acute hypoxemic respiratory failure in patients with covid-19 date: 2020-10-01 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.075 sha: doc_id: 330704 cord_uid: 4piesfxu aim: noninvasive ventilation (niv) is known to reduce intubation in patients with acute hypoxemic respiratory failure (ahrf) [1]. we aimed to assess the outcomes of niv application in covid-19 patients with ahrf. materials & methods: in this retrospective cohort study, patients with confirmed diagnosis of covid-19 and ahrf receiving niv in general wards were recruited from two university-affiliated hospitals. demographic, clinical, and laboratory data were recorded at admission. the failure of niv was defined as intubation or death during the hospital stay. results: between april 8 and june 10, 2020, 61 patients were enrolled into the final cohort. niv was successful in 44 out of 61 patients (72.1%), 17 patients who failed niv therapy were intubated, and among them 15 died. overall mortality rate was 24.6%. patients who failed niv were older, and had higher respiratory rate, paco(2), d-dimer levels before niv and higher minute ventilation and ventilatory ratio on the 1-st day of niv. no healthcare workers were infected with sars-cov-2 during the study period. conclusions: niv is feasible in patients with covid-19 and ahrf outside the intensive care unit, and it can be considered as a valuable option for the management of ahrf in these patients. the novel coronavirus disease 2019 (covid-19) outbreak that began in 2019 and spread rapidly across the world has been observed to cause viral pneumonia and acute hypoxemic respiratory failure (ahrf) [2] . for patients who are unresponsive to conventional oxygen therapy, high-flow nasal cannula (hfnc) oxygen, noninvasive ventilation (niv) or invasive mechanical ventilation (imv) may be administered [3] . several studies suggested high mortality for patients with covid-19-associated ahrf who received imv [4] , raising the concern that these patients may be particularly vulnerable to ventilator-induced lung injury [5] . noninvasive oxygenation strategies that could at least safely spare patients of imv could be of enormous importance. however, there were major concerns that hfnc or niv may create risks for health care workers (hcws) because of sars-cov-2 transmission via aerosols [6] while the data on the efficacy of noninvasive modalities in covid-19-associated ahrf are still limited [6] [7] [8] . the aim of this study was to assess the outcomes of niv application in covid-19 patients with ahrf. this retrospective cohort study was conducted in covid-19 care units of two university-affiliated hospitals between april 8 and june 10, 2020. the study was approved by the local ethics committee (approval number [16] [17] [18] [19] [20] . as this was a retrospective study, the requirement for informed consent was waived. we analyzed all patients aged ≥ 18 years with the laboratory-confirmed sars-cov-2 infection admitted to the general wards (outside intensive care units) for ahrf. the inclusion criteria were the need for oxygen greater than 6 l/min to maintain oxygen saturation (spo 2 ) above j o u r n a l p r e -p r o o f 92% and symptoms of respiratory distress (dyspnea, tachypnea, and activation of respiratory accessory muscles). the exclusion criteria were as follows: the need for immediate endotracheal intubation (eti), niv duration less than 60 minutes, chronic respiratory diseases (chronic obstructive pulmonary disease, obesity hypoventilation syndrome, etc), and unstable hemodynamics (requiring vasopressor support and/or lifethreatening heart rhythm abnormalities). all included patients were managed in isolated neutral pressure rooms. demographic data, comorbidities and clinical laboratory data were recorded at admission, and respiratory parameters were recorded before niv start and on the 1st day of niv. we used niv ventilators equipped with air-oxygen blender (trilogy 202, philips respironics, usa) and non-vented oronasal masks; the expiratory limb of the circuit was equipped with an antimicrobial filter. the primary niv mode was the continuous positive airway pressure (cpap), the pressure was initially set at 10 cm h2o and then adjusted according to spo 2 and clinical tolerance. a pressure support ventilation (psv) was considered over cpap in patients who showed respiratory acidosis (ph<7.35), tachypnea >30/min or a vigorous activity of respiratory accessory muscles. fio 2 was adjusted to maintain the arterial oxygen saturation of more than 92% during niv. patients with bilateral posterior infiltrates were placed in the prone position for at least 8 hours a day. the failure of niv was defined as intubation or death during the hospital stay. the ng/ml, p<0.0001) ( table 1) table 1) . d-dimer was the best predictor of niv failure with the area under the roc curve of 0.82 (95% ci 0.64-1.00), p=0.002, sensitivity 82% and specificity 80% for d-dimer level > 1190 ng/ml). all hcws who were exposed to niv patients used appropriate personal protection equipment (ppe) composed of ffp2/ffp3 masks, eye and head protections, disposable protective suits, gloves, and overshoes and nobody of hcws was infected with sars-cov-2 during the study period. this study suggests that the use of niv is feasible in acute hypoxemic respiratory failure in patients with covid-19 outside intensive care unit and can be considered as an effective means to improve oxygenation in patients not responding to conventional oxygen therapy. about 28% of our covid-19 patients with ahrf failed niv and required eti and imv with an associated mortality of 88%, compared with 0% when niv succeeded. our results are in accordance with recent reports on the use of niv in covid-19-associated ahrf, where the niv failure rate varied from 23% to 45% [7] [8] [9] . no significant difference between the success and failure groups in baseline pao 2 /fio 2 was found in our study, although a low baseline pao 2 /fio 2 was shown to be a risk factor of niv failure in several studies [10] . interestingly, the median pao 2 /fio 2 values in our patients were lower than those from a cohort study of mechanically ventilated [11] . we identified elevated d-dimer levels as a strong predictor of niv failure. in a study by wang et al, describing a nationwide cohort of critically ill covid-19 patients in china, elevated ddimer (>1.5 mg/l) at admission was also an indicator of increased possibility of imv requirement [12] . it was shown that d-dimer elevation in covid-19 was associated with the progression of the disease [13] , so, progressive underlying processes can predispose to prolonged respiratory support and niv failure [14] . we found that patients who failed niv had some important characteristics of gas exchange. this concerns minute ventilation and ventilation ratio during niv, which in general may be associated with increased alveolar dead space and impaired carbon dioxide clearance. higher minute ventilation in patients with niv failure was due to slightly higher tidal volume and higher respiratory rate, which, of course, may increase the risk of lung injury [15] . the time to niv failure and eti had a very wide range that can be explained by different time from disease onset to niv start, different volumes of lung injury and different rate of disease progression. no healthcare workers helping to treat the patients on niv were infected with sars-cov-2 during the study period. these data could be confirmed from other studies. in an observational study by oranger et al. the proportion of hcws contaminated by sars-cov-2 was similar before and after the implementation of cpap in the management of covid-19 patients (6% vs 10%) [7] . in a recent study of gaeckle et al. there was no observed increase in the concentration of aerosolized viral particles with the use of niv or hfnc when compared to breathing room air [16] . so, with appropriate ppe, the hcw infections can be avoided even caring for patients with niv. j o u r n a l p r e -p r o o f this study has several limitations. first, its retrospective design is susceptible to selection bias, however, all clinical and laboratory parameters were collected prospectively. second, the small study population precludes subgroup analyses and extensive multivariate analysis due to the limited size of events. third, our study is a single-center study (although it was performed in two university-affiliated hospitals) with respect to practice of niv, and so might not be generalizable to other centers. in summary, we have shown that niv is feasible in patients with covid-19 with acute hypoxemic respiratory failure outside the intensive care unit, and it can be considered as a valuable option for the management of ahrf in these patients. no healthcare workers helping to treat the patients on niv were infected with sars-cov-2 during the study period. bmi, body mass index; pao 2 /fio 2 , arterial oxygen tension to inspired oxygen fraction ratio; crp, c-reactive protein; wbl, whole blood leucocytes; v t , tidal volume; ibw, ideal body weight. association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure: a systematic review and meta-analysis clinical characteristics of coronavirus disease 2019 in china surviving sepsis campaign: guidelines on the management of critically ill adults presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area high incidence of barotrauma in patients with covid-19 infection on invasive mechanical ventilation epidemiology of and risk factors for coronavirus infection in health care workers: a living rapid review continuous positive airway pressure to avoid intubation in sars-cov-2 pneumonia: a two-period j o u r n a l p r e -p r o o f journal pre-proof retrospective case-control study helmet cpap treatment in patients with covid-19 pneumonia: a multicenter, cohort study feasibility and clinical impact of out-of-icu non-invasive respiratory support in patients with covid-19 related pneumonia effectiveness and predictors of success of noninvasive ventilation during h1n1 pandemics: a multicenter study respiratory pathophysiology of mechanically ventilated patients with covid-19: a cohort study patients with mechanical ventilation: a nationwide study in china risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in wuhan, china noninvasive ventilation for acute hypoxemic respiratory failure/ards -is there a role? ventilator-related causes of lung injury: the mechanical power aerosol generation from the respiratory tract with various modes of oxygen delivery key: cord-017786-kfl6xt31 authors: curiel-balsera, emilio; garcía-trujillo, elena title: guidelines for health organizations: european perspectives and experience in pandemics date: 2013-05-29 journal: noninvasive ventilation in high-risk infections and mass casualty events doi: 10.1007/978-3-7091-1496-4_41 sha: doc_id: 17786 cord_uid: kfl6xt31 in europe, the rate of noninvasive ventilation (niv) use in intensive care units (icus) is about 35 % for ventilated patients and higher (roughly 60 %) in respiratory icus or emergency departments. in north america, this form of ventilation is begun most often in emergency departments (eds), most patients being transferred to the icu or step-down units in hospitals with such facilities. this low rate of use in some hospitals is related to scarce knowledge on or experience with this technique, insufficient technical equipment, and inadequate funding. despite these limitations, niv is increasingly being used outside traditional and respiratory icus, including eds, postsurgical recovery rooms, cardiology, neurology, and oncology wards, and palliative care units. infectious disease transmission. despite the paucity of epidemiological data, the idea that niv leads to increased occupational risk has gained currency. in fact, some organizations such as the canadian diseases advisory committee have published recommendations to avoid niv in patients with febrile respiratory illness [ 2 ] . other studies show that niv can be used effectively and safely in such situations by applying strict infection-control procedures [ 3 -5 ] . the european society of intensive medicine and the european respiratory society guidelines recommend when niv should be considered (or not) after reviewing studies following the last h1n1 pandemics in europe [ 6 ] : niv must not be considered in patients with severe hypoxemic acute respiratory failure (arf), rapid development of ards, or multiorgan failure. invasive ventilation is recommended for these patients. niv may be considered to prevent further deterioration and intubation needs in patients with mild-to-moderate hypercapnic arf due to cardiogenic pulmonary edema or exacerbation of a chronic respiratory disease secondary to h1n1 infection in the absence of pneumonia, multi-organ failure (mof), or refractory hypoxemia. it can also be used to prevent postextubation respiratory failure in patients with resolving ards secondary to h1n1 infection, preferably when patients are no longer contaminated. there is growing concern about droplet dispersion during niv, but it is important to note that similar exposures may occur during routine oxygen therapy by mask, coughing or sneezing, or procedures such as bronchoscopy and aerosol delivery. recommendations for droplets include patient isolation with protective measures for health care providers and other patients, use of double-circuit tubes and special fi lters for nonrebreathing devices, minimization of leaks, preferably fullface mask or helmet interfaces, avoidance of heated humidifi ers, and disposing of mask and tubes after use according to routine infection control procedures [ 7 ] . the spanish society of intensive care medicine, after collecting data from its hospital network, developed a document with recommendations for the management of severe complications in the h1n1 fl u pandemic [ 8 ] . the document states that: …noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, but could be useful in experienced centers and in cases of respiratory failure associated with exacerbation of chronic obstructive pulmonary disease or heart failure. it can be used in highly experienced centers, with appropriate helmet-type interfaces and patients who have reported very good results, although only in a few cases. the use of niv and its risks have been discussed in many documents. in 2009, the scottish government published a guide on niv in pandemic fl u patients. the recommendations on niv are somewhat complex, but they ultimately suggested that niv could be used effectively and safely in such situations under strict infection-control procedures. these conclusions were reached in the united kingdom are shown in table 41 .1 [ 9 ] . the recommended equipment and materials are shown in table 41 .2 . in some circumstances, a continual leak of unfi ltered gas from the exhalatory circuit may be anticipated, and consideration should be given to adopting a policy for the staff working close to the patient of wearing ffp3 respirators and eye protection for extended periods throughout a shift. examples of leaks of unfi ltered gas include: (1) situations where no bacterial/viral fi lters are available and therefore staff should be trained in infection control. gown, gloves, and eye protection should be worn for all aerosol-generating procedures. the use of an ffp3 respirator instead of a surgical mask may be advisable until there are data that allow better assessment of the risk associated with the various procedures. patients should be managed in negative-pressure single rooms with anterooms, where this condition is available. if such facilities are not available, the patients should be cared for in standard single rooms or, if there is no other option, in cohorted groups. a nonvented patient mask or helmet should be used. although bilevel pressure support (bipap) niv is likely to be preferred, cpap ventilation may be used in certain circumstances. a high-effi ciency bacterial/viral breathing system fi lter (bs en 13328-1) should be used between the nonvented mask and the expiratory port and at the outlet of the ventilator. expiratory port options include a whisper swivel or controlled leak valve (each with a proximal fi lter, as above). ideally, expiratory fl ow should be directed through a single jet away from patients and staff. niv masks should be applied to the patient's face and secured before the ventilator is turned on. double-tube circuit ventilators may be advantageous. the ventilator should be turned off before removing the close-fi tting mask or when lifting the mask away from the face (e.g., for mouth care or fl uid sips). water humidifi cation should be avoided. disposable patient respiratory equipment must be used wherever possible. reusable equipment must be decontaminated in accordance with local policy and the manufacturer's guidelines. closed systems should be used wherever possible (e.g., suction). all respiratory equipment used on patients, including transport ventilator circuits and manual resuscitation aids, should include a high-effi ciency bacterial/viral breathing system fi lter (bs en 13328-1). breathing fi lters should be changed in accordance with the manufacturer's guidelines. the ventilatory circuit should not be broken unless absolutely necessary. staff should be alert regarding power supply due to unplanned breathing circuit disruption: (1) breathing circuits should be checked regularly for tightness of fi t in component parts. (2) caution is necessary when moving or performing other care on ventilated patients to minimize the risk of accidental disconnection. for planned circuit breaks, appropriate ppe and ffp3 respirators should be worn as for aerosol-generating procedures. procedures for the rapid deployment and use of appropriate ppe and ffp3 respirators in the event of an unplanned breathing circuit disruption should be developed and rehearsed. ventilator circuits have to be used unfi ltered and (2) when high-frequency oscillatory ventilators are used. the world health organization recommends special considerations in nivtreated patients, including additional precautions in eds and icus [ 10 ] . • noninvasive ventilation [bilevel positive airway pressure (bipap), continuous positive airway pressure (cpap)]: standard and droplet precautions unless indicated otherwise by new evidence of increased transmission risk. • nebulization: standard and droplet precautions. nebulizer treatment should be performed in an area that is physically separated from other patients (e.g., treatment room, screened enclosure). in relation to supportive therapies for hypoxemia treatment, oxygen support is recommended but with no distinction between invasive and noninvasive ventilation, except in lung-protective ventilation strategies [ 1 ] . regarding niv in pandemics, italian and french guidelines refer to the world health organization or the centers for disease control and prevention for its implementation, without further information. the currently suggested best practice for niv delivery in patients with pandemic fl u pneumonia in europe are summarized in table 41 .1 . after a revision of the necessary organization and infrastructures in case of a pandemic, the following conclusion was drawn: each hospital bed must dispose of its oxygen supply and suction, especially in areas involving expected niv use [ 11 ] . • noninvasive mechanical ventilation cannot be considered a technique of choice in patients with ards but could be useful in experienced centers and in cases of respiratory failure associated with exacerbation of chronic obstructive pulmonary disease or heart failure. • it is preferable to perform niv using an appropriate helmet-type interface. • concerning droplet dispersion during niv, similar exposures may occur during routine oxygen therapy by mask or procedures such as bronchoscopy and aerosol delivery. • water humidifi cation should be avoided. • all respiratory equipment used on patients, including transport ventilator circuits and manual resuscitation aids, should include a high-effi ciency bacterial/viral breathing system fi lter (bs en 13328-1). clinical management of human infection with pandemic (h1n1) 2009: revised guidance preventing febrile respiratory illnesses. ottawa: ontario ministry of health and long term care effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome non invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome high success and low mortality rates with noninvasive ventilation in infl uenza a h1n1 patients in a tertiary hospital on the role of non-invasive ventilation (niv) to treat patients during the h1n1 infl uenza pandemic exhaled air dispersion distances during noninvasive ventilation via different respironics face masks recommendations of the infectious diseases work group (gtei) of the spanish. society of intensive and critical care medicine and coronary units (semicyuc) and the infections in critically ill patients study group (geipc) of the spanish society of infectious diseases and clinical microbiology (seimc) for the diagnosis and treatment of infl uenza a/h1n1 in seriously ill adults admitted to the intensive care unit guidance on infection control for critical care and non-invasive ventilation provision. published by the scottish government & health protection scotland world health organization. standard precautions in health care surge capacity and infrastructure considerations for mass critical care key: cord-010850-zj6k7wz9 authors: holbird, samantha; holt, tanya; shaw, adam; hansen, gregory title: noninvasive ventilation for pediatric interfacility transports: a retrospective study date: 2020-05-13 journal: world j pediatr doi: 10.1007/s12519-020-00363-3 sha: doc_id: 10850 cord_uid: zj6k7wz9 background: to characterize pediatric patients supported with continuous positive airway pressure and bilevel positive airway pressure (cpap/bipap) or high-flow nasal cannula (hfnc) during interfacility transport (ift). methods: a retrospective study with a provincial pediatric transport team from a tertiary hospital pediatric intensive care unit. pediatric patients aged 28 days to < 17 years, who required ift between january 2017 and december 2018, were identified through a transport registry and were included in the study. results: a total of 118 (26.7%) patients received cpap/bipap or hfnc support for ift. the most common respiratory diagnosis was bronchiolitis (46%). these patients were placed on respiratory support, 31.4 minutes after the transport team’s arrival. none required intubation during their ift, despite mean transport times of 163 minutes. conclusions: this study may provide important information for programs with large catchment areas, in which large distances and transport times should not be barriers to niv implementation. with critically ill neonates and children in acute respiratory distress, conventional mechanical ventilation (cmv) has frequently been employed during interfacility transports (ifts). with advancements in noninvasive technologies that mitigate some of the risks and complications associated with cmv, an increased interest and utilization have been documented [1, 2] . noninvasive ventilation (niv)-in the form of continuous positive airway pressure (cpap) and bilevel positive airway pressure (bipap)-was first reported in adult ifts for chronic obstructive pulmonary disease, acute cardiogenic pulmonary edema, and pneumonia [3] . in pediatrics, niv in the pediatric intensive care unit (picu) first demonstrated improved vital signs and decreased both mortality and need for mechanical ventilation [2, 4, 5, 6] . pediatric niv during ifts would follow [4] by mimicking its increased utilization in the picu [3, 7, 8] . a recent systematic review suggested that niv is safe and feasible in the transport environment [9] , but mortality, intubation rates, and effect on length of stay have not been fully established. the objectives of this retrospective chart review study were to characterize pediatric patients requiring ifts and niv and to examine their clinical outcomes, including the need for airway instrumentation. in saskatchewan, over 450 patients per year are transported from referring centers to the royal university hospital in saskatoon. the province offers unique challenges including inclement weather and vast geography (651,900 km 2 ) with a population of nearly 1.2 million. pediatric intensivists, who provide medical oversight and triage for all ift missions, have trained the specialized pediatric transport team to provide advanced treatment including airway instrumentation, chest tubes, and emergency cricothyrotomies. utilization of niv and high-flow nasal cannula (hfnc) on ifts began in the year 2014. niv was provided via large bore cannula, total face mask, or full-face mask depending on patient size and compliance, and hfnc is provided via the optiflow jr. interface. the device used for cpap and bipap was the hamilton t1 transport ventilator with niv and niv-st modes. a trial of hfnc, as we have previously described [10] , is undertaken at the referring center after ruling out immediate need for intubation and balancing variables such as time to tertiary care, road versus air transport, and diagnosis trajectory. niv was typically not initiated by referring centers owing to their lack of equipment and/or in-house respiratory therapy support. at present, a protocol for niv has not been established for our ifts. instead, the decision to proceed with niv and preliminary settings was made following discussion with the pediatric intensivist and transport team and following appropriate observation of respiratory symptom improvement. in addition, an approach to escalation of settings during transport was discussed, with the most common triggers being increased oxygen requirements or work of breathing. blood gas analyses were routinely performed prior to initiation of niv or hfnc, but end tidal co 2 was not, because interface leaks led to unreliable trends or to inability to measure with certain modes. pediatric patients who required ift between january 2017 and december 2018 were identified through the provincial pediatric transport program's registry. all children aged 30 days to < 17 years who were subsequently admitted to the picu were included in the study. children with a prior advanced care directive or tracheostomy were excluded. baseline patient demographics and transport metrics included season of transport, distance and time of return leg (transport team departure to picu admission), transport team assessment, transport risk assessment in pediatrics (trap) score [11] , picu arrival trap score, mode of ventilatory support, highest ventilatory support, highest fraction of inhaled oxygen (fio 2 ), and need for sedation. data on hfnc were also collected but analyzed separately from niv. trap is an objective assessment tool in which an elevated score is associated with a picu admission for more than 24 hours [11] . mode of transport (ground or fixed wing) was determined. lastly, transport and patient outcome measures were collected and recorded. the university of saskatchewan biomedical research ethic board approved the study (bio-reb 921). discrete variables were reported as percentages, and continuous data as means and standard deviations (sd). proportions were compared using a two-tailed fisher's exact test. difference in means and their 95% confidence intervals (ci) were calculated. significance level was considered at p = 0.05. stata 14 software (statacorp. 2015. stata statistical software: release 14. college station, tx: statacorp lp) was utilized for all analyses. a total of 120 patients (table 1 ) on niv or hfnc for ift were studied (26.7% of transport cohort), but 2 had incomplete records and were excluded from analysis. the most common respiratory diagnosis was bronchiolitis (n = 54, 45.8%). ift metrics are also summarized in table 1 . differences of mean trap scores between transport team arrival and tertiary center handover were significant (95% ci − 0.90 to − 0.04, p = 0.03). respiratory support during ift is summarized in table 2 . eleven patients were already on niv or hfnc before the outcomes, including maximal respiratory support, duration of support, length of stay, and mortality are summarized in table 3 . of note, 16.1% (n = 19) required conventional mechanical ventilation and were intubated an average of 57.6 (sd 33.4, range 0-528) hours after admission. one patient (0.8%) died due to complications associated with acute respiratory distress syndrome. this study provides a synopsis of the use of niv and hfnc during pediatric ifts and their outcomes by a provincial pediatric transport program. our primary observations suggest that its utilization is safe and does not lead to untimely intubations. this review's results are similar to those described in previously published literature and suggest that niv is safe for ifts [12, 13] . the only negative outcomes were significant hypoxemia in three patients that were resolved with stimulation or with bag valve mask ventilation. there was also one case of bag valve mask use which was required due to an equipment issue, but niv was replaced without incident once the issue was resolved. an overall improvement of trap scores during transport suggests that vital signs and clinical status are grossly stabilized. together, these results highlight the importance of an experienced transport team capable of appropriately selecting patients and promptly recognizing and responding to complications. it is also prudent to note that none of our patients required conversion to cmv during ift, despite long transport times and distances. higher than previously reported [14] , 16% of patients eventually required cmv in the picu. although this percentage may seem large, patients typically were intubated later (mean 57 hours post picu admission) and required longer ventilator times (mean 8 days), which perhaps suggests disease progression rather than a failure of niv. at the very least, questions of what percentages are acceptable need to be considered. with a more aggressive strategy of instrumenting airways be employed, several patients could have been unnecessarily supported with cmv and exposed to its associated risks, such as ventilator-associated pneumonia, airway injury, and sedation. a recent canadian study reported prehospital and picu niv use in bronchiolitis and demonstrated similar outcomes with less complications and with fewer interventions than patients receiving cmv [14] . surely a balance exists in providing patients safe opportunities to declare clinical trajectory on niv support, but this has not yet been clearly elucidated. finally, our study also may have captured a growing and unique patient cohort in pediatric intensive care: patients that cannot be supported by low-flow nasal cannula, but require a short duration of ventilatory support. the majority of our patients were supported for less than 3 days of niv and > 1 day of hfnc despite respiratory compromise in referring centers. because bronchiolitis and asthma diagnoses accounted for nearly 60% of our cohort, short duration positive pressure for lung recruitment or maintenance of lower airway patency could have been responsible for these rapid turnarounds. furthermore, this cohort is particularly important because a certain percentage would certainly have been intubated in the past. our crude ift data showed that in 2019, 62% of patients requiring respiratory support were initiated on niv; in 2014, it was less than 10%. there are a few limitations to our study. first, the retrospective nature of the study is a major limitation because the data depend on accurate recording. however, significant events during ifts should have been captured by overlapping quality control processes, thereby mitigating the potential of missing serious adverse outcomes. second, the lack of a protocol for niv management during ifts should be stated. this is an excellent area for ongoing research that we are currently pursuing. finally, interpretation of our results should be done by considering that we did not utilize a historical cohort control in our methodology. niv and hfnc are common during pediatric ifts especially for bronchiolitis. after our specialized transport team initiated niv or hfnc, escalation to cmv was not necessary during the ift, despite mean transport times of 2.5 hours. this retrospective study may suggest the utility of an niv trial in suitable patients, so that instrumentation of the airway and cmv are avoided whenever possible. author contributions gh conceptualized the study and analyzed the data. th co-conceptualized the study and interpreted the data. as acquired the data from the transport registry. sh acquired the data from the hospital charts and wrote the initial manuscript. all authors revised and approved the final manuscript. funding none. ethical approval ethical approval granted by the university of saskatchewan (bio-reb 921). noninvasive ventilation during pediatric interhospital ground transport evolution of noninvasive mechanical ventilation use: a cohort study among italian picus early out-of-hospital non-invasive ventilation is superior to standard medical treatment in patients with acute respiratory failure: a pilot study noninvasive respiratory support during transportation respiratory support for infants with bronchiolitis, a narrative review of the literature outcomes for children receiving noninvasive ventilation as the firstline mode of mechanical ventilation at intensive care admission: a propensity score-matched cohort study out-ofhospital continuous positive airway pressure ventilation versus usual care in acute respiratory failure: a randomized controlled trial effect of out-of-hospital noninvasive positive-pressure support ventilation in adult patients with severe respiratory distress: a systematic review and meta-analysis noninvasive ventilation during pediatric and neonatal critical care transport: a systematic review pediatric early warning score and deteriorating ward patients on high-flow therapy transport disposition using the transport risk assessment in pediatrics (trap) score noninvasive respiratory support during pediatric ground transport: implementation of a safe and feasible procedure highflow nasal cannula (hfnc) support in interhospital transport of critically ill children variability of care in infants with severe bronchiolitis: lessinvasive respiratory management leads to similar outcomes no financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. key: cord-309518-seonrtn3 authors: alraddadi, basem m.; qushmaq, ismael; al‐hameed, fahad m.; mandourah, yasser; almekhlafi, ghaleb a.; jose, jesna; al‐omari, awad; kharaba, ayman; almotairi, abdullah; al khatib, kasim; shalhoub, sarah; abdulmomen, ahmed; mady, ahmed; solaiman, othman; al‐aithan, abdulsalam m.; al‐raddadi, rajaa; ragab, ahmed; balkhy, hanan h.; al harthy, abdulrahman; sadat, musharaf; tlayjeh, haytham; merson, laura; hayden, frederick g.; fowler, robert a.; arabi, yaseen m. title: noninvasive ventilation in critically ill patients with the middle east respiratory syndrome date: 2019-03-18 journal: influenza other respir viruses doi: 10.1111/irv.12635 sha: doc_id: 309518 cord_uid: seonrtn3 background: noninvasive ventilation (niv) has been used in patients with the middle east respiratory syndrome (mers) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. methods: patients with mers from 14 saudi arabian centers were included in this analysis. patients who were initially managed with niv were compared to patients who were managed only with invasive mechanical ventilation (invasive mv). results: of 302 mers critically ill patients, niv was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive mv. patients who were managed with niv initially had lower baseline sofa score and less extensive infiltrates on chest radiograph compared with patients managed with invasive mv. the vast majority (92.4%) of patients who were managed initially with niv required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive mv. icu and hospital length of stay were similar between niv patients and invasive mv patients. the use of niv was not independently associated with 90‐day mortality (propensity score‐adjusted odds ratio 0.61, 95% ci [0.23, 1.60] p = 0.27). conclusions: in patients with mers and acute hypoxemic respiratory failure, niv failure was very high. the use of niv was not associated with improved outcomes. middle east respiratory syndrome (mers) has emerged as a cause of severe respiratory illness in humans. 1, 2 as of march 1, 2019, 2279 cases of mers have been reported including 806 deaths. 3 the disease presentation ranges from asymptomatic infection to severe respiratory illness, multiorgan failure, and death. [4] [5] [6] acute hypoxemic respiratory failure (ahrf) develops in up to 70% of hospitalized patients with mers and is associated with high mortality. 7, 8 to date, there is no specific antiviral therapy for mers of proven effectiveness; supportive therapy remains the cornerstone of management. noninvasive ventilation has been increasingly used in the management of ahrf with variable success. [9] [10] [11] [12] while niv may initially avoid the need for intubation and invasive mechanical ventilation (mv) , several studies have reported high failure rates and the need for invasive ventilation among patients with severe acute respiratory distress syndrome (ards) and an association with increased mortality. 12 in a recent analysis from the lung safe study on unselected patients with ards, niv was associated with higher intensive care unit (icu) mortality in patients with the ratio of partial pressure of oxygen to the fraction of inspired oxygen (pao 2 /fio 2 ) lower than 150 mm hg. 12 the role of niv in ahrf secondary to viral respiratory infections is unclear. although some uncontrolled studies suggested that niv was effective and safe in management of patients with severe acute respiratory syndrome (sars), [13] [14] [15] others have highlighted concern of increased transmission risk to healthcare workers when patients with sars are treated with niv. 16 use of niv in ahrf caused by pandemic h1n12009 virus (pdmh1n1) infection has been reported from several countries, [17] [18] [19] with reported niv failure reaching up to 85%. 17 all studies were limited by their retrospective nature and, often, small sample size. noninvasive ventilation has been used in patients with mers, 5, 8 but its value in preventing intubation and impact on clinical outcomes has not been studied. the objective of this study was to assess the success of niv in mers patients with ahrf in avoiding intubation and its association with mortality and icu and hospital length of stay. our secondary objective was to identify factors associated with niv failure in mers patients. we conducted this analysis on a multicenter retrospective cohort of critically ill mers patients from 14 in this study, we included all patients with ahrf who required mechanical ventilation support in the icu, whether invasively or noninvasively. all patients who were managed initially with niv were compared to those who were managed with invasive mv without niv. for this analysis, we extracted baseline data including demographics, comorbidities, duration from onset of symptoms to emergency room admission, icu admission, and intubation. arterial blood gases, continuous variables were described as medians and interquartile ranges (q1, q3) or means and standard deviations and were tested we performed a secondary comparison of patients who had failed niv to those who had been successfully treated with niv. all statistical tests were two-sided with significance set at α < 0.05. analyses were conducted using sas version 9.2 (sas institute, cary, nc). in 105 patients who were managed initially with niv, niv was used for a median duration of 1 (1, 3) day and 97 patients (92.4%) eventually required intubation and invasive mv ( [11, 35] , p = 0.6). there was no significant difference in the duration of invasive mv and total duration of niv and invasive mv between the two groups, although invasive mv-free days and total niv and invasive mv-free days were significantly longer among niv patients compared to invasive mv patients (table 2, figure s2 ). overall, only 8/105 (7.6%) of the niv patients avoided subsequent intubation (table s1 ). these patients were significantly younger than tables s1 and s2). crude 90-day mortality was significantly higher in patients who failed niv compared with patients successfully treated only with niv (table s3 and figure s3 ). we have shown that among patients with mers-related ahrf, niv was commonly used, but nearly always resulted in subsequent transition to invasive ventilation. our results suggest that while the initial niv use in mers patients was not associated with reduction of mortality or length of icu or hospital stay, these patients had greater requirement for subsequent inhaled nitric oxide. a minority of patients were successfully managed with niv-those who were young and had less severe disease. these findings have important implications for early management of patients infected with mers, specifically, that there is little advantage to initial niv treatment for most patients with mers-related ahrf and that niv may be associated with greater subsequent need for oxygenation rescue therapy such as inhaled nitric oxide. noninvasive ventilation has been proven to be useful as a means to avoid intubation and improve clinical outcomes in certain conditions, generally, with the possibility for rather rapid reversal of respiratory failure-for example, pulmonary edema due to congestive heart failure, and respiratory failure due to copd exacerbations. 22, 23 for conditions that typically worsen or do not improve in the range of many hours (eg, most causes of pneumonia), there appears to be little advantage in using niv as a means to avoid intubation. 9, 24, 25 in choosing to use niv for as initial treatment for patients with hypoxemic respiratory failure, there is a practical risk of patients worsening on niv and requiring intubation at a time when they already have more advanced organ failure. few studies have assessed the effectiveness of niv in patients with ahrf secondary to ards and acute lung injury. the overall effectiveness of niv in reducing intubation rate or improving clinical outcome in these patients remains controversial. [26] [27] [28] post hoc analysis of the lung safe study found that niv was used in 15% of patients with ards and was associated with higher icu mortality in subset of patients with severe ards. 12 a randomized controlled trial of patients niv is generally not recommended for patients with hypoxia secondary to respiratory infections due to lack of efficacy and the potential for pathogen transmission. 16, 31, 32 it is also considered one of the aerosol-generating procedures that may increase risk of transmission to healthcare workers. 32 broad dispersion of exhaled air during niv via a face mask has previously been shown using a simulated patient encounter. 33 in conclusion, we report the results of niv use in mers patients from a large cohort of critically ill patients. we observed that there is little advantage to initial niv treatment for most patients with mers-related ahrf and that niv may be associated with greater subsequent need for oxygen rescue therapy. we would like to thank the international severe acute respiratory and emerging infection consortium (isaric) for their support in the database. the authors have no conflict of interest to disclose. bma: conception and design, data acquisition, analytical plan, interpretation of data for the work, drafting of the manuscript, critical revi middle east respiratory syndrome isolation of a novel coronavirus from a man with pneumonia in saudi arabia epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from saudi arabia: a descriptive study clinical course and outcomes of critically ill patients with middle east respiratory syndrome coronavirus infection mers-cov outbreak in jeddah-a link to health care facilities description of a hospital outbreak of middle east respiratory syndrome in a large tertiary care hospital in saudi arabia clinical aspects and outcomes of 70 patients with middle east respiratory syndrome coronavirus infection: a single-center experience in saudi arabia a multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome use of noninvasive ventilation in patients with acute respiratory failure changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries noninvasive ventilation of patients with acute respiratory distress syndrome. insights from the lung safe study effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome non-invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome noninvasive positive pressure ventilation treatment for acute respiratory failure in sars transmission of severe acute respiratory syndrome during intubation and mechanical ventilation critically ill patients with 2009 influenza a(h1n1) infection in canada intensive care adult patients with severe respiratory failure caused by influenza a (h1n1)v in spain clinical findings and demographic factors associated with icu admission in utah due to novel 2009 influenza a(h1n1) infection critically ill patients with the middle east respiratory syndrome (mers): a multicenter retrospective cohort study infection prevention and control guidelines for patients with middle east respiratory syndrome coronavirus (mers-cov) infection noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease non-invasive positive pressure ventilation (cpap or bilevel nppv) for cardiogenic pulmonary oedema predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome noninvasive ventilation for acute lung injury a meta-analysis of randomized controlled trials role of noninvasive ventilation in acute lung injury/acute respiratory distress syndrome: a proportion meta-analysis high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial clinical management of pandemic 2009 influenza a(h1n1) infection aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review exhaled air dispersion during noninvasive ventilation via helmets and a total facemask why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? additional supporting information may be found online in the supporting information section at the end of the article. how to cite this article the saudi critical care trials group noninvasive ventilation in critically ill patients with the middle east respiratory syndrome key: cord-017282-rahtmu3h authors: marvisi, maurizio; balzarini, laura; mancini, chiara; ramponi, sara title: pneumonia date: 2019-08-06 journal: ventilatory support and oxygen therapy in elder, palliative and end-of-life care patients doi: 10.1007/978-3-030-26664-6_12 sha: doc_id: 17282 cord_uid: rahtmu3h pneumonia is a common cause of hospital admission and community-acquired pneumonia (cap) is a growing health problem in developed country and worldwide. elderly patients suffer from more severe disease, require intensive care unit (icu) admission, and exhibit higher mortality compared with their younger counterparts. the immunological changes that occur with age called “immunosenescence” (decreased efficiency of the adaptive and innate immune systems) are known to be responsible for the increased susceptibility of elderly persons to infectious diseases and for their limited response to vaccines [1]. smoking habit, alcohol consumption, alterations of level of consciousness (dementia, cerebrovascular diseases, parkinson's disease), and an increased burden of chronic diseases (copd, bronchiectasis, heart failure, uremia) are important risk factors for susceptibility to pneumonia. impaired nutritional status is an important modifiable risk factor for pneumonia in elderly patient [1] . cap can vary from indolent to fulminant in presentation and from mild to fatal in severity. the classic triad of fever, cough, and dyspnea is present only in a minority of elderly patients hospitalized for cpap. tachypnea appears to be a sensitive indicator of the presence of lower respiratory tract infection in this subset of patients [3] [4] [5] . the vast majority of consensus guidelines suggest that all patients with suspected pneumonia should undergo chest x-ray. radiographic findings, in elderly patients, may include risk factors for increased severity (e.g., cavitations or multilobar involvement). occasionally, radiological pattern suggests an etiological diagnosis: pneumatoceles suggest infection by s. aureus, and an upper lobe cavitary lesion suggests tuberculosis. ultrasound examination of the lungs can be performed bedside for the visualization of pulmonary infiltrates. several studies and meta-analyses support that ultrasound performs well for the diagnosis of pneumonia if performed by an experienced physician. however, ultrasound examinations are difficult to compare over time and the results may vary between performers [1, 6] . all patients should undergo an assessment of disease severity by using validated system of diseases severity (pneumonia severity index, curb-65, etc.). blood cultures should be obtained for patients with severe disease who are at high risk of bacteremia. the yield of blood cultures in elderly subjects is low: about 11%. sputum samples for stain and culture are important in subjects with atypical presentation, cavitary lesions, failure of previous treatment, immunodepression, icu admission, and in all clinical conditions at risk for less common etiologies (gram-negative organism, staphylococcus, and so on) [6] . serological testing is not recommended for routine use. urinary antigen test should be performed for legionella pneumophila (sensitive >80%; specific >95%) and streptococcus pneumonia (sensitive >70%; specific >95%). the role of pcr technologies is limited and could be crucial for mycobacterium species. if a pleural effusion is present, thoracentesis should be performed, with gram staining, culture, determination of ph, measurement of leukocyte, and ldh [2, 6] . the distribution of pathogens associated with pneumonia in elderly patients appears to differ from that in younger counterparts. streptococcus pneumonia the most common etiological agent causing about 50% of infections. haemophilus influenzae, moraxella, pseudomonas, and enterobacteriaceae increase in patients with underlying bronchopulmonary diseases, and staphylococcus aureus are getting more common, above all during influenza outbreaks [7] . viral pneumonia is frequent in outpatients (>30% of cases); influenza and respiratory syncytial virus remain the predominant viral agents of cpap in elderly subjects [6, 7] . nearly 40% of cap episodes in seniors will result in a hospitalization with an average length of stay of 5.6 days. early recognition and prompt initiation of treatment in severe cap is associated with reduced mortality. hypoxemia, confusion, and the onset of respiratory or metabolic acidosis are all signs of disease progression and the need for further interventions [8] . the presence of respiratory frequency > 30 breaths/min, diastolic blood pressure < 60 mmhg, and bun > 7 mm induced a 21-fold increased risk of death. severe cap was defined according to the 2007 infectious disease society of america/american thoracic society guidelines. these guidelines revised the criteria, retain the major criteria as absolute indications for intensive care, and combine the ats major criteria (hypotension requiring aggressive fluid resuscitation, multilobar infiltrates, and pao 2 /fio 2 ratio < 250), the curb variables, and three additional minor criteria (white blood cells < 4000/mm 3 , platelets < 100,000, and temperature < 36 °c) [2, 8, 9] . in cap patients, the inflammatory process causes a leakage of edema fluid into the lung and inflammatory cellular infiltrates cause diffusion abnormalities and mismatch between ventilation and perfusion. thus, the mechanism of respiratory failure is based on several factors, that is, alveolar flooding, intrapulmonary shunting, and bacterial cytotoxic effects on the epithelial barrier [10, 11] . all patients with cap should receive oxygen treatment as needed with the aim of maintaining an arterial oxygen saturation (spo 2 ) of 92% corresponding to a partial pressure of oxygen in the blood of about 60 mmhg. lower values are accepted in cases of underlying severe pulmonary disease with a risk of carbon dioxide retention. oxygen can be delivered via nasal cannula up to 5 l/min or by mask 0-15 l depending on the type of mask, alternatively via a high-flow system. the spo 2 value should always be interpreted in relation to the respiratory rate and the oxygen fraction in the inspiratory air. blood gas analysis should be performed liberally in patients with severe cap. oxygen treatment of copd patients should be monitored with repeated blood gas analysis. hypercapnia indicates the need for more intensive ventilatory support. noninvasive positive pressure ventilation (nppv), which is the primary treatment for exacerbation of copd, may be a good tool for patients with severe cap [12] . while the clinical practice guidelines on evidence-based application of niv for community-acquired pneumonia did not provide a recommendation for its use, the infectious disease society of america/american thoracic society guidelines on management of cap did suggest a cautious trial of niv [2, 12] . most studies on niv and treatment of acute hypoxemic respiratory failure, including cap, have been carried out in the critical care setting and have reported controversial results with varying failure rates for niv use. nevertheless, niv continues to be commonly used for the treatment of severe cap, especially in the emergency department [12, 13] . a recently published retrospective cohort study involving 163 subjects with severe cap treated with niv demonstrated that most patients who presented to the ed with cap and respiratory failure received niv as first-line ventilatory therapy. the niv failed in 50% of cases. risk factors that predicted niv failure at baseline was: no history of chronic obstructive pulmonary disease, apache ii score, need for hemodynamic support and number of cxr quadrants involved. risk factors for failure after 2 h of therapy were respiratory rate, serum ph, and hemodynamic support. hemodynamic support was the most strongly associated with failure of niv [14] . a recent study by carteaux et al. demonstrated differences in expired tidal volume in patients with hypoxemic respiratory failure who failed and succeeded niv [15] . higher tidal volume was a significant risk factor for niv failure on multivariable analysis. a paper by paolini et al. proposed a protocol to evaluate cpap responsiveness in patients with acute respiratory failure due to cap. the responders were defined as patients hemodynamically stable with a paco 2 < 45 mmhg, those with partial pressure of arterial oxygen to the fraction of inspired oxygen (pao 2 / fio 2 ) increase >20% and/or reduction of respiratory distress. in this setting, 66% of subjects benefit from cpap application. cpap-responders were less likely to present comorbidities compared to cpap-non-responders, and responsiveness does not seem to be associated with better outcomes, with the exception of a shorter length of hospital stay [16] . high-flow nasal cannula oxygen therapy (hfnc), which delivers high flow (up to 60 l/min) of blended, humidified oxygen through a nasal cannula, is a promising tool for respiratory support. the key mechanisms of action of hfnc are effective delivery of up to 100% oxygen, washout of the pharyngeal dead space, decreased inspiratory resistance, airway hydration, and positive end-expiratory pressure effect (peep range from 3 to 5 cmh 2 o). several clinical trials have demonstrated the effectiveness of hfnc in a variety of clinical situations, such as acute hypoxemic respiratory failure, post-cardiac surgery, post-extubation, and during invasive procedures [17] [18] [19] [20] . kim se designed a retrospective study involving patients with acute respiratory failure with hypercapnia. pneumonia (36.4%) and acute exacerbation of chronic obstructive pulmonary disease (33.4%) were the most common reasons for oxygen therapy. the mean fraction of inspired oxygen and hfnc flow rate were 0.45 ± 0.2 and 41.1 ± 7.1 l/min, respectively; mean duration of application was 3.6 ± 4.1 days. the partial pressure of arterial carbon dioxide (paco 2 ) was 55.0 ± 12.2 mmhg at admission and increased by approximately 1.0 ± 7.7 mmhg with conventional oxygen therapy. in contrast, with hfnc therapy, paco 2 decreased by 4.2 ± 5.5 and 3.7 ± 10.8 mmhg in 1 and 24 h, respectively, resulting in significant improvement in hypercapnia (p = 0.006 and 0.062, respectively). they suggest that hfnc can improve hypercapnia in some patients through clearance of anatomical dead space, which improves alveolar ventilation, thus leading to reduction of paco 2 and an increase of pao 2 [21] . ito j et al. performed a retrospective cross-sectional multicenter survey evaluating adult patients receiving hfnc in 33 participating hospitals in japan. they included 312 patients with acute respiratory failure due to various clinical situations: cardiogenic pulmonary edema, ards, aecopd, interstitial lung disease, and pneumonia (54 patients, 16.8% of cases). median duration of hfnc was 4 days; median total flow rate, 40 l/min; and median fio 2 , 50%. hfnc significantly improved pao 2 , paco 2 , spo 2 , and respiratory rate from baseline. two-thirds of patients finally survived to be discharged [22] . a systematic review of five randomized clinical trials was recently published by leong bl and colleagues. the studies compare at least niv with hfnc or niv + hfnc with niv in acute respiratory failure. primary outcomes included intubation/re-intubation rates; secondary outcomes were icu mortality and morbidities. patients were post-cardiothoracic surgery, mixed medical/surgical patients, and those with pneumonia. two trials were conducted after extubation, two before intubation, and one during intubation. three trials reported intubation/re-intubation rates as the primary outcomes. the results were conflicting because of differences in patient populations, primary outcomes, trial design (superiority vs. noninferiority) as well as comparison arms. despite these differences, hfnc is a viable option in patients with less severe hypoxemic respiratory failure from pneumonia and ards as well as patients at risk of post-extubation respiratory failure [23] . pneumonia is a common cause of hospital admission in elderly patients. the classic triad of fever, cough, and dyspnea is present only in a minority of elderly patients hospitalized for cpap. tachypnea appears to be a sensitive indicator of the presence of lower respiratory tract infection in this subset of patients. streptococcus pneumonia is the most common etiological agent causing about 50% of infections. haemophilus influenzae, moraxella, pseudomonas, and enterobacteriaceae increase in patients with underlying bronchopulmonary diseases, and staphylococcus aureus are getting more common, above all during influenza outbreaks. nearly 40% of cap episodes in seniors will result in a hospitalization with an average length of stay of 5.6 days. early recognition and prompt initiation of treatment in severe cap is associated with reduced mortality. the presence of respiratory frequency > 30 breaths/min, diastolic blood pressure < 60 mmhg, and bun > 7 mm, induced a 21-fold increased risk of death. all patients with cap should receive oxygen treatment as needed with the aim of maintaining an arterial oxygen saturation (spo 2 ) of 92% corresponding to a partial pressure of oxygen in the blood of about 60 mmhg. oxygen treatment of copd patients should be monitored with repeated blood gas analysis. hypercapnia indicates the need for more intensive ventilatory support. noninvasive positive pressure ventilation (nppv), which is the primary treatment for exacerbation of copd, may be a good tool for patients with severe cap. high-flow nasal cannula oxygen therapy (hfnc), which delivers high flow (up to 60 l/min) of blended, humidified oxygen through a nasal cannula, is a promising tool for respiratory support in these patients. 1. tachypnea appears to be a sensitive indicator of the presence of lower respiratory tract infection in elderly subjects. 2. early recognition and prompt initiation of treatment in severe cap is associated with reduced mortality. 3. all patients with cap should receive oxygen treatment as needed with the aim of maintaining an arterial oxygen saturation (spo 2 ) of 92% corresponding to a partial pressure of oxygen in the blood of about 60 mmhg. 4. high-flow nasal cannula oxygen therapy is a promising tool for respiratory support in these patients. chapter 8: community acquired pneumonia in the elderly infectious disease society of america\american thoracic society consensus guidelines on management of cap in adults advances in the cause and management of community acquired pneumonia in adults hospitalized community acquired pneumonia in the elderly: age and sex related pattern of care and outcome in isa pneumonia: still the old man friend? clinical approach to community acquired pneumonia comparison of viral infection in healthcare-associated pneumonia (hcap) and community-acquired pneumonia (cap) incremental risk of long-term mortality with increased burden of comorbidity in hospitalized patients with pneumonia validation of a predictive rule for the management of community acquired pneumonia guidelines for the management of adult lower respiratory tract infections-full version clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients with acute respiratory failure: a randomized clinical trial predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study outcomes and predictors of failure of non-invasive ventilation in patients with community acquired pneumonia in the emergency department failure of noninvasive ventilation for de novo acute hypoxemic respiratory failure: role of tidal volume positive end expiratory pressure in acute hypoxemic respiratory failure due to community acquired pneumonia: do we need a personalized approach? high-flow nasal cannula oxygen therapy in adults: physiological benefits, indication, clinical benefits, and adverse effects high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure efficacy of highflow nasal cannula therapy in acute hypoxemic respiratory failure: decreased use of mechanical ventilation effect of postextubation high-flow nasal cannula vs standard oxygen therapy on reintubation in lowrisk patients: a randomized clinical trial effectiveness of high-flow nasal cannula oxygen therapy for acute respiratory failure with hypercapnia the clinical practice of high-flow nasal cannula oxygen therapy in adults: a japanese cross-sectional multicenter survey high flow nasal cannula oxygen versus noninvasive ventilation in adult acute respiratory failure: a systematic review of randomized-controlled trials key: cord-017240-2vqehqfh authors: trindade e silva, luis paulo; gonçalves, ana paula; lopes, maria luísa; de los ángeles zazo, maria title: noninvasive mechanical ventilation for hypoxemic respiratory failure-related infectious diseases date: 2013-05-29 journal: noninvasive ventilation in high-risk infections and mass casualty events doi: 10.1007/978-3-7091-1496-4_7 sha: doc_id: 17240 cord_uid: 2vqehqfh the strict range of applicability of noninvasive ventilation (niv)—which had been applied only to patients with an exacerbation of chronic obstructive pulmonary disease (copd) or acute cardiogenic pulmonary edema (acpo)—has been extended during the last two decades. • evidence level 2-derived from systematic reviews with homogeneity of cohort studies, individual cohorts, and/or poor-quality rcts. niv is applied in patients with a "do not intubate" order, as a palliative measure in terminally ill patients, to prevent extubation failure in patients with copd or heart failure, for communityacquired pneumonia (cap) in copd patients, to prevent and treat postoperative respiratory failure, and to prevent arf due to asthma. also in this category, but with greater caution and according to the case, niv may be indicated for severe cap and for preventing extubation failure in patients without copd. • evidence level 3-derived from systematic reviews with homogeneity of casecontrol studies and an individual case-control study. niv is suggested for neuromuscular diseases and kyphoscoliosis, partial obstruction of the upper airway, thoracic trauma, and treatment of arf in patients with asthma. with more caution and strict surveillance, niv may also be indicated for acute lung injury and acute respiratory distress syndrome (ards). • evidence level 4-derived from case series and poor-quality cohort and casecontrol studies. niv is suggested for obesity-related hypoventilation, cystic fi brosis, and in the elderly (>75 years) with arf. with greater caution and according to the case, it is also indicated for idiopathic pulmonary fi brosis. numerous rcts have focused on niv during the last decade. the studies, however, have reported confl icting evidence regarding any permanent benefi t for patients with acute hypoxemic respiratory failure (ahrf). these confl icts probably arise because most of these studies are small, have many differences among them, and the success of niv varies according to the cause of hypoxemic respiratory failure. for example, in the 2006 meta-analysis of keenan et al. [ 2 ] , which included eight rcts that had studied patients with ahrf secondary to causes other than acpo, the niv reduced the eti rate by 23 %, the length of stay in the intensive care unit (icu) by 2 days, and icu mortality by 17 % (absolute risk reduction). in contrast, in a 2008 observational study by schettino et al. [ 3 ] that included 449 patients, of whom 144 underwent niv for ahrf, unfavorable results were obtained. these authors found that 60 % of this population were in need of eti, and the hospital mortality rate was 64 %. in 1996, meduri et al. [ 4 ] were among the fi rst to show the potential of niv for preventing eti specifi cally in patients with ahrf secondary to communityacquired pneumonia (cap). however, the sample was very small: only 14 patients had cap, and among them only 7 had hypoxemic failure. the observational study comprised 158 patients, 41 of whom had hypoxemia and 74 had hypercapnia. the results of this study showed the same percentage of eti requirement (34 %) in patients with hypoxemic failure as in those with hypercapnia. the mortality rate among those requiring eti was higher in the group with ahrf (34 % vs. 20 %). in 1999, confalonieri et al. [ 5 ] demonstrated the effectiveness and safety of niv in a prospective, controlled trial that included 56 patients admitted to the icu. the authors showed that niv was well tolerated and, relative to the control group (who underwent conventional medical treatment), provided a signifi cant reduction in the respiratory rate and the number of patients who required eti (21 % vs. 50 %, p = 0.03), and it shortened the icu stay (1.8 vs. 6.0 days, p = 0.04). there were no statistically signifi cant differences in the two groups regarding hospital mortality or survival rates after 2 months of follow-up. moreover, at 2 months there was a reduced workload for the nursing staff and improved survival among patients with copd who were treated with niv (88.9 % vs. 37.5 %, p = 0.05). in 2001, jolliet et al. [ 6 ] reported on 24 patients with severe pneumonia (the criterion for which was an average pao 2 /fio 2 of 104 mmhg) but no history of chronic lung disease. the authors showed a high eti rate (66 %) despite niv. the positive aspects were the initial improvement in arterial oxygenation, shorter hospital stay, and no overworked nursing staff. that same year, antonelli et al. [ 7 ] presented a prospective multicenter study on predictors of niv failure in 350 patients with ahrf. niv had a failure rate of 30 %. the eti was especially high when ahrf was due to cap (50 %) or ards (51 %). in 2002, domenighetti et al. [ 8 ] , in a prospective observational study, compared the effi cacy of niv in patients without copd but with hypoxemic respiratory failure due to acpo (15 patients) or severe cap (18 patients). one patient (6.6 %) with acpo and seven (38 %) in the group with severe cap were intubated ( p = 0.04). the mortality rate was higher in the cap group (28.0 % vs. 6.6 %, p = 0.2). in another prospective rct conducted in three icus, ferrer et al. [ 9 ] selected 105 patients with ahrf, including 51 given niv and 54 with conventional oxygen therapy. the eti rate in the 34 patients with severe ahrf due to cap who received niv was 26.3 % compared to 73.3 % in the control group ( p = 0.017). based on a multivariate analysis, the authors concluded that niv functioned as an independent factor in reducing the risk of eti and mortality at 90 days. they suggested that niv was a fi rst-line intervention in patients with severe ahrf in the absence of contraindications to using it. in 2010, cosentini et al. [ 10 ] evaluated the effectiveness of continuous positive airway pressure (cpap) administered by helmet in patients with moderate ahrf (pao 2 /fio 2 210-285) secondary to cap. this multicenter, prospective rct examined 47 patients (37 without copd) and concluded that cpap by helmet provides faster oxygenation (pao 2 /fio 2 > 315) in a larger number of patients with ahrf due to cap than in those who were given conventional oxygen therapy. in 2012, carrillo et al. [ 11 ] examined the effectiveness of niv in 184 patients with severe respiratory failure due to cap. among them, 102 were classifi ed as having "de novo" inadequate breathing, and 82 had previously been diagnosed with heart or respiratory disease. all patients were given niv. those with de novo respiratory failure had a higher failure rate than the patients with a history of heart or respiratory disease (46 % vs 26 %, p = 0.007). another important population in which the ventilation strategy with niv has been attempted comprises immunosuppressed patients with pulmonary infi ltrates and arf. they are especially vulnerable because their rate of morbidity secondary to eti is high (up to 70 % depending on the series). most of the studies conducted in this population have been observational and/or retrospective. we point out two studies that are prospective rcts. in 2000, antonnelli et al. [ 12 ] studied 40 immunosuppressed patients after solid organ transplant. half of the patients ( n = 20) were treated with niv and the other half ( n = 20) with oxygen. overall, 10 % of the 40 patients had ahrf secondary to pneumonia and were assigned in equal numbers to the two groups. the eti and mortality rates in the ahrf subgroups with pneumonia were the same, although, in this randomized trial, niv signifi cantly reduced the all eti requirement rates, the number of fatal and septic complications, and mortality in the icu. in 2001, hilbert et al. [ 13 ] examined 52 immunosuppressed patients with pulmonary infi ltrates, fever, and ahrf. in all, 28 % of the patients had hematological malignancies and neutropenia. one group of patients ( n = 26) underwent niv intermittently, and the other group was treated with conventional oxygen therapy ( n = 26). patients treated with intermittent niv required eti less often (12 vs. 20, p = 0.03), had fewer serious complications (13 vs. 21, p = 0.02), and had a lower icu mortality rate (10 vs. 18, p = 0.03) and shorter hospitalization (13 vs. 21, p = 0.02). more specifi cally, in 2012, anjos et al. [ 14 ] studied patients with acquired immunodefi ciency syndrome (aids) plus ahrf secondary to pneumonia. the authors compared a randomized sequence of niv using positive end-expiratory pressure (peep) (5, 10, or 15 cmh 2 o) for 20 min. the results showed a linear improvement in oxygenation with increasing levels of peep. earlier, in 2002, confalonieri et al. [ 15 ] conducted a prospective case-control study of, more specifi cally, niv versus imv in patients with ahrf secondary to pneumocystis jiroveci . the use of niv prevented the need for eti in 67 % of patients and improved survival (100 % vs. 38 %, p = 0.003). despite avoiding the use of more invasive devices and having a lower incidence of pneumothorax and shorter stay in the icu, at 6 months the mortality rate was the same for the two groups. in several countries on all continents, more retrospective [ 16 , 17 ] than prospective [ 18 ] trials have been conducted to study the pandemic caused by infl uenza virus a (h1n1). the authors discussed their experience with niv in the approach to ahrf secondary to pneumonia caused by h1n1 virus. some of the conclusions were contradictory and controversial [ 18 , 19 ] . we point out two trials that specifi cally addressed the issue. in 2010, liu et al. [ 20 ] conducted a retrospective observational study of 18 patients with ahrf secondary to severe pneumonia due to infl uenza a (h1n1) virus. they found that niv can improve the patients' respiratory conditions and may lower the mortality (8.3 %) and eti (24.0 %) rates. in 2011, belenguer-muncharaz et al. [ 19 ] conducted a retrospective observational study using niv in seven (70 %) patients admitted with infection due to infl uenza a (h1n1) virus. overall, 28 % of these patients experienced therapeutic failure with niv, but there were no fatalities. niv was effective in 100 % of the fi ve patients in the hypoxemic group, with improved gas exchange and no need for eti. thousands of years in existence and catastrophic, tuberculosis has not gotten the same attention as the more recently identifi ed h1n1 infection. only a few retrospective observational trials [ 21 , 22 ] have recognized the importance and benefi ts of niv in acute respiratory exacerbations in patients with pulmonary tuberculosis sequelae, most of which are in patients with ahrf. again, non-rcts have specifically dealt with ahrf secondary to tuberculosis and/or co-infection from pulmonary sequelae. for example, in 2010 aso et al. [ 22 ] reviewed 58 patients with an acute exacerbation of pulmonary tuberculosis sequelae. among them, 77.6 % had chronic respiratory failure made acute by co-infections. these patients had all been initially treated with niv. the mortality for this group with arf due to co-infections was barely 13.3 %. noninvasive ventilation has radically changed the treatment of ahrf, although its use in patients with severe cap remains controversial (especially in the presence of ards). the controversy arises because niv is associated with higher rates of treatment failure in patients with ards-related ahrf than in those with severe ahrf due to other factors. these data suggest that the effectiveness of niv varies depending on the cause of the patient's ahrf. on the other hand, use of niv with specifi c objectives and clear criteria, associated with knowledge of the ventilatory failure predictors to avoid delaying initiation of eti, make this technique one of the best for patient with conditions such as immunosuppression, copd, or heart failure. the selection and exclusion criteria or failure when using the technique are therefore of great relevance for therapeutic success or failure. as a guide, in 2007 the infectious disease society of america/american thoracic society [ 23 ] recommended icu admission of patients with severe cap based on their meeting one of the following major criteria: (1) arf with imv requirement and/or septic shock requiring vasopressors; or (2) three of the following criteria: respiratory rate ≥ 30 bpm, pao 2 /fio 2 ≤ 250, multilobar infi ltrates, confusional state, blood urea nitrogen ≥ 20 mg/dl, leukopenia (<4 × 10 9 /l), thrombocytopenia (<100 × 10 9 /l), hypothermia (<36 °c), hypotension requiring aggressive fl uid therapy. regarding criteria for predicting niv failure in the context of severe cap, in 2010 carron et al. [ 24 ] conducted a prospective observational study with 64 cap patients. the authors reported the following as the most signifi cant factors that predicted failure after 1 h of exposure to niv: increases in the sepsis-related organ failure assessment (sofa) score (from 9 to 11), oxygenation index ([fio 2 × mean airway pressure × 100]/pao 2 ) (from 5.0 to 8.6), and respiratory rate (from 23 to 28) as well as decreases in ph (from 7.44 to 7.37) and pao 2 /fio 2 (from 228 to 127). as demonstrated by the study's analysis, the best evidence that allows the strongest recommendation about the use of niv in patients with ahrf secondary to infection comes from studying the subgroup of patients with a chronic underlying condition (e.g., immunosuppression, heart failure, copd). in this same perspective niv is recommended in mild infectious situations, unlike severe cap. here, although the niv is not an absolute contraindication, do require a more cautious approach with greater emphasis on the risk-benefi t equation and on clinical context due the nosological severity and because there are no suffi ciently large, specifi c and homogeneous rcts to support its use. specifi cally in patients with ahrf due to infl uenza virus a (h1n1), niv is recommended only for less severe forms. this especially applies to patients who have ards, who should be treated in a specifi c room with negative pressure because of the risk of spreading contaminated aerosols. emphasis should be placed on transmission prevention by using double breathing circuits and basic rules of safety and hygiene (especially hand washing and the use of appropriate masks). other forms of ahrf and other infectious agents have been addressed but without enough coherence to generate recommendations. in these cases, the only observations, after critical review and proven experience, is common sense, weighing the risk-benefi t equation, and involvement of the patient and/or if he or she is responsive. in the end, one must adhere to the hippocratic maxim: primum non nocere. • the use of niv in ahrf secondary to infection must obey, as in any other situation, clearly indicated criteria (early onset) during the processes of selection, monitoring, and prognosis failure (appropriate withdrawal without delaying the start of eti). also, the operator should pursue clear objectives and improve oxygenation and o 2 delivery (do 2 ), relieve dyspnea, and avoid eti and mortality. • niv may be benefi cial in patients with ahrf secondary to moderately severe pneumonia in selected cases, especially in immunocompromised patients with heart or lung chronic disease (especially copd) and when bronchial secretions can be easily controlled. • using niv in patients with severe ahrf due to cap without meeting these preexisting conditions should be more cautious and under strict monitoring and control (preferably in the icu) because unnecessary delay in applying eti after niv failure increases morbidity. non-invasive ventilation in acute respiratory failure does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure? a systematic review noninvasive positive-pressure ventilation in acute respiratory failure outside clinical trials: experience at the massachusetts general hospital noninvasive positive pressure ventilation via face mask. first-line intervention in patients with acute hypercapnic and hypoxemic respiratory failure acute respiratory failure in patients with severe community acquired pneumonia. a prospective randomized evaluation of noninvasive ventilation non-invasive pressure support ventilation in severe community-acquired pneumonia predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study noninvasive pressure support ventilation in non-copd patients with acute cardiogenic pulmonary edema and severe community-acquired pneumonia: acute effects and outcome noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial helmet continuous positive airway pressure vs oxygen therapy to improve oxygenation in community-acquired pneumonia: a randomized, controlled trial non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial noninvasive ventilation in immunosuppressed patients with pulmonary infi ltrates, fever, and acute respiratory failure a randomized trial of noninvasive positive end expiratory pressure in patients with acquired immune defi ciency syndrome and hypoxemic respiratory failure noninvasive ventilation for treating acute respiratory failure in aids patients with pneumocystis carinii pneumonia clinical features of pneumonia caused by 2009 infl uenza a (h1n1) virus in beijing clinical characteristics and outcomes of patients with 2009 infl uenza a (h1n1) virus infection with respiratory failure requiring mechanical ventilation infl uenza a (h1n1)-associated pneumonia noninvasive mechanical ventilation in severe pneumonia due to h1n1 virus the application of bi-level positive airway pressure in patients with severe pneumonia and acute respiratory failure caused by infl uenza a (h1n1) virus noninvasive positive pressure ventilation in patients with acute exacerbations of pulmonary tuberculosis sequelae noninvasive ventilation in patients with acute exacerbation of pulmonary tuberculosis sequelae infectious diseases society of america/ american thoracic society consensus guidelines on the management of community-acquired pneumonia in adults predictors of failure of noninvasive ventilation in patients with severe community-acquired pneumonia key: cord-276238-2hv46ftk authors: ing, richard j.; bills, corey; merritt, glenn; ragusa, rosalia; bremner, ross m.; bellia, francesco title: the role of helmet-delivered noninvasive pressure support ventilation in covid-19 patients date: 2020-05-08 journal: j cardiothorac vasc anesth doi: 10.1053/j.jvca.2020.04.060 sha: doc_id: 276238 cord_uid: 2hv46ftk nan like its predecessors, sars-cov and middle eastern respiratory syndrome (mers)-cov, sars-cov-2 is a coronavirus that can be transmitted to humans and cause significant respiratory disease. 1 as of april 24 th 2020, there are over 2.85 million reported sars-cov-2 positive patients globally, resulting in at least 198,000 deaths. 2 the disease associated with sars-cov-2 infection is now known as covid-19. although most sars-cov-2 infections cause very mild symptoms, approximately 5% of patients develop acute respiratory distress syndrome (ards) with some patients progressing to multiorgan dysfunction. this disease has been reported to have a case fatality ratio (cfr) of 1-4%. 3 in just over a month, covid-19 has become the leading cause of death in the united states of america in 2020, overtaking both heart disease and cancer. 4 currently many hospitals around the world are struggling to meet the needs for mechanical ventilators and expand intensive care unit (icu) capacity. 5 the reserve capacity for ventilators is necessary given the expected surge in hypoxemic patients presenting with progressive covid-19, and an uncertain future when our seasons change. 5 the aim of this stand-alone editorial is to examine the role of helmet delivered continuous positive airway pressure (cpap) noninvasive ventilation (niv) as an adjunct to mechanical ventilation in patients requiring respiratory support in covid-19. the recent surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 consensus statement agrees that; following admission for covid-19, each patient may progress at a variable rate to either recovery, with minimal oxygen requirements and no ventilatory support, or a worsening of the disease process and the need for an escalation in niv and mechanical ventilation. 6 when covid-19 progression is identified, the current critical care management recommendation is to initiate early endotracheal intubation and mechanical ventilation. 6 this recommendation aims to avoid emergent intubation in a rapidly decompensating patient should worsening hypoxemia develop if intubation is delayed. this recommendation is also aimed at source control, decreasing the risk of cross contamination from droplet and aerosolized viral particles to other patients and health care workers (hcw). 6 all persons under investigation (pui) for covid-19 and all covid-19 positive patients should wear a mask. 6, 7 it is also recommended that all hcws should wear droplet and contact personal protective equipment (ppe) to provide a mechanical barrier to droplet spread and ideally be greater than 2 meters from the patient. 6, 7 additional airborne ppe is required during any aerosol generating medical procedures (agmp) in these patients. 6, 7 these recommendations are based on reports that 11% of critically ill patients in wuhan required high flow nasal cannula (hfnc) and this increased the risk of viral aerosolization and droplet transmission . 3, 6, 8, 9 while hfnc poses significant risks for providers, patient mortality associated with mechanical ventilation is also significant. mortality among covid-19 patients over 65 years of age in the seattle was at least 62%. 10 a recent report from the experience in new york found the mortality associated with intubation and mechanical ventilation in 5700 patients hospitalized with covid-19 was 76% in the those aged 18 to 65 years and 97% in patients over 65 years of age. 11 the usual features of typical ards, recently termed the h-type, in covid-19 patients are a progressive deteriorating lung compliance requiring increased inspired oxygen concentration(fio 2 ), high positive end expiratory pressure (peep), prone ventilation, sedation with paralysis and inotropic support. 12 there is growing evidence that a subset of covid-19 patients present with atypical ards which has recently been termed to l-type ards: severe hypoxemia but well-preserved pulmonary mechanics, good lung compliance and low lung congestion. 12, 13 (table 1) the respiratory support requirements for covid-19 patients with l-type atypical respiratory ards physiology may require different respiratory support principles than that usually provided to patients presenting with the typical h-type classic ards. 14 as a result, several have advocated a ventilation strategy focused on the principle where less is more. [12] [13] [14] [15] mechanical ventilation should be delivered with low tidal volumes, low plateau pressure and a low peep level, 15 albeit with a higher inspired fraction of oxygen (fio 2 ). 14 it is postulated that the hypoxemia in this subset of covid-19 patients with more compliant lungs may be due to a large shunt secondary from the loss of the protective mechanism of lung perfusion regulation and the loss of pulmonary hypoxic vasoconstriction and microthrombi in pulmonary vascualtrure. 12, 16 as a result of the coagulopathy seen in this disease, anticoagulation in the treatment algorithms is an important therapeutic modality in covid-19. 17 the fact that many of these covid-19 patients with l-type ards with good lung compliance show improved oxygen saturation during prone positioning, may be related to improved lung perfusion and the force of gravity affecting pulmonary blood flow. 12 the high mortality associated with intubation and mechanical ventilation in covid-19 patients, coupled with the concerns over provider risk from aerosolization via traditional forms of niv have led to the following questions: "do many mild to moderate covid-19 patients undergo endotracheal intubation too early in order to limit aerosolized and droplet viral particles; and does this potentially delay or worsen some patient's recovery ?" 8 , and, "what is the role of helmet based cpap via niv for respiratory support in covid-19 patients to limit the spread of aerosolized viral particles and potentially avoid endotracheal intubation?" 18, 19 the main reason for early endotracheal intubation over initiating niv support in patients with covid-19 is to limit possible aerosolization of covid-19 particles from hfnc and niv as was reported in the early chinese experience. 6 airway procedures in these patients are all classified as medical aerosol generating procedures (magps). these magps include; niv and hfnc bag-mask ventilation, endotracheal intubation or tube suctioning, bronchoscopy, transport, tracheostomy tube change, and high-frequency oscillatory ventilation, etc. 6, 20, 21 we do know that niv can play a significant role in respiratory support. a recent systematic review and metanalysis concluded that niv can improve survival in the acute care settings when it is applied early for respiratory failure, however the benefit is lost when it is used too late in respiratory deterioration. 18 continuous positive airway pressure (cpap) is a mode in niv used to treat hypoxemic acute respiratory failure (harf). this mode of respiratory support delivers a constant positive airway pressure during both inspiration and expiration. 22, 23 helmet cpap is an important and evidence-based airway adjunct. 18, 19, 24, 25 while it is not intended to replace endotracheal intubation and mechanical ventilatory support in the critically ill patient, it can be used for more patients than intubation and confines aerosolized viral particle spread within the helmet. determining which patients will undergo rapid progression from mild respiratory disease, or the l-type better compliance form of respiratory failure, to overt h-type ards in covid-19 is often not clear in the early course of the disease. 13, 14 recent literature suggests that although only 10-14% of covid-19 patients need icu, 60-70% of those will develop progressive ards and 20-25% will require endotracheal intubation and ventilation. 6, [26] [27] [28] helmet cpap, as used in italy, can play a significant role in helping to determine patient severity. it provides good respiratory support in the moderately ill patient in the earlier stages of the disease. 19 these patients can still breath well on their own but remain significantly hypoxic despite conventional treatment. the helmet can be fitted at this stage. it provides a significant increase in inspired oxygen with up to 10 cm h 2 0 cpap through adaption with a traditional cpap machine or wall oxygen regulated by a simple device. it further enables patient self-proning to improve oxygenation, which limits the need for multiple personnel to perform this in the intubated patient the helmet allows for a safe means of containing droplet and aerosolization of virus particles by the use of a heat moisture exchange (hme) filter on the inspiratory and expiratory limb of the helmet. the comfort of the helmet also limits the need for sedation and subsequent inotropic support when compared to endotracheal intubation. with the use of the helmet, the need for rapid early intubation can often safely be delayed while a patient is observed carefully for any improvement in disease or deterioration in their condition. this may enable endotracheal intubation to be avoided in a subset of patients. previous data supports the use of helmet cpap as a safe and effective evidence-based approach to respiratory failure. an independent metanalysis, inclusive of four randomized clinical trials in italy, found helmet cpap to be a beneficial mode of respiratory support when used for the correct indication. influenced by type of arf and ventilation mode (p <0.00001). 29 the authors in this study concluded that niv with a helmet was associated with reduced hospital mortality and endotracheal intubation requirement. the helmet was as effective as the mask in gas exchange with no additional advantage. large randomized controlled trials are needed to provide more robust evidence. 29 patients presenting with mild-to-moderate covid-19 or the l-type ards, initially supported with hfnc low (cpap) or niv must be observed very closely for any clinical deterioration due to disease progression. 6, 12, 14, 34 one of the early signs of disease progression is the use of excessive inspiratory work being generated by the patient. if observed, the patient should undergo endotracheal intubation because any increased work of breathing and the generation of excessive negative intrathoracic pressure to move air has been shown to cause a self-inflicted lung injury (sili). 14, 35 determining patient breathing effort during progression of respiratory disease is not always easy. to more precisely quantify patient breathing work effort, esophageal manometry although not commonly used, may be needed in these patients to measure the generation of changes in intrathoracic pressure . 34 esophageal pressure changes of 5 to 10 cmh 2 o may be well tolerated. however, if an esophageal pressure change greater than 15 cmh 2 o is generated, the risk of self-inflicted lung injury (sili) is increased and endotracheal intubation should be performed promptly. 14 if endotracheal intubation is delayed in this situation, and a further sudden clinical deterioration occurs, it can be associated with hypoxemia, cardiovascular collapse and an emergent endotracheal intubation may be required, which puts the hcw team at risk during the magp. 6, 7, 36 naturally it is not practical to monitor respiratory effort with manometry in a pandemic situation. it remains unclear that delaying intubation in the covid-19 patient who ultimately requires intubation has any benefit. however, the data discussed above is promising that some patients may benefit, and others may avoid intubation at all. the current surviving sepsis campaign recommendations for covid-19 discuss the use of helmet niv and cpap compared with mask niv. 6 helmet cpap is certainly a therapeutic option that has been used in italy for over a decade, and has been used extensively during the covid-19 pandemic. 8, 19, 37 however, in the current surviving sepsis campaign recommendations, consensus could not be reached on its safety or efficacy in covid-19, especially in those patients that ultimately require endotracheal intubation and mechanical ventilatory support. 6 the first helmet prototypes were developed in 1991 by maurizio borsari. one of the problems with cpap helmets available in other parts of the world is that they are not all fda approved and most u.s. physicians are unfamiliar with the helmet. (figure 1 ) however, the concept and fitting of the mask is relatively simple. patients typically can sit up or lie down on some pillows. it is likely that the cpap helmet niv, is best used in the early phase of the disease or during recovery after extubation. the cpap helmet consists of a transparent plastic hood that surrounds the patient's head. the helmet does not have any pressure points on the face, thereby reducing patient discomfort and improving device tolerance without the risk of skin necrosis. 25 the helmet allows the patient to see, read, talk, and interact more easily than other niv respiratory devices. it is available in various sizes that can fit small children and adults. 23 it has a soft latex free collar constructed of silicon-polyvinyl chloride that creates a pneumatic seal around the patient's neck. the presence of two or more inlet and outlet ports enable connections of standard respiratory inspiratory and expiratory limb tubing. a high efficiency particulate (hepa) filter is placed on the expiratory limb of the circuit to minimize exhaled aerosolized viral particles. 8 additionally, there is a distal variable cpap valve. the extra ports allow a sealed site for the insertion of a naso-gastric tube, or the administration of a nebulizer. this port also enables the patient to drink from a straw. a monitor controls the gas flow in the helmet (n= 30-60 liters to prevent rebreathing and co 2 retention), temperature and fio 2 . the presence of a zip in the helmet allows easy access if needed. the noise level in the cpap helmet is equal 100 db which can be reduced with a hme filter on the helmet gas inspiratory limb. 38 helmet cpap requires a fairly cooperative patient with an intact neuromuscular system but tolerance appears to be excellent especially in those patients who feel claustrophobic with a tight fitting cpap face mask. armpit straps can be replaced with a counterweight system that results in better patient comfort and humidification can be added to the system. 8 occasionally, it may be necessary to reduce anxiety with the administration of very light sedation. patients in a cpap helmet must be monitored closely. an inability to maintain a pao 2 /fio 2 ratio of 150 during use, with no reduction in respiratory rate and an increasing fio 2 requirement, defined as an fio 2 > 80% after one hour of initiating helmet cpap therapy, are considered indications for endotracheal intubation and mechanical ventilation. (table 1) the challenge in covid-19 patients is to identify those patients most likely to benefit from cpap helmet niv, and to monitor them closely for any signs of worsening respiratory therapy that would require an escalation to endotracheal intubation and mechanical ventilation. 37 patients with covid-19 are all recommended to receive regular respiratory therapy to help mobilize inspissated respiratory secretions associated with this disease. 37 in this critical time of unparalleled medical challenges of caring for vast numbers of covid-19 hypoxemic patients requiring respiratory support, any alternative respiratory support device with evidence of extensive use in other parts of the world deserves consideration. we submit that the helmet delivered niv pressure support device could be a low-cost addition to the ventilatory options for covid-19 patients. identification of a novel coronavirus causing severe pneumonia in human: a descriptive study clinical characteristics of coronavirus disease 2019 in china top 15 causes of death in the projecting hospital utilization during the covid-19 outbreaks in the united states surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (covid-19) personal protective equipment (ppe) for both anesthesiologists and other airway managers: principles and practice during the covid-19 pandemic the "helmet bundle" in covid-19 patients undergoing non invasive ventilation. intensive crit care nurs.102859, 2020. (epub ahead of print) exhaled air dispersion distances during noninvasive ventilation via different respironics face masks covid-19 in critically ill patients in the seattle region -case series presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area. jama. 2020. (epub ahead of print covid-19 does not lead to a "typical" acute respiratory distress syndrome covid-19 pneumonia: ards or not? crit care covid-19 pneumonia: different respiratory treatments for different phenotypes? intensive care med. 2020. (epub ahead of print) (epub ahead of print) intensive care med comparison of clinical and pathological features between severe acute respiratory syndrome and coronavirus disease 43:e040, 2020. (epub ahead of print) covid-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up noninvasive ventilation and survival in acute care settings: a comprehensive systematic review and metaanalysis of randomized controlled trials minimise nosocomial spread of 2019-ncov when treating acute respiratory failure clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to sars-cov-2 infection nosocomial transmission of emerging viruses via aerosol-generating medical procedures. viruses. 11, 2019.(epub ahead of print) viruses noninvasive ventilation treatment of acute respiratory failure by helmetdelivered non-invasive pressure support ventilation in children with acute leukemia: a pilot study helmet cpap vs. oxygen therapy in severe hypoxemic respiratory failure due to pneumonia effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial characteristics of covid-19 infection in beijing clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china. jama. 2020.(epub ahead of print) jama clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study noninvasive ventilation with helmet versus control strategy in patients with acute respiratory failure: a systematic review and meta-analysis of controlled studies helmet cpap versus oxygen therapy in hypoxemic acute respiratory failure: a meta-analysis of randomized controlled trials helmet continuous positive airway pressure vs oxygen therapy to improve oxygenation in community-acquired pneumonia: a randomized, controlled trial continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial early cpap prevents evolution of acute lung injury in patients with hematologic malignancy targeting transpulmonary pressure to prevent ventilatorinduced lung injury patient self-inflicted lung injury: implications for acute hypoxemic respiratory failure and ards patients on non-invasive support mechanical ventilation to minimize progression of lung injury in acute respiratory failure an example of an older version of the italian helmet cpap. note the counterweight for added patient comfort. figure used with permission reference the new version of the italian helmet cpap. figure used with permission author. 7 key: cord-000619-3bakci02 authors: zhang, peng-jun; li, xiao-li; cao, bin; yang, shi-gui; liang, li-rong; gu, li; xu, zhen; hu, ke; zhang, hong-yuan; yan, xi-xin; huang, wen-bao; chen, wei; zhang, jing-xiao; li, lan-juan; wang, chen title: clinical features and risk factors for severe and critical pregnant women with 2009 pandemic h1n1 influenza infection in china date: 2012-02-01 journal: bmc infect dis doi: 10.1186/1471-2334-12-29 sha: doc_id: 619 cord_uid: 3bakci02 background: 2009 pandemic h1n1 (ph1n1) influenza posed an increased risk of severe illness among pregnant women. data on risk factors associated with death of pregnant women and neonates with ph1n1 infections are limited outside of developed countries. methods: retrospective observational study in 394 severe or critical pregnant women admitted to a hospital with ph1n1 influenza from sep. 1, 2009 to dec. 31, 2009. rrt-pcr testing was used to confirm infection. in-hospital mortality was the primary endpoint of this study. univariable logistic analysis and multivariate logistic regression analysis were used to investigate the potential factors on admission that might be associated with the maternal and neonatal mortality. results: 394 pregnant women were included, 286 were infected with ph1n1 in the third trimester. 351 had pneumonia, and 77 died. a pao(2)/fio(2 )≤ 200 (odds ratio (or), 27.16; 95% confidence interval (ci), 2.64-279.70) and higher bmi (i.e. ≥ 30) on admission (or, 1.26; 95% ci, 1.09 to 1.47) were independent risk factors for maternal death. of 211 deliveries, 146 neonates survived. premature delivery (or, 4.17; 95% ci, 1.19-14.56) was associated neonatal mortality. among 186 patients who received mechanical ventilation, 83 patients were treated with non-invasive ventilation (niv) and 38 were successful with niv. the death rate was lower among patients who initially received niv than those who were initially intubated (24/83, 28.9% vs 43/87, 49.4%; p = 0.006). septic shock was an independent risk factor for failure of niv. conclusions: severe hypoxemia and higher bmi on admission were associated with adverse outcomes for pregnant women. preterm delivery was a risk factor for neonatal death among pregnant women with ph1n1 influenza infection. niv may be useful in selected pregnant women without septic shock. pregnant women are at an increased risk for contracting influenza and its complications associated with influenza [1] . like previous epidemic and pandemic diseases, 2009 pandemic h1n1 (ph1n1) influenza posed an increased risk of severe illness among pregnant women [2] [3] [4] [5] [6] [7] [8] [9] . a report from the first month of the ph1n1 outbreak noted that the rate of hospitalization among pregnant women was approximately four times the rate in the general population in the usa [3] . as reported by the california department of public health (cdph), a total of 10% of the 1088 patients who were hospitalized or died from the 2009 ph1n1 influenza were pregnant [10] . according to the ministry of health (moh) of the people's republic of china, pregnant women accounted for 13.7% of deaths associated with 2009 ph1n1 influenza [11] . pregnant women with influenza appear to have an increased risk of miscarriage, premature birth and stillbirth [2, 12, 13] . reports from victoria in australia [14, 15] , new york [16] , and california [17] , demonstrate that 2009 ph1n1 infection was associated with substantial maternal and fetal morbidity and mortality. however, information is limited concerning the risk factors for maternal and neonatal death when pregnancy is complicated by severe or critical illness related to 2009 ph1n1 influenza. in this report, we described the characteristics of ph1n1 influenza in pregnant women and the risk factors for maternal and neonatal death. all patients who were admitted to hospitals with confirmed 2009 ph1n1 influenza from sep. 1 to dec. 31, 2009 from 27 chinese provinces were screened if they fulfilled the diagnostic criteria for severe or critical cases. a confirmed case was a person whose ph1n1 virus infection was verified by real-time reverse-transcriptase polymerase chain reaction (rrt-pcr) with or without the presentation of other clinical symptoms. patients were excluded if they had been treated as outpatients or in emergency rooms or duration of hospitalization < 24 h, or if they had incomplete records of clinical outcomes. severe and critical cases were defined according to the h1n1 2009 clinical guidelines (third edition, 2009) released by the moh (additional file 1: table s1 ). our research retrospectively collected the patient's clinical information and did not involve the patient's personal information and samples, so there was no informed consent. the case report form included demographic information, underlying conditions, gestational age, vaccination status, treatment, intensive care unit (icu) admission, complications, and maternal and neonatal outcomes. body mass index (bmi) was calculated using height and weight recorded in the case report form, patients with bmi ≥ 30 were categorized as obesity. indications for applying noninvasive ventilation (niv): pregnant women who complained shortness of breath or blood gas analysis confirmed hypoxemia pao 2 to fio 2 < 300. one nonpulmonary major organ dysfunction or unconsciousness was contraindications for niv. indications to change from niv to invasive ventilation: a cautious trial of niv was attempted and response to niv was monitored after the first hour or two. if there was a deterioration of oxygenation, invasive ventilation was considered. definition of successful niv: pao 2 to fio 2 improved and respiratory rate decreased during one or two hour niv therapy. the patients successfully weaned off niv and survived. definition of failed niv: during the one or two niv trial, a deterioration of oxygenation was observed and invasive ventilation was needed. data collection and analysis were coordinated by the moh. a standard data collection form was used for each study site. site investigators were primarily infectious disease physicians closely involved in taking care of such patients at their centers. the data were entered in duplicate into a computerized database. patient confidentiality was maintained by recording only patient date of birth and gender on the data collection form. the research ethics board at beijing chao-yang hospital and the first affiliated hospital, school of medicine, zhejiang university approved the study. we analyzed the reported demographic characteristics, underlying conditions, symptoms, treatments, complications, clinical course and maternal and neonatal outcomes. means (standard deviations, sd) or medians (interquartiles, iqr) were calculated as summaries of continuous variables. for categorical variables, percentages of patients in each category were calculated. we compared clinical characteristics and clinical outcomes by using an anova test, chi-square test, or fisher's exact test or wilcoxon rank-sum test as necessary. the primary outcome was in-hospital mortality. we performed univariable logistic analysis to investigate the potential factors on admission that might be associated with the maternal mortality. factors with statistical significance (p < 0.05) in the univariate analyses were included in the multivariate logistic regression analysis. a p value of less than 0.05 was considered to indicate statistical significance. all analysis was carried out using spss for windows (release 13.0). clinical description of cohort 3570 severe or critical cases were screened and 394 cases involved pregnant women ( figure 1 ). demographic characteristics, underlying conditions, symptoms, and lab findings of the 394 pregnant women are illustrated in diseases were rare in this analysis. none of the patients had been immunized against seasonal influenza or 2009 ph1n1. the median apache ii score was 7.0 (iqr, [4] [5] [6] [7] [8] [9] [10] [11] . at the time of admission, 351 patients (90.0%) had pneumonia with an abnormal chest radiography or chest computed tomography. the most common symptoms were cough (372; 94.7%) and dyspnoea (199; 50.6%). the median pao 2 /fio 2 on admission was 154.7 (iqr, 89.5-320.5) ( table 1 ). of the 394 hospitalized patients, 246 (63.7%) were admitted to an icu at a median of 8 days from onset of illness (iqr 5 to 14; table 2 ). medication 378 (95.9%) patients received oseltamivir. the median time from onset of illness to oseltamivir therapy was 5 days (iqr 3 to 7), among them only 52 patients (14.0%) received oseltamivir within 48 h of onset of illness. 387 out of 394 patients received antibiotics. 244 received traditional chinese medicine. corticosteroid therapy was administered to 242 patients ( table 2) . the most commonly reported complication in this study was acute respiratory disease syndrome (ards) (151; 53.4%) ( table 2) . 211 (59.4%) women delivered at a median of 6 days (iqr 3 to 12) after ph1n1 symptom onset. 122 out of 211 women delivered prematurely (additional file 2: table s2 ). the most common delivery method was cesarean delivery (172 patients, 82.7%) ( table 2 ). among 143 live-birth deliveries for which the gestational age was known, 68 were premature (additional file 2: table s2 ). among the 394 pregnant women in the study, 77 died (table 2) , 56 out of the 77 patients who died were in their third trimester. the main cause of death was refractory hypoxemia (66 patients, 85.7%). of 5 patients with secondary infection, three patients had acinetobacter baumannii, one patient had aspergillus spp, and one patient had both acinetobacter baumannii and aspergillus spp. 62.4% of women included in the study required intensive care and 47.2% required mechanical ventilation. 83 (table 5 ). the first case of 2009 ph1n1 virus infection in china was documented on may 10, the virus has rapidly spread throughout the mainland. a total of 126,000 confirmed cases were reported by mar 31, 2010, including 7414 patients severe and 800 patients died. among all these severe cases, about 13.7% of patients were pregnant women [18] . in this large study of pregnant women who were hospitalized with severe 2009 ph1n1 influenza, the clinical characteristics were similar to those reported by others [3, 4, 17, 19] . 95.6% of patients were infected in the second or third trimester. in our study, the most common comorbidities were cardiovascular diseases (3.3%), diabetes mellitus (1.0%), respiratory diseases (2.8%), and obesity (18.5%). in our study, the prevalence of underlying diseases was much lower than reports from the united states (49.3%) [19] , 56% in australia [14] , 34% in california [17] , 22 .8% in brazil [20] , and 62% in france [4] . in those studies, the main cause of underlying disease was asthma. a study compared asthma prevalence of chinese adolescents living in canada and in china. the authors found that for girls, the range of asthma was 4.3% in guangzhou to 9.8% in canadian-born chinese adolescents. these results suggest that the lower prevalence of pre-existing asthma in our samples reflects prevalence of the disease in the chinese population [21] . the mortality rate for severe or critically infected pregnant women in our study was 20%, similar to what was reported in canada, mexico, and new zealand [22] [23] [24] [25] , but higher than in france (8% death in icuhospitalized pregnancy women) [4] . risk analysis showed that a pao 2 /fio 2 ≤ 200 and higher bmi (i.e. ≥ 30) on admission were risk factors for maternal death. pregnancy and ards are associated with increased oxygen consumption, which can result in hypoxemia in the mothers and the neonates. we reported that a higher bmi was associated with maternal mortality after adjusting for baseline clinical factors. observations of a high prevalence of obesity in severe and fatal cases of 2009 ph1n1 infection have been reported in chile, canada, the united kingdom and mexico [10, 26, 27] . as observed in australia, 42% of patients had a bmi of more than 30 and 22% of patients more than 35, while the corresponding proportions in the general australian pregnant population was 24% and 10% respectively [28] . however, our research retrospectively collected the patient's clinical information recorded in crfs. proportion of obesity has been overestimated based on bmi in the 3 rd trimester of pregnancy. data from previous pandemics and seasonal influenza epidemics suggested that the risk of complications associated with influenza might be higher in the second and third trimester of pregnancy than in the first trimester [2, 3, 17] . we also observed a higher proportion of maternal death occurring in the second and third trimester. during the 2009 h1n1 influenza pandemic, in the united states, the rate of premature birth (30.2%) was higher than the rate of premature births (13%) reported [29] , consistent with data demonstrating a higher rate of premature delivery during previous pandemics [2] . among women in our study for whom data on pregnancy outcomes was available, the rate of premature birth was 57.8%. in a multivariable analysis, preterm delivery contributed to fetal mortality. delivery in severe and critically infected women after 37 weeks' of gestation had improved neonatal outcomes compared to similar patients who delivered before 37 weeks of gestation. evidence on the useful role of niv in pregnant patients with ards secondary h1n1 viral infection was lacking. dr. amit banga [30] reported a 28-year-old pregnant female with ards (pao 2 /fio 2 155) due to community-acquired severe pneumonia who successfully treated with niv. in 2009, dr. michel djibre and collegues [31] reported a 38-year-old pregnant woman at 31 weeks' gestation with pao 2 /fio 2 98 who was successfully treated with niv. in our study, the success rate among pregnant women with h1n1 infection for niv was 45.8%. a recent prospective multicenter survey also found that when niv was used as first-line therapy for selected ali/ards patients (those with 2 organ failures, hemodynamic instability, or encephalopathy were excluded), 54% avoided intubation and had excellent outcomes [32] . apart from previous findings that major organ dysfunction and obtunded sensorium would obviously be unsuitable candidates for niv, we found that pregnant women complicated by septic shock were less likely to be successfully treated by niv. our data also support that cautious selection of appropriate patients is important for successful application of niv. patients should be monitored closely for signs of niv failure until stabilized. if there are signs of niv failure, patients should be intubated promptly before a crisis develops. our investigation has several limitations. firstly, we only evaluated pregnant women admitted to a hospital who fulfilled the diagnostic criteria of severe or critical cases. secondly, it was an observational study, and could therefore only demonstrate associations and could not infer cause. thirdly, we lacked follow up visits for maternal and neonatal outcomes. lastly, despite the use of a standardized data-collection form, not all information was collected for all patients. the clinical data reported herein is consistent with previous studies that demonstrate that pregnant women with influenza are at an increased risk of serious illness and death. our novel findings included: 1) niv was useful for some selected pregnant women with ph1n1 virus infection complicated by respiratory failure, but septic shock should be considered a contraindication; 2) a pao 2 /fio 2 ≤ 200 and higher bmi (i.e. ≥ 30) on admission were independent risk factors for maternal death; 3) premature delivery was an independent risk factor for neonatal death. additional file 1: the diagnosis criteria for severe and critical cases. additional file 2: maternal and neonatal outcomes by different delivery methods in different trimesters. data are presented as no. (%)/total no.(%), if otherwise stated. percentages are based on patients with complete information in the respective categories. * two patients missed the detailed information in maternal outcomes. neonatal outcomes were unknown in four cases. ** one patient missed the detailed information in maternal outcomes. neonatal outcomes were unknown in two cases. pandemic influenza and pregnant women influenza occurring in pregnant women h1n1 2009 influenza virus infection during pregnancy in the usa french experience of 2009 a/h1n1v influenza in pregnant women deaths from asian influenza associated with pregnancy impact of influenza on acute cardiopulmonary hospitalizations in pregnant women novel influenza a (h1n1) virus infections in three pregnant women-united states prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices (acip) h1n1 influenza in pregnancy: cause for concern factors associated with death or hospitalization due to pandemic 2009 influenza a(h1n1) infection in california progress in prevention and treatment of the 2009 h1n1 pandemic of pregnancy women best practices in perinatal care: prevention and treatment of novel influenza a (h1n1) virus during pregnancy and the immediate postbirth period bonar be: pandemic influenza and pneumonia in a large civilian hospital the anzic influenza investigators and australasian maternity outcomes surveillance system: critical illness due to 2009 a/h1n1 influenza in pregnant and postpartum women: population based cohort study h1n1 influenza a and pregnancy outcomes in severity of 2009 pandemic influenza a (h1n1) virus infection in pregnant women severe 2009 h1n1 influenza in pregnant and postpartum women in california official report of ministry of health, people's republic of china pandemic 2009 influenza a(h1n1) virus illness among pregnant women in the united states outcomes for pregnant women infected with the influenza a (h1n1) virus during the 2009 pandemic in porto alegre, brazil prevalence of asthma among chinese adolescents living in canada and in china critically ill patients with 2009 influenza a(h1n1) infection in canada critically ill patients with 2009 influenza a(h1n1) in mexico the anzic influenza investigators: critical care services and 2009 h1n1 influenza in australia and new zealand factors associated with death or intensive care unit admission due to pandemic 2009 influenza a (h1n1) infection epidemiology of fatal cases associated with pandemic h1n1 influenza uk obstetric surveillance system pregnancy outcome in south australia births: preliminary data for use of non-invasive ventilation in a pregnant woman with acute respiratory distress syndrome due to pneumonia non-invasive management of acute respiratory distress syndrome related to influenza a (h1n1) virus pneumonia in a pregnant woman a multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome all authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data, reviewed and approval of the final manuscript. drs. pjz, xll, bc and sgy contributed equally to this article. cw and lj l, the principal investigator, takes full responsibility for the integrity of the submission and publication, and was involved in the study design as part of the steering committee, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. drs z pj, l xl, cb, y sg had full access to all of the data in the study, and they take responsibility for the integrity of the data and the accuracy of the data analysis and draft of the manuscript. drs l lr and glwere involved in the study design as part of the steering committee. drs xz, hk, z hy, y xx, h wb, cw, z jx were responsible for the patient enrollment and the data collection. the authors declare that they have no competing interests. key: cord-015548-zjrkfe9b authors: popat, bhavesh; jones, andrew t. title: invasive and non-invasive mechanical ventilation date: 2012-05-18 journal: medicine (abingdon) doi: 10.1016/j.mpmed.2012.03.010 sha: doc_id: 15548 cord_uid: zjrkfe9b early recognition of patients who might potentially require ventilatory support is a key goal of critical care outreach programs and an important skill for all hospital medical staff. decisions about the initiation and timing of invasive ventilation can be difficult and early discussion with critical care colleagues is essential. appropriateness of invasive ventilatory support may also be an issue requiring advanced discussion with patients and their families. in the past 10–15 years, the role of non-invasive ventilation (niv) has expanded, not least in an attempt to minimize the complications inherent with invasive ventilation. as such, niv is now considered first-line therapy in some conditions (chronic obstructive pulmonary disease, pulmonary oedema, mild-to-moderate hypoxaemic respiratory failure in immunocompromised patients), and a ‘trial of niv’ is often considered in respiratory failure resulting from an increasingly wide range of causes. when using niv, the importance of the environment (setting, monitoring and experience of staff) and forward planning cannot be overemphasized. when used for other than the standard indications, niv should be employed in a high-dependency/intensive care setting only in patients for whom invasive ventilation would be considered. indications for ventilation early identification of critically ill patients, before the occurrence of significant cardio-respiratory decompensation, is one of the major goals of critical care outreach programmes. patients who require ventilatory support often develop a common pattern of physiological deterioration including: increasing respiratory rate asynchronous respiratory pattern a change in mentation and level of consciousness frequent oxygen desaturation despite increasing oxygen concentration hypercapnia and respiratory acidosis circulatory problems, including hypotension and atrial dysrhythmias. the modern ventilator is a complex computer-driven tool and a detailed description of its modes and use are beyond the scope of this article (see further reading). in simple terms, it mixes air under pressure with variable oxygen concentrations to provide inspiration and expiration, each 'breath' is characterized by three factors, which can be adjusted by the operator; trigger: the ventilator can deliver a breath according to a timer that defines a specific set rate (ventilator initiated/ mandatory breaths), or as a result of the patient's own breathing efforts effecting a change in the pressure or flow in the ventilator circuit (patient-initiated/spontaneous breaths). target: the flow of air into the lung can be to a specific target flow rate (volume control) or pressure (pressure control; pressure support; bi-level) termination: the signal for the ventilator to finish inspiration and allow expiration (passive) may be the achievement of a specific volume (volume-cycled: volume control), after a specific time (time-cycled: pressure control/bi-level) or following the reduction of inspiratory flow to a preset level (flow-cycled: pressure support) niv refers to the provision of respiratory support without direct tracheal intubation. as such, it aims to avoid some of the complications inherent with invasive ventilation, such as the need for sedation with risks of haemodynamic instability and subsequent risk of delirium, nosocomial infection, etc. 1 in a recent worldwide survey, use of niv increased from 4% to 11% of all episodes of mechanical ventilation between 2001 and 2004 respectively, with even higher rates of use in some european countries. 2 indeed, for some situations it is considered the first-choice mode of ventilatory support ( niv today consists almost exclusively of the delivery of positive pressure ventilation via an external interface. there are six broad types of interface available, each with its own particular benefits and drawbacks (see further reading): total face masks (enclose mouth, nose eyes) full face masks (enclose mouth and nose) nasal mask (covers nose but not mouth) mouthpieces (placed between lips and held in place by lip seal) nasal pillows or plugs (inserted into nostrils) helmet (covers the whole head/all or part of the neck e no contact with face). niv can be delivered using most modern 'intensive care' ventilators. for sicker patients this has several advantages (ability to deliver higher and precise concentrations of oxygen; separate inspiratory/expiratory limbs minimizing re-breathing of co 2 ; better monitoring/alarm features; and rapid access to invasive ventilation). outside of the icu, niv is commonly applied using smaller, 'simpler' but increasingly sophisticated 'non-invasive' ventilators, which can provide a range of respiratory support modes. pressure-cycled modes are generally preferred (accommodation of leaks), and breaths can be either patient-triggered (pressure support or bi-level positive airway pressure (bipap)), or initiated and controlled by the ventilator (pressure control). indeed, both modes are often used synergistically to provide back up when triggering is poor or if patient respiratory rate is unreliable, and to cover potential apnoeic episodes. acute hypercapnic respiratory failure patients with acute hypercapnic respiratory acidosis secondary to an acute exacerbation of chronic obstructive pulmonary disease (copd), represent the most extensively studied group, and the greatest evidence for benefit exists in copd. 3e6 numerous studies and meta-analyses have confirmed that use of niv is associated with reduced risks of treatment failure (rr 0.48), lower intubation rates (rr 0.41) with lower incidence of nosocomial infections, and a reduction in mortality (rr 0.52) with subsequent reduced hospital length of stay and costs. 7 these benefits have been shown predominantly in patients with mild-to-moderate hypercapnic respiratory failure (ph 7.30e7.34). as such, niv should be considered first-line therapy for this patient group, and can be safely used in appropriately staffed and monitored environments outside of the icu. 4 this does not preclude the use of niv in patients with more severe respiratory failure, 8e10 and a ph as low as 7.20 may still be compatible with favourable outcomes. however, such patients should be managed in a high-dependency environment, to allow for rapid escalation to intubation and invasive ventilation if appropriate. the importance of an established structure for effective niv delivery cannot be overemphasized. early initiation by experienced and skilled staff, appropriate environments and monitoring, and protocols to aid patient selection and subsequent decision making are key to the successful and safe application of niv in all forms of respiratory failure 11 ( figure 1 ). although treatment failure is uncommon in mild-to-moderate respiratory failure, it becomes increasingly frequent in sicker (lower ph and/or significant hypoxaemia) patients (table 2) . common causes of niv failure include interface leaks and patient asynchrony with the ventilator ( table 2 ). in experienced hands, such issues can be recognized early and rapidly remedied; if this is not possible, intubation and invasive ventilation will need to be considered. 11, 12 the appropriateness of invasive ventilation in patients with copd can be a contentious issue. however, recent evidence suggests more favourable outcomes than predicted, with stable or even improved quality of life in most patients. 13 decisions about the extent of future intervention should be made by a senior physician, taking into account factors such as functional status, previous pulmonary function tests, existing comorbidities, body mass index, the need for long-term oxygen therapy and the patient's expressed wishes; ideally before the initiation of niv. the outcome should be documented in the medical record and communicated to the patient/family as appropriate. recommendations based on levels of evidence 21 level 1 evidence systematic reviews (with homogeneity) of rcts and individual rcts (with narrow cis) evidence of use (favourable) acute pulmonary oedema the use of niv (including continuous positive airway pressure (cpap)) to treat respiratory failure secondary to acute pulmonary oedema is widespread. 14e17 several meta-analyses have established benefit, including decreased intubation rate (cpap/ bi-level) and mortality (cpap) compared to standard medical therapy. 18 however, these findings were not borne out in a recent randomized control trial, 19 even though physiological improvements occurred earlier in the niv arms (cpap/bi-level). the low rate of intubation (<3%), and the potential for crossover between the study arms may have limited the ability to document improvements with niv. the european cardiology task force 20 for diagnosis and treatment of cardiogenic pulmonary oedema recommends niv/cpap as first-line treatments in addition to standard medical therapy when respiratory failure is present. there is conflicting evidence for the use of niv in hypoxaemic respiratory failure. 21e24 a recent meta-analysis where niv in addition to standard therapy was compared to standard therapy alone, in hypoxaemic respiratory failure not related to •diagnose need for niv ( fig. 1;2 pulmonary oedema, reported improvements in intubation rate, mortality and hospital length of stay with the use of niv. 22 however the literature in this area is hampered by marked heterogeneity between the study populations in both cause and severity of respiratory failure e in particular the frequency of pre-existing copd. therefore, although some studies suggest benefit, routine use of niv in severe pneumonia or acute respiratory distress syndrome (ards) cannot be recommended. however, in immunocompromised patients, studies have shown early niv use to be beneficial in the management of hypoxic respiratory failure, particular in patients with solid organ transplantation, haematological malignancies and hiv infection. 25e27 niv should be considered in such patients, preferably in a highdependency/icu environment with rapid access to invasive ventilation and multi-organ support. in an attempt to limit exposure to the risks of invasive mechanical ventilation, niv is being used increasingly to promote earlier extubation and prevent re-intubation. present evidence suggests it is most likely to be beneficial in copd patients, medical patients with multiple morbidities who are likely to fail on extubation and those with hypercapnia during spontaneous breathing trials. 28 with increasing expertize in its use, it is not surprising that clinicians have been keen to exploit the potential benefits of niv over invasive ventilation in other 29, 30 forms of respiratory compromise (table 1) . it is important to recognize that in some conditions the literature represents small series from experienced centres and the importance of the environment and forward planning cannot be overemphasized. in these circumstances we would recommend that niv should be employed in an intensive care setting only if invasive ventilation would be considered for the patient. invasive mechanical ventilation requires access to the trachea, most commonly via an endotracheal tube, and represents the commonest reason for admission to the icu. large multinational surveys confirm the common indications for invasive ventilation to be: 2 coma 16% copd 13% ards 11% heart failure 11% pneumonia 11% sepsis 11% trauma 11% postoperative complications 11% neuromuscular disorders 5%. decisions about the initiation and timing of invasive ventilation can be difficult and early discussion with critical care colleagues is essential. appropriateness of ventilatory support may also be an issue requiring advanced discussion with patients and families. once a decision to intubate has been made, the transition from an awake and self-ventilating patient to controlled invasive ventilation can be very difficult in the critically ill. most patients will have evidence of developing or established organ dysfunction, particularly cardiovascular dysfunction (ischaemic heart disease, sepsis), and commonly such patients are hypovolaemic. both anaesthetic induction agents and positive pressure ventilation (which decreases venous return) produce cardiovascular depression and peri-intubation hypotension is common. in addition, cessation of spontaneous ventilation can lead to very rapid desaturation in such patients, due to their marginal respiratory reserve and circulatory problems. such consequences need to be anticipated: large-volume cannulae should be in place; access to plasma expanders and inotropes should be immediately available; and following induction of anaesthesia the airway must be rapidly secured by an experienced member of the critical care team e ideally in an appropriately equipped area of the hospital. descriptions of individual ventilatory strategies are beyond the scope of this chapter. however, over the past 10e20 years there has been increasing recognition that invasive ventilation, although lifesaving, can be associated with significant complications, such as nosocomial pneumonia, critical illness neuromyopathy syndromes and barotrauma (pneumothoraces); and ventilation itself may be associated with propagation of underlying lung injury and subsequent worsening of multi-organ failure. 31, 32 the landmark nih ards network trial 33 confirmed that in patients with acute lung injury, the use of a reduced tidal volume (6 ml/kg) and avoidance of high airway pressures (<30 cmh 2 o) were associated with improved mortality (31% vs. 39.8% (nntz11)) when compared with a conventional ventilatory approach. although it is not without controversy, 34 this and subsequent studies form the basis for management of patients with hypoxaemic respiratory failure. although individual patients differ, key concepts include: low tidal volume (6 ml/kg ideal bodyweight) and avoidance of high inspiratory pressures (p plat < 30) to minimize the risk of volutrauma 33 reduced oxygenation targets (sao 2 88e95%; po 2 7.5e10.5) e 'permissive hypoxia' acceptance of mildemoderate respiratory acidosis e 'permissive hypercapnia' greater use of positive end-expiratory pressure (peep), particularly in more severe hypoxaemia 35 (nb: peep should be used cautiously and may be contraindicated in obstructive airways disease) early use of neuromuscular blockade in severe cases 36 general strategies avoidance of excessive fluid administration minimizing sedation once acute insult has settled e daily sedation holds (interruption of sedation), use of sedation scores 37 daily trials of spontaneous breathing and protocolized weaning once initial insult has resolved 38 early and appropriate nutritional support deep vein thrombosis prophylaxis stress ulcer prophylaxis more recently, attention has turned to the use of extracorporeal support in patients with extreme gas exchange abnormalities. in the recent cesar study, 39 transfer to a centre capable of delivering extracorporeal membrane oxygenation (ecmo) was associated with improved outcome (death or disability) at 6 months. this study and the high-profile success of ecmo in the h1n1 40 influenza pandemic has resulted in a resurgence of interest in this technique. simpler forms of extracorporeal support exist where hypercapnia is the predominant problem. 41 the development of these and other specialist techniques, along with a recognized volumeeoutcome relationship for mechanical ventilation, 42 has promoted the concept of advanced respiratory support centres to manage the sickest patients. longer term, there is an increased recognition that survivors of critical illness can be left with significant physical, mental and psychological sequelae 43 and early rehabilitation and icu followup programmes have evolved to address these issues. principles and practice of mechanical ventilation evolution of mechanical ventilation in response to clinical research non-invasive ventilation in chronic obstructive pulmonary disease: management of acute type 2 respiratory failure early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial clinical practice guideline for the use of noninvasive positive pressure ventilation in copd patients with acute respiratory failure non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: cochrane systematic review and meta-analysis non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. cochrane database syst rev noninvasive vs. conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease d nejm the use of noninvasive mechanical ventilation in copd with severe hypercapnic acidosis nippv e niv in acute respiratory failure guideline non-invasive ventilation in acute respiratory failure survival and quality of life for patients with copd or asthma admitted to intensive care in a uk multicentre cohort: the copd and asthma outcome study (caos) randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema noninvasive pressure support ventilation vs. continuous positive airway pressure in acute hypercapnic pulmonary edema non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial noninvasive ventilation in patients with acute cardiogenic pulmonary edema effect of non-invasive positive pressure ventilation (nippv) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis noninvasive ventilation in acute cardiogenic pulmonary edema executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the task force on acute heart failure of the european society of cardiology the evidence for noninvasive positive-pressure ventilation in the care of patients in acute respiratory failure: a systematic review of the literature does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure? a systematic review failure of non-invasive ventilation in patients with acute lung injury: observational cohort study noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial noninvasive ventilation for treatment undergoing solid organ transplantation noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure noninvasive ventilation for treating acute respiratory failure in aids patients with pneumocystis carinii pneumonia use of non-invasive ventilation to wean critically ill adults off invasive ventilation: metaanalysis and systematic review non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma the use of non-invasive ventilation for life-threatening asthma attacks: changes in the need for intubation overview of ventilator-induced lung injury mechanisms cellular responses to mechanical stress: invited review: mechanisms of ventilator-induced lung injury: a perspective ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. the acute respiratory distress syndrome network how best to ventilate? trial design and patient safety in studies of the acute respiratory distress syndrome higher vs lower positive endexpiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis neuromuscular blockers in early acute respiratory distress syndrome efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (awakening and breathing controlled trial): a randomised controlled trial use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: cochrane systematic review and meta-analysis efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation for 2009 influenza a(h1n1) acute respiratory distress syndrome the novalung ò ila membrane ventilator: technical aspects hospital volume and the outcomes of mechanical ventilation one-year outcomes in survivors of the acute respiratory distress syndrome key: cord-011222-7aha5b07 authors: huang, cheng-chi; muo, chih-hsin; wu, tain-fung; chi, tung-yun; shen, te-chun; hsia, te-chun; shih, chuen-ming title: the application of non-invasive and invasive mechanical ventilation in the first episode of acute respiratory failure date: 2020-03-30 journal: intern emerg med doi: 10.1007/s11739-020-02315-1 sha: doc_id: 11222 cord_uid: 7aha5b07 acute respiratory failure (rf) is a life-threatening syndrome. this study investigated the application of two major clinical strategies, non-invasive mechanical ventilation (niv) and invasive mechanical ventilation (imv), in the first episode of acute rf. data from the longitudinal health insurance database, which included 1,000,000 insured citizens, were used. the niv group consisted of 1201 patients and the imv group consisted of 16,072 patients. chi-square test and t test were applied to determine the differences in categorical and continuous variables. further analysis was performed by using univariate and multivariable logistic regression and poisson regression. there was a significant increase of 733% in the number of niv users from 2000 to 2012. niv use was frequently observed in old-age persons (aor 3.99, 95% ci 3.06–5.21 for those aged ≥ 80 years), women (aor 1.33, 95% ci 1.18–1.50), patients admitted to a high-level hospital (aor 1.95, 95% ci 1.63−2.34 for those admitted to a medical center), and patients with a higher charlson comorbidity index (cci, aor 1.38−1.66 for those cci ≥ 2). in addition, patients with chronic pulmonary disease, cancer, and congestive heart failure were predominant in niv users and were significantly associated with niv use. overall, the use of niv has markedly increased over the past few years. persons of advanced age, women, patients admitted to a high-level hospital, and patients with multiple comorbidities were associated with more frequent niv use. chronic pulmonary disease, cancer, and congestive heart failure were most important comorbidities for niv use. electronic supplementary material: the online version of this article (10.1007/s11739-020-02315-1) contains supplementary material, which is available to authorized users. respiratory failure (rf) is a syndrome in which the respiratory system fails to perform one or both of its gas exchange functions, oxygenation and carbon dioxide elimination [1] . rf can be classified into either acute or chronic according to its clinical course. acute rf is characterized by life-threatening derangements in arterial blood gases and acid-base status, and the common etiologies include cardiogenic or noncardiogenic pulmonary edema, pneumonia, and pulmonary hemorrhage (hypoxemic) and drug overdose, neuromuscular disorders, chest wall abnormalities, and obstructive airway disorders (hypercapnic) [2] . the treatment for acute rf is complex and must be immediate. severe hypoxemic and hypercapnic status must be corrected in time, and the underlying pathophysiologic process that led to acute rf must be identified and managed [3] . mechanical ventilation (mv) is often performed in this critical situation to assist or replace spontaneous breathing to maintain and sustain life [4] . the invention and application of mv has been considered as one of the cornerstones of modern medicine. mv comprises the following two major clinical settings: non-invasive mechanical ventilation (niv) and invasive mechanical ventilation (imv) [5, 6] . niv refers to the administration of ventilatory support without the use of an invasive artificial airway such as an endotracheal tube or a tracheostomy tube. the general indications of niv for acute rf include acute exacerbation of chronic obstructive pulmonary disease, acute cardiogenic pulmonary edema, asthma, community-acquired pneumonia, post-operative support, and post-extubation support [7, 8] . other indications of niv may include palliative care of life, immunocompromised patients, acute respiratory distress syndrome, chest trauma, chest wall and neuromuscular disorders, obesity hypoventilation syndrome, obstructive sleep apnea, and during bronchoscopy [9] . the role of niv and imv in acute rf is under vigorous and enthusiastic investigation. the general concept is that niv is preserved for patients having any of the above-mentioned indications and having no contraindication including the need for airway protection, inability to fit an interface, high severity of illness, or an uncooperative patient [7] . however, cumulative evidence has shown that the use of niv has markedly increased over the past few decades and that niv has become an integral tool in the management of acute rf [10−15] . in the present study, we investigated the trend in the use of niv and imv, the baseline characteristics of niv and imv users, the associated discharge diagnoses of niv and imv users, and the mortality of niv and imv users during their first episode of acute rf in a population in taiwan. the taiwan national health insurance administration (tnhia) had established a single-payer national health insurance (nhi) program in 1995. almost the entire taiwanese population has to compulsorily participate in this program. the tnhia established several national health insurance research databases (nhirds) from the nhi program. these databases included information of the insurant and all the medical records of each insurant. the coding of the international classification of diseases, ninth revision, clinical modification (icd-9-cm) was used for identification of diseases. the identification of insurant in the databases was re-coded according to the personal information protection act. this study was approved by the research ethics committees of china medical university and hospital (cumh104-rec2-115). data from the longitudinal health insurance database, which included 1,000,000 insured citizens, were used for this study. we identified all adult patients with acute rf (icd-9-cm 518.81) from 2000 to 2012. the date of the first acute rf diagnosis was defined as the index date. we excluded inadequate patients as follows: (1) with any diagnosis of rf or use of mv before the index date; (2) without the use of mv for the first episode of acute rf; (3) with overlapping use of niv and imv for the first episode of acute rf. all the enrolled patients were further categorized into the following two groups: the niv group and the imv group. the variables of interest in the study included age, gender, level of hospital, comorbidity, and charlson comorbidity index (cci). individuals were categorized into the following four age groups: 20−49, 50−64, 65−79, and ≥ 80 years. hospitals were categorized into the following three levels: medical center, regional hospital, and district hospital. first-level hospitals are medical centers affiliated to colleges of medicine, with high volume of medical personnel and much greater resources with at least 500 beds. secondlevel hospitals are metropolitan hospitals with at least 250 beds, indicating regional hospitals. third-level hospitals are local community hospitals with less health care personnel and resources, indicating district hospitals. the cci was defined based on charlson's and devo's reports [16, 17] . the detailed comorbidities included diabetes mellitus, congestive heart failure, myocardial infraction, peripheral vascular disease, cerebrovascular disease, hemiplegia or paraplegia, dementia, chronic pulmonary disease, liver disease, peptic ulcer disease, renal disease, rheumatic disease, cancer, and human immunodeficiency virus infection and acquired immune deficiency syndrome (hiv/aids). all comorbidities were identified from 1995 to the index date. in addition, we have analyzed the associated discharge diagnoses accompanied by acute rf during the same hospitalization among niv users. the outcomes of interest included mortality at discharge and mortality within 90 days. the number of individuals and the probability of the use of niv and imv between 2000 and 2012 were calculated. chi-square test was used to determine the differences in age group, gender, hospital level, comorbidity, and cci between the niv group and the imv group. a t test was carried out to determine the differences in mean age between the two study groups. the odds ratios (ors) and the 95% confidence intervals (cis) for niv and niv-associated factors were estimated by logistic regression. the model 1 was adjusted for age group, gender, hospital level, and cci and the model 2 was adjusted for age group, gender, hospital level, and comorbidities. furthermore, we calculated the distribution of the most prevalent associated discharge diagnoses in the niv group and compared with the imv group by logistic regression. finally, the rate ratios (rrs) and 95% cis of mortality at discharge and within 90 days for the niv group were compared with those for the imv group by poisson regression. the model was adjusted for age group, gender, hospital level, and cci. additionally, we performed another overall matched method for mortality comparison (propensity score matching based on age, gender, hospital level, and cci). all analyses were performed using sas software (sas 9.4, sas institute, cary, north carolina, usa). the level of significance was set at p < 0.05 of two-tailed tests. from the database of 1,000,000 population, 37,479 individuals were identified to have been diagnosed with acute rf during 2000−2012, of whom 17,273 individuals were enrolled in this study (supplement data). the niv group consisting of 1201 (7.0%) individuals had received niv treatment, and the imv group consisting of 16,072 (93.0%) individuals had received imv treatment for the first episode of acute rf. we observed that the overall number of mv users increased by 40. compared with imv users, the niv users included a greater number of older persons (84.6% vs. 69.0% for those aged ≥ 65 years), a greater number of women (45.5% vs. 36.9%), a greater number of patients admitted to a medical center or a regional hospital (84.9% vs. 78.2%), a greater number of patients with a higher cci (65.2% vs. 53.9% for those cci ≥ 2), and a greater number of patients with chronic pulmonary disease (43.1% vs. 24.8%), cancer (25.8% vs. 14.0%), congestive heart failure (20.7% vs. 14.2%), and dementia (7.74% vs. 6.17%). on the other hand, the imv users included a greater number of patients with renal disease (12.7% vs. 8.91%), diabetes mellitus (9.87% vs. 7.49), liver disease (8.89% vs. 5.25%), and peripheral vascular disease (3.30% vs. 2.25%) than the niv users (table 1) . table 2 shows the association between niv and niv-associated factors. compared with patients aged 20−49 years, niv choice was found with increasing age, but a significant difference was observed only for patients aged ≥ 65 years (aor 1.90, 95% ci 1.45 − 2.49 at 65−79 years and aor 3.99, 95% ci 3.06−5.21 at ≥ 80 years in the model 1). women had a 1.33-fold niv choice compared to that of men (95% ci 1.18−1.50 in the model 1). compared with patients admitted to a district hospital, those who were admitted to a regional hospital or a medical center had an about 1.9-fold niv choice in the model 1. compared with patients with cci at 0−1, the highest niv choice was at 2−3 (aor 1.66, 95% ci 1.45−1.90) and followed by at > 5 (aor 1.40, 95% ci 1.11−1.77) and at 4−5 (aor 1.38, 95% ci 1.15−1.65). in the model 2, there were the same trend in age group, gender, and hospital level as in the model 1. patients comorbid with a medical history of cancer (aor 2.57, 95% ci 2.23−2.97), chronic pulmonary disease (aor 2.24, 95% ci 1.97−2.55), and congestive heart failure (aor 1.27, 95% ci 1.08−1.49) had a significantly higher niv choice compared to that of individuals without those medical history. in contrast, patients comorbid with a medical history of renal disease (aor 0.59, 95% ci 0.48−0.74) and liver disease (aor 0.65, 95% ci 0.50−0.85) had a significantly lower niv choice. in addition, we also presented the association between niv and niv-associated factors stratified by (presence or absence of) cancer history. the most notable finding was that the impact of increasing age on niv choice was weakened (aor 1, 0.92, 1.20, and 2.06 in model 1 and aor 1, 0.91, 1.06, 1.62 in model 2) in patients with a history of cancer but strengthened (aor 1, 1.37, 2.80, and 6.53 in model 1 and aor 1, 1.32, 2.36, 5.11 in model 2) in patients with no cancer history (supplementary data). table 3 shows the most frequent associated discharge diagnoses with acute rf in the niv group (no. = 22, > 2%). we categorized these associated disorders into four groups: (1) possible cause of rf, (2) comorbidity, (3) co-existing acute illness, and (4) table 4 ). stratified analysis for the presence of cancer history showed that patients with cancer in the niv group had a higher mortality rate at discharge (77.4% vs. 62.6%) and within 90 days (89.7% vs. table 4 ). similarly, we observed that patients in the niv group had a significantly higher overall mortality rate at discharge than those in the imv group. patients with cancer in the niv group had a higher mortality rate at discharge and within 90 days than patients with cancer in the imv group. no difference was observed in the mortality rate of noncancer patients who had received niv and imv treatment. this work is a large population-based study evaluating the application of niv and imv in the first episode of acute rf. we observed that the use of niv has markedly increased over the past few years, which implies that niv application has largely expanded. characteristic analysis of the study population showed that the elderly, women, patients admitted to a high-level hospital, and patients with a high cci were more predominant users of niv than their counterparts. we also found that individuals who had received niv treatment had a higher mortality rate than those who had received imv treatment; however, there was no difference in the mortality rate of non-cancer individuals who had received niv treatment in comparison with those who had received imv treatment. in the present study, we have provided valuable information about underlying comorbidities among patients with acute rf. we found that cancer, chronic pulmonary disease, and congestive heart failure were associated with a high niv choice, whereas renal and liver diseases were associated with a low niv choice. in addition, we have provided the most frequent associated discharge diagnoses among niv users and the influence of these associated discharge diagnoses on the use of niv. these results are consistent with the general concepts of niv and imv indications. cumulative evidence has shown that the use of niv has markedly increased over the past few decades. in a recent review, niv is suggested for application in broad conditions in acute rf: (1) to prevent endotracheal intubation; (2) as an alternative to imv; (3) as a tool for facilitating early weaning from imv; or (4) as palliative care in do not resuscitate (dnr) patients [18] . the indications for niv have also been extended, such as for immunocompromised patients and patients with chest trauma, post-operative lung resection, community-acquired pneumonia, acute respiratory distress syndrome, and terminal stage diseases (palliative care) [7] [8] [9] 18] . the improvement of intensive monitoring and care, the application of integrated therapeutic tools, and expert integrated teams all contribute to the increased use of niv. among the abovementioned indications for niv, palliative use may contribute an important role for niv application. in this study, the extremely elderly and patients with cancer comprised a very high proportion (52.0% of those aged ≥ 80 years and 25.8% of those with a history of cancer) of niv users, and cancer occupied the second place among the associated discharge diagnoses in niv users. this phenomenon may be influenced by the administration of palliative care for individuals with extremely old age and advanced stage of cancer [19] [20] [21] [22] . palliative niv could be administered either to offer a chance for survival or to alleviate the symptoms of respiratory distress in terminally ill patients [19] . the use of niv in patients with dyspnea in terminal states remains controversial, but it is reportedly effective in reducing dyspnea and in decreasing the dose of morphine in palliative use in patients with end-stage cancer [21] . one of the primary benefits of using niv in this setting is the preservation of communication between the patient and the family. this technique is also widely used in patients with acute rf and in a dnr order, particularly for the extremely elderly [22] . unfortunately, information on the number of persons who had dnr orders or received hospice care was absent from the database. the role or exact proportion of palliative niv in all niv users should be clarified in further research. in this study, the overall mortality was higher in the niv group than in the imv group. in general, niv is applied for patients with low disease severity; therefore, we believe that palliative niv plays a vital role in clinical practice. we further conducted a stratified analysis of the presence of cancer history and found that patients with cancer who had received niv treatment had a much higher mortality rate than patients who had received imv treatment. by contrast, no difference was found in the mortality rates of patients without cancer between the niv and imv groups. this finding supported our hypothesis because palliative niv was applied in a considerable number of patients with and without cancer. however, the exact proportion of palliative niv users in this study was unknown. the application of palliative niv for non-cancer patients needs further investigation. the strength of this study is that it is a nationwide population-based investigation evaluating the application of niv and imv in the first episode of acute rf. the nhi program in taiwan covers more than 99.5% of the population. this universal coverage has reduced the barriers to healthcare access for all citizens, irrespective of the socioeconomic background and the residential location [23] . in the present study, a real-world scenario has been depicted, wherein all diagnoses and medical practices were directly made during a medical consultation. several limitations were considered in this study. first, we evaluated the role of niv and imv only in the first episode of acute rf. some people may have repeated episodes of acute rf and would have received different opinions regarding treatment. second, we excluded the overlapping use of niv and imv as we could not differentiate the time sequence of niv and imv use in the database. clinically, imv can be used after niv for the management of disease progression, and niv can be used after imv for post-extubation support. third, the cause of acute rf was unavailable in the database. we attempted to apply associated discharge diagnoses to overcome this limitation, but only minimal success was achieved. we could only categorize these associated diagnoses into four groups: possible cause of rf, comorbidity, co-existing acute illness, and uncertain acute or chronic condition. fourth, disease severity such as the degree of hypoxemia and hypercapnia and the acute physiology and chronic health evaluation (apache) score were unavailable. the apache score is associated with patients' prognosis and in-hospital mortality [24] . we could only collect cci data to represent the overall degree of severity. finally, we were unable to identify patients with dnr orders or who received palliative and hospice care. therefore, the results of the present study must be interpreted with caution. the use of niv has markedly increased over the past few years. persons of advanced age, women, patients admitted to a high-level hospital, and patients with multiple comorbidities were associated with more frequent niv use. chronic pulmonary disease, cancer and congestive heart failure were predominant in niv users and were significantly associated with niv use. conflict of interest the authors declare that they have no conflict of interest. this article does not contain any studies with human participants or animals performed by any of the authors. not necessary, all patient information in the nhird was anonymized and de-identified prior to analysis. publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. respiratory failure acute respiratory failure management of acute renal failure mechanical ventilation: past lessons and the near future indications for mechanical ventilation in adults with acute respiratory failure mechanical ventilation: invasive versus noninvasive noninvasive ventilation for acute respiratory failure non-invasive ventilation in acute respiratory failure noninvasive ventilation in acute respiratory failure noninvasive positive pressure ventilation in the intensive care unit: a concise review noninvasive ventilation for critical care noninvasive ventilation in acute respiratory failure noninvasive ventilation for patients presenting with acute respiratory failure: the randomized controlled trials non-invasive ventilation in acute respiratory failure changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries a new method of classifying prognostic comorbidity in longitudinal studies: development and validation adapting a clinical comorbidity index for use with icd-9-cm administrative databases noninvasive ventilation in acute respiratory failure: which recipe for success? key: cord-260220-f1tpkw1o authors: timenetsky, karina t; aquino, silvia hct; saghabi, cilene; taniguchi, corinne; silvia, claudia v; correa, luci; marra, alexandre r; eid, raquel ac; dos santos, oscar fp title: high success and low mortality rates with non-invasive ventilation in influenza a h1n1 patients in a tertiary hospital date: 2011-09-28 journal: bmc res notes doi: 10.1186/1756-0500-4-375 sha: doc_id: 260220 cord_uid: f1tpkw1o background: in 2009, an outbreak of respiratory illness caused by influenza a h1n1 virus occurred worldwide. some patients required intensive care unit (icu) admission. the use of non-invasive ventilation (niv) in these patients is controversial, as the aerosol dispersion may contaminate the environment and health-care co-workers. methods: describe the respiratory profile, the mortality rate, and the benefit of using niv in patients with confirmed diagnosis of influenza ah1n1 who were admitted in the icu during the year 2009. results: a total of 1, 401 cases of influenza a h1n1 were confirmed in our hospital by real-time rt-pcr in 2009, and 20 patients were admitted to the icu. the patients' ages ranged from 18 to 74 years (median of 42). acute respiratory failure (arf) was present in 70% of patients. the median acute physiology and chronic health evaluation ii score was 7 (range 7 to 25). of the 14 patients who developed arf, 85.7% needed niv and 14% needed invasive mv at admission. our success rate (41.6%) with niv was higher than that described by others. the hospital mortality rate was 2.1%. when influenza a h1n1 arrived in brazil, the disease was already on endemic alert in other countries. the population was already aware of the symptoms and the health-care system of the treatment. this allowed patients to be properly and promptly treated for influenza a h1n1, while health-care workers took protective measures to avoid contamination. conclusion: in our study we found a high success and low mortality rates with non-invasive ventilation in patients with influenza a h1n1. in late march of 2009, an outbreak of respiratory illness caused by swine-origin influenza a h1n1 virus occurred in mexico. all patients developed acute respiratory distress [1] , of which 38% died. this pandemic disease spread quickly throughout the world [1] [2] [3] [4] [5] [6] [7] [8] . some individuals with influenza a h1n1 develop severe forms of the disease that require hospitalization in the intensive care unit (icu), mostly due to acute respiratory failure (arf). different studies have reported that between 62 and 100% of the patients require mechanical ventilation (mv), with a mortality rate varying from16 to 58% [1] [2] [3] [4] [5] [7] [8] [9] . although frequently used, invasive mv has several complications, such as ventilator-associated pneumonia, which is a risk factor for mortality and for diaphragmatic dysfunction, which may lead to diaphragm myofiber atrophy [9] [10] [11] . only two studies have addressed the issue of using noninvasive ventilation (niv) in patients with influenza a h1n1 virus, but the controversies regarding its benefit are still unresolved [2, 8] . there is a concern that niv might lead to aerosol dispersion, which may contaminate health-care co-workers [2, 8, 12] . on the other hand, niv prevents the need for endothracheal intubation in patients with arf, minimizing related complications [9, 12, 13] . in our hospital we had a total of 1, 401 confirmed cases of influenza a h1n1. in this study we describe the respiratory profile, the mortality rate, and the benefit of using niv in patients with confirmed diagnosis of influenza ah1n1 who were admitted in the icu during the year 2009. we retrospectively evaluated the medical charts and laboratory exams of all influenza a h1n1 virus-suspected patients who were admitted to the icu during the year of 2009. this study was conducted in a 38-bed medical-surgical icu of a tertiary-care private hospital in sao paulo, brazil. this is an open-staffing-model icu where approximately 2, 200 patients are admitted annually. we have a nurse:bed ratio of 1:4 in our icu. this study was approved by the ethics committee of the albert einstein jewish hospital and patient's consent was waved due to the study design. to confirm the cases of swine-origin influenza a h1n1 virus by real-time rt-pcr (rt-rtpcr), nasopharyngeal-swab samples were collected at hospital admission and respiratory secretions obtained from intubated patients. rt-rtpcr testing was performed in all patients with suspected signs of influenza a h1n1 that were treated at our hospital according to published guidelines from the center for disease control (cdc) [14, 15] . all influenza a h1n1 virus-confirmed patients admitted to the icu were included in the study. we also collected demographic data and information on coexisting medical conditions, microbiology findings, incidence of arf, the requirement of mv (whether invasive or noninvasive at icu admission and during icu stay), laboratory findings, and gas exchange ratio at admission (pao 2 /fio 2 ), for each patient. for those patients who required invasive mv, we evaluated the need for alveolar recruitment maneuver, mv time, and mv weaning success. to determine the severity of illness, the acute physiology and chronic health evaluation (apache) ii score was determined in all patients within 24 hours of admission in the icu. we also collected information on the length of the entire hospital stay (including the time in the icu) and on mortality rate. mv weaning success was considered when the patient was able to tolerate at least 48 hours without invasive mechanical ventilation. noninvasive mechanical ventilation was instituted in the confirmed influenza a h1n1 when there were signs of acute respiratory failure at hospital admission or during icu stay. the signs of acute respiratory failure were tachypnea (respiratory rate higher than 35 rpm), hypoxemia (pao2 < 80 mmhg), use of accessory respiratory muscles, and need of high oxygen concentration (higher than 40% delivered by simple facial mask or using mask with a non re-breathing system). niv success was considered when patient was able to improve oxygenation, respiratory rate (lower than 35 rpm), carbon dioxide concentration, the use of accessory respiratory muscles within 2 hours of niv. in case this improvement was not achieved or patient did not tolerate the use of niv, they were promptly intubated and assisted with invasive mechanical ventilation. patients were informed of the reasons to use niv to treat acute respiratory failure, or the need to initiate invasive mechanical ventilation. patients needed to collaborate with niv to use it, being alert and responsive to commands without agitation. niv was delivered by a specific ventilator, bipap ® vision ® (philips -respironics) providing a pressure support ventilation through a total face mask. the respiratory therapists were responsible for this therapeutic intervention. our icu has a respiratory therapists:bed ratio of 1:5. patients that were admitted with signs of acute respiratory failure as described above, with extreme levels of hypoxemia (pao2 lower than 60 mmhg with a high oxygen concentration delivered by a mask with a non re-breathing system -100%), low level of consciousness, or refuse to use niv were promptly intubated at icu admission. mv weaning success was considered when the patient was able to tolerate at least 48 hours without invasive mechanical ventilation. categorical variables were expressed as absolute and relative frequencies (percentages). the quantitative variables were expressed as mean and standard deviation if normally distributed, or as median and interquartile range if distributed otherwise. the software r, version 10.1 was used to compute the descriptive statistics [16] . during the year of 2009, we had a total of 4, 308 suspected cases of influenza a h1n1 that were treated in our hospital. of these, 1, 401 patients had confirmed diagnosis of influenza a h1n1 and only 139 of these patients needed hospital admission. there were 86 patients admitted to the icu with suspected cases of swine-origin influenza a h1n1 virus. of these cases, 20 patients were confirmed with rt-rtpcr test. our analyses were based only on the 20 patients with confirmed influenza a h1n1 that were admitted to the icu. all patients with suspect signs of influenza a h1n1 admitted to our hospital were treated with oseltamivir within 48 hours of symptoms initiation. the characteristics of the 20 patients admitted to the icu with confirmed cases of influenza a h1n1 virus are listed in table 1 . the patients' ages ranged from 18 to 74 years (mean of 42.6 years). eleven patients (55%) were male. ten patients had coexisting medical conditions as follows: asthma (in two patients), diabetes mellitus (in three patients, two of whom were also transplanted patients), coronary insufficiency (in two patients, one of whom had also chronic obstructive pulmonary disease), chronic obstructive pulmonary disease (in one patient), renal transplant (in two patients), liver transplant (in one patient), and non-hodgkin's lymphoma (in one patient). as shown in table 2 , arf was present in 14 patients (70%), due mainly to pneumonia (9 patients, 64.3%) and also to acute respiratory distress syndrome (ards; 5 patients, 35.7%), none of the patients presented acute hypercapnic respiratory failure. the apache ii score ranged from 7 to 25 (median of 7). gas exchange ratio (pao 2 /fio 2 ) at hospital admission ranged from 59 to 361 (median, 226.5). of the 14 patients who developed arf, 12 (85.7%) needed niv and 2 (14%) needed invasive mv at admission. the number of days on niv ranged from 1 to 11 (median of 3 days), being successful in 5 patients (41.6%; table 2 ), none of them had hypercapnic respiratory failure. the median carbon dioxide arterial pressure (paco 2 ) before using niv was 33.8 mmhg (range of 21 to 45 mmhg) and after 2 hours of niv was 35.8 mmhg (range of 30 to 43 mmhg). the remaining patients had to be intubated. we had no icu health-care co-workers contaminated by influenza a h1n1 during the study period, the contamination was monitored by the hospital infection control department, evaluating all health-care co-workers that were treating these patients with rt-rtpcr testing. there were no signs of skin breakdown with the use of total face mask to deliver niv and all these patients cooperated with niv. invasive mv was required in 2 patients at admission and in 7 after niv during hospitalization, with a total of 9 patients undergoing invasive mv. of these 9 patients, we implemented alveolar recruitment maneuver in 5 patients, but none of them responded successfully, and 8 (88.8%) were successfully weaned from mv. invasive mv time ranged from 1 to 12 days (median, 6 days; table 2 ). icu length of stay ranged from 1 to 14 days (median, 4 days) and hospital length of stay ranged from 1 to 56 days (median, 10 days). the icu mortality rate was 15% (3 patients) and hospital mortality rate was 2.1% for the confirmed cases of influenza a h1n1 virus. the 3 patients who died in the icu had a coexisting medical condition. one patient had arterial hypertension, the second was a transplanted patient, and the third had coronary insufficiency. in this study we identified all patients with confirmed diagnosis of influenza a h1n1 admitted to the albert einstein jewish hospital during the year of 2009. we identified 1, 401 patients with the infection and who were treated in our hospital. of these, only 139 (9.9%) patients needed hospitalization. of these 139 patients, 20 (14.3%) were admitted to the icu. our icu admission incidence was lower than that reported in most studies [3, 9] . the exception was a study done in canada that reported an even lower incidence (8.1%) [8] . cases of acute respiratory failure due to influenza a h1n1 affecting patients younger than the expected age for patients with seasonal influenza have been previously reported [1] [2] [3] [4] [5] [6] [7] [8] . our findings are consistent with these reports. in regard to the severity of illness, our apache ii score (7) was lower than that of other studies, which reported a median score around 13 to 19 [1, 2, 8] . our apache ii score was probably lower than other studies because the disease was already an endemic disease when it reached brazil and the population and healthcare co-workers were already alert to the disease signs and received early treatment. this is probably also the reason for our low number of patients admitted to the icu as reported by other studies. similar to other studies, our study identified chronic lung disease as the most frequent coexisting medical condition [1] [2] [3] 5, 8, 9] . on the other hand, a study by cao et al. described arterial hypertension as the most frequent coexisting medical condition [6] . most of our patients had arf, as seen in other studies, with the exception of one study from japan that did not report any case of arf between may and june of 2009 [1] [2] [3] 8, 9] . in our study, we had 85.7% of the patients who used niv at icu admission to treat arf. our incidence was higher than that of the other two studies that mentioned the use of niv at icu admission (around 33%) [2, 8] . in this study we had a success rate with niv in 41.6% of the patients, showing greater success with niv when compared with the other two studies (25% in spain [2] and14.6% in canada [8] ). we believe that this difference in niv success is due to the disease severity, because our apache ii score was lower than that described by others [2, 8] . because of the low niv success rate and high endotracheal intubation incidence previously reported in several studies, many researchers stated that niv should not be routinely used in patients with pandemic respiratory infections [1, 2, 8, 17] . many researchers are concerned about using niv during pandemic respiratory infections due to the infectious exhaled aerosol that can reach the environment through the exhalation ports in the niv mask or tubing, which may contaminate health-care co-workers [17, 18] . for instance, in a recent study from australia [9] in which a significant correlation with the need for invasive mv and mortality rates was observed (odds ratio 5.51; 95% ci 3.95-9.94; p < 0.001), niv was never considered as an option. in the study by perez-padilla et al. [1] , the authors reported 22 (11.5%) cases of health-care co-worker contamination with influenza a h1n1, while treating the first 3 patients who were admitted to the hospital. none of these patients were undergoing niv. after an infection-control measure that enforced patient isolation in specific hospital areas, use of n95 respirators in addition to goggles, gowns, and gloves, and constant use of gelalcohol hand sanitizer, no more health-care co-workers were contaminated by the disease. this was not the case in our hospital, where our niv success rate was higher than everywhere else, and no health-care co-worker was contaminated through niv and all health-care co-workers used infection control measures to avoid contamination, such use of goggles, gowns, gloves, and use of gel-alcohol hand sanitizer. all influenza a h1n1 icu patients stayed in individual and isolated hospital bed, to avoid contamination to other patients. our success rate with niv indicates that patients with influenza a h1n1 can benefit from it, thus preventing the need for invasive mv, and minimizing the incidence of complications such as ventilatorassociated pneumonia [11] . this was the situation described in mexico [1] , where 4 (22%) patients underwent invasive mv and had ventilator-associated pneumonia. cheung et al. [17] reported their experience with 20 patients undergoing niv during severe acute respiratory syndrome (sars) in 2003 at a hong kong hospital. to reduce the risk of contamination the staff used a viral/ bacterial filter, n95 respirators, and an oronasal mask to prevent large leaks through the mouth and exhalation valve. they were able to prevent endotracheal intubation in 14 patients (70%) and none of the health-care coworkers were contaminated. in our hospital all the protective measures were used to prevent contamination of health-care co-workers and other icu patients. the fact that influenza a h1n1 arrived in brazil after being already an endemic alert in other countries provided the necessary time for the government to set strategies to control its spread. additionally, the population was already aware of the symptoms and the health-care system of the treatment. this allowed patients to be properly and promptly treated for influenza a h1n1, while health-care workers took protective measures to avoid contamination. in this scenario, niv can be safely used in patients with influenza a h1n1. nevertheless, the same indication for using niv in patients requiring mv for arf should be considered for patients with influenza a h1n1. in regard to invasive mv, our study had a lower incidence at admission, when compared to other studies [1] [2] [3] 8, 9] . this can also be related to our low apache ii score, as the study by rello et al. [2] described that patients who failed niv had a higher apache ii score than those who were successful. our mechanical ventilation time was lower than that described by others [1, 2, 8, 9] . in our study 5 patients developed ards and were intubated. of these patients, all underwent alveolar recruitment maneuver with high end-expiratory pressure levels to improve oxygenation, without any related complications. in the studies on influenza a h1n1 patients currently available [1] [2] [3] [4] [5] [6] [7] [8] [9] , none mention using this maneuver to improve oxygenation. in one study, kumar et al. [8] reported using inhaled nitric oxide, high frequency oscillatory ventilation, and extracorporeal membrane oxygenation and had 8.3% incidence of barotraumas. regarding the icu length of stay, our findings were lower than those reported in previous studies [8, 9] . however, in regard to our hospital length of stay, our findings were similar to those from a study from australia [9] . so far, patients with influenza a h1n1 admitted to hospitals worldwide had a high mortality rate (13 to 39%) [1] [2] [3] [4] [5] [6] [7] [8] [9] . however, in our study the hospital mortality rate was 2.1%. beside the low apache ii score of our patients, it is possible that our low mortality rate is also associated with a lower number of patients undergoing invasive mechanical ventilation, as compared to other studies [1] [2] [3] [4] 8, 9] . in our study we found a high success and low mortality rates with non-invasive ventilation in patients with influenza a h1n1. although our study is limited to one center only and cannot be representative of the scenario in brazil, we had 1, 401 patients with confirmed influenza a h1n1, of whom most were successfully treated in our hospital as described. pneumonia and respiratory failure from swine-origin influenza a (h1n1) in mexico león-gil c: intensive care adult patients with severe respiratory failure caused by influenza a (h1n1)v in spain h1n1 influenza in the united states pediatric hospitalizations associated with 2009 pandemic influenza a (h1n1) in argentina epidemiology of influenza a(h1n1)v virus infection in japan clinical features of the initial cases of 2009 pandemic influenza a (h1n1) virus infection in china clinical characteristics of paediatric h1n1 admissions in canadian critical care trials group h1n1 collaborative, et al: critically ill patients with 2009 influenza a (h1n1) infection in canada the anzic influenza investigators: clinical care services and 2009 h1n1 influenza in australia and new zealand a comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure ventilator-associated pneumonia: epidemiology and impact on the clinical evolution of icu patients rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans noninvasive ventilation for patients presenting with acute respiratory failure: the randomized controlled trials geneva: world health organization design and validation of real-time reverse transcription-pcr assays for detection of pandemic (h1n1) 2009 virus team: r: a language and environment for statistical computing. r foundation for statistical computing effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome american association for respiratory care: aarc sars guidance document high success and low mortality rates with non-invasive ventilation in influenza a h1n1 patients in a tertiary hospital authors' contributions ktt participated in the study design, data collection, performed statistical analysis, and writing the manuscript. shcta participated in the study design and data collection. cs and ct participated in the data collection. cvs and lc were responsible for collecting the rt-rtpcr testing results and also helped with drafting the manuscript. arm participated in the statistical analysis and in drafting the manuscript. race and ofps participated in the study design and in drafting the manuscript. all authors read and approved the final manuscript. the authors declare that they have no competing interests. key: cord-016744-jzhuq4te authors: hui, david s. c. title: noninvasive mechanical ventilation: models to assess air and particle dispersion date: 2013-05-29 journal: noninvasive ventilation in high-risk infections and mass casualty events doi: 10.1007/978-3-7091-1496-4_2 sha: doc_id: 16744 cord_uid: jzhuq4te respiratory failure is a major complication of viral infections such as severe acute respiratory syndrome (sars) [1], avian influenza h5n1 infection [2], and the 2009 pandemic influenza (h1n1) infection [3]. the course may progress rapidly to acute respiratory distress syndrome (ards) and multi-organ failure, requiring intensive care. noninvasive ventilation (niv) may play a supportive role in patients with severe viral pneumonia and early ards/acute lung injury. it can act as a bridge to invasive mechanical ventilation, although it is contraindicated in critically ill patients with hemodynamic instability and multi-organ dysfunction syndrome [4]. transmission of some of these viral infections can convert from droplets to airborne during respiratory therapy. particles generated during tidal breathing [ 8 ] , niv may disperse potentially infected aerosols, especially when patients cough and sneeze frequently, contributing to nosocomial transmission of infl uenza. pulmonary tuberculosis (tb) is well known to spread by the airborne route. a recent study showed that a small number of patients with pulmonary tb (28 %) produced culturable cough aerosols [ 9 ] . thus, it is important to examine the exhaled air directions and dispersion distances during application of niv to patients with respiratory failure via commonly used face masks. the data can improve our understanding of and knowledge about infection control. such knowledge can facilitate the development of preventive measures to reduce the risk of nosocomial transmission during application of niv to high-risk patients with respiratory infections. as there is no reliable, safe marker that can be introduced into human lungs for experimental purposes, the laser smoke visualization method and the human patient simulator (hps) model have been adopted as the method for studying exhaled air dispersion during application of various types of respiratory therapy in hospital medical wards, including the negative-pressure isolation room [ 10 -13 ] . the hps represents a 70-kg adult man sitting on a 45°-inclined hospital bed ( fig. 2.1 ) . the hps contains a realistic airway and is programmed to remove oxygen and inject carbon dioxide into the system according to a preset respiratory exchange ratio and oxygen consumption. the lung compliance can also be changed to simulate different degrees of lung injury during chest infection. by varying the oxygen consumption (200, 300, and 500 ml/min) and lung compliance (70, 35, and 10 ml/cmh 2 o), these sets of values produce a range of tidal volumes, respiratory rates, and peak inspiratory fl ow similar to those of patients with minimal (essentially normal lung function), moderate, or severe lung injury, respectively. for example, lung compliance is set at 35 ml/cm h 2 o and oxygen consumption at 300 ml/min to mimic mild lung injury. tidal volume and respiratory rate are regulated so a respiratory exchange ratio of 0.8 is maintained during measurements. typically, this is achieved with a tidal volume of 300 ml and a respiratory rate of 25 breaths/min [ 10 -13 ] . lung compliance and airway resistance also responds in a realistic manner to relevant respiratory challenges. the hps produces an airfl ow pattern that is close to the in vivo situation. it has been applied in previous studies to simulate human respiration [ 14 -17 ] . deliberate leakage from the exhalation ports of the mirage mask (resmed, bella vista, nsw, australia) [ 10 ] , comfortfull 2, and image 3 masks (respironics, murrysville, pa, usa) [ 11 ] fi rmly attached to a high-fi delity hps (hps 6.1; medical education technologies, sarasota, fl, usa) has been evaluated. niv was applied using a bilevel positive airway pressure device (vpap iii st; resmed) via each mask. the inspiratory positive airway pressure (ipap) was initially set at 10 cmh 2 o and gradually increased to 18 cmh 2 o. the expiratory positive airway pressure (epap) was maintained at 4 cmh 2 o throughout the study [ 10 , 11 ] . visualization of airfl ow around each niv face mask was facilitated by marking the air with smoke particles produced by a m-6000 smoke generator (n19; ds electronics, sydney, australia), as in our previous studies [ 10 -13 ] . the oil-based smoke particles, measuring less than 1 μm in diameter, are known to follow the airfl ow pattern precisely with negligible slip [ 18 ] . the smoke was introduced continuously to the right main bronchus of the hps. it mixed with alveolar gas and then was exhaled through the airway. sections through the leakage jet plume were then revealed by a thin, green laser light sheet (532 nm wavelength, continuous-wave a laser beam located on the right side of the bed lateral to the human patient simulator illuminates the exhaled air particles leaking from the exhalation ports of the face mask in the coronal plane. a camera was positioned along the sagittal plane at the end of the bed to capture lateral dispersion of exhaled air illuminated by the laser device. positions of the camera and the laser device would be exchanged when the exhaled air dispersion from the face mask is examined along the sagittal plane mode) created by a diode-pumped solid-state laser (oem ugh-800 mw; lambda pro technologies, shanghai, china) with custom cylindrical optics to generate a two-dimensional laser light sheet [ 10 -13 ] . the light sheet was initially positioned in the median sagittal plane of the hps and subsequently shifted to paramedian sagittal planes. this allowed us to investigate the regions directly above and lateral to the mask and the patient [ 10 -13 ] . all leakage jet plume images revealed by the laser light sheet were captured by a high-defi nition video camera-sony high-defi nition digital video camcorder (hdr-sr8e; sony, tokyo, japan); clearvid complementary metal oxide semiconductor sensor (sony) with a carl zeiss vario-sonnar t* lens (carl zeiss, jena, germany)-with optical resolution of 1,440 × 1,080 pixels per video frame. the normalized smoke concentration in the plume was estimated from the light intensity scattered by the smoke particles [ 10 -13 ]. the normalized smoke concentration in the mask leakage air was estimated from the light scattered by the particles. the analysis was based on scattered light intensity being proportional to the particle concentration under the special conditions of constant-intensity laser light sheet illumination and monodispersion of small (submicron) particles [ 18 ] . in short, the thin laser light sheet of near-constant intensity illuminated the smoke particle markers in the mask airfl ow leakage. smoke particles scattered laser light perpendicular to the light sheet. the pictures were then collected and integrated by the video camera element and lens [ 10 -13 ]. a motion video of at least 20 breathing cycles for each niv setting was captured and individual frames extracted as gray-scale bitmaps for intensity analysis. frames were extracted at time points starting from the beginning of each inspiration to generate an ensemble average for the corresponding instant of the respiratory cycle [ 10 -13 ] . the time at which the normalized concentration contours spread over the widest region from the niv mask was chosen for the ensemble average to estimate the greatest dispersion distance. this was found to be approximately at the mid-respiratory cycle [ 10 , 11 ] . all gray-scale frames were read into a program specifi cally developed for these studies [ 10 -13 ] (mathcad 8.0; mathsoft, cambridge, ma, usa) [ 19 ] along with the background intensity images obtained with the laser switched off. the background intensity image was subtracted from each frame, pixel by pixel, to remove any stray background light. the pixel intensity values were averaged over all frames to determine the average intensity. the resulting image was the total intensity of light scattered perpendicular to the light sheet by the smoke particles. it was directly proportional to the smoke concentration under the conditions mentioned above. the image was normalized against the highest intensity found within the leakage jet plume to generate normalized particle concentration contours [ 10 -13 ] . as the smoke particles marked air that originated from the hps's airways before leaking from the mask, the concentration contours effectively represent the probability of encountering air around the patient that has come from within the mask and the patient's respiratory system. the normalized concentration contours are made up of data collected from at least 20 breaths. a contour value of 1 indicates a region that consists entirely of air exhaled by the patient, where there is a high chance of exposure to the exhaled air, such as at the mask exhaust vents. a value near 0 indicates no measurable air leakage in the region and a small chance of exposure to the exhaled air [ 10 -13 ]. the results are presented with reference to the median sagittal plane. with the resmed mirage mask, a jet plume of air escaped through the exhaust holes to a distance of approximately 0.25 m radially during application of ipap 10 cmh 2 o, with some leakage from the nasal bridge. the leakage jet probability was highest about 60-80 mm lateral to the sagittal plane of the hps. without nasal bridge leakage, the plume jet from the exhaust holes increased to a 0.40 m radius circle, and exposure probability was highest about 0.28 m above the patient. when ipap was increased to 18 cmh 2 o, the vertical plume extended to about 0.5 m above the patient and the mask, with some horizontal spread along the ward roof [ 10 ]. with the comfortfull 2 mask, a vertical, cone-shaped plume leaked out from the mask exhalation diffuser and propagated well above and almost perpendicular to the patient at an ipap and an epap of 10 and 4 cmh 2 o, respectively. the maximum dispersion distance of smoke particles-defi ned as the boundary with a region encountering <5 % normalized concentration of exhaled air (light blue contour smoke concentration scale)-was 0.65 m, whereas that of a high concentration (containing >75 % normalized concentration of exhaled air, red zone, and above) was 0.36 m. there was no signifi cant room contamination by exhaled air (as refl ected by the blue background in the isolation room) other than the exhalation jet plume [ 11 ] . when the ipap was increased from 10 to 14 cmh 2 o, the maximum exhaled dispersion distance of low-concentration exhaled air was similar at 0.65 m, but that of high-concentration exhaled air increased to 0.40 m, with contamination of the isolation room. also, there was some exhaled air concentration outside the exhalation jet plume. when ipap was increased to 18 cmh 2 o, the dispersion distance of lowconcentration exhaled air was 0.85 m, whereas that of high-concentration exhaled air increased to 0.51 m along the median sagittal plane. more background contamination of the isolation room by smoke particles was noted at higher ipaps owing to interaction between the downstream ceiling-mounted ventilation vent and the upstream exhaled air from the hps (images at left in fig. 2.2 ) [ 11 ]. the image 3 mask required an additional exhalation device (whisper swivel) to prevent carbon dioxide rebreathing. the exhaled air leakage was much more diffuse than that with the comfortfull 2 mask because of the downstream leakage of d.s.c. hui exhaled air through the whisper swivel exhalation port. at an ipap of 10 cmh 2 o, the maximum dispersion distance of a low concentration in exhaled air (light blue zone on the smoke concentration scale) was 0.95 m toward the end of the bed, whereas that of a medium concentration (containing >50 % of the normalized concentration of exhaled air, green zone, and above) was about 0.6 m along the median sagittal plane. as the ipap was increased from 10 to 14 cmh 2 o, the exhaled air with a medium concentration increased to 0.95 m toward the end of the bed along the median sagittal plane of the hps [ 11 ] . when the ipap was increased to 18 cmh 2 o, the exhaled air with a low concentration dispersed diffusely to fi ll up most of the isolation room (i.e., beyond 0.95 m, as captured by the camera), whereas that with a medium concentration, occupying wider air space, was noted to spread 0.8 m toward the end of the bed, with accumulation of a high concentration of exhaled air (red zone on scale) within 0.34 m from the center of the mask, along the median sagittal plane of the hps (images on the right in fig. 2. 2 ) [ 11 ] . there is no reliable, safe marker that can be introduced into human lungs for experimental purposes. hence, the maximum distribution of exhaled air, marked by very fi ne smoke particles, from the hps during application of niv using three face masks was examined by the laser smoke visualization method on a high-fi delity hps model. the studies showed that the maximum distances of exhaled air particle dispersion from patients undergoing niv with the resmed ultra mirage mask was 0.5 m along the exhalation port [ 10 ] . in contrast, the dispersion distances of a low, normalized concentration of exhaled air through the comfortfull 2 mask exhalation diffuser increased from 0.65 to 0.85 m at a direction perpendicular to the head of the hps along the sagittal plane when ipap was increased from 10 to 18 cmh 2 o. there was also more background contamination of the isolation room at the higher ipap [ 11 ] . even when a low ipap of 10 cmh 2 o was applied to the hps via the image 3 mask connected to the whisper swivel exhalation port, the exhaled air leaked far more diffusely than from the comfortfull 2 mask, dispersing a low normalized concentration of 0.95 m along the median sagittal plane of the hps. the higher ipap resulted in wider spread of a higher normalized concentration of smoke around the hps in the isolation room with negative pressure [ 11 ] . simonds et al. [ 20 ] applied the laser visualization method to assess droplet dispersion during application of niv in humans with an optical particle sizer (aerotrak 8220; tsi instruments, high wycombe, uk) and showed niv as a droplet-(not aerosol-) generating procedure, producing droplets measuring >10 μm. most of them fell onto local surfaces within 1 m of the patient. noninvasive ventilation is an effective treatment for patients with respiratory failure due to copd, acute cardiogenic pulmonary edema, or pneumonia in immunocompromised patients. however, evidence supporting its use in patients with pneumonia is limited. niv was applied to patients with severe pneumonia caused by a 2009 pandemic infl uenza (h1n1) infection with a success rate of about 41 %. although there were no reported nosocomial infections [ 21 ] , there is a potential risk of applying niv to patients hospitalized with viral pneumonia on a crowded medical ward with inadequate air changes [ 7 ] . in this regard, deliberate leakage via the exhalation ports may generate droplet nuclei and disperse infective aerosols through evaporation of water content of respiratory droplets, resulting in a superspreading event. nonetheless, niv was applied using a single circuit to treat patients effectively with respiratory failure due to sars in hospitals with good infection control measures (including installation of powerful exhaust fans to improve the room air change rate and good protective personal equipment at a level against airborne infection). there were no nosocomial infections among the health care workers involved [ 22 , 23 ] . in contrast, a case-control study involving patients in 124 medical wards of 26 hospitals in guangzhou and hong kong identifi ed the need for oxygen therapy and use of niv as independent risk factors for superspread of nosocomial sars outbreaks [ 6 ] . similarly, a systematic review has shown a strong association between ventilation, air movement in buildings, and airborne transmission of infectious diseases such as measles, tuberculosis, chickenpox, infl uenza, smallpox, and sars [ 24 ] . these studies of infection with the hps model [ 10 , 11 ] and in humans [ 20 ] have important clinical implications for preventing future nosocomial outbreaks of sars and other highly infectious conditions such as pandemic infl uenza when niv is provided. niv should be applied in patients with severe community acquired pneumonia only if there is adequate protection for health care workers because of the potential risk of transmission via deliberate or accidental mask interface leakage and fl ow compensation causing dispersion of a contaminated aerosol [ 10 , 11 ] . pressure necrosis may develop in the skin around the nasal bridge if the niv mask is applied tightly for a prolonged period of time. many patients loosen the mask strap to relieve discomfort. air leakage from the nasal bridge is defi nitely a potential means of transmitting viral infections. fitting a mask carefully is important for successful, safe application of niv. addition of a viral/bacterial fi lter to the breathing system of niv, between the mask and the exhalation port, or using a dual-circuit niv via full face mask or helmet without heated humidifi cation may reduce the risk of nosocomial transmission of a viral infection [ 11 , 25 ] . in view of the observation that higher ventilator pressures result in wider dispersion of exhaled air and more air leakage [ 10 , 11 ] , it is advisable to start niv with a low ipap (8-10 cmh 2 o) and increase it gradually as necessary. the whisper swivel is an effi cient exhalation device to prevent carbon dioxide rebreathing, but it would not be advisable to use such an exhalation port in patients with febrile respiratory illness of unknown etiology. this is especially true in the setting of an infl uenza pandemic with the high potential of human-to-human transmission for fear of causing a major outbreak of nosocomial infections. it is also important to avoid the use of high ipap, which could lead to wider distribution of exhaled air and substantial room contamination [ 11 ] . there are some limitations regarding the use of smoke particles as markers for exhaled air. the inertia and weight of large droplets in an air-droplet two-phase fl ow would certainly cause them to have less horizontal dispersion than occurs with the continuous air carrier phase during which the particles travel with increased inertia and drag. however, evaporation of the water content of some respiratory droplets during coughing or sneezing when exposed to niv may produce droplet nuclei suspended in air, whereas the large droplets fall to the ground in a trajectory pathway [ 10 -13 ] . as smoke particles mark the continuous air phase, the data contours described refer to exhaled air. the results would therefore represent the "upper bound" estimates for dispersion of the droplets-which would be expected to follow a shorter trajectory than an air jet due to gravitational effects-but not fully refl ect the risk of large-droplet transmission [ 10 -13 ] . in summary, the laser visualization technique using smoke particles as a marker in the hps model is a feasible means of assessing exhaled air dispersion during application of niv and other modes of respiratory therapy [ 10 -13 ] . substantial exposure to exhaled air occurs within 1 m of patients undergoing niv in an isolation room with negative pressure via the comfortfull 2 mask and the image 3 mask connected to the whisper swivel exhalation port. it must be noted that there is far more extensive leakage and room contamination with the image 3 mask, especially at higher ipaps [ 11 ] . health care workers should take adequate precautions for infection control. they especially must pay attention to environmental air changes when providing niv support to patients with severe pneumonia of unknown etiology complicated by respiratory failure . a major outbreak of severe acute respiratory syndrome in hong kong review of clinical symptoms and spectrum in humans with infl uenza a/h5n1 infection clinical management of pandemic (h1n1) infection infl uenza a/h5n1 infection: other treatment options and issues transmission of severe acute respiratory syndrome during intubation and mechanical ventilation why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? possible role of aerosol transmission in a hospital outbreak of infl uenza infl uenza virus in human exhaled breath: an observational study variability of infectious aerosols produced during coughing by patients with pulmonary tuberculosis non-invasive positive pressure ventilation: an experimental model to assess air and particle dispersion exhaled air dispersion distances during application of noninvasive ventilation via different respironics face masks exhaled air dispersion during oxygen delivery via a simple oxygen mask exhaled air and aerosolized droplet dispersion during application of a jet nebulizer breathing pattern and workload during automatic tube compensation, pressure support and t-piece trials in weaning patients patient simulation for training basic and advanced clinical skills a model for educational simulation of infant cardiovascular physiology an audible indication of exhalation increases delivered tidal volume during bag valve mask ventilation of a patient simulator fluid dynamics of multiphase systems mathcad 8.0 for windows, users guide evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic infl uenza and other airborne infections early non-invasive ventilation treatment for severe infl uenza pneumonia effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome noninvasive positive pressure ventilation treatment for acute respiratory failure in sars role of ventilation in airborne transmission of infectious agents in the built environment-a multidisciplinary systematic review on the role of non-invasive ventilation (niv) to treat patients during the h1n1 infl uenza pandemic. ers and esicm guideline • the laser visualization technique using smoke particles as markers in the hps model is a feasible means of assessing exhaled air dispersion during application of niv and other modes of respiratory therapy. • substantial exposure to exhaled air occurs within 1 m of patients undergoing niv even in an isolation room with negative pressure. • during application of niv, it is advisable to choose face masks with predictable exhaled air directions and distances through the exhalation port without addition of the whisper swivel device. • it is important to avoid using high inspiratory pressures and any face mask that requires connection to the whisper swivel exhalation port as they would lead to wider distribution of exhaled air and substantial room contamination. key: cord-002078-38rmx65j authors: korkmaz ekren, pervin; basarik aydogan, burcu; gurgun, alev; tasbakan, mehmet sezai; bacakoglu, feza; nava, stefano title: can fiberoptic bronchoscopy be applied to critically ill patients treated with noninvasive ventilation for acute respiratory distress syndrome? prospective observational study date: 2016-05-31 journal: bmc pulm med doi: 10.1186/s12890-016-0236-y sha: doc_id: 2078 cord_uid: 38rmx65j background: noninvasive ventilation (niv) is a cornerstone for the treatment of acute respiratory failure of various etiologies. using niv is discussed in mild-to-moderate acute respiratory distress syndrome (ards) patients (pao(2)/fio(2) > 150). these patients often have comorbidities that increase the risk for bronchoscopy related complications. the primary outcome of this prospective observational study was to evaluate the feasibility, safety and contribution in diagnosis and/or modification of the ongoing treatment of fiberoptic bronchoscopy (fob) in patients with ards treated with niv. methods: ards patients treated with niv and who require fob as the diagnostic or therapeutic procedure were included the study. intensive care ventilators or other dedicated niv ventilators were used. niv was applied via simple oro-nasal mask or full-face mask. pressure support or inspiratory positive airway pressure (ipap), external positive end expiratory pressure (peep) or expiratory positive airway pressure (epap) levels were titrated to achieve an expiratory tidal volume of 8 to 10 ml/kg according to ideal body weight, spo(2) > 90 % and respiratory rate below 25/min. results: twenty eight subjects (mean age 63.3 ± 15.9 years, 15 men, 13 women, pao(2)/fio(2) rate 145 ± 50.1 at admission) were included the study. overall the procedure was well tolerated with only 5 (17.9 %) patients showing minor complications. there was no impairment in arterial blood gas and cardiopulmonary parameters after fob. pao(2)/fio(2) rate increased from 132.2 ± 49.8 to 172.9 ± 63.2 (p = 0.001). no patient was intubated within 2 h after the bronchoscopy. 10.7, 32.1 and 39.3 % of the patients required invasive mechanical ventilation after 8 h, 24 h and 48 h, respectively. bronchoscopy provided diagnosis in 27 (96.4 %) patients. appropriate treatment was decided according to the results of the bronchoscopic sampling in 20 (71.4 %) patients. conclusion: fob under niv could be considered as a feasible tool for diagnosis and guide for treatment of patients with ards treated via niv in intensive care units. however, fob-correlated life-treathening complications in severe hypoxemia should not be forgotten. furthermore, further controlled studies involving a larger series of homogeneous ards patients undergoing fob under niv are needed to confirm these preliminary findings. noninvasive ventilation (niv) is defined as any form of ventilatory support applied without endotracheal intubation [1] . application of niv is a cornerstone for the treatment of acute respiratory failure of various etiologies [2] . it reduces intubation rate in patients with exacerbations of chronic obstructive pulmonary disease (copd) and acute cardiogenic pulmonary edema [3] and in immunocompromised patients with hypoxemic respiratory failure [4, 5] . using niv is discussed in mildto-moderate acute respiratory distress syndrome (ards) patients (pao 2 /fio 2 > 150) [6] . fiberoptic bronchoscopy (fob) may be required in some patients with acute respiratory failure in intensive care units (icu), mainly as diagnostic tool or to remove abundant secretions [7, 8] . as a matter of fact it may also be applied to determine the cause of diffuse pulmonary infiltrates (infection, diffuse alveolar hemorrhage, organizing pneumonia) [9] . other indications for fob in critically ill patients consist of atelectasis, hemoptysis and suspicion of lung neoplasia. patients in icu for acute respiratory failure often have comorbidities that increase the risk of bronchoscopy related complications. feasibility of bronchoscopy during niv in patients with respiratory failure was shown previously and niv was found to be superior to conventional oxygen supplementation for preventing gasexchange deterioration during fob [10, 11] . in those studies, niv was used to facilitate bronchoscopy and niv was not required prior to bronchoscopy. however, there is limited data on the feasibility and usefulness of fob in patients who are already treated with niv for acute respiratory failure [12] and in particular there is not enough evidence for using niv in patients with ards [6] . therefore, we aimed to evaluate the feasibility and safety of fob in patients with ards ventilated with niv and its contribution in the diagnosis and/or modification of the ongoing therapy. the patients hospitalized in 8-bed icu at ege university medical school department of chest diseases were assessed in terms of ards, niv treatment and fob application. the decision both to initiate niv and to perform fob were made by the pulmonologist. this prospective observational study was approved by the ege university ethical and research project committee (2010-tip-088). all study participants or legal representatives provided written informed consent before the procedures. the study population was obtained from the specified respiratory intensive care unit (january 2010-december 2014). inclusion criteria were: 1. ards diagnosed by berlin criteria or the american-european consensus conference [13, 14] , 2. age ≥ 18 years, 3. treated with niv before the bronchoscopy 4. requiring fob with or without bronchoalveolar lavage (bal) for diagnostic or therapeutic apporach, 5. informed consent. exclusion criteria were: 1. refusal of niv, 2. presence of contraindications for niv such as facial deformity, upper gastrointestinal bleeding, upper airway obstruction, inability to protect the airway, significantly altered mental status, severe haemodynamic instability, respiratory or cardiac arrest and acute coronary syndromes, 3. tracheostomy or intubation before admission, 4. presence of contraindications for bronchoscopy procedure such as insufficient platelet number (<70,000 cells/μl) and coagulation disorders, 5. patients with niv use at home prior to icu admission. demographic characteristics, comorbid diseases, presence of immunosuppression, acute physiology and chronic health evaluation ii (apache ii) score [15] and radiologic and laboratory findings were recorded for each patient. acquired immunodeficiency syndrome, immunosuppressive medication, organ transplantation, high dose chemotherapy during the past 60 days, absolute neutrophil count < 1000/ml were defined as immunosuppression. standard microbiological diagnostic measures before fob and additional serological studies were ordered in immunosuppressed patients as indicated. heart and respiratory rates, blood pressures and arterial blood gases were assessed 15 min before and 1 h after the fob for this study. these measurements and ventilator settings were monitored during fob. all patients were on niv prior and throughout the bronchoscopic sampling in the icu. niv was applied via simple oro-nasal mask (af 531 oro-nasal mask, philips respironics) or full-face mask (performax total face mask, philips respironics) (fig. 1 ) and the ventilator settings were adjusted by the pulmonologist. icu ventilator (servo 900c, siemens) or dedicated niv ventilator (vivo 40, general electric) devices were set with the optimal required fio 2 . pressure support or inspiratory positive airway pressure (ipap), external positive end expiratory pressure (peep) or expiratory positive airway pressure (epap) levels were titrated to achieve an expiratory tidal volume of 8 to 10 ml/kg according to ideal body weight, adjusted to maintain spo 2 > 90 % and respiratory rate below 25/min. throughout the niv treatment and bronchoscopy procedure electrocardiography, intra arterial blood pressure, pulse oximeter and ventilator parameters were monitored continuously. the icu bronchoscopy team was composed of two well-trained pulmonologists (fb, mst) and two nurses. all bronchoscopies were performed while patients were in upright position and in their own beds. 10 % lidocaine spray solution and 2 % lidocaine solution were used for topical anaesthesia of nasopharynx and tracheobronchial tree, respectively. a connector (bronchoscopy elbow, philips respironics) was used between the ventilator tubing and the mask for the insertion of fob (olympus bfu 180f) (fig. 1 ). fiberoptic bronchoscopy was performed via nasal route. short term sedation was administered in some patients according to their respiratory and hemodynamic situations. sedation was started using 2 mg midazolam at the beginning of the procedure. the patients who did not achieve stabilisation received repetitive applications of 1 to 2 mg midazolam. maximum total dose of midazolam was 5 mg. patients were supplied with the necessary fio 2 which provided spo 2 > 90 % during fob procedure (one or more of these procedures were performed in same fob application: bal, bronchoscopic brushings and biopsy, aspiration) under niv. the bronchoscopic samples were sent to microbiology and pathology laboratories. antimicrobial treatment was started empirically while the sampling was performed and, later treatment was adjusted according to microbiological results. primary outcomes were: 1. safety with the recording of any complications [such as fever, arrhythmia, hypoxemia (spo 2 < 90 %), hypotension (systolic and diastolic blood pressure below 90 mmhg and 60 mmhg, respectively), haemorrhage and pneumothorax]. 2. contribution of fob in diagnosis and/or modification of the ongoing treatment. 3. requirement for endotracheal intubation was specifically observed within two hours and eight hours after the fob. criteria of two and eight hour limit for endotracheal intubation were adopted from previous studies [16, 17] . data management and analysis of all data were conducted via spss for windows 16.0 software (spss, version 16, chicago). kolmogorov-smirnov test was used to present the distribution of all recorded variables. arterial blood gases and haemodynamic parameters before and after fob were compared with wilcoxon test. statistical significance level was set at p < 0.05. twenty eight subjects (mean age 63.3 ± 15.9 years, 15 men, 13 women) were included the study. 20 patients (71.4 %) had immunosuppression. patients had hematologic malignancy, solid-organ tumor, renal transplantation, long-term corticosteroid treatment due to interstitial lung disease or connective tissue disease that caused immunosuppression. the most common admission diagnosis to icu was pneumonia ( table 1 ). as shown on the median duration of niv prior to fob was 3 h (range 0-72 h). vasopressor/inotropic agents before the fob application were begun in 4 patients (14.3 %) due to hemodynamic instability. thirteen patients (46.4 %) received sedation for niv and/or fob. maximum duration of the bronchoscopy was 20 min and fob application was performed only once for each patients. arterial blood gas analyses, pao 2 /fio 2 rates and cardiorespiratory parameters before and after fob were shown in table 3 . there was no impairment in these parameters after bronchoscopy. pao 2 /fio 2 rate increased from 132.2 ± 49.8 to 172.9 ± 63.2 after procedure. pressure support, ipap, epap/ peep and fio 2 levels did not change during fob. respiratory and hemodynamic variables were followed up very closely for the required intubation. complications other than endotracheal intubation developed in 5 (17.9 %) patients within 12 h after fob. fever (n = 2), hypoxemia (n = 1) and hypotension (n = 2) occurred as complication of bronchoscopy. in one of these patients, hypotension developed within the first four hours. no other adverse effects were observed such as haemorrhage and pneumothorax. endotracheal intubation was not required within 2 h after the bronchoscopy. intubation was performed only in three patients ( the study demonstrated that bronchoscopy under niv is feasible, safe and an effective diagnostic procedure, therapeutic approach and guide for treatment in ards patients. after the procedure, arterial blood gas values, pao 2 /fio 2 rate, and cardiac parameters did not change and none of the patients needed intubation within two hours after bronchoscopy. fiberoptic bronchoscopy can be performed safely without major complications in this group of patients. diagnostic or therapeutic bronchoscopy is necessary for some icu patients treated for acute respiratory failure, however it can be associated with various complications as well as mortality. because of these risks, fob can be challenging in these patients. bronchoscope covers 10-15 % of the tracheal lumen and may increase respiration efforts and decrease pao 2 by 10-20 mmhg causing respiratory and cardiac complications [18] . additionally, bal sampling may cause worsening of oxygen desaturation [19] . the american thoracic society recommends avoiding fob and bal in patients with hypoxemia (pao 2 < 75 mmhg or oxygen saturation <90 % with supplemental oxygen) [20] . although alternative approaches in these patients with higher-risk are empirical treatments or intubation for fob, the observational study and the randomized controlled trials have shown that niv may be an alternative to endotracheal intubation in these critically ill patients who are not previously ventilated [10, 11, 21] . early etiological diagnosis in critically ill patients is important for appropriate treatment. baumann et al. [12] showed that bal during niv yielded diagnostic information in 68 % of the patients with acute respiratory failure. diagnostic success of fob was 59 % in another study in which oxygen supplementation or niv application was used during the procedure [22] . our immunosuppressed patient ratio was higher than the study population of bauman et al. and cracco et al. (71.4 % vs 53 %, 53 %, respectively). clouzeau et al. [16] found that diagnostic or therapeutic information ratio was 75 % in patients who underwent fob under niv. 83.3 % of their patients were immunocompromise. in our study, diagnostic accuracy of fob in ards patients was 96.4 %. high diagnostic rate in our study can be interpreted with the fact that we performed sampling with fob just as the patients apply to icu. at the same time, fob application allowed the therapeutic approaches such as aspiration. furthermore, agarwal et al. [23] have shown that niv-assisted bronchoscopic lung biopsy is another diagnostic method in hypoxemic patients with diffuse lung infiltrates. azoulay et al. [24] found that deterioration in respiratory status occurred in 44.8 % of patients who had bal with oxygen. but only 18.7 % of their patients underwent bal with niv. chiner et al. [21] showed that there were no significant differences in arterial blood gas levels in patients with acute respiratory failure before fob and 2 h after fob. another study showed a significant improvement in arterial blood gas levels of patients with acute decompensated copd due to community-acquired pneumonia second hour after fob with niv [25] . secretion aspiration might lead to improvement. in our study, there were no significant changes in arterial blood gas analyses and cardiac parameters after fob. other complications such as cardiac arrhythmia, pneumothorax or hemoptysis did not occur in our study population. only three patients (10.7 %) were intubated within 8 h after fob (5 h, 7 h and 8 h, respectively). underlying diseases of these patients were interstitial lung disease and lung involvement due to connective tissue disease. the patients were receiving systemic corticosteroid therapy before admission to hospital and fob was applied to diagnose opportunistic infections. three patients died within 24 h after the procedure. fob should not be considered in these cases, because they had severe underlying diseases and infections when they were admitted. identified mixt infectious agents had a major effect in their fast progression. cytomegalovirus and pneumocystis jiroveci in two patients, acremonium and cytomegalovirus in another patient were shown as opportunistic infectious agents. fiberoptic bronchoscopy usually causes alteration in gas exchange. in hypoxemic intubated patients, pao 2 returns to baseline within 2 h [26] . none of the patients in the current study needed intubation within 2 h after fob. based on this information, fob may not have led to intubation in three patients. baumann et al. [12] found that 40 patients required niv prior to the decision to use fob. four of them ( shown as risk factors for intubation [22] . intubation rate in the current study is acceptable according to presented rates in the literature. intubation rate reached to 54 % in patients with acute respiratory failure who received niv. also, niv failure ratio was 62 % in moderate and 84 % in severe ards [27] . cases in the current study were not intubated due to sudden gas exchanges and hemodynamic deterioration after bronchoscopy. severe underlying diseases and infection situations should be taken into consideration for imv. the authors of this study aware of the discussions about using niv in patients with ards. but a recent study which assessed intubation rate and risk factors of niv failure in patients with non-hypercapnic acute hypoxemic respiratory failure showed significant differences for intubation rate among four groups (non-ards, mild ards, moderate ards, severe ards). however, the mortality rate was not statistically significant and the time to intubation had no effect on patient mortality [27] . in patients with hematologic malignancies and acute respiratory failure, delayed (after niv failure) vs. immediate imv was associated with increased hospital mortality which was not statistically significant (65 % vs. 58 %) [28] . early diagnosis and beginning time of true treatment in patients with immunosuppression may be as important as ards severity. the authors think that fob under niv treatment due to ards may be applied to patients whose pao 2 /fio 2 ratio is close to 100 when their hemodynamic status is stable and procedure is performed in icu where all intubation equipment for emergency intubation exist. this study has some limitations. first, there are no control groups. enrolment of a control group was not possible due to ethical reasons, because treatment with niv requires in patients with acute respiratory failure. in other words, it is believed that intubation is not advisable solely for fob applications. second, the study population in the current study was small. third, the study population was composed of patients with hypoxemic and hypercapnic respiratory failure. fourth, the data about excluded patients was not given and limited number arterial blood gas analyses were assessed after fob. fifth, these results were from a single center. in conclusion, fob under niv may be safely and effectively applied for diagnosis and treatment of patients with ards in icu units that is adequately equipped and staffed for intubation. there are high risks associated with intubation during fob and after procedure. therefore, these patients should be closely followed up for ventilation and for other vital parameters. fob with niv may be considered in patients with ards for diagnosis and treatment, so intubation and its complications may be avoided in this patient group. more studies with large sample sizes are required to make a more thorough assessment of fob application under niv in patients with ards. abbreviations apache ii: acute physiology and chronic health evaluation ii; ards: acute respiratory distress syndrome; bal: bronchoalveolar lavage; copd: chronic obstructive pulmonary disease; epap: expiratory positive airway pressures; fob: fiberoptic bronchoscopy; icu: intensive care unit; ipap: inspiratory positive airway pressure; niv: noninvasive ventilation; peep: positive end expiratory pressure. the dataset of this article are stored in department of chest diseases of ege university medical faculty and can be made available upon request. authors' contributions pke participated in the design of the study, performed the statistical analysis and was the largest contributor to the manuscript. bba was involved in drafting the manuscript and the acquisition of the data. fb was the main designer of this study and revised the manuscript critically for important intellectual content. mst participated in the design of this study. ag was one of the designers of this study and was involved in drafting the manuscript. sn was the other main designer of this study and revised the manuscript critically for important intellectual content. all authors have read and approved the final manuscript. the european society of intensive care medicine, and the société de réanimation de langue française, and approved by ats board of directors non-invasive ventilation in acute respiratory failure noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure outcome in noninvasively and invasively ventilated hematologic patients with acute respiratory failure recent advances in mechanical ventilation in patients with acute respiratory distress syndrome unusual applications of noninvasive ventilation tratado de ventilación mecánica no invasiva. práctica clínica y metodológica. madrid: grupo aula médica acute respiratory failure in patients with severe community-acquired pneumonia. a prospective randomized evaluation of non-invasive ventilation noninvasive positive-pressure ventilation vs. conventional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy continuous positive airway pressure during fiberoptic bronchoscopy in hypoxemic patients. a randomized double-blind study using a new device fiber optic bronchoscopy in patients with acute hypoxemic respiratory failure requiring noninvasive ventilation -a feasibility study acute respiratory distress syndrome: the berlin definition the american-european consensus conference on ards. definitions, mechanisms, relevant outcomes, and clinical trial coordination a severity of disease classification system fiberoptic bronchoscopy under noninvasive ventilation and propofol target-controlled infusion in hypoxemic patients safety and efficacy of bronchoalveolar lavage using a laryngeal mask airway in cases of acute hypoxaemic respiratory failure with diffuse lung infiltrates effects of transoral and transnasal fiberoptic bronchoscopy on oxygenation and cardiac rhythm cardiac arrhythmias. frequency during fiberoptic bronchoscopy and correlation with hypoxemia clinical role of bronchoalveolar lavage in adults with pulmonary disease fiberoptic bronchoscopy during nasal non-invasive ventilation in acute respiratory failure safety of performing fiberoptic bronchoscopy in critically ill hypoxemic patients with acute respiratory failure bronchoscopic lung biopsy using noninvasive ventilatory support: case series and review of literature of niv-assisted bronchoscopy diagnostic bronchoscopy in hematology and oncology patients with acute respiratory failure: prospective multicenter data early fiberoptic bronchoscopy during noninvasive ventilation in patients with decompensated chronic obstructive pulmonary disease due to community-acquired-pneumonia fiberoptic bronchoscopy in ventilated patients. evaluation of cardiopulmonary risk under midazolam sedation non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors italian group for the evaluation of interventions in intensive care medicine). noninvasive versus invasive ventilation for acute respiratory failure in patients with hematologic malignancies: a 5-year multicenter observational survey the authors except sn declare no conflict of interest. sn has conflict of interest: advisory board for philips and breas, speaking fee from philips and resmed, travel grants from weinman. not applicable. this study was approved by the ege university ethical and research project committee (2010-tip-088).• we accept pre-submission inquiries • our selector tool helps you to find the most relevant journal submit your next manuscript to biomed central and we will help you at every step: key: cord-016844-lq2bgu7a authors: teksam, ozlem; bayrakci, benan title: noninvasive mechanical ventilation in patients with high-risk infections and mass casualties in acute respiratory failure: pediatric perspective date: 2013-05-29 journal: noninvasive ventilation in high-risk infections and mass casualty events doi: 10.1007/978-3-7091-1496-4_29 sha: doc_id: 16844 cord_uid: lq2bgu7a respiratory problems are common symptoms in children and common reason for visits to the pediatric emergency department (ped) and admission to the pediatric intensive care unit (picu). although the great majority of cases are benign and self-limited, requiring no intervention, some patients need respiratory support. invasive mechanical ventilation (imv) is a critical intervention in many cases of acute respiratory failure (arf), but there are absolute risks associated with endotracheal intubation (eti). on the other hand, noninvasive ventilation (niv) is an extremely valuable alternative to imv. a major reason for the increasing use of niv has been the desire to avoid the complications of imv. it is generally much safer than imv and has been shown to decrease resource utilization. its use also avoids the complications and side effects associated with eti, including upper airway trauma, laryngeal swelling, postextubation vocal cord dysfunction, nosocomial infections, and ventilator-associated pneumonia. there are a number of advantages of niv including leaving the upper airway intact, preserving the natural defense mechanisms of the upper airways, decreasing the need for sedation, maintaining the ability to talk while undergoing niv, and reducing the length of hospitalization and its associated costs [1–3]. of niv including leaving the upper airway intact, preserving the natural defense mechanisms of the upper airways, decreasing the need for sedation, maintaining the ability to talk while undergoing niv, and reducing the length of hospitalization and its associated costs [ 1 -3 ] . noninvasive ventilation in the pediatric population with arf as a therapeutic tool has become an option in recent years and is being applied increasingly. it can be initiated wherever the patient presents with arf-in the ped, picu, or other areas of the hospital. over the last decade, several studies have suggested successful application of niv in patients with arf. although numerous controlled studies and meta-analyses have shown its effi ciency in different forms of arf (e.g., exacerbation of chronic obstructive pulmonary disease and acute cardiogenic pulmonary edema in adults), the evidence supporting its using in infants and children with arf is still limited, and there are no generally accepted guidelines for its use. however, the most recent physiological and randomized studies indicate that the early application of niv improves the breathing pattern and gas exchange and reduces respiratory muscle effort in children [ 1 -7 ] . today, niv is considered a fi rst-line intervention for various causes of arf and may be considered in the context of pandemics such as h1n1 or severe acute respiratory syndrome (sars). in these circumstances, most of the studies showed that the use of niv decreased the rate of ventilator-associated pneumonia and reduced the duration of oxygen requirement without prolonging the hospital stay [ 4 -8 ] . on the other hand, there is controversy about the possibility that niv increases the spread of viral infections during pandemics. moreover, since the outbreak of sars in 2003, pandemic planners around the world have classifi ed niv as a high risk procedure that should be used cautiously because of possible spread of the infection [ 9 ] . similarly, ontario's provincial infectious diseases advisory committee in canada recommended that niv be avoided for patients with febrile respiratory illness during the 2009 infl uenza pandemic (h1n1) [ 10 ] . additionally, the world health organization's interim guidelines on the prevention and control of acute respiratory diseases associated with health care have included niv among the aerosol-generating procedures in which there is possibly an increased risk of respiratory pathogen transmission [ 11 ] . however, there has been no evidence-based information to support the claim that the use of niv increases the risk of transmitting infectious diseases. the use of niv for children with arf caused by viral infections and experiences using niv in these children are increasing worldwide. in the literature, most of the studies related to using niv in the case of arf have been done during pandemics. also, there is still a large variety of practices and a paucity of published data in pediatrics. nonetheless, after the most important two viral pandemics during the last decade, especially the last one with infl uenza a(h1n1), most of the societies including above-mentioned and the european respiratory society, european society of intensive care medicine, and the american association for respiratory care have recommended that niv not be used to treat arf due to h1n1, particularly in severely ill patients. thus, niv is accepted as a high-risk procedure that should be used cautiously because of possible spread of infection [ 9 -15 ] . during the last decade, we experienced two viral pandemics that ultimately spread worldwide. one was occasioned by severe acute respiratory syndrome (sars), which is an emerging infectious disease that fi rst manifested in humans in china in 2002. in an observational study of the sars outbreak that included adult patients from china, the effectiveness of niv in the treatment of arf was investigated. it was shown that niv was effective in preventing the use of endotracheal intubation in 70 % of patients because of its early initiation in the sars patients. in this study, none of the health workers, including doctors, nurses, and health-care assistants, acquired sars from the patients. as an explanation, niv was applied in a negative-pressure environment with strict personal protection and close monitoring of the health status of all involved staff [ 4 ] . in another study from toronto during sars, the use of niv was discouraged especially after clinicians contracted the disease when a patient was intubated following niv failure [ 9 ] . therefore, some clinicians considered niv contraindicated for arf due to airborne respiratory diseases unless it is used in a negative-pressure isolation room and strict precautions are taken [ 4 , 9 ] . the second viral pandemic was infl uenza a(h1n1) in 2009. the role of niv in children with arf due to infl uenza a(h1n1) was also the subject of controversy, although niv has become an important mechanism for ventilator support for pediatric arf. severe respiratory failure is a well-recognized complication of pandemic h1n1 infl uenza infection. rello et al. [ 16 ] applied niv to a small number of critically ill patients with pandemic h1n1 infection complicated by arf. most of these patients subsequently required imv support. therefore, niv is generally not recommended for patients with the novel infl uenza infection complicated by pneumonia and ards. niv temporarily improves oxygenation and reduces the work of breathing but does not necessarily alter the course of the disease. the need for niv is an indication of severe disease and likelihood of imv. in addition, hemodynamic instability and multi-organ failure are contraindications for applying niv [ 2 , 16 , 17 ] . in a multicenter study from india that included adult patients with infected infl uenza a(h1n1) during the outbreak of infl uenza a(h1n1) in 2009, patients requiring invasive ventilation at admission had a higher mortality rate than those managed with niv and those not requiring ventilation. niv was considered based on guidelines regarding arf that included severe dyspnea at rest [respiration rate (rr) > 35/ min], pao 2 /fio 2 < 200 while breathing oxygen through a mask, and use of accessory muscles of respiration or paradoxical abdominal motion. criteria for a response to niv, or lack of it, were rr improvement, the glasgow coma score (gcs), and blood gases improvement. intubation was considered if there was intolerance to the mask or there was a contraindication to continued use, including nasal bridge necrosis, persistent hypoxemia not responding to appropriate and tolerated levels of positive end-expiratory pressure (peep), or persistent or worsening respiratory acidosis. in all, 32.1 % of patients were managed with niv. however 17 % of all patients failed niv and were intubated and ventilated invasively. patients who could be started on and managed with niv had signifi cantly better survival compared with those who required imv at the onset. the need for invasive ventilation at admission was found to be associated with a higher mortality rate [ 18 ] . in another multicenter observational study, nicolini et al. [ 19 ] showed that niv was effective in preventing endotracheal intubation in 48 % of the patients with arf and pulmonary infi ltrates due to an h1n1 infection. moreover, niv success was found to be associated with a lower incidence of "new" infectious complications and increased icu survival compared to those patients who failed niv. additionally, a high simplifi ed acute physiology score (saps ii) and a low pao 2 /fio 2 are related to high risk of intubation and mortality. therefore, they emphasized that the timing of niv application is crucial in determining its success [ 19 ] . in a multi-center study investigating the outcome of critically ill children with h1n1 in picus from turkey, niv was applied 7.2 % of all patients. two of them survived (3.4 %) and four did not (16.0 %). in the same study, mortality rates were found to be higher in patients with h1n1 infection and conventional mechanical ventilation. however, multi-organ failure and high mortality and organ dysfunction scores were associated with increased mortality. the nonsurvivor group required conventional mechanical ventilation, high-frequency oscillatory ventilation, renal replacement therapies, inotropes, and vasoactive treatment. however, this study is not enough to discuss niv effi ciency because niv was applied in a small number of patients and high mortality rates were found [ 20 ] . torres et al. [ 7 ] described the clinical characteristics and outcome of children admitted to the picu with infl uenza a(h1n1) from argentina during the 2009 pandemic. niv was applied to 13.3 % of all patients (19/142) and the success rate was 63 % with no deaths. twelve of these patients recovered from niv without mechanical ventilation. although there was a high rate of mortality (47 %) in their study, all of the children who received niv survived. age < 24 months, mechanical ventilation, use of inotropes, respiratory co-infections, and a history of asthma were found as predictors of mortality [ 7 ] . the use of niv versus conventional ventilation was addressed in another randomized trial that included a selected small group of hypoxemic patients. according to the results, serious infections secondary to intubation developed more frequently in the conventional ventilation group. the duration of ventilation and the icu stay were shorter in the niv group [ 1 ] . another controversial aspect of niv application is whether niv should be used in patients with acute respiratory distress syndrome (ards) due to pneumonia or other causes. according to a consensus in spain, niv cannot be considered a technique of choice in adult patients with ards, although it may be useful in experienced centers and in cases of arf. within this consensus, the failure rate of niv in patients with arf secondary to ards due to infl uenza virus a(h1n1) infection was 75 %, the mortality rate among the patients in which niv failed was 38 %, and delays in starting intubation were associated to an increase mortality risk. the general recommendation was that early intubation of patients with evidence of niv failure should be instituted for better results [ 21 ] . there is also controversy about the use of niv in children with ards. there are only two studies in children with ards, and they encourage the use of niv. essouri et al. [ 6 ] , in a descriptive study, recommended that niv be used as the fi rst line intervention in children with severe arf due to community-acquired pneumonia or respiratory failure in immunocompromised patients, although the failure rate in their study was 78 % among patients with ards. munoz-bonet et al. [ 5 ] reported an niv success rate of 81 % regarding control of arf due to pneumonia, thereby avoiding tracheal intubation and its complications. two parameters were associated with niv failure, including map > 11.5 cmh 2 o and the fio 2 (0.6). on the other hand, the niv success rate was 50 % in patients with ards. therefore, the authors thought that the diagnosis of ards should not be a contraindication for the use of niv, especially in immunosuppressed patients because it prevents tracheal intubation they also recommended that niv be applied as early as possible. fowler et al. [ 22 ] investigated the risk of contracting sars among physicians and nurses who cared for patients with sars during the epidemic. they showed that the nurses and physicians who directly participated in endotracheal intubation had a dramatically increased risk of developing sars. similarly, nurses caring for patients undergoing niv may have been more likely to develop sars than nurses caring for patients with sars treated with conventional ventilation. the difference, however, was not statistically signifi cant. their study indicated that tracheal suctioning was one of the certain high-risk components of sars nursing care, but it was not generally performed in patients with sars ventilated with niv. therefore, endotracheal suction might be considered not to increase the risk of respiratory droplet dispersion. during the sars outbreak, sars working groups developed guidelines for procedures, including endotracheal intubation, cardiopulmonary resuscitation, and mechanical ventilation. these guidelines specify that the use of personal protection devices is mandatory, the most qualifi ed individual available should perform the endotracheal intubation, and procedures such as prolonged niv and aerosolized bronchodilator or humidifi cation therapies generally should not be initiated where safe alternatives are available. at that time, many clinicians seeing patients during the asian sars outbreak thought that niv was preferred over early endotracheal intubation and mechanical ventilation because of the risk to hcws involved with endotracheal intubation [ 21 -24 ] . infl uenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear. droplets in the respirable range (~5 μm) may play a signifi cant part in transmission, but the role of aerosols has been questioned. there are few studies that have quantifi ed the viral load in droplets or aerosols. a subgroup of patients, often with underlying chronic disorders or risk factors such as immunosuppression, can develop pneumonia/respiratory insuffi ciency with h1n1 swine fl u or other infl uenzal infection and require treatment by oxygen therapy, nebulized medication, and ventilatory support. these therapies are thought to generate droplets or aerosols. based on pandemic experience, gas leakage via exhalation ports may also disperse infectious particles into the environment. during pandemics, hcws and other patients are at risk for contamination because of the virus. in addition, pandemic planners have highlighted the potential need for providing mechanical ventilation in environments that are safe for hcws. they have recommended airborne precautions for hcws who are managing patients with pandemic infl uenza with increased transmissibility and during procedures that may generate small aerosol particles of respiratory secretions. however, it is not known how exhaled air and particles may disperse during niv in clinical settings. there is no reliable marker that can be safely introduced to the patients [ 23 -25 ] . previous studies have not assessed droplet or aerosol generation during respiratory support interventions in clinical practice. hui et al. [ 24 ] assessed the risks of single-circuit niv in spreading infectious particles through the bleeding port and orofacial mask interface using a high-fi delity human patient simulator. they showed that substantial exposure to exhaled air occurred within 0.5 m from patients receiving niv, and higher ventilator pressures result in a wider distribution of exhaled air (fig. 29.1 ) . therefore, they recommended that hcws be aware of the potential risks of viral transmission during niv and take strict contact and droplet precautions, wearing full personal protective equipment. an observational study of infl uenza a and infl uenza b in exhaled breath also showed viral rna in one-third of infected patients, and 99 % of particles had a diameter of <5 μm when sampled during tidal breathing [ 25 ] . generally, niv and chest physiotherapy are accepted as droplet-generating procedures, producing droplets of >10 μm. because of their large mass, most fall on local surfaces within 1 m. therefore, hcws providing niv and chest physiotherapy working within 1 m of an infected patient should have a higher level of respiratory protection. infection control measures designed to limit aerosol spread, such as negative-pressure rooms, may have less relevance. the results of these studies may have infection control implications for other airborne infections, such as sars and tuberculosis, as well as for pandemic infl uenza infection [ 10 , 22 , 25 ] . simonds et al. [ 23 ] showed the characteristics of droplet/aerosol dispersion around delivery systems during niv treatment by measuring droplet size, geographical distribution of droplets over time after the interventions were discontinued, and the impact of modifi cation of the niv circuit in clinical practice. they found that niv using a vented mask produced large droplets (>10 μm) from patients and coryzal subjects compared with baseline values. this increase in large droplets was not seen using the niv circuit modifi cation. preliminary analysis suggests that droplet size falls to within a baseline range within 20-40 min of discontinuing niv [ 23 ] . noninvasive ventilation is an effective treatment modality for patients with arf due to pneumonia or acute cardiogenic pulmonary edema and for immunocompromised patients, both adults and children, with pneumonia and postextubation respiratory failure. it is also known that niv can markedly reduce the need for endotracheal intubation and the rate of complications. it shortens the hospital length of stay and improves survival. niv can be used to decrease a patient's dyspnea and work of breathing and improve gas exchange. therefore, patients with hypercapnic forms of arf are most likely to benefi t from niv. however, clinicians should not forget that niv is a complementary technique and cannot replace endotracheal intubation under all conditions. the success of niv relies on several factors, including the type and severity of arf, very low arterial blood ph, marked alteration in mental status, underlying disease, location of treatment, and the experience of the team. the time factor is also important. to prevent further deterioration, early niv must become an important part of the fi rst-line treatment of arf. in addition, the success of invasive ventilation is dependent on various clinical aspects and the organisation of care-but also on a number of technical issues. these technical points are the ventilator interface, type of humidifi er, and ventilator used and its capabilities for triggering and pressurization. the general care of the niv patient is different from that for a patient undergoing invasive ventilation and potentially has a great infl uence on the success of the technique. noninvasive ventilation has become an important mechanism for ventilator support in children with arf. however, if the arf is due to the infl uenza a(h1n1) virus, niv has become controversial. future prospective randomized controlled studies should help determine, with more methodology, the physiological effects of niv and the most appropriate group of patients potentially able to benefi t from this promising technique during a pandemic. the studies have shown that in critically ill children with confi rmed or probable h1n1 viral infection and severe ards the use of niv can result in signifi cant improvement in oxygenation. it may improve the mortality rate for this very high-risk population. we believe that niv is a promising alternate to standard therapies in the treatment of arf in pediatric patients. in our experience, patients placed on niv should be monitored closely and the mode of ventilation reviewed if there is a lack of response within a few hours after starting therapy. treatment of early ards associated with respiratory viral infections-e.g., infl uenza a(h1n1)-using niv could also be tried after identifying patients who require endotracheal intubation in negative-pressure rooms under strict precautions. because of the high demand for critical care beds during a pandemic, niv may have a role in reducing the estimated icu load as it can be applied anywhere in the hospital. in conclusion, the effi ciency of niv in children with arf depends on the degree of hypoxia, the underlying disease, and illness severity scores. niv can even be used in immunosuppressed patients, although cautiously, because intubation is a strong predictor of mortality and nosocomial infections. the success rate of niv depends on early application, the experience of the institution, and the team's familiarity with the technique. • noninvasive ventilation can be regarded as an option of choice in children with arf and ards due to respiratory viral infections in centers with a large experience and under conditions of strict personal protection. • initiating procedures that may be associated with increased dispersal of respiratory droplets-as in patients with sars or infl uenza a(h1n1)must be conducted with caution. there may be risks that require many forms of support. decisions must be made on an individual patient basis with due attention to the hazards for both patients and hcws. • the outcome of niv in patients with arf due to acute lung injury, ards, or pneumonia depends on the degree of hypoxia, the presence of co-morbidities and complications, and the illness severity score. in these circumstances, niv should be cautiously considered early and not delay needed intubation. a comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure causes of failure of noninvasive mechanical ventilation what are the current indications for noninvasive ventilation effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome predictive factors for the outcome of noninvasive ventilation in pediatric acute respiratory failure noninvasive positive pressure ventilation: fi ve years of experience in a pediatric intensive care unit high mortality in patients with infl uenza a ph1n1 2009 admitted to a pediatric intensive care unit: a predictive model of mortality noninvasive ventilation as primary ventilatory support for infants with severe bronchiolitis identifi cation of severe acute respiratory syndrome in canada preventing febrile respiratory illnesses. ottawa: ontario ministry of health and long term care infection and control of epidemic-and pandemic-prone acute respiratory diseases in health care. who interim guidelines. world health organization noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome on the role of noninvasive (niv) to treat patients during the h1n1 infl uenza pandemic clinical characteristics and outcomes of patients with 2009 infl uenza a(h1n1) virus infection with respiratory failure requiring mechanical ventilation the consequences of withholding noninvasive ventilation during an epidemic (letter) h1n1 semicyuc working group. intensive care adult patients with severe respiratory failure caused by infl uenza a (h1n1) in spain clinical management of pandemic 2009 infl uenza a (h1n1) clinical profi le and predictors of mortality of severe pandemic (h1n1) 2009 virus ınfection needing ıntensive care: a multi-centre prospective study from south india effectiveness and predictors of success of noninvasive ventilation during h1n1 pandemics: a multicenter study critically ill children with pandemic infl uenza (h1n1) in pediatric intensive care units in turkey recommendations of the infectious diseases work group (gtei) of the spanish society of intensive and critical care medicine and coronary units (semicyuc) and the infections in critically ill patients study group (geipc) of the spanish society of infectious diseases and clinical microbiology (seimc) for the diagnosis and treatment of infl uenza a/h1n1 in seriously ill adults admitted to the intensive care unit transmission of severe acute respiratory syndrome during intubation and mechanical ventilation evaluation of droplet dispersion during noninvasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic infl uenza and other airborne infections noninvasive positive-pressure ventilation: an experimental model to assess air and particle dispersion infl uenza virus in human exhaled breath: an observational study key: cord-313639-qpt47sx2 authors: zheng, yi; sun, li-jun; xu, mi; pan, jian; zhang, yun-tao; fang, xue-ling; fang, qiang; cai, hong-liu title: clinical characteristics of 34 covid-19 patients admitted to intensive care unit in hangzhou, china date: 2020-05-20 journal: j zhejiang univ sci b doi: 10.1631/jzus.b2000174 sha: doc_id: 313639 cord_uid: qpt47sx2 objective: this study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (icu) for complications from coronavirus disease 2019 (covid-19) at the first affiliated hospital, school of medicine, zhejiang university, hangzhou, china from jan. 22 to mar. 5, 2020. methods: a total of 34 patients were divided into two groups, including those who required noninvasive ventilation (niv) and invasive mechanical ventilation (imv) with additional extracorporeal membrane oxygenation (ecmo) in 11 patients. clinical features of covid-19 patients were described and the parameters of clinical characteristics between the two groups were compared. results: the rates of the acute cardiac and kidney complications were higher in imv cases than those in niv cases. most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the imv group. in both groups, t lymphocyte counts were below typical lower limit norms compared to b lymphocytes. on admission, both groups had higher than expected amounts of plasma interleukin-6 (il-6), which over time declined more in niv patients. the prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (bun), d-dimer, lactate dehydrogenase (ldh), and il-6 were higher in imv cases compared with niv cases during hospitalization conclusions: data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, bun, d-dimer, ldh and il-6, and prothrombin time in these icu patients were significantly different between imv and niv cases. in december 2019, a series of patients became stricken with an acute respiratory illness of unknown cause, which has emerged in wuhan, hubei province, china. researchers now know these patients had coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) which has been classified in the β-coronavirus 2b lineage. within several months, this disease rapidly and widely spread in china and many other countries, causing an outbreak of covid-19 worldwide. by the end of april 2020, the cumulative number of confirmed cases of covid-19 infections in china is more than 80 000 and includes more than 4000 deaths, according to the notification from the national health commission of the people's republic of china (nhc, 2020b) . covid-19 was the third lethal illness caused by a coronavirus, surpassed only by severe acute respiratory syndrome (sars) (who, 2020) and middle east respiratory syndrome (mers) (who, 2019) . about one third of covid-19 inpatients were admitted to intensive care units (icus) in wuhan, china (huang et al., 2020) and doctors are recognizing that a critical ingredient in managing the impacts of the disease is effective treatment of severe and critical patients. recent data (nhc, 2020b) showed that covid-19 fatality rates in hubei province and outside of the province were significantly different, prompting researchers to seek more information about the characteristics and treatments of covid-19 patients in icus. deeper analyses of related data may help in developing more effective treatment protocols for future severe patients. here we describe clinical and laboratory characteristics, treatments, and outcomes of confirmed covid-19 patients who were admitted to the icu of a tertiary teaching hospital in hangzhou (zhejiang province, china), about 775 km from the outbreak city of wuhan. the department of critical care medicine in this hospital is a key clinical center at the national level and regional critical diagnosis and treatment center in zhejiang province. during the dates studied, nine severe covid-19 patients were transferred from surrounding cities to the regional hospital and represent the surrounding population at a regional level. for this retrospective study, we analyzed data from patients admitted between jan. 22 and mar. 5, 2020, who had been diagnosed (according to the guidance of nhc (2020a)) with sars-cov-2 pneumonia in the icu in the first affiliated hospital, school of medicine, zhejiang university, hangzhou, china. this icu and hospital had been designated for covid-19 treatment and written informed consent was obtained from all participants in the study. to be included in this analysis, patients' data had to meet one of the specific conditions for admission to icu including dyspnea and respiratory rate of ≥30 times/min, oxygen saturation of ≤93% at rest without oxygen inhalation, pao 2 /fio 2 (p/f) of ≤300 mmhg (1 mmhg=0.133 kpa), and other organ dysfunction such as shock. two researchers independently reviewed patients' medical records during the period of study for epidemiological, demographic, clinical, laboratory, management, and outcome information. disease onset was defined as the day that any related symptom was noticed by patients or family group members, as ascertained through researcher communications. diagnoses were identified according to standard international definitions including: (1) acute respiratory distress syndrome (ards; berlin definition) (ranieri et al., 2012) ; (2) acute kidney injury (aki; kidney disease: improving global outcomes (kdigo) clinical practice guidelines) (khwaja, 2012) ; (3) acute liver injury defined as an increase in alanine aminotransferase (alt) over two times the upper limit of the normal range (uln) or an increase in conjugated bilirubin or a combined increase in aspartate aminotransferase (ast), alkaline phosphatase and total bilirubin provided that one of them was above two times uln (ferrer et al., 2016) ; (4) cardiac injury following the definition described by huang et al. (2020) . noninvasive ventilation (niv) included nasal oxygen therapy, mask oxygen inhalation, and highflow nasal cannula (hfnc). we recorded the duration of disease onset to first positive nucleic acid testing of respiratory tract specimen, icu admission, ards, hfnc, invasive positive pressure ventilation (ippv), and extracorporeal membrane oxygenation (ecmo). using the hospital laboratory, we tested patient blood including complete blood count, serum biochemistry, coagulation profiles, lactate dehydrogenase (ldh), and c-reactive protein. plasma cytokines from all patients (interleukin-2 (il-2), il-4, il-6, il-10, tumor necrosis factor-α (tnf-α), interferon-γ (ifn-γ)) were detected by enzyme-linked immunosorbent assay (elisa) method according to the manufacturer's instructions (elabscience biotechnology co., ltd., wuhan, china). t, natural killer (nk), and b lymphocyte cell counts were tested by flow cytometry. respiratory specimens of all patients including sputum, pharyngeal swabs, bronchoalveolar lavage fluid, and bronchial aspirates were tested for sars-cov-2, using real-time reverse transcription polymerase chain reaction (rt-pcr) assays (huang et al., 2020) . only one patient did not receive antiviral or systematic corticosteroid treatment. thirty (88.2%) were given empirical antibiotic treatment, and 27 (79.4%) were given γ-globulin treatment. indications for hfnc included p/f of <200 mmhg, resting respiratory rate of more than >20 per minute, and the patient presenting as conscious and cooperative. the timing of invasive ventilation included p/f of <150 mmhg, a resting respiratory rate of more than 30 per minute, and patients presenting as uncooperative, and/or onset of serious complications such as shock. indications for ecmo (brodie and bacchetta, 2011) included severe hypoxemia (e.g., p/f of <80 mmhg, despite the application of high levels of positive end expiration pressure (typically 15-20 cmh 2 o (1 cmh 2 o= 0.098 kpa)) for at least 6 h in patients with potentially reversible respiratory failure, uncompensated hypercapnia with acidemia (ph<7.15) or excessively high end-inspiratory plateau pressure (>35-45 cmh 2 o, according to the patient's body size) despite the best accepted standard of care for management with a ventilator. we compared clinical and laboratory data from the two groups. continuous variables were described with medians in interquartile ranges (iqrs) and compared with the mann-whitney u test. two sets of data at different time points were compared using a twoway repeated measures analysis of variance (anova). categorical variables were described using frequency rates and percentages and compared by χ² test or fisher's exact test. a two-sided α of less than 0.05 was considered statistically significant. all analyses were performed using spss software (version 22.0). the patients in our cohort were divided into cases only receiving niv and cases requiring invasive mechanical ventilation (imv), because the way of respiratory support was independently associated with the process and outcome (lindenauer et al., 2014; gacouin et al., 2015) . none of the 34 patients included in this study was a resident of wuhan city and none had direct exposure to the huanan seafood market. nine of the patients had been exposed to individuals with con-firmed sars-cov-2 infection or clustering onset and 17 had traveled within the epidemic area or had close contact with one or more people from the epidemic area. eight patients had no history of any of the above. other characteristics of study patients include ( fig. 1) : (1) median duration from symptom onset to the first positive nucleic acid test was 4 (1-7) d; (2) median duration from symptom onset to icu admission was 10.0 (7.0-11.3) d; (3) median duration from symptom onset to hfnc was 10 (7-11) d in 27 patients; (4) median duration from onset to imv was 11 (8-12) d in 15 patients; (5) median duration from symptom onset to ecmo was 23 (18-29) d in 11 patients; (6) median age was 66 (58-76) years and 23 (67.6%) were men; (7) 24 (70.6%) patients had chronic diseases including hypertension (64.7%), diabetes (23.5%), cardiovascular disease (11.8%), chronic obstructive pulmonary disease (5.9%), chronic liver disease (11.8%), and chronic kidney disease (5.9%). the most common symptoms at onset of illness (table 1) were fever (58.8%), dry cough (20.6%), and expectoration (29.4%). relatively less common initial symptoms were myalgia (14.7%), fatigue (5.9%), diarrhea (5.9%), and headache (5.9%). the proportion of different comorbidities and the distribution of first symptoms did not differ obviously. the blood cell counts on admission showed that nearly half of the patients had leukocytosis (white blood cell count more than 10×10 9 l −1 , 15 (44.1%) cases) while the incidence of leucopenia (white blood cell count less than 4×10 9 l −1 , 2 (5.9%) cases) was very low. lymphopenia (lymphocyte count less than 0.8×10 9 l −1 , 22 (64.7%) patients) was present in more than half of the patients on admission. platelet count in the niv group was higher than that in the imv group, which were in normal range in most patients of both groups. as shown in table 2 , no significant differences were found between the niv and imv groups in terms of other biochemical indexes, inflammation or immune indicators, or coagulation indices on admission to hospital. eighteen patients (52.9%) received hfnc without escalation of respiratory support. fifteen (44.1%) received imv and 11 (32.4%) patients required ecmo. five (14.7%) patients required continuous renal replacement therapy (crrt). common complications among the 34 icu patients included ards (33 (97.1%)), acute liver injury (14 (41.2%)), acute cardiac injury (13 (38.2%)), and aki (7 (20.6%)). table 3 shows that the complication rates (including acute cardiac injury and aki) were significantly higher and discharge rate was notably lower in imv than in niv patients. during the progression of the disease in this cohort of covid-19 patients, we observed dynamic changes of the main laboratory indicators including changes in blood cell counts, biochemical parameters, coagulation profiles, and inflammatory cytokines every other day from day 1 to day 9 or discharged. white blood cell counts and neutrophil counts were at high levels during hospitalization, but for niv patients were declining at the time of discharge. during hospitalization, most patients had marked lymphopenia, with imv patients developing more severe flow cytometry showed that median t lymphocyte counts were less than one third of the lower normal limit, compared to b lymphocytes in inpatients. t lymphocyte counts stayed low during hospitalization; however, the counts gradually rose to normal level until discharge in nearly half of niv patients. nk cell counts in more than 75% of patients were below the lower normal limit, and the counts declined progressively in imv cases rather than in niv cases during hospitalization. platelet counts and hemoglobin levels were higher in niv cases than in imv cases, and hemoglobin levels dropped progressively in imv cases during hospitalization. c-reactive protein levels in both groups showed gradual downward trend during hospitalization. alt and d-dimer levels showed upward trends in both groups during hospitalization, while, for total bilirubin and blood urea nitrogen (bun), the upward trends only occurred in imv cases. the progressive decreases in ldh, il-6, and il-10 levels occurred in niv cases rather than in imv cases during hospitalization. the prothrombin time was increased, and bun, d-dimer, ldh, and il-6 levels were higher in imv cases compared with niv cases during hospitalization (figs. 2 and 3) . we reported 34 icu patients with laboratoryconfirmed sars-cov-2 infection, characterized by severe or critical coronavirus pneumonia. of the 34 the dotted lines show the lower normal limits in lymphocyte, t lymphocyte, b lymphocyte, natural killer cell, and haemoglobin, and show the upper normal limit in crp. data are expressed as median (iqr). imv: invasive mechanical ventilation; niv: noninvasive ventilation; wbc: white blood cell; plt: platelet; crp: c-reactive protein; iqr: interquartile range. * p<0.05, vs. day 1 within group patients, 19 patients (55.9%) received noninvasive respiratory support (including nasal oxygen therapy in one case and hfnc in 18 patients) and 15 (44.1%) required imv. by mar. 5, 2020, the rates of complications (e.g., acute liver, kidney, or cardiac injury) and discharge rates were significantly different between these two groups (a notable and positive outcome is that the oldest patient, a 94 years old man, was successfully treated and discharged). more than 100 covid-19 patients were admitted to the first affiliated hospital during our study period. patients housed in the general isolation ward had mild to moderate symptoms, and as of mar. 5, 2020, most icu patients who did not require imv have recovered and been discharged. however, by the end of mar. 5, 2020, the majority of icu patients requiring imv are still receiving respiratory support including 11 patients who continue to require ecmo treatment. the high proportion of patients needing support in an icu strongly suggests that a critical component to effectively fight covid-19 and to protect the population will be to improve the management and treatment of severe and critical patients in hospital icus. this focus on effective hospital treatment for the critically ill is particularly important now because despite some progresses being made, to date no antiviral treatment has been proven to be effective for coronavirus infection. in this study, the most common complication in patients was ards (33 (97.1%) of 34 patients), underscoring the critical role of respiratory support in recovery. in this cohort, 33 infected patients received single or combined antiviral drugs including lopinavir/ ritonavir, baloxavir, favipiravir, darunavir, arbidol, and interferon-α inhalation. corticosteroid and γ-globulin were administrated to about 80% of patients, but the efficacy of this treatment needs to be further confirmed. most patients in our cohort had neutrophilia, which is consistent with the results of sars-covinfected patients as described by wong et al. (2003) . as mentioned in previous studies, for critically ill patients with sars-cov (gu et al., 2005) , sars-cov-2 (yang et al., 2020) , and mers (chu et al., 2016; liu et al., 2017) infection, lymphocytopenia is a prominent feature, indicating that targeted invasion by viral particles causes lymphocyte destruction. at admission to the hospital, 60% of the patients in our study already had lymphocytopenia and other patients in the study developed the condition as the disease progressed. in the imv group, those with more severe illness, lymphocyte levels dropped progressively, and more severe lymphopenia occurred compared to the niv group, suggesting that the severity of lymphocytopenia reflects the severity of sars-cov-2 infection. research of sars-cov suggests that patients with more severe clinical illness and those who died had significantly more profound lymphopenia (he et al., 2005) . in our cohort, the lymphocyte counts in patients gradually rose as they recovered and were normal at time of discharge in the niv group. these results differ from those of patients with sars-cov, in which lymphopenia was prolonged and lymphocyte levels did not return toward normal until patients were ill for five weeks (he et al., 2005) . our findings also differ from those of patients with h1n1 influenza a infection whose lymphocyte levels did not return to normal until 2-3 weeks after the disease onset (cheng et al., 2019) . further analysis in our cohort showed that t lymphocytopenia was more pronounced than b lymphocytopenia, which was similar to previous study in sars patients (cui et al., 2003) . the mechanism behind these dynamics is not clear and calls for further study and confirmation in cell and animal experiments. we noted that sars-cov-2 infection caused increase in plasma il-6 level, which was consistently at a high level in imv cases in our cohort. early studies also have shown increased concentrations of proinflammatory cytokines (e.g., il-6, tnf-α, and ifn-γ) in sars (wong et al., 2004) and mers-cov (mahallawi et al., 2018) cases. increased levels of anti-inflammatory cytokine, il-10, in plasma were found in sars-cov-2-infected patients with imv, which differed from sars-cov infection (wong et al., 2003) but was supported by huang et al. (2020) in patients with the same disease. bun is a key element reflecting the intricate interrelation between nutritional status, protein metabolism, and renal situation of the patient (arihan et al., 2018) . bun was significantly elevated in imv patients compared with niv cases, which may be caused by high catabolism. the characteristics of inflammation and metabolism suggested that we have to be on the alert of the existence of persistent inflammation-immunosuppression and catabolism syndrome (pics) in covid-19 patients with prolonged mechanical ventilation. pics, often leading to secondary infections and viral reactivation in the critically ill, has been associated with increased morbidity and mortality (limaye et al., 2008; kalil and florescu, 2009; libert et al., 2015) . the baseline characteristics (including age, sex, and comorbidities) and laboratory indexes of patients in our cohort showed no statistical difference. however, the cases developed into different conditions needing different oxygen therapies and were complicated by injury to different organs impacting the probabilities and specifics of disease progression. whether or not there are correlations or causal relationships among viral loads, lymphocytopenia, imv, and organ injury remains to be verified by future research. this study has several limitations. first, we had limited samples from our cohort to analyze and in places outside hubei province, and the total number of cases and the number of critical patients were relatively small, also limiting available samples to study. a previous report enrolled 52 critically ill patients with sars-cov-2 infection from wuhan jinyintan hospital (yang et al., 2020) . second, at the time of this writing, 13 imv patients had not been discharged, so we cannot use survival or death as a clinical end point. the case mortality rate and other outcome indicators need to be reported later. in this single-center case series of 34 icu patients with sars-cov-2 infection in hangzhou, china, 97.1% (33 cases) of patients had complications caused by ards, 44.1% (15) received imv, 55.9% (19) only needed noninvasive respiratory support. compared with cases in the niv group, patients receiving imv more readily developed complications from organ injury, had higher inflammatory markers, and developed more severe lymphopenia. hong-liu cai and yi zheng conceived and designed the study, drafted the paper, and took responsibility for the integrity of the data and the accuracy of the data analysis. li-jun sun, mi xu, and jian pan collected the data. yi zheng, xue-ling fang, and yun-tao zhang did the analysis. qiang fang revised the manuscript. all authors agree to be accountable for all aspects of the work and have read and approved the manuscript. yi zheng, li-jun sun, mi xu, jian pan, yun-tao zhang, xue-ling fang, qiang fang, and hong-liu cai declare that they have no conflict of interest. this study was approved by the national health commission of china and ethics commission of the first affiliated hospital, school of medicine, zhejiang university, hangzhou, china (no. iit20200077a). all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the helsinki declaration of 1975, as revised in 2008 (5). informed consent was obtained from all patients for being included in the study. blood urea nitrogen (bun) is independently associated with mortality in critically ill patients admitted to icu extracorporeal membrane oxygenation for ards in adults dynamic changes of lymphocyte counts in adult patients with severe pandemic h1n1 influenza a middle east respiratory syndrome coronavirus efficiently infects human primary t lymphocytes and activates the extrinsic and intrinsic apoptosis pathways expression of lymphocytes and lymphocyte subsets in patients with severe acute respiratory syndrome systematic review and meta-analysis: macrolides-and amoxicillin/clavulanateinduced acute liver injury trends in prevalence and prognosis in subjects with acute chronic respiratory failure treated with noninvasive and/or invasive ventilation multiple organ infection and the pathogenesis of sars effects of severe acute respiratory syndrome (sars) coronavirus infection on peripheral blood lymphocytes and their subsets clinical features of patients infected with 2019 novel coronavirus in wuhan prevalence and mortality associated with cytomegalovirus infection in nonimmunosuppressed patients in the intensive care unit kdigo clinical practice guidelines for acute kidney injury epstein-barr virus reactivation in critically ill immunocompetent patients cytomegalovirus reactivation in critically ill immunocompetent patients outcomes associated with invasive and noninvasive ventilation among patients hospitalized with exacerbations of chronic obstructive pulmonary disease t-cell immunity of sars-cov: implications for vaccine development against mers-cov mers-cov infection in humans is associated with a pro-inflammatory th1 and th17 cytokine profile nhc (national health commission of the people's republic of china), 2020a. diagnosis and treatment of covid-19 nhc, 2020b. notification of 2020-ncov infection acute respiratory distress syndrome: the berlin definition middle east respiratory syndrome coronavirus summary of probable sars cases with onset of illness from 1 plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study key: cord-034578-i9rdubix authors: vaschetto, rosanna; barone-adesi, francesco; racca, fabrizio; pissaia, claudio; maestrone, carlo; colombo, davide; olivieri, carlo; de vita, nello; santangelo, erminio; scotti, lorenza; castello, luigi; cena, tiziana; taverna, martina; grillenzoni, luca; moschella, maria adele; airoldi, gianluca; borrè, silvio; mojoli, francesco; della corte, francesco; navalesi, paolo; cammarota, gianmaria; baggiani, marta; baino, sara; balbo, piero; bazzano, simona; bonato, valeria; carbonati, sara; crimaldi, federico; daffara, veronica; de col, luca; maestrone, matteo; malerba, mario; moroni, federica; perucca, raffaella; pirisi, mario; rondi, valentina; rosalba, daniela; vanni, letizia; vigone, francesca title: outcomes of covid-19 patients treated with continuous positive airway pressure outside icu date: 2020-10-30 journal: erj open res doi: 10.1183/23120541.00541-2020 sha: doc_id: 34578 cord_uid: i9rdubix aim: we aim at characterising a large population of coronavirus 19 (covid-19) patients with moderate-to-severe hypoxemic acute respiratory failure (arf) receiving cpap outside intensive care unit (icu), and ascertaining whether the duration of cpap application increased the risk of mortality for patients requiring intubation. methods: in this retrospective, multicentre cohort study, we included covid-19 adult patients, treated with cpap outside icu for hypoxemic arf from march 1(st) to april 15(th), 2020. we collected demographic and clinical data, including cpap therapeutic goal, hospital length of stay (los), and 60-day in-hospital mortality. results: the study includes 537 patients with a median age of 69 (iqr, 60–76) years. males were 391 (73%). according to predefined cpap therapeutic goal, 397 (74%) patients were included in full treatment subgroup, and 140 (26%) in the do-not intubate (dni) subgroup. median cpap duration was 4 (iqr, 1–8) days, while hospital los 16 (iqr, 9–27) days. sixty-day in-hospital mortality was overall 34% (95%ci, 0.304–0.384), and 21% (95%ci, 0.169–0.249) and 73% (95%ci, 0.648–0.787) for full treatment and dni subgroups, respectively. in the full treatment subgroup, in-hospital mortality was 42% (95%ci, 0.345–0.488) for 180 (45%) cpap failures requiring intubation, while 2% (95%ci, 0.008–0.035) for the remaining 217 (55%) patients who succeeded. delaying intubation was associated with increased mortality [hr, 1.093 (95%ci, 1.010–1.184)]. conclusions: we described a large population of covid-19 patients treated with cpap outside icu. intubation delay represents a risk factor for mortality. further investigation is needed for early identification of cpap failures. noninvasive ventilation (niv) administered as bi-level positive airway pressure (bipap) or continuous positive airway pressure (cpap) is commonly used in various critical care settings across a variety of aetiologies of acute respiratory failure (arf). for hypercapnic arf, mainly consequent to chronic obstructive pulmonary disease exacerbation, bipap can be used at an early stage to prevent intubation, at a later stage as alternative to first-line endotracheal intubation, or as a mean to facilitate weaning [1] . for hypoxemic arf, recommendations strongly support the use of both bipap and cpap in patients with episodes of cardiogenic pulmonary edema [2, 1] , while fewer data suggest their use in immunosuppressed [3, 1] and in post-operative [4, 1] patients. in patients with de novo hypoxemic arf evidences and recommendations on the use of niv are still to be determined [1] . moreover, the application of niv in patients with acute respiratory distress syndrome (ards) complicating viral pneumonia is controversial [5] . during coronavirus disease 2019 pandemic, piedmont together with lombardy, emilia-romagna and veneto was one of the most affected italian regions. due to the exceptional demand on intensive care unit (icu) resources, hospitals increased the number of icu beds and converted many general wards in respiratory intermediate care units (ricu) to treat patients with severe pneumonia and ards-needing respiratory support and monitoring. indeed, niv in patients with different therapeutic indications i.e., full-treatment and do-not-intubate [6] has been shown to be successfully applicable also outside the icu [7, 8] , when appropriate monitored setting and trained personnel are employed. data on niv during covid-19 pandemic, so far, consider predominantly patients admitted to the icu [9, 10, 11, 12, 13] . the rate of patients receiving niv at icu admission ranges from 11%, as reported by an italian multicentre investigation [10] , to 56% according to a chinese single centre study [11] . exposure to noninvasive forms of respiratory support might have been even more diffuse outside icu, though only data from two monocentre studies are presently available, accounting overall for 40 patients, 38 treated with cpap [14] and two with niv or high flow oxygen therapy [15] . we designed this retrospective multicentre study to describe the clinical characteristics of patients with laboratory-confirmed covid-19 treated with cpap outside icu, to assess 60-day in-hospital mortality, and hospital length of stay (los), and to ascertain whether the duration cpap application prior to cpap failure affects outcome in patients requiring endotracheal intubation. this is a multicentre, retrospective observational study performed in six hospitals from the area of eastern piedmont in northern italy. all the participating centres obtained ethic committee approval. more details on study design and ethics approval are provided in the supplementary material. all patients admitted to one of the participating hospitals from march 1 st to april 15 th 2020 with hypoxemic arf secondary to confirmed sars-cov-2. inclusion criteria were: 1) age ≥18 years, 2) respiratory distress and partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 200 mmhg during venturi mask oxygen therapy, 3) cpap initiation outside icu. patients who received post-extubation cpap were excluded. patients were classified according to predefined cpap therapeutic goal applied by the medical team, in two subgroups [6] : 1) full treatment, i.e. patients scheduled to receive intubation in the case of cpap failure; and 2) do-not-intubate (dni), when cpap was ceiling of treatment. in case patient changed the therapeutic goal during hospital stay, the last cpap goal has been considered. the therapeutic goal of cpap was collegially discussed within the multidisciplinary teams, with the patients and with the families, taking into account comorbidities [16] , quality of life and patient wishes. possible discrepancies between patients and relatives were solved through additional discussions between patient, relatives, and the medical team. demographic characteristics, body mass index (bmi), blood sample exams performed at hospital entrance (white blood cell count, lymphocytes count, creatinine, alanine transaminase, aspartate transaminase, lactate dehydrogenase, c-reactive protein, d-dimer, ferritin), arterial blood gas (abg) values obtained prior to cpap initiation and 2 to 24 hours after; and coexisting comorbidities were also recorded. charlson comorbidity index (cci) [17] was also computed on the first day of hospital admission. this index contemplates 17 categories of comorbidity recorded via anamnesis. age is not included as comorbidity in the cci version adopted. finally, we collected data about the clinical outcomes such as duration of cpap use, hospital length of stay (los), intubation and hospital mortality. for patients still in the hospital on may 15 th (n=32), the outcomes have been censored on that day. details on cpap setting, schedule, ricu organization and criteria for intubation are described in the supplementary material. descriptive statistics are used to summarize the main demographic characteristics and the results of laboratory findings of all patients included in the study. categorical variables are reported as absolute frequencies and percentages, while numerical variables as median and interquartile range (iqr). the frequency and percentage of missing values for all variables is also reported. mann whitney u test is used to assess the difference between two independent samples, while wilcoxon signed-rank test for repeated measurements. chi-square statistic is used for testing relationships of categorical variables. curves of cumulative incidence of in-hospital mortality are drawn to describe mortality along 60 days, either overall and stratified for treatment goal, and in the full treatment subgroup separately for patients succeeding cpap or receiving intubation. in order to avoid immortal time bias, in the survival analysis of patients receiving intubation, observation period started at the day of intubation. in the other analyses, observation period started at the day of cpap initiation. since discharge must be considered an informative censoring [18], cumulative incidence was calculated using methods accounting for competing risk. to evaluate the cumulative incidence of in-hospital mortality for patients not undergoing intubation, all full treatment subjects are considered, and intubation is treated as a competing event allowing to account for the contribution of the time spent by intubated patients on cpap. the gray's test is used to assess the difference between cumulative incidence functions. fine and gray multivariate competing risk model is adopted to calculate the sub-distribution hazard ratios (shr) and the corresponding 95% confidence intervals (95%ci) for the association between cpap duration and in-hospital mortality risk in intubated patients, considering discharge as competing event. in the main analyses, missing data are managed by listwise deletion. we also carried out a secondary analysis using multiple imputation to evaluate the impact of missing values on the association estimates. missing imputation is performed using the expectation-maximization algorithm (500 imputations) and considering the "missing at random" mechanism. more details about the model are provided in the supplementary material. all hypothesis tests are two-tailed and a significance level of 0.05 is considered. all statistical analysis was performed using stata (stata statistical software: release 15. college station, tx, usa: statacorp llc), sas (version 9.4; sas institute cary, nc, usa) and r (version 3.5.1). from march 1 st to april 15 th , a total of 2845 patients with confirmed covid-19 were admitted to the six hospitals of the eastern piedmont ( figure 1s ). of these, 326 (11%) patients were treated in icu, 31 (1%) and 295 (10%) with noninvasive and invasive mechanical ventilation, respectively. cpap was applied to 537 (22%) patients in ricu. 1 . median white blood cell count was 6.9 (iqr, 5.1-9.5) x 10 3 /µl, with lymphopenia, i.e., 0.8 (0.6-1.1) x 10 3 /µl. median values of creatinine, aspartate-aminotransferase, alanine-aminotransferase were in the normal range, while c-reactive protein, ferritin, lactate dehydrogenase and d-dimer were all above the normal range. cci median value was 1 (iqr, 0-2), chronic arterial hypertension was present in 278 (52%) patients, diabetes in 138 (26%) patients, and ischaemic heart disease in 66 (12%) patients. the most common interface was the helmet, in 399 (74%) patients, while face masks were used in 123 patients (23%); 15 patients (3%) alternated both interfaces. median cpap duration was 4 (iqr, [1] [2] [3] [4] [5] [6] [7] [8] days. overall cumulative 60-day in-hospital mortality was 34% (cumulative incidence, 0.344, 95%ci, 0.304-0.384), as depicted in figure 1a , while hospital los was 16 (iqr, [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] days. demographic and clinical patients' characteristics stratified by pao 2 /fio 2 performed 2 to 24 hours after cpap initiation and interface applied, are provided in the supplementary material in table 2s and 3s, respectively. overall cumulative 60-day in-hospital mortality stratified according to pao 2 /fio 2 and interface applied is also depicted in figure 2s a within the full treatment subgroup, 60-day in-hospital mortality was 42% (cumulative incidence 0.418, 95%ci, 0.345-0.488) for patients receiving intubation (figure 2 ), and 2% (cumulative incidence 0.018, 95%ci, 0.008-0.035) for patients succeeding cpap (figure 3s ). cpap duration was 2 days (iqr, 1-3 days) in patients who survived and 3 days (iqr. 1-5 days) in patients who died (p=0.061). table 3 shows that duration of cpap application was an independent predictor of mortality for patients requiring intubation. the model, adjusting for age, gender, comorbidities, ldh, c-reactive protein values, and lymphocyte count, indicates a 9.3% [hr, 1.094 (95%ci, 1.010-1.184)] increase of the risk of death for each day of treatment. the association between duration of cpap and mortality does not substantially change in the secondary analysis using multiple imputation [hr, 1.060 (95%ci, 1.001-1.121)], as presented in table 7s . 60-day in-hospital mortality was significantly higher in patients subjected to cpap for more than 3 days (cumulative incidence 0.510, 95%ci, 0.393-0.615) as compared to those receiving cpap for 3 days or less (cumulative incidence 0.350, 95%ci, 0.259-0.441), as shown in figure 4s . this multicentre retrospective observational study on 537 patients hypoxemic arf secondary to laboratory-confirmed covid-19 infection, shows that cpap applied to different therapeutic goals i.e., candidate to intubation in the case of cpap failure and do-not-intubate in which cpap is considered the ceiling of treatment, is feasible outside icu. treatment duration for patients failing cpap prior to intubation represents a risk factor for mortality. cpap can be delivered both in icu and outside icu. grasselli et al. [10] , found that 11% of the patients entering icu needed niv, while early data from china revealed a higher percentage i.e., 41.7% [13] , 43.3% [19], 56% [11] , 62% [15] . in keeping with data by grasselli et al. [10] , as cpap was delivered to 31 out of 326 patients (9.5%) entering icu. data on the use of cpap in covid-19 patients treated outside icu are scarce. two over 28 patients (7%) received niv or hfnc outside icu in a single centre study in wuhan [15] . oranger et al., treated 38 patients with cpap in a respiratory ward [14] . although the study included a limited patients' number, cpap resulted to be feasible and the authors also suggest a potential benefit for both full treatment and dni patients, as opposed to those treated with oxygen only [14] . as far as mortality concerns, we showed an overall cumulative 60-day in-hospital mortality of 34% in patients with moderate to severe forms of arf covid-19-related needing cpap. the rate of mortality observed in our study, is not divergent from those reported in several prior studies [9, 10, 15, 12, 13] for icu patients, predominantly intubated, which varied from 17% [13] to 67% [9] . lastly, our study includes 26% of dni patients, for whom cpap was considered ceiling of treatment. rate of dni patients reported in our study is similar to 15% observed in a small cohort of patients treated outside icu during covid-19 pandemic [14] , i.e., as well as to 30% reported by a large italian multicentre observational study in patients with pneumonia non-covid-19 related, treated with niv outside icu [20] . in our study, 60-day in-hospital mortality for dni patients was 73%. a major concern when treating patients with hypoxemic arf with niv, is related to niv-failure rate that might occur in up 50% of the cases with consequent recourse to intubation [21] . undue prolongation of niv may worsen lung injury resulting in the so-called patient self-inflicted lung injury [22] , while the direct consequence of niv failure is delaying intubation and adequate treatment with invasive ventilation [23, 1] . our data confirm that intubation delay for those requiring afterward invasive ventilation is associated with increased risk for mortality. in other pandemics, such as influenza, h1n1, and severe acute respiratory syndrome (sars), niv failure ranges from 10 to more than 70% [24], reaching 90% with middle east respiratory syndrome [25] . in our study, cpap failure rate was 45%, which indicates that effective treatment occurred in more than half of patients, who avoided invasive ventilation through an endotracheal tube, which is a life-saving procedure, but it is also prone to several side-effects and complications [26] . the study has several limitations. first, we were not able to compare our population with an historical control. second, most of data have been retrospectively derived from the medical records. according to the retrospective nature of the study, formal criteria to start cpap treatment were not defined a priori, and the time span between cpap initiation and control abg was relatively long. third, definitions of full treatment and dni patients, although internationally accepted [6] , are influenced by patients, families, and clinicians thinking and might be influenced by cultural, religious and geographical factors. fourth, due to the diversity of interfaces and devices used in our study, the actual applied pressure could somewhat differ from the preset value [27] . fifth, due to the number of missing data among many important variables such as d-dimer and respiratory rate, we were not able introduce them in the model that explore the correlation between cpap duration and mortality. lastly, because of the exceptionality of pandemic outbreak, our results are not generalizable to other conditions. to the best of our knowledge, this is the largest retrospective cohort study on patients with covid -19 treated with cpap outside icu. we show that cpap is feasible outside icu with overall in-hospital mortality similar to that reported in other studies treating critically ill icu patients. in-hospital mortality is closely related to the therapeutic goal, patients having dni order being affected by much higher mortality. intubation delay is confirmed to be an independent risk factor for mortality. further studies are necessary to ascertain the potential infective risk related to cpap treatment outside icu among healthcare workers. chronic arterial hypertension, n (%) 278 (52) diabetes, n (%) 138 (26) ischaemic heart disease, n (%) 66 (12) cpap, days 4 (1-8) curves and corresponding 95% confidence intervals (dashed lines). cpap, noninvasive continuous positive airway pressure; dni, do not intubate. eti, endo-tracheal intubation. outcomes of covid-19 patients treated with continuous positive airway pressure outside icu this was a multicentre, retrospective observational study performed in six hospitals of the eastern piedmont region, northern italy i.e., "maggiore della carità" university hospital in novara, "ss. antonio biagio e cesare arrigo", hospital in alessandria, "s. andrea" hospital in vercelli, "vco asl" in domodossola, "nuovo ospedale degli infermi" hospital in biella. one centre i.e., an as-needed basis. when respiratory parameters improved, cpap support was gradually reduced with a progressive increase of time off cpap, until discontinuation. nurse to patient ratios varied from a maximum of 1:6 both during day and night to a minimum of 1:8 and 1:12, respectively during days and nights. in three hospitals, medical staff treating cpap covid-19 patients was an ad-hoc mixed team, mainly internists, pneumologists, emergency physicians, cardiologists, anaesthesiologists/icu physicians, while in the other three hospitals the medical team was the same as before covid-19 pandemic. cpap was prescribed mainly by anaesthesiologists actively working with the ad-hoc covid-19 ward team, but also by pneumologists and emergency doctors or by consulting anaesthesiologists. personnel was adequately trained for niv; those who were not, received a short-organized training during pandemic. ward monitoring included spo 2 , non-invasive blood pressure, ecg applied continuously or at a defined time point depending on the severity of the patient. blood gas analysis was performed when clinically relevant. patients received daily visit from the consulting physician who prescribed cpap if not present in the ad-hoc ward team. fine and gray model included as adjustment age, gender, comorbidities i.e., charlson comorbidity index and hypertension, ldh, c-reactive protein levels and lymphocyte count. the model was further adjusted by centre. the adjustment variables were selected on the base of their clinical relevance. multiple imputation procedures were applied to account for missing data. ospedale ss. trinità, department of anesthesia and critical care azienda ospedaliera sant'andrea, department of anesthesia and critical care maggiore della carità via dei ponderanesi, 2 -13875 ponderano via gallucci maggiore della carità raoof s members of the task force. official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients with acute respiratory failure: a randomized clinical trial effect of noninvasive ventilation on tracheal reintubation among patients with hypoxemic respiratory failure following abdominal surgery: a randomized clinical trial noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy noninvasive ventilation outside the intensive care unit from the patient point of view: a pilot study an international survey on noninvasive ventilation use for acute respiratory failure in general non-monitored wards characteristics and outcomes of 21 critically ill patients with covid-19 in washington state clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china continuous positive airway pressure to avoid intubation in sars-cov-2 pneumonia: a two-period retrospective case-control study clinical features of patients infected with 2019 novel coronavirus in wuhan, china a new method of classifying prognostic comorbidity in longitudinal studies: development and validation clinical characteristics of coronavirus disease 2019 in china non-invasive positive pressure ventilation in pneumonia outside intensive care unit: an italian multicenter observational study high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure mechanical ventilation to minimize progression of lung injury in acute respiratory failure noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review noninvasive ventilation in critically ill patients with the middle east respiratory syndrome evolution of mortality over time in patients receiving mechanical ventilation helmet with specific settings versus facemask for noninvasive ventilation mg/dl 13 noninvasive continuous positive airway pressure; feu, fibrinogen-equivalent unit table 3s general characteristics of patients according to cpap interface applied values are median (interquartile range) or number (percentage) feu, fibrinogen-equivalent unit helmet vs. mask: * p =0.030, † p=0.002, § p=0.001, °p<0.0001, ‡ p=0.032. helmet (n=399) mask (n=123) mask and helmet (n=15) we acknowledge all health-care workers involved in the diagnosis and treatment of patients in the eastern piedmont region. we thank dr. davide crimaldi for database support. the study received no funding. preliminary data have been sent, in abstract form, to the european society of intensive care medicine congress 2020. male 537body mass index 239white blood cell count 533lymphocyte count 529creatinine 531aspartate-aminotransferase 335alanine-aminotransferase 503 abbreviations: abg, arterial blood gas analysis; cpap, noninvasive continuous positive airway pressure; paco 2 , arterial partial pressure of carbon dioxide; pao 2 , arterial partial pressure of oxygen; spo 2 , peripheral oxygen saturation; hco 3-, bicarbonate; fio 2 , inspired oxygen fraction; pao 2 /fio 2 , arterial partial pressure of oxygen to inspired oxygen fraction ratio; spo 2 /fio 2 , peripheral oxygen saturation to inspired oxygen fraction ratio a arterial blood gas analysis performed before cpap initiation b first arterial blood gas analysis performed 2-24 hours after cpap outset key: cord-029392-5s5686i9 authors: zayed, yazan; kheiri, babikir; barbarawi, mahmoud; rashdan, laith; gakhal, inderdeep; ismail, esra’a; kerbage, josiane; rizk, fatima; shafi, saadia; bala, areeg; sidahmed, shima; bachuwa, ghassan; seedahmed, elfateh title: effect of oxygenation modalities among patients with postoperative respiratory failure: a pairwise and network meta-analysis of randomized controlled trials date: 2020-07-17 journal: j intensive care doi: 10.1186/s40560-020-00468-x sha: doc_id: 29392 cord_uid: 5s5686i9 background: postoperative respiratory failure is associated with increased perioperative complications. our aim is to compare outcomes between non-invasive ventilation (niv), high-flow nasal cannula (hfnc), and standard oxygen in patients at high-risk for or with established postoperative respiratory failure. methods: electronic databases including pubmed, embase, and the cochrane library were reviewed from inception to september 2019. we included only randomized controlled trials (rcts) that compared niv, hfnc, and standard oxygen in patients at high risk for or with established postoperative respiratory failure. we performed a bayesian network meta-analysis to calculate the odds ratio (or) and bayesian 95% credible intervals (cris). results: nine rcts representing 1865 patients were included (the mean age was 61.6 ± 10.2 and 64.4% were males). in comparison with standard oxygen, niv was associated with a significant reduction in intubation rate (or 0.23; 95% cr.i. 0.10–0.46), mortality (or 0.45; 95% cr.i. 0.27–0.71), and intensive care unit (icu)-acquired infections (or 0.43, 95% cr.i. 0.25–0.70). compared to standard oxygen, hfnc was associated with a significant reduction in intubation rate (or 0.28, 95% cr.i. 0.08–0.76) and icu-acquired infections (or 0.41; 95% cr.i. 0.20–0.80), but not mortality (or 0.58; 95% cr.i. 0.26–1.22). there were no significant differences between hfnc and niv regarding different outcomes. in a subgroup analysis, we observed a mortality benefit with niv over standard oxygen in patients undergoing cardiothoracic surgeries but not in abdominal surgeries. furthermore, in comparison with standard oxygen, niv and hfnc were associated with lower intubation rates following cardiothoracic surgeries while only niv reduced the intubation rates following abdominal surgeries. conclusions: among patients with post-operative respiratory failure, hfnc and niv were associated with significantly reduced rates of intubation and icu-acquired infections compared with standard oxygen. moreover, niv was associated with reduced mortality in comparison with standard oxygen. postoperative respiratory failure is associated with increased perioperative complications such as reintubation, invasive mechanical ventilation, and healthcareassociated infections, which can lead to increases in mortality, intensive care unit (icu) and hospital length of stay, delays in hospital discharges, and higher healthcare resource utilization [1] [2] [3] [4] . several post-operative pulmonary complications may result in post-operative hypoxemic respiratory failure, including pneumonia, atelectasis, bronchospasm, pneumothorax, and pleural effusion. the incidence of these complications is variable and ranges between 5 and 40% according to the type of surgery, as well as other risk factors including anesthetic technique, duration of surgery, and severity of illness [5] [6] [7] [8] [9] . cardiac surgery has the highest rate of post-operative respiratory complications (up to 40%), followed by thoracic surgery (30%), while abdominal and vascular surgeries have a low incidence of post-operative pulmonary complications (6-7%) [5] [6] [7] . in nonsurgical patients, oxygenation modalities for hypoxemic respiratory failure are varied. non-invasive ventilation (niv) has shown promising results for reducing intubation rates among patients with cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbations [10] [11] [12] . high-flow nasal cannula (hfnc) is a new oxygenation strategy that delivers oxygen at high concentrations and a high flow rate and has been increasingly utilized due to its ease of application, tolerance, and potential clinical benefits [13, 14] . nevertheless, the current european respiratory society/ american thoracic society (ers/ats) guidelines have conditional recommendations regarding the use of niv in postoperative respiratory failure [15] . in addition, few randomized controlled trials (rcts) have been conducted to evaluate the efficacy of hfnc vs niv in postoperative patients. therefore, we conducted a metaanalysis to compare the efficacy and safety of hfnc, niv, and standard oxygen therapy in the treatment of patients who developed or were considered high risk for post-operative respiratory failure. our study is a meta-analysis and systematic review performed according to the preferred reporting items for systematic reviews and meta-analyses protocols (pris ma-p) 2015 statement [16] . two reviewers (m.b., i.g) independently and separately performed a literature search utilizing electronic databases including pubmed, cochrane library, and embase from inception to september 2019 without language restrictions. articles were first screened by titles and abstracts before exclusion. full texts of eligible articles were reviewed for final inclusion or exclusion. mesh terms used were as follows: "postoperative respiratory failure", "respiratory failure", "postoperative", "hypoxemic", "hypoxic", "non-invasive ventilation", "niv", "high-flow nasal cannula", "hfnc", "high-flow nasal therapy", "hfnt", "high-flow nasal oxygen", "hfno", "oxygen", "facemask", and "ventilation". references of relevant articles were also reviewed for possible inclusion. a third reviewer (yz) resolved any discrepancies. only rcts were eligible for inclusion in our analysis. we included studies that compared different oxygenation strategies in patients who developed or were deemed at high risk for developing post-operative hypoxemic respiratory failure. patients at risk were defined to have intermediate to high risk for development of post-operative pulmonary complications according to either assess respiratory risk in surgical patients in catalonia (ariscat) score of ≥ 26 points [4] . patients who failed spontaneous breathing trial and those who passed spontaneous breathing trials but had risk factors for failed extubation such as cardiac dysfunction, obesity (bmi > 30), or failure of previous extubation were also considered high risk. post-operative hypoxemic respiratory failure was defined as the development of tachypnea with a respiratory rate of ≥ 25 respirations per minute, intense work of breathing with the use of accessory muscles, hypoxemia (oxygen saturation ≤ 92% or partial arterial oxygen pressure to fraction of inspired oxygen ≤ 300) in the immediate post-operative period or within 7 days post-operatively. we excluded studies that investigated prophylactic use of niv and hfnc as a routine therapy in the post-operative period. data were extracted into a predesigned table independently and separately by two reviewers (l.r and s.s.). any discrepancies were solved by consensus with a third reviewer (y.z.). cochrane collaboration's tool for assessing risk of bias in randomized controlled trials was used for quality assessment for the included rcts [17] . each of the included rcts was assessed for random sequence generation, allocation concealment, blindness of participants and health-care personnel, blindness of outcome assessment, incomplete outcome data, selective reporting, and other biases if any were present. our main outcome was the intubation rate following surgery. secondary outcomes included mortality at the longest follow-up period provided by each study and icu-acquired infections. an informative prior bayesian framework for the network meta-analysis was performed using the markov chain monte carlo simulation to derive the posterior distribution of the parameter estimates. we used a beta distribution of (0, 2) for binominal likelihood. we used the brooks-gelman-rubin method to assess for convergence. a consistency model which contains treatment as a fixed effect and trial as a random effect was used. results were reported as odds ratios (ors) and bayesian 95% credible intervals (cr.is). inconsistency was assessed using the deviance residuals and deviance information criteria statistics. sensitivity analysis was performed by including only trials that included patients who had developed respiratory failure. furthermore, subgroup analysis according to the type of surgery (cardiothoracic or abdominal) was performed. in addition, to show the validity of our results, we performed a direct pairwise meta-analysis for comparisons that have three or more studies comparing directly the two interventions. in an exploratory analysis, we performed a metaregression analysis to explain any significant heterogeneity (> 25%) for niv vs standard oxygen therapy direct meta-analysis. moderators included study-level covariates: age, gender, body mass index, simplified acute physiology score (saps) ii, respiratory rate, pao2/fio2 ratio, and partial arterial pressure of carbon dioxide (paco2). all data were analyzed using revman v5.3 windows, comprehensive meta-analysis software v3, netmetaxl v1.6.1, and winbugs v1.4.3. after review of 1369 articles, 9 studies were included in the final analysis representing 1865 patients [18] [19] [20] [21] [22] [23] [24] [25] [26] . figure 1 illustrates the search process. the mean age was 61.6 ± 10.2, and 64.4% were males. four rcts included patients undergoing cardiac and/or lung surgeries [19, 20, 24, 26] , 3 rcts involved patients undergoing abdominal surgeries [21] [22] [23] , and 2 rcts included patients following organ transplantation [18, 25] . two trials included patients considered at high risk of post-operative pulmonary complications and respiratory failure [23, 26] and one trial included patients at risk for respiratory failure or patients with established respiratory failure [20] while six trials included patients who developed respiratory failure in the immediate post-operative period or up to 7 days postoperatively [18, 19, 21, 22, 24, 25] . two trials compared hfnc vs niv [18, 20] , five trials compared niv vs standard oxygen therapy [19, 21, 22, 24, 25] , and 2 trials compared hfnc vs standard oxygen therapy [23, 26] . table 1 explains the characteristics of the included trials, and supplementary figure 1 illustrates the network geometry. niv was the most commonly used treatment (41.2% of patients), hfnc was used in 31.6% of cases, and 27.2% of patients were treated with standard oxygen therapy. table 2 explains the baseline and demographic characteristics of included patients. included studies were noted to have inevitable performance bias as blinding of participants and personnel was difficult given the nature of the intervention. detailed quality assessment was not performed for one study as we only found the abstract with no full article explaining the methods. supplementary figure 2 shows the risk of bias in each included rct based on the authors' judgment. niv and hfnc were associated with significant reductions in intubation rates when compared to standard oxygen therapy (or 0.23; 95% cr.i. 0.10-0.46) and (or 0.28; 95% cr.i. 0.08-0.76), respectively. however, there was no significant difference between hfnc and niv with regard to the intubation rates (or 0.82; 95% cr.i. 0.30-2.50), fig. 2 . sensitivity analysis was performed by including only patients who developed acute hypoxemic respiratory failure (but not patients at increased risk), which showed similar results. in a subgroup analysis for patients undergoing cardiothoracic surgery, both niv and hfnc were associated with a similar reduction in intubation rates compared with standard oxygen therapy (niv vs standard oxygen (or 0.08; 95% cr.i. 0.03-0.19) and hfn vs standard oxygen (or 0.08; 95% cr.i. 0.03-0.21)) ( fig. 3a) . however, in patients undergoing abdominal surgery, niv (but not hfnc) was associated with significantly reduced intubation rates compared with standard therapy (niv vs standard oxygen (or 0.51; 95% cr.i. 0.26-0.87)) (fig. 3b) . in an exploratory meta-regression analysis, we found that higher paco2 was associated with lower risk for intubation when niv was compared to standard oxygen therapy (p < 0.05) (supplementary figure 3) . niv was associated with a significant reduction of mortality in comparison with standard oxygen therapy (or 0.45; 95% cr.i. 0.27-0.71). additionally, there was no significant difference between niv and hfnc (or 0.78; 95% cr.i. 0.41-1.50) or hfnc and standard oxygen (or 0.58; 95% cr.i. 0.26-1.22) as shown in fig. 4 . in a subgroup analysis based on the type of surgery (cardiothoracic or abdominal), mortality benefit of niv was limited to those undergoing cardiothoracic surgery compared with standard oxygen therapy (or 0.31; 95% cr.i. 0.13-0.70), unlike those undergoing abdominal surgeries (or 0.56; 95% cr.i. 0.27-1.08) (fig. 5) . hfnc and niv were associated with a decreased risk for icu-acquired infections in comparison with standard oxygen therapy (or 0.41; 95% cr.i. 0.20-0.80) and (or 0.43; 95% cr.i. 0.25-0.70), respectively. no significant difference was found between hfnc and niv (fig. 6 ). we have performed direct pairwise meta-analysis comparing niv versus standard oxygen which showed consistent results of the network meta-analysis (supplementary figure 4) . however, we did not perform the direct meta-analysis for hfnc vs niv or hfnc vs standard oxygen because studies that compared directly between these interventions were one or two studies. supplementary figures 5 and 6 show the results of these individual studies for different outcomes. in this first network meta-analysis comparing various oxygenation strategies in patients at risk for hypoxemic respiratory failure or established respiratory failure within 7 days of surgery, we have found that niv and hfnc were associated with a significant reduction in intubation rates and icu-acquired infections when compared to standard oxygen therapy. however, when compared to standard oxygen therapy, only niv was found to have a mortality benefit in this patient population. we found hfnc and niv to have no significant differences in the primary or secondary outcomes. furthermore, in a subgroup analysis, patients undergoing cardiothoracic surgery had a significantly lower rate of intubation when treated with hfnc or niv in comparison with standard oxygen therapy, but mortality was significantly lower in patients treated with niv in comparison with standard oxygen therapy. additionally, in patients with abdominal surgeries, only niv was associated with a significant reduction in intubation rates compared to standard oxygen, but there was no significant difference in mortality between competing interventions. hypoxemia occurs frequently in the post-operative period and can lead to acute respiratory failure. several [27] [28] [29] . non-invasive ventilation (niv) improves oxygenation by recruiting collapsed alveoli and increasing tidal volume participating in gas exchange without hemodynamic adverse events [1, 30] . however, previous studies and meta-analyses had not shown a significant reduction in intubation rates with prophylactic use of niv after surgery, despite the reduction in the incidence of postoperative pulmonary complications [31] [32] [33] . currently, niv is recommended in the treatment of patients with post-operative respiratory failure according to the ers/ats guidelines [15] . our results indicate that intubation rates and mortality are significantly lower in patient populations who are at an increased risk or have developed postoperative respiratory failure treated with niv in comparison with standard oxygen. in our subgroup analysis, mortality benefit was only noted in patients undergoing cardiothoracic surgeries but not in abdominal surgeries. in an rct examining niv vs standard oxygen therapy in patients with respiratory failure after abdominal surgeries, jaber and antonelli found that niv was associated with lower intubation rates, less days on mechanical ventilator, and significantly lower rates of healthcare-associated infections, including pneumonia. although mortality rates were lower in the niv group (14 vs 21%), the difference did not reach a statistical significance in their study [22] . similarly, patients undergoing cardiothoracic surgery and treated with niv for postoperative respiratory failure had lower rates of intubation and mortality when compared to patients treated with standard oxygen therapy [19, 24] . hfnc is a new oxygenation strategy that has been used more frequently in patients with respiratory failure. it is found to be more comfortable than niv and can deliver concentrated oxygen reaching 100% with a high flow rate up to 60 ml/min [34, 35] . furthermore, it can provide positive end-expiratory pressure up to 2-3mmhg [34, 35] . the use of hfnc has shown beneficial effects in patients who developed post-extubation respiratory failure or when used during intubation to prevent hypoxemia when compared to standard oxygen [36] [37] [38] . additionally, frat et al. found lower mortality rates with hfnc in comparison with niv and conventional oxygen in patients with non-hypercapnic hypoxemic respiratory failure. however, other trials did not find differences between hfnc and standard oxygen therapy [39] [40] [41] [42] . the use of hfnc in the post-operative data are provided percent (%), mean ± sd, or median (interquartile range) hfnc high-flow nasal cannula, so standard oxygen, niv non-invasive ventilation, bmi body mass index, saps simplified acute physiology score, pao2/fio2 partial pressure of arterial oxygen to fraction of inspired oxygen ratio, paco2 partial pressure of arterial carbon dioxide, na not available period was investigated by several rcts. in a large rct involving more than 800 patients after cardiac surgery, the use of hfnc and niv in the treatment of high-risk patients or those who had developed post-operative respiratory failure was similar between both interventions with similar intubation rates, mortality, and rates of hospital-acquired infections [20] . in our analysis, there was no difference between hfnc and niv in intubation rates, mortality, and icu-acquired infections. similar results were also found in both subgroups (cardiothoracic surgeries and abdominal surgeries). in addition, hfnc was associated with lower intubation rates in patients following cardiothoracic surgeries but not following abdominal surgeries when compared to standard oxygen therapy. this could be explained by the fact that in thoracic surgery, hfnc could minimize lung decruitment post-extubation by providing some level of continuous positive airway pressure through high-flow ventilation, though this positive pressure can be variable due to the leak around the nasal cannula and nonguaranteed closed mouth of the patients [26] . furthermore, we found lower rates of infections with hfnc and niv when compared to standard oxygen are attributed to lower intubation rates in both interventions, which avoids the need for mechanical ventilation and decreases catheter-associated infections. although there was no significant difference between hfnc and niv with regard to rates of intubation, mortality, and icu-associated infections, when each of these two strategies was compared to standard oxygen, niv was associated with a survival benefit especially in patients who had cardiothoracic surgery. additionally, there was a trend toward lower mortality in abdominal surgeries, but hfnc had no mortality benefit in the total patient population and both subgroups. whether a lower number of patients included in the comparison between hfnc and standard oxygen or certain other factors could have contributed to the inability to detect a mortality benefit despite a significant reduction of intubation rates is needed to be addressed in further larger and well-controlled trials. nevertheless, due to the low events, further rcts are needed to compare between both interventions in different types of surgeries to determine its effect on various long-term clinical outcomes and quality of life and also to examine whether certain patients' risk factors could affect the beneficial effects of these interventions towards reduction of intubation rates and mortality. our analysis has several limitations. first, we were unable to perform analysis based on various risk factors, duration of surgery, severity scores, and different surgical types as we lack patients' level data. second, blinding of intervention and personnel was impossible given the nature of intervention. third, there were few sample size and limited events, and therefore, larger trials and longterm outcomes are needed. fourth, we used informative prior module for our analysis which could affect the results given the small number of included trials. fifth, there was a significant time gap between included studies through which there was a significant development in the icu management, preoperative and postoperative evaluation and care, supportive management, and criteria for admission to the icu. among patients who are at risk for developing postoperative respiratory failure, or have developed postoperative respiratory failure, the use of niv was associated with reduced rates of intubation, mortality, and icu-acquired infections in comparison with standard oxygen therapy. in addition, hfnc was associated with reduced rates of intubation and icu-acquired infections but not mortality in comparison with standard oxygen. there was no significant difference between hfnc and niv on the various studied clinical outcomes. supplementary information accompanies this paper at https://doi.org/10. 1186/s40560-020-00468-x. non-invasive ventilation in postoperative patients: a systematic review mortality after surgery in europe: a 7 day cohort study incidence of mortality and morbidity related to postoperative lung injury in patients who have undergone abdominal or thoracic surgery: a systematic review and meta-analysis prediction of postoperative pulmonary complications in a population-based surgical cohort prospective external validation of a predictive score for postoperative pulmonary complications post-operative pulmonary complications: understanding definitions and risk assessment participants in the national veterans affairs surgical quality improvement program. development and validation of a multifactorial risk index for predicting postoperative pneumonia after major noncardiac surgery a trial of intraoperative low-tidal-volume ventilation in abdominal surgery postoperative respiratory failure: pathogenesis, prediction, and prevention noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? a systematic review of the literature non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: cochrane systematic review and meta-analysis non-invasive ventilation or high-flow oxygen therapy: when to choose one over the other? open-label, phase ii study of routine high-flow nasal oxygen therapy in cardiac surgical patients official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure preferred reporting items for systematic review and meta-analysis protocols (prisma-p) 2015 statement the cochrane collaboration's tool for assessing risk of bias in randomised trials high flow nasal cannula (hfnc) as an alternative to noninvasive ventilation (niv) in acute respiratory failure (arf) in immunosuppressed patients-an indian post liver transplant experience efficacy and safety of noninvasive positive pressure ventilation in the treatment of acute respiratory failure after cardiac surgery high-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial effect of noninvasive ventilation on tracheal reintubation among patients with hypoxemic respiratory failure following abdominal surgery: a randomized clinical trial effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a french multicentre randomised controlled trial (opera) noninvasive ventilation reduces mortality in acute respiratory failure following lung resection noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial effect of high-flow nasal cannula versus conventional oxygen therapy for patients with thoracoscopic lobectomy after extubation dysfunction of the diaphragm postoperative pulmonary complications reducing atelectasis attenuates bacterial growth and translocation in experimental pneumonia preventive or curative postoperative noninvasive ventilation after thoracic surgery: still a grey zone? intensive care med prophylactic nasal continuous positive airway pressure following cardiac surgery protects from postoperative pulmonary complications: a prospective, randomized, controlled trial in 500 patients effect of adding postoperative noninvasive ventilation to usual care to prevent pulmonary complications in patients undergoing coronary artery bypass grafting: a randomized controlled trial continuous positive airway pressure (cpap) during the postoperative period for prevention of postoperative morbidity and mortality following major abdominal surgery. cochrane database syst rev physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients nasal high-flow versus venturi mask oxygen therapy after extubation. effects on oxygenation, comfort, and clinical outcome high-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. respir care effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: a randomized clinical trial high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure the effects of a 2-h trial of high-flow oxygen by nasal cannula versus venturi mask in immunocompromised patients with hypoxemic acute respiratory failure: a multicenter randomized trial randomized controlled trial of humidified high-flow nasal oxygen for acute respiratory distress in the emergency department: the hot-er study effect of high-flow nasal oxygen vs standard oxygen on 28-day mortality in immunocompromised patients with acute respiratory failure: the high randomized clinical trial publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgements na authors' contributions y.z.: study design, literature search, data analysis, data extraction, drafting the manuscript, final approval of the manuscript. key: cord-009375-2hflah2h authors: wang, xi-jun; hu, sen; ge, jin-ying; wang, qing-hua; qin, li-ting; bu, zhi-gao title: study of fusion protein and attachment glycoprotein of nipah virus expressed in recombinant baculovirus date: 2006-06-15 journal: nan doi: 10.1016/s1872-2075(06)60038-1 sha: doc_id: 9375 cord_uid: 2hflah2h the envelope attachment glycoprotein (g) and fusion protein (f′) of nipah virus (niv) play a key role in viral entry and induction of neutralization antibody. in this study, recombinant baculoviruses, rbac-nf and rbac-ng, were generated to express f and g proteins of niv. the expressions of recombinant g (rng) and f (rnf) proteins in rbac-nf and rbac-ng-infected cells were confirmed by western blot. both rng and rnf showed sensitive and specific antigenic reaction to rabbit serum anti-nipah virus in indirect immunofluorescence detection and indirect elisa. immunization with rbac-nf and rbac-ng-infected insect cells elicited g and f protein-specific antibody responses in mice. furthermore, the g and f protein-specific antibodies could neutralize the infectivity of the vsvδg*f/g, the niv f and g envelope glycoproteins of pseudotype recombinant vesicular stomatitis virus expressing green fluorescence protein. the results demonstrated that the f and g proteins expressed by the recombinant baculoviruses could be safe diagnostic antigens for the surveillance and monitoring of niv and could also be promising subunit vaccines for the prevention of niv. in late september 1998, a group of patients associated with pig farming in the suburbs of ipoh city within the kinta district of perak state in peninsular malaysia were infected with acute febrile encephalitis that was associated with high mortality [1] . initially, the illness in pigs was attributed to classical swine fever. the mortality in humans was attributed to japanese encephalitis (je), a mosquito-borne rna virus. however, the vaccination for swine fever and je and efforts to control mosquitoes failed to arrest the epidemic. by december 1998, the outbreak had spread to sungai nipah village and bukit pelandok (the biggest pig-farming region) in the state of negeri sembilan. a month later, a group of 11 human cases of febrile encephalitis illness along with one case of death was reported among abattoir workers in singapore who had handled pigs from the outbreak regions in malaysia [2] . in march 1999, a novel paramyxovirus, nipah virus (niv), was isolated from the cerebro-spinal fluid of a patient from sungai nipah village, who was subsequently identified with encephalitis; this virus was the aetiological agent that was responsible for the outbreak. by december 1999, a total of 283 human cases of acute febrile encephalitis including 109 cases of death associated with the outbreak were reported, with a mortality rate of 38.5 % [3] . the niv and the related australian hendra virus (hev) form the henipavirus genus within the paramyxovirus family. among the paramyxoviruses, these viruses had remarkable copyright © 2006 , institute of microbiology, chinese academy of sciences and chinese society for microbiology. published by elsevier bv. all rights reserved. abilities to infect and cause potentially fatal diseases in a number of host species, including humans. the natural reservoir of hev was fruit bats of the pteropid genus [4, 5] . therefore, fruit bats were suspected to be the natural reservoir of niv [6] . in 2002, niv was isolated from the urine samples and swabs from partially eaten fruits by flying foxes of pteropus genus. the world distribution of flying foxes extends from the western indian ocean islands through southeast asia, including southwest pacific islands, and australia excluding tasmania [7] . in 2001 and 2002, serological evidences indicated that the neutralizing antibody to niv was found in fruit bats from bangladesh, the northern india, and cambodia. in 2004, there was an outbreak of niv in bangladesh, in which 30 people were infected and 18 were killed. the envelope attachment glycoprotein (g) and fusion protein (f) of niv are major structural proteins that mediate membrane fusion between the virion and the host cell and elicite neutralization antibody. in this study, the recombinant baculoviruses, rbac-nf and rbac-ng, were generated to express f and g proteins of niv. recombinant g (rng) and f (rnf) proteins expressed by rbac-nf and rbac-ng showed sensitive and specific antigenic reaction to rabbit serum anti-niv. immunization with rbac-nf and rbac-ng-infected insect cells elicited g and f protein-specific antibody responses in mice. furthermore, the g and f protein-specific antibodies could neutralize the infectivity of the vsvδg*f/g, the niv f and g-envelope glycoproteins of pseudotype recombinant vesicular stomatitis virus expressing green fluorescence protein. the results demonstrated that the f and g proteins expressed by the recombinant baculoviruses could be safe diagnostic antigens for the surveillance and monitoring of niv and could also be promising subunit vaccines for the prevention of niv. 1 materials and methods plasmids puc 18-niv-f (full-length orf of niv f gene was inserted into sam i site of vector puc18) and pmd18-t-niv-g (full-length orf of niv g gene was inserted into ecor v site vector pmd18-t) were stored in our laboratory. polyclone serum from rabbits immunized with inactivated niv was kindly provided by dr. l. wang, csiro, australia. sf9 insect cells and vero e6 cells were stored in our laboratory. the recombinant vesicular stomatitis virus pseudotype, vsvδg*g, in which the vsv envelope protein g gene was replaced with the green fluorescent protein gene and complemented with vsv g glycoprotein expressed in trans, was kindly provided by dr. whitt ma. vsvδg*f/g pseudotype was prepared by cotransfecting 293t cells with pcagg-g and pcaagg-f following infection with vsvδg*g, as described previously. the infection unit (iu) of vsvδg* f/g in filtered supernatant of 293t cell culture was determined on bhk-21 cells by account of cells expressing gfp under a fluorescence microscope, typically about 10 7 /ml without concentration [8, 9] . the vsvδg*f/g stocks were stored at − 80 °c until use. pfastbac1-niv-f was generated by cloning ecor i-pst i fragment from puc 18-niv-f into the ecor i-pst i site of pfastbac1. to generate pfastbac1-niv-g, a fragment encoding niv g protein was excised from pmd18-t-niv-g by digestion with sal i and xba i and then cloned into the sal i-xba i site of pfastbac1. briefly, pfastbac1-nf and pfastbac1-ng were transformed into dh10bac competent cells containing bacmid (baculovirus shuttle vector plasmid) and helper plasmid and were plated on lb solid medium plates containing 50 µg/ml kanamycin (takara dalian, china), 7 µg/ml gentamicin (takara dalian, china), 10 µg/ml tetracycline (takara dalian, china), 100 µg/ml x-gal (takara dalian, china), and 40 µg/ml iptg (takara dalian, china). after 24-48 h of incubation at 37 °c, white colonies were selected and grown overnight in lb medium with the antibiotics. plasmid recombinant bacmids were extracted from the overnight cultures as described in the manual, and were identified by pcr with primers m13-48f andm13-47r. sf9 insect cells were transfected with 1 µg of the recombinant bacmids dna using the cellfectin ® reagent (invitrogen). recombinant viruses were identified by pcr with primers m13-48f and m13-47r. a single recombinant virus plaque was isolated. the virus was further amplified using sf9 cells. the iu of the recombinant baculoviruses, rbac-niv-f and rbac-niv-g, were measured by account of plaque. the recombinant baculoviruses were stored at −80 °c until use. according to reference 10, the monolayer of sf9 insect cells were infected with 1:10 dilutions of rbac-niv-f, rbac-niv-g, and wild-type baculovirus. the infected cells were harvested until 90 % of the cells showed cpe, and were then spread on glass slides for air drying. following this, the cells were fixed with 95 % ethanol and were allowed to interact with 20-fold dilution of serum from rabbits immunized with inactivated niv and with nonimmunized rabbit serum, respectively. the glass slides were washed with pbst and then interacted with 1:50 dilution of the fluorescein isothiocyanate-conjugated anti-rabbit igg antibodies. the glass slides were then washed again with pbst and observed under afluorescence microscope (leica dmires2). pet-niv-f was generated by pcr-amplifying niv f gene fragment (976-1 479 nt) with the primers niv-f-f: 5′-gtg ttcgaattcatcgagatcgggttctg-3′ and niv-f-r: 5′-gatgatgtcgacggagagcatggag-3′ and cloned into the ecor i-sal i site of prokaryotic expression vector pet-30a(+). pet-niv-g was generated by pcr amplification of niv g gene fragment (319-1 002 bp) with the primers, niv-g-f: 5′-accgacgaattccccaagg tgtccctgat -3′ and niv-g-r: 5′-gaggacgtcgacctggtgctggt tgta-3′ and cloned into the ecor i-sal i site of prokaryotic expression vector pet-30a(+). pet-niv-f and pet-niv-f were transformed into bl21 competent cells and were expressed by iptg inducing, and the proteins that fused to his-tag at its both termini were purified using ni-nta (pierce). ten-to eight-week-old female balb/c mice (weitong lihua experimental animal inc., beijing) were immunized by subcutaneous injection with 10 µg of the proteins, respectively, by boosting with the same dose of proteins at 21 days and 42 days after priming. the proteins were emulsified with freund's complete adjuvant (cfa) in initial immunization and then emulsified with freund's incomplete adjuvant (fia) in second and third immunizations. mouse blood was collected by retro-orbital bleeding at 14 days after final proteins immunization and stored at −20 °c until use. according to reference 11, sf9 cells were infected with 1:10 dilutions of rbac-niv-f, rbac-niv-g, and wild type baculovirus and harvested 72 h postinfection. the cells were then collected by 1 000 r/min for 10 min. the cell pellet was resuspended in 10 % volume pbs of primal culture fluid and frozen and thawed twice, and then shattered by supersonic waves. cell debris was removed by centrifuging at 1 000 r/min for 10 min and the supernatant was stored at −80 °c as antigens. elisa plates were coated with recombinant partial niv f or niv g, which were generated from e. coli bacteria, at 5 µg/ml in carbonate buffer (ph 9.6) overnight at 4 °c, and then blocked for 2 h at 37 °c with 5 % nonfat dry milk in pbst. serum samples (serum from mice immunized with recombinant niv f and g expressed by the recombinant baculoviruses and serum from nonimmunized mice) were tested in 1:50 dilutions in 5 % nonfat milk in pbst. hrp-conjugated goat anti-rabbit igg was diluted 1: 2 500 in pbst. the substrate solution used was opd. after 25 min of incubation in the dark, the reaction was stopped by the addition of 50 µl of 2 mol/l h the lysates of rbac-niv-f, rbac-niv-g, and wild-type baculovirus-infected sf9 cells were separated on 12 % sds-page. for western-blot analysis, the proteins were transferred from the gels to nitrocellulose filter. following transfer, the membranes were blocked with 10 % nonfat dry milk and incubated overnight with a 1:100 dilution of polyclone serum from mice immunized with purified recombinant partial niv f or niv g, which were generated from e. coli bacteria, suspended in buffer (1× pbs, 0.05 % tween 20, and 5 % nonfat dry milk). a 1:2 500 dilution of hrp-conjugated goat anti-mouse igg (sigma) was used to detect protein-antibody complexes, which were subsequently visualized with dab. elisa plates were coated with the above-mentioned lysates of sf9 cells infected with rbac-niv-f, rbac-niv-g, and wild-type baculovirus at 1:100 dilution in carbonate buffer (ph 9.6) overnight at 4 °c and then blocked for 2 h at 37 °c with 5 % nonfat dry milk in pbst.serum sample (serum from rabbits immunized with inactivated niv and serum from nonimmunized rabbits) were tested in 1: 200 dilutions in 5 % nonfat milk in pbst. hrp-conjugated goat anti-rabbit igg was diluted 1: 4 000 in pbst. the substrate solution used was opd. after 25 min of incubation in the dark, the reaction was stopped with the addition of 50 µl of 2 mol/l h 2 so 4 and the optical density at 490 nm was measured in an elisa microplate reader (bio-rad, benchmark plus). sera were run in triplicate. negative and positive control sera were included in each assay. 1.9 immunization of mice sf9 cells were infected by rbac-niv-f, rbac-niv-g, and wild-type baculovirus. when 90 % of the cells showed cpe, cells and the supernatant were harvested as immunizing antigens. ten-to eight-week-old female balb/c mice (weitong lihua experimental animal inc., beijing, china) were immunized by an intraperitoneal injection with 250 µl of the immunizing antigen and intramuscular injection with 100 µl of the immunizing antigen, respectively, by boosting with the same dose of proteins at 21 days after priming. mouse blood was collected by retroorbital bleeding at 21 days after final immunization and was stored at −20 °c until use. 1.10 immunogenicity of the recombinant proteins expressed by recombinant baculovirus 2 so 4 and the optical density at 490 nm was measured in an elisa microplate reader (bio-rad, benchmark plus). sera were run in triplicate. negative and positive control sera were included in each assay. it has been reported that hamsters passively administered with neutralization antibody were protected from lethal challenge of niv. because of the unique biological and genetic features, niv are categorized as biological safety level-4 (bsl-4) pathogens, which severely limits the laboratory facilities that are required for study with live viruses. in this study, we developed a highly safe and sensitive, single-round infectivity system was developed for the neutralization antibody assay without the need of live niv. the vsvδg*f/g mimicked the infection of real niv and entering niv susceptible target cells bhk-21 by f and g-mediated fusion, and was used to replace live niv for the neutralization antibody assay. to perform the neutralizing antibody assay, 1×10 5 iu vsvδg*f/g was added at each step of a serial two-fold dilution of heat-inactivated immunized mouse sera (serum from mice immunized with recombinant baculovirus expressed recombinant niv f protein (rnf), serum from mice immunized with recombinant niv g protein (rng), and serum from mice immunizied with wild type baculovirus, 30 min at 56 °c) in triplicate wells. after incubation for 1 h at 37 °c, the mixtures containing 5×10 4 iu vsvδg*f/g were added to the rinsed vero e6 monolayers. sera (serum from rabbit immunized with inactivated niv and serum from non-immunized rabbits) were included in each test as controls. the gfp-expressing cells were counted at 16 h postinfection (hpi) under a fluorescence microscope. the neutralizing titers were expressed as the reciprocal of the highest serum dilution that gave 80 % reduction in the number of gfp-expressing cells. niv f gene and g gene, encoding full-length f and g proteins, were cloned into pfastbac1, pfastbac1-niv-f and pfastbac1-niv-g were constructed, which were transformed into dh10bac competent cells. the recombinant bacmids were extracted and pcr amplification of rbacmid-niv-f and rbacmid-niv-g with primers m13-48f and m13-47r produced 3.9 kb and 4.1 kb fragments, respectively. sf9 insect cells were transfected with the recombinant bacmids to generate the recombinant viruses, rbac-niv-f and rbac-niv-g. pcr amplification of the recombinant virus with primers m13-48f andm13-47r produced also 3.9 kb and 4.1 kb fragments. the results demonstrated that niv f gene and g gene had inserted into the recombinant baculoviruses rbacmid-niv-f and rbacmid-niv-g, respectively. lysates of rbac-niv-f, rbac-niv-g, and wild-type baculovirus-infected sf9 cells were separated by 12 % sds-page and western blot. the niv f0 (61 kd), f1 (49 kd), and g (66 kd) specific band were probed with polyclone serum from mice that were immunized with purified recombinant partial niv f or niv g which was generated from e. coli bacteria ( fig. 1 and fig. 2 ). for detecting reactionogenicity of rnf and rng expressed by the recombinant baculoviruses, elisa plates were coated with the lysate of sf9 cells that were infected by rbac-niv-f and rbac-niv-g and detected with 1:200 dilution of polyclone serum from rabbits immunized with inactivated niv (kindly provided by dr. l. wang, csiro, australia). the results showed that the average od 490nm for rnf and rng were 0.181 and 0281, respectively, in indirect elisa, in which rnf and rng were detected using serum from rabbits immunized with inactivated niv; the average od 490nm for rnf and rng were 0.063 and 0.055, respectively, in detecting serum from non-immunized rabbits in indirect elisa; the p/n values were 2.9 and 5.1 (fig. 3) . for detecting reactionogenicity of rnf and rng expressed by the recombinant baculoviruses, sf9 cells infected by rbac-niv-f or rbac-niv-g or wild-type baculoviruses were detected using serum from rabbits immunized with inactivated niv in ifa. the sf9 cells infected by rbac-niv-f and rbac-niv-g showed strong positive fluorescence signal in detecting serum from rabbits immunized with inactivated niv (fig. 4a, 4b) and negative fluorescence signal in detecting serum from non-immunized rabbits (fig. 4c, 4d) . the sf9 cells infected by wild-type baculoviruses showed negative fluorescence signal in detecting using serum from rabbits immunized with inactivated niv (fig. 4e) . the results showed that rnf and rng expressed by the recombinant baculoviruses possess good sensitivity and specificity in ifa. for detecting immunogenicity of rnf and rng expressed by the recombinant baculoviruses, elisa plates were coated with purified recombinant partial niv f or niv g which were generated from e. coli bacteria and detected using 1:50 dilution of polyclone serum from mice immunized with rnf or rng. the results showed that the average od 490nm for recombinant partial niv f and niv g were 0.236 and 0.208, respectively, in indirect elisa, in which purified recombinant partial niv f or niv g were detected using serum from mice immunized with rnf or rng expressed by the recombinant baculoviruses; the average od 490nm for recombinant partial niv f or niv g were 0.059 and 0.052 in detecting serum from nonimmunized mice in indirect elisa; both p/n values were 4 and 4, respectively ( fig. 5 and fig. 6 ). the vsvδg*f/g mimicked the infection of real niv and entering niv susceptible target cells bhk-21 by f and g-mediated fusion, and was used to replace live niv for neutralization antibody assay. the result showed that immunization with insect cells infected with rbac-nf and rbac-ng elicited g and f protein-specific antibody responses in mice. furthermore, the g and f protein-specific antibodies neutralized the infectivity of the vsvδg*f/g. the neutralizing titers were expressed as the highest serum dilution that gave 80 % reduction in the number of gfpexpressing cells. the titers of serum from mice immunzed with rng, serum from mice immunized with rnf, and serum from rabbits immunized with inactivated niv were 128, 64, and 32. however, serum from nonimmunized rabbits and serum from mice immunizied with wild type baculovirus could not neutralize the infectivity of the vsvδg*f/g (fig. 7) . in this study, recombinant baculoviruses, rbac-niv-f and rbac-niv-g, were generated for expressing f and g proteins. the expressions of recombinant g (rng) and f (rnf) protein in rbac-nf and rbac-ng-infected cells were confirmed by western blot. both rng and rnf showed sensitive and specific antigenic reaction to rabbit serum anti-niv in indirect immunofluorescence detection and indirect elisa. furthermore, the results of the neutralization tests and indirect elisa demonstrated that cell suspension of sf9 insect cells infected by the recombinant baculoviruses, rbac-niv-f and rbac-niv-g, elicited g ad f protein-specific antibody responses in mice. moreover, the g and f protein-specific antibodies neutralized the infectivity of the vsvδg*f/g entering niv susceptible target cells. therefore, the recombinant niv f and g proteins expressed by the recombinant baculovirus could be to play a significant role in the study of epidemiology of niv encephalitis, the serological monitoring of wildlife, and the appraisal to specific immune response of protective immunogen in the development process of a new generation vaccine. paramyxoviruses have two glycoproteins at the surface, namely, attachment glycoprotein and fusion glycoprotein. the attachment glycoprotein is associated with virion attachment to the cellular receptor and has been designated as the hemagglutinin-neuraminidase protein (hn), the hemagglutinin protein (h), or the g protein, which has neither hemagglutinating nor neuraminidase activities, whereas, the f glycoprotein induces fusion between the viral and cellular membranes. g and f acted in concert to bring about fusion. the existing studies showed that only coexpression of the attachment glycoprotein and fusion glycoprotein of newcastle disease virus [12] , human parainfluenza virus [13] , and measles virus [14] induced fusion. in addition, only coexpression of the g protein and f protein of niv also induced fusion. the binding of g protein and the cellular receptor induced a series of configuration changes in the f protein, which further induced the fusion of viral envelope and cellular membrane or the fusion of cellular membranes, resulting in the entry of the nucleocapsid into the cytoplasm and the formation of typical syncytia. for most paramyxoviruses, the heterotypic fusion activity that has been measured is considerably lower than a virus's homotypic fusion activity. however, the niv and hev envelope glycoproteins could efficiently mediate fusion in heterologous envelope combinations with each other. the existing studies confirmed that the g and f proteins of niv could mediate high-level fusion of bsc-1 cells, u373 cells, bhk 21 cells, and cat embryonic cells [15] . this study demonstrated that the f protein precursor f0 expressed by the recombinant baculovirus could be cleaved to produce f1 subunit and f2 subunit similar to natural f proteins. in this study, the recombinant baculoviruses rbac-niv-f and rbac-niv-g coinfected sf9 insect cells that induced quiet syncytia, which suggested that the recombinant f and g proteins possess partial biological activity. the envelope glycoprotein of rna virus plays key role in binding the virus to the host cells, viral entry into host cells, and in eliciting the neutralization antibody. the recombinant vesicular stomatitis virus (vsv) possesses the same competence of producing pseudotype virus to bear foreign viral envelope proteins as the retrovirus. the vsv envelope protein g gene was replaced with the foreign viral envelope protein gene by the reverse genetic technique of negative strand rna virus. the foreign envelope proteins were assembled on the envelope of vsv to produce the vsv-pseudotype, which resemble the donor virus of the foreign envelope protein in the function of binding acceptor, the mechanism of viral entry and the sensibility and specificity of the neutralization antibody. therefore, the envelope protein g gene of vsv and retrovirus were replaced with the report gene and complemented with vsv or retrovirus g glycoprotein expressed in trans to produce vsv pseudotype, which was used to replace the biosafety high-level virus or the virus that the observation of its cytopathic effect (cpe) is difficult in the study of the detecting of neutralization antibody, the characteristics of receptor binding, antigenicity and epitope [16, 17] . presently, niv does not exist in china and niv was not assented to initiate live virus. therefore, vsv envelope protein g gene, in this study, was replaced with the green fluorescent protein gene, and complemented with niv g and f glycoprotein expressed in trans, which produced a safe, stable, and high titer vsv pseudotype that possessed the competency of infection and duplication. the vsv pseudotype replaced live niv. the neutralizing antibody assay obtained satisfactory effectiveness when the vsv pseudotype replaced live niv. the passive immunization protection test, in small animal model, demonstrated that the neutralization antibody formed the effective protection to lethal challenge of niv [18] . g and f of niv were major viral structural proteins, which induced neutralization antibody responses. in this study, immunization with insect cells was infected by the recombinant baculoviruses, thereby expressing niv g and f proteins, eliciting g and f protein-specific antibody responses in mice. furthermore, the g and f protein-specific antibodies neutralized the infectivity of the vsvδg*f/g. rng that induced higher titer of neutralization antibody (>128) than rnf (>64). both rng and rnf induced higher titer of neutralization antibody than the titer of neutralization antibody of serum from rabbits immunzied with inactivated niv (>32).the study of the measles virus showed that hn protein induced higher titer of neutralization antibody than f protein, in vivo [19] . in addition, the comparative study of dna immunization of niv g and f protein showed that g protein induced higher titer of neutralization antibody and elisa antibody than f protein (the result is reported in other article). baculovirus possess the competence of transient infection to mammalian cell. therefore, the recombinant baculoviruses that expressed specific immunogen induced effective specific immune responses [20] . in this study, the cell suspension of sf9 insect cells infected by the recombinant baculovirus immunized mice, in which rnf, rng and the recombinant baculovirus were the immunogen to form immunostimulation. at present, the vaccine against niv has not been successfully developed. consequently, f and g protein expressed by the recombinant baculoviruses could be safe diagnostic antigens for the surveillance and monitoring of niv and promising subunit vaccines for the prevention of niv. update: outbreak of nipah virus--malaysia and singapore nipah virus encephalitis--investigation of a new infection fatal encephalitis due to nipah virus among pig farmers in malaysia serologic evidence for the presence in pteropus bats of a paramyxovirus related to equine morbillivirus isolation of hendra virus from pteropid bats: a natural reservoir of hendra virus nipah virus infection in bats (order chiroptera) in peninsular malaysia the natural history of hendra and nipah viruses properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses a system for functional analysis of ebola virus glycoprotein complete nucleotide sequences of nipah virus isolates from malaysia animal virology. 2 nd ed mutations in the newcastle disease virus hemagglutinin-neuraminidase protein that interferes with its ability to interact with the homologous f protein in the promotion of fusion association of the parainfluenza virus fusion and hemagglutinin-neuraminidase glycoproteins on cell surfaces measles virus envelope glycoproteins hetero-oligomerize in the endoplasmic reticulum membrane fusion tropism and heterotypic functional activities of the nipah virus and hendra virus envelope glycoproteins longitudinally profiling neutralizing antibody response to sars coronavirus with pseudotypes s protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell linesand is targeted by neutralizing antibodies in infected patients nipah virus: vaccination and passive protection studies in a hamster model measles virus baculovirus infection of nondividing mammalian cells: mechanisms of entry and nuclear transport of capsids key: cord-030131-klhg7x8z authors: tan, dingyu; walline, joseph harold; ling, bingyu; xu, yan; sun, jiayan; wang, bingxia; shan, xueqin; wang, yunyun; cao, peng; zhu, qingcheng; geng, ping; xu, jun title: high-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial date: 2020-08-06 journal: crit care doi: 10.1186/s13054-020-03214-9 sha: doc_id: 30131 cord_uid: klhg7x8z background: high-flow nasal cannula (hfnc) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. however, evidence to support the use of hfnc in chronic obstructive pulmonary disease (copd) patients with hypercapnic respiratory failure after extubation is limited. this study was conducted to test if hfnc is non-inferior to non-invasive ventilation (niv) in preventing post-extubation treatment failure in copd patients previously intubated for hypercapnic respiratory failure. methods: copd patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to hfnc or niv at extubation at two large tertiary academic teaching hospitals. the primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (niv for patients in the nfnc group or vice versa). results: ninety-six patients were randomly assigned to the hfnc group or niv group. after secondary exclusion, 44 patients in the hfnc group and 42 patients in the niv group were included in the analysis. the treatment failure rate in the hfnc group was 22.7% and 28.6% in the niv group—risk difference of − 5.8% (95% ci, − 23.8–12.4%, p = 0.535), which was significantly lower than the non-inferior margin of 9%. analysis of the causes of treatment failure showed that treatment intolerance in the hfnc group was significantly lower than that in the niv group, with a risk difference of − 50.0% (95% ci, − 74.6 to − 12.9%, p = 0.015). one hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation (p < 0.050). twenty-four hours after extubation, the respiratory rate of the hfnc group had returned to baseline, but the niv group was still higher than the baseline. forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline. the average number of daily airway care interventions in the niv group was 7 (5–9.3), which was significantly higher than 6 (4–7) times in the hfnc group (p = 0.006). the comfort score and incidence of nasal and facial skin breakdown of the hfnc group was also significantly better than that of the niv group [7 (6–8) vs 5 (4–7), p < 0.001] and [0 vs 9.6%, p = 0.027], respectively. conclusion: among copd patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of hfnc after extubation did not result in increased rates of treatment failure compared with niv. hfnc also had better tolerance and comfort than niv. trial registration: chictr.org (chictr1800018530). registered on 22 september 2018, http://www.chictr.org.cn/usercenter.aspx chronic obstructive pulmonary disease (copd) is one of the leading causes of death worldwide. acute hypercapnic respiratory failure is a common serious complication of copd, and invasive mechanical ventilation is often required for severe cases. longer durations of invasive mechanical ventilation will increase the incidence of ventilator-associated pneumonia and difficulty weaning off ventilation [1, 2] . multiple studies have shown that a sequential strategy with non-invasive ventilation (niv) using a pulmonary infection control (pic) window as the switching point can reduce the duration of invasive ventilation in copd patients and significantly improve prognosis [3, 4] . the success of niv is closely related to the experience and abilities of the treating medical staff, the level of education and compliance of patients, and the performance of the niv device [5, 6] . due primarily to poor patient tolerance, niv fails in approximately 15 to 25% of patients, potentially leading to endotracheal intubation [7] [8] [9] . for post-extubation patients with copd who cannot tolerate niv or have contraindications to niv, alternative respiratory support methods are urgently needed. high-flow nasal cannula (hfnc) oxygen therapy is a new type of respiratory support system which can supply high flow mixed gases through special nasal prongs at a sufficient temperature and humidity for patient comfort. many studies have confirmed that the comfort and tolerance of hfnc is significantly higher than that of niv [10] [11] [12] . as an alternative to niv, hfnc has been shown to be as efficacious as niv in preventing post-extubation respiratory failure or re-intubation in patients with hypoxemic respiratory failure [13, 14] . however, the postextubation application of hfnc in copd patients with hypercapnic respiratory failure has not been widely studied. in a pilot study, hfnc was reported to maintain similar patient vital signs and arterial blood gases as niv in post-extubated hypercapnic copd patients [15] . this trial was conducted to test the hypothesis that hfnc immediately after extubation is non-inferior to niv in reducing treatment failure in copd patients previously intubated for hypercapnic respiratory failure. this was a multicenter, unblinded, non-inferiority, randomized controlled trial, registered at chictr.org (chictr1800018530). from january 2019 to february 2020, the study was performed in the intensive care units (icus) of two large tertiary-care hospitals. this study was approved by the human subjects ethics committees of the two hospitals involved (2018ky-081 and 20180012), and informed consent was obtained from all enrolled patients or their relatives. copd patients with hypercapnic respiratory failure who received invasive ventilation were screened for enrollment. the diagnosis of copd was established according to the gold criteria [16] . other inclusion criteria included patients who were ≤ 85 years of age, able to care for themselves within the past year, respiratory failure induced by broncho-pulmonary infection, and meeting criteria of the pic window. exclusion criteria were age less than 18 years; lacking informed consent; contraindications to niv (oral or facial trauma, poor sputum excretion ability, hemodynamic instability); poor shortterm prognosis (high risk of death within7 days or receiving palliative treatment); heart, brain, liver, or kidney failure; tracheotomy; or a weak cough ability during the pic window. the following types of patients were secondarily excluded: withdrawn informed consent, loss to followup, uncertain 28-day survival, discharge from hospital within 48 h after enrollment, and patients who refused to use their assigned device. the settings of the enrolled patients' invasive mechanical ventilation were adjusted by the attending physician according to the patient's ventilation status and blood gas analysis. the patients were randomly divided into the hfnc group and the niv group when the pic window appeared. randomization was performed using a computer-generated random number generator, and allocation was concealed through an opaque envelope. these envelopes were kept in permuted blocks of ten, five each for niv and hfnc, to ensure an even distribution of subject numbers in both groups at both centers. all subjects receiving niv (philips v60 or bipap vision) were set in s/t mode with a standard oral-nasal (full-face) mask (rt040). niv settings were adjusted with an adaptive method: the initial expiratory pressure airway pressure was set to 4 cmh 2 o, and the pressure level was gradually increased to ensure that the patient could trigger the niv device with each inhalation. the inspiratory airway pressure was initially set to 8 cmh 2 o and gradually increased to achieve a satisfactory tidal volume with acceptable tolerance. the pressure level and the fraction of inspiration oxygen (fio 2 ) were adjusted to maintain a respiratory rate ≤ 28/min, a pulse oxygen saturation (spo 2 ) of 88-92%, and a partial pressure of arterial carbon dioxide (paco 2 ) of either 45-60 mmhg or the last paco 2 level recorded prior to extubation. subjects randomized to the hfnc group (airvo™ 2, fisher & paykel healthcare, auckland, new zealand) were given suitable large-bore nasal prongs selected according to the size of the patients' nostrils. the initial airflow was set at 50 l/min and adjusted according to patient tolerance. the hfnc was set to an absolute humidity of 44 mg h 2 o/l, temperature was set to 37°c, and fio 2 was adjusted to maintain an spo 2 of 88-92%. the patient's initial respiratory support was targeted to last at least 2 h and then continued as needed. nasal cannula oxygen was administered during any interruptions to niv. niv or hfnc were discontinued when the total daily treatment duration was less than 4 h and could be reused if needed. treatment success was defined as no need for respiratory support within 72 h after stopping niv or hfnc. the primary outcome was treatment failure, defined as a return to invasive mechanical ventilation, or a switch in respiratory support modality (i.e., changing from hfnc to niv or from niv to hfnc). secondary outcomes included arterial blood gas analysis [ph, pao 2 (partial pressure of oxygen in arterial blood), paco 2 , and fio 2 ] and vital signs such as respiratory rate, heart rate, and blood pressure at 1, 24, and 48 h after extubation, as well as the total duration of respiratory support after extubation, the daily number of nursing airway care interventions, the patients' comfort score, the patients' dyspnea score, the incidence of nasofacial skin breakdown, 28-day mortality, and total icu and hospital lengths of stay. airway care interventions were defined as the need for nursing staff to correct unplanned device displacement due to intolerance, discomfort, or another reason, or the need for nursing staff to assist in the removal or fixation of the device due to sputum, eating, or drinking. the patient's comfort score was assessed using a modified 10-cm visual analog scale, in which 1 meant very uncomfortable and 10 meant very comfortable [11] . the patients' dyspnea was evaluated with a borg rating scale [17] . the criteria for reintubation in this study were [18, 19] cardiac arrest or obvious hemodynamic instability, refractory hypoxemia (pao 2 < 50 mmhg with sufficient oxygen therapy), significant hypercapnia with ph ≤ 7.20, severe disturbances of consciousness such as coma, respiratory depression (respiratory frequency < 8/min), or severe dyspnea (respiratory frequency > 40/min). based on previous studies [20, 21] , we estimated that niv would fail in 22% patients (either intubation or intolerance) of included copd patients, and the absolute difference of treatment failure rates between hfnc and niv was likely to fall between 4 and 12% [14] . after discussions with three senior pulmonologists, we set the non-inferiority cutoff at 9%. to assess non-inferiority using an α = 0.50, β = 0.20, and 1-sided testing, 44 subjects were needed in each group (88 total). for the primary outcome, analysis was performed both on an intention-to-treat and on a per-protocol basis. the kaplan-meier method was used to draw the cumulative survival and failure curves. the kolmogorov-smirnov test was used to test the normal distribution for measurement data. normally distributed data were expressed as means ± standard deviation, and the skewed distributed data was reported as medians with interquartile (25th-75th) percentiles. the two groups were compared using t tests or mann-whitney u tests. numeric data were expressed as a percentage (%), using χ 2 or fisher's exact probability tests. the comparison of vital signs and blood gas analyses at multiple time points was performed by repeated measures analysis of variance, or non-parametric test of multiple correlated samples (friedman test for heterogeneity of variance or the skewed distributed data), in which the significance level was adjusted using the bonferroni correction method. all data analysis was conducted using spss 26.0 (ibm corporation, armonk, ny, usa). among 149 copd patients who received invasive ventilation in our enrolling centers during the study period, 96 (64.4%) patients were randomized to the niv or hfnc groups after 53 patients were excluded for various reasons (see fig. 1 ). six patients in the niv group and four patients in the hfnc group were secondarily excluded. finally, 42 patients in the niv group and 44 patients in the hfnc group were included in the analysis. demographic, relevant comorbidities, smoking history, copd medications, respiratory therapy at home, available pulmonary function tests, the simplified acute physiology score ii (saps ii), and the acute physiological and chronic health status score ii (apache ii) at admission in the two groups were similar (see table 1 ). seventeen (38.6%) patients in the hfnc group and 18 (42.9%) in the niv group initially received niv or hfnc after admission before invasive ventilation, and the remaining patients received invasive ventilation directly. there were also no significant differences in respiratory parameters, blood gas analyses, and vital signs between the two groups at the time of enrollment (pic window before extubation). the stable fio 2 after extubation in the hfnc group was 0.32 (0.28-0.38), which was not significantly different from 0.35 (0.30-0.40) in the niv group. treatment failure occurred in 10 patients (22.7%) in the hfnc group and 12 patients (28.6%) in the niv group (risk difference, − 5.8%; 95% ci, − 23.8 to 12.4%; see table 2 ). additionally, kaplan-meier curves showed no statistical difference in cumulative failure rates between the two groups (log-rank test 0.521, p = 0.470, see fig. 2 ). among the patients with treatment failure, the intubation rate in the hfnc group was similar to that of the niv group (− 0.65%; 95% ci, − 16.01 to 14.46%), and the treatment switch rate was lower than that in the niv group (− 5.2%; 95% ci, − 19.82 to 9.05%). however, there were no significant differences between the two groups in intubation or treatment switch rate. analysis of the causes of treatment failure showed that treatment intolerance was significantly lower in the hfnc group than in the niv group, with a risk difference of − 50.0% (95% ci, − 74.6 to − 12.9%, p = 0.015, see table 2 ). there was no significant difference between the two groups in exacerbated respiratory distress, hypoxemia, or carbon dioxide retention. the causes for six intolerances in the niv group were feelings of data are shown as means ± standard deviation, number (%) patients, or median (interquartile range) hfnc high-flow nasal cannula oxygen therapy, niv non-invasive ventilation, copd chronic obstructive pulmonary disease, nco nasal cannula oxygen, icu intensive care unit, apache ii acute physiology and chronic health evaluation ii, saps ii simplified acute physiology score ii, imv invasive mechanical ventilation, pic pulmonary infection control, peep positive end expiratory pressure, paco 2 partial pressure of arterial carbon dioxide, pao 2 partial pressure of arterial oxygen, fio 2 fraction of inspiration oxygen *twenty-five cases in the hfnc group and 27 cases in the niv group claustrophobia (n = 2), excessive air flow or pressure (n = 2), breathlessness (n = 1), and headache (n = 1). heart rate and mean arterial pressure within 48 h after extubation in the two groups were not significantly different from baseline levels before extubation. respiratory rate in both groups was faster than before extubation at 1 h after extubation (p < 0.050, see table 3 ). the respiratory rate 24 h after extubation in the hfnc group had decreased to its baseline and was lower than the respiratory rate in the niv group [20 (17.3-24.5)/min vs 24.5 (18-27)/min, p < 0.050]. the niv group's respiratory rate was also higher than its baseline level. there was no significant difference in respiratory rate between the two groups at 48 h after extubation. arterial blood gas analyses showed that the pao 2 /fio 2 and ph values in the hfnc group were lower than their baseline levels, while paco 2 was higher than the baseline level 1 h after extubation (all p < 0.050, see table 3 ). the pao 2 /fio 2 , ph, and paco 2 in the hfnc and niv groups 24 h and 48 h after extubation were not statistically different from the baseline levels. there were no significant differences in the duration of post-extubation respiratory support, dyspnea scores, icu, or hospital total lengths of stay between the two groups (all p < 0.050, see table 4 ). the 28-day mortality in the hfnc group was 15.9%, which was not significantly different from the 11.9% in the niv group (logrank test 0.288, p = 0.591, see fig. 3 ). the number of daily airway care interventions was significantly lower in the hfnc group than in the niv group [6 (4-7) vs 7 (5-9.3), p = 0.006]. the comfort score in the hfnc group was also significantly higher than that in the niv group [7 (6-8) vs 5 (4-7), p < 0.001], whereas the incidence of nasofacial skin breakdown was significantly lower in the hfnc group than in the niv group (0 vs 9.6%, p = 0.027). this multicenter, randomized controlled trial showed that hfnc was not inferior to niv at preventing postextubation treatment failure and re-intubation for copd patients recently extubated after hypercapnic respiratory failure. compared with niv, hfnc was more comfortable and better tolerated. the number of airway care interventions and the incidence of nasofacial skin breakdown associated with hfnc were significantly lower than in niv. hfnc appears to be an effective means of respiratory support for copd patients extubated after severe hypercapnic respiratory failure. invasive ventilation is sometimes necessary to rescue copd patients with severe hypercapnic respiratory failure. weaning strategies which include niv are recommended as the standard treatment to reduce rates of ventilator-associated pneumonia and mortality without increasing the risk of re-intubation or weaning failure [22] . however, niv intolerance appears in more than 15% patients due to various reasons, which increases the risk of treatment failure and re-intubation [23, 24] . like in this study, many others have found that hfnc is often better tolerated than niv, but data on copd patients so far has been limited. hfnc has been increasingly suggested for use in patients with copd with acute hypercapnic respiratory failure. bräunlich et al. reported that in 38 patients with an acute exacerbation of copd and a ph of less than 7.38, hfnc increased the ph by 0.052 and reduced carbon dioxide by 9.1 mmhg [25] . in a prospective observational study involving 30 patients with moderate hypercapnic respiratory failure who were intolerant to niv, patients' ph improved and respiratory rate decreased with hfnc treatment, and the non-response rate to hfnc was only 13.3% [26] . subsequently, two cohort studies with larger samples showed that for copd patients with acute moderate hypercapnic respiratory failure, similar tracheal intubation and mortality rates were observed between hfnc and niv, while hfnc was better tolerated [27, 28] . other efforts to observe the efficacy of hfnc in copd patients after invasive ventilation have been limited. in a cross-over study comparing hfnc to conventional low-flow oxygen therapy, hfnc was found to significantly decrease post-extubation work of breathing and neuroventilatory drive in copd patients recovering from acute hypercapnic respiratory failure [29] . in a small randomized controlled trial, hypercapnic copd patients received either hfnc or niv immediately after extubation [15] . at 3 and 24 h after extubation, the ph in the hfnc group was higher than niv group. no significant differences of vital signs and arterial blood gases were found at 48 h after extubation. unlike in the above study, the respiratory rate in both groups of our study increased at 1 h after extubation, which may be related to the relatively lower intensity of respiratory support after extubation. the respiratory rate in the hfnc group decreased to its baseline level 24 h after extubation, while the respiratory rate in the niv group was still high at 24 h. this can be explained by the relatively poor tolerance of niv and the increase in effective alveolar ventilation caused by the washout effect of dead space in hfnc. one hour after extubation, the ph in the hfnc group of this study decreased and the paco 2 increased, while the niv group had no significant change from its baseline level. the difference between the two groups may be because hfnc does not have the added pressure support of niv, resulting in decreased ventilation and oxygenation. however, the excellent tolerance and increased effective alveolar ventilation gradually made up for the above deficiencies, so that there was no significant difference in blood gas values between the two groups at 24 and 48 h after extubation. to the best of our knowledge, this is the first randomized controlled trial to compare the failure rate of hfnc and niv in patients with copd after invasive ventilation. treatment failure in this study was defined as reintubation or switch to the other treatment modality. although the latter criterion added an element of patient subjectivity to the definition, this composite end-point reflects the pragmatic application of hfnc or niv in everyday clinical practice [30] . analysis of the causes of treatment failure in this study showed that treatment intolerance was significantly higher in the niv group than in the hfnc group, suggesting that poor tolerance is an important reason for the failure of niv treatment. doshi et al. also found that 29% of niv failures were attributed to treatment intolerance, which was significantly higher than the 4% rate of hfnc [31] . hfnc's design does not lead to a sense of claustrophobia, which significantly improves compliance. at the same time, the heating and humidifying function of hfnc enables the gas delivered to reach an absolute humidity of 44 mg h 2 o/l and a temperature of 37°c, which effectively promotes the discharge of secretions while avoiding side effects such as dry mucous membranes [32] . because of these characteristics, patients can easily tolerate a gas flow rate of up to 50-60 l/min. the better tolerance of hfnc over niv is clearly seen in comparing the comfort scores between the two groups. the number of airway care interventions and cases of nasofacial skin breakdown in the hfnc group were also significantly lower than those in the niv group, which was related to the hfnc nasal plug design and better comfort. due to intolerance, drinking and eating, sputum clearance, communication, discomfort, or displacement of the niv mask, niv patients frequently remove their masks and significantly increase the nursing workload [28] . patients in the hfnc group were not restricted by respiratory support in eating, drinking, and communicating. the incidence of skin breakdown and displacement of nasal prongs was extremely low. there were some limitations to this study. first, the primary endpoint of this study was a composite of reintubation rate and switching to the other treatment modality, which has potential limitations described above. as for the re-intubation rate, the possibility of obtaining a positive result by increasing the sample size cannot be ruled out. second, the settings for the hfnc gas flow in this study were based on each patient's tolerance level, which is subjective. in subsequent studies, the hfnc gas flow could be titrated through diaphragmatic potential or ultrasound assessment of diaphragmatic muscle movement for better standardization. finally, attending physicians could not be blinded to the study group since the devices were clearly different. however, investigators were excluded from clinical decisions and randomization was employed to help reduce bias. among copd patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of hfnc as compared with niv after extubation did not result in increased rates of treatment failure, while hfnc had better tolerance and comfort. these findings support the use of hfnc in such patients, especially for those who cannot tolerate niv. abbreviations copd: chronic obstructive pulmonary disease; niv: non-invasive ventilation; hfnc: high-flow nasal cannula oxygen therapy; pic: pulmonary infection control; icu: intensive care unit; apache ii: acute physiological and chronic health status score ii; saps ii: simplified acute physiology score ii; paco 2 : partial pressure of arterial carbon dioxide; pao 2 : partial pressure of arterial oxygen; fio 2 : fraction of inspired oxygen weaning from mechanical ventilation the attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. the canadian critical trials group efficacy of two noninvasive weaning strategies in intubated patients with chronic obstructive pulmonary disease: a meta-analysis and indirect treatment comparison pulmonary infection control window as a switching point for sequential ventilation in the treatment of copd patients: a metaanalysis practical insight to monitor home niv in copd patients causes of failure of noninvasive mechanical ventilation evolution of mechanical ventilation in response to clinical research complications of noninvasive ventilation in acute care a multicenter randomized trial assessing the efficacy of helium/oxygen in severe exacerbations of chronic obstructive pulmonary disease high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure nasal highflow improves ventilation in patients with copd high-flow oxygen therapy after noninvasive ventilation interruption in patients recovering from hypercapnic acute respiratory failure: a physiological crossover trial can high-flow nasal cannula reduce the rate of reintubation in adult patients after extubation? a meta-analysis effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial comparison of high flow nasal cannula with noninvasive ventilation in chronic obstructive pulmonary disease patients with hypercapnia in preventing postextubation respiratory failure: a pilot randomized controlled trial clinical guideline highlights for the hospitalist: the gold and nice guidelines for the management of copd perceived exertion as an indicator of somatic stress what determines immediate use of invasive ventilation in patients with copd? global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. gold executive summary non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: cochrane systematic review and meta-analysis collaborating research group for noninvasive mechanical ventilation of chinese respiratory, s. pulmonary infection control window in treatment of severe respiratory failure of chronic obstructive pulmonary diseases: a prospective, randomized controlled, multi-centred study non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease noninvasive ventilation intolerance: characteristics, predictors, and outcomes treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: a randomized controlled trial nasal high-flow in acute hypercapnic exacerbation of copd efficacy and safety of high-flow nasal cannula oxygen therapy in moderate acute hypercapnic respiratory failure. rev bras ter intensiva high flow nasal cannulae oxygen therapy in acute-moderate hypercapnic respiratory failure high flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: an observational cohort study high-flow nasal cannula oxygen therapy decreases postextubation neuroventilatory drive and work of breathing in patients with chronic obstructive pulmonary disease high-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial high-velocity nasal insufflation in the treatment of respiratory failure: a randomized clinical trial high-flow nasal cannula oxygen therapy in adults: physiological benefits, indication, clinical benefits, and adverse effects publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations none. the datasets used and analyzed during the current study are available from the corresponding author in response to reasonable requests. this study was approved by the human subjects ethics committees of the two hospitals involved (2018ky-081 and 20180012), and informed consent was obtained from all enrolled patients or their relatives. not applicable. the authors declare that they have no competing interests. key: cord-000705-w52dc97h authors: ríos, fernando g; estenssoro, elisa; villarejo, fernando; valentini, ricardo; aguilar, liliana; pezzola, daniel; valdez, pascual; blasco, miguel; orlandi, cristina; alvarez, javier; saldarini, fernando; gómez, alejandro; gómez, pablo e; deheza, martin; zazu, alan; quinteros, mónica; chena, ariel; osatnik, javier; violi, damian; gonzalez, maria eugenia; chiappero, guillermo title: lung function and organ dysfunctions in 178 patients requiring mechanical ventilation during the 2009 influenza a (h1n1) pandemic date: 2011-08-17 journal: crit care doi: 10.1186/cc10369 sha: doc_id: 705 cord_uid: w52dc97h introduction: most cases of the 2009 influenza a (h1n1) infection are self-limited, but occasionally the disease evolves to a severe condition needing hospitalization. here we describe the evolution of the respiratory compromise, ventilatory management and laboratory variables of patients with diffuse viral pneumonitis caused by pandemic 2009 influenza a (h1n1) admitted to the icu. method: this was a multicenter, prospective inception cohort study including adult patients with acute respiratory failure requiring mechanical ventilation (mv) admitted to 20 icus in argentina between june and september of 2009 during the influenza a (h1n1) pandemic. in a standard case-report form, we collected epidemiological characteristics, results of real-time reverse-transcriptase--polymerase-chain-reaction viral diagnostic tests, oxygenation variables, acid-base status, respiratory mechanics, ventilation management and laboratory tests. variables were recorded on icu admission and at days 3, 7 and 10. results: during the study period 178 patients with diffuse viral pneumonitis requiring mv were admitted. they were 44 ± 15 years of age, with acute physiology and chronic health evaluation ii (apache ii) scores of 18 ± 7, and most frequent comorbidities were obesity (26%), previous respiratory disease (24%) and immunosuppression (16%). non-invasive ventilation (niv) was applied in 49 (28%) patients on admission, but 94% were later intubated. acute respiratory distress syndrome (ards) was present throughout the entire icu stay in the whole group (mean pao(2)/fio(2 )170 ± 25). tidal-volumes used were 7.8 to 8.1 ml/kg (ideal body weight), plateau pressures always remained < 30 cmh(2)o, without differences between survivors and non-survivors; and mean positive end-expiratory pressure (peep) levels used were between 8 to 12 cm h(2)o. rescue therapies, like recruitment maneuvers (8 to 35%), prone positioning (12 to 24%) and tracheal gas insufflation (3%) were frequently applied. at all time points, ph, platelet count, lactate dehydrogenase assay (ldh) and sequential organ failure assessment (sofa) differed significantly between survivors and non-survivors. lack of recovery of platelet count and persistence of leukocytosis were characteristic of non-survivors. mortality was high (46%); and length of mv was 10 (6 to 17) days. conclusions: these patients had severe, hypoxemic respiratory failure compatible with ards that persisted over time, frequently requiring rescue therapies to support oxygenation. niv use is not warranted, given its high failure rate. death and evolution to prolonged mechanical ventilation were common outcomes. persistence of thrombocytopenia, acidosis and leukocytosis, and high ldh levels found in non-survivors during the course of the disease might be novel prognostic findings. on april 2009, a novel influenza a (h1n1) virus emerged in mexico and spread rapidly across the world [1, 2] . as of 17 june 2010, more than 214 countries had reported confirmed cases of infection with pandemic 2009 influenza a (h1n1) virus, including at least 18,156 deaths [3] . unlike seasonal influenza, in which hospitalizations occur among patients younger than 2 and older than 65 years, or in those with underlying diseases [4] , this novel virus affected otherwise healthy young and middle-aged adults and obese individuals [2, 5] . patients with previous respiratory disease, immunocompromised hosts and pregnant women were affected as frequently as with seasonal influenza [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] . although a mild form of the disease was prevalent, it soon became evident that the 2009 influenza a (h1n1) virus could also provoke severe, acute respiratory failure requiring admission to the intensive care unit (icu) for mechanical ventilation [16] , which was reflected in the severe pathological injury found at autopsy [17] . the argentinian population was greatly affected during the pandemic, with a total of 1,390,566 cases of influenza-like illness requiring 14,034 hospitalizations. of the 11,746 confirmed cases of patients infected with the new strain, 617 died [18] . this represents a death rate per infection of 4.3% in hospitalized cases; an intermediate figure compared to 3.6% in brazil, 1.2% in chile, and approximately 6% in uruguay, colombia and venezuela [19] . it should be noted that these numbers reflect great uncertainty, particularly with regard to case diagnosis. lack of testing of mild disease and difficulties due to laboratory overload have also been well described [15, 20] . these general problems have been acknowledged by experts [21] . the severity of disease was rapidly perceived by health authorities and scientific societies. hence, a committee of experts of the argentinian society of intensive care medicine decided to focus on the most acutely ill patients: those presenting with diffuse viral pneumonitis requiring mechanical ventilation. they designed an epidemiological study, recently-published, to determine risk factors and outcomes [15] ; this is one of many series up to the present that have described epidemiological and clinical aspects of the 2009 influenza a (h1n1) pandemic [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] . there remains, however, a paucity of data published on physiological evolution during icu stay [22] . this present study, concurrently planned with the first by the same committee of experts, thus aims to provide such information. our objectives were: first, to characterize alterations of oxygenation, respiratory mechanics and the use of mechanical ventilation; second, to explore compliance with protective lung ventilation; and, finally, to assess the evolution of laboratory findings and organ dysfunctions throughout the course of the disease. this was a multicenter, inception cohort study that included patients aged > 15 years admitted to the icu with a previous history of influenza-like illness, evolving to acute respiratory failure that required mechanical ventilation during the 2009 winter in the southern hemisphere. these patients had confirmed or probable disease caused by the 2009 influenza a (h1n1) virus and were included in the registry of cases of the argentinian society of intensive care medicine (sati), created to characterize local aspects of the pandemic. on 27 june 2009, a form to collect online epidemiological data was posted on the official sati website. a detailed description and analysis of this information was recently published [14] . there was also an optional, more comprehensive casereport form to complete, developed by experts of the sati's respiratory committee for recording certain prespecified variables throughout icu stay, which included mechanical ventilation (mv), respiratory mechanics, oxygenation, blood chemistry and organ failure variables. this information was collected over 10 days and is analyzed in the present study. patients were characterized as confirmed, probable or possible cases of 2009 influenza a (h1n1) [20] according to the findings in the respiratory samples collected on admission. some specimens, however, were not analyzed because laboratories soon became overloaded, especially at the beginning of the pandemic. as of 25 september 2009, the weekly update of the ministry of health reported that in patients ≥5 years with influenzalike illness, the 2009 influenza a (h1n1) virus had displaced other respiratory viruses in 93.4% of the samples processed [23, 24] . as a result of this, probable and suspected cases were considered as caused by the novel virus and were so included in the study. we collected dates of hospital and icu admission, and of mv onset; demographics; risk factors for influenza a; actual weight; height; severity of illness (acute physiology and chronic health evaluation ii, apache ii), organ failures (sequential organ failure assessment, sofa); type of mv used, as noninvasive (niv) and invasive; and date of intubation. ideal body weight (ibw, ml/kg) and body mass index (bmi) were calculated; obesity was defined as a bmi > 30. at mv onset (day 0) and on days 3, 7 and 10, until death or discharge, whichever occurred first, we recorded: (1) mv-related variables. (2) mv modes: volume-controlled ventilation (vcv); pressure-controlled ventilation (pcv); bilevel mode; pressure support ventilation (psv); other. (3) tidal volume (vt, in ml/kg of ibw) (4) pressures: peak, plateau pressures, total positive end-expiratory pressure (peep) and driving pressure (plateau pressure -peep), in cmh2o. the main outcome measure was hospital mortality; secondary outcomes were length of mv, of icu (losicu) and of hospital (loshosp) stays. in case of missing observations, local study coordinators were contacted to provide the corresponding values. proportions were calculated as percentages of existing data. no assumptions for missing data were made. statistical analysis was performed with spss 17.0 (spss inc., chicago, il, usa). data were analyzed for the entire population; for the subgroups of survivors vs. non-survivors; and for patients receiving niv on admission vs. those who did not. descriptive statistics used were: mean ± standard deviations (sd) and median and 25-75% interquartile ranges (iqr) for continuous data of normal and non-normal distribution, respectively; and percentages for categorical data. differences between subgroups were analyzed with unpaired t test, mann-whitney u test, and chi-square tests, as appropriate. a p-value of <.05 was considered statistically significant. a kaplan-meier curve was constructed to evaluate survival over the follow-up period. over time, normally distributed data were analyzed with two-way repeated measures of anova. at the pre-specified time points, differences within the entire group and subgroups, and between subgroups, were tested using paired and unpaired t tests, respectively. in non-normally distributed data, differences over time within the entire group and the subgroups were analyzed with friedman's and wilcoxon tests. comparisons between subgroups at the pre-specified time points were tested with mann-whitney u test. the bonferroni correction was used to adjustments for multiple comparisons. the local institutional review boards waived the need for informed consent, given the general lack of knowledge on the clinical and outcome characteristics of the ongoing pandemic and to the non-interventional study design. general characteristics (table 1) between 6 june and 28 august 2009, the sati's online registry included 337 patients admitted to 35 icus with confirmed/probable/possible diffuse viral pneumonitis caused by influenza a (h1n1), with acute respiratory failure requiring mv (14) . of these, 178 consecutive patients admitted to 20 icus were followed over time, and are presented in this study. to address any potential concern that unconfirmed cases could belong to a different population of patients, we performed a sensitivity analysis of clinical and outcome characteristics data after exclusion of these patients. the results of this analysis did not differ from those of the primary assessments, so the 178 patients are considered for evaluation. briefly, patients were middle-aged, with no gender preponderance; they had a history of symptoms of nearly one-week duration and were ventilated at 1 [0 to -2] day after hospital admission. pre-existent respiratory diseases, obesity, and diseases causing immunosuppression were the most frequent comorbid conditions; and prevalence of pregnancy was higher than in the general population, as expected [25] . non-survivors were sicker on admission; duration of previous symptoms was longer; and organ failures were more severe. obesity and immunosuppression were significantly more frequent as predisposing conditions. ninety-three patients survived (52%) (see figure 1 ). (table 2) during the study period, the entire group had vt values between 7.8 to 8.1 ml/kg of ibw, with plateau pressures remaining always < 30 cmh 2 o. non-survivors displayed a trend towards lower vt and higher plateau pressures, which differed significantly from survivors only at day 7. intermediate peep levels were used, and decreased in survivors from day 3 onwards. driving pressures were similar over time in all patients; only at admission did non-survivors exhibit higher values. pao 2 /fio 2 increased significantly over time in all patients and in survivors. it remained, however, < 200 in the whole group throughout the entire icu stay due to non-survivor values. non-survivors displayed significantly lower pao 2 /fio 2 at all time points. lung infiltrates (in quadrants) peaked at day 3 (3.1 ± 1.0 vs. 2.9 ± 1 at day 0, p < 0.01) and then decreased during the study in the entire group, especially at day 10 (2.8 ± 1.1, p < 0.83 vs. day 0), which reflected the improvement in survivors (3.1 ± 1.0 at day 3 vs. 2.9 ± 1.0 at day 10, p < 0.01). in figure 2 , the utilization of ventilation modes and rescue therapies in the entire group are shown. briefly, pcv use equaled vcv at day 10, preceded by deterioration in oxygenation and respiratory mechanics: pao 2 / fio 2 78 ± 24 vs. 128 ± 33, (p = 0.03); paco 2 44 ± 4 vs. 35 ± 3 mmhg (p = 0.04); ph 7.29 ± 0.03 vs. 7.39 ± 0.05 (p = 0.05), and plateau pressures of 30 ± 2 vs. 25 ± 3 cmh 2 o (p = 0.03). recruitment maneuvers became significantly more common in non-survivors at day 3 (46%, vs. 29% in survivors; p = 0.03), as did prone positioning (24%, vs. 14%; p = 0.001). after that, only prone positioning remained significantly more used in nonsurvivors (at day 7: 38%; vs. 14%, p = 0.004; and at day 10: 25%; vs. 5%, p = 0.02). six patients received tracheal gas insufflation; only one survived. neuromuscular blockers were prescribed in 18% of patients on admission; and their use was subsequently more frequent in non-survivors (day 3: 14% vs. 8%, p = 0.02; and day 7: 14% vs. 8%, p = 0.04). the main causes of death were refractory hypoxemia (64%); followed by multiorgan dysfunction syndrome (15%) and shock (10%). prolonged mechanical ventilation and long icu and hospital stays were frequent (table 1) . tracheostomy was performed in 29 patients (16%) at day 14 [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] . acid-base variables and fluid balance (table 3) arterial ph increased over time in the whole cohort and in both subgroups, perhaps secondary to general resuscitation measures. despite this, non-survivors displayed significantly lower ph at all time points, owing to changes in base excess on days 0 and 3, and to pco 2 elevations thereafter. respiratory rates remained unchanged, only increasing at day 10 in non-survivors; nevertheless, this corresponded to the highest pco 2 values, indicating the more severe respiratory compromise. bicarbonate paralleled ph behavior. changes in fluid balance did not show clear trends: only at day 10 they decreased significantly, expressing survivors' behavior. forty-nine patients (28%) underwent a trial of niv on admission; they were significantly less ill and had a lower incidence of immunosuppression. oxygenation and outcome variables were similar to those of patients not receiving niv. sixty-one percent of patients (n = 30) receiving niv survived; duration of niv was of 8 (2 to 18) hours. there were no differences between survivors and nonsurvivors in the duration of the procedure, or in the type of interface or respirator used. of note, most patients on niv (46 out of 49; 94%) had to be intubated and ventilated invasively for hypoxemic failure. characteristics associated to niv success/failure are shown in table 5 . niv was also used for treating post-extubation respiratory failure in 12 of 178 patients (7%), with success (reintubation not needed) in 8 cases (66%). the most consistent changes over time were found in platelet count, which increased significantly in the whole cohort (p < 0.000 for days 3, 7 and 10 vs. day 0), secondary to elevations in survivors. at all time points, platelets differed between survivors and non-survivors. conversely, white blood cell count showed a progressive creatine-kinase and markers of liver injury (alanine/ aspartate aminotransferases, serum bilirubin; not shown) were mildly elevated and displayed no substantial changes. on the contrary, lactate-dehydrogenase levels were significantly higher in non-survivors throughout the study. creatinine levels were stable over the period, but were significantly higher in non-survivors on days 0 and 3. finally, sofa score diminished over time in all patients (p < 0.000 for days 7 and 10 vs. day 0), as a result of the decrease in survivors. sofa was significantly lower in survivors throughout the study. in figure 3 , the differences between survivors and non-survivors are displayed. we report on a large, prospective cohort of 2009 influenza a (h1n1) patients that were mechanically ventilated for acute respiratory failure due to diffuse pneumonitis during the pandemic in argentina. though most were middle-aged, previously healthy adults, patients with preexistent lung disease, immunosuppression, obesity and pregnancy were also affected. mortality was high and evolution to chronic critical illness was common, as shown by prolonged mechanical ventilation, high needs of tracheostomy, and lengthened icu and hospital stays. patients had characteristically a history of protracted symptoms and displayed severe compromise of oxygenation compatible with ards throughout the study period, which only improved in survivors. at all time points, pao 2 /fio 2 differed significantly between survivors and non-survivors, requiring higher fio 2 and peep in this last subgroup. yet the levels of applied peep were only in the intermediate range, similar to mean values of 8.7 cmh 2 o of peep in an international study on mechanical ventilation [26] , which may explain the relatively high fio 2 used in our study. driving pressures were similar in both subgroups most of the time, suggesting an intention to limit alveolar excursion as part of a protective strategy. it is striking that, as has been described in similar studies on mechanical ventilation performed during the 2009 influenza a (h1n1) pandemic [6, 7] , tidal volumes used were between 7.5 and 8.3 ml/kg ibw, certainly higher than the 6 ml/kg demonstrated as being lungprotective [27] . indeed, barriers to implementing lowtidal volume have been identified and might explain physician behavior [28] . despite this, plateau pressures did remain below 30 cmh 2 o [29] , indicating that lung compliance might have been preserved. perhaps clinicians focused on plateau pressures rather than on tidal volumes [30] since it still remains unclear which should be limited to avoid ventilator-induced lung injury [31] . we, like others [6, 7, 32, 33] , could not find differences in utilized tidal volumes between survivors and non-survivors. even so, non-survivors tended to display lower values, probably reflecting physician efforts to intensify protective ventilation strategies in the most severely compromised. some researchers [34, 35] have suggested that allowing higher tidal volumes in a population of young and previously healthy patients with strong ventilatory drive might reveal an attempt to restrain heavy sedation and neuromuscular blocker use. notwithstanding this, we believe that these findings may also represent clinicians' inadequate prescription, as described in other scenarios [36] . not unexpectedly, vcv was the most common ventilator mode used. pcv use increased throughout the study period, peaking at day 10. this is in contrast with the recently identified trend towards decreased pcv utilization. transition to pcv mode was associated with preceding physiological worsening, so clinicians might have perceived pcv utilization as part of a global lungprotective strategy [37] . refractory hypoxemia was the main cause of death. as in other studies [6, 7, 11] , rescue therapies were frequently applied, with utilization highest 72 hours after admission. recruitment maneuvers and prone positioning were the primary adjuvants utilized; ecmo and hfov are currently not available in argentina. a table 3 oxygenation and acid-base variables, and fluid balance in all patients, and in survivors and non-survivors. prolonged mechanical ventilation course was frequent as reported elsewhere [6] . niv was the first ventilation approach in 28% of cases, with 94% later requiring invasive ventilation, as has been documented in other studies [6, 7, 11] . these common experiences should caution against delaying proper ventilatory support in this group, given that rapid deterioration is common. a recent meta-analysis suggests that niv does not decrease the need for intubation, so evidence to support its use in severe ards is questionable [38] . in our study, improved outcomes with niv could be due to milder disease, evidenced by apache ii. the small number of patients that were not intubated precludes a statistical analysis; however, they were younger, with less severe disease and better oxygenation. significant changes in fluid balance were late and reflected changes in survivors. negative fluid balances could never be obtained, perhaps suggesting a continuing need for hemodynamic support: 72% of patients presented with shock [14] . on the whole, fluid balances remained between those achieved by "liberal" and "conservative" strategies of the fluids and catheters treatment trial, depending on the day evaluated [39] . thus far, it is not clear whether the negative fluid balance has a causal role in improving outcome in ali/ards, or if it simply expresses the global recovery of patients. another important finding was that arterial ph consistently and significantly differed between survivors and non-survivors, as described elsewhere [40, 41] . during the first 72 hours acidosis had a major metabolic component, likely as a sign of hemodynamic impairment. after the first week, respiratory acidosis ensued, indicating either the effects of protective ventilation, or merely deterioration due to progressive shunt, profound ventilation/perfusion mismatch and increased deadspace. with respect to blood chemistry, the usual findings of thrombocytopenia, leukocytosis and mildly elevated creatine-kinase blood levels were present [21, 42] . regrettably, the lymphocyte count was not recorded. in viral infections, thrombocytopenia occurred frequently. although the mechanisms by which the 2009 influenza a (h1n1) virus causes thrombocytopenia are unknown, its lack of resolution is a marker of poor prognosis. both leukocytosis and leucopenia have been found in hospitalized patients with 2009 influenza a (h1n1) [2, 43] ; in our study, persistent leukocytosis was associated with increased mortality. ldh elevations have been previously described in fatal cases [2] , which corresponded to our finding of higher ldh levels in non-survivors at all time points. such elevations have also been reported in seasonal influenza [44] . in experimental studies, increased ldh is a marker of human fetal membrane cell apoptosis induced by influenza virus [45] . finally, multiorgan failure was frequent, and predictably more severe in non-survivors. this study has several strengths: first, the clinical characteristics and time course of pandemic 2009 influenza a (h1n1) are thoroughly described and analyzed. second, data were collected prospectively in consecutive patients and with a standardized casereporting form, representing a large, nationwide cohort. third, temporal patterns of mechanical ventilation use, acid-base and blood chemistry variables, as well as fluid balance and organ failures, are carefully analyzed. prognostic implications are highlighted. finally, we present the largest experience with niv use during the pandemic. study limitations include the focus on mechanically ventilated patients, excluding less severe cases also admitted to the icu. many cases could not be confirmed because laboratories were overwhelmed with clinical samples, which is also described elsewhere [7, 14] . data about transmission to healthcare workers were not recorded, especially regarding niv. currently, most information about its use during an epidemic relies upon expert opinion [46] . in 178 patients with diffuse viral pneumonitis caused by the 2009 influenza a (h1n1) virus admitted to the icu and followed over time, ards was the rule, requiring high ventilation support and frequent use of rescue therapies. death, organ failures, and evolution to prolonged mechanical ventilation were common. in most cases, noninvasive ventilation failed to prevent endotracheal intubation. finally, elevated ldh levels, lack of recovery of platelet count and persistent acidosis and leukocytosis in non-survivors behaved as prognostic findings. • in 2009 influenza a (h1n1) patients, hospital admission with prompt indication of mechanical ventilation -a marker of severe disease -was associated with a history of symptoms of nearly one-week duration. • an initial niv trial was not effective to avoid intubation in most patients; thus, this ventilation approach should likely be discarded in this setting. • mortality and morbidity were frequent: death was common and was mainly caused by persistent, refractory hypoxemia. prolonged mechanical ventilation and icu and hospital stays were typical. • ph, platelet count, ldh and sofa differed significantly between survivors and non-survivors over time. lack of recovery of platelet count and persistence of leukocytosis might be markers of poor prognosis. • every effort should be done to increase adherence to protective ventilation in the real world. abbreviations ali: acute lung injury; ards: acute respiratory distress syndrome; bmi: body mass index; cxr: plain chest x-ray film; ibw: ideal body weight; icu: intensive care unit; ldh: lactate dehydrogenase assay; los: length of stay; mv: mechanical ventilation; niv: non-invasive ventilation; pao2/fio2: relation between patient arterial po 2 and inspired oxygen fraction used; pcv: pressure-controlled ventilation; peep: positive end-expiratory pressure; psv: pressure support ventilation; rr: respiratory rate; rt-pcr: real-time reversetranscriptase-polymerase-chain-reaction; sati: argentinian society of intensive care; sofa: sequential organ failure assessment; vcv: volumecontrolled ventilation; vt: tidal volume. the registry of the argentinian society of intensive care department intensive care, hospital general de agudos velez sarsfield, calderón de la barca 1550, (c1407ahh) department critical care department intensive care, hospital lagomaggiore, gordillo s/n 16 department intensive care mar del plata, argentina. 19 intensive care unit, hospital universidad abierta interamericana, portela 2975, (c1069aab) group on influenza: pneumonia and respiratory failure from swine-origin influenza a (h1n1) in mexico pandemic (h1n1) 2009 -update 104. weekly update influenza-associated hospitalizations in the united states intensive care patients with severe novel influenza a (h1n1) virus infection-michigan critically ill patients with 2009 influenza a (h1n1) infection in canada critically ill patients with 2009 influenza a (h1n1) in mexico critical care services and 2009 h1n1 influenza in australia and new zealand pandemic influenza a (h1n1) virus hospitalizations investigation team: hospitalized patients with 2009 h1n1 influenza in the united states h1n1) working group: factors associated with death or hospitalization due to pandemic 2009 influenza a(h1n1) infection in california intensive care adult patients with severe respiratory failure caused by influenza a (h1n1) in spain influenza a pandemics: clinical and organizational aspects: the experience in chile national influenza a pandemic (h1n1) 2009 clinical investigation group of china: clinical features of the initial cases of 2009 pandemic influenza a (h1n1) virus infection in china registry of the argentinian society of intensive care sati: pandemic 2009 influenza a (h1n1) in argentina: a study of 337 patients on mechanical ventilation novel influenza a (h1n1) pregnancy working group: h1n1 2009 influenza virus infection during pregnancy in the usa severe respiratory disease concurrent with the circulation of h1n1 influenza pathology in fatal novel human influenza a (h1n1) infection influenza pandémica (h1n1) 2009. república argentina worldwide statistics of the h1n1 influenza a pandemic practical lessons from the first outbreaks: clinical presentation, obstacles, and management strategies for severe pandemic (ph1n1) 2009 influenza pneumonitis writing committee of the who consultation on clinical aspects of pandemic (h1n1) ventilator management for hypoxemic respiratory failure attributable to h1n1 novel swine origin influenza virus guidance on case definitions to be used for investigations of novel influenza a (h1n1) cases influenza pandémica (h1n1) 2009. república argentina. influenza pandémica (h1n1) 2009. report of the 34 epidemiological week direccion de estadisticas e informacion de salud. sistema estadístico de salud. serie 5 -número 51 evolution of mechanical ventilation in response to clinical research the acute respiratory distress syndrome network: ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and acute respiratory distress syndrome barriers to providing lung-protective ventilation to patients with acute lung injury tidal volume reduction in patients with acute lung injury when plateau pressures are not high. ards clinical trials network express) study group: positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial anzueto a: tidal volume in mechanical ventilation: the importance of considering predicted body weight pressure-and volume-limited ventilation strategy group: evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome the multicenter trail group on tidal volume reduction in ards: tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome mechanical ventilation in critically ill patients with 2009 influenza a (h1n1) mechanical ventilation in critically ill patients with 2009 influenza a (h1n1) the finnali study on acute respiratory failure: not the final cut effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome is there a role for noninvasive ventilation in acute respiratory distress syndrome? a meta-analysis the national heart, lung, and blood institute acute respiratory distress syndrome (ards) clinical trials network: comparison of two fluidmanagement strategies in acute lung injury metabolic correlates of oxygen debt predict posttrauma early acute respiratory distress syndrome and the related cytokine response osatnik j: incidence, clinical course, and outcome in 217 patients with acute respiratory distress syndrome swine influenza (h1n1) pneumonia: clinical considerations influenza pneumonia: a descriptive study lactate dehydrogenase leakage as a marker for apoptotic cell degradation induced by influenza virus infection in human fetal membrane cells should noninvasive ventilation be considered a high-risk procedure during an epidemic? on the role of non-invasive (niv) to treat patients during the h1n1 influenza pandemic lung function and organ dysfunctions in 178 patients requiring mechanical ventilation during the influenza a (h1n1) pandemic the authors declare that they have no competing interests. key: cord-016416-h3cjylcl authors: javouhey, etienne; pouyau, robin; massenavette, bruno title: pathophysiology of acute respiratory failure in children with bronchiolitis and effect of cpap date: 2013-05-29 journal: noninvasive ventilation in high-risk infections and mass casualty events doi: 10.1007/978-3-7091-1496-4_27 sha: doc_id: 16416 cord_uid: h3cjylcl acute bronchiolitis is the most common lower respiratory tract infection (lrti) during the first year of life. respiratory syncytial virus (rsv) infection is the most prevalent virus found in these children, accounting for 60–80 % of cases. the rate of hospitalization is less than 2 %. up to 8 % of those hospitalized require ventilatory support [1, 2]. prematurity, young age, and preexisting chronic respiratory and cardiac diseases are the main risk factors for severe bronchiolitis [ 1 , 6 ] . when the wob increases or persists for a long period, ventilatory support is required to prevent severe hypoxemia or hypercapnic coma. noninvasive ventilation (niv) is most often delivered by continuous positive airway pressure (cpap) via nasal prongs or mask. some studies have reported the use of assisted spontaneous breathing (asb) and biphasic positive airway pressure (bipap) as other niv modalities [ 7 -12 ] . high-fl ow cannulas (hfcs) deliver positive end-expiratory pressure (peep) that can attain 3 or 5 cmh 2 o, and some studies suggested that it could obviate the need for endotracheal intubation [ 7 , 8 , 13 -15 ]. there is no strong level of evidence that niv avoids intubation and is benefi cial for patients compared to intubation. during the last decade, however, increasing numbers of clinical and physiological studies have reported a good experience of niv as the primary ventilatory support mode. currently, cpap is widely used as the fi rst ventilatory support in many centers, with a decreasing rate of intubation. the objective of this chapter is to summarize the impact of niv techniques in the management of children with severe bronchiolitis requiring ventilatory support. physiological knowledge is fi rst discussed followed by clinical studies assessing the impact of niv on the intubation rate and outcome. we then address the technical and practical aspects of niv application in children according to age and clinical condition. in a physiological study of 37 infants, hammer and colleagues showed that rsv infection could lead to two pulmonary function abnormalities [ 5 ] . the most common is bronchiolitis, an obstructive airway disease characterized by increased airway resistance (respiratory system resistance, r rs ), air trapping [high functional residual capacity/total lung capacity (frc/tlc)], reduced tlc, and low respiratory system compliance ( c rs ) compared with normal values. typically, chest radiography of these children shows bilateral perihilar infi ltrates and hyperinfl ation. of the 37 infants, 10 had a resistive profi le, corresponding to the criteria of acute respiratory distress syndrome (ards), with very low c rs and r rs . radiography revealed bilateral alveolar consolidations. this form corresponded to rsv pneumonia. the mechanism of apnea associated with rsv infection is not completely understood. immaturity of central ventilatory centers is likely to be one of the explanations, which can explain the high prevalence of apnea in infants born prematurely and infants <2 months of age. the real incidence of apnea varies among studies, from 2.5 to 28.0 %, depending on the case mix. among children admitted to the pediatric intensive care unit (picu) the incidence is much higher [ 3 ] . it is probably important to distinguish primary apnea from apnea occurring after several hours of respiratory distress and a high level of wob. the latter is likely to be due to muscle fatigue, which occurs more rapidly in young infants and those born prematurely. obstruction of small airways is the main physiological phenomena of rsv infection in infants. it is the consequence of bronchial and peribronchial infl ammation, plugging of airways by mucus and cellular debris, and bronchial smooth muscle constriction ( fig. 27.1 ) . consequently, the airway resistance and respiratory load increase. to preserve their pulmonary function, infants use their accessory respiratory muscles, increasing their wob. they also increase their respiratory rate, but because of airway obstruction the duration of the expiratory period is too short to expire completely. air is then trapped in the alveoli, generating dynamic hyperinfl ation and auto-peep. the inspiratory time/total respiratory time ( t i / t tot ) ratio increased as t i decrease ( fig. 27.1 [ 7 , 16 , 17 ] . these measures were obtained using an esophageal and gastric probe with balloons. the ptp es per breath was obtained by measuring the area under the diaphragmatic pressure ( p di ) and the esophageal pressure ( p es ) signal between the onset of inspiration and the end of inspiration. essouri et al. showed in ten infants with severe bronchiolitis that the median level of auto-peep generated was 6.05 cmh 2 o (range 3.9-9.2 cmh 2 o) [ 16 ] . they showed that the decrease in wob was greater with a cpap level of 7 cmh 2 o compared to 4 or 10 cmh 2 o. this suggested that application of extrinsic peep decreased the pressure gradient between the mouth and alveoli at end-expiration. it allowed air to pass through the airways, reducing the work required for the next inspiration. the montpellier team in france confi rmed these results and the role of cpap in a randomized controlled trial (rct). they compared ten children treated with nasal cpap at 6 cmh 2 o to nine children managed with oxygen alone [ 17 ] . the t i / t tot and transcutaneous carbon dioxid partial pressure (tcpco 2 ) were decreased in the cpap group and the wob was signifi cantly reduced compared to that in control patients. this improvement of the wob was correlated with the clinical improvement assessed by the modifi ed wilson clinical asthma score (mwcas). beasley and jones [ 18 ] and soong et al. [ 19 ] were the fi rst to report niv use, especially cpap, in infants with severe bronchiolitis. these preliminary studies showed that cpap was able to decrease the paco 2 and rr of infants with severe bronchiolitis. since 2004, numerous prospective or retrospective studies have been published and reported an increasing use of cpap in this clinical setting (table 27. 2 ) [ 8 -12 , 17 , 19 -21 ] . however, there is no clear consensus on clinical use of cpap compared to intubation and invasive ventilation [ 22 ] . complications of intubation and mechanical ventilation are well known. in infants, endotracheal intubation can be complicated by subglottic edema with a risk of evolution to tracheal stenosis. mechanical ventilation of children with severe airway obstruction is challenging and may expose the airways and the lungs to high pressures or high volumes, causing lung injury. most of infants who are mechanically ventilated require sedative drugs and sometimes muscle paralysis. the need for central venous access is common. these invasive procedures are associated with blood loss and expose children to nosocomial infection (e.g., pneumonia, urinary tract infection, bacteremia). the safety of sedative drugs in immature brains is not completely established. hence, niv represents a good alternative because its use rarely requires sedative drugs. on the other hand, the main risks of niv are pneumonia aspiration in a child with an altered level of consciousness and potentially delayed intubation. most of studies have confi rmed the results of early studies that cpap and niv improve gas exchange and the rr. physiological studies suggested that application of cpap improved gas exchange by decreasing the wob and respiratory efforts, as assessed by the mwcas. median los was reduced in children in whom niv succeeded compared to those with iv and those who failed niv few studies have compared this approach to the classic invasive ventilatory strategy on clinical outcome, such as the duration of ventilatory support, length of picu stay, length of hospital stay (los), or ventilator-assisted pneumonia (vap). javouhey et al. in a pre/post study design showed that niv as the primary ventilatory support was associated with a signifi cant decrease in the intubation rate: from 89 to 52 % [ 10 ] . the niv failure rate was 33 %. this approach was associated with a decreased incidence of vap and a decrease in the number of children with oxygen requirement for >8 days [ 10 ] . ganu et al. reported their 10-year experience of niv for infants with severe bronchiolitis in their picu from the children's hospital at westmead in sydney. among the 520 infants admitted for bronchiolitis, 399 required ventilator assistance-285 with a trial of niv, mainly cpap [ 9 ] . they reported a signifi cant increase in the use of niv (2.8 % increase per year) along with a decline in the intubation rate (1.9 % per year). the percentages of infants failing niv decreased over the study period, from 31.8 to 13.5 %. this decline was also observed in centers in which niv was widely used as the primary mode of ventilatory support [ 9 ] . in our center, for example, this percentage decreased from 33 to 5 % during the 2011-2012 epidemics (personal data). the median hospital los was longer for infants who were intubated and invasively ventilated than for those in whom niv succeeded. the hospital los was also signifi cantly longer for children who failed niv than for those with invasive ventilation. the same tendency had been found in a previous study [ 10 ] . even with no control study, these results suggested that a strategy using niv (mainly cpap) as the primary ventilatory support was able to obviate the need for tracheal intubation. more recently, a system of oxygen delivery was developed using heated and humidifi ed high-fl ow gases delivered via nasal cannulas that can generate peep. the level of peep provided depends of the fl ow and the leaks but can reach 3-5 cmh 2 o. this system has been used in children with severe bronchiolitis, with results similar to those achieved with cpap, including improved alveolar ventilation and decreased rr, obviating the need for tracheal intubation [ 14 , 15 , 23 ] (table 27. 3 ). physiological studies showed that high-fl ow cannulas (hfcs) are able to improve lung mechanics and ventilatory function by a washout of the nasopharyngeal dead space, a decrease in airfl ow resistance, and improved mucociliary clearance [ 24 ] . an rct pilot study performed in 19 infants with moderately severe bronchiolitis showed that heated/humidifi ed hfc therapy at 4-8 l/min improved the spo 2 compared to a head-box oxygen group at 8 h (100 % vs. 96 %, p = 0.04) and 12 h (99 % vs. 96 %, p = 0.04) [ 13 ] . the stability of peep is not guaranteed and the level of peep reached can be insuffi cient to counterbalance the wob. an in vitro study from sivieri et al. showed that the airway pressure varied widely with the degree of nares occlusion by the prongs and by the amount of mouth leakage [ 25 ] . at 6 l/min hfc with the mouth open the airway pressure was <1.7 cmh 2 o. it was <10.0 cmh 2 o when the mouth was closed. complete nares occlusion can generate high airway pressure (up to 20 cmh 2 o) when the mouth is closed. further studies comparing cpap and hfcs would be useful to understand which children should benefi t from cpap rather than hfc. the latter system has the advantage of being simple to apply, usable in emergency units, and minimally expensive. criteria used to initiate hfc or cpap should be better defi ned and validated. a selection bias cannot completely be excluded because the level of severity of the infants treated is diffi cult to compare among studies. moreover, as criteria to initiate ventilatory support are not well defi ned, those used in the various studies are likely to be different. some authors have included children with severe respiratory distress and severe hypercapnic acidosis, whereas others have put children on ventilatory support considering only the signs of retraction or the level of tachypnea. criteria to initiate ventilatory support in children are not well defi ned and have not been validated. most epidemiological studies have shown that infants with low weight and age < 42 days were more likely to be admitted to a picu and ventilated. other factors predisposing to mechanical ventilation were factors linked to a medical history of lung and cardiac diseases, prematurity, and/or neuromuscular disease [ 2 , 9 , 20 ] . evans et al. analyzed criteria for cpap requirement in a retrospective cohort of 163 patients admitted to their center for severe bronchiolitis [ 20 ] . among these 163 children, 28 required cpap. the authors found seven predictors for cpap requirement: young age, low gestational age, low spo 2 , high level of oxygen requirement, respiratory and heart rates (rr, hr), and glasgow coma score (gcs). using receiver operator characteristic (roc) curve analyses, they identifi ed several thresholds: age < 11 weeks, spo 2 < 95 %, rr > 54, hr > 163, and gcs < 15. the strongest predictor was a low spo 2 . the authors found a negative correlation between spo 2 and o 2 requirement ( r = −0.656), a positive correlation between age and weight ( r = 0.836), and a positive correlation between gestational age and birth weight ( r = 0.824). they did not fi nd blood gas analyses as predictors of cpap requirement [ 20 ] . their results were limited by the retrospective nature of the study and by the small sample size. mansbach et al. identifi ed factors associated with cpap and/or intubation requirement in a prospective multicenter study that included 161 children [ 26 ] . in the multivariate analysis, factors associated with cpap and/or intubation requirement were age < 2 months [odds ratio (or) 4.3, 95 % confi dence interval (ci) 1.7-11.5], maternal smoking during pregnancy (or 1.4, 95 % ci 1.1-1.9), birth weight < 5 lb (or 1.7, 95 % ci 1.0-2.6), breathing diffi culty began <1 day before admission (or 1.6, 95 % ci 1.2-2.1), severe retractions (or 11.1, 95 % ci 2.4-33.0), and room air spo 2 < 85 % (or 3.3, 95 % ci 2.0-4.8) [ 26 ] . identifying patients at high risk of cpap requirement is important because it can help the physician's decision about transferring the patient to the unit able to initiate the ventilatory support required. curiously, blood gas analyses have not been found to be good indicators of ventilatory support requirement except in the study of campion et al., where a high level of co 2 before cpap was predictive of niv failure defi ned as the need for invasive ventilation [ 8 ] . similarly, composite scores of respiratory distress failed to identify the group of patients requiring ventilator support. in two french studies, high prism scores were predictors of the need for invasive ventilation. however, as this score is calculated 24 h after admission, it cannot help the physician make clinical decisions [ 8 , 11 ] . the criteria for initiating cpap should differ from those used to initiate invasive ventilation. unfortunately, no reported studies have made such a comparison of these criteria. therefore, the ventilatory strategy for children admitted with severe bronchiolitis is based on little evidence. cpap and hfc can be proposed as fi rstline ventilatory support in most cases, although hfc is probably insuffi cient in children with severe hypercapnic acidosis. response to this fi rst line of ventilatory support must be assessed within the fi rst 2 h following its initiation. nonresponders are at high risk of complications and often require invasive ventilation. niv in bipap or asb mode or in pressure control mode can be attempted provided that rapid assessment is done and strict supervision is observed. for better selection of patients who will respond to cpap, some studies have assessed risk factors of niv failure. most of these studies were retrospective and compared patients whose ventilatory support was niv alone versus those who were intubated after an niv trial [ 8 , 10 , 20 , 27 -29 ] . failure was defi ned as the need for intubation. most of these studies included children with all types of respiratory distress, not bronchiolitis alone. the level of fio 2 , ards and a high level of fio 2 (over 80 %) 1h after starting niv were found as factors associated with niv failure in children with severe respiratory distress of various causes [ 27 , 28 ] . larrar et al. identifi ed the absence of a reduction in pco 2 as a predictive factor of niv failure in a cpap study. abboud et al., in an hfc study, came to the same conclusion [ 11 , 23 ] . neurological failure altered level of consciousness with low reactivity or agitation not responding to oxygenation a french prospective multicenter study noted that a minimal reduction in co 2 and a low increase in ph measured 2 or 4 h after niv initiation were strong predictors of niv failure [ 30 ] . in that study, the various centers had defi ned criteria for ventilatory support and absolute criteria for invasive ventilation (tables 27.4 and 27 .5 ). the results suggested that early assessment of the response to niv is crucial. noninvasive ventilatory supports include a number of systems that deliver pressure support to the patient via an interface. the cpap delivery system has to be reliable, with good stability of the pressure during all the respiratory cycle length. it also has to be easy to use and install in children. interfaces are chosen according to their ability to be connected to the cpap delivery systems while minimizing air leaks, dead space, and discomfort. to deliver heated/humidifi ed oxygen, an air-oxygen fl ow generator is required combined with a heated humidifi er. the circuit tubing and the size of the cannula differ according the age of the child. for infants weighing <10 kg, small-volume circuit tubing is required. infant or pediatric cannulas can be used. adult circuit tubing and cannulas are used for children weighing ≥10 kg. as children with severe bronchiolitis requiring ventilatory support are young (<42 days) and of low weight, cpap systems developed for neonates are used, such as infant flow (eme, electro medical equipment, brighton, uk), infant star 950 (nellcor puritan bennett, san diego, ca, usa), and bubble cpap (fisher and paykel healthcare, auckland, nz). in the latter system, a water column delivers peep. in picus, an icu ventilator or cpap machine may be preferred. no study has compared the stability of peep in these delivery systems. it is well known that peep stability can be affect by the level of leaks, the degree of mouth opening, and the level of airfl ow in the circuit. the choice of the interface is crucial. the ideal interface is one that is easy to install, minimizes leaks, and does not cause skin or mucosal injury. low-resistance nasal prongs or cannulas are the interfaces most frequently used in infants with bronchiolitis. the nasal approach is preferred because infants predominantly breathe through the nose. in infants with bronchiolitis, the tolerance is reportedly good, although no study has specifi cally addressed skin or mucosal injuries in the context of bronchiolitis. as nasal breathing has to be preserved, nasal obstruction, which frequently occurs during rsv infection, should be systematically treated and monitored. nasal obstruction is a source of discomfort and agitation for children treated by nasal cpap. consequently, nasal lavage with nacl 0.9 % every 3 or 4 h is recommended. the choice of the cannula's size is important to limit leaks and avoid nose injuries. it is recommended that nasal prongs of different sizes with different inter-nostril distances be readily available. to limit mouth leaks, a dummy is frequently used and sometimes a chinstrap is required. to avoid skin irritation or ulceration and to improve the patient's comfort, colloid ulcer dressings (e.g., comfeel, coloplast) are applied to protect the nasal bridge as well as the nostrils. in our experience, nasal prongs or cannulas are well tolerated by infants weighing up to 5 kg. for larger infants, nasal masks are often better tolerated. during the last decade, manufacturers have designed small nasal masks specifi cally intended not to leak. they allow us to put small infants on cpap with standard ventilators in the picu. these masks are also available for the bubble cpap system and the infant flow cpap generators. it is also possible to use a nasal mask with intentional leakage to connect infants to a cpap or bipap machine. the resmed sullivan infant bubble mask (resmed, waterloo, australia) is used for the smallest infants and the small child profi l lite mask (philips respironics, murrysville, pa, usa) for the others. skin protection can be used to minimize skin irritation. the choice of the headgear or bonnet fi tted to the head's form and size is important to avoid mask displacement, which can increase leaks, and fastening the mask too tightly on the face, which could increase the risk of skin injuries. bucconasal masks are used only when the leaks are interfering with synchronization of the infant with the ventilator for niv. when the mouth is open or if the nose is obstructed, application of nasal cpap becomes ineffective. a major concern is the absence of specifi c bucconasal masks for infants. most often, anesthesia masks or adult nasal masks are used. however, in these cases, the risk of skin injury is much higher than with nasal masks, particularly laceration or ulceration of the nasal bridge. skin protection with colloid dressings must be used to prevent these injuries. progress in the design of bucconasal masks is needed to enable niv in infants and young children. helmets represent an alternative in children weighing >5 kg. they cannot be used in smaller children because the helmet compresses the chest, reducing its effi cacy. some experiences with helmets have been reported even in small children. they report rather good tolerance and improvement of alveolar ventilation [ 31 , 32 ] . essouri and colleagues showed that a cpap level of 7 cmh 2 o was better than either 4 or 10 cmh 2 o in 10 children admitted to a picu for severe bronchiolitis [ 16 ] . the decrease wob, assessed by ptp di and ptp es , was more signifi cant with 7 cmh 2 o. this level was closest to the auto-peep level (6.3 cmh 2 o) and is consistent with the level of cpap used in the main clinical studies (table 27. 2 ). based on these results, starting with a level between 6 and 8 cmh 2 o is recommended. for hfc, the recommended fl ow by the manufacturer is 1-2 l/kg/min. in a retrospective study, schibler et al. used a fi xed fl ow of 8 l/min but did not explain the reason for this choice [ 15 ] . in practice, we start with a fl ow of 1 l/kg/min and increase it to 2 l/kg/min according to the tolerance of the child. as already noted, the optimal level of fl ow is unknown and depends of the degree of nares obstruction and mouth leakage. concerning the bipap or asb ventilation modes, as no study has been performed comparing different ventilatory settings we are not able to make any recommendations. the studies that have reported the use of bipap or asb in patients with bronchiolitis used a level of peep varying from 4 to 8 cmh 2 o and inspiratory pressures between 10 and 20 cmh 2 o. the level of pressure support varied from 4 to 12 cmh 2 o. niv pressures >20 cmh 2 o are associated with a high risk of gastric dilatation by gas. to minimize this phenomenon, a nasogastric tube is routinely inserted to defl ate the stomach when necessary. in our clinical practice, when an infant is switched from cpap to niv on pressure support, we start with a level of peep equal to the level of cpap used and then add pressure support of 6 cmh 2 o above peep or an inspiratory pressure of 6 plus peep. then, after assessing the effi cacy and tolerance, we adapt the ventilator setting or the interface, avoiding exceeding 20 cmh 2 o. the inspiratory pressure is titrated by 2 cmh 2 o increments to a level where the rr, signs of wob, and blood gases are improved. the main problem with niv in pressure support mode, such as bipap, is asynchrony. the sensitivity of ventilatory triggers is sometimes insuffi cient for young infants, who are unable to trigger a ventilatory cycle. on the contrary, when the sensitivity of the trigger is too high, and when the leaks are important, autotriggering may appear, generating discomfort and asynchrony. control of leakage is another factor contributing to synchrony: if the ventilator is unable to compensate for the leaks, the inspiratory time can be prolonged into the period when the child wants to expire. these causes of asynchrony are a source of discomfort and poor tolerance of niv in infants. no study has been performed comparing different ventilatory modes with different ventilators in infants who suffer from severe bronchiolitis. neurally adjusted ventilatory assistance (nava) is a promising mode that would limit the incidence of asynchrony. liet and colleagues reported three cases of infants with severe bronchiolitis treated with this mode during invasive mechanical ventilation and showed that nava was able to improve synchrony, decrease the oxygen requirement, and decrease peak airway pressure from 28 ± 3 to 15 ± 5 cmh 2 o [ 33 ] . it has been shown in 15 neonates and children that nava decreased patient-ventilator asynchrony and the peak inspiratory pressure [ 34 ] . the percentage of time in asynchrony was lower in the nava group (8.8 %) than in the pressure (33.4 %) and fl ow (30.8 %) trigger groups (ventilated either in pressure control or pressure regulated volume controlled). moreover, the peak inspiratory pressure was 1.9-2.0 cmh 2 o lower in nava than in the pressure and fl ow groups, respectively ( p < 0.05 for both) [ 34 ] . we reported our experience of nava in niv mode in 18 infants with severe bronchiolitis. the tolerance and the feasibility were good, and 16 of 18 infants had nava mode success, thereby avoiding invasive ventilation (personal communication). as no study comparing classic niv to nava niv has been reported, this technique cannot be recommended but represents a new mode to be considered when asynchrony is detected frequently with classic niv. during the last decade, ventilatory support for children with severe bronchiolitis has radically changed. nasal cpap is become the fi rst mode of niv for children who meet the criteria for ventilatory support. numerous studies have suggested that this strategy is associated with a decreased need for intubation and invasive ventilation. although the level of evidence of improved outcomes related to this strategy is low, in the absence of prospective controlled studies the data published have shown that children can be safely managed less invasively without prolonging the picu stay. some studies suggested that responders to nasal cpap had a lower length of picu stay than those who were intubated. physiological studies have provided some evidence that a cpap level of 6-7 cmh 2 o is able to decrease the wob and improve alveolar ventilation in children with obstructive bronchiolitis [ 7 , 16 , 17 ] . the application of extrinsic peep to the airways at a level greater than the level of auto-peep generated by dynamic obstruction of small airways allowed reduction of efforts made by the child to initiate the next inspiratory cycle. this mechanism is responsible for the clinical improvement observed in the children after initiation of nasal cpap. the responders are those whose rrs are reduced and co 2 levels and heart rates are decreased within 2-4 h of starting niv with cpap. early identifi cation of those who will respond is crucial so as not to delay applying niv with two levels of pressure or intubation with invasive ventilation. more recently, the hfc, which is able to deliver humidifi ed/heated oxygen, has been reported to be another alternative to nasal cpap [ 14 , 15 , 23 ] . this system has been shown to generate a low level of peep, induce washout of nasopharyngeal dead space, match inspiratory fl ow rates in infants, and improve mucociliary clearance [ 24 ] . children with apnea and those with severe hypercapnic acidosis are more likely to fail hfc and can be treated by nasal cpap. as no study has been conducted comparing hfc to nasal cpap, no recommendation can be drawn. there is a crucial need of studies to better distinguish groups of children who will respond to hfc, to cpap, or to niv because the level of expertise and equipment differ significantly between these modes. hfc can be initiated in the emergency or intermediate care units, whereas cpap and niv should be reserved for use in an intermediate care unit or an icu according the level of the teams' experience. stratifi cation of respiratory distress severity is required for better patient selection at admission. we know that patients with a medical history of chronic lung, heart, or neuromuscular diseases are at higher risk of complications and failure of hfc or cpap. young infants, particularly those born prematurely and those with low weight, are more likely to require ventilatory support [ 1 , 6 ] . however, the clinical score, biological markers, and blood gas criteria associated with ventilatory support and with cpap failure, are not well defi ned and require further study. moreover, as no study has been performed on niv at two pressure levels in bronchiolitis, there is no evidence that niv after cpap or hfc failure can obviate the need for intubation and invasive ventilation. only a multicenter prospective study comparing different ventilatory strategies would be able to determine the best ventilatory support treatment. technically, manufacturers have improved their products to facilitate cpap application. nasal masks and nasal prongs of different sizes are now available, allowing us to fi t the equipment to the child's facial and head morphology. the objectives of these interfaces are to facilitate setup, limit the dead space, and reduce air leaks. experience and the use of specifi c nursing protocols are factors associated with a high success rate of niv techniques, suggesting that only teams with a high level of training and experience should apply niv. review of epidemiology and clinical risk factors for severe respiratory syncytial virus (rsv) infection epidemiology and prevention of respiratory syncytial virus infections among infants and young children risk factors for respiratory syncytial virus associated apnoea incidence of apnea in infants hospitalized with respiratory syncytial virus bronchiolitis: a systematic review key major recommendations • nasal cpap and hfcs are the best fi rst option for ventilatory support of children with severe bronchiolitis. their use may avoid intubation and invasive mechanical ventilation • there is an insuffi cient level of evidence of the effi cacy of niv on mortality or morbidity criteria • niv with pressure support is an option when cpap fails • early assessment (within the fi rst 2 h) of responders to cpap or hfc is required to prevent secondary critical deterioration • improved blood gas levels after cpap is a good indicator of response to cpap • infection, apnea, and young age are associated with niv failure. • nasal cannulas are the most appropriate interface for infants weighing <5 kg acute respiratory distress syndrome caused by respiratory syncytial virus hospitalizations for respiratory syncytial virus bronchiolitis in preterm infants at <33 weeks gestation without bronchopulmonary dysplasia: the castor study nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis non-invasive ventilation in infants with severe infection presumably due to respiratory syncytial virus: feasibility and failure criteria increase in use of non-invasive ventilation for infants with severe bronchiolitis is associated with decline in intubation rates over a decade non-invasive ventilation as primary ventilatory support for infants with severe bronchiolitis effects of nasal continuous positive airway pressure ventilation in infants with severe acute bronchiolitis non-invasive ventilation for severe bronchiolitis: analysis and evidence pilot study of vapotherm oxygen delivery in moderately severe bronchiolitis high fl ow nasal cannulae therapy in infants with bronchiolitis reduced intubation rates for infants after introduction of high-fl ow nasal prong oxygen delivery optimal level of nasal continuous positive airway pressure in severe viral bronchiolitis 6 cmh(2) o continuous positive airway pressure versus conventional oxygen therapy in severe viral bronchiolitis: a randomized trial continuous positive airway pressure in bronchiolitis continuous positive airway pressure by nasal prongs in bronchiolitis clinical predictors of nasal continuous positive airway pressure requirement in acute bronchiolitis randomised controlled trial of nasal continuous positive airways pressure (cpap) in bronchiolitis use of continuous positive airway pressure (cpap) in acute viral bronchiolitis: a systematic review predictors of failure in infants with viral bronchiolitis treated with high-fl ow, high-humidity nasal cannula therapy research in high fl ow therapy: mechanisms of action effect of hfnc fl ow rate, cannula size, and nares diameter on generated airway pressures: an in vitro study prospective multicenter study of children with bronchiolitis requiring mechanical ventilation predictive factors for the success of noninvasive mask ventilation in infants and children with acute respiratory failure noninvasive positive pressure ventilation: fi ve years of experience in a pediatric intensive care unit predictive factors of non invasive ventilation failure in critically ill children: a prospective epidemiological study non invasive ventilation in children with acute respiratory failure during rsv epidemic period: a prospective multicenter study air-oxygen helmet-delivered continuous positive airway pressure to manage respiratory failure due to bronchiolitis helmet-delivered continuous positive airway pressure with heliox in respiratory syncytial virus bronchiolitis respiratory support by neurally adjusted ventilatory assist (nava) in severe rsv-related bronchiolitis: a case series report comparison of pressure-, fl ow-, and nava-triggering in pediatric and neonatal ventilatory care key: cord-103020-ckuma42j authors: mcdowell, g.; sumowski, m.; toellner, h.; karok, s.; o'dwyer, c.; hornsby, j.; lowe, d.; carlin, c. title: two-way remote monitoring allows effective and realistic provision of home-niv to copd patients with persistent hypercapnia. date: 2020-11-12 journal: nan doi: 10.1101/2020.11.08.20227892 sha: doc_id: 103020 cord_uid: ckuma42j background outcomes for chronic obstructive pulmonary disease (copd) patients with persistent hypercapnic respiratory failure are improved by long-term home non-invasive ventilation (niv). provision of home-niv presents clinical and service challenges. the aim of this study was to assess outcomes of home-niv in hypercapnic copd patients managed remotely. methods retrospective analysis of a dataset of 46 copd patients with persistent hypercapnic respiratory failure who commenced home-niv managed by two-way remote monitoring (lumis, airview, resmed) between february 2017 and january 2018. the primary outcome of this study was time to readmission or death at 12 months in patients receiving home-niv versus a retrospectively identified control cohort of 27 patients with hypercapnic copd who had not been referred for home-niv. results the median time to readmission or death was significantly prolonged in patients who commenced home-niv (median 160 days, 95% ci 69.38-250.63) versus the control cohort (66 days, 95% ci 21.9-110.1; p<0.01). average time to hospital readmission was 221 days (95% ci, 47.77-394.23) and 70 days (95% ci, 55.31-84.69; p<0.05), respectively. median decrease in bicarbonate level of 4.9mmol/l (p<0.0151) and daytime pco2 2.2kpa (p<0.032) demonstrate efficacy of home-niv. a median reduction of 14 occupied bed days per annum versus previous year prior to niv was observed per patient who continued home-niv throughout the study period (n=32). conclusion these findings confirm the benefits of home-niv in clinical practice and support the use of two-way remote monitoring as a feasible solution to managing the delivery of home-niv for copd patients with persistent hypercapnia. copd is the second most common cause of emergency hospital admission in the uk, accounting for over 1 million bed days at a cost to the nhs of over £800 million a year (1) . around a third of those admitted to hospital following an exacerbation of copd are readmitted within 90 days, which is also strongly associated with post-discharge mortality (2) . avoiding copd exacerbations and hospitalisations is noted to be a key priority by copd patients (3, 4) , and targeting a reduction in these is necessary to address the substantial health and economic burden imposed by copd. the risk of hospital readmissions and further life-threatening events is particularly high among patients with a severe exacerbation of copd that leads to hypercapnic respiratory failure (5) . the first-line treatment for these patients in the acute setting is non-invasive ventilation (niv) (3) , which has been shown to prevent intubation and invasive mechanical ventilation and reduce hospital mortality (6, 7) . however, it was previously reported that more than 75% of patients treated with niv for acute hypercapnic respiratory failure were readmitted and nearly 50% died within the first year after discharge (5) . a growing area of interest to improve outcomes for patients with severe copd focuses on the application of long-term niv in the home setting. in a recent landmark study, murphy et al. (8) showed that the addition of home-niv to long-term home oxygen therapy in patients that remained severely hypercapnic 2 to 4 weeks after an exacerbation delayed and reduced hospital readmissions at 12 months. a benefit on 12month overall survival was noted in an earlier randomised controlled trial involving stable hypercapnic patients treated with home-niv (9) . the driver of clinical improvements across both studies can be attributed to higher inspiratory pressures targeting a reduction in co 2 in patients who were persistently hypercapnic. a task force of the european respiratory society has since adopted home niv as recommended treatment for copd patients presenting with persistent hypercapnic respiratory failure (10) . overall, the existing body of research suggests that there are some open questions with regards to patient selection and timing of home-niv (11, 12) . for example, only 5% of patients screened in hot-hmv study were recruited to the trial, raising questions about the external validity of niv randomised controlled trial (rct) results. many of the patients excluded from niv rcts meet current guidance critieria for home niv provision. establishing whether beneficial outcomes from home niv copd rcts can be matched with routine clinical adoption is required. the feasibility of delivering home-niv to patients outside of controlled clinical trial settings also remains to be established, particularly in the context of covid-19 pandemic. provision for elective inpatient niv initiation and titration beyond clinical trials is limited, patients generally wish to avoid hospitalisations and severity of their illness limits capacity for outpatient attendances. regular follow-up helps to monitor the effectiveness of ventilation, encourages treatment adherence and optimises patient comfort and ventilator settings, but realistic delivery of intensive follow-up is problematic (13) . the covid-19 pandemic has presented additional challenges to home niv provision. overall healthcare service pressures, social distancing requirements including need to protect vulnerable patients from nosocomial covid-19, and infection control requirements for clinicians, with niv classified as an aerosol generating procedure will all continue to impact on breathing support service capacity. it has been demonstrated that copd patients at high risk for exacerbations can be taught to self-manage when offered ongoing support (14, 15) . early evidence that compares remotely monitored copd patients with usual face-to-face care is encouraging in terms of patient quality of life and number of hospital admissions (16) . with the recent advent of two-way tele-monitoring, healthcare providers can view live niv data from patients, adjust ventilator settings remotely and facilitate personalised care. a combination of patient education, self-management and remote monitoring may therefore be a realistic support pathway for home-niv. using this to channel shift service provision, replacing some aspects of inpatient niv setup and/or . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint face-face outpatient niv follow-up on an individualised basis is attractive, particularly to mitigate risks and bolster service provision in face of covid-19 related challenges. nhs greater glasgow and clyde (gg&c) implemented a remote-monitored home-niv model for its copd population in 2017. the present study retrospectively analysed all patients who were commenced on therapy over the first 12 months of this service, with aim of determining whether outcomes similar to rcts were achieved in a real-world cohort of hypercapnic copd patients with typical comorbidities (which would have excluded many from niv rcts) who are managed with remote-monitored home niv. the primary outcome was median time to readmission or death over 12 months in patients receiving home-niv versus a control cohort. this study is part of programme of work analysing outcomes in a dataset of copd patients provided by nhs gg&c safe haven. local privacy advisory committee approval was obtained for release of deidentified data for this study. two cohorts were sampled from the database as outlined in figure 1 . the home-niv cohort consisted of 42 consecutive patients with copd who commenced home-niv between february 25 th 2017 and january 25 th 2018 at the queen elizabeth university hospital. copd diagnosis was confirmed as per gold guidelines, and was the primary diagnosis responsible for hypercapnic respiratory failure in all patients in this cohort. hypercapnic respiratory failure was defined as pco 2 >7kpa at least 2 weeks after index acute exacerbation and/or presence of persisting hypercapnia across current and previous copd episodes, with deferred niv assessment for attempted follow up post episode judged inappropriate. 28 patients in this cohort continued home-niv throughout the 12-month study period ('niv users'). 14 patients discontinued home-niv due to poor acceptance despite individualised interventions to optimise therapy during the study period ('niv non-users'). the control cohort comprised 27 patients treated with acute niv at the queen elizabeth university hospital between march and november 2017 following a life-threatening exacerbation of copd that resulted in hypercapnic respiratory failure. this was in the period prior to adoption of routine screening of all acute niv patients for home niv at our institution. retrospective review noted that patients in this group were suitable for home-niv but they were not referred to the home-niv service during the follow up period of this study. none of these patients 'crossed over' to commence home niv during the study's observed follow up period. all patients were noted to be receiving guideline-based copd care, including home oxygen therapy unless contraindicated. since early 2017 our practice has been to offer trialling home niv to copd patients with persistent hypercapnia (pcco2 >7kpa) at stable status, or during an acute episode if there has been recurrent hypercapnic respiratory failure where deferring commencing home niv to outpatient review is judged impractical or unsafe by patient-clinician consensus. often this decision to offer home niv within an acute episode is informed by high serum bicarbonate levels (implying chronic hypercapnia) and/or presence of suspected or confirmed osa overlapping with severe copd. patients in the home-niv cohort were commenced on remote monitored home-niv in ivaps auto-epap mode (lumis 150 st-a, airview, resmed) if persisting hypercapnia was present at day case review 2 to 4 . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint weeks following hospital discharge (n=14/42) or during the index hospital admission if persisting hypercapnia had been demonstrated across previous copd episodes as per above noted criteria (n=28/42) patients initiated on home-niv consented to their data being accessed and shared on the airview platform by the necessary healthcare professionals. airview data review was used to inform routine clinical care and identify niv therapy issues (usage, leak) as well as ventilation data patterns supporting optimized niv provision. patient telephone, community or clinic follow up was individualized based on and informed by the remote monitoring data. airview platform was used to make niv device therapy changes, when indicated. the supplementary material provides an overview of the copd niv therapy protocol implemented at nhs gg&c, with typical follow-up schedule as well as representative remote monitoring data. remotemonitoring pathway is used to support daycase niv initiation (rather than elective hospital admission), early hospital discharge (if niv initiated during inpatient episode our institution) or inpatient niv initiation at another hospital (rather than hospital-hospital transfer). remote-monitoring data is reviewed at day 1-2, day 5-7 and weekly thereafter, combined where required with telephone or video consultation, until treatment is optimized. remote-adjustments to ivaps-autoepap niv settings, adjustment to niv interface and face-face at home or daycase review arrangement are made where remote-monitoring and consultation data indicates requirement. stability is judged based on patient comfort and symptoms, acceptable niv usage durations, minimized unintentional leak and appropriate pressure support and other ventilator parameters. clinic follow up within 8-12 weeks including repeat capillary blood gases is scheduled for stable patients who can attend. patients who are having persisting difficulties establishing home niv despite remote-monitoring inputs are offered elective admission. baseline descriptive data were recorded including gender, age, bmi, predicted fev1% as well as comorbidities that could potentially contribute to hypercapnia. the primary outcome was time to readmission or death, censored at date of admission, date of death or 25 th january 2019. secondary outcome measures included time to hospital admissions and overall survival in the home-niv and control cohort. subgroup analyses of the home-niv cohort explored differences between niv users and niv non-users in the primary and secondary outcome measures. changes in healthcare usage (number of hospital admissions, occupied bed days (obds) and respiratory nurse home visits) were evaluated in niv users and niv non-users before and after home-niv. changes in capillary blood gases were analysed in the home-niv cohort in the form of capillary blood gas pco 2 and bicarbonate (where available). baseline characteristics of the study population are presented as mean (standard deviation), median (interquartile range) or count (percentage), as appropriate. primary and secondary study outcome measures were compared between the home-niv and control cohort using kaplan-meier survival analysis and the mantel-cox log rank test. additional subgroup analyses compared primary and secondary outcome measures between the niv user group and the niv non-user group alongside the control cohort using kaplan-meier and mantel-cox tests. changes in healthcare usage (number of hospital admissions, obds, and respiratory nurse home visits) and capillary blood gas pco 2 and bicarbonate between niv users, niv non-users and the control cohort were analysed using wilcoxon signed-rank test. statistical analyses were conducted using ibm spss statistics v.24 (ibm, new york, usa) and graphpad prism v7.0 (graphpad software, san diego, usa). . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint due to the nature of a retrospective analysis, the research was undertaken without patient involvement. patients were not invited to comment on the study design and were not consulted to develop patient relevant outcomes, interpret the results or to contribute to the writing or editing of this document for readability or accuracy. . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint baseline characteristics are shown in table 1 . gender, bmi and age are similar across all study cohorts except for a higher rate of males, lower bmi and a lower rate of notable comorbidities (suspected or confirmed overlapping osa, long term opiate therapy) in the niv non-user subgroup. the fev1% predicted value was around 40% across all study groups, in line with a "severe" classification of copd (3) particularly as in many patients the spirometry was an historical rather than contemporary result. the median time to readmission or death was significantly prolonged in patients with persisting hypercapnic respiratory failure treated with home-niv compared to a control cohort of hypercapnic copd patients (p<0.01, see figure 2a ). subgroup analyses showed significant differences between the niv user subgroup versus both the niv non-user group and the control cohort (both p<0.001). improvement in time to readmission or death was not achieved in patients who discontinued home-niv (figure 2b ). table 2 summarises time to readmission or death for each group. time to hospital readmission followed the same pattern as time to readmission or death. median time to hospital readmission was 221 days for the home-niv cohort (95% ci, 148 -294) and 68 days (95% ci, 18 -118; p<0.05) for the control cohort. subgroup analyses showed that time to hospital readmission was significantly improved in niv-users when compared to niv non-users and the control group (both p<0.01). there was no significant difference comparing the control group and niv non-users (p=0.38). 12-month overall survival was 78.6% in the home-niv cohort and 59.3% in the control cohort. patients that continued to use home-niv during the study period had a 12-month overall survival rate of 85.7%. due to the low number of recorded mortality events, group differences were not statistically significant in the primary (p=0.066) or subgroup analyses (p=0.07). service usage in nhs gg&c by the home-niv cohort in the 12 months prior to commencing home-niv (pre-niv) and the 12 months following initiation of home-niv (post-niv) are outlined in table 3 . a significant reduction in total number of admissions and obds is noted following initiation of home-niv across all patients in the home-niv cohort, but is particularly pronounced in niv users (p<0.001, figure 3 ). the data equate to a median reduction of 14 obds per annum per patient who continued remote-monitored home-niv. requirements for respiratory nurse home visits did not change significantly with the initiation of home-niv. capillary blood gas measurements were available in 21 patients before and after home-niv. significant improvements in median pco 2 (2.2kpa, p<0.05) and bicarbonate (4.9mmol/l, p<0.05) measured at followup after initiation of home-niv relative to measurements at baseline indicate control of hypercapnic respiratory failure (figure 4 ). . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. table 1 baseline characteristics table 3 changes in healthcare usage before and after home-niv . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint this study confirms the benefits of home-niv in copd patients with persisting hypercapnic respiratory failure in clinical practice. patients in the home-niv cohort had significantly fewer hospital readmissions compared to the control cohort, with the greatest improvements seen in those who continued with home-niv throughout the 12-month observed follow-up period. moreover, these data support the use of two-way remote monitoring as a feasible solution to managing the delivery of home-niv, maintaining care-quality while also substantially reducing demand on healthcare resources. the current results are consistent with the hot-hmv trial by murphy et al. (8) reporting delayed and reduced hospital readmissions in copd patients randomised to receive home-niv compared to patients treated with home oxygen therapy alone. while there are some important differences to consider between the hot-hmv trial and this study -less severe documented airflow obstruction and higher bmi in this study's patient cohort -reporting similar outcomes to the hot-hmv trial is encouraging. our data indicates that home-niv is effective in a typical population of patients presenting in routine clinical practice with phenotypes which would have potentially excluded them from rct inclusion. the secondary analyses also broadly support the interpretation of hot-hmv and other landmark copd home-niv trials (9, 17) indicating that patient selection for home-niv should be based on persisting hypercapnic respiratory failure, and that optimising niv to target improvement in hypercapnia is appropriate. the comparable outcomes of this study and hot-hmv importantly provide reassurance about safety and quality of a copd home-niv service model utilising assistive two-way remote-monitoring technology. in the hot-hmv trial, home-niv was noted to reduce exacerbation-related costs (by £1,141 per case) and patient-reported costs (by £2,337) relative to the control arm. niv device cost and cost per physician visit had the greatest impact on cost per qaly (18) . in line with this, the present study notes a considerable reduction in healthcare usage among home-niv users. in addition to significant decreases in hospital admissions, a median reduction of 14 occupied bed days per annum was observed per patient who continued home-niv. it seems likely that a copd home-niv management strategy based on remotemonitoring and individualised follow-up will reduces physician visit and patient travel costs and impact positively on patient quality of life. remote-monitoring based service model should reduce home niv costs and potentially further improve the quality of life benefit. future assessments are required to expand on the cost-effectiveness of home-niv and a proactive copd service model based on remote-monitoring. among various patient groups using niv at home, remote monitoring has been found to be non-inferior and at times more effective than usual face-to-face support, preferred by patients and associated with reduced healthcare utilisation (16, (19) (20) (21) . the additional channel of two-way patient engagement -that is, early intervention with an niv therapy change to optimise settings based on remote-monitoring data -may prove particularly valuable to ensure continued treatment adherence (22) . monitoring patients is a prerequisite for successful continuation of niv at home. maintaining the required level of contact face-to-face is particularly challenging for severe copd patients, who are often not fit to travel or who may require immediate intervention. remote-monitoring data can be utilised to support and enhance routine clinical care allowing positive endorsement to be relayed when monitoring data is reassuring, prioritising and focusing patientclinician interactions when issues are noted. we show for the first time that initiation and follow-up based exclusively on niv two-way remote monitoring can be an effective and realistic solution to providing access to home-niv to severe copd patients at the necessary scale. benchmarking of outcomes, with similar findings to published rct data provides reassurance about safety and maintained care-quality with a remote-monitoring based approach to home niv for hypercapnic copd. our findings broadly complement those from recent study reported from the netherlands, which demonstrated cost-effective provision of home initiation of niv for stable hypercapnic copd patients utilising remote-monitoring of ventilator and transcutaneous co2 data (23) . as key additions, our data suggest that remote-monitoring can be used to . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint safely support patients with persisting hypercapnia who are commenced on home niv at an acute episode as well as at stable status, and that overnight transcutaneous co 2 monitoring can be omitted from routine follow-up of copd patients on home-niv. undertaking routine transcutaneous monitoring in this patient cohort would not be realistic in routine clinical practice at scale. continued supervision of this approach with reporting of outcomes to ensure safety and quality of home-niv therapy, alongside continued evaluation of other endpoints for respiratory failure monitoring is required. our approach to home-niv setup for hypercapnic copd patients differs from published protocols. we have accrued considerable experience with volume assured pressure support niv modes at our centre. our experience is that these allows niv optimisation to be undertaken more efficiently with enhanced patient comfort and improved treatment quality as well as additional benefits including anticipation that treatment will be responsive to predictable fluctuations in a patient's condition. we commence niv treatment for copd patients in ivaps autoepap mode, targeting symptom benefit, remote-monitored ventilation patterns and follow-up capillary blood gas results (see supplementary data file), rather than in-hospital titration of niv in st mode, targeting high pressure support with transcutaneous co 2 monitoring. satisfactory clinical outcomes and follow-up blood gas data (median reduction pco2 2.2 kpa) in this study provide reassurance about the quality and safety of this niv setup protocol. clinical user experience with this approach is positive, and it achieves reduction in occupied bed days with no additional staffing support required to deliver the service. whether matched clinical outcomes and similar efficiency would be achieved with remote-monitored niv utilising st mode (potentially with at home titration) requires additional study. our subgroup analyses consistently showed that outcomes in patients who discontinue home-niv align closely with outcomes from the control cohort. this suggests that patients with severe hypercapnic copd are not negatively affected by the process of initiating home-niv. further exploration is indicated in this sub-population of patients who do not tolerate long-term niv at home. it could be that greater attention to patient activation, treatment provision, ventilation optimisation or level of contact is required. the patients who discontinued home niv had significant remote-management based scrutiny and input, and were offered 'standard' in-hospital and/or outpatient face-face attendance to try and maintain niv use. other centres have noted progressive improvements in home niv adherence rates with multi-disciplinary 'niv failure' clinics 25 . adoption of remote-monitoring can improve the workflow and prioritisation of niv mdt activity. whether additional mdt input than that provided in our described model would improve long term niv adherence is uncertain. the possibility that there are different responder groups regardless of optimisation efforts should also be considered. in our cohort, there was a higher proportion of female patients and higher mean bmi in niv users. we can speculate that these differences might reflect home support or early symptom benefit differences from home niv: obese patients may be more likely to have osa overlapping with hypercapnic copd. characterisation of these and other factors with remotemonitoring data comparing sustained users and non-users in future studies may allow further evaluation to a service model with evidence-based proactive prioritisation: intensive focused mdt input to those patients who require it, and minimised input to those where it is unnecessary or will be non-contributory. lastly, the presence of a control cohort, which consisted of patients who may have benefited but were not referred for home-niv from within an active tertiary niv centre, highlights the need for clinician education and other efforts to ensure equitable patient access to this evidence-based intervention. this study had several strengths, including the use of clinically meaningful outcomes and the real-world nature of the patient cohorts. however, we acknowledge several limitations. treatment allocation was not randomised and the impact of unrecognised confounding factors cannot be ruled out. we also did not have complete data on demographics, comorbidities or provision of and adherence to other copd treatments to ensure cohorts were otherwise matched. the statistical analyses of some of the subgroup analyses should be considered exploratory due to the limited sample size and the potential issue of multiple testing. finally, this study was not powered to find a difference in survival. while a survival benefit of home-niv has been . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint previously demonstrated in a similar patient population (9) , clear evidence of improved survival is still lacking and should be investigated in larger prospective trials. copd patients with persistent hypercapnic respiratory failure have poor outcomes with limited treatment options available. to our knowledge, this is the first study to confirm the benefits of remote-managed home-niv in this group of copd patients as they typically present in clinical practice. home-niv prolonged the time to readmission or death within 12 months in patients with persistent hypercapnia following an acute exacerbation of copd. in addition to being the outcomes that copd patients rate as most important (24) , exacerbation and hospitalisation avoidance address the substantial economic burden imposed by copd. we report significant reductions in healthcare usage among home-niv users and demonstrate that twoway remote monitoring can be an effective and realistic solution to providing access to home-niv for hypercapnic copd patients. the covid-19 pandemic has presented considerable challenges to home-niv service provision. our data provides reassurance that a service model based on outpatient or truncated inpatient niv initiation and remote-monitoring based follow up allows face-face contact to be safely minimised, reducing covid-19 transmission risks whilst maintaining niv care-quality. we gratefully acknowledge the comprehensive contribution of the respiratory physiologist and nurse specialist teams in nhs gg&c to the positive outcomes reported in this paper: they have adapted service models to realise benefits from assistive technologies, and continue to be enthusiastically committed to improving patient outcomes and providing realistic medicine. study participant flow diagram. kaplan-meier plot of time to readmission or death from study initiation to the end of study follow-up. (a) primary analysis shows significant differences between the home-niv and the control cohort. (b) subgroup analyses showed that the improvement in 12-month readmission avoidance is noted only in patients who continue home-niv throughout the study period. . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint changes in healthcare usage before and after home-niv for niv users (circle) and niv non-users (triangle). changes in blood gas measurements at baseline and follow up after home-niv initiation. . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint arnal jm, texereau j, garnero a. practical insight to monitor home niv in copd patients. copd. 2017;14(4):401-10. . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint study participant flow diagram . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint kaplan-meier plot of time to readmission or death from study initiation to the end of study follow-up. (a) primary analysis shows significant differences between the home-niv and the control cohort. (b) subgroup analyses showed that the improvement in 12-month readmission avoidance is noted only in patients who continue home-niv throughout the study period. . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint changes in healthcare usage before and after home-niv for niv users (circle) and niv non-users (triangle). data on respiratory nurse home visits was not available in electronic health records for the 18 patients whose residence is outside our health board. . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint changes in blood gas measurements at baseline and follow up after home-niv initiation in niv users. data availability limited to subset of patients who attended for face-face follow up and had some or all components of post niv blood gas results inputted into electronic health record (including 2 patients who had pco2 but not bicarbonate result available). 2 patients had pco2 <7kpa at time of niv initiation but had other standard indications to commence home niv. . cc-by-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted november 12, 2020. ; https://doi.org/10.1101/2020.11.08.20227892 doi: medrxiv preprint nhs. copd commissioning toolkit: a resource for commissioners /chronic-obstructive-pulmonary-disease-copd-commissioning-toolkit.pdf: nhs medical directorate risk of death and readmission of hospital-admitted copd exacerbations: european copd audit global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: gold executive summary readmission rates and life threatening events in copd survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure effects of non-invasive ventilation in patients with acute respiratory failure excluding post-extubation respiratory failure, cardiogenic pulmonary edema and exacerbation of copd: a systematic review and meta-analysis non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease effect of home noninvasive ventilation with oxygen therapy vs oxygen therapy alone on hospital readmission or death after an acute copd exacerbation: a randomized clinical trial non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial. the lancet respiratory medicine european respiratory society guidelines on long-term home non-invasive ventilation for management of copd noninvasive ventilation in stable hypercapnic copd: what is the evidence? home noninvasive ventilatory support for patients with chronic obstructive pulmonary disease: patient selection and perspectives glasgow supported self-management trial (gsust) for patients with moderate to severe copd: randomised controlled trial innovative approach to copd improves disease impact, quality of life and reduces hospital admissions in glasgow telehealthcare for chronic obstructive pulmonary disease nocturnal non-invasive ventilation in copd patients with prolonged hypercapnia after ventilatory support for acute respiratory failure: a randomised, controlled, parallel-group study cost-effectiveness of home oxygen therapy-home mechanical ventilation (hot-hmv) for the treatment of chronic obstructive pulmonary disease (copd) with chronic hypercapnic respiratory failure following an acute exacerbation of copd in the united kingdom (uk). a102 determinants of outcomes and high-value care compliance with home noninvasive mechanical ventilation in patients with chronic respiratory failure: telemonitoring versus usual care surveillance -a randomized pilot study remote monitoring of home non-invasive ventilation: a feasibility study home telemonitoring of noninvasive ventilation decreases healthcare utilisation in a prospective controlled trial of patients with amyotrophic lateral sclerosis effect of a patient engagement tool on positive airway pressure adherence: analysis of a german healthcare provider database home initiation of chronic non-invasive ventilation in copd patients with chronic hypercapnic respiratory failure: a randomised controlled trial a systematic review of how patients value copd outcomes long term adherence to home mechanical ventilation: a 10-year retrospective, single-centre cohort study key: cord-027526-ohcu28rk authors: zhou, xiaoyang; yao, shengmi; dong, pingping; chen, bixin; xu, zhaojun; wang, hua title: preventive use of respiratory support after scheduled extubation in critically ill medical patients—a network meta-analysis of randomized controlled trials date: 2020-06-22 journal: crit care doi: 10.1186/s13054-020-03090-3 sha: doc_id: 27526 cord_uid: ohcu28rk background: respiratory support has been increasingly used after extubation for the prevention of re-intubation and improvement of prognosis in critically ill medical patients. however, the optimal respiratory support method is still under debate. this network meta-analysis (nma) aims to evaluate the comparative effectiveness of various respiratory support methods used for preventive purposes after scheduled extubation in critically ill medical patients. methods: a systematic database search was performed from inception to december 19, 2019, for randomized controlled trials (rcts) that compared a preventive use of different respiratory support methods, including conventional oxygen therapy (cot), noninvasive ventilation (niv), high-flow oxygen therapy (hfot), and combinational use of hfot and niv (hfot+niv), after planned extubation in adult critically ill medical patients. study selection, data extraction, and quality assessments were performed in duplicate. the primary outcomes included re-intubation rate and short-term mortality. results: seventeen rcts comprising 3341 participants with 4 comparisons were included. compared with cot, niv significantly reduced the re-intubation rate [risk ratio (rr) 0.55, 95% confidence interval (ci) 0.39 to 0.77; moderate quality of evidence] and short-term mortality (rr 0.66, 95% ci 0.48 to 0.91; moderate quality of evidence). compared to cot, hfot had a beneficial effect on the re-intubation rate (rr 0.55, 95% ci 0.35 to 0.86; moderate quality of evidence) but no effect on short-term mortality (rr 0.79, 95% ci 0.56 to 1.12; low quality of evidence). no significant difference in the re-intubation rate or short-term mortality was found among niv, hfot, and hfot+niv. the treatment rankings based on the surface under the cumulative ranking curve (sucra) from best to worst for re-intubation rate were hfot+niv (95.1%), niv (53.4%), hfot (51.2%), and cot (0.3%), and the rankings for short-term mortality were niv (91.0%), hfot (54.3%), hfot+niv (43.7%), and cot (11.1%). sensitivity analyses of trials with a high risk of extubation failure for the primary outcomes indicated that the sucra rankings were comparable to those of the primary analysis. conclusions: after scheduled extubation, the preventive use of niv is probably the most effective respiratory support method for comprehensively preventing re-intubation and short-term death in critically ill medical patients, especially those with a high risk of extubation failure. invasive mechanical ventilation (imv) is universally recognized as a first-line therapy for rescuing acute respiratory failure. although it is a life-saving treatment in nature, prolonged imv is always accompanied by an increased risk of ventilator-associated pneumonia and lung injury [1, 2] and neurocognitive sequelae associated with prolonged sedation [3, 4] , thus resulting in a longer duration of intensive care unit (icu) stay and increased mortality [5, 6] . therefore, it is essential for mechanically ventilated patients to receive daily assessments of weaning readiness [6] and timely extubation when they meet the criteria of weaning from imv. however, approximately 10-20% of patients will experience extubation failure and require re-intubation within 24-72 h after scheduled extubation [7] [8] [9] [10] , and extubation failure is associated with poor outcomes and increased mortality [8] . it is therefore essential to receive prophylactic respiratory support for post-extubated patients. conventional oxygen therapy (cot) is the most frequently administered respiratory support method after extubation. cot can only deliver a maximum flow of oxygen (o 2 ) of 15 l/min using the venturi mask or reservoir mask [11] , and the delivered fraction of inspired oxygen (fio 2 ) is unstable because the fio 2 also depends on the inspiratory flow, respiration rate, and tidal volume of patients in addition to the o 2 flow [12] . hence, apart from improving oxygenation, cot seems to have no or minimal effects on changes in lung aeration, hemodynamics, or neuromuscular function, which are the main pathophysiological mechanisms that contributed to extubation failure [12] . in recent years, noninvasive ventilation (niv) and high-flow oxygen therapy (hfot) have been increasingly used as alternative respiratory support methods in post-extubated patients. both niv and hfot are anticipated to prevent extubation failure and improve prognosis by delivering more stable fio 2 [12, 13] , promoting alveolar recruitment and preventing alveolar collapse [14] [15] [16] , and reducing the work of breathing [17, 18] . nevertheless, the latest meta-analysis [19] of randomized controlled trials (rcts) suggested that compared to cot, preventive use of niv after extubation had no effect on the re-intubation rate or mortality in post-extubated patients. meanwhile, several recent metaanalyses [20] [21] [22] also revealed neutral effects of hfot used after planned extubation on the re-intubation rate or mortality compared with cot or niv. more recently, a multicenter rct [23] proposed a novel method that combined the use of hfot and niv (hfot+niv) and proved its superiority over hfot in the prevention of re-intubation in post-extubated patients. however, the method did not affect mortality. although the above studies are informative, the relative effectiveness throughout various respiratory support methods remains unknown. unlike conventional pairwise meta-analysis that only include head-to-head comparisons, network meta-analysis (nma) can compare multiple treatments simultaneously in a single analysis by combining direct and indirect evidence [24] and inform on the relative effect of indirectly compared treatments. therefore, we conducted an nma to evaluate the comparative effectiveness of various respiratory support methods used as a preventive strategy after planned extubation in critically ill medical patients. this nma was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses (prisma) extension statement for reporting network meta-analyses [25] . the study protocol was registered at the international prospective register of systematic reviews (prospero registration number: crd42020164357). relevant studies regarding preventive use of various respiratory support methods, including cot, niv, hfot, and hfot+niv, after planned extubation in critically ill medical patients were searched systematically by two independent reviewers (xu z and chen b) from database inception through december 19, 2019, in pubmed, embase, web of science, and cochrane central register of controlled trials. the detailed search strategy is presented in additional file 1. a manual search of reference lists from previous relevant studies and reviews was also conducted to further identify relevant literature. this nma had no restrictions on language or date of publications. after filtering duplicate records, two reviewers (xu z and chen b) independently screened the title and abstract for eligibility. the full text of records deemed eligible during preliminary screening was reviewed to determine whether these studies met the inclusion or exclusion criteria. the reasons for the exclusion of irrelevant studies are recorded in additional file 1 (table s1 ). no restrictions were applied on study period, primary disease leading to imv, ventilation mode in niv, or risk of extubation failure. a third reviewer participated in the discussion to adjudicate disagreements. the inclusion criteria included the following: (1) participants: adult critically ill medical patients (age ≥ 18 years) admitted to the icu who received imv > 12 h, successfully passed the spontaneous breathing trial (sbt), and were ready for extubation; (2) interventions and comparisons: one of the following respiratory support methods compared with one another: cot, niv, hfot, and hfot+niv. all of these methods were used after planned extubation for preventive purposes; (3) outcomes: the primary outcomes were re-intubation rate and short-term mortality, and the secondary outcomes included post-extubation respiratory failure, length of icu stay and in-hospital stay, and comfort score. studies reporting on at least one of the above outcomes were included. the short-term mortality was predefined as death within 30 days after randomization irrespective of the cause of death; and (4) study design: prospective rcts. the exclusion criteria included the following: (1) non-rcts, including reviews, retrospective studies, cohort studies, and crossover studies; (2) studies conducted in post-surgical patients; (3) studies enrolled patients who underwent an unplanned extubation; (4) studies in which respiratory support was used for therapeutic or facilitative purpose [12] ; (5) studies did not report any outcomes of interest; and (6) conference abstracts without full-text manuscripts. two reviewers (yao s and dong p) independently reviewed the complete text of each included study and extracted data using a standardized form. the abstracted data included the name of the first author, publication year, sample size, details of the population enrolled, primary diagnosis leading to imv, characteristics of interventions, study period, acute physiology and chronic health evaluation (apache) ii score, and atrial partial pressure of carbon dioxide (paco 2 ) at end of sbt. data on primary and secondary outcomes were also recorded in detail. if a study reported various mortalities, the longest follow-up short-term mortality was used for analysis. data on the occurrence of re-intubation and respiratory failure within 72 h after extubation was preferred, and it would, if unavailable, be substituted by data on occurrence during icu admission. we also used the paco 2 measured during sbt or at extubation instead of that measured at the end of sbt when it was unavailable. the disagreement was resolved by a joint review of the full text to reach consensus. the criteria for diagnosing post-extubation respiratory failure were defined by the authors in the included trials. according to the previous studies [23, [26] [27] [28] , we predefined "high risk" of extubation failure as the presence of at least one among the following factors: (1) age > 65 years; (2) heart failure or chronic obstructive pulmonary disease (copd); (4) apache ii score > 12 at extubation; (5) body mass index > 30 kg/m 2 ; (6) airway patency problems, including high risk of developing laryngeal edema or inability to deal with respiratory secretions; (7) 2 or more comorbidities; (8) more than one sbt failure; and (9) imv > 7 days. two independent reviewers (yao s and dong p) evaluated the quality of each included trials using the cochrane risk of bias tool [29] . each trial was judged as low, unclear, or high risk with respect to adequate sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. we resolved disagreements by a discussion with a third reviewer to reach consensus. the random effects nma was performed using a frequentist framework to calculate risk ratios (rr) for dichotomous outcomes, mean differences (md) for continuous outcomes, and corresponding 95% confidence intervals (ci). the conventional pairwise metaanalyses were also conducted for each comparison using a random effects model. all statistical analyses were performed using the netmeta package in stata/se 15.0 (stata-corp, college station, tx, usa). two-sided p value less than 0.05 was considered statistically significant. homogeneity and consistency assumptions underlie the validity of evidence from nma [30] . to evaluate heterogeneity across studies within each direct comparison, we visually inspected the forest plots and quantified using the q test and the i 2 statistic [31] . inconsistency between direct and indirect estimates in the entire network for each outcome was assessed locally with a loop-specific approach and globally with design-bytreatment interaction model [32] . we also ranked the treatment effects of various respiratory support methods according to the probabilities of leading to the best results based on the surface under the cumulative ranking curve (sucra) for each outcome [33] . the value of scura ranges from 0 to 100%, the higher the value, the better the effectiveness of the method [33] . given that the risk of extubation failure and hypercapnia (paco 2 > 45 mmhg) at the end of sbt might affect the relative effectiveness of various respiratory support methods [34] , we performed two sensitivity analyses to evaluate the robustness of the nma results for the primary outcomes by excluding studies with low or unclear risk of extubation failure or studies that enrolled patients with hypercapnia at the end of sbt. we assessed the quality of evidence from direct comparisons, indirect comparisons, and nma estimates for each outcome using the modified grading of recommendation, assessment, development and evaluation (grade) tool for nma [35, 36] . the contribution matrix was constructed to evaluate the information contribution of direct evidence to entire nma estimates [36] . because only one loop (niv-cot-hfot) was connected in this nma, we assigned the quality of the indirect comparison with the lower quality rating in the two contributing direct comparisons within this loop. additionally, the higher confidence in the direct and indirect estimates was preferred as the quality rating of overall nma estimates. the quality of evidence would be rated down for the presence of risk of bias, imprecision, publication bias, indirectness, intransitivity, or incoherence between direct and indirect estimates [36] . we initially identified 3466 citations through the electronic database search. an additional 64 records were identified from the manual search of the references in previous publications. after excluding 334 duplicates and 3134 irrelevant citations, we reviewed the full text of the remaining 62 records. finally, a total of 17 eligible rcts [23, [26] [27] [28] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] , representing 3341 patients, were included in this nma. the prisma flowchart for study inclusion is shown in fig. 1 . of the 17 included rcts [23, [26] [27] [28] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] , 10 [23, 26-28, 38, 41, 43-46] were multicenter, and 7 [37, 39, 40, 42, [47] [48] [49] were single-center. all included rcts were published in the last 15 years, and the number of participants ranged from 38 to 614. participants in 5 trials [23, [26] [27] [28] 41] were at high risk of extubation failure, and participants in 1 trial [45] were at low risk. the specified definition of risk of extubation failure was unavailable in 11 trials [37-40, 42-44, 46-49] . among these trials, however, 9 trials [37-40, 42, 44, 47-49] fulfilled the predefined criteria of a high risk of extubation failure in our nma and were therefore classified as high risk, and the risk in the remaining 2 trials [43, 46] was unclear. niv was compared with cot in 9 trials [26, [37] [38] [39] [40] [41] [42] [43] [44] . four trials compared hfot with cot [28, [45] [46] [47] . three trials compared niv with hfot [27, 48, 49] , and 1 trial [23] compared the combinational use of hfot and niv (hfot+niv) with hfot alone. in all trials that involved niv [23, 26, 27, 37-44, 48, 49] , niv was used with bilevel positive airway pressure mode. the paco 2 level at the end of sbt was less than 45 mmhg in 11 trials [23, 26-28, 40-42, 45-47, 49] , greater than 45 mmhg in 4 trials [38, 39, 44, 48] , and unavailable in 2 trials [37, 43] . details regarding the characteristics and outcomes of each included study are described in additional file 1 (table s2 and s3) . the quality assessment is presented in detail in figs. 2 and 3. all trials were assessed to be at low or unclear risk of bias in terms of adequate sequence generation and allocation concealment except for one trial [37] in which randomization was performed based on the admission number. of note, all trials were judged as having a high risk of bias in blinding of participants and personnel because it was clinically impracticable due to virtual practice issues. apart from one trial [38] that had a high bias in detection, all other trials had a low or unclear risk of bias in detection, attrition, and reporting. additionally, three trials [28, 46, 49] had a high risk of other bias associated with the funding source. we downgraded the quality of evidence for several direct comparisons due to imprecision, limitations of risk of bias, or statistical heterogeneity. we had no significant concerns on intransitivity. although no statistical evidence of incoherency was found in the network for any outcomes, we downgraded the quality of evidence for the length of icu stay and length of in-hospital stay in two comparisons due to the presence of problematic incoherence that was evaluated by visually inspecting the direct and indirect estimates. the summary of evidence grading is presented in table 1 . all included rcts [23, [26] [27] [28] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] involving 3341 patients reported re-intubation rates. no statistically significant heterogeneity was noted among the included trials within each comparison ( table 1 ). the inconsistency test at the global and local levels indicated no significant inconsistency (fig. 4, fig. s1 in additional file 1). the quality of evidence for nma estimates was rated as moderate (table 1) . compared with cot, niv and hfot were similarly effective in reducing the reintubation rate (rr 0.55, 95% ci 0.39 to 0.77 and rr 0.55, 95% ci 0.35 to 0.86, respectively) (fig. 4) . indirect evidence showed that compared to niv or hfot, hfot+niv likely decreased the re-intubation rate ( table 2 ) despite the lack of statistical significance. thus, hfot+niv ranked best according to the sucra statistic followed by niv, hfot, and cot (table 3) . sixteen rcts [23, 26-28, 37-46, 48, 49] enrolling 3281 patients reported short-term mortality. we found no heterogeneity across the included trials, and no significant inconsistency existed in this network (table 1 , fig. s2 in additional file 1). nma estimates provided moderate to low-quality evidence and indicated that compared to cot, niv decreased the risk of short-term death (rr 0.66, 95% ci 0.48 to 0.91) (fig. 5 , table 1 ). hfot had no beneficial effect on the short-term mortality compared with cot (rr 0.79, 95% ci 0.56 to 1.12). we found no difference in short-term mortality among niv, hfot, and hfot+niv (table 2) . niv ranked first among the four respiratory support methods (table 3) . although hfot+niv ranked highest for prevention of re-intubation, indirect evidence suggested that compared to niv, hfot+niv likely increased short-term mortality ( table 2 ). in summary, niv is probably the most effective method for comprehensively preventing re-intubation and short-term death (fig. 6) . the network geometry and weight contribution matrix for the primary outcomes are shown in fig. s3 -s6 (see additional file 1). two sensitivity analyses were performed for the primary outcomes by exclusively using 14 trials that enrolled patients with a high risk of extubation failure or 11 trials that enrolled patients with paco 2 < 45 mmhg at the end of sbt. the results suggested that the comparative effectiveness of various methods remained similar, and the sucra rankings were comparable to those of the primary analysis (additional file 1: table s4 and s5, fig. s7 -s10). eleven trials [23, 26-28, 37, 38, 43-46, 48] reported post-extubation respiratory failure. heterogeneity was statistically significant across trials in the comparison of niv and cot ( table 1 ). the consistent assumption in this network was acceptable (fig. s11 in additional file 1). the network estimates were ranked as moderate to low quality. both niv and hfot were superior to cot in preventing post-extubation respiratory failure (table 1 , fig. s12 in additional file 1). although hfot+niv had the highest scura value, its 95% ci was wide and contained the null effect when compared with niv or hfot (table 2) . therefore, the treatment ranking should be interpreted with caution. fifteen trials [23, 26-28, 37-42, 44-46, 48, 49] reported the length of icu stay. substantial heterogeneity was noted across trials within the comparison of niv and cot (table 1) . a problematic incoherence was found by visually inspecting the direct and indirect estimates despite no statistical significance (additional file 1: fig. s13 and s14). no evidence revealed the superiority of one particular respiratory support method because all the confidence intervals were very wide and included the null value (table 1) . thus, the rank order should be interpreted cautiously. length of in-hospital stay was reported in 8 trials [23, 26-28, 38, 39, 41, 45] . we found a suspicious inconsistency in this network through visual inspection of the direct and indirect estimates (additional file 1: fig. s15 and s16). the network estimates provided low-to very low-quality evidence of no difference among cot, niv, hfot, and hfot+niv in terms of length of inhospital stay (tables 1 and 2 ). however, hfot might reduce the length of in-hospital stay compared with cot (table 1) . hfot ranked best among the four respiratory support methods (table 3) . only 3 rcts reported the comfort score, of which 2 compared hfot with cot [46, 47] , and 1 compared hfot with niv [48] . therefore, we did not perform an nma for this outcome. according to the results from pairwise meta-analysis (table 1) , the comfort score of hfot was lower than that of cot or niv. the network geometry and weight contribution matrix for each secondary outcome are available in the supplementary material (additional file 1: fig. s17-s22 ). this nma of 17 rcts comprising 3341 participants evaluated the relative effectiveness of four preventive respiratory support methods in critically ill medical patients. the findings suggested the superiority of niv over cot in terms of re-intubation, short-term mortality, and post-extubation respiratory failure. compared to cot, hfot had beneficial effects on the re-intubation rate and post-extubation respiratory failure but not short-term mortality. there were similar treatment effects on the primary and secondary outcomes among niv, hfot, and hfot+niv. although hfot+niv ranked best for reducing the risk of re-intubation, it exhibited the potential to increase short-term mortality compared with niv. therefore, to comprehensively prevent re-intubation and short-term death, prophylactic use of niv after scheduled extubation is probably the most effective respiratory support method in critically ill medical patients, especially those with a high risk of extubation failure. respiratory support has been widely applied to prevent post-extubation respiratory failure, treat respiratory failure that developed after extubation, or facilitate early weaning from imv in patients who have failed sbt [12] . currently, routine use of cot remains the mainstay of preventive respiratory support in post-extubated patients. since the low-flow oxygen delivered by cot is insufficient to generate positive airway pressure, cot may not guarantee adequate gas exchange to meet the demand of critically ill patients, especially those who were intubated for medical diseases, such as heart failure and copd. several rcts have proven that preventive use of niv or hfot after planned extubation was an effective alternative approach [26, 37, 38, 41, 42, [44] [45] [46] . however, the most recent pairwise meta-analysis by maitra et al. [19] concluded that niv was not superior to cot in terms of prevention of re-intubation or death. interestingly, in addition to trials that used niv as a preventive strategy after planned extubation, the meta-analysis by maitra et al. [19] also included trials in which niv was applied as a facilitative or therapeutic strategy and trials in which patients received unplanned extubation. moreover, at least two studies [37, 40] were missed in their meta-analysis [19] . thus, substantial heterogeneity was identified across the included trials in their study [19] , and their evidence had a low quality. regarding the comparison of hfot and cot, the two latest meta-analyses [20, 22] drew contradictory conclusions. the meta-analysis by xu et al. [22] found a beneficial effect of hfot on re-intubation. however, the meta-analysis by zhu et al. [20] revealed no effects on re-intubation or mortality with the use of hfot. unfortunately, the two meta-analyses included a heterogeneous population that comprised post-surgical patients and critically ill medical patients. moreover, the study by zhu et al. [20] pooled results from rcts and crossover studies. these factors might contribute to the above conflicting results. in contrast, a relatively homogeneous population of critically ill medical patients who received preventive respiratory support after planned extubation was recruited in our nma. network estimates suggested the benefits of niv on the reintubation rate and short-term mortality and the benefit of hfot on the re-intubation rate compared with cot. these findings raised the question of why the benefits of hfot on re-intubation could not be translated into survival benefits, but niv could. it might be explained by the following: first, niv could provide a higher positive airway pressure than hfot. the high positive airway pressure delivered by niv increases the intrathoracic pressure, which is analogous to imv; reduces the left ventricular preload and afterload; and improves the cardiac performance [12] ; these features might translate into a better prognosis in medical patients with cardiac failure. in addition, copd is another one primary disease leading to icu admission in most of the included trials in our study. due to the generation of higher positive airway pressure, niv may be more effective than hfot in facilitating decarboxylation in copd patients. this may be another one reason for interpreting the survival benefits of niv. finally, hfot is more comfortable compared with cot or niv [46] [47] [48] . for patients treated with noninvasive respiratory support that would fail, apparent improvement in patients comfort could mask deterioration to some extent [27] because prolonged noninvasive respiratory support no. number, rcts randomized controlled trials, cma conventional meta-analysis, nma network meta-analysis, niv noninvasive ventilation, hfot high-flow oxygen therapy, cot conventional oxygen therapy, icu intensive care unit, rr risk ratio, md mean difference, ci confidence interval, ne not estimable a p < 0.05 1 quality of evidence for direct estimate rated down by one level for serious risk of bias because of the high risk of unblinding of participants and personnel in all included trials 2 quality of evidence for direct estimate rated down by one level for serious imprecision because 95% ci include values favoring either treatment 3 quality of evidence for direct estimate rated down by one level for substantial heterogeneity 4 quality of evidence for direct estimate rated down by two levels for very serious imprecision because 95% ci are very wide and include values favoring either treatment 5 quality of evidence will be not downgraded for intransitivity in the indirect comparisons 6 quality of evidence for indirect estimate rated down by one level for serious risk of bias 7 quality of evidence for indirect estimate rated down by one level for serious imprecision 8 not estimable because no loop can be constructed for the two treatments in the evidence network 9 quality of evidence for indirect estimate rated down by one level for serious incoherence 10 quality of evidence for indirect estimate rated down by two levels for very serious imprecision 11 quality of evidence for network estimate rated down by one level for serious risk of bias 12 quality of evidence for network estimate rated down by one level for serious imprecision 13 quality of evidence for network estimate rated down by one level for potential serious incoherence fig. 4 forest plot of network meta-analysis for re-intubation rate. niv noninvasive ventilation, hfot high-flow oxygen therapy, cot conventional oxygen therapy, ci confidence interval resulting from comfort and tolerance could improve oxygenation ostensibly and thus might disguise signs of respiratory distress for an extended period [45] and ultimately lead to delayed re-intubation and increased mortality. this view is supported by the results of the study by kang et al. [50] . this study suggested that the failure of hfot might delay intubation and increase mortality. there is limited information about the comparison of hfot and niv in post-extubated patients. theoretically, preventive hfot might be noninferior to niv in post-extubated patients because hfot had some distinctive advantages over niv, including increased comfort [46] [47] [48] 51] , easier clearance of secretions [52] , and reduced risk of adverse effects [51, 53] . a multicenter rct [27] found similar effects on the re-intubation rate and icu mortality between hfot and niv. our nma also further confirmed the similar effectiveness of niv and hfot on the re-intubation rate and short-term mortality, which was consistent with the results of previous meta-analyses [21, 22] . combinational use of hfot and niv seems to be a promising method in postextubated patients because the addition of hfot to niv could, at least theoretically, further improve gas exchange and decrease the work of breathing. the high-wean study [23] indicated that re-intubation rate and post-extubation respiratory failure were reduced with hfot+niv compared with hfot alone. our nma also suggested that hfot+niv ranked first for the prevention of re-intubation rate and post-extubation respiratory failure. however, only one study has compared hfot+niv with other methods to date, and its direct estimate suggested that the 95% ci contained the null effect. one should thus be cautious in the interpretation of these findings. the risk of extubation failure and paco 2 level at the end of sbt might be the effect modifiers in this nma. therefore, we conducted sensitivity analyses for the primary outcomes. our evidence was in favor of the preventive use of niv after planned extubation in high-risk critically ill medical patients, which was consistent with the conditional recommendation from the european respiratory society/american thoracic society clinical practice guidelines [34] . sensitivity analysis also indicated that niv remains the most effective method in nonhypercapnic critically ill medical patients. however, an observational study by gong et al. [54] found a conflicting result that prophylactic niv could not reduce re-intubation or hospital mortality in copd patients with paco 2 < 45 mmhg. it is noteworthy that in our nma, most trials that enrolled nonhypercapnic patients had a high risk of extubation failure. in addition, highcot conventional oxygen therapy, niv noninvasive ventilation, hfot high-flow oxygen therapy, icu intensive care unit risk factors were not limited to copd; they also comprised other factors, which might be one of the causes of the above conflicting results. several strengths in this nma should be mentioned. first, to our knowledge, this is the first nma to evaluate the comparative efficacies of various respiratory support methods in post-extubated critically ill patients. nma allows the comparison of multiple treatments simultaneously in a single analysis and improves the precision by combining direct and indirect estimates. second, a more homogeneous population was enrolled in this nma. to improve the transitivity across comparisons and reduce the heterogeneity across included trials, we set strict inclusion criteria that only critically ill medical patients who were treated with preventive respiratory support after planned extubation could be included. third, we performed sensitivity analyses to eliminate the influence of two potential effect modifiers on the nma results and confirmed the robustness of the nma results. other strengths included a comprehensive literature search and application of grade methodology to assess the quality of evidence. this nma had some limitations. first, we did not construct a comparison-adjusted funnel plot to assess the presence of small-study effects due to limited studies in each direct comparison. therefore, the possible overestimation of effect size in studies with a small sample size should be considered when interpreting the results. second, although it is difficult to identify the effect modifiers in an nma, we performed two sensitivity analyses to assess the robustness of the nma results. however, there were also other differences among the included studies that potentially influenced the nma results, including sample size, duration of respiratory support, and primary disease lead to imv. unfortunately, we did not perform sensitivity analysis for these factors given the limited information in the included studies. third, the adverse complications were not analyzed in this nma because the definition of adverse complications was largely different among included trials. thus, we had no insight into the safety of various respiratory support approaches. fourth, the pooled results of this nma might have a potential bias given the lack of blindness in all included trials. finally, we redefined forest plot of network meta-analysis for short-term mortality. niv noninvasive ventilation, hfot high-flow oxygen therapy, cot conventional oxygen therapy, ci confidence interval high risk of extubation failure according to the previously published studies given that no consistent definition of "high risk" is available to date. as a consequence, this limitation may impact the certainty of the sensitivity analysis results. in critically ill medical patients, especially those who are at high risk of extubation failure, preventive use of niv after scheduled extubation is probably the most effective respiratory support method for comprehensively preventing re-intubation and short-term death. this network meta-analysis showed a promising result for hfot+niv to prevent re-intubation. however, sufficient evidence regarding head-to-head comparisons of hfot+niv and other methods is still lacking. more high-quality studies comparing hfot+niv to other modalities of respiratory support are needed in the future. fig. 6 clustered ranking plot based on cluster analysis of sucra values for the two primary outcomes. treatment lying in the upper right corner is more effective in preventing re-intubation and short-term mortality than the other treatments. scura surface under the cumulative ranking curve, niv noninvasive ventilation, hfot high-flow oxygen therapy, cot conventional oxygen therapy the manuscript. xu z and chen b performed the database search and study selection and helped in data analysis. yao s and dong p performed the data extraction, quality assessment, and evidence rating. the authors have read and approved the final manuscript. this work was supported by the grants from zhejiang medicine and health science and technology project (no. 2019ky184) and natural science foundation of zhejiang province (no. ly19h190001). the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: diagnosis and treatment towards ultraprotective mechanical ventilation sedation, delirium and mechanical ventilation: the 'abcde' approach intensive care unit drug use and subsequent quality of life in acute lung injury patients clinical and economic consequences of ventilator-associated pneumonia: a systematic review weaning from ventilatory support tracheal extubation the decision to extubate in the intensive care unit evolution of mortality over time in patients receiving mechanical ventilation outcomes of extubation failure in medical intensive care unit patients aarc clinical practice guideline: oxygen therapy for adults in the acute care facility-2002 revision & update ventilatory support after extubation in critically ill patients high-flow oxygen therapy in acute respiratory failure evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures physiologic effects of noninvasive ventilation during acute lung injury reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure respiratory response and inspiratory effort during pressure support ventilation in copd patients noninvasive ventilation and oxygen therapy after extubation in patients with acute respiratory failure: a meta-analysis of randomized controlled trials high-flow nasal cannula oxygen therapy versus conventional oxygen therapy in patients after planned extubation: a systematic review and meta-analysis can high-flow nasal cannula reduce the rate of reintubation in adult patients after extubation? a meta-analysis high-flow nasal cannula in adults with acute respiratory failure and after extubation: a systematic review and meta-analysis effect of postextubation high-flow nasal oxygen with noninvasive ventilation vs high-flow nasal oxygen alone on reintubation among patients at high risk of extubation failure: a randomized clinical trial network meta-analysis: an introduction for clinicians the prisma extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial high-flow nasal cannula to prevent postextubation respiratory failure in high-risk non-hypercapnic patients: a randomized multicenter trial the cochrane collaboration's tool for assessing risk of bias in randomised trials assessing key assumptions of network meta-analysis: a review of methods cochrane handbook for systematic reviews of interventions consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure a grade working group approach for rating the quality of treatment effect estimates from network meta-analysis evaluating the quality of evidence from a network meta-analysis non-invasive mechanical ventilation after the successful weaning: a comparison with the venture mask noninvasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomized controlled trial non-invasive ventilation after extubation in patients with chronic obstructive airways disease: a randomised controlled trial role of non-invasive ventilation in limiting reintubation after planned extubation noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial preventive use of noninvasive ventilation after extubation: a prospective, multicenter randomized controlled trial intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (vhyper) effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: a randomized clinical trial nasal high-flow versus venturi mask oxygen therapy after extubation. effects on oxygenation, comfort, and clinical outcome the value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure comparison of high flow nasal cannula with noninvasive ventilation in chronic obstructive pulmonary disease patients with hypercapnia in preventing postextubation respiratory failure: a pilot randomized controlled trial a study on the effects and safety of sequential humidified high flow nasal cannula oxygenation therapy on the copd patients after extubation failure of high-flow nasal cannula therapy may delay intubation and increase mortality high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure sequential application of oxygen therapy via high-flow nasal cannula and noninvasive ventilation in acute respiratory failure: an observational pilot study noninvasive ventilation not all copd patients benefit from prophylactic noninvasive ventilation after scheduled extubation: an exploratory study publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. zhou x designed the study, performed the data analysis, and drafted the manuscript. wang h participated in the conception and design of the study, helped to perform the quality assessment and study selection, and revised supplementary information accompanies this paper at https://doi.org/10. 1186/s13054-020-03090-3. key: cord-352850-as12ll8s authors: wang, tao; tang, chunli; chen, ruchong; ruan, honglian; liang, wenhua; guan, weijie; sang, ling; tang, ruidi; zhong, nanshan; li, shiyue title: clinical features of coronavirus disease 2019 patients with mechanical ventilation: a nationwide study in china date: 2020-06-23 journal: crit care med doi: 10.1097/ccm.0000000000004473 sha: doc_id: 352850 cord_uid: as12ll8s objectives: the outbreak of coronavirus disease 2019 is becoming a worldwide pandemic. mechanical ventilation is lifesaving for respiratory distress, this study was designed to delineate the clinical features of the coronavirus disease 2019 patients with mechanical ventilation from a national cohort in china. design: prospective observational study. setting: the rapid spread of severe acute respiratory syndrome coronavirus 2 has infected more than 7.7 million people and caused more than 423,000 deaths. patients: adult hospitalized coronavirus disease 2019 patients with mechanical ventilation from 557 hospitals from china. interventions: none. measurements and main results: from a nationwide cohort, 141 coronavirus disease 2019 cases with mechanical ventilation were extracted from 1,590 cases. cigarette smoke, advanced age, coexisting chronic illness, elevated systolic blood pressure, high body temperature, and abnormal laboratory findings are common in these ventilated cases. multivariate regression analysis showed that higher odds of in-hospital death was associated with invasive mechanical ventilation requirement (hazard ratio: 2.95; 95% ci, 1.40–6.23; p = 0.005), and coexisting chronic obstructive pulmonary disease (hazard ratio, 4.57; 95% ci, 1.65–12.69; p = 0.004) and chronic renal disease (hazard ratio, 5.45; 95% ci, 1.85–16.12; p = 0.002). compared with patients with noninvasive mechanical ventilation, patients who needs invasive mechanical ventilation showed higher rate of elevated d-dimer (> 1.5 mg/l) at admission (hazard ratio, 3.28, 95% ci, 1.07–10.10; p = 0.039). conclusions: the potential risk factors of elevated d-dimer level could help clinicians to identify invasive mechanical ventilation requirement at an early stage, and coexisting chronic obstructive pulmonary disease or chronic renal disease are independent risk factors associated with fatal outcome in coronavirus disease 2019 patients with mechanical ventilation. o utbreak of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is becoming a worldwide pandemic, the rapid spread of the virus has caused more than 7.7 million coronavirus disease 2019 (covid-19) cases and more than 423,000 deaths globally (1) (2) (3) . covid-19 patients exhibit a spectrum of respiratory symptoms like cough and dyspnea, and some patients may develop hypoxemia (4) . most of the hypoxemic patients could be managed by oxygen therapy. however, there are some critically ill patients who require mechanical ventilation (mv) (5, 6) . here, by collecting a nationwide data through china, we sought to provide a delineation of the clinical features of covid-19 patients with mv. on behalf of the national clinical research center for respiratory disease, together with the national health commission of the people's republic of china, we performed a retrospective study to collect clinical information of covid-19 cases throughout the country. the study was supported by national health commission and designed by the investigators, and approved by the institutional board of national health commission. written informed consent was waived in light of the urgent need to collect data. by january 31, 2020, a cohort of 2007 hospitalized cases from 575 hospitals in china was established (7, 8) . medical history, epidemiological, and laboratory data were obtained. four hundred and seventeen cases were excluded because of insufficient medical records. data were analyzed and interpreted by the investigators. continuous variables were expressed as medians and interquartile ranges (iqr). wilcoxon rank-sum tests were applied to continuous variables, and chisquare tests or fisher exact test were applied to categorical variables as appropriate. to estimate the hazard ratio (hr) associated with mortality or the requirement of invasive mv (imv), variables including baseline characteristics, laboratory findings were analyzed by univariate cox regression analyses, significant variables were further included in multivariate cox regression analyses. the adjusted kaplan-meier survivor curve was used to estimate time-dependent hazards categorized by risk factors. among the 1,590 cases included in this study, 141 (8.9%) received mv, 122 received noninvasive mechanical ventilation (niv), and 50 received imv through trachea intubation. there were 31 cases (62% of total imv) who received niv before transition to imv, these patients were grouped in imv group for further analysis. thus, there were 91 and 50 cases in niv and imv group, respectively. of the 141 ventilated covid-19 cases included in this study, the median age was 64 years (iqr, 55-70 yr) , 70% were men and 70% were smokers. there were 89 (63%) cases with one or more coexisting medical conditions, the most common coexisting conditions were hypertension (45%), diabetes (26%), cerebrovascular disease (9.2%), and coronary artery disease (8.5%). the duration from admission to niv and imv were 3 days (1.0-8.0 d) and 5 days (1.8-10.0 d), respectively. the physical signs were shown in table e1 (supplemental digital content 1, http://links.lww.com/ccm/f609), the most common abnormal signs of these ventilated cases at admission were elevated respiratory rate (>20/min, 57%), elevated systolic blood pressure (≥ 140 mmhg, 30%), and high body temperature (>37.3°c, 36.2%). as shown in table e2 (supplemental digital content 1, http://links.lww.com/ccm/ f609), among the patients who underwent laboratory tests at admission, most patients showed lymphocytopenia (87%), elevated level of c-reactive protein (crp) (82%), lactate dehydrogenase (88%), aspartate aminotransferase (62%), and d-dimer (53%). multivariate regression indicated that higher odds of in hospital death was associated with imv requirement (hazards ratio [hr], 2.95; 95% ci, 1.40-6.23; p = 0.005), and coexisting chronic obstructive pulmonary disease (copd) (hr, 4.57, 95% ci, 1.65-12.69; p = 0.004) and chronic renal disease (hr, 5.45; 95% ci, 1.85-16.12; p = 0.002) (fig. 1a) . the adjusted survivor curve showed time-dependent hazards of these factors (fig. 1b-e) . compared with niv group, imv cases had higher levels of lactate dehydrogenase, d-dimer, crp and wbc count, and lower levels of albumin and oxygenation index (table e2 , supplemental digital content 1, http://links.lww.com/ccm/ f609); and showed a higher incidence of elevated d-dimer at admission with multivariate logistic regression analysis (>1.5 mg/l; hr, 3.05; 95% ci, 1.07-8.69, p = 0.037) ( table 1) . the secondary infection rate in the imv group (14/50, 28%) was higher than niv group (15/91, 16.5%), though not statistically different (p = 0.106). and there was no statistical significance in any of the coexisting chronic conditions between niv and imv group. by the time of data collection, 19 (17%) and 25 (50%) cases died in niv and imv group, respectively, 4 (4.4%) and 0 (0%) patients recovered and discharged from hospital in niv and imv group, respectively (p < 0.01); the remaining cases were still under treatment in the hospital, and imv were successfully removed in two cases. in the diagnosis and treatment protocol for covid-19 (trial version 7) released by national health commission & state administration of traditional chinese medicine in china: niv is recommended to covid-19 patients with respiratory distress and/or hypoxemia, which cannot be alleviated with standard or high-flow nasal cannula oxygen therapy; whereas imv is recommended to be applied in a timely manner if the oxygen saturation or respiratory distress do not improve or even get worse within 1-2 hours after niv. among the 122 cases who initially received niv in our study, 31 progressed to imv, and these cases demonstrated higher level of crp (p = 0.016), and no significant difference of the other laboratory findings at admission compared with those remained with niv ( in this study, we reported critically ill covid-19 cases who required mv from a nationwide cohort for the first time. consistent with the severe covid-19 cases in previous reports (6, 9) , patients in our cohort are aged population with a high rate of comorbidities including cardiovascular diseases and diabetes. and patients with coexisting copd or chronic renal disease is associated with higher mortality risk, which may suggest that intensive surveillance should be considered in case of rapid deterioration in covid-19 patients with these chronic conditions. mv is the cornerstone in the management of respiratory failure via aiding patients to get adequate oxygen and clear carbon dioxide. for patient with respiratory failure, niv as an initial ventilation support has been reported to reduce mortality and the need of intubation in viral pneumonia (10) . in our cohort, with the support of niv, four cases (4.4%) recovered from respiratory failure and two cases in our cohort was successfully removed from imv. however, mv, especially niv, is considered as of high infection risk because of increased aerosolization; however, patients with imv may have a higher demand of medical resources and a higher rate of secondary infection. so, in our covid-19 management protocol, niv is first introduced to covid-19 patients with respiratory distress, and imv is recommended to be applied if niv failed to improve the respiratory distress or hypoxemia. after covid-19 outbreak, 3,387 healthcare workers have been infected in china, but we do not worry about sars-cov-2 transmission in hospital because covid-19 patients are separated from other patients, and healthcare workers wear personal protective equipment including caps, n95 masks, gloves, gowns, and face shields, and follow strict hygiene steps. in china, most of the healthcare worker infections occurred at the early stage of covid-19 outbreak because the strong infectivity was not fully recognized and thus personal protection was not adequate at that time. with appropriate personal protection, the healthcare worker infections can be avoided even when the patients are with niv, which were evidenced by few healthcare worker infections at the late period (february and march 2020) of covid-19 outbreak in china. our data suggest that advanced age, coexisting chronic illness, and abnormal laboratory findings are common in the ventilated cases. elevated d-dimer (>1.5 mg/l) at admission may suggest an increased possibility of imv requirement with the progress of the disease, and coexisting copd or chronic renal disease could help clinicians to identify covid-19 patients with poor prognosis at an early stage. the ors and p values were calculated using multivariate logistic regression. from china: hope and lessons for covid-19 control clinical characteristics of coronavirus disease 2019 in china review of the clinical characteristics of coronavirus disease 2019 (covid-19) clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (covid-19) clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study comorbidity and its impact on 1590 patients with covid-19 in china: a nationwide analysis clinical characteristics and outcomes of hospitalised patients with covid-19 treated in hubei (epicenter) and outside hubei (non-epicenter): a nationwide analysis of china clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome we thank all medical staff who are fighting against this public crisis and all the patients involved in the study. we also thank the hospital staffs for their efforts in collecting the data. we express sincere sympathies and deep condolences to the victims and bereaved families. drs wang, tang, chen, and ruan contributed equally and are joint first authors.dr. li had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. dr. li was responsible for concept and design. drs. wang, tang, chen, liang, guan, sang, tang, and ruan were responsible for acquisition, analysis, or interpretation of data. drs. wang, tang, chen, and ruan drafted the manuscript. drs. zhong and li were responsible for critical revision of the manuscript for important intellectual content. drs. chen, tang, and ruan were involved in statistical analysis. drs. zhong and li provided administrative, technical, and material support. dr. li supervised the project.supplemental digital content is available for this article. direct url citations appear in the printed text and are provided in the html and pdf versions of this article on the journal's website (http://journals.lww.com/ ccmjournal).the authors have disclosed that they do not have any potential conflicts of interest.for information regarding this article, e-mail: lishiyue@188.com key: cord-313816-7d8x7fjp authors: cinesi gómez, c.; peñuelas rodríguez, ó.; luján torné, m.l; egea santaolalla, c.; masa jiménez, j. f.; garcía fernández, j.; carratalá perales, j. m.; heili-frades, s. b.; ferrer monreal, m.; de andrés nilsson, j. m.; lista arias, e.; sánchez rocamora, j. l.; garrote, j. i.; zamorano serrano, m. j.; gonzález martínez, m.; farrero muñoz, e.; mediano san andrés, o.; rialp cervera, g.; mas serra, a.; hernández martínez, g.; de haro lópez, c.; roca gas, o.; ferrer roca, r.; romero berrocal, a.; ferrando ortola, c. title: clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to sars-cov-2 infection date: 2020-05-07 journal: nan doi: 10.1016/j.redare.2020.05.001 sha: doc_id: 313816 cord_uid: 7d8x7fjp abstract coronavirus disease 2019 (covid-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in wuhan, china, in december 2019. currently, the world health organization (who) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. while most people with covid-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. in severe cases, covid-19 can be complicated by the acute respiratory distress syndrome (ards), sepsis and septic shock, and multiorgan failure. this consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four spanish scientific societies (spanish society of intensive care medicine [semicyuc], spanish society of pulmonologists [separ], spanish society of emergency [semes], spanish society of anesthesiology, reanimation, and pain [sedar]) with experience in the clinical management of patients with covid-19 and other viral infections, including sars, as well as sepsis and ards. the document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of covid-19 with acute respiratory failure. this consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials. specific situations encountered outside routine clinical practice in hospitals, and must be adapted to the particular circumstances of any given scenario. this consensus document has been drawn up by the scientific societies involved in treating acute respiratory failure in adult patients. it includes a more detailed description of the recommendations for the use of non-invasive respiratory support (nirs) in the management of acute respiratory failure (arf) secondary to infection by the new sars-cov-2 coronavirus that causes the disease called covid-19 that is intended to supplement the regularly updated recommendations issued by the ministry of health, consumer affairs and social welfare (mh) 1,2 . the world health organization (who) recently declared the disease caused by sars-cov-2 (covid-19) 3 a public health emergency of international concern. the ongoing covid-19 pandemic is devastating, despite the implementation of extensive control measures. in reality, there are significant regional differences in the availability and accessibility of healthcare resources among the more than 70 countries currently affected by the virus. these differences might partly explain the low mortality rates despite the high number of cases. health authorities and governments worldwide have developed contingency plans to manage local outbreaks 4 , and these measures are essential for controlling the epidemic, protecting health workers on the front line, and mitigating the severity of patient outcomes. a recent study of clinical characteristics in a selected cohort of 1,099 covid-19 patients across china 5 showed that up to15% (173/1,099) developed severe disease according to the american thoracic society's clinical criteria for severe community-acquired pneumonia 6 , and of these 20.6% were at risk of admission to the icu (33/173, 19%) , invasive and non-invasive mechanical ventilation (81/173, 46%) or death (14/173, 8%), while 2.9% (5/173) required extracorporeal oxygenation systems. extrapolating these figures to the current situation in spain compels us to anticipate events and demand that both national and regional health authorities draw up a contingency plan for managing healthcare resources and staff safety. in conclusion, we cannot predict how many seriously ill covid-19 patients we will receive, but we must learn from the experience of other countries and anticipate scenarios, distribute resources as rationally as possible, and do the best we can to be prepared and work together to overcome the epidemic. monitoring, preferably non-invasive, is a key element in the management arf in patients with covid-19. these patients need to be placed in individual rooms, ideally with negative pressure, and this calls for centralised monitoring (pulse oximetry, respiratory rate) and, preferably, video surveillance. the escalation therapeutic strategy proposed by scala and heunks for processes that cause arf can also be used in sars-cov-2 infection 10 . conventional oxygen therapy, consisting in the administration of oxygen at different concentrations, is the base of the therapeutic pyramid. the next step is high flow nasal oxygen (hfno) therapy, in which a mixture of varying proportions of air and oxygen (fio2) are deliver at a high flow rate (up to 60 l/min) through a nasal cannula. the gas must be heated and 100% humidified 11 . hfno, compared with conventional oxygen devices, maintains fio2 at a constant level, reduces dead space, generates positive pressure that redistributes intra-alveolar fluid, and promotes alveolar recruitment 12 . the next step is non-invasive ventilation (niv), which is administered under spontaneous breathing, so patients require very little sedation, or none at all 13 . the penultimate step is invasive mechanical ventilation (mv). in this case, volume control mode is usually used, and the patient must be intubated 10 . the last step is extracorporeal membrane oxygenation (ecmo) 14 . the respiratory therapies currently used in nirs are hfno and niv. on the basis of the above, the general criteria for starting respiratory support in arf secondary to covid-19 are as follows 15 : clinical criteria:  moderate to severe dyspnoea with signs of respiratory effort and use of accessory muscles or paradoxical abdominal movement.  tachypnoea over 30 bpm.  pao 2 /fio 2 < 200 (or the need for fio 2 greater than 0.4 to achieve an spo 2 of at least 92%).  acute ventilatory failure (ph < 7.35 with paco 2 > 45 mm hg). in patients meeting none of the above criteria, the initial treatment indicated is conventional oxygen therapy. in patients meeting one or more of the criteria, respiratory support, either invasive or non-invasive, is indicated. the use of nirs for sars and other viral pandemics is controversial, and in this context niv failure rates are around 30% 16 . more recently, niv was also used in patients with arf secondary to swine flu, with failure rates ranging from 13% to 77% [17] [18] [19] . despite the uncertainty of the evidence and the absence of randomised clinical trials, most observational studies suggest that niv can be considered in carefully selected patients treated in a protected environment (ideally negative pressure rooms) in hospitals with experience in this technique. in the current epidemic in china, 5.1% of patients required niv, 2.3% required mv and 0.5% ecmo 5 . therefore, the choice of therapy will also depend on the patient's basic pathology, mainly respiratory, their location (negative pressure room, sealed individual room with air changes) and the potential need for aerosol-generating procedures. overall, clinicians can encounter three clinical scenarios: 1. patients with no previous pathology (de novo arf) and hypoxemic respiratory failure who, therefore, are at risk for escalation to ecmo. the failure rate of nirs, mainly niv, in this clinical scenario is extremely high, and there is evidence of higher mortality if mv is delayed. therefore, we do not recommend nirs in these patients 1, 20, 21 . nirs should only be considered in carefully selected patients, provided all the following criteria are met 19,21-27 :  pao 2 /fio 2 > 100 despite conventional oxygen therapy.  no multi-organ failure (apache < 20).  availability of an expert team and continuous monitoring. for this reason, nirs should be administered in special units with a pre-established nursing ratio, such as icus and ircus.  early intubation (within the hour) if there is no improvement. for example, in addition to standard intubation criteria, intubation could be considered in patients treated with hfno who have an rox index (ratio of spo 2 /fio 2 to respiratory rate) < 3, < 3.5 and < 4 at 2, 6 and 12 h from the start of hfno therapy. similarly, intubation could be considered in patients with a heart rate, acidosis (ph), consciousness (gcs), oxygenation, and respiratory rate (hacor) score > 5 after 1 h of niv. extrapolating the evidence in de novo arf, hfno would be the treatment of choice 21,28 . niv is the second line option if response is poor but mv criteria are not met. 2. patients with hypoxemic respiratory failure, a do not intubate order, in whom niv is the ceiling of therapy. nirs is indicated in these patients, provided precautionary measures are in place. in this case, it is essential to establish the treatment objectives with the patient and their family by defining the ceiling of therapy. generally speaking, treatment should start with hfno before progressing to niv 21,28 . nirs should be administered as follows 29,30 :  titrate fio 2 to achieve an spo 2 target of around 95% 31 .  if hfno is used, set the flow rate to over 50 l/min; if possible, start at 60 l/min.  if niv is used, use high peep and low support pressure (in order to obtain a vte < 9 ml/kg of ideal weight) 31,32 . 3. patients with severe exacerbation of copd with acute or exacerbated hypercapnic respiratory failure: perform a therapeutic test with nirs, particularly niv. in these cases, hfno can be useful if the patient cannot tolerate niv, or it can be used during niv rest periods 33-36 . to limit transmission of infection to both healthcare personnel and other patients. j o u r n a l p r e -p r o o f b) the feasibility of performing aerosol-generating procedures will depend on the patient's location within the hospital. most of the evidence available on nirs devices as invasive procedures and the risk of transmitting respiratory pathogens to healthcare staff concerns orotracheal intubation, patients with artificial airways, and non-invasive ventilation, although the results come from small, low-quality studies and are therefore difficult to interpret (table 1 ). in mild cases, therefore, the patient should be placed in a negative pressure room. if this is not available, the patient should be place in a single-occupancy room with bathroom. the door of the room must be closed at all times 39 . serious cases with severe hypoxaemia should be admitted to special units. c) for intrahospital transfer, both the patient and the staff member transferring the patient must wear surgical masks. during transfer, the patient's bed must be covered with a clean disposable sheet that is then removed and disposed of as hazardous medical waste (group 3, biological agents) 39 . the ministry of health, consumer affairs and social welfare recommends administering oxygen through masks with an exhalation filter, but these masks are not universally available in our setting. in the absence of such masks, a surgical mask can be safely placed over the nasal prongs or oxygen mask to limit the spread of the virus. there are no studies comparing the efficacy of exhalation filter masks and surgical masks in reducing the spread of sars-cov-2 39 , but oxygen therapy is considered a low-risk aerosol-generating procedure 39,40 . the aforementioned general recommendations should be followed, observing a minimum distance of 2 m between patients and healthcare personnel without adequate protection 42 . although the extent of particle dispersion in this type of therapy remains unclear, and the benefit of placing a surgical mask over the nasal prongs has not been studied, it is an option in an extreme situation. a minimum distance of 2 m should be maintained between patients and healthcare personnel without adequate protection. in general, according to the available evidence, the use of nirs is not contraindicated in patients with covid-19, but the respiratory therapy used will not only depend on the severity of the respiratory failure but also on the availability of a room that complies with the isolation and safety recommendations of the world health organization (who). the most serious cases that will probably require rapid intubation should be placed in the icu in order to avoid intubation delays that would affect the patient's evolution (fig. 1 ). • although there are uncertainties surrounding particle dispersion in covid-19, in the sars epidemic some articles showed particle dispersion to a radius of no more that 4 feet (1.25 m) when using a single-limb circuit with a leak port 8,43,44 . • double limb circuits are preferable, since they prevent air leaks from both the inspiratory and expiratory breathing circuits. high efficiency antibacterial expiratory filters should be used to avoid reverse contamination from the patient to the ventilator 39 . • if double limb systems are unavailable and single limb ventilators are unavoidable, attach a high-efficiency, low resistance antimicrobial filter to the leak port of the single limb to minimize dispersion of exhaled gas that may contaminate ambient air. it also appears feasible to connect a t valve to the circuit in order to place the filter and leak port distal to the valve, although this will increase dead space. • if an antimicrobial filter cannot be connected to the leak port, a similar filter must be placed between the patient/ventilator interface (no leak ports) and the circuit. in this case, the ventilator settings may need to be adjusted to increase pressure support to compensate for the increased resistance. • instead of double limb or single limb systems with leak port, a single-limb systems with an active valve can be used, placing an antimicrobial filter at the outlet of the active valve. • we do not recommend using heat and moisture exchangers (hme) 4,5 . the interface is the device that facilitates both the physical and functional relationship between two independent elements: the ventilator and the patient. it is an indispensable element in niv, and delivers positive pressure to the patient without the need for an artificial airway. the recommendations for niv interfaces in sars-cov-2 infection are as follows 40,41,46,47 : • an interface without a leak port should be used, and accessory ports, if any, should not be used. • the use of helmets should be prioritised if available and staff are trained in the placement and use of this device. • in general terms, the first alternative to the helmet is the full face mask and, failing that, the oronasal mask. • face mask should be monitored for leaks, particularly oronasal interfaces. any leaks should be corrected, primarily to avoid injuries to the patient's skin, but also to ensure the integrity of the closed circuit and prevent exhalation of contaminated air. protective patches, which can increase leakage, should be avoided, and hyper oxygenated oil should be applied as required. • nasal masks are not recommended as they generate more aerosols, and because sars-cov-2 infection usually involves acute hypoxemic failure. 3. choice of elbow 46 : • we recommend using elbows without an anti-asphyxia valve. these elbows are usually colour-coded blue, and require strict monitoring to guard against possible ventilator malfunction. however, the risk/benefit balance (asphyxia vs. dispersion) favours these elbows, and there is little risk of accidental disconnection that remains undetected or is not corrected in time, since these patients are located in highly complex rooms under the continuous care of specialised healthcare personnel. nevertheless, the nurse-patient ratio must remain above the minimum safe level. • we advise against the use of anti-rebreathing elbows (which have anti-asphyxia valves) due to the risk of greater dispersion of exhaled air. inhaled therapy 1,39 the if inhaled therapy is indicated, we recommend using vibrating mesh nebulizers with a mouthpiece or face mask. the risk of dispersion can be reduced by placing a surgical mask over the device. bear in mind that a higher drug dose may be needed if a mouthpiece with an anti-dispersion valve is used (particularly in the case of beta2-adrenergic agonist bronchodilators), so the prescription should be adjusted accordingly. jet systems have a greater capacity for particle dispersion than other nebulizers, and should therefore be avoided. if unavoidable, the nebulizer must be covered with a surgical mask. when using inhaled therapy in combination with nirs, we recommend the following:  generally speaking, inhaled therapy should be administered via a pressurized cartridges with an adapter or spacer chamber. if used in combination with niv, the nebulizer should be connected to the inspiratory limb of the ventilator and the aerosol drug should be delivered during inspiration.  if aerosol therapy is used, the first choice should be a circuit with a vibrating mesh nebulizer elbow. failing this, a vibrating mesh nebulizer can be connected to the niv circuit using a t valve. being a "closed system" there is no risk of dispersion, provided the mask is closely monitored for unintentional leaks.  jet nebulizers with a t tube generate greater turbulence, larger particles, and therefore a higher risk of particle dispersion.  in patients receiving hfno, pressurized metered dose inhalers with spacer, a mouthpiece with a vibrating mesh nebulizer or a mesh nebulizer connected to the dry limb of the water reservoir should be used.  generally speaking, pressure support in niv and temperature in hfno should be reduced, respectively, when combined with aerosol therapy. references figure 1 treatment sequence to identify early failure and proceed to elective orotracheal intubation.  to correctly identify patients with arf who may require non-invasive respiratory support (nirs) key: cord-290684-3f6prlqy authors: duan, jun; chen, baixu; liu, xiaoyi; shu, weiwei; zhao, wei; li, ji; li, yishi; hong, yueling; pan, longfang; wang, ke title: use of high-flow nasal cannula and noninvasive ventilation in patients with covid-19: a multicenter observational study date: 2020-07-29 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.071 sha: doc_id: 290684 cord_uid: 3f6prlqy background: the use of high-flow nasal cannula (hfnc) and noninvasive ventilation (niv) in patients with covid-19 is debated. methods: this study was performed in four hospitals of china from january to march 2020. we retrospectively enrolled 23 and 13 covid-19 patients who used hfnc and niv as first-line therapy, respectively. results: among the 23 patients who used hfnc as first-line therapy, 10 experienced hfnc failure and used niv as rescue therapy. among the 13 patients who used niv as first-line therapy, one (8%) used hfnc as rescue therapy due to niv intolerance. the duration of hfnc + niv (median 7.1, iqr: 3.5–12.2 vs. 7.3, iqr: 5.3–10.0 days), intubation rate (17% vs. 15%) and mortality (4% vs. 8%) did not differ between patients who used hfnc and niv as first-line therapy. in total cohorts, 6 (17%) patients received intubation. time from initiation of hfnc or niv to intubation was 8.4 days (iqr: 4.4–18.5). and the time from initiation of hfnc or niv to termination in patients without intubation was 7.1 days (iqr: 3.9–10.3). among all the patients, c-reactive protein was independently associated with intubation (or = 1.04, 95% ci: 1.01–1.07). in addition, no medical staff got nosocomial infection who participated in hfnc and niv management. conclusions: in critically ill patients with covid-19 who used hfnc and niv as first-line therapy, the duration of hfnc + niv, intubation rate and mortality did not differ between two groups. and no medical staff got nosocomial infection during this study. at the end of 2019, a new coronavirus, now named severe acute respiratory syndrome coronavirus 2 (sars-cov-2), was first isolated at wuhan, china [1] . the coronavirus causes a cluster of acute respiratory illness, now named coronavirus disease 2019 (covid-19) [2] . it has been demonstrated that the most dangerous feature of covid-19 was person-to-person transmission [3] . with the spread of the epidemic, many countries have reported confirmed cases associated with sars-cov-2. on march 11, 2020, the world health organization (who) declared the outbreak of covid-19 was a global pandemic. in the covid-19 population, 14% of the patients were categorized as severe cases and 5% as critical cases [4] . a systematic review and meta-analysis has pooled 31 articles involving 46959 cases with covid-19 and reported that the incidence of icu admission was 29.3% [5] . at the early stage, the high-flow nasal cannula (hfnc) or noninvasive ventilation (niv) was used in 24% of hospitalized patients [2] . and in the critical ill patients, the use of hfnc and niv was 31% and 37%, respectively [6] . in lombardy region, italy, the niv was used in 11% of icu patients [7] . in seattle region, usa, the hfnc was used in 42% of critically ill patients [8] . however, these studies failed to report how the hfnc or niv was used. here, we aimed to report the clinical features, settings and outcomes of hfnc and niv in patients with j o u r n a l p r e -p r o o f medical center). in the suspected patients, the real-time reverse transcription polymerase chain reaction (rt-pcr) assay was performed according to the guideline made by our national health commission [9] . the covid-19 was confirmed by a positive rt-pcr. all the patients with a confirmed covid-19 were candidates to our study. we enrolled all the patients who used hfnc or niv as first-line therapy. among the hfnc patients, 17 cases extracted from a previous study were secondarily analyzed [10] . this study was approved by the local ethics committee and institutional review board (the first affiliated hospital of chongqing medical university, no. 20200201). given its observational nature, informed consent was waived. the application of niv and hfnc was in the negative pressure ward or intensive care unit (icu). to protect the medical staff, the n95 respirator, eye protection (mask with a visor), disposable gown, disposable surgical gloves, and disposable shoe covers were provided. before entering the ward, all the medical staffs had wore these devices and checked each other. niv was managed according to current guidelines and the experts' suggestions [11] [12] [13] [14] . face mask was the first choice to delivery the niv to the patients. optimal size of the mask was selected based on the face type in each patient. hearted humidification was provided to improve oral or nasal dryness. the initial continuous positive airway pressure (cpap) or positive end expiratory pressure (peep) was 4 cmh 2 o. when the patient tolerated this pressure, it was gradually increased to improve the oxygenation. the initial inspiratory pressure was 8-10 cmh 2 o. j o u r n a l p r e -p r o o f hfnc was managed also based on current consensus and the experts' suggestions [13] [14] [15] . the temperature was set between 31 and 37 °c, the flow was set between 30 and 60 l/min, and the fio 2 was set to maintain the spo 2 more than 93%. when the hfnc failed to maintain the oxygenation or relieve dyspnea, the niv as a rescue therapy was an alternative if the patient did not require urgent intubation. when the respiratory distress was relieved and the oxygenation was improved, the intermittent use of niv or hfnc was performed. we gradually increased the time of conventional oxygen therapy and shortened the duration of hfnc or niv until it was totally weaned. when the respiratory distress and oxygenation progressively deteriorated, intubation for invasive mechanical ventilation was performed based on the criteria made by our society of critical care medicine [16] . however, the intubation was decided at the discretion of the attending physicians. before the use of hfnc or niv, the demographics, vital signs, laboratory tests and the arterial blood gas tests were collected. the baseline pao 2 /fio 2 was measured with the use of conventional oxygen therapy before the use of hfnc or niv. we estimated the fio 2 as follows: fio 2 (%) = 21+4*fow (l/min) [17] . using these data, the acute physiology and chronic health evaluation ii (apache ii) score and sequential organ failure assessment (sofa) score were calculated. data were analyzed by statistical software (spss 17.0; ibm corp., armonk, ny). student's t test was used to analyze the normally distributed continuous variables and mann-whitney u test was used to analyze the non-normally distributed continuous variables. chi-squared test or fisher's exact test was used to analyze the categorical variables. variables with a p value <0.1 in univariate analyses were entered into logistic regression analyses to identify independent risk j o u r n a l p r e -p r o o f factors associated with intubation. the ability to predict intubation was tested by the area under the receiver operating characteristic curve (auc). the value at maximum youden index was selected as optimal cutoff value [18] . a p value < 0.05 was considered significant. among all the enrolled patients, 35 cases were in the negative pressure ward and one was in the icu. among them, hfnc was used as first-line therapy in 23 patients and niv in 13 patients ( figure 1 ). the clinical characteristics of the hfnc and niv patients were summarized in table 1. the mean age was 65 ± 14 years in hfnc group and 50 ± 14 years in niv group (p ＜0.01). the proportion of male was 52% in hfnc group and 92% in niv group (p =0.03). there were no differences in disease severity, the proportion of comorbidity, and the level of oxygenation between the two groups. patients in hfnc group had higher chlorine, low alanine aminotransferase (alt) and lower total bilirubin than that in niv group. others laboratory tests were no differences between the two groups. table 2 shows the settings of the hfnc and niv at the initial 24 h. in hfnc group, the temperature was around 35℃, flow was around 40 l/min, and fio 2 was around 40%. in there were no differences in vital signs and arterial blood gas tests between hfnc and niv groups except the respiratory rate (table 3) . at 1-2 h, 12 h and 24 h, the respiratory rate was lower in hfnc group than that in niv group. the outcomes between the two groups were summarized in table 4. in hfnc group, 10 (43%) patients used niv as a rescue therapy. in niv group, one (8%) used hfnc due to niv intolerance. there was no difference in the duration of hfnc + niv between the patients who used hfnc and niv as first-line therapy (median 7.1 days, iqr: 3.5-12.2 vs. 7.3 days, iqr: 5.3-10.0, p =0.67). there was also no difference in intubation rate (17% vs. 15%, p ＞0.99) and mortality (4% vs. 8%, p ＞0.99) between the two groups. among all the patients, 6 received intubation and 30 avoided intubation (table 5 ). in multivariate analyses, only c-reactive protein was independently associated with intubation ( table 6 ). the auc for prediction of intubation was 0.92 (95% confidence interval [ci]: 0.77-0.98) ( figure 2 ). using c-reactive protein of 59 mg/l as cutoff value to predict intubation, the sensitivity was 100% and specificity was 79%. in addition, no medical staff got nosocomial infection in our study. nearly half of the patients who used hfnc as first-line therapy were transitioned to niv as a rescue therapy. however, only fewer patients who used niv as a first-line therapy were transitioned to hfnc. the intubation rate and mortality were relatively low. the duration of hfnc + niv, intubation rate and mortality did not differ between the two groups. among all the patients, c-reactive protein was independently associated with intubation. and it had high distinguishing power to predict intubation. in china, use of hfnc ranged from 21% to 31% (pooled incidence: 26%) among the critically ill patients, and the use of niv ranged from 14% to 37% (pooled incidence: 28%) [6, 19, 20] . however, the use of hfnc and niv were largely different between china and other countries. in lombardy region, italy, niv was used in 11% of icu patients but no patients used hfnc [7] . in seattle region, usa, the hfnc was used in 42% of critically ill patients but none used niv [8] . maybe, the availability of the hfnc and niv, and suggestions or recommendations made by experts or consensus were various between different countries. in china, the experts have suggested that the hfnc and niv can be used in covid-19 patients with pao 2 /fio 2 ≥150 mmhg, and niv can be cautiously used in those with pao 2 /fio 2 between 100 and 150 mmhg [13, 14] . the asian critical care clinical trials group has suggested that the hfnc and niv only can be used in covid-19 patients with mild acute respiratory distress syndrome (ards) [21] . the surviving sepsis campaign covid-19 subcommittee (most of the experts came from european and usa) has suggested that the hfnc is superior to niv in covid-19 patients with acute hypoxemic respiratory failure, and the niv can be tried with close monitoring if the hfnc is unavailable [22] . however, most of the recommendations were based on the experts' suggestion. the level of evidence is weak. to the best of our knowledge, there were no studies to focus on the use of hfnc or niv in covid-19 patients except our previous one paper [10] . different with the experts' suggestions, 10 patients (17% in hfnc and 46% in niv) with pao 2 /fio 2 between 100 and 150 mmhg have used hfnc or niv as a first-line therapy. and among all the patients, the duration of hfnc + niv, intubation rate and mortality were similar between two groups. these data provide an important reference for clinical physicians to select respiratory support device on patients with covid-19. among all the patients who used niv as first-line therapy, the intubation rate was 92% in patients with middle east respiratory syndrome, 30% in patients with severe acute respiratory syndrome, and 59% in patients with influenza pneumonia [23] [24] [25] . in hypoxemic patients whose respiratory failure caused by other reasons, the intubation rate was 36% [26] . however, in our study, the intubation rate was only 15% in covid-19 patients who used niv as a first-line intervention. among the patients who used niv as a rescue therapy, the intubation rate was 20%. and no medical staff in our study was infected by the airborne transmission. therefore, the niv is an alternative respiratory support for covid-19 patients but all safety measures should be taken. early identification of the high-risk patients and early application of intubation decreased mortality [27] . on the contrary, delayed intubation significantly lead to mortality increase both in patients with hfnc and niv [28, 29] . in our study, we found that the c-reactive protein collected at the initiation of hfnc or niv had high distinguishing power to predict intubation. therefore, hfnc and niv should be cautiously used in patients with high level of c-reactive protein. close monitoring should be taken to avoid delayed intubation. fear of aerosolized transmission was the major problem during the use of hfnc or niv in covid-19 patients. in theory, niv generates more aerosols than hfnc as niv usually generates higher pressure than hfnc [30] . in our study, use of hfnc and niv was in the negative pressure ward or icu, adequate protective supplies (n95 respirator, eye protector, disposable gown, j o u r n a l p r e -p r o o f peep/cpap, cmh 2 o 6 (6-9) 6 (6-9) 6 (6-10) j o u r n a l p r e -p r o o f hfnc = high flow nasal cannula, niv = noninvasive ventilation, apache ii = acute physiology and chronic health evaluation ii; sofa = sequential organ failure assessment, alt = alanine aminotransferase, ast = aspartate aminotransferase, *p <0.05 for comparison between patients with and without intubation j o u r n a l p r e -p r o o f a novel coronavirus from patients with pneumonia in china clinical features of patients infected with 2019 novel coronavirus in wuhan, china early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72314 cases from the chinese center for disease control and prevention imaging and clinical features of patients with 2019 novel coronavirus sars-cov-2: a systematic review and meta-analysis clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study baseline characteristics and outcomes of 1591 patients infected with sars-cov-2 admitted to icus of the lombardy region covid-19 in critically ill patients in the seattle the experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of chongqing clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure critical care committee of chinese association of chest physician. [conventional respiratory support therapy for severe acute respiratory infections (sari): clinical indications and nosocomial infection prevention and control respiratory support for severe 2019-ncov pneumonia suffering from acute respiratory failure: time and strategy respiratory & critical care medicine group of chinese thoracic society society of critical care medicine of chinese medical association respiratory care equipment index for rating diagnostic tests clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study covid-19 with different severity: a multi-center study of clinical features intensive care management of coronavirus disease 2019 (covid-19): challenges and recommendations surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (covid-19) noninvasive ventilation in critically ill patients with the middle east respiratory syndrome effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome early non-invasive ventilation treatment for severe influenza pneumonia noninvasive ventilation failure in patients with hypoxemic respiratory failure: the role of sepsis and septic shock assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients failure of high-flow nasal cannula therapy may delay intubation and increase mortality non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure exhaled air dispersion during high-flow nasal cannula therapy versus cpap via different masks key: cord-303292-iheq50ub authors: de jong, audrey; wrigge, hermann; hedenstierna, goran; gattinoni, luciano; chiumello, davide; frat, jean-pierre; ball, lorenzo; schetz, miet; pickkers, peter; jaber, samir title: how to ventilate obese patients in the icu date: 2020-10-23 journal: intensive care med doi: 10.1007/s00134-020-06286-x sha: doc_id: 303292 cord_uid: iheq50ub obesity is an important risk factor for major complications, morbidity and mortality related to intubation procedures and ventilation in the intensive care unit (icu). the fall in functional residual capacity promotes airway closure and atelectasis formation. this narrative review presents the impact of obesity on the respiratory system and the key points to optimize airway management, noninvasive and invasive mechanical ventilation in icu patients with obesity. non-invasive strategies should first optimize body position with reverse trendelenburg position or sitting position. noninvasive ventilation (niv) is considered as the first-line therapy in patients with obesity having a postoperative acute respiratory failure. positive pressure pre-oxygenation before the intubation procedure is the method of reference. the use of videolaryngoscopy has to be considered by adequately trained intensivists, especially in patients with several risk factors. regarding mechanical ventilation in patients with and without acute respiratory distress syndrome (ards), low tidal volume (6 ml/kg of predicted body weight) and moderate to high positive end-expiratory pressure (peep), with careful recruitment maneuver in selected patients, are advised. prone positioning is a therapeutic choice in severe ards patients with obesity. prophylactic niv should be considered after extubation to prevent re-intubation. if obesity increases mortality and risk of icu admission in the overall population, the impact of obesity on icu mortality is less clear and several confounding factors have to be taken into account regarding the “obesity icu paradox”. electronic supplementary material: the online version of this article (10.1007/s00134-020-06286-x) contains supplementary material, which is available to authorized users. obesity (defined by a body mass index (bmi) ≥ 30 kg/ m 2 ) is a disease caused by excess or abnormal distribution of fat tissue and resulting in chronic diseases related to chronic inflammation and metabolic dysfunction [1] . obesity has become a global epidemic with prevalences rising both in developed and developing countries. front runners in 2020 are the united states of america (usa, 36%) and australasia (30%), with a prevalence expected to increase in the usa until 50% by 2030 [2] , whereas european countries have prevalences between 20 and 30%. the percentage of patients with obesity in the intensive care unit (icu) can be expected to increase concomitantly or even more since obesity increases the risk for a more severe disease course with more need for icu admission and mechanical ventilation [3] as has been shown in trauma [4] , traumatic brain injury [5] patients, out-of-hospital cardiac arrest [6] , during the h1n1 pandemic [7] and recently also in patients affected by coronavirus disease 2019 (covid-19) [8] [9] [10] [11] . obesity, especially abdominal obesity (android fat distribution) and severe obesity [12] , results in altered respiratory anatomy and physiology and, therefore, complicated airway management and adapted ventilator settings during mechanical ventilation. obesity appears to be associated with an increased risk of acute respiratory distress syndrome (ards) [13] and infection, mainly pneumonia [14] , probably related to an imbalanced production of adipokines [15] . in ventilated patients, obesity increases icu length of stay and the duration of mechanical ventilation [16] . the phenomenon whereby obesity increases morbidity but seems to protect against mortality in selected critically ill patients, known as "obesity paradox", has been evocated in patients with ards [13] and in those on mechanical ventilation [16] , even if it remains highly debated. this narrative review will summarize current insights into the impact of obesity on the respiratory system and the measures to be taken to optimize airway management and mechanical ventilation in icu patients with obesity. the patient with obesity suffers from increased respiratory workload and impaired gas exchange. both disturbances reduce physical capacity and health margin if exposed to respiratory stress. a basic triggering factor is reduced lung volume, caused by cranial displacement of the diaphragm by increased tissue mass in the abdomen, and by increased chest wall tissue. the decrease in resting lung volume after normal expiration, functional residual capacity (frc), is 5-15% per 5 kg/m 2 increase in bmi [17] . the consequence of the increased tissue mass will be greater in the supine than upright position, due to a stronger cranial displacement of the diaphragm. in addition, a further decrease in the frc can be seen during anesthesia with loss of respiratory muscle tone and, most likely, in icu by the use of sedatives and muscle relaxants. the fall in frc promotes airway closure and atelectasis formation, as will be discussed later, and an illustration of one representative case with no ventilation in the dorsal part of the lung, likely because of dependent atelectasis formation [18] , is shown in fig. 1 . there are several causes of increased work of breathing in the patient with obesity. one is the increased displacement of tissue during the breathing, both in the abdomen and in the lung and chest wall. another is increased airway resistance because of smaller airway dimensions, and increased asthma incidence. finally, increased tissue resistance adds to the work of breathing [19] . the patient with obesity may easily develop respiratory fatigue on physical exercise and, in the most severe cases, already at rest. it is often assumed that chest wall elastance or its inverse, chest wall compliance, is affected by obesity. however, the increased weight of the abdomen and of the chest wall requires work when moving the tissue, but when the move is over, no additional pressure is required [19] . end-inspiratory and end-expiratory pauses should be long enough when measuring chest wall compliance. lung compliance, on the other hand, is reduced [20] . the decreased lung volume may require pressure during inspiration to open closed units, and that may be recorded as a decrease in compliance. airways may close in dependent lung regions during an expiration, a normal age-dependent phenomenon. in patients with obesity, using non-invasive ventilation (niv) is advised both to prevent and treat acute respiratory failure. when invasive mechanical ventilation is needed, pre-oxygenation with niv and appropriated choice of intubation devices will decrease complications. during invasive mechanical ventilation, patients with obesity are more prone to lung collapse and require higher peep to avoid it; low v t is calculated on predicted body weight. when acute respiratory distress syndrome occurs, careful recruitment maneuver might be used associated with prone positioning. fig. 1 impedance changes due to regional ventilation in a patient with obesity. thoracic transversal electric impedance tomography images show impedance changes due to regional ventilation summarized for tidal ventilation cycles in a patient with a body mass index of 57 kg/m 2 . images were recorded during spontaneous breathing before intubation (a) and about 1 h after extubation (c) in a patient without lung pathology. note the ventral shift of ventilation during mechanical ventilation with a positive end-expiratory pressure (peep) of 5 cmh 2 o (b), which is likely due to atelectasis formation in dependent lung areas. obviously, the peep level was insufficient to keep the lung open while this has been known for many years, a more extensive, indeed complete airway closure has been shown during the last few years in anesthetised patients with obesity [21] or icu patients with obesity on mechanical ventilation. this means that a certain airway pressure is needed to start inflation of the lungs and it is not caused by a time-dependent intrinsic positive end-expiratory pressure (peep). where the complete closure occurs is not clear but may be in the most central airways and not in the periphery. the latter would require simultaneous closure of thousands of airways, as recently discussed [22] . hopefully, the morphology behind complete closure can be demonstrated in the near future. a consequence of the classic airway closure is impeded ventilation where the closure occurs and the decrease in ventilation will be larger the longer the closure lasts during the respiratory cycle. if airways are continuously closed, as can be seen during anesthesia and most likely in icu, the alveoli distal to the closure will collapse because of gas absorption [23] . the higher the oxygen concentration is in the inspired gas, the faster is the collapse. with pure oxygen, it can take a few minutes and with air, a couple of hours. the complete closure, on the other hand, will delay onset of inspiration without affecting the distribution per se. uneven ventilation distribution caused by airway closure will occur primarily in dependent lung regions. perfusion of the lung, on the other hand, increases down the lung independent of anatomy. regions that are poorly but still ventilated will cause ventilation-perfusion mismatch and regions that collapse because of continuous airway closure will cause shunt [23] . both impede oxygenation [24] and a large shunt may even impair carbon dioxide (co 2 ) elimination. with an extreme shunt, oxygenation is poorly or not at all improved by increasing oxygen in the inspired gas. finally, in patient with obesity, there is significant heterogeneity in both resistance and compliance, therefore, inhomogeneous inflation or deflation of the lungs can cause dynamic pressure differences between regions and lead to interregional airflows known as pendelluft effect. however, the patients with obesity are not a homogeneous group regarding the physiological modifications, the level of obesity and the fat distribution (gynoid versus android) being confounding factors that should be taken into account. although hypoxemic acute respiratory failure (arf) is not the first cause of arf in the patient with obesity [25, 26] , hypoxemia is frequent as it is favored by increased oxygen consumption or work of breathing and atelectasis formation, especially in cases of patients with morbid obesity and during arf [27] . non-invasive strategies should first optimize body position with reverse trendelenburg position, "beach chair position" or sitting position, which improve respiratory compliance and gas exchange in patients with morbid obesity [28, 29] . in patients having postoperative hypoxemia or arf, non-invasive ventilation (niv) is recommended with moderate certainty of evidence, justified by a decreased need of intubation, mortality and morbidity as compared to standard oxygen [30, 31] . an observational study including 72 patients with arf after abdominal surgery reported that niv avoided intubation in 67% of cases [32] . in a post hoc analysis of a large trial of 830 postoperative thoracic patients [33] , it was shown that among the 272 patients with obesity (mean bmi of 34 kg/m 2 ), niv was not superior to high-flow nasal cannula oxygen therapy (hfnc), with treatment failure occurring in 15% and 13% in niv and hfnc groups, respectively. therefore, niv could be considered as the first-line therapy in patients with obesity having a postoperative arf [34] , but further studies are needed to confirm the role of continuous positive airway pressure (cpap) and/or hfnc in this setting [35, 36] (table 1) . data addressing the management of hypoxemic arf with non-invasive ventilatory/oxygen strategies are scarce, especially in patients with obesity. the recent international guidelines failed to offer a recommendation on the use of niv in hypoxemic arf [30] . one large trial has compared niv with standard oxygen and hfnc in 310 non-selected patients with hypoxemic arf [37] . results showed lower mortality rates with hfnc than niv, thereby suggesting deleterious effects of niv. similarly, an observational study including 76 patients with bmi > 40 kg/m 2 showed that, after adjustment on high severity scores, hypoxemic arf caused by pneumonia was associated with niv failure [38] . however, according to physiological abnormalities in patients with obesity, niv could play a role, especially in patients with morbid obesity, through peep that may improve oxygenation and lung volume or alveolar recruitment [39] . finally, possible use of niv or hfnc as alternative to standard oxygen in patients with obesity and hypoxemic arf is not determined, and future trials are needed (table 1) . hypercapnic arf in patients with obesity can not only be part of the clinical course of cardiogenic pulmonary edema, pneumonia, asthma, and exacerbation of chronic lung diseases, but also may be due to exacerbation of obesity hypoventilation syndrome (ohs) [40] . positive airway pressure, i.e. cpap (refer to one level of airway pressure) or niv (refer to two levels of airway pressures), is the recommended ambulatory treatment for ohs patients [40] . similarly, niv is the usual treatment applied in ohs exacerbation, but no trial has evaluated its benefit as compared to other oxygen strategies. niv brings together potentially beneficial physiological effects, including peep preserving upper airway patency and pressure support to control central hypoventilation. however, an observational study including 33 severely patients with obesity reports a lower bmi (47 kg/m 2 ) in patients with niv success versus 62 kg/m 2 in those who failed niv [26] . in this setting, niv may be an appropriate treatment, but hfnc interspaced between niv sessions should be evaluated. in addition to the pathophysiological modification of the respiratory system discussed above, patients with obesity have peculiar morphological alterations potentially associated with difficulties during mask ventilation and airway management: reduced neck mobility, limited mouth opening, increased size of pharyngeal and glossal soft tissues, unfavorable conformation and positioning of the larynx, increased neck circumference and decreased thyromental distance [41] . moreover, patients with obesity have a high incidence of obstructive sleep apnea [42] , which is directly related to many of the complications occurring during airway management of this sub-population of critically ill patients [43] . obesity contributes to airway compression through increased airway fat deposits [44] , and placing the patient with obesity recumbent may lead to sudden death [36] . it is very important to encourage upright positioning and avoid supine positioning. overall, obesity, especially super obesity (bmi ≥ 40 kg/m 2 ) with android fat distribution, is an important risk factor for major complications, morbidity and mortality related to intubation procedures in the icu [45] . most of the literature existing on the airway management of patients with obesity is related to the operating room setting [46] . in this context, several strategies are often recommended, including the adoption of ramped position using specific devices or pillows/blankets under the patient's head and shoulder, pre-oxygenation with positive pressure ventilation [39] and the use of videolaryngoscopes [47] . however, compared to the elective surgical patient with obesity, the intubation of the critically ill patient has profound differences in indications, timing and co-existing conditions; therefore, caution should be applied when translating in the icu the recommendations based on evidence in the operating room. in the icu, the incidence of difficult intubation is double compared to the or and the occurrence of severe complications is dramatically higher [46] . pre-procedural patient preparation is key to successful intubation. an ideal preparation aims at prolonging timeto-desaturation, which in patients with obesity is mainly related to the rapid loss of frc after sedation. concerning positioning, a randomized controlled trial questioned the usefulness of the ramped position applied in critically ill patients [48] ; however, the study included a large proportion of patients without obesity. therefore, patient positioning should be individualized on the patient anatomy, based also on the intensivist's expertise. a semi-sitting position during pre-oxygenation could help to decrease positional flow limitation and air trapping [43] . conventional bag-mask ventilation can result in rapid desaturation in patients with morbid obesity. several studies confirmed that pre-oxygenation with cpap or niv improves oxygenation allowing a longer time window for intubation [39, 49] . for these reasons, positive pressure pre-oxygenation should be considered the reference in critically ill patients with obesity, considering that obesity carries an intrinsic increased risk for difficult mask ventilation. hfnc might also have a role [50] , especially in rapid sequence intubation in non-severely hypoxemic patients, where avoidance of bag ventilation might be desirable but is associated with higher incidence of severe desaturation [51] . however, the value of hfnc value in patients with obesity must be clarified, and cannot replace a preoxygenation using positive pressure [52] . the intubation maneuver should be always considered as potentially difficult in patients with obesity [46] , with older age, higher bmi, high mallampati and macocha scores and reduced neck mobility being independent risk factors for both difficult mask ventilation and intubation. a meta-analysis in surgical patients with obesity suggested an advantage of videolaryngoscopes over direct laryngoscopy [47] . in icu patients with obesity, it seems reasonable to consider the use of videolaryngoscopes by adequately trained intensivists, especially in patients with several risk factors. obesity is associated with abdominal and thoracic tissue mass, which transmit additional hydrostatic pressure via the chest wall and diaphragm to the pleural space and, thus, the alveoli. if pleural pressure is higher than intraalveolar pressure, the alveoli will collapse, and compression atelectasis will occur predominantly in dependent lung areas, where hydrostatic pressure is highest. for example, functional residual capacity is impaired by up to 21% in non-ventilated subjects with obesity in the supine position [18] and total lung and vital capacity are reduced as well. induction of anesthesia with muscle relaxation following pre-oxygenation with 100% o 2 further reduces end-expiratory lung volume (eelv) by about 50%, if a positive end-expiratory pressure (peep) of 5 cmh 2 o is used after initiation of mechanical ventilation (fig. 1 ) [18] . the main mechanism of gas exchange impairment is, therefore, shunt (atelectasis) in patients with obesity [24] . because the opening pressure of alveoli is higher than the pressure needed to keep them open, application of an initial recruitment maneuver (rm) followed by adequate peep after intubation or disconnection of the patient from the ventilatory circuit seems intuitive. due to the high pleural pressure in patients with obesity, opening pressures up to 50 cmh 2 o applied during a rm in patients with obesity without lung injury may not result in full lung recruitment [53] . potential side effects of applying such high airway pressures include a decrease in venous return and, thus, cardiac preload with a drop in cardiac output and systemic blood pressure. in addition, barotrauma such as pneumothorax or pneumomediastinum especially in patients with pre-existing structural lung damage such as emphysema, and a mechanically triggered boost of pre-existing lung inflammation may occur. thus, rm is not generally recommended, and their use remains a decision based on individual risk/benefit considerations. in mechanically ventilated patients, peep is used to keep alveolar pressure above the closing pressure of alveoli thereby maintaining end-expiratory lung volume (eelv) and arterial oxygenation. in another words, peep does not strictly induce alveolar recruitment but peep avoids alveolar derecruitment by maintaining open alveoli. thus, protective ventilation strategies may improve clinical outcomes even in patients without ards [54] . due to the superimposed pressure transmitted by adipose tissue on the pleural space, closing pressures in patients with obesity are higher and lungs of these patients are more prone to such complications (fig. 2) . despite these considerations, routinely used peep levels applied for ventilation of patients with obesity are often not higher than in normal weight patients [55] . in previous studies, different methods to find the individualized "best" peep in patients with obesity have been used. these approaches targeted improvements in oxygenation, lung mechanics, and regional ventilation distribution. in patients undergoing bariatric surgery, individualized peep resulted in a range of peep levels between 10 and 26 cmh 2 o with a median of 18 cmh 2 o [18] and restored eelv to the same level before intubation and initiation of mechanical ventilation. other studies regularly found peep levels > 15 cmh 2 o [56, 57] . however, a large trial of ventilation in patients with obesity during anesthesia did not demonstrate a difference in postoperative pulmonary complications for constant peep levels of 4 versus 12 cmh 2 o [58] . the peep levels in this pragmatic study, however, were not aiming at and resulting in full lung recruitment. as mentioned above, use of higher airway pressures is often associated with hemodynamic depression and higher requirements for fluids and vasopressors [58] . at least in the perioperative setting, evidence from meta-analyses and clinical trials are somewhat conflicting regarding improved clinical outcomes [54, 59] . limiting tidal volume (v t ) has been shown to reduce ventilation-associated lung injury and inflammation in non-selected patients with and without ards. the idea of normalizing v t for predicted body weight (pbw) is based on the expected lung volume (dependent on patient's height and sex) and aims to limit the v t /eelv ratio, i.e., mechanical lung strain. as mentioned above, eelv is regularly below the values in a normal weight population. thus, referencing v t to pbw per se can result in higher strain than in normal weight patients. if pbw is not formally calculated but just estimated, there is a tendency to overestimate pbw and, thus, v t in patients with obesity [55] . positioning patients with obesity in ramped or sitting positions and even early mobilization may facilitate unloading the diaphragm from increased abdominal pressure and may thereby improve aeration of dependent lung areas. early implementation of spontaneous breathing activity can preserve diaphragmatic tension, redistribute ventilation to dependent lung areas [60] , may avoid diaphragmatic muscle atrophy caused by muscle relaxation [60] and reduce duration of mechanical ventilation [61] . anzueto et al. [62] and karla et al. [63] showed that ards patients with obesity were ventilated with higher v t (per kg of pbw) compared to ards patients without obesity. it is tempting to speculate that the amount of atelectasis was different between patients with and without obesity and that the higher v t was chosen by the clinicians to maintain an adequate alveolar ventilation. a study by grasso et al. [64] tempted to confirm this hypothesis by reporting a decrease in the use of extracorporeal membrane oxygenation (ecmo) in patients with abdominal hypertension by increasing the airway pressure-often above 30 cmh 2 o-based on a transpulmonary pressure target. interestingly, in the study by karla et al. [63] , the airway plateau pressure and driving pressure were similar between patients with and without obesity. of note, in both studies, the outcome was similar between the two groups. similarly, de jong et al. [65] , in ards patients with obesity did not find any difference in driving pressure between survivors and non survivors [66] . when 21 ards patients with obesity were compared to 44 patients with ards but with a normal bmi, it was found that the two groups had similar recruitability and changes in oxygenation when peep was increased from 5 to 15 cmh 2 o [67] . in these two groups, abdominal pressure and chest wall elastance were also similar. in contrast, fumagalli et al. [68] found an impressive improvement in oxygenation and lung elastance using higher peep (22 cmh 2 o) compared to lower peep (13 cmh 2 o). the higher peep was selected according to transpulmonary pressure, while the lower peep was selected according to a peep/fio 2 table. once again, the abdominal pressure was not measured (or reported). the same authors in a retrospective study of patients with severe ards found better gas exchange, respiratory mechanics, and survival in 50 patients treated according to a personalized approach (based on transpulmonary pressure) compared to 70 patients treated with a standard protocol [69] . the personalized approach resulted in much higher peep levels of 20 cmh 2 o compared to 9 cmh 2 o used in the standard approach. a retrospective analysis of the alveoli trial showed improved outcome using peep 12 cmh 2 o compared to 9 cmh 2 o [70] . in this trial, however, patients with a weight > 1 kg/cm of height and bmi usually > 50 kg/m 2 were not included. we may wonder why the reported effect of different levels of peep differs among studies. we have to note that the bmi of the population of the different studies was 31 kg/ m 2 , as in the study of chiumello et al. [67] and likely in the alveoli study [70] , versus a bmi higher than 50 kg/m 2 in the study by fumagalli et al. [68] . given such a different bmi, it is likely that the abdominal pressure and mechanical impairment were different in the different populations. the normalized mechanical power, that has been shown being strongly associated with mortality [71] , was not monitored. moreover, rm was not consistently used, and their use and timing remain a matter of debate in ards patients with and without obesity [72] . a peep decremental trial preceded by a rm may decrease lung overdistension and collapse in ards obese patients [73] . in 21 ards patients with severe obesity (bmi = 57 ± 12 kg/ m 2 ) [74] , rm was performed during pressure controlled fig. 2 effect of obesity in main pressures of the respiratory system. the respiratory system includes the lung and the chest wall, and the airway pressure is related to both transpulmonary and transthoracic pressures, which differ in the patient with obesity compared to the patient without obesity. the relative part of pressure due to transthoracic pressure is often higher in the patient with obesity than in the patient without obesity (elevated pleural pressure, which can be estimated by esophageal pressure). the plateau pressure represents the pressure used to distend the chest wall plus lungs. in patients with obesity, elevated plateau pressure may be related to an elevated transthoracic pressure, and not an increase in transpulmonary pressure with lung overdistension. frc functional residual capacity ventilation with delta pressure of 10 cmh 2 o, peep was increased until a plateau pressure of 50 cmh 2 o for 1 min. after, the ventilator mode was switched to volume controlled ventilation (5 ml/kg of pbw), and the peep dropped by 2 cmh 2 o every 30 s. the optimal peep was determined by the peep value with the best compliance of the respiratory system plus 2 cmh 2 o. finally, a second lung rm was performed and the selected optimal peep was set. required peep was increased to 8 [7, 10] cmh 2 o above traditional ardsnet settings with improvement of lung function, oxygenation and ventilation/perfusion matching, without impairment of hemodynamics or right heart function. moreover, in a retrospective study [69] , the same authors also reported that patients treated with rm and with higher peep were weaned from vasopressors agents faster (and improved survival) than patients who were treated with low ardsnet peep table. future investigations would be beneficial to clarify the lungheart interaction when high airway pressure is used in the settings of high pleural pressure. given that the setting of mechanical ventilation (v t , peep) and the indicators of ventilator-induced lung injury (mechanical power, driving pressure) are crucially dependent on chest wall elastance, it is our opinion that it is difficult to propose any treatment if key variables such as transpulmonary pressure and intra-abdominal pressure are not measured or ignored (fig. 2) . prone position [75] also deserves attention in patients with ards and obesity. the safety and efficiency of this therapeutic were similar between patients with and without obesity, and the ratio of alveolar pressure in oxygen over fraction of inspired oxygen (pao 2 /fio 2 ) was significantly more increased after prone position in patients with obesity compared to patients without obesity [76] . prone position is a therapeutic of choice in patients with severe ards and obesity, and the mechanisms of action, caution and clinical effects are detailed in fig. 3 . in case of severe ards after failure or inability to use prone positioning and neuromuscular blockers, veno-venous extracorporeal membrane oxygenation (ecmo) can also be safely used in ards obese patients [77, 78] . the spontaneous breathing trial should be clearly separated from the level of pressure support and peep set before extubation and the respiratory support following extubation. a physiological study specifically assessed the inspiratory effort during weaning of mechanical ventilation in critically ill patients with morbid obesity [79] . the main result of this study was that for patients with obesity, t-piece and pressure support ventilation 0 + peep 0 cmh 2 o were the weaning tests predicting post-extubation inspiratory effort and work of breathing the most accurately [79] . if the work of breathing is closely the same between t-tube and after extubation [79] , the patient with obesity remains prone to atelectasis, and therefore, atelectases should be avoided as much as possible. that is s why after a t-tube, the obese patient should be reconnected to mechanical ventilation, as already demonstrated in patients without obesity [80] , and put again under pressure support with sufficient peep and pressure support. similarly, following extubation, as detailed below, preventing atelectasis has to start as soon as possible, using cpap or niv. moreover, to perform extubation as soon as possible, sedation should be stopped as early as possible and benzodiazepines avoided, even more than in patients without obesity due to prolonged release of drugs in patients with obesity [81] . prophylactic niv after extubation decreases the risk of arf by 16% and length of icu stay [82] . in hypercapnic icu patients with obesity, using niv after extubation is associated with decreased mortality [82] . a randomized controlled trial performed in patients with morbid obesity undergoing bariatric surgery found an improvement of ventilatory function when cpap was implemented immediately after extubation as compared to cpap started 30 min after extubation [83] (table 1 ). in case of positive pressure therapy already used at home, it should be reintroduced as early as possible in the icu as soon as higher levels of assistance requiring the use of an icu ventilator are no longer needed. home positive pressure therapy could also be introduced in icu for selected patients with obesity. cpap is indicated for use in patients with severe obstructive sleep apnea syndrome, as first-line therapy in these indications. in the case of combined obstructive apnea syndrome and moderate hypercapnia between 45 and 55 mmhg, a cpap device will be offered as first-line therapy, and a niv device, allowing ventilation at 2 pressure levels, will be offered in case of failure. if there is a history of respiratory decompensation with acute hypercapnic respiratory failure, hypercapnia greater than 55 mmhg and/or no associated obstructive sleep apnea syndrome, a niv device will be offered [84] . hfnc was not found to be superior to standard oxygen to prevent extubation failure in 155 post-cardiac surgery patients with obesity [85] . among cardiothoracic surgery subjects with obesity with or without respiratory failure, the use of continuous hfnc compared to niv did not result in a worse rate of treatment failure [33] (table 1) . similarly, in the study by hernandez et al. [86] including 20% of patients with obesity, among high-risk adults who have undergone extubation, preventive hfnc was not inferior to preventive niv for reducing reintubation rate and postextubation respiratory failure. in a randomized controlled trial of the same team comparing hfnc to standard oxygen [87] in high-risk non-hypercapnic patients including 22% of patients with obesity, the study was stopped due to low recruitment after 155 patients, without any difference in extubation failure rate found between the two groups. the specificities of weaning and extubation in icu patients with obesity are summarized in supplemental table 1 . a summary of the main respiratory physiological modifications and some suggestions for mechanical ventilation in critically ill patients with obesity are proposed in fig. 4 . in the general population, obesity is one of the top 10 risk factors of chronic diseases and a risk factor for death. consistent with this trend in the general population, the number of obese patients admitted to the icu is rapidly increasing [88] . obesity decreases life expectancy in the population, and obesity in childhood is now a healthcare crisis for our next generation with unknown consequences. there are overwhelming scientific data on overall mortality/morbidity, the healthcare system shortcomings to deliver adequate care, and the social discrimination and injustice that individuals with obesity are subject on daily basis. however, in icu, patients with obesity may be more likely to develop ards, but their survival sometimes appeared to be better, a phenomenon called the 'obesity paradox' [89] . patients with obesity have immunological and pulmonary mechanics differences compared to patients without obesity detailed in the supplemental content (see supplemental content 1). these differences are increased for patients with higher level of obesity. furthermore, clinicians may overestimate the lung size of patients with obesity, by considering real instead of pbw, and use higher v t during mechanical ventilation, risking ventilator-induced lung injury. the mentioned patient factors may also cause respiratory muscle fatigue and difficult weaning. indeed, 2 meta-analyses show that in close to 200,000 ards patients, obesity is linked to a higher risk of developing ards and patients with obesity need mechanical ventilation for a longer period of time, compared to critically ill patients without obesity [13, 16] . as a consequence, icu-length of stay is also prolonged in patients with obesity, while hospital length of stay is not [13, 16] . while patients with obesity are on mechanical ventilation for a longer period of time, these meta-analyses also demonstrate a survival advantage for patients with obesity. this observation is coined the 'obesity paradox' as a survival benefit may appear counterintuitive in view of the detrimental alterations in respiratory function as described above. several reasons to explain the obesity paradox in ards patients with obesity have been put forward. apart from the described immunological differences, patients with obesity have more metabolic reserve and may, therefore, tolerate the catabolic stress of critical illness during ards better, because of energy stores in the form of adipose tissue. it is important to also address the possibility that patients with obesity may have a lower threshold for icu admission, e.g., because of the need of more nursing staff not available on the ward or monitoring purposes. this would mean that patients with obesity admitted to the icu are less sick and therefore may show a better survival because of selection bias, not representing a real phenomenon. as in the meta-analyses, adjustments for covariates like disease severity were not possible; this may appear plausible. in a large study in over 150,000 icu patients, however, the obesity paradox remained present even when adjusted for several covariates including disease severity [90] . also, patients with obesity may have been misclassified as ards if atelectasis is interpreted as bilateral infiltrates. using a causal inference approach to reduce residual confounding bias due to missing data, it was found that the survival of patients without obesity would not have been improved if they had obesity [91] , findings which question the obesity paradox. in summary, patients with obesity are more likely to develop respiratory complications, including arf and ards. considering some physiological studies, for non-invasive management, using niv has to be considered both for preventing and treating arf, even if the level of proof is low, especially in comparison with hfnc. airway management in critically ill patients with obesity poses specific challenges, and adequate patient evaluation, pre-oxygenation and choice of intubation devices might improve outcomes. after intubation procedure for invasive mechanical ventilation, patients with obesity being more prone to lung collapse require higher peep to avoid it. low v t according to pbw should be used both in non-ards and ards fig. 4 main respiratory physiological modifications and suggestions for mechanical ventilation in critically ill patients with obesity. the main respiratory physiological modifications (functional residual capacity decreased, abdominal pressure often increased, pulmonary and chest wall compliance often decreased, cephalic ascension of diaphragm, oxygen consumption and work of breathing increased) lead to shunt via atelectasis and gas exchange impairment. comorbidities are often associated with obesity: obstructive apnea syndrome and obesity hypoventilation syndrome. consequences on airway management, potentially difficult, include the preparation of adequate material for difficult intubation as videolaryngoscopes, preoxygenation with noninvasive ventilation in a semi-sitting position, considering adding apneic oxygenation (optiniv method), rapid sequence induction and recruitment maneuver following intubation after hemodynamic stabilization. ventilatory settings include low or limited tidal volume (6-8 ml/kg/pbw or less), moderate to high peep (7-20 cmh 2 o) if hemodynamically well tolerated, recruitment maneuver (if hemodynamically well tolerated, in selected patients), monitoring of esophageal pressure if possible, use of prone positioning in a trained team in case of severe ards, without contra-indicating ecmo. after extubation, cpap or niv should be considered early, as implementation of positive pressure therapies at home after evaluation. pbw predicted body weight, peep positive end-expiratory pressure, ards acute respiratory distress syndrome, ecmo extracorporeal membrane oxygenation, cpap continuous positive airway pressure, niv noninvasive ventilation, hfnc high-flow nasal cannula oxygen patients. rm is not systematically recommended, and their use remains a decision based on individual risk/ benefit considerations. prone positioning should be used in severe ards patients with obesity. body-mass index and all-cause mortality: individual-participant projected us state-level prevalence of adult obesity and severe obesity obesity in the critically ill: a narrative review prevalence of cardiovascular and respiratory complications following trauma in patients with obesity isolated severe blunt traumatic brain injury: effect of obesity on outcomes obesity was associated with worse neurological outcome among japanese patients with out-ofhospital cardiac arrest obesity is associated with higher risk of intensive care unit admission and death in influenza a (h1n1) patients: a systematic review and meta-analysis comorbidities and the risk of severe or fatal outcomes associated with coronavirus disease 2019: a systematic review and meta-analysis increased mortality in patients with severe sars-cov-2 infection admitted within seven days of disease onset how important is obesity as a risk factor for respiratory failure, intensive care admission and death in hospitalised covid-19 patients? results from a single italian centre implications of obesity for the management of severe coronavirus disease 2019 pneumonia the role of visceral adiposity in the severity of covid-19: highlights from a unicenter cross-sectional pilot study in germany obesity paradox" in acute respiratory distress syndrome: asystematic review and meta-analysis body mass index and the risk of infection -from underweight to obesity obesity altered t cell metabolism and the response to infection is body mass index associated with outcomes of mechanically ventilated adult patients in intensive critical units? a systematic review and meta-analysis the effects of body mass index on lung volumes individualized positive end-expiratory pressure in obese patients during general anaesthesia: a randomized controlled clinical trial using electrical impedance tomography physiology of obesity and effects on lung function the effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia airway closure during surgical pneumoperitoneum in obese patients airway closure, more harmful than atelectasis in intensive care? respiratory function during anesthesia: effects on gas exchange oxygenation impairment during anesthesia: influence of age and body weight impact of obesity in mechanically ventilated patients: a prospective study outcomes of morbidly obese patients requiring mechanical ventilation for acute respiratory failure the impact of morbid obesity on oxygen cost of breathing (vo(2resp)) at rest effects of sitting position and applied positive end-expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechanical ventilation the effects of the reverse trendelenburg position on respiratory mechanics and blood gases in morbidly obese patients during bariatric surgery official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure effect of noninvasive ventilation on tracheal reintubation among patients with hypoxemic respiratory failure following abdominal surgery: a randomized clinical trial outcomes of patients with acute respiratory failure after abdominal surgery treated with noninvasive positive pressure ventilation high-flow nasal cannula therapy versus intermittent noninvasive ventilation in obese subjects after cardiothoracic surgery noninvasive respiratory support in the hypoxaemic peri-operative/periprocedural patient: a joint esa/esicm guideline use of nasal high flow oxygen during acute respiratory failure prevention and care of respiratory failure in obese patients high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during and after intubation of morbidly obese patients: a randomized controlled study evaluation and management of obesity hypoventilation syndrome. an official american thoracic society clinical practice guideline perioperative care of the obese patient respiratory management of the obese patient undergoing surgery mechanical ventilation in obese icu patients: from intubation to extubation pathophysiology of sleep apnea cardiac arrest and mortality related to intubation procedure in critically ill adult patients: a multicenter cohort study difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units videolaryngoscope versus macintosh laryngoscope for tracheal intubation in adults with obesity: a systematic review and meta-analysis a multicenter, randomized trial of ramped position vs sniffing position during endotracheal intubation of critically ill adults positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients nasal high-flow preoxygenation for endotracheal intubation in the critically ill patient: a randomized clinical trial bag-mask ventilation during tracheal intubation of critically ill adults focus on noninvasive respiratory support before and after mechanical ventilation in patients with acute respiratory failure prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis: a computerized tomography study protective versus conventional ventilation for surgery: a systematic review and individual patient data meta-analysis intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients noninvasive monitoring of lung recruitment maneuvers in morbidly obese patients: the role of pulse oximetry and volumetric capnography positive endexpiratory pressure optimization using electric impedance tomography in morbidly obese patients during laparoscopic gastric bypass surgery effect of intraoperative high positive end-expiratory pressure (peep) with recruitment maneuvers vs low peep on postoperative pulmonary complications in obese patients: a randomized clinical trial a trial of intraoperative lowtidal-volume ventilation in abdominal surgery spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial nava in acute respira-tory failure (naviator) network (2020) neurally adjusted ventilatory assist in acute respiratory failure: a randomized controlled trial influence of body mass index on outcome of the mechanically ventilated patients higher class of obesity is associated with delivery of higher tidal volumes in subjects with ards ecmo criteria for influenza a (h1n1)-associated ards: role of transpulmonary pressure impact of the driving pressure on mortality in obese and non-obese ards patients: a retrospective study of 362 cases driving pressure in obese ventilated patients: another brick in the (chest) wall effect of body mass index in acute respiratory distress syndrome transpulmonary pressure describes lung morphology during decremental positive end-expiratory pressure trials in obesity a lung rescue team improves survival in obesity with acute respiratory distress syndrome high positive end-expiratory pressure is associated with improved survival in obese patients with acute respiratory distress syndrome mechanical power normalized to predicted body weight as a predictor of mortality in patients with acute respiratory distress syndrome effect of lung recruitment maneuver on oxygenation, physiological parameters and mortality in acute respiratory distress syndrome patients: a systematic review and meta-analysis lung recruitment in obese patients with acute respiratory distress syndrome lung rescue team investigators (2020) high pleural pressure prevents alveolar overdistension and hemodynamic collapse in ards with class iii obesity a prospective international observational prevalence study on prone positioning of ards patients: the apronet (ards prone position network) study feasibility and effectiveness of prone position in morbidly obese patients with ards: a case-control clinical study class iii obesity is not a contraindication to venovenous extracorporeal membrane oxygenation support lack of association between body weight and mortality in patients on venovenous extracorporeal membrane oxygenation spontaneous breathing trial and post-extubation work of breathing in morbidly obese critically ill patients reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial reduces reintubation in critically ill patients: a multicenter randomized controlled trial immediate interruption of sedation compared with usual sedation care in critically ill postoperative patients (sos-ventilation): a randomised, parallel-group clinical trial noninvasive ventilation for prevention of post-extubation respiratory failure in obese patients continuous positive airway pressure via the boussignac system immediately after extubation improves lung function in morbidly obese patients with obstructive sleep apnea undergoing laparoscopic bariatric surgery how can i manage anaesthesia in obese patients? direct extubation onto high-flow nasal cannulae post-cardiac surgery versus standard treatment in patients with a bmi >/=30: a randomised controlled trial effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial high-flow nasal cannula to prevent postextubation respiratory failure in high-risk non-hypercapnic patients: a randomized multicenter trial intensive care in the obese the obesity paradox in surgical intensive care unit patients body mass index is associated with hospital mortality in critically ill patients: an observational cohort study the obesity paradox in critically ill patients: a causal learning approach to a casual finding key: cord-011269-j2rogzm7 authors: stefan, mihaela s.; pekow, penelope s.; shea, christopher m.; hughes, ashley m.; hill, nicholas s.; steingrub, jay s.; lindenauer, peter k. title: protocol for two-arm pragmatic cluster randomized hybrid implementation-effectiveness trial comparing two education strategies for improving the uptake of noninvasive ventilation in patients with severe copd exacerbation date: 2020-05-06 journal: implement sci commun doi: 10.1186/s43058-020-00028-2 sha: doc_id: 11269 cord_uid: j2rogzm7 background: copd is the fourth leading cause of death in the us, and copd exacerbations result in approximately 700,000 hospitalizations annually. patients with acute respiratory failure due to severe copd exacerbation are treated with invasive (imv) or noninvasive mechanical ventilation (niv). although imv reverses hypercapnia/hypoxia, it causes significant morbidity and mortality. there is strong evidence that patients treated with niv have better outcomes, and niv is recommended as first line therapy in these patients. yet, several studies have demonstrated substantial variation in the use of niv across hospitals, leading to preventable morbidity and mortality. through a series of mixed-methods studies, we have found that successful implementation of niv requires physicians, respiratory therapists (rts), and nurses to communicate and collaborate effectively, suggesting that efforts to increase the use of niv in copd need to account for the complex and interdisciplinary nature of niv delivery and the need for team coordination. therefore, we propose to compare two educational strategies: online education (ole) and interprofessional education (ipe) which targets complex team-based care in niv delivery. methods and design: twenty hospitals with low baseline rates of niv use will be randomized to either the ole or ipe study arm. the primary outcome of the trial is change in the hospital rate of niv use among patients with copd requiring ventilatory support. in aim 1, we will compare the uptake change over time of niv use among patients with copd in hospitals enrolled in the two arms. in aim 2, we will explore mediators’ role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and implementation effectiveness. finally, in aim 3, through interviews with providers, we will assess acceptability and feasibility of the educational training. discussions: this study will be among the first to carefully test the impact of ipe in the inpatient setting. this work promises to change practice by offering approaches to facilitate greater uptake of niv and may generalize to other interventions directed to seriously-ill patients. trial registration: name of registry: clinicaltrials.gov trial registration number: nct04206735 date of registration: december 20, 2019 chronic obstructive pulmonary disease (copd) is the fourth leading cause of death in the us, and copd exacerbations result in approximately 700,000 hospitalizations annually [1, 2] . patients who do not respond to pharmacotherapy are placed on invasive (imv) or noninvasive mechanical ventilation (niv). while invasive mechanical ventilation (imv) administered through an endotracheal tube is an effective method of treating acute respiratory, it requires treatment in an intensive care unit, and places patients at risk for a wide range of complications, including ventilator-associated pneumonia. niv (continuous positive airway pressure, cpap or bilevel positive airway pressure, bipap) provides positive pressure ventilation via a face mask without the need for intubation. multiple randomized controlled trials [3, 4] , meta-analysis [5, 6] , and analyses of real-world data [7, 8] have demonstrated that treatment with niv, when added to usual care, reduces the risk of intubation, lowers the incidence of ventilator associated complications, and results in better short-term survival. based on this evidence, niv receives a grade a recommendation in current global initiative for chronic obstructive lung disease (gold) guidelines [9] . furthermore, the european respiratory society and american thoracic society joint guidelines [10] as well as british thoracic society guidelines [11] make a strong recommendation for the use of niv as a first-line treatment for patients with copd exacerbation and acute respiratory failure. although the evidence supporting the use of niv is compelling, prior research has demonstrated substantial variation in the use of niv in routine clinical settings, highlighting a persistent gap in niv adoption. in a recent study of more than 77,500 patients with copd cared for at 400 us hospitals, median hospital percentage of niv use among ventilated patients was 75.1% (range 9.2-94.1%) and the bottom 20% of hospitals offered a trial of niv to less than half of ventilated patients [12] . more importantly, institutions with higher rates of niv had lower imv use and better clinical outcomes. thus, low hospital rates of niv in patients admitted for severe copd represents an evidence practice gap and a missed opportunity to improve the outcomes among this vulnerable population. appropriate delivery of niv is a complex, multicomponent intervention that requires timely recognition, and effective communication, and coordination across multiple disciplines. figure 1 depicts the flow for a patient who comes to the emergency department with severe copd exacerbation and each clinician's responsibilities in the process of niv initiation and monitoring. only few studies have tested strategies for supporting niv implementation. a single site, before-after study from canada found that multidisciplinary guidelines for the use of niv in patients with stefan acute respiratory failure (arf) were associated with greater niv utilization but included only patients in the intensive care unit [13] . for this study, we used the intervention mapping process model to develop and select implementation strategies to increase the uptake of niv [14] . figure 2 summarizes the steps in the development of our implementation strategy to increase the use of niv in severe copd exacerbation. in step 1 (formative evaluation), we conducted semistructured interviews with key informants in a sample of hospitals with high rates of niv and good copd outcomes (low mortality and niv failure rates). the analysis of the interviews revealed 3 different professional identities and roles in niv delivery: physicians, respiratory therapists (rts), and nurses. although several clinicians' tasks are distinct, fig. 1 shows the connections between physicians, nurses, and rts indicating the need for coordination to ensure optimal patient outcomes. the three groups encounter significant professional boundary issues with regards to their work responsibilities and priorities. for example, nurses were concerned about patient's inability to eat or take medications while on niv. rts considered that nurses do not have a good understanding of the vital role of niv. however, the two professions agreed that when there was a shared understanding of the treatment plan and when the concerns from both sides were openly addressed, the collaboration was considerably improved. rts perceived themselves as experts in initiating and managing niv; in some institutions, there was a strained relation between the rts and physicians, with rts complaining about a lack of autonomy and the need to wait for physicians when niv was immediately indicated. we identified the following contextual factors and strategies associated with successful niv implementation: provider buy-in, respiratory therapists (rt) autonomy to deliver niv independently, interdisciplinary teamwork, collegial, trusting relationships between rts, physicians, and nurses, and ongoing staff education [15] . in step 2, we organized the specific types of determinants that influence niv delivery using the theoretical domain framework (tdf) [16] . the tdf was used as a guiding theory for this project because the desired behavior change is primarily at the individual level, e.g., convincing providers to consider niv in any patient with severe copd exacerbation. we summarized the barriers in the tdf domains with an eye toward choosing an implementation strategy which could overcome several of the identified barriers. eight of the 14 domains (knowledge, skills, professional roles and identity, beliefs about capabilities, beliefs about consequences, environmental context and resources, social influences, and emotion) were present in the existing literature and our research. interdisciplinary teamwork, on-going education, providers buy-in, and rts autonomy were found as the top four determinants for successful niv delivery in copd exacerbations. these findings suggest that to succeed, implementation strategies need to account for the complex and interdisciplinary nature of niv therapy and the need for team coordination. step 3: to guide the selection of implementation strategies, we used the expert recommendations for implementing change (eric) [17] . the main themes that emerged from the qualitative analysis and literature review mapped to the tdf domains and the implementation strategies most likely to address those barriers are shown in table 1 . systematic analysis of the barriers suggested that to succeed, implementation strategies for knowledge transfer need to account for the complex and interdisciplinary nature of the niv therapy and the need for team coordination; however, these hypotheses need to be carefully tested. interprofessional, dynamic team training for physicians, rts, and nurses was the implementation strategy selected as targeting several key determinants [16, 18, 19] . niv is delivered in high acuity environments by teams in which membership is dynamic, decisions must be made quickly, and members are not always face-to-face (asynchronously taking care of patients). this creates a critical need for effective communication, conflict management, and shared mental model [20] skills that are well suited to ipe approaches [21] [22] [23] . by contrast, conventional education regarding niv is administered to individual clinicians or groups of clinicians of the same discipline via lectures or online modules. educating individual care providers in silos does not address the interprofessional collaboration inherent to niv delivery. on the other hand, ipe competencies emphasize the importance of establishing awareness and knowledge regarding interprofessional team roles. in this way, leveraging an ipe platform enables learning via interaction between two or more professions who learn from, with, and about each other's roles and responsibilities (in this case, in regards to niv) [24, 25] . the overall objective of this study is to conduct a pragmatic, parallel, 2-arm randomized cluster trial to compare the effectiveness of two implementation strategies: on-line education (ole) and interprofessional education (ipe) on the uptake of niv. the central hypothesis is that ipe will outperform conventional education, and that rt autonomy and/or team functionality will act as mediators. we will accomplish this goal by completing three specific aims. aim 1: to compare the effectiveness of ole and ipe for increasing the delivery of niv in appropriate patients hospitalized with copd exacerbation. aim 2: to examine the effect of ole and ipe on rt autonomy and team functionality as potential mediators of niv uptake. aim 3: to evaluate the acceptability and feasibility of the ole and ipe strategies to inform further refinement of the strategies. in this cluster randomized controlled 2-arm parallel trial, 20 hospitals will be randomized to ope or to ipe. patients and clinicians are clustered within the hospitals because the ipe encourage facility-level change in clinicians' communication and care coordination. the study will be conducted in 20 hospitals with riskadjusted niv proportion below median that have at least 35 eligible copd admissions in an 18-month period. potential eligible hospitals are those participating with data in premier database, a voluntary, fee-supported database containing highly detailed hospital billing data pooled from more than 600 geographically and structurally diverse hospitals whose makeup closely resembles that of us hospitals. hospitals that demonstrate interest in participating in the study will be asked to commit to form a copd-niv team composed of one physician, one rt, and one nurse that will be in close contact with the investigators and are responsible for delivering the educational intervention in their institution. eligible hospitals will be contacted in a random order until the sample of 20 hospitals is achieved. to assess for potential participation bias, we will compare participating and refusing hospitals using available data such as size, ownership, teaching status, and location. the overall study design is shown in fig. 3 . the explanatory continuum indicator summary (pre-cis) framework was used to assess the pragmatism of the trial (fig. 4) . we will randomly allocate hospitals to one of the study arms, stratified by the baseline niv proportion and hospital bed size. a researcher not involved in the study and blinded to the identity of the hospitals will use a computer-generated randomization scheme. the randomization scheme will be concealed to the investigators. due to the character of the intervention, it will not be possible to blind participants or investigators providing the educational program; however, the investigators will not be aware of the results of the study by intervention arm until the analysis is finalized. the trial will compare two implementation strategies: one active control consisting of traditional, online education (ole) learning and a strategy of in-person interactive inter-professional education (ipe). consent for participation in the educational strategies will be sought as a waiver of consent via an email sent to all potential participants after the randomization period and prior to the implementation at each site. participants in the copd-niv teams and the training will be physicians, rts, and nurses who are involved in treating patients with severe copd exacerbation. the following domains will be targeted in the educational training interventions: the hospital-based copd-niv teams will be responsible throughout the trial period for encouraging clinicians from each specialty to complete the courses. the investigators will have a conference call with the copdniv team after the institutions have been randomized to discuss recruitment and surveys' delivery. (e.g., rt autonomy, team functionality, and organizational readiness for implementing change). conference calls between the investigators and the individual copd-niv team will continue every quarter for the duration of the 18 months of active implementation period with a follow-up call at the end of the study. active control group: online education (ole) sites will be given access to free continuing education modules customized for each discipline; rt and nurse online education training will be approximately 30 min long, and physician's online education training will be about 1 h. the modules will be delivered online through a secure website that will allow us to count the number of providers completing the course. we will use traditional powerpoint presentations with embedded whiteboard animation videos. we selected an active control instead of usual care, because it will allow stronger inferences about the benefits of ipe when compared to more traditional learning approaches. the online modules will be offered for the entire period of the study for all the new staff. it will consist of a 60-minute in-person interprofessional educational workshop. training of the facilitators we will organized a one day in-person training for all the niv-copd teams. the training will consist of 2 modules: (1) niv knowledge and skills: delivered by niv experts and (2) ipe: delivered by an expert in ipe and team training. the didactic training regarding niv use in copd will include a review of the evidence supporting the benefits of niv, advantages of niv as compared to invasive mechanical ventilation (imv), selection of patients, contraindications to niv, and management of patients while on niv including monitoring, ventilator settings, attention to patient comfort, weaning from niv, and decision about niv failure and need for intubation. the didactic module will emphasize the importance of early initiation of niv in patients with severe copd. the second half of the training will concentrate on teaching interprofessional collaboration. specifically, the interprofessional education collaborative (ipec) recommends four key competencies in successful ipe, which include roles and responsibilities, teams and teamwork, values and ethics, and interprofessional communication [26] . we selected the following core competencies for our interactive ipe. professional roles and identity: each team member learns about abilities, tasks, duties, responsibilities, and concerns of their fellows' team members; values/ethics: work with individuals of other professions to maintain a climate of mutual respect and shared values; teams/teamwork: apply relationship-building values and the principles of team dynamics to perform effectively in different team roles to deliver patient-center care that is safe, timely, effective, and efficient [27] . given the demands for team coordination in niv delivery and findings in our qualitative work, we anticipate that ipe will contribute to greater rt, physician, and nurse understanding of each other's roles, increase team communication and functionality, and stimulate the development of shared mental models which facilitate coordination for niv. we will use positional clarification which involves verbally presenting team members with information about their teammates' jobs through discussion [28] . psychological safety and speaking up will be encouraged and facilitated. for example, an rt may assume that physicians have more knowledge about niv delivery for a particular patient than they do (because physicians are generally more knowledgeable about treatments) and remain quiet; when in fact, the rt has important information about how the patient may respond (cognitive bias) [29] . the sessions will be recorded, so that participants will have ongoing access to the content. we anticipate that the members of the copd-niv team who will become the training facilitators at their hospital will not be subject matter experts in the training context, especially the ipe. therefore, a special instructor script will be written and will be paired with the presentation. delivery of the ipe sessions at institutions randomized to ipe training sessions for clinicians at ipe sites will be led by the copd-niv teams and will include information (e.g., 30-min lecture), demonstration (providers will be provided with contextualized examples), and practice (30min, action-based approach with guided practice). it will contain a scenario of a patient with severe copd coming to the emergency room with shortness of breath. they will review the guidelines for patient selection and monitoring and niv settings and management. each participant will be able to try the niv mask and understand the importance of appropriate settings and attending to patient comfort. the three core competencies for interprofessional collaboration and how they apply to the niv delivery will be explained. the ipe sessions will be offered up to twice a month for 3 months-the number will vary by institution depending on the number of providers that need to be trained. for the entire period of the study, we will continue to have every other monthly breakfast/lunch meetings where cases of patients with copd in need of niv will be presented with emphasis on interprofessional work structure, rt autonomy, and team functionality. full ipe sessions will be offered once a month every 6 months for the new staff, as part of on-boarding. table 2 outlines the implementation and effectiveness outcomes at the cluster (hospital) level, their implementation timing, how they will be measured, and the source of data collection. to compare the effectiveness of ole and ipe for increasing the delivery of niv in appropriate patients hospitalized with copd exacerbation. primary outcome hospital-level risk-standardized (rs) initial niv proportion among patients hospitalized with a copd exacerbation that were ventilated with niv or imv is assessed via administrative records of patients discharged from participating premier hospital who were 40 years or older and received a principal diagnosis of copd, or a principal diagnosis of acute respiratory failure paired with a secondary diagnosis of copd. we will use a previously validated set of icd-10-cm codes that achieve a reasonable balance of sensitivity and specificity while minimizing potential biases [30] . secondary outcomes rs hospital rates of niv failure (imv after a trial of niv), mortality, length of stay, and 30-day readmission among all patients with copd. all outcomes will be measured at the hospital level: (1) at baseline using prior 18 months of data, (2) at 18 months post-implementation to assess immediate/short term impact, and the following 18 months to assess sustainability. the 18-month assessment period is necessary to have adequate numbers of eligible copd admissions for assessing hospital rates of niv utilization. the time from randomization to the completion of the educational sessions with an expected duration of 3 months will not be included in the calculation of rs-niv post-intervention. to examine penetration, we will measure providers' exposure to educational training using participation logs. patient and hospital information demographics, comorbidities, prior year number of admissions for copd, prior year use of niv or imv, and outcomes will be identified from icd-10 procedure codes and billing codes. for each participating hospital, we will record the number of beds, the annual number of admissions for copd, teaching status, geographic region, and whether it serves an urban or rural population. we will also collect information about staffing: number of rts, hospitalists, emergency room physicians, and nurses. we will record if hospitals use protocols for niv initiation and management, and if niv can be delivered on the regular medical floor or only in an intensive care unit. these factors will be used to describe participant hospitals and evaluated as potential confounders or effect modifiers. noninvasive and invasive ventilation for each patient, we will examine standardized charge codes generated daily by respiratory therapists as well as dated icd-10procedure codes to determine whether or not they were treated with assisted ventilation, and, if so, whether ventilation was niv or imv. we define the primary method of ventilation as the first method by date and distinguish between patients treated with niv as an initial strategy from those in whom niv use follow exposure to invasive mechanical ventilation (imv). we have previously validated the niv icd procedure codes and respiratory therapy charge codes by retrospective medical chart review. using icd-9-cm codes alone yielded a sensitivity of 86% (95% ci, 81-92%) and specificity of 92% (95% ci, 84-98%). the approach of using icd-9-cm procedure codes and/or respiratory therapist charges increased sensitivity to 99% (95% ci, 98-4 100%) without reducing specificity (92%, 95% ci, 84-99%) [31] . statistical analysis of aim 1 we will generate descriptive statistics overall, by hospital and educational strategy, including counts and percentages for categorical data, means, standard deviations, and percentile distributions for continuous data. we will compare characteristics of hospitals, including staffing characteristics, in the two study arms via chi-square tests and t tests or wilcoxon tests. characteristics of patients in the enrolled hospitals in the two arms will be compared via gee models accounting for clustering by hospital. we will calculate the percentage of patients treated according to each of the primary ventilatory strategies: no assisted ventilation, niv, and imv. we will then calculate the proportion of patients initially treated with niv among those who received assisted ventilation. we will estimate a risk-standardized proportion of ventilated patients initially treated with niv (rs-niv) for each hospital and for each data collection period (baseline period, 18 months post-intervention, and between 18 to 36 months post-intervention). we will use hierarchical logistic regression with a random hospital effect to model initial use of niv among patients started on ventilation, adjusting for demographics, and comorbidities. from the model, a predicted niv percentage for each hospital will be computed as the niv percentage that would be anticipated at a particular hospital by using its hospital random effect, given the patient case mix. the expected niv percentage will be computed as the rate that would be expected if the same patient mix were treated at an "average" hospital, using the average hospital effect. the rs-niv percentage is then computed as the ratio of predicted to expected niv percentage standardized by the overall unadjusted mean niv percentage for all admissions in our model. risk standardization has 2 key advantages: it adjusts for differences in patient mix, which may impact the suitability of niv; it also provides more stabilized estimates based upon bayesian shrinkage towards the overall mean among hospitals with small numbers of ventilated patients [32, 33] . the mean and median rs-niv rates of the two arms will be computed for each study period. the primary analysis will use an analysis of variance model to compare ipe to ole on change in rs-niv rates from baseline to 18 months post-intervention. additional analyses will adjust for hospital characteristics that are unbalanced between the study arms. a secondary analysis will compare the post-intervention levels, adjusting for baseline rs-niv. to assess sustainability, similar models will be used to compare level of rs-niv after an additional 18 months have passed. for the secondary outcomes, our analysis will calculate hospital rs-rates of niv failure, mortality, 30-day readmission, and length of stay among ventilated patients, as well as all copd admissions for each study period. we will compare outcomes of ole and ipe hospitals using models described above. although we assume that the patients treated in ipe hospitals will have better clinical outcomes, we do not expect it to be able to detect an effect of these strategies on secondary outcomes due to overall low outcome rate, the small projected change, and relatively small number of clusters. organizational readiness the implementation of the educational strategies to increase the use of niv in copd exacerbations will require the coordinated action of many organizational members (e.g., physicians, rts, and nurses). the organizational readiness for implementing change (oric) survey can assess this construct at the supra-individual level (team, department, or organization) [34] . when organizational readiness is low, clinicians at these hospitals are likely to see the implementation (educational strategies) for the intervention (niv use in copd exacerbations) as undesirable and potentially avoid or resist planning for the implementation or participating in the implementation [34, 35] . the oric will allow us to identify the difference between organizations resisting the change (increasing niv utilization) and sites that are unable to implement the educational strategies due to difficulties inherent in organizing and conducting the educational strategies at their hospital. to assess the readiness of the organization to implement the change, we will use a 7item survey adapted from the original 10-item organizational readiness for implementing change (oric) [34] . this survey will measure change commitment and change efficacy of the organization towards increasing the rate of niv use for copd exacerbations. power and sample size for aim 1 the minimal number of hospitals participating in the trial was based on the analysis of premier 2016-2017 data. hospital rs-niv proportions were calculated for the 457 hospitals with at least 35 eligible copd admissions. the median rs-niv rate among this group of hospitals was 82% (iqr 74-86%). we then selected the 48 hospitals with rs-niv proportion less than 55%, based on the clinical impression that these hospitals would have sufficient room for improvement, as potentially eligible sites. among these hospitals, the median number of eligible copd patients was 197 over a 12-month period, ranging from 23 to 556 patients. the number of ventilated patients per hospital ranged from 7 to 163, with a median of 37. to achieve stability in estimation of hospital level rs-niv, we will assess our primary endpoint at 18 months post-intervention expecting a minimum of 10 ventilated patients per hospital in which to assess niv rates. power analysis was conducted to determine the number of hospitals needed to assess the primary outcome of difference between the study arms in change in the hospital level risk-standardized proportion of ventilator starts that are niv (rs-niv). using a type i error rate of 0.05, and standard deviation of change in rates over time derived from our prior work with the premier data base, a total sample of 20 hospitals, 10 in each arm will give 80% power to detect difference of 15% in change (e.g., 5% increase among ole hospitals, vs. 20% increase among ipe hospitals). power is > 90% to detect a 20% difference in change between the intervention groups. to examine the effect of ole and ipe on rt autonomy and team functionality as potential mediators of niv uptake. study design to complete this aim, we will survey clinicians at baseline, 1 year, and end of the study period. participants and settings we will select a random sample of 10 rts for the rt survey and 21 providers (7 from each discipline) for team functionality and organizational readiness for change surveys. a waiver of consent will be sent to all potential participants via email, the survey link will be included at the end of the email. to maximize participation, we will provide $25 incentives to participants. rt autonomy job autonomy is defined as the degree of perceived control that an employee has over how they perform tasks and the degree to which they operate independently. prior studies showed that it mediates the relationship between employment status, work attitude, and performance [36, 37] . in our previous study, indepth interviews with key stakeholders from a sample of hospitals with high use of niv suggested that rt autonomy is critical to achieving timely initiation of niv, often facilitated by the use of protocols [15] . these results are in line with prior literature [38] that supports the benefits of autonomous rt practice for weaning from imv [39, 40] . factors identified by the interviewees to contribute to rt autonomy were rt-driven protocols, rt expertise, and collegial relationship between rt and physicians. we assume that ipe will increase the physicians trust in rts by allowing them to learn about their abilities and duties and concerns, and that ipe will facilitate team member recognition of their own knowledge with rts being more likely to "speak up" (e.g., to suggest niv use instead of intubation). to assess rt autonomy, we adapted a survey from the 11-item job autonomy measure from aarons et al [37] . team functionality the iom 2001 and 2006 quality chasm reports brought widespread attention to clinical teamwork as a means of improving safety and quality in healthcare [41] . engagement in training-related activities designed to disseminate knowledge, skills, and attitudes for teamwork (such as ipe) is one way to acquire attitudes and behaviors consistent with teamwork and improve downstream impact on care quality and safety for patients [42] [43] [44] . get all clinicians (physicians, rts, and nurses) involved in the delivery of niv with the goal of promoting mutual trust and effective communication which will improve team functionality and hopefully promote niv use. to assess team functionality, we adapted questions from the 4-point likert scale assessment of collaborative environment survey (ace-15), a 15-item questionnaire which measures the perception of interprofessional "teamness" [45] . we created an 18-item questionnaire that has been divided into two parts: the first is the 9-item measure team functionality in managing patients with copd exacerbation and the second is the 9-item measure team functionality in initiating niv. statistical analysis we will develop a series of models evaluating associations among the intervention, mediators, and outcome, including a structural equation model (sem) to estimate the role of mediators as well as the direct effect of intervention on the outcome [46] [47] [48] [49] . first, to evaluate the impact of educational intervention on the mediators rt autonomy and team functionality to implement change, multi-level models will be fit, clustering on hospital. additional models will adjust for hospital and practitioner characteristics. next, models for the primary rs-niv outcome will be fit, with these potential mediators as the primary predictors. main effects and interaction models will be evaluated. then, the mediators will also be included as covariates in multi-level models including intervention, to evaluate whether rt autonomy and team functionality have effects on outcome, and after controlling for intervention. finally, multi-level structural equation modeling will then be employed to estimate the indirect effect of the educational intervention on rs-niv in the presence of mediators. analysis will be performed using stata's gsem. this model will allow estimation of the direct effect of ipe intervention relative to ole, in addition to the impact through the mediators (fig. 5 ). power and sample size for aim 2 for aim 2 analyses, power was assessed for educational mode impact on job autonomy for respiratory rt measured by aaron's job autonomy survey (ajas), and team functionality measured by the ace-15 tool. estimating sample size to achieve 80% power, using a type i error rate of 0.05, a sample of 10 rt's per hospital, will allow us to detect a moderate (cohen's d = .4) difference in ajas at a 1-year post-intervention. this is accounting for clustering on hospital with intraclass correlation (icc) in the range of .10-.20. based upon data from local area hospitals, we estimate staffing of 8-10 rts per 100 beds. for a few smaller hospitals, we will hope to include all rts and may fall short of 10. similarly, for the ace-15, a sample size of 21 clinicians (7 each of rts, rns, and mds) will achieve 80% power to detect a moderate effect size difference, accounting for clustering within hospitals, with icc in the range of .10-.20 [50] . to evaluate the acceptability and feasibility of the ipe and ole strategies and to inform further refinement of the strategies. study design to achieve this aim, we will perform a qualitative study using semi-structured interviews with providers to assess relative importance of various barriers and determinants on the implementation of the two strategies. participants and settings we will recruit a random sample of nurses, physicians, and rts. as it is typical in qualitative research, the total sample is not fixed; depending of the size of the program, we will select 2-4 individuals from each profession in each hospital and expect to enroll approximately 40-50 providers enabling us to reach thematic saturation. potential participants will be contacted via email by the study research assistant and invited to conduct an interview. a waiver of consent will be included in the body of the email prior to the contact information for the interview. those who are interested in participating will be contacted by telephone to arrange an interview time over the telephone. to maximize participation, we will provide $50 incentives and schedule sessions at a time convenient to the participants. data collection we anticipate that interviews will last approximately 30 min. all interviews will be audio recorded and transcribed verbatim. the interview team will consist of one research associate who will be trained by the investigator. the focus of the interviews will be to explore the implementation process-the acceptability and feasibility of the educational training strategies, participation in the training sessions, barriers to participation, adaptation made to the training sessions, and how the niv protocol was incorporated into the clinical workflow. expected outcomes this qualitative analysis will allow us to gain a broader perspective on the process of implementation from the perspective of the participants. we expect to understand and identify barriers and facilitators and their relative importance for this implementation strategy to be the most successful. the knowledge gained from this aim will be important for further application and refinement of ipe for other therapies/interventions directed to the critically ill patients. data analysis transcripts will be reviewed by the interviewer for accuracy. qualitative data management and analysis software (nvivo) will be used to organize and code the data [51] . the nature of the interviewee role and the setting in which they work will be summarized and reported by location. we will use directed qualitative content methods to analyze interview content, beginning with a coding framework based on our prior work [52, 53] . coding will occur concurrently with the interviews to ensure that the interview guide is eliciting data related to the domains of interest. two team members will be primarily responsible for coding and will be supervised by one co-investigator proficient in qualitative analysis. the first 2 interviews will be read by each researcher with the goal of agreeing on the use of the domains and or constructs. this codebook will be used for all interviews going forward, with the team meeting periodically to discuss the emergence of any new codes or to clarify the relevance of domains and constructs to the text. each transcript will be coded twice, once by each researcher. discrepancies will be discussed until consensus is reached. through regular investigators meetings, we will generate overarching themes. the investigation will collect the following information to calculate the costs to initiate the intervention: (1) cost of the training of the copd-niv team in the ipe arm of the study and inclusive of salary/fringe costs of the implementation specialists travel to the one day training session, (2) cost of webinars inclusive of speaker costs and video recording costs, and (3) cost of the continuing educational credits provided to the clinicians attending the ipe sessions at their hospitals and to the copd-niv team for their attendance of the 1-day session and for teaching the copd-niv-ipe course at their hospital. we propose the following strategies for dissemination: (1) after study completion, we will host webinars to share the results with the participant hospitals; (2) we will develop a one-page information sheet with the results and conclusion of the study and distribute it on the premier inc. website; (3) we will develop a toolkit and implementation manual with step-by-step guidance to help other institutions implement the ipe strategy; (4) publications and presentations at national and international respiratory and d&i conferences; and (5) we will work with society of hospital medicine and copd foundation to share the finding of the study to their members. table 3 present the proposed timeline for the study. potential limitation and rational for key decisions why study only education? we have carefully considered other implementation strategies such as audit and feedback, which is an electronic medical records decision support tool and academic detailing. when mapping the barriers within eric compilation of implementation strategies, we found that ipe covered several of identified barriers. additionally, we were concern that using multiple strategies would complicate our attempt to understand the educational intervention impact. interprofessional care is essential to the management of seriously ill patients and in the absence of robust studies to determine if ipe indeed impact patient outcomes, it is critical to be able to assess it in randomized controlled trial. for this pragmatic clinical trial, we need to be able to calculate hospitals' niv rates and identify low performing hospitals to be able to invite them to participate in the trial and determine the rates after the implementation period. our intention was to have these rates calculated directly from the administrative or electronic data without a need for data collection. we did not come across any other database which provides the needs for this trial. still, if the trial shows that ipe is effective in improving the niv rates, individual hospitals will be able to calculate their own rates and decide if they want to implement the ipe strategy. this study will be among the first to carefully test the impact of ipe in the inpatient setting. over the last 20 years, there have been increasing interest in linking ipe with interprofessional collaboration and team-based care [26, 54] ; however, only recently have researchers begun to look beyond the classroom and beyond learning outcomes on such issues as patient safety, patient and provider satisfaction or quality, and cost of care. consequently, the 2015 institute of medicine report "measuring the impact of interprofessional education on collaborative practice and patient outcomes" questions calls for purposeful, well-designed, robust studies to understand the link between ipe and patient and health systems outcomes [55] . therefore, our study will add to the evidence by comparing an ipe strategy specifically designed to improve team functionality for niv delivery in a pragmatic randomized controlled trial against an active, realistic control. centers for disease control and prevention. faststats -chronic lower respiratory disease copd exacerbation frequency and its association with health care resource utilization and costs noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: cochrane systematic review and meta-analysis contemporary management of acute exacerbations of copd: a systematic review and metaanalysis comparative effectiveness of noninvasive ventilation vs invasive mechanical ventilation in chronic obstructive pulmonary disease patients with acute respiratory failure outcomes associated with invasive and noninvasive ventilation among patients hospitalized with exacerbations of chronic obstructive pulmonary disease nhlbi/whi global strategy for the diagnosis, management and prevention of copd bts/ics guidelines for the ventilatory management of acute hypercapnic respiratory failure in adults. british thoracic society hospital patterns of mechanical ventilation for patients with exacerbations of copd evaluation of a practice guideline for noninvasive positive-pressure ventilation for acute respiratory failure intervention mapping: theory-and evidence-based health promotion program planning: perspective and examples. front public health successful use of noninvasive ventilation in chronic obstructive pulmonary disease. how do high-performing hospitals do it? validation of the theoretical domains framework for use in behaviour change and implementation research a refined compilation of implementation strategies: results from the expert recommendations for implementing change (eric) project making psychological theory useful for implementing evidence based practice: a consensus approach. qual saf health care the behaviour change wheel: a new method for characterising and designing behaviour change interventions the influence of shared mental models on team process and performance knowledge translation interventions for critically ill patients: a systematic review* facilitators of an interprofessional approach to care in medical and mixed medical/surgical icus: a multicenter qualitative study organizational learning: creating, retaining and transferring knowledge new approaches to interprofessional education and collaborative practice: lessons from the organizational change literature a best evidence systematic review of interprofessional education: beme guide no core competencies for interprofessional collaborative practice team effectiveness 1997-2007: a review of recent advancements and a glimpse into the future cross-understanding: implications for group cognition and performance psychological safety and learning behavior in work teams the validity of international classification of diseases, ninth revision clinical modification diagnosis codes for identifying patients hospitalized for copd exacerbations a26s: validity of noninvasive and invasive ventilation billing and procedure codes in patients with acute respiratory failure comparison of hospital risk-standardized mortality rates calculated by using in-hospital and 30-day models: an observational study with implications for hospital profiling organizational readiness for implementing change: a psychometric assessment of a new measure using organization theory to understand the determinants of effective implementation of worksite health promotion programs national employment systems and job autonomy: why job autonomy is high in the nordic countries and low in the united states, canada, and australia the impact of evidence-based practice implementation and fidelity monitoring on staff turnover: evidence for a protective effect effectiveness and safety of a protocolized mechanical ventilation and weaning strategy of copd patients by respiratory therapists a randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation large scale implementation of a respiratory therapist-driven protocol for ventilator weaning crossing the quality chasm: a new health system for the 21st century does team training improve team performance? a meta-analysis saving lives: a meta-analysis of team training in healthcare teamwork in health care: maximizing collective intelligence via inclusive collaboration and open communication development of the assessment for collaborative environments (ace-15): a tool to measure perceptions of interprofessional "teamness practical issues in structural modeling structural equations with latent variables improper solutions, and starting values in lisrel maximum likelihood estimation the robustness of lisrel modeling revisited sample size requirements for structural equation models: an evaluation of power, bias, and solution propriety three approaches to qualitative content analysis basics of qualitative research: techniques and procedures for developing grounded theory core competencies for interprofessional collaborative practice board on global health, institute of medicine. measuring the impact of interprofessional education on collaborative practice and patient outcomes springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations karen riska acted as a research coordinator and participated in manuscript revisions. taylar clark acted as a research assistant and completed literature review activities and provided editorial feedback on manuscript drafts. authors' contributions ms designed the protocol, wrote the first draft of the manuscript, and provided senior-level conceptual feedback on manuscript revisions. pkl, psp, jss, amh, and cms acted as co-i during the implementation, participated in the design of the protocol, and provided senior-level editorial feedback on manuscript preparations. all authors read and approved the final manuscript. sources of funding: this study protocol has been approved and funded by the nhlbi (nih), r01hl146615.availability of data and materials not applicable for this section ethics approval and consent to participate baystate irb has approved this study and deemed it ethical. baystate irb has also declared that this study is minimal risk, and therefore approved our waiver of consent for the participants of this study. key: cord-010669-rg2p3kal authors: fubini, pe; suppan, l title: prehospital reversal of profound respiratory acidosis and hypercapnic coma by non-invasive ventilation: a report of two cases date: 2020-05-07 journal: int j emerg med doi: 10.1186/s12245-020-00284-y sha: doc_id: 10669 cord_uid: rg2p3kal background: in chronic obstructive pulmonary disease (copd) patients with acute respiratory failure (arf), non-invasive ventilation (niv) is generally recommended and has proven its benefits by reducing endotracheal intubation (eti) rates, intensive care unit (icu) admissions, complications, and mortality. choosing between immediate eti or niv trial is often difficult when such patients present with an altered mental status. some guidelines recommend avoiding niv when consciousness is impaired given the risk of aspiration, and some authors suggest that a ph < 7.25 is highly predictive of niv failure. though clinical response to a well-adjusted niv treatment can be both swift and spectacular, these contraindications probably encourage physicians to proceed to immediate eti. some studies indeed report that niv was not even considered in as many as 60% of patients who might have benefited from this therapy, though eti related complications might have been avoided had niv been successfully applied. case presentation: we report two cases of arf in copd patients who were successfully treated by niv in prehospital setting and avoided eti despite contraindications (altered mental status with a glasgow coma scale < 8) and failure risk factors (severe respiratory acidosis with ph < 7.25). conclusion: in copd patients presenting arf, niv trial could be considered even when relative contraindications such as an altered level of consciousness or a severe respiratory acidosis are present. acute respiratory failure (arf) in chronic obstructive pulmonary disease (copd) patients is a well-known indication for non-invasive ventilation (niv) trial [1] . the benefits provided by this therapy are numerous and well-studied, the most prominent being reductions in mortality as well as in endotracheal intubation (eti) and intensive care unit (icu) admission rates [2, 3] . the main contraindication to niv is the need for emergent eti, considered to be mandatory when consciousness is severely impaired, when the patient is unable to cooperate, or when the airways need to be protected because of a high aspiration risk [4] . unfortunately, copd patients with arf often meet these criteria because of hypercapnic coma, and the role of niv in this setting is therefore still debated [5, 6] . furthermore, some authors suggest that a ph < 7.25 is linked to a high risk of niv failure event if a trial might still be considered [7, 8] . the underutilization of niv in hypercapnic copd exacerbations suggested by some reports might be at least partially due to these contraindications, which could encourage physicians to immediately proceed with eti [9] . in geneva, an emergency mobile unit called "service mobile d'urgence et de réanimation" (smur), staffed by an advanced paramedic and a physician, can be dispatched to assist a regular ambulance in case of lifethreatening emergencies [10] . all smur vehicles have been equipped by a hamilton t1 ventilator (hamilton medical, bonaduz, switzerland) since 2013, and the decision to initiate niv is made by the physician according to his clinical evaluation. a portable blood gas analyzer (istat, abbott point of care inc., princeton, usa) is available to guide treatment decision and assess the patients' evolution. we report here two cases of arf in copd patients with severe respiratory acidosis and hypercapnic coma successfully treated by niv in the prehospital setting. case 1: a 71-year-old woman known for global initiative for chronic obstructive lung disease (gold) stage 3 copd under long-term supplemental oxygen therapy was found in respiratory distress the morning after having received oxazepam 30 mg for anxiety and insomnia during the previous evening. upon arrival, prehospital providers noted a glasgow coma scale (gcs) of 6 with no focal deficit, shallow breathing with a respiratory rate over 40 breaths per minute, and a pulsed oxygen saturation of 80% under supplementary oxygen (6 l/min) through nasal cannula. there was no hemodynamic compromise, and the patient was apyretic. reservoir oxygen face mask was applied and arterial blood gas obtained, showing severe respiratory acidosis (ph 7.17, pco 2 15.6 kpa, po 2 24.1 kpa, bicarbonates 43 mmol/l). a niv trial was started using bi-level positive airway pressure ventilation mode, targeting a tidal volume of 6 ml/ kg ideal body weight. patient was under continuous medical surveillance during transport to the emergency room (er) and showed progressive neurological improvement with a gcs rising to 10. after 60 min of ventilation, a new arterial blood gas sample was drawn showing improvement of her respiratory acidosis (fio 2 21%: ph 7.31, pco 2 10.0 kpa, po 2 7.1 kpa, bicarbonates 37 mmol/l). she was then admitted to icu to continue niv, which was successfully continued. eti was never required, and the patient was transferred to the internal medicine ward after 2 days before being discharged from the hospital after 14 days. case 2: a 70-year-old man known for gold stage 4 copd under long-term supplemental oxygen therapy who had been treated by bronchodilators, antibiotics, and steroids for a week, called the ambulance dispatch central because of increasing dyspnea and chest pain. when prehospital providers arrived on site, the patient was unconscious (gcs 3) and in severe respiratory distress with central cyanosis, rapid/shallow breathing. the pulsed oxygen saturation was of 70% under supplementary oxygen (6 l/min) through nasal cannula. he was hemodynamically stable. ventilation using a bag-valve mask was quickly initiated, and arterial blood gas obtained, showing severe respiratory acidosis (ph 7.07, pco 2 > 17.0 kpa, po 2 40.1 kpa, bicarbonates not recorded due to equipment error). the patient had signed a legal document asking not to be resuscitated nor intubated. a bi-level positive airway pressure ventilation niv trial was started, and both intravenous aspirin and unfractionated heparin were administered. constant medical surveillance was provided during transport. upon arrival in the er after 30 min of niv, the patient had a gcs of 14. after 70 min of ventilation, a new arterial blood gas sample was drawn showing improvement of his respiratory acidosis (fio 2 32%: ph 7.24, pco 2 12.2 kpa, po 2 7.6 kpa, bicarbonates 38 mmol/l). pulmonary embolism was ruled out by ct scan and, because of chest pain and elevated cardiac biomarkers, coronary catheterization was performed showing chronic proximal anterior-interventricular artery occlusion that was treated by stenting. the patient was then admitted to the icu to continue niv before being transferred to the internal medicine ward after 2 days and finally discharged from the hospital after 20 days. though eti should have been performed in both these patients according to some guidelines [4, 7] , use of prehospital niv allowed us to avoid this high-risk procedure and its potential complications. the decision to perform eti in advanced copd patients must be carefully weighed as such patients frequently present a prolonged and difficult ventilation weaning and as eti has been linked with an increased mortality rate [11] . some authors therefore suggest that it might be worth trying niv even in patients showing altered level of consciousness [5, 6] . in-hospital underutilization of niv is nevertheless often reported, with eti being chosen in as many as 60% of patients meeting criteria for niv trial. the contraindications found in some guidelines are probably among the most important factors leading the physicians to favor immediate eti [9] . in the prehospital setting, the proportion of niv underutilization might be even greater, as logisticrelated issues might cause delays in both time before first medical contact and niv instauration. such delays might lead to further respiratory and neurological compromise, finally making emergent eti unavoidable. the cases we reported are examples of situations in which the choice between niv trial and eti is particularly challenging. the first patient presented with arf induced by benzodiazepine intoxication, while the second patient had a copd exacerbation probably precipitated by nstemi, assuming that cardiac ischemia was not a consequence of severe hypoxia. in both cases, we believe that clinical improvement was entirely due to niv as it was the only effective treatment administered by the prehospital team. indeed, no flumazenil was given to the first patient despite probable benzodiazepine intoxication, and the second patient was given aspirin and heparin, but no nitrates, diuretics, or inotropic medication. even if these two patients presented with arf of different etiologies, their clinical picture at first medical contact was similar. they both had baseline advanced copd, a ph < 7.25, and a gcs < 8. within the first hour, respiratory acidosis regressed (with a ph increase of 0.14 and 0.17 respectively) and neurological status improved (with gcs improving from 6 to 10 and from 3 to 14 respectively) in both cases, making it possible to avoid eti. for the first patient, niv was tried because of the potential harmful effects of eti and mechanical ventilation in the context of advanced copd. conversely, while the second patient undoubtedly met criteria for immediate eti, the procedure was not performed to respect his will. nevertheless, clinical improvement was even more spectacular in this case, with the patient recovering an almost normal level of consciousness in only 30 min. the main limitation of this report is that it only describes two cases. nevertheless, both cases show that niv could reasonably be attempted in patients in whom eti should have been performed according to some guidelines. indeed, though some authors argue that all patients at high aspiration risk should be intubated, it is our opinion that the risks linked to niv should be weighed against the risks linked to eti, and that the kind of clinical surveillance that can be provided should be taken into account. as a physician-staffed emergency mobile unit assists regular ambulances in case of life-threatening emergencies such as arf in our prehospital system, critical patients are constantly monitored by an emergency physician throughout transport [10] . in a system allowing well trained healthcare providers to immediately react by withdrawing the niv mask, tilting the patient on the side, suctioning the airways, or even performing immediate rapid-sequence intubation, we believe that niv can be considered even in situations where eti is still often considered as a first choice. in conclusion, for copd patients presenting arf, niv trial could be considered even when relative contraindications such as an altered level of consciousness or a severe respiratory acidosis are present. in such cases, continuous medical surveillance is mandatory, and physicians should be ready to perform eti should complications arise or the trial fail. official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. cochrane database of systematic reviews early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial international consensus conferences in intensive care medicine: noninvasive positive pressure ventilation in acute respiratory failure noninvasive positive-pressure ventilation to treat hypercapnic coma secondary to respiratory failure noninvasive positive pressure ventilation in patients with acute exarcerbations of copd and varying levels of consciousness a chart of failure risk for noninvasive ventilation in patients with copd exacerbation noninvasive vs invasive ventilation in copd patients with severe acute respiratory failure deemed to require ventilatory assistance missed opportunities for noninvasive positive pressure ventilation: a utilization review effect of noninvasive ventilation on intubation risk in prehospital patients with acute cardiogenic pulmonary edema: a retrospective study characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation authors' contributions pef and ls contributed equally to this work. both authors read and approved the final manuscript. the authors report no sources of funding. the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.ethics approval and consent to participate not applicable consent for publication not applicable the authors declare that they have no competing interests.received: 19 february 2020 accepted: 26 april 2020 key: cord-335078-z7k59k8o authors: burton-papp, helmi c.; jackson, alexander i. r.; beecham, ryan; ferrari, matteo; nasim-mohi, myra; grocott, michael p. w.; chambers, robert; dushianthan, ahilanandan title: conscious prone positioning during non-invasive ventilation in covid-19 patients: experience from a single centre date: 2020-07-31 journal: f1000res doi: 10.12688/f1000research.25384.1 sha: doc_id: 335078 cord_uid: z7k59k8o critically ill patients admitted to hospital following sars-cov-2 infection often experience hypoxic respiratory failure and a proportion require invasive mechanical ventilation to maintain adequate oxygenation. the combination of prone positioning and non-invasive ventilation in conscious patients may have a role in improving oxygenation. the purpose of this study was to assess the effect of prone positioning in spontaneously ventilating patients receiving non-invasive ventilation admitted to the intensive care. clinical data of 81 patients admitted with covid 19 pneumonia and acute hypoxic respiratory failure were retrieved from electronic medical records and examined. patients who had received prone positioning in combination with non-invasive ventilation were identified. a total of 20 patients received prone positioning in conjunction with non-invasive ventilation. this resulted in improved oxygenation as measured by a change in pao (2)/fio (2) (p/f) ratio of 28.7 mmhg while prone, without significant change in heart rate or respiratory rate. patients on average underwent 5 cycles with a median duration of 3 hours. there were no reported deaths, 7 of the 20 patients (35%) failed non-invasive ventilation and subsequently required intubation and mechanical ventilation. in our cohort of 20 covid-19 patients with moderate acute hypoxic respiratory failure, prone positioning with non-invasive ventilation resulted in improved oxygenation. prone positioning with non-invasive ventilation may be considered as an early therapeutic intervention in covid-19 patients with moderate acute hypoxic respiratory failure. the critical illness characterised by the sars-cov-2 viral infection (coronavirus disease 2019; covid-19) often results in respiratory symptoms leading to acute hypoxic respiratory failure (ahrf) necessitating mechanical ventilation. supplemental oxygen is the initial mainstay of therapy. non-invasive ventilation (niv) has been shown to be a successful alternative to mechanical ventilation in the early stages of the related coronavirus severe acute respiratory syndrome (sars) and in covid-19 without a subsequent need for invasive mechanical ventilation 1, 2 . despite covid-19 being a novel single disease entity, various phenotypic variations based on biological markers of immunity, prothrombotic features, ventilator mechanics and radiological changes have been documented 3 . consequently, the response to specific therapies may vary between covid-19 patients with ahrf. prone positioning has been often adopted to improve gas exchange in mechanically ventilated patients with moderate to severe refractory hypoxia associated with acute respiratory distress syndrome (ards). prone position was not associated with an improved outcome in a cochrane review of ards patients receiving invasive mechanical ventilation 4 . however, subgroup analysis demonstrated a better outcome among those patient groups with severe ards. the proning severe ards (proseva) multicentre randomised-controlled trial has demonstrated improved survival in patients with severe ards who had received early, long sessions of prone positioning when compared to the control group of supine patients 5 . despite most covid-19 patients with ahrf fulfilling the ards clinical definition, there are demonstrable variations in response to therapy between covid-19 lung disease and ards. although the use of prone position in covid-19 ahrf has not been formally evaluated by clinical trials, its use is supported by several international guidelines, including the surviving sepsis campaign and anzics covid-19 guidelines 6,7 . moreover, recently a study demonstrated improved oxygenation during a single episode of prone positioning in awake non-ventilated covid-19 patients 8 , while another has demonstrated its feasibility in a non-critical care environment 9 . a recent review of conscious proning in ards and covid-19 infection which included a handful of studies with small number of patients and concluded short term improvements in the oxygenation 10 . here we build on this literature offering an examination of changes in oxygenation, as measured by pao 2 /fio 2 , across multiple episodes of prone positioning in conscious patients, with moderate to severe hypoxia, undergoing non-invasive ventilation following admission to the intensive care unit for advanced respiratory support. we collected data from all covid-19 reverse transcriptase polymerase chain reaction (rt-pcr)-confirmed (nasal and throat swab specimens) admissions to the general intensive care unit, university hospital southampton nhs foundation trust between 4 th march 2020 and 11 th may 2020. when clinical stability allowed, all patients presenting with ahrf needing additional respiratory support, beyond standard oxygen therapy, were trialled on non-invasive ventilation (either continuous positive airway pressure (cpap) or bilevel positive airway pressure ventilation (bipap)). moreover, depending on their tolerability, patients were encouraged to self-prone. all patients that deteriorated while on niv went on to have endotracheal intubation and mechanical ventilation. ethical approval was obtained as part of the react covid observational study (a longitudinal cohort study to facilitate better understanding and management of sars-cov-2 infection from hospital admission to discharge-across all levels of care): rec reference 17/nw/0632 srb reference number; srb0025. due to the nature of the study, the need for individual informed consent was waived. data collection and processing data was collected from our electronic clinical information (cis) system using a combination of semi-automated data extraction and manual collection. we collected baseline demographics (age, gender, duration of symptoms, critical illness severity scores, presence of other comorbidities and laboratory variables), medical treatments received, ventilatory parameters, and position data. position data are recorded hourly by the icu nursing staff in the cis and from this we derived number of prone cycles, timing and total duration. we defined niv failure as the need for mechanical ventilation. on admission we also collected severity indices such as acute physiology and chronic health evaluation (apache ii), sequential organ failure assessment (sofa) scores and oxygenation status. arterial blood gas (abg) results were collected alongside patient observations (heart rate (hr) and respiratory rate (rr)) from our cis to measure change in parameters before, during and after prone position. we assessed the change in oxygenation by measuring the change in the arterial oxygen partial pressure (pao 2 in mmhg) to fractional inspired oxygen (fio 2 ) ratio (δp/f), change in respiratory rate (δrr) and heart rate (δhr). all statistical analysis and data processing were performed using r (r core team, vienna, austria). data were tested for normality; those found to be normally distributed were presented as mean and standard deviations (sds), while non-normally distributed data are presented as median and iqr. changes in physiological parameters across prone cycles were tested using a paired t-test and are presented and mean and 95% confidence interval. significance testing between groups was carried out using an independent 2-group t-test for normally distributed variables and the mann-whitney u-test for non-normally distributed variables. there were 81 covid-19-confirmed patients admitted to the general intensive care unit between 4 th of march and 11 th of may 2020. the outcomes are up to date as of 26 june 2020. of those, 20 patients (25%) had a combination of both non-invasive ventilation and self-prone positioning. the mean age of these patients was 53.4 ± 8.3, 55% were male and median admission apache ii and sofa severity indices were 11.5 (iqr 5) and 3 (iqr 0) respectively. among those, 7 patients failed niv and were subsequently intubated (niv+imv group). the characteristics of these patients with severity indices are presented in table 1 . raw results for each patient are available as underlying data 11 . there was a total number of 141 prone cycles performed between these patients. although the duration of each cycle was variable between cycles and among individual patients, the median duration for each cycle was 3 hours (iqr 2) and the number of proning cycles per patient was 5 (iqr 6.3). five patients continued with prone positioning beyond 96 hours. most cycles (46%), were between 1 and 3 hours, a summary detailing prone cycles and duration characteristics is shown in table 2 . additionally, figure 1 is a graphical representation of each patient's time on niv, demonstrating time spent in prone and supine positions. it follows each of the 20 patients, tracking their position throughout the duration of their admission, up until discharge from icu or point of intubation. the outcomes are shown in table 3 . overall, there was an increment in p/f ratio of 28.7 mmhg (3.83 kpa) (95% ci 18.7-38.6 mmhg, p<0.01) with no change in the heart rate or respiratory rate. the patients who had a successful niv and prone table 1 . patient demographics for all patients admitted and received non-invasive ventilation and self-prone positioning. all niv and prone patients (n=20) only niv (n=13) age, year* 53.4 ± 8.3 54.6 ± 9.1 51.3 ± 6.8 male sex, n (%) (55%) (42.9%) (61.5%) duration of symptoms (days) † 7 (6) 7 (4.25) 9 (6.5) admission apache ii score † 11.5 (5) 11 (4) 11 (10.5) admission bilirubin (μmol/l) 11.5 (4) 12 (4) 11 (4) wbc (n x 10 9 /l) 9.4 (6.1) 11 (5.9) 7.9 (6.5) lymphocytes (n x 10 9 /l) 0.95 (0. trial (65%) had a greater increment in p/f ratio of 40.8 mmhg (5.44 kpa) (95% ci 28.8-52.7 mmhg, p<0.01), while those who went on to be intubated did not have a significant improvement in p/f ratio (+5.06 mmhg (0.67 kpa), 95% ci -9.5-19.7 mmhg, p=0.48). those patients who avoided imv had a significantly shorter length of hospital stay (11 vs. 28 days, p<0.01) but no other significant differences in outcome or baseline characteristics were observed. most of the improvement was seen within 24 hours and after this time point the incremental beneficial effect is less for both groups (figure 2 ). on average the niv+imv group spent 24% of their intensive care unit time pre-intubation in the prone position compared to only 12% for the niv only group. there were no deaths recorded in either group and all patients who had successful niv and prone positioning without the need for mechanical ventilation were discharged home. among those 7 patients who failed niv (35%), 2 were transferred to the regional extra-corporeal membranous oxygenation (ecmo) centre, both were later discharged home ( table 2 ). there were no reported cases of any adverse events from these proning episodes. this is a single-centre retrospective observational study of the clinical outcomes of covid-19 patients who received a combination of conscious proning and non-invasive ventilation as part of their initial ventilation strategy. conscious proning and non-invasive ventilation was found to be feasible in 20 patients. despite variations in patient tolerability and cycle duration, oxygenation improved during prone position period without adverse changes in respiratory rate or heart rate. this response was most marked in patients that did not require escalation to invasive ventilation (65%). patients that went on to require invasive mechanical ventilation (35%) did not have an improvement in their p/f ratio: modest improvements observed in the first 24 hours (figure 2) were not sustained beyond this initial period. these patients were similar to patients who received only niv with respect to apache ii, sofa scores and degree of hypoxia defined by p/f ratio on admission. the strain that the coronavirus pandemic has placed on national healthcare infrastructure is unprecedented. although there is only limited data available on the effectiveness of non-invasive ventilation (niv) in covid-19, early provision of niv in moderate to severe acute hypoxic respiratory failure is associated with reduced icu mortality and intubation rate 12 . niv is less resource intensive than imv and can be managed outside of a critical care environment. nhs england covid-19 specific guidance suggests that prone position may be of use in niv patients to improve ventilation/perfusion mismatch, work of breathing and oxygenation 13 . whilst the use of prone positioning is well defined and has been extensively evaluated in patients with ards by several randomised controlled trials, the benefits of prone positioning in awake, conscious patients with moderate to severe ahrf or ards has not been fully explored. reports from the covid-19 pandemic from various countries suggests prone positioning in spontaneously ventilating patients may be of value in preventing progression to mechanical ventilation. our findings suggest that for a proportion of covid-19 patients with moderate ahrf (p/f ratio <200 mmhg), non-invasive ventilation in combination with conscious proning can lead to an improvement in oxygenation, less requirement for invasive ventilation and potentially better overall outcomes. all patients with a sustained (>24 hours) positive response to prone positioning avoided intubation, affording them a shorter overall length of hospital stay. however, 35% of patients receiving niv progressed to invasive mechanical ventilation, despite a similar overall number and duration of proning cycles per patient between both groups. although none of these patients died, they required a much longer period of hospitalisation and therefore caution is advised when implementing noninvasive ventilation and prone positioning outside of a critical care environment with adequate resources to manage niv failure. the use of prone positioning in covid-19 pneumonia is supported by our understanding of the pathophysiology of the disease. there is inhomogeneity in the lungs, and ct scans of covid-19 patients typically shows areas of peripheral ground glass changes that later develop into linear consolidations 14 . areas of exudation, macrophage infiltration, fibrosis and mucous plugs are typical findings on autopsy of deceased patients with covid 19 15 . placing patients in the prone position may help to drain secretions from the lung peripheries, improve lung dyshomogeneity, recruitment and ventilation/perfusion mismatch. many international guidelines recommend prone positioning for intubated and mechanically ventilated patients for these reasons, so it seems reasonable to conclude that similar benefits may be gained by prone positioning in non-invasively ventilated patients with similar underlying pathology. there are obvious risks associated with treating patients with ahrf with non-invasive ventilation. the primary risk to the patient is inappropriate delay in intubation and ventilation. covid-19 ahrf frequently meets the criteria for ards and previous studies have suggested that in ards, delaying intubation due to the use of niv is associated with increased mortality 16 . likewise, the sars-cov-2 virus is transmitted by respiratory droplets; non-invasive ventilation has been shown to produce droplets of >10 μm in size that are largely deposited on surfaces within a 1 meter radius 17 . therefore, niv could potentially increase the risk of virus transmission to individuals in close proximity with the patient. this needs to be a consideration when devising guidelines for personal protective equipment and appropriate cohort allocation of infected patients to minimise infection risk. there are some limitations of this study. this is a singlecentre, retrospective cohort study only limited to small number of covid-19 patients admitted to the intensive care unit setting with the option of subsequent escalation of care to mechanical ventilation. most patients were in general young, with a median age of <60 years old and able to self-prone with non-invasive ventilation. these findings may not be transferable to older patient's group or patients with severe acute hypoxic respiratory failure with p/f ratio of <100mmhg. the study was observational, there were no set criteria for niv proning and niv failure with subsequent endotracheal intubation. the clinical judgement and subsequent interventions provided may have been variable between individual senior clinicians and may not be reflective of other centres. additionally, position data are only recorded hourly and as such some granularity of the data may be lost when the cycles were much shorter period of less than an hour. despite these limitations, our results are in line with the other recently published studies of conscious prone positioning in covid-19 pneumonia. several case reports and small (up to 25 patients) observational studies conducted in multiple settings (outside icu, emergency department) with variations in respiratory support (non-invasive ventilation/high-flow nasal oxygen/standard face mask oxygen therapy) and varying severity of hypoxemia has demonstrated beneficial effects of prone positioning in covid-19 pneumonia. all these studies suggest conscious prone position is associated with an increment in oxygenation and recovery without the need for mechanical ventilation in most cases 8-10 . our results demonstrate, specifically that a sustained response across multiple cycles, for a period >24 hours, is associated with successful treatment with niv. taken together, these results indicate that prone positioning in awake, non-intubated patients, in combination with non-invasive ventilation is feasible and may be considered as an early intervention in covid-19 respiratory failure, particularly in the context of a severe pandemic to prevent mechanical ventilation and its subsequent complications. they also suggest that a loss of response to prone position may potentially be a sign of niv failure and warrant early evaluation and consideration for endotracheal intubation. in conclusion we demonstrate that prone positioning in conjunction with niv can improve oxygenation in patients with covid-19. this can be achieved without significant adverse effects and particularly in those with a sustained response, may avoid intubation. when used in a suitably monitored environment, with access to experienced clinicians able to facilitate invasive mechanical ventilation if required, prone positioning alongside niv may be a useful tool in treating covid-19 patients with moderate acute hypoxic respiratory failure. is the study design appropriate and is the work technically sound? yes are all the source data underlying the results available to ensure full reproducibility? yes department of anesthesiology and critical care, duke university, durham, nc, usa in this retrospective observational cohort study, 20 spontaneously ventilating patients admitted to critical care with hypoxic respiratory failure consequent to covid 19 pneumonia, who underwent proning while receiving non-invasive ventilation were identified from the ehr. the primary outcome examined was a change in pao2/fio2 (p/f) ratio while prone as compared with supine, which the authors report as improved while prone. in terms of data quality and study design, since this is a retrospective study, no single protocol for awake proning was used, creating a large amount of variability in duration, cycle length and frequency of intervention. similarly, total length of time spent on niv, and total number of hours /days spent awake proning appears very varied. this reduces the utility of the data significantly. no comparative statistics are presented between groups (correctly). in terms of trajectory of illness, it would be helpful to plot the overall p/f ratio over time for both intubated and non intubated groups, since from the data available it would appear that those patients who were ultimately intubated started with worse oxygenation and benefited least from the intervention. it may also be useful to examine a control group of patients who did not self-prone, but did receive non-invasive ventilation during the study period. the data presented do however, provide reassurance in terms of safety of the intervention in terms of hemodynamic and respiratory stability. i do not agree that the data presented in this study demonstrate the potential for better overall outcomes with awake proning in covid-19. more data is required to demonstrate that the trajectory of illness was altered by proning, which is not available in this study. rather, the observation that patients who avoided intubation overall spent lower percentage of time prone and had a increased response to proning in terms of p/f ratio, suggests that those patients on the trajectory (who are not well described in this study) towards intubation did not have their outcome altered by proning. rightly, in the discussion the authors discuss the risks associated with applying awake proning. in summary burton-papp et al. have shown that p/f ratio may improve in proned patients on noninvasive ventilation with covid-19 respiratory failure. their data also suggests that awake proning on niv in covid-19 positive patients is safe in terms of cardiorespiratory stability in those patients who are able to tolerate the intervention. this intervention may therefore provide some clinical benefit, but it is not possible to determine from this study with limited numbers where no control group was presented. what they have not demonstrated is whether proning on niv alters clinical course, prevents intubation, what protocol is most effective or who might benefit most from this intervention all of which would require prospective study or matched controlled. they further did not describe which features prevented patients from tolerating awake proning on niv which may be useful in understanding the impact of the intervention. are all the source data underlying the results available to ensure full reproducibility? effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome this is a retrospective report on a subgroup of 20 patients with severe covid-19 who were able to self-prone while receiving non-invasive ventilation in the icu, among a grand total of 81 patients admitted to the icu during the study period.the primary outcome reported by the authors is change in pao2/fio2 ratio while in prone position. clinical outcomes, such as mortality and the incidence of intubation, are also reported.the retrospective nature of the report precludes any causal inferences with regards to the efficacy of awake proning. however, the authors do show that intubation can indeed be avoided in some patients with moderate ards due to covid-19, and that awake proning is associated with improvements in pao2/fio2 ratios.the authors assert that improvement in pao2/fio2 ratios predicted avoidance of intubation. their data do not allow us to conclude whether this improvement is solely the response to awake proning, or natural evolution of patients who were already getting better in the first place, and would have avoided intubation whether or not they were subjected to awake proning. one may also wonder if reverse causality was also at play, and if patients who didn't improve their pao2/fio2 ratio were intubated precisely for that reason. intubation is a soft outcome that relies on treating physician judgement, and it is difficult to disentangle cause and effect in this scenario.in summary, the authors have shown that pao2/fio2 ratios may improve in response to awake proning, and they did not identify any obvious safety signals in this cohort of patients that were able to tolerate awake self-proning. although this paper does not demonstrate efficacy of awake proning, it does add to the growing body of knowledge on this subject and allows comparisons with other cohorts which used different strategies in terms of duration of proning, as well as the type of respiratory support. publication of such prelimary data is important, especially while awaiting definitive answers from randomized controlled trials. reviewer expertise: emergency medicine; respiratory support with hfnc, awake proning. key: cord-027805-p0bhju1s authors: wong, an-kwok ian; cheung, patricia c.; happ, mary beth; gay, peter c.; collop, nancy a. title: consequences and solutions for the impact of communication impairment on noninvasive ventilation therapy for acute respiratory failure: a focused review date: 2020-06-15 journal: crit care explor doi: 10.1097/cce.0000000000000121 sha: doc_id: 27805 cord_uid: p0bhju1s objectives: with over 2 million cases of acute respiratory failure in the united states per year, noninvasive ventilation has become a leading treatment modality, often supplanting invasive mechanical ventilation as the initial treatment of choice. most acute respiratory failure patients use a full face (oronasal) mask with noninvasive ventilation, which is known to impair communication, but its popularity and benefit has led many providers to accept the communication impairment. medical staff periodically remove masks to communicate with patients, but patients are often limited to short utterances and risk lung derecruitment upon removal of positive pressure. these problems can lead to noninvasive ventilation failure, which is often linked to worse outcomes than first initiating invasive mechanical ventilation and can lead to increased hospitalization costs. data sources: we searched medline and google scholar for “speech,” “communication,” “impairment,” “failure,” “complications,” “nippv,” “niv,” and “noninvasive ventilation.” study selection: we included articles with patients in acute respiratory failure. we excluded articles for patients using noninvasive ventilation therapy for obstructive sleep apnea. data synthesis: communication impairment has been associated with increasing noninvasive ventilation anxiety (odds ratio, 1.25). of patients using noninvasive ventilation, 48% require early discontinuation, 22% refuse noninvasive ventilation, and 9% are ultimately intubated. improvements to communication have been shown to reduce fear and anxiety in invasive mechanical ventilation patients. analogous communication problems exist with effective solutions in other fields, such as fighter pilot masks, that can be easily implemented to enhance noninvasive ventilation patient care, increase adherence to noninvasive ventilation treatment, and improve patient outcomes. conclusions: communication impairment is an underappreciated cause of noninvasive ventilation complications and failure and requires further characterization. analogous solutions—such as throat microphones and mask-based microphones—that can be easily implemented show potential as cost-effective methods to reduce noninvasive ventilation failure. w ith landmark trials demonstrating the efficacy of noninvasive ventilation (niv) in cardiogenic pulmonary edema and acute exacerbations of chronic obstructive pulmonary disease, niv has changed the standard of care for acute respiratory failure (arf) and reduced the amount of invasive mechanical ventilation (imv) being used (1) (2) (3) (4) . the rate of niv use increased from 16% in 1997 to 37% in 2011 in france (5) and around the world (6) . with 2 million cases of arf per year in the united states and rising, the number of patients receiving niv therapy has continued to increase. in contrast to imv, where an endotracheal tube prevents the direct passage of air past the vocal cords, niv allows air to flow past the vocal cords, permitting phonation. unlike imv, niv interfaces can be more easily removed and replaced. for patients receiving palliative care, intermittent niv mask removal during www.ccejournal.org 2020 • volume 2 • e0121 niv treatment (7) allows more effective communication than imv (8) (9) (10) (11) . classically, many providers of acute care for patients in respiratory failure do precisely this. however, mask removal can result in derecruitment, which is detrimental in arf and may lead to further lung injury. the ideal solution would be a technique that allows maintenance of continuous niv support while substantially reducing the communication impairment (ci) inherent in the use of current full face mask technology. this may result in a dilemma between allowing the patient to communicate or potentially worsening respiratory status with mask removal. ci-where speech is insufficient to meet all communication needs-resulting from the use of a full face mask is a widely known side effect of niv and can lead to impaired patient care (12, 13) . to our knowledge, there has yet to be a thorough review of the literature to better our understanding of the current problems surrounding the ci associated with niv therapy for arf. as critical care has developed into an interdisciplinary field, it is important to recognize numerous perspectives, especially those from physicians, nurses, and speech language pathologists. although this review is directed at critical care, emergency medicine, and internal medicine physicians and providers, it is intended to educate niv treatment providers about the underappreciated consequences of ci and potential strategies for overcoming ci caused by niv. we searched medline and google scholar for "speech, " "communication, " "impairment, " "failure, " "complications, " "nippv, " "niv, " and "noninvasive ventilation. " we included articles with patients in arf and excluded articles for patients using niv therapy for obstructive sleep apnea. some studies from prolonged niv in chronic respiratory failure are used to highlight complications from niv ci. through the course of this review, we will define ci, explore its consequences through imv and niv, and demonstrate methods by which verbal communication can be restored. the american speech-language-hearing association defines severe ci as an acute speech pathology condition "where speech is temporarily or permanently inadequate to meet all of the individual's communication needs, and the inability to speak is not due primarily to a hearing impairment." (14) in the context of this article, we focus on severe ci and will refer to it as such thereafter. ci can be broadly grouped into several etiologies, including: language (comprehension or production), motor (e.g., dysarthria), cognitive (e.g., aphasia), and acquired (e.g., device related, such as intubation) categories (15) . of these, dysarthria has a strong body of work in characterizing ci due to poststroke patients, which can help characterize other acquired ci etiologies. in this review, we use niv and imv studies to examine the effects of ci on niv distress, claustrophobia, fear, and anxietyall of which are factors contributing to niv intolerance and, consequently, niv failure (16) (17) (18) (19) . although treatment failure endpoints may differ between niv and imv, many similarities exist in imv studies that can better inform our understanding of ci consequences (20) . characterizing the degree of ci is fundamental in understanding not only how communication is impaired in patients using niv, but to devise methods to improve it. unlike imv, where patients are completely unable to phonate due to inability to use their larynx, niv permits natural audible speech. however, the niv mask alters speech transmission. speech dysarthria can be similar, in that speech is audibly generated but is altered from baseline. one of the many causes of ci is reduced intelligibility, or "how well a speaker's acoustic signal can be accurately recovered by a listener. " (21) nonverbal factors contribute to comprehension, including message length, predictability, context, listener relationship, and facial cues. intelligibility can be measured in multiple ways. most commonly, orthographic transcription of a speech sample, with transcription accuracy can be used as the metric. additionally, intelligibility metrics should be context independent-it is important that sentence context does not heavily influence word and sentence recognition. we propose the use of speech dysarthria metrics, such as the assessment of intelligibility of dysarthric speech (aids) published by yorkston et al (22) , to evaluate the ci inflicted by full face mask niv. the aids tool is commonly used in stroke induced speech dysarthria, but has also been used in characterizing communication in alternative situations. leder et al (23) used aids to assess vocal ci in tracheostomy patients. rose et al (24) also used aids to evaluate intelligibility of electrolarynx-generated speech in imv patients and found that improved communication was associated with significantly reduced anxiety (p = 0.007) (23). numerous studies describe ci resulting from imv and how it contributes to fear (25, 26) , anxiety (27, 28) , anger (26, 29, 30) , and distress (31, 32). patak et al (33) surveyed 29 critically ill patients postextubation and found that 62% of imv patients were frustrated and distressed at the inability to communicate. these data are corroborated by many other studies, such as khalaila et al (26) and rotondi et al (34) , whose surveys of critically ill patients postextubation found ci was the most commonly remembered (92%, 78%) experience in imv patients. khalaila et al (26) and rotondi et al (34) note that 80-90% of those patients were moderately to extremely bothered by the inability to speak. khalaila et al (26) also demonstrated positive correlations between difficulty with communication and psychologic distress, fear, and anger (p < 0.01). furthermore, the study by menzel (35) study of 48 postextubation patients found that increased ci was correlated with more intense anger resulting from the inability to talk (p < 0.001). these psychologic outcomes can have a clinical impact. chen et al (36) found in 67 intubated patients that those experiencing anxiety and psychologic distress are 50% less likely to wean from imv. schmidt et al (37) and persichini et al (38) both demonstrated that anxiety and dyspnea are highly correlated in groups of 96 and 220 patients, respectively. dyspnea may, in fact, be underreported, as persichini et al (38) also demonstrated that dyspnea can be hard to assess in verbal ci (38) . ci has also been associated with adverse consequences in niv. schmidt et al (20) conducted the parvenir study with 1,063 icu physicians and nurses and 541 patients and relatives from 32 french icus. in patients undergoing niv, there was a significant association between the inability to be understood and high patient anxiety (p < 0.0001), and between inability to be understood and a greater chance of feeling dyspneic (16% increase; p = 0.001). relatives of patients undergoing niv who were experiencing high anxiety also reported feeling that the patient was worried about not being understood (p < 0.0007). furthermore, patients were 25% more likely to be anxious when relatives observed patients being misunderstood (p < 0.001). demoule et al (39) demonstrated that, in 54 belgian and french icus, moderate to severe patient anxiety during niv treatment is associated with 4.9 times more niv intolerance (p < 0.001) and 1.7 times more niv failure (p = 0.027) (40) . increased patient anxiety while on niv is correlated with physicians (p = 0.0002) and nurses (p = 0.0001) being less willing to provide niv (20) . patients themselves also exhibit mask intolerance or refuse niv (41) . as niv requires adherence, nonadherence, or intolerance often leads to conversion to imv (42). carlucci et al (43) found that of 689 patients across 42 french icus, 52 of 108 patients (48%) on niv were discontinued early (i.e., discontinuation of niv when the physician desired to continue it), 22% of which were specifically due to patient refusal. of the 52 patients, 43 patients (77%) with early niv discontinuation eventually required endotracheal intubation. increasing intolerance (16/43 [59%] vs 6/65 [9%]; p < 0.001) was also independently associated with niv failure. antonelli et al (44) observed that, of 108 of 354 acute hypoxemic respiratory failure patients (30%) who failed niv, nine intubations (9%) were specifically attributed to mask intolerance or inadequate patient cooperation. in addition, antonelli et al (44) (64/108 vs 13/246; p < 0.001) and carlucci et al (43) show that niv failure was significantly more associated with icu mortality. conversely, carlucci et al (43) indicated that continued niv use was independently linked to a 625% increased chance of survival (p < 0.004). although survival is confounded by sickness severity, these data suggest the potential impact that niv failure can have on mortality and complications. in particular, in the large observational study to understand the global impact of severe acute respiratory failure (lung-safe) study, which examined 349 acute respiratory distress syndrome (ards) patients on niv, niv failure was two (pao 2 /fio 2 [p/f] ratio < 150) to three (any p/f) times more associated with icu mortality and 1.8 times more associated with hospital mortality than propensity matched patients with successful niv (45) . notably, these findings were independent of ards severity (p/f < 150, ≥ 150). furthermore, demoule et al (46) , in a study of 524 patients in 70 french icus, found that niv failure itself is independently associated with poorer outcomes in comparison to either patients directly intubated without niv or in comparison to patients who succeeded at niv from the outset. consequently, outcomes may be improved if patients who would fail would be intubated first and avert failure. ci increases rates of preventable adverse events in acute care settings (47, 48) . bartlett et al (47) found in 2,355 retrospectively reviewed admissions across 20 quebec hospitals with 217 adverse events-63 preventable-that hospitalized patients with ci were thrice as likely to have a preventable adverse event (odds ratio, 3.00; p = 0.004), and more than twice as likely to have multiple adverse events (46% vs 20%; p = 0.05). an analogous domain is ci secondary to language barriers. divi et al (48) found in 1,083 adverse incident reports across six hospitals that patients with language barriers were over three times as likely to experience moderate harm or worse. as niv refusal has been associated with poor outcomes, addressing patient rejection of niv will be critical for ensuring niv success. some causes of niv tolerance are easily addressable-the niv interface may contribute to patients' tolerance of the masks. nasal interfaces can improve tolerance, but many patients in respiratory distress breathe through their mouths, which can lead to reduced niv efficacy (42, 49) . however, approximately half of patients with hypoxemia, especially with ards, are not helped by face mask ventilation beyond nasal masks (50, 51 as anxiety has been associated with niv failure, treating nivinduced anxiety with sedation can alleviate niv intolerance (40). scala (12) compiled a review of 183 patients across eight studies using niv. a number of small studies have examined the use for sedation specifically in arf patients with poor niv acceptance, acutely decompensated heart failure, and severe asthma (52) (53) (54) (55) (56) (57) . these small studies show improved arterial blood gases and respiratory rate within sedation usage, along with possible improvement in mortality and endotracheal intubation need. as such, it is possible that treating agitation and anxiety could improve clinical outcomes. some studies suggest that active communication during niv improves niv tolerance (7) . in a case series study conducted by ando (58) among 10 patients with chronic respiratory failure from motor neuron disease using niv, improved communication increased improved tolerance. adaptive and alternative communication (aac) methods, such as communication boards and electrolarynxes have been used to ameliorate ci in imv (59) , improve patient satisfaction (60) , and reduce symptoms of fear, anxiety (61) , and distress (32, 59, 62) . most critical care studies currently examine imv patients using communication boards, nurse training, and electronic devices (63) . as there are many similarities between imv and niv ci, improvement of ci in niv may analogously decrease fear, anxiety, and distress, and could possibly reduce niv intolerance while improving quality of care. we therefore propose an investigation into the consequences of using aac methods for enhancing communication in niv patients. analogous communication problems exist with fighter pilots, astronauts, and scuba divers-roles in which full face masks or helmets are used to facilitate breathing via positive pressure ventilation. speech enhancement for all of these applications involve introducing a microphone to capture a speech signal, which may be placed inside the oral cavity (64, 65) , around the throat (66) (67) (68) , or within the mask (69, 70) . these approaches may be useful in solving this problem for niv in modern medicine, and reducing niv intolerance and improving niv quality of care. examples of these implementations are shown in figure 1 and categorized accordingly in table 1 . intraoral solutions, such as the molar mic from sonitus technologies (san mateo, ca) (64, 65) , are currently used in military settings. these have the distinct benefit of use without modification of any current hardware. given its short range, the molar mic is generally paired with a neck-mounted short-range receiver, which then rebroadcasts over another communication method, such as bluetooth or military radio. primary limitations in the hospital setting are the ability to be sterilized between patients and batterylimited duration, along with constant subjection to a corrosive salivary environment. additionally, since phonation actively leverages the mouth and lips, the spoken audio may be altered. throat solutions are also used in military settings, and are often classed as silent speech interfaces since these can measure subvocalized speech. these methods leverage direct measurement of vibration from the larynx, which effectively rejects ambient noise (68) . due to alternate transmission, speech audio may be conducted differently, but still supports high quality audio. since proper skin contact is necessary for effective vibration transmission, patient tolerance of a constrictive throat band is important. additionally, heavier beards are problematic and will limit adequate contact (66, 68) . current mask-based communication options are commonly used in fighter pilots and scuba divers. most of these users chose acoustic microphones directly embedded into the mask. the u.s. military standard mask breathing unit (mbu)/12 flight masks with in-mask microphones are designed for a pressurized mask for use at altitude (a lower pressure environment) while still permitting effective communication (69, 70) . by virtue of their design at a relatively pressurized state, these most closely mimic the niv environment. since these microphones are exposed to the pressurized environment if applied to niv masks, they are also subject to both ambient noise and humidity, in addition to equipment noise generated by the niv machine. initial studies show that some of these solutions have already been designed for use in the medical environment. examples of these implementations are shown in figure 2 and categorized accordingly in table 1 . throat microphones are currently offered for niv by delores speech products (wellesley, ma), with two patents (71, 73, 75) . in a 16-patient case series, ijssennagger et al (76) demonstrated improvement in ci in eight of 15 patients (53%) in awake critically ill patients. two of 15 patients were on niv and both experienced improvement in ci. an analogous solution to the in-mask microphone is the contact microphone, which is currently offered for niv by ataia medical (dallas, tx) (74). characterization has not yet been published. ci significantly affects care and patient management, especially for patients undergoing niv therapy. this impairment is correlated with both physical and psychologic distress, both of which appear to contribute to niv intolerance and may result in endotracheal intubation. failure of initial niv therapy is associated with worse outcomes than direct intubation, highlighting the potential benefit of reducing ci (46) . studies to investigate sedation as a method to alleviate patient anxiety have shown promise. as stated above, a significant amount of this anxiety may be a downstream effect of ci (20) . consequently, alleviating the ci may circumvent the need for chemical sedation. several studies have revealed the impact of ci on the success of niv/imv and highlight the need to further pursue additional novel treatment (20, 26, 34) . this review on niv-related ci indicates that there is a critical need for further studies in this area, as opposed to drawing indirect conclusions from imv studies. analogous domains, such as fighter pilot oxygen masks, provide potential methods for treating this impairment and should be explored, and some methods are already in use. since patients can still talk while using niv, potential exists for research into muffled speech enhancement using mask-based, throat, or intraoral microphones, which can restore efficient and natural communication. future research is needed to measure the degree of niv-related ci and the clinical consequences attributable to or associated with niv. additional research is also needed to study the degree of improvement that communications devices can achieve. finally, explicit studies are required to establish whether remedying niv cis reduces the frequency of poor outcomes in acute care settings. dr. wong was supported by t32-gm095442, a t32 grant at emory university. for information regarding this article, e-mail: aiwong@emory.edu ten important articles on noninvasive ventilation in critically ill patients and insights for the future: a report of expert opinions reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients history and epidemiology of noninvasive ventilation in the acute-care setting ovni study group; reva network (research network in mechanical ventilation): changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries trends in assisted ventilation and outcome for obstructive pulmonary disease exacerbations. a nationwide study striving for habitual wellbeing in noninvasive ventilation: a grounded theory study of chronic obstructive pulmonary disease patients with acute respiratory failure new advances in the use of noninvasive ventilation for acute hypoxaemic respiratory failure noninvasive mechanical ventilation via face mask in patients with acute respiratory failure who refused endotracheal intubation noninvasive ventilation role of non-invasive ventilation in managing life-threatening acute exacerbation of interstitial pneumonia challenges on non-invasive ventilation to treat acute respiratory failure in the elderly positive pressure mechanical ventilation ad hoc committee on communication processes and non-speaking persons (1981) non-speech: a position paper communication culture in acute speech pathology settings: current issues not being able to talk was horrid": a descriptive, correlational study of communication during mechanical ventilation noninvasive ventilation outside the intensive care unit from the patient point of view: a pilot study how to cope with the mask? experiences of mask treatment in patients with acute chronic obstructive pulmonary disease-exacerbations experiences of noninvasive ventilation in adults with hypercapnic respiratory failure: a review of evidence differential perceptions of noninvasive ventilation in intensive care among medical caregivers, patients, and their relatives: a multicenter prospective study-the parvenir study the relationship between listener comprehension and intelligibility scores for speakers with dysarthria assessment of intelligibility of dysarthric speech verbal communication for the ventilator-dependent patient requiring an inflated tracheotomy tube cuff: a prospective, multicenter study on the blom tracheotomy tube with speech inner cannula feasibility of the electrolarynx for enabling communication in the chronically critically ill: the eeccho study the experience of being mechanically ventilated communication difficulties and psychoemotional distress in patients receiving mechanical ventilation patients' memory and psychological distress after icu stay compared with expectations of the relatives anxiety and agitation in mechanically ventilated patients patient's experiences of communication during the respirator treatment period long-term mechanical ventilation in a critical care unit: existing in an uneveryday world integration of palliative care in chronic critical illness management electronic voice-output communication aids for temporarily nonspeaking patients in a medical intensive care unit: a feasibility study communication boards in critical care: patients' views patients' recollections of stressful experiences while receiving prolonged mechanical ventilation in an intensive care unit factors related to the emotional responses of intubated patients to being unable to speak vagal withdrawal and psychological distress during ventilator weaning and the related outcomes dyspnea in mechanically ventilated critically ill patients diagnostic accuracy of respiratory distress observation scales as surrogates of dyspnea self-report in intensive care unit patients anxiety in patients receiving non-invasive ventilation for acute respiratory failure: prevalence, risk factors and prognostic impact. c104. critical care: body and mind in and out of the icu-sedation, delirium, mobilization, and long term functional and cognitive outcomes sedation in non-invasive ventilation: do we know what to do (and why)? does noninvasive ventilation reduce the icu nosocomial infection risk? a prospective clinical survey clinical practice guideline for the use of noninvasive positive pressure ventilation in copd patients with acute respiratory failure group on mechanical ventilation: noninvasive versus conventional mechanical ventilation. an epidemiologic survey predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study lung safe investigators; esicm trials group: noninvasive ventilation of patients with acute respiratory distress syndrome. insights from the lung safe study benefits and risks of success or failure of noninvasive ventilation impact of patient communication problems on the risk of preventable adverse events in acute care settings language proficiency and adverse events in us hospitals: a pilot study effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors a multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome rescue treatment for noninvasive ventilation failure due to interface intolerance with remifentanil analgosedation: a pilot study remifentanilbased sedation to treat noninvasive ventilation failure: a preliminary study the efficacy of dexmedetomidine in patients with noninvasive ventilation: a preliminary study dexmedetomidine facilitates induction of noninvasive positive pressure ventilation for acute respiratory failure in patients with severe asthma target-controlled infusion of propofol for sedation in patients with non-invasive ventilation failure due to low tolerance: a preliminary study dexmedetomidine versus midazolam for the sedation of patients with non-invasive ventilation failure exploring reasons for declining and withdrawing from non-invasive ventilation among motor neurone disease patients: an interpretative phenomenological analysis communicating with mechanically ventilated patients: state of the science effectiveness of communication chart on patient satisfaction among conscious intubated patients: a randomized controlled trial the effect of using communication boards on ease of communication and anxiety in mechanically ventilated conscious patients admitted to intensive care units listening to the voiceless patient: case reports in assisted communication in the intensive care unit communicating with conscious and mechanically ventilated critically ill patients: a systematic review method and apparatus for tooth bone conduction microphone. us patent two-way communication system and method of use. us patent the physiological microphone (pmic): a competitive alternative for speaker assessment in stress detection and speaker verification us patent language identification in noisy environments using throat microphone signals oxygen inhaler mask with sound pickup device. us patent anthropometric sizing, fit-testing and evaluation of the mbu-12/p oral-nasal oxygen mask communication and speech enhancement system -us9344781. us patent throat microphone. us patent communication and speech enhancement system -us9943712 systems and methods for communicating through a hard plastic mask. us patent dolores speech products: speech enhancement for respiratory patients a new speech enhancement device for critically ill patients with communication problems: a prospective feasibility study key: cord-355450-v3eh1rtk authors: boattini, matteo; almeida, andré; christaki, eirini; cruz, lourenço; antão, diogo; moreira, maria inês; bianco, gabriele; iannaccone, marco; tsiolakkis, georgios; khattab, elina; kasapi, diamanto; charrier, lorena; tosatto, valentina; marques, torcato moreira; cavallo, rossana; costa, cristina title: influenza and respiratory syncytial virus infections in the oldest-old continent date: 2020-06-27 journal: eur j clin microbiol infect dis doi: 10.1007/s10096-020-03959-9 sha: doc_id: 355450 cord_uid: v3eh1rtk sars-cov-2 dramatically revealed the sudden impact of respiratory viruses in our lives. influenza and respiratory syncytial virus (rsv) infections are associated with high rates of morbidity, mortality, and an important burden on healthcare systems worldwide, especially in elderly patients. the aim of this study was to identify severity predictors in the oldest-old admitted with influenza and/or rsv infections. this is a multicenter, retrospective study of all oldest-old patients (≥ 85 years old) admitted for laboratory-confirmed influenza and/or rsv infection in three tertiary hospitals in portugal, italy, and cyprus over two consecutive winter seasons. the outcomes included the following: pneumonia on infection presentation, use of non-invasive ventilation (niv), and in-hospital death (ihd). the association with possible predictors, including clinical features and type of virus infection, was assessed using uniand multivariable analyses. a total of 251 oldest-old patients were included in the study. pneumonia was evident in 32.3% (n = 81). niv was implemented in 8.8% (n = 22), and ihd occurred in 13.9% (n = 35). multivariable analyses revealed that chronic obstructive pulmonary disease (copd) or asthma was associated with pneumonia (or 1.86; 95% ci 1.02–3.43; p = 0.045). copd or asthma (or 4.4; 95% ci 1.67–11.6; p = 0.003), rsv (or 3.12; 95% ci 1.09–8.92; p = 0.023), and influenza b infections (or 3.77; 95% ci 1.06–13.5; p = 0.041) were associated with niv use, respectively, while chronic kidney disease was associated with ihd (or 2.50; 95% ci 1.14–5.51; p = 0.023). among the oldest-old, chronic organ failure, such as copd or asthma, and ckd predicted pneumonia and ihd, respectively, beyond the importance of viral virulence itself. these findings could impact on public health policies, such as fostering influenza immunization campaigns, home-based care programs, and end-of-life care. filling knowledge gaps is crucial to set priorities and advise on transition model of care that best fits the oldest-old. introduction sars-cov-2 dramatically revealed the sudden impact and the utmost importance of respiratory viruses in our lives. influenza and respiratory syncytial virus (rsv) infections are associated with high rate of morbidity, mortality, and an important burden on healthcare systems worldwide, especially among elderly patients [1] [2] [3] [4] [5] [6] . oldest-old is a term meant to include people aged 85 years and older that represent a growing population in the old european continent. despite being a non-homogeneous group, they are professionally retired individuals that usually experience multimorbidity and disability and may face a limited life expectancy. recent evidence suggests that there is a high research interest towards addressing their needs and establishing the best standard of care [7, 8] . especially in epidemiological research, oldest-old patients are considered to be a part of the wider age group of the elderly (≥ 65 years old), and there is limited published evidence about predictors of severity of illness and mortality in viral infections, such as caused by influenza and rsv. the aim of this study was to describe the clinical features of an oldest-old population admitted with influenza and/or rsv infections in three southern european hospitals over two consecutive winter seasons and identify predictors of pneumonia, non-invasive ventilation (niv), and in-hospital death (ihd). such knowledge might provide insight to assist healthcare policymakers managing chronic conditions, improving patient satisfaction, and reducing hospital utilization. this is a multicenter, retrospective study of all oldest-old patients (≥ 85 years old) who were either admitted to the hospital for laboratory-confirmed influenza and/or rsv infection or developed it during the course of admission for other causes, from 1 october 2017 to 30 april 2018 and from 1 october 2018 to 30 april 2019 in three tertiary hospitals in portugal, italy and cyprus. the laboratory confirmation was based on a positive xpert flu/rsv pcr (cepheid diagnostics, sunnyvale, ca, usa) and/or allplex respiratory panel (allplex, seegene, republic of korea) on naso/ oropharyngeal swabs obtained from patients with signs or symptoms of viral infection. for patients with more than one positive pcr in a seasonal period, the first episode was considered for study purposes. the infection was characterized as hospital-acquired if symptoms pertaining to viral infection began after 72 h from admission. variables assessed included demographics, smoking status, co-morbidities, virus type, nosocomial acquisition, pulmonary infiltrate on chest x-ray taken when symptoms were observed, neuraminidase inhibitor use, length of stay (from admission to discharge), niv, mechanical ventilation, and ihd. this study was conducted in accordance with the declaration of helsinki. formal ethical approval was obtained by the institutional review board of the coordinating center (central lisbon hospital center, no. 762_2019). informed consent was not deemed required for the purposes of this study. descriptive data are shown as absolute (n) and relative (%) frequencies for categorical data and as mean ± standard deviation (sd) and median and interquartile range (iqr), as appropriate, for continuous variables. on univariate analysis, chi-square test for categorical variables and student's t test or wilcoxon rank-sum test, as appropriate, for continuous variables were carried out to identify factors associated with pneumonia, niv, and ihd. odds ratios (or) and their 95% confidence intervals (95% ci) were also calculated to estimate the strength of those associations. multivariable analysis models were then fitted to investigate the independent effects of type of virus infection and clinical variables that turned out to be significantly associated with the outcomes at univariate analysis, adjusting for possible confounders like age and gender. for all tests, a p value ≤ 0.05 was considered significant. all analyses were performed with stata 14. a total of 1151 patients aged ≥ 18 years old were admitted for influenza a/b and/or rsv infections during the study period in the three centers. oldest-old patients were 251 (21.8%), of which 30 (12%) had hospital-acquired influenza a/b and/or rsv infections. clinical features of oldest-old patients included in the study were reported in table 1 . mean age was 89.4 ± 3.9 (range, 85 to 103) years, 79 (31.5%) were men, and 3.6% was current active smoker. the co-morbidities mainly observed were diabetes (22.7%), copd or asthma (24.7%), chf (47%), and ckd (19.5%). the viral agents identified were influenza a (56.6%), influenza b (15.9%), rsv (25.9%), influenza a + influenza b (1.2%), and influenza a + rsv (0.4%) co-infections. among influenza a infections, h3n2 was the most common (68.5%) followed by h1n1 (13%), 18.5% not having been subtyped. radiological signs of pneumonia were present on the chest x-ray exams of 32.3% (n = 81) following laboratory diagnosis of viral infection; 8.8% (n = 22) were submitted to niv and only one patient (0.4%) was invasively mechanically ventilated. a total of 35 patients (13.9%) did not survive admission. among patients submitted to niv, 72.7% (n = 16) survived admission. antiviral treatment with a neuraminidase inhibitor was started in 60.6% of patients. mean length of stay of patients with community-and hospitalacquired infections was 12 ± 11.1 (median 9, iqr 6-14) and 27.8 ± 28.7 (median 20, iqr 8-30) days, respectively (p < 0.01). overall, ihd was 13.9%, being 14% and 13.3% for community-and hospital-acquired infections, respectively, with no significant difference. results of univariate and multivariable analyses were shown in table 2 . at univariate analysis, copd or asthma was significantly associated with pneumonia (or 1.93; 95% ci 1.06-3.49) and use of niv (or 3.49; 95% ci 1.43-8.51); rsv infection turned out to be another significant factor associated with niv use (or 3.51; 95% ci 1.27-9.68), while ckd was the only clinical feature significantly associated with ihd (or 2.52; 95% ci 1. 15-5.52 ). finally, we considered three logistic regression models, where, for each outcome, age, gender, copd or asthma (for pneumonia and use of niv models), ckd (for ihd model), and type of virus infection were the independent variables. among all patients, multivariable analyses revealed that copd or asthma was significantly associated with radiologically confirmed pneumonia (or 1.86; 95% ci 1.02-3.43; p = 0.045); copd or asthma (or 4.4; 95% ci 1.67-11.6; p = 0.003), influenza b (or 3.77; 95% ci 1.06-13.5; p = 0.041), and rsv infections (or 3.12; 95% ci 1.09-8.92; p = 0.023) were associated with niv use; ckd turned out to be the only predictor significantly associated with ihd (or 2.50; 95% ci 1.14-5.51; p = 0.023). sars-cov-2 pandemic and its unsustainable burden supplanted every hierarchy of interest in medical research but highlighted how viral infections' knowledge is crucial in clinical practice. among the aged population, influenza and rsv infections are important causes of hospital admission during autumn and winter months. the highlights of this study are the following findings: (1) the proportion of oldest-old patients among total hospitalizations was remarkable; (2) radiological pneumonia, use of niv, and ihd were considerable; (3) influenza a h3n2 infection was the most prevalent; influenza b and rsv infection were significantly associated with niv use; (4) copd or asthma was associated with both pneumonia and niv use; (5) ckd was a predictor of ihd. to the best of our knowledge, our line of research is quite novel and barely comparable to previous reports given the higher mean age of patients involved. overall, the number of hospitalizations over the study period was remarkable comparing to recent reports [9] , showing that over two years one out of five admissions with influenza and/or rsv infections involved oldest-old. moreover, in our study, hospital-acquired influenza and/or rsv infections were not identified as predictors of pneumonia, use of niv, and ihd for patients aged 65 years and older, moving away from evidence available so far [9, 10] . pneumonia on infection presentation was very frequent, in line with more recent reports [9] [10] [11] [12] [13] [14] [15] [16] [17] , revealing how an important proportion of patients showed a direct viral injury in lung parenchyma and/or bacterial co-infection. however, despite being a life-threatening condition, it was neither predictive of niv use nor of ihd. the use of niv was considerable when comparing with available evidence in a cohort of younger patients [9] . this finding might be related to both the type of respiratory failure on infection presentation and a remarkable rate of diagnosed or likely under-diagnosed chronic obstructive lung disease [18] . similarly, in our population, niv seemed to be effective since data about its use in respiratory viral infections are limited and uncertain, especially in the presence of pneumonia, hypoxemic respiratory failure, and sofa ≥ 5, and no copd and/or cardiogenic pulmonary edema [19] . on the other hand, invasive mechanical ventilation rate was performed only once, probably according to ethical and prognostic considerations, such as coexistence of frailty and patient end-of-life preferences. the discrepancy between the use of these two modalities of ventilation could be presumably due to accept niv as a ceiling of therapeutic effort. ihd was also remarkable. studies suggest mortality rate ranging from 4.1 to 9.8% [9-13, 15-17, 20] and up to 24% in icu patients [14] . nevertheless, these studies were performed on elderly people with lower median age while our data should be comprehensible for an oldest-old cohort of patients. infection due to influenza a h3n2 was the most prevalent, rsv infection was also very frequent, confirming that epidemic viral subtypes and their affinity for the lower respiratory tract differ according to the study period [21] . severity of illness and ihd due to rsv infection were similar as compared to influenza viruses, but according to literature, these can vary from season to season [9, 22] . therefore, the role of virus type in morbidity and mortality remains controversial. our findings might suggest that rsv and influenza b probably caused infections with a clinical scenario that benefited from application of niv [23] more than influenza a. copd or asthma was independently associated with pneumonia on infection presentation and niv use, suggesting the importance of the aged lung [18] and the attempt to overcome respiratory failure through this widespread and generally welltolerated ventilation technique. ckd was the only significant predictor ihd, and it could represent an interesting clinical tool. indeed, previous studies included acute kidney injury and renal disease as predictors of mortality and disease severity, respectively [9, 12] , but no prognostic factors have been identified for the oldest-old. our study had limitations. a 72-h period might have led to misclassify the community-vs. hospital-acquisition of the viral infection since evidence suggests longer incubation periods [24] . several factors contributing to disease severity and mortality, including nursing home residency, frailty scores, bedridden status, immunization status, malnutrition, sarcopenia, presence of mixed viral and bacterial pneumonia, respiratory failure, occurrence of systemic complications, and physicians' attitude towards more intensive care, were not assessed. moreover, our study lacks an assessment of postdischarge disability and follow-up. in conclusion, this study provided one of the largest assessments available so far of clinical features and factors contributing to severity of illness in the oldest-old admitted with influenza and/or rsv infections in southern europe. chronic organ failure, such as copd or asthma and ckd, predicted pneumonia and ihd, respectively, surpassing the importance of viral virulence. these findings could impact on public health policies, such as fostering influenza immunization campaigns, home-based care programs [25] , and endof-life care. filling knowledge gaps is crucial to set priorities and advise on transition model of care that best fits the oldestold. european all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza b be reconsidered? estimates of global seasonal influenzaassociated respiratory mortality: a modelling study respiratory syncytial virus infection in adults respiratory syncytial virus infection in older adults: an under-recognized problem respiratory syncytial virus infection in elderly adults caring for critically ill oldest old patients: a clinical review a bibliometric study of research pertaining to the oldest-old (age eighty-five and older) analysis of acute respiratory infections due to influenza virus a, b and rsv during an influenza epidemic predictors of mortality of influenza virus infections in a swiss hospital during four influenza seasons: role of quick sequential organ failure assessment postpandemic influenza a/h1n1pdm09 is associated with more severe outcomes than a/h3n2 and other respiratory viruses in adult hospitalisations clinical characteristics of influenzaassociated pneumonia of adults: clinical features and factors contributing to severity and mortality clinical and radiographic comparison of influenza virusassociated pneumonia among three viral subtypes intensive care admissions and associated severity of influenza b versus a during influenza b vaccinemismatched seasons comparative outcomes of adults hospitalized with seasonal influenza a or b virus infection: application of the 7-category ordinal scale outcomes and prognostic features of patients with influenza requiring hospitalization and receiving early antiviral therapy: a prospective multicenter cohort study high morbidity and mortality in adults hospitalized for respiratory syncytial virus infections the aging lung critical care management of adults with community-acquired severe respiratory viral infection rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults seasonal influenza activity during the sars-cov-2 outbreak in japan risk of mortality associated with respiratory syncytial virus and influenza infection in adults official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure incubation periods of acute respiratory viral infections: a systematic review avoiding hospital admission through provision of hospital care at home: a systematic review and meta-analysis of individual patient data publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgments the authors thank dr. miguel toscano rico for supporting the project and sharing his knowledge and expertise. key: cord-352059-1bjskqyg authors: gupta, nivedita; potdar, varsha; praharaj, ira; giri, sidhartha; sapkal, gajanan; yadav, pragya; choudhary, manohar lal; dar, lalit; sugunan, a.p.; kaur, harmanmeet; munivenkatappa, ashok; shastri, jayanthi; kaveri, krishnasamy; dutta, shanta; malhotra, bharti; jain, amita; nagamani, kammilli; shantala, g.b.; raut, sharmila; vegad, m.m.; sharma, ajanta; choudhary, aashish; brijwal, megha; balakrishnan, anukumar; manjunatha, jayaswamy; pathak, manish; srinivasan, sivasubramanian; banu, hasina; sharma, himanshu; jain, parul; sunita, pakalpati; ambica, r.; fageria, babita; patel, disha; rajbongshi, gitika; vijay, neetu; narayan, jitendra; aggarwal, neeraj; nagar, anu; gangakhedkar, raman r.; abraham, priya title: laboratory preparedness for sars-cov-2 testing in india: harnessing a network of virus research & diagnostic laboratories date: 2020-04-28 journal: indian j med res doi: 10.4103/ijmr.ijmr_594_20 sha: doc_id: 352059 cord_uid: 1bjskqyg background & objectives: an outbreak of respiratory illness of unknown aetiology was reported from hubei province of wuhan, people's republic of china, in december 2019. the outbreak was attributed to a novel coronavirus (cov), named as severe acute respiratory syndrome (sars)-cov-2 and the disease as covid-19. within one month, cases were reported from 25 countries. in view of the novel viral strain with reported high morbidity, establishing early countrywide diagnosis to detect imported cases became critical. here we describe the role of a countrywide network of vrdls in early diagnosis of covid-19. methods: the indian council of medical research (icmr)-national institute of virology (niv), pune, established screening as well as confirmatory assays for sars-cov-2. a total of 13 vrdls were provided with the e gene screening real-time reverse transcription-polymerase chain reaction (rrt-pcr) assay. vrdls were selected on the basis of their presence near an international airport/seaport and their past performance. the case definition for testing included all individuals with travel history to wuhan and symptomatic individuals with travel history to other parts of china. this was later expanded to include symptomatic individuals returning from singapore, japan, hong kong, thailand and south korea. results: within a week of standardization of the test at niv, all vrdls could initiate testing for sars-cov-2. till february 29, 2020, a total of 2,913 samples were tested. this included both 654 individuals quarantined in the two camps and others fitting within the case definition. the quarantined individuals were tested twice at days 0 and 14. all tested negative on both occasions. only three individuals belonging to different districts in kerala were found to be positive. interpretation & conclusions: sudden emergence of sars-cov-2 and its potential to cause a pandemic posed an unsurmountable challenge to the public health system of india. however, concerted efforts of various arms of the government of india resulted in a well-coordinated action at each level. india has successfully demonstrated its ability to establish quick diagnosis of sars-cov-2 at niv, pune, and the testing vrdls. coronaviruses (covs) are a group of enveloped viruses with non-segmented positive sense rna belonging to the family coronaviridae and the order nidovirales. on the basis of phylogenetic clustering, they are classified into three different genera: alpha, beta and gamma. while alpha and beta types have mammalian hosts, gamma type covs have avian hosts. alpha-and beta-covs are widely distributed in humans and other mammals including bats and cause mild respiratory infections 1 . however, two beta coronaviruses causing severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers) were responsible for widespread epidemics with a case fatality rate of 10 per cent for sars 2 and 35 per cent for mers covs 3 . the world health organization (who) reported cases of pneumonia of unknown aetiology in wuhan city, hubei province of people's republic of china, on december 31, 2019 4 . on january 7, 2020, chinese authorities officially announced that the illness was caused by a novel cov. the who has named the disease as covid-19 5 , and based on its similarity to sars-cov (2002 -2003 , the cov study group of the international committee on taxonomy of viruses (ictv) has named the virus as sars-cov-2 6 . a viral genome sequence was released in public domain on january 10, 2020 (wuhan-hu-1, genbank accession number mn908947 7 ), followed by four other genomes deposited on january 12, in the viral sequence database curated by the global initiative on sharing all influenza data (gisaid). the novel beta coronavirus shows 89 and 82 per cent nucleotide identity to bat cov, covzxc21, and sars-cov (2002) (2003) , respectively 8 . since its emergence, the disease has rapidly spread to neighbouring provinces of china as well 53 other countries through international travel 9 . infection is spread through droplets or prolonged contact with infected patients 10 . virus isolate is the gold standard for establishment and standardization of assay performance. since sars-cov-2 virus isolate was not available earlier, based on the genetic sequence of sars-cov-2 and closely related sars-cov (2002 -2003 , the who shared protocols (e, n, rdrp and s genes) for screening and confirmation of probable cases 11 . here, we briefly describe the efforts made by the government of india (goi) towards reducing the risk of emergence of covid-19 in india. we also provide a detailed description of the role of a well-established countrywide network of virus research and diagnostic laboratories (vrdls) which could be rapidly enabled to scale up testing capacity for sars-cov-2 in different parts of india. identifying suspected cases and contacts: screening of passengers returning from china was initiated on january 18, 2020, at seven different airports throughout india and subsequently extended to 21 different airports. universal thermal screening of all passengers has been made mandatory for all flights from singapore, japan and south korea besides china and hong kong. screening of passengers was also initiated at 12 major and their past performance. the case definition for testing included all individuals with travel history to wuhan and symptomatic individuals with travel history to other parts of china. this was later expanded to include symptomatic individuals returning from singapore, japan, hong kong, thailand and south korea. seaports and all minor ports in the country to identify crew and passengers travelling back from china and to undertake required measures for isolation if found symptomatic. in addition, the goi also initiated screening at all integrated checkposts from nepal in the states of uttar pradesh (up), uttarakhand, west bengal, sikkim and bihar. individuals evacuated from china and japan: the goi evacuated indian citizens residing in wuhan and neighbouring cities in the hubei province of china. two subsequent evacuations were undertaken on january 31 and february 1, 2020. a total of 654 individuals (including 645 indians residing in wuhan, 7 maldivian nationals and 2 members from the crew) were brought back in dedicated aircrafts. similar operations were conducted to evacuate 112 individuals from wuhan (including 76 indians and 36 people from madagascar, maldives, myanmar, south africa and the usa) and 124 from diamond princess ship, japan (including 119 indians and 5 people from nepal, peru, south africa and sri lanka) on february 27, 2020. all the individuals were quarantined in two separate facilities close to new delhi, india. the facilities were managed by the army and indo-tibetan border police. the following inclusion criteria were followed for considering samples for covid-19 testing: (i) symptomatic (fever, sore throat, running nose, dyspnoea, etc.)/asymptomatic individuals returned from wuhan, china, after 15 january 2020; (ii) only symptomatic individuals returned from rest of china, which was subsequently expanded to include hong kong, japan, south korea, singapore, iran and italy, were also included; (iii) close contacts of confirmed positive cases of covid-19 infection; and (iv) all individuals evacuated from wuhan, china, and diamond princess ship, japan, in four different operations. inclusion criteria for laboratory testing are evolving in india, given the increased number of cases of covid-19 being reported from different countries 10 . sample collection and transport: for all suspected cases with symptoms and/or travel history, nasopharyngeal and/or oropharyngeal swabs were collected in viral transport medium. samples were sent to testing laboratories at 4ºc with ice packs within 24 h of collection. special provision was made with the national and international courier agencies to facilitate uninterrupted sample transport from field to laboratories and for quality control purpose. for a subset of the individuals, blood samples were collected in serum separator and edta (ethylenediaminetetraacetic acid) tubes for serum and plasma, respectively. stool and urine samples were also collected from the laboratory-confirmed positive cases. since sars-cov-2 is a new virus and diagnostic tests are evolving rapidly, it was considered critical to have various types of clinical samples for standardization and validation of new tests. however, owing to very low positivity rates of sars-cov-2 infection, it was subsequently decided to collect blood samples from only laboratory-confirmed positive cases and review the strategy later. diagnostic assays for sars-cov-2: following release of the first sequence results of the sars-cov-2 virus by china 7 , candidate diagnostic real-time reverse transcription-polymerase chain reaction (rrt-pcr) assays were designed and made available in the public domain for researchers 12 . the first-line screening assay targeted the sars-cov-2-specific e gene. confirmatory assays targeted the 'rdrp gene', 'n gene' and 'orf-1b'. positive control materials for these assays were obtained from charité, berlin, via evag 13 . known copy numbers of in vitro transcribed rna standard were used as the positive controls for the rrt-pcr assays. detection of rnase p gene was used as an internal positive control to monitor sample quality, rna extraction and detection of pcr inhibitors. the indian council of medical research (icmr)-national institute of virology (niv), pune, which is the apex laboratory for viral diagnosis and research in india, optimized the conventional and real-time pcr assays targeting different genomic regions of sars-cov-2 and initiated testing of suspected cases. the department of health research (dhr)/icmr initiated establishment of a network of public health laboratories to enhance capacity for diagnosis and detection of viruses of public health importance in the indian setting in 2013. over the years, this network has been expanded, and currently, a total of 106 vrdls have been established throughout the country (fig. 1) . detection of viral pathogens using serological methods and molecular diagnostic tools is the major focus of the vrdls. in addition, a subset of these also have capabilities to perform cell culture and virus cultivation. all established vrdls are equipped to perform testing for viral aetiologies at least under biosafety level 2 (bsl-2) conditions. further, 10 vrdls are in various stages of operationalization of a bsl-3 facility for detection of high-risk pathogens 14 . the niv, pune, functions as the resource centre for the vrdl network and is responsible for providing technical training for performing molecular and serological assays for virological diagnosis. it also performs the important task of standardizing assay procedures for the network as well as quality control and quality assurance activities. in the last week of january 2020, the dhr/icmr provided directives on sample collection and transport to all the 106 vrdls currently under the network. video conferences were held with vrdls where the directives were explained and issues regarding sample collection and shipment were discussed. from each state or union territory, one vrdl was designated as the nodal centre for coordination of collection and shipment of samples to testing laboratories. on collection of sample(s) from any suspected case, the hospital or nearest vrdl was expected to contact the designated nodal centre for that state. the role of the nodal centre was to enable timely the apex laboratory at niv, pune. vrdls were chosen based on their location in cities with international airports receiving travellers from china, the capability of the vrdls to perform real-time pcr assays and their involvement in the ongoing testing for influenza viruses within the network. a total of 13 vrdls across 11 states were selected for sars-cov-2 testing. after february 29, 2020, based on the upsurge in the number of suspect cases, primarily due to outbreaks reported from countries other than china (iran, south korea, italy and japan), the number of testing laboratories was scaled up to a total of 31 laboratories. it is eventually proposed to involve all 106 vrdls in covid-19 testing or sample collection and transportation. the distribution of covid-19 testing (operational and new) laboratories in india is depicted in figure 3 . before initiating testing of clinical specimens from suspected cases of sars-cov-2, each vrdl shared results from the rrt-pcr runs performed with positive and negative controls with the apex laboratory (niv, pune). after satisfactory performance of the laboratories, independent testing was initiated in the designated catchment areas. frontline screening rrt-pcr test targeting sars-cov-2-specific e gene was performed. initial support was also provided to ncdc, new delhi, for initiation of sars-cov-2 testing. and proper transport of the collected samples from the vrdls to the designated testing laboratory. the national centre for disease control (ncdc), ministry of health and family welfare, integrated disease surveillance programme (idsp) and state public health departments were informed regarding the nodal centres and assigned testing laboratories for the respective states. the vrdls complemented the idsp in an effective way. flow diagram depicting the complete process from sample collection in the field, transportation, testing and reporting of results is shown in figure 2 . all the laboratories were supplied with the primers, probes, pcr reagents, positive and negative controls and standard operating procedure (sop) for the real-time rt-pcr (rrt-pcr) assay by niv, pune. a stringent inventory control was maintained at niv and vrdls based on the upsurge in number of cases and evolution of the disease. expansion of testing capabilities and selection of testing laboratories for sars-cov-2: following the increase in the load of screening samples from suspected cases with symptoms and travel history to china or asymptomatic persons with travel history to wuhan after january 15, 2020, it was decided that strategically located vrdls needed to start testing for sars-cov-2 in addition to thereafter, ncdc, delhi, initiated independent testing; however, results were shared with icmr on a daily basis. figure 4 depicts the organization of laboratories for sars-cov-2 diagnosis and their respective roles. quality control for sars-cov-2 testing at vrdls: niv, pune, coordinated the quality control activities for sars-cov-2 testing vrdls. the laboratories shared first 10 negatives, all positive and equivocal samples for sars-cov-2 to niv, pune, for confirmation. samples tested positive at vrdls were subjected to confirmatory tests at niv, pune. the final result for any sars-cov-2-positive samples was released only after confirmation at the apex laboratory. ten negative samples from vrdls were also randomly picked up and subjected to next-generation sequencing (ngs). college, ahmedabad (n=12). repeat testing of suspect cases was also done at vrdls (numbers excluded). eleven vrdls initiated independent testing between february 1 and 3, 2020. two vrdls at ahmedabad and guwahati were added from february 8, 2020 as per need. time taken by all vrdls from receipt of reagents to initiation of independent testing ranged between 24-36 h. the turnaround time for testing was 12-24 h depending on the number of samples tested. results were communicated to the state idsp and/or the referring contact point. initial numbers referred to the testing network were high due to increased number of travellers returning from affected countries. however, this number declined after travel restrictions were imposed. as the vrdls established testing for sars-cov-2, the number of samples referred to niv dropped. figure 5 depicts the incremental decline in number of samples referred to niv after testing at vrdls was established. testing of evacuees from quarantine camps: on january 31 and february 1, 2020, the goi evacuated 654 individuals from wuhan. all these evacuees were quarantined for 14 days at two centres (armed forces medical services camp at manesar and indo-tibetan border police chhawla camp) 15 . on the day of arrival (day 0), nasopharyngeal and/or oropharyngeal samples were collected from all these individuals. the samples were tested for sars-cov-2 at icmr-niv, pune, and dhr/icmr regional vrdl at aiims, new delhi. all samples were tested negative. between days 0 and 14, symptomatic quarantined individuals were subjected to repeat testing of sars-cov-2. at the end of two weeks, repeat samples were collected from all the 654 individuals and retested at the two sites. all samples were again tested negative. subsequently, samples were tested from the second set of evacuees from wuhan (112) and diamond princess ship, japan (124), on day 0 at the same sites. a total of 1,544 samples were tested, and all were negative. evacuees from china and japan quarantined at army and border police camps: of the 654 evacuees from the second batch of quarantined individuals at these two camps arrived on february 27, 2020 which included a total of 236 evacuees from china and from the cruise ship diamond princess off the coast of japan. the second batch of quarantined individuals included a total of 41 females and 195 males. the mean age was 29.4 yr (median: 29 yr; range: one year nine months-56 yr); 76.3 per cent (180/236) were between 25 and 50 yr of age. all these were also tested negative. individuals tested for sars-cov-2 other than evacuees who were quarantined: of the 1,369 individuals other than evacuees who were tested, all demographic details were available for a total of 1,263 (843 male, 420 female) individuals. the mean age of the individuals who underwent testing was 25.9 yr (median: 27 yr; range: eight months-76 yr). a little more than half of these individuals were in the 25-50 yr age group (54.2%). samples from three suspected cases with symptoms of acute respiratory illness were tested positive for sars-cov-2 at niv, pune. the first positive case was confirmed on january 30, 2020, followed by two other cases on february 2 and 3, 2020. all the three positive cases had travel history to wuhan, china, and belonged to the state of kerala. a total of 67 samples from 64 individuals with contact history with the three confirmed cases who developed respiratory symptoms were also tested for sars-cov-2. all the samples from the 64 contacts were negative for sars-cov-2. of the total 1263 individuals, 19 per cent (n=240) did not report any specific symptoms for inclusion for covid-19 testing. among those reported as symptomatic, complete details of clinical history were accessed for 292 individuals. the presence of cough was the most common symptom reported in 49.7 per cent (n=145). sore throat was reported by 21.2 per cent (n=62), whereas 34.6 per cent of the individuals (n=101) were febrile at the time of presentation; 17.1 per cent (n=50) of all symptomatic individuals presented with nasal discharge and rhinitis. diarrhoea was a presenting symptom for only 1 a total of 126 samples which tested negative by the e gene rrt-pcr screening assay at the 13 testing vrdls were shared with niv, pune, till february 29, 2020, and these were all confirmed negative . the concordance for the negative samples was, therefore, 100 per cent. the vrdls also shared 13 samples which were borderline positives and showed amplification at late ct values (range: 33-37 cycles) for confirmation. these included seven follow up samples collected from the three laboratory-confirmed positive cases which were also tested positive for the e gene at the testing vrdl. testing results were concordant for five of seven follow up samples. the remaining six samples which showed borderline positivity with the screening qpcr at the testing vrdls were found to be negative with the confirmatory qpcr assays performed at niv, pune. inventory control: inventory control posed several challenges. primers and probes were ordered by the niv, pune, once the laboratory protocols were shared by the who on january 15, 2020. since nature of spread of the disease was unknown, testing reagents were stockpiled for only 5000 tests initially. niv initiated testing from january 21, 2020. however, in view of upsurge in global cases and deaths, the testing capacity was upscaled to another 13 laboratories and inventory at niv was scaled up to 25,000 tests by february 1, 2020. following further upsurge in global cases and deaths by february 25, 2020, the inventory was upscaled to 70,000 tests. daily situational analysis of inventory at the apex and testing laboratories was undertaken to ensure optimum supplies and avoid exhaustion of reagents at the apex and testing laboratories. global epidemics due to emerging/re-emerging infectious diseases have become common over the past two decades, with the major reason being increased trade and travel, leading to movement of people across borders. a recent example is the epidemic of sars-cov-2 in hubei province of china which has spread to more than 70 countries within a two-month time. during the initial period, virus sequences were unknown, there were no known sources for acquiring positive controls and the virus isolates were not available. in view of this, the challenge to develop diagnostics for a new disease with a pandemic potential initially seemed unsurmountable. however, once the virus sequences were made available in public domain and source of positive controls and probes could be identified, india immediately established a network of testing laboratories for the new sars-cov-2 virus very swiftly. starting with availability of validated diagnosis at the icmr-niv, pune, testing capacity was further upscaled to another 13 dhr/icmr vrdls. the apex laboratory standardized the testing protocols within one week, and the vrdls initiated testing within two weeks of release of laboratory protocols by the who. in addition, 35 laboratories fully equipped in terms of availability of adequate infrastructure and trained staff for sars-cov-2 testing were kept on a standby. an impressive model wherein the vrdls have closely worked with the field surveillance programme of goi (idsp) has been operationalized during this public health crisis. however, this model worked well only in some states, but there were gaps in other states. kerala, karnataka, telangana, rajasthan and uttar pradesh clearly leveraged the capacity of existing vrdls. the sample transport mechanisms from idsp to vrdls at these places were also good. the number of tests conducted by vrdls in these states depicted the effective screening of suspect cases implemented at nearby airports, idsp and state health programmes. however, in cities such as kolkata, chennai and mumbai, despite the presence of a testing facility, the number of suspect cases referred was low. liasoning between vrdls and idsp needs to be further strengthened in such areas. quality control programme implemented by niv, pune, for the vrdls revealed 100 per cent concordance between the testing at vrdls and niv for negative samples. for borderline positive samples (ct values between 33 and 35 cycles), concordance was low. this emphasized the need to continue reconfirmation of all positive samples at niv, pune. this has also indicated that e gene screening assay may not be sufficient to declare positivity. further confirmatory tests as currently done by niv, pune, are required for confirming true positivity. to enhance the robustness of testing, it is essential to equip the sars-cov-2 testing vrdls with additional confirmatory assays. inventory control posed challenges at every step. it was imperative to maintain optimum stocks of reagents, but simultaneously, it was important not to overestimate and waste the limited resources. thoughtful optimization of inventory was undertaken. planning of availability of tests at a given point was done in such a way that the excess tests could be used for routine surveillance in case the situation of covid-19 does not worsen in india. the threat of a potential pandemic due to sars-cov-2 has brought out the strength of the judiciously established network of vrdls in india and also the capability of this network to rapidly adapt in times of any public health emergency, with appropriate quality checks. this already operational platform was able to switch gears to provide countrywide diagnosis for sars-cov-2 within a month after discovery of this novel virus. vrdls offer a robust platform for early detection of emerging/re-emerging viral infections in all parts of india, facilitating early containment and prevention of larger epidemics. fields virology, 6 th ed severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection middle east respiratory syndrome coronavirus: another zoonotic betacoronavirus causing sars-like disease naming the coronavirus disease (covid-19) and the virus that causes it severe acute respiratory syndrome-related coronavirus: the species and its viruses -a statement of the coronavirus study group novel 2019 coronavirus genome. virological genomic characterization of the 2019 novel humanpathogenic coronavirus isolated from a patient with atypical pneumonia after visiting wuhan coronavirus disease 2019 (covid-19) situation report -40. who; 2020 a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster world health organization. laboratory testing for 2019 novel coronavirus (2019-ncov) in suspected human cases: interim guidance. geneva: who detection of 2019 novel coronavirus (2019-ncov) by real-time rt-pcr european virus archive -global establishment of a network of laboratories for managing epidemics and natural calamities (vrdl) for correspondence: dr priya abraham, director, icmr-national institute of virology key: cord-344641-rog2h4g7 authors: franco, cosimo; facciolongo, nicola; tonelli, roberto; dongilli, roberto; vianello, andrea; pisani, lara; scala, raffaele; malerba, mario; carlucci, annalisa; negri, emanuele alberto; spoladore, greta; arcaro, giovanna; tillio, paolo amedeo; lastoria, cinzia; schifino, gioachino; tabbi’, luca; guidelli, luca; guaraldi, giovanni; ranieri, v. marco; clini, enrico; nava, stefano title: feasibility and clinical impact of out-of-icu non-invasive respiratory support in patients with covid-19 related pneumonia date: 2020-08-03 journal: eur respir j doi: 10.1183/13993003.02130-2020 sha: doc_id: 344641 cord_uid: rog2h4g7 introduction: the coronavirus 2(sars-cov-2) outbreak spread rapidly in italy and the lack of intensive care unit(icu) beds soon became evident, forcing the application of noninvasive respiratory support(nrs) outside the icu, raising concerns over staff contamination. we aimed to analyse the safety of the hospital staff, the feasibility, and outcomes of nrs applied to patients outside the icu. methods: in this observational study, data from 670 consecutive patients with confirmed covid-19 referred to the pulmonology units in nine hospitals between march 1st and may 10th,2020 were analysed. data were collected including medication, mode and usage of the nrs (i.e. high-flow nasal cannula (hfnc), continuous positive airway pressure (cpap), noninvasive ventilation(niv)), length of stay in hospital, endotracheal intubation(eti) and deaths. results: forty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalisation. data are reported for all patients (69.3% male), whose mean age was 68 (sd 13) years. the pao(2)/fio(2) ratio at baseline was 152±79, and the majority of patients (49.3%) were treated with cpap. the overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total eti rate was 27% with 29%, 25% and 28%, for hfnc, cpap, and niv, respectively, and the relative probability to die was not related to the nrs used after adjustment for confounders. eti and length of stay were not different among the groups. mortality rate increased with age and comorbidity class progression. conclusions: the application of nrs outside the icu is feasible and associated with favourable outcomes. nonetheless, it was associated with a risk of staff contamination. on february 20 th 2020, coronavirus disease 19 severely hit the northern part of italy. it was reported that, in lombardy, the most populated region of the country, more than 1500 patients required intensive care unit (icu) admission over only 4 weeks, largely exceeding the actual capacity (1) . in the same period, the number of hospital admissions was 7285 (2) . approximately 35% of these patients experienced acute respiratory failure (arf) requiring any form of respiratory support. a mathematical model of the occupation of intensive care resources in italy predicted saturation of the theoretically available beds in the national territory by mid-april 2020 (3) . under these circumstances, despite extraordinary efforts aimed at increasing the availability of icu resources, the italian societies of respiratory medicine proposed a protocol to provide ventilatory support outside the icu in dedicated respiratory covid units, reinforced by a higher number of nurses and noninvasive monitoring (4) . this recommendation was somehow in contrast to most of the available guidelines that contraindicated using noninvasive respiratory support (nrs) in these patients due to the major concerns over using bio-aerosol producing techniques, because of possible contamination of the hospital staff (5) . this "emergency" situation gave us the unique opportunity to challenge the hypothesis that nrs should not be used outside the icu during pandemics. we have therefore analyzed the feasibility and safety, in terms of staff contamination, of nrs applied to severely ill patients outside the icu. patients' characteristics and clinical outcomes were also analyzed. the study was conducted in four out of five hospitals in the area vasta emilia network and in five hospitals in the neighbouring regions, serving a population of approximately 8 million people. institutional review boards reviewed the protocol and authorized prospective data collection. informed consent was waived. a confirmed case of covid-19 was defined as a patient with a positive result on high throughput sequencing or real-time reverse transcriptase-polymerase chain reaction assay of nasal and pharyngeal swab specimens. data were collected from registries of the respiratory disease units coordinators at the nine hospitals identifying all of the patients receiving nrs outside the icu. excluding standard oxygen administration, patients were treated with three different types of nrs, namely high-flow nasal cannula (hfnc), continuous positive airway pressure (cpap), or noninvasive ventilation (niv), which also represented the three different groups in the analysis. the triage of patients was performed according to the italian respiratory societies joint guidelines based on severity. in particular, the following categories were proposed: a) green (sao 2 >94%, respiratory rate (rr)<20 breaths/min); b) yellow (sao 2 <94%, rr>20 but responds to 10-15 l/min oxygen); c) orange (sao 2 <94%, rr>20 but poor response to 10-15 l/min oxygen and requiring cpap/niv with very high fio 2 ); d) red (sao 2 <94%, rr>20 but poor response to 10-15 l/min oxygen, cpap/niv with very high fio 2 or presenting respiratory distress with pao 2 /fio 2 <200 and requiring eti and intensive care). patients belonging to these latter two categories were therefore considered eligible for nrs in dedicated respiratory covid areas (see below) set up for the isolation of confirmed cases and arf treatment. these patients were not "usually" treated outside the icu but, given the "emergency" situation, the lack of icu beds and only once multiorgan disfunction was excluded, they still resulted eligible for an nrs trial. the transfer of severely ill patients to the icu for intubation, with compromised haemodynamic parameters, low pao 2 /fio 2 or 'not responding to nrs', was discussed with the intensivists, based on prognosis, and obviously was only possible if beds were available. although not specifically mentioned in the guidelines, hfnc was also used in these two categories, during breaks in ventilation or as a stand-alone support. the use of helmet cpap devices was suggested as first-line treatment, mainly for safety reasons. clearly, this technique requires a sufficient supply of helmet interfaces (which ran out quite rapidly) and a high flow of o 2 (which exceeded the o 2 capacity in some hospitals), so that niv and hfnc were used as alternatives, the first when it was necessary to "save" oxygen, and the second when cpap availability finished. the respiratory covid areas consisted mainly of two different units, both present in all of the hospitals. the first one, formerly a respiratory ward, was an ad-hoc dedicated respiratory monitoring unit consisting of specialized monitored areas with an active full-day shift run by a fixed group of pulmonologists and with a "reinforced" nurse-patient ratio varying from 1:4 to 1:6 depending on the hospital. the second unit, called respiratory intermediate care units, consisted of a fixed medical team. these had a monitoring system similar to that of the respiratory monitoring units, together with the availability of icu ventilators and a nurse-patient ratio from 1:2 to 1:4, where more severely affected patients were usually treated. patients were continuously monitored with electrocardiogram trace, noninvasive blood pressure, arterial oxygen saturation, and respiratory rate (rr). intensive care medicine doctors were eventually available around the clock at the request of the ward teams. great care was taken to keep a distance of >1.5 metres between each bed and to provide natural ventilation and airflow of at least 160 l·s -1 per patient. concerning staff protection, first of all, courses were quickly organized for staff in the correct use of personal protective equipment (ppe), dressing and undressing. filtering facepiece class 3 (ffp3) or ffp2 masks, double non-sterile gloves, long-sleeved water-resistant gowns, goggles or face shields were mandatory in the presence of aerosol producing procedures. niv was delivered mainly by dedicated single circuit niv platforms provided with an oxygen blender and ad-hoc filters placed in the single tube circuit before the non-rebreathing devices to minimize bio-aerosol dispersion, or by icu ventilators. hfnc was delivered using standard devices (nasal high flow therapy, fisher and paykel healthcare ltd, new zealand), while helmet cpap dedicated devices, designed for pandemics, were simply activated by connecting them to the o 2 source available in the hospital with blender systems applied to obtain adequate values of delivered fio 2 (intersurgical spa, mirandola, italy and dimar srl, medolla, italy). data were collected prospectively from registries of the respiratory disease units identifying all of the patients receiving nrs outside the icu. variables recorded for each patient were obtained for the period from march 1 st until may 10 th 2020 and included the following: demographics (age, sex), comorbidities (type and number), respiratory condition at admission (respiratory rate (rr), pao 2 /fio 2 ratio), medications (type of drugs prescribed), mode and usage of the nrs (ventilatory settings for niv and cpap, and flow rate for hfnc), and stay in hospital (days). the number of patients who died, either in the respiratory unit or in the hospital, and the patients who received endotracheal intubation (eti) within the same time frame were recorded. patients who were still hospitalized at the time of data analysis were excluded. the health status of the staff working in the respiratory unit was closely monitored. all staff with fever or respiratory symptoms underwent chest radiography, and nasal and pharyngeal swab specimens were taken. serology for sars-cov-2 antibodies and pharyngeal swab was also periodically performed for all staff. no statistical sample size assessment was performed a priori, and sample size was the number of patients treated during the study period in the participant centres. baseline characteristics of patients treated with hfnc, cpap and niv were compared. across the treatment subgroups, continuous variables were expressed as means and standard deviation (sd) and were compared with the kruskal-wallis test and one-way anova test, while categorical variables were expressed as numbers and percentages (%) and were compared using the χ2 test or fisher's exact test. percentages of available data for the overall study population were based on the total number of patients included in the study, while the distribution of available data over the treatment subgroups was based on the available data for that variable, and the percentages were calculated using the number of available data for that subgroup. the fraction of infected professional health care workers was presented as numerical and percentage values. the association between ventilatory treatment and clinical outcomes was calculated using a logistic regression model. the 30day mortality rate was calculated adjusted for baseline confounders (age, p/f ratio, steroid usage and number of comorbidities). a total of 704 patients were considered and of these, 670 patients were included and their data analyzed. table 1 lists the patients' characteristics. cpap, as applied by helmet, was used on the majority of patients (supplementary table 1 ). twenty-eight out of 670 (4.2%) had a do not intubate (dni) order. figure 1 illustrates the patients' allocation to nrs and clinical outcome. a total amount of 180 patients died at 30 days. twenty of the 28 dni patients died (9% of the total number of deaths). in total, 114 patients died on spontaneous breathing without an expressed written dni order. most of the study patients were male (69.3%). hypertension, diabetes, dyslipidemia, obesity and chronic cardiovascular disorders were the comorbidities most represented, evenly distributed among the groups with the exception of obesity, which was more prevalent in the niv group. hydroxychloroquine, methylprednisolone, low molecular weight heparin and tocilizumab were the drugs most used for treatment. the frequency distribution of age and pao 2 /fio 2 ratio in the whole study population are shown in supplementary figure 1 . table 2 , 353 health care workers, including doctors, nurses, and health-care assistants, had been taking care of patients receiving nrs. forty-two of them (12%) tested positive for sars-cov-2 infection showing symptoms of mild (n=9) or moderate disease requiring hospitalization (n=3). all infected workers recovered well. the overall rate of workers infected, in personnel not specifically involved in the care of covid-19 patients, in the nine hospitals was 3.8±1.9%. outcome measures stratified by pao 2 /fio 2 ratio classes and according to nrs are reported in table 5 . patients with a pao 2 /fio 2 ratio below 50 mmhg presented a higher 30-day mortality rate and a higher rate of eti (p<0.001 and p<0.001, respectively). supplementary table 1 . niv was used as much as the patients could tolerate and in a small percentage of cases (43/177=24%), hfnc was applied during the intervals. patients with bilateral posterior infiltrates were also usually placed in the prone position for few hours a day, in all three nrs groups, with a schedule dependent on their tolerance. this study showed that using nrs devices is feasible in patients with arf due to sars-cov-2 infection treated outside icus, in newly developed dedicated covid respiratory monitoring units, formerly respiratory wards, and in respiratory intermediate care units. despite using the recommended ppe, a 11.4% contamination rate was observed among healthcare workers treating the infected patients. after adjusting for potential confounders, 30-day mortality rates using hfnc, cpap and niv were not significantly different. one of the major concerns of using bio-aerosol generating devices is that healthcare workers are at high risk of contracting the infection and therefore most international guidelines recommend being cautious or even contraindicate their use (6) (7) (8) . nevertheless, who advocate using cpap or niv for the management of respiratory failure in covid-19 patients, provided that appropriate ppe is worn by the personnel (9) . several studies have found that the maximum exhaled air dispersion via different oxygen administration and ventilatory support strategies is minimal for cpap through an oronasal mask or niv through a helmet equipped with an inflatable neck cushion, and is much less when compared with any kind of oxygen delivery system (10). interestingly enough, so far, studies have been conducted in negative pressure hospital rooms with at least six air changes per hour (minimum number of air changes recommended by who is 12 per hour). when these rooms were not available, as was the case for most of our patients, alternative hospital areas including rooms with natural ventilation (expressed as the product of room volume and air change rate) of at least 160 l·s -1 per patient were routinely employed, in keeping with the who statement (11) . indeed, according to the italian recommendations (4), the large majority of our study population received cpap (by helmet or face mask), mask-niv, and hfnc with a medical mask over the nasal prongs. taking all these precautions into account and using all of the appropriate protection, the number of health workers who tested positive at serology or pharyngeal swab was still quite high (11.4%); however, those who became ill (12/369, i.e. 3.3% of the staff involved) were in line with the 3.5% of health care workers requiring hospital admission in china (12) , the only study so far that has reported this outcome during the covid-19 outbreak. one may claim that our staff could have been infected in the community rather than by exposure to nrss; however, in the nine hospitals in this study, the overall rate of infection of health workers, in personnel not specifically involved in the care of covid-19 patients. the dramatic and rapidly increasing wave of the pandemic obliged us to treat a high number of severely hypoxic patients with nrs outside the icu. these patients are usually admitted to "protected" environments. the ats/ers guidelines (13) for example suggested using niv in de-novo respiratory failure only when managed by an experienced clinical team, and closely monitored in the icu. concerning the first point, all of the units involved had extensive experience in nrs use over a long period, and the nurse-patient ratio was "unusually" high for a ward, since during the outbreak, the nursing staff was reinforced in the locations where the acutely ill patients were admitted. in addition, fully equipped noninvasive monitoring systems were available. this is by far the largest report on the use of nrs outside the icu; however, our covid dedicated respiratory units cannot be considered equivalent to the "usual" respiratory wards. previous studies conducted in icus where nrs use was reported (1,15-21) account for 188 patients treated with niv and 61 by hfnc, without showing their characteristics and severity or the outcomes (in all but one study). interestingly, this latter study (19) showed a very high mortality rate both with niv and hfnc (80% and 52%, respectively). indeed, only a few patients were treated in the respiratory ward or unit, namely 80 and 33 patients using niv and hfnc respectively, with a poor survival rate (22, 23) . despite the fact that comparison among studies is extremely difficult due to the potential heterogeneity of patients included and/or to differing local hospital organization, the failure rate (i.e. mortality and/or eti) was much lower in our population, even when adjusted for potential confounders (see table 3 ), and it was comparable to what was observed (26%) in a large italian study performed in the icu in patients mostly intubated and with a pao 2 /fio 2 ratio similar to ours (1). in addition, in a recent two-period retrospective case-control study, oranger et al. (24) demonstrated that cpap could avoid intubation at 7 days and at 14 days, particularly in covid patients with a previous dni decision. the mortality rate was similar with all of the nrs modes used after adjustment for confounders; however, it has to be noted that hfnc was usually applied in less sick patients compared with niv and cpap, and this may reflect the attitude of the clinicians to start these latter two modes in patients where they judged that applying a relatively high level of external positive end expiratory pressure (peep) was more appropriate. it has been suggested that using any form of nrs might unduly delay the start of eti; however, it should be noted that 28 patients received a dni order (20 of them died), and that an icu bed was not promptly available at the time of deterioration, as reported in a specific small subset of the patient population. it may also be argued that "only" less than 5% of patients signed a dni order. in italy, the very large majority of the population are not sufficiently aware of the new advanced directive law (25), or they do not want to complete in advance any document in this respect. therefore, most of our patients arrived at hospital without any dni or do not resuscitate directives. the reasons for not proceeding to eti in the absence of a written dni order might be explained by: presumed lack of benefit from eti or mechanical ventilation (mv) based on clinical judgement, sudden death, or verbal refusal from the patient at the time of clinical deterioration. however, the majority of patients received "full treatment" when needed. despite the fact that this retrospective analysis in a large population indicates that nrs may help to treat severely affected covid-19 patients outside the icu, in newly dedicated respiratory areas with experienced staff, it also presents three main limitations. first, the design was retrospective, like most of the studies published during this terrible period. second, the decision to start one of the nrs modes was left to the attending physicians and mainly relied on the actual availability of equipment, so that the proportion of devices used was not evenly distributed. third, as in most reallife studies dealing with the covid-19 pandemic (1), missing data may be quite relevant; however, the critical nature of the situation did not always allow detailed information to be collected. to conclude, this is the first observational, large multicentre study showing that the application of noninvasive respiratory devices outside the icu is feasible but is associated with a risk of staff contamination; however, the retrospective study design precludes drawing firm conclusions about its effectiveness despite the fact that the mortality and intubation rates compare favourably with those of previous reports. baseline characteristics and outcomes of 1591 patients infected with sars-cov-2 admitted to icus of the lombardy region, italy official bulletin of lombardy region, date march 18 th covid-19 and italy: what next? managing the respiratory care of patients with covid-19. available at www.aiponet.it and www.sipirs.it date last accessed nosocomial outbreak of 2019 novel coronavirus pneumonia in wuhan, china intensive care society, association of anaesthetists and royal college of anaesthetists. critical care preparation and management in the covid-19 pandemic. available at: www.icmanaesthesiacovid-19.org date last accessed the australian and new zealand intensive care society covid-19 guidelines (version 1 surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (covid-19) clinical management of severe acute respiratory infection (sari) when covid-19 disease is suspected. interim guidance -13 protecting healthcare workers from sars-cov-2 infection: practical indications infection prevention and control during health care when covid-19 is suspected: interim guidance. available at www.who.int. date last accessed death from covid-19 of 23 health care workers in china official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure characteristics and outcomes of 21 critically ill patients with covid-19 in washington state clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china clinical course and outcomes of 344 intensive care patients with covid-19 clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in wuhan, china covid-19 in critically ill patients in the seattle region -case series clinical features of patients infected with 2019 novel coronavirus in wuhan, china clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study china medical treatment expert group for covid-19. clinical characteristics of coronavirus disease 2019 in china continuous positive airway pressure to avoid intubation in sars-cov-2 pneumonia: a two-period retrospective case-control study the italian law on informed consent and advance directives: new rules of conduct for the autonomy of doctors and patients in end-of-life care key: cord-013149-y0dbhtef authors: wohlfarth, p.; schellongowski, p. title: hämatoonkologie und intensivmedizin: vom tabu zur conditio sine qua non date: 2020-10-12 journal: med klin intensivmed notfmed doi: 10.1007/s00063-020-00737-5 sha: doc_id: 13149 cord_uid: y0dbhtef intensivists are confronted with a broad spectrum of specific clinical problems while caring for critically ill cancer patients. these include defining proper goals of intensive care treatment, managing acute respiratory failure with diverse differential considerations, treating immunologic side-effects of ever new and innovative cancer therapies, as well as numerous clinical scenarios which may exclusively arise in cancer patients. to help clinicians handle such challenges, the initiative intensive care in hematologic and oncologic patients (ichop) has been dealing with these topics for several years. supported by several austrian and german medical societies of intensive care medicine, hematology and oncology, the first “consensus statement for cancer patients requiring intensive care support” has only recently been released. acute respiratory failure and its management continues to be a major focus in critically ill cancer patients due to its frequency and its prognostic impact. while noninvasive oxygenation strategies were considered the gold standard of therapy, more recent high-quality data do not show clinical benefits of such techniques including high flow nasal oxygen. on the contrary, several studies revealed an unidentified etiology of an acute respiratory failure as the only potentially modifiable risk factor for adverse outcome. consequently, evidence-based and rigorously applied diagnostic algorithms are of utmost importance in these patients. furthermore, intensivists are increasingly confronted with the rising incidence of various and new immunotherapy-associated toxicities and their management. die versorgung kritisch kranker krebspatienten erfordert durch die große bandbreite spezifischer problemstellungen mit ständiger dynamik eine zunehmende spezialisierung von intensivmedizinisch tätigen ärzten (. tab. 1). der erste konsensus deutschsprachiger intensivmedizinischer und hämatologisch-onkologischer fachgesellschaften spricht auf dem boden der vorhandenen evidenz empfehlungen zum klinischen management aus [1] . dieser review behandelt neben allgemeinen themen speziell rezente daten zur oxygenierungsstrategie bei akutem respiratorischem versagen (arv), die wichtigkeit einer rigorosen ursachenabklärung sowie die zunehmend auftretenden toxizitäten nach immuntherapie. die vorhandene literaturzeigtkonklusiv, dass sich das outcome kritisch kranker krebspatienten in den vergangenen jahrzehnten stetig verbessert hat [2, 3] . diese tatsache ist 4 1) auf ein verbessertes intensivmedizinisches management analog zu nichtimmunsupprimierten patienten, 4 2) auf spezifische fortschritte und erkenntnisse bei kritisch kranken krebspatienten, beispielsweise im infektmanagement und in der verabreichung von systemischen therapien bei malignombedingten akuten organversagen sowie 4 3) maßgeblich auf eine verbesserte therapiezielfindung in dieser patientengruppe zurückzuführen [1, 4, 5] . so bedeutet eine "inadäquate" entscheidung im rahmen einer intensivstationsaufnahme im fall einer überbehandlung möglicherweise eine für den patienten und seine familie sinnlos belastende erfahrung am lebensende. hingegen kann eine ablehnung bei bestehenden onkologischen therapieoptionen hinsichtlich des malignoms eine fatale vertane chance darstellen. "full-code"-management an prinzipiellen therapiezieloptionen besteht das "full-code"-management ohne zurückhaltung intensivmedizinisch vorhandener therapieoptionen. diese kategorie trifft in der regel auf patienten mit kurativen therapieansätzen, patienten in remission, sowie patienten mit beträchtlicher langzeitüberlebenswahrscheinlichkeit, also eventuell auch im aus onkologischer sicht nichtkurativen, palliativen setting in abhängigkeit etwaiger komorbiditäten zu [1, 4] . im konträren gegensatz dazu sind "no-icu"-entscheidungen in der regel die zutreffendste option für patienten, die einen sehr schlechten performancestatus haben (mit ausnahme von situationen, in denen spezifische therapien aussicht auf substanzielle besserung bieten), für die keine lebensverlängernden therapien bestehen, sowie für patienten, die eine intensivmedizinische behandlung ablehnen [1, 4] . für patienten mit "intermediärer prognose" kann ein icu trial, also ein zeitlimitiertes "full-code-management", das angemessene herangehen darstellen, wobei die adäquate dauer solcher "trials" schwer zu bestimmen ist, in der regel jedoch mehrere tage nicht unterschreiten sollte [6] . die vertrauensvolle zusammenarbeit zwischen intensivmedizinern und krebsspezialisten, insbesondere im kontext weniger klarer situationen hinsichtlich der malignomassoziierten prognose, ist eine entscheidende voraussetzung für diesen therapiezielfindungsprozess [7] . timing der intensivstationsaufnahme die vorhandenen daten über kritisch kranke krebspatienten mit den häufigsten intensivstationsaufnahmegründen, arv und sepsis, zeigen einmütig, dass eine möglichst frühzeitige verlegung auf die intensivstation, also bei manifestem oder eventuell auch nur drohendem organversagen, erfolgen sollte [8, 9] . um einen solchen frühen zeitpunkt nicht zu übersehen, empfiehlt es sich, bereits im umfeld der normalbettenstation ein regelmäßiges screening bezüglich sepsiskriterien und des auftretens von organversagen durchzuführen [1] . beatmung die beatmung eines onkologischen patienten mit arv stellt einen paradigmenwechsel dar. die zur verfügung stehenden optionen werden nachfolgend dargestellt. bei patienten mit "chronic obstructive pulmonary disease" (copd) und hypertensivem lungenödem stellt die nichtinvasive beatmung (niv) den goldstandard der therapie dar und es gibt keine evidenzbasierte rationale, dass dies nicht auch bei krebspatienten gelten sollte. bei krebspatienten mit akutem hypoxischen respiratorischen versagen (arv) ist die rolle der niv jedoch zunehmend weniger gut belegt. eine ältere randomisierte studie zeigte zwar die überlegenheit einer niv gegenüber einer konventionellen sauerstofftherapie bei immunsupprimierten (zumeist hämatologischen patienten) hinsichtlich intubations-und mortalitätsraten [10] . im einklang damit zeigte eine metaanalyse mit insgesamt 2380 immunsupprimierten, in erster linie hämatologischen patienten, dass eine initiale niv im vergleich zur intubation mit niedrigerer mortalität vergesellschaftet ist. jedoch mussten 61 % (interquartilsabstand [iqr] 40-78 %), also nahezu 2 von 3 patienten, nach initialer niv sekundär intubiert werden, was mit einer erhöhten mortalität assoziiert war [11] . im rahmen einer weiteren multizentrischen beobachtungsstudie trat bei 1004 immunsupprimierten mit arv, erneut überwiegend krebspatienten, in 71 % der fälle niv-versagen auf, was ebenfalls mit erhöhter mortalität vergesellschaftet war [12] . » die nichtinvasive beatmung zeigte in einer multizentrischen studie weder vorteile noch nachteile eine große multizentrisch randomisiert-kontrollierte studie, in der niv mit konventioneller sauerstofftherapie bei immunsupprimierten (vor allem hämatologischen) patienten mit akutem hypoxischen arv, konnte keine klinischen vorteile (aber auch keine nachteile) einer niv zeigen. ein akutes kardiales lungenödem oder eine hyperkapnie, i.e. paco2 >50 mm hg, stellten bei dieser studie ausschlussgründe dar. die unerwartet niedrige mortalität in der o2-gruppe führte jedoch dazu, dass die studie eine zu geringe power aufwies. darüber hinaus erhielten mehr patienten in der niv-gruppe im vergleich zur o2-gruppe intermittierend nasalen high-flow-sauerstoff (hfno), sodass die niv-gruppe möglicherweise nicht repräsentabel war [13] . während sich in der analyse der sekundären outcomevariablen der flo-rali-studie (hfno bei hypoxischem arv, eine prinzipiell negative studie!) hinweise ergaben, dass hfno im vergleich zur gewöhnlichen o2-gabe oder niv mit einer niedrigeren intubationsund mortalitätsrate bei älteren patienten mit pneumonie [14] und in einer post-hoc-analyse auch bei immunsupprimierten patienten [15] vergesellschaftet sein könnte, konnte eine aktuelle große studie mit knapp 800 immunsupprimierten patienten und hypoxischem arv keinen unterschied zwischen hfno und o2-insufflation hinsichtlich intubationsund mortalitätsraten zeigen [16] . interessanterweise wurden in dieser bis dato größten studie zum einsatz der hfno bei hypoxischem arv auch keine unterschiede hinsichtlich der symptomatik der patienten nachgewiesen. etliche studien zeigen eine deutlich verbesserte mortalität von primär intubierten immunsupprimierten patienten mit arv. so lag beispielweise die mortalität bei arv mit kriterien eines "acute respiratory distress syndrome" (ards) bei invasiv beatmeten patienten bei "nur mehr" 52 % [12] . zusammenfassend bestehen bei deutlich gesunkenen mortalitätsraten invasiv beatmeter krebspatienten mit arv in den vergangenen jahren keine eindeutigen hinweise mehr für die vorteile einer niv oder hfno im vergleich zu einer konventionellen o2-insufflation. das ehemalige paradigma, immunsupprimierte patienten nach möglichkeit med klin intensivmed notfmed https://doi.org/10.1007/s00063-020-00737-5 © der/die autor(en) 2020 krebs · intensivstation · akutes respiratorisches versagen · immuntherapie · ichop intensivists are confronted with a broad spectrum of specific clinical problems while caring for critically ill cancer patients. these include defining proper goals of intensive care treatment, managing acute respiratory failure with diverse differential considerations, treating immunologic side-effects of ever new and innovative cancer therapies, as well as numerous clinical scenarios which may exclusively arise in cancer patients. to help clinicians handle such challenges, the initiative intensive care in hematologic and oncologic patients (ichop) has been dealing with these topics for several years. supported by several austrian and german medical societies of intensive care medicine, hematology and oncology, the first "consensus statement for cancer patients requiring intensive care support" has only recently been released. acute respiratory failure and its management continues to be a major focus in critically ill cancer patients due to its frequency and its prognostic impact. while noninvasive oxygenation strategies were considered the gold standard of therapy, more recent highquality data do not show clinical benefits of such techniques including high flow nasal oxygen. on the contrary, several studies revealed an unidentified etiology of an acute respiratory failure as the only potentially modifiable risk factor for adverse outcome. consequently, evidence-based and rigorously applied diagnostic algorithms are of utmost importance in these patients. furthermore, intensivists are increasingly confronted with the rising incidence of various and new immunotherapy-associated toxicities and their management. cancer · intensive care unit · acute respiratory failure · immunotherapy · ichop und womöglich "um jeden preis" nicht zu intubieren, kann somit als überholt, ja im fall sekundärerintubationenbeiniv-versagen sogar als potenziell gefährlich angesehen werden. beatmung soll bei indikation ohne verzögerung erfolgen konträr dazu kann nunmehr der grundsatz formuliert werden, dass krebspatienten mit aus intensivmedizinischer sicht kurativer therapiezielsetzung (also keine therapielimitierungen hinsichtlich des einsatzes intensivmedizinischer therapiemodalitäten) bezüglich der oxygenierungsstrategie nicht anders als nichtkrebspatienten geführt werden sollten. folgerichtig empfiehlt der "konsensus zur versorgung kritisch kranker krebspatienten" der initiative "intensive care in hematologic and oncologic patients" (ichop), unterstützt von der österreichischen gesellschaft für internistische und allgemeine intensiv-und es ist daher nicht überraschend, dass eine nichtidentifizierte ätiologie des arv einen starken negativ-prognostischen einfluss hat. etliche rezente daten konnten dies eindrucksvoll belegen. zwei landmark-studien an über 2200 patienten, eine davon prospektiv durchgeführt, zeigten sogar, dass von allen untersuchten faktoren eine nichtidentifizierte ätiologie den einzigen potenziell modifizierbaren risikofaktor für ein schlechteres outcome darstellt [17, 18] . während nichtinvasive oxygenierungsstrategien im gegensatz zu früheren ansichten also keinen einfluss auf den verlauf der patienten haben dürften, sollte das augenmerk heutzutage vielmehr auf eine rigorose abklärung der arv-auslösenden ursachen gelegt werden. eine randomisierte studie zum einsatz einer bronchoalveoläre lavage (bal) bei nichtintubierten immunsupprimierten patienten zeigte, dass ihre durchführung bei respiratorischer beeinträchtigung, jedoch bei einer peripheren sauerstoffsättigung (spo2) >90%, hinsichtlich intubationsraten und weiterem verlauf in erfahrenen händen als sicher anzusehen ist [19] . jedoch konnte die ausbeute hinsichtlich einer ursachenidentifizierung im vergleich zu einem arbeitsintensiven nichtinvasiven diagnosealgorithmus nicht erhöht werden. [18, 21] . ein rezenter review des nine-i-netzwerks liefert weitere ausführungen zum differenzierten diagnostischen vorgehen bei schweren respiratorischen infekten des immunsupprimierten patienten [29] . in den vergangenen jahren wurde eine flut an neuen immuntherapeutika zur behandlung von krebserkrankungen zugelassen. im zuge der äußerst vielgestaltigen toxizität benötigt jeder dritte mit diesen medikamenten behandelte patient eine notfallmedizinische versorgung. auch für intensivmediziner rückt bei auftreten von organdysfunktionen die differenzialdiagnose einer immuntherapieassoziierten problematik somit zunehmend in den mittelpunkt. wiewohl eine ausführliche besprechung dieses themas den fokus dieses reviews sprengen würde, soll an dieser stelle in kürze auf die wichtigsten punkte eingegangen und auf die entsprechenden nachschlagwerke bzw. leitlinien verwiesen werden. insbesondere die sog. checkpointinhibitoren sind mittlerweile in den verschiedensten hämatologischen und onkologischen indikationen in verwendung [23, 24] . die mit ihnen assoziierte toxizität betrifft in vielgestaltiger form den dermatologischen und gastrointestinalen bereich (diarrhö, kolitis, hepatitis), manifestiert sich in diversen endokrinopathien, rheumatologischen krankheitsbildern sowie in der für den intensivmediziner besonders relevanten pneumonitis mit möglichem arv. seltener befallene organsysteme stellen das zentrale nervensystem, die niere, das auge, das kardiovaskuläre sowie das blutbildende system dar. sämtliche unklare befundkonstellationen sollten zur abklärung bzw. kontaktaufnahme mit einem experten für diese therapien führen. die therapie besteht im einfachsten fall in einem absetzen der medikation, mitunter muss jedoch auch eine (eventuell hochdosierte) steroidtherapie und bei deren versagen eine weitere immunsuppressive oder immunmodulatorische therapie eingeleitet werden. wiewohl die evidenz zu diesem vorgehen in vielen assoziierten bereichen bis dato noch recht oberflächlich erscheint, sprechen etliche rezente leitlinien und übersichtsartikel empfehlungen zum management aus [23, 24] . die sog. chimeric-antigen-receptor(car)-t-zell-therapie stellt für erwachsene patienten mit ungünstig verlaufendem diffus großzelligem b-zell-lymphom sowie für kinder und junge erwachsene mit akuter lymphoblastischer b-zell-leukämie eine neue therapieoption dar. dabei werden t-zellen consensus statement for cancer patients requiring intensive care support changes in critically ill cancer patients' shortterm outcome over the last decades: results of systematicreviewwithmeta-analysisonindividual data critical care of patients with cancer intensive care of the cancer patient: recent achievements and remaining challenges critically ill patients with cancer: chances and limitations of intensive care medicine-a narrative review timelimited trials of intensive care for critically ill patients with cancer: how long is long enough? ccc meets icu: redefining the role of critical care of cancer patients outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from france and belgium-a groupe de recherche respiratoire en réanimation onco-hématologique study intensive care unit management of patients with newly diagnosed acute myeloid leukemia with no organ failure noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acuterespiratoryfailure impact of initial ventilatory strategy in hematological patients with acute respiratory failure: a systematic review and meta-analysis acute respiratory distress syndrome in patients with malignancies effectofnoninvasiveventilationvsoxygentherapy on mortality among immunocompromised patients with acute respiratory failure: a randomized clinical trial high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure effect of noninvasive oxygenation strategies in immunocompromised patients with severe acute respiratory failure: a post-hoc analysis of a randomised trial effect of high-flow nasal oxygen vs standard oxygen on 28-day mortality in immunocompromised patients with acute respiratory failure: the high randomized clinical trial increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a groupe de recherche en réanimation respiratoire en onco-hématologique (grrr-oh) study acute hypoxemic respiratory failure in immunocompromised patients: the efraim multinational prospective cohort study diagnostic strategy for hematology and oncology patientswithacuterespiratoryfailure: randomized controlled trial clinical assessment for identifying causes of acute respiratory failure in cancer patients acute respiratory failure in immunocompromised adults leukostasis and tumor lysis: important complications of hyperleukocytosis a review of cancer immunotherapy toxicity new drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management tisagenlecleucel in adult relapsed or refractory diffuse large b-cell lymphoma immuno-oncology meets intensive care medicine: car-t cells axicabtagene ciloleucel car t-cell therapy in refractory large b-cell lymphoma diagnosis of severe respiratory infections in immunocompromised pattients key: cord-354330-pud2rqxk authors: pirzada, abdul rouf; aleissi, salih a.; almeneessier, aljohara s.; bahammam, ahmed salem title: management of aerosol during noninvasive ventilation for patients with sleep-disordered breathing: important messages during the covid-19 pandemic date: 2020-06-17 journal: sleep vigil doi: 10.1007/s41782-020-00092-7 sha: doc_id: 354330 cord_uid: pud2rqxk with the advent of covid-19 infection and its rapid spread, preventive strategies are being developed worldwide, besides following the universal infection control guidelines. prevention of spread through aerosol generation is one of the essential strategies in this regard, particularly for patients with sleep-disordered breathing at home and during hospital admission. aerosols are produced, at home and in health care facilities, by natural processes and aerosol-generating procedures. to address this impinging problem, aerosol-generating procedures, like non-invasive ventilation (niv), are to be handled meticulously, which might warrant isolation and sometimes device/interface modifications. first reported in wuhan, china, in december 2019, with subsequent global spread, "coronavirus disease 2019" (covid 19) infection was later declared as a pandemic by world health organization (who). the sheer number of persons infected, along with the rapid worldwide dispersion, it has threatened the health care systems all over the world. covid-19 is mainly transmitted through respiratory droplets: close unprotected contact, and intense aerosolsgenerating procedures [1] . thus, the community spread from person to person, and through fomites, the spread of infection in healthcare workers is a more formidable threat. the spread of infection among healthcare workers has more implications since it jeopardizes the already reeling system [2] . as the spread of infection in covid 19 is by droplets, which happens during close contact or through fomites; thus, the management of droplet dispersion forms the soul of the prevention strategy [3] . droplets or large aerosols are usually of the size of more than 20 μm. these are produced either during natural processes like coughing, sneezing or during aerosol-generating procedures, like non-invasive ventilation (niv) [2] . it has been shown that masks, particularly common medical/surgical masks can prevent the natural process of droplet spread though it is "easier said than done" and the n95 masks are to be reserved for high-risk encounters; however, aerosol management during aerosol-generating procedures is still a challenge [4] . this review aims to formulate guidelines and advisories for aerosol management during niv [particularly for patients with sleep-disordered breathing (sdb)] and related procedures after critically reviewing the scientific literature available so far; nevertheless, these guidelines and advisories are dynamic due to the evolving nature of the pandemic. aerosols are particles suspended in the air that can contain a variety of pathogens, including viruses, and their classification is debatable. arbitrarily, aerosols are categorized as small droplets (which are usually called aerosols exclusively) and large droplets, with small droplets having the potential to desiccate and form droplet nuclei that travel long distances, while large droplets do not evaporate before settling on surfaces [5] . this aerosol classification has clinical relevance in relation to their dispersal properties and patterns, but it is also important to classify aerosols according to where they deposit in the respiratory tract, upper or lower, because it has a bearing on pathogenesis [5, 6] . most often, 5 microns in diameter is taken as a cutoff for small droplets, while another possible cutoff between aerosol types is 20 microns, since aerosols less than or equal to 20 microns in diameter can desiccate to form droplet nuclei, and aerosols more 20 microns do not deposit substantially in the lower respiratory tract [5] . in the case of covid 19, it has been experimentally postulated that the epidemiological characteristics of this virus probably arise from other plausible factors like high viral load in the upper respiratory tract and the potential for infected persons to shed and transmit the virus while asymptomatic [4, 5, 7] . besides, aerosol and fomite transmission of covid 19 is highly possible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed) [8, 9] . aerosol generation can occur during natural processes like coughing, sneezing, or expectorating; however, current evidence suggests that, while it is possible that coronaviruses can survive in the aerosol from within fluid particles, under certain conditions, this is not the primary mechanism for transmission in the community. however, the natural processes are presumed to be a potential transmission mechanism in health care workers, besides therapeutic or diagnostic aerosol-generating procedures. the procedures that are believed to have a potential to generate aerosols and droplets as a source of respiratory pathogens include positive pressure ventilation (bilevel positive airway pressure (bpap) and continuous positive airway pressure (cpap)), endotracheal intubation, airway suction, high-frequency oscillatory ventilation, tracheostomy, chest physiotherapy, nebulizer treatment, sputum induction, and bronchoscopy [5] [6] [7] . in experimental studies, this phenomenon of aerosol generation and dispersion has been studied. however, those experimental studies had some practical short-comings because they used smoke to simulate aerosol, and experiments were conducted in the absence of negative pressure [3] . during niv, studies demonstrated that the dispersion had been grossly variable depending upon multiple factors like the interface used, pressure level, and the device used [3] . respiratory procedures are known to stimulate coughing and promote the generation of aerosols; however, their risk of transmission of infection is not quantified. thus, these procedures are to be handled meticulously to minimize the spread among health care workers and at times in the household [10] [11] [12] . this short review aims to formulate guidelines and advisories for home and hospital use of niv. since the aerosolgenerating procedures take place at home and in the hospital, we will divide this article into two sections, at home and in the hospital. aerosol generating procedures that take place at home are home niv systems, either cpap or a bpap, home oxygen therapy, and sometimes home diagnostics like "home sleep apnea testing" systems. niv, bpap, and cpap are currently listed by the who as a high-risk aerosol-generating procedure. niv accounts for high-dose viral transmission risk to family and carers during the treatment of chronic respiratory diseases, especially obstructive sleep apnea [13] [14] [15] [16] [17] . the viral load is comparable in nasal and throat swabs of symptomatic and asymptomatic patients with covid-19 [17] , suggesting that niv-induced aerosolization of nasopharyngeal secretions from asymptomatic patients may pose similar risks for high-dose viral transmission in households. aerosolised severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has a half-life of 1.1 h in the air, and therefore, a period of prolonged isolation may be required following niv usage [3, 8, 9] . however, patients with sleepdisordered breathing need to use their positive airway pressure (pap) devices during this pandemic that may last for months to come, besides cpap use can have a bearing on overall mortality and morbidity in these patients if infected with sars-cov-2 [18] [19] [20] . based on the literature review and personal experience [16, 17, [21] [22] [23] , the following is suggested: • universal isolation for niv at home is impractical; hence it has to be individualized. • temporary cessation is a plausible option, taking into consideration the risks of withholding niv in patients with hypercapnia; however, this needs to be discussed with the treating physician. in patients with whom niv therapy cannot be temporarily stopped, such as patients with severe obesity hypoventilation, complete home isolation is preferred to minimize the risk of aerosol spread among the household. • other plausible options are modifications in the device and interface of niv to reduce the risk of aerosol dispersion (will be discussed down). • following routine hygiene advisories are highly recommended: changing machine filters routinely, cleaning surfaces, cleaning masks and tubing with hand-hot soap water (washing-up liquid), and washing hands regularly. • for home oxygen therapy, isolation is a must to prevent the viral dispersion if there is suspicion or confirmation of covid-19 infection as viral load and dispersion inhome oxygen systems, though not quantified, is highly infective. • portable home sleep studies and auto-adjusting pap at home are recommended to be suspended, particularly in endemic zones; however, they can be considered in emergent conditions in sporadic zones, only after ruling out any suspicion of covid-19 infection. in such circumstances, the applications of a disposable nasal pressure transducer for sleep study and disposable or personal masks and ventilator tubing for niv are strongly recommended [16, 17, [21] [22] [23] . in the hospital, the procedures that are believed to or have a potential to generate aerosols and droplets as a source of respiratory pathogens include positive pressure ventilation (bipap and cpap), endotracheal intubation, airway suction, high-frequency oscillatory ventilation, tracheostomy, chest physiotherapy, nebulizer treatment, sputum induction, and bronchoscopy [5, 8] . it is imperative to mention that titration studies during polysomnography fall under the same category. hence, in countries with endemic zones, it is recommended to suspend sleep studies except in emergent conditions after examining the risk-benefit ratio with a strict precondition of pre-procedural evaluation for covid-19 [21, 24] . besides, it is necessary to follow the infectious disease protocol of negative pressure isolation and proper personal protective equipment (ppe), whenever indicated. indication for infectious disease protocol is, nevertheless, ambiguous and hence has to be individually tailored [21, 23, 25] . in the regions/areas with sporadic covid-19, sleep study and niv can be continued, but it is recommended to have portable home sleep studies and auto-adjusting pap at home. the applications of a disposable nasal pressure transducer for sleep study and disposable or personal masks and ventilator tubing for niv are strongly suggested. however, it is recommended to suspend sleep studies and niv titration trials for subjects who report to having recent travel or residential history in a high epidemic area [21] , contact history with covid-19 infected patients, contact history with febrile patients or subjects with respiratory tract symptoms from the high epidemic or cluster outbreak area, report of fever or respiratory tract symptoms, or newly emerging ground-glass opacities on a computerized chest tomography (ct) scan [21, 23, 25] . for the recovered patients with robust evidence of negative results of nucleic acid testing, sleep studies and niv can be performed [21, 23, 25] . for in-hospital niv, dispersion of virus is common if robust preventive measures are not applied. niv in hospital, in a setting of suspected or confirmed case of covid-19, warrants infectious disease protocol of isolation in negative pressure room preferably with an anteroom and attached washroom (well ventilated) and personal protective equipment for attending staff; however, it is not possible in high volume patient inflow. even under such unavoidable conditions, ppe for the attending staff is mandatory [3, 16, 17, 26, 27] . a practical approach is to work on and modify the niv device, mostly interface and tubing to minimize the dispersion and protect the health care workers. setup of cpap or niv/bilevel ventilators for patients with sdb is built to work with a single tube and a relatively constant intentional leak. the leak occurs in three parts: mouth leak, if a nose mask is used, leak around the mask/face contact, and leak through the intentional leak port. interventions to reduce leak include the use of a full-face mask (discarding nasal masks) with the optimal fit; moreover, the mask needs to be non-vented with an exhalation port in the circuit. thus, the choice of a mask to minimize viral dispersion would be [3, 24, 26, 28] : • first choice, a full-face non-vented mask with an expiratory viral filter. a good mask seal for face masks is important to minimize droplet dispersion and maximize effectiveness. • second choice, a helmet with air cushion for cpap. • third choice, a helmet without air cushion for cpap. • fourth choice, a standard face mask it is important while using a mask-system to humidify the gas flow. a heat and moisture exchanger (hme)/viral filter should be fitted to all exhaust systems to reduce droplet spread. hme filters need a close watch to look for any waterlogging that warrants a change to prevent any high and unidirectional flow. it must be ensured that the ventilator mode employed supports the use of non-vented masks and exhalation ports. likewise, the sequence of events protocol should be: to put the mask on, tie it, and then put the ventilator on; to disconnect, first put the ventilator off, and then take off the mask. to manage intentional leak, a viral/bacterial filter can be placed in the circuit between the mask and the oxygen and exhalation ports to ensure that if the oxygen tubing becomes dislodged accidentally, the filter will stop exhaled breaths escaping via the ports (fig. 1) [22] . this viral/bacterial filter can replace any filter at the machine end of the circuit and ideally needs to be changed every 24 h to prevent any resistance to flow due to the absorption of moisture, which can mimic clinical deterioration. it is important to mention that external humidification should not be used in such systems [22] . whenever oxygen is to be used, it can be entrained into the circuit, and this should be done at the patient end of the filter fig. 1) . once a patient is admitted to the hospital with suspicion/confirmed covid-19 and is using home niv systems, it is essential to ensure that the used mask is nonvented, the filter is entrained in the system, and there is no humidifier [22, 26, 29] . to act during the exigencies of patient volume and meager resources, it is suggested to follow "jury rig," which is a system tailored to circumvent the lack of a commercial bilevel circuit with an exhalation port; this can be done so by connecting a t-or y-connector to the mask, then fit a filter in the new limb; besides, introducing an exhalation port (or resistor containing leak), which can be inserted before (or after) the filter [30] . this addition of a "t" or "y" tube piece with an "overflow" port allows filtering of all, but the unintentional face leak (which can be managed using an appropriate mask); however, it creates dead-space, which can be minimized by connecting the y or t piece as close as feasible to the mask (fig. 2) . merely adding a filter on the end of the "overflow" tube will dissipate much of the delivered pressure from the ventilator, unless, it is combined with a resistor. thus, the combination of a filter and a resistor/ restrictor in the right range will correct this issue. if a resistor is not commercially available, it can be tailored using a plug with a single 3.5 mm (1/8 or 5/32 inch) hole drilled in it or 20 0.8 mm holes drilled in a standard medication pillbox that fits the tubing; holes are punctured/ melted into the bottom with a hot paper clip or 18-gauge needle) [30] . this arrangement should provide leak flow of 12 l/min at 3 cmh20, and 35 l/min at 25 cm h20, providing adequate ventilation at most bilevel settings without significant co 2 rebreathing [30] . the setup would replicate the typical leak port flows of existing masks or expiratory port circuits directed to a filter (fig. 2) . sterility of this part of the circuit is not a significant issue as the flow is unidirectional away from the patient, even when the patient is intubated [29, 30] . other aerosol-generating ward procedures like nebulization and oxygen therapy in suspected or confirmed covid-19 patients warrant a standard infectious disease protocol, as already mentioned. procedures like bronchoscopy and endotracheal intubation are beyond the scope of our discussion. fig. 1 a scheme of niv setup, a non-vented mask is fitted to a bacterial filter, and then connected to a safety valve and an oxygen entrainer port in between, at the end an exhalation port with a valve fig. 2 a schematic representation of a modified bilevel circuitry setup to minimize aerosol dispersion by adding a y-connector, with one limb connected to the device and the other limb to a filter through a restrictor aerosol management during niv use can be achieved through multiple methods, besides suspending the use, whenever possible. standard infectious disease protocols form the backbone of the preventive strategy; however, modifications in the interface and the tubing can be tailored through commercially available add-ons or using home available materials to limit the aerosol dispersion during niv use. funding this work was supported by the strategic technologies program of the national plan for sciences and technology and innovation in the kingdom of saudi arabia (med511-02-08). the study sponsors played no role in the study design, the collection, analysis or interpretation of data, writing the manuscript, or the decision to submit the manuscript. the epidemiology and pathogenesis of coronavirus disease (covid-19) outbreak consensus statement: safe airway society principles of airway management and tracheal intubation specific to the covid-19 adult patient group protecting healthcare workers from sars-cov-2 infection: practical indications medical masks vs n95 respirators for preventing covid-19 in healthcare workers: a systematic review and meta-analysis of randomized trials. influenza other respir viruses nosocomial transmission of emerging viruses via aerosol-generating medical procedures exhaled air dispersion during high-flow nasal cannula therapy versus cpap via different masks particle size and pathogenicity in the respiratory tract aerosol and surface stability of sars-cov-2 as compared with sars-cov-1 sars-cov-2 viral load in upper respiratory specimens of infected patients al hosani fi. transmission of middle east respiratory syndrome coronavirus infections in healthcare settings probable crimean-congo hemorrhagic fever virus transmission occurred after aerosolgenerating medical procedures in russia: nosocomial cluster a review of the risks and disease transmission associated with aerosol generating medical procedures use of noninvasive ventilation for patients with covid-19: a cause for concern? noninvasive ventilation and the potential risk of transmission of infection noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review case for continuing community niv and cpap during the covid-19 epidemic covid-19: community cpap and niv should be stopped unless medically necessary to support life coronavirus disease 2019 and obstructive sleep apnea syndrome is sleep apnoea a risk factor for covid-19? findings from a retrospective cohort study (pre-print). medrxiv and sleep apnoea management in europe during the covid-19 pandemic: data from the european sleep apnoea database (esada) sleep health service in china during the covid-19 outbreak home pap devices in covid-19 infected patients guidance regarding coronavirus (covid-19) and obstructive sleep apnoea (osa): for people who routinely use continuous positive airway pressure (cpap), their families and health care workers covid-19 mitigation strategies for sleep clinics and sleep centers-reopen-ing epidemiology and transmission of covid-19 in 391 cases and 1286 of their close contacts in shenzhen, china: a retrospective cohort study covid-19: respiratory support outside the intensive care unit niv to patients in hospital with uncertain or detected covid-19. recommendations on practical implementation (nonpeer-review article) respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease european centre for disease prevention and control. infection prevention and control and preparedness for covid-19 in healthcare settings-third update non invasive ventilation (niv) by mask and use of niv systems for intubated patients in the time of corona patient surge the authors have no conflict of interest to declare. key: cord-352577-h3652seb authors: kopić, jasminka; paradžik, maja tomić title: expanding the use of noninvasive ventilation during an epidemic date: 2014-08-27 journal: disaster med public health prep doi: 10.1017/dmp.2014.71 sha: doc_id: 352577 cord_uid: h3652seb noninvasive ventilation (niv) is a proved and effective therapeutic option for some patients with respiratory failure. during an epidemic, niv can free up respirators and other intensive care unit equipment for patients with respiratory insufficiency whose survival depends exclusively on invasive ventilation. some guidelines have indicated that niv is potentially hazardous and should not be recommended for use during epidemics, given the perceived potential risk of transmission from aerosolized pathogen dispersion to other patients or medical staff. conversely, some reports of previous epidemics describe niv as a very efficient and safe modality of respiratory support, if strict infection control measures are implemented. we discuss niv use during epidemics and indicate the need for prospective randomized clinical studies on the efficacy of niv in epidemic conditions to provide important information to the current body of literature. meanwhile, the use of niv under strict infection control guidelines should be incorporated into epidemic preparedness planning. (disaster med public health preparedness. 2014;8:1-5) n oninvasive ventilation (niv) provides ventilatory support through a patient's upper airway using a facial mask or similar device connected to a respirator, in contrast to invasive ventilation, which requires the placement of an invasive airway such as an endotracheal or tracheostomy tube. first developed in the 1940s as an intermittent positive pressure breathing device for use in highaltitude aviation, nivs were subsequently used by motley and colleagues at bellevue hospital to treat acute respiratory failure in patients with pneumonia, pulmonary edema, near-drowning, acute severe asthma, and guillain-barré syndrome. 1 the application of niv in clinical settings became widespred in the 1980s. in 1989, meduri and colleagues successfully applied niv via full-face mask in patients with respiratory insufficiency and chronic obstructive pulmonary disease (copd), congestive heart failure, or pneumonia. 2 thereafter, niv has become increasingly adopted by critical care clinicians for the treatment of acute respiratory failure in both emergency and critical care settings. 3 the medical conditions for which critical care clinicians have recognized the importance of niv have also rapidly increased during this period. 4 when appropriately indicated and promptly administered, niv offers an alternative to tracheal intubation, sedation, risk of infection, and myriad complications associated with invasive ventilation, and it can promote rapid respiratory recovery, and reduce a patient's dependence on critical care facilities. in addition to strongly proved benefits in patients with acute hypercapnic respiratory failure due to acute exacerbation of copd and pulmonary edema resulting from heart failure, 5 niv has become a useful therapeutic option for respiratory failure in patients who are immunosupressed 6 and in patients with chest trauma. 7 successful use of niv has also been seen in patients with chronic respiratory failure due to neurological and neuromuscular diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and muscular dystrophies 8 and during the respirator-weaning process. 9 in contrast, the utility of niv in hypoxic respiratory failure due to pneumonia is still doubtful. 10 in spite of very well-known indications, the use of niv in clinical practice is far from uniform. in a study of niv use in 82 us hospitals, the average niv rate of use was 20% of ventilator starts. the rate of use of niv differed from 0 to more than 50% of ventilator starts within the same region. lack of knowledge, insufficient training, and inadequate equipment were perceived as the most common reasons for the underuse of niv. a very important finding of this study was that most clinicians who had used niv as a regular clinical routine considered their experience with niv as good to excellent. 11 in a european study of 42 french hospitals, the niv rate of use was 16% of ventilator starts, but even in 20% of the reported hospitals niv had never been used. 12 one of the important issues of preparedness planning for an epidemic caused by a respiratory pathogen is to reevaluate the use of niv in the treatment of respiratory failure, 13 especially when shortages of respirators present a real concern. during the past 20 years, 2 epidemics have emerged, severe acute respiratory syndrome (sars) in 2003 and h1n1virus in 2009. both outbreaks resulted in a significant number of patients developing serious disease and acute respiratory failure, the recovery from which depended on the availability of intensive care resources, especially respirators. during the 2003 sars epidemic, 14% to 25% of patients progressed to acute respiratory failure, requiring mechanical ventilation. 14 during the 2009 h1n1 epidemic, approximately 10% to 30% of the hospitalized patients were admitted to an intensive care unit (icu), most of them due to respiratory failure. 15 in both events, the medical community faced the difficult task of making the icu facility during an epidemic available to all critically ill patients, in addition to providing the required number of respirators and other necessary respiratory equipment. the use of niv in patients with h1n1 influenza has been reported with varying rates of success. rello et al described niv use at icu admission in 1 of 3 patients with h1n1 virus and respiratory failure, but 75% of them had an unfavorable clinical course and required tracheal intubation and invasive mechanical ventilation. 16 the study of 337 patients with h1n1 admitted to icus in argentina reported that niv was used in 64 (19%) patients, with favorable outcomes in 43 patients who survived (67%). 17 masclans et al reported 685 patients with confirmed h1n1 viral pneumonia who were admited to spanish icus, 489 of whom required mechanical ventilation. 18 niv was used in 177 patients, and successful outcomes were seen in 72 patients (40.7%), while the other patients required invasive ventilation (table 1) . patients in whom niv was successful had shorter hospital stays and lower mortality rates, similar to those of the nonventilated patients. the mortality of patients in whom niv failed was similar to that of the patients requiring intubation from the start. 18 another critical preparedness task was to ensure a safe hospital environment for other patients and for health care workers (hcws) during an epidemic. in the course of the 2003 sars epidemic in vietnam, 57% of sars patients were hcws; in canada, 43% were hcws; and in singapore, 41% were hcws. worldwide, about 21% of sars patients were hcws 20 ( table 2) . recognizing the occurrence and outcomes associated with superspreading events (sse) since the 2003 sars outbreak was another reason critical care physicians have rejected the use of niv during an epidemic. during the 2003 epidemic, about 75% of sars infections in hong kong and singapore were associated with sses, confronting epidemiologists and clinicians with the task of identifying the hospital procedures contributing to this phenomenon and modifying their infection control measures. 21 yu et al analyzed the factors responsible for hospital spreading of sars infection and found 6 significant risk factors: minimum distance between beds (≤1 m), the availability of washing or changing facilities for staff, administering resuscitation in the ward, staff members working while experiencing symptoms, and whether the host patient (index patients or the first patient admitted to a ward) required oxygen therapy or bilevel positive airway pressure ventilation. 22 the experience in singapore, however, demonstrated that following the development of proper infection control measures, which consisted of staff personal protection, patient risk categorization, and reorganization of operating room workflow process, no transmission of sars had occurred within the operating room complex. 23 moreover, it was well known that niv is not the only procedure that carries an increased risk of transmitting acute respiratory infection pathogens to staff. in their systematic review of literature concerning aerosol-generating procedures and the risk of transmitting acute respiratory infection to hcws, tran and coworkers found that tracheal intubation, tracheotomy, and manual ventilation before intubation were procedures with significantly increased risk of transmission-as much as with niv. furthermore, they found that tracheal intubation was the procedure most consistently associated with the transmission of sars virus to hcws. 24 several reports on the 2003 sars epidemic reported good clinical results with niv use, which was also associated with reduced intubation rate and mortality. 19, 25, 26 zhao et al compared 4 treatment modalities for hospitalized sars patients and reported that the best clinical improvement was achieved in patients who received early high-dose steroids combined with nasal continuous positive airway pressure. 26 importantly, in a retrospective analysis comparing the efficacy of niv against invasive ventilation in sars patients with respiratory failure, yam et al reported that no hcw caring for niv patients was infected and that standard personal protective equipment, including surgical masks, was as effective as the more sophisticated protective equipment used later in the outbreak. 24 cheung et al reported the use of noninvasive positive pressure ventilation (nippv) in 20 patients with acute respiratory failure due to sars. their results showed that in patients with nippv, tracheal intubation was avoided in 14 cases. also, the length of stay in icu was shorter compared to that for intubated patients, and, importantly, no hcw caring for patients with nippv was infected. 19 following the 2003 to 2007 avian influenza a (h5n1) epidemics in asia, africa, europe, near east, and the pacific, the world health organization's document "clinical management of human infection with avian influenza a(h5n1) virus" included a statement that nippv cannot be recommended for patients with respiratory failure resulting from a (h5n1) virus infection. this document highlighted concerns associated with the potential increased risk of generating infectious aerosols in the course of this method of respiratory support. 27 research using experimental lung models demonstrated that exposure to exhaled air from patients receiving niv with face mask occurs within 1 m. 28 likewise, guidelines for the acquisition of ventilators to meet the demands for pandemic flu and mass casualty incidents, published in 2006 by the american association of respiratory care, recommended the avoidance of niv in case of contagious respiratory diseases due to contamination risk. 29 the task force on mass critical care voiced similar opinions regarding noninvasive ventilation during their summit meeting in january 2007. their suggestions regarding interventions for emergency mass critical care and the use of mechanical ventilation during a disaster recommended only the "provision of a basic mode of sustained, positive pressure ventilation" without any reference to niv. 30 the task force further declared niv a high-risk procedure due to the potential for air flow from the mask to increase the risk of infectious transmission to the staff and to other patients. 27, 29 since 2009, however, some published documents have mentioned niv as a possible procedure during an epidemic. in a position statement, the australian society for infectious diseases recommends "reserving negative-pressure ventilation rooms (if available) for intensive care patients, especially those receiving non-invasive ventilation." 31 the uk department of health, in "guidance for infection control in critical care for pandemic influenza," approved the use of niv under strict infection control measures. emphasis was given to staff training in infection control and the use of personal protection by gown, gloves, eye protection, and a filtering half mask with exhalation valve (ffp3) respirator; negative pressure rooms; nonvented mask or helmet; applying and fitting the mask before turning on the respirator; and removing the mask after turning off the respirator. 32 the recommendation for niv use during an epidemic is also consistent with the institute of medicine's 2012 "crisis standards of care: a systems framework for catastrophic disaster response." the institute's expert panel emphasized the obligation for matching patients' health care needs with a level of care capable of meeting those needs during a disaster, such as an epidemic. 33 for some patients during a disaster, regardless of the cause of their respiratory insufficiency, niv will serve this need very well. in most health care systems, mechanical ventilation is usually the first limited resource in disaster situations. based on information from previous influenza epidemics in the united states, almost 100% of the available ventilators were in use. 34 ventilator-allocation plans, increasing the supply of ventilators, and use of ventilator "alternatives" are solutions, 34 and niv fits perfectly into all of these plans. consistent with addressing crisis standards of care, the use of niv is not only directed to individual patient outcomes, but it fulfils a noninvasive ventilation during an epidemic disaster medicine and public health preparedness responsibility to the population. significant effort must be focused on applying the most ethical triage concepts associated with ventilator-allocation principles for patients with respiratory insufficiency during disasters. 35, 36 as such, incorporating niv in the allocation and decision-making process for preparedness planning will augment the capacity for respiratory support and reduce patient and population mortality during a disaster. the institutes of medicine emphasizes the importance of this point: "plans and protocols that shift desired patient care outcomes from the individual to the population must be grounded in the ethical allocation of resources, which ensures fairness to everyone…the emphasis in a public health emergency must be on improving and maximizing the population's health while tending to the needs of patients within the constraints of resource limitations." 33 in disaster situations, medical care occurs across 3 phases on a continuum 33 : • conventional care, with the maximal use of the resources; • contigency care, with the aim of ensuring functionally equivalent care; and • crisis care, with care provided to the highest level possible and incorporating prioritized strategies for fixed resources. the implementation of niv in epidemic situations can be incorporated into all 3 phases of the continuum, especially as functionally equivalent care for some patients. another benefit associated with resource utilization strategies is that niv is very suitable to the principle of resource adaptation; for the niv application we can use almost all types of respirators, anesthesia machines, and bi-level positive pressure machines. 37, 38 the strict adherence to infection-control guidelines, including pre-exposure prophylaxis for vaccine-preventable diseases, 39, 40 such as hand hygiene before and after patient care 41 and wearing protective equipment such as gloves, gowns, surgical masks, n95 respirators, or surgical masks and eye shields, is paramount to the safety of hcws. 39 regardless of whether the infected patient is receiving niv, has been intubated, or merely has a cough or a sneeze, wearing protective equipment is imperative for any close contact and is one of the best protective measures. for niv use, it is very important to apply and fit the mask tightly to the face before turning on the respirator and removing the mask after turning off the respirator. 32 another key element in preventing patient-to-patient transmission of respiratory infection is rapid patient isolation in a negative pressure room with air being directly exhausted out, or cohorting similarly exposed and infected patients. 42 isolation and patient cohorting are very important regardless of which type of respiratory support is used, because the risk of transmission is uniformly increased in all procedures with airway manipulation and artificial ventilation. 23 reducing the spread of hospital infection and protecting hcws requires continual re-education, staff training, and monitoring infection-control guidelines. by incorporating all of these infection-control measures, our hospitals can be appropriately prepared for the safe and successful use of niv during epidemics. evidence points to niv as a preferred clinical choice for some patients with respiratory failure. [6] [7] [8] [9] [10] the use of niv can contribute to a shorter length of stay in an icu and less dependency on respiratory support compared to invasive ventilation. 19 we emphasize that niv should primarily be allocated for patients with strong and proved indications for niv such as copd, pulmonary edema resulting from heart failure, or neuromuscular diseases. using niv under epidemic conditions, frees up respirators and other icu equipment for patients with respiratory insufficiency who require invasive ventilation. to our knowledge, no prospective, controlled randomized studies have been conducted at present on niv utilization during an epidemic. however, clinical experiences from previous epidemics and reports from hospitals where niv has been used during an epidemic should be systematically reviewed for consideration of future niv use in a variety of clinical settings. the threat of pandemics and other catastrophic events that will place high demands on resources and personnel should catalyze objective considerations of niv use. we consider the use of niv during an epidemic an important strategy that will balance the clinical and ethical obligations addressing the needs of affected individuals and populations. observations on the clinical use of intermittent positive pressure noninvasive face mask ventilation in patients with acute respiratory failure mechanical ventilation: invasive versus noninvasive clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: cochrane systematic review and meta-analysis continuous positive airway pressure by face mask in pneumocystis carinii pneumonia treatment of multiple rib fractures: randomized controlled trial comparing ventilatory with nonventilatory management intermittent positive pressure ventilation via the mouth as an alternative to tracheostomy for 257 ventilator users early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure utilization of noninvasive ventilation in acute care hospitals noninvasive versus conventional mechanical ventilation: an epidemiologic survey should noninvasive ventilation be considered a high-risk procedure during an epidemic? a major outbreak of severe acute respiratory syndrome in hong kong clinical management of human infection with pandemic (h1n1) 2009: revised guidance. geneva, swtizerland: world health organization intensive care adult patients with severe respiratory failure caused by influenza a (h1n1) in spain influenza a in argentina: a study of 337 patients on mechanical ventilation early non-invasive ventilation treatment for severe influenza pneumonia effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome global alert and response: summary of probable sars cases with onset of illness from 1 predicting super spreading events during the 2003 sars epidemics in hong kong and singapore why did outbreaks of severe respiratory syndrome occur in some hospital wards but not in others? infection control measures for operative procedures in severe acute respiratory syndromerelated patients aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. ottawa, on: canadian agency for drugs and technologies in health non-invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome description and clinical treatment of an early outbreak of severe respiratory syndrome (sars) in guangzhou, pr china clinical management of human infection with avian influenza a (h5n1) virus: updated advice 15 exhaled air dispersion distances during noninvasuve ventilation via different respironics face masks guidelines for acquisition of ventilators to meet demands for pandemic flu and mass casualty incidents. irving, tx: american association of respiratory care definitive care for the critically ill during a disaster: a framework for optimizing critical care surge capacity asid (hicsig) position statement: infection control guidelines for patients with influenza-like illnesses, including pandemic (h1n1) influenza 2009, in australian health care facilities pandemic influenza: guidance for infection control in critical care guidance for establishing crisis standards of care for use in disaster situations: a letter report pandemic influenza: implications for preparation and delivery of critical care services allocating scarce resources in disasters: emergency department principles concept of operations for triage of mechanical ventilation in an epidemic crisis standards of care: a systems framework for catastrophic disaster response clinical review: allocating ventilators during large-scale disasters-problems, planning and process lessons learned: protection of healthcare workers from infectious disease risks influenza vaccination of health-care personel guideline for hand hygiene in health-care settings: recommendations of the the health-care infection control practices advisory committee and hicpac/shea/ apic/idsa hand hygiene task force guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings key: cord-346565-vsgbmxzv authors: cascella, marco; mauro, immacolata; de blasio, elvio; crispo, anna; del gaudio, alfredo; bimonte, sabrina; cuomo, arturo; ascierto, paolo antonio title: rapid and impressive response to a combined treatment with single-dose tocilizumab and niv in a patient with covid-19 pneumonia/ards date: 2020-07-27 journal: medicina (kaunas) doi: 10.3390/medicina56080377 sha: doc_id: 346565 cord_uid: vsgbmxzv treatment of acute respiratory distress syndrome (ards) due to covid-19 pneumonia (cards) represents a clinical challenge, requiring often invasive mechanical ventilation (imv). since the pathogenesis of cards it probably involves a direct viral attack to pulmonary and endothelium cells, and immune-mediated inflammation with dysfunctional coagulation, it was suggested to interfere with interleukin-6 (il-6) activity by using the il-6 receptor monoclonal antibody tocilizumab (tcz). we reported the case of a 54-year-old 100 kg male covid-19 patient (bmi 29) with severe respiratory insufficiency featuring dyspnea and hypoxia (spo(2) 89% on room; pao(2) 53 mmhg). despite treatment with antiviral and non-invasive ventilation (niv), after 24 h there was a progressive worsening of clinical conditions with higher fever (40 °c), increased dyspnea, and hypoxia (pao(2)/fio(2) or p/f ratio of 150). the patient was at the limit to be sedated and intubated for imv. he was treated with tocilizumab (8 mg/kg i.v., single shot 800 mg) and niv in the prone positioning. after only 96 h, the clinical, laboratory, and imaging findings showed incredible improvement. there was an important gain in oxygenation (p/f 300), a decrease of c-reactive protein values, and a decrease of the fever. both the neutrophil-to-lymphocyte ratio (nlr) and the derived nlr ratio dropped down to 44%. chest imaging confirmed the favorable response. this case suggested that for cards management efforts are needed for reducing its underlying inflammatory processes. through a multiprofessional approach, the combination of il-6-targeting therapies with calibrated ventilatory strategies may represent a winning strategy for improving outcomes. pneumonia can represent a serious clinical expression of covid19 distress syndrome (ards) [1] . ards is characterized by hypoxemic respiratory failure of different degrees with bilateral lung infiltrates. its treatment represents a clinical challenge and often requires tracheal intubation and invasive mechanical ventilation (imv). in particular, in covid-19-associated ards (cards) over 50% mortality has been reported [1] . despite that at the beginning of the pandemic, early invasive mechanical ventilation was indicated as the optimal strategy for cards management, in covid-19 pneumonia the clinical picture of severe hypoxemia contrasted with the typical ards respiratory mechanics. in most cases of cards, indeed, mechanical properties of the respiratory system surprisingly showed good pulmonary compliance [2] whereas in classic ards the lungs exhibit a reduced ability to stretch and expand itself (i.e., reduced compliance). evidently, cards represents a separate chapter of ards and common therapeutic strategies must necessarily be updated [2, 3] . clinical experience, for example, suggested that non-invasive ventilation (niv) has a role of primary importance in the management of cards as it can improve oxygenation, limiting the work of the respiratory muscles and preventing the onset of the patient self-inflicted lung injury (p-sili) [2] . in this setting, adding the prone position to niv could improve oxygenation, decrease respiratory effort, reducing self-induced lung injury, and avoid the need of intubation and invasive ventilation, which could be particularly useful in the case of reduced availability of intensive care unit (icu) beds [4] [5] [6] . nevertheless, as in cards there is often a rapid and sudden clinical worsening, which mainly affects the respiratory performance in terms of gas exchange, niv can have serious limitations and not infrequently is it necessary to quickly resort to invasive mechanical ventilation. furthermore, dyspneic patients with greater respiratory drive and work of breathing could not tolerate the prone position. in this context, the pathophysiology of the disease can clarify many doubts, offering the possibility of pharmacological strategies, which, in turn, allow treating lung damage through less aggressive approaches. although the exact pathogenesis of this covid-19 pneumonia is still unclear, a complex cascade involving a direct viral attack toward pulmonary and endothelium cells as well as immune-mediated inflammation with dysfunctional coagulation seems to play a pivotal role [7] . for instance, previous investigations conducted on the coronavirus-induced severe acute respiratory syndrome (sars) and the middle east respiratory syndrome (mers), focused on the so-called cytokine storm, expressed as high release of proinflammatory cytokines such as interleukin-6 (il-6), tumor necrosis factor α (tnf-α), il-1β, il-8, and il-12 as well as interferon gamma inducible protein (ip10), macrophage inflammatory protein 1a (mip1a), and monocyte chemo attractant protein 1 (mcp1) [8] . il-6 is a pleiotropic proinflammatory multifunctional cytokine produced by several cell types and can modulate the b-lymphocytes and t regulatory lymphocytes function. as increased tissue and serum levels of il-6 are involved in the pathogenesis of many inflammatory and autoimmune processes, including those expressing cytokine release syndrome (crs) features, it was suggested to interfere with il-6 activity for improving cards outcome [9] . for this purpose, preliminary data from clinical studies indicated that tocilizumab (tcz) could be a winning strategy for reducing the covid-19-associated inflammatory cascade and, in turn, the severity of the disease [10] . tcz is a recombinant humanized monoclonal antibody of the igg1 class, targeting the soluble il-6 receptor (sil-6r) and the membrane receptor (mil-6r). it is prescribed for rheumatoid arthritis, juvenile arthritis, giant cell arthritis, castleman's syndrome as well as for reducing toxicity in immune checkpoint inhibitors-treated patients with steroid refractory [11] , and in cytokine release syndrome due to chimeric antigen receptor t cell therapies [12] . by interfering with the excessive and aberrant sars-cov-2-induced host immune response, the effect of therapeutic strategies for covid-19 management, including approaches of mechanical ventilation, can be probably strengthened. we report a case of cards managed with tcz and niv performed in prone positioning (pp). this combined approach of immunomodulatory therapy with pp-niv led to a rapid clinical improvement associated with an evident gain in the chest computerized tomography (ct) scans. a male 54-year-old 100 kg caucasian patient, bmi 29, was admitted to the hospital for dyspnea and tachypnea (>30 breaths/min), fever (higher than 38 • c), malaise, and dry cough. the clinical evaluation showed hypoxia with a peripheral oxygen saturation (spo 2 ) of 89% in room air. the partial pressure of oxygen (pao 2 ) was 53 mmhg. the patient had no pre-existing comorbidities. he was conscious and hemodynamically stable. laboratory tests indicated a white blood cell count (wbc) 5.1 × 10 9 /l in peripheral blood with a percentage of lymphocytes of 17.5% (0.89 × 10 9 /l), and of neutrophils of 75.0% (3.83 × 10 9 /l). the neutrophil-to-lymphocyte ratio (nlr) was 4.30 and the derived nlr ratio (d-nlr; neutrophil count divided by the result of wbc count minus neutrophil count) was 3.01. eosinophils were 0.034 × 10 9 /l. the elevated c-reactive protein (crp; 193 mg/l), lactate dehydrogenase (ldh; 467 u/l), and ferritin values (937 µg/ml) were also found. the d-dimer was 0.92 µg/ml and prothrombin time 12.2 s. il-6 concentration in plasma was 93 pg/ml. after a short cycle (5 min) of oxygen therapy with a 40% oxygen venturi mask, niv was started due to the lack of response. the ventilation was set in continuous positive airway pressure (cpap) through an oro-nasal mask with end-expiratory positive airway pressure (peep) of 14 cm h 2 o, and a fraction of inspired oxygen (fio 2 ) of 60%. in this stage the patient s condition was not optimal to obtain collaboration for pronation. the diagnosis of covid-19 was confirmed by real-time reverse transcriptase polymerase chain reaction, and he started therapy with lopinavir/ritonavir 400/100 mg (two 200/50 mg) tablets twice daily, hydroxychloroquine 400 mg (two 200 mg) tablets twice a day for the first day, then 200 mg twice a day, azithromycin (500 mg per day), and enoxaparin 1 mg/kg twice daily. despite therapy, in the next 48 h the clinical picture showed no improvement, with a persistent fever (up to 40 • c), and a low pao 2 /fio 2 ratio (150). ct scans confirmed the picture of a severe bilateral inflammatory process ( figure 1 ). thus, the patient received tocilizumab (8 mg/kg i.v., 800 mg). after 2 h the fever disappeared and clinical condition progressively improved, allowing a trial of niv in the prone position that was performed through three cycles of pronation per day. the mean period of each course of prone position was 90 min, with a good tolerance to the technique. medicina 2020, 56, x for peer review 3 of 8 we report a case of cards managed with tcz and niv performed in prone positioning (pp). this combined approach of immunomodulatory therapy with pp-niv led to a rapid clinical improvement associated with an evident gain in the chest computerized tomography (ct) scans. a male 54-year-old 100 kg caucasian patient, bmi 29, was admitted to the hospital for dyspnea and tachypnea (>30 breaths/min), fever (higher than 38°c), malaise, and dry cough. the clinical evaluation showed hypoxia with a peripheral oxygen saturation (spo2) of 89% in room air. the partial pressure of oxygen (pao2) was 53 mmhg. the patient had no pre-existing comorbidities. he was conscious and hemodynamically stable. laboratory tests indicated a white blood cell count (wbc) 5.1 × 10 9 /l in peripheral blood with a percentage of lymphocytes of 17.5% (0.89 × 10 9 /l), and of neutrophils of 75.0% (3.83 × 10 9 /l). the neutrophil-to-lymphocyte ratio (nlr) was 4.30 and the derived nlr ratio (d-nlr; neutrophil count divided by the result of wbc count minus neutrophil count) was 3.01. eosinophils were 0.034 × 10 9 /l. the elevated c-reactive protein (crp; 193 mg/l), lactate dehydrogenase (ldh; 467 u/l), and ferritin values (937 μg/ml) were also found. the d-dimer was 0.92 μg/ml and prothrombin time 12.2 s. il-6 concentration in plasma was 93 pg/ml. after a short cycle (5 min) of oxygen therapy with a 40% oxygen venturi mask, niv was started due to the lack of response. the ventilation was set in continuous positive airway pressure (cpap) through an oro-nasal mask with end-expiratory positive airway pressure (peep) of 14 cm h2o, and a fraction of inspired oxygen (fio2) of 60%. in this stage the patient′s condition was not optimal to obtain collaboration for pronation. the diagnosis of covid-19 was confirmed by real-time reverse transcriptase polymerase chain reaction, and he started therapy with lopinavir/ritonavir 400/100 mg (two 200/50 mg) tablets twice daily, hydroxychloroquine 400 mg (two 200 mg) tablets twice a day for the first day, then 200 mg twice a day, azithromycin (500 mg per day), and enoxaparin 1 mg/kg twice daily. despite therapy, in the next 48 h the clinical picture showed no improvement, with a persistent fever (up to 40 °c), and a low pao2/fio2 ratio (150). ct scans confirmed the picture of a severe bilateral inflammatory process (figure 1) . thus, the patient received tocilizumab (8 mg/kg i.v., 800 mg). after 2 h the fever disappeared and clinical condition progressively improved, allowing a trial of niv in the prone position that was performed through three cycles of pronation per day. the mean period of each course of prone position was 90 min, with a good tolerance to the technique. after 96 h from tcz administration, there was a paramount clinical improvement. dyspnea was resolved, and oxygen saturation was 96% with an important gain in oxygenation (pao 2 /fio 2 ratio 300) and decrease of crp (35 mg/l). there was a rise in lymphocyte percentage (24%; wbc of 3.6 × 10 9 /l with a count of lymphocytes of 0.86 × 10 9 /l). a decreased value was calculated for nlr (2.75) and d-nlr (1.92); both indices dropped up to 44%. there was 0.01 × 10 9 /l of eosinophiles. il-6 concentration increased to 267 pg/ml. the ct scans showed a significant improvement in the inflammatory pulmonary process. although the pathological findings were not completely resolved, there was a rapid and evident reduction of the extensive multiple patchy ground-glass opacities demonstrated in the ct scans before tcz treatment ( figure 2 ). axial unenhanced ct images demonstrated multiple patchy ground-glass opacity with a peripheral and subpleural distribution. various reticular opacities are also detected within fields of ground glass (crazy-paving pattern). carenal and prevascular lymphadenopathy is found. after 96 h from tcz administration, there was a paramount clinical improvement. dyspnea was resolved, and oxygen saturation was 96% with an important gain in oxygenation (pao2/fio2 ratio 300) and decrease of crp (35 mg/l). there was a rise in lymphocyte percentage (24%; wbc of 3.6 × 10 9 /l with a count of lymphocytes of 0.86 × 10 9 /l). a decreased value was calculated for nlr (2.75) and d-nlr (1.92); both indices dropped up to 44%. there was 0.01 × 10 9 /l of eosinophiles. il-6 concentration increased to 267 pg/ml. the ct scans showed a significant improvement in the inflammatory pulmonary process. although the pathological findings were not completely resolved, there was a rapid and evident reduction of the extensive multiple patchy ground-glass opacities demonstrated in the ct scans before tcz treatment (figure 2 ). over the next 24 h, because the pao2/fio2 ratio was stable >300, we started the niv weaning, by progressively reducing both peep and fio2. nine days after tcz administration, the patient performed a spo2 of 98% in room air, and he was discharged from the hospital completely recovered from covid-19 symptoms (figure 3 ). over the next 24 h, because the pao 2 /fio 2 ratio was stable >300, we started the niv weaning, by progressively reducing both peep and fio 2 . nine days after tcz administration, the patient performed a spo 2 of 98% in room air, and he was discharged from the hospital completely recovered from covid-19 symptoms (figure 3 ). covid-19 patients may have severe pictures of respiratory failure [13] . according to the berlin criteria for ards, a p/f value of 150 falls in the category of moderate ards. although generally it corresponds to a mortality of 32% [14] , in cards it is associated to a higher mortality [1] . while at the beginning of the covid-19 crisis it was suggested to prefer the miv adopting it after only a short challenge (1-2 h) of niv-despite awareness that long time miv treatments may lead to ventilator-induced lung injury (vili) and higher risk of infection-a greater knowledge of the pathophysiology of the disease combined with the possibility of using drugs that may interfere with its pathogenic cascade, has drastically changed the therapeutic scenario and, consequently, outcomes. as a consequence, the premises for less aggressive lung ventilation approaches were created. the rationale for niv in ards is the application of the peep and ps. the former works by improving the functional residual capacity, opening collapsed alveoli, and by a redistribution of the perfusion into the lungs. the effect is an enhanced ventilation-perfusion ratio with a lowered intrapulmonary shunt and a better lung compliance. on the other hand, ps reduces muscle fatigue. these effects are enhanced by an early pp and by the possibility of performing pronation cycles for maintaining the advantage obtained [4, 5, 15] . nevertheless, in a context of inflammatory syndrome with severe dyspnea associated with a poor general clinical picture, this therapeutic approach can be difficult to perform. the keystone may be the management of inflammatory underlying processes. as previously found in sars and mers, elevated plasma levels of cytokines including il-6 have been demonstrated also in cards patients. moreover, these findings usually correlate to the severity of the clinical course [13] . il-6 may have a key role in the inflammatory storm, which underlies the covid-19 pathogenesis. recently, ciceri et al. [16] proposed the term of microclots (microvascular covid-19 lung vessels obstructive thromboinflammatory syndrome) for indicating the lung viral damage combined with the inflammatory reaction and the microvascular pulmonary thrombosis. covid-19 patients may have severe pictures of respiratory failure [13] . according to the berlin criteria for ards, a p/f value of 150 falls in the category of moderate ards. although generally it corresponds to a mortality of 32% [14] , in cards it is associated to a higher mortality [1] . while at the beginning of the covid-19 crisis it was suggested to prefer the miv adopting it after only a short challenge (1-2 h) of niv-despite awareness that long time miv treatments may lead to ventilator-induced lung injury (vili) and higher risk of infection-a greater knowledge of the pathophysiology of the disease combined with the possibility of using drugs that may interfere with its pathogenic cascade, has drastically changed the therapeutic scenario and, consequently, outcomes. as a consequence, the premises for less aggressive lung ventilation approaches were created. the rationale for niv in ards is the application of the peep and ps. the former works by improving the functional residual capacity, opening collapsed alveoli, and by a redistribution of the perfusion into the lungs. the effect is an enhanced ventilation-perfusion ratio with a lowered intrapulmonary shunt and a better lung compliance. on the other hand, ps reduces muscle fatigue. these effects are enhanced by an early pp and by the possibility of performing pronation cycles for maintaining the advantage obtained [4, 5, 15] . nevertheless, in a context of inflammatory syndrome with severe dyspnea associated with a poor general clinical picture, this therapeutic approach can be difficult to perform. the keystone may be the management of inflammatory underlying processes. as previously found in sars and mers, elevated plasma levels of cytokines including il-6 have been demonstrated also in cards patients. moreover, these findings usually correlate to the severity of the clinical course [13] . il-6 may have a key role in the inflammatory storm, which underlies the covid-19 pathogenesis. recently, ciceri et al. [16] proposed the term of microclots (microvascular covid-19 lung vessels obstructive thromboinflammatory syndrome) for indicating the lung viral damage combined with the inflammatory reaction and the microvascular pulmonary thrombosis. since in a scenario of multiple organ dysfunction syndrome these thromboinflammatory processes may extend beyond the boundaries of the lung, it is mandatory to identify treatments that, by acting on the pathogenic cascade, can enhance the efficacy of non-pharmacological approaches such as non-invasive ventilation and prone position, for instance through improved tissue oxygenation. thus, although severe ards patients are probably not fitting candidates for niv, this approach can be suggested also in cards featuring a lower pao 2 /fio 2 ratio, especially if performed by adopting the prone position. of note, despite that higher il-6 levels were associated with the need for invasive ventilation due to a more severe disease [17] , in preliminary data on cards patients treated with tcz, favorable outcomes were observed in non-intubated patients [10, 16, 18] . probably, interfering with the inflammatory storm when it is in its greatest acute phase could avoid the need to resort to aggressive therapies and timing of anti-cytokine therapy could be a key issue [19] . specifically an early treatment with tcz could turn off the inflammatory response and avoid the invasive treatments [20] . interestingly, in our case the tcz administration produced an important effect on the systematic inflammatory response expressed as decreased values of crp, nlr, and d-nlr. results from an italian phase ii trial on tcz for cards treatment (nct04317092), and from the phase 2/3, randomized, double-blind, placebo-controlled investigation on the use of the anti-il-6r antibody sarilumab (nct04315298), will certainly provide valuable information on efficacy and safety. to date, although other reports have shown favorable outcomes and imaging improvement after tcz administration [21, 22] , the peculiarity of our case was the rapid (96 h) and impressive positive results after only a single dose of tcz. pending the results of ongoing clinical trials on il-6-targeting therapies for covid-19, our clinical practice suggests that due to the effects of the immune-modulatory agents and through a multiprofessional approach that exploits the skills of immunologist and intensivist/pulmonologist experts in mechanical ventilation, fewer and fewer patients are referred to imv. in patients with severe cards, indeed, reducing lung functional impairment is a priority and often a decisive goal. on these bases, the ventilatory strategies of cards can be revised, resorting above all to the niv and avoiding, when possible, imv and possible ventilation sequelae such as p-sili and vili. although recently, other reports have shown a marked improvement in the clinical-radiological picture, the particularity of the case described is the speed with which the significant results were achieved. probably, the possibility of combining a therapeutic approach focused on the pathophysiology of the disease with a non-aggressive ventilation strategy and conducted by exploiting the advantages of decubitus changes, have led to this exceptional result. risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease covid-19 pneumonia: different respiratory treatments for different phenotypes? the baby lung and the covid-19 era feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to covid-19 (pron-covid): a prospective cohort study respiratory parameters in patients with covid-19 after using noninvasive ventilation in the prone position outside the intensive care unit prone positioning in conscious patients on medical wards: a review of the evidence and its relevance to patients with covid-19 infection covid-19: towards understanding of pathogenesis delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel middle east respiratory syndrome coronavirus: implications for pathogenesis and treatment the cytokine release syndrome (crs) of severe covid-19 and interleukin-6 receptor (il-6r) antagonist tocilizumab may be the key to reduce the mortality why tocilizumab could be an effective treatment for severe covid-19? tocilizumab for the management of immune mediated adverse events secondary to pd-1 blockade a new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy clinical features of patients infected with 2019 novel coronavirus in wuhan acute respiratory distress syndrome: the berlin definition efficacy and safety of early prone positioning combined with hfnc or niv in moderate to severe ards: a multi-center prospective cohort study microvascular covid-19 lung vessels obstructive thromboinflammatory syndrome (microclots): an atypical acute respiratory distress syndrome working hypothesis can we use interleukin-6 (il-6) blockade for coronavirus disease 2019 (covid-19)-induced cytokine release syndrome (crs)? outcomes in patients with severe covid-19 disease treated with tocilizumab. a case-controlled study profiling covid-19 pneumonia progressing into the cytokine stormsyndrome: results from a single italian centre study on tocilizumab versusstandard of care tocilizumab for the treatment of severe covid-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in favorable changes of ct findings in a patient with covid-19 pneumonia after treatment with tocilizumab tocilizumab, an anti-il6 receptor antibody, to treat covid-19-related respiratory failure: a case report the authors would like to thank all members of the multidisciplinary emergency unit for covid-19 campania, naples, italy. the authors declare no conflict of interest. key: cord-267537-akzydy7l authors: dang, ha v.; chan, yee-peng; park, young-jun; snijder, joost; da silva, sofia cheliout; vu, bang; yan, lianying; feng, yan-ru; rockx, barry; geisbert, thomas w.; mire, chad e.; broder, christopher c.; veesler, david title: an antibody against the f glycoprotein inhibits nipah and hendra virus infections date: 2019-09-30 journal: nat struct mol biol doi: 10.1038/s41594-019-0308-9 sha: doc_id: 267537 cord_uid: akzydy7l nipah virus (niv) and hendra virus (hev) are zoonotic henipaviruses (hnvs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. no vaccines or licensed therapeutics currently exist to protect humans against niv or hev. hnvs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (g) and fusion (f) glycoproteins, the main targets of the humoral immune response. here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing niv and hev. cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in niv f and hev f glycoproteins, and prevents membrane fusion and viral entry. this work supports the importance of the hnv prefusion f conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with nivand hev-infected individuals. n ipah virus (niv) and hendra virus (hev) are related zoonotic paramyxoviruses, belonging to the henipavirus (hnv) genus. they cause severe encephalitis and respiratory illness, with fatality rates of 50-100%, and are classified as biosafety level 4 (bsl-4) select agents 1 . unlike several other paramyxoviruses, hnvs have a broad species tropism (as is the case for canine distemper virus 2 ) and can infect animals from at least six mammalian orders 1 . pteropid fruit bats (flying foxes) appear to be the predominant natural reservoir hosts of hnvs 3 . since the first outbreaks of hev in australia in 1994 and of niv in malaysia in 1998, hev repeatedly infected horses in australia with resultant human exposures 4 , while food-borne mediated niv spillovers have occurred nearly every year in bangladesh 5 . furthermore, niv outbreaks have occurred in the philippines and in india 6 . besides asia and oceania, the detection of anti-hnv antibodies in humans and pteropus bats in africa, a continent in which no documented niv or hev outbreaks have occurred, further suggests that future hnv zoonotic emergence is likely to happen 7 . although more than two billion people live in regions threatened by potential hnv outbreaks, there are no clinically approved vaccines or specific therapeutics against these pathogens. paramyxoviruses deliver their genome to the host cytoplasm by fusing their lipid envelope with the cellular membrane to initiate infection. this process requires the concerted action of two surface glycoproteins, attachment (g/h/hn) and fusion (f), which sets the paramyxovirus entry machinery apart from all other class i fusion proteins. g is a type ii homotetrameric transmembrane protein with an ectodomain comprising a stalk and a c-terminal β-propeller head, and the latter domain is responsible for binding to ephrinb2 or ephrinb3 (ephrinb2/b3) receptors [8] [9] [10] [11] [12] . f is a homotrimeric type i transmembrane protein that is synthesized as a premature f 0 precursor and cleaved by cathepsin l during endocytic recycling to yield the mature, disulfide-linked, f 1 and f 2 subunits [13] [14] [15] . viral fusion proteins are believed to exist in a kinetically trapped metastable conformation at the virus surface 16 . upon binding to ephrinb2/b3, niv g has been proposed to undergo conformational changes leading to f triggering and insertion of the f hydrophobic fusion peptide into the target membrane 8, 17, 18 . subsequent refolding into the more stable postfusion f conformation drives merger of the viral and host membranes to form a pore for genome delivery to the cell cytoplasm, as shown for other paramyxoviruses and pneumoviruses 13,19-24 . paramyxovirus g/h/hn and f glycoproteins are the main targets of the humoral immune response and neutralizing antibodies are the key vaccine-induced protective mechanism against measles virus, for example 25 . among the few well-characterized anti-hnv g neutralizing monoclonal antibodies (mabs), m102.4 was previously isolated from a naïve human phage display library and shown to neutralize all known strains of niv and hev [26] [27] [28] . moreover, m102.4 protected ferrets and african green monkeys from hev/niv lethal challenges when administered up to several days post infection [29] [30] [31] [32] . anti-f mouse polyclonal antibodies and hybridoma-secreted mabs were shown to protect hamsters from niv and hev challenge [33] [34] [35] . we further demonstrated that immunization of mice with prefusion niv f or hev f led to strong homotypic serum neutralization titers, with lower heterotypic titers, whereas postfusion f failed to elicit a robust neutralizing response 17 . so far, no information is available about the epitopes recognized by hnv f mabs and their potential for use as therapeutics in humans or to guide reverse vaccinology initiatives. we previously isolated a hybridoma secreting a murine mab that recognizes prefusion niv f and hev f glycoproteins, which we designated 5b3 17 . we report here the cloning, sequencing and humanization of 5b3 (h5b3.1) and demonstrate it bound with high affinity to prefusion niv f and hev f. neutralization assays, carried out under bsl-4 containment, showed that 5b3 and h5b3.1 potently inhibited niv and hev infection of target cells. we determined a cryo-electron microscopy (cryo-em) structure of the niv f trimer in complex with 5b3 and found the antibody binds to a prefusionspecific quaternary epitope that is conserved in niv f and hev f. our structural data, combined with f-triggering and membrane fusion assays, demonstrate that 5b3 locks f in the prefusion conformation and prevents membrane fusion via molecular stapling, providing a molecular rationale for its potency. these results define a critical neutralization epitope on the surface of the niv and hev f glycoproteins and pave the way for the future use of h5b3.1 for prophylaxis or as therapeutic for niv-and hev-infected individuals. 5b3 and h5b3.1 antibodies potently neutralize niv and hev. to understand the humoral immune response directed at the hnv f glycoprotein, we cloned and sequenced the 5b3 neutralizing mab from hybridomas previously obtained upon mice immunization with a prefusion niv f ectodomain trimer 17 . the resulting antibody was subsequently humanized (and designated h5b3.1) to enable future therapeutic use in humans. we used biolayer interferometry to characterize the binding kinetics and affinity of the 5b3 and h5b3.1 fab fragments to prefusion niv f and hev f ectodomain trimers immobilized on the surface of biosensors. the 5b3 fab bound to hev f/niv f with equilibrium dissociation constants of 4.6-10 nm, compared to equilibrium dissociation constants of 31-61 nm for interactions with the h5b3.1 fab (fig. 1a -d and supplementary table 1 ). analysis of the determined association and dissociation rate constants indicate that the weaker binding affinity of h5b3.1, compared to 5b3, largely resulted from an enhanced dissociation rate of h5b3.1 (supplementary table 1) . subsequent neutralization assays were carried out using authentic niv-malaysia (niv-m), niv-bangladesh (niv-b) and hev virions under bsl-4 containment. plaque reduction assays were performed to analyze the neutralization of viruses pre-incubated with varying amounts of 5b3 or h5b3.1 antibodies. we determined mean half-maximal inhibitory concentrations of 1.2 µg ml −1 (5b3) and 0.9 µg ml −1 (h5b3.1) for niv-m, 1.3 µg ml −1 (5b3) and 0.6 µg ml −1 (h5b3.1) for niv-b and 1.4 µg ml −1 (5b3) and 1.3 µg ml −1 (h5b3.1) for hev ( fig. 1e-g) . these results show both 5b3 and h5b3.1 potently inhibited infectious niv and hev, the two hnvs responsible for recurrent outbreaks of lethal encephalitis and respiratory diseases in humans. cryo-electron microscopy structure of 5b3 in complex with the niv f glycoprotein. to elucidate the mechanism of 5b3-mediated neutralization of niv and hev, we determined a cryo-em structure of a stabilized niv f ectodomain trimer in complex with the 5b3 antibody fab fragment at 3.5 å resolution (fig. 2a,b , table 1 and extended data 1). to assist model building, we also crystallized the isolated 5b3 fab fragment and determined its structure at 1.5 å resolution using x-ray crystallography ( table 2 ). in agreement with the features observed in the cryo-em map, the local resolution is highest for most of the niv f and the 5b3 variable domains, including the interface between niv f and 5b3, whereas the fab constant domains are poorly resolved, due to elbow flexibility between constant and variable domains, and were not modeled. the final model includes niv f residues 27-480 with a chain break between residues 105 and 112. 5b3 binds to a quaternary epitope on domain iii of the niv f globular head, with a stoichiometry of three fabs bound to an f trimer (fig. 2a,b , table 1 and extended data 1 and 2). the cryo-em map resolves the four n-linked oligosaccharides present on each niv f protomer (at positions asn67, asn99, asn414 and asn464) and reveals 5b3 recognizes a glycan-free epitope on the f surface. we could not detect an oligosaccharide at position asn64 in the cryo-em reconstruction (fig. 2a,b) , in agreement with previous biochemical studies [36] [37] [38] . all six complementarity-determining regions (cdrs) (and the light chain framework region 2) contribute to the paratope and bury 980 å 2 at the interface with the niv f epitope, which mostly resides within one protomer (fig. 3a,b) . cdrl1 contacts the niv f heptad-repeat a (hra) β-hairpin via electrostatic interactions between gln27 5b3 and lys160 f , gln162 f and thr168 f (fig. 3a -c, extended data 2). cdrl1, cdrl3 and cdrh3 bind to the core β-sheet in domain iii via contacts with both f2 (residues 53-55) and f1 (residues 282-285) subunits (fig. 3a-c) . cdrh2 protrudes at the interface between two niv f protomers and interacts with a segment c-terminal to the central helix and with the upstream helix of a neighboring protomer (fig. 3a -c and extended data 2). comparison with the unliganded niv f structure reveals that 5b3 binding induces a local reorganization (or stabilizes a different conformation) of the hra β-hairpin (residues 160-170) and of residues 248-252 (extended data 3). 5b3 relies on an atypical binding mode to niv f with nearly equal contributions of the heavy (48%) and light (52%) chains to the antibody buried surface area. this, in part, results from the fact that cdrl1 is making a greater contribution to the paratope than the nine residue-long cdrh3 (268 å 2 versus 190 å 2 of buried surface area, respectively), in contrast with the canonical cdrh3-dominated antibody/antigen interfaces. to confirm these findings, we probed the niv f binding ability of single-chain (scfv) chimeric constructs in which either the variable heavy (vh) or variable light (vl) h5b3 chains were replaced with an unrelated chain from a human scfv library. although h5b3 scfv immunoprecipitated full-length niv f, none of the scfv chimeras did, in agreement with the equivalent contributions to binding of the heavy and light chains observed in our structure (fig. 3a,b and extended data 4a). the structural data were further validated using site-directed mutagenesis of selected residues participating in the niv f epitope followed by 5b3-mediated immunoprecipitation to assess residual binding (extended data 4b). we also used the prefusion f specific 12b2 antibody as well as a cell-cell fusion assay to probe the conformational integrity of the f mutants analyzed (extended data 4b,c). the niv f k55a substitution inhibited 5b3 recognition, which is probably explained by the loss of interactions with cdrl1 trp32 5b3 and cdrl3 tyr92 5b3 residues, as visualized in our structure. furthermore, abrogation of 5b3 binding to niv f l53d or l53s probably resulted from reduction of favorable interactions with cdrl1 trp32 5b3 , cdrl3 phe91 5b3 and crh3 tyr102 5b3 . given that the tested mutants bound to the12b2 antibody and retained 40-100% of the wild-type f fusion activity (extended data 4b,c), we conclude that the observed loss of binding largely resulted from specific disruption of interactions with 5b3, without major effects on the overall f structure. analysis of the structure rationalizes the observed cross-neutralization of niv and hev because 35 out of the 39 niv f residues buried upon 5b3 binding are strictly conserved. variable positions are thr81 niv , asn84 niv , thr88 niv and arg336 niv , which are conservatively or semi-conservatively substituted to ser81 hev , thr84 hev , ser88 hev and lys336 hev , respectively (fig. 3d ). isolation of a niv neutralization-escape mutant. as for other rna viruses, the high mutation rate of hnvs could yield variants able to overcome 5b3 inhibition. for example, we showed that passaging niv or hev with anti-hnv g antibodies led to the isolation of viral mutants escaping neutralization by the respective antibody 28, 39 . to assess the possibility of generating 5b3 neutralization-escape virus mutants, such as the aforementioned bindingdeficient f mutants identified by site-directed mutagenesis, we passaged authentic niv for three rounds in the presence of 5b3 in bsl-4 containment. plaque purified resistant viruses were isolated, and viral rna from five niv isolates was reverse-transcribed into cdna for sequencing of the f gene. all five niv escape mutants harbored the same f k55e substitution. this finding supports our aforementioned mutagenesis data because the niv f k55a was completely defective in 5b3 binding. we recombinantly produced the k55e f mutant and observed it could not bind 5b3 while maintaining its ability to interact with 12b2 and to promote wild-type cell-cell fusion activity (extended data 4b,c). these experiments are in full agreement with our structural and biochemical data and show that niv could escape 5b3 neutralization without affecting f-mediated fusion, although the impact of the identified substitution on viral growth is not known. the 5b3 antibody inhibits f-mediated fusion. our structural data suggest 5b3 prevents fusogenic conformational changes leading to membrane fusion by locking niv f in the prefusion state. the antibody recognizes a discontinuous epitope, spanning two neighboring protomers, present only in prefusion f, based on the conformational 3a-c and 4a,b). furthermore, cdrl1 interactions with the hra β-hairpin hinders refolding of the latter motif to contribute to the formation of an elongated central helix, observed in the postfusion f state. this antibody-mediated molecular stapling strategy, involving simultaneous interactions with protein segments that are close to each other in prefusion f but far apart in postfusion f ( fig. 4a,b) , is conceptually equivalent to the disulfide stapling approach implemented for stabilizing the prefusion conformation of measles virus f 40 , respiratory syncytial virus (rsv) f 41 , hev f 42 and piv f 43 glycoproteins. finally, we predict unfavorable steric clashes would occur with a 5b3 antibody bound to a neighboring protomer upon f refolding. to validate the hypothesis that 5b3 locks niv f in the prefusion conformation, we used an in vitro f triggering assay entailing (1) cleavage of the wild-type niv f 0 ectodomain trimer with trypsin, under limited proteolysis conditions, to recapitulate the in vivo cathepsin l-mediated production of f 1 and f 2 14,15 and (2) incubation at 50 °c to promote refolding of the trypsin-cleaved prefusion f trimer to the postfusion conformation 17, 19 . we previously showed peptides derived from the heptad-repeat b (hrb) sequence of niv f or hev f prevent completion of f refolding and are potent inhibitors of fusion and live virus infection 44, 45 . furthermore, when the triggering assay was carried out in the presence of a biotinylated hrb peptide, a conformational intermediate of the fusion reaction was captured and could be used as a reporter of f activation. using this approach, we demonstrate here that addition of 5b3 or h5b3.1 during the triggering assay blocked fusogenic conformational changes in a concentration-dependent manner, whereas a nonneutralizing control antibody (13g5), specific for postfusion f, did not ( fig. 4c,d) . subsequent antibody affinity purification (protein g) of the material not captured by the hrb peptide showed 5b3 (or h5b3.1) remained bound to f (fig. 4d) , supporting the hypothesis that 5b3/h5b3.1 trap niv f in the prefusion conformation. finally, capture of an f intermediate could be partially rescued by raising the temperature to ≥60 °c, indicating that binding of 5b3/h5b3.1 stabilizes niv f by raising the energy barrier for transitioning to the postfusion state (fig. 4e ). in summary, the structural and biochemical data presented here show 5b3/h5b3.1 inhibited fusogenic conformational changes by locking f in the prefusion state and raising the free energy of activation for fusion triggering. to further study the mechanism of action of 5b3/h5b3.1 in the context of a full-length, membrane-embedded f glycoprotein, we carried out cell-cell fusion assays in the presence of varying concentrations of mabs. we observed that 5b3 and h5b3.1 prevented niv f-and hev f-mediated membrane fusion in a concentration-dependent manner, consistent with the expectation that trapping f in the prefusion conformation actually resulted in inhibition of membrane fusion (figs. 4f,g and 5). the paramyxovirus and pneumovirus f glycoproteins are key players of viral entry, promoting fusion of the viral and host membranes through large-scale structural rearrangements 13,20-24 . the f conformation presented to the immune system can be a major determinant of the antibody response elicited by these glycoproteins. previous work showed that most of the rsv-neutralizing activity in human serum is conferred by antibodies specifically recognizing prefusion f 46 . structure-based physical stabilization of the rsv f prefusion state via mutations and fusion to another protein (domain) as well as multivalent display on a computationally designed nanoparticle platform correlated with increased elicitation of neutralizing mabs 22, 41, 47, 48 . prefusion stabilized f also induced greater neutralizing humoral immune responses than postfusion f against parainfluenza viruses in mice and rhesus macaques 43 . however, antibodies present in the sera of mice immunized with human metapneumovirus prefusion or postfusion f ectodomain trimers bound similarly to either protein conformation and equally neutralized virus infectivity, demonstrating that prefusion and postfusion f share most neutralizing epitopes for this virus 49 . we previously established that fusing a gcn4 trimeric motif at the c-terminal end of the niv f and hev f ectodomains resulted in the production of prefusion stabilized trimers that could elicit a neutralizing antibody response in mice 17 . no hnv f mab, however, had been characterized at the molecular level. here, we have sequenced and humanized the 5b3 neutralizing mab and demonstrated its ability to cross-neutralize authentic niv and hev. we show 5b3 and h5b3.1 inhibited membrane fusion by locking f in the prefusion conformation upon binding to a conformational (quaternary) epitope, which is reorganized during the fusion reaction. this mechanism of action rationalizes the potent 5b3/h5b3.1-mediated neutralization of niv and hev entry into target cells and is reminiscent of d25 inhibition of rsv via binding to and stabilization of prefusion f 22 . these findings are also in line with the enhanced properties of rsv and parainfluenza virus prefusion-stabilized f glycoproteins as candidate vaccine immunogens compared to the corresponding postfusion f 41,43,48 . accordingly, the previously developed disulfide-stabilized prefusion hev f 42 , and the corresponding prefusion niv f construct engineered here, bear the promise of eliciting stronger neutralizing antibody titers than gcn4-only stabilized f glycoprotein ectodomains, by preventing refolding to the postfusion conformation. core β-sheet fig. 3 | the 5b3 neutralizing antibody recognizes a conserved quaternary epitope on the niv f glycoprotein. a, ribbon diagram of the niv f trimer in complex with the 5b3 fab fragment. one f protomer is rendered in teal and the other two protomers in grey. only one fab fragment is shown for clarity. b, molecular surface representation of the niv f trimer with the 5b3 cdr loops shown as ribbons, highlighting the quaternary nature of the epitope. c, enlarged view of the interface between niv f and 5b3 with selected residues rendered as sticks. niv f residues are colored teal with oxygen and nitrogen atoms colored red and blue, respectively. in a-c, the 5b3 variable heavy (vh 5b3 ) and light (vl 5b3 ) chains are colored purple and pink, respectively. d, molecular surface representation of the niv f trimer showing the 5b3 footprint colored by residue conservation among niv f and hev f glycoproteins. conservative sub.: conservative substitution; semi-conserv. sub.: semi-conservative substitution. showing the 5b3 footprint colored violet. upon refolding, the 5b3 epitope is reorganized. the latter model was obtained by threading the niv f sequence onto the human parainfluenza virus 3 postfusion f structure 20 (pdb 1ztm). c, 5b3 concentration-dependent inhibition of streptavidin-mediated pulldown of a biotinylated hrb/niv f conformational intermediate complex in a triggering assay. the non-neutralizing control antibody (13g5), which is specific for postfusion f, had no effect. d, niv f triggering assay carried out in the presence of 5b3 or h5b3.1 iggs showing both mabs prevented f fusogenic conformational changes. subsequent protein g immunoprecipitation of f/5b3 and f/h5b3.1 complexes that were not pulled down by the biotinylated hrb peptide indicated the antibodies remain bound to f. e, capture of an f fusogenic conformational intermediate could be partially rescued by raising the temperature to ≥60 °c, as detected by comparing streptavidin-mediated pulldown and protein g immunoprecipitation of f/5b3 and f/h5b3.1 complexes. in a and b, a single 5b3 epitope is colored for clarity. in all panels, precipitated samples were analyzed by western blotting using a rabbit anti-f antibody. f,g, niv f (f) or hev f (g) mediated cell-cell fusion could be inhibited by 5b3 or h5b3.1 in a concentration-dependent manner. d54 is an hiv envelope antibody used as negative control. data shown are mean and s.d. for n = 2 technical replicates. uncropped images for d and e are available in the source data online. so far, m102.4 is the only human mab that has been used for hnv protection studies in ferrets and african green monkeys [29] [30] [31] . murine antibodies have limited clinical use due to their short serum half-life, inability to trigger human effector functions and the risk of mounting an anti-mouse antibody response. we successfully engineered a humanized version of 5b3 (termed h5b3.1), which retained comparable breadth and potency to the parental mouse mab and inhibited f-mediated membrane fusion. therefore, similar to the anti-hnv g m102.4 neutralizing mab, h5b3.1 could potentially be used for prophylaxis or for post-exposure therapy with individuals exposed to niv or hev. between 2010 and 2017, m102.4 was used on a compassionate basis to treat individuals with significant hev or niv exposure risk in australia, the usa and india (https://www. who.int/blueprint/priority-diseases/key-action/nipah/en/). these individuals showed no evidence of infection or known health complications after administration of the mab. the fact that m102.4 was used in humans despite the lack of clinical trials or approval by the fda (or equivalent agencies) emphasizes the urgent need for developing therapeutics and other counter-measures against highly pathogenic hnvs that have fatality rates of 50-100%. escape mutants have been isolated upon hnv passaging with m102.4 39 or with 5b3 (here), but they have never been observed during m102.4 in vivo efficacy tests against niv or hev, putatively due to the very high doses of antibodies utilized in those experiments in conjunction with the effective adaptive immune responses of the subjects. we postulate that similar outcomes could be expected with comparably high doses of 5b3/h5b3.1 mabs. furthermore, neutralization escape mutations to such an f-specific mab could have a potentially negative impact on viral growth, replication and virulence, as observed with mutants obtained with anti-g antibodies 28 . finally, the use of antibody cocktails has been proposed for ebola virus 50-52 or severe acute respiratory syndrome coronavirus (sars-cov) 53 and implemented as a commercially available therapeutic for hepatitis c virus (xtl-6865, xtl biopharmaceuticals) to prevent and/or limit the emergence of such mutants as well as enhance neutralization breadth. we suggest a similar strategy: combining h5b3.1 and m102.4 or other anti-hnv mabs, targeting multiple antigenic sites on g and f, could be implemented for treating future niv and hev infections. any methods, additional references, nature research reporting summaries, source data, statements of code and data availability and associated accession codes are available at https://doi.org/10.1038/ s41594-019-0308-9. expression medium (life technologies), cultured at 37 °c with 5% co 2 and 150 r.p.m. hek293t/17 is a female human embryonic kidney cell line (atcc). hek293t/17 cells (kind gift from g. quinnan) were cultured at 37 °c with 5% co 2 in flasks with dmem + 10% fbs + penicillin-streptomycin + 10 mm hepes. veroe6 cells (atcc) were grown in serum-free medium (vp-sfm, thermofisher) at 37 °c and 5% co 2 . hela-usu and hela-atcc (atcc) cells 12 were maintained in dmem (quality biologicals), supplemented with 10% cosmic calf serum (hyclone), and 2 mm l-glutamine. hela-usu cells, ephrin-b2 and ephrin-b3 negative, (kind gift from a. maurelli, uniformed services university) and hela-ccl2, ephrin-b2 positive (atcc), have previously undergone cytogenetic analysis. other cell lines were not authenticated. cells were not tested for mycoplasma contamination. antibodies and peptides. the rabbit anti-f polyclonal antibody was produced by spring valley laboratories using the niv f ectodomain trimer fused to gcn4 17 as an immunogen. the horseradish peroxidase-conjugated rabbit anti-s-peptide antibody was purchased from bethyl laboratories. anti-f murine monoclonal antibodies were produced as previously described 17 . the n-terminal biotinylated niv f hrb peptide (residues 453-488) 44 was synthesized by global peptide services. niv f and hev f construct. the niv f and hev f ectodomain constructs used for biolayer interferometry and niv f triggering assay include the codon optimized niv f (isolate ummc1; genbank sequence accession no. ay029767) or hev f (isolate horse/australia/hendra/1994) ectodomain (residues 1-487) fused to a c-terminal gcn4 followed by a factor xa sequence and an s-tag (klketaaakferqhmds) cloned in a pcdna hygro (+)-cmv+ vector for transient expression using freestyle 293f cells. for epitope mapping, conversion of specific residues of niv f to alanine, serine, glutamic acid or aspartic acid was performed via site-directed mutagenesis using the quick-change ii sitedirected mutagenesis kit (stratagene). the template for the reactions consisted of a c-terminal s-peptide tagged version of the codon optimized full-length niv f (ummc1 isolate) cloned in the pcdna hygro (+)-cmv+ vector. all mutationcontaining constructs were sequence verified. the niv f ectodomain construct used for cryo-em experiments includes a human codon-optimized niv f ectodomain trimer (amino acid residues 1-494) with a flag tag (dykdddk) introduced between residues l104-v105 and a c-terminal gcn4 motif (a kind gift from h. aguilar-carreno) . this construct was engineered by subcloning into a pbs sk(+) vector and introducing the previously described n100c/a119c substitutions 42 by site-directed mutagenesis using a quikchange kit (agilent) before subsequent subcloning into a pcaggs vector for transient expression in freestyle 293f cells. cloning and sequencing of mab 5b3 cdna. the 5b3 cdna was amplified from hybridomas using a superscript iii cells direct cdna synthesis kit (invitrogen) with random hexamer and igg2-specific primers 54 . pcr amplification of vh and vl was performed using the cdna as a template and degenerate forward primers for the signal sequence or the conserved framework 1 (fr1) of the vh-and vlencoding sequences and reverse primers for the fr4 or the 3′ end of the constant heavy chain 1 (ch1)-and constant light chain (cl)-encoding sequences 54, 55 . the pcr products were cloned into pcr-blunt ii-topo vector (invitrogen) and transformed into one shot top10 chemically competent escherichia coli (invitrogen). plasmids were extracted from colonies and the cloned pcr products were sequenced using m13 forward and reverse primers. humanization of 5b3 to generate h5b3 and h5b3.1. to engineer a humanized version of 5b3, a human scfv library was first generated based on fr1 and fr4 sequence similarity with 5b3. we adapted previously described methods and pcr primers employed for the generation of naive human scfv library constructed from peripheral blood b cells of several healthy donors 56 by using only the vh subfamily iii and κ vl subfamily i primers. vh and vl were first amplified separately from the igm cdna library. for vh, we used forward and reverse primers probing the fr1 and fr4 of vh iii with restriction site sfii added to the 5′ end of the forward primer and (g 4 s) 3 linker sequence added to the 3′ end of the reverse primer. for vl, we used forward and reverse primers probing the fr1 and fr4 of vlκ i with (g 4 s) 3 linker sequence added to the 5′ end of the forward primer and restriction site sfii added to the 3′ end of the reverse primer. the scfv library was assembled by overlapping pcr combining the vh and vl pcr products as template and using the vh iii fr1 sfii forward and vlκ i fr4 sfii reverse primers. the amplified scfv was then cloned into a pcom3x vector harboring a c-terminal hexa-histidine tag. colonies from the scfv library were grown and expressed as previously described 57 . we selected the 12 best expressing clones for dna sequencing based on coomassie blue staining and western blot analysis using an anti-histidine tag antibody. the translated human scfv fr sequences were then aligned against that of 5b3. for humanization of 5b3, conserved human residues from the alignment were identified and replaced into the homologous positions of 5b3 to generate h5b3. to further humanize h5b3, a version named h5b3.1 was generated from h5b3 where one residue on each of the cdr1 and cdr2 and two residues on cdr3 were mutated into conserved human residues based on the sequences from the human scfv library mentioned above. scfv and igg1 constructs. the scfv constructs were designed with vh and vl separated by a flexible linker (g 4 s) 3 , codon-optimized, synthesized by genscript and cloned into a promoter-modified pcdna hygro (+)-cmv+vector 58 with a immunoglobulin κ chain leader sequence and a c-terminal s-peptide tag followed by a hexa-histidine tag. for igg constructs, vh and vl were cloned into a pdr12 vector that harbors the κ cl and igg1 ch fragments as separate open reading frames with independent promoters 59 . subsequently, the entire expression cassette of the heavy and light chain of pdr12-h5b3.1 was amplified and sub-cloned into pcdna hygro (+)-cmv+ vector for the development of stable cell lines. generation of scfv-and igg1-expressing stable cell lines. hek 293t cells grown in d-10 were transfected with different scfv or igg1 constructs using fugene transfection reagent (roche diagnostics). cells were transfected with 2 µg dna and 6 µl fugene per well of a 60% confluent six-well tissue culture plate following the manufacturer's instructions. at 48 h post transfection, the culture medium was either replaced with selection medium (d-10 supplemented with 150 µg ml −1 of hygromycin b, invitrogen) for stable cell line development or harvested for s-protein agarose (emd biosciences) or ni-nta agarose (qiagen) precipitation for transient expression evaluation. to generate a cell line for stable expression, hygromycin-resistant cells were then subjected to two rounds of limiting dilution cloning, as previously described 58 . large-scale expression and purification of igg1. production and purification of mouse iggs (5b3, 12b2 and 13g5) from hybridomas was carried out as previously described 17 . transient expression of h5b3.1 igg1 was carried out by transfecting freestyle 293f suspension cells in serum-free freestyle 293 expression medium (invitrogen) in shaker flasks at a density of 1 × 10 6 cells ml −1 using 293fectin transfection reagent (invitrogen) following the manufacturer's protocol. production of h5b3.1 igg1 from a stable cell line was carried out by culturing the freestyle 293f cells expressing h5b3.1 igg1 in 70 ml of freestyle 293 expression medium in 500 ml shaker flasks at a density of 1 × 10 6 cells ml −1 . the transfected cells or stable cells were allowed to grow for an additional 3-4 days with 50 ml of culture medium added for every subsequent day. culture supernatants expressing igg were collected and centrifuged at 4 °c for 15 min at 5,000g. the supernatant was then filtered through a 0.2 µm low protein binding membrane (corning) and passed through a hitrap protein g hp column (ge healthcare biosciences) equilibrated in phosphate-buffered saline (quality biologicals). the column was washed with five column volumes of phosphatebuffered saline. the bound mab was eluted with 0.1 m glycine ph 2 followed by immediate neutralization with 1 m tris ph 8.0, concentrated, and bufferexchanged into phosphate-buffered saline using an amicon ultra centrifugal concentrator (millipore). generation of fab fragments from igg. the 5b3 fab was obtained by fragmentation of mouse 5b3 igg using pierce mouse igg1 fab and f(ab′)2 preparation kits according to the manufacturer's protocol. the h5b3.1 fab fragment was obtained by fragmentation of h5b3.1 igg with lys-c protease (emd millipore) and affinity purification using protein a agarose resin (genscript). briefly, 1.0 mg igg was incubated with 0.5 µg lys-c for 7 h at 37 °c. the reaction was quenched by addition of pmsf to 1 mm final concentration and the undigested and fc-containing portion of the sample was removed using a protein a resin. the fab-containing flow-through from the protein a affinity step was collected. the fab-containing fraction was concentrated and further purified using a superdex 75 10/300 gel filtration column equilibrated in a buffer containing 50 mm tris ph 8.0 and 150 mm nacl. niv f and hev f ectodomain production. soluble niv f and hev f were produced by transient transfection of freestyle 293f cells at a density of 1 × 10 6 cells ml −1 with the corresponding plasmid using 293-free transfection reagent (millipore) and opti-mem (thermo-fisher) according to the manufacturer's protocol. after five days in a humidified shaking incubator, maintained at 37 °c and 8% co 2 , the cell supernatant was harvested and clarified of cell debris by centrifugation. subsequent affinity purification was carried out using an anti-flag resin (genscript) and elution with 1 mg ml −1 flag peptide dissolved in tris buffer ph 8.0, 150 mm nacl or with s-protein agarose (millipore sigma, novagen) and elution with 0.2 m citric acid ph 2.0 followed by immediate neutralization with 1.0 m tris ph 9.5. the eluted fraction was buffer-exchanged into 50 mm tris buffer ph 8.0, 150 mm nacl using a 30 kda cutoff centrifugal concentrator (millipore). biolayer interferometry. assays were performed with an octet red 96 instrument (fortebio) at 30 °c while shaking at 1,000 r.p.m. all measurements were corrected by subtracting the background signal obtained from biosensors without immobilized hev f or niv f. s-peptide tagged hev f or niv f in phosphate buffered saline at ph 7.4 was diluted to 14 µg ml −1 in 10 mm acetate buffer ph 5.0 before immobilization on n-hydroxysuccinimide-(1-ethyl-3-(3dimethylaminopropyl)carbodiimide hydrochloride (nhs-edc). nhs-edcactivated amine reactive 2nd generation (ar2g, fortebio) biosensors for 300 s. the sensors were then quenched in 1 m ethanolamine (fortebio) for 300 s and incubated in kinetics buffer (kb: 1× pbs, 0.01% bsa, 0.02% tween 20 and 0.005% nan 3 (fortebio)) for 300 s to establish the baseline signal (nm shift). hev f-or niv f-loaded sensors were then immersed in solutions of purified fab (5b3 or h5b3.1) diluted in kb to the desired concentrations for kinetics analysis (300-1.23 nm for 5b3 fab and 900-3.7 nm for h5b3.1 fab). curve fitting was performed using a 1:1 binding model to determine the binding kinetics with fortebio data analysis software. mean k on and k off values were determined with a global fit applied to all data. experiments were performed twice with independent niv f and hev f protein preparations, yielding identical results and kinetic parameters. crystallization, data collection and processing of the 5b3 fab. crystals were grown in hanging drops set up with a mosquito at 20 °c using 150 nl protein solution and 150 nl mother liquor containing 0.2 m magnesium chloride, 0.1 m tris-hcl ph 8.5 and 20% peg 8000. the diffraction dataset was collected at als beamline 5.0.1 and processed to 1.5 å resolution using xds 60 and aimless 61 . the structure was solved by molecular replacement using phaser 62 and s230 sars-cov fab 63 as search model. the coordinates were subsequently improved and completed using buccaneer 64 and coot 65 and refined with buster-tnt 66 and refmac5 67 . the quality of the final model was analyzed using molprobity 68 (score 1.13) and clashscore (3.35) . the percentage of poor rotamers was 0.92%; ramachandran statistics were 98.84% favored and 100% allowed. other crystallographic data collection and refinement statistics are summarized in table 2 . purification of the niv f-5b3 complex. purified flag-tagged niv f n100c/ a119c ectodomain was combined with an excess molar ratio of 5b3 fab and incubated on ice for 1 h before injection on a superose 6 increase 10/300 column (ge healthcare) equilibrated in a buffer containing 50 mm tris ph 8.0 and 150 mm nacl. the fractions containing the complex were quality-controlled by negative staining em, pooled, buffer-exchanged and concentrated. cryo-electron microscopy specimen preparation and data collection. a 3 µl volume of the purified flag-tagged niv f n100c/a119c 5b3 fab complex at a concentration of 0.1 mg ml −1 was applied onto glow-discharged c-flat (cu 200 mesh, cf-1.2/1.3, protochips) holey carbon grids covered with a thin layer of continuous home-made carbon and incubated for 30 s on grids. grids were then plunge-frozen in liquid ethane and cooled with liquid nitrogen, using an fei mk4 vitrobot with a 3.0 s blot time. the chamber was kept at 20 °c and 100% humidity during the blotting process. data acquisition was carried out with the leginon data collection software 69 on an fei titan krios electron microscope operated at 300 kv and equipped with a gatan bioquantum energy filter (slit width of 20 ev) and a gatan k2 summit camera. the nominal magnification was 105,000× and the pixel size was 1.37 å. the dose rate was adjusted to 8 counts per pixel per second and each video was acquired in counting mode fractionated in 50 frames of 200 ms each. a total of 2,686 micrographs were collected with a defocus range between 1.5 and 2.5 µm. cryo-electron microscopy data processing. video frame alignment was carried out with motioncor2 70 . particles were automatically selected using dog picker 71 within the appion interface 72 . initial defocus parameters were estimated with gctf 73 . a total of 380,459 particles were picked, extracted and processed with a box size of 256 pixel 2 and preprocessed using relion 3.0 74 . reference-free twodimensional (2d) classification with cryosparc was used to select a subset of particles, which were used to generate an initial model using the ab-initio reconstruction function in cryosparc 75 . this 3d map was subsequently used as a reference for running 3d classification with c3 symmetry in relion on the entire dataset. 262,879 particles were selected from the set of all picked particles for 3d refinement using relion. ctf refinement in relion 3.0 was used to refine per-particle defocus values and particle images were subjected to the bayesian polishing procedure in relion 3.0 76 and 3d refinement before performing another round of ctf refinement and 3d refinement. the particles were subsequently subjected to another round of 3d classification in relion 3.0 without refining angles and shifts. 38,756 particles from the best class (showing a resolved stem) were used for non-uniform refinement in cryosparc to obtain the final 3d reconstruction at 3.5 å resolution. reported resolutions are based on the goldstandard fsc = 0.143 criterion 77, 78 and fourier shell correlation curves were corrected for the effects of soft masking by high-resolution noise substitution 79 . local resolution estimation and filtering was carried out using cryosparc. data collection and processing parameters are listed in table 1 . model building and analysis. ucsf chimera 80 was used to rigid-body fit the crystal structures of the niv f ectodomain 13 and of the 5b3 fab crystal structure into the cryo-em density. the model was subsequently rebuilt manually using coot 81 and refined using rosetta [82] [83] [84] . glycan refinement relied on a dedicated rosetta protocol, which uses physically realistic geometries based on prior knowledge of saccharide chemical properties 85 and was aided by using both sharpened and unsharpened maps. models were analyzed using molprobity 68 immunoprecipitation. to evaluate the binding of niv f mutants with different antibodies, sub-confluent hek 293t cells were transfected with untagged full-length wild type or one of the mutant niv f constructs using the fugene transfection reagent, as described above. cells were harvested at 48 h post transfection and were lysed in 500 µl buffer containing 0.1 m tris ph 8.0, 0.1 m nacl supplemented with complete protease inhibitor cocktail (roche) and clarified by centrifugation. clarified lysates were added to 2 µg of igg followed by 50 µl of 20% slurry protein g sepharose for samples incubated with iggs or 30 µl of 50% slurry s-protein agarose for those that were not. to evaluate h5b3 chain binding to f, 300 µl of clarified untagged full-length f-expressing hek 293t cell lysate was added to the h5b3 scfv-expressing culture supernatants and precipitated with 30 µl of 50% slurry of s-protein agarose. in all cases, immunoprecipitation/pulldown were performed overnight at 4 °c. the samples were washed three times with a buffer containing 1% triton x-100, 0.1 m tris ph 8.0, 0.1 m nacl and subsequently boiled in reducing sdspolyacrylamide gel electrophoresis (page) sample buffer followed by sds-page and western blot analyses. hrb peptide triggering assay. the capture assay was performed as previously described 17 with the addition of a competition step in the presence of increasing amounts of iggs. briefly, 1 µg of purified s-peptide tagged niv f ectodomain trimer was cleaved with 10 ng of trypsin (new england biolabs) in a 10 μl reaction volume of buffer at 4 °c overnight to generate the mature f1 and f2 subunits. the reaction was stopped with 1 μl of 10× complete protease inhibitor cocktail (roche). subsequently, 2 µg of biotinylated niv f hrb peptide was added in the presence or absence of competing igg. the sample was heated for 15 min at 50 °c, 60 °c, 65 °c or 70 °c and the niv f/hrb complex was subsequently pulled down using 30 µl of 50% avidin-agarose slurry for 1 h at 4 °c (thermo fisher scientific). when indicated, the unbound fraction was pulled down with protein g sepharose. samples were washed three times with a buffer containing 1% triton x-100, 0.1 m tris ph 8.0, 0.1 m nacl and boiled in 50 µl of reducing sds-page sample buffer. to analyze the precipitated product, a 25 µl sample was applied to a 4-12% bt sds-page (invitrogen) followed by western blotting and detection using a rabbit anti-niv f polyclonal antibody. cell-cell fusion assays. fusion between niv f and g glycoprotein-expressing effector cells and permissive target cells was measured using a previously described β-galactosidase assay 89 . briefly, plasmids encoding s-peptide tagged wild-type niv f or each mutant of f and niv g or no dna (control/mock transfection) were transfected into hela-usu effector cells using lipofectamine ltx with plus reagent (thermo-fischer scientific). the following day, transfected cells were infected with vaccinia virus-encoding t7 rna polymerase. hela-atcc cells served as receptor-positive target cells and were also infected with the e. coli lac z-encoding reporter vaccinia virus. cells were infected at a multiplicity of infection of 10 and incubated at 37 °c overnight. cell fusion reactions were conducted by incubating the target and effector cell mixtures at a ratio of 1:1 (2 × 10 5 total cells per well; 0.2 ml total volume) in 96-well plates at 37 °c. cytosine arabinoside (40 µg ml −1 , sigma-aldrich) was added to the fusion reaction mixture to reduce non-specific β-galactosidase production. nonidet p40 (emd millipore sigma) was added (0.5% final concentration) at 2.5 or 3.0 h, and aliquots of the lysates were assayed for β-galactosidase at ambient temperature with the substrate chlorophenol red-d-galactopyranoside (roche). assays were performed in triplicate, and fusion results were calculated and expressed as rates of β-gal activity (change in optical density at 570 nm min −1 × 1,000) in a versamax microplate reader (molecular devices). equal amounts of leftover f/g-expressing effector cells from each fusion reaction were lysed and clarified by centrifugation. the lysates were then subjected to s-protein agarose precipitation followed by sds-page and western blotting to evaluate the expression level of each f mutant as compared to wild type. the individual cell fusion reactions mediated by each mutant were converted to percentages of wild-type fusion activity and normalized with the total expression of f and each f mutant as measured by densitometry from the images of western blot bands using imagequanttl software (ge healthcare biosciences). normalization of each f mutant percentage of wild-type fusion was calculated with the formula: normalized percentage of wild-type fusion = (100/percentage of wild-type expression) × percentage of wild-type fusion. niv and hev f mab neutralization assays. the virus infectivity neutralization concentrations of a control antibody d10 igg2a anti-hiv gp41 90 , 5b3 igg anti-f and h5b3.1 igg1 anti-f were determined for niv and hev using a plaque reduction assay. briefly, antibodies were serially diluted fivefold from 150 μg ml −1 to 1.9 ng ml −1 and incubated with a target of ~100 p.f.u. (plaque-forming units) of niv-m, niv-b or hev for 45 min at 37 °c. virus and antibody mixtures were then added to individual wells of six-well plates of veroe6 cells. plates were stained with neutral red two days after infection and plaques were counted 24 h after staining. neutralization potency was calculated based on p.f.u. for each virus in the well without antibody. the experiments were performed in triplicate with independent virus preparations and duplicate readings for each replicate. mean half-maximal inhibitory concentrations were calculated as previously described 91 . escape mutant analysis. neutralization-resistant niv mutants were generated by incubating 1 × 10 5 50% tissue culture infective dose (tcid 50 ) of each virus with a sub-neutralizing concentration of 40 μg of 5b3 igg, in 100 μl medium for 1 h at 37 °c and then inoculated onto 1 × 10 6 veroe6 cells in the presence of igg at the same concentration. the development of cytopathic effects was monitored over 72 h and progeny viruses were harvested. igg treatment was repeated two additional times, with cytopathic effects developing slowly with each passage. viruses from the third passage were plaque purified in the presence of igg and neutralization resistant viruses were isolated. the experiment was performed in duplicate and the f and g glycoprotein genes of five individual plaques were sequenced. the neutralization titers between wild type and the neutralizationresistant virus were determined using a micro-neutralization assay. briefly, the 5b3 igg was serially diluted two fold and incubated with 100 tcid 50 of the wild-type and neutralization-resistant niv for 1 h at 37 °c. virus and antibodies were then added to a 96-well plate with 2 × 10 4 veroe6 cells per well in four wells per antibody dilution. wells were checked for cytopathic effects three days post infection and the mean half-maximal inhibitory concentrations was determined as the mab concentration at which at least 50% of wells showed no cytopathic effects. reporting summary. further information on experimental design is available in the nature research reporting summary linked to this article. the sharpened and unsharpened cryo-em maps and atomic model have been deposited in the emdb and wwpdb with accession codes emd-20584 and 6tys, respectively. the 5b3 fab crystal structure has been deposited in the wwpdb with accession code 6u1t. uncropped images for fig. 4d ,e and extended data 4 are available online. fig. 1 | cryo-em characterization of the niv f glycoprotein in complex with the neutralizing antibody 5b3 fab fragment. a, representative micrograph. scale bar, 100 nm. b, reference-free 2d class averages. scale bar, 100 å. c, gold-standard (black) and map/model (red) fourier shell correlation curves. dotted lines indicate 0.143 and 0.5 thresholds. d, two orthogonal views of the cryo-em reconstruction colored by local resolution computed using cryosparc. e, enlarged view of the model with the cryo-em reconstruction rendered as a blue mesh. fig. 3 | 5b3 binding is associated with a local structural reorganization of the hra β-hairpin. a, ribbon diagrams of the superimposed 5b3-bound and apo niv f trimers. the 5b3 fab fragments are omitted for clarity. the cyan square highlights the region of the structure shown in b-e. b,c, enlarged views showing the hra conformational change. d,e, enlarged views rotated 45° relative to b and c. in all panels, 5b3-bound and apo-niv f trimers are rendered grey and orange, respectively. in c-e, one 5b3 fab fragment is shown with its heavy and light chains colored purple and pink, respectively, whereas the cyan star indicates clashes that would occur between 5b3 and the hra β-hairpin conformation observed in the apo-niv structure 13 (pdb 5evm). hendra and nipah viruses: different and dangerous cross-species transmission of canine distemper virus-an update henipaviruses: an updated review focusing on the pteropid reservoir and features of transmission hendra virus and nipah virus animal vaccines epidemiology of henipavirus disease in humans outbreak investigation of nipah virus disease in kerala, india evidence for henipavirus spillover into human populations in africa monomeric ephrinb2 binding induces allosteric changes in nipah virus g that precede its full activation host cell recognition by the henipaviruses: crystal structures of the nipah g attachment glycoprotein and its complex with ephrin-b3 ephrinb2 is the entry receptor for nipah virus, an emergent deadly paramyxovirus structural basis of nipah and hendra virus attachment to their cell-surface receptor ephrin-b2 ephrin-b2 ligand is a functional receptor for hendra virus and nipah virus crystal structure of the pre-fusion nipah virus fusion glycoprotein reveals a novel hexamer-of-trimers assembly a mature and fusogenic form of the nipah virus fusion protein requires proteolytic processing by cathepsin l cathepsin l is involved in proteolytic processing of the hendra virus fusion protein viral membrane fusion biochemical, conformational and immunogenic analysis of soluble trimeric forms of henipavirus fusion glycoproteins unraveling a three-step spatiotemporal mechanism of triggering of receptor-induced nipah virus fusion and cell entry refolding of a paramyxovirus f protein from prefusion to postfusion conformations observed by liposome binding and electron microscopy structure of the uncleaved ectodomain of the paramyxovirus (hpiv3) fusion protein structure of the parainfluenza virus 5 f protein in its metastable, prefusion conformation structure of rsv fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody structure of respiratory syncytial virus fusion glycoprotein in the postfusion conformation reveals preservation of neutralizing epitopes structural basis for immunization with postfusion respiratory syncytial virus fusion f glycoprotein (rsv f) to elicit high neutralizing antibody titers immune responses during measles virus infection exceptionally potent cross-reactive neutralization of nipah and hendra viruses by a human monoclonal antibody potent neutralization of hendra and nipah viruses by human monoclonal antibodies escape from monoclonal antibody neutralization affects henipavirus fitness in vitro and in vivo a neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection a neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge therapeutic treatment of nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody pathogenic differences between nipah virus bangladesh and malaysia strains in primates: implications for antibody therapy antibody prophylaxis and therapy against nipah virus infection in hamsters acute hendra virus infection: analysis of the pathogenesis and passive antibody protection in the hamster model immunization strategies against henipaviruses n-glycans on nipah virus fusion protein protect against neutralization but reduce membrane fusion and viral entry role of n-linked glycosylation of the hendra virus fusion protein influence of n-glycans on processing and biological activity of the nipah virus fusion protein crystal structure of the hendra virus attachment g glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody overpassing an aberrant vκ gene to sequence an antiidiotypic abzyme with β-lactamase-like activity that could have a linkage with autoimmune diseases universal pcr amplification of mouse immunoglobulin gene variable regions: the design of degenerate primers and an assessment of the effect of dna polymerase 3′ to 5′ exonuclease activity construction of a large naive human phagedisplayed fab library through one-step cloning antibody fragment expression and purification preparation of recombinant viral glycoproteins for novel and therapeutic antibody discovery scaling-up and production of therapeutic antibodies for preclinical studies how good are my data and what is the resolution? phaser crystallographic software unexpected receptor functional mimicry elucidates activation of coronavirus fusion the buccaneer software for automated model building. 1. tracing protein chains features and development of coot refinement of severely incomplete structures with maximum likelihood in buster-tnt refmac5 dictionary: organization of prior chemical knowledge and guidelines for its use molprobity: all-atom structure validation for macromolecular crystallography automated molecular microscopy: the new leginon system motioncor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy dog picker and tiltpicker: software tools to facilitate particle selection in single particle electron microscopy appion: an integrated, database-driven pipeline to facilitate em image processing gctf: real-time ctf determination and correction new tools for automated high-resolution cryo-em structure determination in relion-3 cryosparc: algorithms for rapid unsupervised cryo-em structure determination a bayesian approach to beam-induced motion correction in cryo-em single-particle analysis prevention of overfitting in cryo-em structure determination optimal determination of particle orientation, absolute hand and contrast loss in single-particle electron cryomicroscopy high-resolution noise substitution to measure overfitting and validate resolution in 3d structure determination by single particle electron cryomicroscopy visualizing density maps with ucsf chimera tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions modeling symmetric macromolecular structures in rosetta3 atomic-accuracy models from 4.5-å cryo-electron microscopy data with density-guided iterative local refinement automated structure refinement of macromolecular assemblies from cryo-em maps using rosetta automatically fixing errors in glycoprotein structures with rosetta emringer: side chain-directed model and map validation for 3d cryo-electron microscopy privateer: software for the conformational validation of carbohydrate structures ucsf chimerax: meeting modern challenges in visualization and analysis viral glycoprotein-mediated cell fusion assays using vaccinia virus vectors antigenic implications of human immunodeficiency virus type 1 envelope quaternary structure: oligomer-specific and -sensitive monoclonal antibodies pseudotype neutralization assays: from laboratory bench to data analysis extended data fig. 2 | architecture of the prefusion niv f glycoprotein. a,b, ribbon diagrams of a niv f ectodomain protomer from the cryo-em structure of niv f in complex with the 5b3 fab fragment. hra, heptad-repeat a; hrb we thank m.m. sauer for his assistance with biolayer interferometry assays and n. zheng for providing access to his crystallization robot. this study was supported fig. 4 | validation of the binding epitope on niv f. a, analysis of h5b3 scfv binding to full-length niv f. scfv chimeric constructs in which the variable heavy h5b3 chain (vh 5b3 ), the variable light h5b3 chain (vl 5b3 ) or both chains were replaced with unrelated chains (vh h vl h ) from a human scfv library were assessed for binding to secreted wild-type niv f. vh 5b3 /vl 5b3 scfv was used as a positive control. western blotting was carried out using an anti-f polyclonal antibody to detect niv f or anti-s-peptide antibody to detect the scfv. b, site-directed mutagenesis of the 5b3 epitope. a panel of s-peptide tagged niv f ectdomain mutants were generated and expressed in hek 293t cells. the f-expressing cell lysates were divided equally and incubated with 5b3, 12b2 or s-protein agarose before immunoprecipitation/pulldown. samples in which mab 5b3 or 12b2 were added were precipitated with protein g sepharose. western blotting detection of the precipitated products was carried out using an anti-s-peptide antibody. the gly247ala substitution was used as positive control. c, cell-cell fusion mediated by the niv f mutants shown in b. data are the mean percentage of wild-type fusion levels for each mutant normalized relative to total f expression, as measured by densitometry of western blot bands. the bars represent the standard error from three separate experiments. key: cord-016897-t71f10kv authors: flores, marco v.; cohen, mark title: preventing airborne disease transmission: implications for patients during mechanical ventilation date: 2013-05-29 journal: noninvasive ventilation in high-risk infections and mass casualty events doi: 10.1007/978-3-7091-1496-4_34 sha: doc_id: 16897 cord_uid: t71f10kv the organisms causing respiratory infections such as influenza are spread in droplets or aerosols or by direct or indirect contact with contaminated surfaces. certain medical procedures have been termed aerosol generating because they are associated with high or augmented inspiratory and expiratory flows, which can increase microbial dissemination. invasive ventilation maneuvers and noninvasive ventilation (niv) fall into that category. we discuss the risk of transmitting these procedures and the strategies for mechanical ventilation in future airborne epidemics with special consideration given to the issue of protecting health care workers (hcws). the organisms causing respiratory infections such as infl uenza are spread in droplets or aerosols or by direct or indirect contact with contaminated surfaces. certain medical procedures have been termed aerosol generating because they are associated with high or augmented inspiratory and expiratory fl ows, which can increase microbial dissemination. invasive ventilation maneuvers and noninvasive ventilation (niv) fall into that category. we discuss the risk of transmitting these procedures and the strategies for mechanical ventilation in future airborne epidemics with special consideration given to the issue of protecting health care workers (hcws). pathogens in the air are spread on particles or droplets. the solid matter may come from skin, and the droplets may be generated from the upper or lower respiratory tract, mouth, or nose and under such circumstances as vomiting, dripping water taps, and diarrhea. respiratory droplets, which can carry microorganisms such as bacteria and viruses, constitute a medium for the transmission of infectious diseases. droplets from the nose and mouth contain bacteria but do not travel >2 m. the concept of airborne transmission and large droplet transmission is based on droplet size. the classic study of airborne transmission by wells revealed the relation between droplet size, evaporation, and falling rate. it was determined by studying the evaporation of falling droplets and is referred to as the wells evaporation-falling curve of droplets. wells postulated what is now a widely accepted hypothesis of the distinction between droplet size and airborne transmission routes. small droplets start to evaporate after release, and thus change their size resulting in droplet nuclei that are suffi ciently small to remain suspended in air for a long time and still be infectious. large droplets (>100 μm) can settle on the ground before they become droplet nuclei [ 1 , 2 ] . most respiratory droplets are <100 μm in diameter and evaporate rapidly in the surrounding environment. they become droplet nuclei, which are suspended in the air or are transported away by airfl ow. the size distribution of droplets is a matter of great debate, but in general various particle sizes are generated: large droplets (>20 μm) that fall directly to the ground or surface; medium-sized particles (5-20 μm), fall at a slower rate or remain temporarily suspended by air currents and evaporate; to become droplet nuclei (aerosol) particles <5 μm in diameter, which remain suspended for longer periods of time [ 1 , 2 ] . studies have demonstrated that particles <10 μm in diameter are more likely to cause infection in the lower respiratory tract [ 3 , 4 ] . the suspension of these droplet nuclei may cause infection over greater distances and increase the duration of infection risk following generation of the initial respiratory aerosol. in addition, the concentration of particles in the secretion and the infectious dose of the pathogen affect the risk of infection. droplets in the respirable range (~5 μm) may play a signifi cant part in transmission. a few studies have quantifi ed the viral load in droplets or aerosols [ 5 ] . an observational study [ 6 ] of infl uenza a and infl uenza b in exhaled breath showed viral rna in one-third of infected patients. also, 99 % of the particles had a diameter <5 μm when sampled during tidal breathing. although some individuals recover from seasonal or h1n1 infl uenza after having experienced minimal symptoms, a subgroup of high-risk patients develop complications, including respiratory failure. with the appearance of more pathogenic strains, such as h5n1, respiratory insuffi ciency may occur in >50 % of those affected. these patients are managed with antiviral therapy and antibiotics for secondary bacterial pneumonia. however, but the mainstay of management is supportive respiratory care, which includes titrated oxygen therapy for hypoxemic patients and ventilatory support for those with respiratory insuffi ciency [ 7 , 8 ] . in contrast to the situation regarding severe acute respiratory syndrome (sars) or tuberculosis prevention in hcws, little attention has been given to the importance of hcws personal protective equipment (ppe) (gowns, gloves, masks) for prevention and management of infl uenza. this situation has arisen because vaccination of hcws has been shown to reduce or prevent nosocomial transmission. it seems prudent for nonvaccinated workers to wear n-95 masks, particularly during high-risk procedures or with very ill patients. there is limited evidence that upperair ultraviolet light is effective in reducing infl uenza transmission rates. some medical procedures have been termed aerosol-generating procedures (agps) as their most common feature is that they are associated with high or augmented inspiratory and expiratory tidal fl ows, which may increase viral aerosol dissemination. the list of agps [ 5 ] include bronchoscopy, airway intubation, and invasive ventilation maneuvers such as open suctioning, cardiopulmonary resuscitation, niv, and continuous positive airway pressure (cpap) therapy, high-frequency oscillation ventilation, and induction of sputum. certain other procedures, such as delivery of nebulized medication therapy and high-fl ow o 2 , are considered possible aerosol generators but of lesser infective risk. there is an association between some of these agps and an increased incidence of sars in hcws with super-spreading events on the wards [ 9 ] . much of the evidence for the link between agps and increased transmission of respiratory viral infection was generated during the sars epidemic. in toronto, china, and singapore, hcws constituted approximately 20 % of the critical care cases. infection rates were higher in doctors and nurses carrying out endotracheal intubation [relative risk (rr) 13.29, 95 % confi dence interval (ci) 2.99-54.04, p = 0.03], and nurses caring for sars patients receiving niv may have been at increased risk (rr 2.23), but these fi ndings did not reach signifi cance [95 % confidence interval (ci) 0.25-21.76, p = 0.5] [ 10 ] . in a case-control study of the dissemination of sars from an index case to other patients on the same ward, yu et al. [ 9 ] showed an increased risk associated with the index patient requiring oxygen or bilevel niv. case reports [ 11 , 12 ] have also linked transmission of infection to nebulizer use in the index patient. however, patient variables are also important factors to consider: sicker patients have a higher viral load and are more likely to require oxygen and ventilator support, and those with underlying asthma require nebulizer therapy and cough more because of airway hyperreactivity. both settings increase the risk of aerosol transmission. there is additional evidence concerning agps and the risk they present to hcws. experimental studies that have investigated airfl ows around oxygen masks and during niv [ 13 -18 ] . these studies used human simulator models or normal subjects mimicking respiratory distress. hui et al. [ 16 ] examined smoke particle dispersion from the lungs of a human simulation model receiving oxygen therapy, frequently used in the treatment of patients with respiratory failure. the authors found that a jet plume of smoke could be generated from exhaust holes up to 0.45 m from the mask. although this model provides a visual image of smoke aerosol behavior, and the possible zone of transmission risk, it is not necessarily representative of the behavior of a respiratory aerosol and infectious particles contained therein. two similar studies were carried out on oxygen masks. one indicates that oxygen mask usage might contribute to droplet-respiratory transmission of sars [ 14 ] . the other observed a visible range of the smoke plume of 0.08-0.40 m depending on the type and fl ow rate of the mask used [ 19 ] . simonds et al. [ 20 ] evaluated the characteristics of droplet/aerosol dispersion around delivery systems during niv, o 2 , nebulizer treatment, and chest physiotherapy by measuring the droplet size, geographical distribution of droplets, decay in droplets over the time after the intervention was discontinued, and the impact of modifying the niv circuit in clinical practice. three groups of patients were studied: normal control subjects; subjects with coryzal symptoms; adults with chronic lung disease who were admitted with an infective exacerbation. each group received o 2 , niv using a vented mask system, and a modifi ed circuit with a nonvented mask and an exhalation fi lter. all received nebulized saline and a period of standardized chest physiotherapy. droplet counts in mean diameter sizes ranging from 0.3 to >10.0 μm were measured with a counter placed adjacent to the face and at 1 m distance from the patient at the height of the nose/mouth of an average hcw. niv using a vented mask produce large droplets (>10 μm) in patients ( p = 0.042) and coryzal subjects ( p = 0.044) compared with baseline values but not in normal controls ( p = 0.379). this increase in large droplets was not seen using the niv circuit modifi cation. chest physiotherapy produced droplets predominantly >10 μm ( p = 0.003), with the droplet count (as in the niv patients) falling signifi cantly by 1 m. o 2 did not increase the droplet count in any size range. nebulized saline delivered droplets in the small and medium size aerosol/droplet range, in keeping with the specifi ed performance characteristics of the device, but did not increase the large-droplet count. preliminary analyses suggest that droplet counts fall to within a baseline range within 20-40 min of discontinuing the niv and chest physiotherapy. in conclusion, niv and chest physiotherapy are droplet-(not aerosol-) generating procedures, producing droplets >10 μm. because of their large mass, most fall on local surfaces within 1 m. the only device producing an aerosol was the nebulizer. the output profi le is consistent with nebulizer characteristics rather than dissemination of large droplets from patients. these fi ndings suggest that hcws who are providing niv and chest physiotherapy and are working within 1 m of an infected patient should have a high level of respiratory protection. infection control measures designed to limit aerosol spread (e.g., negative-pressure rooms) may have less relevance. tran et al. [ 21 ] systematically reviewed the literature regarding the risk of transmitting acute respiratory infections to hcws exposed to patients undergoing an agp compared with the risk of transmission to hcws caring for patients not undergoing an agp. the outcome of interest was the risk of acute respiratory infection. they identifi ed fi ve case-control and fi ve retrospective cohort studies that evaluated transmission of sars to hcws. the procedures reported to present an increased risk of transmission included tracheal intubation [ n = 4, cohort: odds ratio (or) 6.6 (2.3-18.9); n = 4, case-control study: or 6.6 (4.1-10.6)] and niv [ n = 2, cohort: or 3.1 (1.4-6.8)]; tracheotomy [ n = 1, case-control: or 4.2 (1.5-11.5)]; and manual ventilation before intubation [ n = 1, cohort: or 2.8 (1.3-6.4)]. other intubation-associated procedures, endotracheal aspiration, suction of body fl uids, bronchoscopy, nebulizer treatment, administration of o 2 , high-fl ow o 2 , manipulation of o 2 masks or bilevel positive airway pressure (bi-pap) masks, defi brillation, chest compression, insertion of a nasogastric tube, and collection of sputum were not signifi cant. these fi ndings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of sars transmission to hcws or were a risk factor for transmission. the most consistent association across multiple studies was tracheal intubation. the results of this report should not be generalized to all acute respiratory infections because the evidence available is strictly limited to sars. noninvasive ventilation and continuous positive airway pressure are likely to play a minor role in the management of moderate to severe acute lung injury caused by infl uenza or secondary bacterial pneumonia, or in patients with multisystem failure. however, niv was used successfully in some sars cases [ 22 ] . there is also potential for niv to reduce the need for intubation in patients with infl uenza pneumonia or chronic respiratory disease, facilitate extubation, and widen the provision of ventilator support outside the intensive care unit (icu). it may also be used as ventilator care in patients with chronic obstructive pulmonary disease, congestive cardiac failure, and other serious co-morbidities. niv is sometimes used to palliate symptoms in those with end-stage disease in whom icu admission is not indicated [ 23 ] . these indications should be set against the risk of droplet dissemination during the delivery of niv. despite the study of simonds et al. [ 20 ] , which indicated that niv generates large droplets adjacent to the patient that fall significantly at 1 m from the patient, and that adding a circuit using a nonvented mask plus a fi ltered exhalate reduces the number of large droplets produced, there is still concern about dispersion of infectious particles. nevertheless, in a hong kong hospital where more than 20 patients were placed on noninvasive positive ventilation, all hcws on the ward performed meticulous infection-control procedures and used ppe. despite the intense exposure, none became infected with sars [ 24 ] . patient selection is important for niv as it has not been shown to improve the mortality rate among patients with acute respiratory distress syndrome (ards) and may be not suitable for patients in whom short-term improvement is not expected [ 25 , 26 ] . protection of the hcw during mechanical ventilation includes isolation of infected patients, use of ppe, and strict hand hygiene by all. the world health organization and the centers for disease control and prevention have issued guidelines that recommend the use of standard, contact, and airborne protection, including respirators of n-95 standard or higher, which fi lter at least 95 % of particles that are ≥1 mm with <10 % face seal air leak. these fi lters not only protect against virus-transmitted diseases but also against tuberculosis (tb), fi ltering at least 95 % of the 3-to 5-mm tb bacilli out of the air inhaled by hcws. the need for n-95 masks depends on the mode of transmission. if transmission is solely by droplet, face shields, eye protection, and surgical masks are adequate. however, if transmission is airborne, n-95 masks should be used. as reviewed earlier, there is evidence that airborne transmission of sars occurred, at least from the super-spreaders or during aerosol-generating activities such as intubation or suctioning. knowing that super-spreaders are identifi ed only in retrospect, it may be prudent for workers to wear n-95 masks at all times. standard personal protective equipment includes n-95 masks, gloves, gowns, caps, and face shields or goggles [ 26 , 27 ] . all staff should be mask fi t-tested to ensure adequate seal. when performing high-risk procedures such as intubation, bag-mask ventilation, or bronchoscopy, protection should be enhanced with powered air-purifying respirators. also, the hcw should be aware that these procedures have been associated with increased risk of infection transmission and should upgrade to airborne infection control precautions [ 28 ] (table 34 .1 ). in view of the high risk of disease transmission during endotracheal intubation, airway management protocols have been proposed: early intubation should be performed, preferably in the icu, rather than performing a crash intubation on the ward. adequate sedation and neuromuscular blockade is recommended during intubation to minimize cough and dispersion of respiratory secretions. finally, the procedure should be performed by the most experienced person available to minimize the dispersal of infectious particles and reduce the number of individuals exposed during intubation [ 29 ] . measures to minimize respiratory droplet transmission include using in-line suctioning to maintain the ventilator circuit as a closed system. humidifi cation should be done via heat-moisture exchangers with viral-bacterial fi lter properties rather than heated humidifi ers. each ventilator should have two fi lters-one between the inspiratory port and ventilator circuit and the other between the expiratory port and ventilator circuit-to provide additional protection from exhaust gases and minimize ventilator contamination [ 26 ] . other general recommendations include using a unidirectional/displacement ventilation system for a single patient room. it should not be used in a multi-bed ward where the potentially aerosol-transmitted infection patient source is unknown as this ventilation system may unintentionally disseminate the infection throughout the ward to other patients. hence, the situation where such a ventilation system is used needs to be considered carefully. even though an ideal isolation unit is fi tted with a negative-pressure system and sliding glass doors (to reduce airfl ow generated by traditional hinged doors), it is possibly the movement of people in and out of the room that produces the most signifi cant airfl ow. of course, it is impossible to prevent such movement in a health care facility, but reducing the number of times the room is entered or exited can reduce the volume of potentially infected air exchanged across the doorway. an essential component of an infection-control strategy is staff training. clear management protocols must implemented, including the use of ppe, monitoring staff health, quarantining staff, transport of patients, transfer to the icu, airway management, aerosol generating procedures, environment and equipment disinfection, and visitation policies. the health care environment could be an important reservoir for viruses, bacteria, and fungi during outbreaks, given their proven ability to survive on surfaces and to become airborne. changes in temperature and humidity in hospitals could have relevance for the viability of microorganisms and their spread to other patients. adequate ventilation is necessary to dilute the airborne microbial load. heat and humidity need to be controlled. it is recommended that upper and lower limits for temperature and humidity be specifi ed according to the outbreak facial respirator (eu ffp2 or us niosh certifi ed as n-95) eye protection (goggles or a face shield) clean nonsterile, long-sleeved gown gloves (some procedures required sterile gloves) procedures performed in an adequately ventilated room (>12 air changes per hour) avoidance of unnecessary individuals into the room attention to hand hygiene before and after patient contact and after removing personal protective equipment pathogen and that air changes at the patient level be tested regularly, especially after any restriction to airfl ow. it is important for intensive care providers to be prepared to meet the challenge of large-scale airborne epidemics causing mass casualty respiratory failure. previous outbreaks have exposed the vulnerability of hcws and highlighted the importance of establishing stringent infection control and crisis management protocols. there should be an established lung-protective, low tidal volume strategy for treating patients with acute lung injury or ards who require mechanical ventilation. the use of niv remains controversial. current infection-control policies that limit or prohibit the use of niv as a high-risk intervention are based largely on supposition [ 30 ] . standard contact and airborne precautions should be instituted in the icu, with special care taken when aerosol-generating procedures are performed (table 34. 2 ). airbone transmission of disease in hospitals preventing airbone disease transmission: review of methods for ventilation design in health care facilities transmission of infl uenza: implications for control in health care settings the airbone transmission of infection in hospital buildings: fact or fi ction? a review of the risks and disease transmission associated with aerosol generating medical procedures infl uenza virus in human exhaled breath: an observational study critical care services and 2009 h1n1 infl uenza in australia and new zealand hospitalised patients with h1n1 infl uenza in the united states why did outbreaks of severe acute respiratory syndrome occur in some hospitals wards an not others? transmission of severe acute respiratory syndrome during intubation and mechanical ventilation a major outbreak of severe acute respiratory syndrome in hong kong index patient and sars outbreak in hong kong dispersal of respiratory droplets with open vs closed oxygen delivery masks. implications for the transmission of severe acute respiratory syndrome noninvasive positive-pressure ventilation. an experimental model to assess air and particle dispersion airfl ows around oxygen mask. a potential source of infection? exhaled air dispersion during oxygen delivery via a simple oxygen mask key major recommendations • the evidence regarding the risk of transmission during niv is confl icting and unclear there have been reports of niv being effective in treating patients during an epidemic, reducing the need for intubation • niv should be used especially in a pandemic scenario when the demand for mechanical ventilation support is overwhelming health care workers performing niv during an airborne epidemic should use standard, contact, and airborne protection, including respirators of n-95 standard or higher exhaled air dispersion distances during noninvasive ventilation via different respironics face masks exhales air an aerosolized droplet dispersion during application of a jet nebulizer airfl ow an droplets spreading around oxygen mask: simulation model for infection control research evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebulizer treatment and chest physiotherapy in clinical practice: implications for management of pandemic infl uenza and other airbone infections aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome noninvasive mechanical ventilation. theory, equipment and clinical applications the critical ill avian infl uenza a (h5 n1) patient avian infl uenza (h5 n1): implications for intensive care mechanical ventilation in an airbone epidemic pandemic infl uenza: implications for preparation and delivery of critical care services clinical management of pandemic 2009 infl uenza a (h1n1) intubation of sars patients: infection and perspectives of healthcare workers should noninvasive ventilation be considered a high-risk procedure during an epidemic? key: cord-312864-km07zhn1 authors: potalivo, a.; montomoli, j.; facondini, f.; sanson, g.; lazzari agli, l. a.; perin, t.; cristini, f.; cavagna, e.; de giovanni, r.; biagetti, c.; panzini, i.; ravaiolo, c.; bitondo, m.; guerra, d.; giuliani, g.; mosconi, e.; guarino, s.; marchionni, e.; gangitano, g.; valentini, i.; giampaolo, l.; muratori, f.; nardi, g. title: sixty-day mortality among 520 italian hospitalized covid-19 patients according to the adopted ventilatory strategy in the context of an integrated multidisciplinary clinical organization: a population-based cohort study date: 2020-08-15 journal: nan doi: 10.1101/2020.08.13.20174615 sha: doc_id: 312864 cord_uid: km07zhn1 background: among covid-19 patients, the decision of which ventilation strategy to adopt is crucial and not guided by existing outcome evidence. we described the clinical characteristics and outcomes of hospitalized covid-19 patients according to the adopted respiratory strategy. methods: population-based cohort study including all covid-19 patients (26/02/2020-18/04/2020) within rimini italian province. hospitalized patients were classified according to the maximum level of respiratory support: oxygen supplementation (group oxygen), niv (group niv-only), imv (group imv-only), and imv after a niv trial (group imv-after-niv). sixty-day mortality risk was estimated with a cox proportional hazard analysis adjusted by age, sex, and administration of steroids, canakinumab, and tocilizumab. findings: we identified 1,424 symptomatic patients: 520 (36.5%) were hospitalized, the remaining 904 (63.5%) were treated at home with no 60-days death. according to the respiratory support, 408 (78.5%) were assigned to oxygen, 46 (8.8%) to niv-only, 25 (4.8%) to imv-after-niv, and 41 (7.9%) to imv-only groups. there was no significant difference in the p/f at imv inception among imv-after-niv and imv-only groups (p=0.9). overall 60-day mortality was 24.2% (oxygen: 23.0%; niv-only: 19.6%; imv-after-niv: 32.0%; imv-only: 36.6%; p = 0.165). compared with oxygen group, the 60-day mortality risk significantly increased for imv-after-niv (hr 2.776; p=0.024) and imv-only group (hr 2.966; p=0.001). conclusions: this study provides a population-based figure of the impact of the covid-19 epidemic. a similar 60-days mortality risk was found for patients undergoing immediate imv and those intubated after a niv trial. many patients had a favorable outcome after prolonged imv. more than 650,000 people died worldwide from the coronavirus-disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2). the percentage of covid-19 patients requiring non-invasive (niv) or invasive mechanical ventilation (imv) is unclear and strongly affected by the hospital organization and the availability of resources. three studies from china, us, and gemany reported the use of imv among hospitalized covid-19 patients to be 2.3%, 12%, and 17%, respectively. 1-3 icu-mortality among mechanically ventilated covid-19 patients varies from 25% to 97%. [2] [3] [4] [5] [6] [7] [8] [9] [10] such wide variations may have different explanations. first, few studies included all patients hospitalized for covid-19 able to provide a complete overview of characteristics and outcomes of covid-19 patients that required hospitalization. second, information regarding the respiratory management of covid-19 patients has been mainly described in the setting of the intensive care units (icus). 4, 8, 9, 11 thus, the number of hospitalized covid-19 patients treated with oxygen supplementation and niv has been markedly underreported leading to inaccurate information regarding the overall use of the different respiratory supports and outcomes. third, most previous reports included a percentage of patients still admitted at the icu at the end of the follow-up ranging from 2.3% 8 to 71% 2 and this may have led to different degrees of inaccuracy in estimating icu-mortality. finally, icu beds and human resources availability is likely to vary across different areas and it has not been generally described in clinical studies, affecting generalizability of the results. 12 the province of rimini in northern italy was one of the areas more severely affected by the covid-19 outbreak. on march 7 th , rimini province was declared "red zone" due to the high number of infected people and, therefore, it was isolated with no possibility of entry or exit. using clinical and demographics information routinely collected in a unique database including all residents in the entire province, we performed the present population-based cohort study with the following aims: 1) to describe the characteristics of hospitalized covid-19 patients, 2) to examine patient outcomes overall and stratified by the adopted respiratory support, 3) to describe the organization of local healthcare system. setting covid-19 patients admitted to the rimini hospital were retrieved in the present observational population-based cohort study, following the strengthening the reporting of observational studies in epidemiology (strobe) reporting guideline. the italian national public healthcare system provides homogeneous and free access to any level of appropriate treatment to all the people including irregular immigrants through the hospital network, family doctors, and district health systems. the province of rimini consists of approximately 340,000 inhabitants and is served by a network of five public hospitals, with rimini hospital being the largest and providing up to 600 beds. since the beginning of the outbreak and for the entire duration of this study, rimini hospital was identified as reference hospital for all covid-19 positive or suspected patients. with the increase of admitted patients, 340 hospital bedsincluding 80 in two newly opened wards-were progressively dedicated to infected subjects and 28 negative pressure rooms -eight set up at emergency department (ed) and 20 already available in the infectious diseases ward-were dedicated to patients requiring niv. during the first decade of march, the number of icu beds was progressively increased from 20 to 53, of which 48 dedicated to covid-19 patients and five to non-covid-19 patients. non-covid-19 patients exceeding local availability were transferred to another nearby hospital equipped with 10 icu beds. all patients evaluated at one of the five eds of the province from february, 26 to april, 18 2020 presenting symptoms suspicious for covid-19 infection (i.e. fever and/or respiratory symptoms) and tested for the sars-cov-2 (real-time rt-pcr) 13 were considered for inclusion. patients with positive swab, as well those with chest x-ray or ct scan evidence of covid-19-related pneumonia despite a negative swab were included. the more stable patients were discharged home and entrusted to the primary care, while patients identified to be at high risk for complications based on symptoms severity and associated comorbidities were admitted at the hospital and represented the study population. all included patients with a first negative swab had at least a positive subsequent swab during the same hospitalization except those patients that died at the ed before a second swab. a daily meeting -always attended by the heads of the emergency, infectious disease, pneumology, radiology, and intensive care departments-was planned regardless of the holidays or sundays respecting airborne and contact transmission precautions, with the aim to ensure a homogeneous and standardized treatment to all covid-19 patients. every day the relevant clinical information (e.g., comorbidities, respiratory status, medical treatments, and active clinical conditions) of the critically ill cases were updated and the overall therapeutic stewardship to be adopted (e.g., off-label medications, change in the respiratory support) was collegially discussed and agreed. moreover, for each patient the appropriate treatment to adopt in the event of worsening conditions was planned, taking into account the limitation of the available resources. all decisions were recorded and promptly communicated to physicians and nurses working at all covid-19 wards, comprising the icu. oxygen administration via ventimask or mask with reservoir was considered the standard of care for moderate/severe patients, while niv (comprising continuous positive airway pressure, cpap) and imv following tracheal intubation were chosen for the most critical cases. to avoid airborne viral transmission, high flow nasal cannulae were used only for respiratory weaning in patients become negative and helmet was identified as the only interface to be used for niv. conditions leading to the decision to start imv were: respiratory fatigue, new hemodynamic instability, or worsening of gas exchange notwithstanding oxygen/niv, also considering prognostic criteria and resources availability (e.g., icu beds and mechanical ventilators). according to the level of the respiratory support, the study population was divided in the following subgroups: oxygen (patients receiving no more than oxygen supplementation); niv-only (patients receiving no more than niv); imv-after-niv (patients undergoing imv after a failed niv trial); imv-only (patients starting imv at hospital admission or after a trial with oxygen). for the whole population, demographic data were retrieved by an administrative and clinical database (maria db, log 80, forlì-italy) and information about administered off-label medications related to the covid-19 treatment (i.e. hydroxichloroquine, antivirals, steroids, canakinumab, and tocilizumab) were collected by clinical documentation. for patients treated with niv and/or imv the charlson comorbidity index was computed, 14 and the spo2 at the hospital admission, the pao2/fio2 (p/f) ratio at the inception of niv and imv, and the duration of ventilatory supports were collected. for those patients the extent of lung damage was estimated from the chest radiogram using the brixia score: each lung was transversally divided into three sectors and to each obtained sector a score ranging from zero (no alteration) to three (interstitial-alveolar infiltrates) was assigned (total score range: 0-18). 15, 16 for patients admitted to the icu (i.e., imv-after-niv and imv-only), the simplified acute physiology score ii (saps 2) 17 and the sequential organ failure assessment (sofa) score 18 at icu admission were computed and the possible implementation of tracheostomy and renal replacement therapy were documented. all patients were followed up to 60 days from hospital admission. the condition of being dead or alive at this time constituted the main study endpoint. accordingly, data collection was concluded on june 18, 2020 to ensure at least 60 days of observation to the patients included last. the investigation conforms with the principles outlined in the declaration of helsinki. the ausl della romagna institutional review board approved the project (registration number nct04348448) with a waiver of informed consent. no additional procedure or investigation potentially related to the study was requested or provided. continuous variables were described as mean ± standard deviation. the differences between the means were analysed by a paired or unpaired student's t-test, as appropriate, after considering whether the subgroups had equal variance using levene's test. one-way analysis of variance (anova) was applied for all comparisons between the subgroups. the nominal variables were presented as numbers and percentages and compared either through  test or fisher's exact test, as appropriate. the ability of the p/f measured before a niv trial to predict niv failure (i.e., death or need of imv) was tested by calculating the area under the receiver operating characteristics curve (auc). the maximum youden index (j) was considered as the optimal p/f cut-off value. sixty-day mortality was computed using kaplan-meier technique overall and among groups. the mantel-cox log-rank test was adopted to assess differences among the survival rates. a multivariate cox proportional hazard analysis was used to estimate 60-day mortality risk among the study groups in comparison to the oxygen group (reference group), adjusted by age, sex, and administration of steroids, canakinumab, and tocilizumab. the results were presented as a proportional hazard ratio (hr) with 95% ci and adjusted cumulative survival curves. finally, in order to examine the potential impact of survival bias among patients treated with imv, especially among patients intubated after niv (a patient had to survive until endotracheal intubation), we computed the adjusted hrs for 10-day and 11 to 60-day mortality, separately, as sensitivity analysis. moreover, minimally to fully adjusted hrs were reported in the supplemenatry material. for all tests, statistical significance was set at an alpha level of p = 0.05. all statistical analyses were performed using the software ibm spss statistics, version 24.0 (armonk, ny, us: ibm corp.). during the study period, 1,424 symptomatic patients were evaluated at the eds in the province and had a positive swab and/or chest imaging suspicious for the covid-19. nine-hundred and four (63.5%) were treated at home without further ed accesses, while the remaining 520 (36.5%) were hospitalized and constituted the study population (males 350, 67.3%; mean age 70.7 ± 14.1, range 19-98). among hospitalized patients, 440 (84.6%) were treated with oxygen supplementation at the time of hospital admission, while the remaining received either niv or imv. during the subsequent days, 57 patients (11.0%) required an upgrade of the ventilatory support. almost all patients were treated with hydroxichloroquine and antiviral drugs. table 1 describes the demographic characteristics and the administered medications of the study population overall and by groups. figure 1 shows a complete synthesis of the respiratory support adopted and the 60-days mortality for each group. the main clinical characteristics of the 112 (21.5%) patients who received any ventilatory support (niv and/or imv, mean age 66.9 ± 9.4 years) are reported in table 2 . among those, 71 (63.4%) patients received at least one trial of niv (mean age 65.1 ± 11.8) with a mean duration of 3.8 ± 2.2 days (range 1-10, figure 2a ) and a mean p/f ratio of 105.9 ± 40.6 at the beginning of niv. thirty-eight (53.5%) of the patients treated with niv improved and were transferred to a covid-19 ward, while 25 (35.2%) were intubated and admitted to the icu to undergo imv. the p/f ratio before starting niv differed significantly between patients with a successful trial and those that failed (successful: 119.4 ± 46.2; failing: 92.1 ± 23.8; p = 0.003). for patients who needed imv a statistically significant but clinically irrelevant improvement in p/f ratio was documented (before niv: 93.1± 23.8; before imv: 113.8 ± 41.5; p = 0.041). the remaining eight patients (11.3%) died without being intubated (p/f ratio before niv 85.3 ± 36.5). the length of niv did not differ among patients with successful or failing trial ( table 2 ). the ability of the p/f ratio obtained before niv to predict the failure of a niv trial showed an auc of 0.71 (95% ci 0.59-0.83; p-value 0.002) and provided a best cut-off of 115.5 (sensitivity 52.6%, specificity 81.8%; j 0.353). overall, 66 patients (groups imv-after-niv and imv-only, mean age 66.9 ± 9.4 years) were admitted to the icu and treated with imv ( figure 1 ). the mean interval between hospital admission and the onset of imv was 5.0 ± 5.9 days (range 0-26) ( figure 2b ). eleven (15.2%) patients were intubated after 10 or more days from hospital admission (p/f before intubation: 113.0 ± 46.7). no difference in p/f ratio at the time of the definitive ventilation support was found among the three study groups (p = 0.993). patients who failed the niv trial (n = 21) had a brixia score of 10.6 ± 3.4 before niv which worsened to 13.4 ± 2.5 (p = 0.002) before imv. similar brixia score was obtain at the time of endotracheal intubation among patients that failed a niv trial and among patients that were treated with imv without a niv trial ( table 2) . among the 66 patients admitted to the icu, mean duration of imv was 22.6 ± 19.0 days (range 2-87). forty-six icu patients (69.7%) received percutaneous tracheostomy (time from intubation: 9.8 ± 3.5 days). renal replacement therapy was performed in 19 (28.8%) patients, with a mean duration of 21.7 ± 18.7 days. none of the 904 patients treated at home died during the follow-up. the overall 60-days mortality for hospitalized patients was 24.2% (n = 126), and was 23.0% (n = 94), 19.6% (n = 9), 32.0% (n = 8) and 36.6% (n = 15) for group oxygen, nivonly, imv-after-niv, and imv-only, respectively (p = 0.165). mortality among the 112 patients receiving any ventilatory support (niv and/or imv) was 27.7%. no between-groups difference in mortality was found by comparing the crude kaplan-meier curves (log-rank test: p = 0.343, figure 3a ). age was a risk factor for death in groups oxygen and niv-only . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august 15, 2020. . but not for patients undergoing imv. the relationships between some characteristics of the study groups and mortality are described in table 3 . the mean duration of imv was 26.5 ± 21.1 days for the 43 patients alive at the end of the follow-up (range: 6-70) and 15.3 ± 11.5 days for the 23 non-survivors (range: 2-51). among the 43 survived, 14 patients (32.6%) underwent imv for more than four weeks (figure 2c) . two patients (one belonging to the imv-after-niv group and one to the imv-only group) were still on imv at the end of follow-up, with an imv duration of 70 and 63 days, respectively. compared with oxygen group, the multivariate cox regression analysis showed a 60-day mortality risk progressively increasing among the other groups being statistically significant for the imv-after-niv group (hr 2.776; 95% ci 1.144-6.734; p = 0.024) and the imv-only group (hr 2.966; 95% ci 1.557-5.652; p=0.001) but not for group niv-only (hr 1.778; 95% ci 0.794-3.980; p = 0.162) (figure 3b ). among the explored covariates, older age (hr 1.097; 95% ci 1.073-1.120; p < 0.001) and male sex (hr 1.597; 95% ci 1.072-2.379; p = 0.021) showed a statistically significant association with the mortality. as expected, the sensitivity analysis showed a higher risk for 10-day mortality in the only-niv group but not in patients receiving imv compared to patients treated with oxygen, while similar results to the main analysis were provided for the 11 to 60-day mortality (table 4 and figure 4 ). the present study showed how an integrated multidisciplinary clinical organization allowed to optimize the allocation of the available resources among 520 hospitalized covid-19 patients. the overall 60-day mortality was 24.2%. approximately 21% of patients were mechanically ventilated, with a mortality ranging from 19.6% in patients treated with niv-only to 36.6% in patients undergoing imv without a niv trial. to our knowledge, this is the first study reporting 60-day mortality in a cohort of hospitalized patients diagnosed with covid-19 overall and according to all adopted ventilatory strategies. a recent chinese multicentric study 19 enrolling icu 258 patients reported an overall 60-day mortality of 64.3%, with 19 patients deceased within 48h after icu admission. among 165 mechanically ventilated patients, the 60-day mortality was 83%, 56%, and 94% for those treated with imv, with niv, and receiving both treatments, respectively. median p/f ratio in the chinese population was 91 (iqr 67-134) and sofa score 6 (iqr 5-7). it should be noted that in our study we documented for patients treated with niv and/or imv -despite a similar p/f ratio (median 98.0; iqr 84.0-124.5) and a higher sofa score (median 8; iqr 6-10)-a considerably lower 60-day mortality rate, overall and in individual groups. a study from six covid icus from us 4 enrolled 217 patients, 165 of which (76.0%) received imv, with a median imv length of 9 days (iqr 4-13). among imv subjects, icu mortality was 33.9% without any difference in imv days between deceased and survived. at the end of follow-up (median observation time 15 [iqr: 9-24] days), hospital mortality was 35.7% (59/165), being 8 patients still in icu on imv. however, no information was provided neither about the adopted respiratory support, nor the outcome, for patients not undergoing imv. despite mortality reported by auld et al. is similar to the mortality reported in our study in the imv-only group, they reported a much shorter follow-up (maximum follow-up 60 days) and 4.8% of patients were still admitted to the icu. therefore, 60-day mortality among those patients is likely to be higher that the reported hospital mortality. recently, a nationwide study from germany including more than 10,000 hospitalized covid-19 patients was published. interestingly, despite the germany health-care system has not been overwhelmed by the pandemic the reported inhospital mortality was markedly higher among patients treated with niv (45% in patients with successfully niv, 50% in patients that failed niv) and imv (53% in patients treated with imv), while it was lower in patients without mechanical ventilation (16%). 3 two further studies considering icu patients reported information about all adopted breathing support strategies. an italian multicentric study 8 enrolling a cohort of 3,355 critically ill patients (median follow-up: 69 days; ventilatory support: imv 87%, niv 10%, cpap/oxygen 2.3%) reported a mortality rate at the censoring (median observation time 70 [range, 38-112] days) of 17%, 36%, and 52% among patients treated with oxygen, niv and imv, respectively. accordingly, niv and imv were associated with an increased risk of death compared with patients treated only with oxygen (hr 2.36, 95% ci 1.33-4.17 and hr 3.77, 95% ci 2.19-6.51, respectively). again, mortality reported in the present study is likely to underestimate 60-day mortality and mortality in the niv and imv groups is higher than the reported in our study population. it should be noted that in all above cited studies the reported mortality for patients treated with standard oxygen and niv was clearly conditioned by the reduced size of these subgroups, related to the study settings limited to icu. compared with the previously reported literature, mortality reported in our study is generally lower. the centralized multidisciplinary approach adopted at rimini hospital may partially explain the difference with the existing literature. the . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august 15, 2020. . sensitivity analysis and the differences between the crude and the adjusted hrs reported in the figure 4 and table 4 may help with the interpretation of the study findings. interestingly, in the present investigation, mortality was higher in the oxygen and niv-only groups in the first 10 days compared to the other two groups. this is partially explained by the survival bias among the mechanically ventilated patients, especially among patients that were intubated after failing a niv trial. indeed, although hrs for the 10-day mortality risk did not reach the statistical significance, mortality risk was lower for patients intubated after a failed niv trial only in the first 10 days of follow-up and not in the 11 to 60-day mortality. on the other side, the fact that the oldest patients and those with severe coexisting disease were treated only with oxygen carrying a higher early mortality was clearly described by the difference between the crude hrs and the hrs adjusted only be age. this finding together with the information of a mean imv length of almost 20 days may support the idea that those patients would have not survived anyway to the imv and, therefore, endorse the decisions taken by the multidisciplinary team. moreover, our results suggest that initial management of severe hypoxemia by oxygen or niv might be a valuable alternative to immediate imv in the occurrence of limited available resources. the decision about the best breathing support to be provided to covid-19 patients is anything but simple. although often severely hypoxic, they tend to present less severe dyspnea than expected, probably because many patients, at least in the early stages of the disease, have normal pulmonary compliance and therefore exert limited inspiratory efforts. in patients whose lung compliance tends to progressively decrease, the inspiratory effort increases and vigorous inspiratory effort can contribute to lung injury (patient self-inflicted lung injury-p-sili). 20 this feature has been supposed to rise morbidity and mortality. therefore, early mechanical ventilatory support has been advocated for covid-19 associated respiratory distress. 21 unfortunately, criteria to intubate covid-19 patients are controversial and the decision may locally reflect the available resources. 22 older age and comorbidities burden have been largely reported as the two main conditions associated with increased mortality risk, 4, 8, 23 so that prioritization of younger patients has been advised in case of shortage of resources. 24 notably, in the present investigation -although age was higher among non-survivors than survivors in each of the four groups and each calendar year was associated with a 10% increased risk for mortality-the age difference was smaller and not statistically significant among survivors and non-survivors undergoing imv. moreover, the median age of patients submitted to imv in our study (69 years) was slightly higher than reported by other authors (59 to 64 years), 2, 4, 8 suggesting that the adopted criteria at our institution were less restrictive in term of age. furthermore, once a patient was considered as potentially salvageable by icu admission and imv, the length of imv was not a criterion to withdrawing treatment. we strongly think that this ethically crucial decision could be widely considered. another interesting finding of our study was that similar p/f ratio was found among patients treated with niv-only or with imv, either preceded by a niv trial or not. therefore, we speculated that a low p/f ratio should not be the only criterion to decide which patient would benefit from imv. it should be noted that among patients intubated after a niv trial or receiving immediate imv, the latter group had a higher sofa score and saps (table 2 ). these findings highlight the fundamental role played by our organizational strategy, allowing to ensure a tailored treatment to each patient by taking into account the level of care that would have more benefited for her/him, and to daily re-discuss each decision at the light of new clinical reasons or changes in the resources availability. for example, during the very early phase of the outbreak not all patients with appropriate indications were treated with niv due to the scarce availability of helmets, while their subsequent increase in availability allowed more targeted choices in the following days. moreover, this strategy contributed to create a more collaborative way to approach difficult decisions, supporting healthcare professionals, especially the younger ones, during such ethically and emotionally demanding decisions. 22 the main strength of the study consisted in having described the impact of the sars-cov-2 epidemic in an entire province. since all patients with moderate to severe covid-19 were managed at the same hospital, a shared and homogeneous standard of care was guaranteed. moreover, follow-up was established at 60 days, taking into account all respiratory supports and without patients' loss. as many covid-19 patients require prolonged imv, a short follow-up time is an important limitation for the majority of the reports published so far. the number of patients requiring ventilatory support was smaller compared to other studies. 2, 3, 10 consequently, the generalizability of our findings should be considered with caution. . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august 15, 2020. . the covid-19 outbreak has strongly challenged the healthcare systems of many countries. a multidisciplinary panel in charge of the decision of the individualized breathing approach to adopt with hospitalized covid-19 patients maybe be a valuable option to maximize 60-day survival, dealing with the imbalance between the available resources and the clinical needs. our findings highlight the need of high quality follow-up data that could support the decision-making for the appropriate ventilatory support strategy for covid-19 patients. . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august 15, 2020. . . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august 15, 2020. . figure 4 . adjusted kaplan-meier curves for the risk of 10-and 11 to 60-day mortality in patients belonging to the study groups according to provided respiratory support. . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august 15, 2020. . measurements are reported as mean and standard deviation or absolute number and percentages. . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august 15, 2020. . https://doi.org/10.1101/2020.08.13.20174615 doi: medrxiv preprint table 2 . characteristics of patients receiving either invasive or non-invasive mechanical ventilation. group imv-after-niv group imv-only p-value n; mean ± sd n; mean ± sd n; mean ± sd . cc-by-nc-nd 4.0 international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted august 15, 2020. . clinical characteristics of coronavirus disease 2019 in china presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area case characteristics, resource use, and outcomes of 10 021 patients with covid-19 admitted to 920 german hospitals: an observational study icu and ventilator mortality among critically ill adults with coronavirus disease clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. the lancet risk factors associated with mortality among patients with covid-19 in intensive care units in lombardy, italy prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with covid-19 in europe: initial report of the international risc-19-icu prospective observational cohort. eclinicalmedicine epidemiology, clinical course, and outcomes of critically ill adults with covid-19 in new york city: a prospective cohort study. the lancet between-centre differences for covid-19 icu mortality from early data in england detection of 2019 novel coronavirus (2019-ncov) by real-time rt-pcr a new method of classifying prognostic comorbidity in longitudinal studies: development and validation radiographic severity index in covid-19 pneumonia: relationship to age and sex in 783 italian patients a new simplified acute physiology score (saps ii) based on a european/north american multicenter study use of the sofa score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. working group on "sepsis-related problems" of the european society of intensive care medicine clinical course and predictors of 60-day mortality in 239 critically ill patients with covid-19: a multicenter retrospective study from wuhan covid-19 pneumonia: ards or not? covid-19 pneumonia: different respiratory treatments for different phenotypes? intensive care med clinical ethics recommendations for the allocation of intensive care treatments in exceptional, resource-limited circumstances: the italian perspective during the covid-19 epidemic characteristics and predictors of hospitalization and death in the first 9,519 cases with a positive rt-pcr test for sars-cov-2 in denmark: a nationwide cohort should we deny icu admission to the elderly? ethical considerations in times of covid-19 breathing support 60-days mortality hr (95% ci); p-value 10-days mortality hr (95% ci) model #0: unadjusted; model #1: adjusted by age; model #2: adjusted by age and sex; model #3: adjusted by age, sex, and administration of steroids; model #4: adjusted by age, sex, and administration of steroids, and canakinumab; model #5: adjusted by age, sex, and administration of steroids, canakinumab the authors thank all nurses and physicians who cared for covid-19 patients during the study period the authors declare that they have no conflict of interest. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. key: cord-327622-ezgufe24 authors: kaur, ramandeep; weiss, tyler t.; perez, andrew; fink, james b.; chen, rongchang; luo, fengming; liang, zongan; mirza, sara; li, jie title: practical strategies to reduce nosocomial transmission to healthcare professionals providing respiratory care to patients with covid-19 date: 2020-09-23 journal: crit care doi: 10.1186/s13054-020-03231-8 sha: doc_id: 327622 cord_uid: ezgufe24 coronavirus disease (covid-19) is an emerging viral infection that is rapidly spreading across the globe. sars-cov-2 belongs to the same coronavirus class that caused respiratory illnesses such as severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers). during the sars and mers outbreaks, many frontline healthcare workers were infected when performing high-risk aerosol-generating medical procedures as well as when providing basic patient care. similarly, covid-19 disease has been reported to infect healthcare workers at a rate of ~ 3% of cases treated in the usa. in this review, we conducted an extensive literature search to develop practical strategies that can be implemented when providing respiratory treatments to covid-19 patients, with the aim to help prevent nosocomial transmission to the frontline workers. coronavirus disease (covid-19) cases were first reported to the world health organization on december 31, 2019 [1] . since then, this illness has spread exponentially in over 200 countries. as of june 9, 2020, there were 7,039,918 confirmed cases of the covid-19 disease globally [2] . even though the exact mode of covid-19 transmission has been debatable, the route of covid-19 transmission is reported to be from personto-person contact and exposure to respiratory droplets (> 5-10 μm) [3] , whereas airborne transmission (< 5 μm) during aerosol-generating procedures remains under investigation [4, 5] . based on the initial data reported [6] [7] [8] [9] [10] [11] [12] , around 5-30% of covid-19 patients develop signs of severe respiratory distress requiring intensive care unit (icu) admission to receive advanced respiratory support in terms of oxygen therapy, non-invasive and invasive ventilatory support with prone positioning (table 1) . standard droplet and contact precautions (gowns, gloves, mask) are known to reduce the risk of contracting severe acute respiratory syndrome (sars) [13] but not under all circumstances, especially when performing high-risk procedures such as intubation [14] . a recent systematic meta-analysis showed that a physical distance of 1 m or more and wearing a mask is optimum to reduce person-to-person virus transmission and to keep healthcare workers (hcws) from contracting the sars-cov-2 infection [15] . during the sars outbreak, many table 1 use of respiratory interventions in covid-19 patient population study huang et al. [5] (n = 41) wu et al. [6] (n = 201) wang et al. [7] (n = 138) guan et al. [8] (n = 1099) yang et al. [9] (n = 52) arentz et al. [10] (n = 21) grasseli et al. [11] (n = 1591) richardson et al. [12] (n = 5700) frontline hcws were infected via nosocomial transmission due to failure to implement adequate infection control precautions, especially when performing aerosolgenerating medical procedures (agmps) [16] [17] [18] , such as bronchoscopy, intubation, suctioning, invasive and non-invasive ventilation (niv), bag mask ventilation, and nebulization [19] [20] [21] . in a prospective study, macintyre et al. [22] reported that clinicians who performed agmps were at greater risk of acquiring the infection as compared to those who were not involved in such procedures [ [23] . until further high-quality evidence, including well-conducted randomized controlled trials, is available to demonstrate the definite role of agmps in spreading nosocomial infection, it is best to use the data available from past outbreaks to implement additional safeguards. in this review, we performed a comprehensive literature search to present practical strategies (table 2) to reduce the risk of nosocomial transmission when delivering agmps to patients with covid-19. these suggestions are to be utilized in addition to the cdc recommendations available for proper personal protective equipment (ppe) for hcws. a literature search was performed via pubmed and scopus databases using the following keywords: ("coronavirus" or "covid-19" or "severe acute respiratory syndrome" or "sars" or "middle east respiratory syndrome" or "mers" or "h1n1") and ("aerosol generating procedures" or "nosocomial infection"). publication types included systematic review, meta-analysis, randomized clinical trials, and observation studies. the study population involved hcws providing respiratory care including agmps to patients infected with sars, mers, influenza a virus subtype h1n1 (h1n1), or covid19. in vitro studies investigating the role of exhaled air dispersion when providing agmps were also included. published letters, book chapters, conference abstracts, and editorials were excluded. the literature search was limited to articles published until may 2020. the detailed selection process conducted is shown in fig. 1 . a common clinical finding with covid-19 is cough [7] . coughing, speaking, laughing, and breathing have been associated with generation of bio-aerosols capable of carrying the virus [46, 47] . the bio-aerosols can range from 0.1 to 100 μm, and particles smaller than 1 μm have been reported to disperse to greater distances and remain airborne for several hours [5, 48, 49] . large particles tend to settle directly on surfaces surrounding the patients, with reports of surface swabs testing positive across the patient's room [5, 50] . a recent experimental study indicated that the covid-19 virus can remain viable and infectious in aerosol for hours and on surface for days [51] and virus-laden aerosol deposition plays a role in surface contamination [4] . some medical procedures that cause/irritate patients to cough or sneeze, such as bronchoscopy and nasal-pharyngeal suctioning, lead to the generation of bio-aerosols from patients. in contrast, other medical procedures do not "generate" bio-aerosols but increase the dispersion of bio-aerosols generated by infectious patients, such as niv and highflow nasal cannula (hfnc) oxygen therapy [5, 19] . based on cdc guidelines, hcws performing agmps should wear n95 or high-level respirators along with eye protection, gloves, and a gown. furthermore, the number of personnel entering patient's room during agmps should be limited and procedures should be ideally performed in an airborne infection isolation room [52] . supplemental oxygen therapy is essential for patients with hypoxemic respiratory failure. while supplemental oxygen has not been shown to generate bio-aerosols, they may have a role in dispersing them. in an in vitro study using a human simulator with smoke (< 1 μm aerosol of solid particles) exhaled through airway, hui et al. examined the exhaled air dispersion during oxygen delivery via nasal cannula. the results showed that exhaled air dispersion increased as oxygen flow was increased from 1 to 5 l/min and substantial exposure occurred within 1 m from the bed in a negative pressure ventilation room [24] . a substantial increase in lateral exhaled air dispersion is reported as the oxygen flows increased [25] [26] [27] . the same group of researchers using a similar model reported that both nonrebreather and air-entrainment masks increased exhaled air dispersion [25] [26] [27] . exhaled air dispersion distance was further with the air-entrainment mask than simple and nonrebreather masks [53] . placing a simple surgical mask on patient's face has been reported to reduce the exhaled dispersion distance [28, 29] and the influenza a virus load [30] during a cough. surgical masks and n95 masks are similarly effective at preventing influence virus exposure [30] . placing either mask on a patient with confirmed covid-19 can help reduce the dispersion of bio-aerosols [15] . based on these findings, when a standard nasal cannula is used to deliver low-flow oxygen therapy, a surgical mask should be placed over the patient's face. the air-entrainment mask should be avoided for patients with covid-19, if possible. if higher delivered f i o 2 is needed, a closed non-breather mask with a filter could be considered [54] . oxygen delivery via hfnc has become widely used in patients with acute hypoxemic respiratory failure due to its benefits of meeting or exceeding patient inspiratory flow demand, reducing oxygen dilution, and washing out pharyngeal dead space [55] . hfnc has been shown to reduce the need for endotracheal intubation when compared to conventional oxygen delivery devices [56] . two retrospective studies examining the effects of hfnc in patients with acute hypoxemic respiratory failure secondary to covid-19 showed that hfnc was able to maintain adequate oxygenation and reduced the need for niv and mechanical ventilation [32, 57] . exhaled smoke dispersion, from a manikin during hfnc treatment, was shown to significantly increase with increased flow rate [58] . interestingly, the dispersion distance from the hfnc at 60 l/min was shorter than an air[24] [25] [26] [27] [28] 3 in vivo [29] [30] [31] • use nasal cannula and place a surgical/procedure mask on the patient's face • avoid venturi mask • avoid nonrebreather mask unless it is filtered 2 high-flow nasal cannula 1 in vitro [32] 2 in vivo [15, 31] • proper nasal cannula fitting • place a surgical/procedure mask over hfnc on the patient's face (fig. 2) 3 nebulization 2 in vitro [33, 34] 2 in vivo [22, 35] • use metered dosed inhaler with spacer when possible • avoid using small volume nebulizer unless it is filtered (fig. 3a , b) • use nebulizer in line with hfnc or via ventilator 4 lung expansion and airway clearance therapy* 3 in vivo [22, 35, 36] • if using ippb, place a filter between circuit and mask or mouthpiece, or on expiratory port • if possible, avoid cough inducing therapies such as intermittent percussive ventilation and cough assist • during high-frequency chest wall oscillation therapy, place a surgical/ procedure mask on the patient's face 5 non-invasive ventilation* 2 in vitro [37, 38] 2 in vivo [39, 40] • use tight fit oral mask without leaks, consider helmet or total face mask if available • avoid using nasal mask • when using non-heated-wire single-limb circuit, place a filter between the non-vented mask and the expiratory port ( fig. 4a ) • if humidification is required, heated wire single-limb circuit with filter placed at the expiratory port for non-invasive ventilator (fig. 4b) • avoid cool aerosol for tracheostomy patient, instead use hme. if the patient needs frequent suctioning (more than once every hour), place an in-line suction catheter with t-piece connected to cool aerosol or heated humidification, the other end of t-piece connected to a filter (fig. 6) . additionally, if the patient has cuffless tracheotomy, place a procedure mask on patient's face • avoid using t-piece trials. if needed, use the setup with a filter described above 8 extubation* • when removing the endotracheal tube, simultaneously turn off the ventilator • avoid disconnecting ett from the ventilator circuit before extubation to reduce spray of contaminated aerosols 9 transport • place a filter between the artificial airway and the transport ventilator circuit • use hme that has filter function (hme-f) • consider clamping the ett before disconnection from ventilator circuit 10 bronchoscopy assist* 2 in vivo [44, 45] • for spontaneously breathing patients, place a surgical mask on patient's face (fig. 7a, b) • use niv mask with examination port for patients on niv (fig. 7d) • use swivel adapter to insert bronchoscope for intubated patient (fig. 7c) abbreviations: hfnc high-flow nasal cannula, ippb intermittent positive pressure breathing, hme heat moisture exchanger, ett endotracheal tube, niv non-invasive ventilation *based on cdc guidelines, these procedures should ideally be performed in airborne infection isolation rooms entrainment or nonrebreather mask [53] . a randomized controlled, crossover non-inferiority study trial reported no difference in gram-negative bacterial and total bacterial counts between hfnc at 60 l/min and simple oxygen mask at 8 l/min when air sample collection plates were placed at 0.4 or 1.5 m away from the patient [31] . it is important to note that a substantial increase of exhaled smoke dispersion was reported when the nasal cannula connection with patient nares was loose [58, 59] . because of these findings, it is suggested that a surgical or procedure mask be worn by patients receiving hfnc (fig. 2) . regular checks on the proper position and connection of the nasal cannula interface under the mask are also necessary. aerosol therapy has been identified as a high-risk procedure for nosocomial transmission, due to its active generation of aerosol, which may carry viruses into the environment [19, 60] . hui and colleagues found the maximum exhaled air dispersion distance was ≥ 0.45 m when a small volume jet nebulizer (svn) was connected to a mask at a gas flow of 6 l/min [33] . this distance was even further than niv at maximum settings (ipap 18 cmh 2 o, epap 4 cmh 2 o), using the same study method [33] . two clinical observational studies also found droplet counts significantly increased immediately after svn started to generate aerosol, particularly, the aerosol/droplet count within small and medium size range 1-5 μm, when compared to the baseline level or other procedures including oxygen therapy and niv [35] or bronchoscopy examination [44] . nevertheless, the aerosol/droplets generated by a nebulizer may not contain a virus; however, if the nebulizer is contaminated, the aerosol can carry viruses to the surrounding environment. mcgrath and colleagues [34] found that mass concentrations of aerosols/droplets were significantly reduced after placing a filter at the end of the mouthpiece for nebulizers. therefore, if aerosol therapy is indicated for covid-19 patients, svn should be avoided unless filtered, and inhalers including metered dose inhaler (mdi) and dry power inhalers (dpis) are preferred for spontaneous breathing patients who can tolerate their use without generating additional cough [61] . with mdi, a spacer with one-way valve is suggested to reduce the need for coordination and to increase lung deposition [62] . if patients are unable to use mdis or dpis, or the required medication is only available in the form of a solution, such as antibiotics, antivirals, mucokinetics, or prostanoids, nebulizers via mouthpiece with a filter placed distal to the reservoir tubing ( fig. 3a and b) should be utilized. for patients who cannot tolerate a mouthpiece or require medication administered over a prolonged period of time, such as continuous bronchodilator for asthmatic patients [63] or inhaled epoprostenol for patients with pulmonary hypertension or hypoxemia [64, 65] , in-line placement of a nebulizer with hfnc setup is recommended. this setup has two advantages: (1) more comfortable and better tolerated when compared to a mask or mouthpiece [63] and (2) a surgical mask to reduce the aerosol dispersion distance or aerosol mass concentration can be placed on the patient [53, 56] . when hfnc is utilized to deliver aerosol treatment, gas flow needs to be set relatively low if possible (10-20 l/min for adults and 0.25 l/kg/min for children), to improve the aerosol delivery efficiency [66, 67] and reduce the dispersion. vibrating mesh nebulizers or valved t-pieces for jet svns can reduce the need to break the ventilator circuit when nebulization is provided during invasive ventilation. little evidence is available regarding lung expansion therapy and nosocomial infection. lung expansion therapy is designed to treat and prevent pulmonary atelectasis. intermittent positive pressure breathing (ippb) utilizes short-term positive pressure ventilation via mask or mouthpiece to promote lung expansion. due to the risk of causing a cough response that might disperse bio-aerosols [21] , ippb should be used judiciously and with filters placed between the breathing circuit and the mask or mouthpiece. the number of particles emitted by cough from an infected patient was greater than that from a recovered patient (p < 0.001) [36] . bronchial hygiene therapies such as intermittent percussive ventilation and vibratory positive expiratory pressure irritate the airway causing the patient to cough forcefully, potentially emitting virusladen aerosols. placing a filter between these devices and patient's mouth is suggested. when intermittent percussive ventilation is utilized, nebulization via its integrated nebulizer should be avoided as the filter placed between the device outlet and patient will capture aerosols. additionally, high-frequency chest wall oscillation can be used for secretion clearance. in addition to hcws wearing proper ppe, a surgical or procedure mask worn by patients receiving the therapy may be helpful. overall, in patients with confirmed covid-19, avoid the indiscriminate use of bronchial hygiene therapies that may not be clinically indicated [61] . niv has been utilized in 10-50% of covid-19 patients in published clinical reports [6] [7] [8] [9] [10] [11] [12] . even though niv delivered by helmet was effective in terms of reducing intubation rate and 90-day mortality rate among ards patients [68] , its role in patients with severe ards remains controversial [69] . during the mers outbreak, niv was commonly used to treat acute hypoxic respiratory failure, but it had a high failure rate and was not associated with improved patient outcomes [70] . niv produces a jet of exhaled gas through the exhalation port or leak from the connection of patient's interface and ventilator, increasing dispersion distance of patient-generated bio-aerosol, and therefore it is counted as an agmp [20, 39] . consequently, niv should be used with caution for covid-19 patients and additional modifications to minimize or reduce exhaled gas/aerosol dispersion are required. in an experimental study, hui et al. reported significant exhaled air dispersion within a 0.5-m radius of the human simulator receiving niv and higher pressure settings increased the spread of exhaled air. however, the exhaled air dispersion is limited if the mask fit is appropriate [37] . when comparing helmet to total face mask, hui et al. [38] in another study demonstrated that niv application via a double-limb circuit ventilator with filters and a helmet with good seal was effective in reducing exhaled air dispersion. in contrast, niv applied via a total mask through a single-limb circuit ventilator caused increased exhaled air dispersion [38] . non-vented masks were shown to have less air dispersion as compared to vented mask [71] . thus, when vented masks are used, additional precautions for protection of the hcw may be appropriate. hcws that are in close proximity to patients receiving niv need to wear high respiratory personal protection including n95 or powered air-purifying respirator (papr). secondly, the niv circuits can be modified to place a filter. during the sars outbreak, cheung et al. demonstrated that a filter placed before the fixed exhalation port in the single-limb circuit was effective in reducing the incidence of nosocomial transmission among hcws [40] . however, due to the lack of a control group, the results of this study should be interpreted cautiously. additionally, simonds et al. showed that modifying niv circuit with a filter was effective in reducing the droplet counts [35] . thus, a filter should be placed between the non-vented mask and the exhalation port to reduce environmental contamination of bioaerosols (fig. 4a) . notably, humidification should be avoided in this type of circuit as the viral filter may capture water vapor in the circuit, resulting in occlusion for exhalation. if humidification is necessary, a modified exhalation port is needed to place a filter at the outlet (fig. 4b ). an alternative is using a dual-limb circuit ventilator with filters to deliver niv. this would allow for both humidification and the reduction in exhaled gas/ aerosol dispersion. regardless of interface/ventilator, the risk of a leak between the patient and the mask interface cannot be overlooked. choosing an appropriate interface size and type, along with the appropriate circuits and ventilators, is crucial. a good fitting oral mask is preferred and avoid using a nasal mask for patients with covid-19. if unable to get a good seal with an oral mask, consider using a total face mask or a helmet, if available. clinicians who perform or assist in endotracheal intubation are directly exposed to patient's lower airway where high concentrations of virus is accumulated. additionally, in patients with an intact cough or gag reflex, intubation may increase exhaled air dispersion [72] . therefore, intubation is considered high risk [73] . the risk of being infected when performing or assisting intubation (rr, 13.29; 95% ci, 2.99-59.04; p = 0.003) was found in the outbreak of sars in a canadian icu [39] . since then, high levels of ppe and negative pressure environments have been recommended to protect clinicians during intubation [74] . to reduce the exposure time to the sars-cov-2, the most experienced provider should perform intubation to avoid multiple attempts. video-laryngoscope has shown to be useful when intubating patients with covid-19 to increase the distance between the provider and the patient airway [74] . for a difficult airway, bronchoscopy is preferred to assist intubation, if a skilled provider is present [75] . rapid sequence intubation is also recommended, in order to minimize cough during the procedure [42, 76] . aerosol boxes [77] as well as protective shields made of glass [78] have been described as practical barriers to limit exposure to patient's exhaled droplets during intubation. while potentially useful, a documented reduction in disease transmission has not been reported and concerns regarding adequate airway view and appropriate ergonomics during intubation have been raised [79] . pre-oxygenation prior to intubation plays a crucial role in avoiding complications during intubation. multiple randomized controlled trials have shown that the utilization of hfnc for pre-oxygenation can help reduce the incidence of hypoxemia during intubation [55, 80] . the cost-effectiveness and the high risk of transmission from high gas flows should be taken into consideration before using it for pre-oxygenation prior to intubation. the traditional method of using manual ventilation via resuscitator and mask for patients prior to intubation also has some risks. exhaled gas dispersion distance has been shown to be 16-27 cm during fig. 7 a bronchoscope insertion via the nose. b bronchoscope insertion via the mouth. c bronchoscope insertion via the endotracheal tube. d bronchoscope insertion via the niv mask manual ventilation, which is similar to the distance between clinicians and the patient's airway [41] . placing a filter between resuscitator and mask (fig. 5) has been found to significantly reduce the exhaled gas dispersion distance [41, 43, 81] . for patients requiring mechanical ventilation via artificial airways, a ventilator with a dual-limb, heated wire circuit in conjunction with filters placed at the ventilator exhalation outlet is crucial [61, 73] . in addition, breaking the ventilator circuit connection should be limited and circuit changes should only be done when visibly soiled [82] . approximately 8-13% mechanically ventilated patients receive tracheostomy to facilitate the long-term need for ventilatory support [83] . for patients with covid-19, open tracheostomy is recommended over percutaneous dilational tracheostomy to reduce the risk of aerosol transmission [84] . recently, pichi et al. described standard steps to promote a safe and effective method when performing open tracheostomy in patients with covid-19 [85] . bertroche et al. [86] created a negative pressure cover to limit the exposure to the aerosols, but these methods need further investigation on the efficacy in reducing nosocomial infections. when transporting a mechanically ventilated covid-19 patient, it is suggested that a filter hme be placed between the artificial airway and the transport ventilator circuit [53] . before pausing the icu ventilator, consider clamping the endotracheal tube (ett) to prevent derecruitment and minimize the spread of bio-aerosols when transitioning patients from the icu ventilator to the transport ventilator [5, 87, 88] . when returning to the icu, clamp the ett and leave the filter connected to it to prevent accidental exposure. when ready for transition to the icu ventilator, disconnect the bacteria filter and place the patient on the ventilator before unclamping ett. the most common methods to perform a spontaneous breathing trial are t-piece trial and pressure support ventilation (psv). subirà and colleagues [89] reported that successful extubation occurred in 82.3% of patients in the psv group compared to 74.0% in the t-piece group (difference, 8.2%; 95% ci, 3.4-13.0%; p = 0.001). with these findings, in conjunction with the need to avoid opening patient's airway to the environment, psv is preferred for covid-19 patients. when a t-piece is needed, hcws should take safety precautions to minimize the exposure to a patient's airway, such as using the in-line suction catheter's t-piece with one end connecting humidified oxygen while the other end is connected to a filter (fig. 6) . this setup can also be applied for tracheostomy patients who are weaned from mechanical ventilation, particularly for patients who need frequent suctioning (more than once an hour), as this device keeps airway sealed and the filter protects hcws during suctioning. however, the filter can be clogged as it captures water vapor; hence periodically checking and replacing the filter are necessary. a filter hme can also be used to provide passive humidity [90] while humidified oxygen via a tracheostomy mask should be avoided. additionally, if the patient has a cuffless tracheostomy tube in place, a procedure mask on patient's face may reduce bio-aerosol dispersion. the process of extubation induces a cough reflex which may spread aerosols; therefore, it is imperative to use proper precautions when removing an ett [91] . during extubation, it is important to maintain the connection of the ventilator circuit and suction catheter to the ett, in order to avoid aerosol dispersion from the ventilator circuit. the extubation procedure should be performed by two hcws. in an in vitro study, a clear plastic drape was shown to significantly reduce aerosol dispersion during the extubation process; however, the feasibility of this practice requires further investigation [92] . bronchoscopy examination is considered an agmp and may be related to an increased risk for transmission of infectious airborne particles [19] . thompson et al. [45] found that bronchoscopy was associated with increased probability of aerosol generation and increased viral copies among different agmps for h1n1-positive patients. o'neil et al [44] found an increase in particle concentration when a nebulized medication administration was performed before and after bronchoscopy, while bronchoscopy examination itself did not increase concentration compared to baseline. according to the american association for bronchology and interventional pulmonology guidelines, bronchoscopy procedures are relatively contraindicated for patients with suspected or confirmed covid-19 infections when less invasive diagnostic procedures are inconclusive [93] . urgent bronchoscopy procedures should only be considered if intervention is deemed as lifesaving in patients with (1) massive hemoptysis, (2) benign or malignant severe airway obstruction, (3) suspicion of secondary infectious etiology, or (4) malignant condition that results in endobronchial obstruction. in the event a covid-19 patient requires bronchoscopic intervention, it is recommended that the patient be placed in negative pressure isolation room and personnel should don appropriate droplet precaution ppe, including a powered air-purifying respirator or n95 mask [93] . some additional precautions might also be considered to protect hcws from exposure during bronchoscopy [94, 95] . (1) for spontaneously breathing patients, if the bronchoscope is inserted via the nares, a surgical or procedure mask should be placed to cover the face (fig. 7a) . if inserted via the mouth with a bite-block, a surgical or procedure mask with a small hole cut for bronchoscope insertion should be placed on the patient's face (fig. 7b) . (2) for non-invasively ventilated patients, a special niv mask with an examination port should be used (fig. 7d) . (3) for invasively ventilated patients, a swivel adapter should be used to facilitate the bronchoscope insertion and to maintain ventilation (fig. 7c) . due to the risk of patient coughing and deep breathing during the procedure, pulmonary function testing is considered a platform for covid-19 transmission. as a result, the american thoracic society recommends limiting testing to only those with immediate treatment needs [95] and, if possible, testing should only be performed upon symptom improvement and negative realtime polymerase chain reaction tests [96] . when performing pulmonary function tests, hcws should adhere to strict infection control measures and use high specification disposable in-line viral/bacterial filters (minimum proven efficiency for high expiratory flow of 600 to 700 l/min) with the mouthpiece [97, 98] . when performing lung function testing in high-risk patients, the european respiratory society recommends that lung function testing should be limited to spirometry and diffusion capacity test. they also recommend the use of negative pressure rooms, when available [99] . currently, there is limited data available if spirometry is an aerosolproducing procedure; therefore, hcws should adhere to wearing full ppe [100] . the frontline hcws are at risk for contracting the covid-19 disease when caring for patients and providing aerosol-generating procedures. until further high-quality studies generate robust evidence, defining the precise nosocomial transmission risk associated with agmps, along with cdc's recommended ppe guidelines, we propose additional respiratory protective measures that could reduce the nosocomial transmission of covid-19 diseases to hcws providing respiratory interventions. world health organization. coronavirus disease 2019 (covid-19) situation report -1 world health organization. coronavirus disease 2019 (covid-19) situation report -141 world health organization. transmission of sars-cov-2: implications for infection prevention precautions aerodynamic analysis of sars-cov-2 in two wuhan hospitals coughs and sneezes: their role in transmission of respiratory viral infections, including sars-cov-2 clinical features of patients infected with 2019 novel coronavirus in wuhan clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china characteristics and outcomes of 21 critically ill patients with covid-19 in washington state baseline characteristics and outcomes of 1591 patients infected with sars-cov-2 admitted to icus of the lombardy region presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (sars) illness in intensive care staff after brief exposure to severe acute respiratory syndrome physical distancing, face masks, and eye protection to prevent person-to-person transmission of sars-cov-2 and covid-19: a systematic review and meta-analysis bc interdisciplinary respiratory protection study group. protecting health care workers from sars and other respiratory pathogens: a review of the infection control literature risks to healthcare workers with emerging diseases: lessons from mers-cov, ebola, sars, and avian flu risk factors for sars transmission from patients requiring intubation: a multicentre investigation in toronto nosocomial transmission of emerging viruses via aerosol-generating medical procedures aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures center for disease control and prevention. coronavirus disease 2019. cases, data and surveillance exhaled air dispersion and removal is influenced by isolation room size and ventilation settings during oxygen delivery via nasal cannula airflow and droplet spreading around oxygen masks: a simulation model for infection control research airflows around oxygen masks: a potential source of infection? exhaled air dispersion during oxygen delivery via a simple oxygen mask exhaled air dispersion during coughing with and without wearing a surgical or n95 mask influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks a quantitative assessment of the efficacy of surgical and n95 masks to filter influenza virus in patients with acute influenza infection comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial the experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of chongqing, china. ann intensive care exhaled air and aerosolized droplet dispersion during application of a jet nebulizer investigation of the quantity of exhaled aerosols released into the environment during nebulisation evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections quantity, size distribution, and characteristics of cough-generated aerosol produced by patients with an upper respiratory tract infection noninvasive positive-pressure ventilation: an experimental model to assess air and particle dispersion exhaled air dispersion distances during noninvasive ventilation via different respironics face masks transmission of severe acute respiratory syndrome during intubation and mechanical ventilation effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome exhaled air dispersion during bag-mask ventilation and sputum suctioning -implications for infection control analysis of bronchoscope-guided tracheal intubation in 12 cases with covid-19 under the personal protective equipment with positive pressure protective hood possible sars coronavirus transmission during cardiopulmonary resuscitation characterization of aerosols generated during patient care activities influenza aerosols in uk hospitals during the h1n1 (2009) pandemic -the risk of aerosol generation during medical procedures inactivation of influenza a viruses in the environment and modes of transmission: a critical review viable influenza a virus in airborne particles expelled during coughs versus exhalations. influenza other respir viruses dynamics of infectious disease transmission by inhalable respiratory droplets guidelines for preventing the transmission of mycobacterium tuberculosis in health-care settings survival of influenza viruses on environmental surfaces aerosol and surface stability of sars-cov-2 as compared with sars-cov-1 high-flow nasal cannula for covid-19 patients: low risk of bio-aerosol dispersion dispersal of respiratory droplets with open vs closed oxygen delivery masks: implications for the transmission of severe acute respiratory syndrome year in review 2019: high-flow nasal cannula (hfnc) oxygen therapy for adult patients high flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis use of high flow nasal therapy to treat moderate to severe hypoxemic respiratory failure in exhaled air dispersion during high flow nasal cannula therapy versus cpap via different masks preliminary findings on control of dispersion of aerosols and droplets during high-velocity nasal insufflation therapy using a simple surgical mask: implications for the high-flow nasal cannula acute febrile respiratory illness in the icu: reducing disease transmission expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia everyone with asthma should have a metered dose inhaler and a spacer nasal high flow in management of children with status asthmaticus: a retrospective observational study epoprostenol delivered via high flow nasal cannula for icu subjects with severe hypoxemia comorbid with pulmonary hypertension or right heart dysfunction the clinical impact of flow titration on epoprostenol delivery via high flow nasal cannula for icu patients with pulmonary hypertension or right ventricular dysfunction: a retrospective cohort comparison study the ratio of nasal cannula gas flow to patient inspiratory flow on trans-nasal pulmonary aerosol delivery for adults: an in vitro study decrease the flow setting to improve trans-nasal pulmonary aerosol delivery via "high-flow nasal cannula" to infants and toddlers effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial noninvasive ventilation of patients with acute respiratory distress syndrome. insights from the lung safe study noninvasive ventilation in critically ill patients with the middle east respiratory syndrome. influenza other respir viruses exhaled air dispersion during noninvasive ventilation via helmets and a total facemask staff safety during emergency airway management for covid-19 in hong kong practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-ncov) patients emergency tracheal intubation in 202 patients with covid-19 in wuhan, china: lessons learnt and international expert recommendations ventilatory and intensive care expert recommendations for tracheal intubation in critically ill patients with noval coronavirus disease barrier enclosure during endotracheal intubation new device and technique to protect intubation operators against covid-19 covid-19): anesthetic concerns, including airway management and infection control high-flow nasal cannula therapy as apneic oxygenation during endotracheal intubation in critically ill patients in the intensive care unit: a systematic review and metaanalysis mask ventilation and dispersion of exhaled air effect of ventilator circuit changes on ventilator-associated pneumonia: a systematic review and meta-analysis trends in tracheostomy for mechanically ventilated patients in the united states tracheotomy in ventilated patients with covid-19 corona-steps for tracheotomy in covid-19 patients: a staff-safe method for airway management negativepressure aerosol cover for covid-19 tracheostomy does endotracheal tube clamping prevent air leaks and maintain positive endexpiratory pressure during the switching of a ventilator in a patient in an intensive care unit? a bench study potential risk for bacterial contamination in conventional reused ventilator systems and disposable closed ventilatorsuction systems effect of pressure support vs tpiece ventilation strategies during spontaneous breathing trials on successful extubation among patients receiving mechanical ventilation: a randomized clinical trial management of tracheostomy during covid-19 outbreak: heat and moisture exchanger filter and closed suctioning system lidocaine sprayed down the endotracheal tube attenuates the airway-circulatory reflexes by local anesthesia during emergence and extubation clear plastic drapes may be effective at limiting aerosolization and droplet spray during extubation: implications for covid-19 american association for bronchology and interventional pulmonology (aabip) statement on the use of bronchoscopy and respiratory specimen collection in patients with suspected or confirmed covid-19 infection expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia protecting healthcare workers from sars-cov-2 infection: practical indications pulmonary function laboratories: advice regarding covid-19 italian pediatric respiratory society recommendations on pediatric pulmonary function testing during covid-19 pandemic task force of pulmonary function testing and clinical respiratory physiology, chinese association of chest physicians; pulmonary function testing group 1 (respiratory function technologists /scientists) lung function testing during covid-19 pandemic and beyond lung function testing in the covid-19 endemic publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we would like to thank j. brady scott for his assistance with the final review of the manuscript. authors' contributions jl, rk, tw, and ap prepared the manuscript. jf, sm, rc, fl, and zl reviewed and edited the manuscript. the authors read and approved the final manuscript. availability of data and materials not applicable ethics approval and consent to participate not applicable consent for publication tyler weiss gives his consent to use his image in fig. 3a . key: cord-268049-7xqln70d authors: montrief, tim; ramzy, mark; long, brit; gottlieb, michael; hercz, dan title: covid-19 respiratory support in the emergency department setting date: 2020-08-08 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.001 sha: doc_id: 268049 cord_uid: 7xqln70d introduction: severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2), which causes the coronavirus disease 2019 (covid-19), may result in severe complications, multiorgan dysfunction, acute respiratory failure, and death. sars-cov-2 is highly contagious and places healthcare workers at significant risk, especially during aerosol-generating procedures, including airway management. objective: this narrative review outlines the underlying respiratory pathophysiology of patients with covid-19 and discusses approaches to airway management in the emergency department (ed) based on current literature. discussion: patients presenting with sars-cov-2 infection are at high risk for acute respiratory failure requiring airway management. among hospitalized patients, 10–20% require intensive care unit admission, and 3–10% require intubation and mechanical ventilation. while providing respiratory support for these patients, proper infection control measures, including adherence to personal protective equipment policies, are necessary to prevent nosocomial transmission to healthcare workers. a structured approach to respiratory failure in these patients includes the use of exogenous oxygen via nasal cannula or non-rebreather, as well as titrated high-flow nasal cannula and non-invasive ventilation. this review offers several guiding principles and resources designed to be adapted in conjunction with local workplace policies for patients requiring endotracheal intubation. conclusions: while the fundamental principles of acute respiratory failure management are similar between covid-19 and non-covid-19 patients, there are some notable differences, including a focus on provider safety. this review provides an approach to airway management and respiratory support in the patient with covid-19. coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) has become a pandemic involving millions of people and causing hundreds of thousands deaths worldwide. 1 covid-19 was first reported within wuhan, china in december 2019 and has spread rapidly. 2 patients presenting with covid-19 are at high risk for acute respiratory failure necessitating advanced airway management. [2] [3] [4] overall, the presence of hypoxic respiratory failure among covid-19 patients approaches 20%. [5] [6] [7] data from china reported that up to 41% of all patients with covid-19 required oxygen therapy, 4% to 13% required noninvasive ventilation (niv), and 2.3% to 12% required intubation and mechanical ventilation. 3, 5 risk factors for developing acute respiratory failure appear to include male gender; age over 60 years; and comorbidities including diabetes, active cancer, and immunocompromising states. 5, [8] [9] [10] healthcare workers (hcws) caring for this population are at high risk of contracting sars-cov-2 via large droplets, respiratory secretions, and contact with contaminated surfaces. 11 airway management is particularly high risk because it involves aerosol-generating procedures. 11, 12 emergency providers must be prepared to manage patients with acute respiratory failure due to sars-cov-2. in this review, we provide an overview of the underlying respiratory pathophysiology of sars-cov-2, followed by an approach to airway management for suspected or healthcare workers should follow the infection control policies at their individual healthcare institutions. many guidelines recommend exogenous oxygen administration as an initial therapy in patients with mild hypoxemic respiratory failure due to covid-19. [15] [16] [17] supplemental oxygen is recommended if the patient"s oxygen saturation (spo 2 ) is less than 90%, with a target spo 2 of no higher than 96%, based on recommendations from several societies, including the society of critical care medicine (sccm). 14, 18 clinicians should assess patient respiratory status inclusive of mental status and respiratory effort (e.g., work of breathing, respiratory rate) rather than oxygen saturation alone, when determining the need for airway intervention. in patients with mild hypoxemia due to sars-cov-2 but no evidence of respiratory failure requiring immediate endotracheal intubation, supplemental oxygen may be provided. 4 a strategy of oxygen escalation therapy may assist patients, in which nasal cannula (nc) can be started at 6 l/min. 19 if the patient does not improve with nc, further steps include venturi mask up to 50% or non-rebreather mask up to 15 l/min, non-rebreather at 15 l/min in addition to nc at 6 l/min, high flow nasal cannula (hfnc), and then niv (figure 1 ). 20 oxygen flow of 6 l/min or greater is considered high-flow oxygen and may cause aerosolization of viral pathogens, although this is controversial. [21] [22] [23] respiratory support of patients with sars-cov-2 requires modification in order to minimize viral spread. for instance, a standard surgical mask should be worn over the nc, non-rebreather, or j o u r n a l p r e -p r o o f venturi mask to reduce the risk of droplet spread. 4 for patients requiring higher oxygen delivery via the use of a simple facemask or nonrebreather, an exhalation filter can be attached; however, this strategy has not been thoroughly evaluated in terms of viral transmission. 4 as a result they are not recommended for routine use in patients with sars-cov-2 respiratory disease. 20 when necessary, non-rebreather masks are preferred over simple facemasks. 19 similarly, nebulization of medications via simple facemask should be avoided in this population. 4, 18, 19 bronchodilators may be administered by metered-dose inhalers if necessary. 4 hfnc has become more prevalent in the years after the sars outbreak and has been found to decrease the need for mechanical ventilation in patients with acute hypoxemic respiratory failure and potentially improve 90-day mortality. [24] [25] [26] hfnc is an emerging support modality for patients with covid-19 and has been associated with increased survival in covid-19 patients when compared to either niv or invasive mechanical ventilation. 9, 27, 28 while the risk of bacterial transmission with hfnc is low, the risk of respiratory viral pathogen transmission remains unclear. [29] [30] [31] [32] based on currently available evidence, the who states that "hfnc and niv systems with good interface fitting do not create widespread dispersion of exhaled air and therefore should be associated with [a] low risk of airborne transmission." 15 the risk of respiratory pathogen transmission when using hfnc is subject to a variety of factors, including the duration of support, maximal flow rate, patient sneezing or coughing, cannula fit, and patient cooperation. 20 special attention must be paid to the connections between the oxygen tubing and the nasal cannula. 19 any disruption to this connection may lead to dispersal of sars-cov-2. 33 some experts have recommended placement of a surgical mask over the hfnc to reduce viral transmission. 19, 34 patients on hfnc should be placed under airborne precautions in a negative-pressure room, if available. 15, 19 j o u r n a l p r e -p r o o f hfnc provides gas flows between 40-60 l/min and may not result in aerosolization when compared to a patient on standard nasal cannula. 35 many guidelines, including those by australian and new zealand intensive care society (anzics), the who, and the surviving sepsis campaign recommend the use of hfnc in covid-19 patients presenting with acute hypoxemic respiratory failure unresponsive to conventional oxygen therapy. 15, 16, 18 several groups have developed management strategies utilizing hfnc preferentially over niv. 9, 36 it is prudent to avoid hfnc in patients presenting with severe respiratory distress or failure, thoracoabdominal asynchrony, increasing vasopressor support, refractory hypoxemia despite other therapies, or a "clinical trajectory that suggests mechanical ventilation is inevitable". 4,25,37 niv may be more effective for other forms of respiratory failure, such as hypercapnic respiratory failure or obstructive airway disease. 18 however, hfnc can increase airway pressures, improve oxygenation, reduce dead space, and reduce a patient"s work of breathing and can be utilized in patients with covid-19. 38 international guidelines on the use of niv for covid-19 patients vary, with many guidelines recommending against the routine use of niv due to increased risk of virus aerosolization and unproven utility in patients with ards. 20 notably, the sccm guidelines on the management of critically ill patients with covid-19 recommend "a trial of niv with close monitoring and shortinterval assessment for worsening of respiratory failure" if hfnc is not available and there is no urgent indication for intubation. 18 current epidemiological forecasts suggest that the requirements for mechanical ventilation may outpace the current ventilator capacity of many hospitals if niv is not routinely used. 18 niv does have limitations. in previous cohorts of patients with acute respiratory failure due to influenza a, niv failed in up to 85% of cases, portending a higher mortality compared to patients j o u r n a l p r e -p r o o f treated with invasive ventilation. 39, 40 in a group of 302 patients with middle east respiratory syndrome (mers) across 14 saudi arabian hospitals, 92% of patients trialed on niv failed to substantially improve, eventually requiring intubation. 41 a relatively similar failure rate was noted in a cohort of patients with covid-19 associated respiratory failure in china. 9 there is also concern that niv may worsen lung injury due to elevated transpulmonary pressures and large tidal volumes. 42, 43 niv use in patients with excessive respiratory efforts may induce substantial intrathoracic negative pressures and self-inflicted lung injury, worsening hypoxemia. 43 additionally, the use of niv may delay initiation of mechanical ventilation until the patient has no reserve, thereby increasing the risk of inappropriate donning of adequate ppe and transmission to hcws due to time pressures to establish a definitive airway. 4 although some centers reported successful management of sars patients with niv, there are documented cases of nosocomial transmission between patients in the same hospital. 44, 45 this risk of aerosolization and viral transmission is variable, depending on a variety of factors, including the support parameters, model of the machine, and mask type. 19, 46 this risk could be diminished by use of appropriate viral exhalation filters on the niv and cohorting high-risk patients in an appropriate airborne isolation room. 19 however, any significant mask leak may render filtration of viral pathogens incomplete. 4 despite these limitations, niv may improve patient respiratory status and is a component of current guidelines. 18, 19 niv should be used in patients with covid-19 with hypercarbic respiratory failure, refractory hypoxemia despite other therapies (including hfnc), or if hfnc is not available. 18 if utilized for patients with covid-19, special attention should be paid to the use of viral filters, closed circuit systems, adequate mask seal, use of helmet systems (if available), appropriate ppe use, and appropriate isolation in a negative pressure room. 19 when available, a helmet-based niv j o u r n a l p r e -p r o o f interface may have several advantages over traditional mask-based niv, including decreased risk of aspiration and environmental contamination. 33, 47 in one randomized clinical trial of 83 patients with ards, a niv helmet reduced intubation rates and 90-day mortality compared to traditional niv facemask. 48 many clinicians have recommended awake proning or repositioning of patients on supplemental oxygen, hfnc, and niv. prone positioning of the patient may improve respiratory status and oxygenation, decreasing the need for endotracheal intubation in early ards. 49, 50 while proning or repositioning may improve oxygenation, clinicians should be aware that this typically induces a temporary, non-sustainable improvement in oxygenation, and patients may require movement to another position (i.e., left lateral recumbent, right lateral recumbent, sitting upright) to maintain the benefit associated with this technique. 49 patient comfort is important during proning/repositioning, and maternity cushioning devices may be beneficial. regardless of oxygenation, these patients remain at risk for deterioration and must be monitored closely. there are currently no evidence-based guidelines describing when to pursue intubation and mechanical ventilation for patients with sars-cov-2. 19 however, in cases of severe respiratory distress or refractory hypoxemia despite oxygen escalation therapy including niv, the patient should undergo endotracheal intubation and invasive ventilation. 14 many patients who develop acute respiratory failure do so with hypoxemia and minimal signs of respiratory distress or tachypnea (so called "silent hypoxemia"), making work of breathing alone a potentially unreliable indicator for failure of niv. 51, 52 thus, clinicians should consider patient mental status, work of breathing, respiratory rate, and oxygen saturation in their decision to intubate. in a series of 202 j o u r n a l p r e -p r o o f journal pre-proof covid-19 patients undergoing tracheal intubation in two hospitals in wuhan, china, more than 75% of patients were hypoxemic (sao 2 <90%) before induction. 53 the authors hypothesized that the shortage of available hospital beds during the covid-19 pandemic, as well as result in delayed recognition respiratory failure severity due to "silent hypoxemia," may have led to delays in the decision to intubate. 53 the chinese society of anesthesiology task force on airway management recommends endotracheal intubation for patients showing no improvement in respiratory distress, tachypnea (respiratory rate >30 breaths per minute), and poor oxygenation (pao 2 to fio 2 ratio ≤150 mmhg) after a 2 hour trial of hfnc or niv. 8 however, these recommendations are expert consensus and lack robust supporting evidence. 54 some have liberalized their criteria, recommending that physicians consider intubation in any patient with respiratory distress (respiratory rate >30 breaths per minute) or spo 2 less than 93% on room air and a pao 2 to fio 2 ratio less than 300 mmhg. 54 we recommend using a combination of factors in deciding to intubate, including progressively increasing oxygenation requirements despite oxygen escalation therapy, increasing vasopressor support, persistent thoracoabdominal asynchrony, increasing work of breathing, increasing respiratory distress, low rox index (determined by oxygen saturation as measured by pulse oximetry divided by fraction of inspired oxygen [fio2] divided by respiratory rate), hypercarbia, and altered mentation. 19, 25, 36, 37, 55 however, this must be balanced with potential resource limitations (availability of ventilators or staff, intensive care unit capability), clinical trajectory, and individual patient wishes. 19 airway management for patients with suspected or confirmed covid-19 shares similarities with techniques in non-covid-19 patients, with some notable exceptions, including an emphasis on j o u r n a l p r e -p r o o f staff safety throughout the procedure. 56 the increased risk of transmission of viral pathogens to hcws with subsequent attempts necessitates the use of familiar and reliable airway techniques to ensure the greatest likelihood of first pass success. 23 airborne precautions are indicated during the peri-intubation period, as the highest viral load appears in airway secretions of patients with covid-19. 5,57 careful preparation and planning at the institutional level addressing appropriate equipment, staff preparedness, development of airway packs and endotracheal intubation checklists (table 1 and figure 2 ), and availability of ppe are essential. 23 this should be augmented and evaluated using frequent in-situ simulation. 23, 58 patient. endotracheal intubation is a high-risk procedure, with 10% of critically ill patients developing severe hypoxemia and 2% experiencing cardiac arrest. 59, 60 the first pass success rate for endotracheal intubation among critically ill patients is typically less than 80%, with a significant proportion requiring two or more attempts. 59 these figures are likely to be worse in the critically ill covid-19 patient due to the use of ppe and the patient"s physiological state. 23, 61 patients with covid-19 may experience myocardial injury which can worsen hemodynamic instability, lead to multiorgan failure, and reduce oxygen reserve. 62 moreover, fogging of eyewear when using ppe during intubation affects up to 80% of providers, which can make intubation attempts more challenging. 23 some clinicians have advocated for placement of a clear drape or box over the patients face to minimize aerosolization, but this may affect first pass success. 63 one study evaluating the use of aerosol boxes to protect hcw found reduced first pass success, longer time to intubation, and decreased laryngoscopic grade. 64 ppe may also decrease the clinician"s field of vision, lead to reductions in manual dexterity, and interfere with team communication. 65 institutions should create a mobile endotracheal intubation pack that is decontaminated after each use (table 1) . 23, 56 this pack should preferentially contain single-use equipment brought to the patient"s bedside during the procedure. 4,23 some institutions may choose to include appropriate ppe for the airway management team. additional airway equipment may be stored outside the negative pressure room as necessary. 4 all essential medications should be present before the procedure. rapid sequence induction (rsi) medications should be drawn up and labeled. depending on the patient"s hemodynamic status, push dose vasopressors or a norepinephrine infusion should be j o u r n a l p r e -p r o o f readily available. 56 ensure appropriate post-intubation analgesia, sedation, and paralyzing medications are present. 56 staff members who are not involved in the procedure should not be present during any aerosolgenerating procedure, including intubation. 4 there should be a clear delineation of roles and responsibilities on the team. three personnel are likely sufficient within the room: an airway operator, an airway assistant, and a healthcare provider to give the medications and monitor the patient (figure 3 ). 23 one to two team members should wait outside the room in ppe ready to enter if the primary team requires help or extra equipment, with an additional team member watching from the outside, ready to summon help rapidly if needed. 23 a designated safety/logistics officer should remain outside the room to observe for strict adherence to team safety and proper donning and doffing of ppe. a single team member may perform more than one role, depending on how many personnel are available. (4) team member to fetch additional equipment or call for help during the procedure, and to observe strict adherence to team safety and donning and doffing of ppe in the peri-procedure period (safety and logistics officer). a single team member may perform more than one role, depending on how many personnel are available. the choice of airway operator encompasses consideration of the available clinicians" airway expertise, predicted difficulty of intubation, patient factors, and clinician risk factors for poor outcomes if infected with sars-cov-2. 23, 56 while little guidance exists to risk stratify hcws who are exposed to potential aerosol-generating procedures, it is prudent to exclude staff who are over the age of 60 years; pregnant; immunosuppressed; and those with cardiac disease, respiratory diseases, and recent cancer. 5, 8, 23 j o u r n a l p r e -p r o o f the airway strategy, including preoxygenation strategy, primary plan, rescue plans, and transitions, should be standardized. the basic algorithm for intubation is similar to the difficult airway society (das) 2018 guideline for tracheal intubation of the critically ill patient (figure 4a and 4b) or the vortex approach (figure 4c) . 23, 67 there is emphasis on appropriate equipment selection, with a focus on closed systems to prevent viral transmission. 4, 23 closed suction systems should be used to minimize aerosolization. apneic oxygenation should be avoided in these patients. however, preoxygenation may be accomplished with a bag valve mask (bvm) and viral exhalation filter. 56, 68 the airway operator should ensure a tight bvm seal with two hands using the "v" grip while applying 10-15 cm of peep ( figure 5 ). this bvm is held passively in order to maintain peep, prevent decruitment and hypoxia. 56, 62 to improve mask seal and decrease airway operator fatigue, a niv mask may be used in conjunction with a bvm to preoxygenate the patient ( figure 6 ). for patients requiring manual ventilation, small tidal volumes are recommended. 68 elevation of the head of the bed and ramping may be utilized. 23 the preferred airway management technique is rsi with the use of a video laryngoscope (vl) by the most appropriate clinician to maximize first pass success. 18, 23, 53 in a systemic review and meta-j o u r n a l p r e -p r o o f analysis of 64 studies, vl reduced the risk of failed intubation with no impact on the rate of first pass success, hypoxia, or time to endotracheal intubation. 69 if possible, the vl setup should include a monitor screen separate from the handle to reduce potential exposure to the patient"s upper airway secretions. when available, a standard geometry video laryngoscope should be used in conjunction with a tracheal tube introducer (i.e., bougie), as this has been shown to improve first pass success when compared to a traditional stylet. 56, 70 awake flexible endoscopic intubation should be avoided, as the atomized local anesthesia may induce coughing. 68 when possible, direct laryngoscopy (dl) should be avoided as it places the face of the intubating clinician close to the patient"s airway and may increase the risk of exposure. 4, 18 rsi is recommended, as inadequate sedation or paralysis can produce coughing during laryngoscopy, generating aerosols. 4,56 a higher dose of sedative, as well as high-dose neuromuscular blockade should be administered during induction. 23, 56 nondepolarizing muscle relaxants such as rocuronium provide an advantage over depolarizing agents due to their extended duration of action, which prevents coughing should attempts at airway management be prolonged. 20 in order to improve ventilator synchrony and decrease aerosolization from inadequate sedation, prepare the patient"s post-intubation analgesia and sedation before the procedure. 56 if the initial intubation is unsuccessful and the patient requires oxygenation, a second-generation supraglottic airway device can be used to reduce aerosolization risk. 22, 56, 71 there is no robust evidence to suggest that supraglottic devices are more effective than bvm in this scenario. however, they are easy to place and have better seal pressure compared to bvm, thus reducing staff exposure. 20 if oxygenation cannot be maintained using a bvm or a supraglottic device, a cricothyroidotomy should be performed. 56 the simplified das 2018 guidance should be followed ( figure 4b) . we recommend the scalpel-bougie-tube technique in order to decrease potential j o u r n a l p r e -p r o o f aerosolization. 20, 56 while attempting an emergency front of neck access (fona) procedure, application of oxygenation from above is not recommended, as this may cause aerosolization when the cricothyroid membrane is punctured. 20 suction during the procedure should consist of a closed system with a viral filter. 72 after successful intubation, it is important to avoid ventilation until an appropriate viral filter is in place and the endotracheal tube cuff is inflated. 23 ensure tight connections between all parts of the ventilator circuit, and avoid unnecessary disconnections whenever possible. however, if the circuit must be disconnected, clamp the endotracheal tube to prevent aerosolization. endotracheal tube placement must be confirmed with waveform capnography, as ppe may preclude reliable auscultation of breath sounds. 4, 73 providers may also observe bilateral chest rise during assisted breaths, or alternatively, the ventilator waveform. 62 ultrasonography is a useful adjunct for confirming endotracheal intubation, as it can allow direct confirmation without the requirement for ventilations. 74 and a negative likelihood ratio of 0.01 (95% ci 0.01 to 0.02). 75 to prevent repeated exposures, a nasogastric tube may be inserted in the immediate post-intubation period. 23 clinicians may also consider obtaining deep tracheal sputum samples. ensure proper analgesia and sedation in order to prevent patient coughing and potential transmission of sars-cov-2. 56 any immediate post-intubation complications should be aggressively investigated and corrected. in a series of 202 covid-19 patients undergoing tracheal intubation in two hospitals in wuhan, china, peri-intubation hypotension (arterial blood pressure less than 90/60 mm hg) occurred in j o u r n a l p r e -p r o o f 22.3% of patients. 53 pneumothorax occurred in 5.9% of patients, while 2% suffered peri-intubation cardiac arrest. 53 peri-intubation hypotension should be managed with intravenous fluids and/or vasopressors, while pneumothorax may be corrected with chest tube drainage. after the immediate post-intubation period, equipment should be disposed of or decontaminated. individual ppe should be removed under the guidance of a trained observer. patients with covid-19 may develop acute respiratory failure and require respiratory support, as well as advanced airway management. 4 airway management in these patients is a high-risk procedure for hcws due to aerosolization and viral transmission. 11 the principles of airway management are similar between cvoid-19 and non-cvoid-19 patients, but with an enhanced focus on hcw safety. 56 a pragmatic approach to respiratory support in this population centers on appropriate infectious precautions (isolation, negative pressure rooms, and ppe), titrated support with exogenous oxygen, hfnc, niv, and endotracheal intubation. world health organization clinical features of patients infected with 2019 novel coronavirus in wuhan clinical characteristics of coronavirus disease 2019 in china practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-ncov) patients characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72314 cases from the chinese center for disease control and prevention baseline characteristics and outcomes of 1591 patients infected with sars-cov-2 admitted to icus of the lombardy region covid-19 in critically ill patients in the seattle region -case series expert recommendations for tracheal intubation in critically ill patients with noval coronavirus disease clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study. the lancet respiratory medicine clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china protecting health-care workers from subclinical coronavirus infection aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review pathological findings of covid-19 associated with acute respiratory distress syndrome novel 2019 coronavirus sars-cov-2 (covid-19): an updated overview for emergency clinicians clinical management of severe acute respiratory infection when novel coronavirus (ncov) infection is suspected the australian and new zealand intensive care society. covid-19 guidelines anzics covid-19 practice management guide: clinical management of covid-19 surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (covid-19) respiratory support for adult patients with covid-19 consensus statement: safe airway society principles of airway management and tracheal intubation specific to the covid-19 adult patient group why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? clinical infectious diseases staff safety during emergency airway management for covid-19 in hong kong consensus guidelines for managing the airway in patients with covid-19 high flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis high-flow nasal therapy in adults with severe acute respiratory infection: a cohort study in patients with 2009 influenza a/h1n1v high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure the experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of chongqing patient self-proning with high-flow nasal cannula improves oxygenation in covid-19 pneumonia comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial nasal high-flow therapy and dispersion of nasal aerosols in an experimental setting assessment of the potential for pathogen dispersal during high-flow nasal therapy risk factors for sars transmission from patients requiring intubation: a multicentre investigation in toronto exhaled air dispersion during high-flow nasal cannula therapy versus cpap via different masks exhaled air dispersion during coughing with and without wearing a surgical or n95 mask optimum insufflation capacity and peak cough flow in neuromuscular disorders severe sars-cov-2 infections: practical considerations and management strategy for intensivists beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study high-flow nasal cannula: mechanisms of action and adult and pediatric indications critically ill patients with 2009 influenza a(h1n1) infection in canada risk factors for noninvasive ventilation failure in critically ill subjects with confirmed influenza infection noninvasive ventilation in critically ill patients with the middle east respiratory syndrome. influenza other respir viruses ventilator-induced lung injury noninvasive ventilation for patients with hypoxemic acute respiratory failure effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome role of air distribution in sars transmission during the largest nosocomial outbreak in hong kong exhaled air dispersion during noninvasive ventilation via helmets and a total facemask minimise nosocomial spread of 2019-ncov when treating acute respiratory failure. the lancet effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial efficacy and safety of early prone positioning combined with hfnc or niv in moderate to severe ards: a multi-center prospective cohort study prone position for acute respiratory distress syndrome. a systematic review and meta-analysis critical care crisis and some recommendations during the covid-19 epidemic in china basing respiratory management of coronavirus on physiological principles emergency tracheal intubation in 202 patients with covid-19 in wuhan, china: lessons learnt and international expert recommendations intubation and ventilation amid the covid-19 outbreak an index combining respiratory rate and oxygenation to predict outcome of nasal high-flow therapy just the facts: airway management during the covid-19 pandemic detection of sars-cov-2 in different types of clinical specimens using simulation for training and to change protocol during the outbreak of severe acute respiratory syndrome airway challenges in critical care guidelines for the management of tracheal intubation in critically ill adults airway management in disaster response: a manikin study comparing direct and video laryngoscopy for endotracheal intubation by prehospital providers in level c personal protective equipment precautions for intubating patients with covid-19 barrier enclosure during endotracheal intubation the aerosol box for intubation in covid-19 patients: an in-situ simulation crossover study use of personal protective equipment during infectious disease outbreak and nonoutbreak conditions: a survey of emergency medical technicians the use of personal protective equipment for control of influenza among critical care clinicians: a survey study the vortex approach outbreak of a new coronavirus: what anaesthetists should know videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation effect of use of a bougie vs endotracheal tube and stylet on first-attempt intubation success among patients with difficult airways undergoing emergency intubation: a randomized clinical trial the laryngeal mask airway proseal(tm) as a temporary ventilatory device in grossly and morbidly obese patients before laryngoscope-guided tracheal intubation surgical considerations for tracheostomy during the covid-19 pandemic auscultation without contamination: a solution for stethoscope use with personal protective equipment ultrasound for airway management: an evidence-based review for the emergency clinician ultrasonography for the confirmation of endotracheal tube intubation: a systematic review and meta-analysis bl, tm, mr, mg, and dh conceived the idea for this manuscript and contributed substantially to the writing and editing of the review. this manuscript did not utilize any grants, and it has not been presented in abstract form. this clinical review has not been published, it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities key: cord-034185-e0am7pa6 authors: piccioni, federico; droghetti, andrea; bertani, alessandro; coccia, cecilia; corcione, antonio; corsico, angelo guido; crisci, roberto; curcio, carlo; del naja, carlo; feltracco, paolo; fontana, diego; gonfiotti, alessandro; lopez, camillo; massullo, domenico; nosotti, mario; ragazzi, riccardo; rispoli, marco; romagnoli, stefano; scala, raffaele; scudeller, luigia; taurchini, marco; tognella, silvia; umari, marzia; valenza, franco; petrini, flavia title: recommendations from the italian intersociety consensus on perioperative anesthesa care in thoracic surgery (pacts) part 2: intraoperative and postoperative care date: 2020-10-23 journal: perioper med (lond) doi: 10.1186/s13741-020-00159-z sha: doc_id: 34185 cord_uid: e0am7pa6 introduction: anesthetic care in patients undergoing thoracic surgery presents specific challenges that require a multidisciplinary approach to management. there remains a need for standardized, evidence-based, continuously updated guidelines for perioperative care in these patients. methods: a multidisciplinary expert group, the perioperative anesthesia in thoracic surgery (pacts) group, was established to develop recommendations for anesthesia practice in patients undergoing elective lung resection for lung cancer. the project addressed three key areas: preoperative patient assessment and preparation, intraoperative management (surgical and anesthesiologic care), and postoperative care and discharge. a series of clinical questions was developed, and literature searches were performed to inform discussions around these areas, leading to the development of 69 recommendations. the quality of evidence and strength of recommendations were graded using the united states preventive services task force criteria. results: recommendations for intraoperative care focus on airway management, and monitoring of vital signs, hemodynamics, blood gases, neuromuscular blockade, and depth of anesthesia. recommendations for postoperative care focus on the provision of multimodal analgesia, intensive care unit (icu) care, and specific measures such as chest drainage, mobilization, noninvasive ventilation, and atrial fibrillation prophylaxis. conclusions: these recommendations should help clinicians to improve intraoperative and postoperative management, and thereby achieve better postoperative outcomes in thoracic surgery patients. further refinement of the recommendations can be anticipated as the literature continues to evolve. thoracic surgery requires an evidence-based multidisciplinary approach that extends across the perioperative period, from preadmission evaluation to postoperative care and discharge. although such perioperative care protocols, known as the enhanced recovery after surgery (eras ® ) "philosophy," have been developed in many surgical settings, including lung surgery (batchelor et al. 2019) , and have been shown to be effective in reducing postoperative complications and length of hospital stay (los) (nicholson et al. 2014) , systematic reviews of studies in thoracic surgery (cerfolio et al. 2001a; das-neves-pereira et al. 2009; muehling et al. 2008; salati et al. 2012 ) have highlighted significant heterogeneity and methodological flaws in many trials (fiore jr et al. 2016; li et al. 2017 ). to address this, an italian expert group, the perioperative anesthesia care in thoracic surgery (pacts) group, was convened to develop evidence-based recommendations for the management of thoracic surgery patients. the pacts group is a joint task force of the italian society of anesthesia, analgesia, resuscitation, and intensive care the methods used to develop the pacts recommendations have been described in full in an accompanying paper. in brief, the project focused on preoperative patient assessment and preparation, intraoperative management (surgical and anesthesiologic), and postoperative procedures and discharge in adult patients undergoing elective lung resection for lung cancer. a series of clinical questions were framed using the pico (patients, intervention, comparison, outcome) approach, and a delphi consensus method was used to reach agreement based on comprehensive literature searches. the quality of evidence and strength of recommendations were graded according to the united states preventive services task force (uspstf) criteria (united states preventive services task force 2019); in addition, the panel classified as "best practice" the recommendations considered to have a high level of certainty despite a lack of direct evidence. for uspstf grade a, b, or c recommendations, consensus required > 70% a/b/c ratings with < 15% d/i ratings. for grade d or i recommendations, consensus required > 70% d/i ratings and < 15% a/b/c ratings. the uspstf system was used in preference to the grade system, which has been used in the eras lung surgery guidelines (batchelor et al. 2019) , because the intention was to produce a position statement rather than full practice guidelines. the grade system involves full appraisal of a limited number of pico questions, and is therefore timeand resource-consuming. it is not always feasible where a number of recommendations are required in fields where no large evidence base exists, or which cannot easily be addressed using a pico framework. each author approved the final version prior to submission. this paper summarizes the final recommendations for intraoperative and postoperative care (table 1) , and the supporting evidence for each recommendation. the recommendations for preadmission and preoperative care are presented in the accompanying paper. airway management recommendation 1: the use of videolaryngoscopy for tracheal intubation with a double-lumen tube might improve visualization of the glottis and the success rate at the first attempt, reducing difficulty and positioning time. videolaryngoscopy can be used in cases of unexpected difficult intubation. level of evidence: poor the use of videolaryngoscopy for tracheal intubation with a double-lumen tube might improve visualization of the glottis and the success rate at the first attempt, reducing difficulty and positioning time. videolaryngoscopy can be used in cases of unexpected difficult intubation. poor c we recommend the use of a double-lumen tube to manage one-lung ventilation. a single lumen tube with a bronchial blocker, rather than a double-lumen tube, is recommended for patients with difficult airways. good a we recommend the use of a flexible bronchoscope to control the position of the lung isolation device. flexible bronchoscopy must always be available, even if not used routinely. thoracic anesthesiologists must have adequate bronchoscopy skills to manage dlt and bronchial blockers for one-lung ventilation. good a we recommend monitoring arterial blood pressure with invasive (intra-arterial) techniques, rather than the non-invasive oscillometric cuff technique, in patients undergoing major thoracic surgery, or when sudden changes in hemodynamics, hemoglobin and blood gas concentrations (oxygen and carbon dioxide) are expected. we suggest considering the use of a central venous catheter on a case-by-case basis in patients undergoing thoracic surgery. peripheral catheters are safe for short-term and low-dose treatment with inotropic vasoactive drugs. in patients undergoing thoracic surgery who are considered at higher risk of postoperative complications, we suggest the use of hemodynamic monitoring with cardiac output estimation systems. we do not recommend the use of dynamic preload indices during open-chest thoracic surgery, because these parameters might not be reliable. we suggest that patients undergoing thoracic surgery under general anesthesia are monitored with processed electroencephalography (peeg) in order to titrate anesthetic administration. we recommend that intraoperative temperature be monitored using an appropriate system in all patients undergoing thoracic surgery lasting more than 30 minutes. a core temperature of at least 36°c should be maintained. we recommend monitoring neuromuscular blockade in all patients receiving neuromuscular blocking agents during general anesthesia for thoracic surgery. in low risk patients (simple procedures, younger patients and without cardiac or renal comorbidities), the use of a bladder catheter is not recommended. we recommend using balanced crystalloid solutions, rather than normal saline (nacl 0.9%), as standard fluid of choice. we do not recommend the use of hydroxyethyl starch as routine fluid therapy in patients undergoing thoracic surgery. we recommend a near-zero, rather than restricted or permissive, fluid balance to patients undergoing thoracic surgery. in high-risk patients a goal-directed approach to fluid therapy should be applied. we suggest using serum hemoglobin concentration in the evaluation of volume status in nonbleeding patients undergoing thoracic surgery. we recommend a protective ventilation approach during one-lung ventilation, based on the combination of low tidal volumes (≤ 6 ml/kg ideal body weight) with alveolar recruitment maneuvers, adequately titrated positive end-expiratory pressure (peep) and the lowest fraction of inspired oxygen (fio2) to maintain satisfactory arterial oxygen saturation. fair a volatile anesthesia cannot be recommended over intravenous propofol administration in order to reduce postoperative complications, although there is evidence of a lower degree of both systemic and local inflammation when volatile anesthetics are used. we recommend the early removal of urinary catheters to promote mobilization in patients undergoing lung surgery, including those receiving thoracic epidural catheters. fair a we recommend the use of pre-emptive locoregional analgesia as part of a multimodal analgesic approach for thoracic surgery. systemic opioids, nonsteroidal anti-inflammatory drugs, and paracetamol have shown no evidence of benefit when used as pre-emptive analgesics. currently, there are no elements to suggest the routine perioperative use of gabapentinoids in patients undergoing thoracic surgery, but their use can be effective in a comprehensive multimodal analgesia protocol. we suggest intraoperative intravenous administration of ketamine to reduce postoperative pain after thoracic surgery. there is no evidence about the best dose and timing of administration of ketamine. we suggest intraoperative intravenous administration of magnesium sulfate to reduce postoperative pain after thoracic surgery. there is no evidence to suggest the routine use of α 2 -agonists as part of a multimodal analgesia regimen to reduce postoperative pain after thoracic surgery. there is no consensus on the best timing and schedule for administration of these drugs. we suggest considering the use of intravenous steroids as part of a multimodal approach to reduce peripheral sensibilization of inflammatory-induced pain in patients undergoing thoracic surgery. adverse effects of single doses of steroids are of trivial clinical impact. we recommend the use of intravenous nonsteroidal anti-inflammatory drugs (nsaids) to reduce peripheral sensitization to inflammation-induced pain in patients undergoing thoracic surgery. combined use of nsaids and paracetamol may give a further analgesic advantage. we recommend the use of locoregional anesthesia for intraoperative and postoperative pain management. poor a we recommend the use of thoracic epidural analgesia in high-risk patients or in major surgical procedures where the parietal pleura (eg chest wall resection) is violated (i.e. thoracotomy, thoracosternotomy, chest wall resection). we recommend thoracic paravertebral block for vats, as part of a multimodal approach. good a we recommend paravertebral block in preference to thoracic epidural analgesia in patients with known or suspected coagulopathy. we suggest that intercostal nerve blockade should be considered only as a second choice for analgesia after thoracic surgical procedures. we suggest erector spinae plane block as part of a multimodal analgesia for thoracic surgery, especially for vats. we suggest the use of fascial pain blocks as part of multimodal analgesia for thoracic surgery, particularly for vats. we suggest considering the use of adjuvants (i.e. opioids, clonidine, dexmedetomidine b , dexamethasone, magnesium) when loco-regional anesthesia is performed, because the use of adjuvants can potentiate and prolong the effect of local anesthetics. we suggest considering the use of a single large-bore chest tube instead of a double tube after thoracic surgery. insertion of more than one chest tube may be considered in selected cases (e.g., bi-lobectomy or bleeding patients). we suggest considering the use of digital chest drainage systems to promote early mobilization of the patient. the routine use of drainage with suction is not recommended in the absence of complications, provided there is full re-expansion of the residual parenchyma after lung resection. we suggest removing chest tubes in lung resection patients when liquid output is ≤ 5 cm 3 /kg/ 24 h of serous fluid. we do not recommend systematic icu admission after thoracic surgery. poor d we recommend that, in adult patients undergoing thoracic surgery, oral intake, including clear liquids, can be initiated 4-6 hours after surgery, in the absence of nausea and vomiting. oral intake should, however, be adapted to individual tolerance. we recommend early mobilization of patients within the first 24 h after both minor and major fair a strength of recommendation: c several studies have compared videolaryngoscopy with the macintosh blade laryngoscope for tracheal intubation, in order to determine whether videolaryngoscopy improves the speed and success of double-lumen tube (dlt) positioning and reduces malpositioning rates (el-tahan et al. 2018; hamp et al. 2015; lin et al. 2012; purugganan et al. 2012; russell et al. 2013; wasem et al. 2013 ). these studies have yielded conflicting results: while some authors have reported that videolaryngoscopy is superior to the macintosh laryngoscope blade in terms of ease of use and higher rates of correct positioning of the dlt (lin et al. 2012; purugganan et al. 2012) , others have found no significant differences between the two techniques in terms of time to intubation and hemodynamic stress response (hamp et al. 2015; russell et al. 2013; wasem et al. 2013 ). there are limited data to suggest that videolaryngoscopy may improve visualization of the glottis, resulting in higher success rates at the first attempt, and reduced difficulty and positioning time (lin et al. 2012; purugganan et al. 2012 ). however, the success rate is highly dependent on the operator's experience (el-tahan et al. 2018) . recommendation 2: we recommend the use of a double-lumen tube to manage one-lung ventilation. a single lumen tube with a bronchial blocker, rather than a double-lumen tube, is recommended for patients with difficult airways. level of evidence: good strength of recommendation: a lung isolation techniques are designed to facilitate surgical exposure of the lung and achieve one-lung ventilation in patients undergoing thoracic surgery (campos and kernstine 2003; narayanaswamy et al. 2009 ). these techniques use either a dlt with both an endotracheal and an endobronchial lumen, or a bronchial blocker inside a single-lumen endotracheal tube, which allows collapse of the lung distal to the site of occlusion. dlts offer a number of advantages over bronchial blockers, including faster and easier positioning (campos and kernstine 2003; narayanaswamy et al. 2009; clayton-smith et al. 2015; dumans-nizard et al. 2009; ruetzler et al. 2011) , and a lower likelihood of displacement requiring repositioning under bronchoscopy (campos and kernstine 2003; narayanaswamy et al. 2009 ). in addition, pulmonary collapse can be achieved more quickly with dlts, because bronchial blockers do not allow adequate suction to cause lung collapse (campos 2002; yoo et al. 2014) . dlts also ensure pulmonary isolation, protecting the contralateral lung from blood or infections (santana-cabrera et al. 2010) , although the incidence of trauma during intubation is comparable with the two types of device (clayton-smith et al. 2015; knoll et al. 2006) . for these reasons, siaarti guidelines recommend dlts for routine clinical use (merli et al. 2009 ). the decision to use a bronchial blocker, rather than a dlt, in an individual patient should be based on the specific clinical circumstances (merli et al. 2009; campos 2007) . recommendation 3: we recommend the use of a flexible bronchoscope to control the position of the lung isolation device. flexible bronchoscopy must always be available, even if not used routinely. thoracic anesthesiologists must have adequate bronchoscopy skills to manage dlt and bronchial blockers for one-lung ventilation. level of evidence: good strength of recommendation: a the use of a flexible bronchoscope to confirm the correct placement of dlts for lung resection is we recommend a physiotherapy program after thoracic surgery. fair a we suggest considering daily chest radiographs only in selected cases under specific clinical indications. we do not recommend the routine use of either continuous positive airway pressure (cpap) or non invasive ventilation (niv) to prevent postoperative pulmonary complications, prolonged length of stay, and mortality (both in icu and in hospital) in patients undergoing major thoracic surgery. cpap or niv could be considered case by case in selected high risk patients. we suggest the use of niv or cpap to treat acute respiratory failure complicating thoracic surgery. poor b we suggest considering the use of high-flow nasal cannula oxygen therapy (hfnc) as an alternative or integrative support to cpap or niv to prevent or treat acute respiratory failure complicating thoracic surgery. dexmedetomidine is currently approved in italy only for sedation, and thus cannot be recommended for analgesic use in italian settings recommended. studies have shown that flexible bronchoscopy after auscultatory or tactile confirmation of the location of the dlt can identify malpositioning in more than one-third of patients (klein et al. 1998; de bellis et al. 2011) , and hence some authors have recommended that the position of the dlt should routinely be confirmed by fiberoptic bronchoscopy (klein et al. 1998; cohen 2004) . however, this requires technical expertise in flexible bronchoscopy, and a detailed knowledge of tracheobronchial anatomy (cohen 2004; campos 2009; solidoro et al. 2019) . it remains unclear whether routine bronchoscopic confirmation of the position of the dlt is necessary. malpositioning of the dlt is a major cause of intraoperative hypoxemia: in one case series, 21 of 56 patients in whom the dlt was positioned too deeply in the left bronchus developed hypoxemia during one-lung ventilation of the left lung (brodsky and lemmens 2003) . for this reason, the position of the dlt must be rechecked by flexible bronchoscopy after the onset of intraoperative hypoxemia, with the patient in the lateral decubitus position (brodsky and lemmens 2003; inoue et al. 2004) . obstruction of the left or right upper lobe bronchus is the most common significant malposition with dlts (slinger 1989 ), but there is no consensus as to the optimal position of the dlt. many malpositions may be attributable to an inappropriate choice of dlt or suboptimal positioning technique (slinger 1989; fortier et al. 2001; seymour and lynch 2002) . to date, no data have demonstrated the clinical relevance of malpositioning to patient outcomes, except in cases of dangerous or critical malposition, and there is no evidence that routine confirmation of dlt positioning by flexible bronchoscopy reduces morbidity after thoracic surgery. when a left dlt is inserted, the use of tubes with integrated high-resolution cameras can facilitate correct positioning and easier one-lung ventilation (massot 2015; schuepbach et al. 2015) . in one study, the mean time to successful intubation was significantly shorter with the vivasight-dl (etview medical ltd, misgav, israel) than with conventional dlts (63 s versus 97 s, respectively, p = 0.03), and all vivasight-dl tubes were correctly positioned (schuepbach et al. 2015) . furthermore, compared with blind placement, the use of tubes with integrated high-resolution cameras can shorten the intubation time and permits continued monitoring of the carina, thereby allowing prompt management of intraoperative tube displacement (massot 2015; schuepbach et al. 2015; belze et al. 2017; chen et al. 2017; heir et al. 2014) . recommendation 4: we recommend monitoring arterial blood pressure with invasive (intra-arterial) techniques, rather than the non-invasive oscillometric cuff technique, in patients undergoing major thoracic surgery, or when sudden changes in hemodynamics, hemoglobin and blood gas concentrations (oxygen and carbon dioxide) are expected. level of evidence: good strength of recommendation: a limited data suggest good concordance between invasive and non-invasive arterial pressure measurements in patients undergoing major thoracic surgery (bardoczky et al. 1992; d'antini et al. 2016; martina et al. 2012) , but further studies are needed in this area. due to the possibility of rapid changes in stroke volume and arterial blood pressure, and the potential usefulness of arterial blood sampling for gas, hemoglobin, and electrolyte analysis, invasive (intra-arterial) monitoring of arterial blood pressure is recommended in patients undergoing major thoracic surgery. in general, the risk of significant blood loss is very low in patients with no history of radiotherapy or chemotherapy who are undergoing primary lung surgery. for patients undergoing minor resections, the use of invasive blood pressure monitoring should be considered on a case-by-case basis according to the patient's comorbidity and surgical complexity. although specific studies on thoracic surgery patients are lacking, studies in mixed surgical populations have demonstrated that even short periods of hypotension significantly increase postoperative complications such as acute kidney injury (aki), myocardial injury after non-cardiac surgery (mins), and death (van waes et al. 2016; walsh et al. 2013; sessler et al. 2019) . in a review of data from 33,330 patients undergoing non-cardiac surgery, the relative risks of both aki and mins increased progressively with increasing duration of hypotension (mean arterial pressure < 55 mmhg), compared with patients with mean arterial pressure above this threshold, even when the duration of hypotension was only 1-5 min (walsh et al. 2013) . a mean arterial pressure threshold of 65 mmhg, or 60-70 mmhg with a systolic arterial pressure of 100 mmhg, has been identified as critical to reduce the occurrence of aki, mins and mortality (sessler et al. 2019; salmasi et al. 2017) . recommendation 5: we suggest considering the use of a central venous catheter on a case-by-case basis in patients undergoing thoracic surgery. peripheral catheters are safe for short-term and low-dose treatment with inotropic vasoactive drugs. level of evidence: fair strength of recommendation: c there is no evidence that central venous catheters are essential for the intraoperative and postoperative management of thoracic surgery patients. measurement of central venous pressure to predict the response to volume expansion may be inconclusive in a significant proportion of patients (cannesson et al. 2011 ). furthermore, several studies have shown that low doses of vasoactive medications can be safely administered via peripheral intravenous catheters, with extravasation rates of approximately 2-4% (cardenas-garcia et al. 2015; lewis et al. 2019; medlej et al. 2018) . for these reasons, the routine use of central venous catheters is not recommended in patients undergoing thoracic surgery: the need for central venous catheterization should be evaluated on a case-by-case basis. recommendation 6: in patients undergoing thoracic surgery who are considered at higher risk of postoperative complications, we suggest the use of hemodynamic monitoring with cardiac output estimation systems. level of evidence: poor strength of recommendation: c there is evidence that hemodynamic monitoring using cardiac output estimation systems to inform goal-directed fluid management is beneficial in thoracic surgery patients at higher risk of postoperative complications (cecconi et al. 2013; kaufmann et al. 2017; michard et al. 2017; searl and perrino 2012; zhang et al. 2013) . furthermore, such monitoring can be useful to avoid hypoxemia during one-lung ventilation, because extreme increases or decreases in cardiac output can impair the hypoxic pulmonary vasoconstriction (lumb and slinger 2015) . the use of this approach should be based on the estimated risk of complications in the individual patient. recommendation 7: we do not recommend the use of dynamic preload indices during open-chest thoracic surgery, because these parameters might not be reliable. level of evidence: good strength of recommendation: d a recent meta-analysis of seven trials has found that pulse pressure and stroke volume are inaccurate predictors of fluid responsiveness in patients undergoing open thoracotomy (piccioni et al. 2017) , and a subsequent study has shown that this is also true in patients undergoing vats procedures (jeong et al. 2017) . recommendation 8: we suggest that patients undergoing thoracic surgery under general anesthesia are monitored with processed electroencephalography (peeg) in order to titrate anesthetic administration. level of evidence: fair strength of recommendation: b processed electroencephalography (peeg) based on bispectral index (bis) reduces recovery times (punjasawadwong et al. 2014; chiang et al. 2018 ). however, the impact of peeg on the risk of intraoperative awareness is unclear (punjasawadwong et al. 2014) . postoperative delirium occurs in approximately 14% of patients (berian et al. 2018) , and it is believed that monitoring the depth of anesthesia by peeg is associated with reductions in the incidence of postoperative delirium and cognitive dysfunction (pocd) (aldecoa et al. 2017; fritz et al. 2016) . a recent meta-analysis of six randomized controlled trials showed moderate-quality evidence that peeg-guided anesthesia could reduce the risk of postoperative delirium and pocd (punjasawadwong et al. 2018) . conversely, the engages study, a rct of 1232 patients undergoing major surgery under volatile general anesthesia, did not find any decrease in the incidence of postoperative delirium among patients managed with peeg, compared with usual care (wildes et al. 2019 ). peeg has been included in guidelines for the prevention of postoperative delirium from a number of organizations (aldecoa et al. 2017; j am coll surg 2015; gelb et al. 2018) . advanced peeg technology is considered useful to improve anesthesia monitoring, individual titration of anesthetics and optimized patient care (eagleman and drover 2018; fahy and chau 2018; montupil et al. 2019) . recommendation 9: we recommend that intraoperative temperature be monitored using an appropriate system in all patients undergoing thoracic surgery lasting more than 30 min. a core temperature of at least 36°c should be maintained. level of evidence: good strength of recommendation: a hypothermia occurs in approximately 35-50% of thoracic surgery patients because the pleural surface on one side of the thorax is exposed to dry air during surgery, leading to evaporative heat loss (batchelor et al. 2019) . avoidance of hyperthermia is essential to prevent deleterious effects on homeostasis and reduce the risk of a systemic inflammatory response. hence, the eras guidelines for thoracic surgery recommend that body temperature should be continuously monitored to guide therapy, and that active warming should be continued postoperatively until the patient's temperature is greater than 36°c (batchelor et al. 2019) . siaarti guidelines recommend that intraoperative temperature should be monitored in all patients undergoing thoracic surgery lasting more than 30 min, and that the aim should be to maintain a core temperature of at least 36°c (di marco and cannetti 2019). suitable monitoring systems include heated servo-controlled sensors, intra-vascular catheters with thermistor tips, or rectal or bladder probes, but esophageal probes may be less accurate (di marco and cannetti 2019). a number of studies in various surgical settings have found that zero-heat-flux systems can be used for non-invasive temperature measurement, and show good agreement with conventional core temperature measurements (eshraghi et al. 2014; iden et al. 2015; makinen et al. 2016) . recommendation 10: we recommend monitoring neuromuscular blockade in all patients receiving neuromuscular blocking agents during general anesthesia for thoracic surgery. level of evidence: good strength of recommendation: a neuromuscular blockade should be monitored in all patients receiving neuromuscular blocking agents (nmbas) during general anesthesia for thoracic surgery (ortega et al. 2018) . quantitative (objective) neuromuscular monitoring is more reliable than subjective and clinical tests to assess the neuromuscular block level and, more importantly, recovery before extubation (naguib et al. 2018 ). neuromuscular monitoring is essential for correct administration of both nmbas and reversal agents. recommendation 11: in low-risk patients (simple procedures, younger patients and without cardiac or renal comorbidities), the use of a bladder catheter is not recommended. level of evidence: fair strength of recommendation: d there is no evidence that urine output should be monitored in all patients undergoing thoracic surgery. recommendation 12: we recommend using balanced crystalloid solutions, rather than normal saline (nacl 0.9%), as standard fluid of choice. level of evidence: good strength of recommendation: a balanced crystalloid solutions differ from normal saline (nacl 0.9%) in that they contain anions other than chloride, such as lactate, acetate, malate, and gluconate, which act as physiological buffers (reddy et al. 2016; vincent and de backer 2016) . although specific studies in thoracic surgery patients are lacking, the available evidence suggests that normal saline is associated with risks of hyperchloremia, hyperchloremic acidosis and aki (reddy et al. 2016; zampieri et al. 2016) . for example, in a study in noncritically ill patients, the 30-day incidence of major renal adverse events in patients receiving balanced crystalloids or saline was 4.7% and 5.6%, respectively (odds ratio [or] 0.82, 95% confidence interval [ci] 0.70-0.95, p = 0.01), although there was no difference in the number of hospital-free days between the two treatments (self et al. 2018) . in general, most authors recommend that balanced crystalloids should be used in preference to normal saline (reddy et al. 2016; vincent and de backer 2016) . administration of normal saline is indicated only in specific circumstances, such as metabolic alkalosis, hyponatremia, or severe brain injury requiring normotonic fluid administration (vincent and de backer 2016) . recommendation 13: we do not recommend the use of hydroxyethyl starch as routine fluid therapy in patients undergoing thoracic surgery. level of evidence: good strength of recommendation: d patients undergoing lung resection surgery are at risk of postoperative respiratory failure, which could be related to the volume of fluid administered during surgery. hydroxyethyl starches could be administered in order to reduce the total amount of fluid given during surgery, but are associated with an increased risk of renal impairment (ahn et al. 2016 ). hence, the use of hydroxyethyl starch as routine fluid therapy should be avoided in patients undergoing thoracic surgery, although it could be considered in patients with severe hemorrhage who are not responding to crystalloid infusion (de hert and de baerdemaeker 2014). recommendation 14: we recommend a near-zero, rather than restricted or permissive, fluid balance to patients undergoing thoracic surgery. in high-risk patients, a goal-directed approach to fluid therapy should be applied. level of evidence: fair strength of recommendation: a there is evidence that a near-zero, rather than restricted or permissive, fluid balance is beneficial for patients undergoing thoracic surgery (searl and perrino 2012) , and hence this approach is recommended in normovolemic patients (chappell et al. 2008; licker et al. 2016 ). in highrisk patients, a goal-directed approach to fluid therapy is recommended because this has been shown to significantly reduce mortality and morbidity, compared with standard hemodynamic fluid management (cecconi et al. 2013; kaufmann et al. 2017; michard et al. 2017; zhang et al. 2013) . for example, a recent meta-analysis of 19 trials involving over 2000 patients found that goal-directed therapy was associated with a significant decrease in postoperative morbidity, compared with controls (or 0.46, 95% ci 0.30-0.70, p < 0.001) (michard et al. 2017 ). similarly, a meta-analysis of 32 trials involving approximately 2800 patients found a significant reduction in postoperative mortality with goal-directed therapy, compared with controls, in patients at highest risk of postoperative complications (or 0.20, 95% ci 0.09-0.41, p < 0.0001); there was also a significant reduction in complication rates (or 0.45, 95% ci 0.34-0.60, p < 0.00001), which was particularly marked in the highest risk subgroup (or 0.27, 95% ci 0.15-0.51, p < 0.0001) (cecconi et al. 2013) . recommendation 15: we suggest using serum hemoglobin concentration in the evaluation of volume status in nonbleeding patients undergoing thoracic surgery. level of evidence: poor strength of recommendation: c because hemoglobin concentrations reflect plasma volume changes in patients without significant bleeding, monitoring of hemoglobin levels may play a role in the evaluation of volume status in patients undergoing thoracic surgery (perel 2017; otto et al. 2017) . recommendation 16: we recommend a protective ventilation approach during one-lung ventilation, based on the combination of low tidal volumes (≤ 6 ml/kg ideal body weight) with alveolar recruitment maneuvers, adequately titrated positive end-expiratory pressure (peep) and the lowest fraction of inspired oxygen (fio 2 ) to maintain satisfactory arterial oxygen saturation. level of evidence: fair strength of recommendation: a although there is an emerging consensus in favor of protective ventilation during one-lung ventilation (lohser and slinger 2015) , relatively few well-designed randomized trials have compared protective and conventional onelung ventilation (lohser and slinger 2015; ahn et al. 2012; kim et al. 2019; yang et al. 2011; zhu et al. 2017) : most published studies have involved small patient populations, or had other methodological limitations. in one of the largest randomized trials, 100 patients undergoing elective lobectomy were randomized to receive either protective ventilation with an inspired oxygen fraction (fio 2 ) of 0.5, a tidal volume of 6 ml/kg, a positive end-expiratory pressure (peep) of 5 cm h 2 o, and pressure-controlled ventilation, or conventional ventilation with higher fio 2 and tidal volume, zero end-expiratory pressure, and volume-controlled ventilation (yang et al. 2011) . the incidence of pulmonary dysfunction (defined as pao 2 /fio 2 < 300 mmhg, lung infiltration or atelectasis) was significantly lower in patients receiving protective ventilation than in those receiving conventional ventilation (4% versus 22% respectively, p < 0.05). a further randomized trial, involving 65 patients undergoing vats lobectomy, found no significant difference in postoperative complication rates between patients receiving either volume-controlled or pressure-controlled protective ventilation (zhu et al. 2017) . by contrast, a randomized study in 50 patients found that protective ventilation did not offer any significant advantage, compared with conventional ventilation, in terms of postoperative pulmonary dysfunction (pao 2 / fio 2 < 300 mmhg or radiographic abnormalities) in patients undergoing vats (ahn et al. 2012) . further evidence supporting the use of protective ventilation in thoracic surgery patients comes from observational studies (blank et al. 2016; okahara et al. 2018) . in a review of data from 1019 thoracic surgery patients (blank et al. 2016) , there was an inverse relationship between tidal volume and the incidence of respiratory complications (or 0.84, 95% ci 0.73-0.96); however, a low (physiologically appropriate) tidal volume had no protective effect in the absence of an adequate peep. a further study found that fio 2 during one-lung ventilation was an independent predictor of the risk of postoperative pulmonary complications: the risk of such complications increased by 30% for each 0.1 increase in fio 2 (okahara et al. 2018) . two small studies have examined the effect of protective ventilation on inflammatory responses following one-lung ventilation. a small randomized study in vats patients found that the combination of protective ventilation with a recruitment maneuver was associated with attenuated inflammatory responses, compared with either conventional ventilation or protective ventilation alone (kim et al. 2019) . by contrast, a non-randomized study in 28 patients found no significant difference in local inflammatory cytokine responses between lung resection patients receiving protective or conventional ventilation (fiorelli et al. 2018) . recommendation 17: volatile anesthesia cannot be recommended over intravenous propofol administration in order to reduce postoperative complications, although there is evidence of a lower degree of both systemic and local inflammation when volatile anesthetics are used. level of evidence: good strength of recommendation: i the clinical impact of the choice of anesthetic in thoracic surgery patients is unclear because published studies differ markedly in their design, and have yielded conflicting findings. it has been suggested that only patients with severe surgical injuries (i.e., those undergoing pneumonectomy) may benefit clinically from the anti-inflammatory effects of volatile anesthetics (beck-schimmer et al. 2016) , but further studies are needed to clarify this. several studies have compared the use of volatile halogenated anesthesia and intravenous propofol administration, most of which have found that volatile anesthetics are associated with a lower degree of alveolar-and possibly systemic-inflammatory responses (de conno et al. 2009; de la gala et al. 2017; potocnik et al. 2014; schilling et al. 2011; sun et al. 2015) . in a meta-analysis of eight randomized controlled trials in patients undergoing one-lung ventilation, volatile anesthetics were associated with significant decreases, compared with intravenous anesthetics, in alveolar concentrations of inflammatory mediators (sun et al. 2015) . other studies have shown that, compared with propofol, the volatile halogenated anesthetics desflurane and sevoflurane reduce the expression of inflammatory mediators in bronchoalveolar lavage fluid, and the inflammatory response of alveolar epithelial cells to one-lung ventilation; these effects may be attributable to protective effects on the endothelial glycocalyx (de conno et al. 2009; de la gala et al. 2017; schilling et al. 2011; duthie 2013; schilling et al. 2007) . in contrast to the consistent evidence for antiinflammatory effects of volatile anesthetics, studies of the effects of volatile or intravenous anesthetics on postoperative complications have yielded conflicting results, possibly due to differences in study designs and the definition of postoperative complications. several studies have shown lower rates of postoperative pulmonary complications with volatile anesthetics, compared with propofol, in patients receiving one-lung ventilation (de conno et al. 2009; de la gala et al. 2017; potocnik et al. 2014 ). in the meta-analysis cited above (sun et al. 2015) , the relative risk of pulmonary complications in patients receiving inhalation anesthetics, compared with those receiving intravenous anesthetics, was 0.42 (95% ci 0.23-0.77, p = 0.005), and the mean duration of hospitalization was approximately 4 days shorter. however, a recent large, multicenter, randomized trial involving 460 thoracic surgery patients found no significant difference in complication rates between patients receiving desflurane or propofol (beck-schimmer et al. 2016) . the proportion of patients with major complications was 13.0% and 16.5%, respectively, during hospitalization (hazard ratio [hr] 0.75, 95% ci 0.46-1.22; p = 0.24) and 39.6% and 40.4%, respectively, at 6 months (hr 0.95, 95% ci 0.71-1.28, p = 0.71). subgroup analyses suggested that only patients with severe surgical injuries benefit from the anti-inflammatory effects of volatile anesthetics (beck-schimmer et al. 2016) . recommendation 18: we recommend the use of a steroid neuromuscular blocking agent because of the availability of sugammadex, a reversal agent that, unlike acetylcholinesterase inhibitors, can be used even in cases of deep residual block, and reduces both extubation time and adverse events (bradycardia, postoperative nausea and vomiting, and postoperative residual paralysis). level of evidence: fair strength of recommendation: a deep neuromuscular blockade, with appropriate reversal prior to extubation, is recommended for patients undergoing thoracic surgery (umari et al. 2018; granell et al. 2018; végh et al. 2014) . complete reversal of neuromuscular blockade after surgery is important because it facilitates ventilator movements and expectoration, thereby decreasing the risk of postoperative respiratory complications (végh et al. 2014) . the use of a steroid nmba, such as rocuronium, with complete reversal, reduces the extubation time, compared with non-steroidal nmbas (carron et al. 2017; hristovska et al. 2017) . the use of a selective relaxant-binding agent such as sugammadex is more efficient and safer than neostigmine for reversing moderate or deep induced paralysis (flockton et al. 2008) . in a prospective observational study involving 3000 patients, the use of neostigmine for reversal of neuromuscular blockade did not improve oxygenation at the time of admission to the postanesthesia care unit, and was associated with a higher rate of atelectasis, compared with patients who did not receive neostigmine (8.8% versus 4.5%, or 1.67, 95% ci 1.07-2.59) (sasaki et al. 2014 ). in addition, high-dose neostigmine (> 60 μg/kg) was associated with longer stays in the post-anesthesia unit (mean 176 versus 157 min) and longer postoperative hospitalization (mean 2.9 versus 2.8 days). by contrast, a 2017 cochrane review found that patients receiving sugammadex for reversal of neuromuscular blockade had 40% fewer adverse events (risk ratio [rr] 0.60, 95% ci 0.49-0.74), including less postoperative nausea and vomiting (ponv), bradycardia, or postoperative residual paralysis, than those receiving neostigmine (hristovska et al. 2017) . furthermore, sugammadex produced faster reversal of neuromuscular blockade than neostigmine, irrespective of the depth of blockade (hristovska et al. 2017) . recommendation 19: we recommend evaluation of the risk of postoperative nausea and vomiting, and the use of appropriate prophylaxis according to the level of risk, in all patients undergoing lung surgery. level of evidence: good strength of recommendation: a there is a lack of specific data on ponv after thoracic surgery. recently, a randomized controlled trial in patients undergoing vats procedures showed a lower incidence of nausea on the day of surgery in patients receiving preoperative treatment with methylprednisolone, compared with placebo-treated patients, although there was no difference between the groups on postoperative days 1 and 2 (bjerregaard et al. 2018) . the 2014 society for ambulatory anesthesia guidelines for the management of postoperative nausea and vomiting recommend preoperative evaluation of ponv risk using validated scores, such as the simplified apfel score, and the use of appropriate prophylaxis (gan et al. 2014 ). strategies to reduce the risk of ponv suggested in these guidelines include the use of propofol rather than volatile anesthetics, and minimization of intra-and postoperative opioids. prophylaxis against ponv is also recommended in eras guidelines (batchelor et al. 2019; ljungqvist and hubner 2018) . recommendation 20: we recommend avoiding the routine placement of a nasogastric tube, and early removal in patients in whom a nasogastric tube is used. level of evidence: fair strength of recommendation: a nasogastric tubes can be used to identify the esophagus, and to reduce gastric distension and risk of aspiration. there are no specific data in the literature on the use of nasogastric tubes in patients undergoing lung surgery, but several studies have identified perioperative nasogastric tube use as a risk factor for postoperative pulmonary complications after abdominal surgery (miskovic and lumb 2017) . guidelines published by the eras society recommend avoiding routine nasogastric tube placement in patients undergoing liver and gastric surgery (melloul et al. 2016; mortensen et al. 2014) , and the removal of nasogastric tubes before anesthesia reversal following elective colonic surgery (gustafsson et al. 2013) . recommendation 21: we recommend the early removal of urinary catheters to promote mobilization in patients undergoing lung surgery, including those receiving thoracic epidural catheters. level of evidence: fair strength of recommendation: a monitoring of urine output to evaluate perioperative aki is included in all classification systems for renal dysfunction (goren and matot 2015) , but a large prospective observational study found no association between intraoperative oliguria (urine output < 0.5 ml/kg/h) and postoperative aki in patients undergoing major noncardiac surgery (kheterpal et al. 2007) . higher rates of urinary retention after early urinary catheter removal (within 24-48 h after surgery), compared with later removal, have been reported in patients who received epidural analgesia for pain management after thoracotomy (allen et al. 2016; hu et al. 2014) , but other studies have found no association between early removal and increased complication rates (chia et al. 2009; ladak et al. 2009; young et al. 2018) . a systematic review recommended early removal of the urinary catheter, on the first postoperative day, in order to promote mobilization and reduce pain and discomfort (zaouter and ouattara 2015) . early removal of urinary catheters is one of the overall eras items intended to promote mobilization and ambulation (ljungqvist and hubner 2018) . in addition, the eras guidelines for lung surgery strongly recommend not to routinely use urinary catheterization solely to monitor urine output in patients with normal kidney function, but to use a urinary catheter in patients receiving epidural analgesia (batchelor et al. 2019 ). pre-emptive analgesia recommendation 22: we recommend the use of preemptive locoregional analgesia as part of a multimodal analgesic approach for thoracic surgery. systemic opioids, nonsteroidal anti-inflammatory drugs, and paracetamol have shown no evidence of benefit when used as preemptive analgesics. level of evidence: fair strength of recommendation: a multiple studies in various surgical settings have shown that the use of pre-emptive locoregional analgesia attenuates postoperative pain scores, decreases supplemental analgesic requirements, and prolongs the average time to first use of rescue analgesia (nosotti et al. 2015; ong et al. 2005; yang et al. 2015) . as a result, preemptive locoregional analgesia is recommended as part of a multimodal analgesic strategy for thoracic surgery patients. there is currently no evidence to support the use of one form of analgesia (opioids, nonsteroidal antiinflammatory drugs [nsaids] , paracetamol, etc) over another. recommendation 23: currently, there are no elements to suggest the routine perioperative use of gabapentinoids in patients undergoing thoracic surgery, but their use can be effective in a comprehensive multimodal analgesia protocol. level of evidence: poor strength of recommendation: i studies evaluating gabapentin in thoracic surgery patients are limited, and have yielded conflicting results. a randomized, active placebo (lorazepam)-controlled, trial in a mixed surgical cohort found that perioperative gabapentin administration until the third postoperative day had no effect on the time to cessation of acute postoperative pain (hr 1.04, 95% ci 0.82-1.33, p = 0.73), but had a moderate effect on the time to opioid cessation (hr 1.24, 95% ci 1.00-1.54, p = 0.05) (hah et al. 2018) . two further studies found no benefit of gabapentin treatment, in terms of postoperative pain relief, opioid consumption, and the incidence of chronic pain 3 months after thoracotomy (grosen et al. 2014; kinney et al. 2012 ); similarly, a small randomized trial found that gabapentin had no significant effect, compared with placebo, on the incidence or severity of post-thoracotomy shoulder pain (huot et al. 2008 ). on the basis of such findings, a 2013 review concluded that there is no evidence to support the role of a single preoperative oral dose of gabapentin in reducing pain scores or opioid consumption following thoracic surgery (zakkar et al. 2013) . more recently, a randomized, placebo-controlled, trial involving 60 patients concluded that pregabalin administration before thoracotomy is effective in reducing postoperative pain, but in this study pregabalin did not form part of a multimodal analgesic strategy (sattari et al. 2018) . in contrast to the studies described above, there are data to support the use of pregabalin or gabapentin as part of a multimodal analgesic strategy to improve postoperative pain and reduce opioid consumption (mishriky et al. 2015; tiippana et al. 2007 ). in a systematic review of 55 studies in surgical patients, pregabalin was associated with significant reductions, compared with placebo, in pain scores and opioid consumption 24 h after surgery; however, it was also associated with significantly higher rates of sedation, dizziness, and visual disturbances (mishriky et al. 2015) . current guidelines for the management of postoperative pain issued by the american society of anesthesiology recommend the use of pregabalin and gabapentin as part of a postoperative multimodal analgesia regimen: this is considered a strong recommendation with a moderate level of evidence (chou et al. 2016) . recommendation 24: we suggest intraoperative intravenous administration of ketamine to reduce postoperative pain after thoracic surgery. there is no evidence about the best dose and timing of administration of ketamine. level of evidence: fair strength of recommendation: b a systematic review of 70 randomized controlled trials including 4701 patients found that the use of intravenous ketamine for postoperative pain management resulted in consistent reductions, compared with controls, in opioid consumption, and increases in the time to first use of analgesic (laskowski et al. 2011 ). the greatest benefits were seen in patients undergoing thoracic, upper abdominal or major orthopedic surgery. based on such evidence, us guidelines for the management of postoperative pain recommend evaluating the use of intravenous ketamine in multimodal analgesia regimens (chou et al. 2016 ). however, there is currently no evidence to determine the optimal dosage of perioperative ketamine. there is evidence that a single dose of ketamine may be inadequate, and therefore some authors recommend the administration of a pre-operative bolus and intraoperative maintenance dosing (mishriky et al. 2015; himmelseher and durieux 2005) . one randomized controlled trial in patients undergoing major abdominal surgery has found that a reduced infusion regimen (0.015 mg/kg/h infusion following a saline bolus) and a conventional low-dose regimen (0.25 mg/kg bolus and 0.125 mg/kg/ h infusion for 48 h) were comparable in analgesic efficacy, in terms of postoperative opioid consumption and rates of hyperalgesia (bornemann-cimenti et al. 2016). other authors have suggested that ketamine can be administered in a series of boluses depending on the duration of the procedure (bell et al., 2006) . ketamine should be used with caution in elderly patients. recommendation 25: we suggest intraoperative intravenous administration of magnesium sulfate to reduce postoperative pain after thoracic surgery. level of evidence: fair strength of recommendation: b magnesium blocks n-methyl-d-aspartate (nmda) receptors, which mediate central sensitization to pain and thus contribute to postoperative pain and hyperalgesia (ko et al. 2001; wilder-smith et al. 1997) . hence, many trials have investigated the use of intravenous magnesium to reduce postoperative pain (albrecht et al. 2013 ). in a meta-analysis of 20 randomized trials including over 1200 surgical patients, magnesium treatment was associated with significant improvements, compared with controls, in pain at rest and on movement, and with reductions in postoperative opioid consumption (de oliveira jr et al. 2013) . a further meta-analysis of 25 trials found that perioperative magnesium administration reduced opioid consumption, and to a lesser extent pain scores, during the first 24 h after surgery (albrecht et al. 2013) . however, other studies have reported that intravenous magnesium does not reduce postoperative pain and opioid consumption (ko et al. 2001; wilder-smith et al. 1997) . a study in gynecological surgery patients suggests that variability in the efficacy of magnesium may be related to baseline magnesium levels: low preoperative magnesium levels were significantly (p < 0.001) associated with increased postoperative pain (ulm et al. 2016 ). clinical trials have consistently shown that intravenous magnesium has a favorable safety profile, even at high doses (albrecht et al. 2013; de oliveira jr et al. 2013; fawcett et al. 1999) . recommendation 26: there is no evidence to suggest the routine use of α 2 -agonists as part of a multimodal analgesia regimen to reduce postoperative pain after thoracic surgery. there is no consensus on the best timing and schedule for administration of these drugs. level of evidence: fair strength of recommendation: i a meta-analysis of 30 studies involving almost 1800 surgical patients showed that both dexmedetomidine, and to a lesser extent clonidine, reduce postoperative opioid consumption and postoperative nausea, compared with controls (blaudszun et al. 2012 ). however, dexmedetomidine was associated with an increased risk of postoperative bradycardia, while clonidine increased the risks of both intraoperative and postoperative hypotension, although none of these adverse events required specific interventions, and recovery times were not prolonged (blaudszun et al. 2012) . furthermore, in a rct involving 10,010 patients undergoing noncardiac surgery, clonidine was associated with an increased rate of important hypotension and nonfatal cardiac arrest, compared with placebo (devereaux et al. 2014) . dexmedetomidine is currently approved in italy only for sedation, and thus cannot be recommended for analgesic use in italian settings. recommendation 27: we suggest considering the use of intravenous steroids as part of a multimodal approach to reduce peripheral sensibilization of inflammatoryinduced pain in patients undergoing thoracic surgery. adverse effects of single doses of steroids are of trivial clinical impact. level of evidence: fair strength of recommendation: c a meta-analysis of 45 studies including almost 5800 patients showed that a single perioperative dose of intravenous dexamethasone resulted in significant reductions in pain scores and opioid use, and was associated with shorter stays in the post-anesthesia recovery room, compared with placebo or antiemetic treatment (waldron et al. 2013) . a further meta-analysis of 24 randomized controlled trials found that preoperative dexamethasone, at doses > 0.1 mg/kg, had a greater analgesic effect than perioperative treatment, although there was no difference in los between the two dosing schedules (de oliveira jr et al. 2011) . in a randomized, placebo-controlled trial in 64 patients undergoing uterine artery embolization, administration of dexamethasone 1 h before surgery resulted in significant reductions in postoperative concentrations of cortisol and inflammatory mediators, and less pain and severe ponv, compared with placebo . although long-term glucocorticosteroid treatment is associated with significant adverse events such as hyperglycemia, increased infection risk, bleeding, and recurrence of disease in cancer patients, such events do not appear to be a concern when dexamethasone is used as part of a multimodal analgesic strategy. studies have generally shown few serious adverse events, and no delay in wound healing, following single perioperative doses of dexamethasone in surgical patients (de oliveira jr et al. 2011; holte and kehlet 2002; snall et al. 2013; thoren et al. 2009 ). recommendation 28: we recommend the use of intravenous nonsteroidal anti-inflammatory drugs (nsaids) to reduce peripheral sensitization to inflammationinduced pain in patients undergoing thoracic surgery. combined use of nsaids and paracetamol may give a further analgesic advantage. level of evidence: good strength of recommendation: a a meta-analysis of 17 trials evaluating the efficacy of nsaids in surgical patients found that these drugs were effective in reducing a composite endpoint of pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption, compared with controls (effect size 0.39, 95% ci 0.27-0.48) (ong et al. 2005) . however, although preoperative administration reduced opioid consumption and lengthened the time to first use of rescue analgesic, it reduced postoperative pain scores in only six of 12 randomized controlled trials. nsaid treatment has also been reported to reduce opioid-related adverse events such as ponv (gan et al. 2004; maund et al. 2011) . there is evidence that the analgesic effects of nsaids on postoperative pain are potentiated by concomitant administration of paracetamol (ong et al. 2005) . a number of studies have examined the efficacy and safety of ketorolac in surgical patients. a meta-analysis of 27 randomized, double-blind, trials in 2314 patients undergoing major abdominal surgery, neurosurgery, or orthopedic surgery showed that ketorolac does not increase clinically significant bleeding, compared with controls (or 1.1, 95% ci 0.61-2.06, p = 0.72); however, there appeared to be a slight trend toward more bleeding with higher doses (> 30 mg) (gobble et al. 2014) . these results suggest that increases in bleeding time observed with ketorolac are not clinically relevant, and that there does not appear to be a significant risk of postoperative bleeding with ketorolac, compared with controls. low doses of ketorolac (10 and 15 mg) appear to be equivalent in analgesic efficacy to ketorolac 30 mg. although no studies were identified that directly compared the analgesic efficacy of different doses of ketorolac in thoracic surgery patients, a double-blind, randomized, controlled trial in patients with moderate or severe acute pain treated in the emergency department found no significant differences in pain score reductions or adverse event profiles between patients receiving ketorolac 10 mg, 15 mg, or 30 mg (motov et al. 2017) . these findings are consistent with those of a prospective, randomized, non-inferiority trial in patients undergoing spine surgery, which found that ketorolac 30 mg was not superior to 15 mg for postoperative pain management (duttchen et al. 2017) . based on such findings, we suggest the use of low doses of intravenous ketorolac (15 mg 2-3 times a day) for a maximum of 2 days; however, we suggest caution in using ketorolac in elderly patients (> 65 years). ketorolac can be also administered orally (10 mg 3-4 times a day) for a maximum of 5 days. recommendation 29: we recommend the use of locoregional anesthesia for intraoperative and postoperative pain management. level of evidence: poor strength of recommendation: a recommendation 30: we recommend the use of thoracic epidural analgesia in high-risk patients or in major surgical procedures where the parietal pleura (e.g., chest wall resection) is violated (i.e., thoracotomy, thoracosternotomy, chest wall resection). level of evidence: fair strength of recommendation: a recommendation 31: we recommend thoracic paravertebral block for vats, as part of a multimodal approach. level of evidence: good strength of recommendation: a recommendation 32: we recommend thoracic paravertebral block in preference to thoracic epidural analgesia in patients with known or suspected coagulopathy. level of evidence: fair strength of recommendation: a multiple clinical trials have shown that, in patients undergoing open thoracotomy or other major surgical procedures, thoracic epidural analgesia (tea) is superior to intravenous opioid administration in terms of postoperative pain relief, length of hospital stay, and incidence of postoperative complications (hazelrigg et al. 2002; block et al. 2003; della rocca et al. 2002; meierhenrich et al. 2011; wheatley et al. 2001) . however, in patients undergoing vats procedures, less invasive procedures such as paravertebral block (tpvb) appear to be at least as effective as tea (kosinski et al. 2016; steinthorsdottir et al. 2014 ). there is moderate-quality evidence that tea may reduce the risk of developing persistent postoperative pain 3-18 months after thoracotomy (weinstein et al. 2018) . clinical trials and meta-analyses have consistently shown that tea and tpvb are comparable in efficacy for the management of postoperative pain in thoracotomy patients (baidya et al. 2014; ding et al. 2014; júnior ade et al. 2013; kobayashi et al. 2013; raveglia et al. 2014; scarfe et al. 2016; yamauchi et al. 2017) . there is also clear evidence that tpvb is associated with fewer intraoperative complications than tea, with improved hemodynamic stability and less need for intravenous colloid therapy (pintaric et al. 2011) , probably due to unilateral segmental block. compared with tea, tpvb is associated with lower rates of minor postoperative complications such as urinary retention, nausea and vomiting, and hypotension (baidya et al. 2014; ding et al. 2014; raveglia et al. 2014; scarfe et al. 2016; biswas et al. 2016; gulbahar et al. 2010; yeung et al. 2016) , and the majority of studies have shown no significant differences in pulmonary function and pulmonary complications between the two procedures (ding et al. 2014; biswas et al. 2016; blackshaw et al. 2018) . furthermore, some studies have found that epidural anesthesia may be associated with serious complications such as epidural hematoma, epidural abscess, and nerve injury: the risk of these potentially devastating complications may be reduced with tpvb, particularly in patients with known or suspected coagulopathy (davies et al. 2006; horlocker et al. 2018) . although data from randomized controlled trials are lacking, several studies have shown that tpvb is associated with a low risk of bleeding complications (naja and lönnqvist 2001; katayama et al. 2012; okitsu et al. 2017) . in some studies, tea has also been associated with higher rates of procedural failure, compared with tpvb (kosinski et al. 2016; ding et al. 2014; gulbahar et al. 2010; hermanides et al. 2012) . there are no studies comparing the efficacy and safety of tpvb when performed by the anesthetist before the beginning of surgery, or by the surgeon under direct vision at the end of surgery. together, the available evidence indicates that tpvb and tea provide comparable analgesia in thoracotomy patients, but tpvb offers advantages in terms of its technical simplicity and better safety profile. tpvb is therefore a valid alternative to tea, particularly in patients who are not suitable for tea. recommendation 33: we suggest that intercostal nerve blockade should be considered only as a second choice for analgesia after thoracic surgical procedures. level of evidence: good strength of recommendation: c several studies have shown that intercostal nerve blockade is not comparable in terms of analgesia to tea or tpvb in thoracic surgery patients (meierhenrich et al. 2011; joshi et al. 2008; wurnig et al. 2002) . this is at least partially due to the shorter duration of analgesia achievable with intercostal nerve blockade (wurnig et al. 2002; linden et al. 2014) , although a recent study has shown that this can be prolonged by a combination of intravenous and perineural dexamethasone (maher et al. 2017) . as a result, we suggest that intercostal nerve blockade should be considered only as a second choice for analgesia after thoracic surgical procedures, because more effective techniques are available. suitable alternatives include tea and (especially for vats) tpvb, and possibly erector spinae plane blockade and serratus anterior plane blockade (see below). recommendation 34: we suggest erector spinae plane block as part of a multimodal analgesia for thoracic surgery, especially for vats. level of evidence: poor strength of recommendation: b erector spinae plane blockade (espb) is a recently developed fascial block that allows sensory blockade over both the posterior and anterolateral thorax. it is relatively safe and simple to administer, because it is performed in a musculofascial plane away from the neuraxis, with minimal risk of serious complications (other than local anesthetic systemic toxicity) (forero et al. 2016; forero et al. 2017) . in an initial series of seven patients with post-thoracotomy pain syndrome, who underwent espb as part of a multimodal analgesia strategy, all patients experienced immediate pain relief and four experienced prolonged pain relief for 2 weeks or longer (forero et al. 2017) . randomized controlled trials are needed to confirm the effectiveness of this technique in thoracic surgery. recommendation 35: we suggest the use of fascial pain blocks as part of multimodal analgesia for thoracic surgery, particularly for vats. level of evidence: fair strength of recommendation: b serratus anterior plane blockade (spb) provides good analgesia, comparable to that provided by tea, for acute post-thoracotomy pain, while maintaining a more stable blood pressure (khalil et al. 2017; okmen and okmen 2017) . like espb, spb offers a less invasive approach in patients with contraindications to more invasive techniques (park et al. 2018) . a recent placebo-controlled trial has suggested that spb reduces postoperative pain and opioid consumption during the first 24 h after vats , but further studies are needed to confirm the potential of the technique in thoracic surgery (park et al. 2018; okmen and okmen 2018) . nevertheless, we suggest the use of fascial plane blocks as part of multimodal analgesia for thoracic surgery, particularly for vats patients. a recent study, involving 60 patients undergoing minimally invasive thoracic surgery, has found that espb provides superior quality of recovery, with lower morbidity and better pain control, compared with spb (finnerty et al. 2020) . recommendation 36: we suggest considering the use of adjuvants (i.e., opioids, dexamethasone) when locoregional anesthesia is performed, because the use of adjuvants can potentiate and prolong the effect of local anesthetics. level of evidence: poor strength of recommendation: c low-to moderate-quality evidence suggests that, when used as an adjuvant to peripheral nerve blockade in upper limb surgery, both perineural and intravenous dexamethasone may prolong the duration of sensory blockade and reduce postoperative pain intensity and opioid consumption (pehora et al. 2017) . specific evidence regarding the use of dexamethasone as an adjuvant in thoracic anesthesia is not available. recommendation 37: we suggest considering the use of a single large-bore chest tube instead of a double tube after thoracic surgery. insertion of more than one chest tube may be considered in selected cases (e.g., bilobectomy or bleeding patients). level of evidence: poor strength of recommendation: c a meta-analysis of nine studies, including 918 patients undergoing pulmonary resection by vats, found that approximately 50% of patients did not have a chest tube inserted. in these patients, postoperative pain scores and los were significantly reduced, compared with patients who had a chest tube inserted, with no difference in 30day morbidity or re-intervention rates between the two groups (li et al. 2018) . these findings suggest that omitting the chest tube is safe and feasible in selected patients. in patients in whom a chest tube is considered necessary, there is consistent evidence that the use of a single large-bore tube to remove both air and fluid is as effective as the use of double chest tubes (filosso et al. 2017; zhou et al. 2016) . furthermore, comparative studies and meta-analyses have shown that, compared with double chest tubes, the use of a single chest tube is associated with less pain, decreases in the amount and duration of drainage, and reduced healthcare costs (zhou et al. 2016; okur et al. 2009; zhang et al. 2016) . recommendation 38: we suggest considering the use of digital chest drainage systems to promote early mobilization of the patient. level of evidence: fair strength of recommendation: b external pleural suction is commonly used after lung resection to promote lung expansion and minimize the duration of air leakage (lang et al. 2016; leo et al. 2013 ). the airintrial, which involved 500 lung resection patients, found that the incidence of prolonged air leakage (defined as still having a chest drain in place 7 days after surgery) was not significantly different in patients in whom external suction was used, compared to those without suction (10% versus 14%, respectively, p = 0.2), although a trend toward significance favoring the use of external suction was seen in patients undergoing anatomical resection (9.6% versus 16.8%, p = 0.05) (leo et al. 2013 ). however, a subsequent meta-analysis of eight randomized, controlled, trials found that, although the use of suction reduced the incidence of postoperative pneumothorax, it was associated with significant increases in los, duration of chest tube drainage, and air leak duration (lang et al. 2016) . the effect of digital chest drainage systems on outcomes after pulmonary resection was studied in a trial including 103 patients who were randomized to either analog or digital drainage systems (de waele et al. 2017) . the use of digital systems had no significant effect on pleural fluid formation, but was associated with a significantly lower incidence of prolonged air leakage, compared with analog systems (3.8% versus 18%, respectively, p = 0.025). there was also a trend toward a shorter duration of chest tube drainage with digital systems, but this did not reach statistical significance. by contrast, an international randomized trial involving 381 lung resection patients found that, compared with traditional drainage systems, digital drainage systems were associated with a significantly shorter duration of chest tube placement, shorter hospital stays, and higher satisfaction scores (pompili et al. 2014) . we suggest using digital chest drainage systems, rather than traditional water seal devices, in order to promote early mobilization. recommendation 39: the routine use of drainage with suction is not recommended in the absence of complications, provided there is full re-expansion of the residual parenchyma after lung resection. level of evidence: good strength of recommendation: d in a prospective randomized trial involving 254 lung resection patients with full parenchymal re-expansion, suction drainage was found to be less effective than nonsuction drainage in terms of time to chest tube removal (5.6 days versus 4.5 days, respectively, p = 0.0014) and incidence of prolonged air leakage (5.6% versus 0.7%, p = 0.032) (gocyk et al. 2016 ). however, no-suction drainage was associated with a significantly higher incidence of asymptomatic residual air spaces, compared with suction drainage (9.4% versus 0.8%, respectively, p = 0.0018). other studies have found that suction drainage does not reduce prolonged air leakage or duration of drainage in patients without complications such as large expiratory leaks (alphonso et al. 2005; brunelli et al. 2004; cerfolio et al. 2001b; coughlin et al. 2012; marshall et al. 2002) . recommendation 40: we suggest removing chest tubes in lung resection patients when liquid output is ≤ 5 cm 3 /kg/24 h of serous fluid. level of evidence: poor strength of recommendation: b in a prospective observational study in 88 patients who underwent posterolateral thoracotomy for lung resection, early removal of the chest tube resulted in an statistically significant improvement in static and dynamic pain scores, and in better functional respiratory outcome (dokhan and abd elaziz 2016) . the criteria for chest tube removal in this study were resolution of air leaks and fluid drainage ≤ 350 ml/day, provided that the drained fluid was macroscopically non-chylous and nonhemorrhagic. several authors have suggested that a cut-off of 3-5 cm 3 /kg of serous liquid is a good option because this is within the normal physiological range of daily pleural fluid filtration, and is suitable for early chest drain removal without increasing complications and re-admission rates (brunelli et al. 2011; mesa-guzman et al. 2015; miserocchi 1997) . based on this clinical evidence, we suggest chest tube removal when fluid output is ≤ 5 cm 3 /kg/24 h of serous liquid. recommendation 41: we do not recommend systematic icu admission after thoracic surgery. level of evidence: poor strength of recommendation: d postoperative pulmonary complications occur in as many as 15-40% of patients after major thoracic surgery, and are associated with prolonged los, and poor longterm outcomes (brunelli et al. 2009; agostini et al. 2018) . although vats procedures are associated with a reduced incidence of postoperative pulmonary complications, compared with thoracotomy, such complications still lead to significant short-term morbidity and mortality in these patients (agostini et al. 2018) . implementation of appropriate postoperative medical strategies, and monitoring and treatment of high-risk patients in dedicated care units, are aimed at improving postoperative outcomes (brunelli et al. 2009 ). currently, many centers routinely admit patients to the icu after surgery, whereas in others icu admission is reserved for patients requiring ventilator support, emergency treatment of perioperative complications, or both (brunelli et al. 2009 ). multiple preoperative factors can influence the likelihood of postoperative admission to the icu in patients undergoing lung resection (brunelli et al. 2009; agostini et al. 2018; ferguson et al. 2009; brunelli et al. 2008; brunelli et al. 2005; cywinski et al. 2009; dulu et al. 2006; keegan et al. 2007; mccall et al. 2015; pinheiro et al. 2015) . these include open thoracotomy, rather than vats (brunelli et al. 2008; dulu et al. 2006; mccall et al. 2015; pinheiro et al. 2015) , more extensive resection (cywinski et al. 2009 ), and impaired preoperative lung function or pulmonary comorbidities such as chronic obstructive pulmonary disease (copd) (brunelli et al. 2008; cywinski et al. 2009; pinheiro et al. 2015) . however, there is evidence that routine admission of thoracic surgery patients to the icu does not reduce mortality rates (brunelli et al. 2005) , and may result in inappropriate icu admission, increased healthcare costs, delayed mobilization, and increased risks of nosocomial infections (brunelli et al. 2009 ). to date, no studies have compared outcomes in thoracic surgery patients admitted to icus, high dependency units (hdus), or surgical wards (brunelli et al. 2009) , and there are no data to identify patients who might benefit from postoperative intensive care, or to determine the necessary degree of postoperative care for an individual patient. for these reasons, we do not recommend systematic icu admission after thoracic surgery. we suggest postoperative admission of high-risk patients to dedicated care units (hdus or dedicated thoracic surgical wards). these facilities may allow icu admission to be limited to patients requiring support for organ failure. identification of high-risk patients, and management of their postoperative course, should be planned according to the number and type of complications, and the available resources. ers/ests working group recommendations (brunelli et al. 2009 ) state that lung resection patients should be managed in a dedicated thoracic surgical ward or respiratory hdu (scala et al. 2011) if available, and that icu admission should be limited to patients requiring organ support. the appropriateness of this policy, and its influence on early outcomes, is still controversial. recommendation 42: we recommend that, in adult patients undergoing thoracic surgery, oral intake, including clear liquids, can be initiated 4-6 h after surgery, in the absence of nausea and vomiting. oral intake should, however, be adapted to individual tolerance. level of evidence: fair strength of recommendation: a although it has traditionally been believed that enteral nutrition should not be resumed in postoperative surgical patients until normal bowel function has been restored, studies have consistently shown that early resumption of oral feeding is safe and well tolerated, and is associated with decreased wound morbidity, fewer septic complications, and less weight loss, compared with delayed enteral nutrition (warren et al. 2011 ). hence, early oral feeding has been endorsed in a number of guidelines in different surgical settings, including the eras/ests lung surgery guidelines (batchelor et al. 2019; muehling et al. 2008; smith et al. 2011; weimann et al. 2017; nelson et al. 2016; nygren et al. 2013) . in patients undergoing lung resection, early resumption of oral feeding does not depend on the surgical technique (open versus minimally invasive) (batchelor et al. 2019; smith et al. 2011; jones et al. 2013) . hence, we recommend that, in the absence of nausea and vomiting, oral intake, including clear liquids, can be initiated 4-6 h after surgery in adult patients undergoing elective pulmonary lobectomy. oral intake should, however, be adapted according to the individual patient's tolerance and the type of surgery carried out. recommendation 43: we recommend early mobilization of patients within the first 24 h after both minor and major thoracic surgery. level of evidence: fair strength of recommendation: a recommendation 44: we recommend a physiotherapy program after thoracic surgery. level of evidence: fair strength of recommendation: a delayed mobilization in patients undergoing lung resection is predictive of increased postoperative morbidity and delayed hospital discharge (das-neves-pereira et al. 2009; rogers et al. 2018) , and hence early ambulation and physiotherapy have been recommended irrespective of the surgical approach (nygren et al. 2013) . several studies have shown that eras programs that include early ambulation are feasible in lung resection patients, and can improve outcomes (das-neves-pereira et al. 2009; cywinski et al. 2009; dulu et al. 2006; keegan et al. 2007; mccall et al. 2015; pinheiro et al. 2015; scala et al. 2011; warren et al. 2011; nygren et al. 2013; jones et al. 2013; rogers et al. 2018; dumans-nizard et al. 2016; kendall et al. 2017; martin et al. 2018 ). there is evidence from a propensity score matching study in 524 patients that patients undergoing vats lung resection require less physiotherapy than those undergoing open thoracotomy (agostini et al. 2017) . recommendation 45: we suggest considering daily chest radiographs only in selected cases under specific clinical indications. level of evidence: good strength of recommendation: c two meta-analyses have concluded that routine chest radiographs offer no advantage over clinically indicated radiographs in cardiothoracic surgery patients (sepehripour et al. 2012; reeb et al. 2013) . in one of these analyses, pulmonary pathology was detected in 2-40% of routine chest radiographs, compared with 79% (p = 0.005) of radiographs that were taken only when clinically indicated (sepehripour et al. 2012 ). furthermore, a prospective comparative study in cardiothoracic surgery patients in an icu/post-icu ward showed that the elimination of daily routine chest radiographs reduced the total number of radiographs per patient per day in the icu, but had no effect on chest radiography practice in the post-icu ward (mets et al. 2007 ). there is also evidence that chest radiographs are poor predictors of postoperative complications in patients undergoing lung resection. in a retrospective chart review of 86 patients undergoing vats lung resection, the sensitivity and specificity of chest radiographs for pulmonary complications ranged from 0-100% and 58-97%, respectively, depending on the reviewer, and there was only slight overall agreement between reviewers (troquay et al. 2013) . for these reasons, we suggest considering daily chest radiographs only in selected patients. bedside, lung ultrasound may also be useful in some patients (chiappetta et al. 2018; touw et al. 2018) . recommendation 46: we do not recommend the routine use of either continuous positive airway pressure (cpap) or non invasive ventilation (niv) to prevent postoperative pulmonary complications, prolonged length of stay, and mortality (both in icu and in hospital) in patients undergoing major thoracic surgery. cpap or niv could be considered on a case by case basis in selected high-risk patients. level of evidence: poor strength of recommendation: d postoperative pulmonary complications are the principal cause of mortality and morbidity after lung resection (torres et al. 2019) . acute respiratory failure has been reported to occur in 2-30% of patients after lung resection (lorut et al. 2014) , and overall pulmonary complication rates have been reported to be as high as 49% (nery et al. 2012) . because prolonged invasive mechanical ventilation has been shown to be an important risk factor for such complications, prophylactic non-invasive ventilation (niv) has been proposed as a means of reducing this intubation-related risk (riviere et al. 2011) . although niv offers the potential to improve lung function, unload respiratory muscles and reduce postoperative hypoxemia and atelectasis, randomized controlled trials have not shown consistent evidence that the addition of either niv or continuous positive airway pressure (cpap) to standard medical therapy offers no significant benefit (lorut et al. 2014; nery et al. 2012; aguilo et al. 1997; barbagallo et al. 2012; danner et al. 2012; garutti et al. 2014; liao et al. 2010; perrin et al. 2007 ). in a recent cochrane review of eight trials involving a total of 486 patients, there were no significant differences between patients receiving niv and control groups in terms of pulmonary complications (rr 1.03, 95% ci 0.72-1.47), intubation rates (rr 0.55, 95% ci 0.25-1.00), mortality (rr 0.60, 95% ci 0.24-1.53), length of icu stay (mean difference − 0.75 days, 95% ci − 3.93-2.43) or length of hospital stay (mean difference − 0.12 days, 95% ci − 6.15-5.90) (torres et al. 2019) . however, the quality of the evidence was poor, due to the limited number of studies, heterogeneity of the patient populations and of the scheduled ventilator treatment, small sample sizes, and low frequencies of outcomes (torres et al. 2019) . however, it could be speculated that selected patients at higher risk of developing pulmonary complications (e.g., obese patients or patients with copd, obese, chronic heart failure, or chronic hypersecretion) are likely to benefit from the administration of cpap or niv in addition to standard medical and physiotherapy, consistent with the established use of these techniques for the prevention of post-extubation failure (rochwerg et al. 2017; scala and pisani 2018) . recommendation 47: we suggest the use of niv or cpap to treat acute respiratory failure complicating thoracic surgery. level of evidence: poor strength of recommendation: b one small study (n = 24) in patients with acute hypoxemic respiratory insufficiency after lung resection found that the addition of niv to standard therapy was associated with significant reductions, compared with controls, in the need for endotracheal mechanical ventilation (20.8% versus 50%, respectively, p = 0.035) and 120-day mortality (12.5% versus 37.5%, p = 0.045); however, there were no differences in length of icu and hospital stays between the two groups (auriant et al. 2001 ). on the basis of these findings, it is suggested that niv or cpap could be used in the management of acute respiratory insufficiency following thoracic surgery, but it should be noted that the availability of only a single study limits the strength of this recommendation. however, it should be remembered that niv is associated with a number of adverse events (e.g., poor compliance, leaks, sensory dysfunction, hypersecretion, unprotected airways, patient-ventilator asynchronies) that are likely to be associated with the need for intubation (scala and pisani 2018) . furthermore, niv failure occurs in approximately 20% of patients, and is associated with increased rates of nosocomial pneumonia and postoperative mortality (riviere et al. 2011 ). in a prospective study of 664 patients admitted to the icu after lung resection or pulmonary thrombendarterectomy, four independent risk factors for niv failure within the first 48 h were identified: increased respiratory rate (or 4.17, 95% ci 1.63-10.67), increased sequential organ failure assessment (sofa) score (or 3.05, 95% ci 1.12-8.34), number of fiberoptic bronchoscopies performed (or 1.60, 95% ci 1.01-2.54), and number of hours on niv (or 1.06, 95% ci 1.01-1.11) (riviere et al. 2011) . risk stratification of candidates for thoracic surgery is likely to be useful for selecting sub-sets of patients who may benefit from either prophylactic or therapeutic niv. these might include patients with copd or severely impaired respiratory function (danner et al. 2012; garutti et al. 2014; perrin et al. 2007 ) and obese patients (stephan and berard 2017) . further research is needed to clarify the potential usefulness of prophylactic or therapeutic niv in such groups, and to determine the most efficacious scheduled regimens. recommendation 48: we suggest considering the use of high-flow nasal cannula oxygen therapy as an alternative or integrative support to cpap or niv to prevent or treat acute respiratory failure complicating thoracic surgery. level of evidence: poor strength of recommendation: c high-flow nasal cannula (hfnc) oxygen therapy is considered to be a non-invasive form of respiratory assistance for spontaneously breathing hypoxemic patients with early stages of acute respiratory failure. this technique delivers high inspiratory flow rates (up to 60 l/ min) that match the oxygen demands of ventilated patients; in addition, hfnc oxygen therapy offers good comfort, efficient wash-out of the upper airway and clearance of co 2 , provision of adequate humidification, and reduction of respiratory effort (although this latter effect is less than can be achieved with niv) (stephan and berard 2017) . a post hoc analysis of a large randomized trial in obese patients undergoing major thoracic surgery investigated the impact of hfnc on rates of treatment failure, defined as the need for re-intubation or switching to alternative treatments, or premature discontinuation (stephan and berard 2017) . this analysis found that hfnc is not inferior to niv in terms of treatment failure rates (13.3% versus 15.4%, respectively, p = 0.62), icu mortality (2.2% versus 5.9%, p = 0.22), length of icu stay (median 5.0 versus 4.0 days, p = 0.63), or length of hospital stay (median 10.0 versus 11.1 days, p = 0.71). however, skin breakdown at 24 h was significantly more common with niv than with hfnc (9.2% versus 1.6%, respectively, p = 0.01). on the basis of these findings, it is suggested that hfnc may be considered as an alternative to cpap or niv for the prevention or treatment of acute respiratory failure complicating thoracic surgery. it should be noted that the lack of corroborating randomized trials limits the strength of this recommendation. however, the demonstration of the effectiveness and acceptability of hfnc in milder degrees of acute (particularly hypoxemic) respiratory failure is consistent with the potential use of hfnc in patients with postoperative pulmonary complications following major thoracic surgery (rochwerg et al. 2019) . it should also be noted that the integrated use of hfnc during times off niv could be an effective strategy, especially in patients showing poor tolerance to the niv interface (scala and pisani 2018; longhini et al. 2019) . recommendation 49: for prophylaxis and management of atrial fibrillation after thoracic surgery, we recommend reference to the society of thoracic surgery (sts) 2011 guidelines. level of evidence: good strength of recommendation: a postoperative cardiac arrhythmias, particularly atrial fibrillation, occur in approximately 10-20% of patients undergoing major noncardiac thoracic surgery, including both thoracotomy and vats lobectomy (garner et al. 2017; onaitis et al. 2010; park et al. 2007 ). potential risk factors for atrial fibrillation include increasing age, male gender, hypertension, comorbidities such as copd or heart failure, extent of lung resection, and postoperative infection (batchelor et al. 2019; garner et al. 2017; onaitis et al. 2010) . postoperative atrial fibrillation can lead to hemodynamic instability, potentially prolonging icu and hospital stay (frendl et al. 2014) . furthermore, atrial fibrillation may persist beyond hospital discharge in a proportion of patients, and some patients may require long-term anticoagulation (garner et al. 2017) . it is recommended that the society of thoracic surgery (sts) 2011 guidelines for the prophylaxis and management of atrial fibrillation (fernando et al. 2011) should be followed in patients undergoing pulmonary lobectomy. these guidelines recommend pharmacological prophylaxis with β-blockers or diltiazem: amiodarone is not recommended for patients undergoing pneumonectomy. electrical cardioversion is recommended for patients who develop hemodynamically unstable atrial fibrillation, and for patients with symptomatically intolerable atrial fibrillation in whom treatment with metoprolol (or diltiazem for patients with severe copd), alone or followed by flecainide, is ineffective. anticoagulation with aspirin (for patients at low thromboembolic risk), or warfarin or heparin (for high-risk patients), is recommended for patients with persistent or recurrent atrial fibrillation after 24 h of metoprolol treatment (fernando et al. 2011) . it should be noted, however, that to date no scoring system has been developed to identify lung resection patients at high risk of atrial fibrillation, although promising results have been obtained with the chads 2 score (kotova et al. 2017) . furthermore, there is little evidence that prophylaxis for atrial fibrillation improves outcomes after thoracic surgery [1]. anesthesia in patients undergoing thoracic surgery is a complex undertaking that requires a multidisciplinary approach to risk assessment, perioperative monitoring, and postoperative care. recognizing this, the pacts group has sought to identify critical issues in the preoperative, intraoperative and postoperative care of patients undergoing lung resection, and to provide appropriate guidance. wherever possible, our recommendations are based on good-quality supporting evidence: where such evidence is limited, the recommendations are framed as suggestions or possibilities for consideration. in a few cases, there was insufficient evidence to make formal recommendations: in such cases, our guidance is based on expert opinion, supported by published literature where possible. our literature reviews and discussions highlighted the importance of the choice of anesthetic and lung isolation procedure, attention to airway management, and comprehensive monitoring of vital signs, hemodynamics, neuromuscular blockade, and depth of anesthesia, for achieving optimal outcomes. postoperatively, a multi-modal analgesic strategy that includes pre-emptive analgesia and locoregional blockade is required for optimal pain control. finally, decisions on icu care, chest drainage, and other interventions should be individualized for each patient. the eras lung surgery guidelines (batchelor et al. 2019) were published while our recommendations were in development. we believe that these recommendations extend and complement those of the eras guidelines for a number of reasons. first, aspects of anesthesiologic care such as depth of anesthesia monitoring, neuromuscular blockade, and hemodynamic monitoring are covered in greater detail than in the eras guidelines. in addition, our recommendations focus specifically on elective surgery for lung cancer. it is hoped that these recommendations will help to achieve optimal postoperative outcomes in the greatest number of thoracic surgery patients. further refinement of our recommendations can be anticipated as the literature continues to evolve. postoperative pulmonary complications and rehabilitation requirements following lobectomy: a propensity score matched study of patients undergoing video-assisted thoracoscopic surgery versus thoracotomy risk factors and short-term outcomes of postoperative pulmonary complications after vats lobectomy noninvasive ventilatory support after lung resectional surgery the risk of acute kidney injury from fluid restriction and hydroxyethyl starch in thoracic surgery comparison between conventional and protective one-lung ventilation for ventilator-assisted thoracic surgery peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis european society of anaesthesiology evidence-based and consensus-based guideline on postoperative delirium optimal timing of urinary catheter removal after thoracic operations: a randomized controlled study a prospective randomized controlled trial of suction versus non-suction to the under-water seal drains following lung resection noninvasive ventilation reduces mortality in acute respiratory failure following lung resection analgesic efficacy and safety of thoracic paravertebral and epidural analgesia for thoracic surgery: a systematic review and meta-analysis. interact cardiovas thorac surg prophylactic use of helmet cpap after pulmonary lobectomy: a prospective randomized controlled study continuous noninvasive blood pressure monitoring during thoracic surgery guidelines for enhanced recovery after lung surgery: recommendations of the enhanced recovery after surgery (eras(r)) society and the european society of thoracic surgeons (ests) which anesthesia regimen is best to reduce morbidity and mortality in lung surgery?: a multicenter randomized controlled trial perioperative ketamine for acute postoperative pain glidescope versus airtraq dl for double-lumen tracheal tube insertion in patients with a predicted or known difficult airway: a randomised study postoperative delirium as a target for surgical quality improvement comparison between thoracic epidural block and thoracic paravertebral block for post thoracotomy pain relief high-dose methylprednisolone in video-assisted thoracoscopic surgery lobectomy: a randomized controlled trial propensity score-matched outcomes after thoracic epidural or paravertebral analgesia for thoracotomy management of one-lung ventilation: impact of tidal volume on complications after thoracic surgery effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials efficacy of postoperative epidural analgesia: a meta-analysis the effects of minimal-dose versus low-dose s-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active-and placebo-controlled clinical trial left double-lumen tubes: clinical experience with 1,170 patients consensus definitions to promote an evidence-based approach to management of the pleural space. a collaborative proposal by ests, aats, sts, and gtsc ers/ests clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy) a scoring system predicting the risk for intensive care unit admission for complications after major lung resection: a multicenter analysis comparison of water seal and suction after pulmonary lobectomy: a prospective, randomized trial elective intensive care after lung resection: a multicentric propensity-matched comparison of outcome current techniques for perioperative lung isolation in adults which device should be considered the best for lung isolation: double-lumen endotracheal tube versus bronchial blockers update on tracheobronchial anatomy and flexible fiberoptic bronchoscopy in thoracic anesthesia a comparison of a left-sided broncho-cath with the torque control blocker univent and the wire-guided blocker assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach safety of peripheral intravenous administration of vasoactive medication role of sugammadex in accelerating postoperative discharge: a meta-analysis clinical review: goal-directed therapy-what is the evidence in surgical patients? the effect on different risk groups prospective randomized trial compares suction versus water seal for air leaks fast-tracking pulmonary resections a rational approach to perioperative fluid management a randomised trial comparing real-time double-lumen endobronchial tube placement with the disposcope((r)) with conventional blind placement optimal duration of urinary catheterization after thoracotomy in patients under postoperative patient-controlled epidural analgesia bispectral index and non-bispectral index anesthetic protocols on postoperative recovery outcomes postoperative chest ultrasound findings and effectiveness after thoracic surgery: a pilot study management of postoperative pain: a clinical practice guideline from the american pain society, the american society of regional anesthesia and pain medicine, and the american society of anesthesiologists' committee on regional anesthesia, executive committee, and administrative council a comparison of the efficacy and adverse effects of double-lumen endobronchial tubes and bronchial blockers in thoracic surgery: a systematic review and meta-analysis of randomized controlled trials double-lumen tube position should be confirmed by fiberoptic bronchoscopy management of chest tubes after pulmonary resection: a systematic review and meta-analysis predictors of prolonged postoperative endotracheal intubation in patients undergoing thoracotomy for lung resection non-invasive pressure support ventilation in major lung resection for high risk patients: does it matter? noninvasive cardiac output and pressure measurements with finger cuff during lateral decubitus and one lung ventilation in thoracic surgery: preliminary results fast-track rehabilitation for lung cancer lobectomy: a five-year experience a comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy--a systematic review and meta-analysis of randomized trials is flexible bronchoscopy necessary to confirm the position of double-lumen tubes before thoracic surgery? anesthetic-induced improvement of the inflammatory response to one-lung ventilation why hydroxyethyl starch solutions should not be banned from the operating room postoperative pulmonary complications, pulmonary and systemic inflammatory responses after lung resection surgery with prolonged one-lung ventilation. randomized controlled trial comparing intravenous and inhalational anaesthesia perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials does the usage of digital chest drainage systems reduce pleural inflammation and volume of pleural effusion following oncologic pulmonary resection?-a prospective randomized trial postthoracotomy analgesia: epidural vs intravenous morphine continuous infusion clonidine in patients undergoing noncardiac surgery buone pratiche cliniche siaarti -normotermia perioperatoria a comparison of the analgesia efficacy and side effects of paravertebral compared with epidural blockade for thoracotomy: an updated meta-analysis influence of timing of chest tube removal on early outcome of patients underwent lung resection prevalence and mortality of acute lung injury and ards after lung resection feasibility and results of a fast-track protocol in thoracic surgery a comparison of the deflecting-tip bronchial blocker with a wire-guided blocker or left-sided double-lumen tube anaesthetic agents for thoracic surgery: what's best? intraoperative ketorolac dose of 15mg versus the standard 30mg on early postoperative pain after spine surgery: a randomized, blinded, non-inferiority trial calculations of consciousness: electroencephalography analyses to determine anesthetic depth a comparison of 3 videolaryngoscopes for double-lumen tube intubation in humans by users with mixed experience: a randomized controlled study an evaluation of a zero-heat-flux cutaneous thermometer in cardiac surgical patients the technology of processed electroencephalogram monitoring devices for assessment of depth of anesthesia magnesium: physiology and pharmacology pulmonary complications after lung resection in the absence of chronic obstructive pulmonary disease: the predictive role of diffusing capacity the society of thoracic surgeons practice guideline on the prophylaxis and management of atrial fibrillation associated with general thoracic surgery: executive summary management of chest drains after thoracic resections comparing erector spinae plane block with serratus anterior plane block for minimally invasive thoracic surgery: a randomised clinical trial systematic review of the influence of enhanced recovery pathways in elective lung resection short-term one-lung ventilation does not influence local inflammatory cytokine response after lung resection reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine the erector spinae plane block: a novel analgesic technique in thoracic neuropathic pain erector spinae plane (esp) block in the management of post thoracotomy pain syndrome: a case series new landmarks improve the positioning of the left broncho-cath double-lumen tube -comparison with the classic technique aats guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures intraoperative electroencephalogram suppression predicts postoperative delirium consensus guidelines for the management of postoperative nausea and vomiting presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects newonset atrial fibrillation after anatomic lung resection: predictive factors, treatment and follow-up in a uk thoracic centre comparison of gas exchange after lung resection with a boussignac cpap or venturi mask world health organization-world federation of societies of anaesthesiologists (who-wfsa) international standards for a safe practice of anesthesia ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials comparison of suction versus nonsuction drainage after lung resections: a prospective randomized trial perioperative acute kidney injury review of difficult airway management in thoracic surgery perioperative gabapentin for the prevention of persistent pain after thoracotomy: a randomized controlled trial a comparison of epidural and paravertebral catheterisation techniques in postthoracotomy pain management guidelines for perioperative care in elective colonic surgery: enhanced recovery after surgery (eras((r))) society recommendations effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort: a randomized clinical trial haemodynamic response at double lumen bronchial tube placement-airtraq vs. macintosh laryngoscope, a randomised controlled trial acute and chronic pain syndromes after thoracic surgery a retrospective evaluation of the use of video-capable double-lumen endotracheal tubes in thoracic surgery failed epidural: causes and management ketamine for perioperative pain management perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: american society of regional anesthesia and pain medicine evidence-based guidelines (fourth edition) efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults early removal of urinary catheter after surgery requiring thoracic epidural: a prospective trial gabapentin does not reduce post-thoracotomy shoulder pain: a randomized, doubleblind placebo-controlled study intraoperative temperature monitoring with zero heat flux technology (3m spoton sensor) in comparison with sublingual and nasopharyngeal temperature: an observational study double lumen tube location predicts tube malposition and hypoxaemia during one lung ventilation postoperative delirium in older adults: best practice statement from the american geriatrics society stroke volume variation and pulse pressure variation are not useful for predicting fluid responsiveness in thoracic surgery a review of enhanced recovery for thoracic anaesthesia and surgery a systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia comparison between continuous thoracic epidural and paravertebral blocks for postoperative analgesia in patients undergoing thoracotomy: systematic review safety of the paravertebral block in patients ineligible for epidural block undergoing pulmonary resection oesophageal doppler guided goal-directed haemodynamic therapy in thoracic surgery-a single centre randomized parallel-arm trial the acute physiology and chronic health evaluation iii outcome prediction in patients admitted to the intensive care unit after pneumonectomy the role of physiotherapy in patients undergoing pulmonary surgery for lung cancer. a literature review ultrasound-guided serratus anterior plane block versus thoracic epidural analgesia for thoracotomy pain predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function efficacy of ultrasound-guided serratus plane block on postoperative quality of recovery and analgesia after video-assisted thoracic surgery: a randomized, triple-blind, placebo-controlled study effect of combining a recruitment maneuver with protective ventilation on inflammatory responses in video-assisted thoracoscopic lobectomy: a randomized controlled trial the effects of single-dose dexamethasone on inflammatory response and pain after uterine artery embolisation for symptomatic fibroids or adenomyosis: a randomised controlled study preoperative gabapentin for acute post-thoracotomy analgesia: a randomized, double-blinded, active placebo-controlled study role of fiberoptic bronchoscopy in conjunction with the use of double-lumen tubes for thoracic anesthesia: a prospective study airway injuries after one-lung ventilation: a comparison between double-lumen tube and endobronchial blocker: a randomized, prospective, controlled trial magnesium sulfate does not reduce postoperative analgesic requirements paravertebral block via the surgical field versus epidural block for patients undergoing thoracotomy: a randomized clinical trial comparison of continuous epidural block and continuous paravertebral block in postoperative analgaesia after video-assisted thoracoscopic surgery lobectomy: a randomised, non-inferiority trial chads2 score predicts postoperative atrial fibrillation in patients undergoing elective pulmonary lobectomy incidence of urinary retention in patients with thoracic patient-controlled epidural analgesia (tpcea) undergoing thoracotomy suction on chest drains following lung resection: evidence and practice are not aligned a systematic review of intravenous ketamine for postoperative analgesia does external pleural suction reduce prolonged air leak after lung resection? results from the airintrial after 500 randomized cases safety of the peripheral administration of vasopressor agents it is safe and feasible to omit the chest tube postoperatively for selected patients receiving thoracoscopic pulmonary resection: a meta-analysis enhanced recovery programs in lung cancer surgery: systematic review and meta-analysis of randomized controlled trials prophylactic use of noninvasive positive pressure ventilation in post-thoracic surgery patients: a prospective randomized control study fluid therapy in thoracic surgery: a zero-balance target is always best! turk a randomised trial comparing the cel-100 videolaryngoscope(tm) with the macintosh laryngoscope blade for insertion of double-lumen tubes in patients with resectable non-small-cell lung cancer, is video-assisted thoracoscopic segmentectomy a suitable alternative to thoracotomy and segmentectomy in terms of morbidity and equivalence of resection? enhanced recovery after surgery-eras-principles, practice and feasibility in the elderly lung injury after one-lung ventilation: a review of the pathophysiologic mechanisms affecting the ventilated and the collapsed lung high-flow oxygen therapy after noninvasive ventilation interruption in patients recovering from hypercapnic acute respiratory failure.a physiological crossover trial early postoperative prophylactic noninvasive ventilation after major lung resection in copd patients: a randomized controlled trial hypoxic pulmonary vasoconstriction: physiology and anesthetic implications the combination of iv and perineural dexamethasone prolongs the analgesic duration of intercostal nerve blocks compared with iv dexamethasone alone novel zero-heat-flux deep body temperature measurement in lower extremity vascular and cardiac surgery suction vs water seal after pulmonary resection: a randomized prospective study implementing a thoracic enhanced recovery program: lessons learned in the first year noninvasive continuous arterial blood pressure monitoring with nexfin(r) evaluation of the doublelumen tube vivasight-dl (dlt-etview): a prospective single-center study paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review critical care after lung resection: calor 1, a single-centre pilot study complications from administration of vasopressors through peripheral venous catheters: an observational study analgesia and pulmonary function after lung surgery: is a single intercostal nerve block plus patient-controlled intravenous morphine as effective as patientcontrolled epidural anaesthesia? a randomized non-inferiority clinical trial guidelines for perioperative care for liver surgery: enhanced recovery after surgery (eras) society recommendations recommendations for airway control and difficult airway management in thoracic anesthesia and lung separation procedures determining optimal fluid and air leak cut off values for chest drain management in general thoracic surgery elimination of daily routine chest radiographs does not change on-demand radiography practice in post-cardiothoracic surgery patients perioperative goal-directed therapy with uncalibrated pulse contour methods: impact on fluid management and postoperative outcome physiology and pathophysiology of pleural fluid turnover impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis postoperative pulmonary complications the raw and processed electroencephalogram as a monitoring and diagnostic tool consensus guidelines for enhanced recovery after gastrectomy: enhanced recovery after surgery (eras(r)) society recommendations comparison of intravenous ketorolac at three single-dose regimens for treating acute pain in the emergency department: a randomized controlled trial reduction of postoperative pulmonary complications after lung surgery using a fast track clinical pathway consensus statement on perioperative use of neuromuscular monitoring somatic paravertebral nerve blockade. incidence of failed block and complications choosing a lung isolation device for thoracic surgery: a randomized trial of three bronchial blockers versus double-lumen tubes guidelines for postoperative care in gynecologic/oncology surgery: enhanced recovery after surgery (eras(r)) society recommendations--part ii cpap increases 6-minute walk distance after lung resection surgery systematic review and meta-analysis of enhanced recovery programmes in surgical patients preventive analgesia in thoracic surgery: controlled, randomized, double-blinded study guidelines for perioperative care in elective rectal/pelvic surgery: enhanced recovery after surgery (eras((r))) society recommendations associations between intraoperative ventilator settings during one-lung ventilation and postoperative pulmonary complications: a prospective observational study risk of hematoma in patients with a bleeding risk undergoing cardiovascular surgery with a paravertebral catheter the efficacy of serratus anterior plane block in analgesia for thoracotomy: a retrospective study evaluation of the effect of serratus anterior plane block for pain treatment after video-assisted thoracoscopic surgery comparison of the single or double chest tube applications after pulmonary lobectomies risk factors for atrial fibrillation after lung cancer surgery: analysis of the society of thoracic surgeons general thoracic surgery database the efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis monitoring neuromuscular function hemoglobin concentration, total hemoglobin mass and plasma volume in patients: implications for anemia video-assisted thoracic surgery does not reduce the incidence of postoperative atrial fibrillation after pulmonary lobectomy a randomised trial of serratus anterior plane block for analgesia after thoracoscopic surgery dexamethasone as an adjuvant to peripheral nerve block iatrogenic hemodilution: a possible cause for avoidable blood transfusions? critical care prophylactic use of noninvasive ventilation in patients undergoing lung resectional surgery a systematic review of pulse pressure variation and stroke volume variation to predict fluid responsiveness during cardiac and thoracic surgery preoperative predictive factors for intensive care unit admission after pulmonary resection comparison of continuous thoracic epidural with paravertebral block on perioperative analgesia and hemodynamic stability in patients having open lung surgery multicenter international randomized comparison of objective and subjective outcomes between electronic and traditional chest drainage systems antiinflammatory effect of sevoflurane in open lung surgery with one-lung ventilation processed electroencephalogram and evoked potential techniques for amelioration of postoperative delirium and cognitive dysfunction following non-cardiac and non-neurosurgical procedures in adults bispectral index for improving anaesthetic delivery and postoperative recovery video laryngoscopy versus direct laryngoscopy for double-lumen endotracheal tube intubation: a retrospective analysis analgesia in patients undergoing thoracotomy: epidural versus paravertebral technique. a randomized, double-blind, prospective study crystalloid fluid therapy are daily routine chest radiographs necessary after pulmonary surgery in adult patients? failure of noninvasive ventilation after lung surgery: a comprehensive analysis of incidence and possible risk factors official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure high flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis the impact of enhanced recovery after surgery (eras) protocol compliance on morbidity from resection for primary lung cancer randomized clinical trial comparing double-lumen tube and ez-blocker for single-lung ventilation a randomised controlled trial comparing the glidescope((r)) and the macintosh laryngoscope for double-lumen endobronchial intubation does fast-tracking increase the readmission rate after pulmonary resection? a case-matched study relationship between intraoperative hypotension, defined by either reduction from baseline or absolute thresholds, and acute kidney and myocardial injury after noncardiac surgery: a retrospective cohort analysis double-lumen endobronchial tube in the emergency management of massive hemoptysis effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes: a prospective study preoperative oral pregabalin reduces acute pain after thoracotomy. open access maced increased number and expertise of italian respiratory high-dependency care units: the second national survey noninvasive ventilation in acute respiratory failure: which recipe for success? continuous paravertebral block for post-cardiothoracic surgery analgesia: a systematic review and meta-analysis effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation effects of volatile and intravenous anesthesia on the alveolar and systemic inflammatory response in thoracic surgical patients intubation with vivasight or conventional left-sided double-lumen tubes: a randomized trial fluid management in thoracic surgery balanced crystalloids versus saline in noncritically ill adults is routine chest radiography indicated following chest drain removal after cardiothoracic surgery? perioperative quality initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery an audit of robertshaw double lumen tube placement using the fibreoptic bronchoscope fiberoptic bronchoscopic positioning of double-lumen tubes perioperative fasting in adults and children: guidelines from the european society of anaesthesiology impairment of wound healing after operative treatment of mandibular fractures, and the influence of dexamethasone competence in bronchoscopy for icu, anesthesiology, thoracic surgery and lung transplantation regional analgesia for video-assisted thoracic surgery: a systematic review high-flow nasal cannula therapy versus intermittent noninvasive ventilation in obese subjects after cardiothoracic surgery effects of volatile vs. propofol-based intravenous anesthetics on the alveolar inflammatory responses to one-lung ventilation: a meta-analysis of randomized controlled trials does perioperative glucocorticosteroid treatment correlate with disturbance in surgical wound healing after treatment of facial fractures? a retrospective study do surgical patients benefit from perioperative gabapentin/pregabalin? a systematic review of efficacy and safety non-invasive positive pressure ventilation for prevention of complications after pulmonary resection in lung cancer patients lung ultrasound compared with chest x-ray in diagnosing postoperative pulmonary complications following cardiothoracic surgery: a prospective observational study chest xray prior to discharge after video-assisted thoracic anatomical pulmonary resection: friend or foe? hypomagnesemia is prevalent in patients undergoing gynecologic surgery by a gynecologic oncologist anesthesia and fast-track in video-assisted thoracic surgery (vats): from evidence to practice united states preventive services task force. grade definitions association between intraoperative hypotension and myocardial injury after vascular surgery clinical observations on reversal of rocuronium-induced residual neuromuscular blockade by sugammadex after thoracic surgery saline versus balanced solutions: are clinical trials comparing two crystalloid solutions really needed? critical care impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension postoperative diet advancement: surgical dogma vs evidence-based medicine comparison of the airtraq and the macintosh laryngoscope for double-lumen tube intubation: a randomised clinical trial espen guideline: clinical nutrition in surgery local anaesthetics and regional anaesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children safety and efficacy of postoperative epidural analgesia perioperative magnesium infusion and postoperative pain effect of electroencephalography-guided anesthetic administration on postoperative delirium among older adults undergoing major surgery: the engages randomized clinical trial is intercostal block for pain management in thoracic surgery more successful than epidural anaesthesia? continuous paravertebral block using a thoracoscopic catheter-insertion technique for postoperative pain after thoracotomy: a retrospective case-control study pain control of thoracoscopic major pulmonary resection: is pre-emptive local bupivacaine injection able to replace the intravenous patient controlled analgesia? does a protective ventilation strategy reduce the risk of pulmonary complications after lung cancer surgery?: a randomized controlled trial paravertebral block versus thoracic epidural for patients undergoing thoracotomy disconnection technique with a bronchial blocker for improving lung deflation: a comparison with a doublelumen tube and bronchial blocker without disconnection risk factors for reinsertion of urinary catheter after early removal in thoracic surgical patients is there a role for gabapentin in preventing or treating pain following thoracic surgery? fluid composition and acute kidney injury how long is a transurethral catheter necessary in patients undergoing thoracotomy and receiving thoracic epidural analgesia? literature review goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study the single chest tube versus double chest tube application after pulmonary lobectomy: a systematic review and metaanalysis single chest tube drainage is superior to double chest tube drainage after lobectomy: a meta-analysis pressure-controlled versus volumecontrolled ventilation during one-lung ventilation for video-assisted thoracoscopic lobectomy publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations medical writing and editorial assistance was provided by michael shaw phd, on behalf of editamed srl, torino, italy. the authors wish to thank the following colleagues who served as external independent reviewers for the final manuscript editing: prof. paolo navalesi (anesthesiology and intensive care unit -university of padua, italy), dr. alessandro pardolesi (thoracic surgery unit -fondazione irccs istituto nazionale dei tumori, milan, italy), dr. giulio rosboch (department of anesthesia and intensive care -azienda ospedaliera città della salute e della scienza, turin, italy), dr. domenico santonastaso (anesthesia and intensive care unit -ausl romagna bufalini hospital, cesena, italy). all the authors contributed equally to the consensus. all the authors revised and approved the final manuscript. this work, including travel and meeting expenses, was supported by an unrestricted grant from msd italia srl. the sponsor had no role in selecting the participants, reviewing the literature, defining consensus recommendations, drafting or reviewing the paper, or in the decision to submit the manuscript. data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.ethics approval and consent to participate not applicable. not applicable. key: cord-014538-6a2pviol authors: kamilia, chtara; regaieg, kais; baccouch, najeh; chelly, hedi; bahloul, mabrouk; bouaziz, mounir; jendoubi, ali; abbes, ahmed; belhaouane, houda; nasri, oussama; jenzri, layla; ghedira, salma; houissa, mohamed; belkadi, kamal; harti, youness; nsiri, afak; khaleq, khalid; hamoudi, driss; harrar, rachid; thieffry, camille; wallet, frédéric; parmentier-decrucq, erika; favory, raphaël; mathieu, daniel; poissy, julien; lafon, thomas; vignon, philippe; begot, emmanuelle; appert, alexandra; hadj, mathilde; claverie, paul; matt, morgan; barraud, olivier; françois, bruno; jamoussi, amira; jazia, amira ben; marhbène, takoua; lakhdhar, dhouha; khelil, jalila ben; besbes, mohamed; goutay, julien; blazejewski, caroline; joly-durand, isabelle; pirlet, isabelle; weillaert, marie pierre; beague, sebastien; aziz, soufi; hafiane, reda; hattabi, khalid; bouhouri, mohamed aziz; hammoudi, driss; fadil, abdelaziz; harrar, rachid al; zerouali, khalid; medhioub, fatma kaaniche; allela, rania; algia, najla ben; cherif, samar; slaoui, mohamed taoufik; boubia, souhail; hafiani, y.; khaoudi, a.; cherkab, r.; elallam, w.; elkettani, c.; barrou, l.; ridaii, m.; mehdi, rihi el; schimpf, caroline; mizrahi, assaf; pilmis, benoît; le monnier, alban; tiercelet, kelly; cherin, mélanie; bruel, cédric; philippart, francois; bailly, sébastien; lucet, jc; lepape, alain; l’hériteau, françois; aupée, martine; bervas, caroline; boussat, sandrine; berger-carbonne, anne; machut, anaïs; savey, anne; timsit, jean-françois; razazi, keyvan; rosman, jérémy; de prost, nicolas; carteaux, guillaume; jansen, chloe; decousser, jean winoc; brun-buisson, christian; dessap, armand mekontso; m’rad, aymen; ouali, zouhour; barghouth, manel; kouatchet, achille; mahieu, rafael; weiss, emmanuel; schnell, david; zahar, jean-ralph; artiguenave, margaux; sophie, paktoris-papine; espinasse, florence; sayed, faten el; dinh, aurélien; charron, cyril; geri, guillaume; vieillard-baron, antoine; repessé, xavier; kallel, hatem; mayence, claire; houcke, stéphanie; guegueniat, pascal; hommel, didier; dhifaoui, kaouther; hajjej, zied; fatnassi, amira; sellami, walid; labbene, iheb; ferjani, mustapha; dachraoui, fahmi; nakkaa, sabrine; m’ghirbi, abdelwaheb; adhieb, ali; braiek, dhouha ben; hraiech, kmar; ousji, ali; ouanes, islem; zaineb, hammouda; abdallah, saousen ben; ouanes-besbes, lamia; abroug, fekri; klein, simon; miquet, mattéo; thouret, jean-marc; peigne, vincent; daban, jean-louis; boutonnet, mathieu; lenoir, bernard; merhbene, takoua; derreumaux, celine; seguin, thierry; conil, jean-marie; kelway, charlotte; blasco, valery; nafati, cyril; harti, karim; reydellet, laurent; albanese, jacques; aicha, narjess ben; meddeb, khaoula; khedher, ahmed; ayachi, jihene; fraj, nesrine; sma, nesrine; chouchene, imed; boussarsar, mohamed; yedder, soumaya ben; samoud, walid; radhouene, bousselmi; mariem, bousselmi; ammar, asma; cheikh, asma ben; lakhal, hend ben; khelfa, messaouda; hamdaoui, yamina; bouafia, nabiha; trampont, timothée; daix, thomas; legarçon, vincent; karam, henri hani; pichon, nicolas; essafi, fatma; foudhaili, nasreddine; thabet, hafedh; blel, youssef; brahmi, nozha; ezzouine, hanane; kerrous, mahmoud; haoui, saad el; ahdil, soufiane; benslama, abdellatif; abidi, khalid; dendane, tarek; oussama, ssouni; belayachi, jihane; madani, naoufal; abouqal, redouane; zeggwagh, amine ali; ghadhoune, hatem; chaari, anis; jihene, guissouma; allouche, hend; trabelsi, insaf; brahmi, habib; samet, mohamed; ghord, hatem el; habiba, ben sik ali; hajer, nouira; tilouch, najla; yaakoubi, sondes; jaoued, oussama; gharbi, rim; hassen, mohamed fekih; elatrous, souheil; arcizet, julien; leroy, bertrand; abdulmalack, caroline; renzullo, catherine; hamet, maël; doise, jean-marc; coutet, jérôme; cheikh, chaigar mohammed; quechar, zakaria; joris, magalie; beauport, dimitri titeca; kontar, loay; lebon, delphine; gruson, bérengère; slama, michel; marolleau, jean-pierre; maizel, julien; gorham, julie; ameye, lieveke; berghmans, thierry; paesmans, marianne; sculier, jean-paul; meert, anne-pascale; guillot, max; ledoux, marie-pierre; braun, thierry; maestraggi, quentin; michard, baptiste; castelain, vincent; herbrecht, raoul; schneider, francis; couffin, severine; lobo, david; mongardon, nicolas; dhonneur, gilles; mounier, roman; le borgne, pierrick; couraud, sophie; herbrecht, jean-etienne; boivin, alexandra; lefebvre, françois; bilbault, pascal; zelmat, setti-aouicha; batouche, djamila-djahida; mazour, fatima; chaffi, belkacem; benatta, nadia; sik, ali habiba; talik, i.; perrier, maxime; gouteix, eliane; koubi, claude; escavy, annabelle; guilbaut, victoria; fosse, jean-philippe; jazia, rahma ben; abdelghani, ahmed; cungi, pierre-julien; bordes, julien; nguyen, cédric; pierrou, candice; cruc, maximilien; benois, alain; duprez, frédéric; bonus, thierry; cuvelier, grégory; ollieuz, sandra; machayekhi, sharam; paciorkowski, frédéric; reychler, gregory; coudroy, remi; thille, arnaud w.; drouot, xavier; diaz, véronique; meurice, jean-claude; robert, rené; turki, olfa; ben, hmida chokri; assefi, mona; deransy, romain; brisson, hélène; monsel, antoine; conti, filomena; scatton, olivier; langeron, olivier; ghezala, hassen ben; snouda, salah; ben, chiekh imen; kaddour, moez; armel, anwar; youness, lafrikh; abdelhak, bensaid; youssef, miloudi; najib, al harrar; mustapha, amouzoun; noufel, mtioui; mohamed, zamd; salma, el khayat; ghizlane, medkouri; mohamed, benghanam; benyounes, ramdani; montini, florent; moschietto, sébastien; gregoire, emilien; claisse, guillaume; guiot, julien; morimont, philippe; krzesinski, jean-marie; mariat, christophe; lambermont, bernard; cavalier, etienne; delanaye, pierre; benbernou, soumia; ilies, sofiane; azza, abdelkader; bouyacoub, khalida; louail, meriem; mokhtari-djebli, houria; arrestier, romain; daviaud, fabrice; francois, xavier laborne; brocas, elsa; choukroun, gérald; peñuelas, oscar; lorente, josé-angel; cardinal-fernandez, pablo; rodriguez, josé-maria; aramburu, josé-antonio; esteban, andres; frutos-vivar, fernando; bitker, laurent; costes, nicolas; le bars, didier; lavenne, franck; devouassoux, mojgan; richard, jean-christophe; mechati, malika; gainnier, marc; papazian, laurent; guervilly, christophe; garnero, aude; arnal, jean michel; roze, hadrien; richard, jean christophe; repusseau, benjamin; dewitte, antoine; joannes-boyau, olivier; ouattara, alexandre; harbouze, nadia; amine, a. m.; olandzobo, a. g.; herbland, alexandre; richard, marie; girard, nicolas; lambron, lucile; lesieur, olivier; wainschtein, sarah; hubert, sidonie; hugues, albane; tran, marc; bouillard, philippe; loteanu, vlad; leloup, maxime; laurent, alexandra; lheureux, florent; prestifilippo, alessia; cruz, martin delgado maria; romain, rigal; antonelli, massimo; blanch, torra lluis; bonnetain, franck; grazzia-bocci, maria; mancebo, jordi; samain, emmanuel; paul, hebert; capellier, gilles; zavgorodniaia, taissa; soichot, marion; malissin, isabelle; voicu, sebastian; garçon, pierre; goury, antoine; kerdjana, lamia; deye, nicolas; bourgogne, emmanuel; megarbane, bruno; mejri, olfa; hmida, marwa ben; tannous, salma; chevillard, lucie; labat, laurence; risede, patricia; fredj, hana; léger, maxime; brunet, marion; le roux, gaël; boels, david; lerolle, nicolas; farah, souaad; amiel-niemann, hélène; kubis, nathalie; declèves, xavier; peyraux, nicoals; baud, frederic; serafini, micaela; alvarez, jean-claude; heinzelman, annette; jozwiak, mathieu; millasseau, sandrine; teboul, jean-louis; alphonsine, jean-emmanuel; depret, françois; richard, nathalie; attal, pierre; richard, christian; monnet, xavier; chemla, denis; jerbi, salma; khedhiri, wafa; necib, hatem; scarfo, paolo; chevalier, charles; piagnerelli, michael; lafont, alexandre; galy, antoine; mancia, claire; zerhouni, amel; tabeliouna, kheira; gaja, ali; hamrouni, bassem; malouch, abir; fourati, sami; messaoud, rihab; zarrouki, youssef; ziadi, amra; rhezali, manal; zouizra, zahira; boumzebra, drissi; samkaoui, mohamed abdennasser; brunet, jennifer; canoville, bertrand; verrier, pierre; ivascau, calin; seguin, amélie; valette, xavier; du cheyron, damien; daubin, cedric; bougouin, wulfran; aissaoui, nadia; lamhaut, lionel; jost, daniel; maupain, carole; beganton, frankie; bouglé, adrien; dumas, florence; marijon, eloi; jouven, xavier; cariou, alain; poirson, florent; chaput, ulriikka; beeken, thomas; maxime, leclerc; haikel, oueslati; vodovar, dominique; chelly, jonathan; marteau, philippe; chocron, richard; juvin, philippe; loeb, thomas; adnet, frederic; lecarpentier, eric; riviere, antoine; de cagny, bertand; soupison, thierry; privat, elodie; escutnaire, joséphine; dumont, cyrielle; baert, valentine; vilhelm, christian; hubert, hervé; leteurtre, stéphane; fresco, marion; bubenheim, michael; beduneau, gaetan; carpentier, dorothée; grange, steven; artaud-macari, elise; misset, benoit; tamion, fabienne; girault, christophe; dumas, guillaume; chevret, sylvie; lemiale, virginie; mokart, djamel; mayaux, julien; pène, frédéric; nyunga, martine; perez, pierre; moreau, anne-sophie; bruneel, fabrice; vincent, françois; klouche, kada; reignier, jean; rabbat, antoine; azoulay, elie; frat, jean-pierre; ragot, stéphanie; constantin, jean-michel; prat, gwenael; mercat, alain; boulain, thierry; demoule, alexandre; devaquet, jérôme; nseir, saad; charpentier, julien; argaud, laurent; beuret, pascal; ricard, jean-damien; teiten, christelle; marjanovic, nicolas; palamin, nicola; l’her, erwan; bailly, arthur; boisramé-helms, julie; champigneulle, benoit; kamel, toufik; mercier, emmanuelle; le thuaut, aurélie; lascarrou, jean-baptiste; rolle, amélie; de jong, audrey; chanques, gérald; jaber, samir; hariri, geoffroy; baudel, jean-luc; dubée, vincent; preda, gabriel; bourcier, simon; joffre, jeremie; bigé, naïke; ait-oufella, hafid; maury, eric; mater, houda; merdji, hamid; grimaldi, david; rousseau, christophe; mira, jean-paul; chiche, jean-daniel; sedghiani, ines; benabderrahim, a.; hamdi, dhekra; jendoubi, asma; cherif, mohamed ali; hechmi, youssef zied el; zouheir, jerbi; bagate, françois; bousselmi, radhwen; schortgen, frédérique; asfar, pierre; guérot, emmanuel; fabien, grelon; anguel, nadia; sigismond, lasocki; matthieu, henry-lagarrigue; gonzalez, frédéric; françois, legay; guitton, christophe; schenck, maleka; jean-marc, doise; dreyfuss, didier; radermacher, peter; frère, antoine; martin-lefèvre, laurent; colin, gwenhaël; fiancette, maud; henry-laguarrigue, matthieu; lacherade, jean-claude; lebert, christine; vinatier, isabelle; yehia, aihem; joret, aurélie; menunier-beillard, nicolas; benzekri-lefevre, dalila; desachy, arnaud; bellec, fréderic; plantefève, gaëtan; quenot, jean-pierre; meziani, ferhat; tavernier, elsa; ehrmann, stephan; chudeau, nicolas; raveau, tommy; moal, valérie; houillier, pascal; rouve, emmanuelle; lakhal, karim; gandonnière, charlotte salmon; jouan, youenn; bodet-contentin, laetitia; balmier, adrien; messika, jonathan; de montmollin, etienne; pouyet, victorine; sztrymf, benjamin; thiagarajah, abirami; roux, damien; de chambrun, marc pineton; luyt, charles-edouard; beloncle, françois; zapella, nathalie; ledochowsky, stanislas; terzi, nicolas; mazou, jean-marc; sonneville, romain; paulus, sylvie; fedun, yannick; landais, mickael; raphalen, jean-herlé; combes, alain; amoura, zahir; jacquemin, aemilia; guerrero, felipe; marcheix, bertrand; hernandez, nicolas; fourcade, olivier; georges, bernard; delmas, clément; makoudi, sarah; genton, audrey; bernard, rémy; lebreton, guillaume; amour, julien; mazet, charlotte; bounes, fanny; murat, gurbuz; cronier, laure; robin, guillaume; biendel, caroline; silva, stein; boubeche, samia; abriou, caroline; wurtz, véronique; scherrer, vincent; rey, nathalie; gastaldi, gioia; veber, benoit; doguet, fabien; gay, arnaud; dureuil, bertrand; besnier, emmanuel; rouget, antoine; gantois, guillaume; magalhaes, eric; wanono, ruben; smonig, roland; lermuzeaux, mathilde; lebut, jordane; olivier, andremont; dupuis, claire; radjou, aguila; mourvillier, bruno; neuville, mathilde; d’ortho, marie pia; bouadma, lila; rouvel-tallec, anny; rudler, marika; weiss, nicolas; perlbarg, vincent; galanaud, damien; thabut, dominique; rachdi, emna; mhamdi, ghada; trifi, ahlem; abdelmalek, rim; abdellatif, sami; daly, foued; nasri, rochdi; tiouiri, hanene; lakhal, salah ben; rousseau, geoffroy; asmolov, romain; grammatico-guillon, leslie; auvet, adrien; laribi, said; garot, denis; dequin, pierre françois; guillon, antoine; fergé, jean-louis; abgrall, gwénolé; hinault, ronan; vally, shazima; roze, benoit; chaplain, agathe; chabartier, cyrille; savidan, anne-charlotte; marie, sabia; cabie, andre; resiere, dabor; valentino, ruddy; mehdaoui, hossein; benarous, lucas; soda-diop, marième; bouzana, fouad; perrin, gilles; bourenne, jeremy; eon, béatrice; lambert, dominique; trebuchon, agnes; poncelet, géraldine; le bourgeois, fleur; michael, levy; camille, guillot; naudin, jérôme; deho, anna; dauger, stéphane; sauthier, michaël; bergeron-gallant, krystale; emeriaud, guillaume; jouvet, philippe; tiebergien, nicolas; jacquet-lagrèze, matthias; fellahi, jean-luc; baudin, florent; essouri, sandrine; javouhey, etienne; guérin, claude; lampin, marie; mamouri, ouardia; devos, patrick; karaca-altintas, yasemin; vinchon, matthieu; brossier, david; eltaani, redha; teyssedre, sonia; sabine, meyet; bouchut, jean-christophe; peguet, olivier; petitdemange, lucie; guilbert, anne sophie; aoul, nabil tabet; addou, zakaria; aouffen, nabil; anas, benqqa; kalouch, samira; yaqini, khalid; chlilek, aziz; abdou, rchi; gravellier, perrine; chantreuil, julie; travers, nadine; listrat, antoine; le reun, claire; favrais, geraldine; coppere, zoe; blanot, stéphane; montmayeur, juliette; bronchard, régis; rolando, stephane; orliaguet, gilles; leger, pierre-louis; rambaud, jérôme; thueux, emilie; de larrard, alexandra; berthelot, véronique; denot, julien; reymond, marie; amblard, alain; morin-zorman, sarah; lengliné, etienne; pichereau, claire; mariotte, eric; emmanuel, canet; poujade, julien; trumpff, guillaume; janssen-langenstein, ralf; harlay, marie-line; zaid, noorah; ait-ammar, nawel; bonnal, christine; merle, jean-claude; botterel, francoise; levesque, eric; riad, zakaria; mezidi, mehdi; yonis, hodane; aublanc, mylène; perinel-ragey, sophie; lissonde, floriane; louf-durier, aurore; tapponnier, romain; louis, bruno; forel, jean-marie; bisbal, magali; lehingue, samuel; rambaud, romain; adda, mélanie; hraiech, sami; marchi, elisa; roch, antoine; guerin, vincent; rozencwajg, sacha; schmidt, matthieu; hekimian, guillaume; bréchot, nicolas; trouillet, jean louis; besset, sébastien; franchineau, guillaume; nieszkowska, ania; pascal, leprince; loiselle, maud; sarah, chemam; laurence, dangers; guillemette, thomas; jacquens, alice; kerever, sebastien; guidet, bertrand; aegerter, philippe; das, vincent; fartoukh, muriel; hayon, jan; desmard, mathieu; fulgencio, jean-pierre; zuber, benjamin; soufi, a.; khaleq, k.; hamoudi, d.; garret, charlotte; peron, matthieu; coron, emmanuel; bretonnière, cédric; audureau, etienne; audrey, winters; christophe, duvoux; christian, jacquelinet; daniel, azoulay; cyrille, feray; aissaoui, wissal; rghioui, kawtar; haddad, wafae; barrou, houcine; carteaux-taeib, anna; lupinacci, renato; manceau, gilles; jeune, florence; tresallet, christophe; habacha, sahar; fathallah, ines; zoubli, aymen; aloui, rafaa; kouraichi, nadia; jouet, emilie; badin, julie; fermier, brice; feller, marc; serie, mathieu; pillot, jérôme; marie, william; gisbert-mora, chloé; vinclair, camille; lesbordes, pierre; mathieu, pascal; de brabant, fabienne; muller, emmanuel; robaux, marie-aline; giabicani, mikhael; marchalot, antoine; gelinotte, stéphanie; declercq, pierre louis; eraldi, jean-pierre; bougerol, françois; meunier-beillard, nicolas; devilliers, hervé; rigaud, jean-philippe; verrière, camille; ardisson, fanny; kentish-barnes, nancy; jacq, gwenaëlle; chermak, akli; lautrette, alexandre; legrand, matthieu; soummer, alexis; thiery, guillaume; cottereau, alice; canet, emmanuel; caujolle, marie; allyn, jérôme; valance, dorothée; brulliard, caroline; martinet, olivier; jabot, julien; gallas, thomas; vandroux, david; allou, nicolas; durand, arthur; nevière, rémi; delguste, florian; boulanger, eric; preau, sebastien; martin, ruste; cochet, hélène; ponthus, jean pierre; amilien, virginie; tchir, martial; barsam, elise; ayoub, mohsen; georger, jean francois; guillame, izaute; assaraf, julie; tripon, simona; mallet, maxime; barbara, guilaume; louis, guillaume; gaudry, stéphane; barbarot, nicolas; jamet, angéline; outin, hervé; gibot, sébastien; bollaert, pierre-edouard; holleville, mathilde; legriel, stéphane; chateauneuf, anne laure; cavelot, sébastien; moyer, jean-denis; bedos, jean pierre; merle, philippe; laine, aurelie; natalie, de sa; cornuault, mathieu; libot, jérome; asehnoune, karim; rozec, bertrand; dantal, jacques; videcoq, michel; degroote, thècle; jaillette, emmanuelle; zerimech, farid; malika, balduyck; llitjos, jean-françois; amara, marlène; lacave, guillaume; pangon, béatrice; mavinga, josé; makunza, joseph nsiala; mafuta, m. e.; yanga, yves; eric, amisi; ilunga, jp; kilembe, ma; alby-laurent, fanny; toubiana, julie; mokline, amel; laajili, achraf; amri, helmi; rahmani, imene; mensi, nidhal; gharsallah, lazheri; tlaili, sofiene; gasri, bahija; hammouda, rym; messadi, amen allah; allain, pierre-antoine; gault, nathallie; paugam-burtz, catherine; foucrier, arnaud; chatbri, bassem; bourbiaa, yousra; thabet, lamia; neuschwander, arthur; vincent, looten; beck, jennifer; vibol, chhor; amelie, yavchitz; resche-rigon, matthieu; pirracchio, jean mantzromain; bureau, côme; decavèle, maxens; campion, sébastien; ainsouya, roukia; niérat, marie-cécile; prodanovic, hélène; raux, mathieu; similowski, thomas; dubé, bruno-pierre; demiri, suela; dres, martin; may, faten; quintard, hervé; kounis, ilias; saliba, faouzi; andré, stephane; boudon, marc; ichai, philippe; younes, aline; nakad, lionel; coilly, audrey; antonini, teresa; sobesky, rodolphe; de martin, eleonora; samuel, didier; hubert, noemie; nay, mai-anh; auchabie, johann; giraudeau, bruno; jean, reignier; darmon, michaël; ruckly, stephane; garrouste-orgeas, maïté; gratia, elisabeth; goldgran-toledano, dany; jamali, samir; dumenil, anne sylvie; schwebel, carole; brisard, laurent; bizouarn, philippe; lepoivre, thierry; nicolet, johanna; rigal, jean christophe; roussel, jean christian; cheurfa, cherifa; abily, julien; lescot, thomas; page, isaline; warnier, stéphanie; nys, monique; rousseau, anne-françoise; damas, pierre; uhel, fabrice; lesouhaitier, mathieu; grégoire, murielle; gaudriot, baptiste; gacouin, arnaud; le tulzo, yves; flecher, erwan; tarte, karin; tadié, jean-marc; georges, quentin; soares, m.; jeon, kyeongman; oeyen, sandra; rhee, chin kook; gruber, pascale; ostermann, marlies; hill, quentin; depuydt, peter; ferra, christelle; muller, alice; aurelie, bourmaud; niles, christopher; herbert, fabien; pied, sylviane; loridant, séverine; françois, nadine; bignon, anne; sendid, boualem; lemaitre, caroline; dupre, celine; zayene, aymen; portier, lucie; de freitas caires, nathalie; lassalle, philippe; le neindre, aymeric; selot, pascal; ferreiro, daniel; bonarek, maria; henriot, stépahen; rodriguez, julie; taddei, mara; di bari, mauro; hickmann, cheryl; castanares-zapatero, diego; deldicque, louise; van den bergh, peter; caty, gilles; roeseler, jean; francaux, marc; laterre, pierre-françois; dupuis, bastien; machayeckhi, sharam; sarfati, celine; moore, alex; mendialdua, paula; rodet, emilie; pilorge, catherine; stephan, francois; rezaiguia-delclaux, saida; dugernier, jonathan; hesse, michel; jumetz, thibaud; bialais, emilie; depoortere, virginie; michotte, jean bernard; wittebole, xavier; jamar, françois title: proceedings of réanimation 2017, the french intensive care society international congress date: 2017-01-10 journal: ann intensive care doi: 10.1186/s13613-016-0224-7 sha: doc_id: 14538 cord_uid: 6a2pviol nan introduction the study of the bacterial cartography in thoracic surgery is extremely important for the treatment of post-operative infections due to the severity of the underlying pathology, the fragility of patients after surgery in addition to the choice of the empiric antibiotic therapy. we led a prospective study following all the patients who underwent a pulmonary resection surgery for a period of 7 months from january to july 2016, jointly with the microbiology department, chu ibn rochd, casablanca. the bronchial secretions were collected by a protected distal bronchial sample using a (combicath) after the intubation. results during the period of the study, 92 patients underwent a pulmonary resection, 65% for a neoplastic pathology. the medium age was 43 years ±8 and 58% of our sample were male. 48% of our patients had smoking habits and 16 of them had pulmonary tuberculosis, 12 had repeated respiratory infections. the antibiotics used in pre-operative: 58% of beta-lactams; 22% of fluoroquinolones; 5% of macrolides. moreover, 60% of our patients were classified asa1. of the 92 obtained samples, 22 were positive (23.9%). the most frequently observed germs were the acinetobacter baumannii (8.7%), pseudomonas aeruginosa (6.5%), klebsiella pneumoniae (4.3%), staphylococcus aureus (4.3%). the acinetobacter baumannii was the most resistant germ (60% sensibility to carbapenem). these patients were followed until their d30 after surgery, 12 of them developed a post-operative pneumonitis with 4 cases of multi-resistant acinetobacter baumanii, 2 of which deceased. conclusion pneumonitis after pulmonary resection are common and severe that's why it is necessary to establish a global prevention strategy mainly based on general patricians and pneumologists' awareness concerning the choice of the prescribed antibiotics, in order to avoid the spread of multi-resistant germs. introduction carbapenemase-producing enterobacteriaceae (cpec) are increasingly reported worldwide and constitutes a real challenge antibiotic for clinicians to preserve the bacterial ecology. its incidence has remarkably increased in our intensive care unit during the last 5 years. the esbl spread has a major consequence in term of antibiotic choices. carbapenem antibiotic are regarded as the most effective treatment. however numbers of authors suggest that alternatives antibiotics (i.e. noncarbapenems) could be used in esbl-pe infections. there are some conflicting data regarding the use of alternatives in case of esbl-pe infections. moreover as far as we know, there are no data in icu. objectives the aim of this study was to describe esbl-pe infections in icu and therapeutic options chosen in these specific situations. patients and methods prospective multicentric observational cohort study conducted in volunteers icu. all consecutive patients hospitalized in icu with esbl-pe infection according to cdc definitions were included. severity of illness was defines according to bone criteria, saps ii and sofa. demographic datas, empirical and definitive antibiotic therapy (et and dt), clinical evolution, and outcome were recorded. in vitro antimicrobial susceptibility testing was performed by the disk diffusion method or the vitek 2 system according to the guidelines of the antibiogram committee of the french microbiologic society. results during the study period 146 patients with esbl-pe infection met eligibility criteria with respectively a median age and saps ii score of 63 (51-74) and 50 (38-70). the median sofa score at first day of antibiotic therapy and icu admission were 7 (4-11) and 7 (5) (6) (7) (8) (9) (10) (11) respectively. the most frequent site of infection were respiratory tract (45%), urinary tract (20%) and abdominal (17%). the most frequent isolated species were: escherichia coli (43%), klebsiella sp (37%) and enterobacter sp (18%). respectively 50, 23 and 27% patients had septic shock, severe sepsis and sepsis according to bone criteria. among esbl-pe, 98.6% were carbapenem and 46.5 were blbi sensitive. among the whole population, 47 (48%) patients received a carbapenems as et. 66 (68%) received a dt with carbapenems and 31 (32%) patients received an alternative dt. the most frequent reasons for maintaining carbapenems as dt were: antibiotic susceptibility tests (38% of cases), severity level (33% of cases) immunosuppression (8% of cases). the median length of icu stay after infection was respectively 12 (6-27) and 11 (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) days for carbapenems and alternatives dt (p = 0.1). the d28 mortality was 24% for patients with carbapenems dt and 24% for patients with alternatives dt (p = 0.02). surprisingly, there were no differences between the 2 groups (carbapenems vs alternatives) in term of severity. conclusion alternatives are frequently used for esbl-pe infections in icu. in our cohort 31 (32%) patients received antibiotics other than carbapenems regardless of the severity. introduction bacterial resistance to antibiotics is a common problem worldwide. in south america, this prevalence is reported to be the highest in the world. however, in french guyana, there is no data on the epidemiology of colonization and infection caused by extended spectrum b-lactamase producing enterobacteriaceae (esbl-pe). we conducted this study to investigate the prevalence of colonization with esbl-pe and subsequent icu acquired infection in french guiana. introduction the implementation of hemofiltration (hf) as a renal replacement therapy in septic shock patients requires the supply of large quantities of replacement solutions. these solutions are either industrially prepared in autoclaved expensive plastic bags (conventional hemofiltration, chf) or continuously provided in unlimited amounts at the dialysis machine directly from the water treatment plant to form the replacing solutions (on-line hemofiltration, olhf).the aim of our study was to evaluate the safety and effectiveness of on-line hemofiltration compared to conventional hemofiltration in septic shock patients. the investigative protocol was approved by the institutional ethics authorities and all patients or their legally authorized representatives provided written informed consent. it was a prospective, randomized, clinical study, including septic shock patients with acute renal failure. patients were randomized to receive either on-line hemofiltration (n = 8) or conventional hemofiltration (n = 25) for renal replacement therapy during 4 days. hemodynamic monitoring was conducted by conventional devises, including: electrocardiogram and a radial arterial catheter for invasive arterial pressure every 6 h during period study. we collected serum samples also every 6 h (urea, potassium and sodium levels, troponin, hemoglobin, platelets, c-reactive protein and lactates). results the evolution of heart rate (hr), mean arterial pressure (map), biological markers were comparable between the two groups over time except a significant decrease in map in the olhf group compared to chf group only at h6 (p = 0.008) and h12 (p = 0.015) and a significant decrease in c-reactive protein level in the olhf group at h48 (p = 0.02). conclusion on-line hemofiltration seems to be a safe and reliable method of renal replacement therapy in septic shock patients. it may be associated with attenuated pro-inflammatory cytokine profile (c-reactive protein). none. introduction therapeutic plasma exchange (tpe) is crucial for the management of auto-immune diseases like thrombotic thrombocytopenic purpura or myasthenia gravis. tpe is performed either by centrifugation, with specific machines which are not routinely available in icus, or by using specific plasma separation membranes with widely spread in icus hemofiltration machines. regional citrate anticoagulation for tpe is well established with centrifugation but has been seldom described for membrane tpe. we are reporting the experience of our icu in this field. patients and methods retrospective study including all patients who received tpe with citrate regional anticoagulation between 2013 and 2016 in an 18-bed icu. tpe is performed solely in the icu in our institution. results 26 patients were included. tpe was required for thrombotic microangiopathy (13 patients), vasculitis (6 patients), hyperviscosity syndrome (2 patients), guillain-barré syndrome (2 cases) and others (3 patients) . mean saps2score was 32 [standard deviation (sd) 16.6] . 281 tpe were performed, with a mean number of 10.5 (sd 11.5; range 2-57) tpe per patients. coagulation of the circuit of tpe occurred in 10 (38%) patients. coagulation of the circuit occurred in 10.3% (29/281) of the tpe. minor adverse events have been reported in two patients: one had a rash during the first tpe (no recurrence during the 56 next tpes) and the other had paresthesia during the first two tpes (the calcium infusion was increased and there had been no recurrence during the 25 next tpes). no serious adverse events related to citrate were observed. conclusion regional anticoagulation with citrate allowed us to perform tpe in 26 patients, without significant adverse events. the rate of circuit coagulation was 10.3% per tpe. none. introduction a reduced incidence of membrane thrombosis after injection of anti-thrombin (at) has been reported in septic patients with acquired deficit in at undergoing continuous hemofiltration. as this strategy was routinely performed in our unit until 2012, we investigated its cost-effectiveness. patients and methods data about the use of hemofiltration, the consumption of at and hemofiltration devices during 2011 (period with routine use of at) and 2012 (period with use of at only if a membrane thrombosis occurred) were extracted from the administrative database of the institution. a decisional tree was built to modelize the impact of at on the consumption of hemofiltration devices and blood products. the decisional tree took into account the probability of membrane thrombosis with and without at and the probability of transfusion after membrane thrombosis. costs were obtained from the pharmacy of the institution (at, hemofiltration devices) and from the literature (blood products). results during 2011, 77 days of hemofiltration were performed, with the use of 45 doses of at (23,202€) and 76 hemofiltration devices (11,632€) . during 2012, 76 (−1%) days of hemofiltration were performed, with the use of 5 (−89%) doses of at (2578€) and 85 (+10%) hemofiltration devices (13,443€) . the mean cost of 1 day of hemofiltration decreased from 449€ to 211€ with the diminution of the use of at. according to the decisional tree, at was almost never cost-effective. the only circumstances associated with a benefit for the use of at was the association of a probability of thrombosis with at inferior to 0.1, of a probability of thrombosis without at equal 1, of a probability of transfusion after thrombosis equal 1 and a cost of transfusion of 424€. in these extremely favorable circumstances, at could decrease the daily cost of hemofiltration of 2.22-19.30€. discussion the model has several limits: the losses of utility related to transfusion and to interruption of hemofiltration due to thrombosis were not taken into account; the cost of at measurement was not estimated; the work load of changing a membrane and of transfusion after membrane thrombosis was not analyzed. conclusion our results suggest that anti-thrombin is not costeffective to reduce the costs of hemofiltration related to membrane thrombosis. none. introduction in intensive care unit (icu), some patients suffering from acute kidney injury need renal replacement therapy (rrt). it requires the circuit anticoagulation, this could be done by a regional citrate method. today, this is a recommended approach for the everyday care, even if the technique isn't widespread yet [1] . the ionized calcemia dosing through the filter ("post-filter" ionized-calcemia) is used to monitor the technique efficacy, with a target of 0.25-0.35 mmol/l showing a good filter anticoagulation. the objective of our study was the assessment of efficacy and safety of our regional citrate anticoagulation protocol, with a less restrictive post-filter ionized calcemia target (0.3-0.6 mmol/l). the main goal was the analysis of the circuit lifespan, considering a lifespan above 24 h, as well as the search of some clinical and biological factors affecting the technique efficacy. moreover, we analyzed the side effects incidence of the protocol (hypernatremia, metabolic alcalosis), and their consequences. the study received the scientific ethical agreement of university hospital of toulouse, and is registered with number 18-0214. patients and methods 57 patients, admitted to one of the two university hospital icus of toulouse, needing a continuous rrt method, without any need for systemic heparin anticoagulation, and without severe hepatocellular failure, were included in the study. 103 filters included over a 1-year period were analyzed. results results show a mean filter lifespan of 48 h, with a lifespan above 24 h for 85.4% of all filters. coagulation was the cessation reason for 29.1% of filters, most of them before 24 h of the filter use. a value of post-filter ionized calcemia at day 1 below 0.54 mmol/l was the main factor influencing a filter lifespan above 24 h. an age older than 51 and a saps ii severity score below 80 were other factors conditioning a filter lifespan of more than 24 h. side effects of citrate were rare and didn't have any clinical impact among our patients. discussion these results suggest that citrate used for anticoagulation in rrt could have an additional anti inflammatory effect through the induced hypocalcemia, as well as an energetic gain which could lead to a renal protection against ischemia-reperfusion mechanism [2] . moreover, these results call into question the need of post-filter ionized calcemia dosing for the monitoring of citrate anticoagulation efficacy, since the method safety is monitored by the total-to-ionized calcium ratio. conclusion during continuous rrt in icu, a regional citrate anticoagulation protocol with a non-restrictive post-filter ionized calcemia target seems to be efficient and could reduce side effects. these results need to be confirmed with a randomised control study. introduction continuous veno-venous haemofiltration (cvvh) is used to treat acute kidney injury in critically ill patients. to optimize its efficiency, cvvh requires effective anticoagulation. systemic anticoagulation with standard heparin, the most used, can lead to major bleeding complications. hemofilters that are able to adsorb heparin molecules on their surface such as an69st and oxiris membranes represent an alternative. the objective of this study was to compare these two types of filters in terms of duration, efficiency, dysfunctions and cost. materials and methods from october 2012 to may 2014, we conducted a retrospective, observational, and non-interventional study. all patients admitted in the intensive care unit needing cvvh were included. the primary endpoint was the filter lifespan: an69st versus oxiris. the secondary endpoint was the filter efficiency (urea reduction ratio: urr). the main analysis did not consider the anticoagulation type. we conducted a subgroup analysis taking into account the use or not of an anticoagulation. results 181 sessions in 93 patients were carried out using 386 filters representing 10,706 h of treatment. the mean an69st filter lifespan was 27 ± 20 h and 28 ± 22 h for oxiris filters (p > 0.05). there is no significant difference in terms of duration between the two filters. the subgroup analysis taking into consideration the use or not of anticoagulation did not show any difference either. the mean urr was 48 ± 23% in the an69st group and 44 ± 25% in the oxiris group (p > 0.05). concerning the dysfunctions, there were no significant difference between the two filters. one hundred and seventy-six an69st filters were used for a total cost of 24,288 euros. two hundred and ten oxiris filters were used for a total cost of 39,060 euros. conclusion the an69st and oxiris lifespans are not significantly different. they were as efficient in terms of blood epuration and had as many dysfunctions. the use of an oxiris filter rather than an an69st to extend the circuit's lifespan in the same clinical conditions is not justified considering the extra cost generated. introduction because oliguria is a poor prognostic sign in patients with acute renal failure (arf), diuretics are often used to increase urine output in patients with or at risk of arf. from a pathophysiological point of view there are several reasons to expect that loop diuretics could have a beneficial effect on renal function. however, a review of literature shows that the use of loop diuretics in patients with arf has been associated with inconclusive results despite the theoretical benefits [1] . to assess the adjunctive effect of diuretics, to alter the progression to kidney injury or failure, in patients at risk for acute renal failure. patients and methods this is a retrospective chart review of consecutive patients who developed arf with oliguria in the intensive care unit. chart abstractors were well trained residents. two chart reviewers (senior intensivists) studied all the charts. an explicit protocol was used to precise all needed definitions. uniform handling of data was ensured especially for conflicting, missing or unknown data. oliguria was defined as urine output lower than 0.5 ml/kg/h for at least 3 h. rifle score was assessed before and after urinary output normalisation. therapeutic intervention to optimize pre-renal perfusion was described. mean arterial blood pressure (mbp) before and after therapeutic initiation, oliguria duration, delay from oliguria onset to diuretic administration, delay from diuretic administration to urinary output normalisation were measured. results 23 patients were studied over a 2 years period. 3] h. the delay from diuretic administration to urinary output normalization was 3 [0. 5, 27] h. after resumption of diuresis, rifle score was assessed as (patients without risk, 74%; r, 17%; i, 8%; f, 1% l, zero; e, zero) (fig. 5) . increased serum creatinine level, above 1.5 fold normal range, was observed only in 6 (26%) patients. conclusion rapid optimization of pre-renal hemodynamic disturbances associated with short delay administration of diuretics could significantly alter the progression to kidney injury or failure in at risk acute renal failure icu patients. the ventilator associated pneumonia (vap) is a common and severe complication of assisted ventilation. it's the leading cause of nosocomial infections in intensive care unit and remain responsible for a high morbidity and mortality because of the emergence of multidrug resistant (mdr) bacterial agent such us acinetobacter baumannii (ab). the aim of this study was to determine the incidence, risk factors and prognosis of ab vap. patients and methods retrospective study extending over a 5 year period (january 2010-january 2016) that included all patients over patients were divided into two groups: one consisting of patients who developed vap to ab and the second developed vap to another bacterial pathogen. results one hundred and forty patients developed vap. the incidence rate of ab vap was 15.3% with a density of incidence of 20.3 per 1000 ventilator days. age, male gender, the time between hospitalization and mechanical ventilation and the medical pathology were risk factors for developing ab vap. ab was resistant to ceftazidime in 100%, to imipenem in 65%, tobramycin in 70% and netilmycin in 35.3%, rifampin in 85% with a sensitivity to colistin in 100% of cases. the resistance of this germ to imipenem increased from 35% in 2010 to 88.5% in 2016. the evolution of patients with ab vap developed frequently septic shock compared to other patients (44 vs 19.3%; p = 0.038). the ab vap mortality was higher (50 vs 33%; p = 0.03). conclusion the increasing incidence of multi-drug resistant ab vap is responsible for a high morbidity and mortality. so we need to identify risk factors and to strengthen the means of prevention of hand contamination and cross transmission during invasive procedures. introduction central line associated bloodstream infections (clabsi) are among the serious hospital-acquired infections. the aim of this study is to determine the incidence of clabsi, the pathogens and the risk factors that play a role in the development of bsi among patients followed in a tunisian medical intensive care unit. patients and methods all patients admitted for more than 48 h were included in the study over a 1-year period in an 8-bed medical icu. the enrollment was based on clinical and laboratory diagnosis of bsi. blood samples were collected from catheter hub of all patients for culture, followed by identification and antibiotic sensitivity testing of the isolates. was higher compared with the mean rate of clabsi in icu reported by the nnis system surveillance for 2004, which is 3.9/1000 catheter.days [1] . duration of catheterization, frequent manipulation of catheter, catheter location, catheter type, underlying diseases, suppression of immune system, and types of fluids administered through the catheter are significant risk factors in development of bsis [2] . in our study both duration of catheterization and number of attempts are independent factors for clabsi. conclusion in a monocenter cohort, clabsi had a moderate density rate but are associated with poor outcome. identifying the risk factors is necessary to find solutions for this major health problem. introduction according to some studies, field-intubated patients have 1.5-3 times greater risk of ventilator associated pneumonia (vap). endobronchial intubation (ei) can be unrecognized by the physicians and may result in complications such as atelectasis which in turn could increase the risk of vap. the aim of our study was to confirm this hypothesis. patients and methods this monocentric retrospective study included all consecutive patients >18 years who underwent an out-of-hospital tracheal intubation before their admission to the intensive care unit (icu) between january 2012 and december 2015. exclusion criteria were suspected aspiration or pneumonia on admission, patients who died within the first 5 days of icu stay, extubation in less than 48 h and underlying disease making radiological interpretation difficult for vap diagnosis. vap were divided into early onset (<7 days) and late onset (≥7 days) events and were independently diagnosed by two experienced intensivists who had no access to the initial chest x-ray performed to check the position of the tracheal tube, based on the clinical pulmonary infection score. onset of ventilator associated tracheobronchitis (vat) was also noted. inadvertent endobronchial intubation was determined by another independent physician based on the interpretation of admission chest x-ray. results 397 patients were intubated out-of-hospital. of the 284 patients excluded, 104 had an extubation in less than 48 h, 114 were died within the first 5 days, 22 had a suspicion of pneumonia, 28 a suspicion of aspiration and 8 an underlying disease making radiological interpretation difficult. of the 121 patients included, 28 (23.1%) had an ei upon admission. no significant difference was observed between the ei and non-ei group for gender, age, saps2, comorbidities and diagnostic category (cardiorespiratory arrest, trauma, coma and cardiorespiratory failure). early-onset vap were diagnosed in 43% in the ei group and in 29% of non-ei patients (p = 0.085). adding early onset vat, the respiratory infection rate was 61% in the ei group and 44% in the non-ei group (p = 0.061) (fig. 6 ). late-onset vap were observed in 8.6% in the non-ei group and 7.1% in the ei group, without difference between groups (p = 0.403). there was no inter-group difference in the duration of ventilation, duration of icu stay and icu mortality. staphyloccocus aureus was the most prevalent pathogen in patients with early-onset vap (23.1%, only one strain was methicillin-resistant). conclusion this study found a high rate of inadvertent prehospital endobronchial intubation with a higher incidence of early-onset vap. these results support the implementation of specific procedures to decrease the incidence of ei. introduction ventilator-associated pneumonia (vap) is associated with increased hospital stay and high morbidity and mortality in critically ill patients. the classic dichotomy between early and late onset vap is no longer helpful available. the aims of this study were to determine the incidence of multidrug-resistant pathogens in the first episodes of vap and to assess potential differences in bacterial profiles of subjects with early-onset versus late-onset vap. patients and methods retrospective cohort study over a period of 18 months including all patients who had a first episode of vap confirmed by positive culture. subjects were distributed into 2 groups according to the number of intubation days: early-onset vap (<5 days) or late-onset vap (≥5 days).the primary endpoint was the nature of causative pathogens and their resistance profiles. results sixty patients were included, 29 men and 31 women. the average age was 38 ± 16 years. the igs 2 at admission was 40.5 [32; 44] apache 19 [15; 22] . monomicrobial infections were diagnosed in of 46 patients (77%).two different bacteria were isolated in 14 cases (13%). a. baumannii was the most frequently isolated in 53% (n = 32) of patients; followed by p. aeruginosa in 37% (n = 22), enterobacteriaceae in 28% (n = 17) and s. aureus in 5% (n = 3). the isolated bacteria were multidrug-resistant in most cases (58/60). the vap group comprised 36 episodes (60%) of early-onset vap and 24 episodes (40%) of late-onset vap. a. baumannii was isolated in 47% of early vap (n = 17) versus 62% of late vap (n = 15) (p = ns), p. aeruginosa in 36% of early vap (n = 13) versus 37% of late vap (n = 9) (p = ns) and enterobacteriaceae in 30% of early vap (n = 11) versus 25% of late vap (n = 6) (p = ns). for the resistance profile of the different pathogens isolated, there was no difference between early and late onset vap. conclusion according to new data from the literature, there were no microbiological differences in the prevalence of potential multidrugresistant pathogens or in their resistance profiles associated with early-onset versus late-onset vap. the bacterial nosocomial infection is a major cause of morbidity and mortality in burned. the bacterial ecology in an icu has a major impact in terms of morbidity and mortality, particularly in the center of burned or length of stay of patients is increased compared to a general intensive care. we conducted an observational study spread over 7 months in icu for severe burned burnt including any who have spent more than 48 h with nosocomial infection (modified cdc criteria), and in which all biological and bacteriological samples were taken. the different types of infections studied were: skin, urinary, lung and bloodstream infections. they excluded all patients belatedly supported or having stayed in other healthcare facilities. results one hundred twenty (120) patients showed nosocomial infection during this period. the sex ratio (m/f) was 1.7 and the mean age was 39 ± 23 years. bacteremia was present in 44.84% of cases, followed by the urinary tract infection that was present in 21.21% of cases, followed by the cutaneous infection in 10.30% of cases, and last pulmonary infection in 9% of cases. infection was polymicrobial in 14.5% of cases. the main bacteria identified were: acinetobacter baumanii (43.45%) of which 74% is resistant to imipenem, enterobacteriaceae (31.5%), pseudomonas aeruginosa (24%) of which 83.25% is resistant to ceftazidime and 68.2% is resistant to imipenem, enterococcus (16%) and staphylococcus aureus (14.29%). conclusion the incidence of nosocomial infection is very high compared to literature. the rate of resistance to common antibiotics is very high. a drastic management of antibiotics in our context, the selection of patients and the frequent use in the operating room for skincare allow a better management of these patients. introduction acinetobacter baumannii (ab) ventilator-associated pneumonia (vap) is common in critically ill patients. the aims of this study were to describing the epidemiological characteristics of ab-vap, to identify risk factors for acquisition and factors predictive of a poor outcome. materials and methods a retrospective-prospective study was conducted at the medical intensive care unit of the university hospital ibn sina, rabat-morocco from january 2013 to december 2015. they were included in the study that all patients developed vap with identified germ. for identification of risk factors of acquisition of ab vap, two groups of patients were compared: patients with ab vap versus patients with vap caused by other germs. to identify factors associated with mortality, two other groups were compared: survivors versus died. results 122 patients presented vap among which 60 were caused by acinetobacter baumannii. among isolates of ab, 8.3% were drug susceptible, and 16.7% were multidrug-resistant while 75% were extensively drug-resistant. they were independent risk factors for acquisition of ab vap in multivariate analysis: the presence of a central venous catheter before the occurrence of vap, duration of prior hospitalization ≥4 days and icu duration of stay ≥5 days. the mortality rate of ab vap was 85%. the independent risk factors for poor outcome in multivariate analysis were: duration of antibiotic treatment >7 days, the reintubation and the presence of a previous hospitalization. discussion our data were similar to those of the literature with a high incidence of vap due to the ab (49%) and a high rate of resistance to this bacterium particularly to carbapenems. however, and compared to the literature, the vap ab were responsible for a death rate much higher (85%). conclusion our data were similar to those of the literature with a high incidence of vap due to the ab (49%) and a high rate of resistance to this bacterium particularly to carbapenems. however, and compared to the literature, the vap ab were responsible for a death rate much higher (85%). introduction ventilator-associated pneumonia (vap) is common in critically-ill patients. in fact, 10-20% of patients requiring invasive mechanical ventilation develop this complication. the onset of vap has been reported to be associated with increased mortality. however, data related to critically-ill elderly patients are scarce. the aim of this study is to assess the prognostic impact of vap in critically-ill elderly patients. patients and methods mono-center, retrospective study conducted from 01/012014 to 30/09/2015. all old patients (age ≥65 years) requiring mechanical ventilation were included. two groups were compared: patients who developed vap (vap (+) group) and those who did not develop vap (vap (−) group). results during the study period, 86 patients were included. the causes of admission in the intensive care unit (icu) were shock (n = 30), acute respiratory failure (n = 41) and disturbed level of consciousness (n = 15). diabetes mellitus, hypertension and chronic obstructive pulmonary disease were the most common comorbidities (44.2, 32.6 and 40.7% respectively). mean age was 73.3 ± 6.5 years. sex-ratio (m/f) was 1.8. mean apache(ii) score was 24 ± 9. the mean duration of mechanical ventilation was 10 ± 15 days. thirty patients (34.9%) developed vap. icu-mortality was significantly higher in the vap (+) group (90 vs 55.4%; p = 0.001). multivariate analysis identified two independent factors predicting icu mortality: shock on admission (or = 22.7, ci 95% [5.1-101.2], p < 0.001) and vap (or = 5.7, ci 95% [1.2-28.1], p = 0.033). conclusion vap is common in critically-ill elderly patients and is associated with worse outcome. therefore, preventing its onset is of paramount importance. increased health-care costs. among pathogens responsible of vap, acinetobacter baumannii which is characterized by its ability to spread in the hospital environment and to acquire resistance leading sometimes to therapeutic impasses is associated with a particularly high mortality reaching 30-75%. objective to describe the epidemiological characteristics of a. baumannii vap, to determine their prognosis and identify factors associated with mortality. patients and methods it is a monocentric observational study conducted over a period of 13 years in a tunisian intensive care unit (icu) including mechanical ventilated patients for more than 48 h with confirmed a. baumannii vap. results one hundred and twenty-three patients were included in the study. a. baumannii was responsible for 31% of vap in our icu. the vap were late in 59% of cases. more than 90% of isolates pathogens were resistant to ticarcillin, piperacillin, piperacillintazobactam, ceftazidime and ciprofloxacin. sixty percent of germs were sensitive to imipenem. resistance to imipenem has increased consistently from 0% at the beginning of the study to 88% in 2015. all pathogens were susceptible to colistin. a. baumannii vap was complicated by septic shock in 63% of cases. the median duration of mechanical ventilation and of icu stay were 17 (iqr: [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] and 25 days (iqr: 17-41) respectively. the use of parenteral nutrition was the only factor associated with the occurrence of a. baumannii vap resistant to imipenem (odds ratio 2.27, 95% ci [1.07-4.80], p = 0.033). icu mortality was 45%. it was higher in patients with a. baumannii vap resistant to imipenem (55 vs 39%, p > 0.05). in the multivariate analysis, the age, the use of renal replacement therapy and the occurrence of vap relapse have been identified as factors associated with mortality. conclusion a. baumannii resistance to imipenem became threatening. the use of parenteral nutrition was the only factor associated with the occurrence of a. baumannii vap resistant to imipenem. the choice of empiric antimicrobial for vap caused by this pathogen must take in consideration the epidemiologic data of each country and each icu. a. baumannii vap was associated with high mortality. the age, the use of renal replacement therapy and the occurrence of vap relapse have been identified as predictive of poor outcome. none. admission in intensive care unit for severe adverse drug event: what finding? julien arcizet 1 , bertrand leroy 1 , caroline abdulmalack 2 , catherine renzullo 1 , maël hamet 2 , jean-marc doise 2 , jérôme coutet 1 introduction adverse drug events (ade) remain a serious public health problem. they represent between 0.16 and 15.7% of hospital admissions and between 0.37 and 27.4% of intensive care unit (icu) admissions. they are defined as any injury related to a drug, and include both adverse drug reactions, expected or not, but also underuse, overuse and misuse, unintended or undesired, preventable or not. indeed, mortality from iatrogenic event would rise between 2.0 and 28.1%, whereas these ade that resulted in icu hospitalization could be prevented in 17.5-85.7% of cases. these unplanned admissions overload icu, limit access to health care for other patients and have serious economic consequences for the health system. it is therefore necessary to study these ade to know their main causes and attempt to find a solution to avoid them. the main objectives of our study were to clinically and pharmaceutically analyze and stratify the different ade leading to hospitalization in our icu. this is a monocentric prospective study, between june 2014 to january 2016, in medico-surgery icu. from all admissions, we had included patients admitted in our hospital for involuntary ade (plausible, likely and very likely causal). we had collected clinical aspects (failure mode, igsii score, mortality in icu) and pharmaceutical aspect (number of drug, offending drugs) at daily medical staff meeting. conclusion hospitalizations in icu for ade are still too common despite their preventability for most cases. many patients with known cognitive disorder manage their treatment themselves and this is probably one of the reasons of iatrogenic events. anticoagulants and antiplatelet agents, by side effects, misuse, underuse or overuse are very often involved. the onset of kidney failure from dehydration and the continuation of nephrotoxic and antidiabetic treatment also remain one of the most common causes. consequently, it is necessary to continue and develop primary, secondary and tertiary prevention strategies to prevent their appearance, to limit their consequences and to reduce recidivism. introduction intensive care unit (icu) is usually identified as a place of acute care, concentrated over a short period. for many reasons, a prolonged stay in the icu has a pejorative connotation for the intensivist physician. the aim of our study is to describe the epidemiological, clinical, paraclinical profile of patients hospitalized for a long time in icu (over 15 days) and to identify the main prognostic factors and those that can predict the duration of stay in icu. we conducted a retrospective study, over a period of 5 years and 6 months (january 2010 to june 2015), enrolling patients whose length of stay was greater than or equal to 15 introduction despite an improvement in prognosis of patients with hematologic malignancies for the last decade, mortality of such patients admitted to the intensive care unit (icu) remains high. yet, it seems that a first icu stay does not modify prognosis of the malignancy. until now, there is no data on readmission in the icu of such patients and its effect on short and long term prognosis impact. patients and methods this retrospective, single-center study conducted on a 5 years period in the medical icu from our university hospital included 265 patients with hematological malignancies admitted for a first stay. objectives were to evaluate the icu, day 28 and 6 months mortality, to identify prognostic factors associated with mortality within uni-and multivariate analysis, to evaluate readmission rate within the 60 days after discharge, to indentify the admission risk factors associated with icu readmission and the prognosis factors associated with mortality during the second icu stay. multivariate analysis poor performance status, igs ii, hlh, mv and anti-fungal administration were associated with increased icu mortality, infections with pseudomonas were associated with higher day 28 mortality. catheter related infections were associated with better icu survival and cr was associated with lower day 28 mortality. 38 of 132 (28.9%) candidate patients for icu readmission after a first stay were readmitted within the 60 days following discharge. median overall survival was lower in readmitted versus non readmitted patients. 6 months mortality was 73.8% for readmitted versus 13.8% for no readmitted patients (p < 0.0001). the second icu stay mortality was 60.5% and 6 month mortality was 78.9%. by multivariate analysis, only mv was associated with prognosis. the 6 months mortality rate of patients who survived to the second icu stay was significantly higher than the patients who survived to the first admission but were not readmitted (46.7 vs 13.8%, p = 0.0007). conclusion main features, short and long term mortality and prognostic factors associated with icu admission are in lines with previous studies. early readmission rate was high with a negative impact on survival. despite admission in the icu of patients with hematologic malignancies seems not to affect long term prognosis, early readmission seems to have a pejorative impact on the course of the malignancy. introduction lung cancer is among all types of cancer, the most common solid tumour admitted in intensive care [1] . recent studies showed that the prognosis of patients with lung cancer during intensive care unit (icu) stay has improved [2] . the aim of our study was to determine the causes of icu admission of lung cancer patients, their prognosis and to identify factors predicting hospital mortality and survival after hospital discharge. in fact, temporary full-code icu management in patients with relapsed aml seems to be appropriate. none of the life-sustaining interventions at admission and on day 3 were able to predict survival. an icu trial of 3 days might not be enough to appraise precisely the outcome. bone marrow transplant was associated with a high mortality in our study. in case of relapsed aml with bmt, icu management is still challenging. the growing population of chronically critically-ill patients has a poor prognosis despite all the resources mobilised [1] . our primary objective was to analyse the prognostic value of different definitions used to describe them. our secondary objective was to look for early clinical and biological factors that could be associated with the in-hospital mortality. we conducted an epidemiological prospective study in 3 intensive care units (neurosurgical, cardiosurgical and medical) of a large french teaching hospital (henri mondor, créteil). we included all the patients hospitalized for at least 7 days. we tested 5 definitions: the prolonged mechanical ventilation, the definition taken up by kahn et al. [2] , the prolonged length of stay, the persistent critical illness and the persistent inflammation-immunosuppression and catabolism syndrome. two biological examinations were performed: upon entering the study and 1 week later. the study endpoint was the in-hospital mortality. results thirty patients were included between april and july 2016. among them, only 40% matched the definition of prolonged mechanical ventilation, which is still the most used in the literature. further, it was not associated with the mortality, but the prolonged length of stay was, with 59% of these patients, that did not survive to their hospital stay. other parameters that were significantly different between the patients who died and those who survived were an advanced age, an elevated igs ii score at hospital admission, an elevated sofa score at study entry, a late healthcare-associated infection and several biological variables: a high c reactive protein, low albumin and prealbumin and a poor percent of monocytes expressing hla-dr, all measured at day 7. conclusion the in-hospital mortality of chronically critically-ill is still high. a prolonged length of stay is the only definition who may be helpful to identify the patients with the poorest outcome. among the early factors associated with mortality, we found a late healthcareassociated infection and a low percent of monocytes expressing hla-dr, pointing to the value of studying the immune system of these patients. introduction as a result of demographic transition, the proportion of «very elderly» (≥90 years) patients is increasing worldwide and more of these patients are nowadays admitted to intensive care units (icu). among physicians the discussion about appropriateness of these icu admissions still remains controversial mostly due to questionable outcome, limited resources and costs. the aim of the study was to determine and evaluate the clinical characteristics and outcome in a very old population admitted to a medical icu in an urban teaching hospital. we present here a monocentric, retrospective and observational study. we reviewed the charts of all patients (≥90 years) admitted to a medical icu between 2000 and 2015 (16 years). we collected epidemiological, clinical and biological parameters and all therapeutic measures during the icu stay. a longterm survival follow-up was also performed. two hundred eighty-four patients were included for statistical analysis. multivariate cox regression was also performed to identify risk factors for 28-day outcome. results a total of 284 patients were included, which represented 1.8% of admissions to the icu during the period of the study. the mean age was 92.6 ± 2.1 years, the sex ratio was 0.41. most of patients (41%) were admitted from the emergency department. 20% of these admitted patients suffered of previous dementia. the mean charlson comorbidity score was 7.7 ± 1.7 and the mean mccabe score was 1.33 ± 0.5. the admission diagnosis in the icu was mainly respiratory distress (51%), septic shock (11%), cardiac arrest (10%) and coma (8%). the mean saps-ii score within 24 h of icu admission was 55.9 ± 21.7. half of these patients required support by mechanical ventilation (mean duration 7.3 days) and vasoactive drugs and 6% of patients received renal replacement. icu and in-hospital mortality rates were 38 and 44% respectively. overall survival at 6 months after hospital discharge was 33%. multivariate regression revealed necessity of catecholamines and mechanical ventilation as independent risk factors and urinary sepsis as protective factor for 28-day outcome. in fine, for 34% of these patients, a limitation of active treatment was decided (on average after 2 days of stay). for all others there was no justification for limiting care because of a well-established treatment plan (with family, gp, icu team). conclusion the proportion of elderly patients remains low, but they are increasingly being treated in intensive care units. nevertheless, the in-hospital mortality is high compared to the average mortality in our icu over the same period (20%). the prognosis is often not as poor as initially perceived by physicians. the indication for icu treatment in our study was mostly justified; in the setting of consistent patient care and good clinical practice. it remains therefore appropriate to discuss every single icu admission of elderly patients without any restriction related to age. thus, the ongoing cluster-randomized trial of icu admissions for the elderly patients (ice-cub 2 study) is deeply awaited to confirm or not these results [1] . keywords intensive care; prognosis; outcome; elderly patients; over 90-years old. introduction regardless of the route of delivery, the postpartum hemorrhage (pph) is defined as blood loss ≥500 ml after childbirth, and severe pph as blood loss ≥1000 ml. pph is the leading cause of maternal mortality in africa. the aim of this prospective study was to assess the quality of the initial management of pph in algeria in oran ehu and to determine the factors of care with the severity of this complication. we conducted a prospective cohort study between april 2014 and september 2014 at the ehu oran. all women who delivered vaginally and showed hpp including the suspected cause was uterine atony were included. the severe pph was defined as bleeding that required invasive surgical treatment (hysterectomy, arterial ligation), a transfusion, a transfer to an intensive care unit or death of the patient. the quality of care was evaluated using objective criteria defined by a delay of diagnosis and care and mortality. results among the 466 women who delivered vaginally during the study period, 23 had a pph, link with uterine atony alleged at diagnosis, 18 of which presented signs of severity. in 41% of cases, the delay in diagnosis of pph was less than 30 min; 70% of women received oxytocin within 10 min after diagnosis. the tranexanique acid was used in 1 case. the examination of the cervix, uterine exploration and uterine massage was performed in 67, 99 and 97%, respectively. the failure of first line treatment involved 24% of patients. among them, the time between the diagnosis of pph and administration of blood derivatives was greater than 1 h in a third of cases. the administration of oxytocin delay exceeds 10 min multiplied by 2.5 the risk of severe pph. however we had 2 deaths in our series. discussion in our study the optimal period of care was not adequate, obtaining blood derivatives in our institution remains among the factors aggravating among the main risk factors for pph, uterine atony was the main source of complication. bleeding postpartum aggravated in our two patients has led to the deaths from late diagnosis and care that was not optimal. these hemorrhages pp is the leading cause of mortality: 21% of obstetric deaths (25% in the confidential survey 1996-1997) [1] . a hysterectomy was indicated after failure to conservative treatment. the death rate is estimated at 8% following a disorder complicated hemostasis of disseminated intravascular coagulation (dic). in some series, the mortality rate is estimated between 2 and 4% [2] . conclusion the management of pph in obstetrics gynecology service the ehu oran was not optimal. the issue of timing of diagnosis and initial treatment is crucial. solutions must be sought locally to ensure the administration of essential medicines in time, especially the injection of oxytocin within 10 min after diagnosis. introduction chronic obstructive pulmonary disease (copd) is a common pathology that would represent the third cause of death worldwide by 2020. its evolution is interspersed with episodes of acute exacerbations (aecopd) that may indicate an admission in intensive care unit in the most. objective to study the evolution of management modalities of patients admitted in our intensive care unit for aecopd, to determine their prognosis and to identify factors associated with mortality. patients and methods it is a retrospective, monocentric study, performed in a tunisian intensive care unit (icu) over a period of 10 years. we including all patients admitted in icu for aecopd. parameters collected were demographic features, comorbidities, regular treatment, dyspnea assessed by the mrc scale, initial clinical severity reflected by saps ii and apache ii scores, modalities and icu admission deadlines, initial arterial blood gas analysis, management of patients in the icu (ventilation modalities, prescription of antibiotics, use of vasoactive drugs) and their outcomes (incidence of nosocomial infections and their sites, length of stay and icu mortality). results a total of 512 patients, which represents 17.5% of all hospitalizations, with mean age of 72 years (iqr: 66-77) were admitted for aecopd during the study period. the mean saps ii and apache ii were respectively 32 (iqr: 24-45) and 18 (iqr: 14-24). of these, 60% were ventilated with niv whose overall failure rate was 48% with a significant decrease between the beginning and the end of the study (94 vs 31% p = 0.001). sixty-four percent of patients received antibiotics at admission. the prescription rate of antibiotics has decreased significantly over the years from 82 to 36%. the incidence of nosocomial infections was 18%. it remained steady between 11 and 27%. their sites were pulmonary in 83% of cases. icu mortality was 16%. in multivariate analysis, icu admission deadlines, niv failure and the use of vasoactive drugs were identified as factors associated with mortality. conclusion our study showed the importance of aecopd in the activity of our icu. the management of these patients has evolved over the years, which was reflected by the significant decrease in the prescription of antibiotics and the enhancement of niv success rate. this result could be attributed to the combination of several factors: precocious management of patients, experience of the healthcare team and the use of efficient ventilators. icu admission deadlines, niv failure and the use of vasoactive drugs were identified as factors associated with mortality. introduction aim. investigate the effect of music therapy on the tolerance of non-invasive ventilation (niv) during its introduction. currently, 50% of the trauma are intubated. thirty-three percent of the patient admitted in intensive care suffers from acute respiratory distress syndrome (ards). the fmhs chose oxygen concentrator as oxygen source in addition to oxygen pressurized bottles. their supply can be uncertain in conflict areas. insufficient data are available concerning the use of oxygen concentrator in intensive care unit. the primary endpoint was to determine over the total duration of oxygen therapy, the number of days on which the use of pressurized oxygen was needed for patients oxygenated by oxygen concentrator. the secondary endpoints were to identify when pressurized oxygen was needed, describe the characteristics of the population with oxygen therapy and estimate the oxygen quantity economised thanks to the use of oxygen concentrator. the study took place in the forward surgical unit of bouffard. it's a french role 3 located in djibouti republic in africa. all patients over 15 admitted in the intensive care and needing oxygen therapy were included. all the patients were oxygenated with an oxygen concentrator. the oxygen concentrators used were sequaltm integra 10 om, that could deliver up to 10 l/min of normobaric oxygen. the ventilator used were pulmonetictm ltv 1000 and 1200. results thirty-six patients were included over the 6 months' study period. sixty percent of the patients were men with an average age of 38 two hundred and fifty-one days represents the total number of days of oxygen therapy divided into 142 days of invasive ventilation, 15 days of noninvasive ventilation and 94 days of oxygen mask. the use of pressurized oxygen was necessary 19 times over the 251 days of oxygen therapy which represents 7.5% of the total time. the causes of its use were in ten cases (52.6%) criteria of severe ards, in six cases an emergency intubation and in three cases a transfer. one dysfunction of an oxygen concentrator happened during our study. the oxygen concentrator produced 1024 m3 of oxygen over the study period, which represents 104 oxygen pressurized bottles of 50 litres. this enabled an economy of 10,000 euros. conclusion it is safe to use oxygen concentrator to take care of critically ill patients in limited resources environment. the use of pressurized oxygen is still compulsory in two situations: in case of electricity failure and in case of high fio 2 (above 60%). oxygen concentrators are sufficient in 92.5% of the time. they enable to deliver oxygen any time which is essential when supply is uncertain in conflict areas. none. table 4 ). for the same mv and level of ofr, fdo2 was in our experiment, with an ofr of 5l/min, when ifr = 18 l/min (mv = 6 l/min and ti/ttot = 0.33), the fdo2 is equal to 41% (±1%) (see table 5 ). to this value of ifr, the fdo2 is in accordance with the formula of ats, but when ifr increase beyond 18 l/min, the fdo2 decrease and the formula is not in accordance with ats. this can be explain because during inspiratory phase, air room (fractional oxygen = 0.21) entry in airway mixes with ofr (fo2 = 1), which modifies the fdo2. in this case, when ifr increase then fdo2 decrease and vice versa. medical and paramedical staff must be aware that with patients who receive ofr by nasal cannula, any change of ofr and/or inspiratory flow changes the fdo2. in this case, for maintain the same fdo2, it is necessary that modify the value of ofr. the actual fio 2 delivered under oxygen mask in patients with acute respiratory failure and the factors that may influence the fio 2 are poorly known. in clinical practice, different methods including formula or conversion tables based on oxygen flow can be used to estimate delivered fio 2 . we aimed to assess first the factors influencing measured values of fio 2 , and second the best method to estimate fio 2 in patients breathing under oxygen mask. we included icu patients admitted for acute hypoxemic respiratory failure from a previous prospective trial [1] in whom fio 2 was measured under oxygen mask using a portable oxygen analyzer. we collected demographic variables and respiratory parameters that may influence measured fio 2 . low fio 2 was defined according to the median measured fio 2 . for each patient, measured fio 2 was compared to "calc + 3%" formula (fio 2 = oxygen flow in liters per minute × 0.03 + 0.21) to "calc + 4%" formula (fio 2 = oxygen flow in liters per minute × 0.04 + 0.21), and to a conversion table [2] . a ± 10% limit of agreement for each estimation method was arbitrarily considered acceptable. results among the 265 patients included, median measured fio 2 was 65% [60-73]. after adjustment on oxygen flow, the three variables independently associated with low measured fio 2 using multivariate analysis were patient's height, a low paco 2 , and a respiratory rate greater than 30 breaths/min. using paired analysis, each estimation methods differed significantly from measured fio 2 (p < 0.0001 for each). values outside the limits introduction acute hyperglycemia is common in intensive care. it was associated with poor prognosis and increased mortality. the purpose of our study is to investigate the frequency of hyperglycemia in our icu, to determine the main causes of high blood sugar and to analyze the impact of this hyperglycemia. our study is prospective during 3 months. it was conducted in the intensive care unit of the university hospital habib bourguiba sfax-tunisia. were included in our study all patients admitted to the service during the period of the study. for each patient included were collected from the icu admission, clinical and biological data. results during the study period, 194 patients were hospitalized in our icu and the diagnosis of hyperglycemia (>8 mmol/l) was admitted in 93 patients (48%). the comparison between patients who developed hyperglycemia and those free hyperglycemia group showed that, the patients of the first group were significantly older (p < 0.001). additionally, hyperglycemic patients had more medical history including history of diabetes (p < 0.001), a higher saps ii (p < 0.05), a more significant frequency of active infections (p < 0.05). moreover, the presence of hyperglycemia was associated with shock (p < 0.05) and respiratory distress (p < 0.05). their evolution was marked by the significantly higher frequency of infectious complications (p < 0.05), thromboembolic complications (p < 0.05) and acute renal failure (p < 0.05). the average duration of mechanical ventilation and the length of stay were also significantly prolonged in hyperglycemia group patients (p < 0.05 for both). finally, the presence of hyperglycemia was significantly associated with a higher mortality rate. conclusion we concluded that hyperglycemia is correlated with poor prognosis of morbidity and mortality. but strict glycemic control remain controversial. thus, further studies on this subject will be recommended to define the exact place of glycemic control in intensive care. none. the rrt was prophylactic in four cases started when phophatemia was more than 2 mmol/l, and therapeutic for renal failure and established tls in three cases. the median duration stay in icu was 5 [4] [5] [6] [7] j. thirteen patients left the icu without major metabolic dysfunction. two patients deceased due to infectious complications. discussion monitoring of electrolytes was done on average, three times a day which is hard to do in onco-hematology unit. the early use of rasburicase and the aggressive iv hydration helped to prevent tls for seven patients. the aggressive iv hydration was made according to echocardiography data and close monitoring of vital signs and urine output which has allowed to avoid volume overload and acute pulmonary edema. the early prophylactic rrt prevented renal failure and metabolic complications. conclusion early management of tls in icu can prevent tls and most of its serious complications and should be considered in tls prophylaxis recommendations. none. the both urinary (expressed as the ratio of ngal on urinary creatinine) and plasma ngal were predictive of aki stage 1. predictive value of plasmatic measurements was higher than the urinary one (auc of 0.627 and 0.758, respectively, p = 0.0273 between auc), but not higher than either baseline serum creatinine (auc = 0.737) or 24 h diuresis (auc = 0.735). backward multivariate regression showed that plasma ngal concentration was associated with serum creatinine, crp and albumin, whereas urinary ngal was associated with leucocyturia and baseline creatinine. discussion previous positive studies with ngal did not compare the performance of this costly biomarker with simple usual clinical parameters to predict aki. moreover, several parameters were associated with ngal concentrations with a high risk of collinearity (crp) and/or false positive results (leucocyturia). our data do not support any added value of ngal concentration over baseline serum creatinine or urine output to predict aki. introduction acute renal failure (arf) is a common entity in intensive care, concern that the heavy morbidity and mortality it is associated [1] . early diagnosis of this entity remains difficult, neither diuresis and creatinine are early parameters in the diagnosis of arf. the kidney is an organ that suffers long to become faulty, the priority is to recognize renal aggression and to achieve a therapeutic allowing reversibility of the infringement. a number of markers have been developed for the diagnosis of the ira but costs remain high not allowing their routine use. the measurement of resistance index with the renal doppler could be a solution for the diagnosis of aggression and also of the etiology. the elevation of creatinine was seen later within 48 h after the ir >90. discussion in our series the resistance index has a value of early diagnosis of renal prognosis aggression in the occurrence and development of renal failure. renal doppler associated with a strictly applied standardized protocol achieves the two goals of monitoring who aid in the diagnosis and guide treatment. although the recommendations of experts to this tool provides that it should probably not use the resistance index measured by renal doppler to diagnose or treat an ira (grade 2) [2] . identifying the cause of kidney aggression is a prerequisite before any therapeutic action. hypovolemia and soda hydro overload are the causes principales. excess filling hyper intra thoracic pressure and hypoxia are the main causes of kidney congestion. conclusion doppler is an early renal medium in the diagnosis of renal aggression. a larger series could assert this observation. none. ), had significantly more pre-eclampsia, 4/5 (80%) versus 7/33 (21%) p = 0.0187. pe were started at an average of 1.6 days after foetal extraction, and with an average of 5 sessions. patients of the pe group had significantly lower nadir of hemoglobin but also lower hemoglobin level at day 2 and day 5. nadir of platelets count was also lower and level remain lower at days 1, 2, 3 and 5. acute kidney injury (using kdigo classification) was more frequent with a higher rate of dialysis in icu, in the pe group (4/5 (80%) vs 3/33 (9%) p = 0.0022) with a more frequent need for dialysis at the exit of icu. proteinuria was significantly higher in the pe group (862.8 mg/mmol vs 308.41 mg/mmol, p = 0.0134). adamts13 dosage was done only in patients with pe. we find a diminution of adamts13 activity (before pe) with an average of 53% [40-70] in this group. there was no death, and adverse effects were not significantly different. discussion this study shows that pe was used when diagnosis was uncertain in the most severe form of pp-tma. low hemoglobin, low platelets, acute kidney injury and high level of proteinuria are the main factors associated with the decision to begin pe. this technique was safe and not associated with major adverse events. several studies show that there are physiopathological crossovers between diseases associated with pp-tma, for example low adamts13 activity in hellp or mutation in alternative complement pathway which induced hellp. moreover, studies and case reports show a benefit of pe in hellp syndrome. our study did not find significant difference in adverse events (maybe due to a lack of power), but this is another argument to discuss pe in the management of pp-tma in severe patients. the main limits of our study are that none of the patients who had a plasmatic exchange had a diagnosis of ptt and that diagnosis tests were not performed in all patients with pp-tma (complements level, adamts13…). conclusion pp-tma treated with pe has lower hemoglobin, lower platelets, higher rate of kidney injury and proteinuria than those treated without pe. no difference were found for adverse events. begining of pe should be discussed for management of a pp-tma without amelioration after foetal extraction. none. introduction diffuse alveolar damage (dad) is the typical histological feature of acute respiratory distress syndrome (ards). however, in a previous study including 356 patients with criteria for ards, we found that only 45% of them had dad at autopsy exanimation [1] . it has been shown that patients with ards and dad on open lung biopsy had higher mortality than those without dad [2] . thus, we aimed to identify markers associated with dad in patients with ards. we included the 356 patients who met criteria for ards at time of death in our large database of clinical autopsies [1] . we assessed the proportion of dad according to the severity of ards including the degree of hypoxemia and the 4 ancillary variables from the berlin definition: use of high levels of positive endexpiratory pressure (peep at least 10 cmh 2 o), radiographic severity (3 or 4 quadrants on chest radiograph), altered respiratory system compliance (≤40 ml/cmh 2 o), and large dead space defined as a corrected expired volume per minute (≥10 l/min). results dad was associated with all the severity markers abovementioned using univariate analysis. after multivariable logistic regression, the three markers independently associated with presence of dad were the gender with an odds ratio ( conclusion dad was significantly more frequent in females. in addition to the severity of hypoxemia, diffuse infiltrates involving the 4 quadrants was a significant marker of dad. introduction ventilation induced lung injury (vili) is responsible for an increased mortality in ards [1] . mechanical ventilation may trigger an inflammatory response, comprising alveolar macrophage activation and recruitment, which may be specifically, repeatedly and spatially assessed by functional imaging techniques such as positron emission tomography combined with computerized tomography (pet/ct) [2] . 11c-pk11195 is a pet radiotracer with potential to quantify macrophage inflammation. we aim to assess its performance to detect lung macrophage recruitment in an experimental highvolume vili model. materials and methods vili was performed in 5 anesthetized pigs under neuromuscular blockade by rapidly increasing the tidal volume (vt) to obtain a transpulmonary pressure (tpp) between 35 and 40 cmh 2 o under zero end-expiratory pressure. pet/ct acquisitions were performed before (t1) and after 4 h of high-volume ventilation (t2), and image-derived measurements were realized on the whole lungs, and regionally on 6 distinct lung regions (divided along the anteroposterior and the cephalocaudal axes). 11c-pk11195lung uptake was estimated using the standardized uptake value (suv), normalized to the ct-derived tissue fraction in the region of interest (roi). mechanical lung aggression was estimated by ct-derived dynamic and static strains, and tidal alveolar hyperinflation (expressed as a fraction of the tidal variation in the roi volume). after euthanasia, alveolar damage and macrophage recruitment were assessed in the 6 lung regions, using semi-quantitative scores. results between t1and t2, vt and tpp significantly increased from 6.0 ± 0.1 to 49.4 ± 2.9 ml/kg and 8.6 ± 1.5 to 37.8 ± 4.4 cmh 2 o, respectively. suv on the whole lung significantly increased from 1.8 ± 0.6 to 3.0 ± 0.5 between t1and t2 and dynamic strain from 0.36 ± 0 to 2.1 ± 0.2, whereas static strain did not significantly vary. tidal alveolar hyperinflation significantly increased from 18 ± 4 to 68 ± 3% on the whole lung between t1 and t2. regionally, dynamic strain, and tidal alveolar hyperinflation significantly differed between regions, as well as between t1 and t2. regional suv differed between t1 and t2 but not between regions. regional static strain did not differ between regions, nor between t1 and t2. in multivariate analysis, regional suv was independently and significantly associated with dynamic strain and tidal alveolar hyperinflation. histologic analysis showed significant regional differences in alveolar damage but not in macrophage recruitment. suv was positively associated with macrophage recruitment but not with alveolar damage. discussion in this experimental vili model, 11c-pk11195 suv was significantly increased after 4 h of injurious ventilation, and was significantly and positively associated with high-volume ct-derived mechanical parameters, such as dynamic strain and tidal alveolar hyperinflation. the radiotracer's specificity for macrophages is confirmed by the suv significant association with macrophage recruitment and the lack of association with alveolar inflammatory edema. conclusion 11c-pk11195is a macrophage-specific pet radiotracer, with potential to dynamically and specifically assess alveolar macrophage inflammation induced by high-volume ventilation. research founded by the french society of intensive care medicine (srlf) and la fondation pour la recherche médicale (dea20140630499). the reverse triggering (rt) is the term used to name the contractions reflexes of the muscle diaphragmatic provoked ("triggered") by the periodic insufflations, delivered by the ventilator, at sedated patients under mechanical ventilation [1] . the rt constitutes a new form of patient-ventilator interaction clinically difficult to detect and little known. the rt could have potential implications during the management of acute respiratory distress syndrome (ards). at present, the management of severe ards consists among others, on the use of an early and systematic perfusion of neuromuscular blockade agents (nmba) during a 48 h' period, continuation to the acurasys essay which showed a reduction of the mortality in the group of the severe ards patient receiving nmba. the reason of the beneficial effect of curare is not perfectly known. it is possible that the phenomenon of rt is a mechanism implied in the deleterious role of the mechanical ventilation during ards. the abolition of this phenomenon by nmba could explain the beneficial effect of nmba in ards [2] . the objective was to look for the phenomenon of rt in two groups of ards patients: a group receiving nmba and a group not receiving nmba. patients and methods physiological observational and comparative study in intensive care units. we record continuous signals of airflow, airway pressure, and esophageal pressure during 24 h of consecutives patients with ards criteria and pao 2 /fio 2 ratio ≤150 at a positive end-expiratory pressure (peep) of 5 cmh 2 o evolving for less than 48 h under mechanical ventilation. recording of esophageal pressure of 21 consecutives moderate to severe ards patients were blinded analyzed (group nmba n = 11; group unless nmba n = 10). any phenomenon of rt was observed in the group of mild ards patients receiving nmba (fig. 8a) . we confirmed the existence of rt on 3 patients of 10 in the group of mild ards who not receiving nmba (p = 0.05) (fig 8b) . discussion one of the main limits was the quality of the collection of the signal of esophageal pressure. the monitoring of esophageal pressure is technically difficult, and can d influence the quality of the signal and the reliability of the results. conclusion this study confirms the existence of the phenomenon of reverse triggering among deeply sedated patients not receiving nmba with a 30% incidence. more research is needed to determine if the reverse triggering is a risk factor independent from vili, associated with the bad prognosis of severe sdra patients and, if a strategy of early treatment based on nmba, could improve the prognosis of reached patients. after ecmo removal had a significant median reduction of 3 days in the bipap-aprv group, p = 0.03 (fig. 9 ). we reported the feasibility of a protocol based on bipap-aprv aiming at resuming sv as soon as possible in ards patients under ecmo. the occurrence of spontaneous inspiratory efforts in ards patients can major variability of transpulmonary pressure and as result jeopardise vt and driving pressure control. this might be an issue if protective ventilation is not guaranteed anymore. vt with bipap-aprv remains within safe range when the ratio fig. 9 circles are pac group, rhombus are aprv group. mv mechanical ventilation, psv pressure support ventilation. data are presented as median (iqr), comparison between the 2 groups at each time mann-whithney test, *p < 0.05 of spontaneous minute ventilation to total minute ventilation is between 30 and 40% [1] . bipap-aprv is more efficient than psv to increase lung aeration in patients with ards [1] . recruitment of dependent region is more likely to achieve if sv is not supported by synchronized positive airway pressure as during bipap-aprv [2] . our strategy targeting a percentage of sv between 30 and 40% with high peep could be viewed as a compromise in order to promote sv and protective ventilation at the same time. conclusion protective ventilation combined with sv under ecmo by using a specific protocol based on bipap-aprv is feasible and safe. it may facilitate weaning and thus reduce the time under mv after ecmo. to what extend this beneficial effect is directly due to the presence of sv deserve further investigations. introduction since the first transplant from a patient in a state of brain death conducted in 2010 at the university teaching hospital ibn rushd of casablanca, the number of transplants has increased. however, it is still inadequate meet the growing needs of organs. the refusal of families remains the main obstacle to the developpement of organ transplantation in morocco. the aim of our study is to monitor and analyse the evolution of family refusal to organ donation in a brain dead patient. patients and methods this is a retrospective and comparative study from august until december 2014.the data were collected from records of brain dead patients candidates for organ donation at the 7 intensive care units on ibn rushed hospital. the coordination registers were also studied. a questionnaire was distributed to families who refused organ donation to investigate the causes of the refusal. results during this period, 79 patients with brain death have been identified and 78 families had been approached. 61 families (78%) refused organ donation. the main causes of refusal were: fear of body mutilation (35%), lack of will (24%) and religious causes in 28% of cases. the refusal rate for families decreased from 85% in 2010 to 50% in 2014. only 2 patients experienced cardiac arrest before transplantation. during this period, 22 cornea transplants from braindead patient were conducted with 20 kidney transplants and two liver transplants. discussion the evolution of the refusal of families saw a decline through awareness and communication campaigns for organ donation. conclusion improvements to our health care system must be proposed including strengthening detection of potential donors and relationships with the donor's family and effective communication policy. in the icu, three major actors are involved in the caring relationship: patient, relatives and caregivers. acting as spontaneous testimonials of the lived experience, thank-you letters from relatives may be considered by icu teams as a source of original information which could help in improving care for critically ill patients and families. this study aimed to investigate the qualitative content of thank-you letters from relatives of patients who stayed in the icu. specifically, our research questions were, with regards to the letters' content, (1) how is the caring relationship tackled and characterized by relatives? (2) to what extent does this relationship impact their experience of icu? materials and methods the study took place in a 16-beds icu during a 6-month period. the research team consisted in a care assistant, a nurse (also clinical research associate), a psychologist (not working in the icu) and an intensivist. the corpus consisted in twenty thankyou letters received in the icu. we conducted a qualitative study according to the thematic inductive approach. the process of coding was intended to create established meaningful patterns. results two main themes emerged as specific determinants of the caring relationship: (1) the temporality, comprising the time dedicated to the patients and their family, the time spent with the icu team, the striking time corresponding to significant events for relatives needed to be shared with the staff, the extension of the link with caregivers by evocating a new life after icu stay, the writing time as a countergift to the caregivers; (2) the caregivers behaviour, including human skills detailed in many core values (kindness, availability, devotion, attention, goodwill, sensitivity) psychological support, emotional sharing, capabilities to give informations. relatives feel to be "at the center of all attention" in the same way as their loved ones. through the narration of icu experience, the caring relationship is characterized as follows: (1) the caregiver becomes a close person with an equal relationship (feelings of friendship, emotional closeness); (2) the icu team becomes a new family (contrasting with the poor living environment of icus); (3) the relative becomes a caregiver (with appropriation of medical terms or speaking of his loved one as a patient); (4) the caregiver is seen as a "super-hero" through an asymmetrical relationship with an overstatement of personal dedication and investment of the staff members (abnegation, vocation, involvement). the caring relationship impacts relatives' experience of intensive care in several ways: (1) relatives are deeply touched by caregivers' human behavior, emotional support being a source of solace and resilience in particular for bereaved families; (2) relatives express the idea that taking care of humans is not a valued and rewarded task and the emerging awareness of hospital realities and difficulties of work in the icu; (3) the most striking transformational change in relatives is the perception of their own vulnerability and humanity, leading them to exhibit an outward-looking attitude (for example filling out their organ-donation card), and encouraging the icu caregivers to continue their missions for the others. conclusion thank-you letters provide both encouraging and informative messages for icu teams about relational care for patients and families notably the indivisibility of the families and their critically ill loved ones. the relatives' experience of the icu appears strongly influenced by the caring relationship in the way they express an authentic revelation of their own humanity and altruistic thoughts. the thematic content of thank-you letters questions determinants and fundamental values at stake in the patient-relatives-caregivers relationship. introduction far from medical paternalism, the doctor-patient relationship has now evolved to respect "the autonomy and patients' rights". changing behavior has been gradual, while the law offered the patient the freedom to consent to care and then of expressing their wishes regarding the therapeutic intensity they would benefit, in critical situations where consent would not be possible, through advance directives (ad) [1] . their use is of paramount interest for intensivist in many critical situations. unfortunately, the use of ad remains marginal because of the unfamiliarity of patients with their use and an appropriation default by clinicians [2] . the aim of our study was to investigate the perspective of the coming family physician generation on advances directives. patients and methods population of interest was general practitioner fellow (gpf) from class of 2012 to 2014. we built an online questionnaire survey about knowledge and the place they want to give to ad in their forthcoming daily clinical activity. this questionnaire was sent to gpf emails obtained by universities, unions and via the official mailing lists of different regionals classes provided by the first contacted. descriptive analysis of quantitative data was expressed as mean and standard deviation, qualitative data in number and percentage. the comparison of continuous variables was performed by the student t-test and the comparison of categorical variables by a chi2 test. analyzes were conducted on biostatgv website and microsoft excel ® . results 2310 gpf answered the survey, mainly from ile de france (n = 218), toulouse (n = 199) and lille (n = 169). for gpf the majority of patients do not know the ad (81.6%) and 54% think that those who know do not know how to use it. 88.4% of gpf think writing ad by patients requires better information. according to them, the information should concern the support offered in the icu (77.1%), the use of mechanical ventilation (58.7%), dialysis (48.2%) and the evolution of patients after hospitalization in icu (50.6%). nevertheless information on the prognosis of chronic diseases or organ failure seems interesting for only 37 and 20.7% of them respectively. 89.8% of gpf wish to propose the drafting of ad to their patients. however, only 60.1% of them are willing to suggest ad to patients with cancer or hematologic malignancies, 56.2% to patients with neurological and/or degenerative disorders, 20.5% to elderly patients. discussion despite the low proportion of the population we think these observations to be of interest because we probably selected the gpf the most interested in ad as the participation was not mandatory. conclusion a large majority of young of future general practitioner is willing to be involved in the implementation of ad with their patients, however the target population remains very limited, considering that half of them do not want to discuss ad with patients suffering from diseases potentially associated with icu admission or therapeutic intensity discussion. this study was conducted in adult intensive care units in public or private hospitals in four countries: canada, france, italy, spain. in each country, 40 health care professionals were solicited for an exploratory interview about the sources of stress in the work environment: 10 senior physicians, 10 residents, 10 experienced nurses (with more than 2 years of experience in the service) and 10 inexperienced nurses (with less than 2 years of experience in the service). all the interview transcripts were analysed using an inductive coding approach. results one hundred and sixty professionals (80 physicians and 80 nurses) were included in the study. eight themes emerged from the analysis, and they concerned the stress linked to (1) patient (2) care, (3) team, (4) family, (5) institutional context, (6) environment, (7) organizational context, (8) individual dimensions. in each theme, sub-themes have been identified and determine more precisely the difficulties at work. discussion our findings emphasize the complexity of work in icus and show the specifics factors not taken into account in the generic stress scales such as stress in relation with family relationships, the end of life decisions and inequity of health care. conclusion the specific stress scale should allow to better identified stress in icu and to develop measures of prevention and support and training programs. introduction intensive care units (icu) is a place where caregivers face many constraints that can affect their physical and mental health due to the use of specific care and strong emotional charge related to patient death and pain of the families. the aim of the present study is to detect anxiety disorders and/or depression among staff working in icus. on september 2016, a questionnaire was distributed to staff (medical and paramedical) operating in 5 icus in the university hospital fattouma bourguiba monastir, tunisia (1 medical icu, 1 surgical icu, 2 cardiologic ccus and 1 nephrologic intermediate care unit). this questionnaire included demographic data of participants (age, sex, marital status, length of service, psychiatric history, consumption of anxiolytic and/or antidepressant) and the hospital anxiety and depression scale (had: scale composed by 14 items to screen the anxiety (a) and/or depression (d) among hospital staff ). results during the study period, 106 participants completed the questionnaire (82%), 58% of them were women, the median age was 32 years ± 8.4. forty-nine participants were doctors (the majority of them residents: 41/49). 12.3% of participants (all paramedics) worked on night shift, seniority of more than a year in the icu was found in 59% of participants. 53.8% of staff interviewed were married and only 14.2% of them reported consumption of anxiolytics and/or antidepressants. 65.9 and 63.2% of the participants had respectively symptoms suggesting anxiety and depression. the median had score was 19 (iqr = 8); the medical function seems to be significantly associated with the occurrence of symptoms of anxiety and depression compared to paramedics, however the type of icu (medical/surgical icus vs cordiologic/nephrologic icus) does not appear to be related to the occurrence of symptoms of anxiety or depression (table 7) . conclusion anxiety and depression are common symptoms among caregivers in icus. improved conditions of work in these units should be a target to avoid burn out syndrome. none. anxiety, n (%) depression, n (%) introduction carbon monoxide (co) poisoning is one of the common causes of poisoning specially in the cold season, which leads to a significant morbidity and mortality. we retrospectively reviewed the medical data of patients who presented to the toxicology emergency department with co poisoning during january 2015 to march 2016. we analyzed patients' characteristics, management, and outcomes. results a total of six hundred and sixty-six patients (523 female and 143 male), aged of 34 ± 14 years, were included; poisoning occurred between december and february in 75% of cases, secondary to an indoor heating system exposure in the majority of cases (89%). the estimated duration of exposure was 2.5 ± 2 h [0.5-13 h], with a mean carboxyhaemoglobin (cohb) level on arrival at 18.6 ± 17%. neurological changes were the most presenting symptoms including headache (n = 652, 98%), dizziness (n = 272, 40%), seizure (n = 15, 2.3%) and loss of consciousness (n = 81, 12.2%). digestive disorders involving vomiting and nausea were observed in 32.1% (n = 214). one woman without cardiovascular risk factors developed non stsegment elevation myocardial infarction complicated by lung edema. the majority of patients (n = 601, 90%) received normobaric oxygen during 6 h (n = 535) and 12 h (n = 66). hyperbaric oxygen therapy was administered at 2.5 ata during 1 h to 65 patients for neurological changes (n = 24), pregnancy (n = 22) and elevated cohb ≥ 25% (n = 19). mechanical ventilation was required for 5 patients, and admission into intensive care unit in 39 patients (6%). death occurred in 5 cases (0.7%). conclusion the carbon monoxide poisoning is a common reason for emergency department visits in winter. the physician should be aware of the serious neurological and cardiovascular complications, if symptomatic treatment and oxygen therapy regimens were not respected. none. neuro-respiratory toxicity of baclofen in the rat: study of the concentrations/effects relationships and role of gabaergic introduction baclofen, a gaba-b receptor agonist is used as muscle relaxant agent and recently for the treatment of alcohol dependence. the number of poisonings has significantly increased since this new indication. clinical presentation of poisoning mainly includes sedation, hypotonia, respiratory depression and seizures. to characterize the neurorespiratory toxicity of this molecule at high doses, we aimed at investigating alterations in sprague-dawley rat ventilation and brain electrical activity after baclofen administration and studied their reversal by gaba-receptor antagonists. materials and methods rat ventilation was investigated using plethysmography and arterial blood gas analysis while brain electrical activity was studied using eeg with one implanted frontal electrode. three baclofen doses were used including 43.5 mg/kg (30% lethal dose-50%), 72.5 mg/kg (50%) and 116 mg/kg (80%). baclofen concentrations were obtained using hplc-msms assay. we modeled baclofen pharmacokinetics and analyzed the doses/effects and effects/concentrations relationships. results baclofen induced early-onset and prolonged dosedependent sedation (p = 0.0002), hypothermia (p = 0.004), eeg and respiratory depression (0.001) characterized by significant increase in the inspiratory (p = 0.0001) and expiratory times (p = 0.02). significant increase in paco 2 and decrease in arterial ph and pao 2 were observed at 116 mg/kg (p = 0.001), peaking at 240 min. eeg showed signal slowing, burst-suppression aspects and spikes peaking at 5-6 h post-injection without normalization at the end of the experiment at 24 h. we did reverse baclofen-induced decrease in tidal volume with saclofen (a gaba-b receptor antagonist) and interestingly no alteration of baclofen-induced respiratory depression was observed with flumazenil (a gaba-a receptor antagonist). pharmacokinetic parameters of baclofen were obtained at the three doses and were dose-dependent. significant but non-linear relationships were observed between baclofen-induced effects and concentrations. conclusion baclofen causes dose-dependent neurorespiratory toxicity in rats. however, due to increased poisonings, its safety profile at high doses remains to be established in humans. none. poisoning was deliberate in 100% of cases. mean ingested dose was 448.5 ± 349 mg. the majority of patients presented to the emergency room at 4.8 ± 5 h after ingestion. digestive decontamination was performed in 9.6% (n = 2) of patients. clinical presentation was dominated by neurological symptoms; including coma (n = 15), hypotonia (n = 5), hyporeflexia (n = 5), agitation (n = 5), seizures (n = 3) and delirium in 1 case. hemodynamic manifestations included bradycardia in 12 patients, three of them required atropine infusion. one patient presented with hypotension responding to vascular resuscitation. sixteen cases required mechanical ventilation. aspiration pneumonia was noted in 6 cases. mean duration of ventilation was 36.6 h ± 27. mean hospital length of stay was 62 h ± 25. complications included ventilation associated pneumonia in one case and moderate rhabdomyolysis in 3 cases. all patients evolved favorably. there is no correlation between coma and assumed ingested dose. conclusion baclofen overdose causes mainly neurological effects and except for bradycardia cardiovascular effects were uncommon. prognosis is good if full supportive care is administered properly. none. introduction the lack of an effective treatment for the maintenance of abstinence from alcohol has led physicians to take an interest in baclofen. beyond efficacy, safety of baclofen, prescribed in high doses, is a concern, especially in case of drug overdose. indeed, patients with chronic alcohol abuse frequently develop psychiatric disorders, and are at risk of voluntary drug intoxications. thus, we set up a retrospective study to describe morbidity and mortality associated with baclofen overdose. conclusion baclofen, prescribed in high doses, may lead to severe intoxications: self-poisonings frequently require endotracheal intubation and are associated with an increased risk of death. dialysis decreases baclofen elimination half-time but clinical relevance of this difference could not be determined. none. introduction baclofen, a gaba-b receptor-agonist with muscle relaxant properties established since 1974, has been recently used at elevated doses to treat dependence to ethanol. the number of prescriptions has exponentially increased without an exact evaluation of its toxicity. we aimed to describe acute baclofen poisoning requiring intensive care unit (icu) admission and study the relationships between the toxic encephalopathy and the plasma baclofen concentration. we conducted a single-centre retrospective study including all baclofen-poisoned patients admitted to the icu in 2013-2016. when requested by the clinical situation, repeated electroencephalograms and measurements of the plasma baclofen concentrations were performed. toxic eeg encephalopathy on a scale of zero to five was graded according to the international rating system (markand, 1984). plasma baclofen concentration was determined using liquid chromatography coupled to mass spectrometry in tandem developed with a quantum ultra apparatus (thermo fisher scientific) and electrospray source ionization in positive mode (limit of quantification: 5 ng/ml). linear regression and chi-2 or mann-whitney tests were used as requested for subgroup comparisons. baclofen pharmacokinetics and the relationships between the toxic encephalopathy and the plasma baclofen concentration were modeled using winnonlin software v. 5 ) were closed to the observed values reported at therapeutic doses. the relationship between baclofeninduced encephalopathy as a function of the baclofen concentrations was described using a sigmoidal emax model. conclusion baclofen poisoning may be life-threatening. toxic encephalopathy is well-described with eeg and its grade correlated to the baclofen concentration. prescribers should be aware of the dangers of baclofen which benefits to treat dependence to alcohol are still lacking. none. results initial examination suggested that an illness other than bacterial meningitis was the cause of patients' complaints. first hypothesis was meningitis receiving uncomplete dosage regimen of antibiotics. thereafter owing to apparent loss of consciousness with abnormal eyes movements, non-tonico-clonic seizures were considered meanwhile. the ratio of individuals less 5 y-o to those equal to and greater was 33/67%. the male to female ratio was 46/53%. the mean duration of hospitalisation was 3.4 ± 0.8 days (extremes 1-10 days). extrapyramidal syndrome predominant on the upper part of the body was noted by paediatrician neurologists who suggested considering a genetic disease. however, signs and symptoms were present in people from different families in different areas at the same time. the definitive diagnosis made on pictures and videos of children and adults and was facio-troncular dystonia resulting from drug-induced adverse effect. four urine samples were collected in children and sent to a toxicological laboratory in france. all urine samples were positive for haloperidol meanwhile the other causes of facio-troncular dystonia were excluded, including other neuroleptics, metoclopramide, antidepressants, amodiaquine, anti-histaminic drugs, anti-epileptics, and cocaine. from january to august 2015, 1021 hospitalisations were recorded in 925 patients. looking for the source of haloperidol showed that tablets sold as 'diazepam' and consumed by symptomatic patients contained haloperidol as the sole active pharmaceutical ingredient, suggesting that this large outbreak was due to haloperidol toxicity from falsified diazepam. initial treatment was diazepam to relieve severe facio-troncular dystonia which was efficient but resulted in long-lasting sedation more especially in children. a dosage regimen using bipéridène administered by intravenous and oral route was refined to prevent adverse effects related to this anticholinergic agent used in children. the complete reversal of the facio-troncular dystonia was the antidotal evidence supporting the toxicological diagnostic. the mortality rate was less than 5% meanwhile the direct causal relationship with adr is questionable. an epidemiological study, including toxicological analysis in controls in ongoing. indeed, facio-troncular dystonia induced by haloperidol does not result from a drug overdose but is an adr occurring in about 20% of patients treated with haloperidol. who is involved in the inquiry related to this counterfeature involving different countries. the cause of the error is presently under investigation. discussion this outbreak emphasizes the need to consider toxicity resulting from counterfeatured medicines when facing collective atypical signs and symptoms in countries with unrestricted access to medication with limited control of qualities of the medicinal drugs. conclusion counterfeatured medicinal drug may result not only in poor efficacy but also in onset of unexpected outbreak of unknown diseases that should suggest a toxic origin. in late 2014-early 2015, médecins sans frontières (msf) had to face an outbreak of severe facio-troncular dystonic syndrome (ftds) in north-east congo. this outbreak resulted from counterfeature of pills sold as diazepam. toxicological analysis revealed one pill contained about 10 mg of haloperidol. ftds induced by haloperidol does not result from a drug overdose but is an adverse drug reaction (adr) occurring in about 20% of patients treated with haloperidol. nine-hundred and twenty-five individuals were admitted in msf structures for 1021 ftds. the ratio of individuals less than 5 y-o and equal to or greater of age was 33/67%, including 35 (3.4%) of children less than 1 y-o. initial treatment was based on diazepam which relieved ftds but resulted in long-lasting sedation, preventing given any drug by the oral route. owing to the definitive diagnosis, a shift to the use of a more specific antidote was chosen. biperiden was selected as existing in the intravenous and oral form in the swiss pharmacopea. the study was approved by the ethical committee of the ministery of health of the republic democratic du congo. patients and methods as a whole, biperiden was used in 223 cases (84% of the total). treated children presented with severe dystonia as evidenced by inability to cooperate and to swallow. verbal informed consent was obtained from relatives. the dosage regimen to treat drug-induced dystonic syndrome in the swiss pharmacopea is as follows: for parenteral use in children, intravenously or intramuscularly: 0.040 mg/kg or 1.2 mg/m 2 bsa every 30, according to response and tolerance; a maximum of four doses per day should be used. the internal msf recommendations for biperiden use in children were 0.01-0.05 mg/kg of body weight that might be repeated four times a day. initially, biperiden administration was administered under medical supervision by the msf referent at the scene. results there was no pediatric preparation of biperiden. accordingly, the adult preparation was used in children. the preparation contained 5 mg of biperiden in one milliter of solvent. the initial planned dose for children of 1 y-o and less and those up to 5 y-o were 1 and 2 mg, respectively. the 5 mg (1 ml) of biperiden was diluted in 4 ml of saline resulting in a final dilution of 1 mg/ml. six children were treated according this dosage regimen. however, the one 1 mg dose was either of limited efficacy while being associated in others of signs suggestive of adr, including agitation, heart rate greater than 160 b/ min, the upper limit for children aged of 1 y-o and less. two children greater than 1 y-o presented severe abnormal behavior resulting in an attempt at escape. owing to question about safety, the dosage regimen was changed, as follows: 5 mg (1 ml) of biperiden was diluted with 9 ml of saline resulting in a final dilution of 0.5 mg/ml. an initial dose of 0.5 mg was administered intravenously as a bolus dose. the effects were looked for over 15 min. in the absence of improvement in facial dystonia, a second bolus dose of 0.5 mg was administered, a third dose could be considered 15 min later if the ftds did not resume. the cumulative initial dose should not be greater than 2 mg. in addition to the reversal of facial dystonia, the therapeutic effect of biperiden included the return of swallowing to normal allowing to give further doses of biperiden by the oral route for three days. the first oral dose was administered no less than 12 h after the last initial dose at a dose equal to the efficient initial cumulative dose. the following doses were halved every 12 h. no adr related to biperiden were reported using this dosage regimen. the mean duration of hospitalisation was 3.4 ± 0.8 days. discussion the bioavailability of biperiden by the oral route is equal to 33%. accordingly, the corresponding intravenous dose should be divided by a factor three. dosage regimen of anticholinergic drugs in children are poorly documented. the dosage regimen recommended by the pharmacopea resulted in frequent and severe adr. titration of biperiden resulted in efficient and safe dosage. conclusion when biperiden administration is required by intravenous route in children of 5 y-o and less, biperiden should be administered intravenously and titred using bolus dose of 0.5 mg till the therapeutic effect is obtained. introduction severe poisoning by rodenticides is frequent. it represents nearly 30% of patients admitted to the new intensive care unit (icu) of the region. that is why we decided to perform this study. the aim of this work was to describe the epidemiology, clinical features and management of all patients admitted to our unit for acute poisoning with rodenticides. patients and methods it was a retrospective study performed in the year 2013 from january to december. the study included all patients admitted in the icu for rodenticide poisoning. results 32 patients were enrolled in the study. our patients were young with a mean age of 30 ± 2 years. poisoning was more common in females (n = 24; 75%). the mean delay between rodenticide poisoning and first medical contact was about 2 ± 2 h in the cases where this information. most of our patients (91%) attended the emergency department of zaghouan with a non-medical transportation. it was a suicide attempt in most cases (62%) and an accidental poisoning in 32% of patients. the most frequent cause of poisoning in our study was organophosphorus pesticide (n = 24; 75%). the second cause was alpha-chloralose poisoning with seven cases (22%). one patient ingested accidentally an anticoagulant rodenticide. most of patients had ingested (oral route) the rat poison (n = 23; 78%). clinical examination found normal vital signs in ten cases (31%). nine patients (28%) had a shock, eight patients (25%) had an acute metabolic disorder and five patients (16%) had acute respiratory failure or were comatose. all patients enrolled in the study were admitted in the icu for a period of clinical observation of 24 h. stomach pumping (gastric lavage) was performed in 30 patients (93%). an antidote which was atropine was needed in twelve patients. three patients (9%) who ingested alpha-chloralose needed intubation and mechanical ventilation. all patients had a good outcome and were discharged from icu and from hospital. the mean icu length of stay was 2 ± 3 days. conclusion this is the first study of acute poisoning with rodenticides admitted in the new icu. the results of our study were similar to those published in recent literature. cases of acute poisoning with rodenticides reported in this work were not severe. none. introduction the systemic arterial load imposed to the left ventricle (lv) is a major determinant of normal/abnormal cardiovascular function. the lv mean ejection pressure (lvmep) is the best estimate of load faced by the lv throughout ejection. the contribution of the steady and pulsatile blood pressure (bp) component of arterial load to lvmep is debated. we studied the hemodynamic correlates of lvmep using carotid tonometry. intensive care unit patients equipped with an indwelling catheter were studied, thus allowing precise calibration of the tonometer. patients and methods carotid tonometry (complior analyse ® alam medical, france) was prospectively performed on 28 hemodynamically stable, spontaneously breathing patients (12f, mean age ± sd = 64 ± 18 years). carotid waveforms were calibrated from diastolic bp and time-averaged mean bp invasively obtained at the radial (n = 18) and femoral (n = 10) artery. all patients were free of aortic stenosis. lvmep was the area under the systolic part of the carotid pressure waveform divided by ejection time. results lvmep (111 ± 17 mmhg) was strongly related to central systolic bp (126 ± 21 mmhg; r 2 = 0.97) and was also related to mean bp (r 2 = 0.82), peripheral systolic bp (r 2 = 0.83), peripheral (r 2 = 0.35) and central (r 2 = 0.50) pulse pressure (each p < 0.05). the lvemp was not related to age, heart rate and stroke volume. systolic pulse wave amplification ratio from carotid to periphery was 1.07 ± 0.08. conclusion lvmep was most strongly related to central systolic bp, which combines the influences of the steady and pulsatile components of central arterial load (r 2 = 0.97). lvmep was less strongly related to peripheral systolic bp, which may be less informative given variable systolic pulse wave amplification across patients. introduction myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. many pathological findings were found in the sepsis induced cardiomyopathy including myocardial ischemia, alterations in microcirculation and proinflammatory cytokines. the aim of this study was to assess the prognostic value of a recently developed highly sensitive cardiac troponin i (hstni) assay in patients with septic shock. we performed a prospective observational study in septic shock icu patients within 72 h of admission. exclusion criteria were age >18 years; pregnancy; post-cardiac arrest and braindead. hstni was measured soon after admission and 12, 24, 48 and 72 h after. patients were subjected to transthoracic echocardiography (tte) at study inclusion and regular biochemical and hemodynamic assessments were performed. pearson's chi square and fisher's exact tests were used. p < 0.05 was considered significant. conclusion circulating hs-ctni is present in patients with septic shock. a rise of hstni may be an indicator of poor outcome. also, right heart functional abnormalities exist in patients with septic shock. none. evolution of the right distribution width as a pronostic marker during the differents state of shock introduction right distribution width (rdw) has been recently proposed as a pronostic factor in different pathologic situations and especially to the septic patients who stay in icu. some works substantiate the relationship between an alteration of the red blood cell rheology during the septic shock and a severe state of the disease. no one has studied the rdw between the differents shocks yet. we are going to determinate the relationship between rdw and apache ii score, mortality rate in the intensive care unit (icu), at the hospital, at the day 30 and 90. we investigated those parameters near 228 patients who were admitted at the icu and needed norepinephrine between the first of march and the 31st of december. they were stratified in différent groups: septic shock n = 101, cardiogenic shock n = 100, hemorragic shock n = 20 and obstructive shock n = 7. results we did not observe any correlation between the rdw and the icu mortality, hospital mortality and at the day 30 and 90. only a poor significant correlation has been found between the cardiogenic shock and the mortality rate: at the hospital (p = 0.01), at day 30 (p = 0.01) and at the day 90 (p = 0.05) but not in the icu (p = 0.89). the receiver operating characteristics (roc) curves do not show significant differences between rdw, apache ii score and icu mortality rate or intra hospital. the sample of the hemorrhagic shock and obstructive shock was not usable for this calculation. compared to other studies which were focused on the septic shock where the mortality was approximately 20%, we determinated a mortality rate near 50%. conclusion the delta of the rdw d3/d1 did not present any correlation with the mortality rate. in our study, the rdw in the different kind of shocks do not look like to be a good predictive marker of the mortality, except for the patients included in the cardiogenic shock where a poor significant correlation could be highlighted. conclusion cardiogenic shock was the most frequent complication of ami who led to icu admission, whereas mechanical complications are rare at the era of early coronary reperfusion strategies. in addition to severity score, serum creatinine and cardiogenic shock appeared as independent factors of hospital death. none. introduction pulmonary embolism (pe) in high-risk is a partial or total obliteration of the pulmonary arterial network by a fibrin-clot cruoric more than 50%, the management requires a rapid reduction of pulmonary arterial resistance and right ventricular post load through rapid revascularization by thrombolysis. our aim is to determine the value of thrombolysis in pulmonary embolism and describe the clinical, paraclinical and outcome pulmonary embolism at high risk. patients and methods this is a descriptive study of 20 cases of pulmonary embolism at high risk admitted to the cardiology department to chu oran between 2008 and 2014. signs of gravity of (pe) comprising: syncope, circulatory collapse, cardiogenic shock or acute pulmonary sonographic sign of heart. it was confirmed in chest ct. all patients received thrombolysis using the protocol accelerated by two types of molecules: streptokinase or actilyse. the sex ratio was 0.11; mean age 44 years, ranging from 20 to 80 years; risk factors were dominated by contraception was 35% and the postoperative 30% the clinical picture was dominated by cardiogenic shock in 75% of cases. 20% cardiovascular collapse and syncope in 5%; doppler echo all patients had signs of dysfunction of the right ventricle represented by the dilatation of the right cavities and pulmonary hypertension. the cta found a (pe) bilateral in 70% right in 20%. thrombolysis using actilyse in 12 patients and streptokinase in 8 cases. the outcome was favorable in 16 patients; with two cases that are complicated by chronic pulmonary heart and the death of 2 patients with cancer. discussion the female predominance is explained by the increase of risk factors hormonal contraception, whose first generation combination hormonal. our patient had a high probability with clinical signs of severity based on the score wells [1] . this diagnosis was confirmed by chest ct; which shows the vascular bed obstruction degree with a very good sensitivity and specificity. the suspect patients with severe pe and that presented signs of acute pulmonary heart ultrasound have effectively (pe). the indication of thrombolysis was chosen on hemodynamic criteria; success is found in 80% of patients with improved hemodynamics dice the early hours. this success is explained by the role of thrombolytic in lysis clot to obtain pulmonary arterial revascularization; and reduce pulmonary arterial resistance and the right ventricular afterload which accelerates the healing of right heart failure and improvement of pulmonary capillary volume. the 02 cases who developed a chronic pulmonary heart; it was done immediately a right ventricular dysfunction with pulmonary arterial outset of very high pressures suggestive that the embolism occurred on an already pathological right heart. no cases of massive bleeding were noted in our series. conclusion severe pulmonary embolism is burdened with high mortality; diagnosis is based on the stratification of risk score, was facilitated by the non-invasive strategies that articlent around the doppler echocardiography and ct angiography; thrombolysis can reduce the high mortality related to severe pulmonary embolism. introduction hypertension is a frequent motif for admission to emergencies. the diabetic is increasingly exposed to this risk [1] . the objective of this study is to evaluate the proportion of diabetic patients presenting to the emergency department with high blood pressure (bp) and to identify their epidemiological and clinical characteristics. introduction sepsis associated liver dysfunction (sld) is usually attributed to systemic and/or microcirculatory disturbance. hypoxic hepatitis, also known as shock liver or ischemic hepatitis, is a life threatening event associated with high morbidity and mortality. doppler ultrasonography is a non invasive method to measure doppler hepatic hemodynamic parameters. the primary objective of this study was to assess the accuracy of the hepatic hemodynamic parameters (portal venous blood flow pvbf and resistance index of the hepatic artery hari) in predicting sld in septic shock patients. the secondary aims were to identify factors associated with sld, investigate the effects of volume expansion (ve) on systemic and intrahepatic hemodynamics and to assess the intra-and interoperator reproducibility. we also analyzed 28-day mortality. in a prospective design, we included 30 consecutive patients with septic shock (24 males; median age: 36.5 years) admitted to the icu with septic shock in charles nicolle hospital of tunis from february to july 2015. all patients were resuscitated following the surviving sepsis campaign guidelines. we measured systemic hemodynamic variables (mean arterial pressure (map), and cardiac index (ci)) and performed hepatic doppler before and after volume expansion. we measured pvbf and computed the hari. we recorded the liver function tests (alt, ast and bilirubin) for 48 h. sld was defined as an increase in serum bilirubin ≥ 20 µmol/l (hepatic sofa ≥ 1). accuracy of the hepatic hemodynamic parameters to predict sld was measured by the area under the roc curve. p < 0.05 was taken to indicate statistical significance. the median sofa score at t0 was 8 points and the median igs2 score was 38 points. the sources of infection were as follows: the lungs (n = 19), the abdomen (n = 4) and the urinary tract (n = 3). the incidence of sld in our cohort was 33.3% (n = 10). there was no significant difference between "sld group" and "no-sld group" in all hepatic hemodynamic parameters especially the pvbf and the hari. lactate levels were significantly higher in patients with sld (median 3.55 vs. 0.85 mmol/l). similarly, the platelet count was significantly lower in the "sld group" [mean (± sd) 149.2 ± 103.9 (109/l) vs. 242.8 ± 104.1 (109/l); p = 0.039]. there was no difference in duration of mechanical ventilation, icu length of stay and 28-day mortality between the 2 groups. the pvbf was significantly lower in patients who died before d28 (median: 558 vs. 826 l/min in the survivors; p = 0.014). volume expansion caused a significant increase in ci, mean hepatic artery velocity and the pvbf. the intra-and interoperator reproducibility was good to excellent for the systolic and mean velocities of the hepatic artery, portal vein diameter and the pvbf. conclusion our results don't support the hypothesis that the hepatic sonography is predictive of sld in septic shock. our pilot study showed higher lactate levels and hematologic sofa in sld group. the pvbf was significantly lower in patients who died before d28. more experience will be necessary to define the ultimate role of doppler ultrasonography in the evaluation of hepatic perfusion in patients with septic shock. introduction early surgery is the current trend for management of patients with valvular disease. that said many of them, particularly from developing countries, are still operated at a very advanced stage of disease. despite improvements in myocardial protection and surgical techniques, postoperative care after multiple valve surgery (mvs) for advanced rheumatic heart disease (rhd) remains to be a clinical challenge. we conducted a study to determine postoperative complications and morbidity-mortality risk factors in this subgroup of patients. results sixty-two patients were included: 25 with out-of-hospital refractory cardiac arrest and 37 with in-hospital refractory arrest. the initial rhythms was shockable rhythm in 25 (40%) cases. at ecls initiation, the mean no flow was 0.8 ± 3.9 min and mean low flow (time between the time of refractory cardiac arrest and time at which an ecls flow was provided) was 71 ± 37 min. the mean ecls flow rate was 4.17 ± 1.31 l/min. initial blood test results were: arterial ph = 7.04 ± 0.20 and plasma lactate = 12.8 ± 5.9 mmol/l. eleven (18%) patients survived (4/30 (13%) acute coronary syndrome, 4/8 (50%) severe poisoning due to drug intoxication, 1/4 (25%) dilated cardiomyopathy, and 2/20 (10%) others). survival was lower for patients with out-of-hospital refractory cardiac arrest, 2 of 25 (8%), than for patients with in-hospital refractory cardiac arrest, 9 of 37 (24%), respectively, p = 0.17. as expected, out-of-hospital refractory cardiac arrest was associated with a more prolonged low flow (89 ± 40 min vs 60 ± 30 min, p < 0.01) and a more profound acidosis (ph 6.9 ± 0.2 vs 7.1 ± 0.2, p = 0.01 and arterial lactate 14.7 ± 6.1 vs 11 ± 5, p = 0.05). in univariate analysis, survival was lower for patient with refractory cardiac arrest unrelated to drug intoxication, 13 vs 50%, respectively, p = 0.03. in addition, mortality was associated with arterial ph (7.01 ± 0.2 vs 7.14 ± 0.15, p = 0.025) and low flow (75 ± 40 vs 55 ± 12 min, p = 0.005 conclusion in a highly selected group of critically ill patients with refractory cardiac arrest, the potential beneficial effect of ecls could be due only to its clinical impact on reversible causes of circulatory failure (i.e. severe drug intoxication in our cohort). further studies are needed to clarify whether the use of ecls could be considered as a disproportionate tool, specifically in patients with out-of-hospital refractory cardiac arrest due to acute coronary syndrome or associated with prolonged low flow or a profound acidosis. none. post-cardiac arrest shock treated with veno-arterial extracorporeal membrane oxygenation: an observational study and propensity-score analysis wulfran bougouin 1 , nadia aissaoui 2 , alain combes 3 average time between introduction and removed of the ecd was 50 h (42-56). among the 16 esogastroduodenoscopy performed, 9 (56%) were strictly normal. endoscopy showed minor gastric injuries in 6 patients (38%). within these patients, 3 (19%) also presented minor esophageal injuries. esogastric injuries characteristics were mostly similar to usual orogastric probe injuries. one patient (6%) experienced a serious ulcerous esophagitis mimicking a peptic esophagitis, not firmly related to the ecd. no patients necessitated hemostatic local procedure and no significant gastrointestinal bleeding was observed. eight patients (47%) were alive at d90, including 5 patients (29%) with a cerebral performance category score of 1. this compares favorably to outcomes from previous studies. conclusion ecd seems an interesting and safe semi-invasive method of cooling in ohca patients treated with 33 °c-ttm. although it seems slower than more invasive devices to reach 33 °c, ecd was able to strictly maintained the tt within the maintenance phase of ttm. further studies will be necessary to define the exact place of this new device within the cooling strategy in patients necessitating a precise ttm-strategy. none. fig. 10 see text for description introduction since post-cardiac arrest care might influence the outcome, characteristics of receiving hospitals should be integrated in survival evaluation of patients transported in hospital. we aimed at assessing the influence of care level center on survival at discharge in a regional registry of out-of-hospital cardiac arrest (ohca). we prospectively collected utstein and in-hospital data for all non-traumatic ohca patients, in whom a successful return of spontaneous circulation (rosc) had been obtained, from a large metropolitan area (great paris). receiving hospitals were categorized in 3 groups (a, b, c) depending on their respective characteristics (annual volumes, 24/7 catheterization availability and temperature management use). we compared patients' characteristics in the 3 groups and performed a multivariable logistic regression using discharge survival at endpoint. results during the study period (may2011-dec2013), 1476 patients were admitted in 48 hospitals (917 in group a, 428 in group b and 91 in group c). overall survival rate at discharge was 433/1436 (30%). patients' baseline characteristics significantly differed, as hospitals from group a treated younger patients and more frequent shockable rhythms (p < 0.001). unadjusted survival rate differed significantly among the 3 groups of hospitals (respectively 34, 25 and 15.4% for a, b, c, p < 0.01). however in multivariable analysis, the category of hospital was no longer associated with survival. conclusion in this population-based study, characteristics of receiving hospitals are not associated with survival rate at discharge. this could result from the strategy used for triage, which aims in matching patients' characteristics and resources. introduction acute kidney injury (aki) commonly occurs after cardiac arrest and is associated with an increased mortality and a delayed awaking. early recognition of aki remains challenging, given that serum creatinine increases belatedly after aggression. introduction out-of-hospital cardiac arrests (ohca) are an absolute urgency and have a very poor prognosis. pediatric guidelines differ from adult guidelines for cardiac arrest management. since 2005, adult guidelines apply from the onset of puberty. the main objective was to describe the epidemiological characteristics and outcome of ohca victims while taking puberty into account. the secondary objective was to determine the prognostic factors for survival at d30. materials and methods all patients less than 65 years of age, victims of ohca between july 1, 2011 and september 1, 2015 care by a mobile emergency and resuscitation service (smur) participating in french national cardiac arrest registry (réac) were included. patients were split into 3 groups: prepubescent patients (named "children": girls 0-9 years, boys 0-11 years), pubescent patients (named "adolescents": girls from 10 to 17 years and boys from 12 to 17 years) and "adults" (men and women 18-64 years). the "adolescents" group was consecutively compared to the "children" group and to the "adults" group. results 644 children, 256 adolescents and 16,566 adults under the age of 65 have been included. ohca in adolescents occurred more often on public roads (30%) or in public places (15%) and were more often traumatic (46%) than those in children and adults. respiratory causes were more frequent in children (27%) than in adolescents (18%) and adults patients (18%). the proportion of shockable rhythm increased with age (3, 7 and 10% for children, adolescents and adults respectively). survival at d30 was greater in adolescents (12%) than in children (7%) and adults (8%) (p = 0.01 and p = 0.02 respectively). in the 3 studied groups, initial shockable rhythm was a survival factor at d30 (respectively or 18 [11.39-17.48 ] for children, adolescents and adults). other risk factors are described in table 11 . conclusion adolescents had better survival at d30 than the 2 others groups. adolescents and adults had shockable rhythm more often than children. moreover, respiratory failure was less frequent in adolescent and adults patients compared to children. puberty seems to be a good limit to differentiate pediatric patients with ohca. none. introduction non-invasive ventilation (niv) is an effective alternative to endotracheal mechanical ventilation (mv) in the management of acute respiratory failure (arf) patients. nevertheless, it can be still difficult to assess its real feasibility, application and outcome in daily clinical practice. therefore, we report our clinical experience with routine use of niv since the last national recommendations (2006). our aims were to evaluate the clinical efficacy and outcome of niv, and to identify predictive factors for niv failure based on a daily use. patients and methods we conducted an observational retrospective single-center cohort study by reviewing all medical records from january 2006 to december 2013 in our 22-bed medical intensive care unit (icu). eligible patients were those having received niv during their icu stay. two groups were defined according to the indication of niv: niv for hypoxemic or hypercapnic arf (arf-niv), and niv used in the post-extubation period for weaning, prevention or treatment of post-extubation arf (post-extubation niv).the main evaluation criteria were the incidence of niv use, success/failure rate of niv and risk factors for niv failure in each group. niv failure was defined as the need for stopping niv whatever the reason (intubation, intolerance, death) within 3 days after its initiation. (2; 9), and was longer in the post-extubation niv group (11 days (6; 19) ) than in the arf-niv (5 days (3; 9) for hypoxemic arf, 4 (2; 6) for hypercapnic) (p < 0.001). the overall icu mortality was 11.0% (15.8% in hypoxemic group, 8.1% in hypercapnic group, and 6.9% in post-extubation niv group) (p = 0.0005). in multivariate analysis, the main risk factors for arf-niv failure were: saps ii on admission (p < 0.0001), absence of cardiologic history (p = 0.0274) and the cause of arf (p = 0.0016) with a higher failure rate for pulmonary infections than acute cardiogenic pulmonary edema (or 2.94, p = 0.0004). for post-extubation niv, the only independent risk factor for failure was normocapnia before niv initiation (p = 0.0011). conclusion our large longitudinal study demonstrates the feasibility and efficacy of niv applied in daily clinical practice. provided it is performed in a suitable environment by an experienced team, niv should be considered as a first-line ventilatory treatment in various etiologies of arf and a very useful ventilatory support in the postextubation period. nevertheless, risk factors for niv failure should be known by icu clinicians, hypoxemic arf remaining the more difficult indication to manage with niv. 1 réanimation médicale, hôpital saint-louis, paris, france; 2 service de biostatistique et information médicale, hôpital saint-louis, paris, france; 3 réanimation, institut paoli-calmettes, marseille, france; 4 réanimation introduction acute respiratory failure (arf) is the leading cause for icu admission in immunocompromised patients. in these patients, oxygenation strategy is of major interest to avoid the need for mechanical ventilation (mv), which is associated with high mortality rates. in that setting, use of non-invasive ventilation (niv) and oxygen therapy with high flow nasal cannula (hfnc) could be interesting alone or in association, but data about initial ventilation strategy in immunocompromised patients are controversial. to assess how initial oxygenation strategy actually influences the risk of mv on the coming day within the three first days of icu stay. the study end-point was the need for mv on the coming day. we restricted analyses to these first three icu days given, based on our own experience, most of mv was expected to occur by then. we performed a post hoc analysis combining three prospective studies of critically ill immunocompromised patients (two randomized control trials, the ivnictus and the minimax studies and one prospective cohort, the trial-oh study). we only considered patients with arf and a delay between icu admission and study inclusion less than 48 h. we excluded patients who required invasive mv within the first day, those with an icu stay less than 1 day and those with acute pulmonary edema diagnosis at icu admission. in order to estimate and compare the causal effect of daily respiratory management strategy on the probability of intubation in the coming day, we computed inverse probability of treatment weights (iptw) using propensity-score, defined as the probability of actual treatment selection conditionally on observed covariates. to handle confounding in such dynamic regimens, we considered marginal structural models (msm), which have been proposed to estimate the causal effect of a time-dependent exposure when time-dependent covariates that can be affected by the previous treatment are present. two treatment exposure models were considered: niv versus oxygen therapy regardless the device (model 1) and hfnc alone, niv alone versus niv + hfnc versus standard oxygen therapy alone (model 2). results 847 patients were included in the study. in model 1, there was no difference between niv and oxygen groups on mv whatever the landmark time. in model 2, while the unweighted or for intubation at day 1 was significantly higher in the niv group (or 2.05, 95%ci 1.29-3.29) and hfnc group (or 2.85, 95%ci 1.37-5.67) than those in the standard oxygen alone group, these differences disappeared in the weighted samples. using msm, no effect of the oxygenation strategy on mv was found, regardless of the oxygenation devices but the landmark time was associated with a reduced occurrence of mv. conclusion we found no evidence of any significant difference from several oxygenation strategies on mechanical ventilation probability during the first 3 days of icu in a large cohort of immunocompromised patients with arf. none. introduction the role of noninvasive ventilation (niv) is debated in the management of patients with acute hypoxemic respiratory failure. a recent study showed that patients treated with high-flow nasal cannulae oxygen therapy (hfnc) had lower intubation and mortality rates than those treated by the association of hfnc with niv (1). high tidal volumes (vt) delivewred with niv may be associated with an increased risk of intubation (2) . we aimed to identify risk factors associated to intubation, in hypoxemic patients with acute respiratory failure and especially the role of vt under niv. patients and methods this is an ancillary study from a multicenter, randomized, controlled trial including patients with acute hypoxemic respiratory failure (florali-study). we focused on only patients with moderate or severe hypoxemia (pao 2 :fio 2 ratio ≤200 mmhg) and we excluded those with mild hypoxemia. the criteria for intubation were predetermined including worsened or persisted respiratory failure, impairment of neurologic status and hemodynamic instability. results after adjustment on the oxygenation strategy, the two factors independently associated with intubation were the presence of bilateral pulmonary infiltrates at admission (or 2. simulation conditions enables to reproduce its occurence, using different types of tools, from physiological parameters to heart rate variability and psychocognitive tests. future research is required to evaluate the impact of these parameters on teaching. none. with stratification by centre and operator experience. an only inclusion criterion was: "patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if: contraindication to orotracheal intubation (e.g., unstable spinal lesion); insufficient time to include and randomize the patient (e.g., because of cardiac arrest); age <18 years; pregnant or breastfeeding woman; correctional facility inmate; patient under guardianship; patient without health insurance; refusal of the patient or next of kin to participate in the study; previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess occurrence of spo 2 <90% during intubation procedure between 4 groups of preoxygenation: bvm (at a minimum flow of 15 l/min, niv (100% fio 2 ), hfnc (at a minimum flow of 60 l/min, with 100% fio 2 ), and nrm (at a minimum flow of 15 l/min). between-groups difference in desaturation occurrence was adjusted for baseline covariates significantly associated with the group membership (p < 0.2). multivariate analysis of the occurrence of a desaturation (<90%) was performed using logistic regression. bag-valve mask was considered reference. results baseline characteristics were showed in table 12 . groups were similar at baseline except for pao 2 /fio 2 ratio. in univariate analysis, age (p = 0.08), saps2 (p = 0.02), pao 2 /fio 2 ratio (p = 0.03),spo2 (p = 0.001) and method of preoxygenation (p = 0.08) were associated with occurrence of desaturation below 90%. in multivariate analysis, spo2 at randomization and method of preoxygenation were only predictors of desaturation below 90%. bvm and hrm were associated with similar risk of desaturation occurrence whereas niv (or 0. introduction intubation procedure is a challenging issue in intensive care unit (icu) [1] . cardiac arrest related to intubation in critically ill adult patients has been poorly studied. the studies were not powered to conclude on this rare outcome [2] . the main objective of our study was to establish the incidence of cardiac arrest and to assess the risk factors of cardiac arrest in a large prospective database of intubation procedures performed in icu. five prospective studies were included, with similar data collected before, during and after intubation procedures using the same methodology. the primary outcome was the incidence of cardiac arrest related to intubation. the secondary outcomes were the death (cardiac arrest without return of spontaneous circulation (rosc)), the cardiac arrests with rosc, the complications related to intubation, the length of icu stay and the 28-day mortality. the factors associated with cardiac arrest related to intubation procedures were assessed by univariate and multivariate analysis based on patient, provider and practice characteristics. results among the 1847 intubation procedures included, 49 cardiac arrests (2.7%) occurred, including 35 with rosc (71.4%) and 14 without rosc (28.6%). main patient, provider, procedure characteristics and outcomes according to cardiac arrest related to intubation are presented in table 13 . in multivariate analysis, the independent predictors of cardiac arrest related to intubation were low systolic blood pressure prior to intubation, hypoxemia prior to intubation, no preoxygenation, overweight or obesity and age >75 years. mortality rate at day 28 was significantly lower in patients intubated without cardiac arrest (30.1%, 541 of 1798) than with cardiac arrests overall (73.5%, 36 patients of 49, p < 0.001) and cardiac arrest with rosc (63%, 22 patients of 35, p < 0.001). conclusion cardiac arrest related to intubation in adult icu is not a rare event occurring in 2.7% of cases with high immediate mortality of 28.6% and at day 28 of 73.5%. we identified five independent risk factors to cardiac arrest which 3 of them could be modifiable. optimal preparation to intubation procedure could help to prevent those cardiac arrests. introduction naasotracheal intubation (nti) has been progressively given up in favour of the orotracheal intubation (oti) in intensive care unit (icu). this could be explained by more frequent infectious (sinusitis and ventilator associated pneumonia) and non-infectious (epistaxis, turbinates bones injury) complications the former being thought to be more frequent with nti. however, whereas infectious sinusitis is a risk factor for vap, no study has yet demonstrated that oti decreases the infectious sinusitis rate compared with nti. furthermore, nasal route could improve patient comfort and decrease auto-extubation. finally nti can be performed without laryngoscopy with less risk of lips and dental injury. in this prospective study, we aimed to compare the complication of nti and oti and to assess the comfort of the patient. we performed a prospective observational study in a 12-bed medical icu including patients requiring endotracheal intubation. the intubation route was let at the discretion of the physician in care of the patient, however oti was compulsory in case of cardiac arrest, severe hypoxemia (p/f < 150 when available) and clotting perturbation. for each patient, age, sex, sapsii, mechanical ventilation duration. intubation route were recorded as well as complications during the placement of endotracheal tube. infectious and non infectious complications during invasive ventilation period were also recorded. in patients who were successfully extubated, pain, burning feeling, dryness and the wish of tube removal were assessed using visual analogic scales (vas conclusion despite its small size, and the absence of randomization, the present study suggests that nasotracheal intubation improves the comfort and the tolerance of tracheal intubation and is not associated to higher rates of vap. none. effect of mode of hydrocortisone administration in patients with septic shock: a prospective randomized trial oussama jaoued 1 , rim gharbi 1 , najla the baseline characteristics of patients were similar between the two groups. sepsis was secondary to community-acquired infection in 54% of cases. there was no difference in mortality between groups (74% in continuous groups and 59% in discontinuous group). sofa score was significantly higher at days 1, 2 and 5 in discontinuous group. length of stay, duration of mechanical ventilation, number of day without vasopressors, and the occurrence of adverse events were similar in the two groups. conclusion the mode of hydrocortisone administration in patients with septic shock has no influence on morbidity or mortality. the occurrence of adverse events was similar. introduction widespread activation of coagulation with platelet consumption is a pathophysiological feature of severe sepsis and septic shock. thrombocytopenia, either defined by platelet count below 150 g/l or by a significant relative 20-40-percent decrease in platelet count is a potent poor prognostic factor in sepsis. besides their role in hemostasis, platelets also carry various immune and inflammatory functions that are likely to impact on host defense against infections. we aimed to assess whether changes in the platelet count induced by sepsis is associated with the development of subsequent nosocomial infections. patients and methods patients were obtained from two prospective studies about immuno monitoring of dendritic cells and innate-like lymphocytes in critically ill septic patients (1, 2) . adult patients with severe sepsis and septic shock were included. exclusion criteria were any immunosuppressive condition (hematological malignancy, hiv infection at any stage, bone marrow or solid organ transplantation, daily corticosteroid therapy >0.5 mg/kg prednisone-equivalent, chemotherapy or any other immunosuppressive treatments), pregnancy, do-not-resuscitate orders on admission. in addition patients who died or who received platelet transfusion during the first week after icu admission were also excluded. platelet counts were collected on the day of sepsis diagnosis (d1) and then on d3, d5 and d7. the relative variation in platelet count at day n compared to day 1 was calculated as follows: (count at day n − count at day 1) × 100/ (count at day 1 between between d1 and d3, between d1 and d5 and between d1 and d7 were also similar between patients with and without icuacquired infections (fig. 12 ). discussion in this preliminary study from selected cohorts of nonimmunocompromised patients, sepsis resulted in mild alterations in platelet counts, making it unlikely to become associated with the development of nosocomial infections. it would be relevant to address this question in larger cohorts of non-selected patients, as well as the impact of platelet transfusions in this setting. conclusion changes in platelet counts were not associated with an increased susceptibility towards icu-acquired infections in non-immunocompromised patients with severe sepsis and septic shock. introduction sepsis is the leading cause of mortality in the intensive care unit (icu) patients despite the progress regarding their care. the immunodeficiency due to sepsis with the consequent profound lymphocyte alterations is now well proven. the objective of this work was to determine the prognostic impact of lymphocytopenia in septic patients in icu. retrospective study including all patients hospitalized for sepsis or septic shock between 01/01/2013 and 31/05/2015. the sepsis and septic shock definitions were adjusted with the third international consensus definitions for sepsis and septic shock. were excluded from the study patients of onco-hematology. lymphocytopenia was defined as an absolute lymphocyte count less than level of 1500/mm 3 during the first 24 h of hospitalization. the prognostic factors analyzed for the lymphopenic and non lymphopenic patients were in hospital mortality, the occurrence of nosocomial infections and hospital length of stay. results among the 52 patients, aged 58 ± 17 years, 23 patients were with septic shock and 29 patients with sepsis. igsii score and sofa score were respectively 42 ± 19 and 5 ± 3. four patients were immunocompromised due to hiv infection in one case and an immunosuppressive therapy in 3 cases. lymphocytopenia was observed in 41 patients (78%). twenty-eight patients (53%) died within an average of 11 ± 13 days. it was noted the occurrence of 10 nosocomial infections. the median length of stay was 7 days with extremes of one and 74 days. the lymphopenic patients were comparable to non lymphopenic patients in terms of medical history and severity scores. mortality was comparable between the 2 groups with a rate of 51% (n = 21) in lymphopenic patients and 64% (n = 7) in non-lymphopenic patients (p = 0.51). the earliness of death was correlated with the duration of lymphopenia (r 2 = 0.32, p = 0.007). the occurrence of nosocomial infections was not different between the two groups: 17% (n = 7) for lymphopenic and 27% (n = 3) for non lymphopenic patients. the hospital length of stay was not different between the two groups but was correlated with the duration of lymphocytopenia (r 2 = 0.29, p = 0.000). conclusion lymphocytopenia is frequently found in sepsis. lymphocytopenia was not associated with excess of mortality nor with the subsequent occurrence of infectious complications during the icu stay. his persistence was associated with an earlier death and a more prolonged hospitalization. none. introduction relative adrenal insufficiency (rai) is common in icu patients, particularly during septic shock (1). it has been shown that the rai also occurs during cardiogenic shock (2) . septic cardiomyopathy occurs in a significant proportion of septic shock patients. the aim of this study was to evaluate the role of rai on septic cardiomyopathy. patients and methods prospective observational study conducted in the intensive care in one university hospital in france. patients meeting the criteria for septic shock without prior corticosteroid therapy and without chronic heart disease were included. total blood cortisol levels were assessed immediately before (t0) a short corticotropin stimulation test (0.25 mg iv of tetracosactrin) and 30 and 60 min afterward. δmax was defined as the difference between the maximal value after the test and t0. rai was defined as an inappropriate adrenal response with δmax < 9 µg/dl and septic cardiomyopathy as the appearance of cardiac systolic dysfunction (left ventricle ejection fraction <45%) within the first 3 days of septic shock. we performed a multivariable analysis using backward stepwise logistic regression to identify independent predictors of septic cardiomyopathy. discussion although the definition of rai is not consensual, a threshold of δmax at 9 µg/dl has been widely used in septic shock, with or without the use of t0 (1). the usefulness of substitutive doses of steroids in septic shock is controversial, but many authors assume this treatment has a potential in reversing overt vasoplegia. our data suggest an implication of rai in septic cardiomyopathy. conclusion we found rai to be an independent predictor of septic cardiomyopathy. these findings may suggest a new role for substitutive doses of steroids in the hemodynamic management of septic shock. introduction regional perfusion parameters, like lactate, pyruvate and glycerol, may predict outcome in septic shock patients. continuous venovenous haemofiltration (cvvh) has been considered beneficial in septic shock patients. the aim of our study was to investigate whether cvvh, in comparison to intermittent haemodialysis (ihd), is able to improve regional perfusion in septic shock patients studied by muscle microdialysis. patients and methods it was a prospective, randomized, clinical study, including septic shock patients with acute renal failure, aged over 16 years. patients were randomized to receive either cvvh (n = 10) or ihd (n = 10) for renal replacement therapy. intermittent haemodialysis was carried out during the first 4 h of the 24 h study period. systemic haemodynamics and interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were obtained at baseline, 6, 12, 18 and 24 h after initiation of renal replacement by using muscle microdialysis. results regarding systemic haemodynamics parameters, cvvh caused a decrease in heart rate in contrast to ihd after 6 h (−4 ± 2 vs +6 ± 3/mn). there were no changes in vasopressor support throughout the 24-h study period and so systolic blood pressure remained stable in both groups. during the 24 h of all renal replacement therapies there was no significant change in muscle pyruvate and glucose levels. during cvvh muscle lactate decreased constantly, as did muscle glycerol levels. this decrease reaches a significant levels at h12 for muscle lactate and at h24 for muscle glycerol (fig. 13) . conclusion our results suggest that among septic shok patients, cvvh may improves regional perfusion in comparison with ihd. none. introduction acquired hypernatremia (h-na) is an independent risk of death among icu patients (1). in the rct "hyper2s" study, we compared normal to 3% hypertonic saline during the first 72 h in patients with septic shock with normal serum na concentration (sna) at baseline. the study was prematurely stopped for potential harmful effect associated with more frequent h-na. we assessed the role of h-na on mortality. patients and methods data are a post hoc analysis of the "hyper2s" study database including 434 patients. sna was measured at h0, every 12 h for 3 days and then daily until d7. study fluids were stopped if sna >155 or >12 mmol/l increase over 24 h. mild, moderate, and severe h-na were defined as sna >145 mmol/l, >150 mmol/l and >155 mmol/l, respectively. sna profiles were compared between d28 survivors and non-survivors. acute kidney injury (aki) was defined by doubling serum creatinine and/or need for dialysis. results 431 patients with available data were analysed. 234 (54%) developed h-na (mild: 28%, moderate: 16%, severe: 10%). no matter the absence or presence and its severity, h-na did not affect mortality (43, 34, 41, and 35%, respectively without, with mild, moderate, and severe h-na, p = 0.41). sna profiles were similar between survivors and non-survivors (table 14) . a sensitivity analysis performed among survivors at d3 did not change the results. compared to patients without h-na, aki occurred in 42% of patients with h-n vs 40% (p = 0.58), atelectasis in 8 versus 10% (p = 0.58) and icu acquired weakness in 7 versus 10% (p = 0.23). conclusion hypernatremia occurrence is not associated with an increased risk of morbidity and mortality during hypertonic fluid resuscitation in septic shock. none. introduction guidelines about the moderate hypokalemia treatment (between 2.5 mmol/l and 2.9 mmol/l) are based on experts estimations, and non-specific ones for patients in the intensive care units (icu). the aim of this study was to evaluate the correction of the hypokalemia in an icu and the compliance of recommendations. materials and methods an observational epidemiological, retrospective and monocentric trial has been realized during a period of 13 months (from january 2015 to february 2016). the study population included hospitalized patients in the icu who have shown a first moderate hypokalemia episode, all cause considered. patients who have presented an acute renal failure with a kdigo (kidney disease: improving global outcomes) score of three the day of their inclusion were excluded. the main primary study endpoint was percent correction of the serum potassium after 24 h. the secondary study endpoints were the incidence rate of moderate hypokalemia and the efficacy about the hypokalemia correction in accordance with the achieved treatment consistent or not with recommendations. results 140 patients had at least one episode of hypokalemia. the incidence rate of the hypokalemia first episode was 1.8%. the study population included 106 patients. igs2 score was 47.1 (± 16). 48 patients required mechanical ventilation at the inclusion. the serum potassium was greater than or equal to 3.5 mmol/l after 24 h about 34 patients (32.1%) (corrected group). at 24 h one patient had a serum potassium higher than 5 mmol/l. the average total potassium was respectively 72. infusion of potassium and 7 (6.6%) patients have been a management compatible with the most common recommendations (input potassium chloride of 100 mmol, use of the enteral administration and lack of continuous intravenous infusion). the percent correction of the hypokalemia after 24 h was respectively of 2/7 (28.6%) in the group in which recommendations had been respected and of 32/99 (32.3%) in the other one (p = 1.00). discussion in our knowledge there are no previous studies that have specifically focused on the correction of the moderate hypokalemia in critically ill patients. in our study the incidence rate of the moderate hypokalemia was lower than data from the literature because we have only considered the first episode of the hypokalemia [1] . among patients without contraindication to the enteral administration, this one was used in less than half of the cases. 62% of these patients received potassium with a continuous intravenous infusion and only 7 patients received medical care conform to the guidelines. the medium potassium quantity provided was very lower to the guidelines. only 32% of the patients have been corrected after 24 h without any difference in the medium potassium quantity which has been provided in relation to the uncorrected group. conclusion only 32.1% of moderate hypokalemia in icu are corrected after 24 h. the intravenous way is considerably used (in 72% of cases) with a poor return. a wide-ranging study is necessary to determine the best correction modes. none. results 1028 patients were included. mean ± sd age was 65 ± 16 years, 64% were male, mean ± sd saps ii was 47 ± 20. icu length of stay was 7 ± 11 days and icu mortality rate was 23%. during the first 7 days in the icu, 60% of patients received at least one nephrotoxic drug. 31% of patients received one, 18% received two, 9% received three and 3% received more than three nephrotoxic medications. diuretics, antibiotics and iodinated contrast media were the nephrotoxic drugs most frequently administered to, respectively, 35, 22 and 15% of patients. aki (kdigo stage 1 or higher) occurred in 58% of patients during the first 7 days in icu. the proportion of patients with aki increased with the number of nephrotoxic drugs received: 189/410 (46%) of the patients not exposed to nephrotoxic drugs developed aki whereas, respectively, 189/315 (60%), 136/184 (74%), 62/91 (68%) and 24/28 (85%) of the patients receiving one, two, three, and more than three nephrotoxic drugs developed aki. the univariate association between the number of nephrotoxic medication and aki persisted in the multivariate analysis adjusted on baseline saps ii score (p < 0.001). conclusion the significant proportion of patients exposed to nephrotoxic drugs and the observed association with aki warrants further investigation. statistical adjustments for multiple potential confounders is needed in order to assess a potential causal relationship which would lay foundations for interventional studies. none. (1) the minimal kidney aggression by current monomeric nonionic low-osmolar contrast media, late serum creatinine increase being explained by the occurrence of later (between the 6th and the 72nd hour) kidney injury due to critical illness or its therapy or (2) insufficient sensitivity of early (6 h) measurements of this biomarker to detect contrast-associated aki. competing interests partial financial support, no implication in data analysis and interpretation. introduction diabetic ketoacidosis, generally resulting from an absolute deficiency of insulin, is a frequent cause of hospitalization in intensive care unit. recommendations for diagnosis of diabetic ketoacidosis, care and site of admission have been published by the english society of diabetology. icu admission are recommended if one of the following criteria is present: gcs < 12, systolic arterial pressure (sap) <90 mmhg, spo 2 < 92%, ketosis >6 mmol/l, hco 3 < 5 mmol/l, ph < 7.1, potassium level < 3.5 mmol/l or anion gap >16 mmol/l. however, it is suspected that adhesion to recommendations remains low. in this study, we aimed at describing patients admitted for diabetic ketoacidosis in icu. we looked at adhesion to published recommendations regarding admission and care. we also described metabolic complications and looked for an association between complications and dose of initial insulin therapy. complications hypoglycemia (<3.9 mmol/l) was observed in 48% of patients within the first 24 h in which 19% were <2.9 mmol/l. this was 47 and 15% of patients between 24 and 48 h of icu stay. hypokalemia below 3.5 mmol/l happened in 44% of patients within the first 24 h and in 52% between 24 and 48 h. neither hypoglycemia nor hypokalemia were correlated with initial insulin bolus or initial dosage of continuous intravenous insulin. hypophosphatemia <0.30 mmol/l was observed in 15% of patients. discussion in this study, admission to icu was consistent with british recommendations since most patients presented at least one clinical or biological criterion indicating icu admission. arterial blood gas were sampled in the large majority of patients despite consistent data showing that venous blood gas might be sufficient in non-hypoxemic patients. also, initial insulin bolus and sodium bicarbonate perfusion were performed in a significant subset of patients despite absence of convincing data or recommendations supporting their use. finally, significant hypokalemia and hypoglycemia were frequent in these patients. these complications are in theory favored by insulin therapy but we did not observe a correlation between administration of an insulin bolus or the dose of continuous intravenous insulin perfusion. conclusion in this retrospective multicentre study, patients admitted in icu for diabetic ketoacidosis were correctly oriented regarding the british recommendations. metabolic complications (hypoglycemia and hypokalemia) were frequent but not correlated with initial dose of insulin. the appropriate rate for hypernatremia (h-na) correction is unknown. under-correction could be associated with worse outcome. experts recommend a rapid correction of acute (<2 days) and sever (> 150 mmol/l) h-na with a rate of −2 mmol/l/h until na < 146 mmol/l (1). correction should be, therefore, obtained within 24 h. in patients with septic shock resuscitated with iso-or hypertonic saline and who acquired acute severe h-na, we assessed if the correction rate was associated with mortality. patients and methods data are a post hoc analysis of the rct "hyper2s" database comparing normal to 3% saline for 72 h in septic shock. serum na (sna) was measured at h0, every 12 h for 3 days and ) . h-na correction rate was more rapid in non-survivors, p = 0.05 (table 15 ). over-correction occurred similarly in survivors (15%) and non-survivors (10%). the time to reach sna normalization was shorter in nonsurvivors (p = 0.05). after adjustment for sapsii and maccabe scores, more rapid correction rate remained significantly associated with mortality: or 0.16; 95% ci (0.03-0.86), p = 0.048. conclusion in the context of acute severe h-na induced by fluid resuscitation, a rapid correction rate might be associated with even aggravated rather than improved mortality. introduction systemic capillary leak syndrome (slcs) is a rare disease characterized by recurrent life-threatening attacks of capillary hyper permeability in the presence of a monoclonal gammopathy (mg). during acute episodes, the leak of fluid and proteins from the intravascular compartment to the interstitium results in clinical signs of both acute hypovolemia and interstitial edema. biological profile is pathognomonic with marked hemoconcentration and paradoxal hypoproteinemia. hypovolemic shock is the classical feature of severe scls attacks. however, beside this typical hemodynamic profile, several case report described myocardial dysfunction during scls attacks. the objectives of this study were to assess frequency, characteristics and outcome of myocardial involvement during severe scls attacks. (64%) mechanical ventilation, 6 (43%) renal replacement therapy, 5 (36%) veno-arterial extracorporeal membrane oxygenation, 1 (9%) intra-aortic balloon pump and 1 (9%) an impella. compartment syndrome occurred in 5 (45%) patients and 4 (36%) died in icu. we then compared the 11 patients with myocardial involvement to the 28 without clinical and biological manifestations were similar in between groups. however, chest pain (54 vs 11%, p = 0.008), dyspnea (82 vs 39%, p = 0.03) and respiratory failure (54 vs 18%, p = 0.044) were more frequent in patients with myocardial involvement than in others. there was no difference between groups regarding treatment received in icu, complication and outcome except for the use of va-ecmo (36.4 vs 0%, p = 0.004). conclusion myocardial involvement seems frequent in patients with severe scls attack, occurring in 22% of the cases. such patients exhibited classical features of scls attacks. myocardial involvement was responsible for altered lvef or transient ventricular hypertrophy. myocardial dysfunction could be severe, even requiring mechanical circulatory support. scls attacks should be known as a cause of severe reversible myocardial dysfunction and hypertrophy. none. introduction in refractory cardiorespiratory emergencies, ecmo appears a good alternative to conventional treatment. its extracorporeal circuit justifies curative anticoagulation explaining haemorrhagic and thrombotic complications. activated clotting time (act) is empirically and commonly used to assess anticoagulation but with large inter and intraindividual variabilities. in practice, antixa activity dosage is available to approach anticoagulant effect of heparin and is less expensive, but data during ecmo are missing. we sought to demonstrate the lack of correlation between antixa and act in patients under ecmo support. we prospectively include patients supported by ecmo in chu toulouse, france, between 01/2014 and 04/2015 for circulatory/respiratory support. anticoagulation was achieved by unfractionated heparin: initial bolus then continuous intravenous infusion (800-1200 iu/h), for antixa target of 0.2-0.4. concomitant dosing of antixa (laboratory) and act (hemocron ® ) was conducted two times a day on the same sample throughout the ecmo period. relationship between act and antixa was analyzed by spearman correlation (rho). after transformation into categorical variables (obtained target = 1; outside the target = 0), analyzes were completed by a concordance study (kappa). as recognized on literature act's targets were between 180 and 220. results 65 patients were included: 46 men (72%), median age 55 yo (53-57). indications were veno-arterial (n = 42) and veno-venous ecmo (n = 23). ecmo median duration was 5 days (hours to 30 days). spearman correlation test found low and inconsistent correlation between antixa and act (rho spearman < 0.4). this correlation lack present from the day one, worsens over time. analyzed kappa showed no discrepancy between the areas "targets" of act and antixa confirming the results (table 16) . conclusion use of act for ecmo anticoagulation monitoring doesn't seem appropriate and high price probably justifies preferential use of antixa in clinical practice. analyzes of relationships between antixa and bleeding/thrombotic events are needed to confirm the antixa place and its target in these indications. introduction postcardiotomy cardiogenic shock (cs) has an incidence of 2% to 6% after routine adult cardiac surgery. in 0.5-1.5% of cases, an venoarterial extracorporeal life support (va-ecls) is requested. the 6-month survival rate is 17.6% (1). survivors may suffer of physical and psychological impairments as well as an alteration of quality of life. this study was designed to assess the outcomes, long-term healthsince icu discharge, 65% of patients reported physical sequelae., ecls-related limb pain occurs in 38% of patients while paresthesia occurs in 23% and chronic-tiredness in 69%. mean karnofsky score was 68% (table 17) . conclusion after va-ecls for postcardiotomy cardiogenic shock longterm physical and psychological sequelae are frequent in survivor discussion interest for fluid management is growing in critical patients. nevertheless, no study has yet investigated its impact in selected patients with cardiogenic shock treated with va ecmo. our study suggested a possible association between fluid overload and mortality but lack the power to confirm these results with multivariate analysis. conclusion fluid management is a key therapy during va ecmo but fluid overload could be associated with worsen outcomes. further studies with larger population are warranted before considering fluid restriction trials. introduction extracorporeal life support (ecls) has taken an important place in the treatment of cardiogenic shock (cs) or refractory cardiac arrest (ca). however, ecls deplore a high mortality rate in the first days raising important ethic and economic consequences. in this context, continuation of support should be reassessed precociously. the aim of this study was the research of prognostic factors of 30-days mortality, 24 h after ecls implantation for cs or ca. materials and methods all patients undergoing ecls in our tertiary center during a 2-year period were prospectively included. the ecls were managed with a multidisciplinary protocol based on consensus. clinico-biological data were collected just before and 24 h after ecls implantation. these data were compared between survivors and deceased at 1 month. , cpc score was respectively 1 for 6 patients, 2 for 2, 4 for 1. at 12 months, cpc score changed only for the 2 patients with a cpc score at 2 (one died after another suicide attempt, one changed his cpc score to 3). in the group without ca (n = 88), 79 had normal neurological status at 6 months and 78 at 12 months (one patient died because of a cancer). among these patients, 96% returned at home and 77% returned to work. 16 (18%) patients re-attempted suicide in the year. the major risk factor of mortality is the presence of a cardiac arrest on hanging site. all the other factors found to be related to mortality are well known risk factors in cardiac arrest of other origin. in univariate analysis, risk factors of neurological sequelae at 6 months were a cardiac arrest on hanging site (p = 0.045) an elevated diastolic blood pressure (87 vs 70 mmhg; p = 0.04), a lower initial glasgow score (4 vs 5; p = 0.04), and an elevated blood glucose (1.39 vs 1.13 g/l p < 0.001) at admission in icu. discussion our cohort of self-hanging patients can be divided in two parts: a) patients with ca in the pre-hospital period with a high mortality and a good neurological recovery in 2/3 surviving patient, but with a small group; b) patients without ca with a very low mortality and a very good neurological recovery. these results seem to be better than in the most important cohort [1] published until now in self-hanging patients without ca and not treated by hbot (mortality at 9.5% and 3.5% of poor neurological recovery). conclusion patients surviving a self-attempted hanging who have not presented ca and treated by hbot have mainly a good neurological outcome. randomized control study should be undertaken to confirm hbot effectiveness in that indication. introduction venoarterial extracorporeal membrane oxygenation (va-ecmo) is increasingly used to treat refractory cardiogenic shock or cardiac arrest. acute brain injury (i.e. ischemic stroke, haemorrhage and/or failure to awaken because of diffuse brain injury) may occur in up to 15% of patients on va-ecmo and is associated with increased mortality and poor functional outcome in survivors. however, early indicators of neurological outcome are lacking in this population. we aimed to assess the prognostic value of early electroencephalography (eeg) alterations during va-ecmo. we conducted a prospective single-center study in the medical icu of a university hospital on consecutive patients cannulated to va-ecmo. a standardized clinical neurological evaluation including the rass score, the gcs score, the full outline of unresponsiveness (four) score and brainstem reflexes was coupled to an intermittent eeg. eeg was recorded as soon as possible within the first 72 h after va-ecmo cannulation. eeg characteristics were analyzed by a neurophysiologist who was blinded to the patient's condition. a severely altered eeg pattern was defined as a predominant delta frequency, discontinuous, unreactive and/or an isoelectric background. the primary endpoint was poor neurological outcome, defined as the composite of death or acute brain injury on neuroimaging within 28 days. data are presented as median (interquartile range) or number (percentage). false-positive rates (fprs, corresponding to 1-specificity) of poor neurological outcome were calculated for each significant predictor, using an exact binomial 95% confidence interval (ci). results sixty-nine (age 58 (50-67) years) patients with a sofa score of 14 (13-17) were included. main indications for ecmo were: post cardiac surgery (n = 25, 36%), terminal dilated cardiomyopathy (n = 12, 17%), and acute myocardial infarction (n = 11, 16%). cardiac arrest before ecmo cannulation was noted in 20 (29%) patients. eeg was recorded 1 (1-2) days after va-ecmo cannulation and 62 (90%) patients were sedated at time of eeg. at day 28, 46 (67%) had a poor outcome (n = 37 deaths and n = 9 patients alive with acute brain injury). in univariate analysis, a lower rass score (p = 0.003), a lower four score (p = 0.001), a lower score on the motor component of the glasgow coma scale (p = 0.001), and a lack of cough reflex (p = 0.033) at the time of eeg were significantly associated with a poor outcome. a severely impaired eeg pattern or presence of a discontinuous background activity were also associated with a poor outcome (p = 0.015 and p = 0.002, respectively). indicators of poor neurologic outcome are presented in the table 19 . among all parameters, a discontinuous background activity was the only variable that constantly predicted poor outcome (false-positive poor outcome prediction rate of 0%, 95% ci 0-15%). conclusion early intermittent eeg has a strong prognostic value for sedated patients on va-ecmo. presence of a discontinuous eeg background activity seems to be more accurate than clinical alterations to predict a bad neurologic outcome at 28 days. none. table 20 ). it was not found a significant association of ctp to mortality (46% in the case group and 30% in control group, p = 0.08). other factors that increased mortality were coma, seizures, shock, oedema, cellularity in csf >1200 units/mm 3 . otherwise, the ventilation length was prolonged with ctp group (8.7 vs 3.4 days, p = 0.034) and neurological sequels namely the epilepsy was more frequent with the group ctp: (23 vs 5%, p = 0.028). conclusion the occurrence of ctp on bacterial meningitis was significantly associated with ct scan lesions which seems to be an association be in both directions. also, the positive culture predisposed more to the ctp. mortality was higher with the presence of ctp but without real significance. the ctp was a factor that extends the ventilation time and exposed to the post infectious epilepsy. introduction acute bacterial meningitis requires rapid triage and therapeutic decision-making. the aim of this study was to assess the overall ability of a point-of-care glucometer to determine bacterial infection in cerebrospinal fluid (csf). we performed a prospective, observational study. we included patients for whom an analysis of csf was indicated by the physician in charge with blood sampling performed for glucose concentration measurement within 1 h. we simultaneously measured the glucose concentrations in csf and blood using a central laboratory and point-of-care glucometer. the diagnosis of bacterial meningitis was determined by two physicians after reviewing the complete medical chart. we compared csf and blood glucose concentrations and csf/blood glucose ratios obtained at the bed-side with a glucometer versus those obtained by the central laboratory. we determined the performance characteristics of the csf/blood glucose ratio provided by a glucometer to detect bacterial infection in the csf immediately after csf sampling. conclusion we demonstrated that the csf/blood glucose ratio measured by a glucometer can serve as a clinical decision support tool for the early detection of csf with a high probability of bacterial infection. this costless point-of-care method has the potential to expedite medical decision-making for the triage of adult patients with suspected meningitis in the emergency department immediately after lumbar puncture. none. introduction cardiac arrest remains a frequent cause of admission in intensive care unit. a majority of patients will die during their hospital stay mainly from consequences of hypoxic-ischemic brain injury after a decision of withdrawal of life sustaining therapy support by a prediction of poor outcome. the reliability of prognostication is crucial, but is still a difficult and uncertain exercise. eeg is the most widely used prognostic tool to support a clinical examination and is accessible in most hospitals. it is recommended for both prognostication and ruling out subclinical seizures. there is no high-level evidence for predicting poor prognosis using eeg because of the wide variety of classification systems used and the interrater variability. our objective is to assess the prognostic value of simple eeg features based on the recent american clinical neurophysiology society (acns) standardized classification and to study the interrater variability. we conducted a retrospective monocentric observational study in a 12 bed medical intensive care unit of the university hospital la timone, marseille, france. all patients aged of more than 18 year-old admitted for a resuscitated cardiac arrest between november 2012 and july 2014 who underwent therapeutic hypothermia and a full multimodal prognostic evaluation including a eeg were included in the study. outcome was classified according to the cerebral performance category score measured at day 28. unfavorable outcome was defined as death (cpc 5), persistent vegetative state (cpc 4), or severe neurological disability (cpc 3). favorable outcome was defined as moderate neurological disability (cpc 2), or no disability (cpc 1). eeg was performed in all patients still comatose after rewarming between 48 and 72 h after admission and after discontinuation of sedation. eeg interpretation was made by 2 independent senior neurophysiologists, blind to the outcome. eeg features are based on the latest acns classification. for each eeg feature, sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv) for predicting an unfavorable outcome were calculated. results during the study period, 122 cardiac arrest were admitted of which 48 patients went through a full neurologic evaluation and were finally included in the study. according to neurological outcome, 19% had a favorable evolution, and 81% had an unfavorable outcome. the presence of burst suppression, and epileptiform activity was constantly associated with an unfavorable prognostic with a 100% specificity and 0% false positive. a non-reactive eeg is strongly associated with an unfavorable evolution with a 89% specificity and 3% false positive. other features including periodic or rhythmic patterns and low voltage were inconstantly associated with unfavorable outcome. kappa score for all eeg feature was slight or fair and always under 0.4. discussion this study allowed us to identify a homogenous cohort of comatose patient after cardiac arrest who underwent therapeutic hypothermia. we identified simple eeg features based on the new classification of the acns constantly associated with unfavorable outcome. these features must be known by intensivists to better integrate eeg in the multimodal evaluation of neurological prognostic. there is important interrater variability that must lead to caution and to always use multimodal approach to prognostic an unfavorable outcome. conclusion bedside eeg is an excellent tool for predicting outcome of post-anoxic coma through simple eeg features. burst suppression, epileptiform activity and non-reactive eeg are strongly associated to neurological outcome after cardiac arrest. however, the interrater variability emphasize the need of being well trained for the standardized methods of evaluating eeg parameters. introduction emergent reintubation is a well-known risk of laryngotracheal trauma and of ventilatory acquired pneumonia. to precisely define its risk before extubation for each patient is a part of quality of care in intensive care units. none of these 43 consecutive children representative of picu activity has been reintubated. the coming prospective muticentric study which aims to validate alt in childhood must precisely define this criteria of evaluation. conclusion the different methods of alt are feasible in real clinical conditions in picu. because of the increasing use of cuffed etts in a wide variation of patients with different body weight, the best alt to use at the bedside must be definitively validated in this population. introduction prolonged mechanical ventilation (pmv) and chronic mechanical ventilation (cmv) in neonates is associated with a high morbidity and mortality. the objective of the study is to identify, among the patients with pmv, those that evolved to cmv, as well as the adverse respiratory, neurological and feeding sequelae. we conducted a retrospective study of the last 10 years at the chu sainte-justine (montreal, canada). chart review included patients with pmv (≥21 days) using the paediatric definition adapted from the 2005 namdrc consensus conference (1) . demographic and clinical data, including follow-up at 6 and 18 months corrected age, was collected for each included patient. the evolution of pmv neonates with cmv (≥125 days) and without (21-125 days) was compared. we identified 174 neonates that met criteria for pmv. patients born between 2004 and 2011 (n = 110, 63% of the cohort) were analyzed. around half of the patients (5-10 patients a year) are transferred from the neonatal unit to the paediatric intensive care unit. in our center, they represent around 1% of total admissions, but their length of stay is among the longest. among these 110 newborns, 79% were preterm (n = 87) with 45% (n = 50) born before 29 weeks gestation. of all patients with a malformation (52%, n = 57), 21 had a thoracoabdominal anomaly and 24 had congenital heart disease. thirty-six patients had cmv with mean ventilation time of 239 days (range 125-753 days). survival at 18 months corrected age was 66% (49/74) in the pmv group and 72% (26/36) in the cmv group. at 18 months corrected age, 30% of patients were dependent on artificial enteral feeding (nasogastric tube or gastrostomy), with 18% in the pmv group and 54% in the cmv group. nine percent of patients had oxygen supplementation (2 patients in the pmv group and 4 in the cmv group), and 7% were mechanically ventilated. ten percent of patients had a tracheostomy (5 patients in the pmv group and 2 in the cmv group). discussion neonates with cmv have more sequelae. their rapid identification (at 21 days of ventilation) is essential to implement multidisciplinary development care in order to minimize neurodevelopment impairment. conclusion most newborns in our pmv cohort have a congenital malformation. survival at 18 months corrected age appears equivalent in both pmv and cmv group. artificial enteral feeding is more frequent in the cmv group and most patients have no respiratory support at 18 months corrected age. none. the value of pressures and volumes in assessing the fluid responsiveness depend on the systolic cardiac function in adult (1). we have studied the relative value of static filling volume and pressure to predict the fluid responsiveness, according to systolic cardiac function in children during acute circulatory failure. patients and methods patients under 8 years old with an acute circulatory failure of two intensive care units during a 1 year period of inclusion were analyzed. an exhaustive cardiac echography was performed initially (indexed end-diastolic volume (edvi) and e/e' from transmitral and tissue doppler were recorded), and the stroke volume index (svi) was measured before and after a fluid challenge (a 10 ml/ kg of crystalloid over 10 min results twenty-five children with acute circulatory failure were included. fluid responsiveness occurred in 6 of the 13 fluid loading events with low lvef, and in 6 of the 12 fluid loading events with normal lvef. pressure approach: for low and normal lvef, the auc-roc for fluid responsiveness was respectively 0.83 (ci 0.56-1)/0.73 (0.39-1) for a e/e' .the best thresholds of e/e' in low lvef was 7.9 with a sensitivity of 87 (ci 62-100) % and a specificity of 67 (ci 33-100) %. for low and normal lvef auc roc was respectively 0.6 (ci 0.21-0.99)/0.52 (ci 0.14-0.9) for the pvc. volume approach: for low and normal lvef, the auc-roc for fluid responsiveness was respectively 0.69 (ci 37-1) and 0.74 (0.4-1). the best thresholds in normal lvef was an edvi below 29 ml/m2 wit a specificity of 83 (ci 50-100) and a sensitivity of 71 (ci 42-100) %. discussion our study shows a variation of the diagnostic value of e/e' and edvi according to the left ventricular systolic function. therefore, the systolic function should be taken into account to analysed the e/e' and edvi value. few preload dependency markers are validated in children and none for children in spontaneous ventilation (2) . our study suffers from a lack of power that calls into question the validity of our results. another limitation is that both approaches with volume and pressure are not very discriminant as it is known for static value in adults. our study illustrates that, on a pressure-volume curve, when the cardiac inotropism is reduced, the filling of the left ventricle is moved to the up and right of the curvilinear diastolic function curve. therefore, pressure variations are larger than volume variations. these values should be monitored on a larger scale to define their exact diagnostic value. conclusion static pvc value is a low preload-dependency surrogate. when lvef is low a pressure evaluation based approach seems more accurate. when lvef is normal a volume evaluation based approach seems informative as predicted by the slope of the end diastolic pressure volume curve. those both static approaches remain of poor diagnosis accuracy. introduction acute viral bronchiolitis is a primary cause of respiratory distress in paediatric intensive care unit (icu). prone position (pp) is commonly used in neonates to improve respiratory mechanics and has been found beneficial to adult patients with acute respiratory distress syndrome. we aimed to evaluate the effect of pp on work of breathing as compared to supine position (sp) in children with severe bronchiolitis requiring non-invasive ventilation. the protocol was approved by our irb (2015-a01200-49). fourteen infants (9 boys) with median age 33 days [firstthird quartiles 25-58] with severe bronchiolitis requiring cpap were included after written informed consent. children were investigated in pp and sp each applied for 1 h in a random order with a washout period of 10 min between them. level of cpap was set at 7 cmh 2 o in both conditions. oesophageal pressure probe was inserted orally (cto-2 pressure transducer, gaeltec, scotland) to measure oesophageal pressure. flow and airway pressure (pmo in fig. 15 ) were simultanuously recorded using a neurovent data acquisition system (neurovent inc, toronto, canada). one hundred breaths were analyzed in each condition, in which work of breathing was estimated from oesophageal pressure-time product (ptpes) and oesophageal swings (fig. 15 ). data were expressed as median (first-third quartiles) and compared by using the wilcoxon two-sample paired sign test. a p-value below 0.05 was considered significant. . the edtb contains data from ventilated patients (invasively and non-invasively) and details concerning ionotropic and sedative treatment during picu courses. discussion as far as we know, this edtb is currently the only one as exhaustive available in picu worldwide. after almost 3 years of multidisciplinary collaboration, we are able to collect many useful physiological, therapeutic and medical data in an ongoing edtb. although many concerns remain concerning data validation, organisation and exploitation, this edtb already contribute to the development of clinical decision support systems and virtual patient validation and we create international collaborations to further develop these tools. three research protocols using the database are ongoing including: validation of a neuromonitoring clinical decision support system, validation of a cardio-respiratory simulator, developement and validation of the automatic diagnosis of pediatric acute respiratory distress syndrome and development of spo2 forecast using artificial neuronal network. conclusion thanks to informatics and electronic devices improvement, data gathering in intensive care units has empowered. we hope that our work in picu will encourage other teams on the way of data gathering, in order to build an international picu edtb in a close future. none. introduction severe trauma is rare in the pediatric setting (15% of all trauma in france). however, its morbidity and mortality remain high, in relation to brain injury. pediatric traumatic brain injury (tbi) prehospital care is challenging for non-pediatric retrieval teams. though, we disseminated pediatric tbi pre-hospital care regional guidelines and thereafter intended to assess severe pediatric trauma pre-hospital care and secondary cerebral insults control. we conducted a retrospective study in a single pediatric trauma center. children admitted in emergency room with severe trauma and moderate to severe tbi (glasgow coma scale ≤12) from june 2014 to march 2016 were included. pre-hospital and hospital data regarding primary care, equipment, medications and secondary cerebral insults control (i.e. blood pressure, oxygenation, co 2 level, temperature, glycemia) were collected from medical files. two pediatric transport team experts assessed the quality of pre-hospital care, based on two major endpoints. results twenty-nine files were analyzed. median iss was 34 . all the children had been referred directly from the trauma scene to the pediatric trauma center. they were all intubated in the prehospital setting, 4 (13.7%) presented with spo2 < 90% before or at emergency room admission, and 17 (58.6%) presented with a pco2 >45 mmhg at admission. at least one peripheral catheter was inserted in all the children. mean total fluid bolus was 26.9 ml/kg (± 14). nor-epinephrine was administered in 16 (55%) children. mean blood pressure was below age threshold in 18 (62%) children during transport or at admission. an intracranial hypertension treatment (apart from sedation) was delivered in 17 (55%) children before admission. body temperature was monitored in 10 patients and 17 were hypothermic at emergency room admission. experts concluded on sub-optimal care in 17 children: major endpoint was "respiratory care", "hemodynamic care" and "neurologic care" in 13, 12 and 9 patients respectively. discussion on this small series, we showed pre-hospital sub-optimal care regarding secondary cerebral insults control, especially regarding co 2 level, blood pressure and body temperature. our results will help to design new care improvement strategies (e.g. sedation, fluid bolus and ventilation optimization, early use of vasoactive drugs, systematic body temperature monitoring…). conclusion data on pre-hospital secondary cerebral insults care are rare in the pediatric setting. based on our results, we aim to improve quality of care of children presenting with traumatic brain injury, and to reduce its morbidity and mortality. introduction unsuccessful extubation from mechanical ventilation increases mortality and morbidity. to reduce the extubation failures in our intensive care unit we used a mechanical ventilator weaning protocol, based on published data. during the first part of the study, risk factors and incidence of extubation failure were first described. afterwards in the second part, our mechanical ventilator weaning protocol was tested to determined its efficiency regarding the extubation failure. patients and methods a monocentric and observational study, was first conducted. we included 245 children aged from birth to 18 old, during a period of 15 months and collected for each patient their medical history, intubation and extubation parameters, and existing events of extubation failure or extubation complication. the second part of the study was prospective, we include 70 patients extubated by applying our mechanical ventilator weaning protocol. results average duration of mechanical ventilation was 51.6 h in the first part of the study. using a univariate analysis, duration of mechanical ventilation was a risk factor of extubation failure with an average duration of 131. discussion our study confirms published data about extubation failure risk factor like duration of intubation, chronic respiratory affection, history of previous intubation, and the administration of benzodiazepine. it is the first pediatric study that shows a reduction of extubation failure by using a specific mechanical ventilator weaning protocol. the mean bias of our its retrospective and prospective character. conclusion our study shows the interest of a mechanical ventilator weaning protocol to reduce the incidence of extubation failure. we currently continue the apply our protocol to include more patients in order to confirm our results. stroke of the child is formidable though it is ten times rarer than in adults, but this scarcity can have adverse consequences on the speed and quality of the management and the consequences on later psychomotor development. our goal is to describe the clinical and therapeutic aspects of these pediatric stroke while bringing our experience. patients and methods retrospective study of cases of children hospitalized in general intensive care unit to the pediatric hospital canastel oran for stroke during the period from january 2014 to january 2016. the clinical, etiological, para clinical, and scalable were studied and transcribed on a standard electronic form.all patients had a brain ct. magnetic resonance imaging(mri) was possible in 02 patients for lack of availability of the technical facilities during the study. results ten cases were selected. the mean age was 64 months (1 month to 15 years), 66% are male, 2 patients had a history of chd like tetralogy of fallot and complicated bronchiolitis myocarditis, one patient had a history of petechial purpura, 1 other was a factor 7 deficiency, headache history was noted in 02 patients, and 04 patients with no particular antecedent was found. all patients arrived comatose 11/15 score on the scale of glasgow, isochores reactive pupils with a motor deficit of hémicorps, 03 patients have degraded their neurological score with onset of clinical signs of hypertension intra cranial namely anisocoria and hypertension requiring osmotherapy, sedation and mechanical ventilation with an average duration of 2-7 day. o1child arrived brain dead, 03 patients had generalized tonic-clonic seizures which yielded after taking a benzodiazepine (diazepam) and phenobarbital (like gardenal). cerebral ct was performed in all cases and could we revealed the nature of the stroke hemorrhagic in 07 cases and ischemic stroke in 03 cases. two patients have benefited from an mri that found a thrombosis of the artery internal carotid right sylvian. besides symptomatic treatment, treatment was initiated based on the type of stroke, 03 patients received low molecular weight heparin (lmwh) at 0.1 ml/kg in addition to symptomatic treatment, 02 patients received vitamin k. four patients died in an array of autonomic disorders and evolved favorably and six patients were transferred to a pediatric unit. the average length of stay in icu was 5.5 days (2-10 days). discussion the mortality rate is important since no specialized center for children, and difficulty especially in the diagnostic imaging field while suspected stroke should be confirmed by imaging and the diagnostic delay. which is due to a poor assessment of the initial situation in half of the cases by the parents, the other half by the swiss magazine consulté.une doctor showed that in a study in 42% of children with stroke, this diagnosis was not primarily discussed and that in 11% of cases the cause of the stroke was poorly evaluated [1] . heart disease certainly represent the second most important risk factor. a collaboration of a team must be multidisciplinary, death has affected mostly older children whose age is between 11 and 15 years, who have a hemorrhagic stroke against by infants who have an ischemic stroke have evolved and oriented they exceed the acute phase to pediatric services for further investigation and monitoring. conclusion the child may also be having a stroke, which usually reaches the elderly. this justifies a good knowledge of this disease, and multiply the initial management efforts to reduce mortality and improve prognosis. anwar armel 1 , benqqa anas 1 , samira kalouch 2 , khalid yaqini 2 , aziz chlilek 2 introduction nosocomial infections are a main problem for public health for their cost as well as for the morbidity and mortality they generate. they are particularly common in intensive care units due to patient's lower defenses and of invasive procedures proliferation. work's purpose: • determine the epidemiology of bacterial noso-comiales infections (ibn) in the medico-surgical pediatric intensive care department of children's university hospital of casablanca. • to identify factors associated with these infections. we led a retrospective study of hospitalized patients, spending more than 48 h in medical-surgical pediatric intensive care department, at the university hospital ibn rochd of casablanca, over a period of 12 months from 1 january 2015 to 31 december 2015. results during the studied period, 420 patients were admitted at intensive care with a stay of more than 48 h. thirty episodes of inb were recorded. the incidence rate was 7.1% and the incidence density was 20.6% per 1000 hospitalization's days. the admission average age was 4.6 ± 22-month starting from 1 month to 12 years with a male predominance (60%). most of admissions (80%) was related to medical background, 50.3% received from other hospital department. furthermore, 40% of the patients received prior antibiotics, usually prescribed before icu admission. invasive procedures (intubation, central catheterization) were used in 93.3% of patients, vvp only in 6.66%, tracheotomy in 33.3 and 6.66% had received surgery. gram-negative bacilli (bgn) were isolated for a lot of patients, dominated by acinetobacter baumannii. these bacteria were isolated throughout the study year. risk factors analysis underlined that the presence of invasive procedures enhances in risk, that is central venous catheter and the need for mechanical ventilation. conclusion nosocomial bacterial infections are dominated by pneumonia and central catheter infections, and are mainly due to bgn. the factors associated with these infections were identified. the guillain-barré syndrome (gbs) is the most common cause of acute flaccid paralysis in children since the acute anterior poliomyelitis eradication. few studies have been held on the topic and knowledge of gbs in children, although it is recognized that the etiologic mechanisms, and clinicobiological background, are the same as in adults, prognosis remains different. our work's aim is to study this disease's mortality factors of children hospitalized in pediatric intensive care. patients and methods it is a retrospective, descriptive, mono centric study to review 35 patients with gbs between january 2009 and december 2015 and hospitalized at pediatric intensive care department of abderrahimharouchi hospital of casablanca. the used software is spss 16.0 to compare the bivariate variables, we used the khi2 test, and to compare quantitative variables, the anova to 1 factor test was used. the level of significance was fixed at 5% with 95% confidence interval. the disease was predominant in male with a sex ratio of 1.7 men/women. after a prodromal event, usually infectious (95.7%) and a free interval of 15 days on average to start motor disorders. these are of two types: either a hypo or areflectic flaccid paralysis of the lower limbs (25.7%) of ascending evolution in 91.4% of the cases. either flaccid tetraplegia or hypo areflectic, (74.3%). ventilation was required in 65.7% of the cases, and specific treatments based on immunoglobulins were administered in 88.6% of the cases. death's rate is still high (22.9%) and mainly due to hospitalization complications. in our study respiratory disease was noted in 65.7% of the cases, also other signs of serious illness such as swallowing disorders (71.4%) and autonomic disorders (14.3%) also noted what led to management in intensive care for all our patients. these patients study allowed to identify some mortality prognosis factors of the disease in intensive care units (such as male gender, ig administration duration, the occurrence of autonomic disorders like blood pressure instability), the most discriminating remains the occurrence of nosocomial infections. conclusion it must be underlined, that in view of our strict inclusion criteria, focusing only on patients admitted at intensive care and of the relatively small sample size (35 cases), our results must be qualified and must be enhanced by additional and more varied studies to better understand this disease in children. introduction early surgical treatment is recommended for refractory intracranial hypertension (htic) in children to improve vital and functional prognoses, whether traumatic or vascular cause. the main objective of this study was to compare the mortality and morbidity of children with severe intracranial hypertension after severe head trauma (tc) or due to vascular cause after decompressive craniectomy (dc) or medical therapy alone. the secondary objective was to identify the initial severity factors associated with higher mortality. patients and methods a retrospective study was performed with data collected from patients aged under 18 years-old admitted to our pediatric intensive care unit for severe intracranial hypertension of traumatic or vascular cause, between january 2000 and january 2016. they were divided into 2 groups: patients who received medical therapy alone and those treated with decompressive craniectomy after optimal medical management. results a total of 83 children were included. among them, 17 were treated with dc (6 htic of vascular cause and 11 htic of traumatic cause), and 66 were supported by medical means only (6 htic of vascular cause and 60 htic of traumatic cause). in the population "traumatic intracranial hypertension", we note that children in the "dc" subgroup are more often in mydriasis upon arrival (p = 0.017) than in the subgroup treated medically. in this same population, children in the "dc" subgroup received higher doses of mida-zolam (p = 0.015), of mannitol (p = 0.0041) and hypertonic saline (p = 0.0006) than in the other subgroup. in the population "vascular intracranial hypertension" the two subgroups were comparable. in the case of traumatic intracranial hypertension, mortality rate in the "dc" subgroup was 54.5% against 13.34% for children treated medically (p = 0.0015); "dc" children had more metabolic complications such as hypernatremia than "not dc" children, p = 0.043. mortality rate in the «vascular intracranial hypertension» group was 0% for children treated with decompressive craniectomy, and 83.3% for children treated medically alone (p = 0.015). patients treated surgically in the «vascular intracranial hypertension» group had longer overall stays (p = 0.009) and longer icu stays (p = 0.016). popc score (pediatric overall performance category) upon discharge for children with intracranial hypertension of traumatic cause treated with decompressive craniectomy was 4.91 ± 1.37 against 3.75 ± 1.31 among children treated medically, p = 0.08. in "dc" children with intracranial hypertension of vascular cause, popc upon hospital discharge was 3.66 ± 0.51 against 5.66 ± 0.81 among non-operated children, p = 0.007. the schooling rate was higher among children treated medically for intracranial hypertension of traumatic cause, p = 0.012. the severity factors related with higher mortality identified in the population "traumatic intracranial hypertension" were mydriasis upon admission, a pim 2 score higher and a lower temperature (<35.5°); the latter being the only factor identified for htic of vascular cause. in the case of traumatic intracranial hypertension, icp monitoring in survivors was 40.35% against 28.6% in children died, with no significant difference. in the population "vascular intracranial hypertension", all the patients who died had not been monitoring pic. discussion the severity factors related with higher mortality identified in the population "traumatic intracranial hypertension" were mydriasis upon admission, a pim 2 score higher and a lower temperature (<35.5°); the latter being the only factor identified for htic of vascular cause. other studies have related other severity factors as initial glasgow scale, tardive decompressive craniectomy. conclusion decompressive craniectomy doesn't seem to improve the mortality rate or the outcome in patients with hypertension of traumatic cause in our study but the dc traumatic subgroup was more serious than the subgroup treated medically. in children with refractory intracranial hypertension of vascular cause dc significantly improves survival and outcome. further studies are needed to clarify the role of decompressive craniectomy and its timing in the therapeutic management of refractory intracranial hypertension. introduction shortage of heart grafts is a major problem, leading to a significant mortality rate in the national waiting list, essentially for young children with low weight. the potential paediatric brain-dead donors often have myocardial dysfunction (md), which seems to be reversible. the aim of this study is to assess prevalence, causes and consequences of md when the potential paediatric donors are taken over, up to multi-organ retrieval, and the evolution after cardiac transplantation. materials and methods this observational, monocentric, retrospective study included all brain-dead children aged 0-18 years old, who had their myocardial function assessed through a cardiac ultrasound performed by a cardiologist and identified from 2004 to 2016. all adult patients and those who didn't undergo a cardiac ultrasound were excluded. md was defined as an lvef ≤50% with or without abnormal segmented cinetic parameters. the main evaluation criteria was the prevalence of md in potential identified donors. the secondary evaluation criteria were the causes and consequences of md on heart retrieval and the origin of this md. results out of 40 included patients, 11 had md. prevalence of md was of 30%. there was no significant difference between 2 groups regarding aetiology of brain death nor administration of catecholamines. having a cardiopulmonary arrest during intensive care unit stay was associated with a significant risk of presenting a md (p = 0.034). having a md had no consequences on organ retrieval in general (p = 0.25), but was significantly associated with a decrease in heart retrieval opportunities (p = 0.036). the cause of heart grafts refusal was a poor ventricular function in 50% of cases (3 cases out of 6). the cause for non-retrieval was parental refusal in one-third of cases. evolution of the cardiac grafts was favorable in 16 cases on 18, one transplanted patient died (from a non-cardiac cause) and 1 patient was lost to follow up. conclusion md in paediatric brain-dead patients has direct consequences on heart retrieval and transplantation, and otherwise, organ shortage is a major ongoing problem. a better transplant management regarding hemodynamics (with the use of a protocol) could increase the number of heart transplants, especially in small children, and reduce mortality rate in national waiting list. the prone positioning (pp) is a strategy widely used in the treatment of severe forms of acute respiratory distress syndrome (ards) in adults. its early use significantly reduces mortality (1). however, the studies do not strongly demonstrate its prognostic impact in pediatric ards. the aim of this study was to describe the prone positioning practices in the french-speaking pediatric intensive care units (picu). patients and methods this survey was conducted by email questionnaire to pediatric intensivists belonging to the french society of intensive care medicine and the french-speaking group of pediatric intensive care and emergency medicine. it was conducted from february to may 2016. the survey was addressed to doctors, nurses, physiotherapists practicing in picu. it included 29 questions about indications, contraindications, techniques and medical devices used, and complications. results one hundred and three persons answered (69 doctors and 33 nurses) which work in 28 french hospitals and 1 canadian hospital. sixty-eight percent of interviewed persons have more than 5 years experience and 57% of them treat each year more than 10 children ards. only 10% of the picu have a pp medical protocol. fifty percent of interviewed persons frequently use pp for the medical care of ards and 30% systematically use it. thirty-six percent begin pp at the early phase of ards during conventional ventilation, while 42% before the introduction of unconventional ventilatory strategies (ohf); only 12% use it after the respiratory failure unless unconventional ventilatory strategies. seventy-three percent report that pp is used with prolonged periods (>12 h/day), 22% with short periods (<12 h/day) and 14% with very long periods (>20 h/day). regarding the weaning criteria, most of interviewed persons seem to use multiple and combinated criteria: 51% use hypoxemia severity parameters (pao 2 /fio 2 , pao 2 , sao 2 ), 39% use the oxygen level (fio 2 ) and 38% use the mechanical ventilation parameters (peep, p max, p plate). finally, despite a low level of scientific evidence in children, 87% of the persons gave a strong recommendation for pp as standard care in severe pediatric ards. see fig. 16 . the survey confirmed the widely use of pp in pediatric ards. however, no specific protocol is avalaible in most of the picu. the timing of the pp beginning can be different according to children, early and prior to use of the conventional ventilation strategy in most cases. the duration of pp seems more consensual. most of the centers use extended periods longer than 12 h/day. these results are close to guérin et al. advocating a duration >16 h/day. finally, the weaning is a great issue and depends on multiple criteria. in guerin et al. (2) pp was interrupted if one of the following criteria were present: pao 2 / fio 2 ≥ 150 mmhg, with peep of ≤10 cm of water and a fio 2 of ≤0.6; decreased pao 2 /fio 2 than 20%, compared to compared to the supine position, or the occurrence of complications. no study has validated pp weaning criteria during pediatric ards. conclusion the prone positioning is a strategy commonly used in pediatric intensive care units for the severe pediatric ards. the criterias of implementation and timing are variable, as well as the weaning criterias. more pediatric multicenter randomized studies will be necessary to confirm the benefits of pp in pediatric ards and to define clear weaning criteria. introduction allogeneic hematopoietic stem cell transplantation (hsct) recipients have profound defects in every immunity compartments that can lead to severe opportunistic infections (oi). 20% of hsct patients require admission to the icu because of diverse infectious or non-infectious complications with dismal outcomes. oi specific course in this population has not been described previously and the management of these infections may be a concern. the aim of this study was to investigate risk factors, management and outcomes of io in hsct recipients admitted to the icu. patients and methods this was a retrospective (2007-2016) single center study of patients admitted to icu after an allogeneic hsct. patients provided written informed consent according to helsinki declaration. data regarding the transplant, infections and life sustaining therapy use were analyzed. oi were considered if present at the time or during icu admission. results hundred and ninety-four patients (pt) were included. median age was 43 [28; 58] years, 63.2% were males. reason for transplantation was acute leukemia in 84 (42%) pt and the hematological condition was still in complete remission at icu admission in 83% of patients. 78 (41%) and 53 (28%) had received a myeloablative conditioning regimen and anti-thymoglobulin serum respectively. 40% had acute graft versus host disease over grade 2 at icu admission. oi was documented in 38 patients (20%). an invasive fungal infection (ifi) was found in 19 pt owing to 3 mucormucosis, 1 trichosporon septicemia and 15 invasive aspergillosis (5 possible, 9 probable and 1 proven according to eortc criteria). serum galactomannane antigen was positive in 10 (67%). median time from transplantation and icu admission to ifi diagnosis was respectively 86 [18; 529] and −3 [−8; 0] days. lung was involved in 90% and patients with aspergillosis were admitted to the icu for acute respiratory failure in 71% (vs. 33% for others p = 0.2). they did not required invasive ventilation more frequently (36 vs. 31% p = 0.8). 32 and 10% required vasopressors and renal replacement therapy with no difference as compared to others. median icu length was 3 [2; 6] days. demographic, stem cell source, and donor type were not associated with ifi occurrence in this population. however 15/19 had received a total body irradiation (78 vs. 47% p = 0.01). ifi occurrence was not associated with icu or day 90 mortality (33 vs. 26% p = 0.7 and 53 vs. 41% p = 0.3 respectively). a viral infection was found in 17 pt owing to 11 cmv, 1 adenovirus, 1 hsv and 1 vrs infections. analyses were focused on cmv reactivation. median time from transplantation and icu admission to cmv reactivation was respectively 111 [50; 151] and −23 [−38; −10] days. reactivation was mainly positive blood pcr but 1 pt had cmv colitis. a preemptive treatment was started on the same day in median and lasts 34 [21; 71] days. patients with cmv reactivation had more frequently multiple organ failure (50 vs. 22% p = 0.06) and higher icu admission sofa score (7 [5; 12] vs. 6 [3] [4] [5] [6] [7] [8] p = 0.05). they trend to have higher admission creatinine serum level (132 [72; 157] vs. 81 [60; 120] umol/l, p = 0.2) and more frequently required emergency renal replacement therapy (36 vs. 7% p = 0.01) mechanical ventilation (64 vs. 30% p = 0.04) and vasopressors (73 vs. 37% p = 0.02). median icu length was 4 [2; 11] days and comparable to others. demographic, stem cell source, conditioning regimen and donor type were not associated with cmv occurrence. cmv reactivation was not significantly associated with icu or day 90 mortality (36 vs. 26% p = 0.5 and 60 vs. 41% p = 0.3 respectively). conclusion oi was found in 20% of allogeneic hsct recipients admitted to the icu. ifi were mainly responsible for respiratory distress and cmv associated to multiple organ failure. non-invasive diagnostic tests were positives in a majority of these patients. in this cohort, io treatment was started quickly after the diagnostic and we did not find an association with mortality. intensivists should always consider oi in their diagnostic panel in this specific population. introduction over the last two decades, targeted therapies in patients with solid tumors have both increased their length of survival and significantly altered their immune functions. however, data on opportunistic infections in this setting remain scarce. in this systematic review, we sought to identify published cases of opportunistic infections in patients with solid tumors, with a special interest on clinical findings, trends over time and outcomes. materials and methods we performed a search of medical subject headings (mesh) on pubmed using the words pneumonia pneumocystis (pcp), invasive aspergillosis (ia), histoplasma, mucor, geotrichum, cryptococcus, coccidioidomycosis combined with the mesh term neoplasms (breast, lung, ovarian, urologic gastrointestinal, digestive system, abdominal, brain, carcinoid tumor, sarcoma, testicular, seminoma). we identify published cases of opportunistic infections in non hiv patients with solid tumors between 01/01/1966 and 05/01/2016 included. results regarding pneumocystis jirovecii pneumonia, 94 cases could be identified. there were 32 men and 62 women, aged of 57.5 (19-80) years. underlying tumors were chiefly brain neoplasms (n = 31, 33%), lung neoplasms (n = 24, 26%) and breast neoplasms (n = 16, 17%). at the time of pneumocystis pneumonia onset, 52 patients (55%) had a history of chemotherapy, 58 (62%) had received long term or high dose steroids, and 21 (22%) had an history of biotherapy targeting the malignancy. of note, 18 patients (19%) had received only chemotherapy, 17 (18%) had received steroids alone, 4 (4%) everolimus therapy alone and 3 (3%) received none of these treatments. regarding invasive aspergillosis 64 cases could be identified. mean age was 66.7 (37-82) and 46 (72%) were men. solid tumors associated with invasive aspergillosis were primarily lung neoplasms (n = 31, 48%) and brain neoplasms (n = 24, 38%). at aspergillosis onset, 38 (59%) patients had a history of chemotherapy, 29 (45%) were receiving long term or high dose steroids and 3 (5%) had received targeted therapy. fourteen (22%) patients had received only chemotherapy, 2 (3%) only steroids, and 1 (1.5%) had received targeted therapy alone. for both infection, there was a trend for a higher number of reported cases throughout the studied period. conclusion this systematic review provides objective data showing that an increased proportion of patients with solid tumors present with opportunistic infections. we are convinced that it is a clinically relevant but still neglected problem. selected oncologic population may be becoming eligible for antimicrobial prophylaxis against pneumocystis or aspergillus. care unit of strasbourg in france. patients were included only if they are non-immunocompromised according to the european organisation for research and treatment of cancer (eortc). invasive aspergillosis was defined as an association of microbiological evidence, a radiological imaging and a clinical context. results eighteen patients (13 males) were identified during the study period. the median of igs ii was 60.5 (interquartile range (irq), 49.25-78.75). ninety-four percent was under mechanical ventilation. fourteen (78%) patients were suffering from liver failure. among liver failure, twelve (86%) were beforehand suffering from cirrhosis. the median meld score was 42 (interquartile range (irq), 30-53). sixty-four percent of aspergillosis were due to aspergillosis fumigatus. hundred percent were pulmonary aspergillosis. fifty-six percent of aspergillosis were associated with bacterial pneumonia. the mortality rate at the date of the latest news (an average of 2 years) was seventytwo percent. discussion invasive aspergillosis is not exceptional in the non-immunocompromised patient especially in patient developing liver failure. an active research of colonization/infection with aspergillus in these patients remain to be discussed. conclusion invasive aspergillosis in icu has a poor prognosis. the liver failure seems to be the most important risk factor in non-immunocompromised patients according eorct criteria. introduction chest wall elastance (ecw) has been found to increase in prone (pp) as compared to supine position (sp) in ards patients [1] . this makes respiratory system elastance (ers) not reflecting lung elastance (el). little is known about the changes of ecw, el and lung resistance (rl) when moving the patient from the sp to the pp via the lateral position (lp). the goal of present study was to measure ecw, el and rl in ards patients in sp, lp and pp during the proning procedure. patients and methods it was a prospective, single-center, controlled study. ards patients intubated, sedated and paralyzed with pao 2 /fio 2 ratio < 150 mmhg, peep ≥ 5 cmh 2 0 and an indication of pp were included. mechanical ventilation was delivered in volume controlled mode with constant flow inflation and end-inspiratory pause 0.100 s included into the inspiratory time. ventilator settings were unaltered during the procedure. an esophageal balloon catheter (nutrivent device) was used for esophageal pressure (pes) measurement. pressure at the airway opening (pao) and airflow were measured by fleish 2 pneumotachograph proximal to endotracheal tube and upstream heat and moisture exchanger. pao, pes and airflow were continuously measured during 30 min in sp, then during 1 min in lp and 30 min in pp. the side for the lateralization was that selected by routine practice (in the opposite side from central venous line). ers and resistance of the respiratory system (rrs) were obtained by fitting flow and pao signals breath by breath to the first order equation. ecw and resistance of the chest wall (rcw) were similarly obtained by fitting flow and pes signals breath by breath to the first order equation pertaining to the chest wall. el and lung resistance (rl) were obtained by subtracting ers and rrs from ecw and rcw, respectively. our ethical committee approved the protocol. data are shown as median (first and third quartiles). comparisons between positions were made by using paired-t-test. results twenty-nine patients, 19 males, of 68 (62-74) years, saps 2 45 (34-55) and sofa score 7 (3-9) were included 1 (0-2) days after ards criteria were met. the ards severity was moderate in 25 cases (86%) and severe in 4 (14%). tidal volume averaged 5.9 (5.6-6) ml/kg predicted body weight, peep 10 (10-10) cmh 2 o, fio 2 60 (50-70) %, pao 2 /fio 2 122 (108-139) mmhg. the cause of ards was pulmonary in 21 cases (72%), extra pulmonary in 3 (10%) and undetermined in 6 (18%). lateral positioning was on the right side in 14 (48.3%) and on the left side in 15 patients (51.7%). the results are shown in the table 21 . conclusion during prone positioning in ards patients, as compared to sp we observed a higher rl in lp and an increased ecw in pp. introduction neuromuscular blocking agents (nmba) could exert beneficial effects in acute respiratory distress syndrome (ards) through properties on respiratory mechanics and particularly in modifying transpulmonary pressures (pl). patients and methods prospective randomized control study in moderate to severe ards patients within the first 48 h of the onset of ards. all patients were monitored by an esophageal catheter and followed during 48 h. moderate ards patients were randomized in two groups according to the systematic administration of a 48 h continuous infusion of cisatracurium besylate or not (control group). the severe ards patients group received a 48 h continuous infusion of cisatracurium besylate. the evolution during the 48 h of the study of the oxygenation and the respiratory mechanics including inspiratory and expiratory transpulmonary pressures and driving pressure were assessed and compared. delta transpulmonary pressure (∆pl) was defined as inspiratory pl minus expiratory pl. results thirty patients were included, 24 in the moderate ards group and 6 in the severe ards group. nmba infusion was associated with an improvement in oxygenation both the moderate and the severe ards patients group accompanied by a decrease in both the plateau pressure and the total positive end expiratory pressure. the mean inspiratory and expiratory pl were higher in the moderate ards patients group receiving nmba as compared with the control group (fig. 17) . in contrast, there was no modification of both the driving pressure and the ∆pl related to nmba administration. conclusion nmba could exert beneficial effects in moderate ards patients through higher observed inspiratory and expiratory transpulmonary pressures. none. introduction prone position (pp) is a major treatment in management of acute respiratory distress syndrome (ards). the use of pp in patients with severe ards associated with brain injury is at high risk of intracranial hypertension. the aim of this study is to analyze the effect of pp on intracranial pressure (icp) and cerebral perfusion pressure (cpp) in patients with ards and acute neurological condition requiring monitoring of icp. patients and methods it is a retrospective descriptive study including sixteen patients with acute brain injury (subarachnoid hemorrhage, severe head trauma, and hemorrhagic stroke) and continuous monitoring of icp who developed a severe ards during icu stay from january 2012 to december 2015 and for which pp was performed. 29 pp sessions were analyzed. hemodynamic and respiratory parameters, blood oxygenation, pic and ppc were studied in supine, before pp and after pp. the study was approved by fics ethic comity. results a significant increase in pao 2 /fio 2 ratio was observed in pp, from 112 ± 34 to 200 ± 84 (p < 0.01). in pp, the icp was increased 11 ± 1.1-17 ± 1.3 mmhg (p < 0.05) while the cpp was stable 74 ± 2 versus 76 ± 2 mmhg (ns). median duration of pp session was 16 h (12) (13) (14) (15) (16) (17) (18) (19) (20) . increasing of icp during pp required medical treatment in 8 sessions (27%). pp session was interrupted in 6 sessions (20%). in subgroup of patients who respond to pp in terms of oxygenation, the increase of icp was lower than in non-responders (43 vs 118%) (p < 0.05). cpp was not modified whatever the nature of the response to pp (76 ± 15-77 ± 11 in non-responders and from 73 ± 10 to 76 ± 10 in responders (ns)) (fig. 18 ). discussion our study shows an improvement of oxygenation during pp in severe ards patient with acute brain injury. we observe a constant increment of pic during pp sessions. the increment of icp is less in responders to pp. significant increased icp requiring an enhancement in the medical treatment was observed in 30% of the cases, and lead in most cases to a discontinuation of the session. our data underlined the absolute necessity to monitor icp during pp session in patients with acute brain injury and ards, even if icp is controlled previously in supine. only 3 prospective (1, 2) and one retrospective studies evaluate the effects of pp on icp in patients with acute brain injury and acute respiratory failure (arf). they results are similar to ours. in all these studies, the severity of arf was often not well specified. roth and al. (2) had included only 10% of ards in a population of patient with icp not controlled. in others studies, monitoring of icp during pp was not systematic. despite the retrospective nature of the study and the small number of patients, it is the only work studying the effects of pp on intracranial pressure in patients with acute brain injury at risk for intracranial hypertension and severe ards according to the berlin's definition. conclusion our work suggest that pp is a quite secure technique for use for the treatment of severe ards even patients at risk of intracranial hypertension with a benefit in terms of oxygenation without major increase of icp particularly in pp responders. introduction influenza-associated acute respiratory distress syndrome (ards) requiring extracorporeal membrane oxygenation (ecmo) support is known to have a good prognosis (1). however, the incidence and impact of co-infection in this setting remain unknown. we conducted a retrospective, observational analysis of data prospectively collected from all patients admitted to our medical icu who received ecmo support for influenza-associated ards between 2009 and 2016. co-infection was defined as isolation of a pathogen in the lower respiratory tract at a significant level or in the blood during the 48 h following hospital admission. when no pathogen was identified in a patient receiving antibiotics prior to bacteriological sampling, an independent adjudication committee reviewed all charts to assess if the patient had a "high probability" or "low probability" for bacterial co-infection, based on clinical, radiological and biological results available. results are presented as median [iqr] . results among the 116 patients hospitalized for an influenzaassociated infection in our icu, 77 had an ards requiring support by either veno-venous-(vv, n = 58), venoarterial (va, n = 15) or venoarterio-venous-(vav; n = 4) ecmo. 3-29.9), pre-ecmo sofa score >14 (or 6.2; 95% ci 1.9-19.8) as independent predictors of hospital mortality, but not co-infection (or 2.5, 95% ci 0.8-7.9). in a second analysis, patients with proven co-infection and high probability of co-infection were grouped and compared to patients with no co-infection and low probability of co-infection; and results were similar. as compared to others co-infected patients, those co-infected with a pvl-positive s. aureus had same characteristics and similar mortality rate, but all received a treatment active against pvl production. conclusion co-infection is frequent in patients with influenzaassociated ards supported by ecmo, occurring in roughly 50% of the cases. mortality of patients with co-infection is higher than those without, but seems mainly due to the severity of the disease. s. aureus was the most frequently identified pathogen, with a high prevalence of pvl-positive s. aureus, infection with a pvl-positive strain was not associated with a poorer outcome as compared to other co-infections. whether a treatment active against pvl production should be given in those patients remains to be determined. none. the pancreaticoduodenectomy (pd) is major surgery in visceral surgery. this technique performed for the first time in 1935 by whipple has seen much progress and development over the years that have enabled a significant reduction in mortality, while the morbidity remains high. the aim of this study was to analyze postoperative morbidity pancreaticoduodenectomies. we retrospectively studied 34 cases of cephalic duodenopancreatectomy at the department of surgical emergencies resuscitation (wing 33) spanning 6 years, between january 2010 and december 2015. the average age of patients was 58.2 years with 43% of females and 57% of males, the frequence of pancreatic resections was 5 years. the indications of cephalic duodenopancreatectomy were: tumors of pancreatic head (65%), ampulla vater (23%), duodenum tumors (12%). the restoration of continuity after cephalic duodenopancreatectomy was realized with a rate of 41% for pancreaticogastrostomy and 59% for pancreaticojejunostomy. the average hospital stay was 11, 7 days, with extreme lengths of 6-27 days. the postoperative course was marked by the occurrence of 8 deaths (24%), the morbidity rate was 29, 25% after pj and 28% after pg; the most frequent complications were the pancreatic fistula (40%), the postoperative peritonitis (40%), the digestive bleeding (20%), the gastroparesis (20%). conclusion advances in the overall care of patients by surgical teams, anesthesiologists and intensivists, the dpc mortality is currently low in experienced centers. the multidisciplinary, involving surgeons, radiologists and especially intensive care, to manage more effectively the complications of this surgery remains burdened with high morbidity. introduction severe acute pancreatitis (sap) is a common but potentially lethal pathology due to the multiplicity and severity of complications that can occur at all stages of evolution. in the last decade, mini-invasive interventional treatments of infected pancreatic necrosis (ipn) have been developed. the aim of the present study was to assess the management and outcomes of sap patients, as well as to identify the role of ipn. this was a retrospective study of prospectively collected data from all consecutive patients admitted in intensive care unit (icu) in a single french center (hospital of nantes) from 2012 to 2015. using logistic regression, we evaluated the association between ipn and patients characteristics at baseline and the outcomes. (fig. 20) , highlighting the prognostic importance of respiratory failure and acute renal failure at the time of lt, as well as complex interactions between donor and recipient features. conclusion ventilator support and/or acute renal failure at the time of lt are major predictors of mortality but complex recipients/donors relationships may moderate these associations, as demonstrated by our cart analysis. none. subtotal gastrectomy (4/5). enlarged gastrectomy was performed in 3 patients (5%). the mean operative time was 244.3 ± 58 min. per-operative transfusion was required in 14 patients (23.3%). the average length of stay in icu was 8.2 ± 5 days. postoperative mortality was 6.7%. in our series, 13 patients (21.7%) had at least one postoperative complication: an anastomotic fistula diagnosed in 7 patients (11.7%), 12 patients (11.3%) had postoperative peritonitis and 6 patients had ventilator associated pneumonia. reoperation was necessary for 13 patients (21.7%), it was performed after 7.2 days (2-18 days). in univariate analysis, risk factors for postoperative morbidity after gastrectomy was hypoalbuminemia (p = 0.0145), anemia (p = 0.0001), bmi (p = 0.001) and malnutrition (p = 0.007). age, sex, neoadjuvant chemotherapy, extended lymphadenectomy, splenectomy or pancreatosplenectomy, total gastrectomy and operative time were not significantly associated with higher postoperative morbidity. in multivariate analysis, malnutrition (p = 0.01) and bmi (p = 0.001) were significantly associated with the occurrence of postoperative complications. conclusion the results of our study are similar to those reported in medical literature. preoperative evaluation and nutritional rehabilitation are crucial to improve patient's outcome and reduce morbidity and mortality after gastrectomy for cancer. the mesenteric ischemia is a condition relatively rarely. it is marked by high mortality. mortality is primarily related to the land on which ischemia occurs and especially the time taken to diagnose. this delay is due to the low specificity of clinical signs and the absence of diagnostic laboratory test. the mesenteric ischemia remains a diagnostic and therapeutic challenge. patients and methods twenty cases of acute mesenteric ischemia have been collected at the surgical resuscitation (resuscitation 33) at the hospital center ibn rochd of casablanca from january 2010 to december 2015. results the mean age of our patients is 50 year old. it is about a disease that the incidence increases these last years, particularly because of the waxing number of old patients and/or suffers from advanced cardiovascular diseases. the cardiovascular risk factor has been present in 35% of our patients. the abdominal pain has been present in all the patients. it is a sudden, intensive pain localized the most often at the level of the epigastria, becomes diffuse in few hours or even few days. other clinical signs have been described as the bilious vomiting that becomes fecaloid after few days. the digestive hemorrhages as the moelena and the hematemeses. a stop of the matter and the gazes was noticed in 25% of our patients. the absence of specificity of the clinical signs forced the realization of complementary examinations. the scanner becomes the reference imaging. it permits a differential diagnosis, the search of direct signs of vascular obstruction and the emphasis of intestinal pain. four etiologies are noticed: the arterial occlusion by emboli (40%), the arterial thrombosis (20%), the venous thrombosis (25%) and the "non occlusive" form (15%). the strategy of management of the acute mesenteric ischemia is multidisciplinary, based on the equips of radiology, vascular surgery and/ or visceral surgery and resuscitation. the treatment consists in measures of general resuscitation, the techniques of endoluminal vascular disobstruction and techniques of surgical revascularization. in spite of the improvements in the diagnosis and the therapeutic procedure of the ima, the disease still know a rate of mortality between 60 and 97% according the studies. in our study, we noticed 8 cases of death (40%), 9 cases of good recovery (45%), 3 cases are unknown evolution (15%). conclusion it is a vital emergency that the evolution still knows great mortality. it is very important to remind the acute mesenteric ischemia in the case of any acute abdominal symptom in order to anticipate about the natural evolution and to act in a reversible stage of the ischemia. none. introduction emergency departments staff are frequently exposed to many complex stressful situations and consequently burnout syndrome. our study aimed to describe epidemiological particularities and determine the risk factors of burnout syndrome in different categories of emergency. patients and methods we studied five academics and four regional hospitals. the level of burnout was assessed using the "maslach burn out inventory" score and the degree of depression with major depression inventory (mdi) test. results one hundred and forty-three correctly completed questionnaires were collected. the mean age of study population was 32 ± 7 years. sex-ratio was at 0.63. fifty-one per cent of the care staff were married. physicians represented 40% and paramedical 60%. the general frequency of burnout syndrome was 85% (n = 127). low level burnout was present in 32%, moderate level in 45% and high level in 23%. the depression frequency was 52%. a statistically significant correlation was found between burnout and depression firstly (p = 0.006) and between burnout and lack of equipment (p = 0.04). their relative risk was 4.7 [1.5, 15] and 9.14 [2.2, 37.6] respectively). main risk factors associated with high level burnout are detailed in table 22 . conclusion burnout syndrome frequency in our emergency departments is alarming. helping to resolve social and psychological problems and improving work conditions may help to decrease it. the healthcare activity is recognized as a major polluting activity. in france, it generates 800,000 tons of waste cremated each year, and represents 12% of the tertiary energy consumptions. in the united states, it generates 7000 tons of waste per day and 7% of total co 2 emissions in 2007 were attributed to him. ultimately, such waste production is associated with adverse environmental and health effects. nevertheless, near half of the hospital waste would be recyclable, particularly in our intensive care units (icu) [1] . furthermore, sustainable development solutions generate profits. the aim of this study is to make an overview of waste produced in a icu and offer solutions to conserve natural resources and reduce the carbon footprint bound to the healthcare activity. materials and methods experimental study, single-center, concerning a period of 6 months in an icu-high surveillance unit compound of 16 beds. we have identified all waste generated. our packaging were given to the recycling company in connection with the hospital. then we have studied the impact of the implementation of sustainable development solutions. results firstly, we have studied the non-recycled waste and the quantity produced over a period of 1 month. approximately 8 kg of waste is produced per patient per day with 45% of infectious waste and 55% of general waste. these results were linked with a bad distribution of garbage bags in the rooms (130 l of infectious waste versus 50 l of general waste). secondly, we have improved our way to sort and consume and we have created recycling dies without compromising patient safety. all these measures have not increased workload. changing bags in the rooms (20 l of infectious waste and 2 bags of 50 l of general waste) allowed to reach the normal goals of 2 sectors with a net benefit estimated at 4500 euros per year. the medical broken glass containing drugs was thrown into plastic containers of 5 l for infectious waste to prevent the risk of cuts. by creating a specific die intended to the general waste, we could quantify the production of this glass to 10 kg per week and to spare the use and the incineration of 350 containers of 5 l per year (global economy of 1000 euros). plastic packaging represented an important proportion of the cremated waste. we have created 3 sectors of recycling including the polypropylene (80-200 kg per month), the polyethylene colorless and colored polyethylene. this plastic is sold to be recycled without additional cost for the hospital. the linerboards was cremated. we have created a recycling die (50 kg per month). this sector was subsequently extended to the entire hospital structure, particularly the pharmacy that produces 12 containers of 400 l per month. they are now sold without additional cost. many unnecessary plastic waste is generated daily. we have removed using mild soap plastic bottles of 30 ml by using the same mild soap in pump of 500 ml (economy of 1000 euros). the use of 100 l plastic bags for the transitional deposit of linen has been deleted (economy of 450 euros). concerning the paper: 100% of the impressions were made in simplex. printers were parametrized on both sides by default allowing the economy of 60 reams per year (30,000 sheets), several thousand liters of water and the reduction of co 2 emissions. discussion recycling is only one component of the sustainable development in health. other avenues that could be considered to improve icu sustainability would include examining water use (for linen), electricity use (reducing non-essential use at night…). beyond these actions, we need to encourage our suppliers to turn to sustainable and recyclable packages to reduce the use of polluting and depletable fossil fuels such as oil. but also to develop with them circular economies where waste is returned to them to be reused. conclusion we must ask the question also resuscitate our tons of waste. our icu produce large quantities of waste (over 2 tons per year per bed). however, a significant proportion, especially plastic, is recyclable with a significant environmental and financial benefit. waste management also requires an optimal and rational use of supplies because "the best waste is that which is not produced" and that excess is not a guarantee of quality. as already said st exupéry in 1939: "we do not inherit the earth from our parents, we borrow it from our children. " so do not expect tomorrow to reduce major adverse ecological impact paradoxically generated by a great profession whose ultimate goal is to cure people. moreover, an external consultant is rarely applied and palliative cares are insufficiently developed after «non-readmission» decisions. for providing corrective measures, this study lead to propose a «nonreadmission» process by integrating the discussion for a real «patient's care project» at the end of the icu hospitalization. this process would lead to collect patient's opinion through advance directives, to ensure a collegial discussion including an external consultant and to allow reevaluation of global patient's clinical status and one or more organ failure(s). then, «non-readmission» decisions would be integrated in a therapeutic project which would promote the initiation of a palliative care program if necessary. the purpose of this process is well to respect patient's autonomy and dignity as required by french law and medical ethics. the proportion of elderly patients is steadily increasing. due to the growth of this part of the population who suffer from multiple pathologies, the need for hospitalization in intensive care increases. according to the simulations, the proportion of octogenarian patients in icu will increase reaching the third of icu patients. while chronological age is not a significant factor of poor prognosis in the icu (1), many factors should be taken into account to evaluate the relevance of icu admission in the senior population and withholding such intensification should be consensually discussed between clinicians and obviously as often as possible with the patient himself (2) . the aim of the study was to assess the role of stakeholders (ward physicians, intensivists, family doctor and patient himself ) in the decision of withholding icu admission for elderly patients in our internal medicine department. we made a prospective observational monocentric study, including all the elderly patients (defined as older than 75) admitted in the internal medicine department from january 2012 to june 2012. the only non-inclusion criterion was patient's refusal to participate to the survey. collected data involve physiological (cognitive, autonomy, nutritional status), morbidities (acute and chronic diseases) and social parameters (marital status, relatives). and evaluation of quality of life by the patient himself using an analog visual scale was also obtained. internal medicine physicians were asked to report any icu withholds decision for their patients. in absence of notification, every physician was questioned again the day of the concerned patient's discharge. results one hundred ninety-one patients were included between january and june 2012. factors associated with a significant reduction of in hospital mortality were higher age (p = 0.002), higher lactate level (p = 0.004), chronic obstructive pulmonary disease (p = 0.04), diabetes mellitus (p = 0.03), immunodepression (p = 0.05) and respiratory failure (p = 0.02). conclusion in patients hospitalized for vs high body mass index, low left ventricular systolic function, high white blood cell count, low creatinine clearance, high lactate level and st-segment depression are the variables correlating significantly with high-sensitivity troponin-t concentrations. peak of hstnt was not significantly associated with in-hospital mortality in this setting. introduction mitochondria are evolutionary endosymbionts that are derived from ancestral aerobic bacteria and so might bear and release bacterial molecular motifs supporting the role of mitochondria in danger signal regulations. free circulating mitochondrial dna (mtdna) is elevated in a wild range of critical illness observed in intensive care units, and is associated with bad outcomes and mortality. the mtdna is a molecular pattern that belongs to mitochondrial damage associated molecular patterns (mtdamps), and can interact with pattern recognition receptors (prr) to induce self defense reaction. free mtdna activates inflammatory signaling pathways through toll-like endosomal receptor 9 (tlr9) interactions. nevertheless, new evidence advocates a role of the receptor for advanced glycation end-products (rage) in mtdna signaling. experimental data suggest a role of mtdna-prr interaction in systemic inflammation and organ dysfunctions as septic acute kidney injury or pulmonary inflammation. impact of free circulating mtdna on endothelial cell is not known. the main purpose of this study was to test whether mtdamps and mtdna can induce endothelial dysfunction. we also evaluated the role of mtdna-rage axis in mtdamps induced endothelial dysfunction. mitochondria were isolated from livers of wild type c57b6 mice. isolated mitochondria were sonicated on ice to obtain mtdamp preparations. semi quantitative evaluation of mtdamp content was tested by qpcr, with specific markers of mtdna (cytochrome b (cytb), nadph oxidase (nd4)). intraperitoneal injection of 1 mg of mtdamps was used as experimental model in wild type and rage ko mice, as previously described [1] . the mtdamps were also administrated after ex vivo dnase preparation. endothelial function was assessed with a mulvany-halpern style myograph, 4 h after mtdamp administrations on aorta (conductive vessel) and on 2d division of mesenteric artery (resistive vessel). endothelial-dependent relaxation was studied by cumulative expositions of the vessels to acetylcholine (1.10-10-1.10-5 m). endothelial-independent relaxation was studied by sodium nitroprussiate exposition. results the mtdamps preparation contains a high quantity of mtdna with a 1/cycle threshold (ct) ratio of 0.062 for cytb expression. intraperitoneal administrations of mtdamps induced a decrease of endothelial-dependent relaxation mainly on conductive vessel (p = 0.0079, n = 5 per group) and to a lesser extent on resistive vessel (p = 0.22, n = 5 per group). rage-ko mice were protected from mtdamps-induced aorta dysfunction (p = 0.53, n = 5 per group). the ex vivo exposition of mtdamps to a dnase preparation decreased mtdna content in mtdamps solution with a 1/ct ratio of 0.038 for cytb expression. eventually, the pretreatment of mtdamps with a dnase preparation prevented the mtdamps-induced aorta dysfunction (p = 0.85, n = 5). discussion more than prognostic markers, mtdamps particularly mtdna seems implicated in endothelial dysfunction in critically ill patient. new evidence suggest rage interaction in endosomal tlr9 pro-inflammatory and pro-oxidant response to mtdna [2] . also in sepsis, physiological clearance of circulating dna might be impaired, this results comfort the possibility of therapeutic regulation of free circulating mtdna to prevent septic organ dysfunction related to mtdamps accumulations. conclusion exogenous mtdamps can induce endothelial dysfunction in mice. the mtdna-rage axis is a key component of the signaling pathway involved in this dysfunction. the use of dynamic parameters to assess fluid responsiveness was supported by cyclic changes in stroke volume induced by mechanical ventilation. however, these parameters have several limits. venous to arterial carbon dioxide difference inversely related to cardiac index. consequently, fluid administration would be beneficial if carbon dioxide gap increases. objective to investigate whether carbon dioxide gap predicts fluid responsiveness in patients with acute circulatory failure. patients and methods we conducted a prospective study in the medical intensive care unit of hospital taher sfar at mahdia, between march 2013 and april 2016. patients with circulatory failure and who required mechanical ventilation were included. we measured the variation of cardiac index between baseline and after volume expansion of 500 ml of saline fluid. the picco2 was used to measure cardiac index. response to fluid challenge was defined as a 15% increase in cardiac index. before and after fluid administration, we recorded carbon dioxide difference and hemodynamic parameters. results among 68 included patients, 33 (49%) were responders. the causes of acute circulatory failure were septic shock (n = 45), cardiogenic shock (n = 11), and hypovolemia (n = 12). carbone dioxide gap was significantly higher in responders group (8 ± 7 vs 4 ± 4 mmhg, p = 0.019). the area under the roc curve for carbon dioxide gap was 0. 68 (95% ci 0.55-0.80). the best cutoff value was 6 mmhg (sensibility = 46%, specificity = 80%, positive predictive value = 52% and negative predictive value = 60%). the area under the roc curve for delta carbon dioxide was 0.54 (95% ci 0.4-0.68). conclusion in this study, baseline carbon dioxide gap was not universal indicator to predict the fluid responsiveness in patient with circulatory failure. introduction supraventricular arrhythmia (sva) is commun in intensive care unit (icu). its incidence seems to be higher in patients with sepstic shock. sepsis-associated myocardial dysfunction promote the occurrence of sva by constituting an arrythmogenic substrate or under the effect of inotropic drugs. the aim of this study is to assess the incidence and prognostic impact of sva in patients with septic shock. patients and methods we retrospectively studied all patients with new onset sva suffering from septic shock in non cardiac surgical icu. myocardial dysfunction was evaluated by transthoracic echography (tte) after an adequate cardiac resuscitation using intravenous fluids expansion and adjunctive vasoactive agents. sva was detected by the electrocardiogram scope. during the study period clinical and biologic characteristics, hemodynamic tolerance (vasopressors doses, arterial pressure changes), current treatment (such as corticoid), duration of mechanical ventilation, duration of vasopressor requirement and hospital mortality were collected. results sixty patients were included in the study. the sva occurred in 28 patients, with an incidence of 46%. the median time to onset was 2 days. cardioversion was performed for 15 patients with an effectiveness of 80%. clinical and biological characteristics were similar between the groups with and without sva: saps 2 and sofa score at the beginning of septic shock, the existence of ards and cardiac biomarkers (nt-probnp, troponin). however, renal failure and the use of corticoid in septic shock were more frequent in the group with sva. the maximum doses of vasopressor agent were not significantly different between the groups with or without sva. myocardial dysfunction in sepsis defined by the left ventricle ejection fraction (lvef) less than 45% (or the need for inotropic drug for lvef > 45%) was not associated with the occurrence of sva (+sva group: n = 8; −sva group: n = 6; p: 0.57). sva was poorly-tolerated, observed by a significant decrease in mean arterial pressure and a significant increase in norepinephrine doses within 1 h of the start of sva. the occurrence of sva was associated with longer duration of use of vasopressor agent and a longer duration stay in icu (+sva group: 21 days, −sva group: 14 days; p = 0.03). there was no difference in duration of mechanical ventilation and hospital mortality between the two groups. conclusion the occurrence of sva is common in septic shock, poorly tolerated hemodynamically and associated with longer duration stay in the icu and vasopressor need. sepsis myocardial dysfunction isn't necessarily associated to the occurrence of sva. introduction a short term beneficial effect of prone position on cardiac index has been shown in 50% of 18 ards patients, and was related to an increase in cardiac preload in preload responsive patients (1) . the aim of this study was to evaluate the long term hemodynamic response to prone position in a larger series of ards patients. patients and methods single center retrospective observational study performed on ards patients hospitalized in a medical icu between july 2012 and march 2016. patients included were adults fulfilling the berlin definition for ards, undergoing at least one prone position session, under hemodynamic monitoring by the picco ® device, with availability of hemodynamic measurements performed before (t1), at the end (t2), and after the prone position session (t3). prone position sessions were excluded if they were performed >7 days after ards onset. the following variables were recorded: demographic, sapsii, ards severity and risk factor, sofa score and cumulative fluid balance at pp onset, delay between ards session and pp session, hemodynamic, arterial blood gas, ventilatory settings, plateau pressure, catecholamine dose and additional treatments. statistical analyses were performed using prone position session as statistical unit and mixed models taking into account both multiple prone position sessions by patient and multiple measurements during a prone position session. p < 0.05 was chosen for statistical significance. data are expressed as mean ± standard deviation. results 85 patients fulfilled the inclusion criteria over the study period, totalizing 149 prone position sessions (2 ± 1 sessions per patient). patients' age was 65 ± 11 y, 67% were male, 75% fulfilled the criteria for severe ards, and sapsii at icu admission was 64 ± 17. ards risk factors were pneumonia in 63 (74%), aspiration pneumonia in 26 (31%), and sepsis in 7 (8%) patients. duration of prone position sessions was 16 ± 3 h. hemodynamic measurements were performed in pp 13 ± 3 h after pp session onset. at session onset, sofa score was 15 ± 4, and cumulated fluid balance was 2.5 ± 7.1 l. vasopressor were used in 87%, inhaled nitric oxide in 22%, and neuromuscular blocking agents in 91% of the sessions. hemodynamic and respiratory parameters before, during and after the prone position sessions are reported in table 24 . cardiac index increased by at least 15%, decreased by at least 15% or remained stable in 35 (24%), 36 (34%), and 78 (52%) of the sessions, respectively. as compared to both other groups, pp sessions with significant increase in cardiac index had the following significant differences at t1 by univariate analysis: lower cardiac index, lower global end-diastolic volume, lower cardiac function index, and lower vasopressor dose. multivariate analysis is under investigation. conclusion prone position is associated with an increase in global end-diastolic volume, reversible after return in supine position that may explain the positive effect of pp on cardiac index observed in ¼ of the pp sessions. introduction make sure that our patient have a good circulatory condition is a daily challenge for the intensivist. one of the therapeutics is fluid and one of his purpose is to increase venous return and then cardiac output. in order to examine that, there are several tools as the transthoracic echocardiogram wich allows the visualisation and the study of the respiratory variability from the inferior vena cava (ivc). unfortunately there are some situations where the ivc visualisation is difficult (obesity, gut surgery, emphysema). the ivc is easily seen by a transhepatic ultrasound in her retrohepatic section. we make the hypothesis that the shape of the ivc could be predictive of fluid responsiveness. we have performed fluid challenge in patients under mechanical ventilation. the need for fluid therapy is the intensivist in charge decision. we performed a echocardiogram and we take two measures of the icv: major axis and minor axis, the icv is measured avec the sus hepatic vena. a elastometry index (ei) is determined which is the ratio of minor axis to minor axis. the fluid challenge is 250 ml of isotonic saline then we perform a new echocardiogram. a tag is written on the patient to take the same ultrasound slice. we retain one increase of 15% of the cardiac index (ic) as a success of the filling. we exclude the presenting patients a right cardiac insufficiency, an arrhythmia and/or a htap. the statistical analysis is realized with the software r. results between august, 2015 and january, 2016 we included 49 patients. the average age is of 59 years (24-81), igs2 of 48 (20-84), ejectionnal fraction of 48% 35-75) and the s wave tricuspid is 14 (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) . the causes of the filling were an oliguria (31%), a low blood pressure (20%), a low cardiac output (30%), a hyperlactatémia (9%) and an other cause in 10% of the cases. we find a positive correlation between the ei and the increase of the ic, also for the area of the vci and the respiratory variations of the vci (p0.05) the other variables are not predictive (bp, e/e' , e/a). the data are summarized in the picture 1. roc curves has been established ( only 16% of the journals studied required authors to use stard. a high impact factor and the year of the study were the items associated with a better sqs the presence of a conflict of interest was associated with a lower sqs in univariate analysis. a higher impact factor (> 5), was the only independent factors statistically significantly (p = 0.037) associated with higher sqs in a multivariate regression model. discussion our study showed that the sqs were very low. assessment of a study depends on quality of reporting. blindness and participant sampling are the cornerstone to evaluate such bias as spectrum, verification, review and selection bias of a study, and were unfortunately scarcely reported compared to existing data in diagnosis accuracy reporting. one of the limitation is the 5 years sample of the study. we have planned to continue the analysis for a 10-year review starting just after the 2003 stard publication. conclusion our study showed that several items remain poorly reported. we recommend systematic use of stard criteria in the elaboration and reporting of future studies that evaluates the preload dependence. introduction neurological impairment, i.e. encephalopathy, is commonly observed in patients with decompensated cirrhosis and/or portosystemic shunts admitted in icu. often ascribed to high plasmatic levels of ammonia, encephalopathy could also be induced by drugs or infection, due to altered blood-brain barrier (bbb) permeability. this latter setting is often underdiagnosed and encephalopathy related to hyperammonemia (so called hepatic encephalopathy-he) being pointed out as the culpit of all neurological symptoms in cirrhotic patients. quinolones and betalactamins were recently found in the cerebrospinal fluid of he patients and it has been shown that the expression of efflux pumps, responsible for drugs passing through the bbb, was altered in animal models of he. the purpose of this study was to assess the incidence of neurological impairment, i.e. encephalopathy, in cirrhotic patients hospitalized in discussion overall, we reported a higher rate of lumbar puncture than those reporting in others studies concerning status epilepticus. furthermore the rate of 16% of pleocytosis directly linked to status epilepticus is slightly higher than in most studies. unfortunately we didn't realize a second lumbar puncture to assess the pleocytosis normalization during the days following the first lumbar puncture. the pathophysiological hypothesis of this phenomenon may be that prolonged/repeated seizures during status epilepticus would induce a blood-brain barrier dysfunction thereby favoring a cerebrospinal pleocytosis. conclusion in our study, 16% of status epilepticus without infectious or neoplastic origin had a cerebrospinal pleocytosis directly linked to status epilepticus. this pleocytosis was significantly associated with myoclonic seizures and blood leukocytosis. these data may help to interpretation of cerebrospinal fluid pleocytosis during status epilepticus. introduction neurological prognostication from cardiac arrest survivor is a current concern. eeg patterns and nse dosage are two important prognostic factors. nse threshold for prediction of poor outcome appear controversial, in part, because of variability in dosage timing and measurement techniques. synek score is routinely used in our center to classify comatose patients in post cardiac arrest. the aim of this study was to assess the prognostic value of nse and synek classification to predict poor neurological outcome. introduction traumatic brain injury (tbi) is a major public health problem. it is the leading cause of death and disability in young subjects. one of the principles of the tbi management is prevention of secondary cerebral insults including maintaining perfusion and cerebral oxygenation, control of intracranial pressure (icp). an increase in icp above 20 mmhg is associated with poor outcome. cerebral hypoxia can occur with normal level of icp and cerebral perfusion pressure (cpp).monitoring of regional partial pressure of brain tissue oxygen (pbto2) is a safe and reliable method for measuring cerebral oxygenation. a retrospective single-center observational study was conducted between january 2012 and december 2013, aimed to study the influence of pbto2 with severe tbi patients outcome at 6 months through glasgow outcome scale (gos). the hourly values of icp, pbto2 and cpp were recovered on daily monitoring sheets. we compared two groups according to their gos. during the study period, 66 patients underwent a monitoring icp and pbto2. results the mean age was 33.7 ± 14.1 years. 78.8% were men. the initial glasgow score was 6.6 ± 3.7. the mean simplified acute physiology score (saps ii) was 43.4 ± 11.2 and injury severity score (iss) 30.5 ± 9.7. at 6 months, 7 patients had died (gos1). forty patients had a good outcome: gos 4-5 (group 1). sixteen patients had poor outcome: gos 2-3 (group 2). in group 2, there are significantly more pbto2 hourly values below 10 mmhg at day0 (5.5 ± 6.4 vs 2.3 ± 3, 2 in group 1, p = 0.025); and more pbto2 hourly values greater than 20 mmhg at day0 (8.4 ± 7.0 vs 4.8 ± 4.9, p = 0.045). conclusion pbto2 less than 10 mmhg or greater than 20 mmhg at day0 is associated with poor outcome at 6 months in the severe tbi. the pbto2 allows a more individual approach of monitored tbi. none. introduction organ donation in patients after a decision to withdraw life-supportive therapies (wlst) (maastricht 3 condition: m3) have been performed in our hospital since may 2015. we report here main characteristics of donors, data on m3 procedure and results on renal transplant recipients. patients and methods all potential donors were included in a survey from may 2015 to june 2016, according to the french national m3 protocol defined by the french organ procurement agency (agence de la biomédecine:abm) [1] .the demographical, clinical and biological characteristics of the donors, the different deadlines and times of the protocol and data of renal transplantation were collected and analyzed. results 28 patients had inclusion criteria. patients were admitted in intensive care unit for cardiac arrest (68%), strokes (14%), traumatic brain injury (14%), ards (4%). of them, 15 procedures (54%) were stopped (6 refusals of organ donation, 4 medical contra-indications discovered with additional exams, 1 failure of vessel cannulation, 4 deaths more than 3 h after extubation). 28 kidneys were harvested and 26 transplantations performed (1 renal cancer discovered during procurement surgery).the characteristics of the donors, deadlines of the protocol and transplant recipients are reported in the table 26 . conclusion the french programm maastricht 3 offered a new possibility of organ donation in our hospital. thanks to these donors, the number of renal grafts increases and the preliminary results on transplant recipients are encouraging in line with the preliminary report of the abm. nevertheless, it is necessary to follow the transplant recipients and extend the procedure to new centres. in this study, we found some relevant risk factors for microaspiration (age, low score at gcs) consistent with literature on the subject. patients with paralytic agents had less gam which may be due to higher peep, higher cuff pressure and less enteral nutrition because of the severity of the underlying diseases. conclusion this study did not show any increased risk of microaspiration in intubated copd patients, whatever stage of copd. introduction protected specimen brush (psb) is considered to be one of the standard methods for the diagnosis of ventilator-associated pneumonia (vap). to our knowledge, there is no study assessing effect of prior antibiotherapy on direct examination, bacteriological culture and concordance of direct microscopy and culture. patients and methods all consecutive episodes of suspected vap were retrospectively evaluated between january 2014 and december 2014 in a 20-bed intensive care unit. patient's characteristics and preexisting conditions were abstracted from the medical charts. after assessment of vap probability using the clinical pulmonary infection score (cpis), psb were performed in patients with a cpis of 6 or more. based on antibiotic treatment in patients when bacteriological specimens were obtained, two groups were defined: no antibiotic group and antibiotic treatment started before psb group. two independent bacteriologists retrospectively reviewed direct examination and culture of psb to assess bacteriological concordance, defined as non-concordant when direct examination and culture were different, concordant when direct examination and culture were similar and partially concordant when either direct examination or culture were comparable but with other microorganisms lacking in one or the other method. results during this 12-months period, among 73 mechanically ventilated patients, 116 episodes of suspected vap with psb were evaluated. we found 60% of psb (n = 70) performed without antibiotic treatment and 40% of psb (n = 46) performed under antibiotherapy. we found no significant differences in patient's demographics, characteristics, and severity between both groups. patients received antibiotics for the following reasons: aspiration pneumonia (n = 12), peritonitis (n = 8), vap (n = 7), community-acquired pneumonia (n = 4), septic shock of unknown origin (n = 4), pyelonephritis (n = 3), meningitis (n = 2), acute pancreatitis (n = 2) and others (n = 4). the median duration of mechanical ventilation in the antibiotic receiving group and in the group without antibiotics was 7.5 days (iqr; 5-12 days) and 9 days (iqr: 5-22), respectively. when psb was performed under antibiotic treatment, direct examination was positive in 26% (n = 12), culture was positive in 28% (n = 13) and those methods were concordant, non concordant and partially concordant in 93% (n = 43), 4% (n = 2) and 3% (n = 1), respectively. on the other hand, when psb was performed without antibiotics, direct examination was positive in 65% (n = 46), culture was positive in 62% (n = 43) and those methods were concordant, non concordant and partially concordant in 71% (n = 50), 18% (n = 12) and 11% (n = 8), respectively. in univariate analysis, we found a significantly higher proportion of negative direct examination and negative culture in the antibiotic group (p > 0.001). moreover, these methods were significantly more frequently concordant (p = 0.01), with a higher rate of both negative microscopic exam and culture when compared to the no antibiotic group (76%, n = 33 vs 38%, n = 18). surprisingly, among the 13 patients previously treated with antibiotics with positive culture, 38% (n = 5) of the microorganisms showed antibiotics sensitivity. discussion whether prior antibiotic treatment may induce false negative of false positive treatment is a well-recognized phenomenon, the precise effect of antibiotics on direct examination and quantitative culture is not well assessed in vap. moreover, despite recent development of clinico-radiological score, diagnosis of vap remains difficult, with no gold-standard. therefore, bacteriological guided therapy is of particular importance. we found psb realization under antibiotic treatment is associated with a lower rate of positive direct examination and culture and suggest performing these bacteriological samples without antibiotherapy. some authors have suggested lowering the diagnostic threshold point of this bacteriological technique in order to preserve its accuracy. however, we can postulate that microorganisms responsible of superinfection in mechanically ventilated patients treated with antibiotics may be resistant and therefore the psb could be positive. conclusion in patients with a high pre-test probability of ventilatoracquired pneumonia, recent introduction of antibiotics significantly reduced the diagnostic accuracy of protected brush specimen by reducing rates of positive direct examination and culture. further studies should evaluate if antibiotic discontinuation may revert this effect. ann. intensive care 2017, 7(suppl 1):7 we have had non conflict of interest in this study. results we included 44 patients in the phase1 and 58 patients in the phase2. baseline characteristics of patients were similar in both groups. compliance with all the measures has been improved between the two period from 0 to 32.75%. the incidence density decreased from 33.74 to 18.05 vap per 1000 ventilator days between observational and interventional period, but the all-cause mortality was almost equal in the 2 groups (88.6 vs. 86%). discussion with the implementation of our bundle, observance of the team were improved in the second group, compared to the first and the incidence density decreased from 33.74 to 18.05 vap per 1000 ventilator days between both period. this result is consistent with the littérature. sure enough, many studies show the same effect of vap prevention with a decrease of nearly 50% of the incidence density of vap, after implementation of a «ventilator -bundle [2] . conclusion the implementation of a "ventilator bundle, " has significantly reduced the incidence of vap in our service. in the contrary, our study failed to demonstrate a reduction in mortality. introduction with an increasing incidence and high mortality rates, sepsis is a public health issue. there is growing evidence that sepsis induces long lasting alterations of transcriptional programs through epigenetic mechanisms that may lead to protracted inflammation, organ failure, sepsis-induced immune suppression (siis), secondary infections and death. we hypothesized that epigenetic changes contribute to the pathophysiology of siis. to test this hypothesis, we studied the effects of histone deacetylases (hdac) inhibition with trichostatin a (tsa) in a double-hit murine model of siis and secondary pneumonia. materials and methods c57bl/6 mice were treated with tsa (2 mg/ kg ip) or saline serum (ctl) 30 min before induction of sepsis by cecal ligation and puncture (clp). surviving mice underwent intratracheal instillation of 1.5 × 10 6 cfu of pseudomonas aeruginosa 8 days after clp. we evaluated the effect of tsa on survival and cellular responses to the primary and secondary infections. cellular responses in the blood, spleen and bal were assessed by flow cytometry after clp (days 1, 3 & 8) and after pneumonia (4 & 12 h). we also studied lymphocyte apoptosis and dendritic cells (dc) expression of cd40, cd86, and mhcii. bacterial clearance was assessed in the bal and in the blood 4 and 12 h after pneumonia. continuous variables represented as mean ± sd were compared using student t test. kaplan-meier curves were compared by the log rank test. p < 0.05 indicated statistically significant differences. results whereas treatment with tsa did not change survival after clp, tsa improved survival after tracheal instillation of p. aeruginosa (p = 0.009, fig. 22 ). tsa-treated mice had significantly higher absolute dc, t and b-lymphocytes counts with reduced lymphocyte apoptosis after clp. four hours after secondary pneumonia, tsa-treated mice had significantly higher dc counts and improved bacterial clearance in the bal, with reduced systemic dissemination of p. aeruginosa. conclusion hdac inhibition with tsa improves survival in our murine model of secondary pneumonia, improves bacterial clearance and attenuate cellular features of siis. these results suggest that sepsisinduced epigenetic changes contribute to the advent of siis. comprehensive characterization of epigenetic changes associated with siis might allow us to identify new therapeutic targets to reprogram immune cells in sepsis and avoid siis. length of icu stay was 16 ± 14 days. 47 patients acquired 58 nis (36.2% bsi, 20.5% pneumonia, 10.3% cri and 10.3% uti. there was no bacteriological documentation of ni in 22.5% of cases. nis occured 4 days post burns. the most three isolated pathogens were: acinetobacter spp. (31%), p. aeruginosa (22.5%) and extended spectrum betalactamase-producing enterobacteriaceae (17%). the most frequently administered antibiotics were polymyxin/carbapenem/teicoplanin combination (21%), polymyxin/carbapenem combination (15%) and carbapenem/tigecycline combination (15%). in our study, mortality rate was 50%. conclusion nosocomial infection occured in 24.7% of cases in burn patients, caused by acinetobacter spp, p. aeruginosa and enterobacteriaceae blse. so, eradication of infection in burn patients require effective surveillance and infection control in order to reduce mortality rates, length of hospitalization and associated costs. introduction infection of the lower respiratory tract is the most common cause of infection in intensive care unit (icu) (1) . although the attributable mortality of ventilator associated pneumonia remains debated, the recurrence of these infections is always associated with a significant morbidity (2) . staphylococcus aureus methicillin-sensitive (sams) is one of the most frequently germs involved in icu pneumonia especially in trauma patients. the aim of the study was to establish the risk factors associated with microbiological treatment failure of pneumonia, caused by sams. materials and methods we retrospectively identified 185 patients who developed a first episode of ventilator associated pneumonia caused by sams during a 6 years-period (2009-2014). the primary end point was the microbiological treatment failure defined as a second episode of pneumonia caused by sams corresponding to either a persistent or a recurrence of the pneumonia (fig. 23) . the primary aim of the study was to identify factors associated with a treatment failure, the secondary objective was to identify factors associated with the occurrence of second episode (i.e. persistent, recurrence, superinfection and/or relapse of pneumonia caused by any bacteria) during or after treatment of the first episode caused by sams. definition of outcomes was based after analysis of current concepts available in the literature. factors associated with primary and secondary objectives in univariate analysis (p-value < 0.20), or clinically relevant ones, were entered in a multivariate logistic regression. the final selection was performed using the stepwise selection based on the akaike criterion. results fifty-nine patients (33.3%) developed a second episode of pneumonia and among them, 30 (16.6%) were considered as a microbiological failure. in a multivariate analysis, the association of oropharyngeal flora (fop) with the sams (or, 3.86; 95% ci, 1.33-11.11; p = 0.011) and the need of emergency surgery (or, 5.26; 95% ci, 1.39-35.2; p = 0.035) were predictive of a microbiological failure. empirical antibiotic therapy with amoxicillin-clavulanic acid (or, 2.28; 95% ci, 1.15-4.51; p = 0.017) and performing emergency surgery (or, 3.60; 95% ci, 1.34-9.65; p = .011) were predictors of a second episode of pneumonia caused by any bacteria. conclusion in this retrospective, monocentric study, the co presence of orophryngeal flora and the need of emergency surgery were associated with microbiological failure of pneumonia caused by sams in icu. introduction ventilator-associated pneumonia is a major iatrogenic problem since it is a cause of hospital morbidity, mortality and increase of health care costs. it has been studied many times, but data's revision is always necessary. our study aimed to describe epidemiology of ventilator-associated pneumonia and identify local causative pathogens. we carried out a prospective study in an intensive care unit. were included patients intubated for more than 48 h, from april 2015 to may 2016, and presenting signs of ventilator-associated pneumonia (fever, abundant and purulent secretion, increase of fio 2 greater than 0.2, signs on chest-x ray) with positive culture of endotracheal aspirate. were excluded patients with germ colonization. results a total of 268 patients were ventilated for more than 48 h. among them thirty-four patients aged of 39 ± 18.5 years presented 54 episodes of ventilator-associated pneumonia (that is 1.58 ± 0.85 episodes per patient). the mean sofa score was 5.2 ± 1.8. the main reasons of mechanical ventilation were loss of consciousness secondary to poisoning (20%), respiratory distress (20%) and status epilepticus (12%). the mean duration of stay was 62.5 days with extremes at 7 and 180 days. the average time between hospitalization and suspicion of ventilator-associated pneumonia was 5.9 ± 2.7 days. the average value of the clinical pulmonary infection score at suspicion was 5 ± 1.26. the average time between recurrences was 16.8 days with extremes at 4 and 39 days. the culture of endotracheal aspirate identified two pathogens in 11%. it reveled acinetobacter baumanii in 35% in which 63% were imipenem resistant, pseudomonas aeroginosa in 33%, klebsielle pneumoniae in 22%, staphylococcus fig. 23 see text for description aureus methicillin resistant in 7%. extended spectrum β-lactamases bacteria were found in 10% and carbapenemases producers in 12%. empirical antibiotherapy was always association of imipenem and colistin. it was necessary to adapt it to antibiograms in 33/54. ventilator-associated pneumonia was complicated by septic shock in 28% and acute respiratory distress syndrome in 24%. patients evolved to healing in 63% of episodes (n = 34), to superinfection in 26% (n = 14) and to death in 9% (n = 5). pseudomonas aeruginosa was the most frequent germ in superinfection (7/14) , acinétobacter baumanii was the most pathogen associated to death (3/5). conclusion ventilator-associated pneumonia is an iatrogenic disease that threatens lives. it's in part avoidable. preventive measures have to be implemented to reduce its frequency, consequences and costs. introduction during mechanical ventilation, mismatch between respiratory muscles activity and the assistance delivered by the ventilator results in dyspnea and asynchrony and is commonly observed in intensive care unit (icu) patients. proportional assisted ventilation (pav) is a ventilatory mode that adjusts the level of ventilator assistance to the activity of respiratory muscles estimated by an algorithm. to date, pav has been mostly studied in patients without severe dyspnea or asynchrony. we hypothesized that, compared to pressure support ventilation (psv), pav will prevent severe dyspnea or asynchrony. patients and methods were included icu mechanically ventilated patient exhibiting severe dyspnea or asynchrony with psv. three conditions were successively studied: 1) psv on inclusion (baseline), 2) psv after optimisation of ventilator settings in order to minimize dyspnoea and asynchrony (optimisation), and 3) pav. ten-minutes recording were performed with each condition. the intensity of dyspnea was assessed by the visual analogic state (vas, only in patients able to communicate) and by the intensive care respiratory distress operating scale (ic-rdos) for all the patients. the electrical activity (emg) of extradiaphragmatic inspiratory muscles was measured. the fig. 24 bayesian nma with random effect prevalence of asynchrony was quantified by the visual inspection of the airway flow and pressure traces. results 34 patients were included, 74% male, aged 66 [58-78] years, saps2 57 [39-66], mechanically ventilated for 6 [4] [5] [6] [7] [8] [9] days. the tidal volume (tv) was higher in the optimisation and pav than in the basal condition (table 27 ). the respiratory rate(rr) was lower with pav than in the other conditions. the dyspnea-vas was lower with optimisation and pav than with the basal conditions. the ic-rdos was lower with pav than with the two other conditions. the asynchrony index was lower with pav than with the two other conditions. parasternal emg activity was lower with pav and optimisation (fig. 25) . conclusion in icu patients receiving mechanical ventilation with psv and exhibiting severe dyspnea or asynchrony, the optimisation of ventilator settings with psv and the pav mode decrease in the simiar way the severity of dyspnea and the prevalence of patient-ventilator asynchrony. introduction in spite of recent research and progress in weaning protocols, extubation failure still occurs in 10-20% of patients and is associated with poor outcomes, with a mortality rate of 25-50%. many risk factors for planned extubation failure have been suggested, including hypercapnia at end of spontaneous breathing trial (sbt). however, performing arterial blood gases at the end of sbt is not routinely recommended whereas etco2may be routinely monitored during a low pressure support sbt. the aim of this prospective observational study was to determine the clinical usefulness of etco2 to predict extubation failure. patients and methods we recorded clinical data and etco2 during a successful 1 h low level pressure support sbt (at the beginning, after 5 min and at the end of the trial). patients ventilated through tracheostomy and unplanned extubations were excluded. extubation failure was defined as death or the need for reintubation within 72 h (1) after extubation; this delay was prolonged to 7 days (2) in case of noninvasive ventilation after extubation, which was systematic in older patients or those with cardiorespiratory disease, as per our weaning protocol. multivariable logistic regression analysis was performed to identify independent variables associated with extubation failure. results one hundred and fifteen ventilated patients were enrolled in our study from july 2015 to june 2016. the median age of these patients was 63 [52-75] years, their median simplified acute physiology score (saps) ii was 48 [38-61] points and 42.5% (n = 49) were female. seventeen (15%) patients had chronic obstructive pulmonary disease. reintubation rate was 15% (n = 18). etco2 at other time points as well as its changes during the sbt were also similar between groups. the three variables predicting extubation failure in the multivariable logistic regression model were a past medical history of cirrhosis, acute respiratory distress syndrome before weaning and lower minute ventilation at the end of sbt. conclusion etco2 during a successful sbt seems useless to predict outcome of extubation. introduction airway management in intensive care unit (icu) patients is challenging [1] . "airway failure", defined as the inability to breathe without endotracheal tube, differs from "weaning failure", defined as the inability to breathe without an invasive mechanical ventilation. however, most of the studies assessing predictive factors of extubation failure did not separate airway from weaning failure. we aimed to describe incidence of extubation failure in critically ill patients, separating for the first time airway from weaning failure, in a prospective multicenter observational study. patients and methods a prospective, observational, multicenter study was conducted in 26 french icus. all adult patients consecutively extubated in icu were included. an ethics committee approved the study design (code uf: 9242, register: 2013-a01402-43). the study was registered on clinicaltrials.gov (identifier no.nct 02450669). clinical parameters were prospectively assessed before, during and after extubation procedure. extubation failure was defined as the need to reintubate less than 48 h after extubation. extubation failure could be due to airway failure, weaning failure or mixed airway and weaning failure. results from december 2013 to may 2015, 1514 intubation-procedures were studied in 1465 patients from 26 centers. 49 patients (3.2%) were intubated twice. the median number of intubation-procedures included by center was 27 . the flow chart of the study is shown in fig. 26 . incidence of extubation failure was 10.4% (157 of 1514 intubation-procedures). incidence of airway failure, weaning failure and mixed failure were respectively 4.6% (70 of 1514), 5.2% (78 of 1514) and 0.6% (9 of 1514). conclusion extubation failure at 48 h occurred in 10.4% of the 1514 extubation procedures recorded, 44% due to airway failure, 50% to weaning failure and 6% to mixed airway and weaning failure. specific risk factors will be determined using this multicenter database. introduction acute on chronic liver failure (aclf) have been recently defined by an acute decompensation of a chronic liver disease associated to organ failure and a high mortality rate. few authors reported on the use of total plasma exchange (tpe) in patients with the current definition of aclf. the aim of this pilot study was to evaluate the efficiency and safety of tpe in critically ill cirrhotic patients admitted with aclf in the icu. patients and methods a prospective cohort of cirrhotic patients admitted to the icu between february 2015 and february 2016. tpe was performed using a plasma filter (tpe2000, hospal ® ) on a cvvhdf machine (prismaflex ® , baxter ® ) connected to the patient with a femoral double lumen 13f catheter. the plasma volume exchanged per session was 1.3-1.5 of the total plasma volume. ratio and type of fluid replacement were 50% with 5% albumin solution followed by 50% with fresh frozen plasma. clinical and biological parameters, and the following scores meld, sofa, clif-sofa, clif-of and child pugh were evaluated prior, after tpe session and 7 days distant of treatment. results seven male patients with a mean age of 50.6 ± 7.7 years comprised the study and had a total of 20 tpe sessions. the etiology of cirrhosis was alcoholic (n = 6) or post-hcv (n = 1). the reasons of aclf were acute alcoholic hepatitis (n = 2), variceal bleeding (n = 2) and sepsis (n = 3). prior to tpe, the mean scores of sofa, clif-sofa, clif-of, meld and child-pugh were respectively 9.4, 12, 11.7, 37.6 and c12.5. mean total bilirubin prior and after tpe sessions was reduced from 392.3 ± 117.8 µmol/l to 244.9 ± 93.2 µmol/l (reduction of 37.5%; p = 3.81e−6); at day 7, mean total bilirubin was still lower at 333 ± 132 µmol/l (p = 0.1). mean inr prior and after tpe improved from 5.54 ± 3.38 to 2.32 ± 0.80 (reduction of inr of 58.1%, p = 4.76e−5) and at day 7 of treatment at 4 ± 1.64 (reduction of 43%, p = 0.125). mean ggt levels reduced by 28.5% (p = 0.01). mean platelet counts (50.8 ± 19.5 g/l) reduced by 10.2% (p = ns). the probability of survival at 10, 28 and 90 days was 42.8, 28.6 and 14.3%. one patient was transplanted and still alive. tolerance during sessions was good similar to cvvhdf. two side effects related to the femoral catheter were observed (bacteremia and hemorrhagic shock post catheter ablation). conclusion this preliminary study of tpe in aclf showed a marked reduction of liver enzymes and improvement in coagulation parameters with a relative good safety. a specific caution should be undertaken regarding catheter related complications. tpe worth to be fig. 26 flow chart of the free-rea study introduction extubation is a key moment for the patient on his way to recovery. extubation failure concerns 10-20% of icu patients and is closely linked to nosocomial pneumonia. the practice concerning enteral feeding interruption at time of extubation has not been investigated. fasting before extubation may prevent aspiration and development of nosocomial pneumonia. thus, fasting and gastric content suctioning before extubation may be reasonably considered as a mean to reduce this burden. fasting before extubation may prevent aspiration and development of nosocomial pneumonia. thus, fasting and gastric content suctioning before extubation may be reasonably considered as a mean to reduce this burden. however, fasting, as recommended before elective general anesthesia is likely to be ineffective in the setting of extubation in the icu, due to patients' gastroparesis and prolonged gastric stasis. beyond the potentially unnecessary burden in terms of paramedical workload, fasting may have some side effects such as caloric deficit, hypoglycemia, or delayed extubation. given the current lack of objective data concerning the clinical practice of feeding/fasting and gastric tube suctioning before extubation in the icu, we undertook this descriptive study to assess current practice. materials and methods we conducted a retrospective, multicenter study in eleven intensive care units in the west of france over a 1 month timespan. all patients extubated were included and data about enteral feeding during the peri-extubation period as well as extubation failure and nosocomial that pneumonia occured within 7 days were recorded. data observed in the eleven participating centers were completed with a short email survey concerning declarative practice performed among 43 intensive care units. results during the study period, 162 patients were included. overall, 25 patients (15%) failed extubation and needed reintubation within the 7 days following planned extubation. pneumonia was significantly more frequent reintubated patients than the other (36 vs. 4%, p < 0.01). hundred patients (62%) received enteral feeding at the time of extubation. compared to patients who did not receive enteral feeding, those patients had a higher disease severity (sapsii score 50, [41; 63] vs. 45 [35; 52], p < 0.01; longer duration of mechanical ventilation 7 [4; 13] vs. 1.5 [1; 3] days, p < 0.01). accordingly, those patients had a higher rate of extubation failure (21 vs. 7%, p = 0.01) and pneumonia (13 vs. 3%, p = 0.05). among the 100 patients receiving enteral feeding, fasting was implemented before extubation for 64 patients (64%). similarly, the incidence of pneumonia was not different between groups (n = 9 (14%) vs. n = 4 (11%), p = 0.76). after extubation, the fasting patients experienced a longer delay until feeding resumption as compared to non-fasting patients (21 h [6; 42] vs. 8 [5; 22] ), but this difference did not reach statistical significance. overall gastric content suctioning before extubation was not commonly performed; before extubation: 30% of the fasting patients and 26% of the non fasting patients. among the 11 participating centers, while some centers imposed a fasting period before extubation to all their patients, some did it infrequently. however, no center never imposed fasting, illustrating between and within center heterogeneity. this heterogeneity was confirmed on the larger scale declarative email survey (88% response rate amont 43 units) which showed that only 44% of the units had a written standardized operational procedure for extubation. survey respondents reported to practice fasting before extubation "always", "frequently" and "never or rarely" in respectively 71, 21 and 8% of cases. conclusion both practices, fasting as well as pursued nutrition until extubation are commonly performed in icus, with little standardization of practice. safety seems equivalent, as no clinically significant difference in terms of reintubation rate and pneumonia were observed. thus, the equipoise condition appears met to undertake a trial evaluating feeding strategies in the peri-extubation period. introduction noninvasive ventilation (niv) has become a cornerstone for the supportive therapy of acute respiratory failure (arf). survival benefits in chronic obstructive pulmonary disease (copd) and cardiac patients have been demonstrated. although arf and copd patients are at risk of malnutrition that adversely affects patient outcomes, few data are available regarding the management of nutritional support in non-invasively ventilated patients. we sought to describe nutritional management in patients receiving niv as the first line therapy for arf. secondary objectives were to assess the impact of early nutrition use on the need for invasive mechanical ventilation, occurrence of icuacquired pneumonia, length of stay, and death. patients and methods we conducted an observational study from the multicenter french database fed by 20 french icus. our institutional review board approved this study. adult medical patients admitted to the icu and receiving niv for more than 2 days were included. exclusion criteria were patients admitted after surgery, readmitted in icu, patients with neuromuscular disease and treatment-limitation decisions on admission. four groups of patients were defined according to nutrition received during the first 2 days of niv: (1) no nutrition; (2) enteral nutrition: patients who received enteral nutrition with or without parenteral nutrition; (3) parenteral nutrition only (3) oral nutrition only. the impact of nutrition on day-28 mortality was assessed through the use of a cox model adjusted on clinically relevant covariates. the impact of nutrition on other secondary end-point i.e. icu-acquired pneumonia occurrence, need for invasive mechanical ventilation were assessed using a fine & gray models. patients were censored after 28 days of follow-up. choice among collinear variables was performed considering clinical relevance, rate of missing variables and reproducibility of definitions. results were given as hazard ratio (hr) for cox models and subdistribution hazard ratios (shr) and 95% confidence intervals (ci). the impact on duration of stay was estimated by a multivariate poisson regression. p values less than 0.05 were considered as significant. statistical analysis was performed using sas 9.4 (cary, nc). results during the study period, 16,734 patients were included in the database and 1075 met inclusion criteria. among them, 622 received no nutrition; 28 received enteral nutrition, 74 received parenteral nutrition only, and 351 received oral nutrition only. overall, 86 patients developed icu-acquired pneumonia (8%), 158 required invasive mechanical ventilation (14.7%) and 161 died before day-28 (15%). median length of stay was 6 days [4; 9]. after adjustment for confounders, type of nutrition support was associated with an increase day-28 mortality (p = 0.02). compared to oral nutrition, enteral nutrition was associated with an increase day-28 mortality [shr 2.91, 95% ci 1.44-5.89; p = 0.003] whereas parenteral nutrition and no nutrition did not influence this outcome. the type of nutrition was not associated with the occurrence of icu-acquired pneumonia (p = 0.18). however, patients who received enteral nutrition experienced more frequently icu-acquired pneumonia [shr = 3.00, 95% ci 1.08-8.37; p = 0.036] as compared to oral nutrition patients. ventilator free days within the 28 days were negatively associated with the type of nutrition (p < 0.0001). compared to oral nutrition, parenteral and enteral nutrition were negatively associated with ventilator free days within the 28 days [rr per day = 1.48, 95% ci 1.22-1.78; p < 0.0001 and rr per day = 1.77, 95% ci 1.37-2.30; p < 0.0001]. delta paco 2 measured between the first 2 days was not associated with any type of nutrition. conclusion more than half the patients receiving niv were fasting within the first two niv days. oral nutrition was prescribed for onethird of them and was well tolerated. lack of feeding or underfeeding had no impact on mortality and ventilator free days within the 28 days. however, enteral nutrition was associated with an increased occurrence of icu-aquired pneumonia and a higher mortality rate. was high, caloric debt during temporary ecls was low in comparison with previous results [1] . overnutrition was frequent in the nec group and would justify implementation of nutrition protocol. incidence of gi intolerance remains frequent and could justify systematic used of motility agents with introduction of en. conclusion enteral nutrition in patients treated with temporary extracorporeal life support is feasible and may be improve with systematic motility agents and implementation of nutritional protocol. introduction cardiac surgery with cardiopulmonary bypass (cpb) is associated with a generalized inflammatory response with concomitant immune paresis which predisposes to the development of postoperative infections and sepsis (1) . lymphocytes are essential agents of innate and adaptive immune responses during infections or inflammation processes. lymphopenia has been associated with immune dysfunction during septic shock, and it has been shown that low absolute lymphocyte count was predictive of postoperative sepsis (2) . furthermore, impaired lymphocyte function probably occurs after cpb. thus, we investigated mechanisms involved in postoperative lymphopenia and impaired lymphocyte function after cpb. the aims of this study were: 1) to describe a potential relationship between lymphopenia and occurrence of postoperative infections. 2) to demonstrate that cpb induces lymphocytes apoptosis. 3) to demonstrate that cpb impaired lymphocyte function (ability to proliferate). 4) to demonstrate that il-10, pd-l1 (programmed cell death 1 ligand 1) and indoleamine 2,3-dioxygenase (ido) could be interesting targets to restore lymphocyte ability to proliferate after cpb. patients and methods blood cell counts with differentials obtained within the first postoperative week were analyzed in 828 patients undergoing cardiac surgery in 2015. postoperative lymphopenia was defined as a lymphocyte count <1.3 × 109 cells l −1 . postoperative infections were defined following cdc criteria. study procedures: the following analysis were performed before (t0) and 24 h after (t1) cardiac surgery with cpb: lymphocyte apoptosis; t-cell proliferation ability following polyclonal stimulation; hla-dr and pd-l1 expression on monocytes; plasma ido activity and il-10 levels; and the ability of lymphocytes to undergo a clonal proliferation when stimulated using specific inhibitors of il-10 and ido. the study was approved by our local ethics committee. patients were informed of the observational nature of the study and gave their consent. 1. early lymphopenia after cpb was associated with the occurrence of postoperative infection: postoperative infections occured with a median delay of 6 days. patients who developed postoperative infections had a significantly lower lymphocyte count at day 4, day 5 and day 6 than patients without postoperative infections. 2. cpb induced lymphocyte apoptosis and decreased t-cell proliferation ability. 3. cpb during cardiac surgery decreased mhla-dr expression. 4. cpb increased ido activity, pd-l1 expression and il-10 plasma levels. 5. il-10 or pd-l1 inhibition of inhibition could restore ability of lymphocytes to proliferate, although ido inhibitors did not show any effect. we provided new evidences that cpb induces immunosuppression. we also demonstrated that il-10 and pd-l1 could be interesting targets to restore ability of lymphocytes to proliferate. as maintaining mv during cpb decreased plasmatic levels of il-10, our study brings new evidences that ventilator strategies could be of interest to decrease postoperative infections. respectively 50.7% (n = 3729), 41.1% (n = 3024) and 16.1% (n = 1174) of the included patients. mortality was of 47.4% in the overall population (n = 3483) and was higher in neutropenic patients (60.3 vs. 43.6% in non-neutropenic patients; p < 0.001). neutropenia was independently associated with poor outcome when adjusted for underlying malignancy, allogeneic stem cell transplantation and severity as assessed by organ support (or 1.45; 95% ci 1.27-1.65). mortality decreased progressively over time in both non-neutropenic (from 54 to 44%; p < 0.0001) and in neutropenic patients (from 72 to 57%; p < 0.0001). when adjusted for confounders, admission during a more recent period was independently associated with favourable outcome and did not change the final model. conclusion this preliminary analysis suggests a meaningful survival in neutropenic critically ill cancer patients despite an independent association between neutropenia and mortality. additional analyses are on-going in order to adjust for study weight, heterogeneity across studies, assess the influence of neutropenia duration or g-csf use, and confirm the influence of neutropenia in a predefined subgroup of patients. introduction candida bloodstream infections (cbi) are frequent and increasing in hospitalized patients, especially in intensive care units. considering the results of some experimental in vitro and animal studies, it seems that yeasts belonging to candida genus are able, so as to survive, to modulate the immune response of the host by guiding t cells polarization to th2 profile. th1 and th17 cytokines are known to be involved in host defense against cbi. however, these data are mainly experimental or collected after candidemia. the aim of this study is to precise kinetic of cytokines network during human cbi. this was an ancillary study of an institutional project dedicated to pathophysiology of candidiasis. we have included 32 patients with candidemia and 54 controls (27 matched hospitalized controls and 27 healthy subjects). the sera of cases were gathered before (almost 5 days before), during and after the isolation of yeasts from blood culture, defined as day 0 (d0). quantitative analysis of 28 cytokines by luminex ® technology and of (1,3)-β-d-glucans by fungitell ® test were performed on 132 samples. the amplitude of th profile response was expressed by summing the amount of the most relevant cytokines for th1, th2 and th17 profiles, in pg/ ml. for each patient, the highest level of response was considered as 100%. results are expressed for the population by means of the results. we then performed univariate analysis (fischer exact test for qualitative variables, mann-whitney and wilcoxon test for quantitative variables, spearman for correlation; graphpad prism v6 software) and a multidimensional analysis by principal component analysis (pca; igorpro software). results patients with candidemia exhibited an increase in proinflammatory cytokines (ifnγ, tnfα and il-12), in comparison with the anti-inflammatory cytokines (il-4 and il-10) before d0 (p = 0.034) in univariate analysis. the ratio between mean values reverses at d2 and d3 (p = 0.02) and the increase of th2 response level from d0 to d4 is correlated to the decrease of th1 response (r = −0.885; p = 0.033) in univariate analysis and pca. a pro-inflammatory response (th1) is associated with a reduced mortality (rr = 0.58 [0.34; 0.98]) and with a lower β-d-glucans levels (p < 0.0001). discussion we describe here a dynamic cytokine profiles in response to candidemia. pro-inflammatory response predominates before d0 and reverses after. this is contradictory to the postulate that an antiinflammatory background could predispose to invasive candidiasis in icu patients and exhibiting a "post-infectious immune suppression conditions". but the relative deficiency in th1 response compared to simultaneous anti-inflammatory cytokines secretion observed after cbi is in accordance with experimental data, suggesting the modulation of the immune response by candida. the link between cytokinic profile and mortality can also raise the hypothesis of an influence by genetic factors on the regulation and direction of the immune response and so, the existence of a high-risk population. conclusion these data suggest a relation between candida and the orientation of the immune response towards a pattern deleterious for the infected host. this could allow to determine the most relevant cytokines varying during cbi. they could be used as biomarkers to identify the patients who could benefit from an early treatment in a preemptive targeted therapeutic strategy. these data will be paralleled to genetic background and to circulating candida derived molecules to precise the relative part of the host and the pathogen in this complex interaction. introduction lung ultrasound is widely used in intensive care, ermergency and pneumology medicine, for assessing acute respiratory pathologies. it is noninvasive, radiation free and rapidly available at the patient's bedside and provides an excellent accuracy. so, lung ultrasound may be an interesting tool for the physiotherapist as it allows to assess with more accuracy the patient improving the chest physiotherapy indication and monitoring (1) . as far as we are aware, no study has evaluated the impact of lung ultrasound on clinical-decision making by physiotherapists in the use of chest physiotherapy. this case report highlights the lung ultrasound interest in chest physiotherapy in patient with lung consolidation. patients and methods this was a case report written following the recommendations of the care guideline (2). the case was a 68-years-old female patient, non intubated, hospitalized in a respiratory icu. she was hypoxemic (pao 2 = 59 mmhg and sao 2 = 89%), with dyspnoea at rest and an increasing radiological opacity at the right lung base. hypoxemia was the indication for physiotherapist referral. at the clinical examination, the physiotherapist's findings were: decreased mobility, dullness and abolished vesicular sound at the base of right hemithorax. this clinical examination and chest x-rays analysis allowed the physiotherapist to propose several clinical hypotheses: pleural effusion, obstructive atelectasis or pneumonia. the chest physiotherapy treatment differs according to the type of lung deficiencies. for example, the physiotherapist must to refer the patient to the medical staff in case of pleural effusion or may implement hyperinflation technique in case of obstructive atelectasis. determining the nature of lung deficiencies is essential to provide the more suitable therapeutic strategy. so, the physiotherapist decided to perform a lung ultrasound examination to retain the more likely hypothesis. results ultrasound examination performed by the physiotherapist highlighted the presence of a lung consolidation at the infero-lateral and posterior parts of the right lung with a pneumonia pattern: presence of tissue-like sign, shred sign, dynamic air bronchogram and fluid bronchogram. the medical staff implemented antibiotic treatment. the ultrasound findings guided the physiotherapist to choose chest physiotherapy technique improving the alveolar recruitment: nearly prone position (left side down) and continuous positive airway pressure during 45 min. the patient response to the treatment was monitored by ultrasound and showed a decrease of the lung consolidation size and apparition of b lines, meaning a gain of lung aeration. these findings were associated with spo 2 improvement but without decrease of dyspnoea. discussion lung ultrasound allowed the physiotherapist to precise the nature of the radiological lung opacity. as it is more accurate than clinical examination or chest x-ray, this suggests a more suitable choice of chest physiotherapy techniques than conventional clinical decision-making process. ultrasound findings suggested a positive response to the chest physiotherapy treatment. the apparition of re-aeration signs (b lines, decreased consolidation size) showed a short-term efficacy of the chest physiotherapy treatment. this allowed the physiotherapist to continue the treatment during 1 week and obtain a substantial clinical improvement. conclusion the use of lung ultrasound in the clinical decision-making process may help the physiotherapist to choose with more accuracy the therapeutic strategy. moreover, it allows to monitor the treatment in real-time and assess the patient's response. the use of this tool may allow the physiotherapist to determine the optimal indications for chest physiotherapy and thus avoid unnecessary or inappropriate treatments. introduction critical illness together with immobilization have deleterious effects on patients outcome, especially in the presence of sepsis. increased muscle catabolism and membrane inexcitability reduce muscular mass and impair function within the first days after sepsis onset (1). early mobilization could potentially limit muscle wasting and functional impairment in this population. the purpose of this study was to test whether exercise during the early phase of sepsis is safe and beneficial and to which extent it can limit skeletal muscle protein catabolism and preserve function. patients and methods adult patients admitted with the diagnosis of severe sepsis were included and randomly allocated to two groups; 1) control group (ctrl-g): manual passive/active manual mobilization twice a day or 2) experimental group (exp-g): additional two times 30 min of passive/active cycling exercise. both groups benefited from a reduced sedation, adjusted nutritional intake and bed to chair transfer as soon as possible. skeletal muscle biopsy and electrophysiological testing were realized at day-1 and day-7. muscle histology, biochemical and molecular analyses of anabolic/catabolic and inflammatory signalling pathways were performed. a group of four healthy subjects was used to obtain non pathological values. hemodynamic parameters and patients perception were collected during each session. results twenty-one patients were included, however 3 died before the second muscle biopsy. ten patients in ctrl-g and nine in exp-g were finally analysed. muscle fibre cross sectional area (µm 2 ) was significantly preserved by exercise (relative changes were ctrl-g: −45 ± 41% vs exp-g:12 ± 19%, p = 0.001). markers of catabolic systems were highly increased during sepsis compared to healthy subjects and reduced in both groups 7 days after admission. however the reduction in mrna (relative change) tended to be more important in exp-g: murf-1 (ctrl-g: −31 ± 67% vs exp-g: −63 ± 45%, p = 0.15), mafbx (ctrl-g: −7 ± 138% vs exp-g: −56 ± 37%, p = 0.23), lc3b (ctrl-g: 5 ± 47% vs exp-g: −21 ± 18%, p = 0.18) and bnip3 (ctrl-g: 27 ± 198% vs exp-g: −59 ± 23%, p = 0.02). anabolic and inflammatory markers were not affected by exercise. electrophysiological testing, including direct muscular stimulation, was abnormal on day-1 in 10 of 13 evaluated patients. since only a limited number of patients could be reassessed a second time, comparison between groups was not possible. in general, all activities were well tolerated by patients with no adverse events. the pulmonary auscultation is used by respiratory therapist (rt) to evaluate the efficiency of a treatment. listen to the noises coming from the primary bronchi (pb) is important because it is the place where secretions can be accumulated. therefore, it is crucial to know exactly where to place the stethoscope's chestpiece on the chest. few studies have analyzed the chest area where the pb were located. our hypothesis is that pb are localized on a line that joins axillary fossa (bi-axillary line: bal). the aim of our study is to evaluate the probability to find the primary bronchi by analysis of chest radiography. patients and methods a retrospective study was performed by analysis of chest x-ray using the software: tm reception ® , which allows precise measures to the tenth of millimeter. all the x-rays were made on confined to bed patients hospitalized within intensive care unit, internal medicine and abdominal surgery rooms. the following measures (in mm) were made between: the exclusion criteria were: bmi < 18.5 kg/m 2 and bmi > 30 kg/m 2 , scoliosis, minor patient, lack of visibility of one of the axillary fossa, lack of visibility of pb, clavicular asymmetry, kyphosis, lack of symmetry in the shot, atelectasis and pneumothorax. statistics: normality test: ks. mean values are expressed with their sd and 95% ci. discussion in this study, we performed analysis of chest x-rays of bedridden patients and we demonstrated that it is possible to localize easily, on either side of the bs, the right and left pb at ± 25 mm distance (lp) above a line joining axillary fossa. this study constitutes a new tool for the rt who, by using stethoscope with a chestpiece of 10 cm 2 surface area, will be able to listen to noise coming from pb. conclusion the data presented herein (fig. 31) show that right and left pb are located at a mean distance of 25 (±5) mm and 27 (±6) mm above the bal, on both sides of the bs. the bal represents thus an easy and precise mode to detect right and left pb by bedridden. finally, the distance between the hyoid bone and the sc is about 12 cm. as the pb are located after the bifurcation, this information constitutes another useful way for the localization the right and left pb by bedridden patient. introduction critically ill patients frequently develop muscle weakness, which is associated with prolonged intensive care unit and hospital stay (1). this randomized controlled trial (clinical trials nct02047617) was designed to investigate whether a daily training session using a tilt table, started early in stable critically ill patients with an expected prolonged icu stay, could improve strength at icu and hospital discharge compared to a standard physiotherapy program. the study protocol was approved by an ethics committee and informed consent was obtained from all patients. patients admitted in adult icu of marie lannelongue hospital, france, who were mechanically ventilated for at least 3 days were included. exclusion criteria were cerebral or spinal injury, pelvic or lower limb fracture. patients were assessed each day for temporary contraindications for mobilization out of bed (rass score <−2 or >1; hemodynamic instability; a continuous intravenous dose of epinephrine/ . no significant difference was observed in terms of mrc score or in terms of pts with or without weakness (mrc > 48) at icu or hospital discharge. however, the number of pts with weakness was significantly higher in the group before tilt mobilization, suggesting a more rapid improvement in the tilt group. the icu and hospital lengths of stay were not different between groups. discussion the prevalence of muscle weakness in our population is high before mobilization (90.6%, 95% ci 85.2-95.6), is still 48.6% at icu discharge but represents only ~ 1% at hospital discharge. this low hospital discharge prevalence is probably related to the early and intense physiotherapy in both groups, which may explain our inability to demonstrate superiority of the addition of tilt table positioning, although a faster recovery is suggested. conclusion training sessions using a tilt table, in addition to early and intense physiotherapy did not improve muscle strength evaluated using mrc score in surgical icu patients with muscle weakness. proposed modifications to the duke criteria for the diagnosis of infective endocarditis quantifying the relationship between staphylococcus aureus bacteremia and s. aureus bacteriuria: a retrospective analysis in a tertiary care hospital recommandations formalisées d'experts «prise en charge des infections intra-abdominales strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric) risk factors for developing esbl e. coli: can clinicians predict infection in patients with prior colonization? kdigo clinical practice guideline for acute kidney injury citrate anticoagulation for continuous venovenous hemofiltration benefits and risks of furosemide in acute kidney injury national nosocomial infections surveillance (nnis) system report, data summary from prospective evaluation of the risk factors, etiology and the antimicrobial susceptibilities of the isolates in nosocomial bacteriemic patients unrecognized endobronchial intubation of emergency patients endobronchial intubation detected by insertion depth of endotracheal tube, bilateral auscultation, or observation of chest movements: randomised trial nosocomial infections in a burn intensive care unit outcomes of critically ill cancer patients in a university hospital setting outcome and prognostic factors of lung cancer patients admitted to the medical intensive care unit intensive care of the cancer patient: recent achievements and remaining challenges chronic critical illness the epidemiology of chronic critical illness in the united states designing and conducting a cluster-randomized trial of icu admission for the elderly patients: the ice-cub 2 study estimation de la mortalité maternelle en france: une nouvelle méthode emergency postpartum hys-terectomy for uncontrolled postpartum bleeding music interventions for mechanically ventilated patients effets de la musicothérapie en réanimation hors sédation chez des patients en cours de sevrage ventilatoire versus des patients non ventilés. annales françaises d' anesthésie et de réanimation evaluation of a low-flow oxygen-conserving nasal cannula performance of six types of oxygen delivery devices at varying respiratory rates high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure international study of the prevalence and outcomes of infection in intensive care units medical intensive care urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature diagnostic strategies for renal impairment in the intensive care unit recommendations formalized expert acute renal failure in the perioperative and intensive care (excluding extrarenal purification techniques) frutos-vivar f. comparison of the berlin definition for acute respiratory distress syndrome with autopsy the presence of diffuse alveolar damage on open lung biopsy is associated with mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury references 1. akoumianaki e. mechanical ventilation-induced reverse-triggered breaths: a frequently unrecognized form of neuromechanical coupling neuromuscular blockers in early acute respiratory distress syndrome driving pressure and survival in the acute respiratory distress syndrome mortality and pulmonary mechanics in relation to respiratory system and transpulmonary driving pressures in ards organ donation, reasons for family refusal: a retrospective study in a french organ harvesting center 2005-370 du 22 avril 2005 relative aux droits des malades et à la fin de vie comité consultatif national d'ethique c. fin de vie, autonomie de la personne, volonté de mourir reliability, validity, and health issues arising from questionnaires used to measure psychosocial and organizational work factors (powfs) among hospital nurses: a critical review aging and death signalling in mature red cells: from basic science to transfusion practice most reliable indices in differentiation between thalassemia trait and iron deficiency anemia stratification du risque dans l'embolie pulmonaire aiguë.realites cardiologiques • n° 219 -cahier 1 • septembre european resuscitation council guidelines for resuscitation 2015: section 1. executive summary breakthrough in cardiac arrest: reports from the 4th paris international conference changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries noninvasive mechanical ventilation in acute respiratory failure: trends in use and outcomes high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure failure of noninvasive ventilation for de novo acute hypoxemic respiratory failure: role of tidal volume réanimation médicale polyvalente, hôpital de la source early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the macocha score in a multicenter cohort study clinical practice and risk factors for immediate complications of endotracheal intubation in the intensive care unit: a prospective, multiple-center study profound and persistent decrease of circulating dendritic cells is associated with icu-acquired infection in patients with septic shock intensive care med specific mait cell behaviour among innate-like t lymphocytes in critically ill patients with severe infections a 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin prognostic value of relative adrenal insufficiency during cardiogenic shock: a prospective cohort study with long-term follow-up. shock calcium supplementation during sepsis exacerbates organ failure and mortality via calcium/calmodulin-dependent protein kinase signaling hypocalcemia in critically ill patients diabetic ketoacidosis traps joint british diabetes societies guideline for the management of diabetic ketoacidosis peter radermacher 18 , for the hyper2s investigators and reva research network 1 réanimation médicale, hôpital henri mondor réanimation medico-chirurgicale, hopital avicenne institut für anästhesiologische pathophysiologie und verfahrensentwicklung département de réanimation médicale et de médecine hyperbare, c.h.u. d' angers, angers, france; 3 service de réanimation médico-chirurgicale réanimation médico-chirurgicale, assistance publique -hôpitaux de paris, hôpital ambroise paré, boulogne-billancourt, france; 14 service de réanimation adulte quantitative measurement of heparin in comparison with conventional anticoagulation monitoring and the risk of thrombotic events in adults on extracorporeal membrane oxygenation elso guidelines for cardiopulmonary extracorporeal life support, version 1.3. ann arbor: extracorporeal life support organization early and late outcomes of 517 consecutive adult patients treated with extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock the french sf-36 health survey: translation, cultural adaptation and preliminary psychometric evaluation weaning of extracorporeal membrane oxygenation using continuous hemodynamic transesophageal echocardiography predictors of successful extracorporeal membrane oxygenation weaning after assistance for refractory cardiogenic shock extracorporeal membrane oxygenation in the adult: a review of anticoagulation monitoring and transfusion back from irreversibility: extracorporeal life support for prolonged cardiac arrest microcirculatory perfusion is preserved during off-pump but not on-pump cardiac surgery extracorporeal membrane oxygenation causes loss of intestinal epithelial barrier in the newborn piglet the pulsatile perfusion debate in cardiac surgery: answers from the microcirculation? a meta-analysis of complications and mortality of extracorporeal membrane oxygenation impact of fluid balance on outcome of adult patients treated with extracorporeal membrane oxygenation cumulative fluid balance and mortality in septic patients with or without acute kidney injury and chronic kidney disease comparison of two fluid-management strategies in acute lung injury renal function and survival in 200 patients undergoing ecmo therapy extracorporeal membrane oxygenation and the kidney plasma concentrations of inflammatory cytokines rise rapidly during ecmo-related sirs due to the release of preformed stores in the intestine in-hospital mortality and successful weaning from venoarterial extracorporeal membrane oxygenation: analysis of 5263 patients using a national inpatient database in japan is the 77.1% rate of in-hospital mortality in patients receiving venoarterial extracorporeal membrane oxygenation really that high? predicting survival after ecmo for refractory cardiogenic shock: the survival after veno-arterial-ecmo (save)-score outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock usefulness of cardiac biomarkers to predict cardiac recovery in patients on extracorporeal membrane oxygenation support for refractory cardiogenic shock etiology of troponin elevation in critically ill patients esc guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (esc) accf/aha guideline for the management of heart failure: a report of the american college of cardiology foundation/american heart association task force on practice guidelines nearhanging injuries: a 10-year experience unité de réanimation neurologique s38 rapid diagnosis of bacterial meningitis using a point-of-care glucometer geoffroy rousseau 1 service d'information médicale, epidémiologie et economie de la santé guillain-barré syndrome outbreak associated with zika virus infection in french polynesia: a case-control study early predictors of mechanical ventilation in guillain-barré syndrome paediatric prolonged mechanical ventilation: considerations for definitional criteria cardiac filling volumes versus pressures for predicting fluid responsiveness after cardiovascular surgery: the role of systolic cardiac function respiratory variation in aortic blood flow peak velocity to predict fluid responsiveness in mechanically ventilated children: a systematic review and meta-analysis. pediatr anesth effect of prone and supine positions on functional residual capacity, oxygenation, and respiratory mechanics in ventilated infants and children positioning effects on lung function and breathing pattern in premature newborns l'accident vasculaire ischémique en pédiatrie. quand y penser -quoi faire outcomes of early decompressive craniectomy versus conventional medical management after severe traumatic brain injury: a systematic review and meta-analysis myocardial dysfunction evaluation in pediatric brain death donor service de régulation et d'appui, agence biomedecine prone position for acute respiratory failure in adults prone positioning in severe acute respiratory distress syndrome effects of the prone position on respiratory mechanics and gas exchange during acute lung injury does prone positioning increase intracranial pressure? a retrospective analysis of patients with acute brain injury and acute respiratory failure prone position in mechanically ventilated patients with reduced intracranial compliance maud loiselle -maud.loiselle@outlook.fr annals of intensive care boulogne-billancourt, france; 5 réanimation polyvalente adulte, centre hospitalier intercommunal andré grégoire, montreuil, france; 6 réanimation médicale an audit of intensive care unit recyclable waste s77 point of care ultrasonography: is there a place for pocket size ultrasonography devices? gabriel preda 1 , vincent dubée 1 , naïke bigé 1 eric maury -ejhmaury@gmail.com annals of intensive care outcome, functional autonomy, and quality of life of elderly patients with a long-term intensive care unit stay berlin: springler; 2010. s81 icu nurses' perception of end-of-life decision making: a french multicenter survey akli chermak 5 , alexandre lautrette 6 ap-hp) anesthésie réanimation et traitement chirurgical des grands brûlés réanimation médicale hôpital d'instruction des armées percy correspondence: fanny.ardisson@gmail.com (fanny ardisson) annals of intensive care circulating mitochondrial damps cause inflammatory responses to injury rage is a nucleic acid receptor that promotes inflammatory responses to dna beneficial hemodynamic effects of prone positioning in patients with acute respiratory distress syndrome stard 2015: an updated list of essential items for reporting diagnostic accuracy studies towards complete and accurate reporting of studies of diagnostic accuracy: the stard initiative s89 neurological impairment in cirrhotic patients admitted to icu: hepatic versus drug-induced encephalopathy unité de soins intensifs d'hépatogastroentérologie réanimation polyvalente, hôpital de mercy, ars laquenexy, france; 5 réanimation médicale, centre hospitalier universitaire d' angers, angers, france; 6 réanimation médicale cerebrospinal fluid findings after epileptic seizures effect of epileptic seizures on the cerebrospinal fluid-a systematic retrospective analysis s92 synek score and nse to predict poor neurological outcome after cerebral anoxia and therapeutic hypothermia réanimation médicale correspondence: dimitri titeca beauport -titeca.dimitri@chu-amiens.fr annals of intensive care guidelines for the management of severe traumatic brain injury. vi. indications for intracranial pressure monitoring reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring s95 organ procurement and kidney transplantation under maastricht 3 condition (m3): update on 1 year of activity coordination prélèvements organes s95 reference 1. conditions à respecter pour réaliser des prélèvements d'organes sur les donneurs décédés après arrêt circulatoire de la catégorie iii de maastricht dans un établissement de santé. agence de la biomédecine. version n°6 mai crcl by cockroft-gault, mean (ml/mn delayed graft function, n (%) 4 (15.3%) réanimation médico-chirurgicale infectious diseases society of america. guidelines for the management of adults with hospital acquired, ventilator-associated, and healthcare-associated pneumonia reducing ventilator-associated pneumonia in intensive care: impact of implementing a care bundle chiche@aphp.fr annals of intensive care national nosocomial infections surveillance system. national nosocomial infections surveillance (nnis) system report, data summary from critères d'infection chez les brulés unité d'épidémiologie et recherche clinique international study of the prevalence and outcomes of infection in intensive care units risk and prognostic factors of ventilator-associated pneumonia in trauma patients ventilator-associated pneumonia: never enough, never give up! sahar habacha 1 , bassem chatbri 1 , aymen m'rad 1 , youssef blel 1 , nozha brahmi 1 sahar habacha -sahar.habacha@gmail.com annals of intensive care weaning patients from the ventilator automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children: a cochrane systematic review and meta-analysis unité de réanimation et de surveillance continue, service de pneumologie et réanimation médicale noninvasive ventilation and weaning in patients with chronic hypercapnic respiratory failure: a randomized multicenter trial risk factors for extubation failure in patients following a successful spontaneous breathing trial s109 a multicenter prospective observational study of 1514 extubation procedures in 26 intensive care units: the free-rea study audrey de jong -audreydejong@hotmail.fr annals of intensive care early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the macocha score in a multicenter cohort study faouzi saliba -faouzi.saliba@pbr.aphp.fr annals of intensive care réanimation médicale polyvalente, hôpital de la source mickael landais -mickaelandais@gmail.com annals of intensive care perioperative fasting in adults and children: guidelines from the european society of anaesthesiology the decision to extubate in the intensive care unit service de réanimation médicale s114 refeeding hypophosphoremia in a medical critical care unit: 3-month observational study gioia gastaldi -gioia.gastaldi@chu-rouen.fr annals of intensive care refeeding hypophosphatemia in critically ill patients in an intensive care unit. a prospective study refeeding syndrome: problems with definition and management biosit and inserm u917, faculte de medecine, université rennes 1 immune dysfunction after cardiac surgery with cardiopulmonary bypass: beneficial effects of maintaining mechanical ventilation s117 influence of neutropenia on mortality of critically ill cancer patients: results of a systematic review on individual data quentin georges 1 brazil; 5 department of critical care medicine and division of pulmonary and critical care medicine united kingdom; 11 department of intensive care centre d'infection et d'immunité de lille equipe 4 -basic and clinical immunity of parasitic di delta nlr") were calculated. statistical analysis used appropriate non parametric tests and cox regression for survival analysis. the ability of the variables to discriminate survivors from non-survivors was determined using roc curves results during the study period, 149 cirrhotic patients were admitted in icu. the etiologies of liver cirrhosis were alcoholic in 87% of cases with severe score: median child-pugh score = 9 1%) deaths after icu discharge during the same hospitalization. nlr decreased for survivors between d0 and d3 univariate analysis, for predicting survival, higher values of nlrd3, delta nlr, meld score at admission, sofa score at admission and at day 3 and delta sofad0-d3 were significant factors. predictors of death in multivariate analysis are shown in fig. 29. area under delta nlr roc conclusion the blood nlr is a novel inflammation index that has been shown to independently predict poor clinical outcomes. we have demonstrated that delta nlr is an independent predictor of mortality in critically ill cirrhotic patients the association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study gene-and exon-expression profiling reveals an extensive lps-induced response in immune cells in patients with cirrhosis celine dupre -duprecece@gmail.com annals of intensive care diagnostic accuracy of procalcitonin in critically ill immunocompromised patients the role of pattern-recognition receptors in innate immunity: update on toll-like receptors esm-1 is a novel human endothelial cell specific molecule expressed in lung and regulated by cytokines thoracic ultrasound: potential new tool for physiotherapists in respiratory management. a narrative review the care guidelines: consensus-based clinical case reporting guideline development department of physical medicine and rehabilitation icu-acquired weakness and recovery from critical illness o82 where should we place the stethoscope's chestpiece to hear the noise of the primary bronchi? frédéric duprez 1 , bastien dupuis 2 , grégory cuvelier 2 , thierry bonus 1 frédéric duprez -dtamedical@hotmail.com annals of intensive care o84 aerosol delivery using two nebulizers through high flow nasal cannula: a randomized cross-over spect-ct study correspondence: jonathan dugernier -jonathan.dugernier@uclouvain.be annals of intensive care introduction in 2005, an international consensus conference took stock of the various measures to be implemented for the prevention of ventilator acquired pneumonia (vap) [1]. these measures are often gathered in groups of 3 or 5 under the term of "ventilator-bundle. " the effectiveness of these "bundles" was poorly evaluated in african environment. objective to establish a vap prevention program and assess its impact on morbidity and mortality of patients under mechanical ventilation in our service. patients and methods prospective, mono centric, quasi-experimental before-after study. it took place in the intensive care unit of the university clinics of kinshasa in the democratic republic of congo (drc). this service is equipped with 8 beds and a respirator for two beds. the observational period (phase1) was carried out from february 1st to december 31st, 2014 and the intervention period (phase2) from february 15st, 2015 to february 15st, 2016. all consecutive patients intubated and mechanically ventilated for more than 48 h were included. five preventive measures were held: hand hygiene, the elevation of the head of the bed at 30°-45°, the daily lifting of sedation, oral decontamination with chlorhexidine and control cuff pressure of the endotracheal tube. compliance with this bundle was assessed by direct observation without the knowledge of caregivers. the diagnosis of "vap" was held before a clinically modified sore (m cpis) >6. the main outcomes were the incidence of vap and mortality. the protocol for this study was approved by the ethics committee of the school of public health of the university of kinshasa, under the approval number: esp/ec/015/2015.introduction nosocomial infections (ni) are common in burn patients due to the loss of the first line of defense against microbial invasion, immunocompromising effects of burn injury, and invasive diagnostic and therapeutic procedures. the objective of this study was to identify the incidence of nosocomial infection (ni), the pathogens and their antibacterial patterns, and prognosis of these burn patients. patients and methods a retrospective study was conducted in a 20 bed intensive burn care unit during 6 months. patients were eligible for the study, if they met the following criteria: total burn surface area (tbsa) > 10%, length of icu stay ≥48 h, and infected in accordance with the criteria of the national nosocomial infections surveillance (nnis) and the criteria of the sfetb [1][2]. in this study, nis were classified into four main groups: pneumonias, bloodstream infections (bsi), catheter related infections (cri), and urinary tract infections (uti). for included patients, skin levy, blood cultures, urine and sputum cultures were drawn during fever or clinical features of sepsis. results during the 6-month study period, 190 patients were admitted to the icu, 47 patients were included (24.7%). 32 were male and 15 female. the mean age was 41 ± 19 yr. the mean tbsa was 41 ± 24%. 63% were admitted from another hospital. burn injuries were due to domestic accidents in 53% and self immolation in 25%. the mean none. none. none. none. none. none. none. none. none. none. ann. intensive care 2017, 7(suppl 1):7none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. consulting activities with fisher & paykel. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. failure extubation in intensive care unit: risk factors, incidence and evaluation of a mechanical ventilator weaning protocol lucie petitdemange 1 , anne sophie guilbert 1 none. none. none. none. none. none. opportunistic infections in patients with solid tumors: a systematic review julien poujade 1 , elie azoulay 2 none. invasive aspergillosis in non-immunocompromised patients hospitalized intensive care unit guillaume trumpff 1 , max guillot 2 , thierry braun 2 , ralf janssen-langenstein 2 , marie-line harlay 2 , jean-etienne herbrecht 2 introduction characteristics and outcomes of adult patients with invasive aspergillosis in intensive care unit have rarely been described. we performed a retrospective study on consecutive adult patients with invasive aspergillosis who were admitted form january 2010 through january 2016 to the intensive none. noorah zaid 1 , nawel ait-ammar 2 , christine bonnal 2 , jean-claude merle 1 , francoise botterel 2 , eric levesque 1 1 anesthesia and intensive care medicine, chu henri mondor, créteil, france; 2 unité de parasitologie-mycologie, département de virologie, bactériologie-hygiène, parasitologie, hopital henri mondor, créteil, france correspondence: eric levesque -eric.levesque@aphp.fr annals of intensive care 2017, 7(suppl 1):s60 introduction liver transplant recipients have high rate of invasive fungal disease (ifd) with high morbidity and mortality, in part due to its delayed diagnosis. the fungal cell wall component (1,3)-betad-glucan (bg) is a biomarker for fungal infection but its utility remains uncertain. this prospective study was designed to review our experience in ifd and to evaluate the impact of bg in the diagnosis of ifd. patients and methods from january 2013 to may 2016, 271 liver transplantation were performed in our institution. serum samples were tested for bg (fungitell; cape cod inc., usa) least weekly between liver transplantation and their discharge from hospital. ifd was defined as proposed by the european organization for research and treatment of cancer/mycoses study group. results nineteen patients (7%) were diagnosed with ifd including 13 cases of candidiasis infection (ci) in eleven out of 271 patients, 8 invasive pulmonary aspergillosis (including one who had previously ci) and one case of septic arthritis of the hip caused by scedosporium spp. ifd was associated with significantly high mortality (log-rank p = 0.003). the area under the roc curves, for bg to predict ifd, was 0.78 (95% ci 0.73-0.83). using a cutoff of 139 pg/ml, the most discriminative cut-off point from the roc curve, the sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) values of bg for overall ifd was 68% (95% ci, 59-77), 79% (95% ci, 76-78), 24% (95% ci, 19-30) and 96% (95% ci, 95-97). conclusion based on its high npv, bg value appears to be a good biomarker to rule out the diagnosis of ifd when the value is below 139 pg/ml. a single point bg may guide the investigation and the decision to start antifungal therapy in patients at risk for ifd. none. monitoring of changes in lung and chest wall mechanics in the supine, lateral and prone positions during the prone positioning maneuver in ards patients zakaria riad 1 , mehdi mezidi 1 , hodane yonis 1 , mylène aublanc, 1 , sophie perinel-ragey, 1 , floriane lissonde 1 , aurore louf-durier, 1 , romain tapponnier 1 , jean-christophe richard 1 , bruno louis, 2 , claude guérin 1 , plug working group 1 réanimation médicale, hôpital de la croix-rousse, lyon, france; 2 inserm, u955, equipe 13, équipe biomécanique cellulaire et respiratoire, université paris-est créteil -faculté de médecine, créteil, france correspondence: zakaria riad -zakaria.riad@icloud.com annals of intensive care 2017, 7(suppl 1):s60 none. introduction systemic rheumatic diseases (srd) are autoimmune diseases that are rare but cause substantial morbidity and mortality. srds chiefly affect the lungs, however, data on critically ill patients with srd admitted for arf are scarce. patients and methods retrospective cohort conducted in 10 french icus (2009 . the major comorbidities were cardiovascular (49%), tobacco exposure (25%), chronic kidney disease (18%) and neoplasia (15%). two-thirds of patients were on systemic corticosteroids at admission, the median dose of 10 (iqr) mg per day. srd diagnosis was made in the icu in 11.5% of patients. clinically or microbiologically documented bacterial pneumonia was the leading arf etiology (40.9%). in 32% of cases, arf was related to an opportunistic infection (mainly aspergillus (n = 8) and pneumocystis (n = 7)). others arf etiologies included specific lung involvement (23.2%) and cardiac pulmonary edema (20.7%). sofa on day one was 5 [3] [4] [5] [6] [7] [8] [9] . associated organ dysfunctions were mainly hemodynamic (42%) and renal (45%). mechanical ventilation was needed in 68% of patients (non invasive only in 17.3% or invasive in 82.7%), 40% needed vasopressors, and 30% renal replacement therapy. systemic corticosteroids were started in 20% of patients and 23% of patients received pulse steroids. cyclophosphamide and plasma exchange were required in 10 and 11% of patients, respectively. length of icu stay was 7 [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] days. icu-acquired infection occurs in 25% of cases. in total, 59 patients (24.9%) died throughout the icu stay. arf etiology was not associated with mortality. by multivariate analysis, shock on admission (or 6.25 [2.71-14 .40], p < 0.001) and the use of invasive mechanical ventilation (or 5.06 [1.84-13 .94], p = 0.02) were independently associated with mortality, whereas non-invasive ventilation was associated with decreased mortality (or 0.31 [0.12-0.81], p = 0.02). by considering among the connective tissue diseases, the groups of myositis and scleroderma (n = 61), these diseases were associated with a trend for a higher mortality (or 2.08 [0.95-4.55], p = 0.06). conclusion in patients with srd, arf is associated with a high case fatality, primarily when mechanical ventilation is needed. particular attention must be given to specific srd-sub groups for which pulmonary flare may require intensive immunosuppression. none. none. none. severe acute pancreatitis in icu: management and outcomes of infected pancreatic necrosis charlotte garret 1 , matthieu peron 2 , emmanuel coron 2 , cédric bretonnière 1 , jean reignier 1 , christophe guitton 1 1 réanimation médicale, chu hôtel-dieu nantes, nantes, france; the acute pancreatitis appears as a pathology that we can define with difficulty because of its clinical presentation or prognosis. patients and methods in our study, we analysed 102 cases of acute necrotic and hemorrhagic acute pancreatitis, hospitalized at the department of resuscitation of the surgical emergencies (p33) of the uhc ibn rochd casablanca during the period (2009) (2010) (2011) (2012) (2013) (2014) (2015) . the purpose of this study is to do a descriptive analysis of the epidemiologic, clinic, radiological, therapeutic and evolutive data of the acute necrotic pancreatitits, we included in our study 102 patients with epidemiologic, clinic, radiologic, biologic criteria of acute necrotic pancreatitits diagnosis whatever is the biliary or alcoholic etiology. the valuation gravity of the pancreatitis has been based on:• ranson bioclinical score >3/apache ii >8; • visceral failure.• spreading of the necrosis. the analysis of the results shows that: about the epidemiologic aspect: mean age (52 year old), the biliary etiology predominates (81%). about the clinical aspect: pain (95%) vomiting (77%), stop of the transit (18%), the visceral distresses are: the shock (34%), respiratory distress (40%), and neurological distress (28%). about the radiological aspect: pleural effusion (42%), abdominal echography: vesicular lithiasis (60%), dilated principal biliary duct (13%), abdominal computerized tomography: stage e (49%). about the biological aspect: hyperglycemia (80%), hyper-amylasemia (68%). the indexes of gravity that have been appreciated in this study are: ranson score >3 (58%), imrie score >3 (66%), igs score ≥6 (47%), osf score ≥1 (70%). the treatment of the anhp has been symptomatic in particular and the evolution has been characterized by mortality about 38%, the cause was particularly infectious. the prognostic factors predetermined in this study are:• female type (p = 0.0004).• hemodynamic distress (p = 0.00005).• respiratory distress (p = 0.0000001).• scores of gravity:• ranson >3 (p = 0.0000001).• imrie >3 (p = 0.02).• osf ≥ 1 (p = 00001).• infection (p = 0.0000001).• duration of the hospitalization (p = 0.02).• rate of c-reagent protein (p = 0.001). in conclusion, the mortality is still high in the anhp, considerable effort of search is necessary to prevent the infectious complications of mortality. none. predicting 90-day mortality following liver transplantation in patients with acute-on-chronic liver failure: a decision-tree model from the french national liver transplantation system, the optimatch study, 2008-2014 none. none. none. none. none. none. the french law and recent expert opinions have emphasized the need for a multidisciplinary approach in decisions to forgo life sustaining therapies for the critically ill. we sought to assess how icu nurses actually rank their involvement and perceive this process. materials and methods we conducted a cross sectional survey using a web-based questionnaire between june and september 2016. results of the 38 icus invited to participate, 22 (58%) agreed. a total of 541 icu participants completed the survey of whom 73% were nurses and 26% assistant nurses. median age was 31 (inter quartile range 27-38) years and 84% were female. median work experience was 7 (4-12) years and time in the icu was 5 (3-8) years. eighty-five percent of the participants have been involved at least once in a multidisciplinary end-of-life discussion. less than half of the participants reported a good (4%) or partial (44%) knowledge of the current end-of-life legal framework. the decision to start a discussion about withdraw life-sustaining therapy (wlst) was initiated by a senior intensivist in 83% of the cases, by a nurse in 5% and an assistant nurse in 0.6%. this decision was approved by 97% of the participants. the decision-making process was considered to be initiated at the right time for 49% of the participants, too late for 48%, and too early for 3%. the discussion occurred mostly in the afternoon (38%) or during the medical staff (22%), in a dedicated place in 63% of the cases. a median of 7 (5-10) health-care professionals attended the wlst discussion. half the respondents reported being reluctant to talk during the discussions and 11% never expressed their own opinion. indeed, although the length of the discussion was 30 (15-45) minutes, participants estimated to talk during only 3 (1-5) minutes. the following reasons were mentioned by the participants to explain these facts: having cared for the patient for too short time (62%), lack of medical knowledge (35%), decision of wlst already taken by the medical staff (31%), their opinion not really taken into account (19%), reluctant to talk during meetings in general (18%), consider that the discussion is limited to a medical expertise (15%), limited professional experience (14%), and fear to express a different opinion (12%). nevertheless, 84% of the participants were partially (76%) or totally (8%) satisfied by the way the decision making process was conducted, 81% considered that collegiality was applied, and 93% agreed with the final decisions.conclusion icu nurses rank favorably multidisciplinary wlst discussions. nevertheless their involvement in the discussion remains limited. beyond factors related to work organization and professional experience, efforts should be made to recognize their role and value, and to encourage them to share their own opinions with the other members of the icu team. none. determinants and prognosis of elevation of high-sensitivity cardiac troponin t in patients hospitalized with vasodilatatory shock marie caujolle 1 , jérôme allyn 1 , dorothée valance 1 , caroline brulliard 1 , none. free plasmatic mitochondrial dna-receptor for advanced glycation end-products: a new signaling pathway of critical illness-induced endothelial dysfunction arthur durand 1 , rémi nevière 2 , florian delguste 2 , eric boulanger, 2 none. quality of reporting of fluid responsiveness evaluation studies: a five year systematic review izaute guillame 1 , matthias jacquet-lagrèze 1 , jean-luc fellahi 1 none. none. none. none. none. introduction microaspiration of gastric and oropharyngeal contaminated secretions occurs frequently in intubated critically-ill patients, and plays a major role in the pathogenesis of ventilator-associated pneumonia (vap). at basic state, patients with chronic obstructive pulmonary disease (copd) have an increased risk of microaspiration (due to gastro-esophageal reflux disease, pharyngo-laryngeal dys-function…), this risk may even be more important under mechanical ventilation. the main purpose of this study is to determine if copd is a risk factor for global abundant microaspiration (gam) in intubated critically-ill patients. we gathered data about two prospective multicentric randomized trials focused on microaspiration in intubated patients. data about copd were retrospectively collected in order to complete previous data. microaspiration of gastric and oropharyngeal secretions was respectively determined by quantitative measurements of pepsin and salivary amylase in all tracheal aspirates during the first 48 h after intubation. gam was defined as the presence at significant level of pepsin (>200 ng/ml) and/or salivary amylase (>1685 ui/l) in at least 30% of the tracheal aspirates. in order to find gam independent risk factors, we realized an univariate and multivariate analysis of the variables collected. results out of 448 patients included in the studies, 415 were analyzed among which 95 patients with copd. 360 patients (87%) had gam. neither copd diagnosis, nor spirometric severity nor specific therapeutics were associated with gam. risk factors for gam in univariate analysis were the age, diabetes, low score in glasgow coma scale (gcs), and no recourse to paralytic agents or vasopressors. after none. none. implementation and impact assessment of a "ventilator-bundle" at the university clinics of kinshasa: before and after study josé mavinga 1 , joseph nsiala makunza 2 , m e mafuta 3 , yves yanga 1 , amisi eric 1 , jp ilunga 1 , ma kilembe 1 none. none. amel mokline 1 , achraf laajili 1 , helmi amri 1 , imene rahmani 1 , nidhal mensi 1 , lazheri gharsallah 1 , sofiene tlaili 1 , bahija gasri 1 , rym hammouda 1 , amen allah messadi 1 1 burn care department, trauma and burn center, tunis, tunisia correspondence: amel mokline -dr.amelmokline@gmail.com annals of intensive care 2017, 7(suppl 1):s100 none. none. none. introduction mechanical ventilation (mv) weaning is a crucial step in critically ill patients. mv duration is associated with an increased risk of ventilator associated events, even though its specific impact on mortality has never been clearly demonstrated (1). automated closed loop systems might help the weaning process. a recently published meta-analysis has reported a reduction in mv duration when using an automated weaning mode as compared to non-automated mode (2) . however, the different automated modes have not been compared to each other. the objective of this network meta-analysis was to compare the performance of the three major automated weaning modes, i.e. the automode°, the smartcare° and the adaptative support ventilation (asv°) for mv weaning in critically ill and postoperative adult patients. we included all randomised control trials that compared automated closed loop weaning applications either to another automated application or standard care, including weaning according to a written weaning protocol or nurse driven protocols. the three modes of automated modes included in the study were asv°, smartcare° and automode°. the primary outcome was the duration of mv weaning, defined as the time between randomization and a successful extubation. we also planned subgroup analyses in the icu and the post-operative populations. the quality of the studies was assessed independently by two blinded investigators, using the evaluation recommended by the cochrane collaboration. a network bayesian meta-analysis using random effect models and based on aggregate data from the included studies was performed using the gemtc package (r project, vienna). this trial was declared in pros-pero in august 2015 (crd42015024742). results search of databased identified 776 articles; 233 were screened for eligibility after removal of duplicates. abstract analysis led to the exclusion of 191 articles with a final full text analysis of 42 randomised control trials. ultimately, 15 trials were included in the analysis, representing 1424 ventilated patients. nine studies included patients in the post-operative period while six were conducted in icu. the automated mode was asv° (a) in 9 studies, smartcare° (c) in 4 studies and auto-mode° (b) in 2 studies. all studies reported the duration of mv weaning as defined in our protocol. in all studies, the control group was standard care with a weaning process driven either by nurses or physicians. in 12 studies (75%) a written weaning protocol was used in the control group. all icu studies used sedation protocols based on sedation scores, none of them including systematic daily sedation interruption. each one of the automated application was associated with a significant reduction in the duration of mv as compared to the control. when comparing all different modes using the network meta-analysis framework, asv° appeared to be the best automated mode when it pertains to reducing the duration of mechanical ventilation weaning (fig. 24) . subgroup analysis showed similar results in the post-operative and the icu populations. conclusion compared to standard weaning practice, the 3 major automated weaning modes significantly reduced the duration of mv weaning in critically ill and post-operative adult patients. asv° was associated with the most significant effect when compared to the two other automated modes (smartcare°, automode°). further physiological respiratory studies would help to understand the underlying mechanisms accounting for the superiority of asv. none. none. introduction in intensive care unit (icu) patients, diaphragm dysfunction is associated with adverse clinical outcomes. ultrasound measurements of diaphragm thickness (tdi), excursion (exdi) and thickening fraction (tfdi) have been proposed as estimators of diaphragm function, but have never been compared to phrenic nerve stimulation. our aim was to describe the relationship between tdi, exdi, tfdi and diaphragm function evaluated using the change in endotracheal pressure after phrenic nerve stimulation (ptr,stim), and to compare their prognostic value. patients and methods ptr,stim and ultrasound variables were measured in mechanically ventilated (mv) patients <24 h after intubation ("initiation of mv", under assist-control ventilation, acv) and at the time of switch to pressure-support ventilation ("switch to psv"). diaphragm dysfunction was defined as ptr,stim <11 cmh 2 o. results 112 patients were included. at initiation of mv, ptr,stim was not correlated to tdi (rho = −0·13, p = 0·28), exdi (rho = 0·10, p = 0·66) or tfdi (rho = −0·03, p = 0·80). at switch to psv, tfdi and exdi were correlated to ptr,stim, (rho = 0·87, p < 0.001 and 0·45, p = 0·001, respectively), but tdi was not (rho = −0·09, p = 0·45). at switch to psv, a tfdi <29% could reliably identify diaphragm dysfunction (sensitivity and specificity of 85 and 88%, respectively), but tdi and exdi could not. this value was associated with increased duration of icu stay and mv, and mortality. conclusion under acv, neither tdi, exdi nor tfdi were related to ptr,stim. under psv, tfdi was strongly correlated to diaphragm strength and, when decreased, was associated with poorer outcome. alexandre demoule has signed research contracts with covidien, maquet and philips; he has also received personal fees from covidien and msd. none. none. none. management of enteral feeding during extubation in the intensive care unit: a multi-center retrospective study in 11 french intensive care units mickael landais 1 , noemie hubert 2 , mai-anh nay 3 , johann auchabie 4 , bruno giraudeau 5 , reignier jean 6 , arnaud w thille 7 , stephan ehrmann 8 1 none. none. nutritional support in patients receiving temporary extracorporeal life support: a retrospective cohort study arthur bailly 1 , laurent brisard 1 , philippe bizouarn 1 , thierry lepoivre 1 , johanna nicolet 1 , jean christophe rigal 1 , jean christian roussel 2 , bertrand rozec 1 1 réanimation ctcv transplantation thoracique, chu de nantes -hôpital nord laennec, saint-herblain, france; 2 chirurgie ctcv transplantation thoracique, chu de nantes -hôpital nord laennec, saint-herblain, france correspondence: laurent brisard -laurent.brisard@chu-nantes.fr annals of intensive care 2017, 7(suppl 1):s113 introduction the optimal nutritional intake in patients receiving temporary extracorporeal life support (ecls), including extracorporeal membrane oxygenation (ecmo) venovenous (vv) or venoarterial (va), remains controversial. enteral nutrition (en) is suspect to increase risk of gastrointestinal (gi) intolerance and intestinal ischemia. so, total parenteral nutrition (tpn) is often preferred. the purpose of this study is to describe the nutrition practices for critically ill patients receiving ecls and identify opportunities for improving nutrition therapy in this population. patients and methods retrospective analysis of patients requiring ecmo-va or ecmo-vv between 2010 and 2014 in the cardiac surgery intensive care unit of the university hospital of nantes. nutritional support was daily monitored with parenteral intake (glucose, lipid and propofol, protein and albumin, parenteral nutrition) and enteral nutrition until ecls weaning. two groups were compared during ecls period: no enteral nutrition delivered (none or tpn) (anec, n = 73) and at least once enteral nutrition delivered (nec, n = 50) including en alone and supplemental parenteral nutrition (spn). primary outcome was incidence of gi intolerance and risk factors. secondary outcomes were nutritional adequacy (calculated as overall of calories and protein delivered divided by the theoretical amount requirements: 20 kcal/kg/d and 1.2 g/kg/d) and clinical outcome. data are reported as median (25th and 75th percentiles) or number (%), and analyzed with student's t test for continuous variables and χ2 test for categorical variables. p < 0.05 was considered as significant. none.introduction refeeding syndrome (rs) is a potentially lethal condition that remains underdiagnosed. it is characterized by severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished patients undergoing refeeding orally, enterally, or parenterally. clinical criteria have been proposed for determination of its risk and reported in the national institute for clinical excellence (nice) clinical guidelines. hypophosphoremia (hp) is a prominent feature of the rs and seems to be the earliest abnormality. phosphorus is a vital component of nucleic acids, enzyme systems, and various metabolic pathways. objective to determine the incidence of refeeding hypophosphoremia (rh) < 0.9 mmol/l, and severe rh < 0.6 mmol/l in a medical critical care unit. patients and methods monocentric, retrospective and observational study with patients from french-speaking icu nutritional survey study frans. critically ill adults (more than 18 yo) were enrolled if they were hospitalized for more than 3 days during a 3-month period and had an artificial nutritional support. refeeding hypophosphoremia is defined by the occurrence of hypophosphoremia after refeeding. we studied the incidence of hr, risk factors, and prognosis. results 34 patients were enrolled between 03/01/2015 and 05/31/2015. rh appears in 73.5% and severe rh < 0.6 mmol/l in 35.3% (fig. 28) . there is no correlation between rs risk factors and rh in our study. logistic regression did not permit to identify neither risk factor nor prognostic modification. there is a lack in phosphoremia measuring (27.6%), and overfeeding during the first 3 days occurs in 29.4%. discussion we define that an hypophosphoremia appearing after refeeding is a refeeding hypophosphoremia, and we do not consider others etiologies, such as mechanical ventilation, alkalosis, sepsis, alcoholism, malabsorptive states, poor intake, some medication. our cohort is too small to find some possible correlations with risk factors or prognosis. conclusion refeeding hypophosphoremia is common in our population. hypophosphoremia is not an independent predictor of icu or in-hospital mortality in critically ill patients. the knowledge of the sri requires the follow-up of the phosphoremia during nutrition after critical illness in particular in the undernourished patients. none. introduction to determine the possible relationship between 10 days cumulated proteins (10 days cpd) and energy deficits (10 days ced) observed in ventilated patients and icu length of stay, duration of ventilator support, incidence of infections and 28 days mortality. patients and methods mixed medical or surgical ventilated for at least 2 days adult patients from 5 icus from chu liège belgium were enrolled into the study. they were fed by enteral route with a target of 25 kcal and 1.25 g of proteins by corrected kg of bodyweight and by day. if 50% of the target was not reached on day seven, parenteral nutrition was added with the same target. ced and cpd were calculated for 10 days, taking into account all the sources of nutrition, and was defined as the difference between the amount of energy or protein intake and the target. results from 10/12/2014 till 30/5/2015, 99 patients were followed. data from 62 patients could be cumulated on the first 10 days. there were 45 males, mean bmi was 26.9 ± 6.3; saps ii score on day 1 was 51.3 ± 15.8, sofa score at day 1 was 9.1 ± 3.5. they were ventilated for a median of 18 days (iqr 13-26), median icu length of stay was 27 days (iqr 19-35). mean sofa max calculated for the first 10 days was 12.1 ± 4.2 and the 28 day mortality was 32.3%. on day 5, only 42% reached the target of 25 kcal/kg and 27% the target of 1.25 g of protein/kg. mean 10 days ced was −5555.2 ± 4639.9 kcal and mean 10 days cpd was −350.8 ± 252.3 g. there was a significant negative relationship between both deficits and the sofa max (p = 0.0064 for ced and p = 0.0053 for cpd). however, there were no correlations between any of the deficits and icu length of stay, duration of mechanical ventilation, occurrence of infections and 28 days mortality. discussion saps ii level, sofa max level, icu length of stay, all these parameters emphasize the high severity of this cohort of patients. it could indeed been thought that it is in this group of critically ill patients that the impact of nutrition could be easily demonstrated. clear relationships between sofamax on day 10 and the 10 days ced and cpd could be seen. however, both the deficit and the level of organ dysfunctions could be cause or consequence. unlike previous studies, usually performed in less severely ill patients, we did not find any relationship between ced or cpd and patient's outcome. conclusion contrary to some recent studies, we found no relationship between ced and cpe and outcome of patients. future studies are needed. none. cardiopulmonary bypass induces lymphopenia and decreases lymphocyte proliferation ability: il-10 and pd-l1 as potential therapeutic targets to reduce postoperative infection fabrice uhel 1 , mathieu lesouhaitier 1 , murielle grégoire 2 , baptiste gaudriot 3 , arnaud gacouin 1 , yves le tulzo 1 , erwan flecher 4 , karin tarte 5 , jean-marc tadié 1 fig. 28 incidence of hypophosphoremia at admission, the first day, and refeeding hypophosphoremia none. the prognostic impact of neutropenia in criticallyill cancer patients remains controversial. hence, several studies in critically ill cancer patients failed to demonstrate the impact of neutropenia on outcome [1] . this lack of statistical association might however, reflect a lack of statistical power. a previous meta-analysis of aggregated data suggested 11% (95% ci 9-14%) raw increase in mortality in neutropenic patients. the available data were, however insufficient to allow adjustment with confounders [2] . the aim of this study was to assess the influence of neutropenia on mortality of critically ill cancer patients using individual data obtained from studies identified by our systematic review. secondary objectives were to assess the influence of neutropenia on mortality of critically ill patients while taking into account underlying malignancy, use of g-csf or changes related to period of admission. patients and methods this systematic review and meta-analysis was performed according to the prisma statements. public-domain databases including pubmed and the cochrane database were searched by using predefined keywords. the research was restricted to articles published in english and studies focusing on critically ill adult patients from may 2005 to may 2015. the methods and objectives of this systematic review were reported in the prospero database (crd42015026347). selected manuscripts' authors were then contacted to obtained part of their dataset. mortality was defined as either hospital or day-28 mortality. this preliminary analysis reports results from the whole dataset before and after adjustment using logistic regression. period of admission and use of g-csf were then assessed and were a pre-planned analysis. results our initial search yielded 1528 citations and 131 studies were retained for further analysis. overall, 9 studies were excluded for redundancy with other included studies, 5 as containing only neutropenic patients, and two as containing only palliative patients. finally 30 datasets (26%) containing sufficient data to allow comparison were obtained from authors. overall, 7356 patients were included in this study, including 1666 patients with neutropenia at icu admission. median age was of 60 years (iqr 49-69). median sapsii score at icu admission was 42 (iqr 28-57). respectively 4101 and 3255 patients had underlying haematological malignancy and solid tumours, and 438 patients underwent allogeneic stem cell transplantation. mechanical ventilation, vasopressors, and renal replacement therapy were required in none. none. (1) . in icus, cirrhotic patients are widely admitted and revalued after receiving optimal treatments for 3 days. however, little is known about how manage these patients after day 3 according to their prognosis. the blood neutrophil-to-lymphocyte ratio (nlr) as a novel inflammation index biomarker has been reported to be a predictor of clinical outcomes in various malignancies and in unselected critically ill patients (2) . nlr has also been identified as a predictor of mortality in patients with stable liver cirrhosis. to our knowledge, the ability of nlr to predict outcome in critically ill cirrhotic patients has never been studied. the aim of this study was to evaluate the usefulness of inflammatory marker such as nlr for diagnosis of infection and predicting the outcome in hospitalized critically ill cirrhotic patients. we performed a retrospective monocentric study including consecutively cirrhotic patients hospitalized in a medical icu from 2010 to 2014. for each patient, clinical and biological data at admission and day 3 were collected. nlr at admission ("nlrd0"), at day 3 ("nlrd3") and the variation of nlr between admission and d3 none.introduction diagnosis of infection in immunocompromised patients can be difficult. however, diagnosing infection is very important, particularly in critically ill. this study aims to evaluate the benefit of procalcitonin (pct) blood level as a diagnostic marker for bacterial infection in patients with hematological malignancies admitted to the intensive care unit (icu). this retrospective single-center study included all consecutive patients with acute myeloid leukemia or high grade lymphoid malignancy admitted to the icu. patients were sorted into three subgroups, according to clinical and microbiological data: «infectious disease», «no infectious disease» and «unknown». initial serum pct and when available at day 3 and day 5 were recorded. receiver operating characteristic (roc) curve, sensitivity and specificity were calculated. serum pct was considered as decreasing when the decrease was ≥25% at day 3 and/or ≥50% at day 5. mortality rates in the icu and at day-90 were also studied. results fifty-four patients were included in the study. at diagnosis, pct levels were significantly different between the "infection disease" group and the "no infection disease" group (p = 0.002). there was no difference between the "infection disease" group and the "unknown" group (p = 0.052). for the diagnosis of bacterial infection, best initial serum pct threshold was 0.65 ng per milliliter. for that threshold, sensitivity was 94.6% and specificity was 78.6%. pct area under the roc curve was 0.93 [ci 95% = 0.855-1]. youden's j statistic was 0.73. pct levels weren't different between groups according to the presence of neutropenia or in case of inaugural disease. there was a significant difference in pct values between groups according to the sofa score (p = 0.027), but not the saps2 score. mortality rate in the icu and at day-90 were significantly lower for the patients with decreasing pct (p < 0.001 and p < 0.001, respectively). when comparing serum pct and crp predictive values, pct was significantly a better marker of bacterial infection (fig. 30 ). discussion we found that serum pct, with a threshold of 0.66 ng/ ml, is a reliable marker of bacterial infection disease in patients with aggressive hematological malignancy admitted to the icu. our study confirms the results of a previous study in unselected immunocompromised patients admitted to the icu, showing a 100% sensitivity, a 63% specificity and an area under roc curve of 0.851 [0.78-0.92] for a threshold of 0.5 ng/ml (1). the main limitations of our study are its retrospective design and the small number of included patients. conclusion pct is a reliable marker of bacterial infection in patients with hematological malignancies admitted to the icu. pct kinetic seems to be an interesting prognostic marker in this population. none. in this study, we have found that kinetics of secretion and expression of endocan is faster with huvecs stimlated by tlr 4 agonist than tlr 3 agonist. this results could suggest that endocan may be not only a marker of septic shock but could be also a specific marker to recognize the nature of pathogenic microorganisms in septic shock. furthermore, other studies with more tlr agonists could be useful to confirm these results. conclusion studying the effects of diverse tlrs agonists could make the plasmatic dosage of endocan more specific and helpful to recognize the nature of pathogenic microorganisms in septic shock. none. lung ultrasound: help to the diagnostic and the monitoring of response to physiotherapy. a case report of pneumonia aymeric le neindre 1 introduction chronic critical illness (cci) syndrome is a new condition affecting an increasing number of patients, who survived an acute critical illness but have persistent severe organ dysfunction, requiring prolonged specialized care. cci is a iatrogenic process, reflecting the efficacy of modern life support technologies(1), and encompasses multiple organ failure, need for prolonged mechanical ventilation (mv), organ support, and palsy due to polineuromyopathy. the transition from acute to cci is gradual: definitions are based on duration of mv, with cut-offs of 7, 14 or 21 consecutive days of mv for ≥6 h/day. cci patients may come from either medical or surgical icu; their health status fluctuates between improvements and deteriorations implying recurrent transitions between different levels of care (1) .the risk of death is reported to be as high as 50%. despite a relatively young age (65 years on average), functional status of cci patients discharged is seriously impaired, thus cci patients require long-term rehabilitation. aim: to estimate the frequency of cci syndrome in careggi, a large academic, tertiary care hospital; to describe the clinical course of cci patients through discharge, and their functional status at discharge. patients and methods administrative data on admission, transfer, death and discharge of all cci patients, consecutively admitted in one of the 56 icu beds at careggi hospital from january 1 to december 31, 2014, were collected. cci was defined with the cut off of ≥21 days of icu stay, representing the index event (ie) without contribution of previous or subsequent hospitalization in other hospitals. reasons for admission were grouped into the 4 broad categories of medical causes, surgery, major trauma and cardio-respiratory arrest. patients discharged were evaluated in daily living, cognitive status, and mobility using barthel index. results we identified 123 subjects who developed cci (71 males; age 61.7 ± 1.5 years, mean ± sem); 36 of them came from an external icu, 87 began their cci course within careggi hospital (60 from the emergency room, 27 from a regular ward). average duration of the ie was 36.1 ± 2.1 days. these sample developed accumulative length of icu stay of 4440 days, corresponding to a 22% icu bed occupation over the theoretical total of 20,440. when days of subintensive care and regular ward were separately added, 5500 days of highly specialized care and 6266 days of total acute hospital stay were reached. surgical patients had longer hospitalizations (p = 0.009).cci patients confirmed to be highly erratic: a total of 302 transitions across different services were recorded in the 123 patients, with a maximum of 9 in 6 of them. mean age was comparable between the 27 patients who died (22%) and the remaining 95 who were discharged alive (66.9 ± 2.5 vs. 60.3 ± 1.7 years; p = 0.058).fourteen subjects continued their icu stay out of hospital. only 6, whose age was lower (37.7 ± 3.7 years), were discharged home; half of the participants (n = 68, 55.2%) were admitted to a residential rehabilitation facility. younger subjects scored better in the domains of self care (p = 0.018) and cognitive status (p = 0.008) but not in the domain of mobility, including walking ability: 45 patients required maximal assistance in performing activities of daily living and transfers, other 12 required medium/maximal assistance, with no statistical difference between dg group. conclusion cci is a relevant clinical condition that need to be assessed and possibly prevented, as it causes severe morbidity, long-term functional impairment and exceeding healthcare costs. none.conclusion early mobilization during the first week of the sepsis onset was safe and preserved muscle fibre cross sectional area. none. none. study of efficacy on icu acquired weakness of early standing with the assistance of a tilt table in critically ill patients none.introduction patients with high flow nasal cannula may benefit from combined aerosol therapy. clinical efficacy depends on pulmonary deposition which is related to the type of nebulizer. all new nebulizers or delivery methods require rigorous evaluation. the aim of this study was to compare lung deposition between two nebulizers (jet nebulizer vs vibrating-mesh nebulizer) through high flow nasal cannula in healthy subjects. patients and methods aerosol delivery of diethylenetriaminepentaacetic acid labelled with technetium-99m (99mtc-dtpa, 4 mci/4 ml) to the lungs using a vibrating-mesh nebulizer (aerogen solo ® , aerogen ltd., galway, ireland) and a constant-output jet nebulizer (opti-mist plus nebulizer ® , convatec, bridgewater, nj) through high flow nasal cannula (optiflow ® , fisher & paykel, new zealand) was compared in 6 healthy subjects. flow rate was set at 30 l/min through the heated humidified circuit. pulmonary and extrapulmonary deposition were measured by single photon emission computed tomography combined with a low dose ct-scan (spect-ct) and by planar scintigraphy. results lung deposition was only 3.3 ± 1.3 and 1.2 ± 0.8% of the nominal dose with the vibrating-mesh nebulizer and the jet nebulizer, respectively (p < 0.05). dose lost in the high flow circuit, humidification chamber and nasal cannula was higher with the vibrating-mesh nebulizer as compared to the jet nebulizer (75.2 ± 8.2 vs 45.0 ± 6.2% of the nominal dose, p = 0.001). expressed as percentage of emitted dose, lung deposition was similar with both nebulizers. conclusion this study demonstrated that aerosol delivery through hfnc is poor in the specific conditions of the study despite the higher efficiency of the vibrating-mesh nebulizer as compared to the jet nebulizer. placing the nebulizer on the hfnc circuit at 30 l/min induces high aerosol loss on the circuit and the oropharynx. key: cord-335975-m6lkrehi authors: nan title: proceedings of réanimation 2018, the french intensive care society international congress date: 2018-02-05 journal: ann intensive care doi: 10.1186/s13613-017-0345-7 sha: doc_id: 335975 cord_uid: m6lkrehi nan introduction: veno-venous extracorporeal co 2 removal (ecco2r) is a promising new therapeutic option in the critical care setting. we conducted a prospective observational study of the use of ecco2r in selected voluntary centers during 2 years aiming to assess the prevalence of the ecco2r use mainly among copd and ards patients. patients and methods: two medical devices: hemolung (alung technologies, pittsburgh, usa) and ila activve (xenios novalung, heilbronn, germany) were selected after literature and medico-economic evaluations. a specific medical and nurses training was provided in table 1 characteristics of 130 patients with known or de novo svv (small-vessel vasculitis) admitted to the intensive care unit for acute respiratory failure (arf) all arf (n = 130) immune arf (n = 67) non immune arf (n = 63) p age , introduction: ineffective triggering is frequent during pressure support ventilation (psv). its occurrence is favored by dynamic hyperinflation that may arise when increasing the pressure support level (psl). decreasing the psl however fails to suppress ineffective triggering in a subgroup of patients that are therefore exposed to refractory ineffective triggering. proportional assist ventilation with load-adjustable gain factors (pav +) decreases the incidence of ineffective triggering in unselected patients but its effect on refractory asynchrony during psv is unknown. the main aim of our study was to assess the effect . the median gain during pav + was 70% [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] . the asynchrony index was significantly lower with pav + than psv (3% [2] [3] [4] [5] [6] [7] [8] vs. 24% respectively, p = 0.02). moreover, the asynchrony index decreased in every patient with pav + (fig. 1) . noticeably, the tidal volume was already protective in psv and decreased even more during pav + (5.71 ml kg [4.6-9.3] vs. 5.71 ml [1.8-7 .1] respectively, p = 0.03); and the neural respiratory rate was high in both modes (41 cycles min in psv vs. 40 [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] in pav + , p = 0.61). total esophageal pressure-time product (ptpes) did not significantly differ between the two modes but the ptpes proportion that was wasted in ineffective efforts decreased with pav + (1% [1] [2] vs. 18% , p = 0.03). conclusion: our preliminary data suggest that: (1) pav + reduces the incidence of refractory ineffective triggering; (2) patients exposed to refractory ineffective triggering during psv seem characterized by rapid shallow breathing despite high ventilatory support, questioning the tolerance of both ventilatory modes. results with further inclusions will be presented. introduction: the use of alternatives to carbapenems to treat patients with extended-spectrum beta lactamase-producing gram negative bacilli (esbl-gnb) infections remains controversial. their use in patients with severe infections in the icu has been poorly studied. the aim of this study was to compare the outcome of icu patients having received carbapenems to those having received a carbapenem-sparing agent (csa). the charts of patients with esbl-gnb infection hospitalized in our icu between 2015 and 2017 were retrospectively reviewed. patients treated with betalactam betalactam inhibitor (bl bli), cefepime or quinolones were considered has having received an alternative to carbapenems (csa). patients having received such a csa were compared to those having received a carbapenems. primary outcome was treatment failure at day 28, defined as esbl-gnb infection recurrence (relapse with same pathogen) or death, whichever first occurred. results: 66 patients with esbl-gnb infection were included. source of infection was the lung for most of them. characteristics of patients are displayed on table 1 . their median saps ii and sofa scores were 59 and 12 [7] [8] [9] [10] [11] [12] [13] [14] [15] , respectively, and 38 (58%) were on septic shock. 40 patients received a carbapenem empirically, among whom 18 were switched to a csa agent when antibiogram was available (csa-definite group), whereas carbapenems were pursued in the 22 others (carbapenem-only group), mainly because pathogens were resistant to others antibiotics. among the 26 patients having received a non-carbapenem agent as empirical treatment, pathogen was susceptible to this agent in 9 and they pursued the same treatment (csa-only group), whereas 17 were switched to a carbapenem (pathogens resistant to empirical treatment, carbapenem-definite group). treatment failure were not different among these 4 groups (table 1) . globally, 27 patients received a csa as their definite treatment (csadefinite and csa-only groups), whereas 39 received a carbapenems (carbapenems-only and carbapenems-definite groups). whereas duration of antimicrobial treatment was similar (8 [6-10] days vs. 9 [7-10] days, respectively, p = ns), treatment failure rate was not higher in the former, as compared to those having received a carbapenems (29 vs. 71%, respectively, p = 0.049). conclusion: treatment of patients with esbl-gnb severe infection in the icu with a csa seems to be safe when the pathogen is susceptible to this csa. however, mic should be first determined before de-escalating to a csa. larger studies are needed. 1 percentages of samplings which attained the pk pd targets for various crcl with potential suboptimal beta-lactam concentration in critically-ill patients with aki treated either with an early or a delayed rrt strategy. patients and methods: ancillary study in a subset of patients with severe aki (kdigo3), receiving a beta-lactam antibiotic, in a trial comparing two rrt initiation strategies. in this trial, patients from 31 intensive care units were randomly assigned to either an early (immediate rrt) or a delayed (late or no rrt) rrt initiation strategy. beta-lactam residual concentrations were sampled at 24 and 48 h after inclusion. the appropriate concentration was defined as a trough of at least 4 times the minimal inhibitory concentration (clinical breakpoint of eucast). the primary outcome was an adequate plasma concentration of the beta-lactam during the first 2 days. results: among the 233 patients included in the 11 centers participating to this ancillary study, a beta-lactam trough concentration was evaluated in 112 subjects, 53 in the early and 59 in the delayed groups. ninety patients (80.4%) had an adequate beta-lactam dosage. rrt initiation strategy had no impact on beta-lactam concentration (p = 0.78). among the 83 septic shock patients (74% of the sampled patients), 73 (88%) had a correct antibiotic concentration. in contrast, only 10 of the 16 patients without definite sepsis (62.5%) had a correct dosage. factors associated with an adequate beta-lactam trough concentration in univariate analysis were admission for a septic shock (p = 0.002), a higher plasma creatinine level (p = 0.024), a higher mean arterial pressure (p = 0.018) and a lower serum bicarbonate level (p = 0.045) at randomization. a higher sofa score was associated with an adequate beta-lactam concentration near to statistical significance (p = 0.053). multivariate analysis will be presented. in the context of severe aki, beta-lactam concentration reached a sufficient level in 88% of septic shock patients. interestingly, rrt initiation strategy was not associated with beta-lactam trough concentration. early rrt did not affect trough concentration of betalactam. we may hypothesize that physicians were highly vigilant and adapted antibiotic administration adequately in these patients. introduction: amikacin infusion requires to target a peak serum concentration (c max ) 8-10 times the minimal inhibitory concentration, corresponding to a c max at 60-80 mg l −1 for the least susceptible bacteria. recent study reported that 33% of critically ill patients do not attain this target with a 25 mg kg dose (1) . membrane sequestration, alteration of the volume of distribution and lack of data in this population make drugs pharmacokinetics (pk) on ecmo challenging. our study aimed to assess the prevalence of insufficient amikacin c max in critically ill patients on ecmo and to identify relative risk factors. patients and methods: prospective, observational, monocentric study of adult patients on venoarterial (va) or venovenous (vv) ecmo receiving a loading dose of amikacin for suspected gramnegative infections. intravenous amikacin was administered with a loading dose of 25 mg kg of total body weight and c max was measured 30 min after the end of the infusion. independent predicators of c max < 60 mg l −1 after the first amikacin infusion were identified by mixed model multivariate analysis. results: from january 2015 to february 2016, 106 patients (median saps 2 (interquartile range) 68(47-81); age 55(45-62) years) under va-ecmo (68%) or vv-ecmo (32%) were included. at inclusion, the sofa score was 15 (12-18) and 54 (51%) patients were on renal replacement therapy. overall icu mortality was 54%. c max was < 60 mg l −1 in 41 (39%) of the patients. independent risk factors of amikacin under-dosing were body mass index (bmi) < 22 kg m −2 (odds ratio (or) 6.38, 95% confidence interval 95%ci 1.8-22.8, p = 0.043) and a positive 24 h fluid balance (or per 500 ml increment: 1.28, 95%ci 1.05-1.65, p = 0.041) (fig. 1 ). our results were comparable to those observed in patients treated with amikacin without ecmo (1) . conclusion: this large prospective study suggests that the prevalence and associated risk factors of amikacin under-dosing are similar in critically-ill patients with or without ecmo. the use of a 30 mg kg dose in low bmi patients and in those with a positive 24-h fluid balance on ecmo is strongly encouraged to obtain adequate therapeutic targets and prevent therapeutic failure. results: fifty patients were included (29 with delirium, 21 controls), at day 4 for controls and day 5 for patients with confusion. delirium patients were more severely ill sofa 5 [3; 9] versus 3 [1; 5] (p = 0.05); with higher rass 1[0; 2] versus 0[0; 0] (p = 0.05). they presented with 41% bl overdosing versus 19% in controls (p = 0.09); with 41% of bl in therapeutic index: 71% in controls (p = 0.04). obesity and renal failure were not associated with bl overdosing but there was a trend with hypoalbuminemia (p = 0.09). discussion: trend in association of bl overdosing with delirium corresponds to previous studies, and would need a larger scale study to be confirmed. severity differences in groups would need changes in inclusion criteria to obtain homogeneous groups. a possible association of bl underdosing with poor evolution of infection and organ failures would need more precise evaluation. hypoalbuminemia could have an impact on bl overdosing. conclusion: delirium was not associated with bl overdosing but with therapeutic index. a high variability of bl concentrations warrants therapeutic drug monitoring. a larger scale study should include changes in design. feasibility and safety of low-flow extracorporeal co 2 removal with a renal replacement platform to enhance lung protective ventilation in patients with mild to moderate ards schmidt matthieu 1 , jaber samir 1 , constantin introduction: extracorporeal carbon dioxide removal (ecco2r) might allow ultraprotective mechanical ventilation with lower tidal volume (vt) (< 6 ml kg ideal body weight), plateau pressure (pplat) (< 30 cm h 2 o), driving pressure, and respiratory rate (rr) to reduce ventilator induced lung injury (vili). the aim of this study was to assess the feasibility and safety of ecco2r with a renal replacement platform (rrt) to permit ultra-protective ventilation in patients with mild to moderate acute respiratory distress syndrome (ards). patients and methods: twenty patients with mild (n = 8) or moderate ards were included. vt was gradually reduced from 6 to 5, 4.5 and 4 ml kg −1 and peep adjusted to reach 23 > pplat > 25 cm h 2 o. standalone ecco2r (no hemofilter associated on the rrt platform) was initiated when arterial paco2 increased by more than 20%. ventilation parameters (vt, rr, peep), respiratory compliance, driving pressure, arterial blood gases, and ecco2r system operational characteristics (blood flow, sweep gas flow, and co 2 removal rate) were collected during a minimum of 24 h of ultra-protective ventilation. complications, mortality at day 28, need for adjuvant therapies and data on weaning from both mechanical ventilation and ecco2r were also collected. results: while vt was reduced from 6 to 4 ml kg −1 and pplat kept below 25 cm h 2 o, peep was significantly increased from 13.4 ± 3.6 at baseline to 15.0 ± 3.4 cm h 2 o at vt = 4 ml kg −1 . as a result, the driving pressure was significantly reduced to 7.9 ± 3.2 cm h 2 o at vt = 4 ml kg −1 (p < 0.05) (fig. 1) . no significant differences in rr, pao2 fio2 ratio, respiratory system compliance were observed after vt reduction. mean extracorporeal blood, sweep gas flow and co 2 removal were 421 ± 40 ml min −1 , 10 ± 0.3 l min −1 and 51 ml min −1 , respectively. mean treatment duration was 31 ± 22 h. main side effects related to ecco2r were membrane clotting which occurred in 7 patients after 19 ± 9 h. conclusion: a low-flow ecco2r device driven by a rrt platform efficiently removed co2 while allowing ultra-protective mechanical ventilation settings in patients with mild to moderate ards (clinicaltrials. gov identifier: nct02606240). morimont philippe 1 , habran simon 1 , desaive thomas 1 , janssen nathalie 1 , amand theophile 1 , blaffart francine 1 , dauby pierre 1 , kolh philippe 1 , defraigne jean-olivier 1 , lambermont bernard 1 introduction: protective lung ventilation (plv) is recommended in patients with acute respiratory distress syndrome (ards) to minimize additional injuries to the lung. however, increased right ventricular (rv) afterload resulting from ards could be enhanced by hypercapnic acidosis resulting from ventilation at lower tidal volume. relative contribution of these factors (ards and plv) in rv afterload is not clearly established. the aim of this study was to compare rv afterload in ards combined with plv to rv afterload in plv alone. patients and methods: this study was performed in an experimental model of severe hypercapnic acidosis performed in 2 series of 6 pigs. in both groups, respiratory tidal volume was decreased by 60%. in the first group (ards group), an ards (obtained by repeated bronchoalveolar lavage) was performed before reducing ventilation, while in the second group (control group), hypercapnic acidosis was resulting from low tidal volume ventilation alone. results: in both groups, systolic pulmonary artery pressure (paps) significantly increased during plv. this increase was significantly higher in ards group than in control group (fig. 1) . severe hypercapnic acidosis occurred in both groups: paco2 increased from 41.7 ± 3.6 to 78.6 ± 8.1 (p < 0.01) and arterial ph decreased from 7.44 ± 0.05 to 7.13 ± 0.04 (p < 0.01) in ards group while paco2 increased from 37.7 ± 9.4 to 93.6 ± 6.4 (p < 0.01) and arterial ph decreased from 7.48 ± 0.05 to 7.11 ± 0.04 (p < 0.01) in control group. pao2 significantly decreased in ards group (178 ± 42 to 54 ± 12.3 mmhg, p < 0.01) but did not significantly changed in control group. conclusion: isolated hypercapnic acidosis resulting from plv was clearly responsible for increased rv afterload and this effect was significantly enhanced in ards. pulmonary vasoconstriction resulting from hypercapnic acidosis is strongly enhanced by factors like hypoxia, endothelial injuries or inflammatory mediators in ards. extracorporeal co 2 removal could be the solution to limit afterload burden on the right ventricle when plv is achieved during ards. introduction: prone positioning has been shown to improve mortality in acute respiratory distress syndrome (ards) patients. the respiratory system driving-pressure (dprs) and the transpulmonary driving-pressure (dpl), measured with esophageal manometry, have been shown to be strongly correlated with mortality. the aim of this study was to investigate the evolution of the dpl during prone positioning and its relationship with evolution of oxygenation in ards patients. patients and methods: ten patients with ards equipped with esophageal manometry were enrolled. dprs, dpl and chest wall driving-pressure (dpcw) were measured before and 1 h after prone positioning. respiratory system, pulmonary and chest wall elastance (ers, el, ecw) were calculated at the same time. finally, we studied the correlation between these respiratory variables and oxygenation indicators. patients were classified as responders to prone positioning if the change in the ratio of arterial oxygen partial pressure oxygen inspired fraction (delta.pao2/fio2) induced by the manoeuvre was larger than the median value observed in the group. results: in the whole population, median value of delta.pao2/fio2 was 53.5 mmhg, and 5 patients were classified as responders and 5 as non-responders. in responders, dpl significantly decreased from 8.8 ± 4.1 cm h 2 o to 5.9 ± 5.4 cm h 2 o (p = 0.02) and el decreased from 21.9 ± 5.1 cm h 2 o l to 14.9 ± 6.5 cm h 2 o l (p = 0.02) after prone positioning. other respiratory variables did not change. in non-responders, respiratory variables did not change. between responders and nonresponders, there was no significant difference between baseline respiratory variables. after prone positioning, delta.pao2/fio2 was not related to baseline respiratory parameters. on the contrary delta. pao2/fio2 induced by prone positioning was strongly correlated with changes in dpl (r = − 0.70, p = 0.02) and changes in el (r = − 0.69, p = 0.03). we did not find any correlation between delta.pao2/fio2 and changes in dpcw or changes in ecw. the correlation between delta.pao2/fio2 and changes in dprs (r = − 0.56, p = 0.09) and changes in ers (r = − 0.55, p = 0.10) did not reach significance. conclusion: in patients who respond to prone positioning by the highest improvement in oxygenation, dpl significantly decrease after prone positioning. the changes in dpl and the changes in el play a major role in the improvement in oxygenation induced by prone positioning whereas the changes in dpcw and ecw do not. introduction: whereas prone positioning (pp) has been shown to improve patient survival in moderate to severe ards patients, its rate of use was 7.4% in lung safe study. however, lung safe study was not specifically focused on pp. therefore, present study aimed to determine prevalence of use of pp in ards patients (primary endpoint), physiologic effects of and reasons for not using pp (secondary end-points). the apronet study was a prospective international one-day prevalence study performed 4 times in april, july, october 2016 and january 2017. at each study day, investigators had to screen every patient staying in icu from 0 to 24 h and to fill electronic crf. for patients with ards (defined from the berlin definition criteria) at each study day oxygenation and ventilator settings were recorded. for those receiving pp these variables were recorded before and at the end of pp session. the reasons for not proning were also collected. values are presented as median (1st-3rd quartiles). prevalence rates of pp were compared by using chi square for trend and groups were compared with nonparametric tests. introduction: although acute respiratory distress syndrome (ards) has been largely focused on, few data are available concerning hypoxemia independently of its cause in intensive care unit (icu) patients. a recent prevalence-point-day (ppd) evaluated the patterns and outcomes of hypoxemia in french speaking icus. here, we describe the main etiologies, management and outcomes of the patients of this cohort presenting with severe hypoxemia. patients and methods: a ppd was conducted among 117 french speaking icus during spring 2016. hypoxemia was defined by a pao2 fio2 ratio below 300. we analyzed the data from patients with severe hypoxemia (i.e. with a pao2 fio2 ratio < 100) and compared their characteristics (causes of hypoxemia, ventilatory and non-ventilatory management) and outcomes to the patients with mild or moderate hypoxemia. results: among the 859 hypoxemic patients the day of the study, 74 (9%) had severe hypoxemia. the main cause of hypoxemia was pneumonia and this diagnosis was more frequent than in mild and moderate hypoxemia. whereas bilateral radiologic infiltrates were present in 56 (84.9%) patients, ards was diagnosed by physicians in only 30 (40.5%) of them. invasive mechanical ventilation (mv) was used in 55 (74.3%) patients. high flow oxygen was administered in 11 (14.9%) of them and 8 (10.8%) were under non-invasive ventilation (niv) the day of the study. median vt was 6.1 (4.8-6.6) ml kg of ibw. positive end-expiratory pressure (peep) was higher than in mild and moderate hypoxemic patients (10 (8-12) vs. 5 (5-8) and 7 (5-10) cm h 2 o respectively, p < 0.001). median plateau pressure was 25.5 (23-29.5) and was higher than in mild and moderate groups. median driving pressure was 13 (10-19) cm h 2 o with no difference when compared to other groups. neuromuscular blocking agents were administered in 28 (51.9%) patients, inhaled nitric oxide (ino) in 7 (13%) patients and only 6 patients (11.1%) were on prone positioning. fourteen (18.9%) patients were under extracorporeal membrane oxygenation (ecmo). icu mortality was higher in severe hypoxemic patients as compared to mild and moderate (50.7 vs. 21.3 and 28.5% respectively, p < 0.001). icu length of stay in icu survivors was not statistically different between groups. conclusion: severe hypoxemia, independently from ards, worsens the prognosis of icu patients. even though ards might be underdiagnosed, a protective ventilation was respected in severe hypoxemic patients. introduction: major changes in septic shock management raise the questions of the relevance of the classical risk factors of nosocomial infections in the current era and the link with the primary infectious insult. we herein investigated the risk factors and the outcomes of icuacquired infections in a recent cohort of septic shock patients. patients and methods: this was a 9-year (2008-2016) monocenter retrospective study. all adult patients diagnosed for septic shock within the first 48 h were included. septic shock was defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors. patients who survived the first three days were eligible for assessment of the risk of the first icu-acquired infections. the diagnosis of nosocomial infections were based on current international guidelines. patients were classified according to the development of pulmonary or non-pulmonary icu-acquired infections. the determinants of icu-acquired infections were addressed in a multivariate logistic regression analysis. results: 938 patients were admitted for septic shock. 788 patients remained alive in the icu after the first three days and could then be evaluated for the risk of icu-acquired infections. hence, 554 patients remained free of secondary infections, 138 patients first developed an episode of nosocomial pneumonia and 96 patients first developed an episode of non-pulmonary infection. the mortality rates of patients with icu-acquired pneumonia, non-pulmonary icu-acquired infections and without secondary infections were 49, 49 and 14%, respectively (p = 0.0001). in multivariate analysis, the development of icu-acquired pneumonia was independently associated with male gender (or 2.23, ci 95% [1.28-3.48 ], p = 0.003), renal replacement therapy (or 2.15, ci 95% [1.35-3.42 ], p = 0.001), platelet transfusion (or 2.38, ci 95% [1.4-4 .04], p = 0.001) and a primary pulmonary infection (or 8.06, ci 95% [2.69-24 .12], p < 0.001). the development of non-pulmonary infections was independently associated with renal replacement therapy (or 4.6, ci 95% [2.7-7 .85], p < 0.001), fresh frozen plasma transfusion (or 2.49, ci 95% [1.42-4.37] , p = 0.001), healthcare-associated septic shock (or 1.8, ci 95% [1.1-2.91 ], p = 0.01). conclusion: icu-acquired pneumonia occurs preferentially in patients with septic shock of pulmonary origin. in addition, we identified the transfusion of blood products as a risk factor for pulmonary and nonpulmonary nosocomial infections. introduction: human serum albumin is used for the restoration of blood volume, emergency treatment of septic shock patients. several experimental studies suggested that albumin could have additional protective effects on the vascular wall and more specifically on endothelial functions. however, the in vivo effect of albumin in human endothelium remains unknown. the aim of this study is to assess the effect of albumin or saline infusion on skin endothelial function in septic shock patients requiring volume expansion. we performed a prospective randomized monocentric study in an 18-bed medical intensive care unit. all patients with septic shock who required fluid administration were included between h6 and h24 after vasopressor starting. patients were randomized to receive either 500 ml of saline solution 0.9% or 100 ml of albumin 20%. norepinephrine dose was not modified 1 h before and during the procedure. endothelium-dependant vasodilatation in the skin circulation was assessed by iontophoresis of acetylcholine before and after fluid administration. the improvement of skin blood flow in response to acetylcholine after fluid administration was compared between groups. for each patient, age, sex, saps ii, site of infection, global hemodynamic parameters and clinical microcirculatory parameters were recorded. results are expressed as mean ± sd. qualitative data were compared using chi-2 or fisher's exact test while quantitative data comparisons used student t test or mann-whitney as appropriate. results: twenty-two patients were included (12 women, age: 79 ± 17, saps ii: 42 ± 12). twelve patients received saline and 10 received albumin. apart from age, no statistical difference was found between groups regarding demographic characteristics and baseline hemodynamic parameters. norepinephrine dose and mean volume of infused fluid before inclusion was not different between groups (table 1) . before fluid replacement, endothelial response to acetylcholine iontophoresis was not different between groups (auc 3514 vs 3378; p = 0.16). volume expansion induced a slight increase of systolic arterial pressure, significantly higher in the albumin group (7 vs 2%; p = 0.02) with no difference regarding cardiac output variations between groups. next, we compared the variations of endothelium response to iontophoresis before and after fluid infusion. the improvement of endothelial response after acetylcholine challenge was significantly higher in the albumin group (196 vs 44%, p = 0.01). conclusion: in the early stage of septic shock resuscitation, we showed that albumin infusion had protective endothelial effects. this result has to be confirmed in a larger cohort. 418] + all p < .001). we found no correlation between cognitive scores at hospital discharge and the severity of eeg-defined encephalopathy during the 7 days of icu or during the first 48 h after admission. however, sepsis survivors' scores were lower than controls' (p < .001) ( table 1) . conclusion: in this study, eeg was more sensitive than clinical tools to detect sae but clinical scales correlated with the eeg grade. encephalopathy was not associated with short-term cognitive function. further study and a larger cohort are needed to determine which early eeg introduction: there is growing evidence that corticotherapy improves survival from septic shock. this observational study aimed at evaluating at bedside resistance to corticosteroids in adults with sepsis. patients and methods: participants-icu adults with septic shock or without sepsis admitted to the raymond poincaré university hospital. we also evaluated 10 healthy controls. intervention-resistance to corticosteroids was assessed using a skin test. 10 µl of dermocorticoid cream (class iii, betamethasone) was applied on a 3 cm 2 surface of the skin. at 24 h, two independent physicians scored the blanching of the skin from 0 to 4-0-no blanching + 1-< 50% of surface + 2-50 to 75% of surface + 3-75 to 100% of surface, and 4-blanching beyond application area. cohen's kappa was used to measure concordance. a mean score of < 2 indicated corticoresistance and a score of 4 indicating normal sensitivity to corticosteroids. we also performed a 250 µg acth test. results: we enrolled 110 patients, 47 patients with septic shock (22 males, ) and 63 patients without sepsis (28 males, ). overall, 81 95 (85%) with two measurements patients had concordant evaluation of score by the two physicians + while 14 had a difference of 1-point in scores, resulting in a kappa of 0.78 (95% ci 0.65-0.91). in patients with septic shock, 32 (78%) have corticoresistance, i.e. a mean score < 2, 8 (20%) a score of 2 or 3, and 1 (2%) has normal sensitivity to corticosteroids. in non-septic critically ill, 30 (56%) have corticoresistance, 20 (37%) a mean score of 2-3, and 4 (7%) have normal sensitivity to corticosteroids. hence, as compared to non-septic patients, patients with septic shock were more likely to have corticoresistance (p = 0.04). discussion: topic application of corticosteroids on the skin results in activation of glucocorticoid receptors present within the vessels. subsequently, activation of lipocortin 1 may inhibit the activity of phospholipase a2, regulator of prostaglandins, leucotrienes and platelet activating factor. then, the coupling of alpha adrenoreceptors to their agonists is potentiated, increasing vessels smooth muscles sensitivity to catecholamines. the subsequent local vasocontriction is reflected by skin blanching. thus, the observed lack of skin blanching in septic patients may reflect altered coupling between gluocorticoids and glucocorticoids receptors. conclusion: roughly one out of two adults with septic shock may develop a resistance to corticosteroids as assessed by a skin blanching test in response to betamethasone. introduction: mild therapeutic hypothermia, currently recommended in the management of cardiac arrests with shockable rhythm could promote infectious complications and especially ventilator-associated pneumonia (vap) (mongardon et al. crit care med 2011). despite high incidence of vap and retrospective trials suggesting a benefit of shortterm (48 h) antibiotics in this setting (davies et al. resuscitation 2013) , systematic use of antibiotic prophylaxis is not recommended in patients treated with mild therapeutic hypothermia after cardiac arrest. the primary objective was to demonstrate that systematic short-term antibiotic prophylaxis with amoxicillin-clavulanic acid can reduce incidence of early vap (< 7 days) in patients treated with mild therapeutic hypothermia after out-of-hospital cardiac arrest. secondary objectives were its impact on incidence of late vap and on day 28 mortality. patients and methods: multicenter two parallel-group doubleblinded randomized trial. adult patients hospitalized in icu, mechanically ventilated after out-of-hospital resuscitated cardiac arrest related to initial shockable rhythm and treated with mild therapeutic hypothermia were eligible. exclusion criteria were pregnancy, need for extracorporeal life support, ongoing antibiotic therapy or pneumonia, known chronic colonization with multiresistant bacteria, known allergy to beta-lactam antibiotics and moribund patients. patients received either intravenous injection of amoxicillin-clavulanic acid (1 g 200 mg) or placebo three times a day for 2 days. the primary endpoint was the onset of early vap. all suspected pulmonary infections were adjudicated by a blinded independent committee. results: out of 198 patients included, 196 were finally analyzed, 99 in treatment group and 97 in placebo group (mean age 60.5 ± 14.4 years, sex ratio = 4, sofa score 8.7 ± 3.1). characteristics of cardiac arrest were similar in both groups (no flow = 3.5 ± 4.8 min vs 3.8 ± 4.0 min, low-flow = 21.8 ± 13.7 min vs 18.2 ± 10.1 min). 51 early vap were confirmed, 19 in treatment group vs 32 in placebo group, with an incidence of 19.2 vs 33.0%, respectively (hr = 0.546 + ic 95% = [0.315 + 0.946], p = 0.031) (fig. 1 ). the procedure did not affect occurrence of late vap (> 7 days), respectively 4 vs 5. day 28 mortality was similar in both arms (41.4 vs 37.5%, p = 0.58) and no adverse event was related to study treatment. conclusion: short-term antibiotic prophylaxis with amoxicillin-clavulanic acid significantly decreases incidence of early vap in patients treated with mild therapeutic hypothermia after out-of-hospital cardiac arrest related to shockable rhythm. introduction: immunosuppressed (is) patients are prone to develop respiratory failure and to need ventilatory support. invasive ventilation shared a grim prognosis in the past and non-invasive ventilation had been recommended in these patients, however niv efficacy has been recently challenged and the advent of high flow oxygen therapy had brought even more complexity in the management of such patients. using the data from a recent point-prevalence-day of hypoxemia in icu, we compare the frequency, management and outcomes of hypoxemia in is and immuncompetent (ic) patients. patients and methods: the spectrum study was conducted in 117 french-speaking icus in 7 countries during spring 2016. is was retained in case of malignant hemopathy, hiv positivity, immunosuppressive drugs, recent chemotherapy, neutrophil count < 0.5 g l. hypoxemia was defined as a pao 2 fio 2 ratio > 300 and separate into severe (> 100), moderate (> 200) and mild (> 300). we focused on the causes of hypoxemia, the ventilatory management and the outcome. results: among the 1604 patients included, 187 (12%) were is out of whom 99 (53%) were hypoxemic, proportion similar to the ic patients. mean age and igs-2 of hypoxemic patients were similar in is and ic patients. hypoxemia was mild in 46 (46%), moderate in 43 (43%) and severe in 10 (10%) is patients with a similar distribution compared to hypoxemic ic patients. the causes of hypoxemia were also similar pneumonia being the leading cause. 24 (24%) hypoxemic is patients fulfilled the berlin criteria for ards in a similar proportion to ic patients. respiratory support used in hypoxemic is patients was ambient air in 3, low flow oxygen in 24, high flow in 11, niv in 5 and invasive ventilation in 56 patients, with a different distribution from the ic patients (more patients on high flow therapy and less invasively ventilated). the day of the study, thoracic ct scan and echocardiography were performed in a similar proportion in is and ic patients whereas broncho-alveolar lavage was more frequently performed in is patients (14 vs 6%, p < 0.001). finally, as expected, icu mortality was higher in hypoxemic is patients (38 vs 25%, p < 0.01). conclusion: immunosuppression in the icu seems not to be associated with hypoxemia, severity of hypoxemia or ards. oxygenation management is slightly different from immunocompetent patients with more frequent use of high flow therapy. 59 (13) mmhg, ph 7.26 (0.1). 142 were included in the 2 l/kg/min group and 145 in the 3 l/kg/min group. no difference was observed between groups for baseline characteristics. failure rate was not different between groups-38.7 vs 39.3% + p = 0.92. no center effect was observed for failure. discomfort was more frequent in the 3 l kg min group-7 vs 17% + p = 0.006. the length of stay was shorter in the 2 l kg min group-5.3 (2.8) vs 6.4 (5) days + p = 0.048. intubation occurred in 4 142 patients in the 2 l/kg/min group vs 10 145 patients in the 3 l kg min group (p = 0.12). conclusion: hfnc with a flow rate of 3 l/kg/min did not reduce the risk of failure compared to 2 l/kg/min at the initial respiratory management of avb in young infants. comparison of epinephrine and norepinephrine for the treatment of cardiogenic shock following acute myocardial infarction. optima cc study levy bruno 1 introduction: despite the frequent use of vasopressors which are administered in 90% of patients in cardiogenic shock (cs), there is only limited evidence from randomized trials comparing vasopressor in cs. hence, the optima cc study was designed to compare epinephrine and norepinephrine in cardiogenic shock following myocardial infarction. patients and methods: multicenter, double-blind, randomized trial in 8 french icu. cardiogenic shock patients due to myocardial infarction treated by pci were randomized to receive epinephrine or norepinephrine to maintain map at 70 mmhg. dobutamine was introduced at the physician discretion according to a combination of parameters-echocardiographic parameters, cardiac index, lactate clearance, svo2 and swan-ganz derived parameters. results: 56/57 patients were ventilated (98%). there were no differences in the duration nor in the maximal dose or cumulated dose of epinephrine or norepinephrine. dobutamine was used in 18/27 (67%) in the epinephrine group and in 20/30 (67%) in the norepinephrine group. there were no differences in the duration, in the maximal or cumulated dose. arterial pressure evolution was similar. heart rate increased significantly in epinephrine group and did not change in norepinephrine group. cardiac index and cardiac power index increased significantly more in the epinephrine group than in the norepinephrine group. cardiac double product, a surrogate of myocardial oxygen consumption increased in epinephrine group and did not change in norepinephrine group. epinephrine use was associated with a lactic acidosis from h2 to h24 while arterial ph increased and lactate level decreased in norepinephrine groupepinephrine was significantly associated with an higher incidence of refractory shock-10/27 (37%) versus 2/30 (7%) p = 0.008). the incidence of arrhythmia was identical (epinephrine-41% versus norepinephrine-33%, p = 0.59). ecmo was used in 3/27 (11%) in the epinephrine group and in 1/30 (3%) in the norepinephrine group (p = 0.34) mortality was 11/30 (37%) in the norepinephrine group and 14/27 (52%) in the epinephrine group (p = 0.25) epinephrine use was associated with a trend to an increased risk of death (p = 0.08) and an increased risk of death plus ecmo (p = 0.031) at 7 days. there was a trend for an increased risk of death plus ecmo at j28 (p = 0.064). conclusion: in patients with cardiogenic shock following myocardial infarction, epinephrine use was associated with a lactic acidosis, an higher incidence of refractory shock and an increased risk of death plus ecmo at j7. high dose immunoglobulins in toxic shock syndrome in children: a pilot randomized controlled study (ighn study) javouhey etienne 1 , leteurtre stéphane 2 , tissières pierre 3 , joram nicolas 4 , wroblewski isabelle 5 , ginhoux tiphanie 6 , dauger stéphane 7 , kassai behrouz 8 1 hôpital mère enfant, bron, france; 2 hôpital jeanne de flandre, lille, france; 3 hôpital du kremlin-bicêtre, le kremlin-bicêtre, france; 4 chu nantes, nantes, france; 5 chu grenoble, la tronche, france; 6 hospices civils de lyon, bron, france; 7 hôpital robert debré, paris, france; 8 hospices civils de lyon, bron, france correspondence: javouhey etienne -etienne.javouhey@chu-lyon.fr annals of intensive care 2018, 8(suppl 1):co-67 introduction: superantigen toxins synthesized by s. aureus or by s. pyogenes are responsible for toxic shock syndromes (tss) which lethality can reach 28%. high dose intravenous immunoglobulins (ivig), able to neutralize these toxins, are frequently used even tough evidence of its efficacy is not supported by randomized controlled study (rct) . moreover, ivig are expensive and possibly harmful. before conducting a rct, a pilot study was first designed to assess the feasibility in the context of pediatric critical care. patients and methods: a double blinded rct was performed comparing 2 g kg of ivig to isovolumic 4% albumin perfusion within the first 12 h of tss in children aged between 1 month to 17 years. a priori criteria to determine the feasibility were defined as a rate of inclusion among eligible patients > 50%, a rate of protocol's deviations < 30% (treatment delivery, non-respect of blinding, premature stop), and by the practical and financial aspects of the protocol. secondary objectives were to assess the efficacy of ivig on organ dysfunction (using pelod-2 score), on mortality at day 60 and their safety. the study was promoted by the hospices civils of lyon, approved by the cpp sud-est and registered at clinical trial (nct02219165). inform consent from both parents was required before randomization. this study was funded by csl-behring company. results: during the 30 months study period, 21 patients were included in 9 centers. the inclusion rate was of 71% (5 parent's refusals, 3 parents were absent at admission). two patients were wrongly included (pneumococcal shocks), one patient didn't receive the treatment because he was transferred for ecmo in a non-investigator center, three patients were treated after 12h, and in two patients one bottle of treatment was missing. the blinding was well respected. missing data on the pelod2 score and mortality was lower than 10%, and no premature stop was reported. the ecrf completion was judged easy by investigators. the inclusion of children within the first 12 h was judged challenging. the treatment delivery had to be improved, requiring the help of research assistants. seven serious and one severe adverse events were registered, all patients recovered and no death was reported. conclusion: this pilot study suggested that a rct is feasible. it provides crucial information to improve the recruitment, the respect of the protocol and the correct measure of organ failure. however, inclusion of international centers is necessary to attain the sample size required. indirect calorimetry-based method for the work of breathing assessment when compared to esophageal pressure (pes) measurement and electrical activity of the diaphragm (eadi) during a spontaneous breathing trial in continuous positive airway pressure. patients and methods: a prospective single center study. all intubated and mechanically ventilated children > 1 months and < 18 years old, hospitalized in the pediatric intensive care unit were eligible. patients considered as ready to extubate were included. simultaneous recordings of vo2, pes and eadi were performed during 3 steps: before, during and after the spontaneous breathing test in continuous positive airway pressure. results: twenty patients, median 5.5 months, were included. half of the patients were admitted for a respiratory reason. predicted resting energy expenditure was overestimated as compared to measured resting energy expenditure (51 [47-55] vs 23 [21] [22] [23] [24] [25] [26] [27] [28] [29] kcal kg day, p < 0.001). spontaneous breathing test was associated with an increase in esophageal pressure-time product from 23 to 83 cm h 2 o s min. the same trend was observed in respiratory drive, assessed by eadi which increased from 7.5 [3.2-16.3 ] to 15.9 [5. 2-22.1] . oxygen consumption obtained by ic was higher during spontaneous breathing test as compared to conventional ventilation (3.8 [3.0-5.2 ] vs 3.6 [3.1-4.6 ] ml kg min) but non significantly. changes in work of breathing as assessed by vo 2 was poorly correlated with measurements from pes and eadi whereas we found a moderate correlation between pes and eadi values. spontaneous breathing test and extubation were successful in 20 (100%) and 18 (90%) patients, respectively. conclusion: during weaning from mechanical ventilation, spontaneous breathing test in continuous positive airway pressure induced an increase in work of breathing, both in respiratory drive, as measured by eadi and in respiratory mechanics, as measured by pes. oxygen consumption measured by indirect calorimetry does not seem to be a reliable tool to assess work of breathing in mechanically ventilated children. ben gheriba khalil 1 , grimaud marion 1 , heilbronner claire 1 , roy emeline 1 , hadchouel alice 1 , renolleau sylvain 1 , rigourd virginie 1 1 hôpital necker enfants malades, paris, france correspondence: ben gheriba khalil -bg.khalil@gmail.com annals of intensive care 2018, 8(suppl 1): introduction: during the winter season 2015-2016 we had evaluated breastfeeding disruption after hospitalization for bronchiolitis in our hospital in infants under 6 month (n = 84). we observed 51% of mothers whose breastfeeding was stopped of modified. clinical severity had no impact on breastfeeding but 63% of mothers stated that lack of support and advice was the first cause of breastfeeding disturbance. we conducted this second phase to evaluate the potential impact of actions to promote breastfeeding on unwanted weaning during hospitalization for bronchiolitis. patients and methods: this is a cross sectional study during two epidemic seasons of bronchiolitis in a tertiary care hospital. all patients aged 6 months or younger hospitalized with acute bronchiolitis and receiving at least partial breastfeeding were eligible for the study. patients discharged at home whose parents accepted to be contacted by phone were included. a bundle of actions to promote breastfeeding in patients with bronchiolitis was implemented (posters, flyers, staff training, equipment with breast pumps) between the two epidemic seasons. the data was extracted from the charts and from a phone survey two weeks after discharge to evaluate breastfeeding in eligible patients in our hospital. phase i (before action) had included 84 patients hospitalized between december 2015 and march 2016 in all wards hosting patients with bronchiolitis. phase ii (after action) included 50 patients hospitalized from october 2016 to december 2016. the data from phase ii was compared with data from phase i. results: fifty patients could be included during the second step of the study, with a mean age of 37 days. breastfeeding was exclusive for 78% of mothers (vs 77% in phase i). the median length of stay was 6 days (vs 3 days in phase i). twenty-one (42%) patients spent time in picu vs. 32% in phase i, 3 21 needed intubation, 18 21 received non invasive ventilation for a median length of 4 days (vs. 3 days in phase i). the number of patients needing nutritional support was 35 50 (70%) during phase ii vs. 44 84(52%) during phase i. after implementation of our actions, 40 50 (81%) mothers kept breastfeeding as before (vs. 49% in the previous epidemic season, p < 0.05), 4 mothers (8%) stopped, 4 (8%) switched to partial breastfeeding and 2 (4%) reduced without stopping. conclusion: bronchiolitis is a high risk event for breastfeeding disruption but staff training and correct advices and support for mothers during hospitalization seems to diminish that risk. benefits of using a high temporal resolution database in the automatic real-time pediatric ards screening nardi nicolas 1 introduction: pediatric acute respiratory distress syndrome (pards) is frequent in pediatric intensive care units (picu), potentially lethal and the diagnosis is often missed or delayed (palicc 2015) . in picu, data are usually recorded between 5 to 60 min which leads to only a minority of the arterial partial pressure of oxygen (pao2) that are usable to calculate a valid oxygenation index (oi). if not available, pao2 should be replaced by the spo2 if < 98% to calculate the oxygen saturation index (osi). using a high temporal resolution (htr) database that records data every 5-30 s, we aim to develop a relevant clinical algorithm of mass data aggregation to improve pards screening with the automatic oi and osi calculation. patients and methods: all the patients admitted to our pediatric icu between may 2015 and august 2017 were included. the htr and the electronic medical records (emr) were queried through structured query language (sql) following these steps-(1) data selection (2) extraction to a linear format (3) date and time synchronization (4) data pivoting (5) aggregation through a 10-min moving average (6) hypoxemia calculation. statistical analysis included proportions, correlations and bland-altman analysis. results: between may 2015 and august 2017, 1793 patients (2210 stays) were admitted to the picu. approximately 46 million rows were retrieved from the databases including 19,189 pao2 values. the algorithm was able to calculate 11,320 (59% of the pao2) oi and 5204 osi. the comparison between oi and osi showed that 97.4% of the results were between the limits of agreements (− 17.2 + 10.6), a bias of − 3.3 and a correlation r2 = 0.643. the comparison between the ois from the htr and emr databases showed that 94.6% of the results were between the limits of agreements (− 5.47 + 5.39), a bias of − 0.04 and r2 = 0.904. conclusion: using a mass data aggregation algorithm on a htr database allows more pao2 to be used to calculate an oi than the usual emr. the oi results differ slightly between the htr and the emr. the accuracy is probably in favor of the htr because of the shorter timelapse between the oi parameters. the osi is possibly a biased oi surrogate and should be interpreted with caution. our next step will be to measure the impact of the algorithm on the pards real-time diagnosis and pards severity categories. introduction: early administration of appropriate antibiotic therapy with adequate concentration is the cornerstone of the severe sepsis and septic shock's treatment. adult studies showed alteration of distribution and elimination which can lead to insufficient drug concentration in septic patients. in children, studies are lacking and antibiotic dosing may be suboptimal. we aim to describe the plasma concentration of the most used beta-lactam in critically ill children, to describe the rate of patients with suboptimal exposure and associating clinical and biological factors. patients and methods: this was a prospective, single center, observational study designed in 32 beds pediatric intensive care unit (picu) and high dependency care at the necker hospital (paris, france) from january 2016 to may 2017. were included, children with severe sepsis or septic shock, aged less than 18 years and weighing more than 2.5 kg, and receiving one or more of the following antibiotics-amoxicillin, cefotaxime, cefazolin, ceftazidime, piperacillin-tazobactam, meropenem and imipenem for suspected or proven infection. betalactam plasma concentrations were analysed using high performance liquid chromatography. results: we enrolled 37 children (severe sepsis, n = 22 (59.5%) + septic shock, n = 15 (40.5%)) with a median age of 19 months (4-64. bacteria were identified in 26 patients (70.3%). a total of 132 blood samples were analysed at a median of 2 days (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) following the onset of sepsis. twenty-four patients (64.8%) had insufficient concentration (cefotaxime 7 14 (43%) + piperacillin-tazobactam, 10 13 (77%) + amoxicillin 6 7 (86%) + meropenem 3 6 (50%), cefazoline 1 4 (25%), imipenem 0 2 (0%) + ceftazidime 0 1 (0%)). insufficient concentrations were associated with early measurements (< 72 h from the sepsis' onset) (p = 0.035) and creatinine clearance increase (p = 0.01). adequate concentrations were associated with small age (p = 0.048). in conclusion, current standard beta-lactam dosing in children with severe sepsis or septic shock could be inadequate to reach the target concentrations. that could lead to the risk of clinical and bacteriological failures as well as the emergence of bacterial resistance. further pharmacokinetic studies are mandatory to improve antibiotic therapy in this vulnerable population. introduction: intermittent hemodialysis is a key support therapy in icu. despite protocol-based optimization, intradialytic hemodynamic instability (ihi) remains a common complication and could account for mortality and delayed renal recovery. the identification of patients at high risk for ihi is crucial but remains poorly explored. our objective was to test whether tissue perfusion parameters assessed at the bedside (mottling, index capillary refill time (icrt), and lactate) predict ihi and to develop and to validate a predictive score of ihi. patients and methods: prospective observational study in a 18-bed medical icu in a tertiary university hospital including hemodialysis sessions performed for acute kidney injury. exclusion criteria were patients with dark skin and dialysis performed in extreme emergency. mean arterial pressure (map), mottling score, icrt, and lactate were recorded just before starting hemodialysis. first episode of ihi requiring therapeutic intervention was recorded 60, 120, and 240 min after hemodialysis starting. results: ninety-six hemodialysis sessions performed in 43 patients were recorded. half of the patients received vasopressors (n = 43, 45%). ihi occurred in 22 (23%) sessions and was more frequent among patients receiving vasopressors (42 vs 7%, p < 0.0001). mottling were more frequent (59 vs 26%, p = 0.005), lactate levels higher (2.8 [1.4-6.9 ] vs 1. 1 [0.8-1.5 ] mmol l, p < 0.0001) and icrt longer (3.3 [1.6-4.6 ] vs 1.1 [0.8-2.0] s, p < 0.0001) before sessions with ihi compared to sessions without, independently of map (p < 0.0001). the incidence of ihi increased with the number of tissue perfusion alterations (3, 11, 41 , and 55% for 0, 1, 2, and 3 alterations, respectively, p < 0.0001). a tissue hypoperfusion score, defined as icrt (seconds) + lactate level (mmol l) + 1 if mottling presence was predictive of ihi independently of map (or 1.18 [1.05-1.32 introduction: epidemiological data suggest an increased risk of longterm chronic kidney disease after acute kidney injury (aki). in survivors of out-of-hospital cardiac arrest (ohca), aki is frequent and is associated with numerous factors of definitive renal injury. we made the hypothesis that aki after ohca was a strong risk factor of long-term chronic kidney disease (ckd). we aimed to evaluate renal outcome of ohca survivors according the occurrence of aki in icu. patients and methods: we used the cohort of consecutive ohca patients admitted between 2007 and 2012 in a tertiary medical icu previously described (geri et al. icm. 2015) . aki was defined by kidney disease improving global outcomes (kdigo) criteria. long-term creatinine level was the last blood creatinine assessment we were able to retrieve. the main outcome was the occurrence of ckd, defined by an estimated glomerular filtration rate (egfr) lower than 60 ml min 1.73 m 2 according to the mdrd equation. long-term mortality was evaluated as well. factors associated with ckd occurrence were evaluated by competing risk survival analysis (fine gray and cox cause specific models providing sub-hazard ratio (shr) and cox sub-hazard (csh)). results: among the 246 ohca patients who were discharged alive, we were able to retrieve the outcome of 133 patients (median age 55 [iqr 46, 68] , 75.2% of male) who were included in the analysis. during a median follow-up time of 1.8 [0.8-2.5 ] years, ckd occurred in 17 (12.7%) patients and 24 (18%) patients died. a previous history of arterial hypertension (shr = 3.28 [1.15 + 9 .39], p = 0.027 + csh = 4.83 [1.57 + 14.9 ], p = 0.006), aki during icu stay (shr = 3.72 [1.40 + 9 .84], p = 0.008 + csh = 5.41 [1.79 + 16.3] , p = 0.003) and an age higher than 55 (shr = 6.13 [1.55 + 24.3] , p = 0.009 + csh = 2.16 [1.72 + 43.8 ], p = 0.006) were independently associated with ckd occurrence. aki was not associated with long-term mortality (shr = 0.73 [0.27 + 1.99], p = 0.55 + csh = 0.75 [0.28 + 2.01], p = 0.57). in ohca survivors resuscitated from an ohca, ckd was a frequent long-term complication. aki during icu stay was a strong determinant of long-term ckd occurrence. introduction: many critically ill patients have a moderate to high risk of bleeding but they also require prolonged intermittent dialysis to ensure a negative water balance without hemodynamic adverse events. thus, a heparin-free easy-to-use anticoagulation within the dialysis circuit is needed but, to date, usual protocols (iterative saline flushes, heparin grafted membranes) lead to 20-50% of premature clotting and sessions that last greater than 240 min are rarely achievable. we assessed the safety and efficiency of heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance (an online measure of the instantaneous clearance of small molecules available in most of dialyzers). patients and methods: we prospectively reported the clotting events that occurred during all the heparin-free dialysis sessions that were performed with a regional anticoagulation based on calcium-zero citrate-containing dialysate (citrasate, hemotech, france) between january 2016 and august 2017 in a 28-beds icu. results: a total of 186 dialysis sessions were performed in 70 patients (mechanical ventilation n = 93 + norepinephrine n = 20). median duration of dialysis was 240 min (iqr, 240-300 + maximum 360 min), and median ultrafiltration volume was 2 l (iqr 1. 3-2.6 ). when assessed, urea and beta2-microglobulin reduction rates were 64.5% ± 0.4% and 48% ± 0.13%, respectively. postfilter ionized calcium was 0.35 ± 0.17 and 0.38 ± 0.14 mmol l at 1 and 3 h, respectively, within the extracorporeal circuit. a major clotting event that led to premature termination of the session occurred in only 5186 sessions (2.7%) . in these five cases, major catheter dysfunction occurred before clotting within the circuit. prefilter ionized calcium remained within narrow ranges (before after change +0.07 ± 0.006 mmol l), and total-to-ionized calcium ratio, a surrogate marker for citratemia, was unchanged and always below 2.5. in 85 sessions, no ionized calcium measurement was required. conclusion: dialysis anticoagulation with calcium-free citrate containing dialysate is an easy-to-use, efficient, and inexpensive form of heparin-free regional anticoagulation. calcium reinjection according to ionic dialysance allows prolonged hemodialysis sessions in critically ill patients without the need to systemically monitor ionized calcium. sessions can be safely extended according to the hemodynamic tolerance to ensure an adequate dose of dialysis and a negative water balance, a major point in patients with severe aki. introduction: brain injury is the first cause of death after cardiac arrest (ca) and multimodal neuroprognostication is a cornerstone of postresuscitation care. among the different usable information provide by electroencephalogram (eeg), the aim of this study was to evaluate the predictive value of eeg reactivity regarding neurological outcome at discharge. patients and methods: using our prospective registry of successfully resuscitated patients admitted to a cardiac arrest center between january 2007 and 2016, we studied all consecutive comatose patients still alive at 48 h and in whom at least one eeg was performed during coma. in addition to usual clinical findings, we collected eeg (patterns and reactivity, status epilepticus) and somatosensory evoked potentials characteristics. the eeg reactivity was evaluated by a blinded neurophysiologist and was defined as a reproducible change of the tracing (in amplitude or frequency) provoked by an auditory and a nociceptive standardized stimulation. we evaluated the predictive values of persistent lack eeg reactivity and other indicators regarding their respective ability to predict a favorable or unfavorable outcome. recovery of a level 1 or 2 on the cerebral performance category (cpc) scale at discharge was considered as a favorable outcome, as opposed to recovery of a cpc level 3-5 (unfavorable outcome). we included 428 patients who were mostly male (71%), with median age of 63 years. ca occurred in a public place in 32% of cases, and it was witnessed in 89% of cases. bystander cpr was initiated in 61% patients and the initial cardiac rhythm was shockable in 49% patients. median time to eeg was 3 days (1-4) and 43% of patients were still sedated during the examination. a favorable neurologic outcome was observed in 85 patients (20%). an eeg reactivity was present in 78 85 patients (92%) with favorable outcome and in 117 343 patients (34%) with unfavorable outcome. the positive predictive value (ppv) of a persistent eeg reactivity for prediction of favorable outcome was 40% . by contrast, the ppv of lost eeg reactivity for prediction of unfavorable outcome was 97% (ic 95% 94-99) with a false positive rate (frp) of 2.8% (1.2-4.4 ). eeg electroencephalogram, ssep short-latency somatosensory evoked potentials, ppv positive predictive value, npv negative predictive value, fpr false positive rate in this population of post-cardiac arrest patients, the presence of eeg reactivity was poorly predictive of a favorable neurologic outcome. the absence of reactivity was highly predictive of unfavorable outcome. in combination with other indicators, searching for eeg reactivity may have important implications in the neuroprognostication process. conclusion: this subgroup analyses of a randomized controlled trial, found no survival benefit when comparing crystalloids to colloids in critically ill surgical patients. introduction: goal of a fluid challenge (fc) is in fine to increase the stroke volume (sv) or the cardiac index (ci) when an episode of hypovolemia or a preload dependence status are suspected. fc is one of the most common practices in icus, however, the way to assess the response to fc is not standardized. the present study aimed to evaluate whether the trans-thoracic echocardiographic (tte) assessment of the response to fc immediately at the end of the infusion or delayed 20 min later could affect the results of the fc. patients and methods: prospective, observational, multicentre study including all icu patients in septic shock requiring a fc. were excluded patients with-arrhythmias, poor echogenicity and severe mitral or aortic regurgitation. fc was performed administering 500 ml of crystalloids over 10 min. fluid responsiveness was defined as a > 15% increase in stroke volume (sv). the following echocardiographic parameters were recorded-e wave, a wave, e a ratio, velocity-time integral (vti), ea wave and sa wave. map, hr and tte variables were collected at baseline (t0), at the end of fluid challenge (t10) and 10 (t20) and 20 min (t30) after the end of fluid challenge. quantitative data are expressed as mean and standard deviation (sd) or median and interquartile (iqr), according to their distribution. qualitative data are expressed as absolute number and frequency (%). results: from may 20th 2014 to january 7th 2016, a total of 143 patients were enrolled in 11 french icus (mean age-64 ± 14 years, median igs ii-53 , median sofa score-10 [8] [9] [10] [11] [12] ). among the 76 143 (53%) patients responders to fc at t10, 37 patients were transient responders (tr), i.e. became non-responders at t30 (49%, 95% ci = [37-60]) and 39 (51%, 95% ci = [38-62])) patients were persistent responders (pr), i.e. remained responders at t30. among the 67 non-responders (nr) at t10, 4 became responders at t30, (6%, 95% ci = [1.9-15.3] ). in the subgroup analysis, no statistical difference in haemodynamic and echocardiographic parameters was found between non-responders, transient responders and persistent responders (fig. 1) . conclusion: the present study shows that, after a 15% vti increase at the end of the fc, vti returns to baseline at 30 min in half of the responders. blood volume status (normo or hypovolemia) before initiating the fluid infusion could explain the transient or persistent response to fc observed in septic patients. mottling score is a strong predictor of day-14 mortality in sepsis patients independently of catecholamine dosing and other tissue hypoperfusion parameters dumas guillaume 1 , joffre jérémie 1 , hariri geoffroy 1 , bigé naike 1 , baudel introduction: sepsis is a frequent critical condition. mottling score, an hypoperfusion parameter, is well correlated with outcome. however, uncertainties persist regarding its value not only as a marker of patient severity but also as an independent predictor of mortality and treatment efficacy. we performed a post hoc analysis of four published prospective studies including sepsis patients with or without shock. we analyzed the relationship between the mottling score (from 0 to 5) and day-14 mortality according to other prognosis covariates such as catecholamine dosing, urine output and plasma lactate levels. first, factors associated with outcome were determined by multivariate analysis. second, mottling score-by-covariate interaction was studied to better understand its effect on mortality. finally, effect of mottling score variation at different time point (h0-h6-h12-h24) was assessed. whereas ecmo was successfully weaned in 6 (33%) patients. proportion of perfused vessel (ppv), perfused vessel density (pvd), micro flow index (mfi) and heterogeneity index (hi) were severely impaired before ecmo. re-establishing high and stable peripheral blood flow with va-ecmo led to a rapid decrease in heart rate and vasoactive inotropic support and significantly improved all microcirculation parameters within 12 h. total vessel density and pvd, measured before and after ecmo initiation, were better in patients successfully weaned from ecmo (p < 0.05) (fig. 1) . conclusion: cardiovascular support with ecmo-va rapidly improved macro and microcirculation in refractory cardiogenic shock patients. total vessel density and perfused vessel density were significantly better in survivors 12 h after ecmo initiation and might therefore help to predict outcomes. further studies are now needed to better define the utility of this technology in larger groups of va-ecmo patients. introduction: thyroid storm is a rare but life-threatening disease related to thyrotoxicosis. it can lead to multiple organ failure including cardiovascular disorders or neurological impairment. to date, data on this disease in icu patients are scarce and limited to case reports. we therefore aimed to describe clinical presentation, outcomes and management of thyroid storm in icu patients. patients and methods: local diagnoses coding database (from january 2000 to july 2017) from 22 french icu were interrogated for main and secondary diagnoses codes including thyrotoxicosis based on the international classification of disease 10th revision. thereafter two investigators reviewed all the medical records selected. inclusion criteria were thyroid storm based on the diagnostic criteria of the japan thyroid association (t. satoh, endocrine journal 2016). it combines thyrotoxicosis with elevated levels of free triiodothyronine (ft3) or free thyroxine (ft4) with at least two of the following symptoms-central nervous system manifestation, fever, tachycardia > 130 bpm, congestive heart failure, or total bilirubin level more than 50 micromol/l. clinical presentation, therapy used, and outcome were recorded. results: sixty-two patients (median age 57 years (interquartile range 44-67) + saps ii 45 (32-66) were included. thyroid storm was the first manifestation of thyrotoxicosis in 18 (29%) patients. graves' disease (27%), amiodarone induced thyroiditis (26%), autoimmune thyroiditis (11%), and toxic multinodular goitre (10%) were the main causes of hyperthyroidism. amiodarone, thyroid hormone toxicity, antithyroid drugs withdrawal or infectious trigger were identified in 59 (95%) patients. organ support including mechanical ventilation, catecholamine infusion, renal replacement therapy and veno-arterial ecmo were used in 34, 31, 11, and 12 patients, respectively. main thyroid storm treatments included antithyroid drugs (81%), betablockers (69%), corticosteroids (45%), and plasmapheresis (13%). lastly, icumortality was 16%, with multiple organ failure responsible of death in all patients. although its incidence appears low, icu physicians should be aware of the multiple clinical features of thyroid storm. our preliminary data reported various specific therapeutic management of this potentially fatal disease. prompt initiation of targeted therapies is required for atypical hemolytic uremic syndrome (ahus) and thrombotic thrombocytopenic purpura (ttp), but no specific therapy is consensual for shiga toxinassociated hemolytic uremic syndrome (stec-hus). thus, rapid differentiation of stec-hus is mandatory to tailor the initial treatment. furthermore, apart from large outbreaks, characteristic features of this syndrome in adults have not been described. in this study, we retrospectively compared the characteristics of stec-hus, ahus and ttp patients at admission in two expert icus. patient were included if they presented with the triad of mechanical hemolytic anemia, thrombocytopenia and organ damage, and tmas were classified using international criteria. other causes than stec-hus, ahus and ttp were excluded. results: amongst 236 tmas admitted between september 2003 and january 2017, 12 stec-hus, 21 ahus and 91 ttp were included. stec-hus patients were older (64) than ahus (36, p = 0.02) and ttp patients (43, p < 0.01). they presented with more frequent digestive symptoms (92 versus 62 and 37% for ahus and ttp, p = 0.01 and < 0.01), but bloody diarrhea was rare (17%) and non-statistically different from other tmas. confusion was more frequent in stec-hus (33%) than ahus patients (5%, p = 0.05). biologically, stec-hus patients displayed elevated fibrinogen levels (5.1 vs 3.2 and 3.6 for a hus and ttp, both p < 0.01) and severe renal failure. forty-two percent required renal replacement therapy and 83% were treated with plasma exchange before the distinction from other tmas could be made. only 1 (8%) stec-hus patient died in the icu (fig. 1) . conclusion: characteristics supposed to identify stec-hus are largely shared with other tmas. in particular, the differential diagnosis between ahus and stec-hus appears to be more difficult than the stereotypical description derived from pediatric studies. severe hyperglycemia in 1000 icu patients: a higher mortality rate and a higher incidence of diabetes in a long-term follow-up study .87], p = 0.04) but not when admitted for coma, sepsis or cardiac arrest. mortality rate was significantly higher in patients with severe hyperglycemia compared to those without, regardless of preexisting diabetes (hnd hd vs. nhnd nhd groups + p < 0.05). patients with severe hyperglycemia had a higher incidence of type 2 diabetes at 6 (16 vs. 8% + p = 0.01) and 12 months (14 vs. 9% + p = 0.08) compared to those who did not. conclusion: severe hyperglycemia occurring in the first 3 days of icu admission was associated with higher mortality rate and an increased risk of diabetes in the following months regardless of preexisting diabetes. introduction: vitamin d deficiency is frequent in northwestern countries and could represent a modifiable risk factor for critically ill patients, in relation with its pleiotropic effects (1) . some studies reported an association between 25oh vitamin d (25oh) deficiency, chronic health status and icu-and hospital-related outcomes. however, a large supplementation study have not been found to improve outcome of patients with moderate 25oh deficiency (< 20 ng ml) (2) . the aim of the study is to analyze the relationship between the severity of 25oh deficiency at icu admission, severity of illness and outcomes and ultimately to identify subgroups of patients in whom the likelihood of benefit of supplementation is larger. patients and methods: consecutive patients admitted over a 4-month period who stayed at least 48 h in a medical surgical 32-bed icu were included. in these patients, demographic data, charlson comorbidity score, severity scores (saps 3 and sofa) and 25-oh (chemiluminescence, diasorin) were collected at admission. icu and hospital length of stay (los) and mortality were recorded. correlations were searched between 25oh and the different scores, and vital outcomes (41-74)). hypothyroidism was unknown before icu admission in 68% patients. median sofa score at icu admission was 6 (4-10). myxedema coma, circulatory failure, respiratory failure, and severe hypothermia were respectively the main admission reason in 60, 18, 10, and 5% patients. a precipitating factor such as drugs thyroid toxicity, thyroid hormone withdrawal or infection was found out in only 13 (32%) patients. main causes of hypothyroidism were thyroiditis and thyroidectomy. thirtytwo (80%) patients had alteration of consciousness with a median glasgow score at 10 (6-13). in addition, median heart rate at icu admission was 50 (35-65) bpm while hypothermia < 35 °c was noted in 24 (60%) patients. median tsh level at admission was 78 (43-135) mui l, t3 and t4 levels respectively 0 (0-0.45) pmol l and 2 (0-5.07) pmol l. rhabdomyolysis was frequent with median cpk level 539 (192-1500) ui l. organ support including mechanical ventilation, catecholamine infusion and, renal replacement therapy were respectively used in 58, 45, and 20% patients. lastly, 70% patients received oral levothyroxine whereas the intravenous form was used in others. overall icumortality was 22%. our preliminary data showed that severe manifestations of hypothyroidism leading to icu admission represent de novo hypothyroidism in two-thirds of patients, leading to a high mortality. introduction: when it comes to infections of the central nervous system (cns), the greatest challenge in the emergency department (ed) is to identify patients that have a rare life-threatening diagnosis. alone or in combination, fever, headache, altered mental status encompass a broad differential diagnosis. antibiotics or antiviral therapy should be given as soon as possible, ideally after both blood and cerebrospinal fluid (csf) have been obtained. early treatment is associated with a lower mortality. patients and methods: we present here, a four-year (2012-2015) retrospective and monocentric study. during the period of the study, we included all adult patients with the diagnosis of cns infection (positive csf culture). we collected and analyzed all clinical, biological, imaging, treatments and evolution datas during the stay. a total of 67 patients with cns infection have been included for statistical analysis. we analyzed a second group (n = 25) with suspected cns infection (negative csf) as a control group. results: in the study population, mean age was 43 ± 21.5 years old and the sex-ratio was 1.2. there were no difference between the two groups in terms of clinical signs except for more altered mental status in the control group (p = 0.02). all patients of the study (n = 92) benefited of lumbar puncture (lp) in the ed with an average time of 381 ± 370 min after admission. this delay was the same between the two groups (p = 0.76) but was significantly higher in the encephalitis subgroup (n = 13, p = 0.03). patients who had imaging (ct or mri) during the ed stay had more likely a delay in lp realization (450 vs 193 min, p = 0.0005). patients where the cns infection diagnosis was firstly evoke by the triage nurse had lp more quickly (p = 0.03). the median door to-antibiotic-time was 339 min with no difference between the two groups of the study (p = 0.7). 94% of all patients were hospitalized for an average length of stay of 11.7 ± 15.5 days and 10% of them were admitted in the icu. the inhospital mortality was 14% in the study population. introduction: there are numerous causes of acute exacerbations of copd (aecopd), the most common of which are bronchial and or pulmonary infections. viral etiologies may account for 30% of aecopd, but this rate is likely underestimated because of the limited performance of the conventional diagnostic tests. multiplex molecular diagnostic tests may identify several pathogens including viruses and bacteria, from a single respiratory tract sample, with high sensitivity. using these tests, respiratory viruses are identified in 30 to 60% of cases, according to the series. the objective of this work was to describe the microbial epidemiology, the management and the outcome of patients admitted to the intensive care unit (icu) with moderate to severe aecopd, in the era of multiplex testing. a prospective non interventional multicenter study conducted in two university-teaching hospitals. in addition to the usual samplings, a nasopharyngeal swab was performed for multiplex polymerase chain reaction (pcr), using respiratory panels fil-marray biomérieux (17 viruses and 3 bacteria) or eplex automaton (22 viruses and 4 bacteria) depending on the center. the preliminary results involve the 37 patients (29 males + 70 years (55-87)) included in tenon hospital over a 6-month period. the mean fev1 was 37% (21-60) median 35% [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] . drug therapies included anticholinergics (n = 21 + 62%) and beta-2-mimetics (n = 24 + 71%), inhaled (n = 16 + 47%) or oral (n = 2 + 6%) steroids, and azithromycin (n = 5 + 23%). a respiratory virus was identified in 11 patients (30%), alone or in combination with a bacterium (n = 6). a bacterial pathogen was identified alone 9 times (21%). therapeutic interventions did not differ depending on whether a virus was detected or not-exposure to antibiotics (10 ± 1.8 vs. 12.5 ± 2 d + p = 0.4), administration of oseltamivir (5/6 vs. 8/18 + p = 0.39), steroids (1/7 vs. 3/15 + p = 0.12) and mechanical ventilation (11/11 vs. 20/26 + p = .08). the icu length of stay (5.8 ± 0.8 vs. 7.8 ± 1.1 d + p = 0.29) was similar. the icu and 90d-mortality rates were 5.4 and 13.5%, respectively. conclusion: respiratory viruses are frequently involved in moderate to severe aecopd. the respiratory multiplex pcr should be performed in this setting and the results should be taken into account to more adequately use the anti-microbial treatments. introduction: prophylactic non-invasive ventilation (niv) is a well established method for prevention of post-extubation acute respiratory failure in hypercapnic patients. however, its role in the postextubation period, in traumatic brain injury patients, is uncertain. especially, because of effects of the brain injury, on respiration and airway control. we perform a study to assess the impact of prophylactic niv after extubation among patients with severe traumatic brain injury. patients and methods: over a period of 1 year, adult patients with isolated severe traumatic brain injury, who were under invasive mechanical ventilation for more than 48 h were eligible for inclusion in the study. they were randomized, after decision of extubation, to receive conventional therapy or conventional therapy associated with niv. conventional therapy consisted of oxygen delivery by facial mask, semi-recumbent position, mucus suctioning and nebulization therapy. the main objective of the study is to assess the impact on reintubation rate. extubation succes was defined by the absence of need for reintubation within the 7 days. the secondary objective is to evaluate the effect on icu length of stay after extubation. the clinical benefit of non-invasive ventilation (niv) in patients with acute hypoxemic respiratory failure (arf) is being called into question. indeed, in a multicenter randomized trial recently conducted in hypoxemic arf patients (pa02 fi02 < 300), intubation rate in the niv group was 50% and intensive care unit (icu) mortality rate was 25%, numbers higher than in the standard-oxygen group (1) . an excessive tidal volume under niv is a hypothesis to explain these bad outcomes (2) . our experience does not seem to support these data. therefore we wanted to-investigate the rate of niv success in hypoxemic arf and global in-icu mortality. estimate the average expired tidal volume and identify predictive factors of niv failure. conclusion: though limited by its design, our study seems to show a similar efficacy of niv following ue as compared to planned extubation, with a safety concern for rescue niv and a potential interest for "prophylactic" niv. further data is warranted. which is yet operator dependent and time-consuming, or by invasive methods including esophageal pressure or diaphragmatic electromyogram measurements. the main purpose of this study was to assess the relevance of curvex as a noninvasive diagnostic and classification tool for asynchronism management. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct02893462) that aims to record 1500 consecutive icu patients, over 3-years. all consecutive patients were recorded for a 2-hours period during 24-h following icu admission. all measurements were recorded with the patient laying supine, with a 30° bed angulation. raw ventilatory pressure and flow curves were transferred to a centralized server using a dedicated network. the physician in charge of the study was informed of the online analysis on a routine basis. physiological recordings were associated with metadata collection. asynchronisms detection is based on a non-parametric hypothesis testing (random distortion testing), that requires no prior information on the signal distribution. beside asynchrony index monitoring (ai), five asynchronism's types were qualified-ineffective efforts (ie), short cycles (sc), multiple cycles (mc), prolonged inspiration (pi) and premature cycling (pc introduction: international guidelines recommend ultrasound (us) guidance for central venous catheter (cvc) insertion. however, evidence is lacking for several aspects of guidance such as probe shape or whether the needle has to be in plane (ip) or out-of-plane (oop). we assessed these issues in a randomized trial. success at first pass, number of attempts (needle passes), success, times between skin contact and needle skin penetration and between needle skin penetration and liquid back flow in the syringe were recorded. qualitative and quantitative values are expressed as number (percentage), and median (range), and were compared using the wilcoxon matched pairs test and the fisher exact test, respectively. results: for ijv puncture, first attempt success rate was more than 80% and was neither influenced by probe shape nor approach (table 1) . conversely for rav puncture, using lp with ip approach was more frequently successful at first attempt (45 vs 34%, p = 0.2). time elapsed between needle skin penetration and liquid back flow was shorter for rav puncture using ip approach (16 s vs 34 s, p = 0.03). time elapsed between probe appliance on skin and liquid back flow was significantly shorter with the linear probe for ijv whatever the approach and for rav using ip approach. rav puncture was more frequently impossible with mcp (10 vs 3%, p = 0.08). arterial puncture occurred more frequently with mcp (7 vs 3%, p = 0.08). lp use and ip approach were associated with more free event puncture ( ± 20) . minimal ani, reflecting intense stress was 33.7 (± 9.9). objective and subjective stress of each team leader is shown in fig. 1 . there was a significant negative linear correlation between minimal ani and maximal hr (rho = − 0.52, p = 0.001). there was no significant correlation between self-reported stress vas (neither pre hfs or maximal stress) and minimal ani. conclusion: hrv monitoring is a feasible method to evaluate continuous physiological stress for team leaders in highly stressful simulationteaching. upgrading signal connection by bluetooth 4.0 or wi-fi could improve the method. focusing on specific stressful time points might improve stress assessment and its correlation with performance. introduction: simulation training has become available in health sciences faculties and proposed in many specialties. intensive care is one of the fields of development of simulation based training. the aim of the present study was to report the experience of the faculty of medicine of monastir simulation center in training medical students and residents in intensive care and to compare their respective perceptions. this was a descriptive study including students (5th year of the medical curriculum) and residents who received training during the last academic year (2016) (2017) , in the simulation center during their icu traineeship. simulation training was based on high-fidelity mannequins for students and seminars with high fidelity and procedural simulation training for residents. three sessions per group were organized for students and a total of five sessions for residents. we collected participant characteristics and used likert scale (from 1 to 5) to assess participant satisfaction, simulation fidelity, impact on clinical practice, stress level and instructor behaviors. chi 2 test was used to compare students' and residents' perception of the simulation based-training. results: during the study period 91 students (of the 269 students' whole promotion) and 88 residents actively participated at least in one of the simulation-based training sessions. median students' and residents' ages were respectively 24 years (24-24) and 29 years ( introduction: hospitals are encouraged to edit local antibiotic therapy guidelines. antibiogarde ® is an electronic antibiotic prescription referential developed by a multidisciplinary team of french physicians, regularly updated, and locally customizable, which has been purchased by more than 170 french hospitals. we compared adequacy fig. 1 team leader's objective (heart rate and ani) and subjective stress (declared vas stress) of initial antibiotic prescription by icu clinicians, antibiogarde ® proposal and national or international guidelines. patients and methods: between january and june 2016, initial antibiotic prescriptions in an icu were retrospectively analyzed when microbiologically documented. antibiogarde ® and guidelines proposals were simulated, considering data available at the time of initial prescription. adequacy was defined when all bacteria responsible for infection were sensitive to at least one prescribed proposed antibiotic. national guidelines were used when published after 2011. otherwise, most recent international guidelines were used. results: 120 initial prescriptions were analyzed (45 monotherapy) in 97 patients (median age 63y, median saps ii 53, median sofa on prescription 7, icu mortality 41%, 17% immunocompromised). main sources of infection were lung (n = 75) and intra-abdominal (n = 23). leading isolated bacteria were enterobacteriaceae (n = 67, antibiotic resistance in 14), streptococci (n = 55), non-fermenting gram negative bacilli (n = 27, antibiotic resistance in 12) and staphylococci (n = 25, resistance to methicillin in 5). in the 120 clinical settings analyzed, there was a proposal by antiogarde ® in 97 (81%) and a guideline available in 102 (85%) (p = 0.39 introduction: intubation is plagued with a high morbimortality, especially in emergency situations. it is now acknowledged that a seated position allows for optimized preoxygenation (1) . however, there is no guideline concerning the patient's position for intubation. the patient is most often laid in a supine position, leading to a higher risk of aspiration (2) . face-to-face intubation in sitting position (ftfi) would allow for an easier intubation and a lower morbidity. we focused on learning the ftfi technique using the macintosh laryngoscope and the airtraq videolaryngoscope in simulated difficult intubation situation and comparing the performance of the ftfi with the classic technique. the participants would intubate a high-fidelity manikin (simman3g, leardal, norway) configured with a tongue edema (cormack 2b-3). for each trial, time to intubate (tti), success and complication rate, intubation difficulty and glottis exposure were noted. in classic position, three trials were performed with the airtraq followed by the laryngoscope in order to obtain baseline parameters. in ftfi, at least 30 intubations were performed by each participant for each device. the utilization order was randomized. results: thirty physicians, with an experience of at least 200 intubations each, were included. figure shows the learning curves of the ftfi based on the evolution of the tti measured for the airtraq and the laryngoscope. in classic position, the mean tti with the airtraq was 30.5 ± 19.1 s versus 27.3 ± 16.7 s with the laryngoscope (p = ns). in ftfi, once the technique mastered, the tti was 14 ± 2.9 s with the airtraq versus 17.5 ± 2.4 s with the laryngoscope (p < 0.05). success rate, tti, complication rate, intubation difficulty and glottis exposure were better using ftfi versus classic intubation (p < 0.05). these parameters were even better with the airtraq than with the laryngoscope (p < 0.05). the learning profile of ftfi is different between the airtraq and the laryngoscope. it could be due to the participants' lesser familiarity with the airtraq. the better performances in ftfi could be due to better ergonomics allowing easier glottis exposure and learning (3) . conclusion: face-to-face intubation in sitting position is easy to learn. it provides better performances and fewer complications than the classic intubation technique which might result in a lower morbidity. the airtraq provides even better results than macintosh laryngoscope. all participants recommend their colleagues to be trained in face-toface intubation. among non-invasive respiratory support, niv with bilevel pressure was the most frequent (n = 68, 50%) before cpap (n = 23, 17%) and high flow oxygen (n = 21, 15%). the proportion of patients on niv was up to 71% in the centres hosting more acs patients. conclusion: despite the absence of evidence from randomized controlled trials niv is nowadays commonly used in picu and hdu for scd patients with acs, especially in centres taking in charge a high number of scd patients. future physiological studies and randomized controlled trials might help to choose between the different ventilatory support options for acs. in transfused patients, the pre-transfusion hemoglobin was 8.1 (7.5-9.3) g dl in moderate pards and 7.5 (6.9-7.3) g dl in severe pards. the evolution of hemoglobin, osi, scvo2 and lactate after the transfusion is reported in the table 1 . in our picu, a relatively restrictive policy of rbc transfusion was observed even in patients with severe pards. decision to transfuse seemed associated with the general severity status of the patient and with the hemoglobin level. further studies are needed to explore the generalizability of these findings, and to investigate the impact of transfusion on oxygen transport consumption balance in pediatric acute respiratory distress. introduction: pharmacokinetic parameters are altered in critically ill patients. for instance, in adult patients, it has been well demonstrated that augmented renal clearance results in subtherapeutic antibiotic concentrations. our objectives were to build a pediatric population pharmacokinetic model for piperacillin, in order to optimize individual dosing regimen. patients and methods: all children admitted in pediatric intensive care unit, aged less than 18 years, weighing more than 2.5 kg, and receiving intermittent piperacillin infusions were included. piperacillin was quantified by high performance liquid chromatography. pharmacokinetics were described using the non-linear mixed effect modelling software monolix. monte carlo simulations were used to optimize dosing regimen, in order to maintain plasma concentration above the minimum inhibitory concentration (16 mg l −1 for pseudomonas aeruginosa) throughout the dosing interval (100% ft > mic). results: we included 50 children with a median (range) post natal age of 27.2 (1.1-222.9) months, median (range) body weight of 11.9 (2.7-50) kg, median (range) pelod-2 score of 4 (0-16) and median (range) estimated creatinine clearance of 142 (29-675) ml.min -1 .m -2 . a one compartment model with first-order elimination adequately described the data. median (range) values for piperacillin clearance and volume of distribution were respectively 3 (0.71-10) l h −1 and 3.8 (0.72-25.8) l. body weight (allometric relationship), estimated creatinine clearance and pelod-2 severity score were the covariates explaining the estimated between subject variability. a third of the cohort attained the target, according to our dosing regimen and to the european guidelines. to reach the target and according to the simulated dosing regimens, children with acute kidney injury should receive intermittent infusion every 6 h, administered on 30 min. those with augmented renal clearance should receive a continuous infusion. to reach the target, standard intermittent piperacillin dosing regimen in critically ill children is not appropriate. in addition to body weight, dosing regimens should take into account the creatinine clearance. continuous infusion is adequate for children with augmented renal clearance. piperacillin individualized dosing regimens and therapeutic drug monitoring are mandatory in pediatric intensive care unit. introduction: all data support the need for early recognition, evaluation of pain in the nicu. multiparametric analysis including physiological parameters could be useful to have a more objective evaluation of pain in the nicu compared to scales built on external-evaluation. the newborn infant parasympathetic evaluation (nipe ® ) was developed to assess pain in newborns and infant, from preterm to the age of 2 years. patients and methods: we conducted a monocentric, prospective study to compare the instantaneous nipe ® index value (nipei ® ) to the dan scale during acute procedural pain (picc line insertion) in preterm infants (under 37 gw). the operators and the nurse were blinded to the continuous recording of nipei ® during the entire procedure. dan scale was assessed every 5 min by a third person, trained to this scale and blinded to nipei ® . a direct correlation assessment between the dan scale and the nipei ® was performed by calculating the pearson's linear correlation coefficient. the differences between the nipei ® of non-painful (dan < 3) and painful (dan ≥ 3) infants were estimated by the wilcoxon-mann-whitney test. the usefulness of nipei ® as a new tool for pain assessment in neonates was estimated by the corresponding roc curve. our study was approved by our local ethic institutional review board. results: thirty-five preterm infants were included, nipei ® data were incomplete in 3 infants. fifty percent of newborns were born before 31 gw, and 66% had non-invasive respiratory support (continuous positive airway pressure cpap). at the time of the procedure, newborns had a median post-natal age of 3 days and a median weight of 1180 grams. there was a moderate correlation between the nipei ® index and the dan scores (r = 0.605 + p < 0.001). the median nipei ® index was 59 for non-painful events vs. 43 for painful events, p < 0.001. the area under the roc curve was 0.92. for a threshold of nipei ® < 50, the sensitivity was 91.3%, the specificity was 83%. positive likelihood ratio was 5.36 and the negative likelihood ratio was 0.10 ( fig. 1) . we showed a correlation between the dan scale and the nipei ® index for pain assessment in preterm infants. the nipe ® monitor could be a useful and non-invasive tool for pain assessment in neonates. further studies are needed to confirm our results and to define more precisely the place of such monitors for pain evaluation in daily clinical practice in the nicu. introduction: the aim was to identify factors associated with the occurrence of acute pituitary hormone dysfunction in children with moderate to severe tbi and to describe the impact of this dysfunction on the stability of the children. patients and methods: prospective bicenter study including all children aged between 1 month to 17 years, admitted to picu for a moderate-severe tbi and with an expected stay > 2 days. setting-pediatric intensive care units of grenoble and lyon, from 2010 to 2017. endocrine explorations at the second morning following admission and 24 h before discharge were performed-cortisol 24 h cycle with free cortisol and acth dosages every 4 h (or 6 h if no central line) + free 24h urinary cortisol + tsh and t4l, 24h urinary lh and fsh, blood level of testosterone or estradiol for children aged > 10 years, and igf1. patients were classified as having cortisol insufficiency if all the cortisol dosages were < 200 nmol l and all acth were < 12 pg l. tsh deficiency was defined as t4 l < 11.5 pmol l and tsh < 4.2 mui l. gonadotropin defciency was defined as urinary lh < 0.14 ui 24 h and urinary fsh < 1.52 ui 24 h for males + urinary lh < 0.018 ui 24 h and urinary fsh < 2.24 ui 24h in female. patients with deficiency (acth and any deficiency) were compared to those without deficiency in terms of hemodynamic instability, respiratory instability, neurological and infectious complications for continuous variables means and 95% confidence interval were calculated and compared by t student test. chi-2 test was used to compare proportions. results: among the 110 patients evaluated, 12 had acth deficiency, and 23 had at least one acute pituitary dysfunction. comparison of patients who presented acth deficiency with those who were not deficient found no differences in terms of patients characteristics, cause of tbi, level of severity and level of injury. paitents with acth deficiency required more frequently fluid bolus at day2 (67 vs 34%, p = 0.03). all the markers of severity were higher and the need of vasoactive drugs were more frequent but the differences were not statistically significant. table 1 shows comparison between patients with at least one pituitary hormone deficiency to those without deficiency. the same result was found. glycemia levels were lower in the group with deficiency. conclusion: we didn't find any predictive factors of pituitary hormone deficiency in children with moderate-severe tbi justifying a systematic screening of those patients. introduction: most intensive care unit (icu) patients cannot make decisions themselves. familiy members are actively involved in the care process as surrogate decision-makers and judges of care quality. however, family satisfaction with care is complex and is not clearly defined. the aim of this study is to evaluate the different procedures (reception book and staff education for aid and relationship) used in a new icu to improve the family care. patients and methods: we included in our study patients who had spent more than 48 h in our department. a questionnairy, adapted to our population, was performed by our staff and validated by the hygiene and quality care departement. we proceded by phone calls, 10 months after the inauguration of our icu. results: sixty-five questionnaires were included (fig. 1 ). the average of age was 52 ± 20 with a sex ratio of 2. the average of the simplified acute physiology score (sapsii) was 36 ± 17. the median stay was 7 days [4-16] with a total mortality rate of 25%. mostly, we interrogated first-degree parents (n = 52). only three families recieved reception book at admission. visit in patient room was autorised only for 27% (n = 17) of family members. only four persons said they were disturbed in visit hours for architectural reasons (tight space). disponibility was found excellent in 40% (n = 24) of cases for medical staff, 45% (n = 26) for paramedicals. informations provided by physicians were clear in 71.5% (n = 53) of cases. fifteen of the family members (23%) asked psychology support. patients were followed up via phone calls during 1 year after discharge. characteristics on admission and outcomes after discharge were analyzed stratified by ventilation modality niv vs imv. the overall survival was analyzed on the basis of the kaplan-meier curves. results: during the predetermined period of data collection, the follow-up involved 60 patients. 24 patients were treated by niv (group1) and 36 patients needed imv (group2). there was no difference between the 2 groups in age (p = 0.69), severity of copd (p = 0.39), physiological reserve at discharge (p = 0.14) and icu readmission (p = 1). short term outcomes were not different between the 2 groups-1-month readmission (16.7 vs 25% respectively in niv and imv, p = 0.52) and 1-month mortality ( introduction: post-intensive care syndrome (pics) has been recently described as a combination of physical, cognitive and mental impairments appearing during a stay in an intensive care unit (icu). the prevention and detection of pics require the participation of each category of healthcare workers. however, the level of knowledge is unknown. we sought to assess the awareness among our icu staff in preparation for a follow-up consultation. the study used a short multiple-choice survey filled on a voluntary basis. all members of the staff were asked to fill the questionnaire over a one-week period. the assessment was composed by seven structured questions which aimed measure basic knowledge of post-intensive care syndrome and general strategies to diagnose that syndrome and the tests used. results: fifth five workers (30% of the staff ) of the department of intensive care answered the questionnaires (67% nurses, 7% physiotherapists, 20% physicians). the estimated ranges of prevalence of psychological problems were very low (0-25%) for 3.63%, low ( introduction: drafting a death certificate (dc) is a procedure considered as a part of doctor's daily practice, especially in emergency and intensive care departments. this certificate represents a civil, social, epidemiological and medico-legal act. it can engage the liability of the certifying doctor. the objectives of our study were to examine the content of dc drafted in emergency and intensive care departments, assess the quality of writing, and analyze drafting errors. patients and methods: a prospective study extended over a period of 12 months from january to december 2015, including all dc emanating from emergency and intensive care departments and received in the forensic department of habib bourguiba hospital in sfax. results: during the study period, 120 dc meeting the inclusion criteria were collected. although confidential, the medical part of the dc was sealed by the doctor in onlyone third of cases. in the administrative section, nine socio-demographic parameters were studied. in 10% of the cases, less than four of the nine criteria were found. in the section concerning the certifying doctor data, 7 parameters were screened. 67.1% of the certifying doctors met at least six criteria. the most frequently missing parameter in this section was the identity of the person to whom the certificate was issued. the identity of the doctor was not mentioned in 10% of the cases. forensic data (4 items) was complete in over three quarters of the certificates. nevertheless, in 26.7% of cases, the medicolegal obstacle to burial box was left empty (8.3%) or not ticked even if judicial investigation was required (18.3%). the section on causes of death was the source of almost all of the drafting errors. we have classified these errors into six major ones, according the classifications reported in the literature. the percentage of certificate without faults was 13%. the most common major error was insufficient cause of death found in 40.4% of cases followed by incorrect sequence of causes of death (28.8%), medicolegal obstacle to burial not ticked although required (26.6%), several causes of death mentioned simultaneously (16.7%), unacceptable cause of death (10.8%) and mechanism of death mentioned instead of the cause of death (5.8%). our study showed that the quality of drafting of dc suffered from several insufficiencies, which encourages us to provide more effort in training doctors and to review the current official model of dc. introduction: septic shock is defined as a sepsis with hyperlactaemia greater than 2 mm after correction of hypovolemia requiring vasopressors to maintain mbp > 65 mmhg [1] . it can be observed in pre-hospital emergency medicine (phem). the use of a reliable portable device for measuring lactate in phem would allow a better evaluation of septic patient facilitating their orientation towards intensive care unit (icu) or emergency department (ed). this portable delocalized biology device must be validated against the laboratory reference method (nfen iso 22870) [2] . the aim of this study was to clarify the validity of a delocalized measure of lactatemia. we performed a prospective study including 47 patients admitted into icu for septic shock (cpp number 2015-08-03 sc). lactate was measured in parallel on 2 samples-one capillary with the portable device (lactate statstrip xpress, nova biomedical) and the other venous on a centrifuge tube for plasma analysis (architect c16000 abbott diagnostics). we evaluated the analytical performance (coefficients of variation (cv) for repeatability and reproducibility evaluated at 2 levels of quality control (qc)-1.6 and 3.6 mm) and then the concordance between lactate levels measured by the devices and lactate levels measured by laboratory analyzer. results: at the qc concentrations tested, the cvs were in agreement with the limits set by the french society of clinical biology-cv < 3% for repeatability and < 5% for reproducibility. an excellent correlation was observed between the 2 measurements-correlation coefficient r2 = 0.98, slope = 0.95 and ordered at the origin = 0.1. the latter suggested a low positive bias of the device not confirmed by bland-altmann graph analysis and graph of the differences. we verified the analytical performance of the device and showed an excellent correlation with the laboratory measurement. the delocalized measure can be used in phem in patients with suspected sepsis syndrome. this measure should allow a more accurate and early assessment of their severity in order to improve triage and hospital orientation between ed and icu. there is an association between mortality at d28 and hyperoxia in patients admitted in icu for refractory ohca requiring ecpr. these data underline the potential toxicity of high dose of oxygen and suggest that control of oxygen administration in such patients is an important part of the treatment. a value of pao2 between 100 and 300 mmhg after starting ecpr seems to be a target during treatment of ohca treated by ecpr. introduction: sepsis has been defined as a dysregulated host response to infection leading to life-threatening organ dysfunction (singer m et al., jama 2016) . a qsofa score relying on 3 simple clinical criteria (respiratory rate, mental status and systolic blood pressure) has been proposed to better identify septic patients with associated higher mortality outside the intensive care unit (seymour cw et al., jama 2016) . the study aim was to evaluate the ability of qsofa to predict the development of organ failure and increased 28-day mortality in patients admitted for suspected sepsis in the emergency department (ed). patients and methods: prospective study conducted over a period of 6 months comparing the prevalence of organ failure and 28-day mortality according to the value of qsofa at admission to the ed between group a (qsofa > = 2) and group b (qsofa < 2). as part of routine care, an electronic sepsis form was specifically created to identify prospectively and exhaustively all eligible patients on-line. for the purpose of the study, sepsis diagnosis was independently validated off-line by an adjudication committee which included three physicians who reviewed clinical, biological and microbiological data. for each patient, demographic data, source of infection, qsofa and sofa score, biological data and 28-day mortality were recorded. seventy-six patients of group a (99%) were hospitalized, of whom 25 were admitted to the intensive care unit (32.5%), and 28-day mortality reached 46.7%. in group b, only 32 patients developed an organ failure (10.7%) and 28-day mortality was 4.3% (table 1) . the present study confirmed that the qsofa score is a reliable and practical tool to predict the development of organ failure and higher 28-day mortality in patients with suspected sepsis in the ed. limits of ct scan criteria and intravascular contrast extravasation to define pelvic angioembolization need: a specific assessment on the risk of falseintroduction: opening of the mitochondrial permeability transition pore (ptp), triggered by cyclophilin-d (cypd) binding under stress conditions, plays a key role in ischemia-reperfusion injury. we sought to determine, using transgenic mice, whether cypd deletion (cypd −) would improve resuscitability and survival after experimental cardiac arrest (ca). additionally, we compared the protective effects of cypd deficiency with that of targeted temperature management (ttm). patients and methods: anesthetized mice underwent a 5 min asphyxial ca followed by resuscitation (cardiac massage, resumption of ventilation, epinephrine). four groups of animals were studied-sham, control (ctrl), cypd-ca using mice lacking cypd (knockout mice), and ttm-ca with fast hypothermia induced by external cooling at reperfusion (33 °c for 1 h). two hours after ca, the following measurements were carried out (n = 6-9 group)-echocardiography, cellular damage markers (including s100b protein and troponin ic) and mptp opening in mitochondria isolated from brain and heart. additional mice (n = 7-12 group) were included in the same 4 groups for survival follow-up (24 h and 7 days). results: characteristics of ca were similar among groups. rate of restoration of spontaneous circulation (rosc) was significantly higher in cypd-and ttm groups compared to controls (p < 0.05). time to rosc was shorter in cypd-versus ttm and ctrl (p < 0.05). genetic loss of cypd and ttm prevented to a similar extent ca-induced myocardial dysfunction, increase in blood levels of both s100b protein and troponin ic (p < 0.05 versus ctrl). ca resulted in a significant increase in ptp opening only in mitochondria isolated from brain (p < 0.05 versus sham). cypd deletion as well as ttm limited ca-induced ptp opening in brain (p < 0.05 versus ctrl). short-term survival (24 h) was significantly improved in the cypd-and ttm groups when compared to controls (p < 0.05). however, only therapeutic hypothermia improved survival at day 7 (p < 0.05 versus ctrl). in our murine ca model, genetic loss of cypd increased resuscitability and short-term survival but, unlike therapeutic hypothermia, failed to improve 7-day survival. introduction: early prediction of neurological outcome of post-anoxic comatose patients after cardiac arrest (ca) is challenging. prognosis of comatose patient relies on multimodal testing-clinical examination, electrophysiological testing and structural neuroimaging (mainly diffusion mri). this prognostication is accurate for predicting poor outcome (i.e. death) but not sensitive for identifying patients with good outcome (i.e. consciousness recovery). resting state functional mri (rs-fmri) is a powerful tool for mapping functional connectivity, especially in patients with low collaboration. several studies showed that rs-fmri can differentiate states of consciousness in chronically brain-damaged patients. a recent study also showed that functional neuroimaging can early detect signs of consciousness in patient with acute traumatic brain injury. however, rs-fmri has not been assessed for the early prognostication of post-anoxic comatose patient. we assessed whole-brain function connectivity (fc) of 17 post-anoxic comatose patients early after ca using rs-fmri. nine patients ultimately recovered consciousness (good outcome) while eight died (poor outcome). we estimated fc for each patient following a procedure previously described. we statistically compared whole-brain fc between good and poor outcome group, to assess which brain connections differed between them. then, we trained a machine-learning classifier (a support vector machine, svm) to automatically predict coma outcome (good poor) based on wholebrain fc of comatose patients. finally, we compared this outcome prognostication based on functional mri to those using standard structural diffusion mri. results: good and poor coma outcome groups were similar in terms of demographics, except for time to rosc. good outcome group showed significant increase in whole-brain fc between most cortical brain regions + with the strongest changes occurring within and between occipital and parietal, temporal and frontal regions ( fig. 1 ). using whole-brain fc and a svm classifier to predict coma outcome yielded to an overall prediction accuracy of 94.4%(auc 0.94). interestingly, automatic outcome prognostication using functional neuroimaging achieved better results that structural neuroimaging methods like dwi (accuracy 70.6%). conclusion: we used rs-fmri to predict coma outcome in a cohort of post-anoxic comatose patients early after ca. we deliberately chose to include only patients with indeterminate prognosis after standard multimodal testing, to assess the contribution of rs-fmri in the early prognostication of coma outcome. we found that automatic prediction based on functional neuroimaging yielded much better results than current dwi methods, notably for identifying patients who recovered consciousness. outcomes of post-anoxic comatose patients early after ca, using rs-fmri in rcts comparing treatment of severe pneumonia that may influence their ability to demonstrate differences between studied drugs. clinical cure was the most frequently used endpoint but its definition was highly variable. these results are not surprising as far as even guidance from regulatory agencies on how to evaluate hap vap treatments differ. the aim of this work was to reach a consensus on the most appropriate endpoint to consider in future clinical trials evaluating the efficacy of antimicrobial treatment for hap vap, using delphi method. patients and methods: twenty-six international experts from intensive care, infectious disease and from the industry were consulted using delphi method (four successive questionnaires) from january 2016 to january 2017. more than 70% of similar answers to a question were necessary to reach a consensus. results: according to 60% the experts, clinical cure was the most desirable primary outcome among those found in the literature but two other endpoints were highly rated-all-cause mortality and mechanical ventilation (mv)-free days. consequently, 88% of the panelists agreed to use a composite endpoints and even a hierarchical composite endpoint to combine these items together in which clinical cure and mv-free days would be assessed at day 28 and clinical cure at day 7 after end of therapy. for vap, mortality was considered as the most clinically significant item by 75% of the experts, followed by mvfree days and finally clinical cure (fig. 1) . for hap, a dual composite endpoint that only included all-cause mortality and clinical cure was chosen ( fig. 1 ). among the various elements of clinical cure definition found in the literature, only three were retained by the experts-resolution at end of therapy of signs and symptoms present at enrolment, no further antimicrobial treatment needed and resolution or lack of progression of radiological signs of pneumonia. finally, we found a consensus on the signs and symptoms that should trigger the suspicion of pneumonia-worsening of gaz exchange, purulent tracheal secretions, hypotension and or vasopressor requirements and fever or hypothermia. we provide here two consensual endpoints (for vap and hap) that would help addressing the efficacy of antimicrobial molecules for hap vap treatment in future clinical trials. (table) . 93 sm-vap were matched with 380 control patients. in univariate analysis, risk factors for sm-vap weremale gender, chronic heart failure, respiratory, cardiovascular and coagulation sofa scores two days before vap, median number of antibiotics used, percentage of time with antibiotics before vap, parenteral nutrition, dialysis, catecholamine use and exposure to ureido-carboxypenicillin, ciprofloxacin, tazobactam or imipenem-meropenem during the week before vap (table) . patients with sm-vap were less likely to receive initial adequate therapy (56 vs 70%, or 0.53, p = 0.01). there was no statistical difference for icu or d30 mortality. d60 mortality was higher for sm-vap (table) . in multivariate analysis, exposure to imipenem-meropenem during the week before vap, respiratory and coagulation sofa scores two days before vap were independent risk factors for sm-vap. sapsii: simplified acute physiology score; sofa: sofa (sequential organ failure assessment); sofa resp: sofa respiratory score; sofa coag: sofa coagulation score; sofa cardio: sofa cardiovascular score conclusion: sm-vap represented 6.2% of vap. we observed no differences in patients characteristics between the groups. imipenem-meropenem use during the week before vap was the most important risk factor for sm-vap. the higher risk of inadequate initial therapy with sm-vap had no impact on d30 mortality but d60 mortality was significantly higher. introduction: education of undergraduate students is key to improve hand hygiene (hh) behavioral changes amongst doctors [1.2] . our aim was to evaluate personal feedback using ultraviolet (uv) light inspection cabinets in a 2 years program. our hypothesis was that its use for alcohol hand rub (ahr) application on first year would increase complete ahr application on 2nd year. patients and methods: this was a simple blind randomized trial comparing hh training with personal feedback using uv cabinet to a control group. on first year, students had access to a theoretical formation then were convened by groups for a demonstration of the correct execution of world health organization's (who) procedure [3] . before hh training, each group underwent a cluster randomization. in the control group, the student hand rubbed under visual supervision and advises of a trainer. in the intervention group after the same visual assessment, completeness of ahr hand application was recorded under uv light and shown to the student. he was given free access to the uv cabinet to repeat the technique, until perfect application complete under uv light. an enhancement with a scenario-based learning was proposed to both groups. on second year, every student were asked to hand rub with the fluorescent ahr. a supervisor blinded to the group of randomization assessed the quality of the hh procedure visually, the completeness of hand application under uv light and compliance with the who's opportunities for hh during the simulation. results: after randomization 140 students were included in the intervention group and 102 in the control group. on second year, the rate of complete application of the ahr under uv was increased in the intervention group as compared with the control group (60% versus 30.4% p < 0.001) ( fig. 1 ) despite that visual assessment of hh procedures was similar between the two groups. in a logistic regression model including gender, intercurrent hh formation, intercurrent uv cabinet use, surgical unit traineeship and report of regular use of ahr, the hazard ratio for the intervention was 3.837 (ic 2.086-7.058). the rate of perfect compliance with the hh opportunities in the intervention group was increased (58.1% versus 42.4% p < 0.018) and the effect persisted in the logistic regression. conclusion: uv cabinets for undergraduate students' hh education improve the technique and the compliance with hh opportunities. included in a multifaceted education program, it must be considered a key tool for training. results: among the 56 patients who underwent ecmo support for more than 48 h, the bsi prevalence was 27.4 cases per 1000 ecmo days and microorganisms associated were most frequently gramnegative bacilli. as for positive ta cultures, microorganisms associated were oropharyngeal germs and gram-negative bacilli. two risk factors were associated with nosocomial bacteria occurrence in ta cultures-prior antibiotics and duration of mechanical ventilation more than 5 days. we demonstrated a link between "positive ta culture" and "positive blood culture" and we showed a protective effect of using an antibioprophylaxis on "positive ta culture" and "global positive cultures" development. introduction: delirium in the icu is often under-diagnosed despite its related burden and impact on patients' morbidity, mortality and prolongation of hospital length of stay. the aim of this study was to assess the medical and paramedical community beliefs and practices regarding delirium in tunisian icus. patients and methods: between august 1st and 31/2017, healthcare professionals working at the icus of university hospitals of monastir and mahdia (tunisia) were asked to participate in the survey by completing a questionnaire anonymously (that specified participants' characteristics (age, gender, function, years of experience in icu) and their knowledge and perception of delirium in icu. the questionnaire consisted in 10 questions of different types: likert style (: widespread scale in psychometric questionnaires in which the respondent expresses his or her degree of agreement or disagreement with an assertion), multiple choice, ranking and yes/no). results: during the study period, 96 respondents out of 163 (60% female, nurses: 52%), aged between 20-30 years in 70%, responded to the questionnaire. healthcare professionals experience in the icu was < 1 year in 39.6%; 1-5 years in 32.3%, and > 5 years in 28.1%. participants asserted that the "most characteristic signs of delirium" were: insomnia (25%); confusion (22%); agitation (21%) and aggressiveness (20%). three-quarters of participants said they did not systematically search for signs of delirium in their patients. 33% thought that delirium was "an insignificant problem" or that "it was not a problem". only one and three participants respectively, said they attended a conference and read an article about delirium in icu the last year. half of the respondents felt that the most appropriate treatment for a patient with delirium was restraint. nearly one-third of participants thought that delirium was an under-diagnosed entity and only 6% felt that it was associated with long-term neuropsychological deficits. factors considered to be determinant in the occurrence of delirium were ards, shock, age, mechanical ventilation, postoperative status in 70, 66, 63, 55 and 17%, respectively. conclusion: most tunisian healthcare professionals consider delirium as a common, underdiagnosed, and serious problem in the icu. yet, few participants actually monitor this condition. the influence of sedation choice on the delirium occurrence in critically ill poisoned patients: a randomized controlled trial khzouri takoua introduction: delirium is a common manifestation of acute brain dysfunction in critically ill patients. it is associated with a healthcare cost increase, and extension of the hospital stay length. the present study aimed to explore influence of patient characteristics and analgesicsedation on delirium incidence and to analyze its risk factors. patients and methods: it is a prospective single blind randomized controlled trial, started on the first july 2017 in a 12-bed toxicological intensive care unit, including all mechanically ventilated patients requiring sedation who were admitted for acute poisoning. they were randomly divided into two groups g1 et g2 receiving respectevily propofol-remifentanil and midazolam-remifentanil. delirium assessment scores were judged not adapted to our population and we retained the diagnosis of delirium on arguments inspired from diagnostic and statistical manual of mental disorders fourth edition (dsm-iv). results: until the 15th september 2017, 35 patients were included, with 22 patients in g1 and 13 in g2. the two groups were comparable in terms of epidemiological characteristics. delirium was developed in 9 patients (26%) (n = 5 in g1 and n = 4 in g2) with an average duration of 18 ± 13 h with no difference between the 2 groups (13 ± 10 h for g1-24 ± 16 h for g2, p = 0.268). compared to those without delirium, no differences were found in the patient characteristics among these two groups with regard to sex, age, psychiatric history and severity of illness (apache ii, igs ii score) and even with regard to hypnotic choice (5 vs 4 p = 0.599). delirium was associated to prolonged duration of mechanical ventilation (69 ± 73 h vs 39 ± 69 h, p = 0.280) and length of icu stay (91.51 h vs 54.05 h, p = 0.132) without significant differences. delirious patients had more hypotension (p = 0.008), and received more atropine (0.026). multiple logistic regression analysis identified atropine (or 2.333, 5%cl 0.992-5.489, p = 0.026) as an independent risk factor for delirium. the diagnosis and prevention of icu delirium are subjects of multiple ongoing investigations. we carried out this study to detect the risk factors of delirium in order to prevent it. it is important to note that our results are influenced by the studied population and are only preliminary. we rely on the study pursuit and the sample enlargement to better inform us as well on risk factors as protective. introduction: background: severe alcohol withdrawal syndrome is a common cause of hospital admission. delirium tremens is a potentially fatal complication of alcohol withdrawal. in severe delirium, very large dosages of benzodiazepines can be required despite well described side effects, such as coma and hypoxic cardiac arrest, although there is no recommendations for standardized treatments. objective -the aim of this study was to describe outcomes and risk factors for complications in patients with severe alcohol withdrawal syndrome treated in intensive care unit with continous infusion of benzodiazepine (bzd). we retrospectively reviewed the medical records of all patients hospitalized for alcohol withdrawal syndrome between 2006 and 2016. only those who received continous-infusion of bzd, associated with close clinical monitoring and the evaluation of rass and cushman scores, without systematic recourse to mechanical ventilation, were included. results: we studied 104 patients hospitalized in icu for severe alcohol withdrawal syndrome. the mean age (sd) was 48.7 ± 8.7 years, mean icu admission saps (simplified acute physiology score) ii score was 20 ± 6.1. all of them have received continous infusion of midazolam, with a median maximum perfusion velocity of 8 mg h (interquartile range, (5, 12)). the median duration of treatement was 2 days (interquartile range, (1, 3) ). thirteen patients (12%) developed pneumonia, and or required intubation, and 8 (8%) have had seizures. no cardiac arrest and death was observed. icu length of stay (los) was 3 days (2, 5) (median, interquartile range). patients who requiried intubation and or developed pneumonia, received substantially more bzd (median total dose, 428 mg of midazolam vs. 147 mg in the non-complicated group + p < 0.001), and their icu los was higher (median, 5 days vs. 3 days + p < 0.001). endotracheal intubation and or development of pneumonia were associated with a higher maximum perfusion velocity of midazolam (> 8 mg h) (or 18.83, ic 95% (2.11-168.15), p = 0.009). previous episodes of delirium tremens before icu admission were associated with higher complications such as mechanical ventilation and or pneumonia (or 11.29, ic 95% (1.45-87.60), p = 0.02). in severe delirium, very large dosages of benzodiazepines can be used without systematic mechanical ventilation with a low incidence of complications. introduction: delirium is frequent in intensive care unit (icu) patients and is associated with increased mortality, increased hospital stay, increased cost and long term cognitive impairment in survivors. numerous pharmacological and non-pharmacological strategies have been investigated for delirium treatment without success. therefore delirium prevention strategies are recommended by current critical care practice guidelines. among the potentially modifiable risk factors for delirium, the impact of daylight exposure on delirium incidence and or duration has not been studied. the objective of this study was to investigate whether daylight exposition would reduce delirium burden in critically ill patients. we conducted a prospective study in a 27-bed medical intensive care unit (icu) over a 1-year period (january 2016-january 2017). all consecutive adult patients receiving invasive mechanical ventilation (mv) for 2 days or more were eligible for the study. patients were assigned to a room with windows allowing daylight exposure ("light" group) or without window ("dark" group), depending on bed availability. delirium was evaluated with the intensive care delirium screening checklist (icdsc) for a maximum period of 28 days. delirium was defined by a icdsc score ≥ 4 for two consecutive days. agitation was defined by a rass > or = +2. the primary endpoint was cumulative incidence of delirium. data are presented as median (interquartile range) or number (percentage). results: a total of 195 patients were included (age-50 [50 + 69] years, saps2-51 [36 + 64], sofa score-9 [7 + 11], medical admission-69%). of them, 110 patients were admitted to a "light" group and 85 to a "dark" group. incidence of known risk factors for delirium was similar in the two groups. delirium occurred in 65 (64%) patients in the "light" group and in 55 (71%) patients in the "dark" group (p = 0.28). the duration of delirium was 3 [1 + 7] days. patients in the "light" group received significantly less neuroleptics to treat agitation than patients in the "dark" group (13 vs. 25%, p = 0.04). this protective association persisted after adjustment for confounders in multivariate analysis (odds ratio = 0.40 + [0.17 + 0.90] + p = 0.03). daylight exposure does not impact on delirium burden in icu mechanically ventilated patients. however, daylight exposure is independently associated with a reduced prescription of neuroleptics to treat agitation. introduction: patients with convulsive status epilepticus (cse) frequently require mechanical ventilation (mv), either for general anesthesia in case of refractory generalized cse, or for airway protection. guidelines for the management of refractory generalized cse currently recommend general anesthesia for 24-48 h, followed by gradual withdrawal. our objective is to evaluate the incidence of refractory generalized cse among patients who required mv during pre-hospital management of status epilepticus, and to describe the management of general anesthesia in intensive care unit (icu). this ongoing multicenter retrospective observational study is conducted in 4 french icus. all patients admitted in icu under mechanical ventilation between 01-01-2014 and 12-31-2016 with disease-code "status epilepticus" are included. exclusion criteria are-age < 18 years, post anoxic se, acute traumatic brain injury, initiation of mv in icu, transfer from another icu, inclusion in a therapeutic trial on se, non-convulsive se. collected data include reason for mv, antiepileptic treatment, dosage and duration of general anesthesia, mode of eeg monitoring. outcomes are-relapse of se, mv duration, in-icu length of stay and mortality. results: among the 211 medical files reviewed, 77 met the inclusion criteria and were analyzed, and 134 were excluded. a minority of patients (18.2%) had a refractory generalized cse, most patients (64.9%) had a non-refractory generalized cse + the others had mostly partial cse. the main reason for intubation was coma (n = 45, 58.4%). the duration of general anesthesia was not significantly different in refractory cse patients compared to non-refractory cse patients (p = 0.18). data regarding main outcomes are summarized below-. these preliminary data suggest that the majority of the patients admitted in icu under mv for cse do not have a refractory status. indication of mv is mainly coma without persistent convulsions. the mean duration of general anesthesia before withdrawal is < 24 h, and thus in discrepancy with guidelines, but does not seem associated with a frequent relapse of se. if this low rate of rse for patients admitted in icu and the safety of rapid withdrawal of ga are confirmed, the recommended 24-48 h duration of general anesthesia in icu could be challenged. introduction: induced coma in intensive care patients protect them against pain and neurologic disorders. however, a few of them may present a delayed wake-up when the sedation is interrupted. the aim of this work is to assess brain imaging findings in patients with this condition. patients and methods: retrospective review of imaging data of 27 patients (21 males and 6 females), aged between 32 and 84 years, admitted in intensive care unit (icu) between june 2015 and september 2017, who had sedation or general anesthesia and presented a delayed wake-up. they were explored either by mri (n = 11) or computed tomography (ct) (n = 16). patients with traumatic lesions were excluded. results: patients were admitted in the icu because of chronic obstructive pulmonary disease exacerbation (n = 7), infectious pneumonia or pleural effusion (n = 6), acute respiratory failure (n = 5), heart disease (n = 2). two patients underwent general anesthesia. septic shock and circulatory collapse occurred in 3 and 5 patients respectively. mri and ct showed lesions that may explain the wake-up delay in 6 of 11 and 4 of 16 patients, respectively. brain anomalies included anoxic lesions (n = 4) with basal ganglia involvement (n = 3), ischemic or hemorrhagic strokes (n = 4), hepatic encephalopathy (n = 1) and herpetic encephalitis (n = 1). conclusion: brain imaging techniques help diagnosing causes of delayed wake-up after induced coma. anoxic lesions and strokes are mostly behind this condition. mri is more accurate than ct. introduction: gastric tubes are common in intensive care units used for enteral feeding, administration of drugs or aspiration of the digestive tract. these tubes offer an excellent tolerance but malposition may have serious consequences that can lead to patient's death. the actualy gold method to confirm their correct placement is chest x-ray. we report a study which evaluate the performance of gastric ultrasonography for the validation of the good positioning of the gastric tube. we carried out a prospective, monocentric study in a medical intensive care units. for each included patient, we compared the results of a gastric ultrasonography to the interpretation of a chest x-ray. results: one hundred and thirteen gastric ultrasonographies were performed from july 2016 to may 2017. in 87 cases, ultrasonography concluded that the gastric tube was correctly positioned, confirmed by chest x-ray. in 24 cases, ultrasonography did not visualize the tube in gastric area. among these 24 cases, only 4 malpositions were detected by the chest x-ray. the sensitivity and specificity of gastric ultrasonography were 0.81 [0.72 + 0.87] and 1 [0.51 + 1]. positive and negative predictive values were 1 and 0.17, respectively. the ultrasonography was performed 54 min [50.3 + 57.6] after the gastric tube placement while the chest x-ray was interpreted 211 min [170.9 + 251.7] after this same placement (p < 0.0001). our results suggest a good performance of gastric ultrasonography to check the positioning of the gastric tube. this result must be interpreted with caution because of a low power of the study. we planned a multi-center study to confirm our results. giabicani mikhael introduction: prognosis of cirrhotic patients hospitalized in intensive care unit (icu) remains poor. in many icus, cirrhotic patients are widely admitted and revalued after receiving optimal treatments. little is known about risk factors involved in the evaluation of the prognosis at day 3, except the persistence of organ failure. this susceptibility to organ failure would be related to an alteration of the regulation mechanisms of the systemic inflammatory response. the blood neutrophil-to-lymphocyte ratio (nlr) is an inflammation biomarker reported to predict clinical outcome in unselected critically ill patients and in patients with stable liver cirrhosis, but has never been studied in critically ill cirrhotic patients. the aim of this study was to evaluate the blood nlr as parameter to predict mortality of cirrhotic patients hospitalized > 3 days in icu. retrospective monocentric study including consecutively cirrhotic patients hospitalized in a medical icu from 2010 to 2016. for each patient, clinical and biological data at admission and day 3 were collected. nlr at admission ("nlrd0"), at day 3 ("nlrd3") and its variation between admission and d3 ("delta nlr") were calculated. statistical analysis used appropriate non parametric tests and cox regression for survival analysis. the ability of the variables to discriminate survivors from non-survivors was determined using roc curves and a net reclassification index (nri). results: 140 patients (median child-pugh score = 9 [7-11], median meld score = 25 [19-30]) were hospitalized more than 3 days in icu. the major causes for icu admission were sepsis (56.4%), gastrointestinal bleeding (15%) or respiratory failure (6.4%). patients were followed up for 38.5d . 74 (53%) patients died-38 (27%) in icu, 21 (15%) after icu discharge and 15 (11%) after hospital discharge. in univariate analysis, factors significantly associated with mortality wereat d3, nlr, meld and sofa scores + and between d0 and d3-delta nlr, delta sofa and delta meld. predictors of death in multivariate analysis are shown in table 1 . area under delta nlr roc curve was 0.74 (ci = 0.69-0.79). nri revealed that delta nlr was more efficient than delta sofa (nri = 8.7%) to identify patients with a 85% mortality risk at least. conclusion: nlr is a novel inflammation index known to predict poor clinical outcomes. delta nlr is an independent predictor of mortality in critically ill cirrhotic patients and could be more effective than delta sofa in predicting hospital mortality in these patients. severe liver dysfunction acute liver failure related to exertional heatstroke: outcomes, histological features and role of liver introduction: severe acute liver injury and failure (sali alf) is a grave complication of exertional heatstroke (eh). liver transplantation (lt) may be a therapeutic option, but the criteria for, and timing of, transplantation have not been clearly established. the aim of this study was to define the profile of patients who require transplantation in this context. this was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related sali alf with a prothrombin time (pt) lower than 50%, with or without hepatic encephalopathy. results: 24 male patients (median age-27.5 years) with ali alf related to exertional heatstroke were studied + nine of them (37.5%) were listed for emergency lt. the latter differed from those who were not listed with respect to their more severe liver failure after d1, a clear deterioration in their pt and alt values between d0 and d3, and more marked organ dysfunction. four of these nine patients were subsequently transplanted. at the time of lt, all had pt levels lower than 10%, a marked rise in bilirubin levels and required support for at least one organ (or x organs were involved). histological findings on the explanted livers demonstrated massive or sub-massive necrosis and little potential for effective mitosis with a mitonecrotic appearance. the 15 unlisted patients (62.5%) were still alive 6 months later and had not experienced any after-effects. conclusion: survival without liver transplantation in patients with heatstroke-related ali alf reaches 83.5%. the indication for liver transplantation is based on an evolving dynamic. the lack of any signs of an improvement in liver function at or after d3, in patients presenting with other organ dysfunctions or failure, means that liver transplantation should be envisaged. the peculiar histological features observed on all the explanted livers, and the aspect of abortive mitoses in hepatocytes could be attributed to the effects of heatstroke. . on admission, the mean pt was 18.5% (8-42), the mean total bilirubin was 157 umol l. paracetamol poisoning was the principal etiology with 45% of the patients-66% in the prometheus group versus 25% in the standard group (p = 0.106). the hepatic encephalopathy grade was significantly higher in the prometheus group-3 versus 0.5 in the standard group (p = 0.029). there was no difference between the two groups concerning mortality on day 28 (p = 1) or day 90 (p = 0.59). there was no difference concerning the length of stay in intensive care unit or in hospital between the two groups. 13 patients (37.1%) were transplanted. there was a statistical difference between the two groups concerning liver transplantation (p = 0.041)-4 transplant (40%) in the prometheus group versus 9 transplant (75%) in the standard medical care group. there was a significant improve of encephalopathy after the prometheus session (p = 0.002). therapy in our icu were included consecutively and prospectively in the cohort. mars ® therapy performed using a double lumen dialysis catheter in the femoral or jugular vein. we used the monitor mars ® 1 tc (teraklin) coupled with the dialysis machine prismaflex ® (gambro). the albumin dialysate circuit consisted of 500 ml of 20% human albumin and was regenerated by an anion-exchange column and an uncoated charcoal column (diamars ® ie250, diamars ® ac250). results: ninety patients were included for 300 sessions. the mean duration was 7 h 38 min (± 1 h 43 min). the population treated consisted of 5 groups-acute-on-chronic liver failure (aoclf), acute liver failure (alf), post-surgery liver failure (post transplantation, post hepatectomy), refractory pruritus and drug intoxication ( fig. 1 ). regarding biological efficacy-total bilirubin was lowered in aoclf and post-surgery groups (p < .001), also in the alf group although not significatively. meld score was lowered in the aoclf and alf group (p < .001). however clinical variables (glasgow score and encephalopathy) didn't improve significatively. in the refractory pruritus group, pruritus decreased in 20 out of 25 patients (p < .001). bile acid levels decreased to 34.8% of its mean baseline level (p < .001). in the drug intoxication group improvement of the richmond agitation-sedation scale (rass) from deeply sedated (rass < = − 3) to minimal sedation (rass > = − 2) was obtained in 5 out of 6 patients. out of 300 sessions, catheter-related adverse effects were low (1.3%), thrombocytopenia was the main adverse effect (26.7%). conclusion: we report our mars ® experience with the largest cohort of patients referred from a single hospital. we showed biological efficacy in all 5 indications, although clinical efficacy was uneven. mars ® therapy in patients with refractory pruritus yielded promising results. tolerance was good and the main adverse effect was thrombocytopenia. global transplantation-free survival was low in patients with liver failure, reinforcing the need for a liver transplantation center when using mars ® . introduction: colonoscopy is crucial for the management of lower gastro-intestinal disorders, but its profitability is discussed in critically ill patients, mainly because of the complexity of colonic preparation. as the profitability of colonoscopy in intermediate or intensive care units (cicu) has been scarcely reported (1), we investigated its indications and usefulness. patients and methods: retrospective bicenter observational study (2004) (2005) (2006) (2007) (2008) (2009) (2010) (2011) (2012) (2013) (2014) (2015) . main endpoint: diagnostic profitability of cicu in unselected critically ill patients. profitability was a priori defined as "high" if cicu led to adapt ongoing therapies; allowed an endoscopic intervention; or participated in the decision to limit therapeutic effort. secondary endpoints: describe the quality of cicu and its preparation; determine its position in diagnosis strategy; describe its morbidity. ) + investigation of a gram negative bacilli sepsis (n = 7, 6%) + sigmoid volvulus (n = 4, 4%) + and cancer diagnosis (n = 4 + 4%). cicu profitability was deemed high in 50% (n = 56), with an endoscopic intervention performed in 32% (n = 35). the cicu lead to antimicrobial adaptation (n = 9), emergent surgery (n = 10), or to limit therapeutics effort (n = 2). in 23 cases (21%) the cicu was considered normal. patients' preparation was rated as good in 27% (n = 30) + and the colonoscopy was complete in 33 (30%). the cicu was mainly performed as a 2nd (58%) or 3rd (40%) investigation after an abdominal ct-scan or an upper digestive endoscopy (respectively performed in first instance in 69 and 55%). three cicu were complicated by 3 hemodynamic and 2 respiratory failures, none were fatal. discussion: in our series of unselected critically ill patients, cicu were mainly performed to investigate lower gastro-intestinal bleeding. despite a low rate of good preparation, cicu is safe and its profitability is high in the majority of cases. conclusion: although performed in poor conditions, cicu seems useful in the diagnostic and the therapeutic management of critically ill patients, and not only in gastro-intestinal bleeding. (1) church, surgical endoscopy 2014. introduction: accurate pain assessment is associated with better outcomes in intensive care unit (icu) patients. specific scales for noncommunicative patients have been developed and validated but their routine use still remains inaccurate and subjective. analgesia nociception index (ani) is based on high-frequency heart rate variability. this study objective was to assess the correlation between the behavioral pain scale (bps) and ani during care procedures in deeply sedated patients. we conduced a french multicentric prospective observational study with blinded continuous recording of ani during 8 h with spotting of care procedures in patients with rass less or equal to − 2. we compared pain assessment using bps and ani before (t1) and during (t2) each care procedure. the cares analyzed included prick glycaemia, turning, catheter insertion, dressing change and others. a behavioral pain reactivity (bpr) was defined by a bps elevation of at least 1 point. we analyzed minimal ani values and its variations with calculation of deltaani (anit1-anit2). because of the analysis of several cares per patient we used a bonferroni's correction in comparison of bpr and no bpr groups with a significant p value < 0.025 for this comparison. for others analyses the p value considered as significant was p < 0.05. correlation between ani and bps was analyzed using a spearman correlation rank test. introduction: the pain associated with burn was one of the most painful injuries to treat. pain was induced by therapeutic acts such as wound debridement, dressing and other painful procedures. burn pain caused changes in neurophysiology and pharmacokinetics that may make standard pharmacologic analgesic therapy less effective than usual.virtual reality has been explored as an adjunct therapy for the management of acute pain for a number of conditions. in our study, we attempt to assess the impact of virtual reality on management of burn pain during dressing changes. patients and methods: before the therapeutic procedure (dressing changes), the concept of virtual reality therapy was explained to the patient (technology and equipment used). the video used was snow mountain. during the act, pain was assessed until the end of the procedure. the assessment of pain was based on visual analog scale (vas). for pain intensity, the scale was most commonly anchored by "no pain" (score of 0) and "very intense pain" (score of 10). results: during the study period, 20 patients were included. the mean age was 32 ± 17 years. 75% of our patients were adults aged over 20 years. they were 17 men and 3 women. the average burned surface area was 30 ± 13%. pain was evaluated before the start of the therapeutic procedure. the mean initial pain severity score was 8.85 ± 0.74 (range 8 to 10). the pain assessment after virtual reality condition showed a significant decrease in the intensity of pain (p < 0.01). the mean pain decreased from 8.85 to 4.6 ± 0.84 with extremes ranging from 1 to 4. conclusion: our study supports the use of virtual reality, simple noninvasive, as an adjunct therapy in the management of pain associated with dressing changes in burn patients. introduction: hypno-analgesia (ha) is used in the operating room and for complex pain. before implementation of ha in our intensive care unit (icu), most protocols for algogenic procedures included intravenous or epidural morphine and nitrous oxid. since 2016, many caregivers have been trained, ha has been implemented and patient comfort is evaluated using 1) a specific analogic scale of comfort (0 to 10) before and after the procedure + 2) at the end of the procedure, a score of patient and caregiver comfort using a five item questionnaire (5 to 20 points). this pilot prospective study compares ha versus the standard protocol in the removal of abdominal drains after digestive surgery. the main objective was to evaluate the patient comfort before after the procedure using a scale of comfort + the secondary objectives were to test the patient and caregiver comfort scores and evaluate in the impact on consumption of analgesic. between may 2016 and september 2017, two groups were obtained, according whether the procedure was performed by ha-trained or non-hatrained professionals (depending on caregivers availability in the unit). the number of subjects required to compare scales of comfort before vs. after drain removal was 66, using a nonparametric wilcoxon-mann-whitney test. results: eighty-eight patients were analyzed. the mean note in the comfort scale remained unchanged after vs. before drain removal in patients without ha (n = 43, +0.04 points, ± 2.8), while it increased in patients with ha (n = 45, +2.07, ± 2.7 + p = 0.001). using our specific five item comfort score, patients and caregivers had a comparable level of satisfaction in ha and non-ha groups (patients 17.4 20 and 16.3 20 + caregivers-19 20 in both). a trend was observed in reduction of the consumption of morphine and nitrous oxid with ha, without altering their comfort. discussion: despite its limitations (mainly, its open non-randomized design), this study suggests that-ha may be used for algogenic procedures and is willingly adopted in icu by patients and professionals + specific scales scores, adapted for ha, may be useful to assess the effectiveness + finally, ha seems to be at least as efficient as classical procedures and could reduce the use of analgesic drugs. conclusion: ha adds value to patients and to all caregivers. prospective randomized studies are needed to valid the comfort scores we proposed, and to prove that ha reduces the consumption of analgesic drugs. introduction: pain has long been a focus of concern for doctors and caregivers. in intensive care unit, the inability to verbalize discomfort and pain are major stressors for patients. music therapy has demonstrated in many international studies its effect on the blood pressure and on the respiratory frequency. in this context, we conducted a study to evaluate the effects of standardized musical intervention on pain during painful cares in vigils patients hospitalized in critical care. patients and methods: design-we conduct a prospective, observational, randomised, single blind, mono center study. 140 painful cares were studied and then distributed in two groups (n = 70 with music, n = 70 without music). the patients were equiped with a bose© helmet, and had or not music therapy during the care. our main criteria was the pain, it has been evaluated by a numeric scale before and after the painful care. we also estimated anxiety with the covi's heteroevaluation scale before and after the car. we also noticed if the care were stopped because of the pain, then we used a semi quantative numeric scale in order to estimate the feeling of the caregiver and the patient on the session. results: concerning pain, there is no significant difference between the two groups (p > 0.005). however, in the music group, pain decreased by 35% after the care (p < 0.001). anxiety was way lower in the music group than in the group without music (p < 0.001). we also noticed a decrease of 50% of the anxiety in the music group. the patients and the caregivers' feeling were the same in the two groups, with no significant difference (p > 0.05). on the other hand, caregivers tended to underestimate the difficulty of the session in comparison with the patients' (p < 0.01) in both groups. conclusion: music therapy did not improve the pain in a significant way, in the music group versus the group without but allowed a decrease of 35% of the pain after the care. nevertheless, music reduced by two patients'anxiety. introduction: sedation and analgesia is one of the basic themes in icu as complications associated with excessive sedation negatively impact the morbidity and mortality of patients. the objective of this study is to show that the nurse implementation of a sedation and analgesia algorithm is beneficial to the patient in terms of sedative drugs reduction and thus overall decrease in duration of mechanical ventilation (mv) and the morbidity and mortality which is associated with it, without altering patient comfort and tolerance of the environment. patients and methods: a before and after prospective, observational, non-interventional study was conducted in surgical icu in caen university hospital, between november 2014 and april 2017. mechanically ventilated patients under sedation predicted to last 48 h or more were included. during the "before" period, sedation and analgesia was managed by the physician, while during the "after" period, it was managed by the nurses according to the protocol. results: 1156 intubated and mechanically ventilated patients were admitted during the study period. among the 145 eligible patients, 100 were included during "before" period and 45 during "after" period. the duration of mv after inclusion was significantly shorter in group "after" (10.5 [7 + 18] vs 8 [5 + 11.5] days, p = 0.042), as the duration of target rass (-2 à 0) was significantly longer ( the patients experienced less of ventilator-acquired pneumonia (vap) and delirium during the "after" period (55 vs 24.4%, p = 0.004, and 41 vs 26.7%, p = 0.015, respectively). the nurse implementation of a sedation and analgesia algorithm was associated with a trend towards reduction in duration of mv, icu and hospital length of stay. moreover, prevalence of vap and delirium was reduced, in correlation to the significant decrease in sedative drugs. this type of algorithm is necessary to reduce morbidity and mortality associated with mv. introduction: central venous catheter insertion is a common practice for anesthetists and intensivsts. this invasive procedure generates pain and anxiety for patients. we aim to demonstrate that remifentanil improves the analgesia during scheduled central venous catheter insertion in mindful patients. patients and methods: a prospective, randomized, double-blind, controlled study in patients requiring central venous access. patients were randomly assigned to receive 3 ng ml −1 remifentanil target controlled infusion (tci) and local anesthesia (la) with lidocaine or placebo and la. all patients were monitored in intensive care or postintervention care unit and systematically received oxygen. patients were asked to assess verbal numeric rating pain scale (vnrps) during the procedure. the primary outcome was the maximal vnrps. secondary outcomes were pain at each step, anxiety, patient satisfaction, operator ease and side effects. results: ninety patients were included (45 in each group). all patients were analyzed. remifentanil significantly reduced maximal pain-vnrps 20 (95% confidence interval [ci] 16-40) vs 50 (95% ci 40-60) in the placebo group p = 0.0009 (table 1) . we did not observe any adverse event during this study, and there were no significant difference between the 2 groups regarding side effects. conclusion: tci remifentanil is a safe procedure to reduce pain during central venous catheter insertion in awake patients. trial registration-clinicaltrials.gov identifier-02206022, remidolcath. introduction: although guidelines on post-resuscitation care recommend the use of short-acting agents for sedation during targeted temperature management (ttm) after cardiac arrest (ca), the potential interests of this strategy have not been clinically demonstrated. patients and methods: before-after study. we compared two sedation regimens (propofol-remifentanil, period p2 vs midazolamfentanyl, period p1) among comatose ttm-treated ca survivors. management protocol, apart from sedation and neuromuscular blockers use, did not change between the two periods. baseline severity was assessed with cardiac-arrest-hospital-prognosis (cahp) score. time to awakening was measured starting from discontinuation of sedation at the end of rewarming. awakening was defined as delayed when it occurred after more than 48 h. results: 460 patients (326 in p1, 134 in p2) were included. cahp score in p2 and p1 did not significantly differ (p = 0.93). sixty percent of patients awoke in both periods (194 326 vs 81 134, p = 0.85). median time to awakening was 2.5 (iqr 1-9) hours in p2 vs. 17 (iqr 7-60) hours in p1. awakening was delayed in 6% in p2 vs. 29% of patients in p1 (p < 0.001). after adjustment, p2 was associated with significantly lower odds of delayed awakening (or 0.08, 95% ci 0.03-0.2 + p < 0.001). patients in p2 had significantly more ventilator-free days, and lower catecholamine-free days between admission and day 28. survival and favorable neurologic outcome at discharge did not differ across periods. time course for awakening according to sedation period. these figures report the time course of patients included after discontinuation of sedation. at each time point, we report in the upper part, proportion of patients awoken after discontinuation of sedation, in the lower part, patients who died without awakening, and in the middle part (in white), patients still comatose. red dots indicate, for each period, the last patient awakening (after 12 days in p1 and 5 days in p2). black dots indicate the median time to awakening (too early to appear for period 2). conclusion: during ttm following resuscitation from ca, sedation with propofol-remifentanil compared with midazolam-fentanyl was associated with an earlier awakening, and an increase in ventilator-free days. the new recommendations of the french society of anesthesia-intensive care (sfar) on perfusion and medication errors were revised in 2016 to promote proper use relating to drug administration with medical devices. to advance that of inquiry, practices of our intensive care unit (icu) were assessed in order to improve drug administration by central venous catheter (cvc). patients and methods: prospective evaluation by pharmacist resident and technical nurse during seven weeks, using a standard evaluation tool, in a 16 bed icu. drug recommendations and sfar documents from 2016 were used as referential of conformity. the following parameters were evaluated-1 central venous lines mounting, 2 drug administration and identification with a focus on narrow therapeutic index (nti) drugs. results: 50 patients with cvc were analyzed between june and july 2017. 19 entered directly in the icu. 23 were hospitalized for surgical reasons. 42 had triple-lumen cvc. regarding the first parameter, no conformity was found due to lack of line identification (100%) or anti-return valve well positioned (96%). perfusion ramp position was above heart level in 10%, infusion tubing had contact with floor in 6%, and absence of plug on non-used lines is found in 8% of cases. regarding second parameter, non-conformities were due mostly to syringe label-absence of drug's concentration (72%), preparator identification (99%), patient identification (99.7%), drug identification (3.5%, all concerning propofol), date and time of medication preparation (67%), lack of color code of labels (100%). regarding nti, 70% were not administrated according to the recommendations-absence of dedicated line (63%), absence of administration on the nearest insertion site of the catheter (67%). conclusion: the evaluation highlight some improvement axis such as complete identification on syringes, sensitizing of icu healthcare team, or homogenization of cvc perfusion system. it calls for a second evaluation round after implementation of improvements. introduction: sedation is a corner stone of the care of patients receiving mechanical ventilation in the icu. sedation was associated with increased comfort and adherence to care, but also with increased morbidity, including delirium, increased duration of mechanical ventilation and length of icu stay. previous studies reported beneficial impact of reduced doses of sedative drugs and careful monitoring of patients comfort and consciousness. our goal was to assess the impact of the introduction of a nurses-dedicated sedation protocol in our icu. patients and methods: this monocentre retrospective before-after study included all the patients admitted in our icu, over two threemonth periods, from july 2015 and january 2016, treated with invasive mechanical ventilation for more than 24 h and older than 18yrs. after the first period, all physicians and nurses were trained to a new sedation management protocol. analysis was performed to assess the prescription and application of the protocol, its impact on the use of sedative drugs, icu length of stay, and duration of mechanical ventilation. major complications were also recorded. results: 134 patients were included-78 before and 56 after the protocol implementation. patients in both groups had similar baseline characteristics (men 67 vs. 50%, p = 0.08 + mean age 56 ± 18 vs. 60 ± 16 years, p = 0.1 + weight 73.2 ± 20.6 vs. 70.2 ± 15.9 kg p = 0.61 + igs2 44 ± 17 vs. 44 ± 19, p = 0.99 + medical admission 91 vs. 88%, p = 0.51). recordings of rass and bps did not differ between groups (9 ± 4 vs 10 ± 9, p = 048 + 19 ± 25 vs, 16 ± 11, p = 0.25). the duration of sedation was significantly shorter after introduction of protocol (4.1 ± 4.7 vs 1.9 ± 1.0, p < 0.0001), as was the duration of mechanical ventilation (9.3 ± 13.8 vs 4.1 ± 3.2, p = 0.001) and icu length of stay (12.3 ± 15.8 vs 7.3 ± 5.3, p = 0.028). there was no difference in major icu complications, nor in mortality between groups (25 and 30%). conclusion: although the implantation of a sedation protocol did not translate in increased recording of rass and bps scores, it was associated with improved outcomes. our data suggest that, more than the protocol by itself, beneficial effects reported after the implementation of a sedation protocol may be ascribed to increased awareness of the care givers and thus better management of sedation. introduction: workload affects the quality of care and the prognosis of critically ills patients. measuring workload in intensive care units (icu) has thus become essential for allowing a better matching between the activities required and the management of resources. in march 2016, the medical icu of the university hospital of monastir (tunisia) moved into new buildings (more space and beds, computerbased prescriptions and monitoring, etc.). the aim of the present study is to compare the level of workload before and after the change of the icu buildings. patients and methods: during the two study periods (period 1-july-september 2015 and period 2-july-september 2017) adult patients consecutively admitted, for more than 24 h, in the medical icu for arf and or sepsis were included in the analysis. data collected were the demographic characteristics (age, sex, body mass index (bmi), comorbidities, simplified acute physiology score (saps) iii), the nursing workload measured using the therapeutic intervention scoring system (tiss-28) and hospital survival. results: thirty-six patients (22 male) were included in the study (14 during period 1 and 22 during the second period). the medians of age, saps iii and bmi were respectively 65 (iqr = 21) years, 46 (iqr = 12) and 27.7 (iqr = 9.4). the main comorbidities were hypertension, copd and neurological disease respectively in 36, 25 and 20%. the demographic characteristics were similar during the two periods. nurse workload was characterized by m tiss-28 = 18 (iqr = 7) and time of nurse's care of 190 min (iqr = 74). these two workload indicators were significantly higher during the second period (table 1) . during the second period, "standard monitoring" and "frequent dressing changes" (> 3 time day) were the activities with significant increase from, respectively 81 to 91% (p < 0.0001) and from 41 to 88% (p < 0.0001). the relocation of our icu in in new buildings was associated with a significant increase of the nurse workload with regard to patients with arf and or sepsis. . bland-altman analysis showed excellent accuracy and precision between recorded and collected data for all tested variables within clinically significant pre-defined limits of agreement. however, 82 (2.5%) data were missing and a delay was observed between videotaped and collected times. this delay was less than 28 s and remained stable through all data for each patient. we identified that the missing data were due to a limit in the number of data being processed in the database at the same time and the delay between data presentation and data collection in the database was due to different server time settings. both technical issues were corrected. conclusion: our study identified two issues in the data collection process that slightly limited the accuracy of our high resolution electronic database. we recommend the performance of such validation study before using a high resolution database for clinical or research purposes. introduction: fluid overload, and also its variations, is known to jeopardize the outcome of icu patients. however, fluid balance remains difficult to assess accurately. in that context, our study aims to assess the prognostic value of body weight variations (bwv) from day 3 to day 7 on the 30-day mortality, length of stay (los) and the occurrence of ventilator-associated pneumonia (vap) and bedsore in critically ill patients with shock. patients and methods: adult patients admitted in icu with shock between 2002 and 2012, and requiring mechanical ventilation during the first 48 h, were extracted from a prospective multicenter cohort for a retrospective analysis. bwv was defined as the difference between the body weight of the day of interest and the body weight on admission. case mix, severity on admission, and outcomes were collected. fine and gray sub-distribution survival models were used, with icu discharge as competing event, adjusted on comorbidity and illness severity at admission at each landmark, from day 3 to day 7. the impact of bwv on icu stay duration was estimated through a multivariate negative binomial regression model. the median age and saps 2 score of the 2 374 included patients were 67 (iqr, 55-77) years and 53 (iqr, 41-65), respectively. the bwv increased from 0.4 kg (iqr, 0-4.8) on day 3 to 3 kg (iqr, − 0.4 to 8.2) on day 7. the 30 day in-hospital mortality, the icu occurrence of bedsore and vap were 27, 3 and 19.6%, respectively. four categories of bwv were defined according to bwv interquartiles: weight loss, stable weight, moderate and severe weight gain. categories of bwv were independently associated with death on day 5 and day 6 (day 5 : shr 1.27; 95% 0.99-1.63 p = 0.06; day 6: shr 1.43; 95% ci 1.08-1.89, p = 0.01) (fig. 1) . a weight loss tended to be associated with increased occurrence of bedsore, and weight gain with increased occurrence of vap. the extent of bwv increased the duration of icu stay independently of other severity factors. discussion: bwv may be another clinically relevant tool to assess the risk of death, mostly after day 4. the increased risk of bedsore in case of weight loss deserved to be confirmed. conclusion: body weight should be daily monitored for better prognostication. bwv-based restrictive strategies should be further evaluated. the clinical effectiveness of multi-layer silicone dressings in preventing icu acquired pressure ulcers: a randomised controlled trial introduction: the development of pressure ulcers (pu) in critically ill icu patients result in additional morbidity and may contribute to mortality in some cases. the minimisation of icu acquired pu remain an international challenge. this paper describes australian research that used multi-layer soft silicone sacral and heel dressings to prevent pu in critically ill patients. patients and methods: a total of 440 critically ill patients were enrolled into an 18-month randomised controlled trial in one of melbourne's trauma centres. patients were randomised on admission to the emergency department and either had standard pu prevention or standard care plus the application of prophylactic sacral and heel dressings. patients were observed daily for pu development for the duration of their icu stay. results: patients in the dressing group has significantly reduced incidence rate of pu development compared to patients receiving standard pu prevention alone (3.1 vs 13.1%, p < 0.03). patients in the dressings group had a relative risk reduction of 80% and a 10% absolute risk reduction for developing a pu regardless of their critical illness. results indicate the number needed to treat to prevent one pu was 10. additionally, we calculated the cost-benefit of this intervention and found the patients treated with prophylactic dressings cost 3.6 time less than the standard care group for wound care. discussion: the use of prophylactic dressings to prevent pu at our hospital have proved to be very effective in icu and subsequent studies have confirmed our results. it appears that the main mechanism of pu protection provided by these dressings is the reduction of pressure and shear forces leading to tissue distortion and cell death rather than the previously accepted ischaemic model of pu development. our current policy is now to use these dressings on all patients with a high risk of developing pu. the use of prophylactic multi-layer silicone dressings to prevent pu in critically ill patients is effective but it does not replace standard pu prevention methods. the use of these dressings sould be considered complimentary to best practice in pu prevention. iatrogenic events in intensive care unit: incidence, risk factors and impact on outcome ayed samia 1 , merhebene takoua introduction: iatrogenic events (ies) are defined as harm resulting from medical intervention and health care, and not explained by underlying disease. mortality is reported to be as high as 13.6% in cohorts of hospitalized patients experiencing ie. both length of stay and cost of hospitalization are increased by ies occurrence. we perform this study to determine the incidence, risk factors, and impact on outcome of ies in intensive care unit (icu). patients and methods: all patients admitted more than 24 h to the 22-bed icu of a teaching hospital were prospectively screened. patients were monitored daily for adverse clinical occurrences. time and data about each ie were collected and they were considered as preventable or life-threatening events. for each patient, the followings were recorded-basic demographic data, indication for admission, severity scores on admission (sapsii and apacheii), need and duration of mechanical ventilation (mv), length of stay (los) in icu, intensive care work load score (omega), global mortality and ies related mortality. results: during the 6 months period, 167 patients were included and 65 (38.9%) were judged to have developed an ie while hospitalized. we recorded 282 ies over 2004 days in icu so a density incidence of 14 ie for 100 patient-day. ies were considered preventable in 34% of cases and life-threatening in 22% of cases. ies occurred in a mean delay of 6 ± 6 days. global mortality rate was 36.5% and ies related mortality rate was 13.7%. patients with ies were significantly severe on admission, with a longer duration of mv and los in icu. omega score was significantly higher. multivariate analysis showed that omega score was the independent risk factor of ies occurrence (or 1.031 ic 95% [1.015-1.047], p < 10 -3 ). dead patients were significantly severe on admission and experienced more ies than survivors. omega score, duration of mv and los were significantly higher. in multivariate analysis, ies and life-threatening ies were independent factors of mortality (or 6.171 ic 95% [3.087-12.339 ], p < 10 -3 and or 21.482 ic 95% [5.077-90.889], p < 10 -3 respectively). conclusion: ies in icu are common and frequent but one-third is preventable. work load icu score is the independent risk factor of their occurrence. ies impact largely the outcome especially the lifethreatening ones. efforts must be focused on preventing programs to reduce ies and improve the outcome. introduction: based on the recent sepsis-3 definitions, septic shock is defined by the combination of vasopressor requirement and serum lactate level > 2 mmol/l. however hyperlactatemia and lactate kinetics may result from both increased production and impaired clearance in the critically ill, and may therefore not only rely on the severity of circulatory failure. we herein addressed the determinants of hyperlactatemia (> 2 mmol/l) and the factors likely to impact on early lactate clearance in septic shock. patients and methods: this was a 9-year (2008-2016) monocentric retrospective study. all adult patients diagnosed for septic shock within the first 48 h were included. septic shock was defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors. the first lactate value (l1) was measured at the time of icu admission. hyperlactatemia was defined as a first lactate level > 2 mmol/l. the second value (l2) was measured within 12 h following the first measurement. lactate clearance was calculated as (l1-l2) l1 time between l1 and l2 measurements) and expressed in mmol hour. parameters associated with initial hyperlactatemia and lactate clearance were investigated using multivariate logistic regression analysis. introduction: cardiac surgery with cardiopulmonary bypass (cpb) induces immunosuppression which has considerable implications for patients. cpb induces a significant increase in circulating neutrophils. neutrophil activation, associated with production of antibacterial peptides, reactive oxygen species (ros), cytokines, and other inflammatory mediators, as well as release of dna into the extracellular milieu (neutrophil extracellular traps (nets)), plays a central role in innate host defense and modulation of inflammation. however, it has been shown that, in septic shock or systemic inflammation as major surgery, immature circulating neutrophils can induce immunosuppression and increase the risk of secondary infections. staphylococcus aureus (sa) is one of the most commonly encountered bacterial pathogen responsible for poststernotomy mediastinitis, and neutrophils alterations may favor postoperative infections. the main objectives of this study were to evaluate the direct effects of cbp on neutrophils functions and to study the impact of different strains of sa on neutrophils bactericidal functions. patients and methods: blood samples were collected before and 24 h after cardiac surgery with cpb and bone marrow samples were harvested directly after sternotomy, before initiation of cpb, and at the end of cpb, before sternal closure. septic patients were included as controls. circulating neutrophils analysis was performed using flow cytometry. we also studied netosis, ros production and bactericidal activity in isolated neutrophils before and after surgery using two strains of sa-one responsible of postoperative mediastinitis and one isolated from nasal carriage. results: blood cell count with differential demonstrated a significant increase in neutrophils 24 h after surgery. flow cytometry analysis of blood samples indicated neutrophils were matures with a significant increase in degranulation marker (cd66b). neutrophils life span was also increased after cbp. flow cytometry analysis of bone marrow samples showed no difference in cell composition and maturation before and after cbp. the neutrophil production of ros was significantly higher after cbp. however, cbp did not impact nets formation, phagocytosis and bactericidial function. moreover, there was no difference regarding the phagocytosis and the bactericidial activity when exposed to the two strain of sa. as expected, immature neutrophils count was significantly increased in septic patients compared to cardiac surgery patients. these results indicate that cbp promotes the recruitment of matures neutrophils via a demargination process. cbp does not induce neutrophil dysfunction. neutrophils should not be targeted to decrease postoperative infection after cpb. introduction: protein tyrosine phosphatase 1b (ptp1b) is a negative regulator of both no production and insulin signaling and has been shown to be an aggravating factor in septic shock. stress hyperglycemia frequently occurs in critically ill patients and is associated with poor outcome. experimental studies on transgenic mice have shown that ptp1b deletion resulted in a reduced insulin resistance and in a better survival during experimental model of sepsis. the main objective was to study the correlation between the ptp1b gene expression and organ failure (through the delta sofa score between day 1 and day 5) or insulin resistance. patients and methods: twenty-seven healthy male volunteers have been included in this clinical trial. the product was administered by continuous intravenous infusion (civ). a single ascending dose design with 8 dose levels was used. cohorts 1 and 2 received a 15-min single dose of motrem (1 and 10 mg and one and two volunteers respectively). then, cohorts 3 to 8 received either a 15-min loading dose (from 0.5 mg kg to 5 mg kg) followed by 7.75-hours maintenance dose (from 0.03 mg kg h to 6 mg kg h) of motrem or a matching placebo (3-1 ratio). all volunteers were carefully monitored. before escalation to the next dose level, safety and pk data of the previous dose level were reviewed by a safety review committee. since immune system is at rest in normal individuals and thus trem-1 pathway is not activated, no pharmacodynamics parameters were analyzed. the main objectives of this trial was then to study the safety and pharmacokinetic profile of motrem. results: no product related changes in vital signs, clinical nor laboratory parameters were observed. no product-related adverse events were reported. the pk of motrem was linear; the main clearance was estimated at 463l/h/70 kg which is higher than the hepatic blood flow in human (i.e., 90l/h/70 kg) and is therefore indicative of an extensive enzymatic metabolism in blood + effective half-life was calculated to be about 3 min. conclusion: motrem was found to be safe and well tolerated up to the highest dose tested (5mg/kg for a 15-min loading dose and 6 mg kg h for a 7.75-hours maintenance dose). safety and pharmacokinetics of motrem is currently being studied in septic shock patients in a phase iia randomised, double-blind, two-stage, placebo controlled, international, multicenter clinical trial (www.clinicaltrials.gov nct03158948). -1) is an immunoreceptor expressed on neutrophils and monocytes macrophages whose role is to amplify the inflammatory response driven by toll-like receptors engagement. the pharmacological inhibition of trem-1 confers protection in several pre-clinical models of acute inflammation. in this study, we aimed to decipher the role of trem-1 on the endothelium. we evaluated the expression of trem-1 in vessels and isolated endothelial cells by flow cytometry, qrt-pcr and confocal microscopy. we generated an endothelium-conditional trem-1 ko mice and submitted them to polymicrobial sepsis through clp. organs and blood were harvested at different time points and analyzed for cellular content, cytokine chemokine concentrations, and vasoreactivity. survival was monitored for 1 week. results: trem-1 was expressed in aorta and pulmonary vessels from animals, and inducible after lps stimulation or during sepsis. these results were confirmed in human pulmonary microvascular endothelial cells. the pharmacological inhibition of trem-1, using the synthetic inhibitory peptide lr12, decreased the lps-induced trem-1 expression. sepsis induced a profound vascular hyporeactivity in wt animals, both in terms of contractility and endothelium-dependent relaxation. although contractility was still impaired in endotrem-1-mice, vasorelaxation was completely restored. soluble trem-1 concentrations, a marker of trem-1 activation, were markedly increased in the plasma, the peritoneal lavage fluid and the lungs from wt septic mice compared to control. in endotrem-1-mice, strem-1 level was reduced. plasma concentrations of soluble vcam-1 and il-6 were also reduced in endotrem-1-animals. we observed an accumulation of neutrophils and inflammatory ly6chigh monocytes in the lung of wt septic mice. this accumulation was dampened in endotrem-1-mice. by contrast, endothelial trem-1 deletion favored the accumulation of reparative cells (ly6clow monocytes). finally, survival was clearly improved in the endotrem-1-group as compared to the wt group. conclusion: we reported that trem-1 is expressed and inducible in endothelial cells and plays a direct role in vascular inflammation and dysfunction. the targeted deletion of endothelial trem-1 conferred protection during septic shock in modulating inflammatory cells mobilization and activation, restoring vasoreactivity and improving survival. the effect of trem-1 on vascular tone, while impressive, deserves further investigations including the design of endothelium specific trem-1 inhibitors. -50.5 ]. 14 patients suffered from pneumonia, 6 from intra-abdominal sepsis. we measured serum levels of total and free thiamine, thiamine mono di and triphosphate (tmp, tdp and ttp respectively), as well as the erythrocyte transketolase activity and arterial lactate at the time of admission. we also recorded the vital status at the end of the icu stay. results: 50% of our subjects exhibited particularly low levels of free thiamine (< 7 nmol/l). there was no correlation between free (r = − 0.4; p = 0.85), or total (r = − 0.19; p = 0.34) thiamine concentration and lactate levels. there was no correlation between tmp (r = 0.02; p = 0.91), tdp (r = − 0.19; p = 0.34), ttp (r = − 0.15; p = 0.46) and lactate levels in the whole population. no correlation was found between the concentration of thiamine derivatives and arterial lactate levels in the subgroup of patients exhibiting the highest levels of lactate (> 2 and > 4 mmol/l). total thiamine and tdp concentration at the time of admission were significantly higher in icu survivors than in non-survivors (p = 0.031 and p = 0.028). during sepsis, we did not find any correlation between thiamine and lactate concentration. lower thiamine diphosphate concentration may be associated with icu-mortality. introduction: a positive fluid balance in sepsis is a determining factor for mortality. in previous experimental studies, sodium lactate has been shown to improve hemodynamic and avoid fluid overload (1). to understand these beneficial effects, we investigated the impact of sodium lactate on capillary leakage, in comparaison to saline on capillary leak in a rat model. the sixteen sedated, mechanically ventilated rats were challenged with intravenous infusion of e.coli lipopolysaccharide (10 mg/kg). two groups of eight animals were randomised to receive a continous perfusion (5 ml/kg/h) of sodium lactate 11.2% (treatment group) or 0.9% nacl (control group). in order to inject the same caloric load in the two groups, a 4.35 ml/kg/h of either water of 10% dextrose solution were perfused. mean arterial pressure, heart rate, urine ouput were measured over a 210 min period. an echocardiography was then performed and evans blue (1%, 30 mg/kg) was intravenously injected 30 min before sacrifice. organs were withdrawn and organs wet dry ratio and evans blue dye extravasation were measured. results: fluid balance, organs wet dry ratio and evans blue dye extravasation were not significantly improved in sodium lactate group. hemodynamics parameters were not significantly enhanced after sodium lactate infusion. discussion: previously, lactate administration has improves renal perfusion. in our study, the volume of urine output was decreased in the 2 groups reflecting the severity of our model. and the vascular filling (9.35 ml/kg/h) higher than in the literature could impact our results. (1) recently, the pressure electricy index-pmus eadi index (pei) has been described. (2) the purpose of this study was to assess muscular pressure (pmus) using pei with our nava protocol. patients and methods: observational study, patients recovering from pneumonitis and acute respiratory failure. sbt was pressure support ventilation with 7cmh20 of assist and no pep. pei was calculated under nava and during sbt from airway pressure drop during end-expiratory occlusions, muscular pressure (pmus) was estimated from pei (2) . another index, patient ventilator contribution index (pvbc) was also measured using the inspiratory peak of eadi and vt (inspiratory) during assisted and non-assisted breaths. we calculated pvbc-squared because it has been shown that it is more correlated to pmus ptot. results: results are summarized in the introduction: in icu, intubation is a high risk procedure associated with high morbidity. despite procedure's improvement with systematic application of fluid loading, early use of vasopressors and checklist use, morbidity remains high. first pass success is strongly correlated with adverse event occurrence. a recent study by semler et al. concluded than "sniffing" position is better than "ramped" position to increase first pass success even the primary outcome prespecifiedpulse pressure saturation was not different between the two groups. we conducted a post hoc analysis of the randomized clinical trial macgrath mac video laryngoscope or macintosh laryngoscope for intubation in the intensive care unit (macman) to determine the best position for intubation in the icu. patients and methods: macman was a multicentre, open-label, randomized controlled superiority trial. consecutive patients requiring intubation were randomly allocated to either the mcgrath mac videolaryngoscope or the macintosh laryngoscope, with stratification by centre and operator experience. an only inclusion criterion was-"patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if-contraindication to orotracheal intubation (e.g., unstable spinal lesion); insufficient time to include and randomize the patient (e.g., because of cardiac arrest); age < 18 years; pregnant or breastfeeding woman + correctional facility inmate; patient under guardianship + patient without health insurance; refusal of the patient or next of kin to participate in the study; previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess association between patient position (sniffing or supine) and first pass success. between-groups baseline difference was adjusted for baseline covariates significantly associated with the group membership (p < 0.2). results: failure of first pass introduction: during acute exacerbation of copd oxygen should be titrated to avoid both hypoxemia and hyperoxia. the recommendations are not followed and automated oxygen titration may be useful in this population. the aim of this study was to evaluate a new device developed to automatically titrate oxygen based on spo2 target (freeo2, oxynov, canada) and to compare oxygenation parameters with usual administration (manual flowmeter). the study is an observational monocentric study. we prospectively included patients hospitalized for acute exacerbation of copd receiving oxygen. written informed consent was obtained from all patient. in the first part of the study, we evaluated oxygen flowrate and spo2 during 30 min at baseline based on management of the physicians in charge. the oxygenation parameters were compared with automated titration (freeo2 during 1 h). in the second part of the study, oxygen was delivered with freeo2 until oxygen weaning or a maximum of 72 h. we evaluated the oxygenation parameters during prolonged utilization, the duration of oxygen administration, a new bluetooth spo2 connection compared to wire spo2 connection (evaluated by visual analog scale 0-10). results: we present preliminary data of 23 copd patients (sex ratio m f = 9 14). mean age (± sd) was 72 ± 11 years, mean fev1 (± sd) was 0.9 ± 0.3l. oxygenation data in both parts of the study are displayed in the table 1 . time in the spo2 target was significantly increased with freeo2 in comparison with manual titration and oxygen flowrate was reduced by half. in the second part of the study, the % of time in the spo2 target with automated oxygen titration was above 80% and time with hypoxemia and with hyperoxia were low. in 11 patients, we compared comfort with wire spo2 connection to bluetooth wireless spo2 connection. the comfort was significantly increased with wireless connection (7.0 ± 2.9 vs. 9.7 ± 0.6, p < 0.001). duration of oxygen administration after inclusion (2.3 ± 4.3 days) and hospital length of stay after inclusion (5.7 ± 5.3 days). conclusion: automated oxygen titration maintains the patients within predetermined spo2 target more than 80% of the time and reduces oxygen flowrate in comparison with manual oxygen titration. the second part of the study demonstrates the feasibility to use automated oxygen titration during several days with similar outcomes as previously reported in similar population. there are several limitations of the study and additional evaluations of this device are required. introduction: hyperoxemia occurs up to 50% of mechanical ventilation days in the icu [1] and is associated with increased mortality as compared to patients ventilated in normoxemia [2] . intellivent-asv is a full closed loop ventilation mode adjusting automatically oxygenation's settings fio2 and peep according to spo2 for passive and spontaneously breathing mechanically ventilated patients. this post hoc analysis of a monocentric randomized controlled parallel group study compared frequency of hyperoxemia (pao2 > 120 mmhg and or spo2 > 96%) and hypoxemia (pao2 < 60 mmhg and or spo2 < 90%) and the percentage of ventilation time with spo2 > 96% and the percentage of ventilation time with spo2 < 88% between intellivent-asv and conventional ventilation mode in mechanically ventilated icu patients. the randomized controlled trial was performed in the general icu of hôpital sainte musse, toulon, france. eligible participants were adult aged 18 or over, invasively ventilated for less than 24 h at the time of inclusion with an expected duration of mechanical ventilation of more than 48 h. exclusion criteria were broncho-pleural fistula, ventilation drive disorder and moribund patients. patients were allocated to intellivent-asv group or to conventional ventilation group (volume assist control and pressure support modes) using blocked randomization. the post hoc analysis was performed by the comparison of all arterial blood gases (abg) performed during the study period-the number of abg with hyperoxemia and hypoxemia, the median pao2 and spo2 for these arterial blood gases and fio2 associated were compared according to group. results: 60 patients were included, 30 patients in each group. the total number od abg was 333 (mode conventional) vs 316 (mode intel-livent-asv) (p = ns). the number of abg with pao2 > 120 mmhg was respectively 54 versus 33 (p = 0.032) with sao2 > 96% was 203 vs 153 (p = 0.001) with pao2 < 60 mmhg was 57 vs 56 (p = 0.121) + with sao2 < 90% was 88 vs 86 (p = 0.951). the percentage of time of ventilation spent with spo2 > 96% was 32% vs 29 (p = 0.438), and with sao2 < 88% was 0.6 vs 0.5 (p = 0.615). the continuous control of oxygenation settings provided by intellivent-asv decreases significantly the number of blood gas with hyperoxemia as compared to manual oxygenation setting without increasing the risk of hypoxemia. introduction: in invasively mechanically ventilated patient, dyspnea is frequent and severe. relying on self-report, its measurement remains challenging in patients unable to communicate. a 5-item observation scale, namely the intensive care-respiratory distress observation scale (ic-rdos), has been proposed as a surrogate of dyspnea-visual analogic scale (d-vas) self-report in intensive care unit (icu) patients [1] . however this scale has been validated among non-intubated patients and included one item "supplemental oxygen" not thoroughly adapted for intubated population. we sought to develop a dyspnea observation scale more suitable for intubated patients and to evaluate its performance to detect dyspnea. patients and methods: ancillary analysis of data prospectively collected from 220 icu communicative patients enrolled for the validation of the ic-rdos. factorial principal component analysis was first performed to select variables that mostly contributed to the principal axes, among a set of 21 observable variables with possible clinical relevance. to identify the best correlation between these variables and d-vas, were performed an iterative partial least square regression process (pls). iterative pls procedure identified five variables, of which the combination and weighting allowed optimal correlation with d-vas (r = 0.61; 95% ci 0.50 to 0.72; p value < 0.0001), which constitute the ic-rdos [1] . in a first step, we removed "supplemental oxygen", not relevant in intubated patients. we obtained a 4-items ic-rdos (r = 0. introduction: lung ultrasound (lus) has emerged in different clinical settings, such as in intensive care medicine (icm). early diagnosis of ventilator-associated pneumonia (vap) remains a challenge to the intensivist. however, scientific evidence is little available on whether lus reliably improves the diagnosis of vap. the aim of this prospective study was to assess whether lus could be an alternative to pulmonary computerized tomography (ct) for assessing diagnosis of vap in icm. patients and methods: twenty-one patients ventilated for duration more than 5 days suspected of vap were included. lus was performed by a well-trained operator who was blinded of the vap diagnosis. the diagnostic gold standard of vap was on the basis of pulmonary ct and positive culture pulmonary. all clinical criteria for the diagnosis were collected the same day of lus and pulmonary ct. the ultrasound exam included anterior, lateral and posterior views from both sides of the chest with superior and inferior views. we classed patient in 4 groups according diagnosis of vap with pulmonary ct (vap + or vap-) and lus (lus + or lus-). lus characteristics of vap diagnosis included 9 profils-asymetric line b (profil a b), without sliding (profil b'), sub pleural consolidation (profil c), consolidation with punctiforme bronchogram (pb), linear air bronchograms (lb) or dynamic bronchograms (lbd), posteror lateral alveolar pleural suffusion (plaps), pleural effusion pathological (pep), shred sign (ss and complications according to insertion site. the advantage of this method is that it gives a pragmatic view of the real clinical situation. patients and methods: ancillary study of the akiki trial, an open pragmatic randomized controlled trial published in 2016, in which patients with severe acute kidney injury were randomly assigned to either an early or a delayed rrt initiation strategy. the present study involved all patients who underwent at least one rrt session. number of rrt catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected. results: among the 619 patients included in akiki, 462 received rrt at least once and 459 patients were finally included in the analysis (3 missing data), leading to a total of 598 rrt catheters. femoral site was chosen preferentially (n = 319, 53%), followed by jugular site (n = 256, 43%) and subclavian site (n = 23, 4%). investigating center was the sole factor significantly associated with the choice of insertion site in multivariate analysis (p = 0.01). higher weight did not affect choice of insertion site. mean duration of catheter use was 6.6 (+-5.0) days without difference according to site. catheter dysfunction was the main reason for replacement (n = 61, 49%). suspicion of infection led to replacement of many catheters (n = 40, 32%) but was actually seldom proven (n = 4, 3% introduction: long standing dialysis (sled or crrt) allows a better hemodynamic tolerance as well as a greater performance to achieve a negative fluid balance in intensive care unit. dialysis alter hemodynamics mainly by short term variation of blood volume. in this study we took advantage of a continuous monitoring of blood volume during dialysis session to decipher the relationship between the variation of relative blood volume (rbv) with mean arterial pressure (map). this study is observational prospective, including all prolonged (> 8 h) dialysis sessions in saint etienne nephrology intensive care unit between january and june 2017. exclusion criteria were ongoing blood transfusion and blood volume controled ultrafiltration. medical records were compiled along with cardiac ultrasonography at the beginning when available. the statistical analysis was perfomed in two parts. the first part studied the performances of the first hour deltarbv (defined by rbv before minus rbv after 1 h of dialysis) to predict a drop of map below 65 mmhg (hypotension). this analysis excluded sessions with hypotension and intervention during the first hour. the second study was the modelization of the relationship between deltarbv and deltamap for every hour of dialysis without any intervention on blood pressure. both analyses were performed using mixed effects linear and generalized models. fig. 1 vancomycin pk during sled results: a total of 82 sessions on 23 different patients were performed during the period. the characteristics of patients were as follows-sex ratio at 1, age (sd) 64.3 (9.0), weight 83.3 kg (17.2), sapsii score 48. 3 (13.6) . 20 patients on 23 were taken in charge for fluid overload. in the first set of analyses (per sessions), 27 sessions were excluded for intervention in the first hour. the adjusted deltarbv did not predict hypotension during the session (generalized mixed effect model, session and patients set as random effects, estimate 0.14, p = 0.71). in the second set of analyses (per hour without any intervention), 535 h were analyzed. adjusted deltarbv correlated strongly and inversly with deltamap (linear mixed effect model, random effects were sessions, patients and hour order in the session, estimate 1.42, p < 0.0001). conclusion: in our mostly fluid overloaded patients, the drop of rbv correlated with an increase of map. introduction: kidney transplant recipients (ktr) are at risk of icu admission because of prolonged immunosuppressive therapy and a higher risk of cardiovascular events, severe infections or drug-related toxicities. several retrospectives studies reported the short-term outcome of ktr admitted to the icu, but data concerning the risk of chronic kidney disease and anti-hla immunization are scarce. patients and methods: in this retrospective study, we addressed the in-hospital and long-term mortalities of the 200 ktr admitted in a french icu (10 beds) between january 2010 and june 2016. predictive factors for death, long-term renal function and hla immunization were identified. results: the main causes for admission were acute respiratory failure (27.5%), sepsis (26.5%), post-operative period (peritonitis, hemorrhage + 23%). at the admission, mean age, saps2 and sofa score were 58 ± 13 years, 52 ± 19 and 6.7 ± 3.3, respectively. renal replacement therapy, mechanical ventilation and vasopressors were required in 103 (51.5%), 107 (53.5%) and 97 (48.5%) patients. immunosuppressive regimen was modified in 155 patients (76.1% + steroids increase 68%, calcineurin inhibitors or antimetabolites withdrawal 25 and 37%, respectively). in-hospital mortality was 20% (30.1 and 38.2% at months 12 and 36). by multivariate analysis, ebv blood proliferation in the 6 months preceding the admission in the icu, and the saps2 gravity score at admission independently predicted the in-hospital and long-term mortalities. among the 113 patients alive at month 6 after the admission in the icu and with available data, 34 (30.1%) and 51 (45.1%) progressed to a more severe ckd stage at months 1 and 6, respectively. both, the severity of the aki and the preexisting ckd predicted the risk of progression of the ckd. last, de novo anti-hla immunization at month 6 was identified in 18 119 patients (15.1%, donor specific antibodies 11 18 (61.1%)) and was significantly associated with the occurrence of acute transplant rejection (p = 0.002). in five patients who developed anti-hla antibodies, rbc transfusion during the icu stay was the only immunological trigger identified. discussion: outcome of ktr is closed to the general population admitted in icu and better than other immunocompromised patient, like patients from oncohematology. conclusion: worsening of the renal function and hla immunization are frequent and may impact mid to long-term prognosis because of the high risk of transplant rejection, end-stage renal disease and further transplantation contraindication. introduction: acute kidney injury (aki) is associated with a poor prognosis. although pulmonary embolism (pe) may promote aki through renal congestion or hemodynamic instability, its frequency as its impact on the prognosis of patients with acute pe have been poorly studied. patients and methods: using data from the registro informatizado de la enfermedad tromboembolica venosa (riete) registry, we assessed the frequency of aki at baseline, and its influence on the 30-day mortality rate of patients with objectively confirmed pe. aki was defined according to the "kidney disease-improving global outcomes" definition. we used multivariate analysis to assess whether or not the presence of aki independently influenced the risk for 30-day death. the study included 21,131 patients with acute pe, of whom 6222 (29.5%) had aki at baseline. of these, 4385 patients (21%) were in stage 1, 1385 (6.5%) in stage 2 and 452 (2%) in stage 3. the proportion of patients with high-risk pe in those with no aki, aki stage 1, aki stage 2 and aki stage 3 was-2.8, 5.3, 8.8 and 12%, respectively (p < 0.001). after 30 days, 1236 patients (5.85%) had died. overall mortality was-4% in patients with no aki, 8.4% in aki stage 1, 14% in aki stage 2, 17% in aki stage 3, all p < 0.001). on multivariable analysis, aki was independently associated with an increased risk of death at 30 days (odds ratio = 1.25 + 95% ci 1.02-1.54), after adjusting for the initial severity of pe, age > 65 years, chronic heart failure or chronic lung disease, cancer, anemia and liver cirrhosis. conclusion: one in every 3-4 patients with acute pe had aki. moreover aki was an independent predictor of poor outcome in pe patients. this study suggests that pe (and its severity) should be considered as a risk factor for aki and aki may deserve to be evaluated as a prognostic factor in patients with acute pe. introduction: metabolic acidosis is frequently observed as a consequence of global ischemia-reperfusion after out-of-hospital cardiac arrest (ohca). we aimed to identify risk factors and assessing the impact of metabolic acidosis on outcome after ohca. patients and methods: we included all consecutive ohca patients admitted between 2007 and 2012. using admission data, metabolic acidosis was defined by a positive base deficit and was categorized by quartiles. main outcome was survival at icu discharge. factors associated with acidosis severity and with main outcome were evaluated by linear and logistic regression, respectively. results: 826 patients (68.3% male, median age 61 years) were included in the analysis. median base deficit was 8.8 [5.3, 13.2] meq/l. male gender (p = 0.002), resuscitation duration (p < 0.001), initial shockable rhythm (p < 0.001) and post-resuscitation shock (p < 0.001) were associated with a deeper acidosis. icu mortality rate increased across base deficit quartiles (39. 1, 59.2, 76.3 and 88 .3%, p for trend < 0.001) and base deficit was independently associated with icu mortality (p < 0.001). the proportion of cpc 1 patients among icu survivors was similar across base deficit quartiles (72.8, 67.1, 70.5 and 62.5%, p = 0.21) and 11.7% of patients with a base deficit higher than 13.2 meq l survived to icu discharge with a good neurological recovery. severe metabolic acidosis is frequent in ohca patients and is associated with poorer outcome, in particular due to refractory shock. however, we observed that about 10% of patients with a very severe metabolic acidosis survived to icu discharge with a good neurological recovery. introduction: precarious socio-economic status can directly influence health, need for hospitalisation and mortality, according to a previous study performed in 22 european countries. similar findings have been reported from anglo-saxon countries in the setting of intensive care. due to the different structure of the healthcare system in france, we aimed to investigate whether socio-economic status influences initial severity of disease and 3 months mortality in patients admitted to intensive care in france. patients and methods: prospective, multicentre, cohort study including 1396 adult patients admitted to one of 8 participating intensive care units (icus) between 2012 and 2016, and presenting failure of one or more major organs. patients were considered to have a precarious socio-economic status if they presented at least one criterion of social vulnerability or a high epices deprivation score. results: data on social vulnerability were available for 1281 patients, of whom 54.3% were considered to be socially vulnerable. compared to non-vulnerable patients, socially vulnerable patients were younger (64.8 vs 67.2 years, p = 0.006), more frequently had chronic disease (18.0 vs 12.0%, p = 0.003 respectively for congestive heart failure and 26.8%vs 18.1%, p = 0.0002 for chronic respiratory disease), had higher levels of physical dependency (9.2 vs 4.7%, p = 0.002), and were more often classed as having long-term health conditions (67.1 vs 62.1%, p < 0.0001). conversely, non-vulnerable patients had greater severity of disease at admission to the icu than those classed as vulnerable, both in terms of saps ii and sofa scores (respectively 53.16 vs 50.09 (p = 0.001) and 8.35 vs 7.77(p = 0.002)). findings were similar after adjusting for major confounders (adjusted odds ratio (or) 0.62, 95% confidence interval (ci) [0.48-0.81], p = 0.0005). mortality at 3 months was not significantly different between socially vulnerable patients and those not considered vulnerable, respectively 34.6 vs 36.10% (p = 0.62), even after adjustment for initial severity. conclusion: despite less severe disease at admission to the icu among patients considered socially vulnerable, 3-month mortality did not differ significantly between those who were socially vulnerable and those who were not. these findings suggest that the french healthcare system provides good protection for the most disadvantaged members of society, particularly when they are admitted to the icu. introduction: an approach of the quality of care may involve assessing the patients' satisfaction. however, the extended caregiverpatient and family relationship, specific to the critically ill patients, may also require to assess the proxies' satisfaction. the opinionfamily tool was developed to assess the satisfaction of the critically ill patients' proxies, in an anonymous and continuous fashion. we conducted a study in the icu of tenon hospital (paris, france) between mars and august 2017. the opinion-family questionnaire, built with 6 categories (4 items each), aimed to measure the proxies' satisfaction regarding their perception of the quality of care. all the proxies were invited to express voluntarily and anonymously his her degree of agreement as a response to a statement by the selection of the corresponding stars (strongly disagree-1 star, disagree-2 stars, neither agree nor disagree-3 stars, agree-4 stars, strongly agree-5 stars) using a secure touch screen disposed 24 7 in the waiting room of the icu. results: altogether, 456 patients were hospitalised during the study period, and 148 proxies completed the questionnaire. all the responders spoke french. only 12 responders (9%) answered more than one time. of the responders, 105 (71%) were the referring person, 47 (32%) were children and 26 (17%) were spouses. during the study period, 50 (34%), 59 (40%), and 38 (26%) responders had visited their relative 1 to 3 times, 4 to 10 times, and more than 10 times, respectively. the different categories assessed by the opinionfamily tool were related to «the family and the patient» (fig. 1a) , «the family and the environment» (fig. 1b) , and «the family and the caregivers-availability, trust, support, and information» (fig. 1c) . the corresponding levels of satisfaction (responses of at least 4 stars) were respectively 67, 78, 65, 77, 78, and 79%. some items were associated with a poor satisfaction (participation to the care, identification and availability of the caregivers). conclusion: the implementation of the opinionfamily tool allowed a continuous evaluation of the satisfaction of the critically ill patients' proxies. a systematic implementation of this tool in the icus may be useful to the caregivers for a better understanding of the needs of the proxies. in addition, this tool may allow rapid changes in icu organizations and behaviours to improve the proxies' satisfaction, which may ultimately, improve the care of patients. many factors influence end-of-life decisions (eol). we describe eol decisions in patients with acute respiratory failure and their impact on patients' prognosis. patients and methods: an international observational study included all patients with acute respiratory distress over a 1-month period. 459 icu in 50 countries were involved. demographic, clinical and biological data were compared between patients with and without decision of lst limitation. we also compared surviving patients after lst limitation decision to those who eventually died. results: among the 4041 patients, mortality was 37.2%. a decision of lst limitation was reported in 948 patients (23.4%). in univariate analysis, patients with lst limitation decision were older and more frequently hospitalized for a medical condition, had a lower body weight, a higher sofa score, and presented active neoplasia immunosuppression or chronic liver failure more frequently (p < 0.001 for all). patients admitted after trauma, drug overdose or pulmonary contusion were less subject to have an lst limitation decision (p < 0.001). in contrast, patients with non-cardiogenic shock were more subject to these decisions (p = 0.018). eol decisions were less frequent in lower-middle income countries as compared to high and middle-high income countries (p < 0.001). multivariate analysis will be presented. among 948 patients with an lst limitation decision, 148 survived (15.6%). mortality was higher in this group than in the whole study population (p = 0.001). in univariate analysis, death after decision of lst limitation was associated with admission for a medical condition (p = 0.02), severe ards, higher inspiratory pressure, non-cardiogenic shock, higher sofa score with or without respiratory component and chronic liver failure (p < = 0.001 for all). on the contrary, admission for trauma was associated with survival (p = 0.001). regarding the 1503 patients who died during their hospital stay, 703 did not receive a decision of lst limitation (46.8%). decision of lst limitation was more frequent in older patients (p < 0.001) and in high-income countries. conclusion: decisions of lst limitation are frequent in the icu, and are associated with increased age and medical severity. however, a significant percentage of these patients survived. interestingly, almost half of the patients who eventually died during their hospital stay had not been subject of a decision of lst limitation. evaluation of the decision-making process leading to a decision not to readmit a patient to the intensive care unit during a same hospital stay introduction: the risk-benefit ratio of (re-)admission to the intensive care unit (icu) has been widely discussed in the literature. however, the ethics of non-readmission during a single hospital stay have not been widely addressed. a decision not to re-admit a patient to the icu could be seen as a limitation of therapy, thus falling within the scope of the law dated 22 april 2005, by denying the patient access to potentially-available healthcare resources. in this context, we aimed to-(1) investigate whether decisions not to re-admit patients to the icu are taken in accordance with french legislation + and (2) identify the characteristics of patients concerned by this type of decision. patients and methods: this study was based on data from the prospective, multicentre ivoire cohort (influence of socio-economic vulnerability on initial severity and prognosis of patients admitted to the icu + phrc-ir 2012). we identified patients included in two large regional university hospitals in the east of france for whom a decision not to re-admit was taken during a single hospital stay. the decisionmaking process was evaluated based on a questionnaire comprising 13 items developed by a sociologist from semi-directive interviews with clinicians. results: among 857 patients discharged from the icu alive, a decision not to re-admit to the icu during a same hospital stay was noted in the medical file of 63 patients (7.3%). this decision was primarily made on the day of discharge (42.6%), and those involved in the decision included-the family, an outside consultant, and the patient themselves in 54, 31.7 and 15.9% of cases respectively. the decision was justified in medical terms in 92.1% of cases, and the main reasons cited were-(1) therapeutic impasse (52.4%) + (2) comorbidities (44.4%) + (3) degree of dependence of the patient (34.9%). patients concerned by decisions of this type were generally older (75 vs 65.6 years, p < 0.0001), with more comorbidities (median 4 vs 2, p = 0.001), greater loss of dependence according to katz's activities of daily living (5 vs 6, p < 0.0001), and longer duration of life-sustaining therapies (7.5 vs 5 days, p = 0.028). conclusion: although the profile of the patients identified in this study likely justified the decision not to re-admit the patient to the icu, there is room for improvement in the decision-making process. introduction: most of organ donors are brain dead patients. in some cases, patients are identified as potential donors before brain death and will undergo intubation and mechanical ventilation for the sole purpose of awaiting brain death. the aim of this study is to evaluate the practices of professionals in charge of potential donors. (table 1 ). in this case, the issue of organ donation was addressed to the relatives before intubation by 42% of icup and 68% of non icup (p = 0.03). 29% of participants never addressed organ donation before the brain death. for the 71% who have done so at least once, organ harvesting never happened in 20% of cases. legitimacy and difficulties ( table 1 )-21% of respondents felt that when a decision of treatment withdrawal or withholding is taken, the patient should not go to icu for any reason and 29% think that these patients should be allowed to die "quietly". the prospect of an extubation if brain death does not occur or in case of organ donation refusal is a problem for 24% of icup and 38% of non icup (p = 0.08). 88% of icup and 93% of non icup think they would need to receive training. conclusion: this study shows that pursuing mechanical ventilation for the sole purpose of awaiting brain death and organ harvesting is a common practice, and that intubating a patient for this purpose alone is done in most of cases but could still be more generalized. on the other hand, information to the relatives should be improved. 1-7.3] . the effect of pp on the monitored parameters varies significantly between each patient but also between each session for the same patient. in positive responders, the effect continues statistically for 7 to 20 h depending on the parameter studied-10.5 h for vd vt, 19.5 for phase 3 slope, 7 for petco2 and 9 for cdyn. the maximum effect of prone positioning on selected parameters seems to be obtained after 20 h of therapy. the acute respiratory distress syndrome (ards) is characterized by lung infiltration with activated neutrophils. neutrophil extracellular traps (nets) are antimicrobial structures released by neutrophils. nets have also been associated with tissue damage in experimental models of acute lung injury. whether nets are involved in the pathogenesis of human ards and could be a potential therapeutic target is unknown. we aimed to quantify alveolar nets production in patients with pneumonia and ards and assess its relationship with outcomes. patients and methods: prospective monocentric study. patients admitted in the icu in 2014 2015 with pneumonia and moderate severe ards were included. immunosuppressed patients were excluded. nets (dnamyeloperoxidase) levels were measured by elisa in broncho-alveolar lavage (bal) fluid and serum samples of ards patients and in those of control patients (n = 4). patients with higher and lower bal fluid nets levels were compared using the median as a cutoff value. results: thirty-five patients with bacterial (n = 18), viral (n = 11) or non-microbiologically documented (n = 6) pneumonia and ards were included. nets levels were significantly higher in bal fluid than in blood of ards but not of control patients (fig. 1 introduction: the ratio of arterial oxygen partial pressure to fractional inspired oxygen (pao2 fio2 or p f) is daily used to assess patients' evolution under ventilatory support. some studies reported the reliability of percutaneous oxygen saturation (spo2) to appreciate pao2 easy to get on bedside. thus two equations have been proposed-rice equation and ellis equation. however, no large prospective study assessed the reliability of such equations to estimate the p f at the bedside in real conditions. using the spectrum (severe hypoxemia-preva-lence, treatment and outcome) study, we aimed to evaluate the reliability of spo2 obtained by rice and ellis equation. this study is a planned companion of spec-trum study, a recent prevalence-point-day conducted by the srlf trial group in 117 french-speaking icu aiming to report the patterns and outcomes of hypoxemic patients (defined by p f < 300 mmhg). we included in the analysis all patients under mechanical ventilation with spo2 < 98% (according to limit of the rice study). spo2 and fio2 were measured simultaneously to arterial blood gas were drawn. results: among 1656 patients of the spectrum study, 421 were on mechanical ventilation and had undergone arterial blood gas with simultaneously recorded spo2 and fio2. of note, p f was < 100 mmhg for 132 + between 100 and 200 for 191 + and between 200 and 300 for 29. pairwise correlations of truth p f with estimated p f was good (rice-spearman's rho = 0.84, p < 0.001-ellis-rho = .85 p < 0.001). bland-altmann test showed an important variability of results (p f vs rice (figure) -0.02 ± 57.8-p f vs ellis-14.3 ± 45.5). the variability decreased with lower p f. caution may be used to interpret our results because we did not reported the quality of spo2 signal at the bedside. conclusion: regarding the variability of the results, whatever the used equation, caution may be used to predict the p f by the spo2 fio2 ratio in patients under mechanical ventilation. introduction: morbid obesity and ards both affect respiratory mechanics mainly through their respective impacts on chest wall and lung elastances. we present a unique series of patients combining very severe morbid obesity and moderate to severe acute respiratory distress syndrome (ards). we describe the use of trans-pulmonary pressures (tpp) measurements for optimization of external peep setting. patients and methods: the monocentric observational study was performed in 8 morbidly obese patients admitted for moderate to severe ards. we performed an incremental peep trial (5 cm h2o steps) with tpp measurement (nutrivent probe, sidam, italy) in a semirecumbent position as previously described. a decremental peep trial after a recruitment maneuver was not performed since the safety of such a maneuver in this specific population is largely unknown. we defined two ways for determination of external peep setting-(1) peep necessary to obtain a positive expiratory tpp and (2) peep necessary to obtain a plateau pressure between 28 and 30 cm h 2 o (maximal alveolar recruitment express strategy). data are expressed as numbers (%) and medians (interquartile range). statistical analysis was made using the xlstat software. results: we enrolled during 5 years 8 morbidly obese patients (bmi 63 (ir 59-69)) admitted for a moderate to severe ards. clinical characteristics are displayed in table 1 . the express strategy indicated a peep setting of 15 cm h 2 o (ir 15-20) whereas tpp-guided peep was 30 cm h 2 o (ir 25-32), p = 0.03. driving pressure was higher in the express strategy peep setting (10.7 cm h20 (ir 9-12)) than in the tpp-guided peep (10.2 cm h20 (ir 9.5-13)), p = 0.92. tpp-guided peep setting was higher than indicated by the express strategy in all but one patient. one patient suffered from transient hypotension when external peep was set at 25 cm h 2 o, while no patient displayed an inspiratory tpp higher than 25 cm h 2 o. additional data will be provided during the meeting-pressure-volume curve at zeep (6 patients), crf measurements (4 patients) and abg and capnometry values at each peep level (3 patients) . in our ards patients with extremely severe obesity, an incremental peep trial with tpp measurements appeared to be safe and indicated a peep setting significantly higher than for the commonly-used ards strategies. such an approach deserves further comparisons with other modalities of monitoring, such as crf measurements, eit studies, etc. severe poisoning by cardiotoxic drugs and circulatory assistance: 5-year experience at french university hospital tardif elsa 1 , conil jean-marie 1 , georges bernard 1 , marcheix bertrand 1 , crognier laure 1 , bounes fanny 1 , delmas clement 1 1 chu rangueil, toulouse, france correspondence: tardif elsa -tardif.elsa@gmail.com annals of intensive care 2018, 8(suppl 1):f-106 introduction: toxicity from cardiac drugs is associated with a large number of fatalities, significant morbidity and healthcare consequences. severity of these poisonings can be explained by a refractory cardiogenic shock not responding to optimal conventional treatment. criteria of circulatory assistance indications remain unclear. the aim of the study was to describe and to compare patients intoxicated by cardiotoxic drug treated with or without veno-arterial extracorporeal membrane oxygenation (va ecmo). patients and methods: retrospective cohort study conducted at french university hospital. all patients intoxicated with cardiotoxic drugs between january 2012 and march 2017 were included. patients were divided into 2 groups-with and without va ecmo. results: among the 105 patients included in the study, 18 patients were treated with va ecmo (17%) and 87 patients with conventional therapies. ecmo was respectively employed for refractory shock and cardiac arrest in 13 and 5 cases, all patient required vasopressor support. in-hospital mortality was 10.5% and was significantly higher in the ecmo group (44.4%). beta-blockers with membrane stabilizing activity and non-dihydropyridine calcium channel blockers poisoning were the most commonly reported in the ecmo group. mean time from hospital admission to initiation of ecmo was 11 h and the average ecmo duration was 2.6 days [1] [2] [3] [4] [5] [6] [7] [8] . no serious adverse reaction was reported during this period. results expressed in median value ± confidence interval conclusion: refractory cardiogenic shock following cardiotoxic drug poisoning requiring circulatory assistance is associated with significant mortality. even if its use seems justified by the literature, the implantation criteria must be specified and this after an optimal conventional treatment to prevent multiple organ failure. the cdv of patients in the edass group was significantly higher (p < 0.0001) at all-time points after the introduction of catecholamines than among those without edass, as early as 6 h from catecholamine initiation (fig. 1) . a strategy in two steps (cdv > 800 µg kg at 6 h and or cdv > 2600 µg kg at 24 h) was able to predict edass with sensitivity of 45%, specificity 97%, positive predictive value 78% and negative predictive value 94%. overall, this two-step strategy identified 18 high-risk patients at 6 h, of whom 15 presented edass. conclusion: overall, our results confirm that early death directly attributable to septic shock could be effectively predicted by the cdv in the first hours of treatment. these results will help to select patients eligible for innovative therapies aimed at improving early mortality in septic shock. introduction: in patients with cardiac arrest, end-tidal co2 (etco2) has been proposed to monitor the efficacy of cardiopulmonary resuscitation (cpr) but uncertainty persists on its interpretation. we hypothesized that exhaled co2 may also by affected by occurrence of "lung airways" collapse previously noticed during cpr. because this closure may possibly also limit oxygenation + analysis of the entire exhaled co2 time waveform-may give information of high clinical value to manage cpr. we report preliminary results from a clinical and bench study aimed at describing the pattern of the capnogram during cpr. induces a systemic inflammatory response associated with an immune dysregulation and a significant pulmonary dysfunction which has been well characterized. surprisingly, there are only a few data available on immunological changes induced by ecls. we believe that ecls leads to immune dysfunction that could expose patients to nosocomial infections. patients and methods: a two-phase study was lead. first we analyzed blood cell count with differential (including lymphocyte, neutrophils and monocyte counts) in all patients who received ecls in our institution from 2014 to 2017 within the first week following ecls initiation. secondly, monocytes, granulocytes, dendritic cells and lymphocytes function were assessed at day 0, day 1 and day 3 using flow cytometry and functional tests in patients receiving ecls and compared to patients with cardiogenic shock without ecls. results: among 159 patients with elcs we found an early and persistent lymphopenia and a late neutrophilia (found to be associated with poor outcome in critically ill patients). compared to control (n = 7), we found in patients who received ecls (n = 6) a significant increase in immature granulocytes (104.107 ± 47.106 on day one versus 95.105 ± 96 ± 105, p = 0.01) and lymphocytes apoptosis. ecls induced changes in myeloid derived suppressors cells proportion (3.69% ± 3.5 on day three versus 0.58% ± 0.49 before ecls, p = 0.05), which has been recently associated with a higher incidence of nosocomial infections and seems to be major actors of sepsis-induced immune suppression. complement component 5a receptor (c5ar) from the neutrophil cell surface, was also decreased after ecls initiation (ratio of mean fluorescence index 0.73 ± 0.22 on day one, p = 0.03) which is a sign of complement-induced neutrophil dysfunction in septic patients. conclusion: ecls induces quantitative and qualitative leukocytes dysfunctions that can lead to a greater susceptibility to nosocomial infections which contribute to the poor outcome observed in several studies. introduction: aspiration pneumonia is a common complication of cardiac arrest. although its real incidence remains undetermined, probabilist antibiotherapy is frequently or even systematically prescribed in these cases. we assessed the incidence of out-of-hospital cardiac arrest-related aspiration pneumonia and the impact of a microbiological documentation in regard to antibiotherapy course. patients and methods: all patients admitted for out-of-hospital cardiac arrest from 1 1 2014 to 1 8 2017 were studied. in our icu, aspiration pneumonia is suspected when a clinical syndrome (fever, per resuscitation constatation) and or chest radiography infiltrates were present. in case of suspected aspiration pneumonia, a microbiological documentation was performed before initiation of probabilist treatment with amoxicillin-clavulanate. we retrospectively defined if patients have aspiration pneumonia using the following criteria-per resuscitation constatation, chest radiography infiltrates, fever. the number of microbiological documentation leading to an antibiotherapy modification was recorded as well as pathogens types. data are expressed as numbers (%) and medians (interquartile range). statistical analysis was made as appropriate using the xlstat software. results: 176 patients were studied. clinical characteristics are displayed in table 1 . 80 (45) received a probabilist antibiotherapy and 79 (45) were retrospectively considered with aspiration pneumonitia. results of microbiological documentation were 94 (53) positive microbiological sample and 68 (38) with a positive threshold whose 6 (3) were considered colonized (i.e. no clinico-radiological sign). on the entire positive culture sample, 51 (54) were positive with oropharyngeal flora as unique pathogen, 14 (15) introduction: this study aimed to assess whether augmented renal clearance (arc) impacts negatively on piperacillin-tazobactam pharmacokinetic pharmacodynamics (pk pd) target attainment in critically ill patients receiving 16 g day by continuous infusion. patients and methods: over an 8-month period, all critically ill patients treated by piperacillin-tazobactam for a suspected or documented sepsis without renal impairment were eligible. during the first three days of antimicrobial therapy, every patient underwent 24-hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at steady state. the main pk pd outcome investigated in this study was the rate of empirical target non-attainment using a theoretical target mic of 16 mg l −1 for piperacillin and 2 mg l −1 for tazobactam. the secondary clinical outcome was the rate of therapeutic failure in microbiologically documented infections, defined as an impaired clinical response with a need for escalating antibiotics during treatment and or within 15 days after end-of-treatment. over the study period, 60 patients were included in the primary pharmacological analysis and 45 in the secondary clinical analysis. using a mic of 16 mg l −1 for piperacillin, the rate of empirical target non-attainment in the overall population was 17%, with a strong association with crcl ( fig. 1 introduction: invasive fungal infections are a major burden in solid organ transplantation, especially in patients receiving liver graft. however, their incidence has decreased thanks to the development of an antifungal prophylaxis in the post-transplantation period. in patients at high risk of invasive fungal infection (ifi), this strategy is recommended, whereas its benefit remains controversial in low-risk patients. however, there is no clear definition of these two patients groups. our aim was to provide recent data on epidemiology, mortality and ifi risk factors in the early post-operative course in a population without any antifungal prophylaxis. results: the number of beta-lactam antibiotics was 119. of these 119 requests, half were for piperacillin (49.6%), and onethird were for amoxicillin (30.3%). the other dosages were mainly for cloxacillin, cefepime, cefotaxime and ceftriaxone. the results confirmed that serum concentrations of piperacillin (21.6 ± 4.0 vs 98.2 ± 16.8 mg l −1 < 0.0001) and amoxicillin (35.8 ± 13.0 vs 157 ± 72 mg l −1 < 0.0001) significantly were higher in patients with neurological disorders or wakefulness delays. the roc curves allowed the predictive values associated with the presence of neurological disorders attributable to antibiotic treatment, corresponding to residual serum concentrations of piperacillin of 66 mg l −1 and amoxicillin of 160 mg l −1 . a predictive value for neurological disorders of these concentrations is proposed for residual serum concentrations greater than 40 mg l −1 for both antibiotics (80% specificity and sensitivity). conclusion: our results suggest that there is an association between a residual concentration of piperacillin and amoxicillin greater than 40 mg l −1 and the occurrence of neurological disorders. pharmacological therapeutic monitoring of beta-lactams in critically ill patients may be a useful intervention to optimize the antibiotic regimens and to avoid antibiotic-related toxicities. (2011) (2012) (2013) (2014) (2015) . patients with a gnb-bsi were included and were divided into two groups according to the resistance (r) profile (bsi due to a r isolate or not). the following resistances were considered-all gnb-bsi including pseudomonas spp., acinetobacter spp., stenotrophomonas spp. and enterobacteriacae (eb) for which the following antimicrobial resistances were considered-ticarcillin and ceftazidime (cefta) (pseudomonas (pa)), third generation cephalosporin (3gc) (eb) and imipenem (all gnb). after variable selection using random forest and univariable mixed logistic regression models, a multivariable analyses using a mixed model with a random effect (center). sub-group analyses were performed according to species (pa and eb) and resistance for eb. results: from 189,020 patients admitted in an annual median of 198 french icus, 6837 experienced an icu-acquired (> 48 h.) bsi, 3462 (51%) bsi due to gnb, including 1345 (41%) bsi due to r isolates. pa was identified in 828 (24%) (mdr-pa bsis 248 (30%)) and eb in 2933 (86%) (mdr-eb bsis (1126 (38%)). the raw mortality rate was 18% in the overall population and 38% in the patient with gnb bsi. it was significantly higher for r gnb bsi (41 vs 36% for susceptible gnb bsi, p < 0.01). after adequate adjustment in a multivariate analysis, we showed that r-gnb bsi was significantly associated with mortality compared to susceptible strains (fig. 1) . by considering species subgroup, the effect was not significant for resistant pseudomonas aeruginosa (p = 0.54) but remained significant when considering only eb. considering eb resistance, the impact of 3gc r showed a trend to an increased mortality risk whatever there was no effect of imi r (n = 45 (2%)) on prognosis. limitation-the absence of information about antibiotic consumption may partly explain the remaining significant center random effect in the final models. conclusion: in a large french database, after adequate adjustment on prognostic factors, resistant bgn-bsi was associated with a higher icu mortality than susceptible one. the effect was mainly due to eb 3gc r. severely injured group versus 3.1 ± 6.4 days for the non-severely injured patients (p < 0.0001). in multivariate analysis, heart rate (> 100 min) and vittel score (≥ 2 criterias) were related to the probability of belonging to the severely injured group (p = 0.03). the 24-hour mortality rate was 0.5% in the ed and the 30-day mortality rate was 1.5%. the development of a network in the ed hosting non vital polytraumas remains crucial. its primary goal will be to meet technical and time requirements and establish in-hospital triage algorithms based on clinical variables, in order to detect these patients at an early stage and offer them priority care in our overcrowded eds. introduction: the trauma of traffic accidents and particularly cranial trauma are, due to their frequency and severe consequences in both the short and long term, a real public health scourge on a global scale. studies of the epidemiology of cranial trauma by traffic accidents and their prognosis are rare at least in underdeveloped or developing countries. in addition, the impact of extracranial lesions on cranial trauma prognosis has long been discussed. the purposes of our study were to examine the epidemiological aspects and to determine the factors correlated to the immediate and distant prognosis of isolated cranial trauma. patients and methods: retrospective cohort spread over 4 years (from 2009 to 2012) and including 242 patients with isolated cranial trauma by traffic accidents (mean age 30.9 years, sex ratio-7). we proposed to study the factors correlated with a poor prognosis in terms of death in hospital and glasgow outcome scale (gos) at 6 months unfavorable in dual analysis (univariate and then multivariate). for the gos study, patients were divided into 2 groups-gos favorable for patients with good recovery (gos = 5), recovery with a light handicap (gos = 4), gos unfavorable for those having survived with a severe disability (gos = 3), a vegetative or pauci-relational state (gos = 2) and those who died (gos class 1). results: hospital mortality was 26% and the gos at 6 months was distributed as follows: death (27.3%), vegetative state (2.9%), severe disability (11.2%), mild disability (28%) and good recovery (30.6%). the 6-month gos was deemed unfavorable in 41.4% of the cases. various after effects were observed in survivors: physical (42%) dominated by headache (24.4%), sleep disorders (14.2%) and epilepsy (7.2%); memory disorders (27.8%) or concentration (16.5%) and finally emotional after effects (32.4%) with irritability (30.7%) and aggressiveness (9.7%). in multivariate statistical analysis, independent predictors of mortality were arterial hypotension, hypoxia extradural hematoma (edh),, acute subdural hematomas (sdh), diffuse axonal injury and ventilator associated pneumonia. those correlated with an unfavorable gos were an age ≥ 38 years, hypotension, cerebral edema, coma duration ≥ 5.5 days, edh and h24 glucose ≥ 7.15 mmol/l. conclusion: although the short-term prognosis of head trauma seems to be improved at present, the long-term consequences of cranial trauma remain fairly frequent, and often underestimated, which underlines the importance of their screening and their proper care. the average age of the survivors (30.83 ± 13.08 years) was lower than the mean age of the deceased (36.81 ± 16.68). ra was the cause of the trauma in 76% of the cases followed by the fall found cat 17% of the patients. prehospital care only concerned 4% of patients. the univariate analysis showed that the main factors of occurrence of death were age (p = 0.02), glasgow score (p = 0.0001) anisocoria (p = 0.0009), shock (p = 0.002) 26% of deaths were due to intracranial hypertension, haemorrhagic shock in 15% of patients and ards in 7% of polytrauma patients. conclusion: the management of polytrauma can not be improvised. the medical teams must be coordinated by an emergency physician in prehospital, a doctor anesthesiologist-resuscitator at the reception. some systematic gestures such as preparation of the reception allow to optimize the management of the time. introduction: benign cranial trauma is a major public health problem due to both its frequency and the health costs it creates. the aim of this study was to identify relevant clinical factors that could predict the achievement of brain ct and situations at risk for neurosurgical care and for which ct was a necessity. patients and methods: this is a 24 month prospective study, including 404 patients with benign traumatic brain injury (glasgow coma score gcs ≥ 13), patients under 16 years of age and patients with gcs < 13 were excluded. epidemiological, clinical, paraclinical, therapeutic and evolutionary parameters were studied. a multivariate and univariate statistical study was carried out to reveal the predictive factors of a ct anomaly and the predictive factors for the neurosurgical care. data were entered and analyzed using spss 16.0 and excel 2007 software. results: the average age of patients was 34 years with a predominance of male, and sex ratio of 4.05. the cause of the btb was mainly represented by the accidents of the public road in 73.27% of the cases. 28.22% of the patients were asymptomatic, the most common symptomatology was dominated by the initial loss of consciousness (52.72%), headache (35.64%). the glasgow coma score was distributed as follows-gcs 15 (54.95%), gcs 14 (35.9%) and 13 (9.15%). 38.9% of patients had clinical signs of trauma to the skulland or face. brain ct was performed in 88.4% of patients, and 25.5% had abnormal ct. the use of neurosurgical care was of the order of 3.22%. in univariate analysis-the predictive factors for a ct abnormality were the intoxication during the brain trauma, the gcs < 15, signs of trauma in the skull face, the vomiting, the initial loss of consciousness, the comitial crisis and the predictive factors of neurosurgical care were the gcs < 15, the anisocoria, headache, the vomiting, the amnesia, the initial loss of consciousness, the comitial crisis, the anormal ct, the extradural hematoma or the subdural hematomat in multivariate analysis-the predictive factors for a ct abnormality were the gcs < 15, the initial loss of consciousness and the predictive factors for the use of neurosurgical care were the gcs < 15, signs of trauma in the skull face, the amnesia, the comitial crisis, the hsd. conclusion: an algorithm must be applied in collaboration between resuscitators and neurosurgeons to improve the quality of benign cranial trauma management. prognostic value of hyperchloremia in patients with traumatic brain injury: a prospective observational study taghouti introduction: background-traumatic brain injuries (tbi) are a major public health problem. they are the leading cause of death among those aged less than 40 years. hyperchloremia is a common electrolyte disturbance in patients with tbi. hyperchloremia has been associated with increased morbidity and mortality in critically ill patients + however, its prognostic significance in tbi patients is poorly documented. the aim of this study is to describe the prevalence and outcomes of hyperchloremia in patients with tbi admitted to the intensive care unit. patients and methods: in a prospective design, we included 43 consecutive patients with tbi (37 males + median age-52 years) admitted to the icu in charles nicolle hospital of tunis from mars to september 2017. adult patients (aged ≥ 18 years) with isolated tbi or associated with minor extra-cranial injuries (defined as all non-head abbreviated injury scale < 3) were included. hyperchloremia was defined as a chloride level > 110meg/l. clinical and laboratory variables were compared between survivors (n = 36) and non-survivors (n = 7). we assessed the association between hyperchloremia 24-h post-admission and 30-day mortality. p < 0.05 was taken to indicate statistical significance. results: the median sofa score at t0 was 7 points and the median igs 2 score was 32 points. the median iss was 25 points. there were 11 cases of mild head injury, 12 moderate head injury and 20 severe head injury. the 30-day mortality was 16%. hyperchloremia occurred in 15 patients (35%) and the incidence was significantly different between survivors and non-survivors (28 vs. 72%, respectively, p < 0.001). in addition to hyperchloremia (p = 0.018), other laboratory variables were associated with 30-day mortality-hypernatremia (p = 0.011) and hypoalbuminemia (p = 0.024). conclusion: hyperchloremia 24-h post-admission was associated with 30-day mortality in patients with tbi. this index could be useful prognostic marker. efforts should focus on the prevention of hypernatremia and hyperchloremia in this vulnerable group of critically ill patients. child traumatic brain injury naili amine 1 1 blida rp, algérie correspondence: naili amine -drnailiamine@yahoo.fr annals of intensive care 2018, 8(suppl 1):p-07 introduction: brain injury in children is common and mild in most cases, but it remains the leading cause of death and disability in children over 1 year of age worldwide. the peculiarity of the child is that he possesses not mature brain and that the consequences of injuries acquired by traumatic brain injury can lead to the loss of capacities, as well as the non-acquisition of function, but above all the risk impact on learning abilities. the objective of the study is to define the incidence rate of cranial trauma in children as well as the mortality and morbidity of this scourge which presents a major public health problem. patients and methods: it is a descriptive retrospective study of a series of 186 children hospitalized in neuro-resuscitation service during the period january 01 to december 31, 2016, including 22 children admitted for cranial trauma. clinical, para-clinical, etiological and therapeutic data were collected from hospitalization records. results: in a series of 186 children hospitalized during the defined period, 22 children were admitted for cranial trauma, i.e. a frequency of 12%. the average age was 6 years [6 h of life-14 years], with a sex ration of 1 among the 22 children, 12 had severe head trauma, a rate of 55% + whose causes are variable-6 road accidents, 3 domestic accidents, 2 traffic accidents, and 1 obstetric accident, admitted with a pediatric glasgow score between 5 and 10, and all required mechanical ventilation of the 22 head trauma, 10 were operated for different lesions-3 extra-dural hematomas, 3 cranio-cerebral wounds, 2 subdural hematomas, 1 decompressive craniectomy, and 1 embarrure. 02 children had died following severe head trauma, i.e. a mortality rate of 9%, the morbidity rate of head trauma in the tipaza wilaya was 1.1 100,000 children year, the average length of stay in intensive care units was 22 days, with several complications of decubitus, and functional due to the primary and secondary lesions of the cranial trauma. the head trauma of the child is a public health problem, its functional prognosis can be dramatic when it is severe, its management must be early and multidisciplinary. introduction: the aim of the study was to identify factors predicting lung contusion in trauma children. patients and methods: retrospective study conducted for a period of 8 years (january 01, 2005-december 31, 2012) in a medical surgical intensive care unit. all trauma patients younger than 15 years were included. two groups were compared-those with lung contusions (c + group) and those without lung contusions (c − group). results: we included 330 patients. the mean (sd) age was 7.6 (4.3) years. chest injury was diagnosed in 70 patients (21.2%). all our patients needed mechanical ventilation. lung contusions were diagnosed in43 patients (13% of all patients and 61.4% of patients with chest trauma). in multivariate analysis, independent factors predicting lung contusion were road traffic accident (odds ratio [or], 3.2 + 95% confidence interval [ci], 1.2-8.6 + p = 0.019), increased pediatric risk of mortality (prism) score (or, 1.1 + 95% ci 1.1-1.2 + p = 0.017), hepatic contusion (or 4.8 + 95% ci 1.3-17.1 + p = 0.017), and pelvic ring fracture (or, 3.5 + 95% ci 1.1-10.5 + p = 0.026). death occurred in 46 patients (13.9%). intensive care unit mortality was significantly higher in the c + group (or, 2.5 + 95% ci 1.2-5.4 + p = 0.021). however, mortality was not differentbetween the 2 groups after adjusting for prism score (or, 1.2 + 95% ci 0.5-2.9 + p = 0.752) or after adjusting for injury severity score (or, 0.7 + 95% ci 0.3-2.1 + p = 0.565). conclusion: lung contusion is common in critically ill children with chest trauma. the diagnosis should be considered in patientswith road traffic accident, increased prism score, hepatic contusion, and pelvic ring fracture. introduction: chest trauma is often associated with pleural effusion (hemothorax and or pneumothorax). drainage of the pleural space by a chest tube is a common intervention in such situations. blunt dissection technique with a kelly clamp is preferred to classical trocar techniques to prevent severe complications, like perforation of thoracic or abdominal organs. despite these precautions, malposition remains the most common complication of tube thoracostomy. we investigated a new technique of bougie-assisted chest tube insertion to prevent chest tube malposition after chest drainage of post traumatic pleural effusion. patients and methods: we performed a controlled before-and-after study to assess the ability of a bougie-assisted chest tube insertion technique, compared to a standard blunt dissection technique, to prevent chest tube malposition. for the bougie-assisted group, we used a disposable eschmann-style bougie, commonly used to guide the endotracheal tube during difficult intubations. technique consisted in blunt dissection until the parietal pleura is opened. thoracostomy tube was preloaded onto the bougie and bougie was advanced alongside the finger, with apical or caudal direction after entering the chest cavity, depending on the type of pleural effusion. thoracostomy tube was then advanced forward utilizing a seldinger technique. the primary end point was optimal position of the chest tube. the tube position was blindly assessed on standard chest x-ray. in pneumothorax, optimal position was apical (above the aortic arch), and in hemothorax or mixed-effusion it was basal (2 cm above the diaphragm or lower). results: a total of 58 patients were enrolled (bougie-assistedn = 30 + conventional-n = 28). chest tubes were optimally position in 29 (96%) in bougie-assisted group and 12 (43%) in conventional group, or 38.5, ic 95% = [4.6-325.16], p < 0.0001. efficacy of chest drainage (defined on chest x-ray as the absence of visible pleural line for pneumothorax and as a clear costophrenic angle for hemothorax) was assessed in 29 (96%) in bougie-assisted group and in 15 (53%) in conventional group, or 25.13, ic 95% = [3.00-210.93], p < 0.001. average procedure time was 281 s (95% ci 120-360 s) for bougieassisted group and 558 s (95% ci 318-900 s) for conventional group, p < 0.0001. no severe complication was observed in both groups. conclusion: bougie-assisted chest tube insertion technique prevents chest tube malposition, is safe, effective and shortens procedure time for the post traumatic pleural effusion drainage. introduction: infectious complications determine the prognosis of burned patients. however, the emergence of bacterial resistance to antibiotics threatens treatment efficacy, which is due to an inadequate antibiotic consumption inqualitative and quantitative terms. the objective of this study was to describe the profil of consumptionand susceptibility to antibiotics. and, to explore the predictive factors for theemergence of mrb in the service of burns and plastic surgery. patients and methods: it is a retrospective study including 122 severe burnedpatients hospitalized for 2 years in the plastic surgery department of theuniversity hospital ibn rochd from january 2015 to december 2016. bacterialecology was described, and the distribution of the seeds by group, by species andby period of time was detailed. the ddd 1000jh (daily defined dosage reportedin 1000 days of hospitalization) was used to assess the consumption of antibiotics. p correlation coefficients were calculated to explore the association betweenconsumption of antibiotics and the emergence of the bmr (multiresistantbacteria), and identified predictors of this emergence. results: on 512 samples taken, 539 bacterial and fungal strains were identified, with a predominance of p. aeruginosa (21.15%), a. baumani i (13%) and s. aureu s (13%), the number of strains increased with the duration of the stay reaching itsmaximum from 28 days in hospital. the ceftazidine (212.7 ddd 1000dh), imipenem (139.7 ddd 1000dh), and amikacin (122.4 ddd 1000dh) were themost used antibiotics during our study, also + the profile of consumption increasedbetween 2015 and 2016.362 bmr were isolated + the eblse were at the top (24.5%) follow up of thecrpa (21.8%), followed by the irpa (20.7%) follow-up of the crab (17.1%) then the irab (13.5%) and finally the mrsa with a portion of 2.2%. the profile of bacterial resistance has varied significantly for severalantibiotics bacteria pairs. conclusion: it remains difficult to show correlations between antibioticconsumption and bacterial resistance. however, these data are particularly usefulin the epidemiological surveillance of bacteria to better guide probabilisticantibiotic therapy. introduction: eclampsia is a rare but serious threat to maternal and fetal well-being. the aim of this study was to assess the incidence of eclampsia and its morbidity and mortality. patients and methods: we conducted a retrospective survey in a third level tunisian university teaching hospital from january 2004 to december 2016. we included all patients with the diagnosis of eclampsia. results: in study period 129847 deliveries were registered. 83 women with eclampsia were identified hence the incidence of eclampsia was 6.39 per 10000 deliveries. the median gestational age at the time of eclampsia was 36 weeks. no maternal deaths due to eclampsia were recorded. the delivery mode was caesarean section in 100% of eclamptic patients. the recurrence of eclampsia despite magnesium sulfate prevention was observed in 6% of patients. severe complications of eclampsia were recorded in 10.8% of patients-4 posterior reversible encephalopathy syndrome, 2 acute pulmonary edema, and 3 hellp syndrome. 10.8% of new born were preterm. there were 5 stillbirths and 2 neonatal deaths. conclusion: the incidence of eclampsia was very high probably due to center effect. it's essential to raise awareness among mothers in the community regarding early signs and symptoms of preeclampsia eclampsia and to design a better tracking system for antenatal care program. introduction: to monitor maternal mortality which is an indicator of the quality of obstetrical care and anesthesia resuscitation, our country worked to set up several programs targeting maternal and child health. the aim of this work was-to evaluate the maternal mortality rate in our department and its evolution. to identify the cause of death and classify it depending on whether it is preventable or not. to spot the deficiencies either in the care management or the organization of the care system. to propose ways to improve our care and to fill the failures. patients and methods: it was a retrospective study about maternal death, performed at the department of gynecology and obstetrics, over a 25-year period (from 1990 to 2015) , that have reported 14 cases of maternal death according to the world health organization definition. results: the maternal mortality rate (mmr) was 22.43 for every 100,000 live births. the average age of our patients was 32.3 years. the main risk factors for maternal mortality are unfavorable socioeconomic conditions, high-risk pregnancies, multiparity, primiparity and a poor follow-up of the pregnancy. the main causes of maternal death are represented by direct obstetric causes (80%) allocated as followspostpartum hemorrhage (45%), pregnancy toxemia (14%), acute fat hepatic steatosis (7%), infection (7%) and complications of anesthesia (7%). indirect obstetric causes were found in 20% of deaths. death was considered avoidable in 78.58% of cases. conclusion: at the end of this work, we were able to pull several recommendations in order to reduce m.m.r. health education. facilitate access to care for the parturient, improve care and conditions of childbirth. continuous training of the medical and paramedical staff. introduction: mechanical ventilation can help improve the prognosis of sepsis. while adequate delivery of oxygen to tissue is crucial, hyperoxemia may be deleterious. invasive out-of-hospital ventilation is often promptly performed in life-threatening emergencies. we propose to determine whether the arterial oxygen pressure (pao2) at intensive care unit (icu) admission affects mortality at day 28 (d28) in patients with septic shock subjected to mechanical out-of-hospital ventilation. patients and methods: we performed a monocentric retrospective observational study on 77 patients with septic shock admitted to the icu. pao2 was measured at icu admission in patients subjected to invasive ventilation before any hospital admission. the primary outcome was mortality at day 28 (d28). results: forty-nine (64%) patients with septic shock were mechanically ventilated before any hospital admission and transferred to the icu. the mean pao2 at icu admission was 153 ± 77 and 202 ± 82 mmhg for alive and deceased patients at d28, respectively. pao2 was significantly associated with mortality at d28 (p = 0.04). using a roc curve, the corresponding auc was 0.70 [0.54-0.85]. for a pao2 > 150 mmhg, the or for mortality at d28 was 4.20 [1.25-15 .95] (p = 0.02), whereas for a pao2 < 150 mmhg, the or was 0.24 [0.06-0.80] (p = 0.02). conclusion: in this study, we report a significant association between hyperoxemia at icu admission and mortality at d28 in patients with septic shock subjected to pre-hospital invasive mechanical ventilation. the adjustment of the pao2 is a crucial prognosis factor in patients with septic shock subjected to invasive out-of-hospital ventilation to avoid the toxic effects of hyperoxemia. however, blood gazometry is hard to get in a prehospital setting. consequently, alternative and feasible measures are needed, such as pulse oximetry, to improve the management of prehospital invasive ventilation. introduction: nowadays, benefit of enhanced ct-scan in positive diagnosis of acute pulmonary embolism (pe) is well established. it also allows evaluation of pe's burden on the right heart and shows several signs of acute cor pulmonale (acp). objectives -we aimed to assess benefits of control ct-scan 24 h after thrombolysis in acute pe. patients and methods: we retrospectively enrolled patients with confirmed pe whom have been thrombolysed between january 2014 and august 2017 and controled with an enhanced ct-scan 24 h after thrombolysis. assessement criteria were: qanadli obstruction index; signs of acp-right ventricle diameter left ventricle diameter (rvd lvd) and paradoxical interventricular septum (ivs). non inclusion criteria were: lack of initial or control ct-scan. results: during the study period (3 years and 8 months) we admitted 1790 patients from whom 98 patients had acute pe (5.5%). very severe patients that were thrombolysed as rescue therapy without initial ctscan and those who died before control ct-scan were not included. we enrolled 33 patients-high risk mortality pe (n = 10, 30.3%) and intermediate high risk pe (n = 23, 69.7%). mean age was 60 years and sex-ratio was 1.06. at admission, mean severity scores were 22.1 ± 9.4 for saps ii and 7.6 ± 4.2 for apache ii. evolution criteria are listed in table 1 . conclusion: control ct-scan is highly useful 24 h after thrombolysis. it allows evaluation of response to pharmacological thrombolysis of acute pe and shows significative resolution of arterial obstruction degree and signs of acp. in december 2016, after cancellation of the budget for a christmas tree, the nurses and caregivers of the night team spontaneously made and hung christmas decorations in our intensive care unit to make patients and their families feel better. the context was difficult with controversies around secularity. the town of paray le monial had been forced to remove a nativity scene and the city of melun had been criticized for setting one up. so we found it important to assess the perception of the approach by patients and relatives. patients and methods: decorations -hand-colored patterns about christmas theme printed on a4 paper decorations brought by the staff or already possessed by the unit-christmas balls, garlands, silver stardecorations made with service equipment-christmas tree consisting of inflated non-sterile gloves, cardboard, figurative nativity scene without a recognizable figure in a cardboard box with cotton, bed sheet to simulate snow. evaluation -all visitors and conscious patients received an anonymous single choice questionnaire with numerical scale and free fields from december 15th to december 31st, 2016. results: 59 answers were received, including-no negative opinion. 1 neutral answer by a person who had not noticed the decorations. 54 positive or extremely positive opinions. no answer without data. the comments pointed out the originality, the good idea, the warm comforting side. some asked for more decorations. others found them sober. the results show the good perception of the spontaneous action by the patients and their relatives. there was no negative response, particularly offend persons. however, it is possible that relatives or patients with negative opinions did not dare to express themselves. the initiative demonstrated a good cohesion of the night paramedical team, encouraging the interns and the day teams to take part in the coloring of the decorations. the initiative was initially aimed at the wellbeing of the patients and their relatives. however it has enabled an activity similar to preventing psychosocial risks among the healthcare team, allowing them to adopt a positive attitude in their approach to care. in addition, no significant costs were incurred thanks to the use of cheap materials, mainly recycled cardboard and standard quality white paper. the spontaneous decoration of our intensive care unit by the night care team was very well received by the patients, their families and their relatives. the initiative also made possible to enhance team cohesion and to value it. the associated costs were negligible. ventricular contractions. bp monitoring revealed a greater diastolic bp throughout 24 h as well as during night-time. systolic bp higher than 125 mmhg during sleep time was observed in 55% of participants. the frequency of arrhythmias and blood pressure variability are correlated with the increase in work stress and conflicts. conclusion: our results highlight the extent incidence of arrhythmia and blood pressure variability during intensive care unit night's shift probably due to the increased neuroendocrine stress response. (55%) and qrs enlargement (50%). ami was responsible for a significantly deeper coma (p < 0.0001) but fewer seizures than clo (p = 0.02). three patients (5%) died. based on a univariate analysis, factors associated with death were cardiac arrest onset (p = 0.003), elevated plasma lactate concentration (p = 0.005), low arterial ph (p = 0.007), reduced pao2 fio2 ratio (p = 0.007) and prothrombine ratio (p = 0.008), increased aspartate aminotransferases (p = 0.009), alanine aminotransferases (p = 0.01) and serum creatinine concentration (p = 0.01) as well as marked catecholamine infusion rate (p = 0.02). the pharmacokinetic study showed significant increase in ami (43 h vs. 24 h) and clo (55 h vs. 21 h) elimination half-lives in overdose compared to pharmacological conditions, highlighting the contribution of organ failure to the delayed elimination of both toxicants. conclusion: ami and clo poisonings did not disappear and are still responsible for significant morbidities and mortality. ami was responsible for deeper coma with fewer seizures in comparison to clo. ami and clo elimination half-lives were significantly prolonged in overdose due to organ failure. introduction: severe poisonings and fatalities have been attributed to buprenorphine (bup) despite its ceiling respiratory effects, mainly if abused in co-ingestion with benzodiazepines. we previously showed that diazepam (dzp) bup combination induces severe respiratory depression in the rat, while each drug by itself does not. the objective of this study was to investigate the mechanisms involved in this drug-drug interaction using 11c-bup pet imaging and diaphragmatic electromyography in the sprague-dawley rat. patients and methods: 11c-bup was administered intravenously, 30 mg kg unlabeled bup intraperitoneally and 20 mg kg dzp subcutaneously. pet acquisition started with 11c-bup pet injection, 15 min after dzp or its vehicle (veh + n = 5 group) administration. suv normalized time activity curves (tacs) were generated and 11c-bup binding potential [bpnd, i.e. the ratio of the total receptor density (bmax) on the equilibrium dissociation constant (kd)] were modeled in different brain regions using a simplified reference tissue model with cerebellum as reference region. dem, implanted under anesthesia 7 days before the experiment, was recorded during 240 min in rats receiving veh veh, dzp veh, veh bup or dzp bup (n = 6 group). after filtering and half-wave rectification, the first 60 min auc of diaphragm contraction and workload were determined and compared between the groups. results: tacs and 11c-bup bpnd were not different between the dzp bup and the veh bup groups in all studied brain regions. diaphragm contraction was significantly increased in the veh bup group in comparison to the dzp bup group (p < 0.05). diaphragm workload was significantly increased in the veh bup group in comparison to the dzp veh and the dzp bup group (p < 0.05 and p < 0.01 respectively). discussion: dzp did not affect the 11c-bup brain distribution and brain binding suggesting that dzp does not affect bup transport across the blood brain barrier and bup receptors density affinity. bup administration induced an increase in diaphragm contraction and workload. this increase was inhibited in the presence of dzp suggesting that dzp bup combination-induced respiratory depression is mostly related to dzp. conclusion: respiratory depression related to dzp bup combination results from a pharmacodynamic drug-drug interaction. introduction: since the banning of dextropropoxyphene from the market, overdoses and fatalities attributed to tramadol, a who step-2 opioid analgesic, have increased markedly. tramadol overdose results not only in central nervous system (cns) depression attributed to its opioid properties but also in seizures, possibly related to nonopioidergic pathways, thus questioning the efficiency of naloxone to reverse tramadol-induced cns toxicity. our objective was to investigate the most efficient antidote to reverse tramadol-induced seizures and respiratory depression in overdose. patients and methods: sprague-dawley rats overdosed with 75 mg kg intraperitoneal (ip) tramadol were randomized into four groups to receive solvent (control group), diazepam (1.77 mg kg ip), naloxone (2 mg kg intravenous bolus followed by 4 mg kg h infusion) and diazepam naloxone combination. sedation depth, temperature, number of seizures and intensity, whole-body plethysmography parameters and electroencephalography activity were measured. for each parameter, we compared the areas under the curves using mann-whitney tests for two-by-two comparisons between the four groups. regarding the effects of treatments on seizures, comparisons were performed using two-way analysis of variance followed by multiple comparison tests using bonferroni's correction. results: naloxone reversed tramadol-induced respiratory depression (p < 0.05) but significantly increased seizures (p < 0.01) and prolonged their occurrence time. diazepam abolished seizures but significantly deepened rat sedation (p < 0.05) without improving ventilation. diazepam naloxone combination completely abolished seizures, significantly improved rat ventilation by reducing inspiratory time (p < 0.05) but did not worsen sedation. based on the eeg study, tramadol-treated rats experienced electro-clinical seizures as soon as 5 min after the injection, characterized by spike-waves and polyspikes with progressive decreased frequencies and inter-critical phases of slow delta waves until the next crisis. after diazepam naloxone injection, eeg waveforms consisted in 8 hz-alpha rhythms and slow-down theta rhythms of drowsiness. none of these treatments significantly modified rat temperature. conclusion: diazepam naloxone combination is the most efficient antidote to reverse tramadol-induced cns toxicity. our experimental data greatly encourage administering this combination rather than naloxone alone as first-line antidote in tramadol-poisoned patients as an alternative to tracheal intubation. introduction: rubigine ® poisoning is a medical emergency that causes a major public health problem in underdeveloped countries, as it is frequently fatal. this poisoning is rare in france, but frequent in the french overseas departments (dom). the rubigine ® , made of fluoride and used as a rust remover, is the main source of poisoning in the caribbean. in martinique, the exact incidence of this intoxication is unknown, as there is no national and regional register. it could represent up to 8-10% of severe acute poisoning. it was not until april 1994 that, following a prefectural order on the declaration, classification, packaging and labeling of substances, the composition of rubigine ® was modified to significantly reduce the mortality induced by its ingestion. the objective of our study was to describe the clinical features and complications that can occur after ingestion of rubigine ® as well as to determine the prognostic factors of death. we conducted a retrospective study over 16 years, from 2000 to 2016, including all patients admitted to emergency and intensive care units of the university hospital center (martinique) for acute rubigine ® poisoning. the usual demographic and clinical data were collected and comparisons between surviving and deceased patients were performed using a univariate analysis. results: fifty-five patients (mean age-43 years (15-82) + sex ratio male female-1,1) were hospitalized at the university hospital of martinique. one-quarter of patients had no significant history. the average length of stay was 3.3 days (1-37). forty percent of patients experienced hypocalcaemia after initial intravenous calcium supplementation. complications included acute respiratory failure requiring invasive mechanical ventilation (22% of patients, duration of ventilation-2.8 days, (1-16)), renal failure (20%, of which 50% required extrarenal treatment, hemodynamic failure (16%), hepatic failure (15%), coagulation failure (15%), neurological failure (12%) and multi-visceral failure (10.9%). three patients presented cardiogenic refractory shock requiring va ecmo (5.5%) and another patient with digestive perforation (1.8%). the mortality was 10.9%, allowing the identification of prognostic factors of death. conclusion: rubigine ® poisoning is responsible for significant morbidity and mortality, despite optimal management. however, its incidence seems to have decreased sharply in recent years thanks to the strong mobilization and awareness of the population following the implementation of an information system by the university hospital 's clinical toxicology and toxico-vigilance unit, and different preventive measures introduced by the health authorities. introduction: since dextropropoxyphene withdrawal from the market, overdoses and fatalities attributed to tramadol, a who step-2 opioid analgesic drug, have increased markedly. besides central nervous system depression, tramadol overdose may result in seizures, usually included in the related serotonin syndrome. however, the serotoninergic mechanism of tramadol-induced seizures has been recently questioned. we investigated the effects of various specific pretreatments on tramadol-induced seizure onset and alterations in brain monoamines in the rat. patients and methods: sprague-dawley rats were randomized into five groups (n = 6 group) to be pretreated with various agonists antagonists before receiving 75 mg kg tramadol intraperitoneally-1.77 mg kg ip diazepam + 2 mg kg iv bolus followed by 4 mg kg h infusion naloxone + 10 mg kg ip cyproheptadine, and 15 mg kg ip fexofenadine. seizure severity was graded according to the modified racine score (1). we measured neurotransmitter concentrations in the frontal cortex using high performance liquid chromatography coupled to flurorimetry or radioenzymatic assay, as required. we used positron emission tomography-computed tomography to investigate interactions of tramadol with gaba-a receptors. the effects of treatments on seizures were compared using two-way analysis of variance followed by multiple comparison tests with bonferroni's correction. the areas under the curves of the effects on monoamine concentrations and the binding potentials in the pet-imaging study were compared two-by-two using mann-whitney u tests. results: diazepam abolished tramadol-induced seizures, by contrast to naloxone, cyproheptadine and fexofenadine pretreatments. interestingly, despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < 0.01), histamine (p < 0.01), dopamine (p < 0.05) and norepinephrine (p < 0.05) while no significant modifications were observed with the other tested pretreatments. based on positron emission tomography imaging using 11c-flumazenil fixation in the rat brain, we demonstrated molecular interaction between tramadol and γ-aminobutyric acid (gaba)-a receptors not related to a competitive mechanism between tramadol and flumazenil on the benzodiazepine binding site. our findings clearly ruled out the involvement of serotoninergic, opioidergic, histaminergic, dopaminergic and norepinephrinergic pathways in tramadol-induced seizures while strongly suggested tramadolinduced specific allosteric change in gabaa receptors that could contribute to seizures onset in overdose. conclusion: tramadol-induced seizures in overdose are mainly related to the gabaergic pathway. introduction: heparin-induced thrombocytopenia (hit) is a serious iatrogenic complication of heparinic treatments. the diagnosis of hit is difficult in the resuscitation environment because thrombocytopenia is a frequent and multifactorial phenomenon. the aim of this work was to study the clinical and biological presentation of patients with hit and the consequences attributable to hit on the evolution of patients in terms of morbidity and mortality and to develop a diagnostic strategy for hit for resuscitation patients. this was a retrospective, monocentric, descriptive and evaluative study conducted in our intensive care unit (icu) over a period of 4 years 6 months. an anti-pf4 antibody test was performed in patients who developed thrombocytopenia or a 30% drop in their initial platelet kinetics and the clinical picture. results: the incidence of hit was 1.71% in patients hospitalized in icu. the clinicobiological severity scores, the reasons for admission to resuscitation were similar in both groups (hit+ and hit−) as well as the characteristics of the heparins used. the time of occurrence of thrombocytopenia was similar in the two groups. the diagnosis of hit was more often the only plausible diagnosis in the hit+ group. the 4t's score was significantly higher in the hit+ group. the evolution of the platelet count was similar in the two groups, in the decay phases as well as in the recuperation phase. hit+ patients showed significantly more thrombosis than hit− patients. there was no significant difference between the transfusion needs of hit+ and hit− patients. mortality was identical in both groups, as was the length of stay in icu. conclusion: hit is a rare disease. there was no evidence of a predisposing factor for the occurrence of the disease in a uniform resuscitation population. the diagnosis of hit is based on a cluster of arguments and not on an isolated event. biological tools are indispensable, in a complementary way to the clinical picture. pulmonary embolism in patients with sickle cell disease in intensive care unit: a challenging diagnosis jamoussi amira 1 , zayet souheil 1 , merhebene takoua results: during the study period, a total of 26 patients with scd were admitted. among them, 20 presented with respiratory distress and chest pain and then benefited first of trans-thoracic echocardiography that often showed right ventricle dilation and systolic pap > 30 mmhg (n = 11). all the 20 patients underwent enhanced ct-scan and the diagnosis of pe was finally retained in 6 cases (18.8%) and hence colliged. the average age was 32.5 years ± 9.4 [20-42 years] with a sexratio = 1. the mean of apach ii score was 7. scd were diagnosed at the age of 8.2 years ± 6.2 [3-15 years] with a regular follow up in 83%. the reason for admission was acute respiratory failure in all cases. patients had clinical symptoms of pneumonia: pleuritic chest pain (n = 6), dyspnea (n = 5) and fever (n = 2). all patients had a chest x-ray showing an alveolo-interstitial syndrome in 4 cases (66.6%) and an associated pneumonia in 2 cases ( introduction: acute chest syndrome (acs) is the most severe complication of sickle cell disease and its evolution is unpredictable. acute pulmonary hypertension (ph) in acs is associated with an increased mortality, but its mechanism remains poorly known. our hypothesis is that acute ph is associated with a biological state of hypercoagulability in acs. in a prospective single center study, all consecutive scd patients with acs admitted to the intensive care unit (icu) of tenon hospital were included. specialized haemostasis dosages were performed on icu admission. a trans-thoracic echocardiogram was also performed on admission, and was repeated at steady state. results: among 29 patients with acs, 22 had a trans-thoracic echocardiogram and 6 had a high echocardiographic probability of acute ph, including 1 patient with bilateral pulmonary embolism and 1 patient who developed multiple organ failure and died. there were no significant clinical, biological or radiological differences between patients with a low-intermediate probability of acute ph and those with a high probability of acute ph+ their evolution was similar. the exploration of haemostasis did not show between-group differences, regarding each parameter of haemostasis. however, when using a hierarchical cluster analysis, distinct profiles of coagulation were evidenced, defining 3 biological classes. the subset of patients with a high echocardiographic probability of acute ph was more frequent in biological classes 2 and 3 which corresponded to hypercoagulability states. acute ph was transient in patients (n = 17) with a repeated echocardiography at steady state. conclusion: acute ph may likely occur in patients with acs and a biological condition of hypercoagulability. further studies are needed to confirm these findings. gorham julie were the two independent predictors of survival after hospital discharge. in lung cancer patients admitted into the icu, the mgps is an independent predictor of survival after hospital discharge but not for mortality during icu stay. this inflammatory score could therefore be used as a long-term prognostic marker in this population of patients and would be more reflective of cancer, than reflecting the acute complication leading to icu admission. prospective and multicentric studies must be carried out to validate these results. introduction: recombinant active factor vii is a pro-hemostatic treatment used in obstetric haemorrhage, but no study has made it possible to specify its exact place in the decision algorithm. the objective of our work is to evaluate the efficacy and the benefit risk ratio of recombinant factor viia in the treatment of severe postpartum hemorrhage. we conducted a prospective study at the ibn jazzar university hospital in kairouan during the period from january 1, 2015to december 31, 2016. in total, we collected 15 cases of recombinant factor viia in one postpartum haemorrhage. results: the mean age of our patients was 31 + 5.96 years. the rate of childbirth was 33.33%. the caesarean was the mode of delivery chosen for 10 patients. the causes of postpartum haemorrhage in our series were-uterine atony in 5 cases, uterine rupture and cervicouterine tear 3 cases each, retroplacental hematoma and placenta accreta 1 cases for each two and placenta praevia in 2 cases. our patients were treated in an intensive care unit and the average hospital stay was 4.1 days. sulprostone was reported in 7 cases (46.6%), and all patients received a massive transfusion. the average time to administer rfviia was 6 h 40 min. the mean dose of factor vila recombinant was 78.8 ± 9.24 μg kg. five patients received a single dose, 8 patients received a second injection and 2 patients received 3 doses. clinical efficacy-after a single injection, clinical efficacy with reduction in bleeding was observed in 8 patients, i.e. 60%. the most frequent complication was insufficiencyrenal in 7 cases including 2 requiring hemodialysis, civd in 4 cases, oap in 2 cases, a multivisceral failure in 2 cases, a septic shock in 1 case and a mesenteric infarction in 1 case. the progression was favorable in 12 patients, while 3 patients died (21.9%). conclusion: it is important that new studies be carried out and shared experiences around the world on this drug appear to be effective and prevent invasive actions in the therapeutic arsenal of postpartum heamorrhage. introduction: post-partum haemorrhage (pph) is a life-threatening complication and remains a leading cause of maternal morbidity worldwide. the woman trial* estabished that early administration of tranexamic acid (ta) reduces mortality due to the bleeding in women with pph. our study purpose was to determine the effects of early administration of ta and fibrinogen concentrate on death, hysterectomy and transfusion in women with severe pph. patients and methods: this retrospective, monocentric study was performed in a third level tunisian hospital providing healthcare for more than 10000 pregnant women per year. were included in this study women with diagnosis of severe post partum haemorrhage after a vaginal or caesarean delivery from 2014 to 2016. patients who received ta and fibrinogen concentrate were assessed in group 1(g1) and who not in group 2(g2). results: the incidence of severe pph was 35/10000 deliveries. 166 women were retained for data analysis g1 (n = 109), g2 (n = 57). anthropomorphic and obstetrics characteristics were not significantly different between the two groups. there was a significant difference between the two groups regarding to transfused units of red blood cells however, no difference in term of the use of frozen plasma and platelets concentrates was observed. perioperative hemoglobin nadir was significantly higher in g 1. the frequency of hysterectomy and pelvic packing were higher in g2 (table 1) . no thromboembolic events and no haemorrhage related mortality were observed in the two groups. conclusion: in this retrospective study, early administration of tranexamic acid and fibrinogen reduces risk of hysterectomy transfusion. these encouraging results strongly support the need for a large, international, double-blind study to investigate the potential of the association "ta-fibrinogen concentrate" to reduce maternal haemorrhage related morbidity and mortality. introduction: immunodeficiency, acquired or congenital, is the first comorbidity associated with poor outcome in pediatric patients with acute respiratory distress syndrome 1(ards). the aim of this study was to describe outcome of pediatric patient with hematologic disease hospitalized in our intensive care unit for respiratory failure and to investigate the clinical variables associated with mortality. patients and methods: it was a retrospective monocentric descriptive study including all immunodeficient pediatric patient (malignant hemopathy, congenital immunodeficiency, bone marrow transplanta-tion…) from hematology hospitalized in our 14 beds pediatric intensive care unit with the diagnosis of respiratory failure between january 2003 and february 2017. results: fifty one patients were included corresponding to 53 admissions. nighty percent of the patients met criteria for pediatric ards-67% were severe, 15% moderate and 2% mild. extracorporeal circulation (ecc) was needed for 7 patients. global mortality rate at picu discharge was 47%. twenty four patients (45%) received noninvasive ventilation (niv). height of them (33%) did not need invasive mechanical ventilation (imv). in patients who received imv, mortality rate was significantly higher if patients received before niv (81 vs. 41%) p = 0.001. all patients who needed imv after more than 24 h of niv died (n = 3). mortality was higher in children with griffon versus host disease (80 vs. 40% p = 0.04). mortality of patients receiving ecc and renal replacement therapy (rtt) was respectively 71 and 80%. conclusion: in our study, most of the patients hospitalized for respiratory failure met criteria for pediatric ards. if niv decrease imv requirement, it could be associated with higher mortality rate in case of failure. this result support recent recommendation2 that immunodeficiency is not a sufficient criteria to delayed imv. . flow and airway pressure were recorded at the asl inlet and mouth pressure into the manikin mouth. we defined "device driving pressure" as the peak mouth pressure minus the tele-expiratory mouth pressure. continuous data are reported as mean ± sd. results: as compared to the oxygen mask, vt increased significantly with m-niv and h-niv whatever the simulated respiratory effort (599 ± 201 and 537 ± 217 vs. 307 ± 121 ml respectively with the moderate simulated effort, p < 0.001; fig. 1 ). hfnc and cpap were associated with a slight but non-significant decrease in vt as compared to the oxygen mask. overall, for a given respiratory effort, vt was influenced by the "device driving pressure", which tended to decrease when using hfnc and cpap and markedly increased with m-niv as compared to the oxygen mask. therefore, vt in m-niv with a simulated low effort was significantly higher than vt in cpap and hfnc with a simulated moderate effort (456 ± 162 ml, 252 ± 95 ml, and 262 ± 90 ml respectively, p = 0.01 for both comparisons). conclusion: in our bench model, the vt value was significantly influenced by the noninvasive ventilatory device. niv was invariably associated with significantly higher vt than with other devices, even when dividing by two the simulated inspiratory effort during niv. introduction: in icu, intubation is a high risk procedure associated with high morbidity. despite procedure's improvement with systematic application of fluid loading, early use of vasopressors and checklist use, morbidity remains high. several recent trials has been conducted with different metrics choose as primary outcome. however any evidence exists to choose one more than another: time to intubation, first pass success, difficult intubation. first pass success sine hypoxia and hypotension (dash-1a) has been highlighted recently and choose by the game program without any scientific evaluation. we conducted a post hoc analysis of the randomized clinical trial macgrath mac video laryngoscope or macintosh laryngoscope for intubation in the intensive care unit (macman) to determine the best metric to choose for primary outcome for the next intubation studies in icu. patients and methods: macman was a multicentre, open-label, randomized controlled superiority trial. consecutive patients requiring intubation were randomly allocated to either the mcgrath mac videolaryngoscope or the macintosh laryngoscope, with stratification by centre and operator experience. an only inclusion criterion was-"patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if-contraindication to orotracheal intubation (e.g., unstable spinal lesion) + insufficient time to include and randomize the patient (e.g., because of cardiac arrest) + age < 18 years + pregnant or breastfeeding woman + correctional facility inmate + patient under guardianship + patient without health insurance + refusal of the patient or next of kin to participate in the study + previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess association and prediction of life threatening complication (mild to moderate, severe, mild to severe) by different metric existing-time to intubation, first pass success, difficult intubation, first pass success sine hypoxia and hypotension. each metric was compared with another one. area under curve was built for every metric and all metrics were then compared. results: dash-1a was superior to all others metrics included in the analysis for prediction of life threatning complications (all p < 0.001). failure of first pass conclusion: all metrics are not equal to predict severe life threatening complications during intubation in the icu. in this context, we recommend adoption of definitive airway sine hypoxia or hypotension at first attempt (dash-1a) as primary outcome for intubation studies in the icu or as metric indicator tracked in quality improvement program. benbernou soumia introduction: introductionacute respiratory failure (arf) is a common cause of emergency use and one of the major reasons for admission to intensive care unit. it associates a vital risk imposing immediate symptomatic treatments and an etiological approach. [1] among the etiologies of the arf, acute lung edema (ale), decompensation of chronic obstructive pulmonary disease (copd), chest trauma and pneumonia are the most frequent @it is a life-threatening pathology with a high incidence of mortality, since mortality is reported to be 20-40% [4, 5] for arf secondary to cardiogenic ale. the prevalence of arf in algeria remains unknown + the tahina study showed that respiratory diseases were the leading cause of consultation in the hospital [2] . the the objective of this study is to estimate the frequency of use of the niv and to determine the associated factors of failure of the niv for the adult patients hospitalized for arf in the emergency department of oran hospital from january 2015 to november 2016. prevalence of copd was found in the 31.5% of tobacco subjects [3] . the number of patients hospitalized for chest trauma continues to increase, resulting in an increase in the number of patients admitted for arf secondary to chest trauma. patients and methods: this is an observational and exhaustive study during the month of november, from the files of patients. the population-all subjects over 16 years hospitalized for an arf at the reception and resuscitation units of the emergency department of oran hospital from january 2015 to november 2016. results: ninety-seven patients were hospitalized for arf during this period. niv was used for 37 patients. 24 patients were acute lung edema. univariate analysis showed that spo2 was the only failure factor in this series. the failure rate of this technique was 32.4%. niv is a technique that should be used more in the emergency rooms, which would make it possible to use less intubation specially in indications where the level of proof in the literature is important. demographic characteristics, etiology of exacerbation, comorbidities, the sapsii score, arterial blood gases at admission, respiratory, hemodynamic and neurological parameters, use of noninvasive or invasive ventilation, nosocomial infection, duration of niv, length of stay and mortality. results: during period study 160 patients (58% women with a sapsii score 29 ± 15) were included. the etiology of exacerbation was bronchitis in 45% of cases and pneumonia in 40%. only 3 patients have niv at home and 6 patients have oxygen. pseudomonas aeruginosa was isolated in 6 cases. twenty percent of the patients had developed a nosocomial infection, acinetobacter baumanii and pseudomonas aeruginosa were isolated in 60 and 25% respectively. niv was used in 89 patients at admission and the rate of niv failure was 29%. the duration of mechanical ventilation was 9 ± 8 days and the length of stay was 12 ± 10 days. the mortality was 12%. niv and oxygen at home were prescribed for 21 patients. in univariate analysis survivors and non-survivors were comparable regarding baseline and clinical characteristics. nosocomial infections (53 vs. 16%), and spassii score were significantly more elevated in non-survivors. in emergency department, the management of hypercapnic acute respiratory failure with hfo is limited. hypercapnia and acidosis remain moderate. patients are old with comorbidities. the mortality rate is high but expected given the number of limitation of active therapy. hfo appears to be effective for a majority of patients, but half of them required niv too. the niv hfo association seems an interesting option. but our methodology is perfectible and would require a randomized control tria. severe chronic obstructive pulmonary disease with chronic respiratory failure in intensive care unit: mortality and prognostic factors arnout chloé 1 , faure morgane 1 , novy emmanuel 1 chu nancy, nancy, france correspondence: arnout chloé -arnout.chloe@gmail.com introduction: last decades, the number of patient with chronic respiratory failure due to chronic obstructive pulmonary disease (copd) admitted in intensive care unit (icu) increased. data about their real prognosis in the icu are lacking. the objective of this study was to evaluate mortality rate at 6 months and to identify prognostic factors of copd patients with chronic respiratory failure, treated with long term oxygen therapy (ltot), admitted in icu. patients and methods: a retrospective cohort study was conducted in the french university hospital of nancy during years 2014-2015 on all copd patients treated with ltot admitted in icu. only the first admission was analysed. patients were included if they had spirometry, blood gas and oxygen flow in the year before admission in icu. other causes of chronic respiratory failure, and patients with tracheostomy before icu admission were excluded of the cohort. hospitalizations were selected using the international classification of diseases, 10 th revision (icd-10). results: one hundred and thirteen patients were included, 37 (33%) died in the first 6 months after icu admission. mortality rate in icu was 10%. severity of copd was-mean bode score 7 ± 2.1, number of exacerbation per year requiring hospitalization 3 ± 1.4. ltot was used for 3.7 ± 3.3 years. acute respiratory failure was the main frequent cause-38% pneumonia, 34% acute exacerbation of copd, 14% acute lung oedema. the sequential organ failure assessment score within the first 24 h of icu admission was 11 ± 4. need for mechanical ventilation was noted in 22% of cases and was associated to mortality with an odds ratio of 3.5 (ci 95% [1.4-9] p = 0.01). in presence of other organ failure, mortality rate tends to increase. patients with median pao2 fio 2 ratio > 196 on first blood gas had a reduced risk of death (or 0.4 + ci 95% [0.1-0.9], p = 0.01). conclusion: this is the first study to assess mortality at 6 month of patients with severe copd requiring ltot admitted in icu. severity of hypoxemia and use of mechanical ventilation are two prognosis factor of mortality. the addition of another organ failure seems to increase the mortality rate. severity of the chronic respiratory insufficiency less influenced short and long term outcome. this data have to be included in the global decision to admit a copd patient with ltot in icu. introduction: the remarkable progress in the outpatient care of the asthmatic patient (development and access to inhaled drugs) has made the admission of these patients exceptional in the icu. we have noticed a recent upsurge in asthmatic afmissions in the icu, and are investigating whether this fact was related to modifiable factors (access to adapted drugs) or an increase in the severity of the disease. patients and methods: retrospective, observational, three-center study conducted in three tunisian medical icu from january 2016 to july, 2017. were included all consecutive patients admitted for severe acute asthma in three icus. were assessed-patient's demographic characteristics, asthma severity and its actual control based on global initiative for asthma classification (gina) 2016, clinical characteristics of the acute episode, length of icu stay, ventilatory free days and mortality. results: out of the1142 patients admitted within the study period, 34 (3%) had severe acute asthma. the mean age was 37 years (iqr32-50.5). sex ratio was 1. asthma was allergic in 84% with an average ancienty of 14.7 years. over all asthma was not very severe with no prior icu admission for acute severe asthma 38.2% were mechanically ventilated at least one time. were classified severe and moderate persistant asthma respectively in 42.9(%) and 19(%). 57.1% were consideredpoorly controlled. low educational level and socio-economic status are the main determinants of poor control-20% of analyzed patients didn't have a social care, and thus no accesse to prescribed anti-asthmatics + 40% didn't have a regular follow up and 23.5% were jobless. when admitted to the icu-23 patients (67.6%) needed invasive mechanical ventilation, one patient received niv. the mean length of stay was 8 days (iqr 3.5-12.5). levels of auto peep and pic pressure at icu admission were respectively 6 (iqr 1-12) and47.5 (iqr 37, 25-58.5) cm h 2 o. mortality rate was 3%. this study suggests that low educational level and socioeconomic status (especially the lack of social care and joblessness) are the main determinants of poor control of asthma and may lead to the increase of rate of icu admission for severe acute asthma requiring mechanical ventilation. introduction: in emergency medicine, the boussignac system (bs) is sometimes used to administer oxygen and continuous positive airway pressure (cpap). in this case, fio 2 value depends on the ratio between o 2 flow and inspiratory flow (if). in some cases, the fio 2 decreases due to the if increase. the aim of this study was to test a modified boussignac system in order to limit the fio 2 decreases during inspiratory flow rate increases. the study was conducted on bench with bs connected to a two compartment adult lung model (dual test lung ® ) (dtl) controlled by a maquet servo i ® ventilator. three minute ventilation (mv-7.5 15 22.5 l min) with ti ttot = 0.33 were investigated. fio 2 and mv measurements were made using an iworx ® ga207 gas analyzer. with a bs, two peep were analyzed-3 and 10 cm h2o. the bs was supplied by an o 2 flow. in order to increase the fio 2 , we have evaluated the addition of a t piece connected to a nebulizer at the air-room admission of a bs. the aerosol was supplied by an o 2 flow of 9 l min. the o 2 flow was analyzed in continuous with a calibrated mass flow meter (red y vogtlyn ™ ). results: when mv increases, the fio 2 decreases (p < 0.05). when peep increases, fio 2 increases too (p < 0.05). the addition of an aerosol (o 2 -9 l min) to a bs increases the fio 2 (p < 0.05). however, in this last case, the gap between both fio 2 decreases with increases mv (fig. 1) . the addition of an aerosol connected to an o 2 flow rate (9 l min) at the entry of a bs limits the fio 2 decreases during the mv increases. introduction: burned patients are at high risk of yeast colonization and thus of invasive fungal infections, particularly to candida (c.) spp., leading to an increase in morbidity and mortality. while pre-emptive antifungal therapy has improved survival, it may lead to an increase in antifungal resistance. the objectives of this work were to describe candida species distribution and to determine the antifungal susceptibility of candida isolates acquired in a burn unit. our study is a retrospective review of 17 severely burned patients admitted to the burn unit of the ben arous traumatology and burns center with one or more positive culture sites for candida, during the 16-month period from may 2016 through august 2017. a total of 42 isolates were thus obtained. the susceptibility to 6 antifungal drugs (5-fluorocytosine, fluconazole, ketoconazole, micronazole, itraconazole, amphotericin b) was determined using the fungitest ® broth dilution method for patients with infected normally sterile body sites or a candida colonization index superior or equal to 0.4. since echinocandin and anidulafungine were recently introduced in tunisia, the susceptibility to these antifungal classes was tested for only one patient from our cohort. results: nasal and buccal sites were the most colonized body sites (21.4% each), followed by axillary (11.9%) and rectal sites (9.5%) and urines (9.5%). c. albicans was the predominant species (45.2%), followed by c. glabrata (38.1%), c. tropicalis (7.1%) and c. parapsilosis (4.8%). among the strains whose antifungal susceptibility was determined, majority of candida isolates were susceptible to fluconazole (77.8%), which is the most frequently used molecule as a pre-emptive treatment in such cases in tunisia due to its availability and its efficiency. on the other hand, 11.1% of the isolates were intermediate and 11.1% were resistant to this antifungal drug, mainly c. glabrata for both groups. as for the other tested azoles, high rates of intermediate strains were noticed (81.5% to itraconazole, 40.7% to ketoconazole and 33.3% to miconazole), mostly c. glabrata. only one strain was resistant to amphotericin b, which is not usually used in these cases due to its nephrotoxicity and the frequency of kidney failure in burned patients. our study demonstrates that c. albicans is the most frequent species in burn unit-acquired candidiasis. no major antifungal resistance was observed, apart from high rates of intermediate strains (mainly c. glabrata) to azole class antifungal drugs. introduction: infection, especially bacteremia, is a major cause of morbi-mortality in severely burned patients. mortalityrelated to bacteremia in burn patients was about 30% [1] . we performed this study to determine the prevalence, the causative agents and outcomes of bacteremia in burned patients. introduction: carbapenems, the last line of therapy, are now frequently needed to treat nosocomial infections, and increasing resistance to this class of β-lactams limit antibiotic options in critically ill patients especially in burns. the objective of our study was to assess the impact of the detection of carbaménépases in optimizing treatments in burned. patients and methods: a prospective, monocentric study was carried out at the intensive care unit of burn in tunisia over 6 months (march-august 2017). were included all patients who have had a carbapenemase research. the sample was carried out by rectal swab. all samples were analyzed by polymerase chain reaction (pcr) methods for presence of carbapenemase. during the study period, 30 patients were included. the mean age was 30 ± 11 years. they were 24 men and 6 women. the average burned surface area was 41 ± 17%. patients were transferred from another hospital structure in 87% of cases with a delay of 86 h. 90% of patients had a septic complication with a delay of 5 ± 3 days. antibiotic treatment was empirical in 23 cases. the therapeutic failure rate was 60%. results of carbame-nepases detected by pcr are detailed in table 1 . in the group of patients pcr (+), the antibiotic treatment was changed in 18 cases. the most association of antibiotics were-tigecycline in combination with colistin or in combination with fosfomycine and fosfomycin in combination with colistin. this leads to reduce therapeutic failure by 20%. conclusion: detection of carbapenemase in our study was higher (80%), allows us to identify regions with high risk of carbapenemase, improve therapeutic efficacy and strengthen infection control measures by isolation of all carbapenemase producing patient. introduction: icu-acquired bacteraemia is prevalent and poses a grave threat. providing information about the main causative bacterial agents and determination of their susceptibility to antibiotics may improve empiric therapy and early detection of emerging antimicrobial resistance. the aim of this study was to investigate the species distribution and antibiotic susceptibility of isolated strains from blood culture in burn intensive care unit during a five-year period. patients and methods: from january 2012 to december 2016, a total of 2,182 non repetitive strains were isolated from blood cultures. incubation of blood culture vials and the detection of bacterial growth were performed by the bactec system. all isolated organisms were identified on the basis of standard microbiological techniques. antibiotic susceptibility testing was carried out by the agar disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm 2013 and 2015 guidelines. data were analyzed using the sir-system. minimum inhibitory concentrations of colistin, imipenem and vancomycin were determined using the etest ® method (biomérieux). results: of the 2,182 strains isolated, the most frequently identified species were staphylococcus aureus (21%), acinetobacter baumannii (11%), klebsiella pneumoniae (10%), and pseudomonas aeruginosa (9%). the rate of methicillin-resistant staphylococcus aureus (mrsa) was 70%. resistance to tigecycline and linezolid was 15 and 1%, respectively. all strains were susceptible to glycopeptides. in addition, isolated acinetobacter baumanii strains showed high rates of resistant to all tested antibiotics except colistin. eighty per cent of these strains were resistant to ceftazidime and 94% to imipenem. resistance to rifampicin was 15% in 2014, and has increased steadily to 67% by 2016. similarly, high resistance rates were observed among klebsiella pneumoniae and pseudomonas aeruginosa to ceftazidime (70 and 39% respectively), ciprofloxacin (68 and 67%) and imipenem (15 and 72%). conclusion: this study investigated on the local distribution patterns of causative organisms of bacteraemia in burn patients and the corresponding antimicrobial susceptibility profiles. multidrug-resistant pathogens, especially mrsa and acinetobacter baumanii, were the most frequently isolated organisms. hygiene measures and antimicrobial stewardship should be implemented to prevent the spreading of these resistant strains. introduction: pseudomonas aeruginosa is known opportunistic pathogen frequently causing serious infections in burned patients. multidrug resistance in this pathogen is increasing throughout the world and is a major problem in the management of these pathogens. analysis of serotype and resistance profile to antobiotics of p. aeruginosa help to establish a prompt control and prevention program. the aim of this study was to evaluate the frequency of antimicrobial resistance and the prevalence of pseudomonas aeruginosa serotypes isolated in the burn unit. patients and methods: during a period of 4 years (from 01 01 2012 to 31 12 2015), 485 strains of pseudomonas aeruginosa were isolated from burned patients. conventional methods were used for identification. antimicrobial susceptibility testing was performed with disk diffusion method and susceptibility data were interpreted according to breakpoints recommended by the french society of microbiology (fsm). serotypes were identified by slide agglutination test using p. aeruginosa o antisera (biorad). the imipenem-resistant strains have benefited from a research of carbapenemase production by the edta test. results: in our study period, 3464 bacterial isolates were found among which pseudomonas aeruginosa was the second most frequent bacterium isolated from burned patients (14%) after staphylococcus aureus (18%). the most frequent sites were-cutaneus infection (36%), blood culture (24%) and catheter (16%). the most prevalent serotypes were-o12 (72%), o1 (10%), o2 (6%), o11 (1%) and o6 (1%). the survey of antibiotic susceptibilily showed high pourcentage of resistance to the different antibiotics-21% of strains were resistant to ceftazidim, 69% to ticarcillin, 66% to ciprofloxacin, 62% to amikacin and 56% to imipenem. among the 272 imipenem resistant strains, 34% were metallo-beta-lactamase producers. the antibiotic to which p. aeruginosa was the most susceptible was colistin (100%). multidrugresistance was associated with o12 serotype in 67% of the cases. the global frequency of serotypes o12, o1 and o2 was more than 88%. multidrug resistance and carbapenemase being associated with serotype o12. serotyping of the strains isolated from burned patients will help to guide the first antibiotherapy. the dissemination of carbapenemases strains must be contained by implementation of timely identification, strict isolation methods and better hygienic procedures. and respiratory disorders (43.5%)…). the therapeutic management was based on per operative resuscitation, organ failure treatment, probabilistic antibiotic therapy and median laparotomy surgery. the main etiologies of abdominal sepsis were-digestive perforations (43.5%), purulent effusion (38%), intestinal necrosis (14%), cholecystitis (12.5%). the bacteriological profile was -predominance of bgn (82.7%) dominated by e. coli (28%) followed by klebsiella pneumoniae and acinetobacter baumanii (13.46%), the mean duration of the hospitalization was 7.03 ± 6.65 days. the mortality rate was 57%. the main prognostic factors in our study in univariate analysis were-the advanced age, the diabetes, the organ failure, the increased gravity scores, the time to management, the use of catecholamines and the development of septic shock. the multivariate analysis showed a statistically significant association between the development of septic shock, the stercoral effusion, the peptic ulcer perforation, the operator and the therapeutic descalation. the abdominal sepsis is a serious affection, with great mortality. the improvement of its prognosis is based on a revision of the medical and surgical protocols, and an adapted antibiotic therapy depending on the direct examination of the samples, also of the bacterial ecology of the service. introduction: severe acute respiratory infections (sari) are common in critically ill patients. viruses can be found in immuno-competent patients. however, the main problem for viral infections is the diagnosis, isolation of the pathogen is often difficult and the symptoms not specific. the aims of this study were to describing the epidemiological characteristics of viral respiratory infections, to identify factors predictive of a poor outcome. introduction: in septic shock there are physiological changes with an increase in the volume of distribution, with implications for pharmacokinetics of antibiotics that make recommended doses potentially inadequate for target organisms with highest minimal inhibitory concentrations. to cover these bacteria, peak serum concentration (cmax) target is 64-80 pg ml. identification of predictive factors for insufficient cmax, in common practice, would make it possible to target the patients at risk in order to optimize dosage of antibiotic to be administered. objective of this study was to determine predictive factors of amikacin's cmax insufficient independently of the dosage. patients and methods: this was a retrospective study carried out between august 2013 and november 2015 in icu of our hospital. all adult patient receiving an initial injection of amikacin between 20 and 30 mg kg were included. clinical data collected were-amikacin dosage, body mass index (bmi), mechanical ventilation (mv), mean arterial pressure (map), use of noradrenaline and continuous hemofiltration (cvvh). biological elements were collected and for each, the last result in the 24 h prior to admission and that at the patient's entry into icu were added to analysis. a comparison of this clinical and biological variables was made between two groups-the first one with an ineffective cmax of amikacin (< 64 pg ml) and the second with an effective cmax of amikacin (> 64 pg ml). results: 191 patients were selected for statistical analysis. median dosage was 22.5 mg kg for a median cmax at 72.1 mg l. for 77 patients, cmax was less than 64 mg l and in 53 patients, it was greater than 80 mg l. there was a statistically significant relationship between a cmax greater than 64 mg l and mv, bmi, pct measured before and after admission, albumin after admission, hemoglobinemia, hematocrit level after admission, the rate of urea after admission (table 1) . a low bmi was associated with cmax < 64 mg l. discussion: these results remain comparable to those found by taccone in 2010, with dosages of 25 mg kg having only 70% of the peaks above 64 mg l + comparable also to montmollin's study in 2014. conclusion: mv, bmi, pre-and post-admission pct, and albumin, hemoglobin after admission, hematocrit and urea after admission seems to be predictive criteria for insufficient amikacin's cmax independently of dosage. our study was limited to one icu, a heterogeneous recruitment, and that all samples have been taken at the right time. introduction: this study aimed to assess whether augmented renal clearance (arc) impacts negatively on ceftriaxone pharmacokinetic pharmacodynamics (pk/pd) target attainment in critically ill patients receiving 2 g day by intermittent infusion. patients and methods: over an 8-month period, all critically ill patients treated by ceftriaxone for a first episode of sepsis without renal impairment were eligible. during the first 3 days of antimicrobial therapy, every patient underwent 24-hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at trough concentrations. the main outcome investigated in this study was the rate of empirical target non-attainment using a theoretical target mic of 2 mg/l. results: over the study period, 21 patients were included (63 samples analyzed for therapeutic drug monitoring). the rate of pk/pd target non-attainment was 62%, with a strong association with crcl (p < 0.0001) ( table 1 ). there was no statistical association between pk/ pd target non-attainment and therapeutic failure. conclusion: when targeting 100%ft > mic of the less susceptible pathogens, patients with crcl > 150 ml/min are at risk of subexposure in ceftriaxone (2 g day). these data emphasize the need of therapeutic drug monitoring in patients with arc, especially when targeting less susceptible pathogens or surgical infections with limited penetration of antimicrobial agents. introduction: the septic shock is a major concern of the intensive care unit in the world because of its frequency and especially of its mortality which remains high in spite of the progress made in the optimizing care. the aim of our work is to analyze the prognosis factors related to death among patients with septic shock in the icu of the military hospital avicenna of marrakesh, and to focus on the physiopathological and therapeutic data of the septic shock in the light of last acquisitions in this field. patients and methods: we proceed to a prospective study including all patients with septic shock at admission to icu or secondary, over a 3-year period (january 2014 -december 2016). prognosis factors related to death in patients with septic shock were studied in univariate and multivariate analysis. results: eighty-six cases of septic shock were collected from 1290 icu admissions, the incidence is 3.33%, the mean age was 58 ± 14.7. the sites of infection most often involved were the abdomen and lung (50%), there was a predominance of gram-negative bacilli, the number of organ failure is in average 2.6 ± 1.1. the overall mortality was 65.1%. prognosis factors related to mortality retained after logistic regression are cardiovascular organ failure followed by neurological. indeed, the number of patients with 3 or more failures was 22 (78%) in the group of patients who died. as the second factor influencing the high mortality found severity score 53.6 ± 14.7, age is also considered a prognosis factor since 21 of 28 patients were over 60 years. the average age of the deceased was 66 ± 7 years versus 51 ± 7 years in survivors (p < 0.001), yet the mortality according to the infectious agent was not found as factor influencing mortality (p = 0.75). conclusion: septic shock is a frequent reason for hospitalization in icu. the improvement of prognosis requires an early and adapted management of sepsis as well as increases efforts for control and prevention of nosocomial infection. introduction: vitamin d deficiency is common in critically-ill patients. in addition to its role in the regulation of phosphor-calcic metabolism, vitamin d is of paramount importance for the immune system. the aim of the current study is to assess the prognostic value of vitamin d deficiency in patients with septic shock. patients and methods: retrospective study conducted over 6 months. all the adult patients with septic shock and vitamin d level screening performed within the first 24 h of admission were included in the study. we excluded patients with chronic kidney disease and those receiving vitamin d supply. two groups were compared: those with a serum vitamin d level < 10 ng/ml (g1) and those with higher level (g2 introduction: since immunity plays a central role in neoplasms surveillance, it is likely that sepsis induced immune dysfunctions may impact on the underlying malignancy. we developed a research project investigating the reciprocal relationships between bacterial sepsis and cancer. we reported that sepsis-induced immune suppression promoted tumor growth in post-septic mice inoculated with cancer. in a reverse cancer-then-sepsis model we observed that sepsis may conversely inhibit tumor growth. this study aimed at investigating the cellular and molecular mechanisms of sepsis-induced tumor inhibition, and most especially the role of monocytes macrophages and toll-like receptor (tlr) signaling. patients and methods: we used c57bl 6 j wild-type (wt), tlr4-/-, tlr2-/-and myd88-/-mice. mice were first subjected to tumor inoculation by subcutaneous injection of mca205 fibrosarcoma cells. fourteen days after, mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (clp). controls were cancer mice subjected to sham surgery. alternatively, cancer mice were subjected to an i.p. challenge with tlr agonist (lps or heat-killed staphylococcus aureus (hksa)). the distribution of tumor-associated immune cells was assessed by facs at days 1 and 7 following surgery. the activation status of tumorinfiltrating monocytes macrophages was assessed by facs (mhcii, cd40, cd86, pdl1, pd1). f4/80 + cells were purified by facs and we assessed cytokines production (rt-qpcr) and bacteria phagocytosis. we confirmed polymicrobial sepsis dampens tumor growth in wt mice. a similar clp-induced tumor growth inhibition was observed in tlr2-/-mice, but neither in tlr4-/-nor myd88-/-mice. a challenge with lps resulted in a marked anti-tumoral effect, whereas a challenge with hksa had no impact on tumor growth. tumor-infiltrating immune cells analysis retrieved monocytes/macrophages predominance with two different subsets based on f4/80 expression (f4/80high and f4/80low). late-onset (day 7) tumors from clp-operated mice displayed increased proportions of f4/80high. as compared to f4/80low cells, f4/80high cells displayed a more immature status with a lower expression of cd40, mhcii and pdl1, and a higher phagocytic activity. interestingly, f4/80high cells from clp-operated mice exhibited a higher phagocytic activity than those from sham-operated mice. conclusion: polymicrobial sepsis drives a potent antitumoral activity in cancer mice, which is associated with changes in the distribution and functions of tumor-associated monocytes macrophages subsets. our results converge on a critical role of tlr4 signaling, that should be further investigated. conclusion: post-agressive immunosuppression in icu is not specific to sepsis. in septic shock, the low counts in circulating ilc3 s could be explained by ilc plasticity (conversion of these cells into ilc1 s), by migration from the blood or by an exacerbated apoptosis. ilc2 s expansion, associated with a higher risk of secondary infection, could be promoted by il-33, released by tissue injuries. ilc2 s could activate regulatory t cells via il-10. these preliminary results must be confirmed on a larger cohort. they play a suppressive role in the immune system by the secretion of negative regulatory cytokines such as interleukin-10 or by immune cell contact inhibition. the objective of this pilot study was to develop and test a protocol to determine the breg level in septic patients. the level of breg were measured on whole blood sample by flow cytometry the first day of hospitalisation in septic patients. b cells were identified on the single-parameter expression cd19 combined with scatter. the breg were identified as subpopulation expressing cd24/hicd38hi or cd24/hicd27+ (see fig. 1 ). the results were expressed as percentage of the parental lineage gate and absolute value per microliter. this protocol has been optimised in order to be able to transfer technic into clinical practice. results: we include 8 patients hospitalized in intensive care unit with severe sepsis or septic shock. the percentage of cd19 + cd24hic-d38hi was 6.6 ± 5.2% with a mean of 4.6 ± 2.3 cells microliter. the percentage of cd19 + cd24hicd27 + was 9.1 ± 4.7% with a mean of 8.8 ± 6.4 cells microliter. we are able to measure and follow the evolution of breg during severe sepsis or septic shock. because breg could inhibit body immune function, we wish to conduct a prospective study to evaluate the correlation between breg level and the prognosis of patients with sepsis. the neutrophil/lymphocyte ratio (nlr) reflects an inflammatory state. the nlr has recently emerged as a prognostic marker in colorectal cancer patients, acute coronary syndrome and pulmonary embolism (kayrak m, heart lung circ 2014). the aim of this study was to assess the prognostic value of nlr in patients with septic shock. we performed a prospective observational study in septic shock icu patients within 72 h of admission from january to july 2017 in charles nicolle hospital of tunis. exclusion criteria were age < 18 years, pregnancy + oncohematological patients, recent blood transfusion, post-cardiac arrest and brain-death. nlr was measured soon after admission and 24h, 48h, and 72h after. demographic, clinical and biochemical parameters, severity scores, life-support therapies (vasopressors, ventilation), and length of icu stay were recorded. the primary endpoint was 28-day mortality. results: sixty-five patients (50 males, median age, 48.5 years) with septic shock were included in the study. the 28-day mortality was 54%. the median sofa score at t0 was 12 points and the median igs2 score was 55 points. the sources of infection were as follows: the lungs (n = 27), the urinary tract (n = 14), the central nervous system (n = 4), the abdomen (n = 8), skin and soft tissue (n = 12). the parameters that were identified through univariate analysis to be associated with 28-day mortality were igs2 score, lactate level, the nlr elevation at h24, h48 and h72. median nlr levels were significantly higher in non-survivors (n = 35) than survivors ( introduction: the autonomic nervous system (ans) is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of ans activity and a relation between hrv and outcome has been proposed in various types of patients. we evaluated the feasibility of a automated hrv monitoring, based on standard electrocardiography monitoring, and investigated the different parameters that should be recorded. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct02893462) that aims to record more than 1500 icu patients over a 3-years period. patients and methods: physiological tracings were recorded from the standard monitoring system (intelliview mp70 philips), using a dedicated network and extraction software (synapse v1, ltsi inserm u1099) that enables simultaneous recording of 5 different physiological curves, at their native resolution (500 hz for ecg, 125 hz for other). raw data were subsequently stored on a dedicated local server, before anonymization and analysis. all consecutive patients were recorded for a 2-hours period during the 24-hours following icu admission. all measurements were recorded with the patient laying supine, with a 30° bed head angulation. physiological recordings were associated with metadata collection by a dedicated research assistant. hrv parameters were derived from electrocardiography monitoring using kubios hrv premium ( introduction: acute cor pulmonale (acp) is a frequent complication of acute respiratory distress syndrome (ards). it occurs in 22% of cases and might be associated with an increased mortality rate. it is defined by a ratio of telediastolic surfaces of right ventricular (rv) on left ventricular greater than 0.6 and a septal dyskinesia. however, systolic dysfunction defined by the guidelines of the american society of echocardiography has not been well studied in ards and in particular concerning the rv free wall longitudinal strain (rv-fw-ls). the aims of the present study were to identify the prevalence of rv systolic dysfunction and acp in ards, and to evaluate the effects of inhaled nitric oxide (noi) and prone positioning. we prospectively included patients to a mild to severe ards, and proceeded to standardization of ventilation and systematic echocardiography in semirecumbent position, with noi and in prone position. interpretation of examination was blinded to the investigator. we evaluated the presence of acp, systolic dysfunction identified by classical cardiologic criteria (rv fractional area change, rv tei index, tricuspid annular plane systolic excursion, velocity of the tricuspid annular systolic motion) and also by rv-fw-ls. results: sixteen patients were included. thirty-seven percent of patients were in severe ards. the prevalence of acp was 25% while right ventricular systolic dysfunction was identified in 37.5% of patients with the classic cardiologic criteria and 68.7% with the impairment of rv-fw-ls which represented the most sensitive test for right ventricular dysfunction detection (table 1) introduction: the use of extra corporeal membrane oxygenation (ecmo) is increasing. brain complications may occur, resulting in an increased morbidity and mortality. the objective of our study was to analyze the incidence of neurological complications while receiving ecmo, the risk factors, and to describe morbidity and mortality in a large cohort of patients in intensive care unit. patients and methods: this was an observational, mono-centric, 2-year retrospective study in patients who received ecmo. primary outcome was the occurrence of neurological complication until d7 after ecmo. results: one hundred and eight patients were included in the analysis. twenty-seven patients (25%) presented a neurological complication. of these, 16 died at d30. there were 13 ischemic sequelae (24.5%), 5 intracranial haemorrhages (9.4%), 4 cerebral edema (7.6%) and one other lesion (1.9%). the median time before occurence of a neurological complication was 8 days after the implementation of ecmo. multivariate analysis revealed the presence of hyperlactatemia > 5.4 mmol l, neurological deficit at the beginning of the management, as well as the history of stroke before the ecmo implementation as predictive factors of neurological complication (or 44.15, . the incidence of neurological complications under ecmo is about 25% and ischemic sequelae are the most frequent. history of stroke and low cerebral flow associated with ischemia-reperfusion seem to increase the occurrence of these complications and must lead to greater vigilance in these patients. -122] . eighteen patients (16%) survived at icu discharge with a good neurological outcome. by multivariate logistic regression analysis, female sex, initial shockable rhythm, and pre-ecmo arterial blood ph ≥ 7.1 were independent predictors of survival with good neurological outcome. all of the patients presenting with cpc score of 1 or 2 at icu discharge had a shockable rhythm and or ph ≥ 7.1 before ecls implantation. 28% of the patients presenting with these criteria had a good neurological outcome at icu discharge. all of the patients presenting with non-shockable rhythm and ph < 7.1 before ecls implantation died in the icu. conclusion: about one third of the patients presenting with shockable rhythm and or ph ≥ 7.1 before ecls implantation had a good neurological outcome at icu discharge. on the contrary, all of the patients presenting with both non-shockable rhythm and ph < 7.1 before ecls implantation died in the icu. these simple parameters might help to identify cardiac arrest patients which could benefit from ecls implantation. radjou aguila introduction: the decrease of lung volume is a keystone for the management of patients under mechanical ventilation in intensive care units. this procedure has not only led to a reduction of morbimortality in ards but also in all patients mechanicaly ventilated in intensive care units as well as in major surjery. nevertheless, the incidence of high volume (vt) on morbimortality is extremely variable (about 8 to 70%). our main objective is to assess the incidence of high volume ventilation (> 8 ml/kg predicted body weight, pbw) in our hospital intensive care units. moreover we were interested in determining the risk factors of high volume ventilation. we conducted a retrospective observational study from january to march 2015 in three intensive care units of a tertiary university hospital. all patients ventilated under sedation in vac mode during the 24 h after admission were included in the study. of the 502 patients admissions during the period, 71 one of them (14%) have no height mentioned in their medical file and were exluded. among the 351 patients considered, 110 (31.3%) were ventilated with high vt (fig. 1 ). 98% of patients had a positive expiratory pressure ≥ 4 cmh2o. in multivariable analysis, height (smaller) and weight (lower) are the only associated factors with a high volume ventilation (p < 0.0001 and p = 0.015, respectively). discussion: the observed incidence on high vt patients is higher than that reported in most papers in literature (jaber et al. 18%, hess et al. 8%) . nevertheless, both studies were conducted in operating room with higher vt cut-off (10 ml/kg). walkey and al showed that 34% of patients in ards were ventilated with vt › 8 ml/kg of pbw. moreover, the same associated factors (smaller height and lower weight) have found in the study. older studies revealed higher bmi as factor to high volume ventilation. this difference could be explained by the use of predicted body weight. conclusion: although the growing literature and the recommandations aim to reduce the lung volume between 6 to 8 ml/kg of pbw, still one third of the patients in intensive care units are ventilated with too high lung volume. (fig. 1 ). with either a nc overlap on one nostril or not. results: when the mv increases, the fio 2 decreases. when the mouth opens, the fio 2 decreases. when the prongs are overlapping one nostril the fio 2 decreases slightly (mean 5 ± 2% in absolute value). statistical differences were found between closed and open mouth and between overlap on one nostril and not (p < .05), except between tmo and cm at two mv (14 and 17 l/min) when nc overlap on one nostril (fig. 1) . conclusion: when the prongs of nc are not correctly placed in the nostrils, the fio 2 decreases, but this impact is limited in our bench study. the impact of mv increases and mouth opening on the fio 2 values is also important. introduction: the weaning of mechanical ventilation is an essential and delicate phase in the management of a resuscitation patient. the neurosurgical patient presents a number of specific problems, such as impaired control ventilatory control, coughing or the pharyngo-laryngeal intersection. however, it often allows short-term ventilatory withdrawal in the neurosurgical patient, probably largely by the simple fact that it authorizes the definitive cessation of sedation. the objective of the study and demonstrate the place of tracheotomy in neuro-resuscitation patients, and prevent its complications. a retrospective descriptive study of 597 patients hospitalized in the neuro-resuscitation unit during the period 1 january to 31 december 2016, of which 113 patients benefited from surgical tracheotomy, is a frequency of 19% of all inpatients during this period. clinical, para-clinical, etiological, and therapeutic data were collected from hospitalization records. in a series of 597 hospitalized patients, during the defined period, 113 patients had surgical tracheotomy, a frequency of 19%, in the literature two studies or the data were extremely variable, with 29% in the study namen versus 2.9% in the coplin study. of the 113 tracheotomies, 6 were performed by neurosurgeons, and 107 by resuscitators at a frequency of 95%. the tracheotomy was performed on average 7 days after the intubation of the patients, after verification of the impossibility of the extubation of the latter either for central affection of the ventilatory controls, or reached the mixed nerves and disorders of the laryngo-pharyngeal intersection and according to expert recommendations in 2017-tracheotomy should not be performed in the intensive care unit before the fourth day of mechanical ventilation. different pathologies that patients suffered and required tracheotomy were: post-operative complications of brain tumors (brain stem and mixed nerves) with 52 patients, a rate of 46%, vascular pathologies (stroke and cvt)), with 32 patients (28%), traumatic pathologies, with 29 patients (26%). 21 cases, 19%, 4 cases of secondary bleeding of the orifice, 2 cases of tracheal stenosis, and 1 case of tracheomalacia. the decan made after pharyngolaryngeal neurological examination, and according to sfar 2017 recommendations experts suggest that a multidisciplinary decanulation protocol available in resuscitation departments. conclusion: tracheotomy in neuro-resuscitation has its place, especially in view of the different complications specific to this type of patient, but no study has demonstrated its improvement in vital prognosis. post-tracheotomy complications can be considerably reduced if the protocols and expert recommendations are applied. introduction: noninvasive ventilation (niv) in intensive care (icu) is associated with the occurrence of frequent asynchronies related to the leaks around the interface, mainly auto-triggering and delayed cycling. their detection requires a respiratory muscles activity monitoring. diaphragmatic ultrasonography is a simple imaging technique available at bedside to assess diaphragm motion. whether diaphragmatic ultrasonography would allow detecting asynchronies due to leaks during niv is unknown. the aim of this study was to assess two methods of diaphragmatic ultrasonography (excursion and thickening), coupled with the airway pressure signal to detect patient-ventilator asynchronies during niv. patients and methods: nine healthy subjects were placed under niv and subjected to intentional inspiratory and expiratory leakage on the ventilator circuit to generate delayed cycling and auto-triggering, respectively. the flow, airway pressure and diaphragmatic electromyogram were collected in order to identify the asynchronies generated by the leaks. in the meantime, an ultrasound recording of the excursion of the right diaphragm and of the thickening of the right diaphragmatic zone of apposition were performed and combined with the display of airway pressure on the ultrasound screen. these records were analyzed a posteriori to define the diagnostic performance [including sensitivity (se), specificity (spe), positive predictive value (ppv), and negative predictive value (npv)] of the excursion and the thickening to detect asynchronies. the experimental setup generated a median of 34 asynchronies per subject (interquartile range 24-44). auto-triggering was correctly identified by continuous recording of both excursion (se = 93%, spe = 99%, ppv = 93%, and npv = 99%, fig. 1a ) and thickening (se = 94%, spe = 99%, ppv = 95%, npv = 99% + fig. 1c ). delayed cycling was detected with a slightly lower performance by diaphragm excursion (se = 85%, spe = 98%, ppv = 84%, npv = 98% + fig. 1b ) and thickening (se = 89%, spe = 98%, ppv = 86%, npv = 99% + fig d) . discussion: these encouraging results may be tempered by a variable effectiveness of the technique from one subject to another, in particular concerning the excursion. moreover, their generalization to critically ill patients may depend on several factors including echogenicity, stability and amplitude of the ultrasound signal in this population. conclusion: ultrasound is a simple clinical tool available at the bedside to detect delayed cycling and auto-triggering associated with niv leaks, provided that the airway pressure curve is displayed on the screen of the ultrasound machine. further studies are needed to assess its usefulness in detecting other types of asynchronies and its feasibility in critically-ill patients. introduction: although extra-corporeal co2 removal (ecco2r) is not recommended, strong rational supports the concept. we aimed to describe our single-center experience of ecco2r in the setting of mild to moderate acute respiratory distress syndrome (ards) and chronic obstructive pulmonary disease (copd). we performed a retrospective case note review of patients admitted to our tertiary regional intensive care unit (icu) and commenced on ecco2r from november 2015 to august 2017. demographic data, physiologic data (including ph and partial pressure of carbon dioxide in arterial blood [paco2]) before ecco2r starting, and at day 1 were recorded. results: twenty one patients received ecco2r. thirteen were managed with hemolung ® device, seven with prismalung ® and one with ila ® . indication for ecco2r were copd exacerbation (n = 11), mild to moderate ards (n = 8), uncontrolled hypercapnia due to pneumonia (n = 1), and hypercapnia due to bronchial compression by mediastinal adenopathy (n = 1). before starting ecco2r, median minute ventilation, ph and paco2 were respectively 7. 2 [6.5, 8.5 conclusion: our observational cohort shows that ecco2r therapy is effective to reduce paco2 and improve ph in the settings of mild ards and copd exacerbation. however, early weaning of sedation and pressure support ventilation might limit the decrease of respiratory rate and tidal volume. introduction: duchenne muscular dystrophy (dmd) is an x-linked recessive genetic disorder, caused by mutations in the dmd gene. respiratory failure is classical in the natural history of this disease. little is known about the diaphragm echographic pattern and the spectrum of patients with diaphragmatic paralysis in this disease. we aimed to assess the relationship between age and diaphragmatic motion and thickening fraction (tf) and to characterize the spectrum of patients with diaphragmatic paralysis. patients and methods: we included retrospectively dmd patients who experienced diaphragmatic echography and spirometry in our institution. diaphragmatic paralysis was defined as a diaphragm with tf < 20%. results: 38 dmd patients were included in this study. all dmd patients were wheelchair bound. dmd patients had severe respiratory insufficiency with a median vc at 11% of predicted value [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] . 87.5% of patients were on home mechanical ventilation (hmv) and 28% were invasively ventilated. right diaphragmatic motion at deep inspiration was severely altered with a median of 8.4 mm [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] . right tf of the diaphragm was severely altered with a median of 13. 3% [7.7-27.2] . 66.6% of patients disclosed a paralyzed diaphragm pattern with a right tf < 20%. the age was inversely correlated with tf of the diaphragm (r = -0.56, p 0.016) and with the right diaphragm inspiration motion (r = − 0.68 p < 0.0001). patients with diaphragm paralysis were older with median age at 32.5 years [31-39.5], with severe respiratory impairment (median sitting cv = 6%) and median cumulated annual hmv duration at 12.5 years. conclusion: in dmd, age is inversely correlated with diaphragm function. diaphragm paralysis is frequent in older adult non-ambulant dmd. . the final probability model included the previous identified factors in addition to age and saps ii score, this model exhibited good calibration (hosmer-lemeshow x 2 , p = .98) and good discrimination (roc-auc, 0.94 + 95% confidence interval, 0.92-0.96) (fig. 1) . conclusion: our cohort study identified risk factors of icu death, mainly collected at admission among patients with aecopd. the proposed probability model has a good performance in predicting the short-term prognosis. further evaluation in other cohorts is needed. introduction: precarity is a complex notion including several components, and its definition is still debated. it is more subtle than financial poverty alone, and can increase population's health insecurity. we hypothesize that patients with precarity features may have different epidemiologic characteristics and icu outcomes than the general population. the aim of this study was to describe precarity features and outcomes of patients admitted to an icu located in a high poverty rate territory. patients and methods: we conducted a prospective single-center observational study of all patients admitted to icu of the saint-denis general hospital, from february to july 2017. precarity features were classified in 4 categories-absence of health insurance, lack of incomes or minimum allowances, homelessness or social home or hotel, and social isolation (no social link, or associations or neighbors). others social data were collected (speaking fluent french and education level) as well as usual clinical icu data. results: among 241 patients included, precarity features were found in 83 patients (35.3%). income precarity was the most common, followed by accommodation precarity, health precarity and relation precarity (table 1) . precarity was not associated with hospital mortality (37 vs. 25.7%, p = 0.20). all types of precarity were significantly associated with each other. precarious patients were younger (63 vs. 40 years-old, p < .01) and had less comorbidities. we found no differences concerning hospital or icu length of stay (12 vs. 11 days, p = 0.53) or concerning education level between precarious patients and the others. conclusion: our pilot study shows that precarity features are indeed very frequent and are often cumulated. with respect to the small patient sample, precarity does not seems to be associated with hospital mortality or length of stay. further investigations with larger patient samples and multicenter designs are warranted to investigate properly the impact of precarity on icu management and outcomes. introduction: population aging is a global and expanding phenomenon. elderly people are particularly vulnerable, and often need health care. this demographic evolution also affects intensive care units, and 80 years old patient are now frequently admitted-it corresponds to 15% of admission in france. indeed we have analyzed the change in management of this very elderly people (80 years old and more) over the past 14 years in a french medical intensive care unit in a provincial university hospital. patients and methods: a retrospective cohort study was conducted using medical intensive care unit registry for demographic, physiological and diagnostic data from january 2003 to december 2016. characteristics and treatment intensity during medical icu stay were specified, and short term and long term mortality were also recorded. results: a total of 6608 admissions, including 689 octogenarians and older, were registered during the period. the proportion of very elderly people gradually increase from 4 to 11%. intensity of treatment (organ support) increased from 1.14 from 1.31 per patient between the primary and the second part of the period, notably linked to mechanical ventilation (56 vs. 66%, p < 0.01) and vasopressor infusion (35 vs. 46%, p < 0.01). even if severity score increased (saps 2 increase from 52.7 to 60.5, p < 0.01), the icu mortality remains constant (34 vs. 32.8%). however, we were surprised to observe an increase in 1 year mortality (62 to 74%, p < 0.01). conclusion: between 2003 and 2016, proportion of admission of very elderly people has increased two fold in our icu. although treatment intensity increases for more severe patients, icu mortality remains the same. nevertheless, absence of beneficial effect after 1 year remains questioning. could icu to ward transfers and care course after hospital be optimized? lived alone at home, 40% in couple or with ther family, 21 (9%) in retirement home and 16 (7%) in nursing home. 40 (17%) had a simplified ald score lower than 4 indicating good functional independence. the more frequent diagnosis were acute pulmonary oedema and exacerbated copd. the mean simplified acute physiology score (saps ii) was 53 ± 21. the treatment were were invasive mechanical ventilation 84 (36%), only with noninvasive ventilation 50 (21%), vasopressor agents 79 (33%) and 4 (2%) with renal replacement therapy. the average length of stay was 5.9 ± 6.1 days. after adjustment on sap-sii (without age), those invasive treatments were not associated with mortality no more than age. global mortality rate was 28%. 53 (22%) were subject of a procedure for limiting therapeutics, among which 35 (66%) died in the unit versus 17% for the other patients. the decision of therapeutic limitation was associated with severity of illness as measured by the sapsii (p = 0.01) but not with age. frequency of therapeutic limitation were similar in icu and intermediate care units. the mortality rate is lower than the older studies (s de rooij 2005-38%). unlike the study of p. biston (2013) which covers only the most serious cases, the mortality for any type of gravity remains reasonable. the procedure for limiting care were frequent especially for the most severe pathologies but all the patients who a decision of limiting care were stated were not dead. the patients over 85 years old admit in french icu are very chosen. any major treatment appear to enhance mortality. introduction: due to advancements in medical technology and management of illnesses, an increasing proportion of critically ill patients are elderly. few information is available on the prognosis of these patients after icu discharge. the aim of this study was to analyze the clinical characteristics and long-term outcomes of elderly admitted to icu. patients and methods: monocentric, observational prospective study was performed. all elderly survivors (aged ≥ 65 years) after an icu stay in a medical tunisian icu between january 2014 and december 2015 were included. data collected were: clinical features at admission, acute management procedures, functional characteristics and vital parameters (blood pressure, heart rate, abg's) at icu discharge. patients were followed during 1 year via phone calls. a multivariate regression analysis was used to identify risk factors for one-year mortality. results: during the two-years study period, 102 elderly patients were discharged alive. 60 (58.8%) were male. clinical features of elderly survivors were: mean age, 74.9 ± 6.54 years, median of charlson index, 2 [0-7], chronic respiratory disease, 70 (68.6%), hypertension, 46 (45.1%) and diabetes 39 (38.2%). the most common reason for admission was acute respiratory failure in 80 (78.43%) patients and mean saps ii was 34.9 ± 9.7. 45 (44.1%) patients required invasive ventilatory support, 43 (42.2%) vasoactive drugs and 3 (2.9%) received renal replacement therapy. the median of icu length of stay was 6 days. the follow up was possible for 80 (78.4%) patients. mortality rate at 1 year was 37.5%. predictors of one-year fatal outcome in univariate analysis were as follows-saps ii (p = 0.009), heart rate at discharge (p = 0.039), decline in functional status (p = 0.000), world health organization (who) performance status at discharge (p = 0.000) and readmission within 1 month (p = 0.000). multivariate regression showed that saps ii (or, 1.11 + 95% ci [1.02-1.20] + p = 0.01), who performance status at discharge (or, 3.64 + 95% ci [1.92-6.9] + p = 0.000) and heart rate (or, 1.06 + 95% ci [1.01-1.12] + p = 0.01) were independent risk factors of one-year mortality. conclusion: this study suggests that age and comorbidities should not be exclusion criteria for icu admission. in the long-term only saps ii, performance status and heart rate were significantly associated with one-year mortality in the elderly icu survivors. introduction: triage is an act performed at the entrance of emergency departments (ed's), it allows the classification of patients in different categories according to the seriousness and the priorities of treatment. vital emergencies are geared towards resuscitation room. in our ed, triage is not codified and is «done» in most cases by an unqualified staff. the aim of this work is to show the impact of absence of triage on the functionning of the resuscitation room. patients and methods: it's a prospective study, conducted in the ed of a university hospital, over 6 months, including all patients over 15 years old, admitted at the resuscitation room. epidemiological and clinical data of patients, their ccmu classification (classification clinique des malades aux urgences) have been specified, as well as their outcomes. we collected 366 patients. the average age was 51.24 years old (15-97 years), for a sex ratio of 1.57. forty patients (10.1%) arrived «standing» at the ed. patients ccmu 1 and 2 represented 41.3% of these admissions. the systolic blood pressure was under 90 mmhg in 25% of cases, the glasgow coma scale < 8.15 in 18% of cases, and the spo2 < 90% in 23% of cases. mortality was 5.5%. the other patients were admitted at the intensive care unit (36%), at the short stay hospitalization unit (33.6%), at the operating room (13.4%), or transferred to other departments (9.2%). discussion: the patients ccmu 1 and 2 arrived by ambulance, «lying» , were considered as severe. the proximity of the resuscitation room of consultation rooms allows it to be used sometimes in flows' management and as a place of triage. the patients transferred straight to services didn't show signs of vital distress motiving their initial admission at resuscitation room or even at ed. those admitted at the short stay hospitalization unit were steady, but needed complementary examinations, specialized expert advice, or were waiting for a downstream bed. conclusion: a triage system must be introduced at the entrance of our emergency departments. the staff involved in that sorting must be identified, and disposing of a triage scale in order to figure out the degree of priority associated to patients conditions, and direct the ones needing urgent care towards the resuscitation room. results: one hundred patients were included, with average age of 59.5 years old (25-84) and sex ratio of 1.12. these patients were brought to emergencies by their family in 83% of cases. reasons for admissions were varied, severe deterioration of their general condition (41%), alteration of consciousness (28%), respiratory distress (13%), convulsive seizures (12%). therapeutic interventions were cardio-pulmonary resuscitation (2%), fluid volume expansion (91%), mechanical ventilation (15%), administration of vasopressors (23%) and anticonvulsants (12%). mortality at the resuscitation room was 13%. thirty eight patients were admitted at the intensive care unit, equally at the short stay hospitalization unit (ssu) of ed. two patients returned home at the request of their family. discussion: these results show that ed's remain the last resort in front of oncology patient who is deteriorating, the occurrence of complications, and sometimes, the psychological exhaustion or family's obstinacy. emergencies departments continue admitting patients with terminal cancer, but are not organized for medium and long term care. the creation of a palliative care unit and the organization of home-based care will allow the prevention and treatment of complications as well as a psychological care, thus improving the living quality of these patients and their relatives. refusal of intensive care admission: assessment of a tunisian icu practices merhabene takoua introduction: need of intensive care exceeds its availability in several countries. as a consequence, rationing intensive care unit (icu) beds is common and often leads to admission refusal. purpose-to report refusal determinants and characteristics of patients associated with decisions to deny icu admission. this study was performed at the icu of abderrahman mami hospital, a 22-bed icu in ariana, tunisia. it was a prospective study enrolled between 1st january and 31th december 2016. no predefined admission criteria were determined. decisions to admit are based on a combination of patient-related factors, severity of illness and bed availability. all consecutive patients referred for admission to icu during the study period were included. 2 groups were defined gi-admitted patients and gii-refused patients. the reasons for refusal were categorized as follows: too well to benefit, too sick to benefit, patient or family refusal, necessity of other exploration not available in our institution and unit too busy. results: during the study period, icu admission was requested for 1081 patients of whom 590 were admitted (54%). of the 491 patients refused, only 41 were admitted to icu later. refusal of icu admission came in 23% of cases from the emergency room and wards of our hospital, in 65% from other hospitals of whom 30% without icu. reasons of refusal were no beds availability (76.2%), too sick to benefit from icu (13%), too well (9.4%) and necessity of other exploration (1.4%). no differences in demographic characteristic between the two groups were noted. among the refused patients, when compared with admitted patients, we found higher proportions of hematologic malignancies (p < 0.01) and cardiocirculatory arrest (p = 0.01). on the other hand, admitted patients were more likely to have cardio-respiratory comorbidities (437/590 vs. 297/491, p = 0.01) and more need to mechanical ventilatory support (404 590 vs. 166 491, p = 0.016). conclusion: our study confirms that icu refusal rate still high. it depends on both icu organization and patient characteristics. acute heart failure syndroms in intensive care: clinical features, management and outcome jamoussi amira 1 , ajili achraf 1 , merhebene takoua introduction: classification of acute heart failure (ahf) into 5 clinical scenari (cs) was first proposed to facilitate early management (1) . a decade after implementation of this approach, epidemiological and evolutive data based on this classification are interesting to investigate. that is why we aim to describe frequencies, management and mortality of each ahf syndrom in intensive care. a prospective study of patients > 18 years with ahf admitted to the medical intensive care unit (icu) of abderrahmen mami hospital from january 2017 to august 2017 was conducted. patients were classified according to the 5 clinical scenari (1). clinical, therapeutic and outcome findings were recorded. results: during the study period (8 months), we admitted 291 patients in icu from whom 43 (14.8%) presented with ahf and then enrolled. the median age was of 63 ± 18.6 years and sex-ratio 1.05. a medical history of copd (20.9%), hypertension (46.5%), diabetes (20.9%), ischemic cardiopathy (28%) and valvular cardiopathy (16.3%) were noticed. at admission, severity assessement scores were: median apache ii 18.5 ± 10.5 and median saps ii 30 ± 17.6. clinical and evolutive characteristics according to clinical scenari are listed in table 1 . conclusion: cs 2 and cs 1 are the most frequent ahf syndroms in icu and also have the best outcome. introduction: in cardiac arrest patients resuscitated from an ischemic ventricular fibrillation or tachycardia (vf/vt), both incidence and risk factors of recurrent severe arrhythmia are unclear. whether it is useful to give a prophylactic anti-arrhythmic (aa) treatment during the first hours and days is debated, particularly when a successful coronary reperfusion was provided. we aimed to evaluate the incidence of severe arrhythmia in patients resuscitated from an ischemic vf vt and to identify risk factors for developing arrhythmia during their icu stay. the procat registry captures all data from patients admitted in a tertiary hospital center after a resuscitated cardiac arrest (ca). we selected patients with an initial vf vt caused by an acute coronary syndrome (acs) and who were successfully treated with early percutaneous coronary intervention (pci) on admission. the primary endpoint was the recurrence of major arrhythmia between icu admission and icu discharge. all arrhythmias resulting in ca recurrence and or severe arterial hypotension requiring infusion of vasopressors were classified as major arrhythmias. multivariate logistic regression identified factors associated with the occurrence of major arrhythmias. results: between 01/2007 and 12/2016, 256 consecutive ca patients were included in the analysis. all patients underwent a successful pci of the infarct-related artery on hospital arrival. the only drug used as a prophylactic aa treatment was amiodarone, which was employed in 104/256 patients (41%). overall, 29/256 patients (11.3%) had a major arrhythmia recurrence during their icu stay. a large majority of these major arrhythmia recurrences (79.3%) occurred during the first 24 h. characteristics of patients with and without major arrhythmia recurrence are described in the table 1 . in multivariate analysis, public place location (or 0.3 [0.1-0.9], p = 0.029) and male gender (or 0.3 [0.1-0.9], p = 0.036) were both associated with a lower risk of major arrhythmia recurrence during the icu stay. prophylactic aa treatment was not associated with a lower risk of recurrences of major arrhythmias (or 0.9 [0.3-3.1], p = 0.870). conclusion: despite an early coronary reperfusion, more than 10% of our post-cardiac arrest patients experienced a recurrent severe arrhythmia during the post-resuscitation period, mostly during the first 24 h in the icu. this proportion is much higher than what is reported in common acute coronary syndrome (without cardiac arrest) and further studies are needed to explore protective strategies. introduction: during symptomatic treatment of septic shock, markers of anaerobic metabolism may be used in a goal-oriented strategy. the recent international guidelines for management of sepsis and septic shock 2016 suggested guiding resuscitation to normalize lactate as a marker of tissue hypoperfusion. the purpose of this study was to evaluate the kinetics of lactate and other markers during the first three hours and to compare their levels between survivors and non survivors. we conducted a prospective, observational, single-center study of patients admitted to a general icu from the may to august 2016. inclusion criteria were patients age ≥ 18, intubated and under mechanical ventilation with septic shock as defined by the third international consensus conference. simultaneous sampling of arterial and central venous blood gas were collected at h0 and h3 to obtain lactate (mmol/l), and scvo2 (%). delta pco2 (mmhg) and delta pco2/cavo2 (mmhg/ml) were computed by our patient data management system and presented as a chart with additional hemodynamic data for clinical decision support. comparisons of values between groups were made by mann-whitney u test as appropriate. p < 0.05 was considered statistically significant. all reported p values are two-sided. statistical analysis was performed using systat ver. 11.0. results: we studied 19 intubated septic shock patients aged 71 ± 10 years, saps ii 68 ± 23, sofa 11 ± 3.6. community pneumonia and peritonitis were the major sources of infection. icu mortality rate was 58%. all patients received norepinephrine (0.62 ± 0.5 µg/kg/ min), two patients received dobutamine (5.5 ± 0.2 µg/kg/min). the evolution of markers is summarized in table 1 . at h0 and h3, arterial lactate levels were higher in non-survivors than in survivors, but did not decrease at h3 in both groups. at h0 there was no statistical difference concerning scvo2, delta pco2 and delta pco2/cavo2. after three hours of resuscitation, delta pco2 and delta pco2/cavo2 ratio decreased and scvo2 increased in survivors. survivors had lower delta pco2 and delta pco2/cavo2 ratio than non survivors. conclusion: although high lactate level is a key signal of anaerobic metabolism, it did not decrease during the first three hours in this group of severe septic shock patients. instead of using lactate, delta pco2 and delta pco2/cavo2 kinetics could be integrated in a goaloriented strategy for septic shock resuscitation. introduction: to assess whether, in patients under mechanical ventilation, fluid responsiveness is predicted by the effects of short respiratory holds on cardiac index estimated by oesophageal doppler (cidoppler). patients and methods: in 28 patients, before infusing 500 ml of saline, we measured cidoppler before and during the 5 last seconds of successive 15-second end-inspiratory occlusion (eio) and endexpiratory occlusion (eeo), separated by 1 min. patients in whom volume expansion increased cardiac index (transpulmonary thermodilution) > 15% were defined as "fluid responders". results: eeo increased cidoppler more in responders than in nonresponders (8 ± 2 vs. 3 ± 1%, respectively, p < 0.0001) and eio decreased cidoppler more in responders than in non-responders (-9 ± 5 vs. -4 ± 2%, respectively, p = 0.0002). thus, when adding the absolute values of changes in ci observed during both occlusions, cidoppler changed by 18 ± 5% in responders and 7 ± 2% in nonresponders. fluid responsiveness was predicted by the eeo-induced change in cidoppler with an area under the receiver operating characteristic (roc) curve of 1.00 (95% confidence interval-0.88-1.00) and a threshold value of 4% increase in cidoppler. it was predicted by the sum of absolute values of changes in cidoppler during both occlusions with a similar area under the roc curve (0.99 (0.86-1.00)) and with a threshold of 9% change in cidoppler, which is more compatible with oesophageal doppler precision. in this case, the sensitivity was 100(77-100)% and the specificity was 93(66-100)%. conclusion: if consecutive eio and eeo change cidoppler > 9% in total, it is very likely that volume expansion will be efficient in terms of cardiac output. the measurement of cardiac output using a signal morphology-based form of impedance cardiography (physioflow ® ) in intensive care unit: comparison with the trans thoracic echocardiography. introduction: in the intensive care units, the cardiac output (co) is one of the main hemodynamic parameters required to manage patients in shock. the physioflow ® is a new non-invasive method using the waveform analysis of the thoracic impedance signal (ti) to assess co. in hemodynamicaly unstable patients, no studies have evaluated the level of agreement between the co estimated by transthoracic echocardiography (co-tte) and that measured using the waveform analysis of thoracic impedance physioflow ® (co-ti). the objective of this study was to evaluate the ability of co-ti relative to co-tte to estimate the absolute co value and detect the expected variation co (v-co) in critically ill patients. patients and methods: fourteen patients sedated and mechanically ventilated, in shock under catecholamines and monitorred with tte and ti physioflow ® were included. hemodynamic datas, stroke volume (sv) and co with two monitoring were performed at baseline 2 min before passive leg raising (plr), 30 s after plr and 2 min after volume expansion (ve) of 500 ml of saline solution. responders were defined by an increase > 12% of cardiac output (v-co) after plr. results: fourteen pairs of tte and ti measurements were compared. the median (iqr) age was 69 years (55-76), igs2 was 54 (40-69). only 3 patients were responders after plr. there was a significant correlation between the co-tte and co-ti measurements (r = 0.807, p < 0.0001). the median bias was 0.8 l/min and the limits of agreement (loas) were −3.5 and 1.9 l/min. there was a significant correlation between v-co-tte and v-co-ti (r = 0.77, p = 0.0022) (fig. 1) . the median bias was-5.2% and the loas for v-co were respectively -26.5 and +16.5%. conclusion: the co measured with physioflow ® , a signal morphology-based impedance cardiography, is correlated to the co measured with tte. however, the high loa observed in this preliminary study underline the necessity to remain careful and wait for further inclusions. -9] vs. 5.5 [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] days, p = 0.05). despite imbalancedunderlying characteristics in terms of demographics and comorbidities, in-icu mortality rates were similar between patients (35.7 vs. 37%, p = 0.75). conclusion: prior bb treatment have limited impact on the severity of acute circulatory failure in septic shock and is not associated with increased mortality despite the underlying frailty of patients. introduction: cardiac output monitoring is a key component in the management of critically ill patients. cardiac output estimated by transthoracic echocardiography is documented in patient with atrial fibrillation, but a large part of transpulmonary thermodilution validation studies excluded this specific population. the objective of this study was to evaluate cardiac output mesurement and trend ability by transpulmonary thermodilution relative to transthoracic echocardiography in critically ill mechanically ventilated patients with atrial fibrillation. patients and methods: thirty mechanically ventilated patients requiring hemodynamic assessment were included in a prospective observational study. cardiac output was mesured simultaneously with transpulmonary thermodilution and transthoracic echocardiography. seventy-four pairs of cardiac output measurements were compared. the two measurements were significantly correlated (r = 0.769 et p < 0.0001). the mean bias was -0.7 l/min, the limits of agreement were -2.9 and +1.6 l/min, and the percentage error was 39.81%. thirty-four pairs of cardiac output variation measurements were compared. there was no significant correlation between cardiac output variation measurements by transpulmonary thermodilution and transthoracic echocardiography. the mean bias was −0.19 l/ min and the limits of agreement were −1.82 and +1.43 l/min. with a 15% exclusion zone, the four-quadrant plot had a concordance rate of 78.6%. the polar plot had a mean polar angle of 14.2° with 95% confidence interval between − 14.2° and 42.7°. conclusion: in critically ill mechanically ventilated patients with atrial fibrillation, cardiac output measurements with transpulmonary thermodilution and transthoracic echocardiography are not interchangeable. introduction: basic critical care echocardiography (cce) relies on transthoracic echocardiography (tte). we sought to assess the diagnostic capacity of a next-generation micro-digital broadband beamformer in patients with cardiopulmonary compromise. all patients with acute circulatory respiratory failure underwent two basic tte assessments using successively a next-generation micro-digital broadband beamformer (64 elements, 1-4 mhz) incorporated in a sector phased array probe with twodimensional, m-mode and color doppler mapping capacities which was connected to a touchscreen interface (lumify, philips), and using a compact full-feature imaging system (80 elements, 1-5 mhz + cx50, philips). tte examinations were independently performed in random order by two intensivists with expertise in cce, within a 10-min time frame without therapeutic intervention. imaging quality was graded from 0 (no image in the corresponding view) to 3 (clear identification of 100% of endocardial boarders). the concordance of qualitative data was assessed using the kappa test and agreement of two-dimensional measurements (left ventricular end-diastolic diameter [lvedd], ratio of right ventricular (rv) and lv end-diastolic diameters [rvedd lvedd] + end-expiratory inferior vena cava diameter [dexpivc]) was evaluated using intraclass coefficient correlation (icc). results: thirty consecutive patients were studied, without any exclusion for absence of tte images (age, 56 ± 19 years, sap-sii, 45 ± 18, 70% ventilated, 60% under catecholamines, lactate, 3.9 ± 3.3 mmol l). the proportion of echocardiographic views eligible for interpretation and mean duration of tte examinations were similar with the miniaturized and full-feature systems (79 vs. 77%, 7.1 ± 2.7 vs. 7.9 ± 4.1 min, p = 0.31). two-dimensional imaging quality grade was lower with the miniaturized system ( system. concordance of two-dimensional measurements was also good-to-excellent (table 1) . conclusion: for basic cce use, next-generation micro-digital broadband beamformer appears providing reliable information with good-to-excellent diagnostic capability, accurate two-dimensional measurements, and adapted therapeutic suggestions. these preliminary data require further confirmation. introduction: acute kidney injury (aki) in very old patients (over 80 years) admitted in intensive care unit (icu) is a frequent issue and is known to be associated with a severe prognosis. we aimed at describing the clinical characteristics and prognosis of such a population. the objective of the study was dual: first to evaluate the short and long term mortality of these patients, second to determine the factors associated with a poor outcome. patients and methods: we conducted a descriptive, retrospective and monocentric study based on the hospital records of patients over 80 years with aki admitted in our icu between january 2013 and december 2016. the patients were selected according to the kdigo criteria (1) . survivals at the discharge from hospital, at day 90 and at 1 year were assessed. the factors associated with mortality at 1 year were scrutinized. results: after excluding 30 patients for an initial therapeutic limitation, the data of 171 remaining patients were reviewed. the patients were 84 years old (interquartile range, iqr 81-86) and were predominantly male gender (61%). saps ii and sofa score at admission were 62 (iqr 57-74) and 8 (iqr 5-10) respectively. 57% of the patients needed for mechanical ventilation and 69% of them needed for catecholamine use. septic (44%), prerenal (38%), iatrogenic (17%) and cardiogenic injury (10%) were the leading cause of aki. dialysis was performed in 42% of patients. the overall mortality at the discharge from icu, at day 90 and at 1 year was 39, 52 and 66% respectively (fig. 1) . neither were the age, the comorbidities, the etiology of aki nor the need for dialysis associated to a significant increase in mortality. a stepwise cox regression analysis revealed saps ii and blood lactate level at icu admission as independent risk factors associated with 1 year mortality. conclusion: aki at admission in icu is associated with a high mortality at 1 year in an elderly population. main long term prognostic factors are linked to the initial severity at icu admission. introduction: the proportion of elderly around the world doesn't stop growing and increases the consumption in health care. however, lots of studies report the impact of the age on the decision to admit a patient to the icu despite no triage recommendation exists. the primary objective was to determine prognostic factors of death for the 80 years and over at admission to the icu and secondly to evaluate their functional prognostic at short and medium term after their exit. patients and methods: prospective and observational study conducted in our icu 30 beds unit from august 2015 to february 2017. patients of 80 years and over were listed. the dying patients arriving after a pre-hospital resuscitation for whom no therapeutic plan has been initiated and those admitted for an organ donation were excluded. the primary outcome was the duration between the admission and the potential death during the follow-up. the secondary outcomes were the necessity to entry an healthcare institution or the loss of one autonomy point on the adl french scale after the hospitalization. results: 107 patients of the 1763 admissions were included. the igs ii and sofa average scores were respectively 70.23 ± 22.47 and 9.02 ± 3.79. the most common diagnosis were a septic shock (23 patients), a cardiopulmonary arrest (21 patients), a cardiogenic shock (9 patients) and a pulmonary oedema or a lung infection (8 patients fig. 1 survival of very old patients with aki in icu (%) each). 75 patients (70.03%) died during the follow up-50 at the icu, 13 during ward and 12 during re-education or after their home return. from a multivariate analysis (table 1) , anisocoria, cardiopulmonary arrest and acute kidney injury (aki > 0) seem to be independent risk factors of death. 32 patients were alive at the end of the follow up. 11 recovered their previous autonomy, 8 needed a place in a specialized institution. all the other lost a part of autonomy 3 months after their home return with the average loss of one point on the adl autonomy french scale. conclusion: anisocoria, aki and cardiopulmonary arrest seem to be independent risk factors of death for those patients. concerning the survivors, a stay at the icu lead to an increased dependency. other studies have to be led to evaluate which of our patients could have get the best benefit of their stay to prevent from a misuse of the structure. introduction: context-among the severe complications of preeclampsia, acute kidney injury (aki) poses a dilemma if features of thrombotic microangiopathy (tma) are present. although a hellp syndrome is considerably more frequent, ruling out a flare of atypical haemolytic and uremic syndrome (hus) is then of utmost importance. objective-to improve the differential diagnosis procedure in cases of post-partum aki. patients and methods: a hundred and five cases of post-partum aki, admitted in the last 5 years (2011) (2012) (2013) (2014) (2015) in french icu from 9 different regions, were analysed. initial and final diagnosis, renal features, haemostasis and tma parameters were all analysed, paying a special attention to their dynamics within the first days following the delivery. results: the main circumstances of aki were severe preeclampsia (n = 40), post-partum haemorrhage (pph, n = 20) and primitive tma (n = 14, including 10 atypical hus and 4 thrombotic thrombocytopenic purpura). among the thirteen cases of renal cortical necrosis, 11 were associated with preeclampsia. congruence between the initial and the final diagnosis was low (63%). thus, none of the women referred to our centers for a suspicion of non-placental tma has received a final diagnosis of non-placental tma (and instead had a pe or a pph). conversely, all women with a final diagnosis of nonplacental tma were referred for a suspicion of pe-related tma, or with a pph which polluted the diagnosis. tranexamic acid was largely used in the context of pph (82%), at a dose up to 5 grams total. taking into account the final diagnosis, we subjectively concluded that plasma exchanges and eculizumab were abusively indicated in 5 and 2 cases, respectively, of typical hellp syndrome. plasma exchanges were in itiated in all 14 cases, a mean 84 h following the admission. dynamics of hemoglobin, haptoglobin, and liver enzymes were poorly discriminant. the dynamic pattern of ldh and of platelets, in contrast, was statistically different between primitive tma-related aki and other groups-at day 3, platelets increased in preeclamptic women, and in other circumstances, but not in patients with primitive tma. a classification and regression tree (cart) independently confirmed the usefulness of platelets and ldh trajectory in the diagnostic algorithm (fig. 1) . conclusion: the trajectory of ldh and platelet count is useful to identify the cause of post-partum aki, and the clinician may reasonably take therapeutic decisions at day 3 post-delivery. introduction: continuous veno-venous hemofiltration (cvvhf) is a common practice in intensive care units (icu). because it is continuous, the choice of anticoagulation is essential-regional anticoagulation fig. 1 analysis of post-partum aki cases with citrate or systemic with unfractionned heparin or low molecular weight heparin (lmwh). filter's lifespan is a major issue regarding filtration's effectiveness and cost. in this study, we compared the filter's lifespan between lmwh and citrate anticoagulation. patients and methods: a monocentric retrospective study was led from january to october 2016. all the cvvhf sessions during this period were included. prismaflex© monitors (hospal) were used. practioners were free to choose between citrate or lmwh defining 2 groups. we aimed a post filter ionized calcemia between 0.25 to 0.5 mmol/l in citrate group + and a post filter anti xa activity between 0.2 to 0.5 ui/ml in lmwh. results: 95 cvvhf sessions were included-64 with lmwh anticoagulation, and 31 with citrate. patients were 62 years old on average, primarly males (65%), with an initial average saps ii score of 73. icu mortality was 51%. patients' hemostasis was measured before each cvvhf session, without any significant difference between the 2 groups. global filter's lifespan was 47 h + 54 h in citrate group versus 44h in lmwh, without significant difference (p = 0.236) (fig. 1) . no serious side effect, especially hemorrhage in the lmwh group, was reported. filtration efficiency, represented by the urea reduction ratio during the first cvvhf session, was similar, 30% ± 20% in lmwh group versus 20% ± 20% in citrate group (p = 0.235). conclusion: both anticoagulation-systemic with lmwh or regional with citrate can be used in icu. both methods enable long and comparable filter lifespan, with similar filtration efficiency and without serious adverse events. our results need to be confirmed by a randomized propective study. introduction: arf during the post-partum period is a rare complication. the main etiologies are post-partum haemorrhage (pph) and thrombotic microangiopathy (tma). rrt may be required. the aim of this study was to identify variables associated with rrt in this population admitted in icu. patients and methods: we conducted a study using retrospectively collected data in a cohort of patient with post-partum arf according to the kdigo criteria and requiring icu in the university hospital of lille from 2008 until 2016. two groups were compared-rrt and non rrt patients. demographic and obstetrical data as well as data during icu stay and patients' outcome were collected. etiologies of arf, kdigo stage, anuria, hemolysis parameters and biological data at icu admission were studied. comparisons were made using a chi-two or fisher exact test or a mann-whitney u test. odds ratio (or) for the statistically different criteria were studied. results: twenty-two patients requiring rrt were compared to the 49 patients without rrt. the two main etiologies of arf were tma (50.7%) and pph (35.2%). vaginal delivery was significantly more frequent in the rrt group compared with caesarian delivery (p = 0.04). use of rtt was significantly increased after pph compared the others etiology of arf (p = 0.03). in the rrt group, the icu length of stay was longer (p < 0.0001) and igs ii score was higher (p < 0.0001). higher kdigo score was observed in rrt patients (in the rrt group-kdigo 1 = 0, 2 = 9%, 3 = 91%, and without rrt-kdigo 1 = 38.8%, 2 = 36%, 3 = 36%, p < 0.0001). anuria 24 h after icu admission was more frequent in cases of rtt (86.3% versus 20.3%, p < 0.0001). hemolysis was greater in rrt patients with lower haptoglobin (p = 0.02) and increased lactate deshydrogenase (ldh) (p = 0.04). the association with rrt requirement was stronger with the duration of anuria, with an or at 6 h at 31. 3 [8.1-121.7 ] and at 24 h at 72. 2 [8.3-622] . a lower haptoglobin was associated with a higher risk of rtt (or 3.7 [1.2-11.7 ]), as well as pph (or 3.1 [1.1-8.8] ) and vaginal delivery (or 2.9 [1.02-8.1]). conclusion: hemolysis parameters and anuria seemed useful criteria to identify patients at higher risk of rrt early during their icu admission. introduction: renal replacement therapy (rrt) has three aimsrestoring homeostasis, ensuring survival and preserving the potential for renal recovery. the main indication of rrt in icu is acute renal failure, correlated with a very important rate of mortality despite the progress made in its management. patients and methods: the objective of this work is to take stock of the indications and the objectives of the rrt in icu. through a prospective study, we report a serie of 39 cases, collected at the multipurpose resuscitation unit of the avicenna military hospital in marrakech between september 2015 and september 2016. results: the average age of our patients is 65, 10 ± 24, 89 years with extremes ranging from 34 to 90 years and a male predominance (77%). the main reasons for admission were hemodynamic distress in 43.5% of cases, followed by septic shock in 30.7% of cases, neurological and respiratory distress were noted in 20.5 and 5.3% of cases, respectively. rrt indications were severe acidosis in 27% of patients, followed by 21% hyperkalaemia, acute pulmonary edema in 13%, hemodynamic instability in patients with chronic renal failure in 12%, acute renal failure in 8%, and hyperuriaemia in 5% of cases. the technique chosen is conventional intermittent hemodialysis with a synthetic membrane. the main duration of the sessions was 2 h 06 min ± 45 mn. vascular access was a right internal jugular catheter in 49.7% of patients and left in 2.5%, right femoral catheter in 34.8% of patients and left in 2.4%, arteriovenous fistula (fav) and a tunneled catheter in 7.9 and 2.7% of patients. mortality was 61, 55%, chronicity progressed in 10.25% of cases and total or partial recovery of normal renal function in 28% of cases. conclusion: we have a high rate of mortality in our icu that's why we will focus on prevention of risk of renal failure in our patients. introduction: there is limited information on the outcome of acute kidney injury (aki) in patients with traumatic intracranial hemorrhage (tich). tich patient with aki was related high mortality rate. the aim of this study is to estimate the outcome using different renal replacement therapy on the survival rate and rate of long term renal-replacement therapy in adult tich patient. patients and methods: we retrospectively identified a total of 310 tich patients with aki who required glycerol or mannitol therapy admitted to the intensive care unit during a 10-year period ending dec 2010 from the national health insurance research database. demographic data, severity of tich, medication, level of care, type of head surgery were collected. all patients subjects were older than > 18 years. we also excluded patients diagnosed with tich before the cohort entry date, hemodialysis before tich, chronic kidney disease cancer coagulation defects purpura and other hemorrhagic conditions, mortality mechanical ventilation ischemic heart disease before tracking. the primary outcome was overall survival at day 30. the secondary outcome was the rate of long term hd therapy. results: a total of 310 patients were enrolled. the kaplan-meier estimates of mortality at day 30 did not differ significantly between the continuous veno-venous hemofiltration (cvvh) and hemodialysis (hd) strategies + 5 deaths occurred among 134 patients receiving cvvh-strategy group and 9 deaths occurred among 176 patients receiving hd-strategy group (adjusted hazard ratio: 0.782, 95% ci 0.239 to 2.558; p = 0.685). the rate of long term hd was higher in the hd-strategy group than in the cvvh-strategy group (15.34 vs. 7.46%, p = 0.021) especially in injury severity score ≥ 16 group (table 1) . discussion: in our study, tich patient with aki receving cvvh may have effect on renal blood flow protection or cytokine removal which lower the rate of long term hd. conclusion: these clinical data provides readers interventions to improve outcomes in this population and future study are needed to confirm the result. this study highlights the importance different renal replecement therapy in the tich with aki population (table 1) . khaleq khalid 1 , hattabi khalid 1 , bensardi fatima zahra 1 , bouhouri m. a 1 , nciri a 1 , hamoudi d 1 , alharrar r 1 introduction: the combined progress of abdominal surgery and anesthesia lead to more frequent surgical indications, including for fragile patients or serious pathologiespostoperative morbidity and mortality is an element that requires evaluation and analysis in surgical resuscitation. although pathological processes and new therapeutic approaches in surgery are currently well known, data on risk factors for morbidity and mortality are less available. the aim of our work is to evaluate the post-operative morbidity and mortality rate and to identify the main predictive factors. patients and methods: a retrospective-cohort, unicentric study that included all consecutive patients hospitalized in the surgical resuscitation department after abdominal surgery regardless of the operated organ, during 3 years. the structured sheet of data collection included more than 100 items on all perioperative data concerning the patient, the disease, and the operating surgeons. postoperative mortality and morbidity were defined as in-hospital death and complications. a first descriptive analysis of the various parameters collected was carried out a bivariate analysis was then performed to study the factors affecting morbidity and mortality in digestive surgery the comparison was made using the student's t test for quantitative variables and the chi square for the qualitative variables. a difference is considered significant when p < 0.05 (5%). results: among 360 patients, the in-hospital death rate was 15.08% and the overall morbidity rate was 41.61%, the mean age was 55.54 ± 15, 10 years with extreme ages of 18 years and 85 years with sex ratio of 1.01. five factors were incriminated in post: operative mortality notably:renal failure p = 0.002, duration of stay p = 0.001, parenteral nutrition p = 0.047, long duration of intubation p = 0.001, perioperative blood transfusion p = 0.001. three factors influencing morbidity were found: duration of stay p = 0.003, parenteral nutrition p = 0.018, long duration of intubation p = 0.0001. conclusion: knowledge of the true frequency of both mortality and morbidity is crucial in planning health care and research and identifying risk factors. introduction: tools to quantify and assess bowl management in critically ill are still very limited and often over-looked. with the primary fig. 1 filter's lifespan concern of optimizing patients to preserve life, the problem of bowel care has been given less priority. the aim of this study was to use ultrasonographic measurements of gastric emptying in the critically ill as a tool of measurement of the impact of different specific factors of icu stay on bowl emptying. patients and methods: this is a prospective study conducted in an intensive care unit for 1 months. it included 32 patients. ultrasonic imaging of antral sections was undertaken every 15 min for the first 1 h and every 30 min thereafter until total emptying. correlation analyses were calculated, applying an adjusted significance level (pb < .0125) to correct for multiple testing. results: all our patients were above the age of 18. the median of age was years old 31. 19 of our patients were male and 13 were female. the total emptying median time was 273 ± 21 min. significant correlation was observed between length of stay and delay in bowl emptying. mechanical ventilation had also significant relation with slower bowl progression and gastric emptying. patients in septic shock had tendencies to earlier delayed bowl emptying compare to others patients included in our study. conclusion: the study we conducted is a pilot study. further studies should be conducted and unltrasonografic gastric assessment could be standardized in protocols to assess clinical decision making and improve nutrition and bowl management in icu patients. introduction: enteral nutrition, via a feeding tube, is often used in intensive care units (icu) to supply artificial nutrition to critically ill patients. the feeding tube is also commonly used to administrate drug therapy as well. however, there is a lack of knowledge of the nurses about this way of administration. this could be a potential source of medicine-related illness. the purpose of this study was first, to evaluate the nurse's knowledge on enteral drug administration, and second, to observe nurses and to evaluate the adequacy of their practices with guidelines, and to report medication-administration errors. patients and methods: this prospective study using the observation technique was conducted in 2 icu (one medical and one surgical). first, a knowledge and practice questionnaire regarding drug administration trough enteral feeding tube was filled by each intensivist nurse. secondly, pharmacist performed observations of nurses during preparation and administration of medications. these practices were compared with the original medical prescription and with the data available in the literature. results: 60 questionnaires were returned. 48 nurses evaluated their knowledge as medium and 9 as inadequate. there was a lack of knowledge on the type of drugs which can be used by feeding tube (65 wrong responses). 30 nurses and 71 different drugs were observed during the drug administration phase. no administration totally complied with our institutional protocol, particularly the crush of tablets. when a tablet was crushed, in 31% an alternative formulation (in syrup for example) existed. the correct administration of drugs in feeding tubes is important and represents a challenge in icu. firstly, crushed tablets is the most frequent cause of obstruction of feeding tubes which have to be changed + secondly, crushed tablets destroys the controlled release of enteric coated dosage forms, resulting in a higher or a lower initial blood level. we have to train nurses for drug administration by feeding tube. on their daily ward, the pharmacist should improve the choice of medication's forms. introduction: acute variceal hemorrhage (avh) is a severe complication of portal hypertension. in addition, the variceal bleeding is still the most common lethal complication of cirrhosis. the most effective modality of treating is based on resuscitation combined with the endoscopic variceal band ligation. the purpose of this preliminary study was to find the factors associated with poor prognosis of avh in cirrhotic patients. patients and methods: this is a retrospective study, spread over 12 months between january 2016 and december 2016. are included all consecutive patients with liver cirrhosis hospitalized for variceal bleeding. we exploited the medical records to identify the clinical, biological and endoscopic parameters. results: a total of 30 patients hospitalized for avh occurred during the study period. the mean age at admission was 60 years, and 12 are female. cirrhosis was post viral in 30% of cases. patients were classified as child-pugh c in 40% of cases. the median presenting model for end stage liver disease (meld) and clif sofa were respectively 17 and 8.4. twelve (12) patients received beta-blockers and 15 have required at least one endoscopic variceal band ligation at the time of the bleeding episode. in the acute phase, pharmacological treatment based on vasopressor (sandostatin)) was instituted in all cases and combining with antibiotic prophylaxis (c3g or fluoroquinolone) in 26 cases. in 8 cases the endoscopy was made within 12 h, active bleeding at endoscopy was observed in 20 patients. esophageal avarices (ov) were grade i (2 patients) grade ii (10 patients) and grade iii (18 patients). the eradication of varices was obtained in 23 patients (76.6% percentage of the cases). the variceal bleeding recurred in 9 of patients (30%of cases) and 6 patients died which 4 within the first 5 days. spontaneous bacterial peritonitis (p 0.010), hepatic encephalopathy (p 0.041) and the hemodynamic instability with schok (p 0.01) are correlated with early mortality at 5 days. hepatic encephalopathy (p 0.028) and bacteremia (p 0.05) are corrolated with 6 week motality. non selective betablocker (p 0.013) and primary use of band ligation when indicated (p 0.008) are protective factors and parameters of good outcome. conclusion: despite developing of endoscopic tools and respect of actual therapeutic guidelines in avh, the outcome is still poor. the prognosis appears to be dependent on the clinical condition at admission and primary prevention. introduction: the french intestinal stroke center based on a multimodal and multidisciplinary management has been developed to improve survival and intestinal viability. open surgical revascularization was decided for patients unsuitable for radiological revascularization and or suspected of intestinal necrosis. we aimed to study the prognosis of patients suffering from aoami in icu and who have benefited from open revascularization. single-center, observational and prospective study was carried out in a surgical icu of a tertiary center. patients with aoami managed in our intestinal stroke center from 01 2016 to 09 2017 and who underwent open revascularization were included. results: data of 15 patients were collected. patients' characteristics are described in table 1 . all patients had abdominal computed tomography angiography at the diagnosis, and 11 patients (73%) presented signs of intestinal injury. thrombosis was the main mechanism of superior mesenteric artery (sma) occlusion (14 patients, 93%). all patients received antiplatelet therapy, curative unfractionated heparin therapy and digestive decontamination. open revascularization was performed by sma endarterectomy (4 patients, 27%), sma surgical bypass (8 patients, 53%), retrograde open mesenteric stenting (3 patients, 20%) and coeliac artery bypass (2 patients, 13%). three patients (20%) underwent a radiologic endovascular revascularization attempt before open repair. small bowel resection (100 cm ) was achieved in 8 patients (53%). four patients (27%) had peritonitis. six patients (40%) had one or more relaparotomy ]), usually for hemodynamic instability (83%). only one patient died in icu (7%). icu lenght of stay was 7 days ] and duration of mechanical ventilation was 3 days [iqr 0-7]. overall, haemodynamic failure was present in 10 patients (67%). median duration of vasoactive support was 2 days [iqr 0-4]). severe acute respiratory distress syndrome was observed in 2 patients (13%) and acute kidney injury in 9 patients (60%, including 2 patients who received renal-replacement therapy, 13%). enteral feeding was initiated in 6 patients (40%) with a delay of 3.5 days [ . parenteral nutrition was administered in 13 patients (87%), including 8 patients (53%) without enteral feeding. five patients (33%) were discharged with small bowel syndrome. conclusion: icu patients who underwent open revascularization to treat aoami as part of a multimodal and multidisciplinary management in a dedicated intestinal stroke center have low mortality and intestinal resection rates. larger studies are needed to confirm these results. introduction: precise consequences of late transit in icu remain elusive. we have previously shown that defining late transit by the absence of stool within 6 days after admission was not relevant because it did not identify a group of patients with specific outcome [1] . to further improve this definition, we investigated the differences in outcome among patients according to their bowel movements frequency. patients and methods: preliminary results of a prospective, two centers, observational study. all patients admitted to icu, with a length of stay (los) of at least 72 h were eligible and included with the following exceptions-abdominal surgery, bowel infection or any baseline condition known to alter transit time. patients were compared according to stool frequency-less than 25%, between 25 and 50%, between 50 and 75% or more than 75% of icu days. we also tested the former constipation definition of more than 6 days after admission without stool passage. we registered demographic data, time spent under mechanical ventilation (mv), icu los, ventilation associated pneumoniae (vap) and vital status at discharge. results: over 10 months, 421 patients were screened and 141 (33.5%) were included, age 64.6 ± 16.7 years, mean saps ii 45 ± 17, 71 (50.3%) mechanically ventilated. the most frequent exclusion criteria were los < 72 h (n = 140). 68% of the patients had stool less than 50% of icu days. patients with fewer bowel movements were more likely to be mechanically ventilated, without association with time spent under mv. there was a link between the time to first stool after admission and the stool frequency during icu (p < 0.0001 vap n(%) 4 (9.5) 6 (11.1) 2 (6.1) 2 (16.7) death n(%) 4 (9.5) 3 (5.5) 5 (15.2) 1 (8.3) discussion: this study is limited by the number of patients leading to an imbalance between subgroups therefore limiting the comparison. conclusion: these preliminary results do not plead for an improvement of the late transit definition based on the frequency of stool. further data is warranted to better define this condition, and the management to provide. introduction: antibiotic therapy during acute exacerbation of copd (aecopd) still controversial and not well supported by clinical evidence. in fact half of these episodes are caused by viruses even during severe episodes with need to ventilator support. procalcitonin is effective to guide antibiotic therapy during acute exacerbation of copd without compromising patients' outcome, its efficacy in the intensive care setting still not well evaluated. we have conducted in a 10 bed icu a before after study. during the first period (january 2012-december 2013) patients with aecopd were included retrospectively and treated with antibiotics according to anthonisen criteria (control group). in the second period (january 2014-may 2017) antibiotics were prescribed only if the procalcitonin level was greater than 0.25 ng ml (procalcitonin group). results: ninety-two patients were included, 41 in the procalcitonin group and 52 in the control group. antibiotics were administered at icu admission in 7 patients (17%) in the procalcitonin group and in 27 (52%) patients in the control group, p = 0.001. only 10% of sputum cultures were positive at icu admission. time to recovery was similar between the two groups [7 iqr (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) , 6 iqr (3-10), p = 0.48]. other patients' outcomes did not differ between the control group and the procalcitonin group with respectively: the mortality (9.5 vs. 19%, p = 0.17), the incidence of pavm (11 vs. 17%, p = 0.44) and niv failure (42 vs. 46%, p = 0.69). readmission to the hospital at day 90 was significantly higher in the control group (38 vs. 17%, p = 0.03). conclusion: using procalcitonin to guide antibiotic therapy during severe aecopd can reduce the use of antibiotics without compromising patients' outcomes. our study aimed to assess whether arc impacts negatively on cefazolin pharmacokinetic pharmacodynamics (pk/pd) target attainment and clinical outcome in critically ill patients. patients and methods: over an 8-month period, all critically ill patients treated by cefazolin for a documented respiratory infection without renal impairment were eligible. patients who underwent an empiric antimicrobial treatment > 48 h before introduction of cefazolin were not included. during the first three days of antimicrobial therapy, every patient underwent 24-hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at steady state. the main outcome investigated in this study was the rate of pk pd target non-attainment defined by an unbound concentration < 16 µg ml (mic value for inoculum > 10 7 ufc ml). the secondary outcome was the rate of therapeutic failure, defined as an impaired clinical response with a need for escalating antibiotics during treatment and or within 15 days after end-of-treatment. results: over the study period, 11 patients were included (33 samples analyzed for therapeutic drug monitoring). in pharmacological analysis, the rate of pk pd target non-attainment was 64%, with a strong association with crcl (p = 0.001) ( table 1 ). in clinical analysis, the rate of therapeutic failure was 36% (4 11), with a strong association with inoculum effect (p = 0.02). there was a strong association between therapeutic failure, crcl > 200 ml min and pk pd target non-attainment adjusted on the inoculum effect (p = 0.04). introduction: vancomycin has long been used as the standard therapy of infections due to methicillin-resistant staphylococcus aureus (mrsa). the side effects of this drug as well as the increasing resistance and its pharmacodynamics effects have fostered the development of newly active drugs. nevertheless it is still widely prescribed and it stands as the mostly used comparator in randomized study. an assessment of our medical practice regarding its use may enhance compliance to guidelines so as to promote a better use of vancomycin. patients and methods: in our 1600 bed hospital, the incidence rate of mrsa fell from 0.38 to 0.24 per 1000 patient days from 2007 to 2012 whereas the current proportion of mrsa isolates is about 11%. vancomycin is the most prescribed empirical or targeted antibiotic therapy covering mrsa in our medical intensive care unit of 20 beds even if a shift towards the use of linezolid in nosocomial pneumoniae has been noticed during the last 3 years. key points regarding the proper use of vancomycin have been implemented in our antibiotic stewardship program. moreover courses concerning this topic are provided to our junior doctors. a retrospective review of the quality of antibiotic use has been carried out in 45 courses of vancomycin therapy and the following criteria have been assessed-indication, dosing schedules, serum levels of vancomycin, duration of antibiotic therapy and the overall degree of conformity of the prescription. results: regarding indication, conformity was observed in42 cases (93%). the dosing schedule was appropriate in 32 cases (71%) only. of the remaining 13 cases (29%), all of them were not adjusted to the serum concentration and in 2 cases (4%) the general dosing recommendation was not respected. the loading dose was inappropriate in 23 cases (51%) and the proper follow up of serum levels of vancomycin has not been carried out in 20 cases (44%). the duration of antibiotic therapy was in compliance with the protocol in 42 cases (93%) and a slight longer duration was observed in 3 cases (7%). finally the overall degree of conformity of the prescription was observed in 7 cases (16%) only. table 1 . in the sfar srlf guideline, the limitation of the echinocandins use to the benefit of ampho deoxycholate explains most of the poor agreement or consensus rate between investigators. the idsa escmid guideline are more helpful to guide indications of empirical treatment which mainly explains their higher rate of both applicability and agreement rate. the rates of agreement do not reflect whether the choice between different class iii antifungal therapies is the best or not. conclusion: the idsa guideline seems to take a broader spectrum of clinical situations into account, particularly in guiding more precisely indications of empirical treatments. escmid or idsa reach more often consensus at the first reading. (6 19), and was discovered during a chest x-ray examination for 68% (13 19). diaphragmatic paralysis was confirmed for all cases with chest ultrasound.39% of patients (7 18) were receiving mechanical ventilation at the moment of the diagnosis. the paralysed hemidiaphragm was left sided in 52% (10 19), and right sided in 48% (9 19). there was no bilateral diaphragmatic paralysis. hemi-diaphragmatic plication was performed in 30% of the patients (6 20), and median time from cardiac surgery to surgical plication was 21 days (range 8-38 days). indications for plication were failure to wean from ventilator (100%, 6 6), and respiratory distress (33%, 2 6). plicatured patients were remarkably younger (median age at cardiac surgery-23 days, range 4-82 days) than non-plicatured patients (7.7 months, range 5 days-5 years). the median ventilation time after plication was 3 days (range 2-6 days). all patients were asymptomatic after diaphragmatic plication. two patients died (10%). cause of death was independant from surgical plication (cardiogenic shock, septic shock). conclusion: diaphragmatic paralysis is a rare but serious complication of cardiac surgery in children. it commonly occurs after open-heart surgery, and specifically after arterial switch operation. plicatured patients were younger than non-plicatured patients and needed more frequently a ventilatory support. a closer monitoring may be required for young patients and mechanically ventilated patients. indeed, both are more likely to be treated by a diaphragmatic plication, reducing mechanical ventilation and intensive care duration. a prospective study. consecutive children aged between 7 days and 18-year-old admitted to the picu, intubated and mechanically ventilated were eligible and they reached inclusion if they had at least one chest tube. ppl was directly measured by a pressure transducer connected through a needle inserted into the existing chest tube. pes was measured by both a specific probe (gaeltec probe) and by the feeding tube after mobilization (pes-ft). results: 12 patients (median age 3 months (interquartile + 1-4)) were included and exploitable signals were finally available in 9 patients, who were included in the analysis. most of patients (n = 11) were admitted after cardiac surgery and 5 had a spontaneous breathing activity. median pes measured by gaeltec probe and by feeding tube was 2.3 (interquartile + 1.8-5.4) and 7.9 (2.8-9.5) cm h 2 o, respectively. median ppl measured into the chest tube was 4.0 (0.6-9.6) cm h 2 o. bland-altman plots are represented in the figure. conclusion: both ppl measured into the chest tube, pes measured by the gaeltec probe or by the feeding tube are reproducible methods. . respiratory syncytial virus was identified in 38 infants (70%). an initial caffeine citrate loading dose of 20 mg kg was usually administered, followed by a 5 mg kg day maintenance dose, for a median treatment duration of 3 days [1] [2] [3] [4] [5] [6] . therapeutic management (invasive and non-invasive ventilation, nutrition support) and clinical outcomes (death, length of stay) were similar between groups. there was no difference in potential caffeine adverse effects between groups or within the caffeine exposed group pre and post-caffeine administration. conclusion: caffeine treatment of bronchiolitis related apnea seems to be a standard practice in our picu. our study failed to show any influence of caffeine on clinical outcomes in this indication when compared with a small number of patients. further studies are needed to assess the efficacy and safety of caffeine treatment in this indication as well as the appropriate treatment regimen as pharmacokinetic data suggest that higher dose could be of great interest in this non-prematurely born population. introduction: during the last decade, many authors have raised awareness concerning the increasing rate of venous thromboembolism (vte) in critically ill children [1] . the presence of central venous catheter (cvc) is one of the most important risk factor for venous thrombosis in children [2] . the purpose of this study was to analyze incidence and risk factors for catheter-related thrombosis in children admitted in our pediatric intensive care unit (picu). patients and methods: all children aged less than 2 years, admitted in the picu from january 2016 to june 2017, and receiving at least one tunneled cvc, were included in our retrospective study. those with venous thrombosis unrelated to cvc placement were excluded. catheter-associated venous thrombosis (cavt) was confirmed using doppler ultrasonography. introduction: weaning from the ventilation is a crucial moment in the icu stay. because of the risks of mechanical ventilation (mv), such as ventilator-associated pneumoniae, it is recommended to begin the weaning process as soon as weaning criteria occurs [1] . however, extubation is also a hazardous period, with 5 to 15% of subsequent respiratory failure requiring reintubation, harboring a dismal prognosis [2] . international guidelines display the criteria triggering the extubation. nevertheless, the physician in charge eventually takes the decision to extubate. in this regard, there could be variations from an individual to another. the main goal of our study was to identify the perceived impediments to mv weaning among physicians, from intubation to extubation. patients and methods: prospective single center study in a 12 bed university icu. all patients admitted between february and may 2017 and undergoing mv were included. we daily registered the existence of the criteria recommending a spontaneous breathing trial (sbt), the occurrence of a sbt, the items recommending postponing extubation, and the occurrence of an extubation. the estimated reasons for all the aforementioned decisions were asked to the physician in charge. results: 25 patients were included, gathering 298 days of mv and 42 sbt. the average duration of mv was 8.25 ± 9.4 days. there was one extubation failure requiring reintubation. there were 9 sbt failures. in 9 cases, sbt was a success but did not lead to extubation because of hypotonia, weak cough, subsequent respiratory failure, hemorrhagic bronchial secretions, hemodynamic instability, absence of weaning criteria, drowsiness (all the aforementioned n = 1), post sbt hypercapnia (n = 2). 23 out of the 42 sbt (55%) were done while one or several weaning criteria were absent. impediments to weaning trials were different according to the time lag since icu admission, with fluid overload, muscular weakness and persistent need for assist control ventilation settings being the most frequent reasons advocated after 7 days (figure). no objective assessment of muscular or cough strength was performed at any time, neither was monitored the rr vt, vital capacity or inspiratory pressure. 8.1% of patients had otolaryngologist follow-up. the overall mortality of the studied population was 30.1% including mortality related to tracheostomy in 2 patients. the tracheostomy for extended mechanical ventilation was significantly associated with an increase of mechanical ventilation duration before tracheostomy (p < 0.0001), duration of mechanical ventilation (p < 0.0001), length of stay in intensive care unit (p < 0.0001) and mortality rate (p = 0.0003). introduction: acute renal failure complicating surgery has a particularly harmful prognosis, with a mortality of 40% to 90%. this high mortality rate is attributed to patient-related factors, the severity of the disease and the type of surgery, but not to the acute renal failure itself. the aim of our study is to elucidate the prognostic factors of acute renal failure in the postoperative sepsis in a series of 100 patients. it is a retrospective analytical descriptive study spread over a period of 4 years (from january 2013 to december 2016), 100 observations of postoperative peritonitis were collected in the service of resuscitation of surgical emergencies of chu ibn rochdof casablanca. the statistical analysis was carried out using the spss 20 software. the results are expressed with or and 95% confidence intervals (ci at 95%). the results were considered significant when p is < 0.05. the mean age of the patients was 46 ± 14 years with a sex ratio of 1.94 (66 m 34) . renal failure was the most frequent failure after hemodynamic failure, 11 patients were oliguric, 4 anuriques and 37 patients had a preserved diuresis, patients were divided according to the rifle (r 49%, i 26%, f 25%) and akin (i 49%, ii 26%, iii 25%). the predictive factors of acute renal failure ari were studied in univariate and multivariate analysis, 2 factors were retained including catecholamines-or 3.362 + ci at 95% between 1.202 and 3.397 + p = 0.021 + the surgical site-or 0.367 + ci at 95% between 0.145 and 0.929 + p = 0.034. conclusion: acute renal failure is an independent factor of mortality in the post-operative sepsis, but remains that its presence is a pejorative prognostic factor. this was a retrospective study performed in a large university hospital. all patients receiving the molecule were included in the analysis. indication for sodium lactate, dose, and modality of administration were collected. we also collected clinical and biological variables before sodium lactate infusion, after 6 h (h6), and after 24 h (h24). an analysis of the evolution of these variables at h6 and h24 was performed. results: between january 2016 and may 2017, 104 patients, aged 64 years, 66% males, sofa score 9 [7-12], received an infusion of molar sodium lactate (250 ml ). main indications for sodium lactate were hyperchloremic metabolic acidosis (68%), vascular filling (15%), mixed acidosis (12%), and intracranial hypertension (5%). 84% of the patients presented with a chloride sodium ratio > = 0.76 at basal time. sodium lactate was associated with a significant increase of mean arterial pressure at h6 (p = 0.009) and h24 (p = 0.003), a decrease of catecholamine dose (p = 0.002) and heart rate (p = 0.05) at h24, and an increase of diuresis in the 6 h period following initiation of the treatment (p = 0.02). we observed an increase of ph, bicarbonate, base excess, and sodium, at h6 and h24 (all p < 0.0001). plasma lactate concentration was increased at h6 (p < 0.0001), but was not different from basal value at h24 (p = 0.99). there were no significant variation of plasma chloride. chloride sodium ratio was significantly reduced. plasma sodium > = 150 mmol l and ph > = 7.50 at h24 were observed in 5% of the patients. this retrospective study reports the largest number of critically ill patients having received sodium lactate. hemodynamic effects observed in this study are concordant with the data of the literature. the metabolic effects observed in this study, with rapid increase of ph, bicarbonate, and base excess, strongly suggest the potential interest of sodium lactate among critically ill patients presenting with acidosis and increased chloride sodium ratio. introduction: acute kidney injury (aki) is a frequent and severe condition in intensive care unit patients that may require renal replacement therapy, most frequently continuous renal replacement therapy (crrt). although hypoglycemia is a well-known complication of crrt using glucose free solutions, euglycemic ketoacidosis (eka) has never been described in this setting. patients and methods: all anuric patients with glucose free crrt solution induced eka (february 2017-may 2017) were prospectively included and evaluated. ketoacidosis was deemed possible when nonlactic metabolic acidosis did not improve in patients on crrt. because all patients were anuric, we measured ketonemia and used urinary test strip in the effluent fluid. eka diagnosis was retained when arterial serum bicarbonate was < 20 meg/l despite crrt, in the absence of lactic acidosis and in the presence of ketones in the serum or crrt effluent fluid. results: eighteen patients (15% of our patients under crrt in this period) developed eka during crrt using glucose free solution (phoxilium ® ). time between cvvhdf initiation and ketonemia detection was 2 (1-3) days. patient characteristics are presented in the table 1 . half of them had for a medical history of diabetes (5 insulindependent). only 3 patients were receiving insulin and most of them had low glucose or food intake. increasing glucose intake and insulin infusion resolved ketonemia in all cases. discussion: we describe for the first time the occurrence of euglycemic ketoacidosis in critically ill patients under crrt using glucose-free replacement solution. common features of the patients were multiple organ failure with anuria, normal glycemia without insulin infusion and low glucose infusion or food intake. critical illness-induced insulin resistance and starvation could altogether contribute to ketoacidosis even if acidosis is unusual in starvation ketosis. by removing substantial amounts of glucose from the blood, crrt with glucose free solution could worsen this condition, mask hyperglycemia and induce euglycemic ketoacidosis. in critically ill patients on crrt using glucose free solution, euglycemic ketoacidosis is common and should be detected, especially in patients with low glucose intake, no insulin infusion and unexplained metabolic acidosis. importantly, the diagnosis can be missed in anuric patients with normal blood glucose and in the absence of known diabetes. since, cvvhdf-induced ketoacidosis may contribute to persistent acidemia and its adverse effects, serum or crrt effluent fluid ketone level should be measured in this setting. 39.5-67] years. main reasons for admission were hypercalcemia (n = 55 (70.5%)), followed by acute encephalopathy (n = 9 (11.5%)). median saps ii and sofa scores were 32 [22.25-39.5 ] and 3 [1] [2] [3] [4] [5] respectively. main causes of hcm were hematological malignancies (n = 46 (59%)), solid tumors (n = 15 (19%)), iatrogenic events (n = 9 (9%)) and endocrinopathies (n = 5 (6%)). median calcium levels at admission, at day 3 and at icu discharge were 3.68 [3.43-4.21 ], 2.75 [2.55-3.12 ] and 2.56 [2.15-3. 14] mmol l respectively. more than half of the patients (n = 46 (59%)) recovered from hcm 5 days after icu admission. acute kidney injury occurred in 65 (83%) patients and 19 (29.2%) patients required dialysis. neurological complications concerned 27 (34.6%) patients, mainly delirium (n = 23, 29.4%). digestive events occurred in 29 (37.1%) patients. cardiovascular events concerned 49 (63%) patients and consisted in de novo hypertension in 18 (23%) patients, and ekg disturbances in 24 (30%) patients. during icu stay, 9 (11.5%) patients required mechanical ventilation and 6 (7.6%) patients required vasopressors. volume resuscitation with crystalloids was the first treatment in 73 (93.5%) patients, 63 (80.7%) received bisphosphonates and 48 (61.5%) received corticosteroids. respective icu and hospital mortality were 11.5 and 21.7%. there was no correlation between the degree of hcm and icu mortality (p = 0.1). icu and hospital mortality were associated with the underlying disease (hematological malignancies (p = 0.04)). conclusion: hcm is associated with high mortality rates. the increased mortality is a consequence of the main mechanism, mainly underlying malignancy rather than hcm per se. the course of hcm may be complicated by organ failures that are most of the time reversible with early icu management. introduction: sepsis is one of the leading cause of death among patients with chronic kidney disease (ckd). the mechanisms of this higher mortality remain poorly understood. sepsis and chronic kidney disease are both conditions associated with a higher plasmatic concentration of bile acids. the farnesoid x receptor (fxr) is a key regulator of the bile acid metabolism and has recently been involved in the regulation of the inflammasome during sepsis. we explored the role of fxr in the prognostic of sepsis in an animal model of ckd. patients and methods: sepsis was provoked by the injection of 0.5 mg kg of lps 6 weeks after the creation of ckd. the ckd was created by unilateral nephrectomy associated with contralateral thermocauterisation. the mice (c57bl6 j) were randomly assigned to one of the following groups-sham placebo, ckd placebo, sham lps or ckd lps. a fifth group of ckd lps mice received a treatment with sevelamer (a bile acid sequestrant) during 6 weeks. survival of the animals, serum biochemistry and molecular biology in the kidney were performed after sacrifice. results: whereas the sham lps animals survived, all ckd lps animals died during the 72 h following the injection of lps. the plasmatic urea, il1beta and tnfa concentrations increased with the creation of ckd (ckd placebo versus sham placebo animals) and with the creation of sepsis (ckd lps versus sham lps groups). whereas the expression of fxr rna did not changed with the injection of lps in the sham animals (sham lps versus sham placebo), the fxr rna decreased with the creation of sepsis in the ckd animals (ckd lps versus ckd placebo groups). the ckd animals treated with sevelamer 6 weeks before the administration of lps (ckd sev lps group) had a lower plasmatic concentration of il1b, tnfa and increased the rna expression of fxr in the kidney compared to the ckd lps group. also, the treatment with sevelamer improved the survival of the ckd lps animals. conclusion: our study demonstrates a relation between fxr and the prognostic of sepsis in ckd animals. the exact link and the potential therapeutic interest of targeting fxr and bile acids metabolism in ckd patients remain to be studied. introduction: dysnatraemia, dyskalaemia and hypomagnesemia are frequent metabolic disorders in intensive care, and their causes represent a major concern for the intensivist, especially in urgent conditions. in the diagnostic approach, we often use the urine analysis. although measurement of 24-hour urine electrolyte excretion (24-hu) is considered the most reliable method, the great burden and difficulty in collecting complete 24-hour urine has prompted the search for more practical methods, such as spot urine analysis. the aim of the present study was to compare electrolyte excretion in urine samples collected over different time periods, in comparison with a 24-hour urine sample collection considered as the gold standard method. patients and methods: this prospective and descriptive study included 30 patients admitted in a tunisian medical icu, between september and december 2015. baseline characteristics, medications and laboratory data including electrolytes and renal function parameters were obtained from all patients. multiple urine specimens for analyzing na + k + mg + urea + ca + phosphate + creatinine + proteins and uric acid were obtained from 2-hour, 12-hour and 24-hour urine samples during day and night time, and results were compared with those obtained from the gold standard method (24-hour urine collection). correlation analysis was performed using the spearman test. results: significant correlation was found for all biochemistry parameters between 24-hour urine results and those obtained from 2-hour and 12-hour samples regardless of day or night sampling. a comparative analysis for sodium and potassium is shown in fig. 1 . conclusion: determination of electrolyte excretion from urine samples taken over 2 different time periods, 2 and12 h, provides a reliable estimation of 24-hour urine electrolyte excretion. it appears practical for early understanding of the mechanism of electrolyte imbalance. however, further studies are warranted to confirm the usefulness of this approach. use of the procalcitonin assay in an adult emergencies department: retrospective experience of a general hospital of the suburb of paris (7.85-13.4 ). other markers of infectious were poorly recorded (fibrinemia in34 (11.5% + 5.5 g l [4.6-6.6] + immature forms on blood count-11.5%). only 172 (53.6%) had blood cultures in the ed (1 patient [1] [2] ) and 163 (50.3%) other(s) microbiological sample(s), mainly urinary (84 patients [25.9% + among them 33% considered as positive]). 5% of blood cultures were positives, mainly for gram negatives (90%). final diagnosis in the ed was considered as infectious disease (id) in only 142 patients (44.1%, including 11 sepsis and 5 septic shocks). 175 (44.6%) was considered as non-infected (nid) and final diagnosis remains unprecise in 8 (1.6%). pct values was of 0.42 (0-1.38) in the id vs. 0 (0-1.37) in the nid (p < 0.001), wbc was of 10.68 in the id vs. 9.75 in the nid (p < 0.013) and crp was of 88 (22.5-185.5) in the id vs. 21 (5-76) in the nid (p < 0.001). no correlation was observed between the pct value and admission to dechocage room admission. . identification of the involved drug was obtained in 60% of the cases, based on qualitative screening. management was mainly supportive and included sedation (13%), naloxone (10%) and flumazenil (1%). tracheal intubation was required in 3 patients (0.4%). one cardiac arrest but no death occurred in the ed. forty-three patients (6%) were transferred to the intensive care unit. conclusion: our dataset provides an interesting insight into the drugs involved in and clinical pattern of toxicity outcome of acute recreational drug toxicity presentations at the ed, despite possible under-declaration and coding. classical recreational drugs were more common (77%) followed by prescription drugs (20%) and nps (3%). and drug (59%) consumers + hiv-infected (58%) and depressive (25%) patients) were admitted to the icu. the main declared compounds were methylenedioxypyrovalerone (mdpv + n = 9), 4-methylethcathinone (4-mec + n = 6), 3-methyl methcathinone (3-mmc + n = 3) and 4-methyl methcathinone (4-mmc + n = 3), more frequently used in drug mixtures sold as bath salts or in poly-intoxication with conventional illegal drugs (mainly cocaine and gamma-hydroxybutyrate). nps was used in a recreational (71%), chemsex (29%) or solitary practice (29%). binge (63%) and intravenous (50%) self-administration was remarkable. patients presented acute encephalopathy with psychomotor agitation (46%), confusion (38% + glasgow coma score-14 [9]), hallucinations (33%), anxiety (17%), seizures (17%), myoclonus (13%) and stereotypes (13%). ecg typically showed sinus tachycardia (70%), qrs qt abnormalities (13%) and atrio-ventricular block (4%). acute cardiac ischemia (17%) and dysfunction (13%), disseminated intravascular coagulation (8%) and multiorgan failure ( results: during the first and the second study periods 204 and 244 patients were respectively admitted in the icu. total micro-organisms density was 48 and 69.5 for 100 patients for the first and the second period, respectively (p < 0.05). acinetobacter spp and pseudomonas aeroginosa were the predominant isolated microorganisms with a respective density of 13.2 and 11.2 isolates for 100 patients. figure 1 summarizes the patterns of bacterial ecology and resistance in our icu before and after transfer to new buildings, showing a significant decrease in pseudomonas aeroginosa resistance for ticarcillin and ceftazidim, whereas acinetobacter resistant to carbapenems and enterobacteriacae esbl significantly increased. our study suggests that transfer of icu to the new buildings was associated with a decrease of pseudomonas aeroginosa resistance, whereas acinetobacter spp resistance and esbl enterobacteriacae incidence increased. introduction: infections caused by antimicrobial-resistant bacteria (amrb) are one of the main issues in the spectrum of critically ill patients as they are associated with higher mortality, morbidity, and length of stay. thus, an appropriate initial antimicrobial therapy is decisive for better patient outcomes. the aim of the study is to determine the adequacy of first-line antibiotic therapy guided by weekly amrb screenings. patients and methods: a 9 months prospective study was conducted in 6-bed micu. were included all patients with more than 48h of icu stay. an amrb screening was conducted upon admission and on weekly basis for all the patients. the choice of antibiotherapy if indicated, was guided by the most recent colonization results. if the patient has received at least one active in vitro antibiotic against the isolated bacteria, the empiric antibiotherapy was considered appropriate. results: 98 patients were included in the study. mean age and saps ii were respectively 56 ± 20 years and 41 ± 20. the median length of stay was 8 days. 11 (11%) patients were colonized by amrb upon admission. the most frequent isolated microorganisms were-escherichia coli 5 (55%) and klebsiella pneumonia 4 (45%). were assessed 57 hospital-acquired infections (hai)-32 (56%) in amrb colonized patients and 25 (44%) in uncolonized ones. the antibiotherapy was considered appropriate in 21 infections (65%). out of the 20 colonized patients, 15 (75%) developed hai. 11 (73%) patients had a concordant colonization body site to the infection. of the 57 nosocomial infections, ventilator-associated pneumonias and central venous catheter infections were the most frequent, both at 38% (n = 22 and n = 22) + followed by urinary tract infections 21% (n = 10) and infective endocarditis 2% (n = 1). (42). overall, the isolates were-extended spectrum betalactamase productrice-enterobacteria (43%), imipenem resistant-acinetobacter baumanii (30%), and multi resistant-pseudomonas aeroguinosa (19%). 50 ni were documented including 35 caused by mdr bacteria and distributed as follows-ventilator acquired pneumonia-vap (n = 19), bacteraemia (n = 6), vap with bacteraemia (n = 4), catheter related infection-cri (n = 3), cri with vap (n = 2) and catheter-related bacteraemia-crb (n = 1). the performance of mdr bacteria-screening in predicting ni was poor with 71% of sensitivity, 58% of specificity, 41.5% of negative predictive value (npv), and 83% of positive predictive value (ppv). nevertheless, the performance of the nasal swab in the prediction of vap was better with 85% of sensitivity and 92.3% of npv. conclusion: mdr bacteria-screening is useful as it allows to identifying the mdr bacteria-carriers and helps for a rational use of antibiotics in severe ni. however, its diagnostic contribution in the occurrence of ni is poor except the interest of the nasal swab in the prediction of vap owing to its good npv. we aimed at determining the respective weight of these phenomenon and the physiological determinants of the respiratory variations of the ivc diameter. patients and methods: in 21 mechanically ventilated patients (tidal volume-6.2 ± 1.0 ml kg of predicted body weight) haemodynamic, respiratory and the intra-abdominal pressure (iap) signals were continuously computerised. cvp, iap and the ivc diameter (transthoracic echocardiography) were recorded during 15-second end-inspiratory and end-expiratory occlusions separated by 10 s, before and after the infusion of 500-ml of saline. patients in whom fluid administration induced an increase in cardiac index (picco-2) > 15% were defined as "responders". the respiratory variations of the ivc diameter, cvp and iap were calculated as the (end-inspiratory-end-expiratory values) mean value. the compliance of the ivc was estimated by the ratio (end-expiratory-end-inspiratory ivc diameter) (end-expiratoryend-inspiratory cvp). results: fluid administration increased cardiac index by more than 15% (3.09 ± 1.12 to 3.90 ± 1.42 l min m 2 , p = 0.0003) in 8 patients. the respiratory variations of the ivc diameter predicted fluid responsiveness (area under the roc curve-0.822 (95% ci 0.595-0.952), p < 0.05). before fluid administration, the ratio of changes in ivc diameter over changes in cvp was not different between responders and non-responders (0.73 ± 0.34 vs. 0.88 ± 1.25 mm mmhg, p = 0.75). before fluid administration, the respiratory variations of the cvp tended to be higher in responders than in non-responders (34 ± 27 vs. 18 ± 8%, p = 0.07). the respiratory variations of the ivc diameter were associated with the respiratory variations of cvp (r = 0.56, p = 0.01) but not with the respiratory variations of iap (r = -0.15, p = 0.52). the respiratory variations of the ivc diameter were not explained by a higher ivc compliance but rather by higher respiratory variations of the cvp in responders than in non-responders. interestingly, it seems that iap, the ivc extramural pressure, was not involved in the respiratory variations of the ivc diameter. inclusions are ongoing. during the hospitalization in icu, there was no significant difference between the two groups regarding the proportion of patients with aki through icu discharge. in the intervention group, 28% of the patients had a glomerular filtration rate lower than 75 ml min 1.73 m 2 compared to 14.8% in the control group (p = 0.25) at day-28. we found no significant difference between the two groups neither on hematopoietic effects of epo or serious adverse events. in patients resuscitated from an ohca of presumed cardiac cause, early administration of erythropoietin compared to standard therapy did not confer any renal protective effect. salvetti marie , and the ratio of end-diastolic areas of both the right and left ventricle in the long axis view of the heart (rveda lveda) were measured. a lvef < 40% defined lv systolic dysfunction, a ci < 3 l min m 2 defined low cardiac output, and a rveda lveda ratio > 0.6 (± associated with a paradoxical septal motion in the short axis of the heart) defined rv dysfunction (± acute cor pulmonale). the preload-dependence was evaluated using deltasvc or deltavmaxao. front-line hemodynamic and metabolic parameters were recorded at the time of tee assessment. results: lvef and ci could be simultaneously measured in 388 of 410 patients (95%). 74 patients (19%) had a low ci related to lv systolic dysfunction (lactate-4.36 ± 3.49 mmol l), 141 patients (36%) had a low ci and a preserved lvef related to a rv dysfunction or to a sustained preload-dependence (lactate-3.58 ± 3.28 mmol l), 146 patients (38%) had preserved ci and lvef (lactate-3.38 ± 3.32 mmol l) including only 23 patients (6%) with a hyperkinetic profile (high ci and lvef > 70%), and 27 patients (7%) had preserved ci but altered lvef (lactate-3.49 ± 2.95 mmol l) due to a marked tachycardia. none of the front-line hemodynamic parameters was discriminatory to identify the circulatory profile identified by tee assessment (table) . introduction: aortic end-systolic pressure (esp) is considered as a reliable index of left ventricular afterload. recently, the effective arterial elastance (ea), i.e., the ratio of esp over stroke volume (sv), has also been proposed as a reliable afterload index. our aim was to document peripheral estimates of ea (eapsap) at the bedside in critically ill patients, and to investigate the haemodynamic mechanisms responsible for ea changes after fluid administration (fa). in the validation study, carotid tonometry (complior) was prospectively performed on 50 haemodynamically stable spontaneously breathing patients equipped with an arterial femoral (n = 21) or radial (n = 29) catheter. ea was defined as the (0.9 × csap) sv ratio, where csap was the central systolic arterial pressure directly measured from the calibrated carotid waveform. eapsap was calculated as the (0.9 x peripheral systolic arterial pressure) sv ratio. sv was obtained by transpulmonary thermodilution or transthoracic echocardiography. in the clinical study, we included 30 patients with invasive haemodynamic monitoring (picco-2), in whom fa was planned. results: in the validation study, the complior allowed estimating ea in all patients (ea = 1.73 ± 0.62 mmhg ml). the (eapsap-ea) bias was smaller at the femoral than radial artery level (0.08 ± 0.08 vs. 0.18 ± 0.16 mmhg ml, p < 0.05) and was strongly related to the systolic pressure amplification between the carotid and peripheral artery (r = 0.89, p < 0.05). ea was more strongly related to sv (r = − 0.80) than to esp (r = 0.48) (each p < 0.05). the four-quadrant plot analysis indicated that 47 patients (94%) exhibited a concordant low ea high sv pattern or high ea low sv pattern, while only 33 patients (66%) exhibited concordant high ea high esp pattern or low ea low esp pattern (p < 0.05). there was a negative relationship between changes in eapsap and changes in sv in the whole population, in fluid responders (cardiac index increases > 15% after fa), in pressure responders (mean arterial pressure increases > 10% after fa) and in non-responders, while no consistent relationship between eapsap and esp changes was documented. conclusion: ea may be reliably estimated at bedside by using the (0.9 x femoralsap) sv ratio. ea value and ea changes induced by fa were related to sv rather than to esp. thus, ea should be considered as an index reflecting sv rather than left ventricular afterload in critically ill patients. this study included a sham group (n = 11), a cpb group (n = 9), an ir group (n = 8) and a cpb-ir group (n = 11). rats were exposed to 45 min of cec, 30 min of left pulmonary ischemia and 15 min of reperfusion. fonctional endothelial dysfunction was evaluated by measurement of the pulmonary artery reactivity. systemic inflammation was evaluated by the plasma assay of il-1 beta, il-10 and tnf-alpha. the endothelial glycocalyx was evaluated by plasma assay syndecan-1 and electron microscopy. the statistics were performed using an anova test, p < 0.05. we showed that cpb associated with ir induce an endothelial vasorelaxation dysfunction mainly mediated by nitric oxyde (no introduction: during circulatory shock, the goal of increasing cardiac output is to correct tissue hypoxia, which can be manifested by an increase in oxygen consumption (vo2) associated with an increase in oxygen delivery. we hypothesized that, in patients in circulatory shock, veno-arterial co2 gradients (pv-aco2) could be a good predictor of an increase in vo2 in fluid responders. patients and methods: we included patients with circulatory shock who received a fluid challenge. circulatory shock was defined by the association of vasopressor requirements to maintain mean arterial pressure (map) and a blood lactate concentration ≥ 2 mmol l. we measured cardiac index (ci) and arterial and central venous blood gases and arterial lactate before and after a volume expansion (500 ml of plasmalyte ® ). cardiac index (ci) was measured using a pulse contour analysis method (picco + pulsion, munich, germany). ci responders were the patients in whom ci increased (δci) by > 15%. in those patients, vo2 responders were those in whom vo2 increased (δvo2) by > 15%. receiver operating characteristic (roc) curves were performed. the data was presented as median (25th percentile-75th percentile). a p < 0.05 was considered as statistically significant. introduction: the autonomic nervous system (ans) is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of ans activity and a relation between hrv and outcome has been proposed in various types of patients. while electrocardiographic hrv assessment seems to be the gold standard, we evaluated the feasibility of an automated hrv monitoring based on standard photoplethysmographic monitoring. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct02893462) that aims to record more than 1500 icu patients over a 3-years period. introduction: diabetic ketoacidosis is an acute complication of diabetes, defined as metabolic acidosis with a high anionic gap, associating hyperglycemia > 16 mmol l (3 g l), positive ketonuria, or superior or equal ketonuria to ++, it is a medical emergency which can occur in a known diabetic patient, or not. objective-to describe the clinical therapeutic and prognostic aspects of diabetic ketoacidosis in the intensive pediatric care unit at the ehs canastel oran, algeria. patients and methods: retrospective study carried out over a period of 2 years. from january 1, 2015 to january 1, 2017, in the intensive pediatric care service. the data was entered and analyzed using excel 2007. results: 16 cases were retained on 450 hospitalizations per year, 95% of cases had no history with diabetes, 5% occurred in known diabetics with insulin, but are not followed medically. our patients were aged from 10 months to 15 years, but the average age of these patients was 6 years and 5 months, with a slight female predominance, coma was preceeded by 75% of cases polydipsy polyuria syndrome and 12% weight loss, triggered by an infectious syndrome including 31% of ent cases, 12% of respiratory infections and 12% of cases with digestive infections characterized by fever, abdominal pain, vomiting. the delay between diagnosis and admission to ice was 24-7 days. at admission 80% of patients were scored at 11 15 on the glasgow scale, with presence of the cough reflex, and 20% were scored at < 7 15 requiring tracheal intubation and mechanical ventilation of 48 h with signs of dehydration and ionic disorders, namely hypokalemia and hypernatremia, blood glucose at admission varies between 3.5 and 5 g l with glycosuria at +++ and ketonesuria between ++ and ++++ in only 18% of the patients had metabolic acidosis, a cerebral computed tomography (ct) performed in 13% of cases found a slight cerebral edema. therapeutic management was the rehydration, correction of metabolic disorders and introduction of insulin into sap, with monitoring and subcutaneous relaying due to ketonuria negativity. the outcome was favorable for all patients. conclusion: diabetic ketoacidosis is a major complication of diabetes which can be avoided by a good prevention campaign and systematic screening of any child suspected of diabetes, recognition of risk situations such as infections and clinical manifestations in order not to delay the management. introduction: scorpion sting is a public health problem world wide with a global distribution of 1500 species. in algeria, scorpionic envenomation occupies a prominent place in declarations. in 2016, 43000 cases were reported. the objective of our study is to describe the epidemiological, diagnostic, therapeutic and evolutionary characteristics of the scorpion sting in children. retrospective study of 07 cases of scorpionic envenomation hospitalized in the pediatric resuscitation department of the ehs canastel oran conducted during the year 2016the inclusion criteria were the presence of traces with at least one locoregional or general clinical signs. the parameters studied-age, sex, city of origin, time of bite, time of management, initial first aid, time limit for admission to pediatric intensive care, and severity criteria. results: 57% of these cases were boys and 43% girls. the mediane age 6.5 90% of the punctures occurred during the day, the site of the injection was the lower limb in 80% of the cases and 20 there were 9 bites scorpion cases in the west of algeria and exactly in oran and tiaret.100 of the cases was the upper limb. the delay of the management was from 1 to 3 h for 30 100 of the cases who were classified in the third classed according to the clinical signs of gravity. the type of the scorpion was not identified. we can classify all the patients that we received in our service into three classes −43% in class i, with local signs such as pruritus, redness, abnormalities and local pain. eva 6-7, calmed by the infusion of 15 mg kg iv of paracetamol and application of xylocaine cream at the site of the sting. introduction: the residence of children in intensive care is most often due to the existence of one or more organ dysfunction which requires heavy treatment (intubation, ventilation, drainage, venous tract) and this in a hostile environment which amplifies the aggression organic. the main objective of our work is to study the consequences of hospitalization of children in pediatric resuscitation. patients and methods: this is a descriptive prospective study on the outpatient consultation file of canastel's ehs multipurpose resuscitation. we studied 18 files and assessed memory, perception of contact and nuisance factors felt by sick children. results: out of 18 children seen in post resuscitation. the sex ratio is 1.25. the average age of children is 4 years (2 months-14 years). the average hospital stay is 13 days. the average gos (glasgow out scale) is 4. (2) (3) (4) (5) . the average duration of ventilation is 8 days. 60% of children had central vascular access. three children describe a total memory of the stay, 2 some memory and 2 none. three children have a good perception about the staff, one child dissatisfied and three others indifferent. the nuisance factors described by the children are pain (3), cold (2), noise (3), hunger (1) and light (1) . conclusion: consequences of psychological trauma, insufficiently evaluated especially by the staff, which result in the appearance of psychological disorders (nightmares and anxiety) with sometimes even severe post-traumatic neurosis. hence the need to adapt the environment and mainly noise and respect for sleep. [3] [4] [5] [6] [7] [8] [9] . the median treatment duration time was at 120(87-180) minutes. femoral vein was used as vascular access (93%) and most of pe procedures (78%) were performed with citrate anticoagulation. median exchange volume was at 3500 [2796-4190] ml and renal replacement fluid was fresh frozen plasma (ffp) in 64%, 50% ffp and 50% human albumin 4% in 22% and human albumin only in 14% of procedures. adverse effects were observed in less than 20% of procedures and 10% were lifethreathening including cardiac arrest, heart rhythm disorders, cerebral oedema and hemolysis. other remaining complications were secondary infections 48%, hemorrhage 23%, and pulmonary oedema 14% in all patients. twenty patients deceaded (icu mortality 26%). icu and hospital lenght of stay was at 19 ± 21 and 47 ± 33 days respectively. 2 3 of survived patients still underwent pe after their icu discharge + 9 totally recovered whereas 49 (63%) were on partial remission. conclusion: pe is a routine and feasible technique in icu. this study showed that tpp was the most commonly indication of its use and that outcome was fair. adverse effects frequently occured but most of them were not severe. further studies would benefit form larger cohort to improve indications, delay of initiation and practice of this treatment. renal replacement therapy was required in 46% of elderly versus 27% (p = 0.047). frequency of ttp, hus and ahus was similar beetween groups. tma was more frequently associated with ongoing cancer and drug use in elderly (39 vs. 8%, p < 0.01 and 23 vs. 6%, p < 0.01, respectively). gastro-intestinal bleeding during icu occurred more often among elderly (35 vs. 15% (p = 0.02)). icu mortality rate was higher (19 vs. 7%, p = 0.049). no difference was found concerning plasma-exchange therapy, steroids use, and rescue treatments for refractory-ttp. discussion: increased complication and mortality rates in the elderly group might be ascribed to more cardiovascular morbidity in this population. the association between tma and ongoing cancer suggests a routine oncological workup among elderly. introduction: neutropenia, defined by an absolute count of polymorphonuclear neutrophils less than < 1500 mm3, exposes patients to infectious complications that can lead to sepsis or septic shock. the mortality risk is higher. the french guidelines published in 2016 were formulated to homogenize the clinical practices and improve survival. we performed a monocentric retrospective study including all consecutive patients admitted to the medical icu of a tertiary hospital to a neutropenia with sepsis or septic shock, between the 30th of december 2012 and the 30th of december 2016. the study protocol was approved by the local ethics committee (2017. ce15) and published on clinical trial (nct03217721). results: 2235 patients were admitted in icu during this period. 130 patients (17%) presented a neutropenia with sepsis or septic shock. among these patients, 92% had hematologic malignancies and 5% had solid tumour. 78 patients (60%) was treated empirically with antipseudomonal beta-lactam or carbapenem and aminoglycoside. 129 (99%) skin or suspected catheter-related infections were treated with anti-mrsa (methicillin-resistant staphylococcus aureus), vancomycin or linezolid. adequate antibiotics as described in guidelines was performed to 76 patients (58%). 76 patients (58%) received aminoglycoside (58 patients received initial dose in icu, 18 patients complement dose) and 100 (77%) received anti-mrsa with antipseudomonal betalactam or cabapenem. 71 patients (55%) had microbiologically documented infections with, 59% of bacteria (16% of gram-posit cocci, 1% of gram-negative cocci, 39% of gram-negative bacillus), 8% of fungi and 3% of viral infection ( table 3) . among of them, 10% (13) of esbl, 2% (2) of mrsa and 2% (2) of emerging highly resistant bacteria (bhre). the icu-mortality rate was 29% (37 130) with 28% of 28-day mortality (36 130). the curves of the cumulative incidence of death risk between d0 and d28 were no different according to adequate empirical antibiotic treatment as like french guidelines (fig 1) . by multivariate analysis, independent factors of adequate antibiotic treatment were septic shock (or, 0.38 + 95% ci 0.15-0.96) and febrile neutropenia > 7 days (or, 0.42 + 95% ci 0.20-0.88) at icu admission. conclusion: according to the usual clinical practice, septic neutropenic patients was already treated empirically by bitherapy including antipseudomonal or anti-mrsa if there is a skin or suspected catheter-related infection. adjunction of aminoglycoside in of the symptomatology in case of overdose, make the diagnosis difficult, especially since the drug in question is often unspecified and the toxicological analysis is not exhaustive. introduction: carbon monoxide intoxication is a public health problem in tunisia and around the world. currently, it is unclear the impact of this type of poisoning in our country for lack of declarations. we propose in our work to study the epidemiological characteristics of fatal carbon monoxide intoxications collected in the forensic pathology department of the university hospital in sfax, tunisia, to describe the different steps used in forensic diagnosis of fatal carbon monoxide intoxication and to propose preventive measures to reduce the rate of these intoxications. patients and methods: it is a retrospective study of 29 cases of fatal carbon monoxide intoxications collected in the forensic pathology department of the university hospital in sfax, tunisia during 06 years (1 january 2011 to 31 december 2016). commemoratives were collected from medical and police records. a forensic autopsy and a toxicological analysis were carried out in all cases. results: fatal carbon monoxide intoxication is the leading cause of toxic death in sfax during the period of our study. we notice a decrease in the incidence of this type of intoxication. the average age of deaths was 36 years and 2 months with male predominance. the peak frequency of intoxication was in cold season. the most frequent form of intoxication was accidental. the source of carbon monoxide was mainly the defective water heater often placed in poorly ventilated areas. the classic carmine red-color of lividity was found in the majority of cases. myocardial distress, favored by hypoxia, has been reported in two subjects with a pathological coronary artery. the mean hbco level was 51.59%. however, account must be taken of the survival time and the time elapsed between death and dosing of hbco. the incidence of fatal carbon monoxide intoxication has decreased since 2011 and the victim profile has not changed too much. the fatal carbon monoxide intoxication is still persists as a public health problem in tunisia. the reduction of its frequency requires the implementation of a well-structured prevention plan based on epidemiological data from a national registry. the identification of these data requires mandatory reporting of this type of intoxication in tunisia. introduction: olanzapine is an atypical antipsychotic drug frequently prescribed in the treatement of bipolar disorder and schizophrenia. acute poisoning with this molecule is rarely reported. through this study we aimed to evaluate the incidence and describe the different clinical features of acute olanzapine poisoning. patients and methods: retrospective analysis of all cases of olanzapine intoxication admitted in 12-bed teaching icu between january 2013 and decembre 2017. inclusion criteria were patient age ≥ 14 year, acute olanzapine intoxication, the intoxication severity was assessed by the poisoning severity score (pss) of the european association of poison centres and clinical toxicologists. the evaluation of electrocardiograms was performed in the first day of hospitalization. the durations of qrs and qtc was measured and arrhythmias and conduction disorders was identified. results: 24 patients were included, the mean age was 35 ± 11 years. they were 11 males and 13 females. long term treatment with olanzapine was noted in 19 patients (79%) who suffered from psychiatic desease. the supposed ingestion dose ranged from 25 to 600 mg. the mean consulting time was 5 ± 4 h after the ingestion. olanzapine was co-ingested with others drugs in 16 patients (66%). co-ingested drugs were-benzodiazepine (n = 5), levomepromazine (n = 5), serotonin recapture inhibitor (n = 3), amitriptilyne (n = 2) and biperiden (n = 1). the pss was moderate in 9 cases (37.5%), severe in 14 cases (58%) and fatal in 1 case. the main clinical signs were tachycardia and miosis in 62% of cases each of them (n = 15), agitation in 33% of cases (n = 8). ecg abnormalities has been detected such as prolonged qtc in 5 cases with a mean duration of 460 ± 28 ms. in the group of monointoxication (8 patients) the pss was moderate in 3 cases (37.5%), severe in 4 cases (50%) and fatal in one case. the coma glosgow scale was < 12 fig. 1 kaplan-meier survival between admission and 28-day according to adequate empirical antibiotic therapy guidelines (log rank, p = 0.53) in 14 cases. mechanical ventilation was required in 58% of cases (n = 14%) with a mean duration of 23 ± 8 heures. the mean duration of icu stay was of 50 ± 30 h. twenty three patients recovered during the hospitalisation, one patient died with severe poisoning. conclusion: as showed in this study, acute olazapine poisoning could be severe, and lead to death sometimes. introduction: voluntary drug intoxication (vdi) continues to be a major health problem in many developed and developing countries. in algeria, this has become a worrying concern. awareness-raising is launched to prevent the public from these dangers. vdi are intentional or rarely accidental and can be individual or collective and affect all age groups. the vdi represents the first reason for hospitalization in the emergency department university hospital of oran. in algeria there is no national or regional register of voluntary intoxication. knowledge of the causes of drug poisoning should therefore be extrapolated from foreign studies. to draw up an assessment of the imvs, a retrospective study was carried out over the 2 years (2015-2016) . this survey consisted of collecting data on the nature of the drug, age, sex, major toxidromes, severe imvs requiring hospitalization in icu, mortality, e.t.c scores and glasgo scores. results: 1650 cases of acute poisoning were collected, with a predominance in patients aged between 16 and 25, a percentage of 31.77%. in addition, most patients were female with 60.98%, a sex ratio of 1.56 with p < 0.05. the main toxidromes were-opioid syndrome in 27% of cases and anticholinergic syndrome in 23% of cases. etc with a score of > 9% accounted for 93% of patients. severe vdi requiring resuscitation hospitalization were 8%. conclusion: acute poisoning remains high and steady in the oran region and the under-25 age group represents the most affected category. awareness campaigns must be launched throughout the year to better conserve and store medicines, phytosanitary products and other chemicals. improved socio-economic conditions would help to reduce voluntary intoxication. introduction: scorpionic envenomation is unevenly distributed throughout the world and is particularly frequent in some regions of the world, notably north africa. the purpose of this work is to describe the epidemiological profile of the scorpionic envenomations admitted to the resuscitation department of mahres. patients and methods: a prospective study conducted at the mahres intensive care unit over a period of 6 months (15 02 2017 until 15 08 2017), including all patients admitted for scorpion envenomation. results: we collected 102 cases of patients admitted to the resuscitation department of mahres from 15 02 2017 to 15 08 2017, including 10 cases of scorpionic envenomations, i.e. 0.098%. the median age was 43 years with extremes ranging from 20 to 78 years. the sex ratio was 4. scorpion stings occurred at night in 80% of patients, 60% in the first half of the night (between 6 pm and 11-59 pm) and 20% in the second half of the night (0 to 5 h). venom inoculation points were in the lower limbs in 80% of cases, followed by upper limbs (20%). the color of the incriminated scorpion was yellow in 80%, black in 10% and unspecified in 10% of the cases. for admission classes, there were 10% class i, 80% class ii and 10% class iii. the traditional therapeutic gestures practiced by the patients or their entourage were the laying scarification (50%) and the suction (10%). all patients received anti-scorpion serum, an analgesic, serum and tetanus vaccine. the progression was favorable in all cases after an average hospital stay of 4 ± 1 days. conclusion: scorpionic envenomations are indeed a reality in mahres with a non-negligible frequency despite under-reporting of cases treated by traditional medicine or in other hospitals. they mostly affect young people and the associated clinical manifestations often remain benign. introduction: severe pediatric poisoning is defined by the need for intensive care monitoring due to the nature, quantity of the substance and or clinical manifestations. it is one of the frequent reasons for admission to emergency and resuscitation. the purpose of this work is to identify poisoning in children admitted to pediatric intensive care units in order to assess the frequency, identify the products involved, and the clinical and evolutionary aspects. patients and methods: this is a descriptive study over a 24-month period in the canastel oran multi-purpose pediatric intensive care unit from july 2016 to july 2017. we included all children aged 0-15 years admitted for ingestion and inhalation of products toxic. results: 39 children admitted to pediatric intensive care, mean age was 5 years, 70% under 6 years with extremes of 02 months and 15 years, a female predominance of 60% was observed with a slight predominance of accidental poisoning (56%) compared to voluntary poisoning (44%). in 87% the toxic is ingested orally. the most frequent toxicants were drugs with 19 cases (35%), mostly antidepressants and antiepileptics, followed by organophosphates with 10 cases (26%), co 5 cases (12%), petroleum products and plants with 5 cases (12%). the main clinical signs were neurological signs (76%) with predominance of coma and convulsions in 19 cases (43%), respiratory distress was present in 6 cases (15%) and digestive signs 8 cases (20%). for therapeutic management gastric lavage, charcoal and antidotes were the most frequent treatments. the evolution was marked by a mortality of 2% or a death secondary to a poly-medicinal intoxication voluntary in a girl of 10 years. mechanical ventilation in 5 cases (12%) and an average hospital stay of 2 days. conclusion: acute poisoning is a medical emergency that may require resuscitation. young children are most exposed with drugs are the most frequently incriminated. we propose, as a preventive measure, companions of information on the dangers of toxic products and especially of medicines by the surveillance of the child and the regulation of certain products. introduction: the place of neuron specific enolase (nse) dosing remains uncertain as an indicator of neurological prognosis after a cardiac arrest, the threshold value for predicting an unfavorable evolution being variable from one study to another. our objective was to determine a nse cut-off value predictive of poor neurological outcome after a cardiac arrest. patients and methods: we realized a monocentric prospective trial in a medical icu of a french university hospital from january 1st 2016 to december 31th 2016. all patients over 18 years old hospitalized for a cardiac arrest in medical icu were included. patients who died during the first 24 h or admitted for cardiac arrest with a neurological cause were excluded. serum nse values (elecsys nse test, cobas ® analyzer) were assessed at h24 and h72 after cardiac arrest. somatosensory evoked potentials were recorded between h24 and h72. the primary endpoint was neurological outcome at 6 month using the cerebral performance category scale (cpcs). cpcs 1 or 2 was considered as favorable outcome and cpcs higher than 2 as poor outcome. data were collected using cardiologic or neurologic consultations report, or by phone call to the patient. using a roc curve we determined the nse value at h24 with higher specificity and acceptable sensitivity. results: we included 48 patients. average age was 62 years old. noflow time and low-flow time were respectively 3.7 and 17 min. hypothermia was performed in 30 (63%) patients. 27 patients (56%) died in the icu. the 30-day and 6-months survival rates were respectively 44 and 42% with a favorable outcome of 35% at 6 months. on the roc curve we found a cut-off value of 41 ng ml with specificity of 0.95 ci 95% (0.75-0.99) and a sensibility of 0.64 ci 95%(0.44-0.81). area under curve was 0.828 ci 95% (0.713-0.942). 9 out of the 10 patients with a rising nse between h24 and h72 had an unfavorable outcome. among patients with nse > 41 ng ml, the cortical n20 responses were bilaterally present in 4 of them. conclusion: in our study nse value over than 41 ng ml at h24 was predictive of poor neurological outcome after cardiac arrest. nse may prove to be a useful marker in patients with present n20 responses, possibly limiting the duration of hospitalization by introducing therapeutic limitation or withdrawal of support. physicians assessment of prognosis in icu patients with brain introduction: outcome prediction in icu patients with severe brain damage is a difficult task with observed heterogeneity in physicians estimation. the aim of the survey was to evaluate the prognostic estimates and treatment recommendation of intensivists in real patients with various causes of severe brain damage. patients and methods: a web anonymous survey including a summarized clinical report of four patients who stayed in the icu was submitted to french intensivists. patient 1 presented with prolonged hypoglycemic coma, patient 2 with intracerebral hemorrhage, patient 3 with central and extra pontine myelinolysis, patient 4 with a brainstem hemorrhage. all these patients received full treatment in the icu and had a 6-month follow-up. physicians were provided with the four clinical vignettes including clinical history, brain imaging and other relevant exams (csf, eeg,…), evolution of symptoms within the first days of the icu stay. they had to estimate 6-month outcome using modified rankin scale (mrs) where a score from 0 to 3 was considered as a good outcome and 4 to 6 as a poor outcome. they had to provide a recommendation about care among the following-full treatment, care limitation, care withdrawal. results: 109 physicians completed the survey. there were 37 (33.9%) female. 48 (44%) respondents were residents and 20 (18.3%) had a > 10-year of experience. patients 1 and 2 had a good 6-month outcome with mrs 1 and mrs 2 respectively while patients 3 and 4 had a poor outcome, both with mrs 5. correct prognosis estimations were 36 (33%), 31 (28.4%), 97 (89%) and 100 (91.7%) in patients 1 to 4 respectively. care limitation or withdrawal was recommended by 70 (64.2%), 40 (36.7%), 73 (67%) and 73 (67%) respondents in patients 1 to 4 respectively. of interest, care withdrawal was recommended by 2 (1.8%), 4 (3.7%), 19 (17.4%) and 25 (22.9%) respondents in patients 1 to 4 respectively. univariate analysis did not display any factor related with a good prediction of prognosis. conclusion: in this study, overall predictions were pessimistic with important variations among respondents. although decisions to withdraw life sustaining care were relatively low with regard to estimated prognosis, both inappropriate care limitation leading to self-fulfilling prophecies and unreasonable prolonged life supportive care could result from these estimations. introduction: organ harvesting is a national priority because of the shortage of organs, responsible each year for the lengthening of transplant waiting lists. among the identified potential donors, the main cause of non-harvesting is the refusal of organ donation (od), which exceeds 30% in france and 40% in paris area. patients and methods: in a network of 6 hopitals, each procedure on a potential donor by the donor co-ordinator is recorded in a report. after selection of the reports with interviews with relatives about od between 2012 and 2015, the data in the reports were collected and a multivariate logistic regression was performed to identify the factors associated with the refusal. results: 571 reports with interviews about od was found. the overall opposition rate is 43.3%. among the 42 children (7.3% of cases) the opposition rate is 47.6%. among adults, 147 (27.8%) expressed their will about od during their lifetime, with an opposition rate of 43.5% and for the 382 (72.2%) of them who never expressed their will, the opposition rate is 42.9%. the factors associated with opposition in multivariate analysis are presented in table 1 . when the deceased had never expressed their will, the reasons given by the relatives to justify the refusal are specified in 87.5% of the reports. these are religious grounds (20%), cultural grounds (12%), respect for physical integrity (15%). in 18% of the cases, relatives believe that the deceased would have been opposed, and in 16% of the cases, they choose to refuse because they do not know the deceased's opinion. discussion: french law is based on presumed consent. despite this, it is noted that when patients had never expressed their opinion about od (and therefore had not refused it), the opposition rate reached 43.5% and was comparable to the patients who had expressed themselves. conclusion: in our study, factors related to refusal of od are mainly related to the characteristics of the deceased (religion, culture, history of ethylism) and those of relatives (disagreement, presence of a spouse), but little to the way of doing the interview. however, there is a trend for less opposition when the interview is conducted during the day (between 8-00 and 20-00). on the other hand, when relatives first address the issue of od, the opposition rate is lower. introduction: french intensive care society guidelines and the claes-leonnetti law recommend that intensive care teams organize collegiate and multidisciplinary discussions regarding limitation and withdrawal of care decisions. these moments, coined ethical staffs in our unit, require freedom and safety of speech, which can be difficult to obtain when people are caught in hierarchical and or power relations. we sought to assess the representations, perceptions and opinions of icu personnel regarding ethical staffs. patients and methods: a questionnaire, developed by the icu psychologist, was distributed to the entire unit (secretaries, nurses, nursing auxiliaries, doctors) over a period of 6 months. this 30-question questionnaire covered session organization and power relations between participants. results: among the 86 questionnaires distributed in the icu, 76 were retrieved and analyzed. medical function was associated by respondents with roles linked with power (leading, knowledge, decision, explanation) whereas paramedical function was associated with roles linked with care (perception, account, spokesperson) (fig. 1) . regarding representations of decision making, nurses were considered as decision makers in 48 cases (63%) and doctors in 76 cases (100%). discussion: although ethical staffs are presented as a place where each opinion counts, stereotypes representation appear in the different roles assigned-on one side doctors are in charge of explanation and decision, and on the other side, nurses are taking care of patient's feelings and assume a role of spokesperson. these stereotypes correspond to gender stereotypes assigning women to positions of care, empathy and relationship, and men to more intellectual and leading skills. these gender stereotypes attest a hierarchy internalized by each one, as highlighted by social sciences and gender studies. conclusion: our results highlight the existence of a global idea, shared by the majority-doctors are decision makers and therefore are in a power relation regarding paramedical staff. this hierarchical relationship persists in this moment wished egalitarian (each opinion would count equally). these is a linkage between professional power relations and gender power relations, which show an association between doctor and masculine "qualities" and caretakers and feminine "qualities". these power relations are rarely acknowledged but could have a significant impact on the decision process of these meetings, and should be further investigated. results. despite the diary, 33% had a qspt score > 51, indicating a higher post traumatic disorders. 9 patients (25%) presented a anxiety score > 11 and 11 patients (30.5%) had a depression score > 11. these results underline the need of psychological support after the stay. conclusion: many survivors of intensive care unit reported a high level of psychological distress. it seems important offer at this patient a psychological support after an intensive care unit stay. most patients needs return in intensive care unit to understand some elements of hospitalization. actually, this support lack to screening and treatment this psychological morbidity. prevalence and description of the complications following a percutaneous coronary intervention for a myocardial infarction in non-cardiac critically ill patients: a retrospective single-center introduction: type 1 myocardial infarction (mi) is an emergency, which immediate invasive strategy by a percutaneous coronary intervention (pci) is based on guidelines for cardiologic patients. conversely, the invasive strategy remains uncertain for patients hospitalized in the intensive care unit (icu) for a primary non-cardiac disease with mi as a complication, given the ischemic and hemorrhagic risks. we aimed to assess the prevalence of-and describe the major adverse cardiac and hemorrhagic events occurring in the icu after an invasive strategy by pci in this context. we conducted a retrospective single-center 5-year (2012-2017) study. all the consecutive icu patients with a suspected mi undergoing a coronarography were screened. patients treated with an invasive strategy (pci performed within 7 days of mi) were included. patients hospitalized in icu for cardiac disease were excluded. the major adverse cardiac events (mace) were defined as post-procedure events occurring in the icu, including death from cardiovascular causes, mi recurrence, need for emergent revascularization and stroke. the major adverse hemorrhagic events (mahe) were defined as post-procedure events occurring in the icu, according to the bleeding academic research consortium. results: 60 icu patients suspected of mi underwent a coronarography. 29 patients (48%) had significant coronary lesions. twelve patients were excluded-tri-truncular coronary involvement (n = 12), delayed procedure (n = 4), cardiogenic shock (n = 1). 17 patients were included (11 men, 70 years [iqr 25-75-68-77], 9 patients mechanically ventilated, 9 patients with sepsis septic shock, median sofa score at the time of mi 8 [3] [4] [5] [6] [7] [8] [9] [10] ). a pci was performed during the first day after diagnosis of mi in 9 patients (53%) (median time-0 day [iqr 25-75-0-2]). a mace occurred in 3 patients (18%), including stroke (n = 2) and mi recurrence without revascularization (n = 1). no patients deceased from cardiovascular causes in the icu, neither at 6 months post-procedure (table 1) . a mahe occurred in 3 patients (18%), 2 of whom had a mace. altogether, the prevalence of major adverse cardiovascular events combining mace and mahe was 0.24 (95% ci 0.01-0.46). there was no difference between septic and non septic patients regarding the prevalence of mace or mahe. the prevalence of adverse cardiovascular events after an invasive strategy by pci is high in non-cardiac critically ill patients with mi. larger studies are needed to determine which patients may benefit from this procedure. introduction: resuscitated cardiac arrest (ca) lead to immune alteration including lymphopenia, decreased monocyte hla-dr (mhla-dr) expression and dysregulated production of cytokines. in a recent multicenter randomized clinical trial, we tested the hypothesis that cyclosprine a (csa) would limit organ failures following out-of-hospital cardiac arrest (ohca). in a substudy, we aimed to determine the influence of csa on ohca-induced immune dysfunction. this study is a predefined substudy of the randomized cyrus trial (cyclosporine in ca resuscitation). patients with non-shockable ohca randomly received either an intravenous bolus injection of csa (2.5 mg kg) at the onset of advanced cardiovascular life support (csa group) or no additional intervention (control group). patients from the coordinating center were sampled at admission (d0) and at 24 h (d1). complete blood count, cd4 + lymphocytes count and mhla-dr were evaluated by flow cytometry. serum levels of il-1, il-6, il-8, il-10 and tnf&#945 + were measured by elisa test on frozen samples. results: a total of 33 patients were sampled-17 patients from the csa group and 16 from the control group. the characteristics of the patients, including resuscitation data, were also similar between the two groups at admission. the severity of organ failure as assessed by the sofa score at admission was similar between groups. all patients introduction: critically ill patients experience major insults that lead to increased protein catabolism and a significant loss of lean body mass with an impact on weaning from the ventilator and muscle recovery. in critically ill patients, severe and persistent testosterone deficiency is very common after icu admission. administration of testosterone may induce skeletal muscle fiber hypertrophy and decreases protein breakdown. the aim of this work is to assess testosterone levels in critical ill patients and to evaluate the safety of testosterone gel administration. this is a single center study realized in a university icu of 10 beds. total testosterone levels were measured in critical ill men with at least one organ dysfunction with sofa > 3. the study drug was androgel, a formulation of 1% testosterone in an alcohol-water gel, approved by the ansm for treatment of hypogonadism in men. androgel was applied to the abdomen, shoulders or upper arms once a day at the same time to dry and intact skin during icu stay. the daily dose was 75 mg in men and 25 mg in women daily. patients with history of prostate or breast cancer or psa > 4 ng ml were excluded. results: total testosterone levels were measured in 19 men. median length of stay at the time of measurement was 7 days in icu and 11 days in the hospital. plasma testosterone levels were low in all but 1 patient. median testosterone level was 58 ng dl (normal values 270-780 ng dl). testosterone levels were not correlated with score sofa or length of icu stay. we found a moderate positif correlation between testosterone levels and length of hospital stay (r = 0.5 =). testosterone gel was administered in 12 men and in 6 women. in these 18 patients, the median score sofa was 10, icu death occurred in 3 patients (22% icu mortality), median length of ventilation was 13 days and median length of stay in icu 30 days. all patients received mechanical ventilation and vasoactive treatment. 9 patients needed renal replacement therapy. androgel was well tolerated. no ischemic cardiovascular events were described. there was no application site reaction or acne. median length of testosterone gel administration was 12 days. conclusion: critical ill patients have low testosterone levels. testosterone gel may be safely administered during the acute phase in icu. randomized clinical trials are needed to evaluate the impact of testosterone gel on physical performance. introduction: stroke is the leading cause of physical disability and the second leading cause of death worldwide. two thirds of all strokes occur in developing countries and is increasingly a public health problem. the aim of this study was to evaluate the epidemiology of strokes in oran, algeria in order to create a stroke registry. patients and methods: a cross-sectional study was conducted on all patients admitted for stroke at the oran chu between january 2014 and september 2017. sociodemographic data, modifiable and nomodifiable risk factors, type of stroke, degree of disability, severity scores (glasgow and nihss) were studied. the spss 20 software, log rank test, was used for data analysis and statistical testing as well as kaplan-meier for survival studies. results: a total of 2305 stroke patients were enumerated, aged 20-99 years (mean ± sd = 68.33 ± 12.99), 74.2% had an ischemic stroke and 15% had a haemorrhagic stroke. 49% of the patients were men and 51% of the women. high blood pressure, diabetes, emboligenous heart disease and smoking were the most common risk factors. intra-hospital mortality was 15.5% and the overall survival rate at 28 days was 77%. conclusion: this epidemiological study demonstrates that strokes at oran hospital may be similar to other locations. however, it seems necessary and useful to design a continuous patient registration system. introduction: the prevalence of hyperosmolar states and the relationship with mortality nevertheless remain unquantified and not objectively demonstrated. the aim of this work is to determine whether hyperosmolarity is a prognosis factor, and to assess the impact of hyperosmolarity on the evolution of patients. patients and methods: this is a retrospective descriptive and analytical study performed at the medical intensive care unit at the university teaching hospital ibn rushd in casablanca on the cases admitted during 1 year. we noted epidemiological, clinical, biological and evolutionary parameters of all the patients and divided them into two groups according to their osmolar states, the first non-hyperosmolar group with plasma osmolarity of less than 320 mosm l, called the control group and the second hyperosmolar group, plasma osmolarity greater than or equal to 320 mosm l. results: 371 patients were included. the first group comprised 293 patients (79%) and the second comprised 78 patients (21%). the two groups did not differ significantly about sex and age. hyperosmolar patients had more diabets 42.3%. patients in the two groups did not show significant differences in clinical outcomes, including apache ii and saps ii scores. significant differences are reported between the two groups, in natremia, creatinemia, liver transaminases. the plasma osmolarity was significantly different between the two groups with a mean in the control group of 269.77 ± 12.73 mol l while in the hyperosmolar group it was 346.95 ± 35.85 mosmol l (p = 0.046). the prevalence of hyperosmolar states in the study was 21% with 60% mortality. in the control group 41% were intubated-ventilated + 21.2% received vasoactive drugs and 68.6% received antibiotic therapy. in the control group + 7%of the patients were complicated by nosocomial infection, 9.9% by septic shock and 1% diseased by thromboembolic complications. the deceased subgroup used intubation artificial ventilation in 89.36%, vasoactive drugs in 68%, and antibiotic therapy in 89.36%. in the surviving subgroup, 6.45% only contracted the nosocomial infection. in the subgroup died 51.1% are of mixed hyperosmolar type + 82.4% hyperglycemic hyperuremic + 55.6% hyperglycemic hypernatremic type. conclusion: hyperosmolar states are an independent a prognosis factor. intubation and ventilation, vasoactive drugs and antibiotic therapy increases considerably in hyperosmolar states. furthermore, it induced serious complications as nosocomial infections and septic shocks that further aggravate the prognosis even within hyperosmolar states. introduction: hyperthermia represents a major life-threatening medical emergency, and is also one of the leading causes of death in young athletes worldwide. its incidence is rare and little understood, but its mortality is on the rise. the objective of this study was to describe the population of patients admitted for exertional hyperthermia in martinique and guadeloupe and to determine the prognostic factors. patients and methods: retrospective and prospective study, including all patients admitted for exertional hyperthermia in both emergency and resuscitation services in martinique and guadeloupe from january 2006 to june 2017. results were expressed as mean ± sd or %. results: in 10 years, 55 patients were observed (age-79 ± 18, 44 men and 11 women), the main antecedents of which were-2 hypertension, 2 chronic oh, 2 psychoses, 1 stress hyperthermia. 10 (18%) of the patients had seizures initially. the pre-hospital management was < 30 min. nevertheless, 20 (36%) patients were admitted to icu due to organ failure (neurologic 74%, hemodynamic 2%, liver 4%). the progression was favorable, 4 deaths, including 3 fulminant hepatitis and multi-visceral failure. the average length of stay in intensive care units was 5 days (± 6). conclusion: despite considerable preventive measures, stress hyperthermia represents a major problem within the military, soldiers and other athletes, with a mortality rate about 10% in most published series. the most effective method is immersion in ice water. there is an urgent need to provide the region with a clear preventive policy, including a relief action plan, training for doctors, athletes and other health professionals at risk of hyperthermia. chapoutot anne-gaëlle 1 , leteurtre stéphane 1 , chamouine abdourahim 2 (2008) . the university hospital of lille is a pediatric center including several itecus in its pediatric hematology or gastrology departments, and more recently in its pediatric surgical department. moreover, there are 4-6 itecu extra-beds within the 12-14 bed pediatric intensive care unit (ivecu). the hospital of mayotte has no pediatric ivecu but a polyvalent one for adults, which receives children when necessary, as well as a 4 bed itecu. the aim of this study was to describe prospectively the pediatric population which was admitted in the itecus of lille and mayotte over a one-year period from june 2016 to may 2017. patients and methods: in this twin-center, prospective and observational study, data were collected for each patient admitted during the test period in itecus of both lille and mayotte pediatric hospitalsgeneral information about the patient, characteristics of each stay, severity scores on admission, type of treatments implemented, the report of the stay and patient's evolution. a standard declaration was made with an authorization granted by the local commission on informatics and liberty (french commission informatique et liberté, cil). results: during the course of the study, about 450 children were admitted in each center. the collected data allow to describe and compare both populations in terms of severity of each patient's condition. this study based on a very large cohort has permitted to compare the population of a regional hospital with that of a university hospital and to demonstrate that a health-care provision including a pediatric intensive care unit is needed on mayotte island. introduction: simulation in intensive care is an innovative method for teaching. respiratory settings are responsible for some morbi-mortality of our patients. for this reason we develop a simulator of artificial ventilation (simva) and virtual patients. mathematical model resolved differential equations of chest and lung movements in order to match with a clinical data base. the goal of this study was to evaluate and compare virtual patients respiratory mechanic with the results of 4 different protocols of ventilation from 2 large randomised controlled trial-arma (1) and express (2). patients and methods: virtual patients had ards, and were defined by different thoracic and pulmonar compliance, total resistance, lung volumes, pressure-volume relation, and pressure and volume recruitment coefficients. ventilatory protocols were high versus low vt (arma study) and max versus min distension according to pep (express study). each virtual patient was titrated on the simulator with the 4 protocols. respiratory frequency was set around 28 cycles minute and adapted to protocols. respiratory mechanic after titration was recorded and compared to results of the 2 studies. results: results are summarised in the table-the difference between virtual and real patients were not significant. vm l/min 12.6 (4.5) 13.3 (1.7) 12.9 (3.6) 13.0 (2.0) 11. ctp: tharacopulmanar compliance (ml/cmh 2 o) discussion: inspiratory plateau pressure and thoraco-pulmonary compliance were able to change according to pep or vt settings within the same range as the 2 large rct studies. mathematical model of recruitment was adapted to create many different results while pep was titrated according to respiratory mechanics with the express protocol. conclusion: simulation of artificial ventilation with a software can be realistic and might be an interesting pedagogical tool to teach interactively and repetidly ventilatory settings and respiratory mechanics interactions in ards without any risk for the patient in our units. introduction: expiratory flow limitation (efl) has previously been investigated in ards patients on zero peep by using negative expiratory pressure (nep) technique on tidal breath. in ards patients with efl peep 10 improved oxygenation from intrinsic peep homogenization rather than lung recruitment. the nep technique is no longer available. as efl should reflect airway closure it is important to assess it. we described a new technique to assess efl. patients and methods: thirty-nine ards patients (6 mild, 32 moderate, 1 severe) were investigated at peep5 and15. they were intubated, mechanically ventilated (evita xl) in volume controlled mode (tidal volume 5 ± 1 ml kg predicted body weight) in the semi-recumbent position. airway pressure and flow measured proximal the endotracheal tube were continuously recorded (biopac150). we measured respiratory mechanics by the occlusion technique at each peep and recruited lung volume between peep15 and 5 by using low flow inflation method associated with measurement in change in end-expiratory lung volume. for the latter, patient was manually disconnected at the end of baseline tidal inflation downstream pneumotachograph to atmosphere til zero flow, then reconnected at previous settings. efl was assessed offline by superimposing flow-volume loops of disconnected and baseline breath. efl was defined if no change in flow occurred over all or part of the disconnected expiration as compared to the baseline breath and no efl (nfl) if any increase in flow during the expiration was present (fig. 1) . the percentage of the tidal volume involved in efl was measured. results: efl was present in 7 patients (18%) over 80% of the tidal expiration. patients with efl had significant higher body mass index (34 ± 7 vs. 28 ± 6 kg m 2 , p < 0.05) and totalpeep at peep5 (7 ± 1 vs. 6 ± 1cmh2o, p < 0.05) than nfl patients and tended to be more hypoxemic. at peep15 efl patients had a significant better compliance (50 ± 21 vs. 30 ± 12 ml cm h 2 o, p < 0.05) with no change in recruited lung volume (393 ± 271 vs. 347 ± 203 ml) and tended to be more hypoxemic than nfl patients. mortality at icu discharge was 57% in efl versus 28% in nfl (p = 0.19). conclusion: measurement of efl is feasible without the nep technique. at higher peep ards patients with efl markedly improved compliance of the respiratory system not related to lung recruitment. further studies are required to better understand efl in ards patients and to assess its impact on patient outcome. limiting factor being carbon dioxide accumulation and hypercapnic acidosis. extra corporeal carbon dioxide removal (ecco2r) intervenes by maintaining ph and pco2 within physiological ranges. this combination is called ultra-protective ventilation. we report our experience with ecco2r in ards and non ards patients with a focus on feasibility and safety. patients and methods: from june 2014 to july 2017 all patients who have undergone ecco2r in our icu were included consecutively and prospectively. venovenous ecco2r was used through a dual lumen venous catheter (femoral or jugular). results: nineteen patients underwent ecco2r for a total of 21 sessions. ecco2r was implemented through a dual lumen venous catheter (femoral or jugular) with 3 different devices-hemolung respiratory assist system ® (alung) (n = 2), ila activve ® (novalung) (n = 5) and prismalung ® (prismaflex system) (n = 12). sessions were 3 (iqr 2.5-4.0) days long. catheter diameters were 13 fr (n = 8), 15 fr (n = 6), 24 fr (n = 4) and 17 fr (n = 1). thirteen patients suffered from ards and 6 had non ards indications for ecco2r, including ultraprotective ventilation. tidal volume decreased during ecco2r from 5.3 (iqr 4.3-5.8) to 3.4 (iqr 2.6-4.1) ml kg of predicted body weight (p < .001) while ecco2r allowed maintaining of ph and pco2 within acceptable range (fig. 1 ). driving pressure decreased from 17 (iqr 11-21) to 8 (iqr 6-14) cm h 2 o (p < .001). the main adverse effect was thrombocytopenia (8 patients). six selected patients had no anticoagulation during ecco2r because of high bleeding risk. discussion: ultra-protective ventilation was achieved with a decrease of tidal volumes (vt < 4 ml kg) and positive pressures. few data on ecco2r are available in patients at high risk of hemorrhagic complications, we report here a subgroup of 6 patients who underwent efficiently ecco2r without anticoagulation. six patients underwent ecco2r for non ards indications, 3 of them had no structural damages to the lungs which has never been reported and eccor allowed implementing ultra-protective ventilation with no major adverse effect. we report our experience on ecco2r for ards and non ards indications. ultra-protective ventilation (vt < 4 ml kg) was safe and feasible. the impact of general practitioners consultation on ards complicating community acquired pneumonia donval ulysse 1 , tadie introduction: community-acquired pneumonia (cap) is a potentially severe infection that results in numerous general practitioner (gp) visits and hospital admissions each year. cap is also the most frequent single cause of acute respiratory distress syndrome (ards). risk factors for development of ards in the course of cap are not clearly defined although prognostic factors associated with mortality have been extensively studied. gp visits, as an early diagnosis and earlier access to antibiotics prescription could significantly affect the course of cap. the aim of the present study was to evaluate the impact of general practitioners consultation on ards complicating cap admitted to our icu. patients and methods: we retrospectively reviewed the medical records of all patients aged over 18 years admitted between october 1, 2006 and december 31, 2015, for ards complicating community acquired pneumonia with a pao2 fio 2 ratio < 200 mmhg after at least 12 h of lung protective mechanical ventilation (mv). ventilatory modalities for ards had been protocolized over the study period as our icu was recruiting patients for two consecutive multicenter trials (acurasys and proseva). consequently, the protective ventilatory strategy used in these two clinical trials was applied to every patient with ards. patients were divided into two groups according to whether or not they visited a gp before icu admission. : 216 patients were admitted for ards complicating cap. 114 patients (53%) had visited a gp before admission in icu (gp +) and 102 did not (gp-). analysis of demographic data, respiratory microbiology patterns, ards severity at admission did not show any differences between the two groups. sofa score at admission was significantly higher in gp-compared to gp + patients (9.5 (8-13) vs. 8.5 (7-10) respectively + p = 0.003) although respiratory sofa scores were not different (4 (3-4) vs. 4 (3-4) respectively + p = 0.31). 71 (70%) gp-(70%) and 60 (53%) gp + patients presented septic shock at icu admission (p = 0.01). multivariate analysis found that gp consultation (0.54 [0.29-0.98] + p = 0.04) with antibiotics prescription (0.46 [0.22-0.99] + p = 0.04) were associated with decreased mortality at day 28 ( fig. 1) . in patients admitted to our icu for ards complicating community acquired pneumonia, gp visits prior to icu admission was associated with a better outcome. the beneficial effect may be due to earlier antibiotic prescription which could significantly lowered severe infection and septic shock. introduction: optimal peep level during ards remains controversial because of its beneficial and adverse effects. the optimal level of recruitment and its effect on oxygenation are not well defined and no technique is currently validated. the aim of our study was to evaluate the correlation between the recruited pulmonary volume estimated by a new technique (crf inview ® ) and the evolution of pao2 as well as the respiratory and hemodynamic tolerance of the application of an increasing levels of peep . patients and methods: a prospective, monocentric study that will last 3 years (january 2015-january 2018), taking place in the intensive care unit at the military teaching hospital of tunis and including patients if they met standard criteria for ards (berlin criteria). the main criterion for judgment was the correlation between the recruited pulmonary volume estimated by a new technique (crf inview ® ) and the evolution of the pao2 after application of three increasing levels of peep (5-10-15). the other secondary criteria were the respiratory and hemodynamic tolerance of the application of increasing levels of peep measured by the picco ® technique. aimed to investigate the concordance between the onset of three vae tiers and valrti, and their impact on outcomes. we performed a retrospective analysis of prospectively collected data from patients requiring mechanical ventilation for more than 5 days in a 50-bed mixed icu of a tertiary university teaching hospital, between january 1 and december 31, 2016. vat and vap episodes were assessed by prospective surveillance of nosocomial infections, according to the american thoracic society criteria. vae were identified retrospectively, according to current cdc definitions. the agreement between vac, ivac, pvap and valrti was assessed by k statistic. the impact of vae and valrti on duration of mechanical ventilation, icu and hospital length of stay and mortality was also assessed for the first episode of vat and vap. results: we included 545 patients (7927 ventilator days). 126 vap (15.9 per 1000 ventilator-days), 80 vat (10.1 per 1000 ventilator-days) and 115 vae (14.5 per 1000 ventilator-days) were diagnosed. there was no agreement between vat and vae and the agreement was poor between vap and vac (k = 0.12, 95% ci 0.03-0.20), vap and ivac (k = 0.23, 95% ci 0.14-0.32) or vap and pvap (k = 0.30, 95% ci 0.22-0.40). patients who developed vat, vap or vae had significantly longer duration of mechanical ventilation, icu and hospital length of stay, compared to patients who did not, with similar mortality rates. conclusion: vae are not relevant for vat diagnosis and have low agreement with vap, despite their negative impact on ventilation duration, icu and hospital length of stay ( fig. 1) . the introduction: post-operative pneumonia (pop) is a frequent and severe complication of major lung resection surgery. in 2002, we changed our surgical antibioprophylaxis protocol from cefamandole to amoxicillin-clavulanate and observed a significant decrease of pop incidence and mortality. in 2012, we additionally implemented in the respiratory intensive care unit (ricu) an antimicrobial stewardship program based on a local antimicrobial guideline and a weekly multidisciplinary review of all antibiotic therapies by ricu physicians, infectious diseases specialists and microbiologists. our objectives were to describe our current epidemiology of severe pop and to assess the quality of antibiotic prescriptions. patients and methods: all patients with severe pop occurring within 30 days after lung resection between january 2013 and december 2015 were included. we collected data on clinical presentation, results of microbiological investigations, antibiotic regimen and outcomes. the quality of antibiotic use was assessed using indicators previously validated in the literature. results: over 1555 patients who underwent major lung resection in our center, 91 matched criteria for severe pop and were included. most were males (n = 71, 78%). the median age was 69 years (minimum-42 + maximum-84). most patients had chronic obstructive pulmonary disease (n = 59, 65%) and 18 (20%) a history of non-pulmonary cancer. the resection consisted in lobectomy in 59% (n = 54). the median length of stay in ricu was 12 days (1 + 90), and 30-day mortality was 9% (n = 8). respiratory microbiological samples were obtained in all patients, in most cases invasively per bronchoscopy (74%). microorganisms were cultured at a significant level in 66 (73%) patients. predominant species were enterobacteriacae (58%), haemophilus influenzae (14%), staphylococcus aureus (11%) and pseudomonas aeruginosa (10%). microorganisms were sensitive to third generation cephalosporins in 52 (79%) and to piperacillin-tazobactam in 57 (86%). in patients treated empirically, antibiotics were prescribed according to the guideline in 80% (69 86). in documented pop, empiric antibiotics were active against documented micro-organisms in 53 62 (86%), and were correctly changed to pathogen-directed therapy in 46 62 (74%). the median duration of antibiotics was of 7 days (2 + 21). conclusion: ten years after implementation of amoxicillin-clavulanate as surgical antibioprophylaxis, the proportion of enterobacteriacae increased. the 30-day postoperative mortality rate remained below 10%. we report high adherence to the guideline for the choice of empirical therapy and treatment duration. the rate of de-escalation to pathogen-directed therapy could however be improved considering the high rate of bacteriologically-documented pop. resistance of pa has reduced between both periods from 42% to 11% (p < 0.01) for ceftazidim, from 74% to 18% (p < 0.01) for cirpofloxacin and from 38% to 18% (p < 0.01) for imipenem. nevertheless, among the cases, the p2 period did not change the risk of developing an infection (rr = 0.77, ci 95% 0.58-1.01), a vap (rr = 0.99, ci 95% 0.76-1.28), a septicemia (rr = 1, ci 95% 0.66-1.51) or the mortality rates (rr = 1.04, ci 95% 0.81-1.33). conclusion: colonization and infection with pa are risk factors of increased mortality rates and alos in icu. an antibiotic stewardship program allows to reduce the incidence of patients having a positive sample with pa, and the antibiotic resistance of pa strains, without reducing the infection rate of these patients. impact of a local care protocol on the duration of antibiotic therapy in community-acquired peritonitis: 10 years of experience introduction: the use of antibiotics is a major public health, economic and ecological challenge. in 2011, a french national warning plan was created to manage the use of antibiotics. it advocates monitoring of the prescription of antibiotics and the implementation of measures to assess professional practices. the great majority of guidelines concerning the duration of antibiotic therapy in community-acquired peritonitis are based on studies with low level of evidence. the objective of this study is to evaluate the implementation of a standardized operational report (sor) with a local antibiotic protocol in the management of community-acquired peritonitis at our institution. patients and methods: this is a monocentric, prospective cohort study-before and after the establishment of the sor. the primary endpoint is duration of antibiotic therapy. secondary endpoints are length of hospitalization, infectious complications, mortality, and changes in local bacterial ecology. we have also evaluated retrospectively these different criteria on cohort was constituted since 2005. results: a total of 205 patients were enrolled from january 2011 to june 2013 and 231 patients from may 2014 to may 2016. the duration of antibiotic therapy was decreased by 7 to 3 days in localized peritonitis (p < 0.0001) and 9 to 7 days in generalized peritonitis (p < 0.0001) (figure) . however, the compliance to the protocol was only 66%, which leads to an increase in the duration of antibiotic therapy and hospital stay when not used (p < 0.0001). the hospital stay decreased from 7 to 4 days in the localized peritonitis (p < 0.0001). amoxicillin clavulanic acid (amc) is the most used antibiotic with an efficiency of 77%. there was no impact on morbidity and mortality when amc was inadequate. the bacterial ecology was not modified, the rate of extended-spectrum beta-lactamase (esbl) producing enterobacteria (esble) was 3%. the use of a standardized antibiotic protocol reduced antibiotic therapy duration and hospital stay, particularly in localized peritonitis despite incomplete compliance to the protocol. to achieve full compliance, we need to continue the training of different physicians and continue the spread of the protocol. introduction: bacterial meningitis is an important public health problem because of its frequency and severity. they remain a major cause of mortality and morbidity in developing countries. the aim of our work is to establish the epidemiological characteristics and the prognostic factors . patients and methods: we did a retrospective descriptive and analytical study and we included all the patients admitted for severe meningitis for 1 year in the medical intensive care unit of the university teaching hospital ibn rushd at casablanca-morocco. results: 70 patients were included. the incidence of severe meningtis was 12.61%, the mean age was 44 years old and the sex ratio h f was 1,06.24,3% were pneumococcal meningitis and 20% were tuberculosis in univariate analysis, factors influencing mortality significantly-the male sex patients with pulmonary tuberculosis as an antecedent.• a low glasgow score at admission. the presence of a neurological deficit arterial ph, mean (sd) arterial lactate, mean (sd) kidney disease-improving global outcomes chronic kidney disease guideline development work group members. evaluation and management of chronic kidney disease-synopsis of the kidney disease-improving global outcomes 2012 clinical practice guideline dramatic increase in venous thromboembolism in children's hospitals in the united states from antithrombotic therapy in neonates and children acute childhood arterial ischemic and hemorrhagic stroke in the emergency department childhood hemorrhagic stroke-an important but understudied problem emergency management of deeply comatose children with acute rupture of a cerebral arteriovenous malformation goulmane mourad -m.goulmane@hotmail.com annals of intensive care we recorded 91 episodes of nosocomial infections-pneumonia (n = 45, 49.5%), bacteremia (n = 26, 28.6%), catheter related infections cri (n = 13, 14.3%) and urinary infections (n = 7, 7.6%). pathogens isolated were largely dominated by non-fermentent gram-negative bacilli (n = 55, 60.4%)-acinetobacter baumanii (n = 39, 42.8%) with 100% resistance to imipenem and tygecycline, pseudomonas aeruginosa (n = 14, 15.4%) with 33.3% resistance to ceftazidim and stenotrophomonas maltophila (n = 2). other gram-negative bacilli were enterobacteries (n = 11), which were wide-spectrum betalactamase secreting (n = 6) and carbapenemase (n = 1). gram-positive cocci were the second highest (n = 22, 24.2%)-coagulase negative staphylococcus (n = 12) which were resistant to methicilline (75%), enterococcus (n = 7) which were resistant to vancomycin (n = 2, 28.6%), staphylococcus aureus sensitive to methicilline (n = 2) and streptococcus (n = 1). candida was incriminated in 2 cases of cri we report here that neonates had a reduction in hla-dr expression after cpb, and those with prolonged decreased hla-dr in the early postoperative period (day 4) could represent a subpopulation at greatly increased risk of later ni. if confirmed in a larger cohort of patients, our findings could indicate that hla-dr may be a useful biomarker of immunosuppression after cpb in neonates. non-traumatic hemorrhagic stroke (nths) in comatose children: epidemiological features and clinical presentation conclusion: compared to normobaric ltot the fio 2 is lower during niv with the same o2 flow. compensation for intentional and nonintentional leaks and so an increase of air flow despite a constant o2 input might explain this. in intermediate care the use of hv for niv may be interesting alternative in which case the clinician must keep in mind that the fio 2 decreases compared to standard oxygen therapy. concerning home usage we hypothesize that this partial removal of o2 treatment could contribute to the poor results of niv in chronic copd. introduction: in february 2016, we opened a 12 beds-post icu rehabilitation center (service de rééducation post réanimation, «srpr»), dedicated to weaning from mechanical ventilation and global post icu rehabilitation. objectives-description of the characteristics and main outcomes of the patients admitted over the first year of activity. patients and methods: retrospective analysis of data extracted from the medical files. results: 96 patients were admitted 100 times in the unit over its 1st year, from 34 different icus (median duration of stay in the icu 38.5 days (iqr 29-61)). 86% were ventilated (11% with niv). 85% had a tracheostomy. 64% had icu acquired weakness + 5% were able to walk. an underlying chronic respiratory disease was present in 53% of cases. 18% were obese. difficult weaning was found to have one or several respiratory components in 77% of cases (including 20 post surgery diaphragmatic paralysis), cardiac in 34%, neurologic in 18%. significant complications occured in 60% of cases. median duration of stay was 19.5 (12-29.5) days. ten patients died in the unit, 13 patients were re-transferred in the icu, where 6 of them died. over half of the patients were discharged at home, in a rehabilitation unit (ssr) or in a hospital ward awaiting a rehabilitation bed. the remaining 24%, that still needed some form of medical or surgical care were discharged in the ward (fig 1) . in intention to treat, successful weaning from invasive ventilation was obtained in 70% of patients. of the patients discharged alive from the unit after completing the rehabilitation program (n = 74), 60% were completely weaned from mechanical ventilation, 35% were discharged with niv or cpap + 4 patients (5%) were considered not weanable from invasive ventilation + decanulation of tracheostomy was obtained in 82% of cases + 87% of the patients could walk. conclusion: srprs offer a new concept of care for difficult to wean patients, with promising results. introduction: scarce data about patients with prolonged weaning from the mechanical ventilation are available in the literature. patients without successful weaning 7 days after their first weaning attempt were classified in the group 3 of the weaning according new definition (wind) classification (1) . we here describe specific data concerning weaning and hospital evolution of group 3 patients included in this prospective cohort. among the 2709 patients included in the wind study, 235 were classified in the group 3. additional data concerning comorbidities, cause of weaning failure and hospital evolution were collected for 213 (91%) of these 235 patients. results: these 213 patients had median [interquartile range] duration of invasive mechanical ventilation of 18 [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] days and 3 [2] [3] [4] separation attempts. etiology of icu hospitalization was medical in 171 (80%). they had a copd in 49 (23%), hearth disease in 33 (15%) and immusoppression in 31 (15%). we noticed a mean saps ii of 53 ± 18, a mean sofa d1 of 8 ± 4 and d3 of 7 ± 4. tracheostomy for weaning was performing in 55 (26%). at the end of their follow-up, 144 (68%) were still alive-44 (21%) were still tracheostomized, 4 still intubated and ventilated, 8 (4%) treated with vni and 88 (41%) were extubated (or decannulated) and breathed without assistance. among the 44 patients still tracheostomized at the end of the follow-up, 14 (32%) were still ventilated (permanently for 8 of them, and partially for 6) and 30 (68%) had spontaneous breathing through their tracheostomy. these patients had a total icu length of stay of 30 days. the destination at discharge from the icu is known for only 49 of the 144 survivors-24 (49%) in medical ward, 15 (31%) in intermediate care units, 4 (8%) in sub acute care, 3 (6%) in icu and 3 in surgical ward. conclusion: a third of the 213 patients of the wind study classified in group 3 and with available additional data died in hospital in 2 months following intubation. at the end of the follow-up, 41% had spontaneous breathing without assistance, and 21% were still tracheostomized. among these tracheostomized patients, one third still required mechanical ventilation. (1)-béduneau, g., pham, t. and co (2017) . epidemiology of weaning outcome according to a new definition. the wind study. ajrccm, 195(6) , 772-783. introduction: copd patients have often polyglobulia because of associated hypoxemia especially in patients at the stage of chronic respiratory failure. we recently reported that anemia was present in 36% of patients with severe aecopd admitted to icu without impact on short-term prognosis. the aim of the present study was to assess the long-term impact of haemoglobin (hb) levels on outcomes of aecopd patients. patients and methods: in a prospectively collected database including consecutive patients admitted between 2007 and 2015 for aecopd in our icu. long-term status of patients following the first icu admission (surviving or deceased) has been verified by consulting the civil status registers. anemia was defined according to who criteria-hb < 13 g dl in males + hb < 12 g dl in females. long-term survival was assessed by kaplan-meier curve. results: the cohort included 213 patients (median age 67, median ph 7.30, 84.5% males, niv as first ventilator mode in 87.4%). anemia was observed in 77 of the 213 patients (36.2%) with median haemoglobin levels at 10.8 and 14.5 g dl, in patients with and without anemia, respectively. anemia was associated with significantly lower 2 years survival (log rank p = 0.043) (fig. 1 ). the final model included age, saps ii score, comorbidities, home oxygen therapy, initial ventilatory mode, niv failure and haemoglobin levels. multivariate analysis identified age (or 1.05 per year + ic 95% 1.01-1.10 + p = 0.028), home oxygen therapy prior to exacerbation (or 2.38 + ic 95% 1.09-5.12 + p = 0.029), intubation at icu admission (or 6.97 + ic 95% 2.31-21.03 + p < 0.001), niv failure (or 11.5 + ic 95% 2.75-47.6 + p < 0.001), and haemoglobin (or 1.20 per decrease of 1 g dl + ic 95% 1.01-1.44 + p = 0.034) as independently associated factors with 2 years mortality . we conducted a prospective observational study including all patients who visited the sis during the last 12 months. the collection of the usual anonymous demographic, medical and toxicological data was performed by the care-givers and social workers in charge of the drug users. data were declarative and no analytical confirmation was available except for the patients admitted in the icu. results discussion during 10 months, 818 drug users [f m sex ratio 0.13 + median age 37.8 years (21-69) + patients without resources (40%), without medical insurance (27%), unstable housing homelessness (52%)] visited the sis for drug injection or inhalation, representing 50,060 drug use including 14,587 inhalations and 35,473 injections by 180 drug users day. drug users had no addictology (48%) or sociomedical (27%) follow-up. they were infected by hepatitis virus c (44%) and or hiv (5%). they declared to continue injecting in the public space (52%), sharing material (13%), and needles syringes (47%). the injected inhaled drugs in the sis were skenan ® (morphine, 42.6%), crack (43% including 1 3 injections), methadone (6.3%), buprenorphine (6.1%), heroine (1.2%), and cocaine (0.89%). these drugs were self-administered by polydrug users declaring concomitantly consuming crack (72.0%), illicit morphine (68.5%), cocaine (34.8%), ethanol (33.7%), cannabis (33.4%), heroin (29.9%), illicit methadone (20.4%), benzodiazepines (13.6%) and illicit buprenorphine (9.5%). forty-five patients required a paramedical intervention in the sis resulting in 17 calls to the emergency department and 15 hospital admissions including 2 transfers to the icu in relation to opioid overdose. no cardiac arrest and no death occurred. conclusion: sis visit for recreational drug self-administration rapidly becomes popular among drug users. illicit morphine (skenan ® ) glycemia (mmol/l) 6.2 (5-7) 6.5 (5-8)ketones in the effluent liquid (g/l) 0.15 (0.025-0.8) 0 (0-0) patients and methods: physiological tracings were recorded from the standard monitoring system (intelliview mp70 philips), using a dedicated network and extraction software (synapse v1, ltsi inserm u1099) that enables photoplethysmographic recordings from oximetry monitoring at a native resolution of 125 hz. raw data were subsequently stored on a dedicated local server, before anonymization and analysis. all consecutive patients were recorded for a 2-hours period during the 24-hours following icu admission. all measurements were recorded with the patient laying supine, with a 30° bed head angulation. physiological recordings were associated with metadata collection by a dedicated research assistant.hrv parameters defined in a previous study were derived using kubios hrv premium ( introduction: preventing post liver transplantation (lt) hepatic artery and portal vein thrombosis is challenging and includes enoxaparin administration. enoxaparin pharmacokinetics (pk) has not been investigated in children following lt. between-subject variability and critical illness may alter pk, leading to the risk of subtherapeutic exposure. patients and methods: clinical, biological and kinetic data were retrospectively collected in a single pediatric intensive care unit center from january 2013 to july 2015. we described an enoxaparin pk model in 22 children the first week following the lt. anti-xa activity timecourses were analyzed using a non linear mixed effects approach with monolix version 2016r. results: anti-xa activity time-courses were well described by a one-compartment open model with first order absorption and elimination. body weight prior the surgery (bwpreop) and the related postoperative variation (bw(t)) were the main covariates explaining cl and v between subject variabilities. parameter estimates were cli = cltyp*(bwpreop 70)3 4 + vi = vtyp*(bw(t) 70)1 + where typical clearance (cltyp) and typical volume of distribution (vtyp) were 1.26 l h −1 and 16.9 l, respectively. standard dosing regimens of 50 iu kg 12 h were insufficient to reach the target range of anti-xa activity of 0.2 to 0.4 iu ml. specifically, 7 children (32%) did never attain the target range during the whole period of treatment and all children were at least once under dosed. according to the final results, we simulated individualized dosing regimens within 4 h following the first administration. more than 100 iu kg 12 h are suggested to reach the target range of anti-xa activity of 0.2 to 0.4 iu ml from the first day. standard enoxaparin dosing regimens is not appropriate to reach the target in pediatric liver transplantation patients. enoxaparin pk modeling should help the physician to achieve the target range from the initial dose and during the maintenance doses. higher dosing regimens, especially in youngest children are suggested to achieve the prophylactic target range. pharmacokinetic analysis of unfractionated heparin in critically ill children during extracorporeal membrane oxygenation: do we achieve the target? introduction: preventing thrombosis in children under extracorporeal membrane oxygenation (ecmo) requiring unfractionated heparin administration. unfractionated heparin pharmacokinetics (pk) has not been well investigated in children under ecmo. we described the unfractionated heparin dosing regimens and resulting anti-xa activities in children with ecmo. patients and methods: this is a single center retrospective study from march 2015 to september 2016. were included children (< 18 years old age) who were under ecmo for refractory hemodynamic failure related to (i) myocarditis or (ii) septic shock. anti-xa activity timecourses were analyzed using a non linear mixed effects approach with monolix version 2016r. results: a total of 12 children were included (septic shock, n = 6 + myocarditis + n = 6 with a median age of 42 months (0-197), a median weight of 17.7 kg (4.9-69) and median admission pelod-2 score of 11 (6-21). bleeding occurred in 2 children and thrombosis in 4. an initial bolus of unfractionated heparin ranging from 30 to 85 iu kg was infused and then continued by continuous perfusion with an initial dosing ranging from 15 iu kg h to 215 iu kg h. a total of 214 anti-xa activity measurements were performed between 1 h empirically antibiotics for these patients with severe infection may be recommended. introduction: prognosis of allogeneic hematopoietic stem cell transplant (hsct) recipients admitted to icu has improved with advances in hsct procedures and critical care management, but also with evolution in icu triage policy. our aim was to describe the outcome of hsct recipients admitted to icu according to a wide admission policy. patients and methods: retrospective multicenter study including all consecutive allogeneic hematopoietic stem cell transplant (hsct) recipients admitted to saint-antoine hospital medical icu, paris, france from to january 2005 to april 2017. admissions were identified through a systematic review of icu database using icd-10 codes z948 and t860. data were extracted from medical charts. qualitative and quantitative values are expressed as number and percentage, and median and interquartile range, respectively. comparisons between groups were performed using fisher's exact test and mann-whitney test for qualitative and quantitative variables, respectively. a p-value < 0.05 was considered to be significant. results: one hundred seventeen patients-77 men (65.8%), median age 53 [36-63] years-were included in the study. underlying hematological malignancies were: acute myeloid leukemia (n = 51, 43.6%), myelodysplastic/myeloproliferative neoplasms (n = 22, 18.8%), acute lymphoid leukemia (n = 22, 18.8%), lymphoma (n = 11, 9.4%), other 11 (9.4%). complete remission was achieved before hsct in 61 (56%) patients. forty-nine (46.2%) patients underwent myeloablative conditioning regimen and 23 (21.1%) received haploidentical grafts. twenty-eight (23.9%) patients experienced disease relapse after hsct and 48 (41%) graft versus host disease prior icu admission. median saps ii was 49 and sofa score at day one 9 [6-11]. the icu, hospital and 90-day mortality rates were respectively 38.5, 54.9 and 57.5%. in univariate analysis, factors associated with 90-day mortality were: saps ii (p = 0.0011), invasive mechanical ventilation (p < 0.0001), vasopressors (p = 0.0012) and renal replacement therapy (p = 0.045). mechanical ventilation was the only independent factor of 90-day mortality (or 2.5-16.4], p < 0.0001) with mortality rate reaching 76.9% and even 86.7% among patients with uncontrolled hematological disease. conclusion: prognosis of unselected hsct recipients admitted to icu remains poor, particurlaly among those receiving mechanical ventilation, and even more if hematological disease is not controlled. these results suggest that the implementation of an icu triage policy determined both by intensivits and hematologists would be helpful to identify good candidates for icu admission. introduction: acute respiratory failure (arf) is a common event in patients with primary malignant brain tumors (pmbt). even if many factors (corticosteroid therapy, swallowing disorders) suggest a specific etiologic spectrum, few data are available regarding its precipitating factors. our first aim was to compare the causes of arf between patients with pmbt and those with other type solid tumors. our second aim was to identify, among pmbt, the factors influencing survival in icu. patients and methods: bicentric case-control study from march 1996 to may 2014. patients with pmbt (cases, primary central nervous system lymphoma included) admitted for arf were compared to patients with other kind of solid tumors (controls). the reason for admission "arf" as well as the causes of arf was determined by three experienced respiratory physicians and were required for inclusion: a respiratory rate > 20 cycles/min and a pao2/fio 2 < 300 for patients in spontaneous breathing and only a pao2/fio 2 < 300 for patients under mechanical ventilation. in both groups were excluded patients with metastatic solid tumors, benign tumors or tumors with more than 5 years of complete remission, recent post-operative patients, and patients with other immunodeficiency. results: a total of 84 cases and 133 controls were included. main patients' characteristics are reported in the table 1 . acute infectious pneumonia was the leading cause of arf in both groups but was more frequent among cases (77 vs. 36%, p < 0.001). cardiogenic pulmonary edema and exacerbation of chronic respiratory diseases were more frequents in controls (10 vs. 37%, p < 0.001). pulmonary embolism was similar between the two groups (10 vs. 4%, p = 0.143). among acute infectious pneumonia, pneumocystis pneumonia (pcp) and aspiration pneumonia were more frequent in cases (19 vs. 2%, p < 0.001 and 19 vs. 8%, p < 0.001 respectively). in multivariate analysis cancer progression (or-7.25 95%ic [1.13-46 .45], p = 0.034), need for intubation (or-7.01 95%ic [1.29-38 .54], p = 0.022) and respiratory rate (or-1.17 95% ci [1.05-1.30], p = 0.003) independently predicted icu mortality of pmbt patients. conclusion: in pmbt patients, the causes of arf differ significantly from other cancer patients. up to 30% of the admissions was related to preventable causes (pulmonary embolism, pcp) and a curable cause was identified in the majority of cases. our results suggest that pmbt alone is not a relevant criterion for icu recusal. introduction: drug intoxication is a common problem encountered in emergency departments. poisoning remains a major cause of hospitalization for young people, and that of the elderly is constantly increasing. objectives 1. determine the epidemiological characteristics of addicted patients 2. know the clinical manifestations of poisoning. patients and methods: a retrospective study of cases of acute poisoning recorded at the university hospital center chuoran between january 2013 and december 2015 was carried out. seizure on data processing by epi-info version 3.5 results: 808 cases of acute poisoning, with an age ranging from 16 to 90 years. female patients predominated with 67%. people between the ages of 16 and 25 are the people most affected by poisoning. the nature of poisoning is varied. in this series, analgesics were found to be the leading cause of acute intoxication, with 81 cases, 31% followed by psychotropic drugs (24%), benzodiazepines (21%), neuroleptics (6%), antiepileptics%) and antihistamines (9%). the majority of acute intoxications were managed within an average time of 2.51 ± 3.03 h with an interval between 0.5 and 48 h. in 74% of cases the poisoning was asymptomatic, there were digestive manifestations in 10% of patients, 7% neurological, 6% cardiovascular and 3% respiratory. we deplore 1 death in this series secondary to many drug poisoning. conclusion: acute drug poisoning is a common reason for admission to the emergency department of oran university hospital. the large number of drug families offered for sale, as well as the heterogeneity introduction: selective serotonin reuptake inhibitors (ssris) have been considered for their low toxicity comparatively to antidepressant agents. the present study aims to describe clinical features and prognosis of poisoning ssris. patients and methods: a retrospective study of patients admitted to our 12-bed teaching icu for acute ssris poisoning over a period of 8 years from january 2009 to december 2016. ssris poisoning was retained on a history of over dose ingestion, clinical signs and positive urine samples for ssris. results: thirty seven patients were collected, the middle age was 32 ± 15 years with a female predominance (86.5%). a psychiatric history with depressive syndrome was noted in 67.6% and a history of suicide in 13.5%. paroxetine was the main invoked drug (n = 20), followed by sertaline (n = 8), then fluoxetine (n = 6), venlafaxine (n = 1) citalopram (n = 1). the mean supposed ingestion dose was 342.9 mg. intoxication was pure in 13 cases and associated with other drugs in 24 cases-benzodiazepines (n = 17), klippal (n = 2), amisulpride (n = 1), non-steroidal anti-inflammatory drug (n = 1), prazin (n = 1) and promethazine (n = 1). neurological examination found drowsiness and mydriasis in 46% of cases (n = 17), coma in 13.5% (n = 5), agitation (n = 5), tremor (n = 5), hyperreflexia (n = 2), hypersudation (n = 1), fever (n = 1) and diarrhea in one patient. the qt was lengthened in five cases. treatment was symptomatic. five patients (13.5%) required mechanical ventilation with average of ventilation duration of 21.2 h. all patients discharged alive the icu. conclusion: ssris poisoning is mainly manifested by serotonergic syndrome. evolution is favorable in the majority of cases. mechanical ventilation could be required. hemodynamic profile of shocks induced by dihydropyridine calcium channel blocker poisoning khzouri takoua introduction: acute calcium channel blockers (ccb) poisoning remains infrequent despite their increasing use. in our country, dihydropiridines are the most prescribed ones. very few works have studied the hemodynamic profile of acute dihydropyridines poisoning either by invasive means (right cardiac catheterization, transpulmonary thermodilution) or non-invasive (cardiac ultrasound). in this perspective, we carried out this study whose main objective was to illustrate the different hemodynamic profiles of shocks induced by dihydropyridine ccb poisoning. patients and methods: it was an observational retrospective study spread over 12 months from 1st january 2016 to 31th december 2016 in a teaching toxicological icu, including all patients admitted for acute dihydropyridine ccb poisoning, who presented a shock and underwent right hemodynamic exploration.results: during the study period, ccb poisoning accounted for 3.15% (n = 24) of all the acute poisoinings requiring hospitalization in our intensive care unit. among them, 21 had taken dihydropyridine which represents 87.5%. four women aged of 29 [21, 47] were eligible. all the exposures were single-drug. the dihydropyridines involved were amlodipine in 2 cases with a median value of supposed ingested dose (sid) of 297.5 mg and nicardipine in the other two ones, the median sid was 1000 mg. the delay of consultation was of 2.25 ± 1 h after ingestion. gastrointestinal decontamination was performed in one patient with activated charcoal. the 4 patients developed a shock within 3 h, treated by initial vascular filling on average 1000 ml of crystalloids, noradrenaline alone in 3 cases and with a combination of dobutamine in one patient. other adjuvant treatments (high dose insulin, calcium salts) have been used in all patients. their hemodynamic profile evaluation by right-handed catheterization swan-ganz was in favour of vasoplegia in 3 cases with median values of systemic vascular resistances (svr) of 224 dynes.s.cm-5, of cardiac output (co) of 14 (l min), and of the arteriovenous oxygen difference of 4.76. the fourth patient's shock had mixed nature with svr of 507 dynes.s.cm-5 and co of 3.7 (l min). all patients were discharged from the icu with a mean length of stay of 14 days. conclusion: the dihydropyridine calcium channel blockers poisoning exposes to the shock risk due to several mechanisms. the clinician must be warned to look for signs of severity and understand its mechanisms by using the hemodynamic study in order to improve its management. goulmane mourad 1 , alachaher djamel 1 , djebli houria 1 introduction: in daily practice, admission to the intensive care unit (icu) usually does not raise any major ethical problems. difficulties arise mainly in acute situations requiring intensive care that have not been anticipated and therefore, not adequately prepared and discussed. we hypothesized that non-admission of a patient to the icu must occur in the following circumstances-(1) with the patient's agreement, expressed either directly or through advance directives (ad), or as relayed by a surrogate or the family + (2) according to a collegial decision-making process (if the patient is decisionally incapacitated) + and (3) after seeking the opinion of an external consultant. the decision-making process must be documented in the patient's medical file. patients and methods: prospective, observational study in two hospitals (one large university hospital, one regional non-acamedic hospital) over a period of 2 months. inclusion criteria were-patients aged ≥ 18 years presenting with failure of at least 1 organ that was directly life-threatening and requiring life-sustaining therapies. complete data collection was performed for each patient. results: a total of 31 patients were included (61% from the emergency department and 39% from medical wards). the decision not to admit the patient to the icu was taken-(1) during night duty for 19 patients (61%) + (2) by a senior physician in 100%, and (3) after clinical examination in 25 (80%). the main reasons justifying the decision not to admit to the icu were-(1) metastatic cancer in 8 patients (26%) + (2) total loss of autonomy in 8 (26%) + (3) severe cognitive impairment in 4 (13%) + (4) premorbid state in 1 (3%) + (5) chronic organ failure for 2 (5%) + and (6) presence of ad (written or oral) specifying that the patient did not wish to be admitted to the icu in 8 (26%). this study raises several points concerning the decision-making process for patients requiring intensive care. first, collegiality is observed in almost all situations of non-admission (97%). second, an outside consultant was contacted in around 30% of cases. third, 26% of patients had ad. fourth, the family or entourage were consulted in less than 40% of cases and finally, in around 75% of cases, the decision-making process was documented. conclusion: this study shows that in emergency situations, it is more difficult to take adequately structured decisions regarding icu admission than, for example, decisions regarding limitation or withdrawal of treatment in the icu. introduction: as known, tracheostomy is performed to improve quality of life (qol) in patients requiring prolonged mechanical ventilation. it is indicated to facilitate care of critically ill patients, in order to minimize risks of oro-tracheal intubation, and enhance recovery, allowing early discharge from icu with home ventilation. we aimed by this study to evaluate long-term survival and qol in tunisian patients discharged from the icu with tracheostomy, as well as related burden assumed by their relatives. patients and methods: patients who were admitted to the icu between 2015 and 2017 were eligible for inclusion in this retrospective cohort if they had a tracheostomy during their icu stay, and were discharged at home with a tracheostomy canula. for survivors, we used the short form health survey (sf12) to assess their qol at home. we estimated the degree of autonomy using the adl scale. to assess burden assumed by caregivers (family members most of the time) we used the short version of zarit burden interview. exclusion criteria were refusal of the interview or unavailability on the phone call. results: fourteen patients were discharged at home with a tracheostomy canula. only twelve responded to the phone call. four patients died 1 month later. amoung the 8 survivors, the removal of the tracheostomy canula was successful in 3 patients after a mean duration of 30 days. main findings are summarized in table 1 . conclusion: tracheostomy shows good acceptance and acceptable qol. it allowed shorter length of stay in the icu and long-term survival after discharge from the icu, and should be encouraged for tunisian patients. in contrast, the qol of patients' relatives was more affected, with significant burden and work load. introduction: intensive care survivors present often some psychological disorders linked with experience memory loss or nightmares. the use of patient diaries has been developed and implemented by clinical staff to improve the quality of life after intensive care. patients received their diaries at icu discharge. this study was conducted in order to understand the potential benefits for patients the diary on prevalence anxiety, depression and post traumatic disorders during recovery. patients and methods: a structured interview study was administered to adult critical illness survivors who received ≥ 48 h of mechanical ventilation in a medical and surgical intensive care unit. after 6 months, this patients answered at two questionnaire-hospital anxiety and depression scale (had) and a screening instrument for ptsd (qspt). results: from the survivors at 6 months, 36 patients answered the questionnaires. we have two groups-18 patients had a diary and 18 patients no diary. but these group are so low currently to compare introduction: in ards patients under ecmo common ventilator strategy aims at resting the lung by lowering tidal volume (vt) in the 1-4 ml kg predicted body weight range found in the literature analysis. we tested on the bench the not previously explored hypothesis that vt was not delivered in the 10% accuracy by most of icu ventilators in this low range. patients and methods: pneumatic test lung set at 20 ml/cmh2o compliance and 20 cm h 2 o/l/s resistance was attached to any of 5 icu ventilators (v 500 (drager), carescape r 860 (ge healthcare), servo u (maquet), pb980 (covidien) and g5 (hamilton)) equipped with heated humidifier (fisher-paykel mr 850) set off and adult ventilator circuit (rt 380 evaqua fisher paykel). each icu ventilator was set in btps condition, at peep 12 cm h 2 o and fio2 0.21. airway pressure and airflow (hans-rudolph pneumotachograph) were measured (biopac m150) proximal to the lung model. for each ventilator a series of vt ranging from 100 to 280 ml was delivered for 10 breaths each, at 30 then at 15 breaths/min respiratory rate (rr). the relationship of vt measured to vt set was assessed by linear regression over the 5 icu ventilators for each circuit-rr combination. in each model, the change from the mean effect was assessed for each ventilator. for each model we obtained the mean effect of the 5 ventilators then we compared the effect of each ventilator to the mean effect. results: for each combination of f and circuit, the mean slope was significantly lower than 1 indicating that, on average, the set vt was under delivered (table) . there were differences in change in slope from the mean across the ventilators with interaction between ventilators and combinations. as an example, for the adult circuit f 15, carestation, pb980 and servo u performed better than g5 and v500. across the combinations, v500 had consistent negative (greater underestimation than average) slopes and servo u consistent positive (lower underestimation than average) slopes whilst the slope sign in the three others changed direction. biomarkers. yet, hla-dr expression on alveolar monocytes was lower in ards than in controls, consistent with sepsis-induced immunosuppression at the alveolar level. functional differences observed between ards and controls suggested a tolerogenic profile of ards monocytes. introduction: despite their recommendation in the prevention of ventilator-associated pneumonia, oral care is not still clearly standardized. it generally includes a time for oropharyngeal and tracheal suctions which can induce a cough reflex in non-paralyzed patients leading to the mobilization of the endotracheal tube and a consecutively increased risk of tracheal microaspirations. during the oral care procedure, drainage of subglottic secretions at particular times before oro-tracheal suctions is expected to reduce microaspiration. the aim of this study is to assess whether this "optimized" oral care including subglottic drainage can reduce microaspirations. this is an open prospective study, including icu ventilated patients. two procedures have been compared in two randomized cross-over consecutive periods of one day each (3 oral cares a day)-on 1 day, they received routine oral care (oral care (o) then tracheal suction (t)) and on the other day they received optimized oral care (subglottic suction (sg1) then o then sg2 then t). the amylase enzymatic activity has been measured in o, t, sg1 and sg2 suctions as a surrogate for the oropharyngeal content. if present in t suctions, it defines microaspiration. since the amylase o content is not similar from a patient to another, the primary outcome was the median amylaset o ratio after routine versus optimized oral care. results: after informed consent, 24 patients were included. 21 were analyzed due to incomplete follow-up in 3 patients. patients (sapsii 51 ± 16) were ventilated since 4.5 ± 4.3 days for a majority of respiratory indications. at day 1, 10 and 11 patients received routine oral or optimized oral car respectively without significant baseline difference. a trend in the reduction (− 35%) of amylase t o median ratio was observed after optimized versus routine oral care (2.3% [0.6-6 vs. 1.5% [0.7-16], p = 0.16. conclusion: despite protection of trachea by the cuff of the endotracheal tube, amylase has been found in tracheal suctions (which represents the last step of oral care). in this pilot study with a limited sample of patients, a trend in the reduction of microaspirations was observed when subglottic suctions were interleaved between oral and tracheal suctions. an increased sample power could show more significant results, but we cannot eliminate that this weak effect could also be due to the inability of subglottic suctions to prevent microaspiration of the oral content. the study has been founded by teleflex. introduction: although necessary, mechanical ventilation can lead to ventilator-induced lung injury (vili) even when using protective ventilation strategies that combine low tidal volume (vt)(6 ml kg predicted body weight) and plateau pressure (pplat) <= 30cmh20. lower positive pressures and tidal volumes could enhance lung protection + the hla-dr and pd-l1 expressions were higher on alveolar than on blood monocytes in both ards patients and controls (figure) . yet, hla-dr expression on alveolar monocytes was higher in controls compared to ards patients (p = 0.004). circulating monocytes had a higher phagocytic activity than alveolar monocytes (p < 0.001), but no significant difference was observed between ards patients and controls. an lps challenge increased the phagocytic activity of monocytes in controls (p = 0.03) but not in ards monocytes (p = 0.88). tnf-α intracellular synthesis was increased after lps exposure in circulating and alveolar monocytes of controls (p < 0.05) but only tended to do so in ards (p = 0.08). conclusion: differences in the phenotype of alveolar and circulating monocytes were observed in ards but also in controls, suggesting a physiological lung blood gradient in the expression of these results: until 31 03 2016, ten patients were included and analyzed for the study. there was a significant difference between the volumes recruited at the three peep levels (p = 0.002). the recruitment evaluated was not correlated with pao2. there is a significant decrease in cardiac index and pam caused by the increase in peep. conclusion: preliminary results from our study suggest that the estimated recruited lung volume estimated by crf inview ® technology appears to be poorly correlated with measured pao2. the hemodynamic repercussions observed should also be considered in order to propose an optimal strategy for the optimal adjustment of peep. were compliant with the re-evaluation. 191 (85%) patients received carbapenems according to the recommendations. a compliant prescription had no impact on hospital or icu length of stay and no impact on duration of mechanical ventilation but seemed associated with increase mortality (p = 0.04). discussion: the high rate of compliant prescriptions can be explained by the broad indications of carbapenems in the icu, especially in patients with septic shock. the increase mortality of patients with a compliant prescription is probably due to the severity of the infections. in order to achieve 100% compliance, we could suggested regularly updating the knowledge of carbapenems prescriptions, collaborating with bacteriology and infectiology teams, and establishing a computerized or paper prescription with feedback control. conclusion: the prescription of carbapenems appears most often in accordance with the recommendations in this icu. however, there is a need for improvement. introduction: bacterial infections are frequent triggers for diabetic ketoacidosis and a significant increase in morbimortality is observed in case of delayed antibiotic treatment. however the unnecessary administration of antimicrobial therapy can also lead to bacterial resistance. early sepsis markers are thus particularly useful for patients admitted in icu for diabetic ketoacidosis. patients and methods: we retrospectively studied cases of patients admitted in icu at avicenne french universitary hospital for ketoacidosis defined by ph < 7.3 and glycemia > 13.75 mmol l. clinical and biological data were analyzed at admission (d0) and on day 2 (d2). results: between 2010 and 2016, among 93 patients admitted for diabetic ketoacidosis, 69 were included. twelve out of 69 were infected (5 urosepsis, 5 pneumonia, 2 others). demographic data and comorbidities did not significantly differ between the infected and non infected group (ig and nig). antibiotics were administered to 33 patients-12 12 (100%) in the infected group versus 21 57 (36.8%) in the non infected group. on d0, there was no difference for-ph, temperature, leukocytes, neutrophils-to-lymphocytes count ratio and pct (table 1) . on d2, temperature, leukocytes, neutrophils-to-lymphocytes count ratio and pct were significantly higher in the ig. in the ig, the biological markers did not vary between d0 and d2, whereas in the nig, leukocytes (p < 0.0001), pnn (p < 0.0001) and neutrophils-to-lymphocytes count ratio (p < 0.0001) significantly decreased. surprisingly average pct levels seem to be particularly high in the nig on do as well as on d2. conclusion: at admission, pct as well as other usual markers do not appear to be useful to differentiate infected from non infected patients admitted for ketoacidosis. however, on day 2, two different patterns can be drawn and help detecting non-infected patients and thus reduce exposure to antibiotics. these results should be confirmed by a prospective study, including a larger number of patients. ventilator-associated events (vae), reflecting worsening oxygenation, are defined as a persistent and significant increase in fio 2 or peep level after a period of stability on the ventilator. vae definition includes ventilator-associated conditions (vac), infection-related ventilatorassociated complications (ivac) and probable ventilator-associated pneumonia (pvap). the relevance of vae for ventilator-associated pneumonia (vap) is low. however, the correlation between the three vac, ivac, and pvap, and the onset of ventilator-associated low respiratory tract infection (valrti), including ventilator-associated tracheobronchitis (vat) and pneumonia (vap), has never been studied yet. we on clinical examination. gravity scores-apache ii and saps ii. for lumbar puncture data, there is the proteinuria, glycorrhaphy resuscitation measures-drug intake and intubationin multivariate analysis, the factors of pejorative evolution-the male sex presence of meningeal syndrome. high proteinorachia. taking vasoactive drugs. the saps ii score. conclusion: according to this work, many factors influence the prognosis of acute meningitis in our population such as severity general scores, hemodynamic state and initial lumbar puncture data. we will need more investigations and prospective multicentric study to have more discrimination parameters. introduction: the emergence of atb-resistant bacteria has become an important public health problem, particularly in resuscitation environments, surveillance and monitoring of atb consumption is essential to combat this threat ecologically and economically. the aim of this work was to evaluate the consumption of atb in surgical resuscitation, to establish the cost, and to list the risk factors for bacterial resistance. patients and methods: it is a retrospective analytical study spread over 1 year, studying 225 patients who have received antibiotic therapy, the data on the consumption of atb were collected from the patient's medical records, the delivered doses were converted into ddd, according to the who standards and the end result is expressed in ddd 1000 days of hospitalization. the statistical analysis was carried out by the spss 16 software. results: in our study, the mean age was 43.15 ± 5.5, with male predominance + sex ratio 1.71, traumatic pathology is the most common reason for admission, pneumopathy was the most frequent infection. overall atb consumption was 1236.11 ddd 1000dh, dominated by the class of betalactamins (cephalosporins 166.89 ddd 1000dh, carbapenemes 179.68 ddd 1000dh), the direct cost of atbs rises to 0.33 million dirhams, these are accounting for a large part of the pharmaceutical budget of the ibn rochd university hospital. bacteria found in order of frequency were acinetobacter baummanii, beta-lactamaseproducing enterobacteria, s. aureus and p. aeruginosa. acinetobacter baumannii showed the highest resistance rate. several risk factors for bacterial resistance were studied, notably the correlation between the use of atb and the emergence of resistant strains, only piperacillintazobactam was associated with the emergence of resistant strains of eblse, as well as 2 other factors that were retained as significantly related to bacterial resistance by multivariate analysis-duration of hospitalization and perfusion of albumin. discussion: despite the limited number of studies done on atb consumption, it seemed that our results were similar to other national and foreign studies, the consumption of atbs is increased in hospital giving rise to the appearance of many multi-resistant bacteria. conclusion: in conclusion, resistance to antibiotics is a serious threat to public health both nationally and globally. it is therefore crucial to implement measures to counter this phenomenon + this is only possible through the proper use of atbs and gaits to prevent nosocomial infections. introduction: ventilaor-associated pneumonia (vap), the leading cause of infection in resuscitation, is also the main respiratory complication in cranial trauma. the aim of this study is to determine the specific risk factors for the occurrence of vap in this type of patient in an intensive care unit. patients and methods: we performed a retrospective study in our intensive care unit for an 18-month period (january 2016, june 2017). all patients admitted for cranial trauma were included in the study and ventilated more than 48 h in intensive care. vap is defined as late as of the 5th day of occurrence. the quantitative and qualitative variables studied were recorded at admission and during hospitalization. a univariate and multivariate analysis using the fischer and mann-whitney tests was performed. p is said to be significant if it is < 0.05. results: our study included 50 traumatic brain injury in older adults, of whom 22 (44%) had one or more episodes of vap during their resuscitation. late vap accounted for almost 2 3 of the cases (33 patients). four independent variables were significantly related to the occurrence of vap-advanced age (p = 0.04), glasgow score (gcs) at admission < 8 (p = 0.01), diabetes (p = 0, 03), and the use of proton pump inhibitors for the prevention of stress ulcers (p = 0.04). the duration of intubation (18 ± 6 vs. 11 ± 3 days) and on intensive care (28 ± 16 vs. 15 ± 3 days) are significantly longer in the case of vap. mortality was significantly higher in vap-45 versus 28% (p = 0.01). the majority of early vap were due to both strepococcus ppneumoniae and haemophilus influenzae. the ecology of late vap was dominated by klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter baumanii. conclusion: of the four independent risk factors found in our study, glycemic balance and rapid airway safety by orotracheal intubation in the case of initial gcs < 8 represent the 2 relevant prevention axes of vap in traumatic brain injury in older adults. unfortunately, it is accompanied by a significant increase in bacterial resistance to antibiotics, leading to an increase in morbidity and mortality in intensive care units. patients and methods: this is a retrospective study carried out in our intensive care unit, covering all patients hospitalized between january 2010 and june 2014 and having contracted a nosocomial urinary infection. patients whose hospital stay was less than 48 h and those fig. 1 agreement between vae and lrti diagnostic with a nosocomial urinary tract infection acquired in another service were excluded. results: the study of resistance of the germs responsible for nosocomial urinary tract infection showed that-escherichia-coli was resistant to third generation cephalosporins in 21% of cases, at imipenem in 8% of cases, and without resistance to ertapenem and amikacin. pseudomonas was resistant to ceftazidime in 61% of cases, to imipenem in 64% of cases and to amikacin in 44% of cases. acinetobacter baumannii was resistant to imipenem in 87% of cases and to amikacin in 85% of cases. enterococcus faecalis had no resistance to vancomycin and ampicillin. staphylococcus aureus was resistant to methicillin in 25% of cases and without any resistance to vancomycin. mortality directly associated with nosocomial urinary tract infection was 11%. the comparison with previous studies has shown a significant increase in the bacterial resistance responsible for nosocomial urinary tract infection, which is of interest in monitoring the ecology of intensive care units and the resistance profile as well as the improvement of the management of antibiotics. introduction: nosocomial enterococcus infections are a constant concern in intensive care units due to their increasing frequency and the emergence of resistant strains to vancomycin. the aim of our study was to compare outcome findings of patients with nosocomial enterococcus infections according to their sensibility to vancomycin, and then to investigate predictive factors of mortality. patients and methods: it was a retrospective descriptive study, including all hospitalized patients in intensive care, between january 1st, 2013 and april 1st, 2017, with nosocomial enterococcus infections. we recorded demographic and clinical findings, severity scores igs ii, apache ii, initial sofa and sofa at the time of infection, microbiological, therapeutic and outcome data. patients infected with vancomycin-susceptible enterococcus (vse) were compared to those having vancomycin-resistant enterococcus (vre) + then we searched for independent risk factors for vre. finally, a multivariate logistic regression was conducted to investigate independent predictive mortality factors. results: during the study period (4 years and 3 months), 35 patients presented a nosocomial enterococcus infection with a median age of 63 years [25-87] and a sex-ratio of 2.18. at admission, 31 patients (83.3%) had respiratory distress. the median scores of igs ii, apache ii, initial sofa and sofa at the time of infection were respectively 45 + 16 + 6 and 6. the infection sites were-urinary infection (n = 17, 48.6%), bacteremia (n = 15, 42.9%) and central line associated infection (n = 3, 8.5%).16 patients had a vre nosocomial infections and 19 vse. a septic shock complicated enterococcus infection in 13 cases including 7 cases of vre and 6 cases of vse (p = 0.458). vre nosocomial infections were significantly related to arterial (p = 0.006) and venous (p = 0.009) femoral catheterization, to a duration of venous femoral catheterization > 3 days (p = 0.035) and to e. faecium species (p < 10-3). no independent risk factor of vre was found. the median duration of hospitalization was 34 days and the overall mortality rate was 68.6%. multivariate analysis identified 2 independent predictive factors of attributable mortality-patients in coma (or 30.44 + ic 95% = 1.99-465.39 + p = 0.014) and the occurrence of septic shock (or 14.4 + ic 95% = 1.45-137.72 + p = 0.023). conclusion: attributable mortality to nosocomial enterococcus infections was high and independent of the susceptibility of the strain to vancomycin. mortality was independently associated to septic schock occurrence and neurologic dysfonction. introduction: ventilator-associated pneumonia (vap) is defined by a lung infection contracted 48 h after the putting under mechanically assisted breathing. risk factors predisposing to the development of vap among mechanically ventilated patients are many. some are related to the patient as age, history of copd, presence of an altered state of consciousness + others are related to care providing. patients and methods: a prospective nested case control study was conducted from marsh 2014 through april 2015. all icu patients mechanically ventilated for more than 48 h with endotracheal intubation or tracheostomy were included. cases of community-acquired pneumonia, non-mechanical ventilated hospital-acquired pneumonia, end-life patients and those aged less than 18 years were excluded. the included patients with vap and those without vap were matched based on the age, the severity score and the comorbidities. for all patients included, preventive measures as assessed by the recent guidelines for preventing vap were applied after an education period of all medical and paramedical staff of the icu. the collected data are-age, comorbidities, admission severity scores, time to onset of vap, prior antibiotic therapy at the onset of vap, need for tracheostomy, duration of mechanical ventilation, length of stay in icu and become. results: during the study period, 71 patients were mechanically ventilated. vap was observed in 42% of cases. vap was observed in 27 cases with an incidence of 38% and incidence density of 21 per 1000 patient-days of mechanical ventilation (mv). in univariate analysis, significant difference was found between the group with vap and the group without vap regarding admission for poly trauma, acute respiratory failure, the concept of prior antibiotic therapy, the need tracheostomy, the number of days alive without antibiotics and without mv, the duration of mechanical ventilation, length of stay and mortality. multivariate analysis showed that prior antibiotic therapy and the use of tracheotomy were independent factors for developing vap. prolonged duration of mechanical ventilation was an independent predictor of mortality in multivariate analysis with or 1.773 + 95% [1.202 to 2.616], p = 0.04. the occurrence of vap was not an independent predictor to mortality. conclusion: the incidence of vap found in our study is similar to that found in the literature. an active strategy of rationalizing the prescription of antibiotics in intensive care units and a well-defined protocol of weaning from mechanical ventilation may reduce the incidence of vap and over-all morbidity and mortality. introduction: hyperoxemia is common in critically ill patients. hyperoxic acute lung injury (hali), reduced bacterial clearance, atelectasis and higher mortality rates were reported in mechanically ventilated patients with hyperoxemia. the aim of our study was to determine the relationship between hyperoxemia and mortality in patients with ventilator-associated pneumonia (vap). this retrospective observational single center study was performed in a 50-bed mixed intensive care unit (icu) during a 1-year period, from january 2016 to january 2017. all patients with vap were included. vap was defined using clinical, radiological and quantitative microbiological criteria. hyperoxemia was defined as peripheral capillary oxygen saturation-spo2 ≥ 98%. spo2 was hourly collected in all study patients during the whole period of mechanical ventilation. the daily percentage of time spent with hyperoxemia was calculated as the number of hours with hyperoxemia divided by 24. results: among the 547 patients receiving invasive mechanical ventilation (mv) > 48 h during the study period, the incidence rate of vap was 11.7 vap per 1000 ventilator-days. 93 patients developed vap and were all included in this study. 30 (32%) vap patients died in the icu. the mean daily time spent with hyperoxemia was 45%. no significant difference was found in mean percentage of time spent with hyperoxemia between survivors and nonsurvivors at icu admission, before, after or at the vap diagnosis. age, and sequential organ dysfunction assessment (sofa) at the day of vap occurrence were independently associated with icu mortality (or 1.04 [1.007-1.075 ] per year, p = 0.02 + 1.19 [1.064-1.339 ] per point, p = 0.003 + respectively). no significant impact was found of time spent with hyperoxemia before vap occurrence, on mv free days, or icu length of stay (fig. 1 ). discussion: several potential explanations could be provided for the absence of negative impact on mortality of hyperoxemia. first, the definition used for hyperoxemia could be debated, as no consensus exists. however, the definition used in our study was rather stringent and the mean daily time spent with hyperoxemia was in line with that reported by studies. second, the impact of hyperoxemia on mortality could have been confounded by a large number of patients included with pulmonary lesions at admission. third, the number of included patients was small. conclusion: our study found no significant impact of hyperoxemia at icu admission, or during icu stay, on icu mortality in vap patient. results: 128 patients collected during this period. 228 distal protected specimens were performed in patients suspected of vap. the diagnosis of this infection was made. in 55 of them with other diagnostic criteria (43%) which represents an incidence density of 8.2 per 1,000 days.80% of pavm are due to gram negative bacilli. the first germ involved in our series and pseudomonas (30%) followed by klebsielles (15%) followed by acintobacter baumanii (8%) enterobacteries representing the rest.12% lung infection with gram-positive cocci (principally sensitive methicillin) pseudomonas was imipenem resistant in 18.4%, baumanii was imipenem resistant in 55%. the resistance profile of the recovered germs (baumanii and pseudomonas) encourages the utmost rigor in the management of these patients, prevention is better attitude to adopt. introduction: the ventilator associated pneumonia (vap) appear in the second rank of the infections acquired in hospital after the urinary infections. the diagnosis is based on a beam of clinical, biological, radiological and bacteriological arguments. this work consisted of an epidemiologic analysis of the vap and aimed at evaluating of it the frequency, the risk factors, the antibioresistance of the isolated bacteria and the mortality factors. patients and methods: this retrospective study related to 906 patients hospitalized in icu during a period of 3 years from january 2014 to december 2016. the study included all patients over 18 years and ventilated more than 48 h and developing vap. results: bgn predominant and represent 80.16% of identified germs, the acinetobacter baumanni leads with 33.88%, followed by klebsiella pneumonia (13.22%), followed by pseudomonas aeruginosa (9.92%), followed by e. coli (6.61%), followed by enterobacter cloacae (3.31%) and citrobacter frendi (1.65%). the cocci gram positive (cgp) constitue 18.19% of isolated germs of witch 14.88% staphylococcus aureus, 0.83% of non aureus staphylococci, 2.48% streptococcus sp. the polymicrobism was found in 33% cases. the isolated germs were multiresistants. in this study, we find a very high mortality and a major additional morbidity of the np by prolongation of hospitalization, of mechanical ventilation and a major additional cost.conclusion: it appears in the light of this work that a strategy of prevention based on the strict application of hygiene measurements, the maintenance of the material of ventilation and the respect of care procedures prove to be urgent in our context. introduction: burns induce modification of distribution volume, increased clearance of drugs and decrease of protein binding. amikacin pharmacokinetics (pk) was altered with subthera-peutic serum concentrations. the aim of our study was to assess the pk of amikacin in burns after a loading dose given once a day according to this equation-dose(mg kg) = 30*pi(30*0,4*dp1) + (30*0,4* dp2). threshold for therapeutic efficacy was a ratio of ≥ 8 between the concentration achieved 1 h after beginning the infusion (c peak) and the minimal inhibitory concentration (mic) of the isolated pathogen. patients and methods: this study was conducted in burn center in tunis. patients with documented and or suspected infections were included. were excluded pregnant women and patients with renal failure. enrolled patients received amikacin at a loading dose in 1 h infusion. blood samples for pk analysis were assessed during 5 days (total duration of amikacin)-immediately after the end of the first infusion (t1) and 30 min after (t2) at day 1. for the 2nd, 3rd, 4th and 5th day, blood samples were taken before the infusion (t0), at the end (t1) and 30 min after the end of it (t2). results: 18 burned patients were included. the mean age was 40 ± 15 years with a body weight of 78 ± 15 kg. the mean dose of amikacin was 26 mg kg day [20-35 mg kg day]. a peak between 60 and 80 μg/ml was reached in 55% of cases, corresponding to 8 times the mic, break-points for enterobactericeae and pseudomonas aeuroginosa. total volume of distribution was 0.55 l kg (0.28-1.32) l kg, half-life time (t1 2) was 4.70 h [1.42-8 h] and the amikacin clearance was 6.4 l h. a correlation was found between cpeak at day 1 and cpeak at day 5 (r = 0.45). conclusion: our study shows that an early achievement of an optimal cpeak mic ratio of amikacin was reached in half of cases with a correlation between cpeak in the beginning and at the end of treatment. so, initial cpeak was useful tu adjuste amk therapy in burns and predicts treatment efficacy. *pi-ideal weight + dp1-admission weight-ideal weight + dp2-actuel weight-admission weight. publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord-005727-li8pwigg authors: nan title: esicm 2010 monday sessions 11 october 2010 date: 2010-08-31 journal: intensive care med doi: 10.1007/s00134-010-1999-x sha: doc_id: 5727 cord_uid: li8pwigg nan methods. for the present investigation, 8 healthy male volunteers with a mean age of 29 ± 3.6 years were recruited for a cardiovascular screening exercise stress test prior to inclusion for the study. during the lbnp protocol, the subjects were exposed to sequential increasing negative pressures of -20, -40, and -60 mmhg while resting in a supine position with their legs sealed in the lbnp chamber at the level of the iliac crest. in addition to continuous registration of cardiac output (co) and mean arterial pressure (map), sublingual perfused vessel density (pvd) (1) and microvascular flow indices (mfi) (2) were measured using sidestream dark-field (sdf) imaging before (t0), during (t1; -60 mmhg), and after (t2) lbnp. results. there were no significant differences in mean co and map in our subjects. introduction. fever management remains controversial in sepsis. control of thermal balance might improve vascular tone but fever could play a role in host defence. objectives. the aim of this multicentre randomised controlled trial was to determine primarily whether external cooling might accelerate the weaning of vasopressors in patients with septic shock. patients with septic shock treated with epi/norepinephrine infusion and fever over 38.3°c were enrolled in 7 centres when also requiring mechanical ventilation and sedation. patients received external cooling to reach normothermia (36.5-37°c) during 48 h (n = 101) or had fever respected (n = 99). a goal of 65 mmhg for mean arterial pressure was used in the two groups. a similar algorithm was used for weaning of vasopressors. the main end point was the number of patients achieving a 50% decrease in the initial dose of vasopressor in the two groups. shock reversal was defined by vasopressor withdrawal for at least 24 h. at inclusion the two groups (cooling/respect of fever) were similar for age 61 ± 14 versus 59 ± 15 years, saps iii (68 ± 12 vs. 70 ± 13), sofa score (11 ± 3 vs. 11 ± 3), and body core temperature (39.0 ± 0.6 vs. 39.0 ± 0.6°c). a similar number of patients received steroids and a pc before enrolment. body temperature became significantly lower in the cooling group within the 48 h of treatment: 36.8 ± 0.7 vs. 38.4 ± 1.1 at h12 and 36.8 ± 0.5 vs. 37.6 ± 1.17°c at h48 (p \ 0.001). the decrease in vasopressor was more rapid in the cooling group (fig. 1 ). shock reversal was 84 vs. 73%, p = 0.07 and in-hospital mortality was 45 vs. 48% in the cooling and the respect of fever groups respectively. conclusions. these preliminary results show that treating fever using external cooling in septic shock patients allows a more rapid decrease in the dose of vasopressor without apparent adverse effect. grant acknowledgment. aphp-scr 06012. we set up to describe the antibiotic treatment regimens prescribed for patients with severe sepsis in spanish icus and to analyze the potential therapeutic benefit of combination therapy. methods. edusepsis subanalysis, including all patients with severe sepsis admitted to the 77 participating icus during 8 months, in three periods between november 2005 and june 2007. there was analyzed the time between the presentation of sepsis and the initiation of antibiotic treatment and empirical antibiotic used in terms of focus and origin of sepsis (community/nosocomial). we also studied the combination therapy compared to monotherapy, assessing the impact on outcomes of combination therapy in particular. the results are presented as frequencies (percentage) or mean ± standard deviation. results. there were included 2,782 patients with severe sepsis (age 62. conclusions. combination therapy is not associated with a better outcome in this large cohort of patients with severe sepsis. nevertheless, there is room for improvement since 61% of patients did not receive antibiotic therapy within the first 3 h from admission, as recommended by the ssc. introduction. tracheostomies are increasingly common in hospital wards and can lead to significant patient harm. this is partly due to bed pressures in uk critical care units and the increasing use of percutaneous and surgical tracheostomies for critical care patients. commonly, hospital wards lack the infrastructure to care for tracheostomies safely. objectives. analyse tracheostomy-related critical incidents reported in the uk over a 2 year period. we wished to identify themes and make recommendations to improve patient safety. methods. the search was conducted from 1st october 2005 to 30th september 2007 and was conducted in february 2008 to allow time for incidents to be submitted. the selected incidents were then incorporated into an access database (microsoft office 2007) and the description of each incident was read and reviewed. we analysed 968 tracheostomy-related critical incidents reported to the uk national patient safety agency over a 2 year period, identified by key letter searches. we categorized the records to identify recurring themes and then performed root cause analysis where possible. results. we identified 1,541 incidents from the npsa incident database originating from hospital wards during the study period having the defined letter sequences. of these incidents, 968 were associated with tracheostomies; 453 directly affecting patients with the remaining 515 not directly affecting individual patients. in the 453 incidents where patients were directly affected 338 (75%) were associated with some identifiable patient harm of which 83 (18%) were associated with more than temporary harm. in 29 incidents (6%) some intervention was required to maintain life and in 15 cases the incident may have contributed to the patient's death. there were 15 cardiac arrests and 26 respiratory arrests described in these incidents. of the 453 incidents, 126 involved equipment and there were 276 blocked or displaced tracheostomy tubes described. note: an individual incident could be classified in multiple fields conclusions. we were able to identify themes in incident reports associated with tracheostomies and identify areas where care could be improved to reduce risks to patients. there were a number of recurrent problems that contributed to incident evolution or severity that would be potentially avoidable. these include: introduction. the study of computerized thoracic tomography patterns can be of great help in the diagnosis of the causes of acute respiratory failure in the icu patients. we hypothesized that the consecutive analysis of a series of thoracic cts will contribute to the management of these critically ill patients. objectives. to study, over a three-month period, the thoracic cts performed in the adult icu in the albert einstein hospital in são paulo, brazil. methods. from may 1st to august 31st, 2009, all the thoracic cts were analyzed by two radiologists from the albert einstein hospital staff according to a pre-established protocol: (1) presence of parenchymal consolidations; (2) ground-glass opacities; (3) septal thickening; (4) atelectasis (5) pleural effusions; (6) pneumothorax (7) pneumomediastinum; (8) subcutaneous emphysema; (9) presence of nodules; (10) presence of masses; (11) presence of cysts; (12) emphysema; (13) bronchial thickening. results. hundred and sixteen thoracic cts were performed and analyzed over the study period, from 64 (55.1%) males and 52 (44.9%) females. the mean age of the patients was 65.30 ± 19.03 years. thoracic ct analysis revealed: (1) parenchyma consolidations: 59 (50.8%); (2) ground-glass opacities: 72 (62%); (3) septal thickening: 41 (35.2%); (4) atelectasis: 78 (67.2%); (5) pleural effusions: 94 (81%) (6) presence of pneumothorax: 10 (8.6%); (7) pneumomediastinum: 3 (2.5%); (8) subcutaneous emphysema: 11 (9.4%); (9) nodules: 30 (25.8%); (10) presence of masses: 2 (1.7%); (11) presence of cysts: 2 (1.7%); (12) emphysema: 21 (18.1%); (13) bronchial thickening: 51 (43.9%). conclusions. thoracic ct is a useful tool for a detailed analysis of the lung parenchyma, specially in the detection of ground-glass opacities, consolidations and atelectasis, improving the diagnostic possibilities and management of acute respiratory failure. s. wolf 1,2 , a. rieß 3 , j.f. landscheidt 2 , c.b. lumenta 2 , l. schürer 2 , p. friederich 3 1 charite campus virchow, department of neurosurgery, berlin, germany, 2 klinikum bogenhausen, neurosurgery, muenchen, germany, 3 klinikum bogenhausen, anesthesiology, muenchen, germany introduction. extravascular lung water index (evlwi) may present a valuable marker for the severity and treatment of acute lung injury and acute respiratory distress syndrome. measured by single indicator transpulmonary thermodilution and indexed to predicted body weight, a threshold of 10 ml/kg is currently regarded as the upper limit of normality. however, so far only critically ill patients were studied and data from subjects with normal cardiovascular function is lacking. objectives. to prospectively investigate evlwi in patients without cardiopulmonary compromise. methods. patients requiring elective brain tumor surgery were equipped with a transpulmonary thermodilution device (picco 7.0, pulsion medical systems ag, munich, germany). triplicate evlwi measurements were performed after induction of anesthesia (time point 1), before (time point 2), during (time points 3 and 4) and after surgery (time point 5) as well as after extubation (time point 6) and before discharge from the neurosurgical icu (time point 7) . data were recorded electronically and investigated with a random effect model to cope for multiple measurements per individual. results. 641 valid measurements were performed in 101 patients (60 female/41 male, fig. 1 ). no patient showed clinical signs of over-hydration or cardiopulmonary failure and all were discharged regularly from the icu on postoperative day one. indexed to predicted body weight, females had a mean evlwi of 9.1 (sd 3.0, range 5-23) ml/kg and males had a mean evlwi of 8.0 (sd 1.9, range 4-19) ml/kg (p \ 0.001). 26% of the measurements in females and 11% in males exceeded the threshold of 10 ml/kg. no significant differences were between the different time points of measurement (p = 0.28) or during anesthesia and after extubation (p = 0.86). conclusions. measured with single indicator transpulmonary thermodilution and indexed to predicted body weight, evlwi frequently shows values above the previously established normality threshold of 10 ml/kg in patients without cardiopulmonary compromise. females present significantly higher values than male patients. as we are not aware of any abnormal hemodynamic profile for brain tumor patients, we propose our findings as a close approximation to normal values for evlwi. introduction. cardiovascular dysfunction is though to be common during weaning from mechanical ventilation. however, its precise incidence is unknown in this setting. in addition, the respective impact of systolic and diastolic dysfunctions on the weaning process have not been studied. objectives and methods. this is an ancillary study of the ''bnp for the management of weaning'' clinical trial. patients were ventilated with an automated weaning system as soon as they tolerated pressure support ventilation with an fio 2 b 50%, a peep level b 8 cmh 2 o, and a total inspiratory pressure b 30 cmh 2 o. a total of 67 patients underwent transthoracic echocardiography (tte) at day1 (initiation of weaning). in addition, serial tte were performed in a subgroup of 31 patients to explore left ventricle filling pressures variations during daily weaning trials (low-pressure support with zero end-expiratory pressure). filling pressures were assessed using the ratio of early transmitral peak velocity (e) over early diastolic mitral annular velocity (e 0 ). results. day 1 tte revealed a systolic (ejection fraction \ 50%) or diastolic dysfunction (defined as e 0 \ 8.5 cm/s) in half of patients. treatment during weaning included diuretics (84% of patients), vasodilators (45%) , dobutamine (28%), amiodarone (28%) and betablockers (3%). diastolic dysfunction was more prevalent in patients with difficult or prolonged weaning as compared to those with simple weaning (weaning duration \ 3 days). serial tte revealed a greater increase in e/e 0 ratio during failed weaning trials as compared to successful trials. conclusions. when treated, systolic dysfunction does not seem to jeopardize weaning. in contrast, diastolic dysfunction is associated with difficult/prolonged weaning. during failed weaning trials, there is a more pronounced increase in filling pressures as compared to successful trials. introduction. monitoring and determination of fluid responsiveness in a critically ill patient who presents with circulatory compromise and septic shock is essential but often, challenging and difficult. continuous haemodynamic monitoring using arterial pulse contour analysis is less invasive compared to the thermodilution method using the pulmonary artery catheter. objectives. we aim to assess the utility of stroke volume variation as measured by the flotrac ò device (edwards lifesciences, irwine, usa) as a predictor of fluid responsiveness in patients with septic shock. we studied 11 mechanically ventilated adult patients with septic shock in the medical intensive care unit (icu) of a university hospital. haemodynamic parameters including stroke volume variation (svv) and stroke volume (sv) were recorded using radial arterial pulse contour analysis (flotrac ò pressure sensor versions 1.10 and 1.14) before and after a crystalloid fluid challenge. fluid responsiveness was defined as an increase of c 10% in sv after the fluid challenge. results. the sensitivity, specificity, positive predictive value and negative predictive value of a svv of c 10% to predict fluid responsiveness were respectively 50.0, 33.3, 33.3 and 50.0%. the area under the receiver operator characteristic curve for the prediction of fluid responsiveness using svv (pre) was only 0.583 . similarly, there was no correlation between svv (pre) and the absolute change in stroke volume (spearman's rho -0.192, p = 0.60). conclusions. our study's findings call for caution with the use of svv measured via versions 1.10 and 1.14 of the flotrac ò device to predict fluid responsiveness in patients with septic shock. further studies are now required to assess if recent software upgrades may provide more accurate svv measurements in severely septic patients. objective. our objective was to assess the recent literature with respect to cco monitor validation. in particular we wished to determine if study protocols reflected the dimension of time. we looked at four different cco monitors: vigileo tm , picco tm , pulseco tm , and oesophageal doppler (odm). human validation studies of cco monitors were sought through the ovid interface, generating over 3,000 hits. manufacturers' websites were also searched. case reports were excluded, as were abstract-only publications, letters, and studies over 10 years old. ultimately, 99 studies were included. a full reference list and search strategy is available from the authors. a recent article provided suggested criteria for assessment of cco monitors [1] : this was used to generate a proforma. to check for interobserver bias, a subselection of five studies was assessed by the three authors independently; no differences were found. the authors summarised the remaining studies individually. results. results are summarised in table 1 . w rows do not add up because some studies evaluated more than one monitor researchers have yet to address the necessity of validating cco monitors with respect to their realtime functionality. while most studies give an assessment of bias based on essentially static measurements, fewer than half document sampling time or directional change reliability. response time and response amplitude to a step change in cardiac output are important variables which may influence patient treatment; in the vast majority of studies, these have not been assessed. in this respect, all four monitors have yet to be validated. this study offers two perspectives: one, for clinicians to realise that the cco monitor in their intensive care unit may not have been as extensively validated as they think; another, for researchers, to realise that work is still to be done. initial distribution volume of glucose rather than right ventricular end-diastolic volume is correlated with cardiac output following cardiac surgery j. saito 1 , h. ishihara 1 , e. hashiba 2 , h. okawa 1 , t. tsubo 2 , k. hirota 1 1 hirosaki university graduate school of medicine, anesthesiology, hirosaki, japan, 2 hirosaki university graduate school of medicine, division of intensive care, hirosaki, japan introduction and objectives. rational decision making for cardiovascular and fluid management in critically ill patients requires reliable assessment of cardiac preload. we have reported that initial distribution volume of glucose (idvg) measures the central extracellular fluid volume and has potential as an alternative preload variable 1) . idvg can be approximated rapidly and simply in any icu using a conventional blood glucose analyzer 2) . right ventricular end-diastolic volume (rvedv) has been shown to be a better indicator of cardiac preload than cardiac filling pressure 3) . this study was intended to determine whether idvg, rvedv, pulmonary artery wedge pressure (pawp) or central venous pressure (cvp) are correlated with cardiac output (co) during the early postoperative days following cardiac surgery in the absence of apparent congestive heart failure. methods. twenty-nine consecutive patients who underwent cardiac surgery such as coronary artery bypass grafting (either off-pump or on-pump: n = 6), valve surgery (n = 10) and aortic arch replacement (either hemi or total: n = 13) were studied. patients associated with excess hyperglycemia ([ 14 mmol/l), arrhythmias or mechanical cardiovascular support were excluded from the study. a volumetric thermodilution pulmonary artery catheter for continuous monitoring of co and rvedv was placed in the operating room. immediately after cardiovascular variables were recorded, idvg was determined using the incremental plasma concentration at 3 min after administration of glucose (5 g) as described previously 2) . three sets of measurements were performed; on admission to the icu and daily at 10 a.m. on the first 2 postoperative days. the relationship between either volumetric or static variables and cardiac index (ci) was evaluated throughout the study period. a p value.05 was considered statistically significant. results. all but one patients required vasoactive drugs during study period. indexed idvg (idvgi) had a moderate correlation with ci (r = 0.56, n = 87, p \ 0.001), even though indexed rvedv (rvedvi) had a slight correlation with ci (r = 0.29, n = 87, p = 0.007). a linear correlation was also obtained between changes in idvgi and those in ci (r = 0.47, n = 58, p \ 0.001). however, changes in rvedvi had not a correlation with those in ci (r = 0.10, n = 58, p = 0.47). neither pawp nor cvp had a correlation with ci (r = -0.02, n = 65 and r = -0.06, n = 87, respectively). although cardiac dysfunction has a significant impact on determining co early after cardiac surgery, our results demonstrate that idvg rather than rvedv is correlated with co. idvg has potential as being an alternative indicator of cardiac preload following cardiac surgery. (spv) are reliable predictors of fluid responsiveness in controlled mechanically ventilated patients [1] . ppv and spv are calculated using an intra-arterial catheter. it is unknown whether an arterial pressure signal obtained with the nexfin tm system [2] using only a finger cuff can be used to calculate ppv and spv. objectives. to validate ppv and spv measured with a finger cuff. methods. after their arrival on the icu, sedated and mechanically ventilated patients after coronary artery bypass graft surgery (cabg) were included. intra arterial pressure (iap) was measured using an arterial catheter inserted in the radial artery, and non-invasively, using the finger cuff of the nexfin tm monitor (bmeye, the netherlands). we took the mean value of ppv and svv in a 1-min time interval before and after the administration of a fluid challenge. agreement of the ppv and spv measured by the finger cuff and from the iap signal were assessed using the method described by bland and altman. results. nineteen patients were included and twenty-eight volume challenges were analyzed, resulting in 56 simultaneous measurements. ppv and spv measured by the finger cuff correlated with ppv and spv from iap (r 2 = 0.92, p \ .0001 and r 2 = 0.93, p \ .0001, respectively), see figure 1 . the mean bias was -0.95 and -0.22% for ppv and spv respectively, and limits of agreement were -4.3 and 2.4% for ppv and -2.2 and 1.7% for spv (see figure 2 ). there was no correlation between the bias and the mean value of the two measurement methods. the correlation between changes in ppv and spv measured by the two different methods was r 2 = 0.82 (p \ .0001) for ppv and r 2 = 0.83 (p \ .0001) for spv. conclusions. in ventilated icu patients, ppv and spv can be reliably calculated using the nexfin tm monitor. reference(s). (1) kramer, a., et al., chest, 2004. 126(5) . (2) eeftinck schattenkerk, d.w., et al., am j hypertens, 2009. 22(4) . introduction. the transpulmonary thermodilution (tptd) technique with integrated pulse contour analysis (picco ò -system) enables continuous monitoring of cardiac index (ci) after calibration by tptd [1] . this monitoring technique is applied in patients with lung failure who undergo prone positioning (pp) which has been shown to potentially improve pulmonary gas exchange [2] . objective. we sought to determine the influence of a modified pp (135°) on the accuracy of pulse contour derived ci (pcci) without recalibration by tptd. patients: after approval by our institutional review board and written informed consent by a legal surrogate we studied 16 critically ill patients (11#, 5$, age 20-71 years) who were mechanically ventilated due to acute lung injury following lung contusions or acute respiratory distress syndrome. methods. all patients were prone positioned and had received an extended haemodynamic monitoring (picco ò , pulsion medical systems ag, munich, germany). before turning from supine position (sp) to pp, ci was measured by tptd (tptdci) and pcci was calibrated. ten minutes after positioning, pcci was read from the monitor and then recalibrated by tptd. after 8-10 h, pp was ended and measurements were performed analogously to prone positioning. volume management between the respective time points remained unchanged. linear regression analysis and bland-altman plots were used for statistical analysis. all data are given as mean ± standard deviation, range in brackets. results. the tptdci in sp was 3.29 ± 0.88 (1.50-4.51 ) l/min/m 2 . after proning, a pcci of 3.51 ± 0.79 (2.15-4.63 ) l/min/m 2 and a tptdci of 3.56 ± 0.75 (2.33-4.63 ) l/min/m 2 were measured. linear regression analysis revealed a correlation coefficient of r = 0.87 (p \ 0.0001). mean bias (tptdci-pcci) was 0.05 ± 0.40 l/min/m 2 . immediately prior to turning back to sp, tptdci was 3.46 ± 0.67 (2.06-4.75 ) l/min/m 2 . after re-positioning, the pcci was 3.28 ± 0.70 (2.00-4.48 ) l/min/m 2 and tptdci was 3.10 ± 0.74 (1.47-4.28) l/min/m 2 , with a mean bias of 0.18 ± 0.37 l/min/m 2 . the correlation coefficient was r = 0.84 (p \ 0.0001). conclusion. pcci is only marginally influenced by prone positioning and is reliable without recalibration by tptd. however, in case of greater differences a recalibration by tptd is nevertheless recommended. objectives. the aim of this study was to analyze the clinical agreement between the intermittent bolus thermodilution technique (tdco) and apco in patients with non-traumatic intracranial hemorrhage requiring intensive care. methods. this was a prospective observational clinical study in a university level icu. we studied 16 adult patients with non-traumatic intracranial hemorrhage, who for clinical indication underwent co monitoring by the tdco (pac, 7.5 fr, criticath tm sp5507h td catheter, becton-dickinson, singapore). in parallel, arterial pressure waveform was applied using the radial arterial pressure curve (flotrac/vigileo tm , version 1.10 and 1.14, edwards lifesciences, ca, usa). tdco measurements were done approximately every 4 h and when needed. the length of data recording was depending on the need for tdco monitoring and icu stays but was no longer than 6 days. every tdco measurements and the simultaneous apco values were recorded and included into the analysis. results. 407 data pairs were obtained. overall, mean co was 7.5 (sd 2.0) l/min for tdco and 6.0 (sd 1.9) l/min for apco. mean bias between tdco and apco was 1.6 l/min ( fig. 1 ), 95% limits of agreement 1.4 to 1.7 l/min and the percentage error 45%. there was a large interindividual variation in mean bias and percentage error (minimum to maximum, -0.7 to 4.8 l/min and 13-51%, respectively). the bias was significantly greater if patient received norepinephrine (0.8 vs. 1.7 l/min, p = 0.04) but not if patient received dobutamine (1.5 vs. 1.9 l/min, p = 0. 28) . only a small correlation between the bias and the rate of norepinephrine infusion was detected (q = 0.16). when cardiac index of 2.5 (l/min/m2) was used as a cut off value for need for intervention, the sensitivity and specificity for apco were 0.50 (95% ci 0.24 to 0.76) and 0.94 (95% ci 0.87-0.93), respectively. conclusions. according to our results the second generation of flotrac ò /vigileo ò monitoring system underestimates the tpco and the sensitivity is poor. there is also a large interindividual variation in bias. the use of norepinephrine may provoke the error. objectives. to compare 5 cardiac output techniques to the reference tte method, which allows accurate measurement of the aortic flow section and of velocity time integral of aortic pulsed wave doppler signal to measure co. methods. monocentric prospective study included patients requiring invasive blood pressure and hemodynamic therapeutic intervention. tte co measurement was performed with aortic diameter measured in parasternal long axis view at the the aortic leflets, and velocity time integral measured using five apical view averaged on 5 cardiac cycles. tod co was measured only when the pac insertion was decided. tte, uscom ò , mostcare ò and vigileo ò were performed in all patients. each value was the average of 5 successive cardiac cycles with 3 consecutive measurements. each patient could have several measures. results. 24 mechanically ventilated patients (60 ± 20 years; sofa 8 ± 3.5) were investigated allowing to obtain 252 measurements (117 under norephinephrine). diagnostics: brain injury (n = 9), sepsis(n = 9) and others (n = 5).1 patient had the 6 methods (9 measurements), 13 patients had 5 techniques (115 measurements), 9 patients had 4 techniques (69 measurements), 6 conclusions. all methods correlated more or less with tte co, with a slope close to identity, and a low intercept. the best correlation was obtained between mostcare ò and tod. agreement for almost all methods was large, within an acceptable range. for the pulse contour method, mostcare is correlated better than vigileo with tte co. the arterial signal has to be accurate as possible and requires a high quality chain for measurement avoiding overdamping or underdamping to allow effective signal digitalization. introduction. the lithium indicator dilution technique is attractive in paediatric intensive care because it is non-invasive. however, it requires calibration. the reliability of cardiac output measurement data rests on the reproducibility of the calibration factor (cf). objectives. to establish the number of calibrations (= x) that are required in a paediatric patient material, if the coefficient of variation for the calibration factor does not increase by 10% or more by (x + 1) calibrations. to establish x it is also required that 80% of the patients do not show an increase in cv by 10% or more and that 0% of the patients show an increase in cv by 20% or more at (x + 1). hemodynamically stable sedated and ventilator treated children under intensive care with a body weight of 3-15 kg were included. to perform calibration, 0.007 mmol/kg of lithium chloride was injected intravenously and the concentration of lithium ions in arterial blood was analyzed by a lithium selective electrode. the calibration process was repeated 5 times and the cf as well as lithium indicator cardiac output (lidco) were calculated. results. results from 6 children with a mean body weight of 7.7 kg are presented below. cv was below 1% throughout the investigation. introduction. stroke volume variation has been shown to be a better indicator of fluid responsiveness than static indices such as cvp or paop. a limitation of dynamic parameters is arrhythmias which produces abnormal svv. beat-to-beat variations reflect altered cardiac filling times not the effects of mechanical ventilation in fluid responsive conditions. a recently developed enhanced algorithm (newsvv) helps eliminate this limitation. newsvv rejects ectopic beats using multi-parameter signal recognition and restores the respiratory variation of the signal using spline-based interpolation. objectives. to evaluate the performance of the new arrhythmia rejection svv algorithm to predict fluid responsive from patient data with frequent arrhythmias. methods. newsvv was developed from data collected in a porcine model to limit the impact arrhythmias had on svv. comparing the current standard svv (svvstd) algorithm (flotrac-vigileo system edwards lifesciences, usa) with the newsvv showed a significantly improved sensitivity and specificity. (1) in this preliminary study 3 sets of patient data with frequent pvcs and atrial fibrillation (afib) were ran through the new algorithm and compared to the data from svvstd. in one patient 13 fluid boluses (195-440 cc platelets and packed red blood) during a period of afib caused newsvv to decrease from 25 to 10% and co to increase from 4.5 to 6.2 l/min, while svvstd algorithm did not show a significant change (varying randomly between 10 and 30%). a second patient had non-paroxysmal afib. svvstd showed abnormally high values ranging between 25 and 35%. patient was a non-responder to fluid and had a co ranging between 10 and 12 l/min. newsvv showed more realistic value of 11% depicting a non-responder range. the third patient had periods of afib followed by normal sinus rhythm (nsr). svvstd algorithm had abnormally high svv values ([ 35%) during the afib. during nsr, both algorithms correlated well with svv of 7%. (fig. 1.) conclusions. the newsvv algorithm improved svv with ectopics and afib and shows promise in eliminating a limitation of svv in those conditions. further studies are needed to fully evaluate the performance in patients with arrhythmia receiving fluid challenges. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 s97 methods. 14 mechanically ventilated pigs (median weight 37 kg) under general anesthesia were investigated. after instrumentation, baseline values were obtained after at least 2 h of stabilization. ''shock'' phase (simulation of aaa rupture): 26 (24-28) ml/kg of blood was gradually withdrawn and hemorrhagic shock maintained for 4 h. abdominal cavity was filled with warmed saline to abdominal pressure of 20 mmhg. ''clamp'' phase: infrarenal aorta was cross clamped for 90 min and hemodynamics was resuscitated with shed blood and fluids. ''post-surgery'' phase lasted 11 h and pigs were subsequently sacrificed. hemodynamics was obtained at baseline, every 30 min for first 2 h of hemorrhage, every 1 h until postoperative phase and every 2 h till the end of the study. data are presented as median (iqr), appropriate non-parametric tests were used for statistical analysis. results. baseline co measured by pac was 145 (122-161) ml/kg/min. both vigileo 214 (185-263) ml/kg/min (p = 0.029) and lidco 77 (60-100) ml/kg/min (p = 0.004) differed significantly. the course of co is shown in fig. 1 , all values are presented as a difference to baseline. the median difference between pac and vigileo was 34 (12-60)% and for lidco 106 (36-171)%. study limitations: both devices were designed for co estimation in humans but we do not expect huge differences in arterial system properties in pigs. young pigs reacted to hemorrhage by severe sinus tachycardia which caused failure in some co measurements but at least 10 pigs are presented at every timepoint. conclusions. absolute co values obtained by both vigileo and lidco differ significantly from pac. unlike lidco rapid, flotrac/vigileo was able to track changes in co during severe hemorrhage. grant acknowledgment. iga mzcr ns 10109-4 and vz msm 0021620819. introduction. most important role of postoperative sedation is suppressing stress of the patients in icu. urinary 8-hydroxy-2-deoxyguanosine (8-ohdg) can be a good biomarker for oxidative stress in clinical research. the aim of this study is to assess the free radical production under sedation in icu and compare the production between with midazolam and dexmedetomidine. subjects and methods. subjects were twenty-five patients with sedation after neck malignant tumor operation and ventilated for 48 h in icu. patients with renal failure were excluded from this study. all patients received fentanyl (2 lg/kg/day), fifteen patients were with midazolam (0.1 mg/kg/h: m-group) and ten patients were with dexmedetomidine (0.2-0.7 lg/kg/h: d-group) we examined the concentration of urinary 8-ohdg by high performance liquid chromatography (hplc) method with coolaray system every morning in icu. results. the average value of urinary 8-ohdg of healthy human volunteer is 4 ng/ml. the values of urinary 8-ohdg were less than 2 ng/ml in the both groups and no significant differences were observed between the groups in this study. conclusions. postoperative sedation with both midazolam and dexmedetomidine were effective in suppressing oxidative stress in icu patients. poorly controlled pain in the postoperative period can lead to slow recovery and life threatening complications, especially in elderly patients. it has also been suggested that the quality of postoperative analgesia could decrease delirium incidence and reduce duration of hospital stay in the elderly patients. however, the ideal postoperative analgesia management of elderly surgical patients in intensive care units remains to be determined. since, continuous epidural analgesia provides the required level of analgesia to support early mobilization and significant reduction in pulmonary and cardiovascular morbidity in the early postoperative period, we postulated that the use of low dose of continuous epidural morphine might improve postoperative analgesia and reduce undesirable side effects in elderly patientstherefore, the present study was designed to evaluate the effects of morphine administered via epidural patients controlled analgesia and intravenous tramadol + metamizol on postoperative pain control and side effects in elderly patients after major abdominal surgery. objectives. the purpose of this study was to compare the analgesic efficacy of morphine administered via epidural patients controlled analgesia (epca) with our standard analgesic for postoperative pain treatment, intravenous tramadol + metamizol in eldery patients undergoing major abdominal surgery. methods. forty patients older than 70 years undergoing major abdominal surgery were randomly assigned to two groups. group i received epidural morphine 1 mg at the end of surgery and used a patients controlled analgesia device programmed to deliver morphine 0.2 mg/h, 0.2 mg per bolus. group ii received intravenous infusion of 400 mg tramadol plus 5 mg metamizol in 500 ml electrolyte infusion. the patients in group ii received 125 ml of the infusion solution as a loading dose over 20 min (corresponding to 100 mg tramadol plus 1.25 mg metamizol) postoperative analgesia was tested at rest on a visual analogue pain scale (0 = no pain, 10 = worst possible pain) at 1, 2, 6, 12 and 24 h after surgery. patients' satisfaction, arterial oxygen saturation, respiratory rate, episodes of nausea, vomiting, pruritus and dizziness were also noted. results. both groups obtained adequate pain relief, and there were no between-group differences in pain scores. there were no significant respiratory differences but the patients in the epidural group were more sedated. in the tramadol metamizol group 10 patients were treated for ponv while 5 of the patients in the morphine group showed ponv. we conclude that combination of tramadol and metamizole provided postoperative analgesia equivalent to that provided by epidural morphine in early postoperative period. the both analgesic regimens were safe and suitable for the management of postoperative pain in elderly patients. h. poon 1 , j. hulme 2 1 sandwell and west birmingham hospitals nhs trust, birmingham, uk, 2 sandwell and west birmingham hospitals nhs trust, intensive care medicine and anaesthesia, birmingham, uk a substantial amount of patients in intensive care units (itu) receive an inappropriate level of sedation with a tendency for over-sedation. although the ideal itu sedation practice is not known, many units use a protocol-based approach incorporating best practice consensus. the use of daily interruption of sedation infusions can reduce oversedation and is included in our current guidelines. objectives. the audit assesses compliance to our current protocols for sedation scoring and adjustment of sedation infusions. provision of sedation breaks in patients sedated more than 1-day is evaluated. methods. retrospective review of itu inpatients' daily record charts during june and july 2009 at sandwell and west birmingham hospitals nhs trust in two 16-bedded itu. 184 charts were reviewed. results. our guidelines recommend hourly sedation scoring from 0600 h to midnight and 3 hourly scoring from midnight till 0600 h; at 0000, 0300 and 0600 h. 86% of the reviewed charts did not have a recorded hourly score. 81% did not have 3 hourly scores overnight. 75% of the charts contain ramsay score -2 or -3; 29% of the charts contain ramsay score 2 or 3. per protocol, sedation infusion is stopped at ramsay score -2 or -3 but in 71% of cases this did not occur. a sedation bolus should be given at a score of 2 or 3. 56% did not receive a recorded bolus. our guidelines advocate restarting a sedation infusion at a lower rate after it has stopped and the patient is less sedated and increasing the rate after a bolus is given. however, correct infusion rate adjustments were only performed in 46% of cases. often, rates were changed but without first stopping, or administering a drug bolus. out of 184 sedation days, there were only 62 true daily breaks. conclusions. there is a tendency to over-sedation in our itu; less so under-sedation. common practice deviates from protocol and there is poor documentation. scores are recorded less often than protocol: there may continuous assessment by nursing staff that is not recorded. boluses are given more often than documented on patient charts. review of the current guidance is required to address appropriate frequency of formal scoring, nurse-led compulsory sedation breaks and pharmacokinetic education about the necessity to stop or bolus before infusion rate alterations. introduction. daily interruption of sedation has been shown to decrease length of stay in icu 1 . recent national guidance in scotland 2 promotes dis as part of a care bundle to decrease ventilator associated pneumonia. a 6 week retrospective first round audit was completed prior to the introduction of dis and demonstrated 30% of patient hours where sedation could be improved. a second round audit of current practice was therefore undertaken to assess the impact of dis on sedation levels. our aim was to identify the frequency of periods where sedation levels were undesirable and investigate any clinical reason behind these. objectives. to assess whether dis would improve sedations levels of our patients already managed with a simple sedation algorithm (sa) aiming at a ramsay sedation score level 3-4 3 . methods. six months following the introduction of dis, a second period of 6 weeks was studied retrospectively where the icu daily charts were examined to look at: demographic data, sedation score, and whether dis had been successfully carried out. results. 21 cases were identified: 13 males and 8 females with an average age 61 years and similar illness severity scores to the first group. dis was carried out on 44 patient days, omitted on 3 days and contraindicated on a further 36. 1,395 patient hours were examined. 419 (30%) were excluded due to contraindications such as refractory hypoxia, drug overdose, and end of life care. the remaining patient hours were compared to the first round group [1,540 patient hours with 308 contraindications (20%)] using the mann-whitney test as shown in fig. 1 . conclusions. we could not demonstrate any difference in sedation levels following introduction of dis on our unit. we found a large proportion of patients where dis was unsuitable. introduction. delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients, occurring in up to 69% of ventilated patients in the united kingdom 1 . delirium is independently associated with more deaths, longer hospital stay, and higher overall cost 2 . hypoactive delirium is much more common, is easily missed and is associated with a worse prognosis than hyperactive delirium 3 . objectives. the aim of our project was to quantify the presence of delirium on our critical care unit and to survey the practice of delirium assessment within our region. we conducted a prospective audit at the critical care unit, birmingham city hospital, uk. we used the confusion assessment method for the intensive care unit (cam-icu) to assess for delirium daily on all our patients for a period of 2 weeks. simultaneously, we conducted a telephone survey to elicit the delirium assessment practice of the other units within the west midlands region of the unite kingdom. results. we carried out our assessment on 24 patients over a 2-week period, which resulted in 68 assessments (55 were on non ventilated patients and 13 on ventilated patients). 12 assessments could not be completed because of deep sedation or language barrier. in total we had 17 assessments positive for delirium giving an incidence of 30% for those patients we could fully assess. all of the patients with a positive assessment had hypoactive delirium. the telephone survey revealed only three of the twenty units in our region routinely assessed for delirium. none of the units had a formal management protocol/guideline for delirium. conclusions. delirium is a significant problem on our critical care unit. the incidence was lower than that reported in the literature this might be because firstly we were unable to assess a number of patients due to the patients being deeply sedated, and secondly we noted many of the patients during the assessment period were high dependency patients with minimal organ dysfunction. despite a large number of recent publications on delirium and increasing awareness amongst critical care professionals most of the units in our region do not routinely assess for delirium. without regular assessment most delirium will go unrecognised and thus opportunities to instigate preventative measures and early management will be missed. methods. six patients aged 20-45 years old (4 females) who all sustained brain injury with cerebral oedema alongside other traumatic damage (i.e., fractures, abdominal trauma) are hereby presented. upon admission to the icu all patients received large propofol doses (25-30 ml/h of propofol infusion 2%), in an attempt to lower cerebral metabolic demand along with vasopressors to maintain a normal mean arterial pressure. three to 5 days following admission all patients developed metabolic acidosis (base deficit ranged from -6 to -12 mmol/l), hyperkalemia (potassium concentration ranged from 5.8 to 6.9 mmol/l), evidence of muscle cell degradation (creatine kinase and myoglobin concentrations ranged from 30,000 to 49,000 u/l and from 1,900 to 2,700 lg/l, respectively) and lipaemia (triglyceride concentrations ranged from 4 to 4.4 mmol/l). at that time all patients were clinically stable and usual laboratory tests as well as cultures were inconclusive, hence a diagnosis of pris was suggested. results. three out of six patients developed global left ventricular dysfunction, which was documented by echocardiographic evaluation, with normal cardiac enzymes, while all patients developed acute renal failure. cardiac and renal failure were observed within 24-48 h following the manifestation of the above abnormal laboratory findings. continuous hemofiltration was initiated promptly on a daily basis in all cases, while the administration of propofol was discontinued. abnormal laboratory findings normalized within 2-4 days, while cardiac and renal function gradually ameliorated within a week, following therapy in all cases. no deaths were recorded. conclusions. the initiation of continuous hemofiltration therapy is a crucial therapeutic tool for the elimination of propofol and its potentially toxic metabolites in cases of pris and may have a beneficial effect upon survival in these cases. l. zurong 1 , w. yichun 1 1 intensive care unit of hunan province tumor hospital, changsha, china objectives. our purpose was to compare the analgesic properties, effect, and side effects of intravenous butorphanol and fentanyl during chest tube removal in cardiac surgery patients. seventy-four patients with cardiac surgery were enrolled before chest tube removal. each patient received standard doses of either fentanyl (50 lg) or butorphanol (1 mg) before chest tube removal in a double-blind manner. pain intensity and pain distress were measured before analgesic administration, immediately after chest tube removal, and 20 min later pain quality was measured immediately after chest tube removal. level of sedation was measured before and 20 min after chest tube removal. results. the fentanyl (n = 37) and butorphanol (n = 37) groups were identical with respect to age, race, sex, and weight. pain intensity, pain distress, and sedation levels did not differ significantly between groups. however, procedural pain intensity (mean 3.26, sd 3.00) and pain distress (mean 2.98, sd 3.18 ) scores for all were low. patients remained alert, regardless of which analgesic was administered. conclusions. if used correctly, either fentanyl or butorphanol can substantially reduce pain during chest tube removal without causing adverse sedative effects. thus, clinicians may choose either safe and effective analgesic interventions during chest tube removal. introduction. delirium is defined as an acute alteration of mental status, with either a disturbance of consciousness or a change in cognition which develops over a short period of time and fluctuates during the course of the day. reported prevalence of delirium in critical care varies widely from 20 to 80%. despite this, delirium remains grossly under-recognised and is often thought to be temporary and of little consequence in critical care. it is however one of the most frequent complications and, after adjusting for age, gender and severity of illness is an independent risk factor for prolonged length of stay and mortality (1) . current recommendations are for the assessment and diagnosis of delirium using simple validated tools (2) . pharmacological intervention should be considered when reversible precipitating factors have been corrected. haloperidol is considered the drug of choice. objectives. the purpose of this study was to detect knowledge and awareness of delirium, attitudes and behaviours towards its assessment and pharmacological management in critical care units of two large uk teaching hospitals a 15-point survey was distributed to all senior medical and nursing staff employed in critical care at the leeds general infirmary and the james cook university hospital, middlesbrough. a total of 114 questionnaires were collected after four follow up rounds via web-based survey tool ''survey monkey''. results. the survey detected a significant awareness of the problem delirium poses in icu. the vast majority (84%) of practitioners did not screen for delirium routinely. of the16% who screened only 1 in 10 used screening tools that were appropriate, the majority lacked the knowledge of suitable methods to do so. 82% of respondents felt that they required tools to aid diagnosis of delirium in their unit. the pharmacological management of delirium varied significantly, with a wide range of drugs used, suggesting the need for guidance. the majority of respondents (95%) felt that they needed guidelines for treatment of delirium, 90% felt that guidelines would change their practice. despite an awareness of the problem delirium poses in icu, data from this survey shows a lack of knowledge of assessment and treatment. given that most respondents needed guidelines, we have developed a delirium treatment protocol and implemented the confusion assessment method for icu (cam-icu) training package for all staff in the james cook icu. following its implementation we plan to re-evaluate in the hope that the awareness of delirium can be met with the appropriate knowledge to implement a sustained change in practice. results. 50 patients were included, 35 male (70%), mean apache ii score 21 ± 5. midazolam was suspended in 77% after 6 h. maximum dose of sufentanyl was 3 mcg/kg/h. bilirrubin and creatinin did not change from initial values and there was no effect in enteral nutrition tolerance. bis values improved 22% from 50 ± 10 to 39 ± 9 (p = ns) and there were less hemodynamic effects as well as less necessity of amines and sedatives. results are shown in table 1 . conclusions. sufentanyl is an efficient and safe sedative that reduces necessity of more sedatives, amines and generates adequate sedation without renal or hepatic effects. a.s. puxty 1 , j. kinsella 1 , k. anderson 1 1 glasgow royal infirmary, department of anaesthetics, glasgow, uk etomidate is a sedative agent often used for the induction of critically ill patients. it is, however, a controversial drug with effects on the steroid axis that have been suggested may lead to a poor outcome. so far this has only been proven in infusions of the drug. despite this some have called for its withdrawal altogether objectives. to determine the attitude of anaesthetists and icu consultants in five hospitals in a major uk city towards the use of etomidate. methods. an online questionnaire was constructed using surveymonkey (portland, oregon, usa). this was then sent out to all anaesthetists in glasgow via an e-mail link. a reminder was sent after 2 weeks. trainees from one of the hospitals were unable to be contacted via e-mail and so hard copies of the questionnaire were sent to them. of a total of 243 anaesthetists in glasgow (trainees and consultants), 175(72%) completed the questionnaire successfully. of those answering the questionnaire, 18.2% were sho level, 23.9% spr, 57.4% consultants and 0.6% sas grade. these respondents sub-specialities/specialist interest were: general (46%), pain (8%), icu (22.2%), obstetrics (14.8%) and cardiac (9.1%). overall 64(95% ci 57-71)% of respondents were concerned about etomidate's effect on steroid synthesis, although when asked about induction of an emergency laparotomy 53 (46-60)% would still use it [with 34 (27-41 )% avoiding it and 12 (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) % responding that they were never involved in emergency laparotomies]. of those using etomidate, 27 (18-36)% would avoid it in a septic patient, and a further 33(23-43)% would give steroid cover. the most common reason for using etomidate was cardiovascular stability [98 (96-100)%]. other reasons given were simple dosing (6 [1-11] )% and habit (13 [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] )%. more than one reason was allowed. looking for differences between groups the following was found: while icu consultants reported more concern over etomidate (75 vs. 50%, p = 0.044), there was no difference in etomidate usage in emergency laparotomy (65% of general vs. 50% of icu consultants, p = 0.31). trainees were more likely to have their habit changed by the recent literature on etomidate (56 vs. 41%, p = 0.035). conclusions. there is concern among anaesthetists and icu consultants regarding the use of etomidate but usage has not changed markedly by most. further evidence of harm would likely need to be demonstrated before abandonment of the drug. introduction. nociception and requirement of additional analgesia before painful procedures in icu are difficult to anticipate. under anaesthesia, the direct pupil light reflex reflects the sympatho-vagal balance and remains altered by pain and sedative drugs. the pupillometry is a reproductive, non invasive method based on automated flash light device assessing pupillary variations [1] . to study pupillometric parameters to anticipate the tolerance to painful stimuli (surgical debridement). methods. eligibility criteria: sedated patients (morphinomimetics + benzodiazepines, bps = 3) in days after invasive surgery for cervical necrotizing fasciitis (cnf), complicated or not with mediastinitis, requiring a surgical debridement three times a day. clinical evaluation performed before and during debridement: heart rate (hr), mean arterial pressure (map) and behavioral pain score (bps) [2] . pupillometric test before debridement (calibrated bright flash of one-second at 150 lux, (neurolight, id med) with recording of pupillary parameters: minimum and maximum diameter, variation rate, latency, velocity. noxious procedure was defined as an increase of at least one point of the bps (change in facial expression, upper limb movement or ventilator synchrony). the additional analgesia was decided blindly from pupillometric values. analysis compared two groups defined on bps variation induced by the procedure: group 1 with dbps c 1 and group 2 with dbps = 0. comparison of pupillometric parameters before procedure between the 2 groups. results expressed as median (interquartile range, iqr), mann-whitney test, significance at p \ 0.05. . 24 patients with cervical cellulitis of which 5 complicated by mediastinitis, h/ fratio = 15/9, age 49 years (40), igs 33 (17). in this population, during the procedure, hr and map were unchanged, the bps increased significantly [from 3(0) to 5 (2) , p = 0.0004] but remained unchanged in 8 patients (33%) (group 2 = high tolerance). pupillometric parameters before procedure before procedure group 1 (n = 16) group 2 (n = 8) p conclusions. all pupillometric parameters, except latency, were discriminant for subsequent debridement tolerance with significantly lower values in the group without pain experience. the pupillometric test seemed adapted to this clinical practice for evaluation of nociception status and may help for rationalizing analgesia for short noxious procedures. introduction. delirium is an acute and fluctuating change in mental status, with inattention and altered levels of consciousness. the incidence of delirium in orthopedic patients was ranges from 5.1 to 61%. delirium may present before or after the patient undergoing surgical procedure and has demonstrate increasing risk, including mortality. objectives. the purpose of this study was to compare the effectiveness and tolerability of intravenous propofol versus midazolam infusions in postoperative agitation/delirium therapy with using an epidural infusion for postoperative analgesia after major orthopedic surgeries in high-risk patients with chronic renal failure. with the institutional ethic committee approval; eighty-two high-risk chronic renal failure patients (asa iii, bun [ 40 mg/dl and serum creatinin value [ 2) after a major hip or knee operations with a diagnosis of agitation/delirium were eligible for the study in the postoperative period. richmond agitation sedation scale (rass) or confusion assessment method for the icu (cam-icu) were used for sedation/orientation levels. all agitated patients had an lumbar epidural catheter was inserted preoperatively in combination with spinal anesthesia intraoperatively. after the surgery the catheter was loaded with 0.25% 25 mg bupivacaine at the t12 to l1 sensory levels and a continuous infusion of 0.125% bupivacaine was commenced at 2-4 ml/h in combination with patient controlled analgesia of meperidine (2 mg/bolus). for agitation/delirium therapy in group p (n = 40) propofol was used with intravenous loading dose of 1-2 mg/kg in a bolus and followed by continuous infusion at 1-3 mg/kg/h and group m (n = 42) midazolam was used with intravenous loading dose of 0.05-0.2 mg/kg in a bolus and followed by continuous infusion at 0.05-0.3 mg/kg/h to ensure a target of rass in +1 and -1 values. hemodynamic parameters (heart rates, systolic and diastolic blood pressures), oxygen saturation with sedation-agitation scales were monitored periodically for 24 h. adverse events were recorded. p \ 0.05 showed statistically significant. results. the groups were demographical comparable (p [ 0.05). group p patients reached the target rass scores earlier in group p (p \ 0.05). hemodynamic values were significantly higher in group m (p \ 0.05). the epidural bupivacaine consumption was significantly lower in group p with a limited analgesic requirement (p \ 0.05) and n treatment required adverse events was seen in group p (p [ 0.05). conclusions. intravenous propofol infusion may be an effective and safe approach adjunct to epidural analgesia for possible postoperative agitation/delirium treatment after major orthopedic surgeries in high-risk patients with chronic renal failure. introduction. ventilator-associated pneumonia (vap) is the most common nosocomial infection among the critically ill patients admitted in the intensive care units (icus). implementation of the available international evidence-based guidelines and recommendations to prevent and manage vap into the clinical setting may not be adequate leading to suboptimal patient care and increased vap rates. objectives. to assess the implementation of selected vap prevention strategies, and to learn how vap is managed by the intensivists practicing in the indian subcontinent. methods. three hundred 10-point questionnaires were distributed during an international critical care conference. 131 (43.7%) were returned and 126 (42%) questionnaires of delegates from india, nepal and sri lanka were analyzed. most of the intensivists (96.8%), reported using vap bundles in their icus with a high proportion including head elevation (98.4%), chlorhexidine mouthcare (83.3%), stress ulcer prophylaxis (96.8%), heat and moisture exchangers (hme, 92.9%), early weaning (94.4%), and hand washing (97.6%) as part of their vap bundle. use of subglottic secretion drainage (ssd, 45.2%) and closed suction systems (css, 74.6%) was also reported by many intensivists, whereas, use of selective gut decontamination was reported by only 22.2% of respondents. most common method for sampling used for diagnosis of vap was endotracheal suction by 86 (68.3%) intensivists, and only 0.8% intensivists reported using protectedsample brush. gram negative organisms (pseudomonas, acinetobacter) were reported to be the most commonly isolated organisms. majority of respondents (39.7%) reported using proton pump inhibitors for stress ulcer prophylaxis. majority (84.1%) believed that vap contributed to increased mortality in their icus with 47.6% treating vap with an antibiotic course lasting for 7-14 days. de-escalating therapy was considered, in patients responding to treatment, by 57.9 and 65.9% considered adding empirical mrsa coverage and 63.5% considered adding nebulised antibiotics in certain high risk patients. overall there was good concordance regarding vap prophylaxis among the intensivists with a majority adhering to evidence based recommendations and guidelines. even though the gap between recommended guidelines and the actual clinical practice is closing, we could identify certain issues like the choice of agent for stress ulcer prophylaxis, use of hme, ssd and css, where there still exists some practice variability and opportunities for improvement to provide better patient care. objectives. to reassess the value of individual levels and dynamic alteration of procalcitonin (pct) in predicting the outcome of ventilator-associated pneumonia(vap) patient. methods. forty adult patients with vap were studied and divided into two groups according to their outcome at day 28 after diagnosis of vap: death and survival. serum pct levels were measured on days 1, 4 and 7 (d1, d4, and d7, respectively) and their alteration between different days (kinetics, 4pct) were calculated. to control the study, acute physiology and chronic health evaluation ii (apache ii), sequential organ failure assessment (sofa), and clinical pulmonary infection score (cpis) and c-reactive protein (crp) were also recorded and analyzed. all parameters have been investigated as independent variables in relation to 28-day death as dependent variable. results. the increase of pct levels on day 1, 4 and 7 were significantly predictive of death in univariate analysis with area under curve (auc) and 95% ci of 0.732 (0.568, 0.896), 0.741 (0.546, 0.937) and 0.797 (0.606, 0.989), respectively. however, kinetics of pct levels among day 1, 4 and 7 did not show a significant difference between favorable and unfavorable outcomes (p [ 0.05). multivariate analysis revealed that only sofa (7) conclusions. neither pct individual levels nor their kinetics during vap course can predict patient outcome. comprehensive evaluation of patients with multiple methods, in combination with pct levels, may increase predictive accuracy in the future. grant acknowledgment. we have no competing interests. introduction. the presence of new or progressive radiological infiltrates, pyrexia, leukopenia or leukocytosis, and the presence of purulent tracheal aspirates are key features defining the presence or absence of vap. the incidence of vap is dependent upon the number of diagnostic criteria applied, and the demographics of the critical care population to which it refers. a uk government directed ''patient safety first'' campaign in the uk, has highlighted vap as a complication related to mechanical ventilation that can be reduced through the introduction of a ''care bundle''. however, benchmarking between different units has practical limitations. objectives. selective data presentation can distort the perceived occurrence of critical events in order to deliver performance targets. we compared the incidence of vap between a neurosurgical and general intensive care unit in the same hospital. a variety of denominators were applied to explore the potential for data manipulation to realise performance targets a local database of neurosurgical and general intensive care admissions, covering a 6 month period, was analysed retrospectively results. 322 and 96 subjects were admitted to gitu and nitu respectively in the 6 month period. 165 (51%) and 59 (61%) subjects were ventilated for more than 2 days. table 1 summarises the demographics and measures of performance between the two units. a p value .05 was considered significant. parametric and non-parametric tests were applied as appropriate. 1 . vap is associated with not only mortality but also considerable morbidity, prolonged duration of ventilation and increased cost of hospitalisation. to determine the incidence of vap in patients ventilated at the qensiu, to calculate mv resource utilisation, and to ascertain whether vap relates to outcome in acute sci. we undertook a retrospective case note review of all patients ventilated at the qensiu during a 5 year period. patients were identified using a local computerised database. the qensiu receives referral of patients with sci from the whole country (pop * 5.1 m). vap was defined pragmatically as deteriorating gas exchange more than 48 h following mv, coupled with a raised crp or wcc, together with either a positive sputum sample or new infiltrates on cxr. statistics: descriptive, median (range); analytical, mann-whitney u and fisher's exact test as appropriate. death occurred in 22% of patients, and was significantly greater in the group who were retrospectively assigned to the vap cohort: vap vs survival of the 13 deaths, 8 occurred following discharge from the unit (6 of whom developed a subsequent vap). conclusions. vap incidence was apparently high in this patient population (56%), particularly in comparison to the reported general icu population incidence (8-20%) 2 . this may partially reflect our pragmatic diagnostic criteria, applied retrospectively. vap was also associated with an increase in mortality following discharge in patients with sci. a modified vap bundle adapted to sci patients is being developed locally, based on recent recommendations 3 . introduction. the implementation of a prevention programme with feedback to nurses and healthcare workers (hcw) was associated with better outcomes and increased compliance [1] . to assess the effects of feed-back in a study based on implementing a 5variables care bundle to prevent vap. a multicenter and prospective study was carried out in 5 icus. the 5 element care bundle consisted in hands hygiene, oral hygiene, monitoring cuff pressure, sedation vacation/adjustment and avoid ventilator circuits changing. beweekly feed-back displaying posters with information was carried out to update hcw in the compliance of the prevention measures and vap incidence. a 6 questions with open answer questionnaire was performed 6 months after the implementation of the feed-back in all icus to assess the knowledge of the compliance measures, vap incidence, opinion of the study and improvement suggestions. results. 82 questionnaires were obtained. the median experience in intensive care was 10.7 years (sd 7.9-15.2). 100% of the staff was aware of the study: 95.8% agree that was useful, 3.1% disagree and 1.0% didn't know. regarding if they thought that in their units they had a high vap incidence, 22.2% answered that they did, 71.6% answered negatively and 1.7% didn't know. asking about the knowledge of the prevention measures' compliance 41.4% answered right, 4.2% said they knew but didn't specify the percentage, 51.1% didn't know and 3.3% didn't answer the question. finally, about the vap incidence, 37.0% answered right, 6.7% said they knew but didn't specify it, 50.8% didn't know and 5.5% didn't answer the question. 14.1% added comments, the most relevant was: 73.3% of the respondents wanted more verbal information. conclusions. poster feed-back failed to improve compliance on vap care bundle due to lack of information. our survey suggests to implement other communication strategies based on direct verbal interaction to improve implementation. objectives. to compare the effectiveness of two different methods of oral dental hygiene on ventilator-associated pneumonia (vap) prevention using the cpis (clinical pulmonary infection score). methods. twenty-seven critically ill patients, aged 21-79 years were studied. patients were randomly separated in 2 groups: group 1 (n = 14) received oral care with tooth brushing using the bass technique followed by lavage with chlorhexidine 0.12% (chx) solution in nacl 0.9% (chx:nacl 0.9% = 3:1). hexetidine 0.1% (hex) was used for oral lavage alone in group 2 (n = 13). demographics, sofa, apache ii, gcs and cpis scores were recorded upon patient admission. on days 2, 5, 8 and 15, bal and tongue surface cultures were obtained. the endpoints taken into account were the cpis on days 2, 5, 8, and 15 as well as the number and species of bacteria cultivated. a cpis c 6 was considered positive for vap. two-way anova, t test for independent samples, mann-whitney u, pearson correlation and kruskal-wallis tests were used for statistical analysis. p \ 0.05 was considered statistically significant. patient data analysis showed that both groups were homogeneous. on days 5, 8 and 15 there were more negative tongue surface cultures in the chx group than in the hex group (p = 0.03). even though the cpis did not differ significantly between the 2 groups, a strong tendency of faster and greater reduction in the chx group was observed. moreover, a continuous gradual improvement of the cpis score was recorded in both groups on days 5, 8 and 15. the overall incidence of vap was similar in both groups: group 1, 14.4% (n = 2) and group 2, 15.4% (n = 2). the same bacteria (p \ 0.001) developed in both bal and tongue cultures on days 8 (p \ 0.001) and 15 (p \ 0.001). nevertheless, the cpis was positive for vap only in the above 4 patients on day 8, while day 15 was totally free of vap. conclusions. even though the cpis improvement was more remarkable in group 1, both group scores showed parallel improvement overtime, the chx group being in a slightly more propitious position. diligence in patient oral care seems to be an additional effective practice for vap prevention, independently of the method used. introduction. specific patterns of cytokine gene expression are reported to be associated with the occurrence of infection in humans [1, 2] . it is unclear whether these characteristic profiles are a consequence of an established disease process or precede the infective process. objectives. our primary endpoint was to determine whether hospital acquired pneumonia was associated with differential gene expression of ifn-c, tnf a and il-12 family of cytokines. secondary endpoint was to identify whether alteration in gene expression preceded the clinical onset of infection. methods. 60 consecutive patients undergoing elective thoracic surgery were recruited. hospital acquired pneumonia was diagnosed as per nnis guidelines, independent of study investigators. mrna and protein levels were analysed pre operatively, 24 h and 5 days post operatively. . 41 patients had an uncomplicated recovery. 19 patients developed hospital acquired pneumonia. il-6, il-10, il12-p35, il-23-p19, il-27-p28, tnf-a, and ifn-c mrna and protein levels of il-6, il-23, and ifn-c in peripheral blood were analysed before surgery, 24 h and day 5 post surgery. il-23p19 mrna levels were reduced in the pneumonia group (15,465; 8,071-51,614) compared to non pneumonia group (31,420; 7,101-206,943 ) day 1 post surgery (p = 0.02). ifn-c mrna levels were reduced in the pneumonia group (305; 102-1,522) compared to non pneumonia group (640; 144-1,820) (p = 0.03) day 5 post surgery. absolute copy numbers of mrna per 10 million copy numbers of b-actin are quoted. all values are quotes as median and 10th to 90th centile range. patients with postoperative hospital acquired pneumonia exhibit distinct patterns of cytokine gene expression. these distinctive patterns manifest before the clinical onset of pneumonia. objectives. the aim of this study was to evaluate the impact of the implementation of a ventilator bundle on the incidence of vap in our intensive care unit (icu). methods. prospective, observational study. during a 1 year period (january 09-10) a ventilator care bundle based on the cdc and canadian guidelines 1,2 was applied to each patient requiring more than 48 h of mechanical ventilation (mv). the ventilator care bundle consisted in:hand hygiene. use of barrier precautions. preference of noninvasive ventilation (niv). orotracheal intubation. semirecumbent position. continuous aspiration of subglottic secretions. manteinance of the endotracheal cuff pressure. oral care with chlorhexidine. daily sedation vacation and assessment of readiness for weaning. no scheduled ventilator circuit changes. ventilation circuit maintenance. stress bleeding profilaxis. we followed general measures for infection control:single patient room. microbiologic surveillance. monitoring and early removal of invasive devices. program to reduce antimicrobial prescriptions. for each ventilated patient the following data was registered:age, apache ii, the reason of admission, risk factors, use niv, mv duration, timing of tracheostomy, time of diagnosis of vap, microbiological data, length of stay and mortality in icu. the compliance with the bundle was registered in a check list. the application of the ventilator care bundle impact was compared with historical data. . 67 ventilated patients were included. the median age was 73 years. the mean apache ii was 22.5 ± 8.4. the reason of admission was in a 87% medical and 13% surgical. the most frequent risk factors were: age [65 years, emergency surgery, pulmonary disease and immunosuppression. niv was used in 23%. the median duration of mv was 8 days. tracheostomy was done in 19.5% patients with a delay of 15 ± 7 days. there were 3 late-onset vap episodes and the rate of vap per 1,000 ventilator days was 4.57. the vap were caused by candida albicans, enterobacter aerogenes and pseudomona aeruginosa. the length of icu stay was 17.6 days. mortality was 26% (only one patient with vap). the rate of compliance with ventilator care bundle was 100%. the rate of vap per 1,000 ventilator days after implementation of the bundle decreased significantly (table 1) . there is currently no consensus on the diagnostic criteria for ventilator associated pneumonia (vap) which has led to significant variation in the reported incidence (9-28%) 1 . icus need a reliable and accurate diagnostic system so that the efficacy of measures to reduce the incidence of vap can be assessed, and if vap is to be considered as a quality indicator of performance. objective. to establish a process to diagnose vap that can be used for continuous surveillance and to assess the effect of new therapeutic interventions. method. potential diagnoses of vap were identified prospectively by a senior intensive care doctor and clinical data was collected to calculate a modified clinical pulmonary infection score (cpis) 2 . each case was subsequently reviewed at a multidisciplinary team (mdt) review forum with intensive care and microbiology clinicians. the case details, modified cpis and semiquantitative microbiological culture results were used to reach a consensus view on the diagnosis. a pilot audit performed over a 6 week period in 2009, gave a vap incidence of 5% (6 vaps; 118 ventilated patients; 483 ventilator days) . a change to our ventilator care bundle was subsequently instigated, with the addition of chlorhexidine paste to daily mouth care before repeat surveillance. result: 366 patients were admitted to the critical care unit over 112 days. 199 patients were ventilated during a total 759 ventilator days. 12 patient episodes were identified as potential vap and discussed at the mdt forum. 3 cases were diagnosed as vap (incidence 1.5%) and 1 patient diagnosed as tube associated pneumonia. the other cases were excluded either due to clinical circumstances (n = 5) or absence of positive microbiology (n = 3). conclusion. we have developed a process for identifying and diagnosing vap within our critical care unit that continues to be used for ongoing surveillance. collaboration between the intensive care team and the microbiology department, along with a mdt forum, has been fundamental to this process. our data highlights the difficulty in diagnosing vap and the need for multidisciplinary expertise. of the 12 patient episodes prospectively identified as potential vap, 9 were deemed not to be vap when clinical data and results were available for review at the mdt forum. the reduction of vap incidence between the pilot study and subsequent screening suggests benefit from the introduction of oral chlorhexidine, however we recognise other contributing factors. controversially, icus in the uk are increasingly being asked to provide data on vap incidence as a quality indicator. we believe that we have a process that is robust and allows us to accurately monitor the incidence of vap. introduction. bacterial biofilm within the internal surface of the endotracheal tube (ett) may contribute to ventilator-associated pneumonia. the gene expression pattern of those bacteria, embedded within biofilm matrix, greatly differs from their planktonic counterpart and allows survival benefits and increased virulence. to compare biofilm production capability of planktonic versus sessile methicillin-resistant staphylococcus aureus (mrsa) retrieved from within etts, and to assess whether antimicrobials can hinder those processes. ultimately, to study any change in planktonic versus sessile bacterial dna. we previously developed a model of pneumonia in pigs mechanically ventilated up to 84 h and challenged into both lungs with mrsa. from those studies, 35 etts of pigs, treated with placebo (n = 10), linezolid (n = 9) or vancomycin (n = 16) were retrieved. distal and medial parts of each ett were processed (70 samples). the planktonic mrsa strain, inoculated to the pigs, was compared with sessile mrsa strains, retrieved from the internal surface of the etts, in capability to form biofilm, assessed through the adhesion-to-aplaque method for gram-positive bacteria. the optical density of biofilm was measured using a microplate reader at wave length k = 450 nm and results are proportional to the planktonic control strain (value = 1). pulsed-field gel electrophoresis (pfge) was used to determine potential bacterial dna recombination. introduction. ventilator-associated pneumonia (vap) is a common complication in mechanically ventilated patients and is associated with increased morbidity, mortality and costs. treatment-related risk factors associated with vap, include prolonged duration of mechanical ventilation, lack of antiseptic techniques, improper patient's position, inappropriate cuff pressure, peptic ulcer prophylaxis, and deep sedation. objectives. the aim of this study is to evaluate the presence of these risk factors and their association with vap development in a multidisciplinary icu. one hundred and fifty-seven critically ill patients consecutively admitted to a multidisciplinary icu, were prospectively studied. forty-one of them, developed vap (32m/9f age: 51 ± 22 years, apache ii score on admission 14 ± 6, sofa score on admission 8 ± 3). inclusion criteria were intubation \12 h prior to icu admission or after 48 h of admission. exclusion criteria included: prior hospitalization in another icu, icu stay\48 h, brain death, age \18 years old and pregnancy. bronchial secretions, samples from the pharynx and gastric secretions were collected from each patient 3 times weekly (on days 1, 3 and 7). we also documented the known risk factors for vap; sedation depth (using the ramsay scale), cuff pressure, head-bed elevation, reintubation, ventilator circuit changes, tracheostomy, the presence of levin, deep venous thrombosis and stress ulcer prophylaxis, three times weekly per patient results. in this selected sample of patients, the incidence of vap was 26 per 1,000 ventilation days. out of this sample, 15% underwent at least one endotracheal tube change, 24% had at least once their ventilator circuit changed, 19% underwent a tracheostomy, 93% had levin, 14% did not have head-bed elevation above 30°, 87% had ramsay scale 5 or 6, 19% had cuff pressure b15 cmh 2 o, 58% did not received deep venous thrombosis prophylaxis and all of them received h 2 -receptors antagonists, as gastric ulcer prophylaxis. these results indicate that several risk factors for vap, do indeed apply for the cases under study and that the incidence of vap is relatively high. therefore, the implementation of preventive strategies and the reinforcement of vap bundles can result in beneficial effects on the appearance of vap, in the monitored icu. introduction. pulmonary inflammatory response and progressive ards may complicate posttraumatic ali. clrt by a motor-driven bed is used in trauma patients to improve gas exchange and to prevent from ventilation-associated complications. we investigated the effect of clrt on the inflammatory response in the posttraumatic course. to assess systemic and pulmonary cytokines (interleukin (il-6, il-8), intercellular adhesion molecule-1 (icam-1) before and 5 days after begin of clrt. conventionally positioned patients served as a control group. after approval by our institutional review board 27 trauma patients presenting with ali (pao 2 /fio 2 \ 300) were prospectively randomized in clrt (n = 13) and control group (n = 14). cytokines were assessed from serum (s) and broncho-alveolar lavage (bal) after admission at the icu and on day 5, respectively. results. the mean age was 44 ± 11 years and mean injury severity score was 48 ± 7. pulmonary gas exchange improved significantly in clrt in comparison with conventional positioning on day 5. changes in cytokine levels are presented in table 1 (median and 25/75percentile values, * = p \ 0.05 within groups and $ = p \ 0.05 between groups, wilcoxon and mann-whitney-u test). serum il-6 and il-8 levels were reduced statistically significant on day 5 in both groups, but this effect was significantly more pronounced in clrt-group. in bal cytokines tended to be increased in clrt and control group on day 5. icam-1 levels were increased in s and bal after 5 days treatment. conclusions. the early use of clrt reduces the systemic inflammatory response (il-6, il-8), but has no influence on regional pulmonary cytokine expression. clrt might be a helpful tool for stabilization in trauma patients with ali. objectives. the aim of this study was to compare the performance of adaptive support ventilation (asv) with and without closed loop control by end tidal co 2 (etco 2 ) (asvco 2 ) to that of pressure control ventilation (pcv) and volume control ventilation (vcv) during simulated ards and to compare the ability of all modes to manage etco 2 , tidal volume (v t ), and plateau pressure (pp) as respiratory mechanics, peep and minute volume changed. methods. asv and asvco 2 were compared to a v t of 6 ml/kg in vcv and pcv using the michigan instruments test lung set up with co 2 titrated into one of the test lung chambers. the compliance of the system was set at 35 and 15 ml/cmh 2 o and resistance at 7.7 cmh 2 o/l/min. at baseline ventilation co 2 was titrated to establish a co 2 production of 3 ml/kg pbw/min (70 kg) or 210 ml/min. after stabilization and data collection co 2 production was increased to 280 ml/ min and then to 350 ml/min then decreased to 140 ml/min. after each co 2 adjustment and stabilization period data was collected. statistical analyses were performed by anova or kruskal-wallis tests where appropriate, a p value.05 was considered significant. overall etco 2 level in asvco 2 (45.3 ± 6.8 mmhg) was higher than in other modes (asv 35.6 ± 13.5, vcv 29.4 ± 9.5, pcv 31.7 ± 9.7 mmhg) (p \ 0.001). at the lowest compliance etco 2 in asvco 2 (48.6 ± 6.8 mmhg) was higher than in vcv (29.8 ± 9.8 mmhg) and pcv (33.4 ± 10.1 mmhg). overall v t was similar in all modes except that v t in asvco 2 (5.3 ± 1.7 ml/kg) was lower than in vcv (6.3 ± 0.2 ml/kg) (p = 0.033). at the lowest compliance v t in asv (3.9 ± 0.5 ml/kg) and asvco 2 (3.7 ± 0.5 ml/kg) were lower than in vcv (6.4 ± 0.1 ml/ kg) and pcv (5.9 ± 0.1 ml/kg) (p \ 0.001). overall, pp in asv (29 ± 1.9 cmh 2 o) and asvco 2 (28.6 ± 2 cmh 2 o) were lower than in vcv ( conclusions. our high mortality in this group of patients despite improved oxygenation concurs with published data. however, potential improvements with adherence to ph and oxygenation targets could be made to ensure optimal use of hfov as a lung protective strategy. objectives. this randomized cross-over controlled study was designed to assess safety, gas exchanges, and ventilator outputs obtained with intellivent ò as compared to adaptive support ventilation (asv) (2) in icu ventilated patients with acute respiratory failure. methods. the study was approved by ethic committee and inform consents were obtained by next-of-kin. 50 intubated, sedated and ventilated patients were included (age = 67 ± 15 years, saps ii = 50 ± 18, 31 and 19 ali/ards and normal lungs patients, respectively). patients were ventilated using a g5 (hamilton medical, switzerland) with a dedicated software. asv and intellivent ò were delivered in random order for two periods of 2 h with half an hour of washout in between. tidal volume (v t ), peak pressure (ppeak), spo 2 , and etco 2 were continuously recorded. blood gas analysis and plateau pressure (pplat) were measured at the end of each period. a paired t test was used to compare ventilation and oxygenation parameters between asv and intellivent ò period. no patient was removed from intellivent ò for major safety issue. intellivent ò delivered a lower mv (7.1 ± 1.8 vs. 7.9 ± 1.7 l/min, p = 0.003), peep (9 ± 5 vs. 10 ± 4 cmh 2 o, p = 0.01), fio 2 (35 ± 13 vs. 45 ± 18%, p \ 0.001), vt/pbw (8.1 ± 0.8 vs. 8.4 ± 0.8 ml/kg pbw, p = 0.003), and pplat (22 ± 6 vs. 24 ± 6 cmh 2 o, p = 0.01) than asv. static compliance, pao 2 /fio 2 ratio and paco 2 were not different between asv and intellivent ò . with both asv and intellivent ò , v t was between 6 and 10 ml/kg pbw in all the patients. figure 1 is showing the distribution of mean of individual breath by breath peak pressure during the two recording periods. conclusions. intellivent ò delivered lower volumes and pressures than asv for equivalent results on gas exchange suggesting more efficient ventilation. introduction. during neurally adjusted ventilatory assist (nava) pressure applied to the airways by the ventilator is moment-by-moment proportional (according to a proportionality factor called ''nava gain'', unit: cmh 2 o/lv) to the electrical activity of the diaphragm (eadi, unit: lv), as measured through a modified nasogastric tube with a multiple array of esophageal electrodes. independently from its physiological correlation with real diaphragm activity, eadi and its variations are the only variables through which different nava gains may affect patient respiratory pattern. objectives. we explored how eadi influence the effect of varying the nava gain on tidal volume and peak airway pressure. we included twelve patients recovering from acute respiratory failure. all patients, connected to a servo-i ventilator (maquet critical care, solna, sweden) able of delivering both psv and nava, underwent to a random application of 7 increasing gains (0.5-1-1.5-2-2.5-3-4 cmh 2 o/lv) during nava and 4 increasing pressure support (4-8-12-16 cmh 2 o) during psv. each level was maintained at least 10 min. all changes in eadi, tidal volume (vt), and peak airway pressure (paw peak ) were referenced respect to their respective values at nava gain 0.5. introduction. lung protective ventilation strategies is considered 'gold standard' for patients with acute respiratory distress syndrome (ards). high-frequency oscillation (hfo) has been used as a rescue measure and claimed to protect the lungs from ventilator induced lung injury (1) . theoretically hfo should be considered early in the course of ards. objectives. we were interested to determine the time course to achieve optimal gas exchange with early hfo and its impact on the use of other adjunctive therapies; inhaled nitric oxide, prone positioning and extracorporeal oxygenation or carbon dioxide removal. after ethical approval, a total of 79 adult patients with ards were enrolled in this prospective observational study. the oscillation (metran co. ltd, 12-18, 2-chome, kawaguchi, saitama, japan) was started when fio 2 [ 0.7 or level of peep [ 15 cmh 2 o were required on a conventional ventilator. hfo frequencies, cycle volume and bias flow were altered until optimal gas exchange achieved. the pattern of gas exchange was observed for the first 24 h and other adjunctive therapies were used when required. the following parameters were recorded: duration of hfo, arterial blood gases during the first 24 h, frequency of need for other therapies, incidence of barotraumas, and re-requirement of hfo once weaned from. a total of 79 patients (age between 18-74 years, male:female ratio = 43:26) were ventilated 1-3 days with conventional ventilator before start of hfo. duration of hfo varied from 2 to 13 days (4 median). there was a significant improvement in pao 2 at 8-12 h (p = 0.001) following the onset of hfo (fig. 1) . the number of patients requiring other therapies are very low; inhaled nitric oxide n = 4, prone positioning n = 2, both prone positioning and nitric oxide n = 1, ecmo/novalung n = 0. seven patients required re-hfo once weaned and another two developed pneumothoraces requiring chest drainage. conclusions. the data of this study demonstrates that significant improvement in gas exchange occurs in patients with ards following 8-12 h of hfo. early oscillation also appears to reduce the need for other adjunctive therapies. further studies of early hfo strategy are warranted. introduction. neurally adjusted ventilatory assist (nava) is a novel method for patient triggering of pressure support. instead of relying on conventional pressure or flow triggering, the peak diaphragmatic emg signal (edi) is used to precisely synchronise patient demand with ventilatory assist. although, the physiology and science underpinning nava has been described, less is known about its clinical application and efficacy (1) . in particular, clinical superiority over conventional pressure support has not been established. objectives. here, we describe the clinical, nursing and operational lessons learnt from the introduction of 10 nava platforms (servo-i, maquet) into a 32-bedded central london intensive care unit over 2 years. in parallel we present some novel data from an observational cohort study examining the effect of nava on sedation use and ventilator days. a protocol for the safe measurement of edi in critically ill ventilated patients was developed through multidisciplinary review and discussion. a 2 year registry of clinical lessons and adverse events from the introduction of nava was kept. in a parallel observational cohort study we examined three populations of ventilated patients (n = 27) matched for apache ii, oxygenation index and compliance. group 1 had no nava catheter; group 2 had edi signal measured during conventional pressure support; and group 3 utilised the edi signal to act as a neural trigger to drive ventilatory support. results. the measurement of edi was not associated with a difference in hospital mortality. there was a significant reduction in sedation use, muscle relaxation, ventilator days and icu days in patients with a nava catheter (fig. 1) . however, there was no significant difference in any of these parameters with edi measurement guiding conventional pressure support versus nava. ventilator days in nava versus pressure support conclusions. in this study we show that neurally adjusted ventilatory assist can be safely and effectively be introduced into a 'non-expert' intensive care unit. we further show that reductions in sedation use and ventilator days appear to be related to the earlier introduction of sedation holds and reductions in ventilatory assist (with consequent earlier spontaneous breathing trials) in order to acquire an edi signal rather than due to an intrinsic advantage gained by improved patient-ventilator synchronisation with nava. the causes of the respiratory failure were: infections n = 8; 47.05% (immunodeficiency n = 3, tuberculosis n = 1, aplastic anemia n = 1, congenital cardiomyopathy n = 2, sepsis n = 1), rsv infection-bronchiolitis n = 3; 17.64%, bronchopulmonary dysplasias n = 3; 17.64%, leukemias n = 2; 11.76%, burn-ards n = 1; 5.88%. the mean duration of hfov was 3.2 days (12 h to 10 days). the parameters of ventillation ranged: fio 2 : 100-50%, mean pressure: 22-29 cmh 2 o, dp:45-75 cmh 2 o. the i time and hertzs ranged within the acceptable for age limits. closed suction circuit was used. we didn't notice any side effects from cardiovascular system or distension of the thorax. eadi and respiratory effort indices decrease when assistance increases in nava. nava should also theoretically allow perfect synchronization between the patient and the ventilator, and no asynchrony has been described with this mode. nava level adjustment at bedside, however, is still a matter of research. we assessed breathing pattern, respiratory effort indices, and patient-ventilator synchronization throughout a titration of nava and of pressure support ventilation (psv). we assessed breathing pattern, respiratory effort indices, and patient-ventilator synchronization throughout a titration of nava and of pressure support ventilation (psv). methods. physiological study conducted in seven patients (preliminary results) during the weaning. airway pressure (paw) and flow, esophageal and gastric pressures and the eadi were continuously recorded. for each patient, the following levels of assistance were consecutively applied: in psv: 7-10-15-20-25 cmh 2 o; in nava: 0.5-1-1.5-2-2.5-3-4-5-7 cmh 2 o/mvolt. results are given as median and [25th-75th percentiles], and tidal volume (vt) in ml/kg of predicted body weight. results. the increase from the lower to the higher level of assistance was associated with an increase in vt from 6.7 [5.8-7 .0] to 9. 4 [8.4-11.3] ml/kg in psv and from 6.7 [6.2-8.7 ] to 8.7 [7.7-11.8] objectives. we describe technical possibilities, tolerance and gas exchange with combination of oscillation device with nimv. a specific oscillator device (sensor medics, vyasis) was selected to change conventional airflow to oscillatory airflow. connected by ''t'' piece with oscillatory devicerespiratory circuit-face mask. we selected bipap ventilator (vision resp inc), facial mask. bipap mode (iap/epap cmh 2 o) to achieve stable mechanical ventilation (t1). a progressive increment in rate of oscillation (hz) and power oscillation to achieve airflow change (t2). to evaluate the differences of peepi during the release phase, referred to mechanical pressure release from p high to p low , and the inspiratory work of breathing (wob) during p high among currently available aprv ventilators, using a lung model (ttl1600, mi). methods. the six aprv ventilators were evaluated in this study: 1) nellcor puritan-bennett 840 (puritan-bennett), 2) evita xl (drager), 3) servo i (maquet), 4) avea (viasys), 5) g5 (hamilton) and 6) engstrom (ge healthcare). ventilator settings in aprv ventilators were set as follows: p high /p low 25 cmh 2 o/0 cmh 2 o, t high /t low 4.5 s/0.5 s. when evaluated peepi during the release phase, t low was diminished by steps of 0.1 s from 1.0 to 0.2 s. the inspiratory pressure-time product (ptp), as an index of wob, was directly measured under with tidal volume/respiratory rate of 300 ml and 30/min. measurement for each setting was performed in a random order. three breaths were analyzed and averaged for each measurement. the results are shown in fig. 1 objectives. to perform bench study to test the hypothesis that ett or trach can reduce the insufflated (vti) and/or exsufflated (vte) volume as provided by coflator ò . methods. coflator ò is connected to a pneumatic model (ttl, michigan instruments) via ett mallinckrodt 6.5, 7.0, 7.5, 8.0, 8.5) or trach (mallinckrodt 6.0, 7.0, 8.0) . the set up is tested in 4 conditions of compliance (c ml/cmh 2 o) and resistance (r cmh 2 o/l/s): c30r0, c30r5, c60r0, c60r5. the device is set in manual mode, at the highest inspiratory flow, inspiratory/expiratory time 3/1, 1 s pause after expiration. three pressures are used, 30, 40 and 50 cmh 2 o in both inflation and deflation. a baseline condition without any tracheal prothesis nor r served as reference. airflow and pressure upstream ett or trach are measured (biopac mp150). five insufflations followed each by an exsufflation are performed in each condition. the data are analyzed by using a linear mixed effects model where ett or trach, and pressure have fixed effects and c or r a random effect. the dependent variable is vti and vte. the main end-point is the slope of the relationships between vti or vte and pressure. results. the vti-pressure slope was significantly lower with any ett than baseline at both c ( fig. 1a and b). the same was true for trach. even though these differences were statistically significant the reduction in vti from the baseline averaged 160 ml with etts as a whole. the vte-pressure relationships were similar for ett and trach and showed no difference from baseline at c 30 ( figure 1d ). however, at c60, the relationships are scattered ( figure 1c ). moreover, expiratory pressure of -40 and -50 cmh 2 o were not reached for ett 6.0, 8.0 and 8.5 and trach 7.0 and 8.0. conclusions. ett and trach slightly but significantly change the performance of the device. however, small sized ett or trach in c60 condition substantially modify the efficacy of the exsufflation. these findings desserves assessment in patients for relevance. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 s109 though humidified high flow nasal canula oxygen (hfnc) has been widely studied in pediatric population, few data in adult is available and its and its precise indications and actual benefits in these patients remains unknown. two studies have shown that hfnc generates a low level of positive airway pressure contributing to decrease the work of breathing. one study has reported a favourable effect on comfort and oxygenation of hfnc as compared to venturi mask and in another preliminary one, fewer patients using hfnc went on requiring non invasive ventilation. objectives. to evaluate the efficiency of hfnc (optiflow, fisher and paykel, auckland) in critical care patients with acute respiratory failure. methods. prospective single centre study in a university hospital intensive care unit. all patients exhibiting acute respiratory failure (arf) as defined by clinical signs and/or failure of haematosis, regardless of the aetiology, were eligible. hfnc was used at a mean output of 48 ± 9 l/min and a mean fio 2 of 80 ± 20% throughout the study period. results. thirty-five patients were included. the mean age was 50.4 ± 16.5 years old and mean saps ii is 35 ± 11. pulmonary infection was the most common aetiology of arf. hfnc was used 2 ± 2 days. all but one patient were discharged alive from icu. optiflow significantly reduced respiratory rate (p \ 0.0001), heart rate (p \ 0.0001), dyspnea score (p = 0.015), sus clavicular recession and thoraco abdominal asynchrony, and improved pulse oxymetry (p = 0.009). there was no significant difference in ph, pao 2 , paco 2 on arterial blood gazes performed before and 1, 12 and 24 h after hfnc use. the pao 2 /fio 2 ratio at 1 and 12 h after hfnc initiation was higher than before use of hfnc (p = 0.03). patients ultimately intubated exhibited a higher respiratory rate 30 min (29.9 ± 3.4 vs. 23.5 ± 5 bpm, p = 0.004) and 45 min ( with an incidence of up to 60% in routine sonography [1] , pleural effusion is one of the most common complications in intensive care patients. the use of bedside 2d ultra-sound to detect pleural effusion is fast, practicable and minimises radiation exposure [2] . however, sonographical volumetry tends to be imprecise, and ct imagingbased volumetry is the more accurate method to quantify pleural fluid in intensive care patients [3] . objectives. the aim of this study was to compare the accuracy of 3d and 2d ultra-sound volumetry of pleural effusion in intensive care patients. methods. 16 icu patients designated for thoracentesis because of radiological support for pleural effusion were examined both with 2d and 3d ultra-sound \6 h before and after the intervention. effusion volume was calculated with the formula ''volume [ml] = sep [mm] 9 20'' [4] for 2d measurements and compared to the 3d volumetry by the ge 4d view software. the difference of volumetry before and after intervention was compared to punctured volume (gold standard). the device used for u-sound measurements was the ge voluson i. . within the group under survey (n = 16), eight patients were on the respirator. mean punctured volume was 605 ml (350 ml; 850 ml). mean absolute value of deviation from punctured volume (gold standard) was 191 ml (28.1%) for the 2d measurements and 18 ml (6%) for 3d measurements. biggest difference between methods was found between 500 ml and 700 ml punctured volume. none of the methods generally measures higher volumes than the other. conclusions. the size of deviations from gold standard in both directions in 2d measurements suggests that the method is not reliable in predicting pleural effusion volume. 3d measurements are more likely to predict the right effusion volume, making the method a better diagnostic tool than 2d u-sound measurements. although thoracocentesis was found to be safe for mechanically ventilated patients [1] and 3d volumetry may not change the therapeutic decision, which depends on high-risk patients' overall clinical condition, it could nevertheless help to avoid unnecessary interventions and thus improve patient safety. ongoing work analyses results for a group of patients with ct imaging-based volumetry of pleural effusion as gold standard. we study the utility of deltacvp changes during pressure support ventilation (psv) as an indication of respiratory effort. patients after several t-trials failures were on psv. the level of ventilatory assistance was changed in order to set the psv. no aditional interventión was used in the management of these patients. we registered data from the ventilator and beside monitor (vt, rr, p01, deltacvp) in two levels of ps. optimal-ps, as the lowest support without respiratory distress and with the middle of this level 50-psv. the inspiratory trigger was used with the highest sensibility without autotrigger, the inspiratory ramp was changed in every patient and expiratory was flow-cycled at 25% of the peak inspiratory flow. results. 14 patients n, 2 acute on chronic respiratory failure, n, 6 heart failure, n, 6 recovery of acute respiratory failure. age 67 ± 14 years, admission apache ii 24 ± 6 and they needed weaning with ps after 10 ± 8 days with control mechanical ventilation. the respiratory mechanics in this time were cst.rs 35 ± 11 ml/cmh 2 o and raw.rs 12 ± 7 cmh 2 o/l/s. the ramsay score was 3 ± 1 (2) (3) (4) (5) (6) . when the optimal level of ps was decreased from 12 ± 4 to 6 ± 2 cmh 2 o, all patients showed respiratory distress, and the variables studied changed significantly: p01: 1.5 ± 0.8 to 2.6 ± 0.9 cmh 2 o, deltacvp 6.2 ± 2.2 to 9.8 ± 3.8 cmh 2 o, vt decreased from 0.534 ± 0.181 to 0.419 ± 0.148 l and rr increased from 19 ± 4 to 22 ± 5 bpm (p \ 0.001). the correlation between p01 and del-tacvp was 0.6 (p = 0.02). central venous pressure swing provided information about the respiratory effort and may be useful during pressure support ventilation. introduction. the use of a tidal volume of 6 ml/kg of predicted body weight is part of the management of patients presenting with ards (1) and prevents ventilator induced lung injury in icu patients undergoing mechanical ventilation (2) . the setting of tidal volume is based on patient height. height seems to be more often estimated by the icu staff than actually measured (3). objectives. our study aimed to assess the accuracy of the visual estimation of patient height and its impact on ventilator settings. thirty-two patients admitted to a surgical icu were prospectively included in this observational study. patients had their height visually estimated by 18 icu staff members (6 doctors, 6 nurses and 6 nurse-assistants) and then measured. we also measured the knee height from which height can be extrapolated. we then compared the mean estimated height for each patient to the actual measured height with the use of bland and altman plots and the consequences of the measurement error on the tidal volume setting. in most patients visual estimation overestimates the actual height. the measurement errors result in an increase in the tidal volume up to +2 ml/kg. this remains true whatever the subgroup studied: all patients (bias: 4.5 ± 5.52, 95% ci: -6.32;15.32), male patients (bias: 4.02 ±6.29, 95% ci -8.3;16.35), female patients (bias: 5.5 ± 2.29, 95% ci 1.01-9.99) and whatever the type of assessor. extrapolated height from knee height results invariably in an underestimation of actual height (bias -1 ± 4.5, 95% ci -11.68; 9.68). our results prove that neither visual estimation nor knee height measurement are reliable surrogates for measured height. therefore, measuring patient height should be mandatory in critically ill patients in order to minimise ventilator-induced lung injury. methods. 3,016 respiratory acts were recorded in 4 icu patients selected because of severe asynchrony with the ventilator (g5, hamilton medical) during psv. by visual analysis (va) of airway pressure and flow trajectory, ineffective efforts and inspiratory/expiratory delays were detected. the results of va were compared with those provided by a new algorithm based on the automatic analysis (aa) of flow trajectory. results. va identified 773 ineffective efforts (26% of patients acts). among 2,243 assisted acts, average inspiratory and expiratory delay was 380 ± 214 ms and 134 ± 215 ms, respectively. significant inspiratory and expiratory delay ([300 ms) occurred in 1,255 (56%) and in 422 acts (19%), respectively. automatic analysis was able to identify 2,994 of 3,016 patients acts (99%). in 2,656 cases (88%), both inspiratory muscles contraction and relaxation were detected. in 338 acts (11%) only relaxation was identified. compared with va, inspiratory and expiratory delay of aa was 138 ± 134 and 29 ± 208 ms, respectively. aa recognized the start and the end of patient's effort before the ventilator in 2,142 (95%) and 1,477 (66%) of assisted acts. sensitivity and specificity of aa in detecting ineffective efforts, inspiratory delays [300 ms, expiratory delays [300 ms were 99 and 98%, 78 and 85%, 81 and 87% respectively. the new algorithm proved to be efficient as a real-time, continuous monitoring system of patient-ventilator interaction. the advantage over traditional flow and pressure based triggers has to be tested. introduction. mechanical ventilation remains as one of the most difficult safety issues in the icu, but parameters commonly monitored by ventilators only depict the most extreme risks for patients. new computerized approaches may manage exhaustive data and may include ''intelligent'' software that mirrors expert decision making. to test the clinical usefulness of a new computerized system as a herald for clinically significant alarms and its possible impact in outcome. methods. twenty-five mechanically ventilated patients were continuously monitored in a single mixed icu in a university-affiliated hospital. we recorded age, diagnosis, pao 2 /fio 2 , apache ii and sofa on admission. the computerized system grabs and process data from different devices, usually a monitor and a respirator, and evaluates the most relevant events in a ventilated patient. all the algorithms were designed and validated with the clinical staff. data of ventilated patients were recorded at the icu during 8 months and a total of 4,615,589 breaths from 25 different patients, each of them with a register of at least 50% of total ventilation time, were collected. data include biomedical signals (waves and trends) as well as all the clinical events detected by the system, including trapped gas at end-expiration, presence of secretions, double-cycling, asynchronies during expiration, pulse pressure variation in patients not triggering the ventilator and stress index ([1.2 or .8) in those ventilated with square airflow. outcome variables were icu length of stay, hospital stay and mortality. statistical analysis included multiple regression models for length of stay and mortality. [4] [5] [6] [7] [8] [9] [10] , icu length of stay 11.5 days [7.5-18] , hospital length of stay 21 days . the frequency of alarms were: trapped gas at end-expiration: 20.7%, presence of secretions 1.3%, double-cycling 1.1%, asynchronies during expiration 5.2%, stress index [1.2 1.1%, stress index .8 2.5%, and pulse pressure variation 5.1%. multiple regression analysis found pao 2 /fio 2 associated with length of mv and close to significance with hospital stay and mortality, but any of the computerized alarms reached yet the level of significance. conclusions. the computerized system is able to detect and review more clinically significant problems than clinical routine. however, its impact to define patient outcomes warrants further investigation. objectives. we have assessed the ability of the ventilator t-bird vs02 and ltv-1000 to deliver to a lung model with ards a set tidal volume (vt) at different simulated altitudes. we used a decompression chamber to mimic the hypobaric environment at a range of simulated cabin altitudes of 1,500, 2,500 and 3,000 m (4,000, 6,670, 8,000 feet). ventilators were tested with realistic parameters. vt was set at 400 and 250 ml in an ards lung model. the positive end expiratory pressures (peep) were set at 10 and 15 cmh 2 o. pressure drop across the pneumotachograph was measured by a differential pressure transducer (enertec tm ). the spirometer was checked at each altitude using a calibration syringe. the inspired oxygen content (fio 2 ) was 100%. respiratory rate was 20 breaths/min. the ratio inspiratory time/expiratory time was 1/1. the protocol included three measurements for each simulated altitude. comparisons of preset to actual measured values were accomplished using a t test for each altitude. a significant difference was defined by p \ 0.05. the standard deviation for the three measurements obtained at each altitude was consistently less than 10 ml. respiratory rate delivered was 20 breaths/min in all cases. variation of peep did not change the volume delivered. the t-bird vs02 showed a decrease in volume delivered. comparisons of actual delivered vt and set vt demonstrated a significant difference starting at 1,500 m for a vt set of 400 ml, at 2,500 m for vt set of 250 ml. at these altitudes, the variations between vt set and delivered were more than 10%. with decreasing barometric pressure, the ltv-1000 showed mostly an increase in volume delivered. comparisons of actual delivered vt and set vt demonstrated a significant difference at 2,500 m for a vt set of 400 ml, at 3,000 m for vt set of 250 ml. the delivered tidal volume remained within 10% of the set vt. assuming that the patient is ventilated at sea level and gas exchange is normal, the movement to altitude would result in an increase in tidal volume which might in fact represent a clinical event. conclusions. the ltv-1000 met the trial targets in all settings, whereas the t-bird-vso2 did not compensate well for altitude and progressively delivered lower volumes as barometric pressure decreased. such variations between delivered and set vt suggest lack of efficacy of altimetric correction in hypobaric conditions in some devices. the ltv1000 showed a moderate increase in volume delivered for ards lung model with increasing altitude, but maintained the delivered volume within 10% of the set vt up to 3,000 m. the accuracy of the vt delivery was superior with the ltv-1000 than with the t-birdvso2. oxygen therapy is commonly used to correct residual oxygenation impairment in the post-extubation period. this is usually done through a venturi mask which allows to deliver predetermined fractions of oxygen humidified with bubble humidifiers. the low humidity delivered by such devices and the use of an oro-nasal mask may, however, reduce patient's comfort, possibly resulting in mask displacement or removal and consequent oxygen desaturations. nasal high-flow (nhf) oxygen therapy allows to deliver high-flow oxygen, humidified with heated humidifiers and delivered through nasal cannulae, with the potential to improve comfort and efficacy. objectives. in patients requiring oxygen therapy after extubation, we compared nhf vs. venturi mask in terms of oxygenation and comfort. patients who were mechanically ventilated for more than 24 h, passed a spontaneous breathing trial, and had pao 2 /fio 2 \ 300 at the end of the trial were randomized to receive oxygen with nhf or venturi mask after extubation. exclusion criteria were: tracheostomy, age \18, pregnancy, or anticipated need for noninvasive ventilation after extubation. in both groups, fio 2 was set to obtain spo 2 between 92 and 98% (88-95% in copd patients). with nhf, flow rate was set at 50 l/min. arterial blood gases, respiratory rate, and discomfort were assessed at 1, 3, 6, 12, 24, 36, and 48 h. discomfort was assessed by asking patients to rate their discomfort with the used device by using a numerical scale from 0 (no discomfort) to 10 (maximum imaginable discomfort). discomfort symptoms were also assessed for the dryness of the delivered oxygen (dryness of the mouth, throat, nose, difficulty to swallow and throat pain). incidence of desaturations and interface displacement was also assessed. objectives. to evaluate the optimal humidifier water temperature when using a helmet for noninvasive positive pressure ventilation. oxygen. each was sequentially tested in the following order: using the helmet without humidification at ambient temperature, with humidification with unheated chamber water, and with humidification with the chamber water at 31, 34, and 37°c. at each setting, after a 20 min stabilization period, measurements were taken. comfort level at each setting was evaluated using a visual analog scale (vas) rated zero (most comfortable) to ten (least comfortable). temperature and relative and absolute humidity inside the helmet, and vas scores statistically significantly increased as the humidification chamber water temperature increased. the lowest vas, 1.6 ± 0.8, was obtained when water in the humidifier chamber was at ambient temperature. conclusions. for patient comfort during cpap using a helmet, the most desirable conditions are likely to obtained by humidifying without heating, that is by leaving the water in the humidifier chamber at room temperature. introduction. the physiological and clinical effects of non-invasive ventilation (niv) on acute post-operative respiratory failure are relatively unknown. the aim of this study was to determine the prediction factors for failure in the use of niv with a helmet in this context. the use of niv was assessed for a period of 2 years, in a post-operative intensive care unit (icu). demographic data was collected, as well as arf and arterial gas readings. haemodynamic changes were assessed using picco tm technology and the clinical development of patients was recorded. all patients who developed acute respiratory failure (arf) were treated using niv as their primary care, and the two groups for the study were determined in this way, depending on whether the technique was successful, or the patients required intubation. the risk factors that determined failure in the application of niv were subsequently determined. of the 56 patients presenting with post-operative arf treated with niv using a helmet, 41 did not require intubation (73.2%). following a multivariate analysis using logistic regression, we determined that there are four independent risk factors for the failure of niv. the primary causes of respiratory failure are as follows: acute respiratory distress syndrome (ards) and pneumonia, and in second place, the high initial evlwi (extravascular lung water index) value, as a protective factor, is the increase in the po 2 /fio 2 ratio after the first hour of niv application. conclusions. niv using a helmet could provide an effective alternative to conventional ventilation in selected patients with post-operative arf. -jaber s, delay objectives. analyze niv practice in emergency departments. we have development an international epidemiology survey (march 2009) by electronic questionnaire to know niv organization, equipment and training in emergency departments (phase i). design. international multicenter prospective. we have enrolled information from 57 hospitals: spain (42); italy (2); india (1); usa (3); slovakia (1); turkey (1); germany (2); australia(2); chile (1); singapore (1); finland (1) during to analyze noninvasive practice in prehospital and emergency medicine, equipment, interfase, ventilatory modes and common clinical applications. major results during 1 month period analysis were: noninvasive mechanical ventilation were applied in prehospital: 3 (57) (5.2%). nimv commonly was applied follow a objective pprotocol of nimv: (54) (57) (94.7%). global rate indication of niv were copd exacerbation (90%) and cardiac pulmonary edema (10-60%). all niv applications were successful applications in emergency departments (avoid eti 80%) with minor complications (12.2%) (skin nose lesion). equipment more relavant were (cpap devices (60%) and facial mask (90%) was more frequent, follow total face(5%); nasal mask (3%); helmet (2%); type ventilary mode: cpap ventilatory mode was frequent used as first line (60% (1) suggest niv should be started within 1 h of not responding to the maximal medical therapy for acute type 2 respiratory failure patients. following an earlier audit presented as an abstract at esicm 2008 (2) , which looked at possible delays in starting niv, protocols were implemented to start niv earlier at russells hall hospital acute admissions unit. objective. the aim was to assess the delays in starting the appropriate patients on niv at admission looking at impact on adverse outcomes. method. data was collected retrospectively using bts niv audit tool. 54 cases admitted with type 2 respiratory failure in our hospital between january and march 2010 who needed niv were included in the audit. delay was subdivided into a) door to first arterial blood gas (abg) sampling b) abg to decision for niv and c) from decision to actual starting of niv. results. the mean time to get an abg from admission was 180 min. 6 cases with delay more than 10 h skewed the data. the median time, which was more representative of the usual delay between admission and first abg, was 51 min. our audit showed that 28 out of 54 (52%) patients had abg within an hour compared to 11 out of 19 (58%) in the last audit. although noninvasive ventilation (niv) has been widely used in patients with acute on chronic respiratory failure (acrf) due to chronic obstructive pulmonary disease (copd), series studying patients with pulmonary restriction due to morbid obesity (mo) are rare (1) , despite the disease is highly prevalent in our environment. objectives. the aim of our study is to analyze and compare the effectiveness of niv in patients with copd and om. we analyzed all patients admitted to icu for a period of 14 years with diagnosis of acrf due to copd or mo and treated with noninvasive ventilation. niv success was defined as the avoidance of endotracheal intubation, survival in icu and at least 24 h on a medical ward with no signs or symptoms of respiratory failure. variables are expressed as means ± standard deviation and percentages. comparison between variables by pearson's v 2 test and student t. we analyzed survival and hospital readmission per year (log rank test). during the study period, 475 patients were admitted with exacerbation of copd and 160 with mo. all patients were treated with two levels of pressure. age differs between copd and om, 70 ± 10 and 73 ± 11 years, respectively (p = 0.003), as well as the percentage of men, 87. 6 adaptive support ventilation (asv) ò (hamilton galileo) has been shown to result in better patient synchrony, reduced weaning times and reduced work load for the icu staff (1, 2) . but, data is lacking on its efficacy, especially as non invasive ventilation (niv) due to the concern of being closed loop ventilation. also, little is known about the risk factors of late niv failure in patients who improve initially ( objectives. to assess end tidal co 2 monitoring in patients with hypercapnic exacerbations of copd requiring niv methods. simultaneous measurement of paco 2 and petco 2 was performed in 3 groups of patients. paco 2 was measured using arterial blood gas analysis and petco 2 was measured using non-invasive capnography. the groups were; phase 1a: 20 mechanically ventilated patients post coronary artery bypass graft, used to establish the reliability of the end tidal carbon dioxide monitor in a homogenous group of previously well patients. phase 1b: 5 patients with copd who did not have symptoms associated with an exacerbation, used to assess the use of a non invasive sampling device and assess the sampling method in stable copd patients. phase 2: 28 patients with a hypercapnic exacerbation of copd requiring niv. capnography was monitored continuously in this group and petco 2 values were calculated based on a mean value 1 min before and after the arterial blood gas sample. this was to avoid any sampling error as it was impossible to isolate the exact moment of arterial puncture. agreement between the sampling methods was assessed using the bland-altman method. phase 1a objectives. we aimed to evaluate the possible harm of niv failure in routine practice among spanish icus. methods. we extracted patients with acute respiratory failure requiring either invasive or noninvasive mechanical ventilation in 32 spanish icus during the 3-month period of the validation of the sabadell score (1). we recorded demographic parameters and treatments received during the icu stay. patients were followed until hospital discharge or death. results. we analyzed 4,132 patients, of whom 1,602 (39%) received only invasive mechanical ventilation (imv) and 529 (13%) received niv. niv succeeded in 50% of patients, but the other 50% required intubation. niv failure was more common in neurologic (70%) and post operatory (13%) and less frequent in coronary patients (11%). mortality was lower than predicted in niv patients (22 vs. 33%) and similar to predicted in imv patients (27 vs. 29%). mortality was lower than predicted in patients in whom niv was successful (12 vs. 28%) and (similar or slightly lower than to predicted) in those in whom niv failed (32 vs. 38%). conclusions. routine use of niv seems to confer a benefit, even when it fails and intubation is needed. reference(s tables 1 and 2 shows the parameters on respiratory muscles. introduction. the effectiveness of non-invasive ventilation (niv) in the setting of hypoxemia de novo remains controversial. it has been detected that patients in whom niv fails and intubation is required have a high mortality. otherwise, in patients in whom niv avoids intubation, survival rate is also high. to identify the factors involved in success or failure of niv in critically ill patients with hypoxemia de novo. we retrospectively studied all the patients admitted in our 26-bed intensive care unit (icu) from january 2008 to december 2009 with the diagnosis of hypoxemia de novo. do-notintubate patients were excluded. the indication of niv was at medical discretion, as well as intubation criteria. we defined the hypoxemia de novo as acute non hypercapnic respiratory failure due to a different cause from cardiogenic pulmonary edema. we defined two groups of patients: 1) niv failure, patients who required intubation, and 2) niv success, patients who did not require intubation. we collected demographical variables (age and gender), etiology of the hypoxemia, severity scores on admission (saps ii and sofa), glasgow coma scale (gcs), respiratory rate (rr), pulsioximetry (spo 2 ), ph and fio 2 , before and 2 h after starting niv, episodes of nosocomial respiratory infection, length of stay (los) in icu and icu mortality. we compared both groups using the mann-whitney non-parametric test. p \ 0.05 was statistically significant. we studied 35 patients (12 women and 23 men) with a mean age of 65 ± 18 years. the etiology of respiratory failure was: ards (n = 12), pneumonia (n = 13) and others (n = 10). there were 20 patients in the niv failure group (57%), and 15 in the niv success group (43%). niv failure rate was higher when hypoxemia was due to ards (p = \ 0.05). objectives. this retrospective analysis aimed to assess outcomes following instigations of niv in a variety of clinical conditions. outcome data for copd/apo and non-copd/apo groups were compared. we assessed whether outcomes differed between these groups. in addition we wished to assess how outcomes varied across non-copd, non-apo conditions. objectives. the aim of this study was to compare patient's respiratory effort with three different noninvasive ventilators currently used on critical care patients and selected from a bench study. six patients treated by niv to prevent respiratory failure after extubation were included. each subject was successively submitted to a randomly assigned 15 min-period of ps-niv with three different ventilators: bipap vision (respironics), elisée 250 (resmed) and oxylog 3000 (dräger medical). these ventilators have different performances in a bench comparison. ventilatory settings were adjusted for the first ventilator and maintained for the followings. ps level was increased in order to obtain a tidal volume of 6-8 ml/kg of body weight (ps 9 ± 2 cmh 2 o). flow, airway and oesophageal pressures were recorded. the oesophageal pressure time product (ptpoes) and tidal oesophageal swing (dpoes) were measured to evaluate patient's respiratory effort. results. no significant differences in tidal volume, respiratory rate and autopeep were found between ventilators. the dpoes and ptpoes, however, were significantly higher with oxylog 3000 as compared to bipap vision and elisée 250, as expected from the bench comparison. there are limited data on niv 0 s efficacy in hypoxic respiratory failure. objective. to investigate the epidemiology and outcomes of patients administered niv as first line respiratory support in a mixed medical-surgical icu over a 2 year period (jan 2008-dec 2009), in an academic medical center. methodology. data abstraction from icu database, clinical care manager and chart review. results. 64 surgical patients (sp) and 260 medical patients (mp) were administered niv. the sp were 58% male, and had a median age of 73 years. the mp were 56% male, and had a median age of 69 years. 42% of sp were admitted with type 1 respiratory failure (t1rf pao 2 \ 9 kpa), 22% were admitted with type 2 respiratory failure (t2rf paco 2 [ 6 kpa) and the remainder were admitted with respiratory distress (rd). 34% of mp were admitted with t1rf (pao 2 \ 9 kpa), 48% were admitted with t2rf (paco 2 [ 6 kpa) and the remainder were admitted with rd. the median length of stay (mlos) was 3 days for sp (range 0-50); the mlos for mp was 3 days (range 0-46). sp were commenced on niv on average 1.52 h after admission (range 0-6 h), and remained on niv for a median of 19.5 (range 1-304) h. 22% of surgical patients required intubation, and the mortality rate was 9.4%. mp were commenced on niv on average 1 h after admission (range 0-6 h), and remained on niv for a median of 20 (range 1-356) h. 30% of medical patients required intubation, and the mortality rate was 22%. logistic regression was applied to all datasets. among medical and surgical patients there was no correlation between the type of respiratory failure, initial blood gas or ph and the need for subsequent intubation, or risk of death. hematology patients had a mortality rate of 65% and accounted for 16% of overall deaths. oncology patients also had a 65% mortality rate, and accounted for 45% of overall deaths. amongst the mp that presented with hypoxemia, the intubation rate was 29% and the mortality rate was 29% (although not all patients that died were intubated). amongst the mp that presented with hypercarbia, the intubation rate was 24% and the mortality rate 13%. summary. niv successfully prevented intubation in more than 70% of patients. patients presenting with hypoxic respiratory failure were no more likely to be intubated than those presenting with hypercarbia. two-thirds of hematology and oncology patients treated initially with niv subsequently died. a microdialysis system was composed and the time delay of the system, recovery time, was introduced and tested with a fluids switching method. twelve sd rats were divided into ir or control group. myocardial ir was induced by ligating (20 min) or releasing (60 min) the suture underlying lad. mycrodialyisis probe was implanted into the left ventricular myocardium perfusion area to be occluded. dialysate samples were collected every 10 min. blood samples were drawn at the beginning and at the end of the procedures. dialysate calcium concentration ([ca++]i) was detected with an atomic absorption spectrophotometer. serum calcium and ctnt were detected. recovery time for the microdialysis system was 20 min, recovery rate was 16%. [ca++]i showed no changes during ischemia and descended immediately after reperfusion,reached the lowest level at 20 min after reperfusion, then escalated slowly while keeping lower than control with significant difference. there was no difference in serum calcium at the beginning ( objectives. to evaluate the causes, incidence and impact on outcome of admission hyperlactatemia in patients admitted to a general micu. methods. data were retrospectively collected from the patient records for all adult patients admitted in the micu during the 15-months period. data regarding patient demographics, probable cause of hyperlactatemia, presence of shock on admission, need for organ support and icu outcome were recorded. patients were divided into two groups based on admission lactate levels: high lactate, with levels of 2 mmol/l or more and normal lactate, with levels less than 2 mmol/l. patients in these two groups were compared in terms of need for organ support and icu mortality. the efficacy to discriminate between survivors and non-survivors was assessed by area under the receiver operating characteristic curve (auroc). introduction. during critical illness alterations in blood flow are thought to predispose to organ dysfunction and hemodynamic therapy is often targeted at maintaining organ perfusion. however, abnormal blood flow distribution during critical illness may cause regional blood flows to correlate poorly with systemic haemodynamics (1) . currently, our understanding of blood flow distribution during critical illness in humans has been limited by the invasiveness of established techniques for its measurement. objectives. phase-contrast mri (pc mri) represents an entirely non-invasive, contrastfree, method of measuring blood flow in major blood vessels (2, 3) . we sought to apply this technique to technique to the measurement of organ blood flow in the critically ill. in a pilot proof of concept study, we measured renal and portal blood flow by pc mri critically ill humans with sepsis, multi-organ dysfunction and acute kidney injury (aki). in 5 individuals cardiac output was measured by thermo-dilution in the icu, in the remaining patients we measured cardiac output (ascending aortic flow) and also descending thoracic aortic blood flow using pc mri techniques. we studied 10 critically ill individuals with severe sepsis and aki. when studied, 8 were mechanically ventilated, 9 were on continuous haemofiltration and 5 required vasopressors. transport and mri examinations were carried out without complication. in these patients, median cardiac index was 3.5 l/min/m 2 (range 1.6-8.7), median renal blood flow 482 ml/min (335-1,137) and median renal fraction of cardiac output 7.1% (4.4-10.8). median portal blood flow was 881 ml/min (550-1,800). descending aortic blood flow (measured in 5 patients) ranged between 65 and 85% of cardiac output (median 75%). conclusions. phase-contrast mri can efficiently and safely assess organ perfusion during critical illness in man. near simultaneous measurement of cardiac output enables organ blood flow to be assessed in the context of the global circulation. preliminary observations suggest renal blood flow is consistently reduced as a fraction of cardiac output in established aki. pc mri may be valuable to future investigation of organ dysfunction and vasoactive therapies in sepsis and critical illness. objectives. we were interested in the effects of the higher pco 2 -levels on the microcirculation of infants with birh weights \1,000 g. data were collected from 12 infants, who were randomized either to treatment with permissive hypercapnia or normocapnia. inclusion criteria were a birth weight between 400 and 1,000 g, a gestational age from 23rd to 28th+6 weeks, intubation during the first 24 h of life and no malformations. the pco 2 target range was increased stepwise and was 15 mmhg higher in the intervention group. skin microvascular parameters were assessed noninvasively with sdf on the right arm every 24 h during the first week of life and on the 14th day. results. pco 2 (auc: 639 ± 62 vs. 744 ± 62) differed significantly between the two groups (p = 0.004). functional vessel density (fvd) was significantly lower in the intervention group on the 14th day of life (395 ± 43 vs. 281 ± 67 cm/cm 2 ; p = 0.04). the proportion of small vessels increased in the control group whereas they decreased slightly in the intervention group, but did not reach stat. sig. increasing target pco 2 lead to a temporary hyperdynamic flow in both groups. conclusions. pco 2 -levels influence significantly the microcirculation in preterm infants. elevation of pco 2 -levels leads to a decrease in fvd, presumably due to shunting and vasoconstriction and might cause temporarily hyperdynamic flow. methods. blood from 6 healthy volunteers were diluted with hes, albumin 4%, rl or autologous plasma to obtain a final hematocrit of 30%. in vitro wbv measurements were made by the rheolog tm device (rheologics, exton, pa), a new viscometer with a u-formed capillary. the flow rate (determined by the rate of change in height of the columns of blood) is directly related to the pressure drop across the capillary tube. the shear rate (from 1,000 to 1 s -1 ) and viscosity of the sample can be mathematically derived. results were expressed as median values (with 25-75% intervals) and compared by anova with bonferroni correction. a p value .05 was considered as statistically significant. hemodilution with rl and albumin decreased significantly the wbv for all shear rate compared with autologous plasma and hes ( fig. 1 ). conclusions. in contrast to albumin and ringer's lactate, hes and autologous plasma increased the whole blood viscosity, suggesting that these solutions may be preferred in severe hemorrhagic shock to better preserve plasma viscosity and microcirculation. we divided into two groups the randomly selected sample from the scope of patients come through open-heart operation assisted with extracorporeal support at the university of pécs: therapeutic (continuous blood gas monitoring/cdi-500) and control (intermittent sampling) group. after the retrospective data collection we carry out the analysis with (prevalence) frequency and confidence interval calculation and khi square test. results. the following accompanying diseases occurred significantly higher rate in the therapeutic group: ami (p = 0.007), kidney disease (p = 0.009), chronic pulmonary disease (p = 0.001), and the aggregation of the accompanying diseases showed also significantly high degree (p = 0.001). the long interval operations occurred significantly higher rate (p = 0.036) in the therapeutic group, and the times of the aorta clinch (p = 0.025) and the perfusion (p = 0.001) was also significantly longer. despite of that during the perfusion in a significantly more cases remained the rates in the normal range concerning to the therapeutic group (ph: p \ 0.001; be: p \ 0.001; pco 2 : p \ 0.001), and the prevalence of the restart of the heart showed also significantly higher rate (p = 0.005). the continuous blood gas analyses assure reliable and the postoperative recovery assisted ecc circulation support. this assists considerably for keeping the parameters in the physiological limits even in the higher rate of the incidences of complex operations and accompanying diseases. this could contribute to lower incidence of side effects, preventing the causeless elevation of the postoperative hospital charges. objectives. describe the changes in capillary perfusion after erythrocytapheresis during severe falciparum malaria. we report two cases of severe falciparum malaria and describe the evolution of the sublingual capillary perfusion after erytrocytapheresis. the sublingual microcirculation has been studied with sidestream dark-field imaging (microscan; microvisonmedical tm , amsterdam). the device was applied on the lateral side of the tongue and the video images (2-3 captures of 5-12 s.) of capillary perfusion were recorded. the microcirculatory scores were analysed offline: small vessels (\20 lm) density (number of vessels/mm), percent of continuously perfused small vessels (ppv%) and mean flow index (mfi). 2 mmol/l. the capillary perfusion has improved: capillary density increased (13.6/mm), the proportion of perfused vessel increased (87%) and flow was continuous in most vessels (mfi: 3). clinical evolution was rapidly favourable and the patient was discharged from the intensive care unit. case 2. severe falciparum malaria with high parasitemia (24%) and acute renal failure. before erythracytapheresis: macrohemodynamic parameters were normal but microcirculation was reduced: vessels density (14.6/mm) with 71% of small vessels perfused and the flow was slow in most vessels (mfi: 2.16). after erythracytapheresis: parasitemia decreased (7.9%). sublingual microcirculation has improved with an increase in small vessels density (18.1/mm) among which 93.6% were perfused with a continuous flow (mfi: 3). the patient had a good outcome. conclusions. microcirculation monitoring should be assessed specifically in some critically ill patients, even if macrocirculatory parameters are in the normal range. during severe plasmodium falciparum malaria, this monitoring could be specifically important to assess the effect of erytrocytapheresis therapy on tissue perfusion. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 s117 objective. perioperative myocardial infarction (pomi) is associated with significant mortality and morbidity in cardiac surgery. the primary objective of this prospective multicenter study is to investigate whether monitoring of coronary sinus metabolic markers can reliably predict ischemia and pomi faster than conventional monitoring. method. 50 patients undergoing cardiac surgery were monitored perioperatively using a transjugular implanted microdialysis catheter (cma microdialysis) to study the metabolic changes of the heart. coronary sinus (sc) samples of lactate, pyruvate and glycerol were obtained continuously through 24-h post-operatively. pomi was defined by ckmb c 100 u/ l and troponin t c 1.0 lg/l. a total of 5 patients met the criteria for pomi. 14 patients showed at least one adverse event during the postoperative course. lactate, lactate-pyruvate-ratio and glycerol levels in the sc sharply increased up to 12 h before rise of cardiac enzymes. analyses of regression and discriminate analyses showed statistically significant (p \ 0.05) relationships between elevated metabolite values and the occurence of pomi. roc analysis revealed that lactate, lp-ratio and glycerol from the sc are sensitive markers to predict pomi and postoperative clinical events. conclusions. coronary sinus metabolic markers are sensitive and early predictors for the detection of perioperative myocardial infarction and severe complications in patients undergoing cardiac surgery. beginning disorder can be detected far earlier than with any existing monitoring device. perioperative red blood cell transfusions (btx) are commonly used in patients undergoing cardiac surgery to correct for anemic conditions caused by blood loss and hemodilution associated with cardiopulmonary bypass circulation and anesthesiological procedures. however, several studies have shown btx might have adverse effects on patient outcome. the goal of btx is to correct anemia and to ensure an improvement in the oxygen delivery to the parenchymal cells by the increased presence of red blood cells in the microcirculation. the aim of this investigation was to test the hypothesis that btx during onpump cardiac surgery have a beneficial effect on sublingual microcirculatory perfused vessel density, and oxygenation. methods. 24 adult patients undergoing on-pump cardiac surgery were selected for this study. sublingual microvascular flow index (mfi), detected vessel length (dvl), and functional capillary density (fcd) were assessed using sidestream dark-field (sdf) imaging in 12 patients. sublingual reflectance spectrophotometry was applied in 12 patients to monitor sublingual tissue oxygen saturation. in group a, btx resulted in increased fcd and dvl as depicted in fig. 1 . mfi for small and medium microvessels was not affected by btx (fig. 2 ). in group b, reflectance spectrophotometry demonstrated increases in microcirculatory hemoglobin and oxygen saturation ( fig. 3 ). the main findings suggest that leukoreduced btx improves the systemic circulation and oxygen carrying capacity of the microcirculation by increasing fcd and thereby reducing diffusion distances without increasing significantly the convection of red blood cells. this reduction in diffusion distances causes an increase in microcirculatory oxygen saturation. d.m.j. milstein 1 , k. yürük 1 , r. bezemer 1 , c. ince 1 1 academic medical center at the university of amsterdam, translational physiology, amsterdam, netherlands aims. anemia is a common adverse effect of oncologic diseases as is the therapeutic options required for their treatment. however, as blood transfusions are directed at correcting for anemia and intrinsic hypoxic conditions, little evidence exists claiming that blood transfusions have successfully resolved anemic challenges as storage can significantly deteriorate rbc function. the aim of this study was to investigate the influence of rbc transfusions on sublingual microcirculatory perfusion and tissue oxygenation in anemic oncology patients. methods. eight consecutive ambulatory patients scheduled to receive 3 packed rbc transfusion bags were selected for this study. baseline sublingual microcirculation functional capillary density (fcd) was measured using sidestream dark-field (sdf) imaging prior to and after 30 min of the completion of the last infused blood bag. sublingual mucosal oxygen saturation (sto 2 ) was measured at the same anatomical location and time points using near-infrared spectroscopy (nirs). results. figures 1 and 2 capillary refill time (crt) is a generally accepted method of assessing the circulatory status of a patient. we have previously showed that using 4.5 s as the upper limit of normality in critically ill patients could discriminate patients with a more unfavourable outcome 1 . however, this upper limit of normality was defined based on variation of crt in an adult healthy population 2 . the best crt in critically ill patients, therefore, should still be redefined. objectives. we aimed to define the best crt as predictor of organic and metabolic dysfunction in an intensive care unit (icu) population. methods. capillary refill time was measured by applying firm pressure to the distal phalanx of the index finger for 15 s, and a chronometer recorded the time of returning to normal colour. we performed receiver operating characteristic curve (auc) to detect the best crt consistent with severe organ and metabolic dysfunction, as evaluated by sequential organ failure assessment (sofa) [11 and acidosis (lactate [2 mmol/l and be\ -3 meq/ l), respectively. in addition, we performed logistic regression analysis using the cutoff crt as binary to investigate its estimated odds ratio (exp(b)). of 170 patients included in the study (age 55±16; 125 male), 115 had circulatory shock, of whom 62 had septic shock. mean crt in all patients was 4.6 ± 2.2. figures 1 and 2 show the roc curve for sofa score[11 and metabolic acidosis, respectively. using the best crt value, logistic analysis revelled the following estimated odds ratio: for sofa score[11: exp(b) = 6.8; p = 0.004); for metabolic acidosis (exp(b) = 5.3; p = 0.001). roc curve for crt relative to sofa score [11 roc curve for crt relative to acidosis conclusions. we found that 5.5 s is the best time to define prolonged crt in critically ill patients, and that using this crt cutoff value could discriminate patients with a more severe organ and metabolic dysfunction. 1 introduction. impairment of microcirculation in acute situations is associated with organ failure and depends on macrocirculation but also on specific factors (1) . micro-perfusion, assessed by tissue hemoglobin saturation (sto 2 measurement) or micro-blood flow (laser doppler, ld) are easy to use and non invasive methods. the obtained data could be an end point in critical care resuscitation or optimization. objectives. to assess the impact on microcirculation of cardiovascular (cv) support on the basis of mean arterial pressure (map) and cardiac output (co), to evaluate when microcirculatory parameters improved or not the modifications observed in map and co. methods. observational study: measure of co, map, svco 2 , and lactate, thenar nirs (inspectra 650; hutchinson technology) baseline sto 2 , with performance of an arterial occlusion test (3 mn, 300 mmhg) so calculate occlusion-os and reperfusion slopes-rs (1). similarly, forearm skin blood flow velocity (ld, blf21d, transonic systems) basal ld, and post-ischemic peak velocity ldmax) (1) were measured. data were collected before and after cv optimization (fluid loading, vasoactive or inotropic drugs). patients were defined: macrocirculatory responders (r) when co increased more than 10% versus nonresponders (nr); microcirculatory responders (rs+) when rs increased more than 10% versus nonresponders (rs-). statistical analysis: nonparametric tests (wilcoxon and mann-whitney test). results. 32 patients (86% in shock) were studied. 20 had sepsis (63%), 5 hemorrhage (16%), 4 pulmonary oedema (12%), or other (9%). 50 therapeutic optimization challenges were performed:40 fluid challenges (500 ml, 0.9% nacl), 4 dobutamine 5c/kg/min, 3 nitrates, 1 diuretic, 1 electric shock and an increase in dosage of norepinephrine. in r group (n=28, 56%), co was increased associated with map (p \ .0001), svco 2 (p = .001) and decreased lactate (p = .02). the micro-oxygenation improved with an increase of rs (2.55 [1.3-4.25] vs. 2.7 [1.6-3.9 ]%/s, p = .002) as microperfusion did: increase in ldmax (7.5[4.8-16.3] vs. 8.7 [6.9-16.3 ] tpu, p = .01). in the nr group, both the macro or the microcirculation did not change. since no microcirculatory differences between r and nr were observed, patients with good or poor microcirculation could not be detected. the study based on microcirculatory responses showed 50% of responders (rs+). in this group, baseline sto 2 (p = .002), basal ld (p = .04) and ldmax (p = .01) increased in a large amount in association with an improved co and map (p = .0076 and p = .0008). in the rs-group, co and map were also improved (p = .0002 and p = .006). conclusions. improvement of macrocirculatory parameters can improve microcirculation but not in all patients. improvement in microcirculation may also be a target, regardless the effects on macrocirculatory parameters. this concept has to be tested prospectively. introduction. hypothermia is regularly used for brain protection after resuscitation from cardiac arrest but its impact on cardiovascular function, however, is not well defined. objectives. the aim of this study was to evaluate the cardiovascular response to mild therapeutic hypothermia and rewarming in a large animal model. seven anesthetized, mechanically ventilated and invasively monitored sheep were cooled with a cold intravenous saline infusion, ice packs and nasal cooling (rhinochill system, benechill, ca) to achieve a core temperature of 34-35°c (the basal temperature in sheep is around 40°c). after maintenance of this temperature for 6 h, sheep were progressively rewarmed to baseline temperature. a positive fluid balance was maintained during the entire study period to avoid any hypovolemia. the sublingual microcirculation was observed using sidestream dark-field (sdf) videomicroscopy and the proportion of perfused vessels (ppv) and perfused vessel density (pvd) evaluated using a semi-quantitative method. results. during cooling, systemic and pulmonary artery pressures did not change, but cardiac output decreased significantly along with the increase in vascular resistance. left and right ventricular stroke work index decreased reflecting altered ventricular function. nevertheless, there was an increase in mixed venous oxygen saturation (svo 2 ), reflecting a decrease in oxygen extraction. sublingual microcirculation analysis showed a significant decrease in ppv and pvd. all the variables returned gradually to baseline during the rewarming phase. conclusions. in this intact healthy large animal model, the alteration in cardiac function during hypothermia was well tolerated because of the simultaneous decrease in oxygen requirements. arterial pressure was maintained by an increase in systemic vascular resistance associated with a reduction in peripheral microcirculatory density. grant acknowledgment. *rhinochill system was supplied by benechill, inc. objectives. to evaluate consequences of hypoxemia occurence on intestinal microcirculatory perfusion in mice submitted to controlled hemorrhage. tracheotomized and ventilated balb/c mice were submitted to systemic hypoxemia (pao 2 = 40 mmhg) during 1 h. controlled hemorrhage to mean arterial pressure of 40 mmhg was associated (from 30th to 60th min). 4 groups were constituted: hh = hypoxia and hemorrhage, hr = hemorrhage, hx = hypoxia, cl = control (neither hypoxia nor hemorrhage). a segment of ileon was exteriorized through an abdominal midline incision. it was opened along the antimesenteric border and placed on a specially designed piedestal to facilitate observation of the villi with transilluminating and epifluorescent microscopy. the bowel segment was superfused with krebs solution maintained at 37°c. villous perfused density (dvp), red blood cell velocity in villous tip arteriole (vart) and villous capillaries (vcap) were observed after fitc-labeled erythrocytes were intravenously administered. 6 mice were included in each group. leucocytes adhesion to intestinal wall venules (20-40 lm) was observed in a separated set of experiments including also 6 mice per group. number of adherent leucocytes (l adh ) and leucocytes flux (l fl ) were observed in each group. measurements and arterial blood gases were collected at 0, 30, 60 min (t 60 ). data were expressed as mean ± sem and were compared by analysis of variance (anova). introduction. despite remarkable progress in hemodynamic monitoring, clinical examination, assessment of peripheral perfusion and comparison of surface and body core temperature still are diagnostic cornerstones of critical care. infrared non contact thermometers provide accurate measurement of body surface temperatures. the picco device using an arterial line with a thermistor tip in the distal aorta-in addition to transpulmonary thermodilution (tptd)-provides continuous body core temperature. objectives. therefore, it was the aim of our study to evaluate the predictive capabilities of surface temperatures and their differences to body core temperature regarding ci, svri and parameters of microcirculation. in 46 icu-patients body core temperature was measured four times per day using a picco-catheter (tp), a thermistor-tipped urinary catheter (tu) and an ear thermometer (te) (thermoscan; braun). additionally, surface temperatures were determined on the great toe, finger pad, forearm and forehead using an infrared non contact thermometer (thermofocus; tecnimed). furthermore capillary refill time (crt), lactate and scvo 2 were measured and peripheral perfusion was clinically assessed (normal, pale, mottled). immediately afterwards tptd was performed to obtain ci and svri. statistics: spss 18.0. spearman correlation. compared to tp, t forehead (-0.4 ± 0.89°), t forearm (-2.95 ± 1.42°), t finger pad (-5.66 ± 3.13°) and t toe (-7.02 ± 4.49°) were significantly lower (p \ 0.001 for all comparisons). in multivariate analysis tptd-derived ci (4.09 ± 1.2 l/min sqm) was significantly correlated (r = 0.552) to the difference ''tp-t forearm '' (p \ 0.001), ''tp-t finger pad '' (p = 0.001), crt (p = 0.004), scvo 2 (p = 0.008) and map (p = 0.012). tptd-derived svri was multivariately associated (r = 0.631) with ''tp-t forearm '' (p \ 0.001) and map (p \ 0.001). scvo 2 was independently correlated to the difference ''tp-t finger pad '' (r = 0.429; p \ 0.001). lactate was independently correlated (r = 0.302) to crt (p \ 0.001). the roc areas were 0.740 and 0.725 for (tp-t forearm ) and (tp-t finger pad ) to predict ''ci \ 2.5'' and ''scvo 2 \ 70'', respectively. the sensitivity, specificity and negative predictive value of ''tp-t forearm [ 2.7°'' were 92, 52 and 98% regarding a ci \ 2.5 l/min/sqm. 1.) measurement of surface temperatures using non contact infrared thermometers and comparison to body core temperature provides useful data on macro-and microcirculation. 2.) the differences (tp-t forearm ) and (tp-t finger pad ) were independently associated to tptd-derived ci and svri, and ci and scvo 2 , respectively. 3.) crt was independently associated to lactate level. v. shilov 1 , a. astakhov 1 1 ural state postgraduate medical academy, chelyabinsk, russian federation introduction. actuality of this problem consists of different disturbances of heart rhythm and heart conductivity (from sinual bradycardia and ventricular extrasystolia till sinuatrial arrest and fibrillation of ventricles) provoked by traction of oculomotorial muscles and pressure on eyeball. this reaction is called oculocardial reflex (ocr). it is necessary to note there is no definite strategy of ocr prevention. objectives. this study was conducted to estimate the possibility of the control of haemodynamic effects of ocr. the haemodynamics and hydrobalance were investigated with electric current probe (28 and 115 khz) using monitoring complex of cardiorespiratory system and hydratation of tissues -km-ar-01 «diamant». data documentation was carried out at 6 stages of evisceroenucleation: 1. before anesthesia and surgery; 2. at induction; 3. during the intubation; 4. at eyeball mobilization and oculomotorial muscles traction; 5. while deepening of endotracheal anesthesia by inhalative anesthetics during 5-10 min after preceding stage; 6. at the end of surgery, after the extubation. results. the study confirmed ocr reflex, to appear at eyeball extraction and to manifest as bradycardia, cardiac output decreasing heart productivity, but peripheric vessel resistansce does not change. monitoring-controlled gradual deepening of inhalative anesthesia during 5-10 min has restored the haemodynamic data to normal eliminated ocr vessel reactions. hydrostatic changes took place only at the end of the operation, after the extubation. it manifested ad increasing of extracellular liquid confirmed by decreasing of low-frequent impedance. intracellular liquid remained intact. it seems the most possible, hydrostatic changes of extracellular liquid to depend on crystalloid infusion in blood vessels up to 1,000 ml during anesthesia and they eliminate with hypovolemia. conclusions. thus we can conclude that vascular manifestations of hemodynamics in ocr at eyeball extraction or active oculomotorial tractions may be eliminated with gradual deepening of inhalative anesthesia and monitoring of registed date of haemodynamic and hydrobalance. probably it's necessary to optimige the anesthesia using of pterygopalatal and pterygoorbital blockade to prevent ocr before the induction as retrobulbal anesthesia may be an ocr trigger. f. corradi 1 , c. brusasco 1 , a. vezzani 2 , f. altomonte 3 , p. moscatelli 3 1 university of genoa, anesthesia and intensive care, genoa, italy, 2 ospedale maggiore di parma, anesthesia and intensive care, parma, italy, 3 azienda ospedaliera universitaria san martino, emergency medicine, genoa, italy introduction. despite improvements in trauma care, uncontrolled bleeding is the leading cause of potentially preventable early in-hospital deaths contributing to 30 to 40% of trauma-related deaths (1) (2) . about 30% more deaths occur within the second/third hour after injury due to occult major internal haemorrhage. failure to recognize this situation may in part be due to lack of sensitivity of hb/hct levels, arterial blood pressure, heart rate, respiratory rate, injury severity score and markers of hypoperfusion (lactate and base excess) in initial assessment of blood loss. to study if early changes in spleno-vascular resistance index predict the development of hypovolemic shock after trauma. a prospective observational study conducted in 40 adult haemodinamically stable patients admitted to the emergency department because of suspected or definite severe trauma and retrospectively divided into 2 groups depending on whether or not they developed haemorragic shock requiring blood transfusion. doppler ultrasound measurements of splenic arterial branches at ilum were obtained and splenic doppler resistance index (sdri) was recorded at admittance (within 1 h from trauma) and related to arterial blood gas analysis (haemoglobin, base deficit, lactate, co 2 , ph), heart rate, and outcome in the first 24 h (intensive care unit admittance, blood transfusion, sepsis, mortality). results. statistically significant differences between patients who developed shock within 24 h and those who did not were the following: higher sdri (0.67 ± 0.12 vs. 0.52 ± 0.05, p \ 0.001), lower base deficit (-4.0 ± 4 vs. 0.1 ± 3 meq/l, p = 0.001) and higher lactate (2.7 ± 1.2 mmol/l vs. 2 ± 1 mmol/l p = 0.015). auc's of roc analysis were significant for sdri (auc = 0.89, ci 0.73-1.05, p \ 0.001) and lactate (auc = 0.76, ci = 0.55-0.96, p = 0.04), and borderline for bd, hr, hb, and ph. by multivariate analysis, sdri at admittance resulted to be the only good independent predictor of hypovolemic shock and bleeding (p \ 0.001), whereas haemoglobin, base deficit, heart rate, lactate and ph were not significant. in trauma patients with stable haemodynamic conditions at admittance spleen constriction occurs very early under heavy adrenergic stimulation in response to occult bleeding and can be non-invasively detected by sdri. the present study proposes sdri as a non-invasive measurement of changes in splanchnic circulation to detect blood loss and occult hypovolemia, which may help activate early surgical or radiological intervention for patients with major trauma and guide therapy to optimize splanchnic perfusion. introduction. approximately 1% of patients require temporary circulatory support due to cardiogenic shock following cardiac surgery. these patients are at risk of a mismatch between oxygen delivery and demand and carry a substantial mortality and morbidity risk. mixed venous oxygen saturation (svo 2 ) is the still the ''gold standard'' for the determination of the ratio between systemic oxygen delivery and consumption (do 2 /vo 2 ratio) in cardiac surgery patients. a nonivasive technique is thought to be cerebral near-infrared spectroscopy determining cerebral oxygen saturation (rso 2 ). purpose. the present analysis aims to compare rso 2 and svo 2 levels in adult patients undergoing ecmo therapy for postoperative cardiogenic shock. methods. data were collected hourly for the first 24 h post operatively. each patient was equipped with a pulmonary artery catheter (pac) for continuous determination of svo 2 connected to a vigilance ii-monitor (edwards lifesciences, irvine, usa) and an invos 5100 monitoring system (somanetics, troy, usa) to determine rso 2 . data were analyzed by parametric testing and bland-altman analysis. a total of 10 patients were enclosed. all svo 2 values were in a range between 47 and 86%. in this range, the linear correlation coefficient between svo 2 and rso 2 was r = 0.983 (p \ 0.0001). the correlation coefficient for svo 2 values below 70% was r = 0.841 (p \ 0.0001) and r = 0.708 (p \ 0.0001) for svo 2 levels equal or higher than 70%. bland-altmann analyses of all collected oxygenation data (n = 250) revealed a bias of 3.4% (mean 95% ci: 2.73 to 4.03) and limits of agreement (1.96 standard derivation) of 13.6 to -6.8% (upper 95% ci: 12.48 to 14.70; lower 95% ci -7.93 to -5.71) for the raw data of the whole group ( figure 1 ). bland-altmann analyses of svo 2 values below 70% (n = 105) showed a bias of 3.5% (mean 95% ci: 2.30 to 4.60) and limits of agreement (1.96 standard derivation) of 15.1 to -8.2% (upper 95% ci: 13.14 to 17.09; lower 95% ci -10.18 to -6.23). bland-altmann analyses of svo 2 values equal or higher than 70% (n = 145) revealed a bias of -3.3% (mean 95% ci: 2.57 to 4.09) and limits of agreement (1.96 standard derivation) of 12.4 to -5.7% (upper 95% ci: 11.09 to 13.68; lower 95% ci -7.03 to -4.42). interestingly, despite svo 2 values [ 70%, we noticed 19 events in 4 patients with rso 2 values less than 50% for more than 5 min. all events had been associated with arterial co 2 levels below 30 mmhg, whereas no other changes in hemodynamic or oxygenation parameters could be determined. conclusions. this pilot study suggest for the first time that rso 2 highly correlates with svo 2 in patients undergoing ecmo therapy due to refractory cardiac and/or pulmonary dysfunction. therefore determining rso 2 may be a noninvasive alternative to monitor global tissue oxygenation under this condition. additionally, it was noted that cerebral hypoxia may be present despite a svo 2 c 70 mmhg. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 results 1 : during severe hypothermia (25°c) cardiac index (ci), stroke index, mean arterial pressure and indexes of lv contractility (prsw 2 and dp/dtmax) were reduced. after rewarming all variables remained reduced, except for ci that returned to prehypothermic values due to increased heart rate. systemic vascular resistance (svr), lv isovolumetric relaxation time (tau) and oxygen content in arterial and mixed venous blood increased during 25°c, while lv end diastolic pressure (lvedp) was constant. after rewarming svr and lvedp were reduced, while tau and the blood oxygen contents normalized. troponin-t and tnf-a were constant during 25°c but increased after rewarming. albumine plasma concentration was reduced during 25°c and remained so after rewarming. conclusions. surface cooling to 25°c followed by rewarming caused reduction of systolic, but not diastolic lv function. there were no signs of inadequate global oxygenation throughout experiments. the posthypothermic increase in troponin-t may reflect degradation of myocyte troponins secondary to a hypothermia-induced calcium overload. the increase in tumour necrosis factor alpha together with a posthypothermic reduction of plasma albumin concentration may indicate that the cooling and rewarming initiated an inflammatory response. we studied 41 patients, mean age 51.6 ± 10.2 years, 68% male. the etiology of cardiogenic shock was: 44% (n = 18) dilated cardiomyopathy, 37% (n = 15) acute myocardial infarction, 12% (n = 5) acute cardiac allograft rejection and 7% (n = 3) acute myocarditis. the duration of ecmo support was 118.8 ± 89.8 h. weaning was possible in 22% (n = 9) and the ecmo was used as a bridge to transplantation in 51% (n = 21). 30-day survival was 60 and 58.5% of our serie were discharged from the hospital. in 7 cases the ecmo was withdrown as a result of a limiting treatment decision. objectives. to describe the characteristics of patients with ca and its management with moderate hypothermia using arctic sun ò device with hydrogel patches. descriptive, observational and retrospective study of patients who suffered ca and received moderate therapeutic hypothermia (33°c) according to the protocol implemented in a coronary intensive care unit of a tertiary hospital. we collected patients from june 2009 to april 2010, first months of this therapy in our hospital. moderate therapeutic hypothermia is applied using the arctic sun ò device consisting of hydrogel patches applied to the skin covering 40% of the body surface. the device is connected to a temperature control console, measuring core temperature with an urinary catheter. we analyzed demographic characteristics, cardiovascular risk factors and other relevant comorbidities. we collected data about the ca, its initial treatment and its icu management with moderate hypothermia, analyzing length of events and systemic and neurological outcome at discharge from icu. we also collected data about the infectious complications during the icu stay. results. during this period, moderate therapeutic hypothermia was applied to 14 patients with a mean age of 56 ± 14 years. 78.6% were male. the most frequent cardiovascular risk factor was cigarette smoking, present in 50% of individuals. the ca cause was an ami by 70% of cases; however, myocardial infarction or angina was documented before the event only in 14.3% of patients. the ca event was outside the hospital in 78.6% of cases and the initial heart rate recorded was ventricular fibrillation in 64.3% of cases. the average ca length was 18.6 ± 8 min. obtaining a temperature of 33°c took between 3 and 6 h from the ca in most cases; and this temperature was maintained for an average of 31 ± 6 h. the average time of induction of hypothermia was 2.5 h. the re-heating was performed between 0.3 to 0.5°c per hour, averaging 9 h to reach temperatures of 36.5°c. midazolam sedation was performed in all patients and severe chills required muscle relaxation with cisatracurium in 71.4% of patients. infectious complications occurred in 64.3% of patients, the most common site of infection was respiratory. the average stay was 18 days. at the time of icu discharge, average gcs was 14 and the average gos was 4. mortality was 14.3% (2 patients). 1-implementation of a therapeutic hypothermia protocol is feasible. 2-infectious complications are common, being respiratory ones the most observed. 3-the arctic sun ò device is quick and safe for induction of moderate therapeutic hypothermia. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 s121 objectives. up to now, it is not clear, however, whether mild hypothermia influences also markers of oxidative stress and nitric oxide production. methods. eleven patients after out-of-hospital cardiac arrest were included into this study, all were treated with mild hypothermia using endovascular system thermodard xp. target core temperature 33°c was maintained for 12 h, re-warming rate was set at 0.15°c per hour, followed by normothermia of 36.8°c. blood samples for measurement of nitrotyrosine and nitrates/nitrites were taken at admission and then every 6 h for 2 days. during hypothermia the levels of nitrotyrosine and nitrates/nitrites were comparable with baseline values. in re-warming period serum levels of both parameters gradually increased and in normothermia the levels were significantly higher as compared with hypothermia: nitrotyrosine 14.87 ± 2.01 vs. 8.03 ± 1.68 lm/l, p = 0.027; nitrates/nitrites 105.47 ± 30.65 vs. 55.62 ± 10.74 lm/l, p = 0.04. our results revealed that during mild hypothermia in cardiac arrest survivors the levels of nitrotyrosine and nitrates/nitrites are significantly lower. these data indicate that the reduction of oxidative stress and suppressed nitric oxide production may be involved in the protective effect of hypothermia. grant acknowledgment. this study was supported by the grant of the czech ministry of health, nr. 00000064203. new volumetric variables of preload, such as total end-diastolic volume index (tedvi) and active circulation volume index (acvi) and central blood volume index (cbvi), have been shown to be good predictors of fluid responsiveness. during acute changes of intravascular volume, such as hemorrhagic shock, these variables allow a more accurate intervention. objectives. the aim of our study was to investigate the changes in tedvi, acvi, cbvi in a juvenile model of hemorrhagic shock. seven anesthetized ponies (1-4 months of age) were studied at normovolemia (base), after blood withdrawal to mean arterial pressure (map) of 40 mmhg (hemo), after infusion of norepinephrine to a map of 75 mmhg (ne), and after retransfusion (resu). tedvi, acvi, cbvi were measured by ultrasound dilution (ud) technology with costatus device. data were analyzed using kruskal-wallis analysis and dunn's t test. comparison of fluid load agreement by blant altman. results. tedvi and acvi had significant change during hemo and resu status. percentage of tedvi and acvi changes agreed with percentage of blood volume removed/ infused with bias and limits of agreement (loa) 4% (-21.4, 29. 3) and -10.6 (-29.5 8.2%) respectively. ne administration induced map and cvp significant changes, whereas tedvi and acvi remained unchanged. cbvi showed high variability and seemed to be inconsistent on the identification of the volume status. conclusions. in this animal model, tedvi and acvi were superior to cbvi in accurately reflecting hemorrhage and were also suitable to predict fluid responsiveness. ne administration did not affect the volumetric variables tedvi and acvi. (1). objectives. we sought to identify independent predictors of post-arrest neurological recovery, and of survival to hospital discharge with neurological recovery. in the course of a pre-planned interim analysis, we analyzed the data from 220 participants of nct00729794. this three-center, double blind, placebo-controlled, clinical trial is ongoing (estimated enrollment = 350 patients) and aims to asses the efficacy of combined vasopressin and epinephrine during cardiopulmonary resuscitation (cpr) and of steroid administration during and after cpr. post-arrest neurological recovery was defined as glasgow coma scale score[9 documented at least once by 2 study-independent physicians in patients not receiving sedation for at least 24 h. we identified a total of 65 patients who were subjected to at least one post-arrest assessment of their neurological status. subsequently, we used backward stepwise logistic regression, and assessed the following potential predictors: cause of cardiac arrest (cardiac vs. non-cardiac); area of cardiac arrest occurrence (monitored vs. non-monitored); use of therapeutic hypothermia; number of cpr cycles; mean arterial pressure and serum lactate at 15 min following resuscitation; and patient group allocation. results. the sole independent predictor of post-arrest neurological recovery was the occurrence of the cardiac arrest in an area of monitored patient care (i.e., intensive or coronary care unit, and operating or emergency room): odds ratio: 3.83, 95% confidence interval = 1.26-11.63; p = 0.018. the sole independent predictor of survival to hospital discharge with neurological recovery was the serum lactate concentration at 15 min after resuscitation: odds ratio: 1.22; 95% confidence interval = 1.02-1.46. conclusions. the results of this preliminary analysis suggest that post-arrest neurological recovery seems to depend more on the use of pre-arrest patient monitoring rather than the employed cpr protocol. also, patients with lower, early post-arrest serum lactate concentration seem to have a better chance of surviving to hospital discharge without concurrent, severe neurological deficits. reference(s). to quantify the attribution of intra-operative defibrillation on markers of myocardial injury (ck, ck-mb, tnt and hfabp). methods. single centre prospective study in which 50 elective cabg patients were included in a 2 month period in 2007. patients with valve, emergency, off-pump surgery or rethoracotomies were excluded. patients were grouped as having had defibrillation or no defibrillation during surgery. serum levels of ck, ck-mb, tnt and hfabp were analyzed in blood samples taken at arrival on the icu and at 4, 8 and 16 h after admission to the icu. levels of these biochemical markers were compared using a paired t test. results. all data presented as mean ± standrad deviation conclusions. atrial fibrillation is a common problem associated with morbidity and mortality in critically ill patients; however, evidence-based recommendations are lacking leading to variability in treatment. our audit confirmed variability and low compliance to nice in treating new af. inconsistency in using appropriate first line drugs for rate control and inadequate thromboprophylaxis reflects lack of familiarity with nice guidelines. educating itu medical staff and promoting the use of well validated, easy to remember chads 2 scoring system 2 might improve compliance with nice guidance. also,promoting hemorr 2 hages scoring system 3 for assessing risk of bleeding and carat tool to guide prescribing antithrombotics may allow itu physicians to anticoagulate more patients with af with less fear of bleeding complications. in patients with acute coronary syndromes (acs) combined antiplatelet and anticoagulant therapy is recommended in addition to percutaneous coronary revascularization. heparins and glycoprotein iib/iiia receptor inhibition can be associated with immune-mediated thrombocytopenia of clinical significance in less than 2%, resulting in major bleedings and increased mortality rate. to evaluate the incidence of thrombocytopenia and its impact on in-hospital complications-bleedings, reinfarctions, in-hospital heart failure and mortality in patients with acs. retrospective evaluation of patients admitted during 3 months, fulfilling the criteria for acs: rest chest pain up to 36 h, changes in standard ecg with or without st-elevation with or without elevated serum troponin i. serum troponin i was estimated by immunochemical method (boehringer, mannheim, germany, normal levels .15 lg/l). patients were treated by combined antiplatelet therapy, heparins and percutaneous coronary revascularization. platelets were estimated by automatic analyzer sysmex xe2100, kobe, japan (normal levels 140-340 9 10 9 /l). thrombocytopenia was defined as platelet count less than 140 9 10 9 /l or a drop in platelet count of more than 50% during inhospital stay. we registered demographic, laboratory, clinical data and in-hospital mortality. we included 78 acs patients, 82.1% (64/78) with and 17.9 (14/78) without stelevation (64.1% men, mean age 63.8 ± 13.3 years). mean admission troponin i was 11.7 ± 24.9 lg/l, platelet count 212.6 ± 68.8 9 10 9 /l. in-hospital thrombocytopenia was observed in 24.4% of patients. in thrombocytopenic patients in comparison to non-thrombocytopenic ones we observed significantly increased mean age (70.2 ± 10.9 vs. 61.8 ± 13.4 years, p = 0.016) and admission serum creatinine (172.7 ± 142.1 vs. 102.3 ± 37.7 lmol/l, p = 0.001), significantly decreased admission systolic blood pressure (123.8 ± 28.9 vs. 139.8 ± 27.6 mmhg, p = 0.034) and hdl-cholesterol (1.1 ± 0.3 mmol/l vs. 1.3 ± 0.4 mmol/l, p = 0.048), significantly increased bleedings (26.3 vs. 6.8%, p = 0.028), in-hospital heart failure (57.9 vs. 22%, p = 0.003), but nonsignificantly increased reinfarctions (5.3 vs. 3 .4%), arrhythmias (36.8 vs. 32.2%) and in in-hospital mortality (21 vs. 6.7%). thrombocytopenic patients were less likely treated by percutaneous coronary revascularization (63.2 vs. 88.1%, p = 0.044). admission thrombocytopenia in comparison to normal admission platelet count was associated with significant increase in inhospital mortality (60 vs. 5%, p = 0.0209) and icu-mortality (42.9 vs. 5.6%, p = 0.0094). conclusions. thrombocytopenia, observed in more than 20% of acs patients, was associated with in-hospital complications and mortality, especially thrombocytopenia on admission. introduction. stress cardiomyopathy, also known apical ballooning or takotsubo cardiomyopathy (tts), has been recognized for several years. this syndrome is characterized by transient systolic dysfunction of the apex or mid segments of the left ventricle (lv) in the absence of coronary artery disease. several forms of mostly physical stress may evoke this syndrome. in this case we describe a very uncommon cause for tts in an unusual situation. a 69-year-old woman without cardiovascular history found her husband non-responsive in bed. after resuscitation he was admitted to icu. visiting her husband, she complained of chest pains, shortness of breath and hyperventilation. physical examination revealed no abnormalities but her ecg showed deep negative t-waves in leads i, ii, iii, avf, v3-v6. her troponin t level was 0.789 lg/l (ref \ 0.03), nt-pro-bnp was 7,812 ng/l (ref \ 301). ck was 226 ng/l with ckmb of 27 ng/l. echocardiography showed very poor lv function with the typical apical ballooning of the lv along with hyperkinesis of the basal ring ( fig. 1 ). there was no coronary artery disease. she was admitted and treated with beta-blockers. within days, the enzymatic changes normalized and echocardiography showed improved lv function with and normalization of the apical segments. she made full recovery within 2 weeks. discussion. icu admittance has significant impact on family members. in the acute phase of the illness, most medical attention goes to the admitted patient. especially when prognosis is poor, stress to the family may be considerable. mostly spouses and relatives with female gender are at the highest risk for depression and anxiety disorders 1 . in contrast, little is known about the occurrence in relatives of broader physical symptoms like pain and nausea 2 or even acute onset severe medical conditions requiring treatment. in our case the wife experienced pain, anxiety and nausea along with hyperventilation. however, the underlying disease was a severe cardiomyopathy requiring admittance and treatment. the tts cardiomyopathy is known to icu physicians in relation to subarachnoid hemorrhage, but most likely not in the context of severe emotional stress. in summary, we stress the importance for intensive care physicians to be alert to the fact that despite many diverse symptoms related to stress and anxiety, relatives can develop acute medical conditions as well. 2001 2 a retrospective observation study. demographic profiles, operative data and short term outcomes in the icu were reviewed in the 22 patients who underwent beating-heart (b-h) operation. we also compared b-h operation group (2003-2010) and conventional cardiac arrest (c-a) operation group (before 2003). both groups of patients were similar with respect to preoperative demographics (age, co-morbidities, lv function). in the b-h operation group, mean age was 70 years (55-78). preoperative mean nyha functional class was 3.5. and the mean lvef was 28.7%. 15 patients underwent single valve operation, and the rests needed combined valve operation or cabg. 17 patients were included in the c-a operation group, with mean age of 63 years (23-82), nyha functional class of 3.5 and mean lvef of 29.3%. in the b-h operation group, no dc shock was needed, whereas 53% of the patient with c-a operation needed dc shock after aortic unclamp. in the single aortic valve replacement, b-h operation group had a tendency of shorter assist perfusion time after intracardiac procedure (38.5 vs. 45.1 min). in the icu, inotropic support (maximum dose of dopamine) was much less (4.6 vs. 7.3 r) than conventional c-a operation (p = 0.002) and additional iabp support was not required (0 vs. 53% in c-a operation). low cardiac output syndrome was not encountered in the b-h operation group (0 vs. 6% in c-a operation). no major postoperative complication was encountered except ventricular tachycardia in one patient. there was no 30 day mortality (0 vs. 6% in c-a operation). conclusions. in our series, valve surgery on the beating-heart had a superior postoperative hemodynamics and lower associated morbidity compared to conventional cardiac-arrest operation. this procedure is recommended especially in the patients with impaired lv function. (2003) objectives. does hrt measured during daytime or nighttime predict: one-year all-cause mortality in acs?; hospital readmission within one-year? methods. secondary analysis of the immediate aim study, prospective clinical trial of patients presenting to the emergency department (ed) with symptoms of acs (n = 1,308): holter recordings of 303 patients, positive for acs and admitted to the hospital, started 45 min (median time) after arrival in the ed; 1-year follow up after hospital discharge in 70% of the sample; recordings scanned to exclude artifact and non-sinus rhythm. hrt analysis performed using research software at the washington university heart rate variability lab; hrt parameters measured: 1) turbulence onset (to), which characterizes the initial rate acceleration after a ventricular premature contraction (vpcs); and 2) turbulence slope (ts), which characterizes the subsequent oscillation in heart rate. results. 187 holter recordings eligible for hrt analysis; 116 eliminated due to unanalyzable rhythm, \5 vpcs needed to calculate hrt, or recording time \12-h. 121 patients were diagnosed with ua, 46 with nstemi, and 20 with stemi. 17 patients died and 84 were re-hospitalized during follow up. hrt measures were dichotomized into low and high-risk groups based on previously reported cutpoints: to \ 0% normal, to c 0% abnormal; ts [ 2.5 ms/beat = normal, ts b 2.5 abnormal. chi square statistics calculated. findings include: abnormal 24-h ts significantly associated with 1-year mortality [odds ratio (or) 3.7 (p = 0.008)]; re-hospitalization significantly associated with both abnormal 24-h to (or 1.83, p = 0.046), and 24-h ts (or 2.1, p = 0.018); abnormal night (0000-0600) to and day (0800-2000) ts also significantly associated with 1-year mortality (or 3.8, p \ 0.05 for both); abnormal daytime to (or 2.4, p = 0.007) and ts (or 2.4, p = 0.012) each significantly associated with re-hospitalization. conclusions. patients with acs who have a ts \ 2.5 measured over 24 h or during the daytime are at higher risk of dying within 1 year after hospitalization. those who either have to c 0% or ts b 2.5 have a greater risk of re-hospitalization. assessment during the daytime only might provide sufficient information for risk stratification. hrt measured close to acs symptom onset may aid in risk stratification. objectives. we tried to find a correlation between trs and the severity of coronary artery disease (cad) found in coronary angiography. we analyzed all consecutive patients with nsteacs admitted to intensive care unit from june 2008 to december 2009. all patients were stratified at admission with trs. pci were performed when it were indicated. for the study we grouped patients according to trs and the severity and extend of cad. considering the trs the patients were classified into three categories: trs 0-2, trs 3-4 and trs 5-7 and considering the results of the coronary angiography were grouped into three categories: normal angiogram, one or two vessel disease and three vessel or left main disease. we excluded patients without pci. qualitative variables are expressed as absolute value and percentage and quantitative variables are expressed as means ± standard deviation or median ± interquartile range when correspond. comparisons between groups were made with the v 2 or fisher's exact test for categorical variables and mann-whitney test for quantitative variables. a total of 51 patients were admitted with nsteacs during the period of the study and 41 underwent to pci. age median were higher in patients with trs 5-7 than other groups (71.1 years ± 7.5 p \ .01). men percentage and in-hospital mortality were similar in all groups (pns). between groups there weren't significant differences in prevalence of diabetes, hypertension, dyslipidemia, smoking, mean first troponin i and mean highest troponin i (pns). the v 2 for all comparisons were 17.1 (p \ .01). normal angiogram were most likely found in patients with trs 0-2 than in those with trs [2 (p \ .05 or 10, 95% ci 1.61-62). one or two vessel disease were found more often in those with trs 3-4 than in those with trs\3 o [4 (p \ .01 or 5.83, . three vessel or left main disease were found more often in those with trs 5-7 (p \ .01 or 10.4, 95% ci 2.3-47.5). conclusions. the relationship between trs and clinical outcomes (recurrent angina, acute myocardial infarction and death) is well known but its relation with the extent and the severity of cad is not well determined. in our study we found a correlation of trs with the number of vessels affected in coronary angiography, making the trs as a good predictor of the extent and the severity of cad. a.b. ratnaparkhi 1 , j. walton 1 1 freeman hospital, anaesthetics, newcastle upon tyne, uk introduction. acute onset atrial fibrillation (af) is common phenomenon in the intensive care unit. atrial fibrillation poses risk for thromboembolism. practice of commencing anticoagulation after acute onset af varies in different intensive care units. anticoagulation comes with its own side effects in the already compromised patients in the intensive care unit. this regional audit was carried out in intensive care units of the north east region of the uk. to assess the practice of use of anticoagulation after acute onset of atrial fibrillation in the intensive care units. postal questionnaire were sent to the 15 intensive care units of the north east region of the uk including two cardiac surgical intensive care units. the questions asked were; is there a protocol in your unit? are you aware of any guidelines? if yes, which guidelines? do you commence anticoagulation for acute onset af? what do you use for anticoagulation and in what dose? after what duration of onset of af you consider starting anticoagulation? how long do you continue anticoagulation? do you commence anti platelet therapy? we also put six clinical scenarios with acute onset atrial fibrillation. the aim was to assess if the units consider stroke risk stratification for commencing the anticoagulation. one example is; how would you manage anticoagulation for a 73 year old patient with hypertension and diabetes, presented with sepsis following pneumonia. results. we received responses from 14 out of 15 intensive care units. the management of anticoagulation strategy was different in different unit. two units were aware of the nice guidelines, one unit was aware of the accp guidelines and two units were aware of the other guidelines. ten units responded that they commence anticoagulation for acute onset af. commonly used anticoagulation was low molecular weight heparin. four units use anticoagulation within less than 48 h of the onset of af. there was no fixed duration for the continuation of the anticoagulation. different units consider various factors before commencing anticoagulation. conclusions. use of anticoagulation in acute onset af varies in the different units. each unit takes into account different factors for the commencement of anticoagulation. this audit highlights the possible need for the evidence based protocol for the use of anticoagulation in acute onset af in intensive care units. objectives. to study of the clinical features and analytical features of those patients with dilated cardiomyopathy treated with ecmo as a bridge to cardiac transplantation in order to determine which parameters are useful to predict the outcome methods. a retrospective study from december 2006 to december 2009. all patients were divided into two groups: the a group: patients who died before transplantation; the b group patients who got transplantation. several clinical and analytical characteristics are compared before starting ecmo, at 12 and 24 h after the onset and immediately before withdrawing (''end time'') ecmo treatment (either for transplantation or for death). qualitative variables are expressed as % and quantitative ones a mean and standard deviation (sd). chi square and t student test are used as appropriated. a p \ 0.05 denotes statics significance. there are statistically significant differences between patients who died and patients who survived to be transplantated. the presence of multiorgan failure and severe tissue oxygen hypoperfusion, and its persistence after initiated treatment, denotes a worse prognose. the study of this differences could be useful to decide which patients benefit of ecmo treatment. objectives. to measure the diagnostic contributions of routinely used (nt b type natriuretic peptide (nt probnp), cardiac troponin i (t), ddimeres (dd), c-reactive protein (crp) and procalcitonin (pct)) and new biomarkers(mid-regional pro-atrial natriuretic peptide-(mr-proanp), pro adrenomedullin (pro adm), pro endothelin (pro et) and copeptin [pro vasopressin (cp)] for diagnosing infection in patients with severe acute dyspnea. we designed a prospective study of patients admitted in the emergency department and in medical intensive care unit in a university hospital. inclusion criteria were acute dyspnea with spo 2 b 92% and/or respiratory rate (rr) c 25 b/min. patients with obvious myocardial infarction or pneumothorax were excluded. clinical-biological data were recorded and biomarkers sampled. an independent blinded expert panel classified the patients according to all the data including response to treatment and outcomes blindly to biomarkers' results. the roles of biomarkers were assessed quantitatively and then using terciles of the distribution. the contribution of the biomarkers in the diagnosis was assessed using auc-roc curves and by multiple logistic regression taking into account other clinical and biological explanatory variables. objectives. to compare differences between a group of patients with lmca treated with percutaneous coronary intervention (pci) and others with cabg. to evaluate direct results and make a long term prognosis analyzing mayor cardiovascular complications (mcc) rate. observational retrospective study that includes a total of 130 patients with lmca submitted to ca between january 2005 and december 2009: 39 patients (30%) were treated with pci and compared to 90 patients (70%) treated with cabg. in the total of the pci cases drug-eluting stents were used. we exclude patients in cardiogenic shock and those with protected left main coronary artery. results. average age of the patients was 68.3 ± 9.7. in the pci group most of the patients were older than 75 years. in the cabg group there was a majority of male patients (64.5 vs. 35.5%, p = 0.02) without significant differences in the rest of demographic information. in the pci group (p = 0.05) there were more previous record of acute myocardial infarction (ami) and pci found, and also a greater percentage of patients with lvef\50% (p = 0.03). average euroscore of patients from the pci group were greater than those from the cabg group. complete revascularization was obtained more frequently in the cabg group. in the cabg group (p = 0.001) the number of days between diagnosis and therapeutic strategy as well as the days hospitalized were greater. in the multivariate analysis, the type of therapeutic strategy wasn 0 t associated to mortality when hospitalize. the median follow-up period was 21 months. according to the classification ccs (p = 0.001), there was no significant difference in the grade of angina. tendency to a greater restenosis of stent, greater mortality during follow-up and greater mcc without statistically significant. in the multivariate analysis surgical strategy was associated to a lower mortality during follow-up (or 0. objectives. our objectives were to analyze the characteristics of the patients who were done a cardiac catheterization, the differences of the procedure and the incidence of complications. methods. we randomized 380 consecutive patients referred to the hospital for cardiac catheterization since august until october 2009. results. among 380 patients, the age (mean ± sd) was 65 ± 10.8 years and more frequently male (65.3%). 34.7% were angioplasty. the radial approach was used in 203 patients (53.4%; 64.8% with 5f arterial sheaths and 35.2% with 6f), and the femoral approach in 177 patients (46.6%). there was no difference in the baseline characteristics of the patients. the time required for the procedure and the fluoroscopy time were longer in the radial group (p = 0.06). a cross over was more often necessary in the radial group (10 patients, 2.6%) due to radial artery spasm, deviousness, loop, unstable catheter or artery dissection. only one patient required cross over from femoral to radial approach (0.26%) due to serious deviousness in iliac artery. the intravascular ultrasound (ivus) and rotablator always were done by femoral approach. the incidence of complications was higher in the femoral approach group (20.9 vs. 12.8%, p = 0.015). in the radial approach group, the most important complication was wrist haematoma (0% radial artery occlusion checked with allen test), however the femoral approach complications were: inguinal haematomas (13.5%), big haematomas required blood transfusions (2.8%), femoral artery pseudoaneurysms (2.8%), arteriovenous fistulas (0.6%), retroperitoneal haemorrhages (0.6%), strokes (0.6%). these complications increased the hospital stay (5.5 ± 2 vs. 1.2 ± 0.4 days, p = 0.001). conclusions. the radial approach reduces peripheral arterial complication rates and allowed earlier ambulation, so also reduces the hospital stay. however, needs higher learned time, and the size of the artery can limit several procedures (ivus/rotablator on the other hand, the development of bundle branch block after that procedure has been associated with higher rates of complete av block, syncope, and sudden cardiac arrest at long term. objectives: our aim is to describe the incidence of cardiac conduction problems after pavi and to identify possible risk factors associated with these conduction problems. patients and methods. a total of 57 consecutive patients who underwent a pavi were included in our analysis. the indication for pavi was a severe symptomatic aortic valve stenosis in patients who were rejected or had a high risk for conventional savr. permanent pacemaker implantation was performed in case of the presence of complete heart block or symptomatic bradycardia, persisting after at least the second postprocedural day. data are expressed as mean value ± sd for continuous variables and as numbers with percentage for categorical variables. between the variables selected for predicting av block after pavi (basal valvular area, annulus diameter, valsalva sinus diameter, left and right bundle branch block), the only independent predictor was the last one (or 11.3, 95% ci 1. (1). implementation of care bundles have been advocated to reduce the infection rate (2). objectives. the aim of the study was to identify the effect of the introduction of the central venous catheter (cvc) bundle on crbsi rate on our critical care unit over a threeyear period. retrospective audit on the rate of crbsi for a 3 months period before the implementation of the cvc bundle provided baseline data. prospective audits for the corresponding 3 months were carried out after the cvc bundle was firmly embedded in clinical practice. the data was collected based on the information recorded in our clinical information system (cis). the cvc bundle consisted hand hygiene, barrier precautions on insertion, 2% chlorhexidine skin preparation, using femoral site as last resort, daily review of necessity of central access, daily inspection of insertion site, use of tpn on a dedicated port and maintaining asepsis when accessing the line. robust educational program was rolled out during the implementation phase for medical and nursing staff. compulsory elements of the care bundle were recorded in our cis. we collected data on overall compliance with the bundle, mean dwell time, number of crbsis, site of infection and whether the patient left the unit with a cvc line in situ. for statistical analysis chi-square test and wilcoxon test were used. our main results are summarised in table 1 . lines removed prior to transfer (n) 33 52 76 we have seen a significant increase in the compliance with the bundle and it resulted a significant and sustained reduction in mean dwell time, cvc related infection rate and number of patients transferred to the ward with cvc lines (all p \ 0.05). the bundle resulted in bigger scrutiny for cvcs, hence the reduction in the number of lines inserted. conclusions. our data shows that implementation of care bundles can significantly and sustainably reduce the rate of crbsi on the icu in a real life setting. our previously unacceptable infection rates were reduced and now are comparable with the recently published data (1) . evidence-based catheter-care procedures, guided by healthcare workers 0 perceptions and including bedside teaching, reduce significantly the crbsi rate and demonstrate that improving catheter care has a major impact on its prevention. to evaluate the incidence of catheter-related bloodstream infection (cr-bsi) and of the use of central venous catheters (cvc) after an intensive improvement program aimed at reducing cr-bsi. before-and-after study in patients admitted to a 12-bed medical-surgical icu from january 2007 through december 2009. in 2008 we implemented an improvement program (analysis of barriers, creation of a working group, review of protocols, and implementation of an educational program and checklist) and a set of measures to reduce cr-bsi during cvc insertion and maintenance based on provonost et al.'s model (1) . in the postintervention period, we suspended the use of the checklist and evaluated the degree of completion of the online training module ''bacteremia zero program'' and analyzed the staff turnover rate. we have monitored cr-bsi using the ''estudio nacional de vigilancia de infección nosocomial en uci'' (envin-uci) criteria since 2002. we calculated the incidence rate ratio of cr-bsi and cvc utilization ratio for 2007, 2008, and 2009 . we compared the incidence rate ratios using the epitab module from the stata program and utilization ratios using chi-square tests. results. nine cr-bsi were diagnosed in 2007, one in 2008, and five in 2009. the incidence rate ratio of cr-bsi in these periods was 3.11, 0.32, and 1.52%, respectively. the incidence rate ratio in the postintervention period (0.94%) was significantly lower than in the preintervention period (3.11%) (3.31: 95% ci 1.05-11.32, p = 0.025.) the increase in incidence rate ratio between 2008 and 2009 was not statistically significant (0.32 vs. 1.52%, p = 0.14). the pre-and post-intervention cvc utilization ratios were 0.83 and 0.86, respectively (no significant differences). during the year 2009, and for existing staff in 2008, 6 rotating residents, 19 nurses (turnover rate 52%), and 5 nurse's aides (turnover rate 50%) joined the icu. the training module was completed by 32% of the new nurses and none of the physicians or nurse's aides. conclusions. the program was effective; its effectiveness may be related to the intensity of the measures. a low preintervention incidence rate ratio does not preclude the usefulness of an improvement program. introduction. in the intensive care unit (icu) the bloodstream infections (bsi) related to the central venous catheters (cvcs) represent a serious clinical complication and are a substantial economic burden. although the data are still somewhat controversial, the use of antibiotic impregnated cvcs is one of the generally accepted approaches in reducing the risk of bsi [1, 2] . objectives. in order to determine the efficacy of antibiotic impregnated cvcs in our clinic we evaluated retrospectively the data of the cultures of cvcs and blood obtained from patients during their stay at icu within the last 2 years (january 2008 till august 2009). conclusions. surprisingly, there was no difference in the incidence of the cvc and bloodstream infections in both groups. we can conclude that the strategy of using mrimpregnated cvcs did not reduce the incidence of catheter related bsi. although earlier studies have indicated that mr-impregnated cvcs are cost saving [3] , our data add further proof to the suggestion that the cost effectiveness of these catheters is at least uncertain. results. from all patients, 27 (42.1%) developed infection from any reason during the icu stay. 8 patients developed crbsi, 12.5% of the total patient number and 29.62% of the patients who developed any infection. we recorded 9 episodes of bacteremia due to cvc during 735 days of cvc placement stay, 12.24% while the standard limit is four episodes of crbsi per 1,000 days cvc placement. during the year 2009, we chanced our practice in order to avoid as risk factors as we can, using only antimicrobial/antiseptic impregnated catheters, improving our hand hygiene and aseptic technique, using only chlorhexidine and semipermeable polyurethane dressings and making catheter replacement at scheduled time intervals as a method to reduce crbsi. the previous year the recorded crbsi incidence was 18.7% respectively. conclusions. the incidence of intravascular catheter related infection is recorded above the standard limits for second consecutive year assuming that we have to improve further our surveillance policy. on the other hand, the incidence is recorded smaller than the incidence of the previous year according to the change to our practice, assuming that our reforming policy, although not fully effective, still is better for the prevention of intravascular catheter related infections. introduction. intravenous catheter related blood stream infection is a major factor contributing to in hospital morbidity and mortality and extending hospital stay by 10 days and expenditure by 10,000 to 30,000 lb 1 . the incidence of central line associated blood stream infections (cr-bsi) in our unit was audited in 2008 and a comprehensive infection prevention program that included staff education, hand hygiene, maximal sterile barrier precautions and daily assessment of the need for a central line was introduced. we are also taking part in the national audit project matching michigan. objectives. assess the effectiveness of the infection prevention programme and re-audit the incidence of cr-bsi methods. data was collected daily for a period of 4 months. this included the number of patients with central venous catheters in the unit, the number of lines removed or re-sited, the indications for line change, the site of line insertion and incidence of line infection. the lines were reviewed daily and removed if indicated clinically (pyrexia or raised white cell count) or if not required. results. over a period of 4 months 206 central lines were used amounting to 716 line days. the lines inserted were subclavian (sc)-13 (6.31%), femoral (f)-108 (52.4%) and internal jugular (ij)-85 (41.26%). the percentage of lines removed for clinically suspected cr-bsi reduced in this period from 30 to 15.04%. the average duration of stay for the lines were sc 4.4 days, ij 5.8 days and f 4 days which was shorter than our previous audit showed. the percentage of microbiologically proven cr-bsi also dropped from 12.5 to 2.5% (4 from internal jugular lines and one from a femoral line). conclusions. introduction of simple and cost effective practices decreased the prevalence of cr-bsi in our unit by a factor of five. daily review of lines led to earlier removal of central lines once they were no longer required. the unit being a neurointensive care unit has a greater proportion of patients in whom femoral lines are often the only option. our survey proves that with strict adherence to guidelines and following infection control protocols diligently the risk of cr-bsi from all line types can be reduced. conclusion. this study implies that the scale of crbsi may be higher than is currently recognised and that the blood culture positivity rate for crbsi is 79%(152/192). as concurrent antibiotic therapy may reduce blood culture and cvc tip positivity, the blood culture rate of 79% suggests that crbsi has an inherently high blood culture positivity rate despite concurrent antimicrobial therapy. (1). in this context, we tested the introduction of chlorhexidine(chx)-impregnated sponges (2) (8), acinetobacter baumannii 11.8% (6), serratia marcescens 3.9% (2), stenotrophomonas maltophilia 3.9% (2), escherichia coli 1.9% (1) jai salmonella enteritidis 1.9% (1) . production of extended-spectrum beta-lactamases (esbls) was detected in 50% of klebsiella spp. and e. coli strains, overproduction of ampc beta-lactamases was recognized in 44.5% of enterobacter spp., while only one k. pneumoniae strain was found to produce metalloenzyme. all eight strains of p. aeruginosa were susceptible to aminoglycosides, ciprofloxacin and carbapenemaces, both strains of s. maltophilia were susceptible to ticarcillin/clavulanate and trimethoprim/sulfamethoxazole. among a. baumannii isolates, 33.3% were susceptible only to colistin. in total, 90.2% of isolates were susceptible to imipenem and ciprofloxacin. conclusions. gram-negative bacteremia, in particular in the critically ill, is associated with significant morbidity and mortality. significant susceptibility to ciprofloxacin and imipenem was demonstrated. empiric treatment regimens should be based on unit-specific data. ben objective. to assess whether implementation of a national safety program to prevent cvc-related bacteremia had an impact on rates of devices-associated infections acquired in icu. methods. prospective, multicenter, incidence, surveillance study of vap, crb and uti carried out from 01-04-2009 to 31-06-2009. simultaneously, a bundle for prevention of cvcrelated bacteremia and a comprehensive safety program were introduced at the national level. infections were diagnosed according helics definitions. the follow-up was carried out until discharge from the icu or to a maximum of 60 days. the severity was assessed by the apache ii score. the rates are expressed as incidence density (id) per 1,000 days of risk factor. rates are compared with those of previous years (2007) (2008) . introduction. acute kidney injury (aki) is one of the most dreaded complications of severe malaria. occurs as a complication of plasmodium falciparum malaria in less than 1% of cases, but the mortality rate in these cases may be up to 45% [1] . to evaluate the incidence of aki and compare akin and rifle classification systems with regard to hospital mortality. a retrospective analysis based on medical records of adult patients with severe plasmodium falciparum malaria admitted in the general icu of clínica sagrada esperança, in luanda, angola, from january 2006 to december 2008. criteria for diagnosis included the standard who definition for severe malaria. only changes in serum creatinine were used to define the presence of aki by both criteria. logistic regression was used to access the association of each rifle and akin with hospital mortality. data are presented as odds ratios with 95% confidence intervals (ci). we enrolled 51 patients. thirty-nine (76.5%) were males. the mean age recorded was 42.9 ± 13.3. the mean apache ii score was 14.0 ± 7.0, with a mean predicted dead rate of 22.2%. the mean sofa score on admission was 7.2 ± 3.4. the mean length of stay in the icu was 5.7 ± 3.5 days. rifle allowed the identification of more patents than akin as having aki (68.9 vs. 58.8% there was no statistic association between corticosteroids therapy and length of icu stay less than 6 days (p = 0.945), duration of mechanical ventilation less than 5 days (p = 0.945), severe infection (p = 0.057), re-intubation (p = 0.448), tracheotomy (p = 0.896), nosocomial infections (p = 0.697), myopathy (p = 0.448) or mortality (p = 0.448). although there is a tendency for a higher prescription of corticosteroids in dni patients with severe infection, the difference did not reach statistical significance. the use of steroids is neither associated with a better outcome nor with a higher frequency of adverse events or side effects, namely critically illness myopathy or nosocomial infections. ozbek introduction. q fever, a zoonosis due to coxiella burnetii, is more frequent and severe in men than women, despite a similar exposure. here we explore whether the severity of c. burnetii infection in mice is related to sex differences in gene expression profiles. methods. experimental study analyzing the transcriptome of 40 c57bl/6 j mice. ten females and 10 males were sterilized at 7 weeks of age. after 3 weeks, 10 males and 10 females (5 intact and 5 castrated animals of each gender) were killed. the other series of mice were injected intraperitoneally with 10 5 c. burnetii organisms and sacrificed at day one after infection. organs were aseptically excised and stabilized in rnalater. total liver rna was retrotranscribed and labelled with cy3. labelled cdna were hybridized onto whole mouse genome oligo microarray 4 9 44 k (agilent). raw signal data were normalized with the quantile method. the significance analysis of microarrays test was used to study the gene expression in uninfected and infected mice. supervised analyses were carried out with r with the library bioconductor. pca was used to visually explore global effects for genome wide trends, unexpected effects and outliers in the expression data (library made4). in another set of experiments, 64 mice (4 intact males, 4 castrated males, 4 intact females and 4 castrated females) were killed at 0, 1, 4 and 7 days after c. burnetii infection (same protocol). liver rna was analyzed by rt-pcr to confirm microarray results. results. multiclass analysis (sex and infection) identified 2,777 modulated genes (fdr = 5%, |fold change| [ 1.75) . we found that 86% of the genes are specifically modulated in males or females. only 14% of the genes are sexindependent. castration showed that sexual hormones are responsible for more than 60% of this sex-specific differential expression. the reduction of gene expression modulation upon castration is seen almost exclusively in males. functional annotation of male specific signature identified 4 groups of keywords linked to cellular adhesion, signal transduction, defensins and cytokines and jak/stat pathway. functional annotation of female specific signature identified two group of keywords linked to intracellular metabolism and circadian rhythm. these results were confirmed by rt-pcr. the increased susceptibility to infection in males may be related to the overexpression of il10 and stat3. the modulation of the circadian rhythm in female is linked to a more efficient bacterial clearance. conclusions. this study showed for the first time that the sexual dimorphism observed in q fever is reflected by sex related gene modulation, and is under the control of sexual hormones. this study also showed that the circadian rhythm seems to play an important role in infection in mice. this work open the way for deciphering the role of sex and circadian rhythm in human infections. the author's report a p.aeruginosa sepsis with skin and heart involvement in a previous healthy woman. a 30 years old woman without a pertinent medical history came to the hospital after 3 days with high fever ([38.5°c), vomiting and diarrhea. at admission she was in septic shock with multiple organ disfunction (hemodynamic, cardio respiratory and renal) and presented genital skin lesions (round, ulcerated, painless lesions with necrotic black eschar and erythematous margin-ecthyma gangrenosum). the laboratory tests showed bicytopenia (leucocytes and platelets), hepatic necrolysis and elevated troponin t, associated with t wave inversion in anterior leads in the ecg. the ecocardiogram showed apical dyskinesis with normal systolic function suggesting tako-tsubo cardiomyopathy. hemocultures (3) were positive to pseudomonas aeruginosa and skin lesions biopsy showed vascular ulcers with local p. aeruginosa inflamation. results. besides the fluid challenge and supportive therapy she began empirically piperaciline-tazobactam with rapid improvement of the clinical picture. she needed vasopressors (norephynefrine and dopamine) for 48 h. the skin lesions have resolved in 7 days and cardiac treatment was conservative and symptomatic. the patient was discharged from the intensive care after 8 days. conclusions. ecthyma gangrenosum although relatively uncommon, was first considered a pathognomonic sign of p. aeruginosa sepsis, but now we known that other bacterias can have the same presentation. tako-tsubo cardiomiopathy or broken heart syndrome is a stress-induced cardiomiopathy characterized by transient systolic dysfunction that mimics myocardial infarction but without coronary disease. although the unusual p. aeruginosa clinical presentation sepsis should be treated with prompt supportive measures and the most adequate antibiotic. objective. we undertook this study to determine the relative frequency of meningitis and sepsis in a paediatric intensive care and to define the clinical and laboratory features at the time of admission and the outcome of these children. we reviewed the medical records of 19 patients with sepsis and meningitis, in our paediatric intensive care, from 2007 to 2010. results. among these patients 42% had meningitis, 37% had sepsis, 16% patients had bacteraemia, and 5% had meningitis and sepsisage ranged from 1 month to 14 years old (37% were 2-6 years old. boys 68%, girls 32%. temperature at the moment of admission was in 53% patients greater than 39°c. leucocytosis was noted in 42% (from 10,000 to 20,000/ mm 3 ) and leucopenia 10% (3,000-5,000/mm 3 ) 74% of the patients had petechiaes, 58% had a positive lumbar puncture and 42% who did not have lumbar punctures had diffuse intravascular coagulationthe species of microorganism were in 58% meningococcus group b, in 21% no organism was found, in 11% were pneumococcus, and meninococcus group d in 5%. on admission, 21% of our patients had seizures. the duration of hospitalization in our picu was 84% (average length of stay from 1 to 3 days) 37% had hemodynamic instability, and 63% had a normal arterial pressure. from the patients who had hemodynamic instability, needed only fluids 14%, and 86% needed fluids and inotropes100% of the patients received intravenous ceftriaxonewe had no mortality. conclusion. meningitis and sepsis remain a serious problem in picu. with the existing guidelines of therapy and prognostic signs at the moment of admission in picu we have a better outcome. howitz introduction. community acute bacterial meningitis is a relatively common disease. three bacteria are responsible in most cases: streptococcus pneumoniae (adults), neisseria meningitidis (older children and young adults) and listeria monocytogenes (in the elderly, alcoholics and immunosuppressed). the mortality rate ranges between 11 and 21% and is higher in case of pneumococcal meningitis (30%) due mainly to increased intracranial pressure and the intense inflammatory reaction that produces pneumococcus in the cerebrospinal fluid. objectives. to study epidemiology, aetiology, clinical and evolution in acute meningitis in the adult community in our icu. methods. retrospective and descriptive study of patients admitted to a tertiary icu with 34 beds from 1 january 2006 to 31 december 2009. a total of 26 patients of whom 14 were males (53.84%) and 12 women (46.15%). the mean age was 45.65 years (range: 17-75). the apache ii at admission was determined in 19 of the 26 patients with an average of 10 points, which is associated initially with a good prognosis. the glasgow coma scale was found in 100% of the cases the majority ranging between 12 and 15 with a range: 4-15. the average stay in icu was 5.69 days. 3 patients died (11.5%). risk factors include: infections in otolaryngology: 3 cases (11.5%) alcohol: 1 case (3.8%) and states of immunosuppression: 8 (30.76%) of which: there were two diabetic patients (7.69%); hiv: 2 (7.69%) were chronic treatment with corticosteroids in one case (3.8%); advp: 1 case (3.8%) liver transplantation: one case (3.8%) and other case cerebrospinal fluid leak (3.8%). in 14 patients (% 53.84) found no risk factor. the most common complication was the need for endotracheal intubation and mechanical ventilation in a 34.61% of patients, hydrocephalus followed by 3.8%. hearing sequelae were found in 3 patients (11.5%) and persistent vegetative state in 1 case (3.8%). the outcome was favorable and without sequelae in 18 cases (69.23%). the etiology was bacterial germs and virus in 20 cases in 6. bacteria, not unknown in 6 cases (23%). filiated of the causative agent in the majority (34.61%) were streptococcus pneumoniae, followed by neisseria meningitidis in 2 cases (7.69%), listeria, staphylococcus aureus, e. coli and mycobacterium tuberculosis were isolated in one case each (3.8%) . in relation to the vhs virus was found in one case (3.8%) and unable to filial the rest. conclusions. community acute meningitis is a disease with low prevalence and mortality in our environment. the agent most commonly streptococcus pneumoniae, clearly associated with increased morbidity. the most frequent complication was the need for endotracheal intubation and secondly hydrocephalus. mortality was associated with longer hospital stays and lower glasgow at the beginning, but not with age. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 s131 evaluated factors: patient characteristics, signs, symptoms, abscess location, time between symptoms and hospital admission and surgery, lab results, microbiology, antibiotic therapy, apache2, saps2, sofa, length of icu stay, surgical re-intervention, duration of mechanical ventilation, infectious complications, critical illness myopathy (cim), renal replacement therapy (rrt), re-intubation, tracheotomy, mortality. descriptive statistics were used to analyze data. objectives. to assess ventriculitis (vg) and to study outcome and disability indices in patients admitted in icu due to cerebral hemorrhage (spontaneous or traumatic). we prospectively studied patients hospitalized due to cerebral hemorrhage in the icu of university hospital of thessaly, between 2006 and 2009. patients were followed for median follow up of 290 (120-690) days. on admission, the neurological status of patients was described by the glasgow coma scale; disability was evaluated at 6 months by the rapid disability rating scale (rdrs). results. one hundred twenty-one patients (85 male) were studied; median (iqr) age was 53(37-66) years, gcs before intubation 8 (5) (6) (7) (8) (9) (10) objectives. to analyze characteristics of patients diagnosed with infective endocarditis in a third-level hospital from january 1996 until december 2008, evaluating the echocardiography findings, the therapeutic strategy used, and both morbidity and mortality rates in hospital and during long term follow-up. observational retrospective study of 107 consecutive patients with following duke criteria with a mean follow-up of 16 ± 2 months. conclusions. this study showed a low mortality of sepsis and its sequential stages in children with meningococcal disease admitted to the picu, which was probably associated with the early use of antibiotics (up to the sixth hour) and aggressive fluid esuscitation. diagnosis and treatment of infections in critically ill patients: 0190-0200 background. about one-third of hospital mortality in critically ill patients occurs after intensive care unit (icu) discharge. post icu deaths may arise from incomplete resolution of the primary condition or from the development of new complications. some authors have recently hypothesized that unresolved or latent inflammation and sepsis may be an important factor that contributes to death following successful discharge from the icu. aim. the aim of our study was to determine the ability of the clinical and inflammatory markers at icu discharge to predict post-icu mortality. a prospective observational cohort study was conducted during a 14-month period in an 8 bed polyvalent icu. acute physiology and chronic health evaluation (apache) ii score, simplified acute physiology score (saps) ii, sequential organ failure assessment (sofa) score, c-reactive protein (crp), body temperature and white cell count (wcc) of the day of icu discharge were collected from patients who survived their first icu admission. results. during this period 156 patients were discharged alive from the icu. a total of 29 patients (18.6%) died in hospital after icu discharge. there were no differences in clinical and demographic characteristics between survivors and nonsurvivors. c-reactive protein levels at icu discharge were not associated with hospital mortality (mean crp concentration of survivors = 8. introduction. early diagnosis of bacterial infection can be challenging in critically ill patients, however prompt recognition and initiation of antibiotics improves outcome. 1 serum procalcitonin (pct) has been proposed as a more reliable marker of bacterial sepsis than white cell count (wcc) or c-reactive protein (crp), however there is no consensus in how it should be used and pct measurement has not disseminated widely into critical care practice in the uk. 2 to identify if clinical recommendations based on procalcitonin levels are being followed. we retrospectively studied pct use between october and december 2008. assay results were interpreted as: .5 ng/ml, possible local bacterial infection 0.5-2.0 ng/ml, possible bacterial systemic infection, moderate risk of severe sepsis 2.0-10 ng/ml, likely systemic bacterial infection, high risk of severe sepsis \10 ng/ml, almost exclusively severe bacterial sepsis or septic shock. 3, 4 this was compared to changes in antibiotic prescribing which were identified from our local audit database and used as a surrogate marker for clinical suspicion of sepsis. to provide context we also compared this to crp and wcc trends in a larger sample from june to december 2008. results. forty-four episodes had matched antibiotic prescribing data and pct results. a further 102 episodes provided synchronous wcc and crp data. pct assays were typically requested on day 6 (median, interquartile range 4-11). distribution of pct results pct value (ng/ml) .5 0.5-2.0 2-10 [10 number (%) 76 (55) 22 (16) 14 (10) 27 (19) there was poor concordance between pct and both wcc and crp trends and also when wcc and crp trends were compared. pct assays did not have significant correlation with antibiotic prescribing. pct conclusions. our study suggests pct results did not influence clinical practice. pct testing may be of greater benefit if used with a protocol with guidance for clinicians based on assay levels. 5 routine and serial quantitative pct testing protocols may also be useful to guide antibiotic initiation and duration, particularly in cases of greater diagnostic uncertainty, for example traumatic brain injury. 5, 6 references. introduction. procalcitonin (pct) is a reliable marker for diagnosis of infection after cardiac surgery, except in patients who previously received antibiotics, but its diagnostic role in patients with post-sternotomy pre-sternal wound infection and mediastinitis has not been studied in detail. (1) . objectives. this retrospective study focused on the role of pct in the differentiation between poststernotomy pre-sternal wound infection and mediastinitis. methods. all patients (n = 19; age: median 80, 49-87 years) who underwent surgical treatment due to poststernotomy superficial pre-sternal wound infection and mediastinitis between january and september 2009 were included in the study. procalcitonin (pct), c-reactive protein (crp) and leukocyte counts were routinely measured within the last 24 h before surgical wound revision. body temperature and hemodynamic parameters were evaluated immediately before operation. bacteriologic samples were also routinely taken intraoperatively. results. the primary cardiac operation was cabg (n = 12), cabg and valve procedure (n = 6) and others (n = 1). time between primary operation and wound revision was in median 15 days (range sensitivity, specificity, positive and negative predictive value for diagnosing sepsis are presented in table 2 . roc curves and auc are presented in figure 1 . roc curves and auc conclusions. patients with sepsis have significantly higher levels of crp, pct, il-6 and lbp on admission to the icu as compared to patients with sirs. pct is more usefull in differentiating between sepsis and sirs than crp, il-6 and lbp. b. ergan arsava 1 , s. bilekli 1 , n. alayvaz aslan 1 , e. er 1 , a. topeli 1 1 hacettepe university, ankara, turkey introduction and objective. the incidence and mortality of bacterial infections significantly increase with age. aging is associated with an impaired immune response, which causes not only an increased susceptibility for infections, but also a poor inflammatory response against them. procalcitonin (pct) is an inflammatory biomarker used as a diagnostic and prognostic tool in bacterial infections. there is no data regarding the diagnostic yield of pct in elderly patient populations. in this study we sought to identify the relationship between age and the magnitude of pct response in patients admitted to the intensive care unit (icu). methods. patients, who were admitted to icu between january 2008 and december 2009, with the diagnoses of severe sepsis, pneumonia and chronic obstructive pulmonary disease exacerbation (copde) were included into the study. patients' demographics, apache-2 scores, admission pct values, intensive care and hospital outcomes were extracted from a database of prospectively collected clinical data. results. we studied a total of 189 admissions (92 female/97 male, mean age ± standart deviation 60.6 ± 18.7 years). median (interquartile range-iqr) apache 2 score was 23 (18-31); the icu and hospital mortalities were 32.8 and 41.8%, respectively. median (iqr) admission pct levels were 7.9 (1.7-24.7) ng/ml in patients with severe sepsis (n = 91), 0.6 (0.2-3.4) ng/ml in patients with pneumonia (n = 60) and 0.2 (0.1-0.3) ng/ml in patients with copde (n = 38). there was a negative correlation between age and pct levels (spearman correlation coefficient: r = -0.21, p = 0.004); the median (iqr) pct levels were 3.8 (0.4-22.5) ng/ml in patients\60 years-old and 1.1 (0.2-6.6) ng/ ml in patients c60 years-old (p = 0.005). in subgroup analyses it was found that the inverse correlation between age and pct levels mainly arised from patients with severe sepsis (r = -0.23, objectives. we intend to define the role of pct in the initial evaluation of the patient with a suspected sepsis admitted to the icu. preliminary data from a prospective observational single centre study (polyvalent icu in a third level university hospital). the ethics committee of the centre has approved this study. we included all patients admitted to our unit with diagnosis of sepsis since june-2009. we measured pct (lgr/ml) at admission and at the second and third day of stay beside the routine screening for the source of infection. then we analyzed the relation of pct with culture results. chi-square and anova have been used for the analysis. (fig. 1 ). pct at admission showed an auc of 0.53 (0.38-0.69) for discriminating bacterial infection. we detected higher mortality in those patients with bacterial infections and sustained high levels of pct the third day ( fig. 2) (p \ 0.05). figure 1, 2 conclusions. in the initial approach to the septic patient, pct does not seem in our experience useful as an aid in decision-making but an early decrement of serum levels can be a marker for response and for a better outcome of patients with bacterial infections. ( 1-3) b-d-glucan (bg) assay in early detecting ici in critically ill pts and assess its reliability on arterial blood specimens compared to venous blood specimens. methods. all pts admitted to the 18-bed icu of our university hospital, between 15th of february and 31th of march 2010, harboring an arterial line for more than 4 days and suspected to have an ici, were prospectively enrolled. from all the pts, two blood samples drawn from the arterial line and direct femoral site were simultaneously obtained and subjected to both conventional cultures and bg assay determinations. candida colonization index (cci) and candida score (cs) were also calculated. results. during the study period, from 62 admissions, 50 pts were enrolled. 98 bg assays, 144 cutaneous and mucosal swabs and 48 urine cultures were collected. in 40 pts bg assays resulted negative from either arterial line and femoral site. all but one did not develop ici. in 10 pts bg assays resulted positive. four of these pts did not develop ici, whereas the other six developed ici (5 fungemias and 1 mediastinitis). the positive and negative predictive values (ppv, npv), sensitivity (se) and specificity (sp) of bg assay, cci, and cs are shown in table 1 . among 7 pts with ici, 3 (median sofa score value 11 ± 3.5; median saps ii value 63.7 ± 13.8) had at the diagnosis bg levels c500 pg/ml and developed septic shock; two of them died within few days. in contrast, the clinical course of pts with bg assay below 500 pg/ml was not complicated by septic shock (median sofa score 7.5 ± 5; median saps ii value 52 ± 14.7) and a rapid clearance of bg levels was observed. in addition, we observed a 100% agreement between arterial line and femoral site bg assays (positive and negative). in particular, we detected bg levels from arterial site specimens that did not significantly differ by those obtained from femoral site specimens (p = 0.5). conclusions. although conventional mycological culture remains the gold standard for ici diagnosis, we showed that bg assay seems to be a diagnostic tool that may help physicians in early detecting ici. sampling blood from the arterial line was shown to give a simple and adequate specimen to be used for bg assay. further studies are in progress in order to define the role of bg as a surrogate marker for an early diagnosis of ici. objectives. to assess which marker, if any, and at which cut-off value could add diagnostic information to enhance clinical assessment in the difficult context of long-term icu-patients. methods. long-term ([6 days) critically ill patients prospectively enrolled in the general icu of a university-hospital. all patients were daily assessed by the attending physician for the accp-sccm classification. c-reactive protein (crp, mg/dl), procalcitonin (pct, ng/ ml), and interleukin-6 (il-6, pg/ml) were measured after patient's discharge on daily stored sera. an independent overall clinical evaluation after patient's discharge, aware of the clinical course but blinded against biomarker's measurement, an ''a posteriori'' accp-sccm classification, was chosen as reference standard for all comparisons. results. we studied clinical variables and biomarkers in 592 patient-days (26 patients). the day by day accp-sccm classification of the attending physician overestimated the severity of the inflammatory response to infection. discriminative ability of each biomarker for diagnosis of sepsis is shown in table 1 . methods. 48 icu patients (31 males and 17 females) with new onset of fever and leukocytosis within the first 3 days of icu admission were prospectively included in the study. exclusion criteria: age \18 or [75 years old, heart or renal failure, hypertension, copd, pregnancy and head trauma. serial plasma samples were taken on days 1, 2 and 4 after the onset of fever for procalcitonin and bnp levels measurement. procalcitonin and bnp values were correlated with severity scores (apache ii and sofa), progression to septic shock and final outcome. statistical analysis was performed. results. patients included in the study were divided in three groups according to clinical and laboratory findings: sirs, sepsis and septic shock. procalcitonin value on days 1 and 4 and bnp value on days 1, 2 and 4 was significantly associated with sofa max value and with sofa value at the first day of fever, but not with apache ii. there was found no correlation between procalcitonin value on days 1, 2 and 4 and final outcome. bnp value on days 1 and 2 was significantly associated with final outcome (p = 0.01 and 0.017 respectively). the optimal cut-off bnp value on day 1 was estimated to be 215 pg/ml (sensitivity = 86%, specificity = 58%). the optimal cut-off bnp value on day 2 was estimated to be 212 pg/ml (sensitivity = 86%, specificity = 75%). procalcitonin value on days 1, 2 and 4 was not able to differentiate between patients with sirs and those with sepsis. also procalcitonin value on days 1, 2 and 4 was not significantly associated with progression to septic shock. bnp value on day 1 was useful in differentiating between patients with sirs and those with sepsis (p =0.026). the optimal cut-off bnp value was estimated to be 159 pg/ml (sensitivity = 74%, specificity = 78%). bnp value on days 1 and 2 was significantly associated with progression to septic shock (p = 0.001). the optimal cut-off bnp value on day 1 was estimated to be 301 pg/ml (sensitivity = 86%, specificity = 81%). the optimal cut-off bnp value on day 2 was estimated to be 213 pg/ml (sensitivity = 86%, specificity = 75%). conclusions. in icu patients with new onset of fever during the first 3 days of icu hospitalization, bnp value on days 1 and 2 seems to be a good predictor of icu mortality and progression to septic shock. also bnp value on day 1 may be useful in differentiating between patients with sirs and those with sepsis. in our study procalcitonin value on days 1, 2 and 4 was not found useful in predicting progression to septic shock nor the final outcome. due to the small number of patients included in our research, further studies are needed to confirm these findings. objectives. as c-reactive protein (crp) is regarded a marker for both inflammation and infection we decided to analyse the pct and eo status next to every crp request of critically ill patients, during 1 month. a two-side immunoassay (sandwich principle) for procalcitonin, using both anti-katacalcin and anti-calcitonin (see fig. 4a ) was used for quantitative analysis of procalcitonin with the roche modular e170. pct concentrations [0.5 lg/l were regarded as positive. crp was measured by immunoturbidimetric analysis using the roche modular p. a positive blood culture was regarded as infection, with exclusion of the coagulase negative staphylococcus aureus since this organism doesn't induce pct expression. every crp request of the icu during 1 month was accompanied by a pct, wbc, and eosinophil count. conclusions. pct at randomly measured at the icu doesn't seem to contribute to an earlier diagnosis of sepsis. pct measurement seems to be useful only when sepsis is suspected and a blood culture request has been summoned. however, its non-specificity for infection, as demonstrated by the high number of pct-positive, no blood-culture requested patients (concerning mostly post-cardiac arrest and post-heart surgery patients), makes it difficult to apply routinely. the recently displayed effort of various companies to market pct in combination with cd64 and neopterin (other potential markers of infection) supports the conclusion that not one marker by itself can substitute the golden standard of blood culture today. objectives. in this prospective observational study we sought to investigate the role of serum c-reactive protein (crp) and procalcitonin (pct) in the diagnosis and prognosis of patients admitted to the icu with suspected 2009 h1n1 infection. all patients older than 14 year-old, presenting with severe acute respiratory disease (cough, fever and respiratory distress) admitted to the icus of an university hospital in southeast brazil were included in this study. serum levels of crp and pct were measured at inclusion and at day 3, 5 and 7. were also were also significantly higher (p \ 0.001 and p = 0.001, respectively) independently from the presence or not of a co-infection. conclusions. as a conclusion, in our experience, some severe forms of influenza a/ h1n1with respiratory failure had elevated levels of pct and/or crp in the absence of proven bacterial co-infection. low values were unusual in the presence of co-infection but high values are not synonymous of co-infection and may be related to the severity of the disease. a large prospective randomized study is needed to assess the clinical interest of these biomarkers during the next pandemic of influenza. methods. descriptive study of pregnant with influenza a admitted in the obstetric section icu. the study period runs from september 2009 to january 2010. during this period 55 patients were admitted. entry criteria (%): gestosis 31%, complicated postoperative gynecology and obstetrics 27, postpartum hemorrhage 9, acute respiratory failure in influenza pneumonia: 7.2, sepsis and others respiratory failure 5 respectively, others (pregnant myocardial infarction, trauma, renal failure, arrhythmias and heart failure) 14. acute respiratory failure due to influenza pneumonia was assessed using severity criteria the ats/idsa (major criteria (1) were admitted in icu 13 cases of severe influenza pneumonia, nasopharyngeal specimens confirmed with rt-pcr positive for influenza a (h1n1): 4 pregnant in icu og, and 6 women and 3 men general icu. the average age of pregnant was 34 ± 5 years, average stay 18 days. 75% were in the 3rd trimester and one in the 2nd trimester (week 24). two-third pregnancy and two primiparous. the apache ii on admission ranged between 13 and 22. only one patient with pre-existing disease (diabetes type 2). admission due: acute respiratory failure complicating pneumonia multilobar in 100%, with more than 6 days of typical symptoms (fever [38°c, malaise, myalgia, headache and respiratory symptoms), no starting oseltamivir within 48 h symptoms. caesarean was performed at 100%; 75% in the first 24 h of admission and one after 15 days (week 26) intrauci, posterior cerebral hemorrhage fetal death. all newborns free of viral disease. invasive mechanical ventilation (mv) in the first 24 h in 3 patients and 1 did not require. required aggressive parameters 100%: bipap, alveolar recruitment and prone. a percutaneous tracheostomy for weaning. the average duration of mechanical ventilation: 19 ± 9 days complications: barotrauma (pneumothorax and a pneumomediastinum 1). 75% required vasoactive drugs. one patient with acute renal failure that required extracorporeal clearance techniques (hdfvvc), recovering renal function, deep vein thrombosis complicated with shaldon catheter. one brain death by massive subarachnoid hemorrhage. nosocomial infections in 2 patients, most common germ staphylococcus epidermidis catheter and candida sp in urine. initial empiric coverage with ceftriaxone and clarithromycin, as well as oseltamivir. conclusions. during pregnancy, especially in the second and third quarters, there is an increased risk of complications associated with infection by influenza a virus h1n1, highlighting pneumonia, with more rapid progression to severe respiratory complications. objectives. the aim of this study was to describe baseline characteristics, management and outcomes of critically ill patients with influenza a (h1n1) infection who were treated at icu. we performed a retrospective observational study which included 20 critically ill patients with influenza a (h1n1) infection admitted to icu between 23rd november 2009 and 15th march 2010. the primary outcome measure was mortality. secondary outcomes included the rate of 2009 influenza a (h1n1)-related critical illness and introduction of mechanical ventilation as well as intensive care unit (icu) length of stay and hospital length of stay. in the early 20th century, burns patients were dying of multi-organ failure due to dehydration and hypovolaemia [1, 2] . the parklands formula was devised to guide fluid resuscitation and prevent multi-organ failure from occurring. however, over enthusiastic fluid resuscitation will lead to other complications [2] . objectives. we aimed to assess the adequacy and complications of fluid resuscitation in the 1st 24 h of a burns patient admitted to our icu, a tertiary centre for burns intensive care. • a retrospective medical case notes audit on all patients admitted to our icu in 2008 with [15% tbsa (total burns surface area). • 1st 24 h of burns resuscitation initiated by the referring hospital and our icu compared to the parkland's formula. • statistical analysis by spss 17. results. 13 patients audited. • mean duration of transfer from burn injury to our unit = 6.5 h • mean age = 41 years, burn area 44%, length of stay 3.9 days • 28 day mortality = 54% • 61% had an inhalational injury • no statistical difference between the emergency department (ed) estimation of tbsa and whiston icu. • mean iv fluids given 6.5l but the actual predicted requirement is 4.7 l, therefore an excess of 1.8 l (p \ 0.01) • average urine output during this period was 0.99 ml/kg/h suggesting that this amount was adequate. iv fluids in the 1st 24 h conclusions. excessive amount of iv fluids in the 1st 24 h is associated with prolonged ventilation and length of stay but is not associated with increased 28 day mortality. the mean amount of fluid required in the 1st 24 h is approximately 6 ml/kg/h which is consistent with other studies [3] . urine output is still an accurate marker of resuscitation. there was no statistical difference between the determination of tbsa by the ed and burns surgeons, contrary to other studies [3] . introduction. icu-acquired hypernatremia appears to be associated with mortality in the icu 1 . to reduce iatrogenic rise of serum sodium the use of balanced colloids has been advocated. objectives. aim of this study was to establish the incidence of clinically relevant hypernatremia on our icu and to evaluate the change in incidence of hypernatremia due to the introduction of a natriumacetate based colloid solution. we performed a single centre retrospective study in a 22-bed mixed icu with all available medical specialities except neurosurgery. sodium measurements of all patients were analyzed during a 3-month period prior to and after a switch from sodium-based (s) to natriumacetate -based (na) colloids. s contains a 6% 130 kda polystarch with a 154 mmol/l na and 154 mmol/l cl concentrations (voluven ò ). na contains a 6% 130 kda hydroxyeethylstarch with a 137 mmol/l na and 110 mmol/l cl concentrations (volulyt ò ). serum sodium measurements were routinely performed 6-hourly. by protocol colloids were provided to a maximum of 2 l/day, independent of bodyweight. patients with hypernatremia at icu admission were excluded. data are expressed as mean ± sd. comparison of na concentrations between groups was performed with a t test for independent samples and comparison of incidence of hypernatremia with a pearson chi-square test. results. patient characteristics and number of samples are summarized in table 1 . after the introduction of na mean serum sodium concentration in the total icu population decreased significantly from 138.8 ± 4.4 to 137.8 ± 4.5, p = 0.000. the incidence of serum na[145 mmol/ l decreased from 8.0 to 6.6%, p = 0.000. the percentage of patients with at least one na measurement[145 mmol/l did not change significantly: 5.6% (s) versus 4.4% (na), p = 0.31. introduction of a natriumacetate based colloid solution in stead of a sodium-based colloid solution reduces the overall incidence of clinically relevant hypernatremia; however, the number of patients with such hypernatremia did not change significantly. patients admitted to intensive care frequently have a metabolic acidosis with previous studies demonstrating an association between the degree of acidosis and outcome. hyperchloraemia is a significant cause of metabolic acidosis and there is increasing interest in the adverse consequences associated with it, which include hypotension, renal dysfunction, impaired gut perfusion and increases in inflammatory cytokines. previous studies, however, have failed to show that hyperchloraemic metabolic acidosis (hcla) has a significant effect on survival. to assess whether patients with hcla had a worse prognosis than our general intensive care unit (icu) population, and the factors associated with the development of hcla. consecutive admissions to the intensive care unit over a 13 month period were studied. patients with a base deficit[5 mmol/l and a serum chloride[110 mmol/l on the same arterial blood sample during their icu admission were classified as having an episode of hcla. apache ii scores on admission, length of stay on the unit, mortality rates and reason for admission were collected. hospital survival was investigated by logistic regression analysis, controlling for illness severity (apache ii) and admission category, and displayed as a kaplan-meier curve. of 743 patients entering the unit during the retrospective study period, 116 had an episode of hcla, with an odds ratio of death of 3.71 (95% ci 2.39, 5.75) compared with those without hcla. after controlling for apache ii score on admission, and admission category the odds ratio reduced to 2.31 but was still statistically significant (p = 0.001, 95% ci 1.37, 3.89). the development of hcla was significantly more associated with medical than surgical admissions with an odds ratio of 3.63 (95% ci 2.19, 6.02). within the surgical admissions, the occurrence of hcla differed significantly with the urgency of surgery, with an odds ratio of 2.59 (95% ci 1.34, 5.00) for emergency surgery versus elective surgery. those with hcla had a longer median duration of stay and were overrepresented in the group of patients whose length of stay was c7 days. kaplan-meier graph showing survival to 14 days conclusions. the results demonstrate that hcla occurs frequently in a general icu population and is associated with a significantly worse outcome. this is in contrast to previous studies which have demonstrated acidosis secondary to lactate and an elevated strong ion gap are associated with poorer outcomes, but not hyperchloraemia. a. dumoulin 1 , a. janssen 1 , j.j. de waele 1 , j. decruyenaere 1 , e.a. hoste 1 1 universitair ziekenhuis gent, gent, belgium increased creatinine clearance or hyperfiltration has been reported in icu patients. enhanced renal clearance of antibiotics in patients with hyperfiltration may result in suboptimal antibiotic serum concentrations, and so affect patient outcomes. there are only limited data on the incidence of hyperfiltration in icu patients. objectives. assess the epidemiology of hyperfiltration in a cohort of icu patients. single center retrospective cohort study, including adult patients hospitalized during the period 12/2008-2/2010 in the 50 bed icu of the ghent university hospital, a tertiary care center. data were retrieved by a specially designed electronic alert from the electronic icu database. urinary creatinine clearance (ccr) was calculated as (24 h urine volume) 9 (urinary creatinine)/([creatinine day -1 + day 0]/2)/time. we retrieved the initial ccr, and the minimum and the maximum ccr. hyperfiltration was defined as a ccr c 120 ml/min. patient days with anuria were excluded from the analysis. data are reported as median (interquatile range). patients with neurological disease. several factors may interfere with water and sodium homeostasis in these patients, including factors that are also present in other icu patients. in addition, these patients may develop a syndrome of antidiuresis (siad), or salt wasting syndrome (sw). the latter by secretion of brain natriuretic peptide (cerebral salt wasting syndrome (csw)), release of atrial natriuretic peptide in volume overload, or renal salt wasting. objectives. assess the epidemiology of hypona in icu patients with neurological disease. methods. retrospective single center study. data were retrieved from electronic icu databases. inclusion criteria were age c15 years, hypona (\135 mmol/l), and neurological disease. only the first episode of hypona was considered. siad and sw was assessed with tonicity balance on data of the preceding 24 h in patients with urinary sodium[20 mmol/l, in whom other etiologies were excluded. sw was defined as negative salt balance and negative fluid balance, and siad as positive fluid balance. to evaluate the prevalence of anaemia among patients attended at the emergency room (er) and to estimate the need of an early diagnose and efficient treatment. observational transversal trial in which 3 days in june were randomly chosen. all patient attending to the er is included. paediatric, gynaecologic and traumatic cases fall out of this research. anaemia was diagnosed according to who criteria. comparison means statistics methods for quantitative variables and chi square for categorical variables were used. prevalence data for the entire cohort, for men and women separately and for different age bands, medical history, anaemia related medication and red blood cells data were extracted. results. 861 patients were interned through the er channel. 44% men, mean age 51.4 ± 22.2 years old (median 49), and 44,6% were subject of blood analysis using classification proceedings. from the 384 analysed 17.7% were anaemic. 8.5% of them were under 65 years old, 23% aged from 65 to 74 and 30.6% elderly patients (over 74 years old). most frequent co-morbidity was chronic obstructive pulmonary disease (copd) (n = 46, 5.3%) and most related drug aspirin (n = 71, 8.2%). 5% of the sample had a bleed but only 0.7% needed red blood cell transfusion. we found statistic difference in mean age, antiplatelets therapy use, bleeding episode, need for transfusion, creatinin value and hospitalisation. anaemia classification according to vcm: microcytic 41.7%, normocytic 48%, macrocytic 10.3%. conclusion. unknown anaemia detection in the er and its following treatment could be a strategy to further reduce allogeneic blood transfusion. the presence of disorders of sodium balance on icu admission could be independently associated with mortality. we decided to study if the existence of dysnatremias at the time of icu admission could be related to mortality in critically ill patients. we conducted a retrospective study in a mixed icu with a database of 3,569 adults admitted consecutively over a period of 7 years (2001-2007) . most patients (72.4%) had normal sodium levels (135 b na b 145 mmol/l) on icu admission. the frequencies of borderline (130 b na b 135 mmol/l), mild (125 b na \ 130 mmol/l), and severe hyponatremia (na \ 125 mmol/l) were 14.3, 3.7%, and 1.8%, respectively. the frequencies of borderline (145 \ na b 150 mmol/l), mild (150 \ na b 155 mmol/l), and severe hypernatremia (na [ 155 mmol/l) were 5.7, 1.3, and 0.8%, respectively. all types and grades of dysnatremia were associated with increased raw and risk-adjusted hospital mortality ratios. multiple logistic regression analysis showed an independent mortality risk rising with increasing severity of both hyponatremia and hypernatremia. odds ratios and 95% confidence interval (ci) for borderline, mild, and severe hyponatremia were 1.34, 1.78 and 1.79, respectively. odds ratios and 95% ci for borderline, mild, and severe hypernatremia were 1.45, 2.23, and 3.45 respectively. conclusions. this observation suggests the possible correlation of natremia on icu admission with hospital mortality and confirms that both hypo-and hypernatremia present on admission to the icu could be independent risk factors for poor prognosis in icu populations. (1) . a relationship between mortality and delay from time of pars trigger to critical care admission for patients not requiring surgery has recently been described (2) . objectives. this study was to test the hypothesis that in cases of emergency laparotomy, prolonged physiological deterioration pre-operatively is associated with higher hospital mortality. we reviewed notes of patients that underwent emergency laparotomy between july 2007 and february 2009 at the northern general hospital, sheffield, uk. time at which patients triggered (pars c 3), time of arrival in theatre and hospital mortality were recorded. two-tailed fisher's exact test was used to test null hypotheses that a delay of more than 10 h after pars trigger does not affect hospital mortality. . 502 patients had an emergency laparotomy during this period. of 108 notes retrieved by our patient record service, 3 were incomplete. of 105 remaining patients 73 patients did not trigger, 6 of whom died (8.2% mortality). 32 patients triggered, 9 died (28.1%). amongst 32 patients that triggered, 17 arrived in theatre within 10 h, 4 of whom died (23.5% mortality); 5 of the 15 patients that arrived in theatre after 10 h died (33.3% mortality). the odds ratio of death for those with a prolonged pre-operative deterioration (n = 15) compared to those without (n = 90) was 4.0 (95% ci 1.14-14.1, p = 0.038). the number needed to treat early to save one life was 5. conclusions. our data suggest that in cases of emergency laparotomy, those who trigger pars pre-operatively have higher hospital mortality than those who do not. specifically, our data indicate that patients triggering pars c 3 should arrive in theatre within 10 h of first triggering. nothing is known about the effect of the duration of icu-related therapies on acute outcome. to identify the importance of the duration of invasive ventilation and of renal replacement therapy for acute prognosis of surgical patients treated in an intensive care unit (icu). we performed a retrospective analysis of prospectively collected data of an icu patient cohort linked to a local database. adult patients (n = 1,462) admitted to a 12-bed icu at a university hospital in munich, germany, between 1993 and 2005 who had an icu length of stay of more than 4 days and who were followed-up until the end of the acute phase after icu admission. cox-type additive hazard regression models were used to analyse linear, nonlinear or time-varying associations of therapeutic variables with survival time. duration of different invasive therapies was evaluated by constructing specific vectors, which tested potential effects of time-dependant variables on outcome after a lag time of 7 days. . 808 patients (56.6%) were still alive at the end of the acute phase after icu admission. during the acute phase, 85.3% of the patients required invasive ventilation, and 16.1% a continuous renal replacement therapy. besides the underlying disease and disease severity at icu admission, the need for invasive ventilation or renal replacement therapy was associated with poorer outcome. duration of invasive ventilation shortened survival (with a lag of 1 week), if treatment lasted for more than 11 days (non-linear association). in contrast, duration of renal replacement therapy was unimportant for acute prognosis. conclusion. prolonged duration of invasive ventilation, but not of renal replacement therapy is inversely related to acute survival. objectives. to identify the prognostic importance of preceding invasive ventilation, renal replacement therapy and catecholamine therapy for long-term survivors after surgical critical illness. we performed a retrospective analysis of prospectively collected data of an icu patient cohort linked to a local database. adult patients (n = 1,462) admitted to a 12-bed icu between 1993 and 2005, who had an icu length of stay of more than 4 days, were followedup until the end of the second year after icu admission. hazard function was explored by weibull modelling and likelihood ratio tests. cox-type structured hazard regression models were used to analyse linear, non-linear or time-varying associations of therapeutic variables with 2-year survival time of a patient subgroup, which had survived the period of high hazard. hazard rate declined exponentially up to day 195 after icu admission, and became constant thereafter. 808 patients reached this stable stage of their disease forming the study population. 648 of these patients (80.2%) were still alive at the end of the second year after icu admission. underlying diseases were major determinants for long-term outcome. long-term mortality was significantly associated with the acute extent of physiological derangement during icu stay (maximum apache ii score), but was independent from the duration of preceding invasive organ support. in surgical patients with a prolonged icu length of stay, an exorbitant mortality exists for about half a year after icu admission. later on, life expectancy of surviving patients is largely determined by the underlying disease and, to a minor degree, by the acute extent of homeostatic disturbance during icu stay. the duration of preceding invasive therapies does not limit long-term survival. b. rozec 1 , a. desdoits 2 , k. asehnoune 2 , c. lejus 2 , y. blanloeil 1 1 chu nantes, hôpital laënnec, anesthesia and intensive care, nantes, france, 2 chu nantes, hotel-dieu, anesthesia and intensive care, nantes, france postoperative stroke could be an endpoint in non-cardiac surgery morbidity studies [1] . therefore, its frequency established in old studies and considered higher than in the non surgical population remains to be estimated more precisely. objectives. the aim of this evaluation was to calculate the frequency of stroke, firstly in a prospective study, and secondly in a review of the literature. strokes diagnosed in the prospective follow-up (30 days) of surgery for hip fracture was confirmed by a neurologist and a ct-scan. retro and prospective studies (except abstract) published in journals (pubmed, ovid) from 1961 to 2009 were included in the analysis. statistics:% ic95, multivariate analysis (effects of population size, date of publication, type of surgery, patient age, prospective vs. retrospective studies were evaluated). results. mean pre-operative possum scores between the two groups showed no significant differences. continuous measurements taken by the odm showed a mean stroke volume increase of 20 mls at the end of surgery (paired t test, p-value = .001). 91 (40.6%) patients following implementation compared to 121 (52.2%) prior to implementation required post-operative critical care admission. following odm implementation, critical care los was reduced from 3.7 to 2.1 days and post-operative length of stay within hospital was also significantly reduced by 6.5 days. introduction. local (skeletal muscle necrosis) and remote (lung neutrophil infiltration) ischemia-reperfusion injury (ir) have been described in animals [1] and humans after aortic surgery. postconditioning with cyclosporina (csa) was recently shown to prevent skeletal muscle infarction in pig latissimus dorsi muscle flaps [2] . objectives. the aim of this study was to investigate local (gastrocnemius muscle, gc) and remote (lung and liver) ir in rats exposed to aortic cross-clamping with special focus on mitochondrial respiratory chain complexes activities and reactive oxygen species (ros) production. we also investigated whether pharmacological post-conditioning with csa would be protective in this setting. methods. anaesthetized (isoflurane) and mechanically ventilated wistar rats underwent laparotomy and were randomly assigned to one of the 3 following groups: sham (n = 8), ir (n = 10, clamping of the infrarenal aorta for 3 h followed by 2 h of reperfusion), ir+csa (n = 7, 10 mg/kg csa administered intraperitoneally 90 and 30 min prior to reperfusion). maximal oxidative capacities (vmax) and complexes i, ii and iv of the mitochondrial respiratory chain were determined using glutamate-malate (vmax) and succinate (vsucc) as substrates in the gc permeabilized fibers and freshly harvested liver and lungs isolated mitochondria. tissue superoxide anion production was assessed with dihydroethidium (dhe) in thin sections of frozen gc. data are expressed as mean±sem and analyzed with anova followed by newman-keuls post-hoc test; a p value.05 was considered significant. esophagectomy with gastric tube reconstruction is associated with frequent postoperative complications due to a (surgery induced) systemic stress response, provoked by the overproduction of proinflammatory cytokines. in elective postoperative esophagectomy patients, we previously showed that levels of serum crp are associated with the occurrence of postoperative complications and reduced survival. plasma ngal (pngal) and urine ngal (ungal) are early predictors of acute kidney injury, however sepsis/sirs seems to accelerate their production even in the absence of aki. objectives. we examined the role of pngal and ungal as early indicators of postoperative complications at the icu in patients undergoing elective esophagectomy surgery methods. in a prospective follow-up cohort study, data of a total of 49 patients admitted to the icu following elective esophagectomy with gastric tube reconstruction were collected in the period from september 2007 to april 2008. patients who developed aki at the icu were not included in this study. postoperative pngal and ungal levels were determined at consecutive time points and the relation between the course of postoperative serum pngal and ungal, development of complications and outcome of the patients was investigated. in our experience, assisted by dv robot radical prostatectomy, despite requiring longer surgery time, was shown to be safer than conventional radical prostatectomy, with a significant less blood loss during surgery, less need for blood transfusion, fewer postoperative complications, included need to reoperate, and also a shorter length of hospital stay than conventional radical prostatectomy. objectives. the aim of the study was to evaluate safety and effectiveness of m infusion, impact on fluid balance and urine output (uo) and also whether we can avoid cvc line insertion. we conducted a prospective analysis of patients (pts) treated with m who were admitted to the shdu between oct 2008 and aug 2009. demographic data and vital parameters were collected through the individual questionnaires before (0) introduction. an ever increasing number of patients over the age of 80 year are being admitted to critical care units [1] . with no marked expansion in the number of critical care beds in our hospital and in the health region as a whole, this may lead to a huge strain on the service provision, with less availability of beds to treat elective and other emergency admissions. to determine the factors that affect outcome following admission to critical care of patients aged 80 years and above(medical and surgical). methods. ethical approval was sought but deemed unnecessary as our study was observational (non-interventional). we prospectively looked at the number of patients (age 80 year and above) who were admitted to icu/warrington general hospital over the period of 1 year. our unit is a modern, 18-bedded general icu with an annual admission rate of approximately 800 (340 level 3 and 460 level 2 care). we examined data that was related to the source of admission, gender, apache 2 scores, the use of vasopressors (including inotropes) and the need for ippv in the first 48 h of admission. we analysed the effect that each factor had on patient mortality (applying chi-square and z tests). we followed the patients up for 6 months post-discharge from icu. the final report produced results that showed icu, hospital and 6-month mortality. results. there were 53 admissions during the period 1st may 2008-30th april 2009. last set of mortality data was obtained in september 2009. female: male ratio was 30:23. the overall 6-month mortality was 64%. in our study, patients admitted through a&e, theatre and ward had mortality rates of 83, 73 and 65% respectively. patients who received vasopressors (including inotropes) in the first 48 h had a significantly lower mortality than patients who did not receive any vasopressor support (27 vs. 31%). invasive ventilation in the first 48 h of admission was associated with significantly higher mortality rates (31 vs. 25%). in this patient cohort, the overall 6-month mortality is higher than the general icu population. factors that determine mortality include the source of admission to icu, the need for vasopressor support and invasive ventilation in the first 48 h of admission. introduction. the optimization of oxygen delivery (do 2 ) is an intervention with fluids and inotropics to achieve supranormal goals of do 2 during surgery, before disturbances of perfusion occur and oxygen debt accumulates. oxygen debt is directly linked to multiple organ failure and death. we aimed to evaluate the temporal pattern of oxygen debt in the intraoperative period in patients included in two studies of goal directed therapy to supranormal values of do 2 . oxygen debt was calculated from data obtained from 87 high risk surgical patients included in two randomized controlled trials were analysed. 1, 2 the oxygen deficit was calculated by subtraction of the basal vo 2 value from subsequential values of vo 2 obtained during surgery and after the icu admission. the oxygen debt was calculated by the product of oxygen deficit and time (minutes) between measurements. patients treated with supranormal goals of do 2 ([600 ml/min/m 2 ) using fluids and dobutamine showed lower levels of oxygen debt during icu stay. the peak of oxygen debt was 4,440 ml/m 2 at 390 min of surgery in the control group in comparison to 2,040 ml/ m 2 in the protocol group. 1 in the second study, the peak of oxygen debt occurred at 240 min in the volume group (14,670 ml/m 2 ) which was significantly higher than in the dobutamine group (2,720 ml/m 2 ). 2 higher oxygen debt during peroperative period correlated with poor outcome as shown on the original studies. conclusion. the use of supranormal goals of do 2 with dobutamine and fluids in the peroperative period results in lower oxygen debt. post-operative nausea and vomiting (ponv) is a common problem in the patients undergoing laparoscopic surgery. the release of serotonin during surgical procedure may induce ponv. we investigated if postoperative increase in plasma serotonin metabolite was associated with ponv after gynecologic laparoscopic surgery. objectives. the patients who experienced nausea after gynecologic laparoscopic surgery (ponv group, n = 20) and patients who had no or mild nausea (control group, n = 20) were enrolled into this study. postoperative nausea was assessed during 1 h in post-anesthetic care unit and ondansetron was administered if needed. blood samples were obtained before anesthesia and 1 h after surgery. plasma serotonin metabolite (5-hydroxy indole acetic acid, 5-hiaa) was analyzed using high performance liquid chromatography (hplc) assay. perioperative change of plasma 5-hiaa and the degree of nausea were compared between groups. results. the degree of post-operative nausea varied from 0 to 100 (100 mm visual analogue scale, vas) and median value was 0 (0-20) in control group and 60 (40-100) in ponv group (p \ 0.001). average 5-hiaa concentration of all patients increased after surgery (3.65 ± 0.90 to 4.36 ± 1.17 ng/ml, p \ 0.001). baseline plasma 5-hiaa concentrations were similar between groups, however, 5-hiaa of ponv group increased higher after laparoscopic surgery compared with control group (3.69 ± 0.89 to 4.62 ± 1.12 ng/ml vs. 3.61 ± 0.93 to 4.10 ± 1.20 ng/ml, p = 0.03). conclusions. the patients who experienced post-operative nausea showed more increase in 5-hiaa concentration. ponv after gynecologic laparoscopic surgery may be associated with a peripheral release of serotonin. introduction. the intracavitary ecg method is an easy, accurate and inexpensive methodology for real time positioning of the tip of central venous catheters. in particular, when the ecg method is performed using not the guidewire but the saline-filled catheter as electrode, the methodology is completely safe and can be applied to any central venous access device (vad). we have tested a new specific device (sapiens tls, romedex) which simplifies and standardizes the ecg method; it consists of a hardware (a small box with cables connecting it to a pc and to ecg electrodes) plus a software (which can be used on any pc). we tested the sapiens tls in 334 patients who underwent positioning of central vads (182 totally implantable ports, 114 piccs and 36 tunnelled catheters, all inserted by ultrasound guided venipuncture). our goal was to position the tip of the catheter at the cavoatrial junction: the length of the catheter was estimated by anthropometric measurements and the correct positioning was achieved by the intracavitary ecg method during the procedure. the final position was checked by a post-procedural chest x-ray. there was no insertion-related complication. the intracavitary ecg method was easily performed in all cases. at the final x-ray control, 97% of all tips were correctly positioned at the cavo-atrial junction (±1 cm), confirming the accuracy of the intracavitary ecg method. the anthropometric measurement tended to overestimate the length of the catheter both in port insertions ([1 cm in 30% of cases) and in picc insertions ([1 cm in 35% and [2 cm in 15% of cases). conclusions. the intracavitary ecg method as performed with the sapiens tls was more accurate than the anthropometric measurement in terms of correct positioning the tip of the catheter during the procedure. the sapiens tls simplified the method, by standardizing the ecg tracking, and making it easy (no need of ecg monitor, no need of ecg commuter since the sapiens tls displays simultaneously the surface ecg and the intracavitary ecg). also, the sapiens tls allows the print-out of the intracavitary ecg reading for documentation, as well as the storing of the ecg reading in a computer-based database. previous studies have shown that hypernatremia impact graft function after orthotopic liver transplant (olt). the purpose of this retrospective investigation was to determine whether differences in serum sodium values after olt influenced postoperative short-term patient outcomes. objectives. the study was aimed at exploring the incidence of hypernatremia after orthotopic liver transplantation (olt) in order to provide critical monitoring and intensive care services. clinical and sicu laboratory data were collected; serum sodium was assessed an average of three times per day. hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. from 2004 to 2005, we analyzed 111 patients with hypernatremia after olt. the major outcome was death in the icu after 14 days. conclusions. in sicu, olt patients are easy to suffer from hypernatremia (42.3%) and have high mortality (34.0%). hypernatremia is associated with an increased risk of death in patients with olt. early active fluid infusion is crucial, besides optional continue venovenous hemofiltration (cvvh). cywinski objectives. the aim of this study was to determine the value of blood lactate sequential dosages during the first 24 postoperative hours for the diagnosis of gd. we conducted a retrospective study on consecutive patients admitted in icu after lt, between july 2006 and june 2008. lt with auxiliary or splited grafts were excluded so were patients with septic or cardiogenic shock occurring during the first 48 h after lt. criteria for gd diagnosis were: sgot [ 2,000 u/l with pt \ 50% between d2 and d7, or re transplantation or death between d1 and d7. demographics and biological data (transaminases, pt, serum bilirubin) were recorded between d0 and d7. hopital bicêtre, kremlin-bicêtre, france, 3 hôpital saint-louis, paris diderot university, biostatistics, paris, france, 4 hôpital hôtel-dieu, medical intensive care unit, nantes, france, 5 hôpital gabriel montpied, nephrology and transplantation, clermont-ferrand, france, 6 hôpital edouard herriot, medical intensive care unit, lyon, france, 7 conclusions. in kidney transplant recipients, arf is associated with high mortality and graft loss rates. increased pneumocystis and bacterial prophylaxis might improve these outcomes. early icu admission might prevent graft loss. a. umgelter 1 , k. lange 2 , p. büchler 2 , h. friess 2 , r.m. schmid 1 1 technical university of munich, transplantationszentrum münchen rechts der isar, ii. medizinische klinik, münchen, germany, 2 technical university of munich, transplantationszentrum münchen rechts der isar, chirurgische klinik, münchen, germany introduction. the shortage of donor organs in the eurotransplant region results in late allocation at a time when liver disease is already very advanced. the severe condition of patients at that stage negatively affects outcomes of orthotopic liver transplantation (olt). to support decision-making in these situations, clinical data are urgently needed. objectives. to evaluate outcomes of liver transplantation (olt) in icu-patients with multi-organ failure due to advanced acute on chronic liver failure (aclf). methods. in our centre, patients on the waiting list for olt are not automatically excluded from the procedure, if their condition deteriorates to multi-organ failure. a consensus of the team in each individual case is based on criteria such as the previously manifested will of the patient, exclusion of current infection, absence of neurologic damage or other organ damage expected to impair the possibility of rehabilitation. we retrospectively analyzed a database comprising data from evaluation for the waiting list of all patients transplanted in our center since implementation of the meld-score for allocation. only cirrhotic patients treated on our intensive care unit before transplantation were included. patients treated on the icu before retransplant for primary graft failure were excluded from analysis. data are presented as median (25 th -75th percentile). wilcoxon or mann-whitney u tests were used for comparisons of paired and unpaired data, respectively. results. from january 2007 until september 2009 15 patients (7 m, 7f; age 58 (52-65) years) fulfilled inclusion criteria. cirrhosis was due to alcohol (n = 7), hcv (n = 3), alcohol+hcv (n = 2), alpha-1-antitrypsin deficiency (n = 1), budd-chiari-syndrome (n = 1) or cryptogenic (n = 1). upon icu admission icu, apache ii scores were 26 (22-31), sofa scores 11 (8-14); meld 25 (21-34). after 14 (3-21) days on the icu, directly before transplantation, sofa scores had deteriorated in all patients to 18 (17-21) and meld scores to 35 (25-38). 7 patients had renal replacement therapy and 4 patients were on single-pass albumin dialysis. the 30-day-mortality was 27%, hospital mortality 47% and 1-year mortality 60%. in hospital survivors, surprisingly, sofa scores (14 (11-16) vs. 8 (8-11); p = 0.029) and inr (3.1 (2.5-3.5) vs. 1.9 (1.3-2.1); p = 0.006) upon admission to the icu were significantly higher than in non-survivors. there were no significant differences in age, gender, meld scores or use of extracorporeal treatment in survivors vs. non-survivors. conclusions. liver transplantation in selected cirrhotic icu-patients with multi-organ failure is not medically futile. outcome, however, is much worse than usually considered acceptable. objectives. this work tries to study the clinical profile and the results with the immediate postoperative outcome of patients suffered from pancreas-kidney transplantation (pkt) and only pancreas transplantation (pt) admitted in our intensive care unit (icu) setting. methods. prospective study during 4 years (from 2006 to 2009). we recorded epidemiological, demographical and clinical data, surgical and postsurgical complications, therapy, morbidity and mortality rate, length of stay in icu, organs survival, etc. the data were expressed in mean±typical deviation, median and percentages. results. we recorded 47 patients. table 1 expresses some of the data. the mean age was 41.8 ± 7.7 years old male 74.5%. pkt from unic deceased donor: 83%. pt: 17%. the mean ischemia time was 12.4 ± 2.4 h for the kidney and 10.27 ± 3.4 for the pancreas. the most frequent surgical complications were bleeding (4.3%), technical difficulties (12.8%) and anesthetic complications (4.3%). postoperative immunosuppression consists in methyl-prednisolone, tacrolimus, mycophenolate mofetil and thymoglobulin (as our protocol recommends) and was administered to the 100% of the patients. prophylactic antibiotic and antiviral therapy (ampicillin, ceftriaxone, fluconazole and gancyclovir) was given to almost the 95% of the patients. table 2 expresses the blood test results. the mean insulin requirements per day during the stay in icu was 0 (0-8.5) iu. table 3 represents the complications in the icu. the first leading cause of reoperation was vascular thrombosis (50%) followed by intraabdominal bleeding (20%). conclusion. the clinical profile of this patient in our setting is a 42 years old man, with high blood pressure, retinopathy, dialysis, pancreas-kidney transplant recipient, with unic decesed-donor. he needs no insulin or minimal requirements. the principal complication is pancreatic vascular thrombosis that frecuently leads to removal of the graft. (1) . in a clinical practice, a specific marker to evaluate and predict ischemic-reperfusion injury in liver transplantation (olt) is not available. poor organ perfusion and high pct levels appeared to predict early graft failure only in the cardiac donor (2) . objectives. we evaluated pct as a predictor of ischemic-reperfusion injury in liver transplantation and pdr, as a predictor of complication and graft outcome. methods. prospective study. 16 patients (age, child-pugh score, aetiology of liver cirrhosis) undergo liver transplant. bilirubin levels and pdr (0.5 mg/kg of ig in a central catheter with limon system ò , pulsion medical system, munchen, germany) was measured once a day for 3 postoperative days (pod). on the same day, aspartate aminotransferase (ast/gpt) and alanine aminotransferase (alt/got) were measured. sofa score was as a patient severity score. serum level of pct, c-reactive protein (crp) was collected at the liver reperfusion time and from the 1st to the 3rd pod. warm and cold ischemia time was collected. statistical analysis was performed with wilcoxon, spearman tests (p \ 0.05). linear correlation was performed too. a small rise on pct levels were observed early after olt, with a peak in the 1st day 1 after olt. it was associated neither with hepatic post-olt dysfunction nor with other non infective complications. pct increased significantly after liver reperfusion (p \ 0.01) and correlate with pdr on the 2nd pod, but not correlation were found with crp, white blood cells, or liver enzymes after olt. crp levels increased rapidly after olt. pct increasing after liver reperfusion correlated with child-pugh olt (r = 0.4 at 2nd pod) in the recipients. the cold ischemia time did not correlate with pct serum levels after liver reperfusion as well as the warm ischemia time. a negative correlation was found between pdr and liver function in the recipient. pdr did not correlate with child-pugh score. the cold ischemia time well correlated with ast and alt on the first day after transplant (r = 0.4). it negatively correlate with pdr (r = -0.6) at the same time. the warm ischemia time did not correlate with pdr, ast and alt. the same results were found between pdr and liver enzymes and lactates. no correlation was found between pdr and sofa score. conclusions. pct peak in the recipient at reperfusion and early post operative was not predictive of graft dysfunction or other non infective complication. it may represent a marker of ischemia-reperfusion injury. crp levels increased rapidly after olt and it could be an expression of surgical procedure, and it doesn't correlate with pct. objectives. the aim of this prospective observational study was to describe the kinetics of ngal following renal transplantation and to assess its ability to predict delayed graft function. introduction. lung transplantation is the recognized therapy for end-stage respiratory failure. many serious medical complications have been described occurring from months to years after lung transplantation, often necessitating admission to an intensive care unit (icu), which has been associated with a high mortality. we examined the factors associated with mortality. methods. all patients admitted to the general intensive care unit between 2000 and 2009 following lung transplantation were included in this retrospective study. data was collected regarding demographic parameters, intensive care unit stay and outcome. over the study period, forty patients were admitted to the icu. the main pretransplant diagnosis was idiopathic pulmonary fibrosis followed by chronic obstructive pulmonary disease. the majority (93%) of patients required mechanical ventilation during their icu stay. the main reason for icu admission was septic shock in 22 patients (55%) of cases. an organism was isolated from 19 of these patients; in 11 cases, the organism was shown to be multi-drug resistant. the icu mortality was 62.5%. non-survivors were characterized by a higher admission sofa score (p = 0.02), an admission diagnosis of sepsis (87.5 vs. 37.5% for all other diagnoses, p \ 0.001), and a requirement for mechanical ventilation (p = 0.02). in addition, the incidence of chronic rejection was significantly higher in the non-survivors (p = 0.02). conclusions. severe sepsis remains the most important factor associated with a poor outcome. new strategies are required to alter the course of this common complication of lung transplantation. (the 80% of the infections were respiratory) and 13 (10%) patients presented pulmonary allograft rejection. according to our immunosuppressive protocol, we started with methylprednisolone and tacrolimus and we added mycophenolate later. the ccd length of stay was 9 (2-102) days and the median days of mechanical ventilation were 4 (1-92). thirteen (10%) patients died, basically due to refractory respiratory failure, multiple organ dysfunction syndrome and haemorragic shock. conclusions. in our large series of lung transplantation a remarkable incidence of complications has been observed. despite this complications, lung transplanted patients presented an excellent short term outcomes. introduction. acute kidney injury (aki) poses a massive challenge after kidney transplantation, especially when kidneys from brain dead adult donors are transplanted into small paediatric recipients. inflammation mediated by cytokines is a key event in experimental models of ischaemic aki. objectives. the aim of this study was to investigate whether remote ischaemic preconditioning (ripc) reduced the inflammatory cytokine load and apoptosis in the kidney after transplantation. methods. kidneys were harvested from eight 65-kg brain dead donor pigs and transplanted into two groups of 15-kg recipient pigs after 21 h of cold ischaemia. in one group (+ripc, n = 8) ripc was performed before the 10-h reperfusion period, while no ripc was performed in the other group (-ripc, n = 6). non transplanted kidneys from 7 brain dead pigs served as controls. concentrations of tnf-a, il-6, il-8, and il-10 in renal tissue were determined by an immuofluorometric assay. renal apoptosis was quantified by immunohistochemistry for activated caspase-3. high concentrations of tnf-a, il-6, il-8, and il-10 were detected in renal cortex in all three groups. no statistical differences between the two transplanted groups were found for any of the cytokines. compared to controls higher cortical levels of il-10 (control vs. -ripc, p = 0.02, control vs. +ripc, p = 0.006) and lower levels of il-6 (control vs. -ripc, p = 0.03, control vs. +ripc, p = 0.01) were found in transplanted kidneys. no differences were detected for tnf-a or il-8. transplantation significantly increased the number of apoptotic cells in both glomeruli and tubuli (control vs. -ripc, p = 0.0005, control vs. +ripc, p = 0.0001). no difference was found between recipients, (p = 0.26). conclusions. in transplanted kidneys from brain dead donors exposed to 21 h of cold ischemia and ±ripc, we found increased tubular and glomerular apoptosis, but no increase in pro-inflammatory cytokines. the levels of il-10 were higher in transplanted kidneys compared to controls. remote ischaemic preconditioning did not modify cytokine load or apoptosis in the kidney graft. objectives. we present the case of a patient with confirmed hit and the management of its status during the perioperative period of the cardiac transplantation. a 45 years old patient with a cardiac myxoma was operated under heparin anticoagulation. thrombocytopenia is noted at day 5 after surgery. an enzymelinked immunosorbent assay (elisa) was performed and since the result was positive, the treatment was changed to lepirudin. the hit was confirmed by a heparin-induced platelet activation (hipa) test. the internal jugular vein thrombosis was observed. the post operative evolution was marked by the necessity of the implantation of a ventricular assisted device. the patient was submitted to two sessions of plasmapheresis which turned the antibodies negative. the patient underwent heparin anticoagulation during the surgery time and bivalirudin as the post operative treatment. the antibodies remained negative. two months later, the cardiac transplantation was performed; heparin was used for anticoagulation during surgery. due to a restored renal function, danaparoid was used postoperatively. conclusions. hit is a serious complication of heparin therapy. the diagnosis is difficult. when hit is strongly suspected, a non-heparin anticoagulant is recommended. the choice of the anticoagulant depends on the hepatic and renal function. plasmapheresis is a solution for the antibody purging prior to cardiac surgery. objectives and methods. a nationwide qualitative study investigating their perception of the meaning of professionalism, and how they learn to behave professionally was performed. all eight dutch icm training centres participated. the moderator asked participants to clarify the terms professionalism and professional behaviour. next, participants were asked to explore the questions 'how do you learn the mentioned items?' and 'what ways of learning do you find useful or superfluous?' qualitative data analysis software (maxqda2007) facilitated analysis: an inductive approach applying open, axial and selective coding principles was used. results. 35 fellows across eight groups participated. results relating to the subtopics 'elements of professionalism' and 'teaching and learning of professionalism' are described consecutively. elements of professionalism relevant to intensivists: the elements most frequently addressed were communication, keeping distance and boundaries, medical knowledge and expertise, respect, teamwork, leadership and organization and management. medical knowledge, expertise and technical skills seem to become more tacit when training progresses, and relate to ethical, cultural and legal dilemmas originating in the specific icu context, and working as a multidisciplinary icu team member. teaching and learning professionalism: topics can be categorised into the themes workplacebased learning, by gathering practical experience, by following examples and receiving feedback on their actions, including learning from own and others' mistakes. formal teaching courses (e.g. communication) and scheduled sessions addressing professionalism aspects were also valued. conclusions. the emerging elements considered most relevant for intensivists were adequate communication skills, and keeping boundaries with patients and relatives. the specific icm context, and working as multidisciplinary icu team member substantially influenced the icm fellows' perception of professionalism. whereas medical knowledge, expertise and technical skills seem to become more tacit when training progresses, professionalism issues continue to be learned during icm training. professionalism is herein mainly learned 'on the job' from role models. formal teaching courses and sessions addressing professionalism aspects were nevertheless valued, and learning from own and others' mistakes was considered especially useful. selfreflection as a starting point for learning professionalism was stressed. the latter can e.g. be stimulated by means of assessment, structured feedback and use of portfolios, for which guidelines are now being developed within the cobatrice project. introduction: during the past decades there has been an increase in mass casualty events with changing geopolitical and climate situations. in a mass casualty event comprehensive care for the individual is expected [4] . to meet these obligations further education in disaster medicine seems obligate [1] . therefore the german home department responsible for mass casualties passed a concept for student education in disaster medicine [2] . objectives. the introduction of a summer academy ''disaster medicine'' (sadm) is a first approach at charité university of berlin to establish a curriculum for disaster medicine. the sadm is sponsored by the german academic exchange service (daad) for 3 years. the enhancement of student education in disaster medicine is supposed to raise the level of skills and knowledge of future physicians in the face of mass casualties [5] . international participants and an interdisciplinary approach are keystones of the sadm concepts. in a globalized world international networking should enable students to exchange knowledge about the handling of mass casualties in different parts of the world. disaster medicine needs an interdisciplinary approach [3, 4] . psychological aspects are always a key factor in the successful handling of mass casualties. the teaching concept of sadm consists of four parts: e-learning ahead of a 2 week training session, emergency medicine training, disaster medicine training and excursions to evaluate already existing disaster concepts. the concept will be evaluated [3] using a knowledge test, a skills test and a structured written interview concerning motivation and satisfaction of the students. conclusion. the support of the daad for three consecutive years allows a further evolution of this concept by integrating the evaluation results. the sadm should enable future physicians to meet the challenges of mass casualties with greater confidence and skills. educational programs are being set up to provide training and skills in these core subjects for dental care professionals. objectives. to evaluate dental practitioner (dp) skills and knowledge prior to a 1 day continuous medical education (cme) training session, and assess training efficacy at the end of the session. methods. nine (9) multiple choice questions concerning medical emergencies and pain treatment were handed out to dps at the beginning of cme training sessions over a 1 year period in metropolitan france. after the 1 day training session, the same multiple choice was taken again and collected for statistical analysis (kruskall-wallis test). examination before and after cme, p \ 0. we evaluated 494 dps and obtained a 100% answering rate. before the cme session, the correct answer rate was below 50% for several items, like the 112 european emergency telephone number or performing back blows before the heimlich manoeuver for severe choking, and below 75% for identifying vasovagal malaise by bradycardia, giving insulin for diabetic malaise or treating anaphylactic shock by epinephrine. more worrisome still is the fact that nearly 1out of 4 dps would prescribe non steroidal anti inflammatory drugs (nsaids) during late pregnancy. the overall impact of cme was highly significant (p \ 0.001), showing real efficacy but correct answering rates after cme still remained between 82 and 94%, which leaves room for improvement. further studies are under way to evaluate long term memorization of cme sessions in order to determine their optimal frequency. conclusions. medical skill and proficiency evaluation before cme training sessions for dps allows to target the training sessions and to evaluate their efficacy in the short run. introduction. the positive impact of immediate bedside echocardiography for rapid diagnosis and management of acute hemodynamic disturbances in the critically ill patient is well established. it is advocated that peri-resuscitation echocardiography should be an integral part of training for all intensivists. however, a major challenge for the intensive care clinician is access to appropriate echocardiography training outside of specific fellowship programmes. objectives. one suggestion to meet this training need is to combine supervised practical instruction with self-learning through the use of on-line educational tools. the internet is ideally suited to studying echocardiography as e-tutorials serve to convey theoretical principles whilst stills/video clips aid image recognition and interpretation. here we review currently available web based learning resources. methods. an online search was performed using google ò and yahoo ò search engines with the following key words: echocardiography, tte, toe, education, training, programme, courses, on-line, web-based, critical care. the resulting hits were screened to identify relevant sites and these were then evaluated independently by each author before an overall consensus was reached. one author had no previous echocardiography training whilst the other had passed the american national board of echocardiography perioperative transesophageal echocardiography examination. a total of 16 sites were identified for evaluation (see table 1 ); these are listed below with a brief description. conclusions. our search demonstrated a number of sites dedicated to facilitating echocardiography training. these varied from those which were essentially atlases, to those with a modular learning programme supported by interactive discussions and self assessment. some were targeted at the beginner seeking a basic understanding of echo whilst others were aimed at the enthusiast preparing for examinations. with growing interest in critical care ultrasound it is likely that we will see the use of such resources increasing. however echocardiography is a practical skill and it is essential that on-line learning is conducted in parallel with supervised bedside training in a process of 'blended learning'. 2. to determine level of supervision for trainees in the elective mri setting as compared with critical care transfers to mri. 3. to gain insight into the learning resources used by medical staff on mri to allow existing training to be improved. methods. two online surveys were conducted in february 2010, with invitations to participate via e-mail. the survey population included all anaesthesia and intensive care medicine consultants in the local tertiary neurosciences centre and all trainees for these specialties in the northern ireland deanery. first year trainees were excluded. results. the response rate was 61% for consultants and 50% for trainees. in total, 35 consultants responded with over 50% having no experience of mri at consultant level, even though 70% worked in areas where mri skills could be required. 54 trainees completed the survey, with 70% having experience of mri in the elective setting, all of whom had been directly supervised by a consultant. 65% of trainees had experience of critical care transfers for mri, but this was in an unsupervised capacity more than 50% of the time. despite this, 44% of trainees did not feel competent to work in mri unsupervised. web based learning was found to be a poorly utilised mri training tool, particularly among consultants. conclusion. we have demonstrated a need to formalize training for mri in our institution and for trainees in the local deanery. we propose to meet this need by a combination of e-learning and experiential sessions with defined competencies. this should increase the cohort of physicians who can provide optimal care 3, 4 in this unique environment and subsequently improve both service delivery and patient safety. was not a priority in health systems. following the 1999 report: ''to err is human. building a safer health system'', by the institute of medicine, which had a great impact on the media, ''patient safety'' is included as an strategic line in most health systems. training in patient safety is essential to implement safety culture and as a result improve it. for that reason we developed a training program (3 courses) in 2009 for 15 physicians and 30 nurses from our icu. objetive. patient safety training program assessment. methods. we designed a 17 h course (70% practical), using simulated scenarios common in icu clinical practice. we pointed out the relevance of human factors such as teamwork and communication, and its leading role in the genesis of error. we discussed a ''sentinel case'', using the root-cause analysis method, and analysed an icu process through failure mode and effects technique. adverse events reported to the department website were reviewed. participants and instructors discussed specific aspects about insertion of central venous catheter, prevention of nosocomial infection and improvement of security in the different groups of icu patients, highlighting the need for fidelity to the established protocols for this purpose. finally, participants completed a survey that assessed various aspects in a score from 1 to 5. results indicated the most and least interesting aspects and suggestions for improvement were included. results. 45 assessment surveys were analysed. participation rate was 100%. overall results: appropriate and clear targets, accomplished goals and utility (4.4) , appropriate content objectives and organization (4.3) , time invested in development activity and oral presentations (4.1), faculty competence (4.6) , interest and faculty adaptability to the group needs (4.7), degree of satisfaction and practices (4.5) . most interesting comments: practice of root-cause analysis (33.3%), continued participation and motivation (25.7%), practices with hps and group discussions (22.2%), importance of human factors (20%), theory and practice good balance (15.6%). least interesting comments: too condensed contents (13.3%), few scenarios (6.7%)suggestions: do it again(33.3%), enhance preventive medicine sessions (15.6%), increase course duration (13.3%). conclusions. overall assessment was positive. adaptability and competence of teaching staff have been the most valued aspects; too condensed contents and oral presentations were the least valued. practice of root-cause analysis ease of participation, ongoing motivation, hps scenarios and group discussions are the most appreciated activities. final comment: good acceptance has encouraged us to continue in 2010 to complete participation of all interested professionals. introduction. our intensive care unit (icu) was one of the first to initiate a humanization program in daily routine in 1996. since then, the program suffered changes, the icu grew up in number of beds and complexity and had great renewal of the members of our interdisciplinary group. objectives. to improve our knowledge we continually re-evaluated the stress factors for the patients from our staff members' perspective, putting them in the patients place. methods. between january and march of 2010, a research form was used with the interdisciplinary icu team. the following items were analyzed: profile of the interviewed, evaluation of the environment of the icu and the stress factors for the patients. the results were compared with the questionnaire form filled by the patients after icu discharge, as a part of our quality improvement program. results. about 84.41% of our icu team answered the research (n = 65). the mean age is 32.61 years (sd 6.74), 58.50% of female, 58.50% married, 50.85% protestants and 38.50% catholics and icu professional experience of 6.75 years (sd 4.65 ). our icu is noisy for 70.80%, very illuminated for 70.80%, easy-going for 53.80%, organized for 44.61%. in a 2005 preview research we found closed results. according to the team, factors that bother the patients are: noise (60.0%), bed bath (58.46%), loneliness (55.38%), lack of privacy (55.38%), anxiety (53.84%), distortion of time perceptions (35.38%) and fear (27.69%). the patients (n = 95) described as main complaints after icu discharged: distortion of perceptions of time (50.70%), anxiety (41.74%), sleeplessness (29.24%), noise (29.24%), loneliness (20.83%), fear (8.32%), pain (4.35%)bed bath (4.35%) and lack of privacy (4.35%). the study showed differences of icu team opinions and the patients' complaints. when the team is placed in the patient's perspective they may experience a better view of how harmful is an icu and how much we can do to improve it. this is our daily challenge: take care with quality, respect, affection and always search for improvement. introduction. endotracheal intubation is a routine procedure to protect the airway in critical care, that is performed by a wide variety of clinicians from different specialities with different levels of experience in airway management. serious complications can result from misplacement of an endotracheal tube (ett) in a main stem bronchus. a widely recommended method for the prevention of this complication is bilateral auscultation of the lungs; but this method frequently provides only inconclusive results (1) . other routinely used tests to verify correct endotracheal tube placement include observation of symmetric chest movements, and inserting the ett to a specific depth, but it remains unclear which of these tests detects endobronchial intubation best. objectives. we therefore designed this study to determine which bedside method has the highest sensitivity and specificity for detecting endobronchial intubation in adults and whether sensitivity and specificity increases as a function of the anesthesiologist's experience. methods. surgical patients were randomized to two study groups. in the first, the ett was fiberoptically positioned 2.5-4-cm above the carina, whereas in the second group the tube was positioned in the right main stem bronchus. first year residents and experienced anesthesiologists randomly performed only one of the following tests to verify the position of the tube: 1) bilateral auscultation of the chest (auscultation); 2) observation and palpation of symmetric chest movements (observation); 3) estimating the position of the ett by the insertion depth (tube depth); and, 4) a combination of all three mentioned tests (all three). results. 160 patients (118 female/42 male) with 320 observations by 32 experienced and 22 inexperienced anesthesiologists were included in the study. tube depth and all three had a higher sensitivity (0.88 and 1) in detecting endobronchial intubation than auscultation (0.65) and observation (0.45) (p \ 0.05). experience increased the sensitivity only for auscultation, with 45% of first year residents versus 90% of experienced anesthesiologists detecting endobronchial intubation by auscultation correctly. the optimal ett insertion depth was found to be 20 cm in women and 22 cm in men. we conclude that auscultation alone is inadequate for assessment of correct ett insertion depth, and that checking for symmetric chest movements is of little use. our results suggest that the hierarchy of the methods used to assess the correct ett insertion depth should be changed and that clinicians should rely more on depth of ett insertion than on auscultation. this is especially true for physicians with less experience in airway management and in situations where auscultation is difficult or impossible. min usa) , uses a new probe measuring hemoglobin saturation at a lesser depth (15 vs. 25 mm before), with more data output (1value/2 s vs. 1value/3.5 s). the new device contains automated software to compute parameters such as occlusion and reperfusion slopes of sto 2 obtained during and after a vascular occlusion test (vot). objectives. to compare nirs parameters obtained with the 2 devices used simultaneously in healthy volunteers and critical care patients to test if the new device gave similar results than the older one. methods. micro-oxygenation parameters were collected simultaneously with the 2 different nirs models, one on each thenar eminence, before (baseline) and during a 3 min upper arm (brachial artery) vot in 25 patients (15 septic shock (g1), 10 trauma (g2)), compared to 21 healthy volunteers (hv)(g3). nirs probes were then shifted to the contra lateral thenar eminence and a second vot was performed. sto 2 occlusion and reperfusion slopes from both devices were calculated in all groups by the same software, using linear adjustment (r 2 c 0.90 to be valid); p \ 0.05 was considered significant. following parameters were collected in patients: saps ii and sofa scores, macrohemodynamic (heart rate (hr), mean arterial pressure (map), central venous pressure (cvp), cardiac output (co) and svo 2 (mixed venous o 2 saturation) or scvo 2 ), and metabolic parameters (ph, base excess, and lactate). results. median ± iqr. patients (g1and g2) did not differ for macrohemodynamic or metabolic data, except map (74 (67-86)mmhg vs. 92 (78-102)mmhg; p = 0.05). baseline nirs sto 2 values were similar for both groups and for both devices, but were lower than in hv. during vot, reperfusion slopes were also lower in patients than in hv regardless the device used. the minimum sto 2 during vot, occlusion and reperfusion slopes were significantly different between the 2 devices: intraclass correlation coefficient (icc) 0.18, 0.16 and 0.26, respectively, and bland and altman poor agreement and large bias. conclusions. data obtained with model 650 largely differ from those obtained with model 325, regardless of the studied population for both sto 2 baseline and slopes. these differences appeared more pronounced in hv than in patients. such differences may result from muscle depth, number of data output allowing to more precise linear adjustment, or the minimum value reached during occlusion. it becomes hazardous to compare data obtained with these 2 devices either in hv or in critically ill patients. crrt is used increasingly for the management of acute renal failure in critically ill patients. one major problem with crrt is coagulation of the filters, leading to decreased efficacy and increased costs. regional anticoagulation with citrate is an effective and established form of anticoagulation during crrt in critically ill patients (1, 2) . objectives. the aim of this study was to investigate the filter life span during regional anticoagulation with citrate and regarding cost effectiveness. methods. this observational, retrospective study was performed in a mixed surgical and trauma icu in a university hospital. clinical characteristics are shown in table 1 . citrate crrt was performed using commercially available equipment and fluid solutions (multifiltrate ò with integrated cica ò -system; fresenius medical care; germany). to maintain stable metabolic and hemodynamic conditions we used an internal standard protocol for citrate crrt. reimbursement for crrt is calculated on procedure related rates (according to german drg). data are shown as mean or median and standard deviation. results. f50 patients treated with citrate crrt from april 2008 through december 2009 were evaluated ( table 1 ). the mean circuit lifetime of crrt for all patients was 49±24 h (fig. 1) . mean daily costs per patient were calculated as 264 eur and mean benefit for crrt as 3095 eur (table 2) . 1 commercially available interstitial glucose sensors have already been evaluated for this purpose with promising results. 2 however, because of the range of medications administered in the icu, potential interference with sensor performance must be characterized. to minimize the undesired offset caused by these medications, an interference rejection membrane (irm) was uniquely developed for a new subcutaneous glucose sensor for in-hospital monitoring. the novel irm was studied within the icu setting to gain a realistic picture of its performance in clinical use. objectives. acetaminophen is known to be an interfering agent for electrochemical sensors. 3 to study the functionality of the new irm, the effect of acetaminophen on sensors worn by critically ill patients was assessed. sensor signals were characterized to identify any undesired response from the medication. methods. icu patients simultaneously wore 2-3-day sensors that were connected to ipro tm (medtronic diabetes, northridge, ca) recorders to gather blinded sensor glucose values. patients were given acetaminophen or a mix of hydrocodone and acetaminophen during their icu stays; staff charted the exact time of each medication administration. to assess whether a signal offset would be introduced by the acetaminophen, 60 min of sensor signals before and after medication administration were compared. the period of 60 min was chosen based on acetaminophen's pharmacokinetic profile and the time to reach maximal plasma concentration. 4 the normalized medians for the signal segments before and after each acetaminophen delivery were calculated. the medians formed 2 vectors, each with elements representing signal characteristics before and after the medication deliveries. a paired t test was used to compare the vectors and assess for any effect (p \ 0.05) on sensor performance. across the 8 patients evaluated for this study, acetaminophen and a mix of hydrocodone and acetaminophen were administered a total of 72 times. one sensor was not available during a medication delivery; thus, 143 occurrences of acetaminophen administration were analyzed. no effect on sensor signals could be identified in the 143 instances of acetaminophen delivery. no statistically significant difference was observed between the signal segments before and after administration (p [ 0.57). conclusions. this study demonstrates that a novel irm effectively reduces the undesired interference of acetaminophen on a continuous glucose sensor signal during clinical use. although this analysis was focused on acetaminophen, the outcome suggests that the irm may also effectively suppress interferences from other medications administered in the icu. [1] . however, assessing elastance requires a highly invasive vena-cava occlusion maneuver and left and right ventricle pressure/volume waveforms, which are not typically available in an intensive care unit (icu) and may raise ethical issues in regular use. a validated, lumped-parameter 8 chamber cardiovascular system (cvs) model is used to evaluate a time-varying elastance estimate at the bedside using standard clinical measurements. objectives. to assess time-varying elastance at the bedside for the left and right ventricles using available icu data, and prove the concept on a porcine model of pulmonary embolism. five pigs had pulmonary embolism (pe) induced via injection of blood clots over 4 h, developing full pe in stages from a healthy state. at each state several data sets were taken (46 in total over 5 pigs), measuring aortic and pulmonary artery pressure waveforms (p ao (t), p pa (t)), left and right ventricular volume and pressure waveforms (vlv(t), vrv(t), plv(t), prv(t)). at each cardiac state in inducing pe, the time-varying elastances are estimated as elv = plv/ vlv and erv = prv/vrv. these values are correlated to readily measured quantities (pao and gedv). these correlations are used to approximate time-varying elastances erv* and elv* for use in a clinically validated 8-chamber cvs model. note these approximations are load dependent and thus change with cardiac state. a fivefold cross validation was used to validate the model. a time-varying elastance is generated from data from 4 pigs and used to simulate the fifth pig. simulated pv loops are compared to the originally measured pv loops to validate the approach. results. p ao (t) and elv were highly correlated over the 46 data sets (r = 0.81 to r = 0.99). p ao (t) and elv, gedv and erv are also well correlated (r = 0.73 to r = 0.98 in this case we report the worldwide first use of the novel deltastream-dp3-system (medos corp.) in a patient suffering from acute right heart failure due to pulmonary embolism following cardiac surgery. in a 68 year-old male patient 6 days after mitral valve reconstruction cardiac arrest occurred during physiotherapy treatment. after failure of restoring circulation, a short-term ecls system (lifebridge ò ) was implanted under cardiopulmonary resuscitation by inserting cannulas in venous and arterial femoral vessels and then switched immediately to the dp3-deltastream system. ct-scan revealed the diagnosis of a massive central pulmonary embolism. transesophageal echocardiography showed a dilated failing right ventricle. a thrombolytic therapy was carried out by administering 100 mg alteplase. following ct-scan showed reduced thrombus burden. the deltastream system was carried out for 148 h. ptt was maintained to 1.5-fold under i.v. heparine therapy. pump blood flow was held at a maximum of 4.5 l/min (7,000-8,000 r/min) for 2 days. despite transesophageal echocardiography showing improved left ventricular function the ecls flow was maintained for further 2 days focussed on the improvement of right heart. further on the pump flow was reduced every 6 h and the system could be explanted after 6 days in now stable cardiolpulmonary situation. the patient was discharged on day 65 at home in good state without any neurological dysfunction. overall duration of the ecls deltastream therapy was 148 h. no system related major complication occurred during the time. even in maximum blood flow of 4.5 l/min no relevant hemolysis was measured. ldh level was only slightly elevated to 250-300 u/l. introduction. airway management has progressed dramatically in the last 10 years but the most significant advance has been video laryngoscopy. several devices have been introduced since, the most important currently available are the glidescope ò , c-mac ò , mcgrath ò , pentax airway scope ò , airtraq ò , among others. a common practice has been to abandon direct laryngoscope intubation (dli) after 3 attempts and move onto advance airway devices such as video laryngoscopy which is becoming the first choice when available. although dli is successful in the majority of patients, poor glottic exposure is more likely to require prolonged or multiple intubations attempts and therefore be associated with complications such as oxygen desaturation or airway and dental injuries. in the intensive care environment an airway should always be considered a difficult airway due to scarce time to perform assessment, to make decisions and to act. should the use of video laryngoscopy be implemented as a routine for airway management in a critical care setting ? objectives. the purpose in this study was to describe for the first time the use of video laryngoscopy, specifically the vel 70, as a routine choice for airway management in the intensive care environment. single center, prospective observational study, from 19 november 2009 to 18 february 2010, was conducted in our intensive care facility, which involved utilization of the vel 70 for all tracheal intubations, no exclusion criteria, rapid sequence intubation (rsi) was the standard procedure. information was recorded by the operator assistant on the same day identifying timings of intubation, number of attempts, success or failure and the difficulties encountered. vel 70 was developed in our institution in 2002 and later adopted as a standard airway management by the department of anesthesia. the device has an original mccoy blade with an attached port that holds a channel for the displacement of an optical shaft 155 mm long, 4.0 mm in diameter with a 70°angle view (tekno-medical ò germany) which is assemble to a video camera (telecandx ii, karl storz, germany), an external light source and to a 24-in monitor. results. there were 49 tracheal intubations performed by 5 operators, 17 crash intubations and 32 rapid sequence intubations. all intubation attempts were successful, mean number of attempts 1. the median time to successful intubation was 22 s with no complications. subjective assessment post intubation showed that in all cases vocal cords were view in full, all operators manifested to feel comfortable with the handling of the apparatus but felt dependent on a assistant specially to maintain view while maneuvering the endotracheal tube. conclusions. routine airway management with vel 70 in critical care setting is effective with a high rate of success and most important, with a positive impact for patient safety. introduction. hypovolemia is a common complication in many clinical scenarios and its detection is considered of prime importance. in previous clinical studies, tissue oxygen saturation (sto 2 ) measured by near-infrared spectroscopy (nirs) has been explored for this purpose; however, results are disappointing. it has been suggested that the sensitivity of nirs for detection of hypovolemia might be improved when nirs is applied in combination with a vascular occlusion test (vot). nirs in combination with a vot, consisting of a 3-min period of arterial occlusion followed by reperfusion, allows quantification of muscle deoxygenation during ischemia (sto 2 downslope; a measure of muscle oxygen consumption rate) and muscle reoxygenation after ischemia (sto 2 upslope; a measure of microvascular reperfusion rate). objectives. in the present study we applied multi-site and multi-depth nirs in combination with a vot in a model of simulated central hypovolemia; lower body negative pressure (lbnp). eight healthy male subjects, with a mean ± sd age of 27 ± 6 years, participated in this study. the lbnp protocol consisted of a stepwise increase of lbnp from 0 to -60 mmhg. stroke volume (sv), heart rate (hr), cardiac output (co), and mean arterial pressure (map) were continuously measured using near-infrared finger plethysmography (nexfin). multi-depth nirs, with probing depths *15 and *25 mm, was performed on forearm and thenar for the measurement of sto 2 . three-min vots were performed by rapidly inflating a pneumatic cuff around the left upper arm before application of lbnp and at lbnp = -60 mmhg. vot-derived sto 2 traces were analyzed for baseline, downslope, and upslope. . from baseline to lbnp = -60 mmhg, sv decreased from 121 ± 18 to 77 ± 14 ml (p \ 0.001), hr increased from 59 ± 10 to 83 ± 11 bpm (p \ 0.001) and co and map were maintained around baseline level. forearm sto 2 baseline decreased significantly from 83 ± 6 to 78 ± 7 (p \ 0.01) and 86 ± 6 to 82 ± 8% (p \ 0.01) for the 15 and 25 mm probing depth, respectively. forearms sto 2 downslope, measured with the 15 and 25 mm probe, decreased from -7.2 ± 1.9 to -8.8 ± 1.9%/min (p \ 0.05) and -8.3 ± 1.3 to -11.4 ± 2.9 (p \ 0.05), respectively. forearm sto 2 upslopes remained unchanged during lbnp. vot-derived sto 2 parameters measured on the thenar did not shown any changes as a result of lbnp. conclusions. vot-derived sto 2 parameters measured on the forearm seem to be more sensitive to the hemodynamic changes associated with lbnp compared to sto 2 parameters measured at the thenar. grant acknowledgment. this project was supported in part by hutchinson technologies inc. introduction. hypovolemia is a common complication in many clinical scenarios and its detection is considered of prime importance. in previous clinical studies, near-infrared spectroscopy (nirs) has been explored for this purpose; however results are conflicting due to inconsistencies in methodology with respect to nirs probing depth and site. objectives. in the present study we applied multi-site and multi-depth nirs in a model of simulated central hypovolemia; lower body negative pressure (lbnp). fifteen healthy male subjects, with a mean ± sd age of 28 ± 5 years, participated in this study. the lbnp protocol consisted of a stepwise increase of lbnp from 0 to -80 mmhg. stroke volume (sv), heart rate (hr), cardiac output (co), and mean arterial pressure (map) were continuously measured using near-infrared finger plethysmography (nexfin). multi-depth nirs, with probing depths *15 and *25 mm, was performed on forearm and thenar for the measurement of tissue oxygen saturation (sto 2 ). . from baseline to lbnp = -80 mmhg, sv decreased from 117 ± 14 to 67 ± 9 ml (p\ 0.001), hr increased from 58 ± 10 to 99 ± 12 bpm (p \ 0.001), and co and map were maintained around baseline level. forearm sto 2 decreased significantly from 84 ± 6.7 to 78 ± 9.9% (p \ 0.001) and 81 ± 6.7 to 75 ± 9.9% (p \ 0.001) for the 25 and 15 mm probing depth, respectively. thenar sto 2 measured with the 15 mm probe remained unchanged, but measured with the 25 mm probe, a decrease from 86 ± 3.6 to 83 ± 3.3% (p \ 0.01) could be observed. conclusions. forearm sto 2 seems to be more sensitive to (simulated) hypovolemia compared to thenar sto 2 and the sensitivity of nirs seems to increase for increasing probing depth. grant acknowledgment. this project was supported in part by hutchinson technologies inc. introduction. sidestream dark field (sdf) is a microcirculatory imaging modality implemented in a hand-held microscope for the non-invasive bed-side visualization of the human microcirculation. despite the many studies showing the importance of microcirculatory imaging in intensive care patients the introduction of sdf imaging into routine clinical practice remains cumbersome. one of the challenges is the need for automatic analysis of the images which currently is subjective and time consuming. objectives. in the present study, we introduce a rapid automated software method for automatic quantification of microvascular density, a key microcirculatory parameter, based on sdf image contrast analysis. methods. twenty-five sequential sdf images (duration = 1 s, resolution = 720 9 576 pixels) were isolated from an sdf movie clip, stabilized, and averaged. subsequently, the mean ± sd gray scale intensity in a sliding 5 9 5 pixel window was calculated and the sdvalue was assigned to the window center pixel, creating an sdf contrast image. this is a simple and rapid algorithm for vessel wall detection as a pixel window at a tissue-vessel junction will have a high sd-value due to the presence of both light tissue cells and dark red blood cells. conclusions. here, we introduce and validate a rapid automated method for quantification of microvascular density in sdf images. as this algorithm detects vessel walls rather than vessel lumen, smaller and larger vessels have similar contribution to the microvascular density assessment. a limitation, however, is that vessel diameters cannot be detected with this algorithm. the preliminary results confirm the proof of concept of the sdf image contrast analysis software, however, further research is required for its optimization. the criteria believed to be necessary for the implementation of hcs in practice were that his name would be written{106(66)}, the document dated{96(60)} and signed{93(58)}. physicians in private practice wanted date(p = .04) and signature(p = .004) more often than in institution. 96(60) physicians thought that the patient must be competent at the designation' time of hcs, especially those who possess advances directives(p = .003) and a hcs(p = .04) themselves. 58(36) thought the hcs should know about the patient's wishes regarding treatment and care objectives. conclusions: more than 1/3 of physicians did not know who the hcs is. more than 3/4 thought hcs useful and at least 2/3 would encourage a patient to designate one before heart surgery. about 10% thought that being a hcs is a too high responsibility and that the hcs could not be the best representative when needed. the potential fear this topic might induce is a barrier for this minority. introduction. the use of a daily goals chart has been shown to improve communication between the multi-disciplinary team leading to an increase in understanding of daily patient goals and a decrease in length of patient stay on the intensive care unit (icu) [1] . we have used a daily goals chart on our icu since 2004. we wanted to assess the value of this initiative in a general adult icu. methods. the royal cornwall hospital is a large uk district general hospital. we conducted the survey over a 4 week period in the icu. each day, after the morning multidisciplinary ward round, the consultant in charge was asked to give the main goals for each patient. these were compared with those written on the daily goal chart, or stated by the house medical and nursing staff. they were graded as complete match (100% of consultant goals matched), partial match (99-50% matched) or non match (\50% matched). results. 73 surveys were conducted. the daily goals sheet matched the consultant completely on 32 (44%) occasions and partially on 29 (40%) occasions. in comparison, the combination of house medical and nursing staff had complete match on 47 (67%) occasions and partial match on 19 (27%) occasions. house medical staff had a 95% complete or partial match, house nursing staff had a 88% complete or partial match. overall house staff understanding of the goals set on the ward round is far better than that recorded on the goals chart. the goals related by medical and nursing staff showed differences that reflected their differing clinical priorities. combining results of all staff led to higher levels of complete match than either group independently. low levels of non-matches indicate that there is good overall understanding and communication within the team. use of daily goals charts is an effective aid to augment communication on the icu multidisciplinary ward round. objectives. to assess the effectiveness of an icu diary on post-icu psychological symptoms of patients (pts) and their families. single centre prospective study. three periods: 1 = control (5 to 11/2008), 2 = diary (12/2008 to 04/2009), 3 = control (05/2009 to 09/2009). all the pts admitted c4 days for the first time to our medical-surgical icu were included. during the intervention period, the diary was filled both by the caregivers and the pts' relatives, without directives except for the first (medical summary) and the last (recovery wishes) ones. at icu discharge, their families were asked to fill a satisfaction questionnaire (ccfni) and the hospital anxiety and depression scale (hads), and to be contacted by phone to assess peri traumatic stress disorders [dissociation and impact of event scale-revised (ies-r)], hads at 3 months and 1 year after icu discharge. we excluded pts if they or their family refused to participate, were not fluent in french, or if their family was not present around the day of icu discharge. the optimal theoretical content of the diary was determined by a delphi technique involving a panel of icu and non-icu caregivers and a voluntary visitor. the content of the diaries was analysed and linked to the outcome measurements. of the 378 admitted patients, 197 were included. after exclusion of 54 pts, 143 formed the basis of the study. the content of diaries and the results of ies-r are under analysis. the 1 year data is not yet available the saps ii at admission, icu and 3 months post icu mortality were not significantly different between the three periods. the family satisfaction score was high and was not significantly different between the three periods. included: patients with failure of two or more organs in the first 24 h, admitted to icu during 2008. excluded: neurocritical and politrauma patients. contact 1 year following discharge from; questions were asked about the patients' different perceptions during their stay in icu. if it was not possible to contact the patient, the next of kin was asked. results. 154 patients included. general characteristics during admittance to icu: 63% male; age 60.2 ± 17.5; sofa * 7 ± 2.8; apache ** ii 16.8 ± 6.4; apache ** iv 57 ± 18.8; length of stay in icu: 5.1 ± 28.4 days; 42.9% on invasive mechanical ventilation and 17.5% on non-invasive mechanical ventilation. data collection was carried out over a period of 18 ± 4.4 months, on average 19 months (range: 12-26 months). 18.2% (28 patients) had died at the time of contact. the person interviewed was the patient in 33.3% of the cases, the spouse in 13.7% and immediate family (patient 0 s parent/child/sibling) in 43.1% of the cases. overall, 43.9% do not have any memory of their stay in icu. for 25.2%, the experience was unpleasant and for 1.6% of patients the memory is very unpleasant. 29.4% experienced fear, 28.7% disorientation, 4.4% a feeling of lack of hygiene, 9.7% a feeling of suffocation/drowning (with the endotraqueal tubes, etc.), 5.1% a lack of privacy (nudity, etc.) and 14.7% pain during procedures. 94.7% were very grateful for our phone interview. 64.8% were satisfied with the staff. conclusions. in patients with high severity scores during their time in icu, less than half have memory of their stay after 1 year. in those who do, the feeling of fear and disorientation predominates. to determine the occurrence of communication failures in clinical icus, identifying their main detection tools and disclosing their effects on patient condition. a prospective cohort was conducted in four icus of a 1100-bed academic, tertiary-care urban hospital in sao paulo, brazil, enrolling critical ill patients older than 15 years from july to august 2009. communication failures were identified by daily direct observation of medical and nursing rounds and also by chart reviews. the association between communication failures and adverse event occurence was determined using multivariate logistic regression. results. among the 54 enrolled admissions, as much as 24 admissions (45%) were affected by communication failures, with 53 occurrences. the vast majority of the communication problems was not registered in patient charts, and could only be identified during the medical and nursing direct monitoring. none of the identified communication failures caused patient harm. nine out of ten communication issues involved exclusively members of the multidisciplinary icu health team, patients and their relatives being seldom included in this scenario. despite communication failures are considered important adverse event risk factors, no association was identified between these two variables. conclusions. the incorporation of direct observation as a research tool for identifying untoward events was essential to the detection of communication failures in our study. almost half of the studied admissions was affected by communication flaws, most of them involving exclusively the healthcare team. nevertheless, these figures are underestimated, since the research team remained in the studied icus for no more than 5 h a day. although patients were not harmed fortunately, the presence of these communication issues suggests the existence of important gaps in the provision of critical care. the issue regarding communication deficiencies in icus setting affecting patient safety deserves attention. relatives of patients in the intensive care unit (icu) are exposed to considerable stress 1 . effective communication with relatives has been shown to provide support and minimise stress whilst improving their wellbeing and decision making for critically ill patients 1 . furthermore, satisfaction is dependent on communication by a senior caregiver 2 . no published guideline or recommendation exists for when relatives should be first spoken to, how often they should be updated, or how these conversations should be documented. to determine how well relatives of patients in the icu are kept informed and to assess the quality of documentation. we retrospectively analysed data from the metavision ò clinical information system of patients staying over 4 days during 01/10/09-01/01/10 on the 20-bed icu at the nnuh. data obtained from the 'relatives communication' page included: when relatives were first spoken to, how often they were spoken to (according to the number of entries made) and the members of staff involved in the conversations. these variables were analysed in relation to patient outcome and length of stay on the icu. . 64 patients were analysed. communication with relatives was not documented in 45% of patients. 60% of communication was carried out by a consultant. discussions were more likely to occur with relatives of patients who died; 83% compared to 48% of patients discharged to the ward. similarly, relatives of patients who died were spoken to more frequently; 90% were talked to on more than one occasion compared to 28% of patients surviving to discharge. relatives were more likely to be spoken to with an increased duration of admission on the icu; communication occurred with only half the relatives of patients staying 1-5 days, compared to 100% of those staying more than 20 days. two-thirds of relatives of patients staying more than 20 days were not communicated with until after the fourth day of admission, although the majority of these were spoken to on numerous occasions and all were seen by a consultant. relatives of patients dying on the icu are more likely to be communicated with, and are updated more often than those of patients surviving to discharge. a delay in communication with relatives of patients staying more than 20 days on the icu was noted, but conversations occurred more regularly and involved a consultant. we suspect that our results demonstrate a lack of documentation rather than actual communication; auditing relatives' satisfaction with communication on the icu may help clarify areas for improvement. assessment of satisfaction with the quality of care provided to patients hospitalized in intensive care units, in most cases, is transferred to the relatives of the same, given the context of the patient himself unable to speak. the diagnosis of the needs of families of critically ill patients has been the subject of several studies. aiming to assess the needs of relatives of patients admitted to the picu (polivalent intensive care unit), we conducted studies in particular through an adapted version of the questionnaire ccfni (critical care family needs inventory) developed from the adaptation made by johnson and col. (1998) and focus group. one of the needs identified in these studies was to improve information about what happens in the picu. with this in mind we designed a manual to support relatives in order to improve communication and understanding in the context of the intensive care unit. objectives. this study aims to assess the impact on the level of family satisfaction of a manual we've created. the manual is available from january 2006 to all visitors at the entrance of that unit. the questionnaire was mailed to all families who had a family member hospitalized in the picu during the year following the introduction of the manual. together followed a letter to present the study and a stamped and addressed envelope for their return. beyond the satisfaction and access to the manual or not, were collected socio-demographic data from relatives and socio-demographic and clinical data of patients. we obtained 90 responses, representing 28% of all potential families. 14 questionnaires were returned because of address failure (6.3%). statistical analysis was performed using spss ò v.17.0 results. the satisfaction of family members who had access to the manual was better in all dimensions tested (support, comfort, information, access, trust), and with a statistically significant difference (p \ 0.05). this difference was clearer in the fields support (med1, 75/ 2.75) and information (1.67/2.33). conclusions. the impact of the manual on the improvement of family satisfaction was positive in the various dimensions assessed. the questionnaire of family satisfaction monitoring and understanding of information given through a manual created by us can contribute to a better understanding of the needs of families and hence for the continued improvement of service quality. johnson introduction. the burnout can be defined in its multidimensionality: emotional exhaustion, understood as a feeling of exhaustion and failure of the person to give more of herself; depersonalization, in which the person's relationship with patients and with colleagues becomes cold, distant and guided by some cynicism, lack of personal and professional completion, which may manifest itself, on one hand, by the sense of incompetence and inability to respond to requests or, on the other hand, by the sense of omnipotence. the provision of intensive care can lead to health care provider's physical, psychological and emotional exhaustion, which may develop to burnout. we notice the absence of specific studies on this syndrome, in portuguese intensive care units. objectives. the study here presented intend to identify the levels of burnout of physicians and nurses working in portuguese intensive care (adult polyvalent units in the north of the country), and to identify factors that can lead to the development of burnout in the portuguese physicians and nurses working in that setting. the methodology presented consist of application of a questionnaire for self fulfilment with 3 items: 1, socio-demographic data of the study population; 2, experiences in the workplace; 3, maslach burnout inventory-general survey. for the application of methodological tools, we requested the authorization by the competent institutional bodies: the board, ethics committee and directors of services. the professionals who participated in the study were asked informed consent, whether in formal or informal. in addition, each instrument was accompanied by a cover sheet of the same. we have also done observation of the work contexts, and interviews. in this study we will focus on the results of the questionnaire. . sample: 6 hospitals with a total of 10 intensive care units. professionals participants in the study 300, 82 physicians 218 nurses. the mean ages of respondents 32, of professional experience 8 years and of experience in intensive care were 4 years. mbi preliminary results:distribution of levels of burnout by occupational category: at the moment, portuguese physicians and nurses who work in intensive care units seam to have medium levels of burnout, obtained through the mbi. results show higher levels at emotional exhaustion in nurses never less in general they showed higher personal and professional completion than physicians. depersonalization were higher in physicians. the results presented here underline the importance of promoting the prevention of burnout at intensive care. the development of the burnout syndrome in physicians and nurses in intensive care has serious consequences, both for themselves, or the consequences that entails for patients and their families. introduction. the hospitalization of a member of the family in the intensive care unit (icu) usually occurs in an acutely and inadvertent way, leaving little time for a family adjustment. facing the stressful situation, the family may feel disorganized, helpless and with difficulties to mobilize themselves, enabling the rise of different types of needs. the scope of those needs leads to the alleviation of tension and uncertainties that could provide to the family the stability needed to cope with the situation disease 1 . to identify the needs of care of family members with persons admitted to the icu. methods. this is a transversal study, held in two icus (a public one and a private one) in the city of feira de santana, bahia, brazil, after approval by ethics and research committees. the relative person is understood by the person who had consanguinity ties or who was closest to the patient, who lived with him and had close relationships. 40 relatives were interviewed when his relative was over 24 h of hospitalization. the the brazilian adaptation of the critical care family need inventory (inefti) was used for measuring the degree of importance, once it has 43 items distributed in five dimensions. descriptive statistics were used for analysis. the inefti reliability was satisfactory (cronbach a = 0.843). results. the needs of care considered most important by family members were those related to the security dimension, expressed by the items ''to know what are the chances of improvement of the patient'' (3.88 ± 0.33), ''to be informed about everything that relates to the evolution of the patient'' (3.85 ± 0.36) and ''to feel that hospital people care about the patient'' (3.80 ± 0.40). in the category information, the item ''be able to talk to the doctor everyday'' (3.70 ± 0.36) obtained more average. in the category proximity was consider more important to ''see the patient frequently'' (3.73 ± 0.45). the needs of the categories support and comfort categories showed lower scores. these results are similar to those presented by literature 1, 2 , what confirms the appreciation of the family to the aspects related to the recovery of the hospitalized relative, in detriment of their own needs. conclusions. having security, information and being around its ill relative is what the families need. the security is provided by the conviction that the person receives the best care in the pharmacological, technological and human aspects, and can be perceived by the information transmitted by the team and by the proximity established in the interaction with the sick relative. a collaborative project was developed between the itu clinical staff of a large, inner city teaching hospital, palliative care clinicians and an academic department of palliative care. qualitative data collection included: (i) semi-structured interviews with staff and relatives of patients thought to be at the end of life; (ii) focus groups with staff (iii) observation of care and (iv) clinical note review. data was analysed using the framework approach to identify key themes. results. semi-structured interviews were carried out with 47 staff and 3 focus groups took place. a total of 24 relatives, representing 20 patients thought to be at the end of life, were interviewed. half the patients represented were female, with diagnoses including infection, hypoxic brain injury, malignancy and liver failure. the participants were aged 28-80 and included a range of ethnic groups and religious affiliations. non-participant observations of care took place for 15 and clinical note review for 16 of these patients. data from the interviews with staff describe that an existing withdrawal of treatment document was working well but could be developed further along with suggestions for amendments. the interviews with relatives, observations and review of clinical notes show 4 key themes: communication, decision-making, patient and family needs, and symptoms and their management. through discussion at itu end of life group meetings, a consensus was reached to pilot a complex intervention comprising an amended withdrawal document; a psychosocial assessment; education and awareness-raising; palliative care team input and increased psychosocial support. the psychosocial assessment document was deemed valuable to all patients and was rolled out for all patients admitted to itu. initial evaluation shows greater staff awareness. documentation of end of life issues and the collaborative research process has improved communication between itu and palliative care staff. introduction. consumer-centric healthcare is a key component of nhs policy. when patients are critically ill, family members act as surrogates. family members alone may inform patients of events that occurred, and provide physical, emotional and socioeconomic support during rehabilitation. thus, high family satisfaction (fs) is important. the fs-icu instrument was developed in canada to quantify family satisfaction 1 and benchmark intensive care units (icus). we have piloted and validated previously an adaptation of the fs-icu such that its language was appropriate for the uk 2 . to date, no intervention has demonstrated improvement in the fs-icu for a critical care unit. we hypothesise that provider-driven interventions fail to recognise central issues. co-production is a framework that enables creation of parity between providers and consumers by validating both individual worth and specialised knowledge 3 . there are no published data on the use of co-production in intensive care. we undertook to co-produce interventions targeted to improve family satisfaction. the fs-icu instrument will be used as an objective measure of their efficacy. objectives. to co-produce some interventions targeted to improve family satisfaction and to use the fs-icu instrument as an objective measure of their efficacy. methods. fs-icu questionnaire responses were used to highlight potential areas for service development. focused interviews with families provided detailed descriptions of the ''the way the icu works''. these data were used to build exercises for a workshop of service users and providers which aimed to co-produce service developments. results. 88 fs-icu questionnaires were received over the 12 months to april 2010 (70% response). quality and consistency of communication between icu doctors and relatives; the level of relatives' inclusion in decision-making processes; and the icu waiting room atmosphere were identified as needing improvement. four families were interviewed in detail. workshop participants included trust directors, managers, clinicians, nurses, patients and their families. proposed interventions from the workshop included: development of a non-clinical family liaison officer role with a dedicated contact number; increasing focus on managing patients' and relatives' expectations of care delivery; specific improvements to the waiting room area. intensive care patients' relatives provided a unique insight into the icu functioning that should be utilised as a resource. co-production was used to design service improvements that may not have been obvious from a provider perspective. workshop transactions were empowering for both staff members and patients' families, generating social capital that creates and improves social provider-consumer networks, now and in the future. to evaluate the degree of satisfaction of icu patients regarding their icu stay. as the result of a fund sponsored by former patients and their relatives, our dept of intensive care is able to provide a small team of assistants to welcome and accompany the relatives of icu patients. one role of this team is to collect and evaluate impressions and criticisms from patients and relatives shortly after the icu stay. we studied a convenience sample of icu patients who stayed in our multidisciplinary dept of intensive care between september 2009 and april 2010. the evaluation included 12 simple questions about the welcome (friendliness of the personnel, explanations), quality of care (including pain control, attention to patient needs, availability of nurses and speed of response) and comfort (temperature, light, noise). data were analyzed using non-parametric (mann-whitney) and chi 2 tests. we collected answers from 100 of 134 patients (22 were incapacitated, 7 had died and 5 declined), including 51 unplanned admissions and 49 patients after major surgery. more than 75% of the patients were very satisfied with all items, except for information provided by the attending physician (67% of patients) and the room temperature (66% of patients) (figure 1 ). post-icu enquiries can provide valuable feed-back information that could improve the quality of care in the icu. introduction. previous research suggests that family members of critically ill patients hospitalized in the icu frequently suffer from severe anxiety. a survey conducted in our unit-a 12-bed, university-affiliated tertiary-care, closed, general icu with restricted visiting hours-revealed a willingness of family members to participate in a support group. such a group was recently introduced and we report on our initial experience over the last year. methods. the purpose of the support group was to provide a forum where family members could freely raise any topic related to the care of their loved one as well as to family-related issues. the meetings were held weekly in the icu and chaired by a senior nurse and the unit social worker. family members were informed of the meetings when the patient was admitted to the icu and notifications were placed in the family waiting room. all family members were encouraged to take part and to raise any topic they felt was relevant. results. since its introduction in 2008, there has been an increase in the percentage of a family representative attending the meetings from 13 to 47%. the most frequently raised issues included staff-family interaction (especially lack of empathy), lack of information regarding the patient's status and prognosis, and the lack of adequate visiting hours. in addition, other issues included technical aspect related directly to the family, in particular, overcrowding and lack of privacy in the waiting room. finally, participants wanted to learn skills in order to cope with their new and uncertain circumstance. we have noted an ongoing readiness of family members to take part in the support group. the issues raised have and will allow us to make appropriate changes and to improve the current situation. in particular, the meetings help us to identify family members at risk who require more immediate and personal attention. introduction. the soap study suggested outcomes of cancer patients admitted to icu are similar to those without cancer in contrast to other reports . 1 we wanted to compare this with our own experience. (1) to determine critical care and hospital outcome of patients with malignancy referred to critical care in the previous 5 years. (2) to identify any factors influencing treatment decisions and survival after admission. retrospective chart review of patients undergoing treatment for malignancy admitted to icu for medical or surgical reasons from may 2006 to feb 2010. leukaemia patients were not included as they are treated at a different hospital by a different group of clinicians. demographic information, tumour/treatment related factors e.g neutropenia, preadmission status and critical care diagnoses e.g. sepsis, were collected in addition to patient outcomes. results. 38 patients were identified (2.8% of all critical care admissions). itu mortality was 39.5% (n = 15), however only 31.6% (n = 12) survived to hospital discharge (comparable overall unit mortality: 20-25%, hospital mortality:30%). hospital survivors were younger (median 54.5 vs. 62 years), and more non-survivors had pre-existing comorbidities, sepsis, ali and required more organ support (all ns). there was no difference between the groups regarding cancer treatment. non-survivors had a longer stay in critical care and treatment withdrawal/limitation decisions were more common suggesting these were often based on lack of medical progress whilst on icu rather than diagnostic nihilism. hospital mortality in patients with malignancy is higher in our specialist centre than reported for a europe wide cohort (68.4 vs. 27% overall and 41% in the medical subgroup). the majority of our patients were medical and not post-surgical unlike in the soap study. this may account for the greater mortality as a larger proportion of our patients had ali, sepsis, neutropenia and required inotropes. numbers admitted to critical care are much smaller than the 15.1% reported in the soap study, suggesting some referral and admission triaging by the oncologists and the icu team. our results are similar to single centre french (hospital survival rate 31.6 vs. 21.8%) and brazilian studies (31.6 vs. 42%), although a majority of our patients did not receive mechanical ventilation. 2,3 a diagnosis of cancer or active treatment for it should not be the major determinant of critical care support, but the patient's general premorbid status and the extent of organ failures appear to be important factors in decision making as for any other critical care patient. figures from the soap study for non specialist centres do not appear to reflect the experience of specialist oncology centres. historically there has been a negative perception of the prognosis for patients with haematological malignancies requiring admission to the intensive care unit (icu). however, advances in chemotherapeutic regimes and haematopoietic stem cell transplantation (hsct), along with improved monitoring and supportive measures have suggested that outcomes for these patients have improved [1] . establishing key prognostic indicators predictive of outcome may be useful in identifying patients most likely to benefit from icu therapy. the aim of this study was to describe clinical outcomes and identify prognostic factors in patients with haematological malignancy requiring admission to icu. following research approval, a retrospective cohort study was undertaken in a 12-bedded specialist cancer icu over a 5-year period (october 2004 -september 2009 . recorded patient variables included demographics, haematological diagnosis, reason for icu admission, hsct, apache ii, admission laboratory data, number of organ failure, use of invasive mechanical ventilation, renal replacement therapy (rrt) and vasopressors. the primary outcome was in-hospital mortality. key prognostic variables in determining inhospital mortality were identified using univariate and multivariate analysis. results. 199 patients with haematological malignancies were admitted to the icu during the study period: mean age 55.3 (sd 15.6); 43.7% female; haematological diagnosis (45.7% leukaemia, 40.2% lymphoma, and 13.6% myeloma); 54.2% emergency admissions and 43.9% were post-hsct. mean apache ii was 21.6 (sd 7.4), mean number of organ failures 2.3 (sd 1.7), 52% required invasive mechanical ventilation, 41.4% rrt and 51.6% vasopressor therapy in the first 24 h of icu admission. icu, in-hospital and 6-month mortality were 32.7, 45.2 and 60% respectively. significantly higher mortalities were seen in patients who were mechanically ventilated (65 vs. 25% non-ventilated patients p \ 0.001), on vasopressor support (57 vs. 25% no vasopressor support p \ 0.001), neutropenic (52 vs. 45% non-neutropenic p \ 0.001) and in multi-organ failure defined as c2 organ failures (84 deaths vs. 15 deaths in patients with b1 organ failure, p \ 0.001). univariate analysis revealed mechanical ventilation, vasopressor support, albumin \20 g/l, neutropenia, platelet count \50 9 10 9 /l and multi-organ failure were all significant with p values .001, .001, 0.003, .001, 0.015 and.001 respectively. multivariate analysis revealed that multi-organ failure was the only independent prognostic predictor of in-hospital mortality. conclusion. mechanical ventilation, apache ii, vasopressor support, albumin\20 g/l, neutropenia, platelets \50 9 10 9 /l and multi-organ failure all had a significant association with mortality; however multi-organ failure was the only independent factor that predicted poor outcome. c.y.c. michael 1 , a. vasu 1 , s. eillyne 1 1 tan tock seng hospital, emergency department, singapore, singapore introduction. coronary heart disease is the leading cause of mortality and morbidity for both women and men. although men are affected in greater numbers, women have been shown to have worse outcomes and higher mortality. objectives. this study aims to examine gender differences in risk factors, angiographic severity, treatment and in-hospital mortality after stemi. methods. in this retrospective study, the medical records of 619 patients with an admitting diagnosis of stemi from tan tock seng hospital, emergency department (ttsh ed) between 1st january 2009 and 31st december 2009 were reviewed. we extracted the data from the electronic records of the emergency case notes and inpatient discharge summaries. results. of the 619 patients studied, 123 (19.9%) were women and 496 (80.1%) men. four hundred and forty-nine (72.5%) patients underwent coronary angiography. one hundred and seventy (27.5%) patients did not undergo coronary angiography, majority (65.3%) were elderly aged c65 years (men 34.1% and women 31.2%). between women and men, there was no significant difference between the number and distribution of diseased coronary vessels (including triple vessel and left main stem diseases). regardless of age, men were frequently treated with a coronary artery stent (67.9%). elderly women (aged c65 years) were more often treated conservatively (67%) while those younger women (aged b64 years) were frequently treated with a coronary artery stent (62.1%). in-hospital mortality rate was significantly higher for women than men (6.5 vs. 3.8%, p = 0.013). amongst the patients treated conservatively, elderly women had the highest in-hospital mortality when compared to the other patients (women c 65 years 19.2 vs. women b64 years 2.7%; men c65 years 13 vs. men b64 years 6.8%). compared to men, women were significantly older (p \ 0.001; 95% ci 12. 6-17.6) , more likely to have a history of hypertension (73.2 vs. 50.2%; p \ 0.001), diabetes (45.5 vs. 28.2%; p \ 0.001), hyperlipidemia (63.4 vs. 46.6%; p = 0.001), peripheral vascular (5.7 vs. 1.2%; p = 0.006) or ischemic heart diseases (28.5 vs. 15 .7%; p = 0.002) and less likely to be smokers (12.2 vs. 57.7%; p \ 0.001) or consume alcohol (0 vs. 10.1%; p \ 0.001). conclusions. elderly women who were treated conservatively had the highest in-hospital mortality during the early management of stemi. hôpital saint-louis, ap-hp, paris diderot university, hematology department, paris, france introduction. aml is considered as an oncology emergency as a proportion of patients experience life threatening complications within the first hours or days after diagnosis. early death had been shown to be statistically related to high white blood cell (wbc) and monoblastic leukemia 1-3 , with leukostasis and lysis syndrome as the most deadful events. objectives. to evaluate the relationship between timing of icu admission and outcomes in high risk aml patients at the earliest phase of the malignancy (before any chemotherapy) methods. retrospective study in a tertiary care teaching hospital. adult patients with newly diagnoses aml from 1998 to 2008 were included. patients admitted for an immediate life sustaining therapy (ventilation, vasopressors or renal replacement therapy) were excluded. 42 patients admitted directly to the icu (early admission) were matched for age, wbc and fab subtype with 42 patients primarily admitted in hematology ward. datasets were extracted from medical charts. results. 84 patients were included (42 early admitted to the icu and 42 admitted first to the wards). median follow up was 10.3 months. median age was 46.5 years (36-57). fab m4 or m5 was retrieved in 58% of the patients. karyotype was favorable for 30% and poor for 19%. median wbc was 103 9 10 9 l -1 . no statistical difference was seen for demographic and hematological parameters between early admitted patients and matched controls. among the 42 patients admitted first to the wards (controls), 20 were subsequently admitted to the icu (lately admitted) and 22 remained in ward during the entire treatment course (never admitted). the median time between diagnostic and icu admission of this last group was 4 (1-9) days. strikingly, patients lately admitted had more frequently dyspnea,oxygen requirement, high respiratory rate, low diastolic arterial pressure and lower first 24 h urine output. lately admitted patients were less likely to receive the complete dose of induction chemotherapy (68 vs. 88%) furthermore, late admission resulted in increased use of invasive mechanical ventilation (60 vs. 33%) and vaso-active drugs (60 vs. 16%). these differences resulted in longer stay in icu and decreased survival. conclusion. patients at the earliest phase of high risk aml who are lately admitted to the icu experience worse outcomes, with increased use of life-sustaining therapies and higher mortality, compared to patients early admitted to the icu. physiologic parameters at the time of aml diagnosis such as respiratory rate, diastolic blood pressure, spo 2 , or oxygen need are likely to help clinicians distinguish those patients at risk of late icu admission and subsequent adverse outcomes. studies are needed to assess the right place for newly diagnosed aml with physiological abnormalities but no organ dysfunction. atrial fibrillation (af) is the most common sustained tachyarrhythmia in the community. it has a prevalence of *10% in those over 75 years of age (1) . the chronic health consequences of chronic af are significant. it can cause impaired cardiac function, a fivefold increased risk of stroke and decreased life expectancy (2) . af is also the commonest arrhythmia in the critically ill, though a recent systematic review (3) was unable to recommend evidence based standards due to the heterogeneity of the studies. objectives. a retrospective cohort study to assess the impact that chronic af has on the outcome from critical illness. methods. all patients admitted with chronic af between 27/04/2006 and 05/09/2009 were identified. we recorded age, apache ii and predicted hospital mortality, actual icu and hospital mortality, past medical history, admitting diagnosis, medication, echo findings, anticoagulants given, therapy instituted, and any further events between icu and hospital discharge. the only data collected for the patients who did not develop af was their age, apache ii and predicted hospital mortality and actual icu and hospital mortality. data analysis using chi square test and mann-whitney u test were used where appropriate. results. 1168 patients were admitted to the icu over the study period, 46 of which had a history of chronic af (3.9%), the remaining results are shown in table 1 . chronic af had a prevalence of 3.9%, in keeping with previous studies, and the mean age in the chronic af group was significantly higher. interestingly, there was no difference in icu and hospital mortality between the 2 groups. despite the chronic af group being older with significantly worse apache ii scores. indeed the hospital mortality (30.4%) of those patients admitted with chronic af was over 30% less than predicted hospital mortality (44.2%). why patients with chronic af are outperforming expectation is not clear. it could be that apache ii is over estimating the severity of illness in these individuals, or is there something about the way chronic af is treated that affects the response to critical illness, for example, anticoagulation therapy? one of the major outcome measurements in burns centers is still mortality after severe burns. there are many predictive factors in admission as well as factors that are related with all the course of the disease responsible for survival after severe burn. many centers have a minimum standard of burn survival or la50 (the body surface area that kills 50% of people) and also have generated computer models of death probabilities based on age and tbsa (total body surface area) burned. objectives. to evaluate the outcome of the severely burned patients treated in the burn center and to develop a predictive model for survival from major burns in albania. the medical records of all acute burn patients admitted to the burn center of the university hospital center ''mother teresa'' in tirana, albania are reviewed retrospectively. statistical analyses are conducted using spss version 15. logistic regression is used for the prediction of death probability for two risk variables, tbsa burned and age. based on the index of evidence the variables are grouped in significant strata, from 1 to 5 for each variable. logistic regression equation is: where z = 3, 0-0 8, age 1-0 2, age 3-0 4, age 4-2 1, age 5+ 1, 5 tbsa1-1, 1 tbsa3-2, 0 tbsa4-2, 5 tbsa5 after calculating the probability of death for each record, we have done respective grouping according the mortality from 0-100%. results. during 1998-2008 are admitted altogether 2,337 patients in the burn center. overall mortality in icu is 10.5% with a significant reduction during the years, up to 4.4 in 2008. row burn mortality is 0.8 for 100,000 persons per year. la 50 for children is 60% tbsa; for adults 65% tbsa and for aged 45% tbsa. based on probability of death, we notice that older age and larger burn size are associated with a higher like hood of mortality. figure 1 gives an overview of death probability in our burn center. conclusions. the mortality reduction speaks up for a better work of our staff toward the patients. the predictive model may assist all the burn team to identify the crucial determinants of clinical outcome to establish a real basis for treatment standards and to allow future comparisons of new treatment strategies. (1) in mechanically ventilated (mv) critically ill patients. methods. prospective observational multicenter study during 2 weeks in november 2009. consecutive patients admitted to the participating icus and requiring mv for at least 6 h were included. maximal, minimal and mean intra-abdominal pressure (iap), were recorded on day 1, 2, 4 and 7. iah was defined as mean iap c 12 mmhg/24 h at least 1 day. following risk factors were recorded if evident during the first icu day or immediately before: respiratory failure, abdominal surgery with fascial closure, damage control laparatomy, major trauma/burns, prone positioning, gastroparesis, ileus, colonic pseudo-obstruction, ascites, hemo/pneumoperitoneum, intra-abdominal fluid collection, acidosis (ph \ 7.2), hypothermia (core t°\ 33°c), massive transfusion ([10 u of packed red cells/24 h), massive fluid resuscitation ([5 l/24 h), coagulopathy, oliguria and sepsis. results. 358 patients from 39 icus were included; mean apache ii score on admission was 19.8 (8.0) and 28-day mortality 31%. mean number of iap measurements was 3.2 per day. iah occurred in 163 patients (45.5%). only 41 pt (11.5%) had none of the studied risk factors, nevertheless 22% of them still developed iah. of the 68 patients with 5 or more risk factors, only 64.7% developed iah (table 1) . objectives. to describe the icu admission of our hospital for serious complications of hematology patients in the last 10 years. compare the characteristics of these patients throughout the study period. analyze mortality and their evolution from their admission to the icu. the evolution of hematologic patients has improved in recent years due to better supportive treatment, sometimes involving the use of specific treatments in the icu. a retrospective study of medical records of all patients with hematologic diseases were admitted to our icu from april 1999 until may 2009. we excluded patients admitted for channeling central catheter, diagnostic tests and bone marrow transplants. we selected a total of 85 patients (60% male) with a mean age of 45 years (range 15-77). the main hematological diagnoses were the most common aml (37%), acute lymphatic leukemia (16%), lymphoma (non-hodgkin's lymphoma) (16%), coagulopathy (7%), myelodysplastic syndrome (5%) and myeloma multiple (5%). the principal reason for admission in the unit were: acute respiratory failure (40%), followed by sepsis (35%) and less cns and cardiac problems (8 and 7%) respectively. as important risk factors of neutropenia and peripheral blood stem cells after transplantation. the icu mortality reached 52.6%. the average stay was 5.4 days. conclusions. the transfer to the icu allows a high percentage of hematological patients survive severe complications and the benefit continues after discharge. the mortality of icu patients in our series has not changed over the past 10 years, keeping both the characteristics of patients transferred. the consensus among the services of hematology and intensive care is essential to select and treat the best candidates to benefit from support in the icu and to improve current survival results. a retrospective (from 1994 to 2004) and prospective (from 2005 to 2008) analysis of obstetric patients (pregnant or postpartum admissions) admitted in our ccd was performed. results are expressed as mean (standard deviation) or frequency (percentage). chi 2 and t student tests were used for statistical analysis according to the different variables (spss 18.0, inc. chicago, il), accepting a p-value .05 as significant. results. 204 obstetric patients were included. mean maternal age was 30.53 (6.2) years and mean gestational age was 30.36 (8) weeks. apache ii score was 10.8 (6) . 97 (47.5%) patients were admitted to ccd due to an obstetric cause. the main diagnosis of this group were thrombotic microangiopathies 60 (29.4%) and hemorrhagic shock 18 (8.8%). thrombotic microangiopathy included 33 (55%) eclampsia-preeclampsia, 12 (20%) acute fatty liver, 9 (15%) hellp syndrome and 6 (10%) ptt-shu. in the remaining 52.5% (107 patients) the main reason for ccd admission not related to the pregnancy was respiratory failure 39 (36.4%). from the whole population included, 87 patients (42.6%) required mechanical ventilation (mv) with a mean duration of 4.94 (7.15) days. furthermore, 59 (28.92%) patients required surgical intervention (15.7% hysterectomy). the ending of pregnancy was made in 164 patients (80.39%), most cases by caesarean 78.04% (128 patients). mean length of stay in ccd was 7.17 (9.12) days. maternal mortality was 3.4% (7 patients), basically in the non-obstetric group (6 vs. 1) . conclusions. this is a large series of young obstetric critically ill patients with a low mortality. however, a non-depreciable part of the population included presented important morbidity. objectives. to identify the association of co-morbidities with mortality. methods. retrospective analysis of clinical process of diagnosing patients with severe sepsis/septic shock admitted to the intensive care unit (icu) in the period of november 2008 to october 2009. we collected demographic data, co-morbidities, and mortality in the icu hospitalization. statistical tests used were student's t and chi-square. we analyzed 85 patients admitted with this diagnosis, median age of 66 years and females 32.9%. in 72.9% (62 patients) appear co-morbidities, distributed as follows: hypertension 56.5%, 41.9% diabetes mellitus, cerebrovascular disease 27.4%, 11.3% chronic kidney disease; 12.9% neoplasic disease and chronic obstructive pulmonary disease 9.7%. the mean age (68.7, p \ 0.0001) was higher in this group. the overall mortality in the icu was 34.1% that has not increased significantly to 37.1% in the group with comorbidities, and the overall in-hospital mortality was 48.2% and rise significantly to 56.5% (p \ 0.03). conclusions. in our study, around 3-4 patients had co-morbidities and these facts and the age were those who contributed to higher mortality. the factors of greatest weight are those related to metabolic disease. the characterization of chronic illness in the icu is important in future larger epidemiological studies to better characterize this group of patients and the factors predictive of mortality to decrease the suffering of the patient and plan for admission to intensive care units. one year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study. introduction. despite the advances in respect to the development of objective criteria for admission of patients with hematologic malignancies to intensive care unit (icu), no evidence exists that they contributed to a reduction in the mortality, which depends from the aggressiveness of the cancer itself, its complications and even as a consequence of therapy. since the decision to admit one of these patients in icus involves a complex decision-making process, it becomes imperative to identify predictors that may help the clinician to discriminate the patients who may benefit from intensive care than those in which intensive care will be associated with just a prolongation of an agony. objectives.: to identify early prognostic factors in the admission of patients with hematological malignancy, admitted in the icu of a central university hospital. analysis of data prospectively collected and registered in a database of patients with hematological malignancy, admitted to the icu between january 2005 and december 2009. we collected for each patient demographic and clinical data (age, sex, length of stay, origin, previous treatment, stage of disease at admission, type of malignancy and aggressiveness, organ dysfunction at admission, co-morbidities, reason of admission), general severity scores (saps ii and apache ii) and organ dysfunction scores (sofa at admission to the icu, maximum sofa score and delta sofa). specific variables were correlated with mortality at the icu and hospital discharge. results. 137 patients (86 males and 51 females) fulfilled the inclusion criteria. the average age was 54 ± 14.79 years (17-84 years). the type of hematological malignancy was acute leukemia (55.5%), multiple myeloma (7.3%), myelodysplastic syndrome (2.9%), chronic leukemia (7.3%), low grade non-hodgkin lymphoma (6.6%), high grade non-hodgkin lymphoma (17.5%). the average length of stay in the hospital was 20.2 ± 23.3 days. most patients were admitted from the department of hemato-oncology ward of the hospital (72.3%), 6.6% of the emergency department and 21.2% of another hospital. the icu mortality was 42.3%, with a corresponding hospital mortality of 75.2%. the discriminative capacity of the severity scores, as assessed by the area under the roc curve (aroc) was 0.775 for saps ii and 0.713 for apache ii. for the delta sofa calculated for each organ dysfunction, progression of respiratory dysfunction/failure and cardiovascular failure demonstrated the best discriminative power (aroc of 0.718). conclusions. none of the variables showed a statistically acceptable relationship with icu or hospital mortality. the general severity indices saps ii and apache ii demonstrated a better discriminative power than the multiple organ failure scores. however, in this group of patients,it is still difficult to know objectively what factor or combination of factors may be useful in deciding the admission of the patient in an icu. recently due to new developments in interventional gastroenterology and new therapeutic options for treatment, gastroenterological and hepatological (geh) admissions to acute care settings has been decreased. for general intensive care units (icu) gastroenterological and hepatological (geh) diseases consititutes the minority of icu admissions. so we planned to find the incidence and clinical course of admissions due to geh complaints in a medical icu. objectives. main objective is to analyze clinical and epidemiological features of patients admitted to icu with geh disorders. other objectives are to analyze the mortality rate and the factors contributing mortality in these patients. and 2010 who stayed for more than 48 h were included. the prospectively developed data including demographics, prognostic scores and clinical features of patients were analyzed retrospectively. patients with geh disorders consituted 17% of patients admitted to icu. one hundred thirthythree patients with an age of 66 [54-77] years and gender of %55 male were included. more than half of these patients (59%) did not have any chronic geh disease. the patients were admitted most often from the emergency department (57%). the most frequent admission diagnosis was gastrointestinal bleeding (50%) followed by hepatic diseases including hepatic failure and acute hepatic encepahalopathy, biliary tract infection (15%), pancreatitis (5%) and enteric diseases including massive diarrhea and bowel obstruction (5%). on admission median apache ii and glasgow coma scores were 18 [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] and 15 [12] [13] [14] [15] [16] [17] [18] [19] , respectively. acute kidney injury (defined by rifle criteria risc, injury or failure) was found in 59 (%44) patients. the most common rifle class was class failure (22%). during icu stay 24 patients (18%) needed renal replacement therapy and 42 patients (32%) received mechanical ventilation. nosocomial infection developed in 23(17%) patients and icu aqıired severe sepsis occured in 22(17%) patients. icu and hospital mortality were 37% and 41% respectively. length of icu and hospital stays were 6 [4] [5] [6] [7] [8] [9] and 12 [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] days respectively. respiratory failure requiring mechanical ventilation, acute renal failure on admission and severe sepsis in the icu were found to be the independent factors determining mortality in these patients (p = 0.000, p = 0.042 and p = 0.002 respectively). patients with geh constitued 17% of patients admitted to icu. they usually do not have any chronic geh disease. gastrointestinal bleeding is the most frequent admission diagnosis. respiratuar and renal failure on admission and severe sepsis occured in the icu are the major determinats of mortality in these patients. introduction. in recent years described series with hematological patients in icu, but these studies are often limited because they are retrospective, single center in a few patients divided over many years. to determine the characteristics of mortality in this group is very important to assess their management in the icu. objective. to analyze prognostic factors associated with icu mortality of patients (pts) with hematologic malignancies admitted to the intensive care unit (ptu). method. an observational, transversal, prospective, multicenter oct conducted between june 2007 and october 2008. we conducted a descriptive analysis, chi-square, bivariate and logistic regression including variables with a value of p \ 0.2 with the sas statistical pauet to assess the factors influencing mortality in icu. we included 450 patients from 34 icus. the mean age was 54 years. the apache ii at admission was 22.89 ± 8.24 ) and the first day sofa ± 4.34 9.24 (8.84-9.64). the crude mortality icu was 51.6% (232 pts). we divide related mortality by infectious etiology (61%) versus other causes (39%). in univariate analysis the variables significantly associated with mortality were: males p \ 0.01, hematology plant from 0.007, 0.04 multiple myeloma, respiratory failure at admission .0001, tachycardia, 0.002, 0.001 hypothermia, tachypnea 0 02, apache ii c 20, more than two organ failures .0001, presence of ards \ 0.0001, invasive mechanical ventilation (imv) \ 0.0001, niv 0.0003, 0.0002 transfusion (of all products: red cells, platelets and plasma), acquisition intrauci infection 0.009, 10 days longer stay in icu 0.002. the presence of neutropenia was not associated (p = 0.0533) at a significantly higher mortality, or personal history, septic shock, bone marrow transplant or other reasons for admission to the icu. table 1 describe the independent factors associated with mortality in logistic regression analysis. variables classics such as septic shock or neutropenia not associated with mortality. and the independent variables associated with increased icu mortality were: vm, ards, severity and need for transfusion of blood products. results. 41 patients were identified. major haematology diagnoses were acute leukaemia 32%, nhl 22% and lymphoma 12%. mean time to icu admission was 13.4 days with 31% admitted within 24 h. the commonest reasons for icu admission were respiratory failure 49%, sepsis 33% and acute renal failure 7%. the mean number of organs supported was 2.9. 65% of patients had c 3 organ failure. mean apache ii score was 24.5. increasing organ failure correlated with increasing mortality. patients with 4 or 5 organ failure had 100% mortality. mean icu stay was 10 days with 35% having an icu stay of less than 48 h. icu mortality rate was 62.7%. 46.5% received invasive ventilation, 16.3% failed non-invasive ventilation (niv) and required invasive ventilation, 16.3% had niv only and 21% received no respiratory support. vasoactive support was given to 74.3% and rrt to 23.3%. invasive ventilation and niv were associated with a higher mortality; 90 and 60% versus 40% in spontaneously ventilating patients. vasoactive support was associated with more organ failure, longer icu stay and higher mortality. rrt was associated with a higher mortality 90 versus 54%. patients with a documented poor haematological prognosis had a higher mortality but also more organs supported. conclusions. from this study invasive ventilation, cardiovascular support and multiorgan failure are strongly associated with increased mortality. the need for rrt was not an independent predictor of mortality. close collaboration is needed between the specialities to allow early resuscitation and critical care support to avoid delayed admissions with multi organ failure. introduction. the prescription of stress ulcer prophylaxis (sup) in critically ill patients is relatively commonplace due to the association between physiological stress and gastrointestinal (g.i.) bleeding. however, recent guidelines recommend that only patients who are mechanically ventilated, and/or have a coagulopathy warrant prophylaxis. they also state that histamine receptor blockers (h2rb's) can be used primarily for sup (1). objectives. the aim of this audit was to compare prescription practice of sup at the itu/hdu at mayday hospital with those set out in the guidelines and to calculate the potential cost savings resulting from following these guidelines. methods. data prospectively collected from consecutive admissions to mayday hospital itu/hdu between october and november 2009. . data was collected on 56 patients, 3 had a g.i. bleed on admission, and 8 were already on sup so were excluded. 27 of 29 (96%) patients with major risk factors were prescribed sup, compared with 11 of 15 (73%) patients with no major risk factors. proton pump inhibitors (ppi's) were prescribed preferentially to h2rb's; 31 versus 14. the cost of sup during the audit period was £5,646. if we had only prescribed it to those at high risk the cost would have been £5,079.86, and if we had only used h2rb's the cost would have been £745.07. prescribing of sup in our unit does not reflect quenot's guidelines. this not only represents an increased cost but there are increased rates of nosocomial pneumonia and c. difficile diarrhoea associated with sup (2, 3) . there is little evidence showing the superiority of ppi's over h2rbs in the prophylaxis of bleeds; and there is evidence of an increased rate of the aforementioned infections with ppi's as compared to h2rb's (3). we prescribed ppi's to a significant majority of our patients; however, it is our opinion that our current unit practice is not dissimilar to that of the rest of the uk. we would encourage all critical care units to review their sup prescribing as our results show that significant savings can be made with judicious prescription of these drugs. . surprisingly little is published on the cost of drug treatment for critically ill patients. critical care is expensive, mainly due to the high staff ratio, expensive equipment but also due to a significant reliance on pharmacological management, which is usually funded with a limited drug budget. objectives. to explore the relationship between drug expenditure, patient acuity and outcome. methods. data was generated by retrospective analysis of consecutive patients admitted to our 35 bedded general adult icu/hdu in a london teaching hospital, during february 2009. patients were excluded from analysis if they were present in icu for less than 24 h. the first and final ccu days stay were not included so that only full days were analysed. daily drug-use per patient was manually extracted from the computerized icu management system (cis, qs, ge medical). costs of prescribed drugs, fluids and parenteral nutrition (pn) were calculated from the pharmacy computer system and analyzed using regression analysis (spss ver18). results. the patient characteristics and outcomes of the 82 patients are described in table 1 table 1 patient characteristics and outcomes age 63 (50-75)* gender (male n and %) 37 (45%) apache ii score 17.9 (8.5)** tiss score/patient 15.9 (6.1)** length of ccu stay (days) 3 (2-6)* ccu survival (n and %) 71 (86.6%) daily drug cost for each patient's stay £28.2 (£17.9-61.5)* daily drug cost for ccu and hospital survivors n = 61 £24.5 (13.8-47.8)* daily drug cost for ccu survivors who died in hospital n = 10 £38.0 (25.2-73.6)* daily drug cost for ccu non-survivors n = 11 £74.1 (39.7-80.3)* *median (interquartile range), **mean (standard deviation) the median daily drug cost was £28.2. of note, the drug cost was highest for ccu nonsurvivors compared with survivors and also compared with patients who died in hospital after ccu discharge (p = 0.01). multivariate regression analysis demonstrated that median daily drug cost/patient = -4.2 + 1.1 (mean tiss score) + 1.4 (apache ii score), r 2 = 35.6%; i.e median daily drug cost/patient was positively associated with tiss and apache ii score explaining 36% of the variation in cost seen. conclusions. this is the first study to show that daily drug expenditure in all general ccu adult patients correlates with patient acuity. median daily drug costs/patient were found to be £28.2. this parameter would make an interesting comparison with other units both nationally and internationally. daily drug costs can be predicted on the basis of apache ii and tiss scores. furthermore, this may be further refined to develop a quality marker of daily drug cost in relation to survivors and non-survivors. material, methods and results. all patients admitted to the icu of neurotrauma, which underwent a tracheostomy after admission. data were collected: affiliation, cause of admission, average stay, indication of tracheostomy, tracheostomy time delay from its indication, place of performance of the procedure (icu or operating room), perioperative complications (event during transfer to operating room, event during surgery: hypoxia, hypotension, arrhythmia, bleeding, premature extubation, false cannulation, cardiac arrest, pneumothorax or death), and postoperative complications in the first week (bleeding, difficulty in changing cannula, stomal infection, pneumothorax, death conclusions. tracheostomie is a simple surgical technique and 64.81% of tracheostomíes could be safely performed in the icu, saving hours of scheduled interventions in the operating room. there were no serious event during the transfer to the operating room or during the performance of tracheostomy. tracheostomized patients in icu, had a higher incidence of hypotension during surgery, although this complication in any case was serious or required treatment with vasoactive amines. when the tracheostomy is performed in the operating room, the delay shows a tendency to be higher, although this difference is not ss introduction. the concept of tight glyceamic control in critically ill has led to the rise of number of insulin infusion protocols designed to keep the blood sugar (bs) in predefined range. at the same time monitoring practices and patients populations vary greatly between intensive care units and thus so do the results. the matter is complicated by the absence of a widely agreed common glyceamic control indicators against which protocols can be evaluated and compared (1). to establish the quality of glyceamic control in two different intensive care units. to compare the quality of glyceamic control between two intensive care units, with different glyceamic protocols and blood sugar measurement practices. we conducted retrospective non-randomized population study comparing quality of glyceamic control in two independent and non-related intensive care units. time spend in pre-defined glyceamic range was chosen as a quality indicator for both units (1, 2) . data was collected from the electronic database and point of care bs measuring devices. the frequency distribution was analyzed to establish the patient-to-patient variability and a degree of bs deviation from the target value. results. units were different in method of sampling, frequency of sampling, target for optimal glyceamic range and instigated insulin protocol. data was collected on 104 patients (5, 234 bs measurement) in itu1 and 120 patients (3, 232 bs measurements) in itu2. mean bs was 7.2 (sd = 1.9) mmol/l in itu1 and 7.6 (sd = 2.3) mmol/l in itu2. conclusions. the performance of both protocols were satisfactory-92.8 and 89.24% of the time patients spend with bs less than 10 mmol/l in itu1 and itu2 respectively. the quality of glyceamic control on both itus is similar in terms of proportion of time spend in different glyceamic bands, with the exception of the longer time spend in a hyperglyceamic state in itu2. this study confirms the notion for a need of unified approach for evaluating quality of glyceamic control for in-patient populations. with an icu mortality of 36.8% and in-hospital mortality of 47.3%. the median transfusion threshold was a platelet count of 35 9 10 9 /l with yearly medians ranging from 21.5 9 10 9 /l to 40 9 10 9 /l. the % of platelet transfusions complying with bcsh guidelines increased from 53.1 to 68.8% during the 10 year study period. the specialties with the highest platelet requirement were general surgery (27.6%), haematology (12.1%) and general medicine (10.9%) as a % of total units transfused. the yearly median threshold for haematology patients fell from 31.5 9 10 9 /l in 2000 to 6 x10 9 /l in 2009, increasing guideline compliance from 16. introduction. numerous protocols (e.g. glycaemic control, hhh, renal rescue) have been introduced into icu. these protocols involve blood sampling to assess gases, haemoglobin, glucose and electrolytes. this may result in anaemia and subsequent transfusion and adverse clinical outcome (1, 2) . reducing blood loss due to sampling is an important blood conservation strategy (3) . currently, our icu processes over 4,000 blood samples per month. objectives. to study the indications for blood gas sampling in our icu and identify strategies to reduce sampling. methods. we performed a prospective, observational study over 1 week in 2009. the nurses completed a questionnaire per shift per patient to assess the primary and any secondary reasons for each sample. subsequent management changes, haemoglobin levels, active bleeding, and transfusion were also recorded. results. 424 blood samples from 25 patients and 106 questionnaires were analysed (61% of the nursing shifts). the range was 1-11 samples per patient per 12 h shift with a mean of 4. the secondary reasons showed that many samples were also being used for potassium (66%) and glucose (61%) monitoring. only 54% of samples changed management (potassium 24%, ventilatory settings 21%, glucose 9%). haemoglobin levels dropped by an average of 1 g/dl per week per patient with no active bleeding. 10 units of blood were transfused during the study period. conclusions. our study shows that reasons for sampling are often relatively weak and sampling is promoted by icu protocols. frequent sampling does not change management for a large proportion of samples and may cause anaemia. there are financial implications to frequent sampling-at the time of the study each sample cost £1.50 (€1.71) to process. each unit of blood transfused cost £140 (€159). we have considered ways to reduce sampling including changing the glucose protocol to capillary sampling, using 1 ml syringes, increased use of end tidal co 2 monitoring, protocol redesign and education of staff. reference(s it has been reported that tight glyceamic control is associated with net savings in terms of length of stay on the itu and critical care bed occupancy (1) . whilst it might be true for the overall length of stay, there is as yet, an un-quantified effect of frequent blood sugar measurement on the overall available nurse-patient time (2) . there is finite amount of nurse-patient time within any given shift and so prioritizing nursing care will be an important factor in critically ill and high dependency patients. this is specifically important for any saving to be realized from the introduction of automated blood sugar measurement devices (3). objectives. to quantify the amount of nursing time devoted to glyceamic control on itu or post-operative critical care environment based on data from four cohort studies on quality of glyceamic control in three intensive care units. a mathematical model, which takes into account frequency of blood sugar measurements and time to take each measurement was developed. stochastic analysis was used to calculate interdependency between quality of glyceamic control and the frequency of blood sugar measurements. introduction. introduction of trans-catheter aortic valve implantation (tavi) has been the latest technological advance in minimizing surgical stress and improving the chances of high-risk patient undergoing a successful aortic valve intervention (1) . the latest technology comes at considerable cost, which relates to both-the cost of the tavi valve and to it's delivery system. currently, there are no randomized controlled trails addressing the issue of cost-effectiveness of tavi versus surgical avr (2) . to build a cost-effectiveness model for patients undergoing either a tavi procedure or a surgical avr based on the level of care: level1 (ward based care), level2 (high dependency unit) and level3 (intensive care unit) during in-hospital stay, taking into account the rate of post-operative complications in both groups. methods. 26 tavi patients were matched against patients who had previously undergone surgical avr. the groups were matched for demographic and physiological risk factors, as well as euroscore. a decision analytical tree was constructed based on the length of stay in hospital and post-operative complications. a markov model was built and the effectiveness was measured in terms of improvement in nyha class, which was translated into the quality adjusted life years (qaly) (3) . results. the average in-hospital cost for tavi was £16,940 versus £13,462 for the surgical avr. the cost did not include the theatre time cost. in the surgical avr group the in-patient mean cost was greater than respective cost of the tavi group due to longer overall length of stay as in-patients. patients in the avr group spent more days in level3 and level2 care as compared to the tavi group. conclusions. the shorter length of stay and reduced rate of post-operative complications in the tavi group has got the potential to substantially reduce the overall in-patient cost and offset high cost of the valve. the effectiveness arm of the models did not differ for both groups, due to the lack of published literature, and raises a need for a qaly assessment for the effectiveness of tavi. the rate of post-operative complications in surgical avr group (higher rate of stroke and need for cardiac pacemaker) substantially affected the projected long-term cost. objectives. to determine if interventions for permanent pacing (ppm) and change of generator are more efficient in small hospitals. retrospective, transversal, observational study, measured through five diagnosis related groups (drg) that make up the casemix of pacemakers from the spanish minimum basic data set in 2007, descriptively analyzing demographic variables (age, gender), clinical (number of secondary diagnoses (nsd) and procedures (np), mortality) and management (total, preoperative length of stay, access, discharge, hospital size), defining inefficient stays exceeding 2 days the average. a bivariate study contrasting quantitative variables and comparisons between nominal and categorical, evaluating the independent association between short stay and different covariates studied building a binary logistic regression model, introducing as independent variables those that were significant in the bivariate as well as those considered that might be associated with the dependent variable. introduction. blood products are in short supply and with an ageing population the demand is likely to increase. blood use has been shown to be declining within the surgical specialties and intensive care, however overall use has remained unchanged. this audit looks at the use of packed red cells amonsgst medical inpatients to determine appropriateness. to determine if red cell use is appropraite among medical inpatients methods. medical blood transfusions were examined between august 2007 and august 2008. 207 patients were selected and pre and post transfusion haemoglobins were determined along with chronicity of anaemia. transfusions with haemoglobins of c8.1 g/dl triggered a case note review. over 12 months 1,071 patients were transfused 5,792 units. 3,593 units (62%) were given to 603 medical patients (56%), of which 207 patients were reviewed receiving 460 transfusions. average age was 70. in 111 patients pre transfusion haemoglobin was b8 g/dl (54%) and in 79 patients c8.1 g/dl (38%). in the group b8 g/dl 49 patients had acute anaemia and 62 had chronic anaemia. in the group c8.1 g/dl 22 patients had acute anaemia and 57 had chronic anaemia. 14 patients were not transfused and 3 had absent data. out of 71 case notes only 28 were available. 11 patients were transfused for acute anaemia, 17 for chronic anaemia of which 5 patients had cardiac disease, 4 had haematological disorders, 3 patients had iron deficiency anaemia and 1 patient was folate deficient. conclusions. chronic anaemia in the over 65 s accounted for the majority of transfusions. documentation was substandard. transfusions in chronic anaemia may be reduced by up-to-date guidance on transfusion triggers and alternative strategies to the use of blood products. (2009) results. the commonest indication for pct was long-term mechanical ventilation (73%) followed by airway protection (25.58%). 9.9% patients had platelets count\1 lac while 1.3% had severe thrombocytopenia (\40,000). 21.26% patients had an additional coagulopathy (hepatic failure and multiple organ failure), with inr [ 1.5 was present in 15.28% and deranged aptt in 5.98% patients. pct was safely performed in all these patients. the patients received platelets or fresh frozen plasma(ffp) before the procedure to optimize coagulation. only 0.66% had minor bleed through stoma, which was stopped in 10-15 min requiring gauze compression. conclusions. pct under videobronchoscopic guidance has low haemorrhagic complication rate in patients with deranged coagulation profile. platelets/ffp should be transfused before the procedure in these patients. introduction. blood components transfusion is common in the critically ill patient, as in the acute bleeding or the acute illness with multiorganic failure context. as any medical intervention, it has clinical indications and associated risks. clinical guidelines have evolved in a restrictive direction, suggesting that decision should be based on particular clinical situation and not only on analytical results. objectives. understand our transfusional practice and how close it is to clinical recommendations, as a quality indicator of our intensive care unit (icu). retrospective study using the icu patients data base. the population consists of patients with more than 24 h icu stay in 2009. the variables analysed are sex, age, diagnostic class (medical, surgical, trauma), saps ii score, mortality, number of transfusional events (erithrocyte concentrate, platelets, fresh frozen plasma and albumin) and the concordance to our hospital clinical guidelines. results. the population is of 334 patients, 63% of male gender, with an average age of 58 years-old. the admission diagnostic is medical in 50% of patients, with an average saps ii score of 44, median icu stay of 10 days and a mortality rate of 27%. 54% (n = 181) of patients received any kind of blood component transfusion, mostly erithrocyte concentrate (85% of patients), followed by albumin (54%). the populations of transfused patients is older (60 vs. 56 years-old), has a longer icu stay (12 vs. 7 days), higher saps ii score (46 vs. 40) and mortality rate (28.8 vs. 24.3%) . pretransfusional values are hemoglobin of 7.5 g/dl, 48,000 platelets/ul, and albumin of 2.1 g/dl. the level of concordance with recommendations is high for erithrocyte concentrate (85%), platelets (89%) and fresh frozen plasma (87%) but not for albumin (49%). conclusions. the level of transfusion is high in icu patients. the population who received transfusion has a more severe clinical condition and higher mortality rate. the level of concordance with recommendations is high with the exception of albumin, which use is still less standardized. with increasing acuity due to escalating icu bed demand, but the impact on patient safety is unclear. sdu continuous non-invasive physiologic monitoring of hr, rr, bp and spo 2 identifies cardio-respiratory instability often unnoticed by caregivers. causes may be alarm fatigue and/or high sdu nurse-to-patient ratios which make bedside monitoring insensitive. instability may become more resistant to intervention the longer it occurs. the impact of instability duration upon sdu patient outcomes is understudied. objectives. the study purpose was to determine the impact of cardiorespiratory instability duration experienced by in-patients being cared for on a monitored sdu upon hospital length of stay (los) and hospital charges. prospective study of monitored patients on a 24-bed trauma sdu over 16 weeks. noninvasive continuous monitoring data were downloaded from bedside monitors and analyzed for vital signs (vs) beyond local instability criteria: hr\40 or [140, rr\8 or [36, systolic bp \80 or [200, diastolic bp [110, spo 2 \85% . vs time plots of unstable patients were further assessed to judge instability as mild or serious. instability duration categorized as: none, [4] [5] [6] [7] [8] [$200 k) . relationships between instability duration and outcomes analyzed with chi-square for mild and serious instability. conclusions. there has been a marked improvement in the overall recording of sews since the previous study. it is of concern that respiratory rate was again the least well recorded parameter as this has been shown to be the best physiological predictor of impending cardiopulmonary arrest 1, 4 . this may be because respiratory rate is not provided by the automated monitoring devices available on the general wards in our hospital, and must be calculated manually. it demonstrated an increase in mortality even when tiss scores were taken into account as an independent risk factor. 4 since these publications critical care outreach and the use of early warning scores have become common place; however it was felt that time of discharge was still impacting on patient outcome. to review our post-unit mortality and readmission rate, with particular focus on the time of discharge. conclusions. our mortality and readmission data compare favourably with a recent publication. 5 there is a clear difference in mortality related to time of discharge; however this is for evening discharges as compared to night discharges in previous papers. [1] [2] [3] [4] the time of discharge may represent logistical issues of planned discharges or early discharge decisions due to pressure for beds. overnight discharge is an uncommon occurrence in our unit; this evidence suggests that previous concern about night discharges should be extended to evening discharges. transferring critically ill patients is a challenging task in the day to day activities of the critical care team. safe accomplishment of these transfers relies on skills of the persons accompanying and the resources available. guidelines have been produced by various professional bodies [1, 2] to safely accomplish these transfers. the competency document released by the royal college of anaesthetists, uk requires that junior trainees have appropriate knowledge, skills, attitude and behaviour in the principles of safe transfer of critically ill patients [3, 4] . to obtain information about trainee's perspective, experience and knowledge in transfer of critically ill. a web based online survey was sent to all the anaesthetic/itu trainees in the west midlands region of the uk. results. total number of respondents were 72. of these, 12.5% had less than 3 months of anaesthetic training before undertaking a transfer. only 33% had formal training on transfer of critically ill patients. 79% of the trainee's didn't have any competency based formal assessment of their skills, attitudes and behaviour in transfer of critically ill patients. majority of them (86%) felt that every one should undergo formal training before undertaking transfers. while 91% of the respondents have undertaken transfers during their training, only 33% have experienced some form of critical incident during these transfers. more than 50% of these adverse events were related to equipment failures while 27% were due to patient deterioration. nearly 75% of the trainees were not aware of terms and conditions of the insurance cover for these transfers. conclusions. this survey highlights the deficiencies involved in training the trainee's for transfer and the transfer itself. the results demonstrates that majority of the trainees would prefer to attend specific transfer courses before venturing out on an actual transfer. we hence recommended the following for implementation: improvement of training process for those undertaking transfers; regular monitoring of this process; regular analysis of critical incidents and acting upon it; making the insurance compulsory for those undertaking the transfers. greek hospitals, including initial management of critically ill patients and primary care for a growing proportion of the population. the impact of ed length of stay (los) on patient outcome has not been covered adequately by existing surveys so far. objectives. the aim of this study was to determine the association between ed overcrowding and outcomes for critically ill patients. in the present study, we included medical and surgical pts that all of them were intubated promptly to ed of 2 general hospitals of athens gr, for 12 months. pts survived [24 h were divided into 2 groups: ed boarding \6 h (group a) and ed boarding c6 h (group b). demographics, apache ii, diagnosis, los, and icu and hospital mortality were recorded. ed boarding time was measured in min. groups were compared using chi-square, mann-whitney, unpaired student's t tests and stepwise regression analysis. the collection of data lasted 12 months. results. in the ed, 196 critically ill patients with a mean age 59.6 ± 20.9 years and apache ii score 24.6 ± 12.7 were intubated. 144 pts were males and 52 were females with a mean age 54.5 ± 20.1 and 72.1 ± 17.5 years, and apache ii score 23.8 ± 13.2 and 26.4 ± 11.5 respectively. main diagnosis was multi trauma (72) objectives. we sought to assess the baseline characteristics and outcomes of the patients presenting af as a cause of met call activation. using the met database of one tertiary teaching hospital, we retrospectively reviewed all patients for which the met diagnosis was atrial fibrillation. we reviewed their clinical history, immediate treatment and outcome. these data were compared to those of a control group of randomly selected met calls with patients being matched for age, gender and ward of origin (surgical or medical). objectives. to ascertain the proportion of preventable in-hospital cardiac arrests occurring at university hospital lewisham. furthermore, to identify any common predictors of poor outcome that were apparent prior to those arrests and whether these are potentially modifiable. a case note review was performed on the cohort of patients who suffered inpatient cardiac arrests and who were admitted for icu (level-3) care post-resuscitation. these patients were identified using our quarterly feedback from the intensive care national audit and research centre (icnarc) case mix program dataset between april and september 2009. we found that half (11 out of 21) of our in hospital cardiac arrests resulted in death despite level-3 care post arrest within the audit period. 9 of these in-hospital arrests were deemed preventable from case note review and trust cardiac arrest call audit forms when available. in addition, in the preventable sub-group an arterial blood gas sample was not obtained in 7 out of 9, 77%. in all of these cases, the icu outreach team was not aware of the patient prior to the arrest. conclusions. in keeping with widely published data regarding survival to discharge after in-hospital cardiac arrest, the high mortality rate of 50% for this cohort of patients emphasises the importance of early recognition of abnormal physiology and timely intervention. with the sensitivity, specificity and validity of ews yet to be validated and no clear benefit proved from the introduction of met/outreach teams, an alternative strategy for earlier recognition of critically ill patients is needed. our data suggests that arterial blood gas sampling, an essential investigation central to the recognition of critically ill patients is being consistently overlooked and is an important factor influencing outcome. results. attended patients were 2,787, with mean age of 58, 7 years, and women represent 41, 2% of them. most demanding services were internal medicine (31%) followed by general surgery, haematology and nephrology. global data may be seen in table 1 . with regards to admissions to the icu of these patients, table 2 depicts the proportion between requested admissions, and refusals. introduction. tradicionally, critical care interventions are highly intensive, expensive and brief. critical illnesses and interventions that we use, can both contribute to posticu disability: catheter-related bacteraemia, polineuropathy, resistant organism, nutricional problems, complications of tracheostomy, prolonged analgesic. all these factors and a premature discharge from an ever full icu, can even have an impact on occult mortality after discharge from icu (between 6 and 20%). in our unit a follow up program have been implanted. when patients are about to be discharged from icu, icu clinicians selected those considered to be recoverable but fragile enough to have poor prognosis. objectives. to quantify the workload that a after icu follow-up entails, and to determine if this program impacts on mortality posticu. prospective and interventional study carried out during a 7 months period. at a 18 beds medical uci of a teaching hospital in malaga icu, 55 patients were enrolled in the follow up program. we assessed prognosis with sabadell score and severity of illness with apache ii score; and registered our interventions after discharge from icu. the final endpoint was status at hospital discharge: survivant or dead. we did 129 interventions in 55 patients: we changed a venous catheter 17 ocasions (40% of patients), changed analgesic schedule 15 times (27.2%), stopped antibiotics 13 times (24%), modified parenteral nutrition 25 times (45%) . we searched and treated sources of sleep deprivation (delirium, anxiety or insomnio) in 5 patients (9%); treated tracheostomy complications in 3 patients. mortality of 55 patients enrolled in this program was 3.7% (2 patients) even if the mean expected mortality by apache ii score was [30%. conclusions. in our study, implementation of a continued follow-up program after icu discharge in selected patients, carried out by icu staff, was associated with an important decrease of mortality. encouraging clinical results and a non-excesive workload for icu staff justify continuing this follow-up. objectives. various therapeutic protocols were used for the management of sepsis including hyperbaric oxygene (hbo) therapy. it has been shown that ozone therapy (ot) reduced inflammation in several entities and exhibits some similarity with hbo in regard to mechanisms of action. thus, we designed a study to evaluate the efficacy of ot in an experimental rat model of sepsis and to compare these effects with hbo. methods. forty male wistar albino rats were divided into sham, sepsis+cefepime (control), sepsis+cefepime+hbo (hbo), and sepsis+cefepime+ot (ot) groups. sepsis was induced by an intraperitoneal injection of 2.1 9 10 9 cfu escherichia coli; hbo was administered twice daily at 2.8-atm pressure for 90 min; ot was set as intraperitoneal injections of 0.7-mg/kg ozone/oxygen gas mixture once a day. the treatments were continued for 5 days after the induction of sepsis. at the end of experiment the lung tissues and blood samples of the study animals were harvested for biochemical and histopathologic analyses. results. lung tissue myeleperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, il-1b and tnf-a, were found to be ameliorated by the adjuvant use of hbo and ot when compared with the antibiotherapy alone group. histopathologic evaluation of the lung tissue samples confirmed the biochemical outcome. some measures indicated significantly more efficacy of ot than hbo. conclusions. our data presented that both hbo and ot reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for ot. these findings suggest that it may be possible to improve the outcome of sepsis by using ot as an adjuvant therapy. objectives. to investigate the regularity for change of paf, tm and vwf in septic rat, and the protective effects of statins on vascular endothelium. methods. fifty-four male sd rats were randomized into simvastatin with lps group (group a, n = 24) and lps group (group b, n = 24) and control group(n = 6). they were respectively accepted 10 ml/kg normal saline (ns) abdominal injection for both control group and group b, 10 ml/kg simvastatin abdominal injection for group a, then 15 h later, total 48 male sd rats from group a and group b were respectively accepted lps (10 mg/kg weight) abdominal injection to establish sepsis model and 10 ml/kg ns abdominal injection for control group. thereafter, detected the serum concentration of von willebrand factor (vwf), thrombomodulin(tm) and antithrombin (at-iii) at different point of time (1, 3, 6 and 12 h after lps abdominal injection) in both group a and group b by elisa, the endothelial cells from thoracic aorta was observed with electron microscope. under electron microscope scanning, endothelial cells in septic rats from group b were found disarranged. under transmission electron microscope, endothelial cells were found to be in prophase of apoptosis characterized by unclear cell membrane, thickened cellcell conjunction, disappeared desmosome and microfilament, dissolved or vacuolized organelles and agglutinated and evaporated chromatin gathering under the karyolemma, but the karyorrhexis were not found. no similar changes were found in group a. (1) introduction. sepsis induced lymphocyte apoptosis is believed to play an important role in the pathogenesis of sepsis and in the development of the immunesuppresion observed in septic patients. lymphocyte apoptosis not only decreases the number of functional lymphocytes but may also modify the immune response towards an anti-inflammatory state. erythropoietin (epo) has recently been recognized as a multifunctional cytokine with antiinflammatory, antioxidative, and antiapoptotic properties. objectives. this study aimed to test whether epo could mitigate peripheral blood mononuclear cell (pbmc) apoptosis and whether epo could modify the dynamic changes in lymphocyte-subsets in a porcine model of acute endotoxemia. methods. twenty-eight anesthetized and mechanical ventilated pigs were randomized to one of three groups: 1) epo group, epo administered 1 h prior to endotoxemia (n = 9); 2) placebo group, vehicle administered 1 h prior to endotoxemia (n = 9); 3) sham group, animals only anesthetized and mechanical ventilated. endotoxemia was induced by an infusion of lipopolysaccharide (lps). after 2 h the lps infusion was reduced to a maintenance dose and the animals were fluid resuscitated. pbmc were isolated at time 0, 60, 240, and 540 min of endotoxemia. apoptosis in pbmc and relevant lymphocyte subsets were assessed by staining with 7-amino-actinomycin d (7aad) and annexin v using multicolor flow cytometry. apoptotic lymphocytes in spleen were quantified by immunohistochemical staining for activated caspase-3. endotoxemia increased the number of apoptotic mononuclear cells in both blood (p = 0.002) and in spleen (p = 0.03), but with no significant modifying effects of epo. the numbers of both cd4+ (t-helper) and cd8+ (cytotoxic) t-cells declined during endotoxemia. cd21+ cells, defining b-lymphocytes, demonstrated a biphasic response with an immediate decline followed by an increase in number of b-cells. the dynamic changes in the lymphocyte subsets were not modified by epo. , and reduced the number of circulating leucocytes. epo had no modifying effects on these dynamic changes. furthermore, epo did not mitigate apoptosis in pbmcs analyzed by flow cytometry or in spleen lymphocytes analyzed by immunohistochemistry. this study does not support that epo confer protection against lymphocyte apoptosis. objectives. aim of this study was to investigate the effects of combined, recombinant human activated protein c (rhapc) and ceftazidime (cef) in our established model of acute respiratory distress syndrome (ards) and septic shock methods. thirty sheep (35-40 kg) were operatively prepared for chronic study, and were randomly allocated either to sham, control, rhapc, cef, or rhapc/cef groups (n = 6 each). after tracheostomy, acute lung injury and sepsis was produced in all groups, following an established protocol (1, 2) , except the sham group that received the vehicle. the sheep were studied for 24 h in an awake state and were ventilated with 100% oxygen. pao 2 /fio 2 ratio was determined intermittently. cef (3 g) was administered intravenously 1 and 13 h post injury. rhapc was given as a continuous infusion (24 mcg/kg/h), starting 1 h post injury. the animals were resuscitated with ringer's lactate solution to maintain filling pressures and hematocrit. lung tissue was obtained during necropsy and analyzed for myeloperoxidase (mpo) using a commercially available kit. statistical analysis: two-way anova and student-newman-keuls post hoc comparison. data are expressed as mean ± sem. significance p \ 0.05. . mpo levels (mu/mg protein) were 70 ± 8 in sham and significantly increased in the control group (140 ± 15*). the rhapc (118 ± 20*) and cef group (120 ± 18*) increased significantly vs. sham and tended to be lower than controls, but not statistically significant. mpo levels of combined rhapc/cef (90 ± 20*) showed no difference to sham, but were significantly lower than controls or rhapc or cef alone. conclusions. combined administration of rhapc and ceftazidime in ards associated with septic shock improved oxygenation more than cef or rhapc alone, and prevented the onset of ards. seleno-compounds, such as sodium selenite (na 2 seo 3 ) show conflicting clinical results in the treatment of sepsis. efficacy, as well as mechanism of action of na 2 seo 3 , are unclear, with prevailing opinion that it acts as an anti-oxidant. however, na 2 seo 3 has also oxidant properties that could have a paradoxical therapeutic role in septic shock by reducing over-activated phagocytic cells. indeed, in septic sheep, high dose na 2 seo 3 injection as bolus rather than continuous administration resulted in a beneficial effect on survival time, macro and microcirculation (1). objectives. to investigate at the endothelial level the mechanism of action of a bolus injection of a high oxidative dose of na 2 seo 3 . in 17 male wistar rats, lipopolysaccharide (lps, 55 mg/kg) or normal saline were injected intraperitoneally, followed 1 h later by either an intravenous bolus injection of na 2 seo 3 (corresponding to 0.4 mg/kg se) or normal saline. after 5 h of lps, extravasation of fluoroisothiocyanate-dextran and leukocyte-endothelium interaction in venules of the cremaster muscle were quantified by intravital microscopy. results. na 2 seo 3 did not alter systemic haemodynamic variables as compared to lps rats. there were no intergroup differences in fluoroisothiocyanate-dextran extravasation. lps significantly decreased leukocyte rolling when compared to control animals (p \ 0.05). bolus injection of na 2 seo 3 did not alter leukocyte rolling but decreased leukocyte adhesion and extravasation levels to control values. our results in endotoxemic rats suggest that a toxic dose of na 2 seo 3 may have a beneficial effect of on leukocyte-endothelium interaction without a significant effect on plasma extravasation. objectives. to design a model of sepsis in pigs characterized by an unchanged q t over time. methods. after a 12 h fasting, pigs (weight 27-30 kg) were sedated with ketamine (10 mg/ kg) and midazolam (0.5 mg/kg) i.m. animals were tracheostomized and anesthetized (propofol 15 mg/kg iv bolus, followed by 10 mg/kg/h), atracurium (0.5 mg/kg/h) and fentanil (5 lg/kg/ h). the internal jugular vein, carotid artery and pulmonary artery were catheterized for iv fluid administration and monitoring. a lumbotomy was performed and an ultrasonic blood flow and a laser-doppler microvascular flow probes were placed in the left renal artery and on the kidney surface to measure renal artery blood flow (rabf) and renal cortical blood flow (rcbf), respectively. a cystostomy was performed to collect and measure urine output (uo). sepsis was induced by the iv administration of live e. coli (1. our previous study showed that citrulline (cit) supplementation during endotoxemia improved microcirculatory flow and endothelial function, and prevented glycocalyx degradation as a consequence of increased arginine (arg)-dependent vascular nitric oxide (no) production. during sepsis the availability of arg, the substrate for endothelial no production, is tempered as a consequence of increased inflammatory no synthase (inos) activity. the reduced endothelial nos (enos) activity and vascular no production is believed to result in endothelial and vascular dysfunction. a shortage of arg availability for enos is considered the main cause of the dysfunction. previous studies have indicated cit as an important, if not exclusive, mediator for enos-derived no production. cit is a substrate for argininosuccinate synthetase, an arg-producing enzyme that co-localizes with enos in the caveolae, thus directly and exclusively supplying arg to enos. objectives. we investigated whether cit supplementation during an ongoing endotoxemia rescues the enos-derived no production in endothelial cells, thereby providing a mechanistic explanation for its positive in vivo effects. mice received a continuous intravenous endotoxin (lps, 200 lg total) infusion for 18 h alone or an 18 h lps infusion with cit (37.5 mg total) during the last 6 h of endotoxin infusion. after the 18 h infusion, the mice were sacrificed, arterial blood was sampled and the carotid arteries were removed. no production in the carotid arteries was measured ex vivo with 2-photon fluorescence microscopy, using a fluorescent copper-based no probe. amino-acid concentrations in plasma were measured by hplc. results. both cit and arg plasma concentrations were significantly increased in the lps-cit group compared with mice treated with lps alone (p \ 0.05). in vivo cit supplementation led to detectable levels of no production ex vivo in carotid smooth muscle cells (smc) and endothelial cells (ec) by using the no-probe with 2-photon fluorescence microscopy. while ec-derived no production was absent in the carotid arteries of mice treated with only lps, the smc-related no signal was undisturbed. no production in the ec of the lps-cit group was not blocked by the inos inhibitor 1,400 w, suggesting enos to be responsible for the observed effect. furthermore, ex vivo incubation of the carotid arteries of the lps-cit mice for 30 min with extra cit (75 mg/ml) resulted in prominently increased no production in the carotid ec, whilst this effect was not observed in the carotid arteries of lps without cit treated mice. conclusions. cit supplementation during murine sepsis rescues the enos-derived no production in carotid artery endothelial cells, providing a mechanistic base for the positive effect of cit supplementation on endothelial no synthase during endotoxemia. grant acknowledgment. objectives. investigated the mechanism involved in the clearance of bacteria observed after rpaf-ah treatment in sepsis model. mice were subjected to clp model, after 15 min, the mice were treated with rpaf-ah. the cfu counts and measured of mediators were determined. results. the numbers of bacteria (cfu) recovered in the peritoneal fluid was inhibited in rpaf-ah treated group (140.0/7.35), suggesting a more efficient clearance of bacteria after rpaf-ah treatment. direct incubation of s. typhimurium, e. coli and s. aureus failed to affect bacterial growth indicating lack of a direct effect of paf-ah on bacteria. administration of rpaf-ah in ccr2 (receptor for mcp-1/ccl2) deficient mice failed to increase bacterial clearance after clp, suggesting that mcp-1 signaling is involved in this phenomenon. rpaf-ah treatment also failed to increase bacterial clearance in inos deficient mice and no levels were found to be elevated (14.07 ± 5.5/22.57 ± 7.5) in peritoneal fluid of the mice treated with rpaf-ah after clp surgery. synergism for no production was also seen when macrophages stimulated with e. coli were treated with rpaf-ah+mcp-1 and correlated with better bacterial killing by macrophages. peritoneal macrophages from knockout mice for mcp-1, stimulated from lps+ifn inhibited no levels when compared to wt mice (60.18 ± 0.46/21.92 ± 0.12). this results indicating that, excessive mcp-1 favors macrophage production of no and hence the ability of macrophages to deal with invading bacteria. conclusions. we conclude that the increase in bacterial clearance is important for the protective effect of rpaf-ah in sepsis and that exist a signaling involving mcp-1/ccl2 and no in this system. introduction. disturbances within the microcirculation represent an important factor in the pathogenesis of multiple organ dysfunction during systemic inflammation and sepsis [1] . dehydroepiandosterone (dhea) has immunomodulatory effects and improves survival in several animal models of trauma, hemorrhage and sepsis but also causes potent vasodilatation [2] . to maintain efficient microcirculation we combined dhea with sodium orthovanadate (sov), which augments vascular contraction. furthermore, sov has been identified to attenuate tissue injury and improve survival related to inflammatory response [3] . objectives. we investigated whether the combined administration of dhea and sov has beneficial effects to microcirculation in experimental sepsis. we divided sixty male lewis rats into six groups: control group; ethanol (solvent) treated control group; dhea (50 mg/kg) + (7.5 mg/kg) treated control group; endotoxemic group (lps 15 mg/kg); dhea + sov treated endotoxemic group; dhea (25 mg/ kg) + sov treated endotoxemic group. two hours after lps challenge we performed intravital fluorescence microscopy of the intestinal wall in order to study leukocyte adhesion and functional capillary density (fcd). tnf-a, il-1a, il-4 and infc, gm-csf and mcp were measured at baseline and following 3 h of endotoxemia in all experimental groups. in comparison to untreated rats subjected to endotoxemia the treatment with dhea (both dosages) and sov resulted in a significant reduced number of adhering leukocytes in intestinal submucosal venules. furthermore, the mucosal functional capillary density was significantly improved. we did not identify any changes in cytokine plasma levels. conclusions. the study demonstrated beneficial effects of combined treatment with dhea and sov within the intestinal microcirculation in experimental endotoxemia. concomitant administration of sov permitted to reduce dhea dosage and prevent potential vasodilation without affecting anti-inflammatory dhea action. 1. spronk pe, zandstra df, ince c: bench-to-bedside review: sepsis is a disease of the microcirculation. crit introduction. sepsis is a disease of the microcirculation and impairment of the intestinal microcirculation during sepsis may cause a breakdown of gut barrier function thus releasing bacteria and their toxins into the systemic circulation [1] . consequently, the protection of the intestinal microcirculation represents a pivotal therapeutic target in severe systemic inflammation. cannabinoids that interact with cannabinoid receptors (cb1r and cb2r) have been shown to have immunomodulatory properties in in vivo and in vitro studies and the endocannabinoid system has been shown to be involved during systemic inflammation [2] . objectives. the aim of the present study was to examine the effects of cb2 receptor modulation on the intestinal microcirculation in experimental sepsis (endotoxemia) using intravital microscopy (ivm). we studied four groups of animals (lewis rats, n = 5 per group): healthy controls (con), endotoxemic animals (20 mg/kg lipopolysaccharide; lps), endotoxemic animals treated with cb2 agonist, hu308 (10 mg/kg iv), and endotoxemic animals treated with cb2 antagonist, am630 (2.5 mg/kg iv). intravital microscopy of the intestinal microcirculation was performed following 2 h lps/placebo administration. leukocyte adhesion and functional capillary density (fcd) were measured offline in a blinded fashion. results. following 2 h of endotoxemia, a significant increase of leukocyte adhesion in the intestinal submucosal venules (e.g., v1 venules: con 86.8 ± 16.8 n/mm 2 , lps 189.8 ± 27.6 n/mm 2 , p\ 0.05) was observed. capillary perfusion of the muscular and mucosal layers of the intestinal wall was significantly reduced (e.g., circular muscular layer: con 109.9 ± 7.8 cm/cm 2 , lps 82.4 ± 3.5 cm/cm 2 ). treatment of endotoxemic animals with the cb2 receptor agonist, hu308, further increased leukocyte adhesion (v1 venules: 259.9 ± 20.0 n/mm 2 ), whereas cb2 receptor inhibition by am630 significantly reduced leukocyte activation (v1 venules: 142.4 ± 16.1 n/mm 2 ) and restored capillary perfusion (circular muscular layer: 107.7 ± 8.9 cm/cm 2 ). conclusions. the data support the hypothesis, that cb2 receptor signalling is involved in the impairment of the intestinal microcirculation during sepsis. blocking cb2 receptor signalling reduces leukocyte activation and improves capillary perfusion in acute endotoxemia in rats. the long-term effect of modulating cb2 receptors in more clinical sepsis models needs further investigation. [1] . this study compares dobutamine and levosimendan for the treatment of circulatory failure in septic shock and assesses survival benefits. objectives. in this controlled randomized doubleblinded study 25 anaesthetized and ventilated pigs (37.1 ± 5.1 kg) were enrolled after approval by the local governmental commission. methods. by continuous infusion of endotoxin (escherichia coli serotype 0111:b4, sigma-aldrich; 7.8 ± 2.0 lg/kg/h) over a time period of 3.5 ± 0.2 h, septic shock was induced. hemodynamic stabilization was performed by either use of the vasopressor norepinephrine alone (control group; n = 5) or in combination with levosimendan (0.4 lg/kg/min; n = 10) or dobutamine (15.0 lg/ kg/min; n = 10). in a setting of 10 h of measurements and treatment heart rate (hr), map, central venous pressure (cvp), pulmonary artery pressure (mpap) and cardiac output (co) were recorded continuously and evaluated hourly. beside norepinephrine requirement and mixed venous oxygen saturation (svo 2 ) mean survival time and survival rate within the measurement period were analysed. results. after endotoxinemia septic shock was marked by reduction of co and svo 2 [p \ 0.05]. mean survival time and survival rate were superior in levosimendan treated animals ( table 1 ). norepinephrine consumption was lowest in the levosimendan group. after 10 h, co of surviving animals was highest in the levosimendan group and statistically different compared with the control group. comparison of parameters hr, map, cvp and mpap showed no differences between treatments. conclusions. the complementary use of the calcium sensitizer levosimendan provides potential survival advantage in endotoxemic septic shock. beside an increase in co, improvement of regional organ perfusion or protection could be an explanation and has to be shown by further analysis. reference(s methods. the study group consisted of 100 patients with shock on vasopressor support and control group had 100 normotensive patients. arterial and capillary samples were taken simultaneously and were tested immediately at the bedside. the results of the paired measurements were analysed as a scatter plot by bland and altman method and were expressed as a correlation coefficient. values were considered to disagree significantly when the difference exceeded 20%. results. mean arterial and capillary sugars (mg/dl) in study and control groups were 164.7 ± 70 and 157.4 ± 68.9, and 167.1 ± 62.2 and 167.5 ± 61, respectively. on bland-altman analysis, 6% in study group and 5% in control group were out of range (acceptable limit \ 5%) [ figures 1, 2] . correlation between capillary and arterial values was less in the study group (r = 0.917, p .001 vs. r = 0.979, p \ 0.001). in addition, the disagreement between capillary and arterial values was more than 20% in 18% of the patients in the study group vs. 3% in control group (p = 0.015) (iso standard \ 5%). conclusions. capillary blood glucose monitoring can be applied reliably to patients in icu. however, caution must be exercised in patients with shock in whom arterial blood may be preferred. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 objectives. our primary objective was to evaluate the safety and efficacy of a single oral high dose vitamin d3 supplementation in an intensive care setting over a one-week observation period. methods. 540,000 iu (corresponding to 13.5 mg) of cholecalciferol (d) dissolved in 45 ml herbal oil or matched placebo (pbo) were given enterally (via nasogastric feeding tube or swallowed) to 25 patients with vitamin d deficiency [25(oh)d b 20 ng/ml] in the medical icu. results. baseline characteristics including age, sex and saps ii were balanced between the two groups (mean age 62 ± 16 years, 76% male, saps ii 36 ± 18). mean serum 25(oh)d levels at baseline were 14 ± 4 ng/ml in both groups. the mean serum 25(oh)d increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). two patients showed a small (7 ng/ml) or no response (1 ng/ml) attributable to gastrointestinal dysfunction after prolonged hypoxia and gastrointestinal gvhd after allogeneic stem cell transplantation. the time course of the 25(oh)d response is given in figure 1 . introduction. considerable controversy has emerged as to whether tight glucose control (tgc) is warranted in all critically ill adult patients. recently, a new blood glucose upper limit (10 mmol/l) has been assessed as more appropriate. rather than blood glucose target ranges, algorithms used to achieve tgc should be numerically evaluated before initiating clinical trials (preclinical validation test). our purpose was to assess performances of tgc algorithms in realistic virtual icu patients. we compared numerically the nice-sugar algorithm (n-s) 1 and the cgao system (cgao) used in the ongoing cgao-rea study [clinicaltrials.gov, id:nct01002482] . a set of virtual patients constituting the test bench was built with 1) real data coming from patients controlled with cgao before starting cgao-rea and 2) a non-linear pharmaco-dynamic glucoseinsulin system model 2 where patient endogenous glucose clearance and insulin-sensitivity were time varying parameters. in order to anticipate how algorithms would manage glycaemic control in clinical settings, delayed controls and inaccuracy of glucometers were implemented. the overall performance of each algorithm over the whole stay was assessed according to standard scores. results. the percentage of time in the target range [4.4-6. 1 mmol/l] with n-s was less than 50% for almost all patients. in insulin-sensitive patients, glycemic fluctuations and sometimes severe hypoglycemia are induced by n-s (fig. 1 ). the mean time in the target range with cgao was about 60% and variability scores were significantly lower than with n-s. mean glucose and standard deviations were always lower with cgao than with n-s. a numerical test bench constituted of realistic virtual icu patients, whose features were defined from real data obtained in patients under glycemic control, enabled to determine the best algorithms candidate for further evaluation in clinical settings. according to this approach, the algorithm used to achieve tgc in nice-sugar would not have been selected for such a large clinical trial while cgao reached the first validation step in simulation. we recommend that further glucose control studies focus not only on the target range but also on the algorithmic properties. introduction. there has been much debate in recent years about the appropriate level of blood glucose for intensive care patients with proposals of different levels of glucose control using insulin infusions. one risk of intensive glucose control is hypoglycaemia and this has been proposed as a measure of quality of care given by delivering the protocol safely. the nice-sugar 1 trial found that intensive glucose control increased mortality among adults in intensive care. objectives. the aim of our study was to record hypoglycaemia and study it's relation to insulin therapy. insulin therapy on our unit follows the recommendations of the nice-sugar trial. methods. hypoglycaemia was recorded as a blood glucose level\3 mmol/l. levels were detected using the blood gas analyser (radiometer 825 m). data was recorded at the time of hypoglycaemia to provide an explanation using the innovian system which is the paperless patient record system on our unit. data was obtained over a period of 3 months between october 2009 and december 2009. data recorded included adverse events which were defined as worsening shock and/or increasing inotropic support. feeding status at the time of hypoglycaemia was recorded. results. there were a total of 375 admissions over this period and there were a total of 13,304 blood glucose measurements. 24 incidents of hypoglycaemia were recorded, of which 13 patients were on insulin and 11 were not. of the 13 patients who were on insulin, 5 had adverse events at the time of hypoglycaemia. all these 5 patients died within 24 h of the adverse event. all except one was on full feed. the others had minimal feed due to poor absorption. of the 8 patients who did not have adverse events, 7 were discharged and one died 2 days after the hypoglycaemic event due to worsening sepsis. of the 13 patients on insulin, there were 3 iatrogenic errors where feeding was stopped and the insulin was left on. none resulted in any adverse outcome for the patients. of the 11 patients who were not on insulin therapy, 8 had adverse events at the time. 7 died within 24 h of the adverse event and 1 died 2 days later. the remaining 3 patients were discharged. none of the 11 patients were on full feeding protocol. conclusions. our findings suggest that hypoglycaemia in our unit is not primarily related to insulin therapy. it is related to adverse events and possibly inappropriate feeding at the time of hypoglycaemia. hypoglycaemia, in the absence of insulin therapy, is associated with a poor outcome. use of hypoglycaemia as a quality indicator should be interpreted with caution. introduction. vitamin d deficiency seems increasingly prevalent. pleiotropic effects of vitamin d like immunomodulation and effects on muscle strength may be of special importance to critically ill patients [1] . however, vitamin d deficiency has only been studied in small and selected groups of icu patients [2] . objectives. to prospectively determine the prevalence of vitamin d deficiency in winter and summer and relate vitamin d status to outcome in cohorts of critically ill patients. results. vit d was measured in 111 patients admitted in winter and 112 patients admitted in summer (table 1 ). mean vit d was significantly lower in winter than in summer. in winter, 85% was deficient, 49% severely deficient. in summer, 50% was deficient, 9% severely deficient. predicted mortality was higher in winter and higher in vit d deficient patients. observed mortality was lower than predicted in all groups, but not different between groups. including both vit d and season in a multiple regression analysis, winter (p = 0.004) and not vit d (p = 0.94) was related to predicted mortality. introduction. glucagon-like peptide-1 (glp-1) lowers blood glucose via stimulation of insulin and suppression of glucagon secretion, as well as slowing gastric emptying. we have previously shown that exogenous glp-1 attenuates hyperglycaemia in non-diabetic critically ill patients [1, 2] . however, islet cell function in critically ill diabetic patients may be so disturbed that pharmacological doses of glp-1 have no effect in this group. objectives. the aim of this study was to evaluate the effect of exogenous glp-1 on glycaemic excursions during intraduodenal nutrient infusion in critically ill patients with preexisting type-2 diabetes mellitus. methods. nine critically ill, mechanically ventilated, patients with pre-existing type-2 diabetes (8 m:1f, age 56 ± 6 years, hba1c 8.7% ± 0.7%, bmi 35 ± 3 kg/m 2 , apache ii on day 1 of study 17 ± 3, days in icu on day 1 of study 5 ± 1) received iv infusions of glp-1 (1.2 pmol/kg/min), and placebo, from t = 0-270 min on separate days in a randomised, double-blind, fashion. between t = 30-270 min a liquid nutrient (ensure) was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric feeding catheter. blood glucose concentrations were measured by glucometer at 15 min intervals. data are mean±sem and comparisons are using student's t test. results. prior to the commencement of iv infusions there was no difference in blood glucose between the groups (at t-0 min: glp-1: 8.1±0.7 mmol/l vs. placebo: 8.8 ±1.1 mmol/ l; p = 0.38). during fasting, glp-1 had no effect on glycaemia (at t = 30 min: glp-1: 7.7 ± 0.6 mmol/l vs. placebo: 8.9 ± 1.1 mmol/l; p = 0.18). however, glp-1 attenuated the overall glycaemic response to the nutrient (auc 30-270 min : glp-1: 2,208 ± 158 mmol/l.min vs. placebo: 2,647 ± 247 mmol/l.min; p \ 0.01), as well as the peak blood glucose (glp-1: 11.1 ± 0.9 mmol/l vs. placebo: 12.5 ± 1.1 mmol/l; p \ 0.04) conclusions. exogenous glp-1 is effective in reducing the glycaemic excursions that occur with enteral nutrient critically ill patients with pre-existing type 2 diabetes mellitus. these data indicating that further studies using glp-1, or its analogues, are warranted in this group. 2, 3, 4, 5 , whilst raising concerns regarding an increased risk of hypoglycaemia. 3, 4, 5 . locally most units adopt a protocol that reflects the practice of the original 2001 study. objectives. this study was conceived due to concerns around the safety of tight glycaemic control (tgc). our objectives were to measure adherence to our local policies and ascertain our true rates of hypoglycaemia. methods. this study was designed as a retrospective audit on four critical care units in the cheshire and mersey critical care network. each site used the same audit tool but adapted it to allow for differences in local practice and protocols. data pertaining to the prescribing and administration of insulin was collected daily over a 1 week period (the time of data collection varied from day to day). the doctors and nursing staff were unaware of the audit and the data was collected by the ward pharmacist who suggested modifications to therapy if it was deemed inappropriate or unsafe. results. 109 patient days worth of data was collected with 897 blood glucoses checked in this period. 100% of patients receiving insulin had insulin prescribed. only 23% of blood glucoses were within the target range set by the local protocol. however, of all the results only 3.5% were ''low'' as defined by the local protocol, and only 0.1% (1/897) were hypoglycaemic episodes as defined in the greet van den berghe paper of 2001 (\2.2 mmol/l). conversely, 73.5% were above the target range. in the 2 trusts that recorded how many of these levels were[8 mmol/l (a proposed alternative upper limit), the rates were 43 and 46%. in response to a blood glucose the policies suggest dosage adjustments/maintenance. on only 46% of occasions were the adjustments made correct. insulin infusions appeared to be managed safely by nursing staff. insulin, if given, was always prescribed and hypoglycaemia (blood glucose \2.2 mmol/l) occurred on only one occasion. although safe, adustments often didn't follow the protocols and the patients' blood glucose were within the target range only 23% of the time, potentially negating many of the perceived benefits of tgc. reasons for non-compliance with the protocols was difficult to objectively establish reference(s). introduction. diabetes mellitus has been associated with an increased risk of adverse outcomes after coronary artery bypass grafting. hemoglobin a1c is a reliable measure of long-term glucose control. it is unknown whether adequacy of diabetic control, measured by hemoglobin a1c, is a predictor of adverse outcomes after coronary artery bypass grafting. material and method. we evaluated 123 consecutive diabetic patients who underwent primary, elective coronary artery bypass grafting at the anadolu medical center. hba1c levels of all patients with diabetes mellitus were measured and value of 7% or greater was used as a threshold for uncontrolled hyperglycemia. all the peroperative variables were recorded and then, statistically evaluated. the statistical analysis was realised by t test for parametric variables and chi-square test for nonparametric variables. results. there were 305 consecutive patients that underwent elective coronary artery bypass graft surgery between january 2009 and april 2010. among them, 123 patients had diabetes mellitus and others not. there were no significant differences between groups regarding each adverse outcomes (table 1) . although, 13 (68.5%) of total 19 surgical site infection in 305 patients had been seen in 123 diabetic patients, there were also no significant differences between groups regarding the rate of infections (table 2 ). there was no early postoperative mortality in 123 diabetic patients. insuline treatment (iit) , by implementing a completely nurse driven protocol as in the leuven i study, to achieve tight glucose control in our 16-bed medical(cardio-)surgical icu and 6 non-ventilator beds. in the last year, the benefit of iit and the possible detrimental effects of hypoglycemia on survival have been heavily debated. objectives. the goal is to analyze our daily practice in all icu patients and compare this with the intensive treated groups from the leuven 1, visep en nice-sugar trial. methods. we compared mean morning blood glucose levels and the percentage of patients who had a hypoglycaemia, defined as glucose below 2.3 mmol/l, from 2006 to 2009. the frequency of control and the insulin dosage was comparable to the leuven 1 study. enteral or parenteral feeding was started at admission. no standard intravenous glucose was used. glucose was measured with arterial blood samples on the abl800flex radiometer as poct. results. in our patients, the mean morning blood glucose was higher than in the leuven 1 study and comparable to the visep and nice-sugar. the percentage of hypoglycemia on our icu was lower in comparison with the visep and nice-sugar. this may be explained by the availability of a poct on our icu which allows quick adjustments of the insulin dosage. conclusions. effective tgc with sprint resolved organ failure faster, and for a greater percentage of patients who had similar admission and maximum sofa scores, compared to a matched retrospective conventional control cohort. these morbidity reductions mirror the reduced mortality seen with sprint. these results suggest that reduced organ failure, assessed by sofa, is a fundamental element in reduced mortality when tgc is implemented effectively. introduction. tight glycaemic control was reported to reduce mortality in selected surgical critically ill patients and lowering of blood glucose (bg) levels was recommended as a means of improving patient outcomes (1) . however, this approach has been linked with significant risk of hypoglycaemia. recently, several studies have confirmed significant associations between variability of bg levels and patient outcomes (2). objectives. to evaluate the association between bg variability and hypoglycaemia in a mixed adult icu. methods. retrospective analysis of the prospectively collected and stored bg measurements over a 1 year period, during which tight glycaemic control was targeted in all patients. every day we have calculated the bg coefficient variation as expressed by sd/mean bg level. we have divided the patients into low, medium and high variability groups (0-15, 16-50 and [50, respectively) . hypoglycaemia was determined if bg was below 4.4 mmol/l. for statistical analysis chi-square test and pearsons correlation test was used. results. 584 patients were admitted over the 1-year period, providing 2357 daily data points. bg variability was high in 16 daily measurements (0.7%), medium in 570 (24.2%) and low in 1771 (75.1%). hypoglycaemia occurred in 401 measurement points (17.0%). hypoglycaemia was observed at all points (100%) when bg variability was high vs. 32.8% when bg variability was medium and 11.2% when bg variability was low and this difference was statistically significant (p = 0.001). we observed a significant correlation between increased bg variability and hypoglycaemia (r = 0.280, p = 0.001). conclusions. increased bg variability as expressed by coefficient variation is associated with hypoglycaemia, when measured daily in a mixed icu population employing tight glucose control. decreasing the variability of the bg concentration may be an important dimension of glucose management. if reducing swings in the bg concentration is a major mechanism behind the beneficial effects of glucose control, it may not be necessary to pursue lower glucose levels with the associated risk of hypoglycemia. ). there were two major outliers which may skew the results in favour of the hypothesis. if these two results are removed (fig. 1 ) the statistical significance remains strong (n v * p \ 0.008; **p = 0.003; ***p = 0.009)). standard multiple regression analysis found the most useful predictors of t 4 [mid] were 'time with aki' and 'serum urea' (beta coefficient 0.33 and 0.31 (p \ 0.05) respectively). 4 crcl, serum creatinine and urine output did not add further predictive statistical power. conclusions. this study demonstrates a reduction in the hepatic metabolism of midazolam associated with aki. this effect is related most strongly to the length of time the patient has suffered with aki. our results are similar to the ncepod report. even with multiple recommendations by ncepod and the national institute for clinical excellence (nice) 2 recognition of the critically ill remains poor. detection of organ failure risk is vital to implement preventative strategies. we found a delay in aki recognition and a lack of risk assessment. observations, included in admission protocols, were recorded, but investigations outside of these, were often absent. nice 2 suggest management should be physiologically and not diagnosis based but few patients had a documented physiological plan. we suggest improving under and postgraduate education to increase awareness of aki. this could occur as an extension to the national, acute life-threatening events recognition and treatment course. an aki admission protocol may allow identification of at risk patients and instigate appropriate monitoring, investigation and management. improved ward based fluid monitoring and management would reduce deterioration. incorporation of a physiological monitoring plan on the icu observation chart may reduce preventable aki. there was no effect in 2 patients with extensive stroke and high severity of a glasgow score (4-6 points in an observational prospective study, a total of 200 patients who admitted during 6 months in a medical and surgical intensive care unit and didn 0 t have any recent history of renal replacement therapy were included in the study. 66(33%) of all patients was in aki (acute kidney injury) group according to the akin (acute kidney injury network) definition. the mean of age in aki group was more than non-aki (54.5 ± 19.1, 43.9 ± 18.7 respectively; p \ 0.001); and had worse condition according to apache ii (acute physiology and chronic health evaluation ii) score (12.3 ± 5.6 vs. 6.9 ± 3.6; p \ 0.001). the aki patients stayed longer in icu rather than non-aki patients (7.6 ± 7.6 vs. 3.7 ± 2.8 days respectively; p \ 0.001); with more mortality rate (19.7 vs. 1%; p \ 0.001). also the mechanical ventilation days, time of vasoacive drugs and the use of dobutamin were more in aki group (p \ 0.001; p = 0.007 and p = 0.007 respectively). the aki was a significant predictor for mortality using the multivariate logistic regression (or adj = 14.8; 95%ci: 1.8-121.98); and had the same sensitivity as the apache ii score in prediction of mortality (sen. = 0.93). objectives. the purpose of this study was to evaluate renal function in children with congenital heart disease (chd) undergoing cardiac surgery with cpb. we conducted prospective, non randomized observational study at the tertiary care university children's hospital 12-bed surgical icu. study protocol was approved by hospital ethics commission. the study included 17 patients with chd with body weight from 2.8 to 17 kg (mean 9.41 ± 5.02 kg) and age from 14 days to 4 years (mean age 20 months). there were 8 patients with ventricular septal defect (vsd), 4 patients had atrioventricular septal defect (avsd), two had total anomalous pulmonary venous drainage (tapvd), one had tetrology of fallot (tof), one had transposition of great arteries (tga), and one had aortic stenosis, requiring ross operation. urine was collected in the postoperative period during the first 24 h after surgery for determination of clcr. the serum creatinine (scr) level was determined by jaffé 0 s method (cobas 6000 analyzer, roche). harrison am et al. [1] shows that estimated creatinine clearence (clcr) using schwartz formula does not accurately predict clcr. therefore we used standard formula for clcr calculations. urine output, inotrope score, duration of aortic cross clamping and cardiopulmonary bypass was recorded. we applied rifle criteria to assess renal functions, using clcr as a variable reflecting glomerular filtration rate (gfr). objectives. evaluate whether a real-time alert of worsening of rifle class, through the physicians' dect telephone system, would affect therapeutic interventions for aki and progression of rifle class. single centre, prospective intervention study during a 6-month period in our 36bed surgical and medical icu. three study phases were compared: a 1.5-month control phase (con1) where physicians were blinded for the electronic alerts, a 3-month intervention phase where electronic alerts of worsening rifle class were made available to the physicians through the dect telephone system (int), followed by a second 1.5 month control period (con2). pasw statistics 18 was used for statistical analysis and a double sided p value of .05 was considered as significant. at study entry, before and after to receive antioxidant or placebo concentration the blood was drawn, to posterior determination of thiobarbituric acid reactive species (tbars), protein carbonyls, total nitrite concentration and il-6. results. the use of nac+dfx decreases oxidative damage parameters. patients at antioxidant arm have, despite not reaching statistical significance, a decrease on plasma il-6 levels 24 h after the start of treatment. as observed to oxidative damage parameters, il-6 returned to the placebo levels after the end of antioxidant administration. the nitrite levels increased 24 h after nac+dfx, returning to placebo levels 48 and 72 h. the incidence of arf using the rifle criteria was not significantly different in the two arms, and this was also true to a number of secondary end points, none of which showed significant differences between the treatment arms. analyzing the subgroups of the sofa score we observed at day 2 a worse cardiovascular sofa in the nac+dfx arm (3.5 ± 1.1 vs. 1.6 ± 1.9, p = 0.01) and a better renal sofa in antioxidant treated patients (0.57 ± 1.0 vs. 1.6 ± 1.2, p = 0.02). conclusions. we demonstrated that nac + dfx administration was able to decrease plasma markers of oxidative damage and to a minor extend il-6 plasma levels. we believe that the use of antioxidants could be an alternative adjuvant therapy to prevent arf in critical ill patients with hypothension. table 1 were found to be independent risk factors for postoperative aki: objectives. we aimed to access prospectively whether the use of antioxindants has beneficial effects in renal function of critical-ill patients undergoing imaging studies with intravenous radio-opaque agents (ivca). patients were recruited from those hospitalized in a tertiary intensive care unit between 2009 and 2010. inclusion criteria were: a) requirement for imaging studies with ivca b) no use of renal replacement therapy. patients were randomized to receive before and after imaging, either antioxidants (n-acetyl-cysteine 1,200 mg and ascorbic acid 2 g and 200 ml ns0.9%) (sg) or 200 cc ns0.9% (cg). renal function was assessed by serum levels of creatinine and cystatin c assessed before and at 24, 48 h following administration of ivca. patients were followed until discharge. systatin c was measured by elisa. conclusions. the results of this study suggest that the use of preventive antioxidant therapy may protect critical-ill patients from contrast-induced nephropathy. our preliminary results have to be confirmed in larger cohorts. acute coronary occlusion is the leading cause of cardiac arrest. because of limited data, the indications and timing of coronary angiography and angioplasty in survivors of out of hospital cardiac arrest are controversial. objectives. using data from the parisian region out of hospital cardiac arrest (procat) prospective registry, we performed an analysis to assess the impact of an invasive strategy on hospital survival. between january 2003 and december 2008, 714 survivors of out of hospital cardiac arrest were referred to a tertiary center in paris, france. in 435 survivors with no obvious extra-cardiac cause of arrest, an immediate coronary angiogram followed if indicated by coronary angioplasty was performed at admission. the prognostic value of pre-hospital and in-hospital characteristics on in-hospital mortality was evaluated using logistic regression analysis. results. at least one significant coronary artery lesion was found in 304 (70%) therapeutic hypothermia has been shown to improve survival and neurological outcome in patients who have suffered out-of-hospital cardiac arrest and in whom the initial rhythm was ventricular fibrillation (vf) [1, 2] . international guidelines now recommend the use of therapeutic hypothermia as part of post-resuscitation care in patients fulfilling the above criteria [3] . objectives. we surveyed current practice regarding the use of therapeutic hypothermia for post resuscitation care in northern ireland (ni) intensive care units. a questionnaire was devised, reviewed and agreed by each author prior to posting to the lead clinician in each of northern ireland's 10 adult intensive care units. a 100% response rate was obtained. we asked about the existence of a protocol for cooling, which patients were cooled, duration of cooling, by what particular method(s) cooling was achieved and how temperature was monitored during cooling. results. 8 out of 10 (80%) adult icus in ni institute therapeutic hypothermia routinely as part of their post-resuscitation care. only 2 out of the 8 units (25%) have a protocol for institution and maintenance of hypothermia. all units that utilise hypothermia do so regardless of the initial cardiac rhythm. 5 out of 8 (62.5%) icus target a temperature of 32-34°c with 3 out of 8 (37.5%) targeting a temperature of 34-36°c. all units utilise surface cooling methods with 2 out of 8 (25%) also using cold intravenous fluids occasionally. 6 out of 8 (75%) units cool for 12-24 h, 1 (12.5%) unit 12-48 h and 1 unit 24-36 h. all units use more than one method of temperature monitoring during cooling. all units sedate patients during cooling and 5 out of 8 (62.5%) also routinely curarise patients during cooling. the 2 units that do not currently use therapeutic hypothermia cited lack of resources/funding as the main obstacle to adopting this evidence based practice. conclusions. the practice of therapeutic hypothermia post cardiac arrest has been embraced by the majority of icus in ni. there appears however to be variation in the target temperature and duration of hypothermia once instituted. icus that cool patients appear to do so regardless of initial cardiac rhythm. regional protocolisation of this therapeutic modality may help standardise practice across ni icus. reference(s we compared our data with those from 2008 retrospective audit [3] . the method of th was via surface cooling technique together with cold intravenous saline infusion but not ivcd. total 73 patients presented with cardiac arrest: 31 underwent th (22 ooh vf/vt and 9 ooh non-vf/vt). in 2009, there was an overall improvement in adherence to the audit standards, as shown in table 1 : table 2: table 2 hospital survival rate of th % gcs 15 of the survivors at icu discharge 2008 12/31 (39%) 7/12 (58%) 2009 12/28 (43%) 11/12 (92%) conclusions. introduction of ivcd has led to an improved compliance with local and ilcor th guidelines. although the total numbers are small, there has been an increase in the patients discharged with gcs 15 from our icu using ivcd. there are areas that require further improvement, notably the time to reach target temperature and prevention of rebound hyperthermia. work continues on protocolised evaluation of neurologically damaged survivors. 23rd esicm annual congress -barcelona, spain -9-13 october 2010 s177 0369 target temperature management after out-of-hospital car-diac arrest, an international, multi-centre, randomised, parallel groups, assessor blinded clinical trial-rationale and design of the ttm-trial n. nielsen 1,2 , and the ttm-trial study group 1 helsingborg hospital, department of anesthesia and intensive care medicine, helsingborg, sweden, 2 lund university, department of clinical sciences, section of anesthesia and intensive care medicine, lund, sweden introduction. experimental studies and previous clinical trials suggest an improvement in mortality and neurological function with induced hypothermia after out-of-hospital cardiac arrest (ohca). previous trials have included highly selected populations and the optimal target temperature is not known. objectives. to evaluate differences in efficacy and safety with target temperature management at 33 and 36°c for 24 h after ohca of presumed cardiac cause. methods. intervention: patients will be managed with 24 h of temperature control at 33 versus 36°c according to randomisation. temperature control will be delivered with temperature management equipment at the discretion of the trial sites. to facilitate cooling, when applicable, and to stabilise the circulation all patients will be treated with 30 ml/kg of crystalloid infusion (4°c or room temperature according to treatment arm). design. randomised trial with 1:1 concealed allocation of 850 ohca patients to temperature control for 24 h at 33 versus 36°c with blinded outcome assessment. sample size is based on a relative risk reduction of 20% with a risk of type-1 error of 5% and a power of 90% with a 5% loss to follow-up. conclusion. this study demonstrated that health care professionals, despite guidelines, are hyperventilating simulated cardiac arrests patients. suboptimal ventilation was a problem across all the backgrounds investigated; although doctors performed best here, they were still found to be hyperventilating to an unacceptable level. hyperventilation has a number of deleterious physiological effects and is associated with poor outcomes. increased training, awareness and recertification may be the answer, and certainly improves short term compliance with guidelines. however, these effects may be short lived and other changes may be needed. a reasonable course of action may be the use of paediatric (1l) self inflating reservoir bags as a first line device. this simple measure may ensure delivery of more guideline consistent ventilation, independent of the level of experience. extracorporeal life support (ecls) has been proposed as the ultimate heroic rescue measure in prolonged cardiac arrest unresponsive to conventional cardiopulmonary resuscitation. ecls effectiveness in out-of-hospital cardiac arrest remains to be addressed. decision to discontinue cpr due to medical futility is based upon presumed prolonged anoxia, with existing guidelines for termination. however, even when ecls is implemented, failure to maintain stable hemodynamic conditions due to marked capillary leak frequently results in patient's death. to evaluate the usefulness of routine laboratory parameters in the decision to treat refractory cardiac arrest patients with ecls . methods. sixty-six adults with witnessed cardiac arrest of cardiac origin unrelated to poisoning or hypothermia undergoing cardiopulmonary resuscitation without return of spontaneous circulation (duration: 155 min [120-180], median, [25-75%-percentiles]) were included in a prospective cohort-study. ecls was implanted under cardiac massage, using a centrifugal pump connected to a hollow-fiber membrane-oxygenator, aiming to maintain ecls flow c2.5 l/min and mean arterial pressure c60 mmhg. introduction. due to the human lifespan increasing, people are living longer. cardiac arrest (ca) in old people could be seen as a natural end of life process and cardio-pulmonary resuscitation (cpr) in this setting as a disturbance. therefore, the question of prognosis in patients has been raised when performing cpr in the elderly. data from the 1980s found 6month mortality in 94% of patients over 80 suggesting that cpr in elderly people could be futile (1) . the recent progresses in the management of resuscitated patients, such as mild hypothermia, were not evaluated in patients older than 75 years (2, 3) . in a recent study, we found that age [60 years was an independent pejorative prognostic factor (4) . hence there is virtually no data of prognosis factor of elderly patients after ca. our aim was to determine the prognosis factors in patients older than 75 years successfully resuscitated. methods. all patients admitted to icu for ca with successful rosc were consecutively included between 2000 and 2009. ca data were prospectively entered in a registry according to utstein recommendations. patients were managed following standardized procedures. good prognosis was defined as cpc 1 or 2 at icu discharge. factor associated with a good outcome were identified using multivariate analysis. results. among 1,210 patients admitted for ca, 225 were older than 75 years. median age was 79.5 years (75-97), ca was from cardiac origin in 50% of patients and 57.3% had a vt/vf initial rhythm. mean no flow (nf) and low flow (lf) were 4.5 (±6.5) and 16.3 min (±13.4). mean blood lactate and creatinine level at admission were 6.5 mmol/l (±4.3) and 132 lmol/l (±49). 47.5% of patients presented post-resuscitation shock (prs) and 67.5% were treated with hypothermia. conclusions. ca in elderly patients is associated with an in-icu 25% good outcome rate. this should promote the cpr in non-severely disable elderly patients with ca regardless of their age. we plan to collect the 6-month mortality and the functional status of survivors. introduction. post-resuscitation phase is often characterized by a ''sepsis-like'' syndrome, which may be associated with the development of organ dysfunction. microcirculatory abnormalities play a key role in sepsis-related organ failure; however no data are available on microvascular function after cardiac arrest (ca). objectives. the aim of this study was to investigate peripheral microcirculation during and after therapeutic hypothermia (th) in ca patients. methods. this prospective, observational study included 10 patients treated by th after ca. sublingual microcirculation was evaluated using sidestream dark-field (sdf, microscan, the netherlands) videomicroscopy at hypothermia and normothermia in all patients. at least 5 images of 20 s each from separate areas were recorded at each time point and stored under a random number to be analyzed, using a semi-quantitative method, by an investigator blinded to time and condition. thenar oxygen saturation (sto 2 ) was measured using a tissue spectrometer (inspectra 650; hutchinson, usa). a vaso-occlusive test was performed at hypothermia and normothermia by rapid inflation of a pneumatic cuff around the arm to evaluate sto 2 reperfusion rate, reflecting microvascular reactivity. results. compared to hypothermia, measurements at normothermia showed a significant increase in functional capillary density (fcd) from 7.2 ± 1.9 to 10.1 ± 1.4 n/mm (p = 0.002), the proportion of small perfused vessels (ppv) from 76 ± 13 to 92 ± 3% (p = 0.006) and mean flow index (mfi) from 2.1 ± 0.5 to 2.8 ± 0.2 (p = 0.01). fcd and ppv values were significantly correlated with body temperature. sto 2 reperfusion rate was largely decreased when compared to healthy volunteers, but it did not change over the study period (from 0.94 ± 0.38 to 1.13 ± 0.54%/sec) and showed large inter-individual variability. the same was found for sto 2 (from 78 ± 9 to 82 ± 8%). conclusions. mild hypothermia is associated with decreased fcd and ppv in the sublingual area when compared to normothermia. microvascular reactivity is decreased but changes are unpredictable. introduction. acute posthypoxic myoclonus (phm) occurs in deeply comatose patients, soon after a hypoxic episode. it is characterized by generalized, severe body jerks with violent flexor movements, but more focal myoclonus is reported too (1) . acute phm and status myoclonus are considered to have a poor prognostic outcome (1, 2) . although the cerebral cortex is known to be the most common origin of myoclonus in ambulant patients (3) , the origin of acute phm is uncertain (2) . to determine whether acute phm originates from damage in cortical or subcortical structures. for this study patients with myoclonus in the first 72 h after admission were selected from the propac ii study, a prospective cohort study including patients admitted after cpr and treated with hypothermia. exclusion criteria: pre-existing disease with life expectancy\6 months and severely disability before cpr. baseline characteristics were used from the main database. additional data of eeg and ssep recordings made after rewarming were collected. eegs were evaluated for presence of epileptic activity, status epilepticus, generalized periodic discharges, burst suppression pattern, iso-electric or low voltage amplitudes and reactivity of the background pattern. data collected from sseps: n20 potential, giant potential (defined as a potential five times the size of a normal potential) and p27/n35 amplitudes (done by jhk). the glasgow outcome scale (gos) was used to assess outcome after 6 months, poor outcome was defined as a gos of 1-3 (death, vegetative state, severe disability), good outcome as a gos of 4-5 (moderate disability, good recovery). . from a total of 391 patients included in the propacii study, 68 (17%) patients developed myoclonus. baseline characteristics of this group: age 67, 79% male, time to rosc 20 min, primary cardiac arrest in 61 patients, hypoxic arrest in 7. ssep recordings were available from 45 patients. n20 potentials were present bilaterally in 39% (23) and giant potentials were seen in 9% (2) of the patients with a present n20 potential. 32 eegs were made, epileptic activity was seen in 34% (11) and a status epilepticus in 22% (7), thus 44% of the eegs did not show any type of epileptic activity. good outcome was seen in 10% of the patients, poor outcome in 90%. mortality was 88%. conclusions. the results of this study show that acute phm is found in 17% of patients admitted after cpr and treated with hypothermia. it did not necessarily lead to a poor outcome, but we did not have information about the type of myoclonus. the available data seem to support the idea that the myoclonus originates mainly from subcortical structures, given the low number of patients with eegs showing epileptiform activity and sseps with giant potentials, which can be seen in cortical myoclonus (3). introduction. the international liaison committee on resuscitation, the american heart association and the european resuscitation council recommend that mild therapeutic hypothermia improve neurological outcome in unconscious adult patients with return of spontaneous circulation (rosc) after out-of-hospital cardiac arrest (ohca) due to ventricular fibrillation (vf) or ventricular tachycardia (vt). in our intensive care unit (icu) we use mild hypothermia in all patients following cpr with successful rosc regardless of initial rhythm. in this study we compared the effect of mild therapeutic hypothermia at neurological outcome and mortality between the patients who had ohca due to vf or vt and them who had ohca due to a different initial cardiac rhythm as asystole or pulseless electrical activity. the study protocol was approved by the local ethics committee on human research. a total of 23 patients were admitted to our icu with rosc after ohca between may 2008 and december 2009. therapeutic hypothermia was initiated after admission in icu by intravenous infusion of cold saline (4°c 1,000 ml bolus) followed by intravenous cooling device (coolline catheter, coolgard alsius corporation irvine, ca, usa). the target temperature was 34°c maintained for 48 h followed by slow active re-warming over a minimum period of 24 h (0.1°c per hour). intravenous anesthesia was induced in all patients by a combination of propofol and remifentanyl with dose adjustment as needed. to prevent shivering, patients received muscle relaxation by iv administration of sisatracurium every 2 h. the primary end point was the neurological outcome at 6 months according to the pittsburgh cerebral performance category (cpc). secondary end point was mortality at 6 months. prehostital cooling procedures were not applied. nine of the 14 patients (64%) of the group of the patients who had ohca due to vf or vt had favourable neurological outcome cpc 1 or 2 as compared with 3 of 9 (33%) of the group of the patients who had ohca due to a different initial cardiac rhythm. mortality at 6 months was 14% (2 of 14 patients died) in the group of the patients who had ohca due to vf or vt as compared with 55% (5 of 9 patients died) in the group of the patients who had ohca due to a different initial cardiac rhythm. in patients who had ohca due to vf or vt mild therapeutic hypothermia inproves the neurological outcome and reduces mortality as compared with the patients who had ohca due to a different initial cardiac rhythm. objectives. we aimed to compare therapeutic hypothermia using either surface or endovascular techniques in terms of efficacy, complications and outcome at our institution, a 30 bedded tertiary referral icu. a local research ethics committee reviewed the proposed study and waived the need for a full ethics submission, as the study met the national criteria for service evaluation. data were collected from 83 patients undergoing therapeutic hypothermia following cardiac arrest over a 2.5 year period by retrospective casenote review and interrrogation of the carevue (phillips uk) database. therapeutic hypothermia was initiated in the icu using iced hartmann's solution, followed by either surface (n = 41) or endovascular (n = 42) cooling; choice of technique was based upon endovascular device availability. the target temperature was 32-34°c for 12 to 24 h, followed by rewarming at a rate of 0.25 deg h -1 . the mean age was 61 ± 16 years; 88% of arrests occurred out of hospital, and 64% were ventricular fibrillation/tachycardia. endovascular cooling provided a longer time within the target temperature range (p = 0.02), less temperature fluctuation (p = 0.003), better control during rewarming (0.04), and a lower 48-h temperature load (p = 0.008). endovascular cooling also produced less cooling-associated complications in terms of both overcooling (p = 0.05) and failure to reach the target temperature (p = 0.04). after adjustment for known confounders, there were no differences in outcome between the groups in terms of icu or hospital mortality, ventilator free days and neurological outcome. conclusions. endovascular cooling provides better temperature management than surface cooling, as well as a more favorable complication profile. the equivalence in outcome suggested by this small study requires confirmation in a randomized trial. introduction. ventricular assist devices (vads) are successfully used in patients with end stage heart failure, usually as a bridge to transplantation or recovery, but increasingly as destination therapy as well. a major threat for patients with a vad is the frequent occurrence of, mainly thromboembolic, stroke, with a reported incidence of up to 50%. manufacture guidelines for anticoagulation therapy are based on relatively small observational studies and common sense rather than evidence, and as a consequence anticoagulation protocols vary widely between centers. objectives. the aim of this systematic review was to provide more evidence in order to determine the optimal anticoagulation protocol to prevent stroke in patients supported with a vad. a systematic search in pubmed and embase was performed in which we included all types of vads. all types of anticoagulation drugs applied to prevent thromboembolism were included and divided in three categories; heparin, coumarins and antiplatelets. we included references with a full text available, written in english, dutch, german or french, and which described patients with a stroke or tia. our primary outcome measure was defined as the onset of any type of stroke. two authors evaluated independently the results of this search; doubtful references were evaluated by two other authors. after critical appraisal 50 articles were selected as relevant, which include 29 cohort studies, 6 case-control studies and 15 trials, totaling 3194 patients with vad support between 1982 and 2008. the mean age was 50 years (range 7-79) and the mean duration of support was 116 days (0-1309). stroke occurred in 0-50% patients supported by vad, with an incidence of 0-23/patient-year. the majority of strokes occurred within the first year. six types of anticoagulation protocols were used that combines drugs from one or all three categories. most protocols used a combination of all 3 categories (1,162 patients with a total follow up of 115,082 days) and had an average stroke incidence of 1.28 events/patient-years. the lowest average stroke incidence was reported in studies that used only antiplatelets (0.62 events/patient-years) and the highest in which only heparin was used (22 events/patientyears). we could not detect a decreased risk for stroke in patients with vad support when coumarines or heparin were used instead of or in addition to antiplatelets. antiplatelets should be part of an anticoagulation protocol to prevent stroke in patients supported by vad. a.m. de la torre 1 , c. marco 1 , d.j. palacios 1 , a. pedrosa 1 , i. lopez de toro 1 , v.a. hortigüela 1 1 hospital virgen de la salud, toledo, spain objectives. to analyze the difference between two groups of patients with ich considering severity, treatment, evolution and mortality. methods. description retrospective study of admitted patients between 1st of january of 1999 to 31st of december 2001 and 1st of january of 2007 to 31st of december 2009 in the icu of virgen de la salud hospital (toledo) with the diagnosis of ich. there are 85 patients in the group of 99-01 and 124 patients in the groups of 07-09 without any difference of age. regarding comorbidity between the two groups no differences can be found regarding the previous presence of hta, but regarding diabetes and dislipemy, we do find a higher prevalence on the second group (11.8 vs. 23.4%, p \ 0.05 and 8.2 vs. 24.2%, p \ 0.01 respectively). reviewing the presence of anticoagulated patients, no differences of significance can be found, but a trend (14.1 vs. 23.4%, p \ 0.1). regarding the location of the hemorrhage, the most frequent is the basal ganglia (31.8 vs. 25%), existing no differences amongst the two groups. we don't find differences either in the presence of a intraventricular component, whether it is neither supratentorial nor infratentorial. there are differences between the ich score of both groups with p \ 0.05: with a score of 0 (9.5 vs. conclusions. an increase in the comorbidity can be observed in the included patients, which can be due to a better screening of these pathologies. we also find that the ich score is higher than in the 07-09 sample, which is attributed to the admittance in the icu of patients with the ultimate goal of organ donations. in the evolution, it can only be observed a longer stay in patients from the second sample, likely because they are more serious patients with a higher ich score. the analysis of the two groups has not been conclusive when it comes to assessing the improvements that might have come out in these last years, although it is necessary a deeper analysis of the data. introduction. sodium dysbalances are frequent medical complications in patients with subarachnoid hemorrhage (sah). hyponatremia is more frequent but it is associated with better outcome than hypernatremia. the aim of this study was to observe differences in outcome between hyponatremic and hypernatremic patients with sah. we performed the prospective 5 years study in incidence of hyponatremia (serum sodium \135 mmol/l) and hypernatremia (serum sodium [150 mmol/l) in 211 patients (pts) with sah. we compared the incidence of cerebral complications, glasgow outcome scale (gos) upon discharge from the neurointensive care unit (nicu) and in mortality nicu. results. there were 82 (39%) pts with dysnatremia, more patients had hyponatremia (46, 22%), less hypernatremia (36, 17%). between these groups there were no diferences in stay in nicu (p = 0.197), duration of dysnatremia (p = 0.055), fluid intake (p = 0.155, ml/day), daily sodium intake (p = 0.440, mmol/day) and fluid output (p = 0.055, ml/day). hyponatremia was more frequent on admission (p \ 0.001) and connected with higher diuresis (p \ 0.001). hypernatremic pts received more antiedematic therapy (p \ 0.001). hypernatremia was arised in pts with significantly lower glasgow coma scale (p = 0.001). these pts had more cerebral complications (p = 0.018), worse glasgow outcome scale upon discharge from nicu (p \ 0.001) and higher mortality in the nicu (p = 0.002). conclusion. dysnatremia is frequent in patients with sah (39%). hyponatremia occurs more often, but hypernatremia is connected with worse outcome. objectives. to analyze clinical, epidemiologic and outcome differences and to identify predictor factors of mortality at discharge from icu of patients admitted after craneoencephalic trauma (cet) according to glasgow coma scale (gcs) score. observational prospective study of patients admitted in the intensive care unit (icu) after cet. we classified the traumatic brain injury, according to gcs score of b8 or c9 points groups. we analyzed clinical and demographic data during icu stay, as well as physiological, functional and emotional data measured with paecc scale (project for the epidemiological analysis of critical patients) at discharge from icu. qualitative variables are expressed as a percentage and quantitative variables as mean and standard deviation. we used chi 2 test, t-student and multivariate analysis as required with a maximum alpha error of 5%. we analyzed 447 patients, 81.2% male. at admission 67.3% had gcs b 8. traffic accidents (45.2% in gcs c 9 and 58.5% in gcs b 8) were the most frequent cause of cet. there was a higher rate of out hospital hypotension in the gcs b 8 group (p = 0.002, or 6.01, 95% ci 1.7-20.1). cranial computed tomography (ct) scan findings in the gcs c 9 group were diffuse injury i and ii (58.9%) after marshall classification versus 28.6% in the gcs b 8 group (p = 0.0001). fewer complications were detected in patients in the gcs c 9 vs. gcs b 8 group (36.3 vs. 66 .8%, p = 0.0001, or 0.82, 95% ci 0.047-0.14). icu mortality rate was significantly lower in the gcs c 9 group than in the gcs b 8 group (10.3 vs. 36.2, p \ 0.01). predictors of mortality were gcs at admission (p = 0.05), ct findings type iii, iv and v (p = 0.014, 0.001 and 0.028 respectively), complications (p = 0.001), tracheotomy (p = 0.025), days on ventilator (p = 0.001), apache ii (p = 0.001) and the length of icu stay (p = 0.001). best overall score in paecc questionnaire at discharge from icu was better in the gcs c 9 vs. gcs b group. (26.5 ± 5.8 vs. 19 .22 ± 7.7, p = 0.0001). conclusions. patients with lower gcs at admission presented higher rate of prehospital hypotension, more severe ct findings, more complications at icu, worse physiologic, functional and emotional outcome, and higher rate of mortality, than patients with gcs c 9. factors associated with increased mortality were coma level, type of findings in ct, complications, prolonged mechanical ventilation, length of icu stay, apache ii, and the need for a tracheotomy. objectives. the aim of our study was to estimate the influence of hyperhaes infusion on haemodynamic regulation. we examined 25 patients with severe brain trauma (gcs score \8, sedation, artificial ventilation). the bp, stroke volume (sv) and their variability (bpv, svv) were determined by the bioimpedance method. additionally we determined the peripheral pulse (pp) and its variability (ppv) using plethysmography curve registration. special attention were paid to the p3 (0.1-0.15 hz) and p4 (0.2-0.5 hz) bands of bpv, svv and ppv, connected with volume state, breathing, and autonomic regulation, especially baroregulation. all the comparisons were made before and after 10 min. of the infusion of hyperhaes (250 ml). all patients had the autonomic dysfunction: the waves of baroregulation (p3) had low power compared with healthy. hypovolemia was moderate: sv (50 ± 4.5) and pp (22 ± 2.6) were slightly decreased, but bp were 135 ± 5.2 mmhg. the bp increasing was registered as the first reaction on the infusion of hyperhaes (151 ± 4.1 mmhg). the same time pp increased more then twice and became 54 ± 3.3, and p4 of ppv decreased from 30 ± 2.8 to 19 ± 3.9, that reflected the improving of the volume state. although sv did not rise significantly, the increasing of p3 were estimated in svv, as a marker of the baroregulation restoration. conclusions. the infusion of hyperhaes in severe brain trauma not only decrease the range of hypovolemia, but restore the baroregulation as a significant part of autonomic regulation, needed for cerebral perfusion support. introduction. continuous measurement of intracranial pressure (icp) using intraparenchymal sensors has become part of the standard management of patients at risk of developing intracranial hypertension. whilst reliability has been explored previously little is published on the accuracy of depth to which the sensor is placed. a difference in sensor location has been shown to affect the reliability of icp readings and could impact negatively on patient management (1). to determine whether icp sensors (codman, j&j) placed by neurosurgical staff were within the optimum depth of 2 cm from the cortex. methods. 50 consecutive patients were identified from a prospectively collected neuro icu database who had had a ct of the head (cth) performed whilst an icp sensor was in situ during 2009. the depth of the sensor tip on cth was measured and patients were stratified according to whether they had surgery or no surgery to determine any differences between open and percutaneous placement. of the 50 icp sensors 36 (72%) were placed deeper than 2 cm. the greatest incidence of deep placement was in surgical patients 26/33 (79%) and in craniotomy patients 71% of these were deeper than 3 cm conclusions. this investigation has shown that the majority of patients admitted to our neuroicu have less than optimally placed icp sensors. inappropriately deep sensors appear more common in surgical patients, particularly following craniotomy. the impact of this on patient outcome is unknown and would require further study. this study has highlighted we need to implement new methods to improve the accuracy of our icp sensor placement. graduated marks on the sensor sheath during manufacture may assist accurate placement. conclusions. if icp is largely used, it remains below 50%. 40% of the cases have been monitored with at least 3 techniques suggesting an acceptance tendency for a multimodal monitoring. among these techniques, the control of pco 2 seemed considered important as the use of tcd to assess perfusion and vessel tone. on-going analysis of these data will provide information on the therapeutic strategy performed and the impact on outcome. introduction. raised intracranial pressure (ricp) can be evaluated sonographically by measuring the optic nerve sheath diameter (onsd). a wide variation in the threshold measurement of onsd for ricp has been reported in literature. it is likely that exaggeration of the hypoechoic edge artifact around the dura by high frequency ([10 mhz) linear transducers and uncertainty over whether to measure 3-mm behind the papilla or behind the globe (posterior margin of sclera) could have resulted in such differences. to determine the optimal site of measurement of onsd by correlating it with ricp determined clinico-radiologically. we also evaluated if different sonographic appearances of the onsd could be used qualitatively to determine the presence or absence of ricp. methods. initially, in order to precisely delineate the anatomical dura sonographically and assess optimal cursor placement, 2 cadaver orbital preparations were studied before and after subarachnoid fluid insufflation. 60 scans were then done by a single sonographer using a 13-6 mhz linear transducer on 8 healthy volunteers and 46 patients admitted to the medical/ neurosurgical intensive care units. onsd was measured at 2 locations; 3-mm behind the papillae and 3-mm behind the globe. in each location 1 measurement was made within the anatomical dura and another between the echogenic margins of retrobulbar fat as described in literature. four patterns (fig. 1 ) of the nerve sheath were identified based on the appearance of the csf space and edge artifact. ricp was diagnosed by clinically correlated computed tomography of the brain. an independent 2 sample t test was done to correlate measurements with ricp. classification of optic nerve sheath appearances results. 14/60 (23%) scans were done on patients with ricp. all 4 measurements independently correlated with ricp (p \ 0.02); albeit cut-offs differed substantially ( table 1) . the presence of a type 3 pattern (fig.) in both eyes strongly suggested ricp (100% positive predictive value) whilst its absence in both eyes ruled out ricp (89% negative predictive value). methods. three years after the introduction of the concept of bs in our icu, a questionnaire was sent to 40 people directly involved in the nursing of critically ill patients to study the current practice during the previous month. responses were received from 26 persons, a 65% response rate. 25 (96%) persons had practiced bs. only 10 (38%) employees used calming bath and 5 (19%) an invigorating bath. guided oral care and guided suction was performed respectively by 18 (69%) and 10 (38%) nursing persons. orientative positioning was used by 12 (46%) nurses. everybody is very satisfied with the instruction manual which can be found in each room. 14 (54%) persons estimated to be well informed about bs. others wanted more practice course and training at the bedside. conclusion. pattern suggested an increasing interest in bs since its introduction. initial touch is well implemented. more effort is needed for continuous education and training. introduction. admittance to hospital for surgical treatment, is often linked with insecurity and anxiety for many patients. to most patients, the postoperative care unit constitutes an unknown environment, and can represent a frightening experience. research has shown that preoperative information leads to subjective outcome as anxiety reduction, and objective outcome as shorter hospital stay and less intake of pain medication. few studies, however, have addressed patients' experiences with preoperative information about the early postoperative phase. objectives. the purpose of this study was to describe patients' experiences with preoperative information about events they may experience during their stay in the postoperative unit. patients' experiences may contribute to increased knowledge about this topic. the study design was exploratory-descriptive, and a semi-structured interview based on thematic guide was used. nine patients met the inclusion criteria, and they had an average age of 65 years. they were admitted to elective surgery for cancer and their stay in the postoperative unit varied from 1 to 3.5 days. the interviews were conducted 5-11 days after surgery and transcribed verbatim. the data material was subjected to qualitative content analysis. results. experience with information before surgery and in the early postoperative phase, was categorized into four themes: being prepared before surgery, reactions to differing experience, discomfort and pain, management of some self-care activities and experiences with the environment of the postoperative unit. conclusions. the patients received a fair amount of information before surgery, but only limited information concerning what to expect while in the postoperative unit. the patients' information needs differed and patients with former experience with surgery were more prepared for what to expect. the patients got mainly verbal information and most of this was given the day before surgery. o.m. peters-polman 1 , m. van roosmalen 2 , j.e. tulleken 3 , j.g. zijlstra 3 1 umc groningen, intensive care, groningen, netherlands, 2 arup nederland, amsterdam, netherlands, 3 umc groningen, groningen, netherlands background. who guidelines concerning sound levels in hospitals requires a maximum of 35 db in daytime, a nighttime sound level below 30 db to allow good sleep quality and peak levels that do not exceed 40 db at all times. in an icu environment, apart from being critically ill, patients are exposed to typical icu environmental noise. sleeping cycles disturbed by illness are further disrupted by care providers performing procedures and taking vital signs and alarms with delirium as a common result. we describe the acoustic environment in our mixed icu. we conducted an observational study in which we continuously measured the sound level (db), frequency and repetition of sound in our icu. we used a splnet microphone and noise monitoring system which was placed, after informed consent, at the ear level of the patient. results. noise sources are numerous and consist of human voices, doors slamming, pagers, telephones, shoes and equipment alarms. there is a round the clock continuous background noise of 45-68 db, staff conversation with levels of 70-75 db and peak levels up to 90-110 db, mainly due to alarms. these levels of sound are comparable to loud conversation at 1 meter distance (45-68 db), walking along a motorway (70-90 db) or standing next to a roaring engine (110 db). conclusion. who guidelines clearly state maximum sound levels of 35 db in daytime, 30 db at night and peak levels of 40 db. the sound level in our unit is exceptionally and unacceptably high throughout day and night and requires a behavioral intervention. further research on the influence of these noise levels on our patients is necessary. objectives. this study has been achieved in order to realize the comparison of efficiency of manual and mechanical compression techniques used for the maintenance of haemostasis after femoral sheath removal. methods. this study was planned and applied as a randomized controlled trial. the study was executed at a military education and research hospital in turkey between january and march 2010. data collecting form was prepared by the investigators after the literature examination. the form consists of 21 questions which are evaluating the demographic data of patients, the compression time, the pain level (before sheath removal, during the manual/ mechanical compression and after the sheath removal), the complications occurring in femoral zone, the mobilization/discharge period and the problems (bruise, oedema, hemorrhage and etc.) occurring the 5th day after the discharge. the patients have been called up in order to evaluate the problems occurring on the 5th day. the 55 persons that were applied mechanical compression have constituted the experimental group and the 59 patients that were applied manual compression have formed the control group. the patients volunteer to participate to the study have been informed in regard with the implementing procedures before the application. descriptive statistics were shown in numbers and percentages for the variables obtained by counting and in mean ± standard deviation for variables obtained by measurement. results. the average of age is 52.70 ± 16.38 in the experimental group and is 47.62 ± 14.88 in the control group. the average of compression time is 39.66 ± 19.65 min in the experimental group and is 13.5 ± 5.03 min in the control group (p \ 0.05). the average of mobilization time after sheath removal is 103.36 ± 40.99 min in the experimental group and is 379.32 ± 50.37 min in the control group (p \ 0.05). it has been observed a lower pain level during compression and after sheath removal in patient that were applied mechanical compression in comparison to the patients that were applied manual compression(p \ 0.05). when the groups were compared in terms of femoral zone complications while no haematoma was observed in the experimental group, haematoma has been occurred in the 10.2% (n = 6) of the control group. conclusions. the mechanical compression provides an earlier mobilization and earlier discharge of the patient. this study shows that mechanical compression is a method as safety as the manual method in order to obtain a haemostasis a correlational survey was conducted in 6 public hospitals located in athens. 143 critical care nurses completed anonymous questionnaires 4,5 , yielding a response rate of 63%. greek critical care nurses believe that open visiting increases family's satisfaction (84.6%), exhausts family members (69.9%) and provides emotional support to the patient (89.5%); nevertheless the effects of visiting depend both on patient and family (91.6%). furthermore open visiting hampers the planning of adequate nursing care (75.5%) and is not a helpful support for the caregivers (84.6%) while increases their physical and psychological burden (87.5%). critical care nurses' attitudes toward visiting hours were rather negative and they didn't want to liberalize the visiting policy of their unit (94.4%). there was a positive correlation between nurses' beliefs and attitudes regarding visiting (r = 0.42, p \ 0.001, r = 0.45, p \ 0.001). the factors ''working experience'', ''adequacy in staff'' and ''the number of shifts'' were found to be independently correlated and they predicted the score of the 3 scales of the questionnaire. greek icu nurses have rather negative beliefs and attitudes toward visiting and open visiting policy. this will be a challenging barrier to overcome when imposing new flexible policies in icus 6 . objectives. our aim was to elucidate potential mechanisms for the beneficial effects of rhapc on ali, as assessed by microarray analysis of lung tissue after sepsis induced by clp in rats. methods. sepsis (n = 14) was induced in rats by clp. a sham-operated group (n = 5) underwent laparotomy and closure without clp. a clp group (n = 7) received subcutaneous saline (30 ml/kg) and a clp + apc group (n = 7) additionally received 24 mg/kg rhapc. twelve hours postoperatively, lung tissue was preserved in mrna later until mrna isolation by promega total rna kit and analyzed using illumina beadarray. data were log2 variance stabilized and quantile normalized using the lumi package in r and the limma package was used for group comparisons and false discovery rate correction. data were further analyzed using panther and david. the clinical outcomes of this study showed a marked attenuation of the sepsisinduced increase in lung permeability in rats treated with rhapc 4 . although no formal statistical significance was reached for the gene expression changes between the clp and the clp + apc groups, there was a clear attenuating effect of rhapc on the changes in gene expression caused by sepsis reflected in generally lower fold change values and fewer significantly differentially regulated genes in the clp + apc versus sham group compared to the non-treated clp vs. sham group (153 vs. 863 genes). nevertheless, there were only 18 genes of which the fold change difference between clp versus sham and clp + apc versus sham was more than one, indicating that although there was a large difference in the number of differentially expressed genes, the difference in fold change between these genes was small. conclusions. these data suggest that the rhapc treatment of septicemic rats does not only cause a down regulation of specific pathways as argued by previous investigators, but leads to a global reduction in the inflammatory response at a mrna level. introduction. septic shock guidelines recommends the use of recombinant human activated c protein (acp) in high risk mortality patients. the aim of our study is to describe the clinical characteristics, and the outcome of patients treated with acp in our hospital. methods. retrospective and descriptive study which includes patients with severe sepsis/ septic shock treated with pca in a tertiary hospital intensive care unit (icu) over 5 years (2005-2009) . we analyze epidemiological data, reason for admission, infectious focus and agent, severity scores, organ failure, complications, stay and mortality. we used chi-square analysis to compare categorical data and student's t test to compare continuous variables. conclusions. in our study most patients were admitted from emergency department, with organic failure caused by pneumonia. we haven't detected deaths related with acp complications, even in patients undergoing surgery. we found as prognostic factors for mortality: organ dysfunction, acp indication, renal failure, pao 2 /fio 2 relation, amount of vasopressors, bicarbonate and base deficit levels, apacheii and icu stay. objectives. to analyze changes on hemodynamics in patients with severe sepsis treated with high volume hemofiltration (35 ml/kg/h) vs. patients treated with very high volume hemofiltration ([55 ml/kg/h). we conducted a prospective randomized trial from january to november 2009 in patients admitted into icu with a diagnosis of septic shock in which hf was indicated. patients were randomized to one of each group of therapy. the control group received high volume hemofiltration therapy and the experimental group received very high volume hemofiltration. the hemodynamic parameters were measured at the admittance in icu and every 24 h onwards. results. data of 30 patients were collected (21 men and 9 women) mean age 59 ± 13 years old. the hemodynamic parameters registered at the admittance and during the therapy had no significant difference between the groups. the control group received hf therapy during 6.4 ± 4.5 days and the intervention group 5.7 ± 3.1 days. there wasn't any difference either in the administration of vasoactive drugs between both groups. the most significant difference between the groups was the 28-day survival rate, 86.7% of the experimental group against 53.3% of the control group (p = 0.46). from these results we can conclude that very high volume hemofiltration therapy should be the therapy of election because it improves the survival of patients with severe sepsis without impairing the hemodynamic parameters. we have to point out the importance of the nursing staff in the assembly and management of the equipment as well as in the patient care and thus avoiding potential complications. introduction. the use of herbal products is increasing, and may result in increased drug-herb interactions or form a potential for adverse reactions in cardiovascular surgery patients. objectives. the aim of this study was to describe the utilization patterns for herbal products in patients with cardiovascular disease. methods. this was a descriptive study which was carried out among adult patients presenting to cardiovascular surgery department for elective cardiac surgery between september 2009 and april 2010 in a research and training hospital. after giving informed consent, patients were interviewed by researchers using a structured survey instrument in the preoperative period. results. interviews were conducted with 289 patients (mean age 68.12 ± 12.85, range: 45-79 years), 92% of them were married, 70% were men, and 62% of the patients had high school or university education. the majority (72%) had coronary artery disease and most of the patients (58%) had concomitant diabetes mellitus and hypertension. the most common used drugs were anti-hypertensives, nsai's, and anti-aggregants. most patients (84%) reported the regular use of drugs. eighty-nine (31%) among the surveyed 289 patients reported the use of herbal products. the most common used herbal products were garlic (43%), apple vinegar (39%), lavandula stoechas (31%), cratageus (29%) and ginger-honey mixture (27%). the average educational degree of herbal product users was found to be higher when compared with the others. many patients report being informed about those products from television, internet, newspapers, herbal-stores personal communications, and report the use of those products after the diagnosis is made. none of those patients have informed physicians or nursing staff about the use of those herbs. the demographic variables of patients and the herbal-product usage has failed to show a statistically significant difference (p [ 0.05). conclusions. the use of herbal products is common among the patients with cardiovascular diseases. health professionals should be aware of the usage of those products in order to prevent possible adverse reactions and drug-herb interactions. introduction. nurses employed in the icu operate in a complex environment, under time pressure, and with limited information available. thus, errors are inevitable and, besides their adverse consequences, they offer the potential for learning 1 . in this concept, properly copying with errors is a prerequisite for avoiding their recurrence and improving nursing practice. objectives. our aim was to investigate how error-copying strategies are associated with constructive and defensive changes in icu nursing practice. methods. 62 questionnaires were completed (a 60% response rate) from nurses employed in the icus of adults, children, and the coronary care unit of two greek hospitals, between january-june 2007. ''ways of copying'' scale as revised by wu et al. 2 was used for evaluating copying strategies. this includes 6 copying subscales, each ranging between 0 and 9. constructive changes in response to error included 7 items (paying more attention to detail, keeping better patient records, reading patient notes more carefully, seeking advice, discussing with colleagues about similar situations, devoting more observation on patients, reading for covering knowledge deficiencies), while defensive changes included 5 items (getting more worried, feeling less confident at work, being more likely not to discuss errors, being less trusting of others, thinking to leave profession.). a four-point likert scale (0-3) was used for evaluating each item, and points were summed to estimate total scores of constructive and defensive changes. . 72.6% of participants were female and 87.1% were registered nurses. mean (±se) age was 36.2 ± 1.0 years and mean icu experience was 11.9 ± 0.9 years. multiple linear regressions with constructive and defensive changes in practice as dependent variables and copying strategies as independent variables are summarized in table 1 . participants were more likely to make constructive changes if they coped by seeking social support (p = 0.015) and accepting responsibility (p = 0.041). at the same time, they were more likely to make defensive changes if they coped by escape-avoidance (p = 0.029). reasons for high risks are e.g. sedation and analgesia, immobility, malnutrition and hemodynamic or oxygenation problems as well as poor identification or unsystematic assessment of the risks. in our unit, we performed a 6 months retrospective review of pressure ulcer risks for all patients (n = 747) using jackson-cubbin calculator. the risk point level in this instrument is 29 and below. 314 patients of 747 (42%) exceeded the risk limit already in the icu admission phase. objectives. to change care practices of pressure ulcer prevention and care with action research. with the measurement tool nurses are able to identify patients at risk of developing pressure ulcers during the whole icu in-patient time, and to prevent risks of pressure ulcer in an early stage. with the assessment tool, the measurement is systematic which enables the benchmarking and have effects on material recourse planning and cost caused by pressure ulcers. the study unit is a 24-bed icu for adults taking care annually circa 1,800 patients with multiple disorders. firstly, the jackson-cubbin pressure area risk calculator was translated into finnish. a few changes which have an effect on pressure ulcer risk were added; weight limits were also defined with bmi values, hyperbaric oxygen therapy was added in deducted points as well as 24 h limit for blood transfusions and limits for hypothermia from 35 celsius or under. secondly, standardized guidelines for different risk levels were developed; if patients have a high risk specialized mattresses should be used and changes of positions and beds should be stressed. thirdly, an electronic evolution form for patient information system was planned and implemented. finally, a systematic education program for icu personnel including special lectures, material demonstrations and familiarization by the nurse responsible for wound care was started. results. after the development project and systematic education the knowledge of personnel about pressure ulcer risks and care has increased. risk points are counted once a day for every patient using the electronic form. all the mattresses at the icu have been changed to medium and high risk mattresses and are chosen for a patient related to the risk assessment points. conclusions. a reliable assessment scale, systematic measurement and continuous evaluation and education are crucial for identification of high risk pressure ulcer patient at the icus. with a systematic measurement and recognizing high risk patients we can also improve patients' quality of life and reduce the cost caused by pressure ulcers. reference(s ) is considered to be one of the main agents in gram negative sepsis. in recent years several adsorption dispositives have been designed in order to achieve low blood endotoxin levels with a theorical clinical improvement. toramyxin (polymixine b fixed to polyesthirene fibers) and alteco lps adsorber (polyethylene discs) are two of these dispositives. both are used with 2 h sessions for several days until patient clinical improvement. • design a nursery prothocol with the most important procedures in gram negative septic shock patients with acute renal failure that undergo adsorption cartridge therapy. • evaluate initial experience in the use of endotoxin adsorption cartridges. methods. nursery prothocol with special attention to the settlement and management of the cartridge therapy, based on library references and practice guidelines. once prothocol was stablised, prospective observational study was started from january 2009 till january 2010. inclusion criteria were: patients admitted to our intensive care department with gram negative confirmed septic shock and acute renal dysfunction requiring continuous renal replacement therapies (crrt). adsorptive cartridge were added and several parameters were studied: heart rate, mean blood pressure, vasopressor support (norepinephrine), pao 2 / fio 2 , and lactate. the information was analyzed in excel. results. nursery protocol was correctly applied in all patients and showed to be basic in the maintenance and early complication detection. hemodynamic improvement that allowed norepinephrine lowering dose and normalized lactate levels with no changes in pao 2 /fio 2 . patient 1 (toraymyxin): 55 years man, acute pancreatitis with septic shock. patient 2 (toraymyxin): 44 years man, pneumococic pneumonia and klebsiella septic shock. patient 3(alteco): 55 years man, acute pancreatitis with enterobacter cloacae septic shock. patient 4 (alteco): 60 years woman, acute peritonitis with e. coli septic shock. results of a program to reduce catheter-related blood-stream infection in the icu: two years' follow-up a systematic review comparing the relative effectiveness of antimicrobial-coated catheters in intensive care units benefits of minocycline and rifampicin-impregnated central venous catheters which antimicrobial impregnated central venous catheter should we use? modeling the costs and outcomes of antimicrobial catheter use when is hit really hit? anticoagulative management of patients requiring left ventricular assist device implantation and suffering from heparin-induced thrombocytopenia type ii -hit happens: diagnosis and evaluating the patient with heparininduced thrombocytopenia informe del registro mami 1996-2003 grupo de trabajo de la sociedad europea de cardiología (esc) sobre marcapasos y terapia de resincronización cardíaca moreno millán e. variación de la estancia preoperatoria en españa según grupos de edad, sexo y modo de acceso hospitalario reference(s). 1. association of anaesthetists of great britain & ireland. safety guideline on interhospital transfer intensive care society: guidelines for the transport of the critically ill adult competency-based st1 st2 training and assessment. a manual for trainees and trainers. royal college of anaesthetists training and assessment of competency of trainees in the transfer of critically ill patients adverse events experienced while transferring the critically ill patient from ed to the icu a modified mccabe score for stratification of patients after intensive care unit discharge: the sabadell score surviving intensive care. 18edicion taurine and niacin block lung injury and fibrosis by down-regulating bleomycin-induced activation of transcription nuclear factor-kappab in mice antioxidants and sepsis: can we find the ideal approach? post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. a scientific statement from the international liaison committee on resuscitation therapeutic hypothermia after cardiac arrest: unintentional overcooling is common using ice packs and conventional cooling blankets it's well known that normobaric hyperoxia (nh) increases arterial and brain oxygen tension. however the influence of nh on intracranial pressure (icp) and cerebral metabolism in patients to investigate the dynamics of icp, jugular bulb saturation (svjo 2 ), brain oxygen tension (pbro 2 ) and cerebral metabolism during nh in patients with ich icp monitoring and tissue microdialysis were used in all patients, svjo 2 monitoring -in 6, pbro 2 -in 5. microdialysis and pbro 2 catheters were placed in lesioned (les) and intact (int) brain tissue. icp, svjo 2 , pbro 2 , glucose and glycerol levels, lactate/pyruvate ratio dynamics during fio 2 3) to 171 ± 28 mmhg (ð \ 0.05) (fio 2 0.5) and 350 ± 64 mmhg (ð \ 0.05) (fio 2 1.0) cerebral metabolism didn 0 t change significantly, except glycerol level increase in lesioned brain tissue from 97 (32; 233) mlmol/l (fio 2 0.3) to 234 (32; 306) mlmol/l (fio 2 0.5) and 205 (23; 233) mlmol/l (fio 2 1.0). fio 2 0.3: glucose (int) -1.1 (0.3; 1.2) mmol/l, glucose (les) -1.35 (0.4; 1.9) mmol/l, lactat/piruvat (int) -20.2 (18.5 icp was stable during investigation (12.1 ± 2.9 mmhg nh is accompanied by pao 2 and pbro 2 increase and doesn't influence icp and cerebral metabolism in ich patients with normal vo 2 /do 2 relationships effects of anesthetics oc cerebral blood flow and cerebral metabolic rate isoflurane preconditioning improves long-term neurologic outcome after hypoxic-ischemic brain injury in neonatal rats this no-profit trial has been supported by depuy/ hemedex, providing the probes. no other economical support has been received effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance a comparison of 3% hypertonic saline and mannitol for brain relaxation during elective supratentorial brain tumor surgery hypertonic resuscitation and blood coagulation: in vitro comparison of several hypertonic solutions for their action on platelets and plasma coagulation effect of the combination of mannitol and ringer acetate or hydroxyethyl starch on whole blood coagulation in vitro no well defined threshold for transfusion or target hemoglobin (hb) level for these patients exists. objectives. to examine associations of anemia and transfusion with adverse outcomes in patients with sah, and better define hb level thresholds associated with these. methods. retrospective, observational study of consecutive patients with sah admitted to icus at mayo clinic in jacksonville and rochester, usa, over 6-year period. data included demographics, nadir hb, blood transfusion, ali/ards, vasospasm, radiographically confirmed cerebral infarction, apache and wfns. primary outcome was association of anemia and transfusion with death and secondary outcomes were vasospasm, cerebral infarction and ali/ards. results. we identified 333 patients, mean age was 56 (±14), 206 (62%) were females. mortality was 17%. seventy-two (22%) of patients were transfused. 155 (46%) patients had vasospasm and 108 (33%) cerebral infarction. there was a strong association between transfusion and increased mortality (p = 0.001), vasospasm (p = 0.007), cerebral infarction (p \ 0.001) and ali/ards (p \ 0.001) outcome prediction in mild traumatic brain injury: age and clinical variables are stronger predictors than ct abnormalities comparison of simultaneous continuous intracranial pressure (icp) signals from a codman and a camino icp sensor therapeutic actions may correct abnormal values and perform potentially cerebral blood flow/oxygen extraction coupling. objectives. aim of this study was to describe the incidence and the type of bedside icu monitoring devices used in the management of patients with severe tbi in french icu's. methods. multicentric observational study including patients having severe tbi (glasgow coma scale (gcs) \ 8) picked on scene by a mobile medical unit for pre-hospital care (samu). inclusion period: 18 months general hospital of athens, department of intensive care unit o poder na relação enfermeiro-utente relacionamento enfermeiro, paciente e família: factores comportamentais associados à qualidade da assistência investigação qualitativa em enfermagem: avançando o imperativo humanista the experiences of families of critically ill patients in greece: a social constructionist grounded theory study. intensive and critical care nursing visiting hours policies in new england intensive care units: strategies for improvement this study was supported by a post graduate programme in nursing surviving the nursing shortage: developing a nursing orientation program to prepare and retain intensive care unit nurses 0423 clinical utility of apc-pci (activated protein c-protein c inhibitor) complex as predictors for severity and prognosis in sepsis: preliminary study republic of korea introduction. recently human recombinant activated protein c (drotrecogin alfa [activated]) has been shown to reduce mortality in severe sepsis. in severe sepsis, conversion of protein c to apc (activated protein c) is impaired due to endothelial dysfunction. apc level is related to coagulation cascade known to be important in sepsis pathophysiology. objectives. in this preliminary study, we checked apc-pci (activated protein c-protein c inhibitor) complex level to evaluate protein c activation using apc-pci elisa kit they were admitted asan medical center (seoul, korea) medical intensive care unit (icu) between sep 1 2 and 11.1, respectively. apc-pci level had no statistically difference among sepsis, severe sepsis, septic shock (5.4, 3.0, 2.9 ng/ml, p = 0.104). between hospital survivor group and non-survivor group there was also no difference in apc-pci level (3.1, 2.9 ng/ml but apc-pci level was tended to decrease in severe sepsis, septic shock group as compared to sepsis group activated protein c versus protein c in severe sepsis endogenous protein c activation in patients with severe sepsis efficacy and safety of recombinant human activated protein c for severe sepsis septic critical patients to evaluate the experience with drotrecogine alfa (da) in septic critical patients (scp) in a analysis of scp admitted in an icu unit between december and which received treatment with da. patients were included or excluded on the approved specifications fda and emea. inclusion criteria were septic patients and apache ii score c25 and/or two or more organ dysfunction (od) thirty-eight patients were eligible od: respiratory 94%, renal 71%, cardiovascular 97%, metabolic 65%, hematologic 36%; sdra 44.74, vmc 86.84, vni, 15.79, all patients received empirical antibiotic treatment in the first 6 h according to epidemiologic characteristics. microbiology: some germens were isolated in 26 patients (78%) mortality (%) by presumed site of infection day 28/day 90: respiratory 18/25, abdominal 21/28, urologic 20/20; skin 66/66. average hours drug administration was 13 h. da was administrated at 70% of the patients between hour 0 and hour 12, the other 30% between hour 13 y 28 critical septic patient treated early with empirical antibiotics, the best standard care and da have a low mortality rate. more early da administration was associated to lower mortality the treatment of severe sepsis in france: overview of a 3-year survey period bichat hospital, surgical intensive care unit lariboisière university hospital, medical intensive care unit cochrane database leptin is an adipocyte-derived cytokine regulating energy homeostasis, metabolism as well as immune-inflammatory processes. leptin also has thermogenic actions and regulates enzymes of fatty acid oxidation. leptin is significantly increased in response to acute infection and sepsis and exerts direct effects on cd4+ t-lymphocyte proliferation, macrophage phagocytosis, and secretion of inflammatory cytokines such as il-1 and tumor necrosis factor (tnf) a. we measured leptin in blood of septic patients we measured leptin serum levels in septic patients leptin levels in septic patients (mw = 30,829.1 ng/ml ± sem = 4,941.1 ng/ ml) are significantly higher compared to healthy controls (mw = 12,115.6 ng/ ml ± sem = 1,944.5 ng/ml, p \ 0.001). serum levels of leptin were significantly higher on day 3 (mw = 63,291.2 ng/ml ±sem = 17,882.8 ng/ml) and day 5 (mw = 66,016.5 ng/ ml ± sem = 19 the aim of this multi-centre retrospective observational study was to resuscitation bundle the above preliminary data indicated that an experienced use of rhapc, when compared to other survey (2), was associated with a reduction of serious bleeding events, a more frequent off-label use and a similar mortality rate. the concomitant adherence to evidence-based guidelines improved significantly the patient survival 1) macias et al. sources of variability on the estimate of treatment effect in the prowess trial: implications for the design and conduct of future studies in severe sepsis use of drotrecogin alfa (activated) in italian intensive care units: the results of a nationwide survey acute lung injury (ali) is one of the most frequent complications of sepsis. although coecum ligation and puncture (clp)-induced sepsis is a frequently used model, we found only three microarray studies of clp-induced sepsis 1-3 , of which one looked at lung tissue 2 . none of them had examined the effects of recombinant human myocardial transcriptional profiles in a murine model of sepsis: evidence for the importance of age molecular signatures of sepsis: multiorgan gene expression profiles of systemic inflammation sepsis gene expression profiling: murine splenic compared with hepatic responses determined by using complementary dna microarrays endothelin-1 in endotoxin-and sepsis-induced lung injury activated) in real-life clinical practice for management of severe sepsis in surgical patients in patients with severe sepsis and multiple organ dysfunction, major surgery is not a contraindication for early (12-24 h after surgery) daa administration retrospective, observational, descriptive cohort study in 75 patients with severe sepsis and multiple organ dysfunction treated with daa the principal focus of sepsis differed between the two groups (p \ 0.0001): in the surgical group it was the abdomen (73.3%) followed by the skin and soft tissues 3%) followed by the urinary tract (24.4%) in the perfusion period, the distribution of severe/ moderate hemorrhages in the surgical group was 0%/16.7 vs. 4.4%/22.2% in the medical group. we found no differences between groups in death from any cause at 28 days (33.3 vs. 33.3%; rr 1; 95% ci 0.52-2.19; p = 1.000). nevertheless, at 90 days overall mortality had increased in both groups, although this difference was not statistically significant: the percentage of increase with respect to the 28-day mortality was 25% in the surgical group and 20% in the medical group in patients with severe sepsis and multiple organ dysfunction, major surgery is not a contraindication for early (12-24 h after surgery) daa administration. given our findings at 90 days, studies including a wider period from the initiation of daa administration are necessary to evaluate the cost-efficacy efficacy and safety of recombinant human activated protein c for severe sepsis recombinant human activated protein c, package labeling and hemorrhage risk reference(s). 1 iom. to err is human incidence of adverse events and negligence in hospitalized patients matrix metalloproteinase-2 promotes repair after ventila-tor-induced lung injury supported by the parker b. francis foundation, physician services incorporate, ontario thoracic society and canadian lung association sepsis-induced immuno-endocrine dysfunction impact of arginine-vasopressin (avp) and apelin (apl) exogenous administrations in a rodent model because the corticotrophic pathway is disturbed during circi, with acth-cortisol dissociation, alternative physiologically nondominant pathways such as the vasopressinergic/apelinergic axis, become essential to the hpa adaptation to stress. objectives. seeking the impact of arginine-vasopressin (avp) and apelin (apl) exogenous administrations on: acth & corticosterone blood contents, and respective pituitary and adrenal gland receptor expression (v1b, apj) in a rodent model of endotoxin challenge. methods. a rodent model of endotoxin (lps e. coli 055:b5, 10 mg/kg i/p)-induced hpa axis has been selected to study the committment of avp/apl and related receptors (v1b/ apj). rats (n = 6) were equipped with subcutaneous osmotic minipumps (alzet, 2001) containing: saline, apl-13 (10, 100, 1,000 lg), or avp (37.5, 75 lg) for 18 h. results. without lps challenge, exogenous apl administration did not alter acth & corticosterone blood contents whereas high dosage of exogenous avp significantly increased corticosterone blood content (p \ 0.05 vs. control). lps i/p challenge induced a huge increased of blood acth & corticosterone, both culminating at 1.5 h (6-and 23-fold increases respectively, p \ 0.05 vs. baseline), which was normalizing at 18 h for acth whereas corticosterone remained high. this dissociation validates the model, matchs with human observations, and suggests non acth-dependent corticosterone release after lps challenge apl administration completely reversed the above down-regulation while avp also partially restored apj pituitary expression by almost 50% in a dose-dependent manner, and to a lesser degree in the adrenal gland (p \ 0.05 vs. lps). selective non-peptide v1b (ssr149415) and peptide apl antagonists (f13a) substitutions confirmed the above effects were directely mediated. conclusions. apl and avp pituitary neuronal and bloodstream contents behave differently, and blood acth & corticosterone contents were dissociated, after acute lps challenge. apl as well as avp exogenous administrations were able to reverse (partially for the later) the lps-induced apj down-regulation in both pituitary and adrenal glands. reference(s) supported by the esicm young investigator award from infection diagnosis to therapy an antimicrobial stewardship program (asp) is a method of optimizing antimicrobial prescribing, altering antimicrobial resistance, reducing costs, and improving patient care. the intensive care unit (icu) is an ideal environment for the application of an asp given the complexity of the patient population, the ecology of resistant organisms, and the fact that selection of inappropriate antimicrobials or delays to determine the impact of the introduction of an icu asp on prescribing, patient outcomes, resistance, and costs we implemented an asp in a 16-bed medical surgical icu of a university-affiliated hospital. the asp team used prospective audit with interaction and feedback providing suggested changes in therapy (e.g. antibiotic choice, dose, duration) on a daily basis. asp provided consultation on all icu patients not followed by the infectious diseases consult service. parameters collected included demographic data, details of antimicrobial regimens, culture results, defined daily doses (ddd)/100 patient days and antimicrobial costs mean monthly antibacterial ddd/100 patient-days post-asp was reduced by 15.6% (146.4 vs. 123.6, p \ .05). the implementation of the asp was associated with a 28.4% decrease in mean monthly antibiotic costs/100 patient-days ($3916 vs. $2805) for a total cost reduction of $53,635. in terms of prescribing and resistance, the introduction of asp was associated with a reduction in the prescribing of anti-pseudomonal agents (compared with antibiotics not covering pseudomonas) (mean monthly ratio 2.0 vs. 1.6), mrsa vs. mssa covering antibiotics (mean monthly ratio 2.0 vs. 1.4) and improved susceptibility pattern for pseudomonas aeruginosa as demonstrated by increases of 17, 9 and 7% to tobramycin, meropenem, and piperacillin-tazobactam susceptibilities, respectively. there was no difference in icu mortality rate the asp team worked collaboratively with the icu team to improve antimicrobial therapy and as a result improved overall antibiotic usage and resistance patterns of important icu microorganisms, and decreased antimicrobial costs. appropriate and judicious antimicrobial use guided by an asp is beneficial to the icu can pct and/or crp help identify associated bacterial infection in patients with influenza pneumonia? procalcitonin (pct) is a recognized marker of bacterial infection and might be a prognostic marker in lower respiratory tract infections. objectives. to determine if pct and/or c-reactive protein (crp) levels at admission in intensive care unit can help identify associated bacterial infection in patients with influenzae pneumonia. methods. a nationwide registry (reva) was set up in france during the 2009 h1n1 influenza pandemic. levels of pct and crp at icu admission were compared between patients presenting with influenzae pneumonia associated or not with a bacterial coinfection. results. 137 patients were included, 48 of whom received antibiotics prior to hospitalization. of the remaining 89 patients, 43 (48%) had documented bacterial co-infection. the bacteria involved in the co-infections were streptococcus pneumoniae (n = 22, 16.5%), staphylococcus aureus (n = 11, 8.3%), streptococcus a group (n = 6, 4.5%). figure 1 shows the initial values of procalcitonin and crp. median values for both pct (28.9 vs. 0.74 ng/ml, p \ 0.001) and crp (263 vs. 95 mg/l, p = 0.008) were significantly higher in patients with bacterial coinfection. the area under the roc curve was 0.88 and 0.79, respectively for pct and crp. a cutoff of[0.8 ng/ml for pct (sensitivity 91% and specificity 59%) best identified patients with bacterial co-infection. for crp, a cutoff of[220 mg/l (sensitivity 75%, specificity 78%) best identified patients with bacterial co-infections. comparison of the 2009 h1n1 pneumonia and bacterial pneumonia group revealed no differences except for a higher saps 3 in the latter pro endothelin (pro et) and copeptin (pro vasopressin cp)) for diagnosing infection in patients with severe acute dyspnea. methods. we designed a prospective study of patients admitted in emergency department (ed) and medical intensive care unit (icu) in a university hospital. inclusion criteria were acute dyspnea with spo 2 b 92% and/or respiratory rate c25 b/min. patients with obvious myocardial infarction or pneumothorax were excluded. all clinical and biological data were recorded and biomarkers sampled. an independent blinded expert panel classified the patients according to all the available data including response to treatment and outcomes blindly to biomarkers' results. the roles of biomarkers were assessed quantitatively and then using terciles of the distribution. the contribution of the biomarkers in the diagnosis was assessed using auc-roc curves and by multiple logistic regression taking into account other clinical and biological explanatory variables. results. 342 consecutive patients (52% male, med age 74 years, 28 day mortality 17%) were enrolled. the final diagnosis was severe sepsis for 126 (36.9%) (pulmonary: n = 104, non-pulmonary n = 22). the parameters independently associated with infection lead to a clinico-biological model with an auc = 0.806 and a good calibration (p (hlchi2) = 0.55) and included temperature, arterial pressure, cyanosis, stupor and coma, orthopnea, localized chest sound abnormalities, pao 2 /fio 2 ratio and localized infiltrate on chest x ray although new biomarkers were different between septic and non septic patients with severe acute dyspnea, only mid pro-anp may add a significant contribution. further analysis about the prognostic value of these biomarkers is ongoing grenoble university hospital and brahms diagnostic czech republic, 2 1st faculty of medicine charles university and thomayers' hospital, anesthesiology and intensive care medicine fluid management with cvp is still common despite lack of efficacy. objectives. implement stroke volume maximisation during major surgery using odm guided fluid challenges. assess impact of odm use on central venous line insertion rates. identify and overcome barriers to adoption of odm technology. methods. nhs technology adoption centre project (ntac) supported an implementation project at 3 hospitals. the audit into central catheter use during major surgery was undertaken at manchester royal infirmary. fourteen anaesthetic consultants volunteered to champion odm use to guide targeted fluid challenges with hes 130/0.4 (voluven, fresenius kabi) within a range of major surgical procedures (colo-rectal, hepatic, pancreaticobiliary, urological, reno-pancreas transplant and emergency surgery). prospective data was collected for 224 patients who underwent major surgery between with no significant differences in preoperative risk, intervention patients had enhanced post-operative outcomes. cvc insertion reduced after anaesthetists had the opportunity to use odm to guide fluid therapy. reference(s) clinically used fluids modify in vitro phenotype and function of circulating immune cells peri-operative fluid loading, i.e. ''hemodynamic optimization'', reduces post-operative complications and hospital length of stay. mechanisms involving perfusion have been studied, but fluid could also alter phenotype and function of circulating immune cells, and consequently the systemic inflammatory response induced by surgery blood from 10 control donors has been diluted in crystalloid fluid (isotonic saline, wsio), colloids (hydroxyethyl starch (hes 130 kd, 0.4%) and 20% albumin solution (alb)), or autologous plasma, which corresponds to clinical situations in programmed anesthesia and surgery. two dilution levels have been studied, to achieve 8-9 g/dl hemoglobin (dilution 1) and 4-5 g/dl (dilution 2) 630)* cd18 mono (sites/cell) 61,982 (16,724) 24,203 (11,543)* 61,689 (18,489) 35,176 (30,463)* 53,103 (19,834)* cd11b pmn (sites/cell) alb only increased ord, but not activation and adhesion markers. conclusions. wsio had clear anti-inflammatory properties, whereas colloids were more inflammatory, with a dissociation of the effects between different types of fluids. mechanisms have to be precised, especially regarding physico-chemical, immuno-inflammatory and metabolic regulations. reference(s). none. grant acknowledgment. plan quadriennal outcome-related factors federacion panamericana e iberica de sociedades de medicina critica y terapia intensiva (fpimcti) our aim was to conduct a multicenter study to evaluate the epidemiology of delirium in intensive care units (icu) a 1-day point-prevalence study was performed with the aim of describing in 104 icus from 11 countries in south and north america and spain 64% were admitted to the icu due to medical causes and sepsis was the main diagnosis (n = 76, 15.3%). 265 patients were sedated and only 232 (46.6%) patients could be evaluated with the cam-icu. the prevalence of delirium was 32.3% (n = 75). as compared to patients without delirium, those with the diagnosis of delirium had a higher severity of illness at admission as demonstrated by higher sofa increased use of invasive devices such as central venous catheter (p \ 0.0001), arterial catheter (p = 0.004) and urinary catheter (p = 0.0001) were more frequent in patients with delirium. on multivariate analysis, delirium was independently associated with increased icu mortality in this one-day international study, delirium was frequent in icu patients and associated with increased mortality and icu los. the main modifiable risk factors associated with the diagnosis of delirium were the use of invasive devices and sedatives the study was funded by the federacion panamericana e iberica de sociedades de medicina critica y terapia intensiva (fpimcti). the fpimcti has used in part an educational grant from hospira recent studies suggest that increased blood glucose variability (bgv) is associated with icu mortality 1 . hypothermia is known to induce insulin resistance, thus potentially increasing bgv. no studies however have examined the effect of therapeutic hypothermia (th) on insulin requirements and bgv. objectives. to examine the effect of th on bgv and its relationship to all patients were treated with intravenous insulin (blood glucose target 6-8 mm), according to a written algorithm, with nurse-driven adjustment of insulin dose. for each patient, standard deviation of repeated blood glucose samples was used to calculate bgv. two time-points, comparable in duration, were studied: th (stable maintenance phase, i.e. 6-24 h, core temp ± 33°c) vs. normothermia (nt, i.e. after rewarming, stable normothermic phase, core temp ± 37°c). mortality and neurological recovery (glasgow-pittsburgh cerebral performance categories, cpc, dichotomized as good = cpc 1-2 vs. poor = cpc 3-5) were assessed at hospital discharge. statistical analysis was performed with anova for repeated measures therapeutic hypothermia is associated with increased insulin requirements and higher blood glucose variability, which in turn correlates with worse prognosis in patients with post-ca coma. strategies aimed to maintain stable glycemic profile and avoid blood glucose variability might contribute to optimize the management of th and may translate into better outcome glucose variability is associated with intensive care unit mortality therapeutic hypothermia post cardiac arrest has been shown to improve survival and neurological outcome 1 . there are approximately 50,000 treated cardiac arrests in the uk each year with one-eighth we aimed to establish if implementation of an agreed care bundle including therapeutic hypothermia reduced mortality and improved neurological outcome patients were categorized according to initial cardiac rhythm, ventricular fibrillation/tachycardia (vf/vt) or non-vf/vt. we recorded the degree of implementation of the post cardiac arrest care bundle, comprising; coronary reperfusion, haemodynamic optimisation, control of ventilation, blood glucose, temperature and seizures. data was compared with survival to discharge and neurological function there were 111 ihas, 73 male (mean age 67.3 years) and 37 female (69.9 years) and 128 oohas, 94 male (61.4 years) and 34 female (62.6 years). the predominant presenting rhythm in oohas was vf/vt (58.8%) compared to ihas which was non vf/vt (89.3%). underlying co-morbidities included 32-34°c) was achieved in 75% of vf/vt oohas compared to 14.3% of vf/vt ihas. the complete care bundle was delivered to 56.3% of oohas and 3.6% of ihas survival rates were higher in all patients with complete bundle of care versus those with an incomplete bundle independent of location or rhythm (53.9 vs. 38.7% p = 0.01). this improval in survival was also demonstrated in vf/vt arrests receiving the complete bundle of those patients who had a vf/vt arrest, survival with full neurological recovery (gcs 15 on discharge) was higher in those receiving therapeutic hypothermia 53.2 versus 17% where therapeutic hypothermia was not achieved adherence to the post cardiac arrest care bundle led to significantly improved outcome following both vf/vt and non vf/vt arrests. there was a trend towards therapeutic hypothermia improving neurological outcome on discharge reference(s). 1. the hypothermia after cardiac arrest study group. mild therapeutic hypothermia to improve the neurological outcome after cardiac arrest royal sussex county hospital intensive care unit, brighton, uk for patient data h. altemimi 1 , s. altaf 1 , j. brown 1 , s. al-juboori 1 , v. jadhav 1 1 queen elizabeth hospital, kings lynn, medical assessment unit, kings lynn, uk introduction. the medical assessment unit (mau) in our district general hospital (with 500 beds) provides assessment and treatment of acute medical patients from general practice (gp) referals and the emergency department (ed). patients arriving in mau are first triaged by the nurses before assessment by junior doctors. the early warning score (ews) is an indepenently verified scoring systems used to prioritise patient assessment. appropriate referal to critical care outreach teams and intensive care units can be triggered by nurses or doctors according to the ews score. clear and seemless referal pathways and communication between those involved with acutely unwell patients is essential. objectives. to measure key performance indicators in the mau and identify specific areas for improvement. methods. retrospective audit of all admissions to medical assessment unit during 1 week in 2009. the following parameters were recorded for 149 patients admitted. patient ages ranged from 16 to 94: [3. of these, only 4 were reviewed within 1 h. 7. 100% of patients reviewed within 15 min. conclusions. in the uk, early warning scores have been developed to trigger early review. the most sophisticated intensive care becomes unnecessarily expensive terminal care when the pre-icu system fails to refer in a timely manner. our results showed that when a patient was recognised as being unwell, they were seen rapidly by the outreach team. however, not all new admissions had their ews documented, overlooking an important opportunity to risk stratify patients before formal medical clerking. our critical care outreach team have prominent role in education to identify abnormal physiology early, and take action as appropriate. immunological host reactions are primarily believed to determine the clinical course of this disease. an overwhelming inflammatory response to microbial invasion may be involved in the pathogenesis of sirs, sepsis and multiple organ failure. it is important to block the inflammatory response and stop or alleviate sepsis injuries. immunotherapy is regarded as effective approach to improve the immunological function. objectives. immunomodulation in the critically ill is an appealing notion because of the abnormal immune responses. the aim of this study is to evaluate the immunomodulation and its mechanism to improve immune function and prognosis in sepsis. methods. experimental part:clp model were divided into three groups including sham group, control group and experimental group. control group only used antibiotic and experimental group used antibiotic plus immunomodulation. blood collection were made after clp model in 3, 12, 24 and 48 h. lymphocyte counting, cd 4 +, cd 8 + t lymphocyte and cd 4 /cd 8 ratio were checked. the apoptosis of lymphocyte in thymus and spleen and survival rate were checked. clinical part: prospective analysis seventy patients conformed to the enrolled standard. it was divided into two groups at random. one was control group with regular therapy, the therapy group with ulinastatin plus thymosin-a 1 in a week. the immune index before and after therapy in the 0, 1st, 3rd, 7thday was observed. results. experimental part: lymphocyte, cd 4 + t lymphocyte and cd 4 /cd 8 ratio in experimental group increased more significant than in control group (p \ 0.05). lymphocyte apoptosis index of thymus and spleen in control group increased more significant than in experimental group (p \ 0.05).72 h-survival rate in experimental group was higher than in control group. clinical part: cd 4 + t lymphocyte, lymphocytes and hla-dr cd 14 + had more significant increase in therapy group than in control group (p \ 0.05). twenty patients died in the control group and thirteen patients died in the therapy group (p \ 0.05). conclusions. immunomodulation in sepsis can improve immune function and alleviate the lymphocyte apoptosis and extend the survival time. in recent years, the antiinflammatory effects of niacin by reducing nuclear factor jb (nf-jb) activation have attracted attention. however, the protective effects of niacin on the development of acute lung injury and systemic inflammatory response during sepsis have not been studied.objectives. we performed this study to determine whether niacin attenuates acute lung injury (ali) and improves survival during sepsis and the beneficial effects of niacin are associated with the down-regulation of nf-jb pathway.methods. lipopolysaccharide (lps) at a dosage of 10 mg/kg was injected into the tail vein to induce endotoxemia in rats. then, vehicle, low dose niacin (360 mg/kg), or high dose niacin (1180 mg/kg) diluted in distilled water with same volume (3 ml/kg) was administered once to the rats through orogastric tube, respectively. we observed the survival of the subjects. at 6 h post-lps injection, we measured serum tumor necrosis factor-a (tnf-a), interleukin-6 (il-6) levels, lung cytoplasmic phosphorylated inhibitor jb-a (p-ijb-a), ijb-a, nuclear nf-jb p65 expressions, nf-jb p65 dna-binding activity, and ali occurrence.results. high dose niacin improved survival during sepsis. niacin induced dose-dependent reduction of serum tnf-a, il-6 levels, lung cytoplasmic p-ijb-a, nuclear nf-jb p65 expressions, nf-jb p65 dna-binding activity, and ali occurrence in endotoxemic rats. in contrast, niacin preserved lung cytoplasmic ijb-a expression dose-dependently in endotoxemic rats.conclusions. niacin attenuated acute lung injury and improved survival during sepsis in rats. the protective effects of niacin were associated with the down-regulation of nf-jb pathway. niacin can be considered as a therapeutic agent for sepsis. f. barbani 1 , m. boddi 2 , r. cammelli 3 , a. cecchi 3 , e. spinelli 3 , m. bonizzoli 3 , a. peris 3 1 university of florence, postgraduate school of anesthesia and intensive care, florence, italy, 2 university of florence, department of critical care medicine and surgery, florence, italy, 3 careggi teaching hospital, anesthesia and intensive care unit of emergency department, florence, italy introduction. acute kidney injury (aki) is a frequent complication in critically ill patients. there is emerging evidence that aki can lead to chronic kidney disease and that even only partial renal recovery after aki is associated with a higher long-term mortality.objectives. we investigated whether measurement of renal resistive index (rri) by ultrasound could predict renal function recovery after aki.methods. rri has been determined in patients who had been admitted (jan 2008 -feb 2010 to our mixed intensive care unit (icu) and referral trauma center (careggi teaching hospital, florence, it) and developed aki. rri measurements were performed within 24 h from aki diagnosis, according to rifle criteria. renal recovery was defined as the return to the normal renal function parameters.results. patients studied were 38 (29 male vs. 9 female) with a mean age of 58.9 ± 20.9 years. aki was due to sepsis (n = 11), shock (n = 8), rhabdomyolysis (n = 7), abdominal compartment syndrome (n = 8) and major surgery (n = 4). mean length of icu stay was 17 ± 12 days. at discharge 18 patients showed a complete recovery of renal function, while 20 patients had persistent altered renal function parameters or needed renal replacement therapy (rrt); mortality rate was 18.4% (7/38) . rri measured at aki onset was significantly higher in patients with persistence of renal failure than in patients with complete renal recovery (0.89 ± 0.13 vs. 0.72 ± 0.14, p \ 0.001). rri [ 0.75 had a sensitivity of 81% (95% ci 67-90%), a specificity of 70% (95% ci 53-82%) and a positive likelihood ratio of 2.75 (95% ) for persistent renal dysfunction at the discharge.conclusions. our findings suggest that doppler-based determination of rri at the onset of aki can identify those patients who are at greater risk for no complete recovery of renal function. further studies on larger populations are required to confirm these preliminary results so to promote therapies dedicated to this high risk population.conclusions. apache2 score on admission, hypothermia and mean arterial pressure are not statistically significant, but age approached significance at 10% level in ccu survival. blood sugar control is not statistically significant at 5% level but approached significance as p value was less than 0.10 for ccu survival. for hospital survival,age is significant at 5% level; apache2 score on admission and mean arterial pressure are significant at 10% level while cardiac index, hypothermia and glycaemic control are not statistically significant . in 2008 the intensive care society (ics) published a care bundle for the management of patients following cardiac arrest 1 . the american heart association now recommends regionalisation of post-resuscitation care following out of hospital cardiac arrest (ohca), in a centre capable of providing rapid therapeutic hypothermia, 24 h emergency angiography and percutaneous coronary intervention (pci) as necessary 2 . objectives. the audit's purpose was to evaluate work load, treatment and outcomes of ohca on the icu following publication of the ics care bundle and inception of a 24 h pci service in our hospital. methods. retrospective audit of ohca patients admitted to icu from 12/2008 to 12/2009 to examine number admitted, cause of arrest, treatment and mortality. predicted mortality from the icnarc model 3 was used to calculated standardised mortality ratio (smr). comparison was made with an audit of ohca patients between 03/2007 and 03/2008. the sample was subdivided into subgroups with cardiac and non-cardiac cause for ohca. the chi-square test was used in analysis. results. comparison conclusions. we demonstrated: 1. a significant increase both in the absolute number of ohca and the proportion due to cardiac causes, due in part to in-region transfers for emergency angiography/pci. 2. a significant increase in the use of angiography and pci, increasing use of therapeutic hypothermia and iabp. 3. improved survival from previous audit. 4. better than predicted survival, particularly in the 'cardiac' group. this audit lends support for the protocolised icu care of post-ohca patients in a regional centre able to offer 24 h emergency pci. there is scope for increased use of cooling for arrests of all causes, and extending provision of angiography/pci to vf arrests and those of unknown cause 2 . reference(s). 1 . despite all the research, education and training that has gone into the field of cpr during the last 50 years, survival rates remain bleak for the majority of patients 2 . so, what is lost in translation? much of the problem is that what the medical community is being trained to do is not being replicated in clinical practice 3 . given this discrepancy, along with the deleterious outcomes, we conducted a manikin-based study to assess the quality of ventilation delivered during simulated cpr, in a large uk centre. objectives. to demonstrate whether uk-based medical personal were adhering to ventilation guidelines and to see how this result varied across specialities. methods. a simulated cardiac arrest scenario was undertaken by 97 (a-0.05, power-90%) participants from a range of medical specialties. participants were asked to asynchronously ventilate our manikin for a period of 1 min during which time tidal volumes (tv), minute volume (mv) and ventilation rates (vr) were recorded. to help limit outside influence, at no point during the trial was any feedback about ventilation technique or als principals discussed with the participant. results. the mean and sd across the sample population for the mv, vr and tv were 13.1 l min -1 (sd 7.3), 21.2 min -1 (sd 9.1) and 647 ml (sd 170) respectively. comparison of groups can be seen in table 1 introduction. mild hypothermia reduces cerebral blood flow (cbf) without concurrent increase of cerebral oxygen extraction rate in the first 24 h after cardiac arrest, indicating a lower cerebral metabolic activity with a preserved metabolic coupling.objectives. the aim of this study was to assess the cerebral blood flow and cerebral oxygen extraction in patients treated with prolonged hypothermia, as previously was performed in newborn infants with perinatal asphyxial encephalopathy 1 . patients were included after restoration of spontaneous circulation (rosc) after asystole, pulseless electrical activity based circulatory arrest or after rosc after ventricular fibrillation based prolonged resuscitation. in this prospective observational study 9 comatose patients after cardiac arrest were treated with prolonged hypothermia for 72 h. after 72 h patients were passively rewarmed. mean flow velocity in the middle cerebral artery (mfv mca ), reflecting cbf, was measured after 0, 12, 24, 36, 48, 60, 72, 84, 96 and 108 h after admission to the icu by transcranial doppler (tcd). jugular bulb oxygenation (sjbo 2 ) and arterial oxygenation were measured at intervals of 6 h. introduction. isoflurane is a volatile anesthetic known for its direct vasodilating effect on cerebral vessels, producing a cbf increase. moreover, it has been shown in animal studies that isoflurane has neuroprotective properties, inducing tolerance to ischemia when used as a preconditioning agent. at the present time, isoflurane is not used as a sedative agent in neuroicu because of the fear of an increase in intracranial pressure (icp) caused by the increase in cbf. however, sah patient at risk for vasospasm may benefit from an increase in cbf. the ischemic risk will peak at day 5-7, leaving a window of opportunity for neuroprotection. objectives. we decided to measure rcbf during traditional intravenous sedation with propofol and during volatile sedation with isoflurane in sah patients not having intracranial hypertension. the clinical trial was approved by the hospital irb and registered on trial.gov (nct00830843). we enrolled 4 sah (fisher 3-4, wfns b3) patients, monitored with an intraparenchimal icp device and a thermal diffusion probe (tdp, hemedex) for the assessment of rcbf. an icp [18 mmhg was an exclusion criteria. cerebral and haemodynamic parameters were assessed at 3 steps:step 1 during sedation with propofol 3-4 mg/kg/ h; step 2: after 1 h of sedation with isoflurane 0.8-1% mac administered through an anesthetic conserving device; step 3 after 1 h of propofol re-started at the same infusion rate. in all 4 patients sedation with isoflurane produced an increase of rcbf although not yet significant in the population (step 1: 23 ± 18 ml/100 g/min; step 2: 58 ± 62 step 3: 19 ± 8). jugular vein oxygen saturation, sjo2, was significantly higher at the end of the isoflurane step (step 1: 74 ± 4%; step 2: 83 ± 5; step 3: 73 ± 4). icp did not change significantly and remained below the pathological threshold (step 1: 6.7 ± 2; step 2: 7.7 ± 3; step 3: 7 ± 4 mmhg).conclusions. the small population of this pilot study phase causes a lack in statistical significance, however our data already suggest that isoflurane induces a marked cerebral vasodilatation and an increase in rcbf compared to propofol. patients with a normal icp did not develop an intracranial hypertension. at short and long term and its correlation with severity scales, scales of quality of life and endovascular treatment m there is not a consensus about which scales should be used to define the outcome after aneurysmal subarachnoid hemorrhage. objectives. the purpose of this study was to determine the risk factors and impact on functional outcome and quality of life 6 months after spontaneous sah due to ruptured intracranial aneurysms. methods. we performed a prospective study of 46 patients with aneurysmal spontaneous sah admitted to our centre from july 2008 to august 2009. diagnosis of sah was done by ct and ethiological diagnosis by brain angiography. we paid attention to previous pathological history, clinical characteristics at admission and radiological characteristics. the severity was measured by the hunt-hess (hh), wfns, graeb and fisher scales. the 6 months outcome was assessed by the glasgow outcome scale (gos) and modified rankin scale. the basic activities of daily living were evaluated with the barthel index. moreover, patients were asked about their subsequent incorporation to their previous occupation. we divided our population into two groups depending on the clinical grade at admission (hunt-hess scale): group i, hh 1, 2 or 3; and group 2, hh 4 or 5. long-term followed up continues. results. during the year of study a total of 46 patients have been included. the mean age of patients was 55 years with a prevalence of 65% in women, being arterial hypertension and smoking history the main factors of related risk. the angiography was performed in 95.6% of the patients. an aneurysm was confirmed as the origin of the bleeding in 78.3%. poor clinical grade at admission (hh 4 or 5) was associated with apache ii, sofa, glucose, more sah computed tomography on admission, and infection and icu stay. there is 29% mortality in the series. after a 6 months period, group 2 patients (hh 4 or 5 grade) had a severe disability and functional dependence to perform instrumental and basic activities of daily living (p = 0.001). only 35% of patients were able to return to their previous occupation 6 months after the initial bleeding. scales and outcome by clinical grade at admission introduction. aneurysmal subarachnoid hemorrhage (asah) remains a therapeutic challenge due to unacceptably high levels of mortality and morbidity. for survivors of the initial insult, cerebral vasospasm and related delayed ischemic deficits are the major determinants of final outcomes. traumatic sah (tsah) occurs in as high as 60% of patients with tbi, and is associated with a twofold increase in risk of death. statins may be an alternative for conventional treatments of vasospasm due to their beneficial pleiotropic effects on cerebral vasomotor reactivity as well as absence of negative haemodynamic influence.objectives. the goal of our study was to examine the effects atorvastatin therapy on cerebral vasospasm after asah and tsah as well as on short term outcomes of icu patients (length of stay and severity of condition upon discharge from icu). hypertonic saline infusion is an alternative to mannitol to decrease intracranial pressure before craniotomy [1, 2] . previous studies have demonstrated that both hypertonic saline and mannitol interfere negatively with various components of blood coagulation [3, 4] . normal blood coagulation capacity is essential during craniotomy and, therefore, we created an in vitro model to examine the effects of hypertonic sodium chloride and mannitol solution on whole blood coagulation. fresh citrated whole blood, withdrawn from 10 volunteers, was diluted with 0.9, 2.5 or 3.5% sodium chloride solution or 15% mannitol to make 10 vol.% and 20 vol.% hemodilution in vitro. the diluted blood and undiluted control samples were analyzed with thromboelastometry (rotem ò ) using two activators, tissue thromboplastin without (extem ò ) or with cytochalasin (fibtem ò ). all the study solutions with the same vol.% hemodilution induced comparable decrease in hematocrit. in extem ò analysis, alpha-angle was smaller in the mannitol group than in the 0.9% or 3.5% sodium chloride group after 10 vol.% dilution (p.05). in 20 vol.% hemodilution, alpha-angle was also more decreased, and clot formation time more delayed in the mannitol group than in the 0.9, 2.5 or 3.5% sodium chloride groups in extem ò analyses (p \ 0.05). maximum clot firmness (mcf) in extem ò analysis was similar with all the study solutions after 10 vol.% dilution, but after 20 vol.% dilution mcf was weaker in the mannitol group than in the other groups. mcf was also weaker in 3.5% than in 0.9% sodium chloride group after 20 vol.% dilution. in fibtem ò analysis, mcf was stronger in the 2.5% sodium chloride group than in the mannitol group after both dilutions (p \ 0.05). a 10 or 20 vol.% dilution of 15% mannitol disturbs whole blood coagulation more than equiosmolar 2.5% sodium chloride. this disturbance seems to be attributed to overall clot formation and strength but also to pure fibrin clot firmness. 2.5% sodium chloride might be more favorable than mannitol before craniotomy in patients with high bleeding risk. introduction. delayed cerebral ischemia (dci) is a major complication after aneurysmal subarachnoid haemorrhage (sah), occurring in around 30% of patients and increasing case fatality 1.5-3-fold. induced hypertension, alone or in combination with haemodilution and hypervolemia (triple-h), is used around the world as a therapy in the treatment of dci, but its efficacy in improving outcome is not based on a randomised clinical trial. objectives. to investigate the outcome of induced hypertension versus no induced hypertension in patients with dci after aneurysmal sah. study design a multi-centre, single blinded, randomized controlled trial. study population patients admitted after recent sah with a treated aneurysm and dci based on the onset of a new focal deficit and/or a decrease of the level of consciousness of at least 1 point on the glasgow coma scale with exclusion of other causes of deterioration, will be randomized to either hypertension (n = 120) or no hypertension (n = 120). interventions in the intervention group, blood pressure will be raised with norepinephrine or additional dobutamin in case of low cardiac output. when clinical improvement occurs, hypertension will be continued for 48 h, after which the dose norepinephrine will be tapered daily, but resumed in case of clinical deterioration. when no clinical improvement occurs within 24 h, induced hypertension will not be continued. patients in the reference group will be treated according to the standardised sah treatment protocol of the participating centre including oral nimodipine and normovolaemia without haemodilution. main outcome measurement the modified rankin scale at 3 months after the sah, will be compared between patients who were randomized to induced hypertension and patients who were randomized to no induced hypertension. objectives. to investigate brain metabolism at different serum glucose levels.methods. six patients with aneurismal sah and vasospasm were enrolled in the study (age 47.5 ± 18.1; male/female 1/5; . cerebral microdialysis was used in all patients. microdialysis catheters were placed into ''lesioned'' (brain tissue perfused by involved artery) and ''intact'' brain tissue. glucose levels in arterial blood (glu art ) and in brain interstitial fluid were compared. we analyzed brain glucose levels, intracranial pressure (icp), lactate/pyruvate (l/p) ratio, pao 2 , paco 2 and cerebral perfusion pressure (cpp) at blood glucose levels b6 mmol/l (group i, n = 50), 6.1-10 mmol/l (group ii, n = 112), 10.1-14 mmol/l (group iii, n = 56), c14 mmol/l (group iv, n = 21). we found out tight correlation between glucose levels in arterial blood and in ''lesioned'' brain tissue (n = 239; r = 0.71; p \ 0.0001) and weak correlation between gluart and glucose levels in ''intact'' brain tissue (n = 177; r = 0.43; p \ 0.0001). pao 2 , paco 2 , icp and cpp were comparable between groups. glu art was 5.3 ± 0.6 mmol/l in group i, 7.5 ± 1.1 mmol/l in group ii, 11.8 ± 1.2 mmol/l in group iii and 16.6 ± 2.9 mmol/l in group iv. normal glucose levels in arterial blood (group i) were accompanied by low glucose levels in ''intact'' (0.52 ± 0.4 mmol/l) and ''lesioned'' (0.49 ± 0.28 mmol/l) brain tissue. arterial blood glucose elevation has led to significant increase in brain glucose levels. but brain glucose levels were in normal ranges during hyperglycemia. glucose levels in ''intact'' brain tissue: 1.16 ± 0.79 mmol/l (group ii), 1.76 ± 1 mmol/l (group iii), 1.24 ± 0.53 mmol/l (group iv). glucose levels in ''lesioned'' brain tissue: 0.99±0.7 mmol/l (group ii), 1.58±0.7 (group iii), 2.7±1.4 (group iv). we didn't find out any significant differences in l/p ratio at different blood glucose levels. however, low glucose levels in ''intact'' brain tissue (b1.4 mmol/l; 0.7±0.4 mmol/l; n = 123) were accompanied by significant increase of l/p ratio (34.2±15.8 vs. 27.6±11.4 at normal brain glucose levels (c1.5 mmol/l; 2.3±0.7 mmol/l; n = 54)). we didn't notice any significant differences in l/p ratio in ''lesioned'' brain tissue at different brain glucose levels, opposite to intact brain tissue. l/p ratio was 29.5 (24.2; 43.1) at glucose levels in ''lesioned'' brain tissue b1.4 mmol/l (0.73 ± 0.4 mmol/l; n = 175) vs. 31(26.3;37) at glucose levels in ''lesioned'' brain tissue c1.5 mmol/l (2.4 ± 0.9; n = 64).conclusions. hyperglycemia is not accompanied by high glucose levels and brain metabolism impairment in ''intact'' and ''lesioned'' brain tissue in severe patients with aneurismal sah. low glucose levels in ''intact'' brain tissue are related with significant increase of l/p ratio. introduction. the 2007 national confidential enquiry into patient outcome and death report found that less than 50% of patients with a severe head injury received a standard of care that was judged to be good [1] . our intensive care unit (icu) at the royal cornwall hospital, a large district general hospital, is one of the few non-neurosurgical centres in the uk to use intracranial pressure (icp) monitoring. we aimed to assess if the practice of icp monitoring in our non-neurosurgical centre was valuable and safe. retrospective audit of case notes and charts of all patients admitted with traumatic brain injury receiving icp monitoring over a 6 year period from 1st january 2004 until 1st january 2010. a total of 23 patients who had icp monitoring for traumatic brain injury were identified. the codman tm strain-gauge catheter was used in all cases, 20 (87%) were male, 3 (13%) were female. mean age was 36 years (range 14-86). median reported gcs at the scene of injury was 3 (range 3-15), median gcs prior to intubation was 7 (range 3-15). median apache score was 16 (range 5-36). all patients were discussed with the neurosurgical referral centre. patients were monitored for a median of 2 days (range [1] [2] [3] [4] . icp was raised in 15 patients (65%). elevation of icp triggered the following interventions: 13 patients (87%) received hyperosmolar agents, 8 patients (53%) were treated with therapeutic hypothermia, 2 patients (13%) with barbiturate coma and none of the patients received steroids. 5 patients were transferred to a neurosurgical centre (33% of patients with elevated icp, 22% of total). complications comprised one minor intracranial haematoma and one monitor failure. review of documented care bundles for head-injury patients revealed: head-up tilt in 96%, gastric protection in 91%, normoglycaemia in 91%, early enteral nutrition in 96%, appropriate thromboprophylaxis in 87%, appropriate sedation in 96% and appropriate analgesia in 96%. 87% survived to hospital discharge.conclusions. in our audit the majority of patients received specific treatment for raised icp, which might have gone undetected without invasive icp monitoring. at the same time most patients were managed without neurosurgical intervention. in light of the paucity of neurocritical care beds [2] this approach appears to help to select a suitable subgroup of patients needing transfer to a specialist centre. our data adds weight to the evidence that icp monitoring is a valuable and safe monitoring modality in a non-neurosurgical icu if used appropriately within established guidelines and in collaboration with a neurosurgical referral centre. introduction. assessment of injury severity and prediction of outcome represent major challenges following severe traumatic brain injury (tbi). objectives. this study was aimed to evaluate relationships between cerebrospinal fluid (csf) levels of purported biomarkers of tbi including glial fibrillary acidic protein (gfap), ubiquitin c-terminal hydrolase (uch-l1) and alpha-ii spectrin breakdown product (sbdp145), and partial pressure of brain tissue oxygen (ptio 2 ) as well as brain temperature during the first 24 h and up to 10 days post-injury.methods. twenty-seven severe tbi patients with csf drainage and invasive monitoring (licox probe) have been studied with quantitative csf-elisa for sbdp145, uch-l1 and gfap on admission and every 6 h up to 10 days. in the first 24 h, biomarker levels decreased while those of ptio2 increased. all three biomarkers correlated with ptio2 (p \ 0.0001, p = 0.016 and p = 0.023, respectively). after the first 24 h, there were statistically significant changes in levels of the three markers as well as in levels of ptio 2 (p = 0.025, p \ 0.0001, p = 0.033, p \ 0.0001, respectively). however, the correlation between biomarkers and brain tissue oxygenation was sustained and, for uch-l1 improved (p \ 0.0001). no significant correlations between biomarker levels and brain temperature were found. the results indicate that cfs levels of sbdp145, uch-l1 and gfap are related to ptio 2 following severe tbi. future studies are on their way to unravel whether these biochemical markers and ptio 2 measurement could serve the better care of the head injured. introduction. this was a pilot study to compare the cerebral neurochemical changes in patients with traumatic brain injury (tbi) who underwent conventional blood glucose level (bgl) control and intensive bgl control with continuous titrated insulin.objectives. to demostrate that intensive glycaemic control using insulin induced a decrease of cerebral glucose.methods. this prospective, randomized study was conducted in 30 traumatic brain injury patients in a surgical and trauma intensive care unit. patients admitted over an 18-month period with tbi were prospectively divided into two groups according to the method used for bgl control: the 0 intensive 0 group consisted of patients who underwent continuous titrated insulin infusion to maintain a lower normoglycemic level of 4-8 mmol/l, and the 0 conventional 0 group consisted of patients whose bgl was maintained at between 8.1 and 10.0 mmol/ l using conventional 0 sliding scale 0 bolus subcutaneous insulin administration. data on cerebral haemodynamics, interstitial brain oxygenation (ptio (2)) and neurochemical monitoring were collected via microcatheters inserted in the penumbral region. we analyzed 2,844 cerebral microdialysis samples. in 15 patients treated with intensive insulin therapy, there was a reduction in microdialysis glucose by 77% of baseline concentration compared with a 8% reduction in 15 patients treated with a conventional blood glucose level control. intensive insulin therapy was associated with increased incidence of microdialysis markers of cellular distress, elevated glutamate (44 ± 34 vs. 8 ± 14%, p \ .01), elevated lactate/pyruvate ratio (40 ± 37 vs. 14 ± 22%, p \ .03) and low glucose (26 ± 17 vs. 11 ± 15%, p \ .05), and increased global oxygen extraction fraction. cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 ± 0.23 vs. 1.04 ± 0.56 mmol/l, p \ 0.05).conclusions. intensive glycaemic control using insulin induced a decrease of cerebral glucose and an increase in microdialysis markers of cellular distress. in patients with severe brain injury, tight systemic glucose control is associated with increased mortality. introduction. we have previously used 11 c-flumazenil positron emission tomography to show that selective neuronal loss in the thalamus is pervasive after traumatic brain injury (tbi) and correlates with functional outcome, 1 findings that are concordant with previous post-mortem data. 2 the mechanisms responsible are unclear, but may involved global hypoxia/ischaemia as well as retrograde degeneration.objectives. we hypothesised that early brain tissue oxygenation would correlate with late diffusion tensor imaging (dti) abnormalities in the thalamus, and therefore, help to provide an explanation for late neuronal loss. nine patients underwent brain tissue oximetry (pbo 2 ) following acute tbi, using a licox pbo 2 probe, sited in structurally normal frontal white matter. mean pbo 2 was calculated for the duration of their intensive care admission. at a median of 11.6 months (range 237-702 days) they underwent magnetic resonance imaging, including dti. apparent diffusion coefficient adc (maps) were created, adc calculated in regions of interest in the frontal lobes, splenium of the corpus callosum and thalami, and correlated with mean pbo 2 using spearman's rho. ethical approval was obtained from the local research ethics committee, and assent from next-of-kin was obtained in all cases.results. mean pbo 2 was inversely related to adc in both frontal lobes (r = -0.73 and -0.72; p = 0.025 and 0.031), and with the adc in the thalamus bilaterally (r = -0.87 and -0.80; p = 0.002 and p = 0.010). in contrast, no correlation was seen between mean pbo 2 and adc in the splenium of the corpus callosum, a common site of traumatic axonal injury (tai; p = 0.265).conclusions. the inverse correlation of mean pbo 2 associated with adcs in the monitored brain region is unsurprising, but the correlations observed with contralateral regions and deep grey matter suggest that the burden of tissue hypoxia has a significant impact on secondary neuronal loss across the brain. in contrast, the lack of correlation with adc changes in an area at risk of tai suggests a less significant impact of hypoxia on the progression or maturation of tai. the correlations with measures of thalamic microstructural injury are particularly significant, since they establish a clear link between acute physiology, tissue fate in key brain regions, and clinical outcome. introduction. earlier studies have suggested that autonomic dysfunction is associated with poor outcome in traumatic brain injury (tbi).objectives. this study was performed to assess changes in baroreceptor sensitivity and heart rate variability as indices of autonomic dysfunction in relation to icu management variables during early tbi.methods. ten patients (3 females/7 males) with a median age of 31 (interquartile range, iqr, 20-51) admitted to icu following tbi were prospectively studied for the first consecutive 6 days. all patients were sedated and mechanically ventilated with icp monitoring in place. high fidelity signals at 300 hz were sampled for ecg and invasive arterial pressure (radial) to monitor baroreceptor sensitivity (brs) based on three or more consecutive beats in which successive systolic pressure and rr intervals increased or decreased with the threshold set at 1 mmhg and 5 ms, respectively. heart rate variability (hrv) was analysed by fourier transformation in the low (lf, 0.04-0.15 hz) and high frequency (hf, 0.15-0.4 hz) domains. the lf/hf ratio and total power (0.01-0.6 hz) were also calculated for hrv. management variables included use of inotropes, vasopressors, icp, use of decompressive craniectomy, icu length of stay (los) and mortality. statistical significance was set at p \ 0.05 using mann-whitney one-way anova and spearman correlation tests. median days (and iqr) were 7.5 (3-9.8) for inotropes, 3.5 (0-9) for vasopressors and 19.5 (17-24.5) for icu los. brs and lf, hf, lf/hf ratio and total power were all depressed throughout early icu management with no significant changes in the first week. no significant correlations were found between brs/hrv and days on inotropes/vasopressors or icu los. four patients underwent decompressive craniectomy and one patient died while in icu. no correlation was found between these events and brs or hrv changes brs, hrv and icp data conclusions. both brs and hrv were depressed early following tbi but did not correlate to icu management variables. while autonomic dysfunction is evident early in the icu treatment of tbi, no evidence to support an association between severity of impairment and icu outcome was found in this pilot study. introduction. in neurocritical care, raised intracranial pressure (icp) is associated to a poor outcome and its detection still leads the therapeutic management of the patients suffering from head pathologies.objectives. although invasive devices are recommended to detect intracranial pressure (icp), we investigated the correlation and the reliability with non-invasive ultrasound techniques as the optic nerve sheath diameter (onsd) assessed by ultrasonography and the pulsatility index (ip) measured by transcranial doppler sonography (tcd). we included 13 patients suffering from intracranial hypertension, sedated and mechanically ventilated and 10 control individuals, chosen among healthy people. all the patients had icp measured invasively either by external ventricular drains (evd) or intraparenchymal catheter. everyone underwent 3 non-invasive measurements of onsd bilaterally and simultaneous medial cerebral artery ip assessment at the side of the best window.results. onsd had a significant difference between volunteers (4.50 ± 0.36 mm) and patients (5.60 ± 0.77 mm). ip's were 0.81 ± 0.16 for the control individuals and 1.27 ± 0.43 for the patients (media icp = 19 ± 12 mmhg) and also revealed a significant difference. onsd strongly correlated with icp (y = 0.026x + 5.005, p \ 0.020, r 2 = 0.66) whereas ip had some correlation but without statistical significance (y = 0.008x + 1.117, p = 0.188, r 2 = 0.59). onsd was found wider (p = 0.047) within patients with both icp and ip abnormal. a strong correlation was found between onsd and ip (y = 0.708x + 4.819, p = 0.004, r 2 = 0.51). however, we could not find the best cut-off values of onsd and ip for predicting an icp [20 mmhg.conclusions. ip and onsd correlated with icp with a stronger reliability results of the latter, suggesting the possibility to integrate their use in the case of icp invasive monitoring would be contraindicated or not available. we studied the effects of normothermic therapy during the acute phase of traumatic brain injury.methods. twenty patients (10 males, 45 ± 18 years old) who were admitted in the intensive care unit due to traumatic brain injury (glasgow coma scale upon admission 5-8, marshall scale ii to iv) were studied. if patients' core temperature was above 38.5°c, a cool line ò , alsius corporation, irvine, ca. usa intravascular heat exchange central venous catheter (coolgard 3000 ò device) was inserted via the femoral or the subclavian route, in order to achieve and maintain a target temperature of 36°c. intracranial pressure (icp) was measured (a) invasively by means of a intraparenchymal catheter (camino, camino laboratories, san diego, ca, usa) and (b) noninvasively by means of transcranial doppler sonography (tcd), using a philips hd11xe (philips medical systems; bothell, wa, usa) equipped with a 2 mhz transducer and a 12 mhz linear transducer. estimated icp was calculated by tcd using the equation proposed by czosnyka and colleagues 1 and the pulsatility index (pi = vs -vd/vm) was assessed in the middle cerebral artery bilaterally. all measurements were conducted at baseline and repeatedly on a daily basis for the next 7 days and the average values were used in the statistical analysis.results. target temperature (t: 36.2 ± 0.3°c) was achieved within the next 6 h of the catheter insertion. at baseline (t: 38.5°c) pulsatility index (pimean) was 1.4 ± 0.18, icpmean/invasive was 24 ± 4.5 mmhg and icpmean/noninvasive was 25.2 ± 5.1 mmhg. invasive and noninvasive icp values correlated significantly (r = 0.8, p \ 0.05). following 24 ± 5 h from the insertion of the catheter the above parameters were significantly decreased as compared to baseline values (pimean = 1.1 ± 0.1, icpmean/invasive = 21 ± 3.4 mmhg, icpmean/noninvasive = 22.1 ± 2.9 mmhg, respectively; all p \ 0.05). out of 20 patients, 1 progressed towards brain tamponade, 10 remained in a persistent vegetative state and 9 were discharged with normal consciousness and motor deficits. however, due to the small number of patients no analysis could be performed to estimate the possible impact of normothermic therapy on the survival of these patients. these preliminary results suggest that normothermia during the acute phase of traumatic brain injury may decrease icp and ameliorate cerebral blood flow. introduction. extracranial organ dysfunctions are extremely common in patients with severe traumatic brain injury (tbi). although it has been shown that development of tbiinduced multiple organ failure (mof) is associated with a poor outcome, the underlying mechanisms leading to mof after tbi have not been investigated.objectives. to investigate in vitro the effect of plasma from tbi patients developing different degrees of organ failure on human endothelial cells.methods. ten consecutive severe tbi patients were included. gcs, iss and sofa score were recorded at admission; sofa was also recorded after 2 days. plasma samples were obtained at the same time points. adhesion of freshly isolated human neutrophils on spontaneously transformed human umbelical vein endothelial cells (ecv 304) was evaluated after 4 h in vitro stimulation with 10% of plasma collected from tbi patients 2 days after admission. expression of intercellular adhesion molecule-1 (icam-1) was assessed by immunofluorescence. to determine the impairment of the endothelial cell barrier function, trans-endothelial electrical resistance (teer) and permeability to fitc-dextran were measured. plasma from healthy volunteers were used as control. data are expressed as mean ± sd. results from different experiments were compared by unpaired t test.results. ten male patients were enrolled, mean age 35 ± 15, gcs 7 ± 1, iss 32 ± 9, sofa was 5.3 ± 1.8 on admission and 8 ± 1.6 on day 2. plasma derived from tbi patients increased the adhesion of neutrophils on ecv 304 cells (80 ± 15 vs. 48 ± 7 cells/field, p \ 0.01), induced a significant reduction of teer (130.1 ± 1.8 ohm/cm 2 vs. 139.1 ± 1.9 ohm/cm 2 , p \ 0.001) and caused a concomitant increase of endothelial permeability to dextran (132.5 ± 27.2 vs. 97.5 ± 7.2%, p \ 0.05) compared to control (healthy plasma). a visual up-regulation of icam-1 expression was also observed. there was a significant correlation between delta sofa score (day 2-day 0), calculated excluding gcs, and neutrophil adhesion on endothelial cells exposed to plasma from tbi patients (p = 0.009, r 2 = 0.70).conclusions. plasma from patients with tbi causes the increase of endothelial permeability and neutrophil adhesion, which correlates with the development of extracranial organ dysfunction expressed by sofa. these results suggest a mechanism potentially responsible for the development of mof after traumatic brain injury.grant acknowledgment. fondi universitari ex-60%, regione piemonte-ricerca sanitaria finalizzata. objectives. the aim of this study is to describe indications of dc and outcomes in our unit.methods. it is a retrospective revue collecting patients who had a dc for severe icht between january 1996 and july 2009. inclusion criteria were: icht refractory to medical management due to cerebral oedema. we define intractable icht as intracranial pression (icp) over 20 cmh 2 o, pupil modification, neurologic deterioration persisting more than 30 min despite medical management or ct scan findings. exclusion criteria were imminent cerebral death, icht due to an acute hematoma, tumour, hydrocephalus and prediction of short life expectancy. objectives. historically, research has targeted problems experienced several months post discharge from critical care, namely using data from follow up clinics \12 months after the critical illness. in contrast, this study aimed to review data from patients recently transferred from critical care to the wards. this data can then be compared with patients' progress after earlier rehabilitation. methods. this was a prospective, longitudinal study, involving long stay critical care patients ([4 days), between april 2008-2010. this cohort included all patients nursed within our itu/hdu, regardless of speciality, age or gender. all reviews took place whilst the patients were still hospitalised. the study used qualitative data, using specifically designed questionnaires which highlighted the type of long term problems our patients suffered. these were developed using data from previous informal patient interviews and the had (hospital anxiety and depression) questionnaire. the latter was considered too intrusive for the ward environment. a data base was used to list the frequency of these problems to provide quantitative data. a total of 116 patients were reviewed over 2 years. the qualitative data highlighted 16 different, common morbidities, in addition to disease specific morbidities. between, april 08-09, 66% of patients demonstrated at least 4 physical or psychological problems and 95% displayed 2 or more. the quantitative data showed the most prevalent morbidities were: poor mobility at 60%, nightmares 53%, loss of appetite 46% and insomnia 35%. year 2 showed similar findings, plus global weakness at 30%.conclusions. this research showed significant post critical illness morbidities in this cohort which appeared to impact on the patients' recovery on the wards. the challenge for our follow up is to target support and rehabilitation whilst the patients are in critical care and then re-evaluate the results. if this expedites a return to a near normal quality of life, it will have improved the efficacy of our service and may impact on follow up care in general. 1 . it may affect the balance of family and change their roles and responsibilities, mainly due to the separation from their relative imposed by hospitalization. this admission may also generate other discomforts to the family, as relationship problems, emergence of diseases, lack of financial resources for expenditures now installed, anxiety, depression, fear and irritability 2 . objective. to get to know the discomfort that characterizes the changes experienced in the daily life of families who have a relative in icu. method. this is a qualitative study, conducted in a general icu of a large hospital in the city of salvador, bahia, brazil, from august to october of 2009. nine relatives of people hospitalized for at least 24 h in icu were interviewed. the data were analyzed by the use of procedures of analysis of grounded theory. results. the hospitalization of a family member in icu produced discomfort for her, as the uncertainty of recovery, the fear of loss and the sudden physical separation of the relative. the interaction between the huge discomfort of life threat and the separation from the relative, in turn, spawned other discomforts in the daily lives of families, expressed by two categories. the first one, having difficulties to answer psychobiological needs, meant for the family member the experience of sleep deprivation, loss of appetite and constant concern with the relative. the second one, suffering a discontinuity in the daily life, meant to the family the disruption of daily activities with the relative, irritability front other family members, removal of the routine of home, loss on work performance and studies and difficulties to enjoy the leisure and recreation.conclusion. the coping of illness and hospitalization of a relative in intensive care produced discomfort for family members, characterized by changing of the routine of the daily life and care for oneself. the family's attention is primarily directed toward the ill relative. it starts to experience the routine of a hospital and disrupts the organization of familiar and personal life, it finds itself suffering a break from daily life. the discomfort experienced by the family can be minimized by practices of the healthcare team, which provide care, information, support, safety and convenience. (fig. 1 ). this is a unique opportunity to study the effects of nursing environment on sleep quality and quantity in icu patients. to study the effects of nursing environment on sleep quality and quantity in icu patients. a total of 20 patients will be included in this ongoing study: ten subjects who were admitted to the old, ward-like icu (fig. 2) , and ten patients who will be admitted to the new, single-room icu (fig. 1) . objectives. in order to understand the family's perception of nursing care, the authors undertook this study, assessing the family satisfaction and use the results to increase the quality of care.methods. this is a qualitative study of inductive nature. data was collected along the time of the study by in-depth interviews, to six relatives of each patient, after discharge the intensive care unit. for data analysis we followed the steps of the phenomenological method, according to max van manen (1990) . results. from data analysis, the results were divided in 5 categories: 1) relative needs; 2) icu environment; 3) relative's feeling; 4) nurses role and 5) suggestions. all this categories were grouped in a central theme called ''being a relative in a general intensive care unit''. the results show that relatives of patients admitted to the intensive care unit often require complete knowledge of the medical condition of the patient, a specific area for that purpose and a comfortable waiting room. they express the need to be near the patient and participate in care. they feel fear and anger with the situation that inevitably are forced to live and think, mostly, that nurses are effective and efficient in meeting the needs of the patient and family. conclusions. it is essential to promote attitudes and behaviors that provide comfort, safety and privacy for relatives, and acknowledge that they have a role in the process of care, reinforcing their importance in decision making process.introduction. heart failure (hf) is a complex syndrome that commonly affects elderly patients in whom it has a major impact upon longevity and quality of life. it is usually associated with symptoms such as dyspnoea, fatigue, and fluid retention, and results in frequent episodes of hospitalisation.objectives. this study was planned to examine the relationship between self-care behaviors and quality of life in patients with hf.methods. this study was planned and applied as a descriptive and a cross-sectional study. introduction. the hospitalization of a relative in icu, especially when it's unexpected, is considered a too stressful experience for the family, usually compounded by the disruption of daily life. from the relative's hospitalization at the icu, the family will necessarily interact with health practices, the rationality that underlie it and institutional objects that may be a source of comfort or discomfort 1,2 .objectives. to understand the situations defined as comfort to relatives of people in critical state of health and the sense of comfort in this situation.methods. this is a qualitative study conducted in the general icu of a large hospital in the city of salvador, bahia, brazil, from june to october of 2009. fourteen family members of persons hospitalized for at least 24 h in icu were interviewed by a specific questionnaire. all recorded interviews were transcribed and the data were analyzed by the use of procedures to encode the data of grounded theory. seven categories expressed the experience and sense of comfort for the relatives who had a person hospitalized in the icu: 1) security: confidence of relatives in technical-scientific and humanistic team and in the possibility of recovery of the person who is hospitalized, 2) reception: comfort experienced by the family by being treated as a person by the professional of icu when they interact with a supportive attitude, 3) information: comfort experienced by the family when it feels conscious of the reality of the health condition of their relative and to receive guidance about the unit 0 s routine, 4) social and spiritual support: comfort experienced by the receiving of help and support of the family, friends and religion, 5) proximity: the comfort of being close of the relative and being able to enjoy the interaction established between them, 6) convenience: comfort experienced in interacting with pleasant elements and support of basic needs of the family, offered by the environment and physical structure of the hospital; 7) integration with itself and the daily: the possibility of the family member to take care of himself, to help the relative and to give continuity to the family routine as it did before the hospitalization.conclusions. the comfort is a positive, subjective and dynamic experience, which changes in time and space, which is the result of the interactions that the individual sets with himself, with those around him and with the situations he faces, without losing view that every family is unique and can experience this process in a proper way. to ascertain the perceptions of icu nurses' about the needs of families of critically ill patients methods. this is a transversal study. the data were collected in four icus in the city of feira de santana, bahia, brazil, after approval by ethics and research committees. all 20 clinical nurses of icus were interviewed. the brazilian adaptation of the critical care family need inventory (inefti) was used for measuring the degree of importance of 43 needs of family members, valued at increasing levels from 1 to 4. descriptive statistics were used for analysis, needs with a mean score [3 were defined as having the greatest importance.results. the nurses identified 70% of needs as important for family members. the items related to security ''to be sure that the best possible treatment is being offered to the patient'' (3.90 ± 0.31), and the information ''to talk to the doctor every day'' (3.80 ± 0.41), were pointed out as the most important, with consistent results with the literature. some needs of support ''to have general guidelines on the icu at the first visit'' (3.80 ± 0.41) and comfort ''to have a bathroom near the waiting room'' (3.20 ± 0.76) were also identified as important. however, the needs of proximity, like being close to their relative was not identified as important to the family for all nurses.conclusions. the nurses identified the need for security and information as important, however the wish that the family has to be near their relative was not considered important, as described in the literature 1, 2, 3 . a movement of nursing towards the family can be perceived, so nurses should plan their interventions based on knowledge of the demands of the family in order to promote care for the relief of immediate distress and anguish, which will consequently encourage the recovery of the ill relative reference(s). nurse educator, realized that with an ongoing critical care nursing shortage world wide, even when retention is high, some turnover is inevitable necessitating an orientation tool to guide charge nurses in assigning new hires to critically ill patients. impetus for this clinical orientation tool arose from observations that new hires were often overwhelmed or disengaged at the bedside, and patient assignments did not consistently foster the development of critical care skills. the orientation tool reflected a staged approach to patient assignments; gradually exposing the new hire to progressive levels of complexity. embedded within the tool were guidelines specifying performance competency expected of new hires at 3 month intervals in their first year of critical care practice. evaluation at this stage involved on the spot interviews. use of the tool began in january 2009. since its introduction, this tool has guided patient assignments for 15 newly hired nurses. in six cases, nurses moved through the stages more quickly than anticipated. reports from staff nurses, clinical educator, patient care coordinator and nurse manager suggest that anxiety and stress of novice critical care nurses related to the complexity of patient assignments have decreased, and that the tool's structure provides clear goals and has enhanced satisfaction with the consolidation experience. our goal was to ensure the tool facilitated an optimal learning experience, structured around orientation standards and leading to the development of confident, competent practitioners. future plans for on-going evaluation include: formal surveys with present msicu staff, and exit interviews with nurses new to critical care who have left their msicu positions prior to the introduction of the orientation tool. (1) has previously been claimed to show an association between improvement of score (or lack of) over time and survival status (2) . severe sepsis in patients is associated with considerable mortality. activated protein c (apc) is a mediator of the inflammatory and coagulation systems, which has shown decreased mortality in severe sepsis (3) beyond 48 h sofa scores showed further distinct improvement over the apc infusion period in the survivor group, whereas minimal improvement was seen in the non survivors.change in daily sofa scores conclusions. our analysis appears to agree with levy's previous findings of increasing sofa (albeit modified) scores and mortality. we, however, looked at a different treatment period, (apc infusion rather than first day of sepsis) but, nonetheless, found the same association of increasing score and mortality and decreasing score and survival. the mean age in survivor group was considerably less than that in non survivors and this age discrepancy largely accounts for the difference in mean apache score (3 points) between groups. the depicted trend in sofa scores is more apparent beyond the initial 48 h of treatment, and suggests that improving sofa scores and outcome prediction is possible beyond the previously reported 48 h. our numbers are small, but lend support to the predictive potential of repetitive sofa scores and outcome.objectives. this real-life registry was implemented to describe clinical characteristics of patients treated with drotrecogin alfa (activated) (daa) in france and the use of this drug.methods. this national multicenter observational study, proposed to intensive care units (icus) which used daa, was conducted by data abstraction from hospital files of patients admitted in icus and treated by daa. two sets of data were obtained: a) retrospective data collected between january 1st, 2006 and beginning of the prospective phase in each site; b) prospective data for patients treated until november 2009. this current analysis aimed to describe the patients retrospectively enrolled and treated between january 2006 and april 2009. statistical analysis was mainly descriptive. conclusions. this study showed a good concordance between the target population and population treated by daa in terms of treating patients with higher disease severity. patients treated in real-life had a particularly severe sepsis as shown by the saps ii score of 60 and high number of organ dysfunctions at time of infusion initiation. the 1-month observed mortality was lower than the predicted hospital mortality of 68% with this level of saps ii. introduction. mortality in severe sepsis is variously described, but is often up to 50% (1) . activated protein c (apc), a mediator of the inflammatory and coagulation system has shown a decrease of hospital mortality from 34.9 to 29.7% (2) at 1 year post apc we found that 23 patients (56%) out of 41 were still alive (5 patients are still less than 1 year post apc and therefore not eligible for consideration). conclusions. this study is limited in size, but demonstrates further favourable evidence to support the administration of apc for patients with severe sepsis, and appears to contradict the cochrane findings (3) . we have shown that our hospital survival has improved since initial report (4) . we attribute this improvement in smr to better targeting of apc to the more severely ill septic patients (as evidenced by the increased apache score).longer term survival data was also encouraging, 56% of our patients were alive at 1 year, post apc. this should be considered against an initial predicted survival to hospital discharge (never mind 1 year) of 47.5%. we find this result very promising, it would appear that initial survival advantage with apc is in fact sustained beyond hospital discharge. objectives. medication errors reported in a self reporting medical incident system were systematically analyzed to identify root causes and obtain preventive measures methods. all medication incidents received within 1 year in a 8-bed mixed icu, were analyzed by 2 trained persons in analyzing medical adverse events. the systematic approach consisted of five steps. 1. description of the incident in a causal tree. 2. all causes were classified into the 5 main categories according to the prisma 2 incident analysis tool (technical failure, organization failure, human failure, patient related and non classified). 3. all medication errors were categories into the 5 broad stages of medication process (prescription, transcription, preparation, dispensation and administration). 4. the recovery phase of all near miss were analyzed. 5. development of an action matrix based on the most suitable solution (equipment, procedures, information/communication, training and motivation) for each root cause. . 236 incidents/near miss were recorded. 37% were medication or fluid therapy related incidents/near miss. human intervention (44%), verification (32%) and organizational/ protocol (17%) were the most common causes of medication incidents/near miss. 48% of all errors occurred in the administration phase and 23% in the prescription phase. the most suitable solution for the recorded medication errors are shown in fig. 1 . conclusions. this systematic approach reveals that introduction of new equipment, such as a patient data management system (pdms), and improvement of the procedures are the most important actions to reduce medication errors in our icu. objectives. this study is a descriptive study which is carried out in order to determine the perspectives of newly graduate and experienced nurses on medication errors working in a military education and research hospital. methods. this study was planned and applied as a descriptive and a cross-sectional study. study was executed at a military education and research hospital in turkey between july and august 2009. totally 169 nurses were involved, 87 of those were newly graduate and 82 were experienced nurses. data collection form which has been prepared by the researches in order to determine the perspectives of nurses on medication errors consists of two parts. the first part consists of 7 questions prepared in order to determine the ages, departments, educational levels, experiences and some informative characteristics of the nurses. in the second part there is questionnaire form on perspectives of the nurses on medication errors which was prepared by gladstone in 1995. 2 the study was applied after written ethical approval of the ethical committee of the military education and research hospital and application permission of the nursing department. the application was realized by surveying on volunteer nurses after making necessary explanations about the aim of the study and the application procedures to the participants. the data were analyzed using percentages, mean ± standard deviation, chisquared test and independent-samples t test. conclusions. in this study among the causes of drug errors; tiredness and exhaustion of nurses is stated in the first place. it is thought that rearrangement of working hours of the nurses, reduction of long working hours by the nursing administration will be effective on preventing drug errors. (1). to test the basic knowledge and practical implementation of picco measurements by icu personnel. descriptive trial in which (para)medical icu personnel were asked to participate in a written or online survey (25 questions based on the information found in the manual of the picco system).results. so far, 125 persons have participated: 95 nurses and 30 medical doctors (8 were residents in training), all of them actively working in an icu. in total, 74% of the respondents knew that a picco co measurement is performed intermittently by transpulmonal thermodilution and on a continuous basis by arterial pulse contour analysis. about 53% is convinced that a picco measurement is an invasive procedure, while in fact it is considered minimally invasive. opinions are divided upon the indications for picco measurement. some participants do not know that the measurement of extravascular lung water provides valuable additional information in pts with acute hypoxic respiratory failure and some even believe that picco can also measure pulmonary capillary wedge pressures. the basic knowledge on co calibration is insufficient: 50% do not know that the temperature of the injection fluid should best be below 8°c and only 6% know that the volume of the calibration fluid depends on the patients' weight. 63% faulty believe that the patient has to be in the supine position to perform a measurement and 75% is not informed on the fact that the co obtained should not differ more than 15% from the mean co value. only 50% of the respondents carry out a rapid flush test before each picco measurement and only 34% know that the calibration fluid has to be injected in less than 10 s to obtain a correct measurement. finally, 33% believe that it is necessary to input the cvp value to calculate a correct co, although 83% of the respondents correctly knew what to do in case the delta t°is too small and 85% could correctly interpret the 3 thermodilution curves displayed in the survey.conclusions. from these data we can conclude that a big variation exists in the knowledge on the basic principles and the practical implementation of picco measurements. some confusion exists with regard to the terminology used. we conclude that (as with any new technique) high quality education on picco measurements is necessary for icu personnel. this education can be facilitated by a good protocol, that can be implemented by nurses and doctors at the bedside to avoid human errors. a.c. beers 1 1 vu university medical center, intensive care, amsterdam, netherlands health insurance companies in the netherlands sign exclusive contracts with hospitals. patients are more critical and independent. they consciously choose a particular hospital or treatment. this is why our management gave high priority to the subject of customer service in their long term policy plan.objectives. in january 2009 a project group was launched, which aimed for a number of specific improvements but also by increasing awareness and enthusiasm for customer experience amongst employees. the project is focused on the experience or perception of patients and visitors.methods. the first step was a baseline measurement by hcg (hospitality consulting group). this measurement included interviews with employees from different icu locations and an online survey that was completed by employees, next of kin and other visitors. this resulted in a high score for commitment of staff towards patients and visitors. remarkably, employees thought that aspects for example reliability, professional care and privacy would be valued higher by customers. they attach more importance to how they are received, to empathy and sympathy. respondents also mentioned other things for improvement for example better signage, improved telephone access, better information about rules and procedures, unambiguity in approach, a better visibility of staff and a pleasant and hygienic department. 1 . several improvements such as product, behavior and environment were achieved: we employed family counsellors, developed an information folder and started a pilot for an improved name badge. we can still make improvements in awareness, behavior and addressing each other on this subject. this year we plan to come to an agreement on standards, competencies and control by means of several management training sessions and workshops for employees. we can measure changes in patient satisfaction by family evaluation surveys or an instrument called netto promotor score. the netto promotor score (nps) indicates how many respondents will recommend our ward or hospital to their family and friends. to quote fred lee: ''if a service is provided as expected, patients or visitors will not remember it, they are merely satisfied. satisfied patients will forget a service quickly, have no story to tell to their family and friends and are not really loyal to your organisation. therefore you must create an unforgettable experience, because an experience that remains in memory, is told to others.'' 2 reference(s). critically ill medical, post-surgical, and trauma patients are at greater risk for hyperglycemia with associated increase in mortality and morbidity. tight glycemic control (tgc) has been well documented as a method to control hyperglycemia by managing blood glucose fluctuations through carefully controlled continuous insulin infusion. in order to determine the amount of time it takes within practice for nurses to implement effectively a tgc protocol within the critical care unit, we conducted a pilot time-in-motion study to elucidate the effect on workload. a time-and-motion study was carried out at a hospital located in london, uk in order to document the time associated with tgc activities. a timing workflow, used to capture the key steps involved with effective tgc implementation when utilizing blood gas analyzers for the determination of whole blood glucose (bg) and the time required to complete each step, was designed and then validated by ccu staff. ccu staff was trained on the timing workflow and mechanism. independent observers shadowed ccu nurses, observing when a blood glucose measurement was taken, which steps were completed, and the length of time required to complete each step. other data such as time of the previous bg measurement and status of the last bg test was collected for analysis purposes. during the past few years, the increased incident rate of medical errors occurring in hospitals under governing of hong kong hospital authority has contributed significant attention from the public and health care policy makers. in such a situation, promote patient safety culture becomes paramount for all health care professionals and hospital settings. interdisciplinary teamwork is important in the intensive care units. the benefits of good teamwork have been well documented in the literatures. they included fewer delays, increase in working moral, increased in job satisfactory and decreased in medical errors. in relation to patient safety, fewer errors occur when there is strong teamwork because patient care activities are planned, well organized and standardized. therefore, substantial attention should be given to decrease of medical errors and nurture patient safety culture within high-risk areas such as icus. objectives.• to examine the perception of teamwork and patient safety culture of doctors and nurses between icus and within icu • to investigate the relationship between teamwork and patient safety culture of icu doctors and nurses methods. a cross-sectional surveyed of doctors and nurses in three intensive care units with various size, level of care and staff to patient ratio of hong kong hospitals. totally 209 icu doctors and nurses have been included in this study. a modification of safety attitudes questionnaire developed by sexton and colleagues in 2006 was adopted. results. the overall response rate was 64.11%. there were no significant difference of perception of teamwork and patient safety attitude among 3 studied icu's doctors and nurses. however, icu (a) and icu (c)'s doctors demonstrated more positively and showed significant different in perceptions of teamwork (p = 0.014; 0.017) than nurses. regarding patient safety attitude, icu (a)'s doctor also showed significant difference (p = 0.018) and rated more positively than nurses working in the same clinical area. a highly statistically significant association between patient safety attitude and teamwork was shown in the spearman rho statistics with r s (134) = 0.61, p = 0.000. conclusions. the rate of agreement on teamwork and patient safety attitude were higher in icu doctors. they were more likely to perceive effective teamwork and patient safety in the working area. nurses tended to rate both items lower. as teamwork has been shown to have strongest relationship with patient safety issues, more attention should be given to improve teamwork for icu nurses. tnf is upregulated within the alveolar space early in the course of ventilator-induced lung injury (vili), and plays a major role in the pathogenesis. we previously found in knockout mice that two tnf receptors play opposing roles during vili, with p55 promoting but p75 preventing pulmonary oedema. this suggests that specific blockade of the p55 receptor within the alveoli is a potential therapeutic strategy for vili. domain antibodies (dabs) are the smallest antigen-binding fragments of the igg molecule, which may have advantages over complete antibodies due to their small size (short half life, enabling regional delivery) and monovalent binding (no receptor cross-linking). objectives. we tested the effects of an intratracheally (i.t.) delivered dab that binds to and inhibits the mouse p55 receptor (biopharmaceutical r&d, glaxosmithkline), on pulmonary oedema and inflammation during vili. methods. c57bl6 mice were ventilated with a high-stretch protocol (plateau pressure 12.5-13.5cmh 2 o, tidal volume 20-22 ml/kg, peep 3cmh 2 o, o 2 with 2-4% co 2 ). immediately after the start of high-stretch, mice were given an i.t. bolus of non-specific 'dummy' dab or p55-specific dab (25 lg in 50 ll) and ventilated for up to 4 h (1-hit model). as a 2-hit model, 20 ng lps was included in the dab bolus. respiratory elastance (ers) and blood gases were monitored, and bal performed at termination. in the 2-hit model, lung cell suspension was analysed for intravascular margination of neutrophils (pmn), and bal fluid (balf) assessed for pmn infiltration and alveolar macrophage (am) activation using flow cytometry. results. high-stretch ventilation produced deteriorations in ers and po 2 , and high balf protein in both models. treatment with the p55-specific dab substantially attenuated all of these changes in the 1-hit model (table 1 ). in the 2-hit model, p55 blockade prevented deteriorations in ers and po 2 , and significantly decreased pmn margination, intraalveolar pmn infiltration and icam-1 expression on ams (table 2) . introduction. ventilator-induced lung injury (vili) triggers a variety of molecular responses within the lungs. however, the contribution of these pathways to lung repair has not been identified.objective. to identify the molecular mechanisms involved in lung repair after vili.methods. vili was induced in mice by ventilation using high pressures (25 cmh 2 o) without peep for 90 min. after this, pressure was decreased to 15 cmh 2 o and peep increased to 2 cmh 2 o for 4 h more to promote lung repair. we quantified histological damage, protein content in alveolar lavage (balf) and different molecules in lung tissue (collagen, matrix metalloproteinases-2 and -9, tnfa, ifnc, il-4, il-10, mip-2 and lix) in the different conditions (baseline, after injury and after repair). additionally, survivors and non-survivors to the repair phase were compared. the effects of the differentially released mediators were studied in a wound model using murine alveolar cells cultured in presence of balf obtained from ventilated animals, and human alveolar cells and balf from ventilated patients. results were compared using an anova, with a significance level of p = 0.05. . 80 mice were studied (21 at baseline, 27 after injury and 32 after repair). high pressure ventilation caused lung tissue injury, with significant increases in balf protein content, mmp-2, mmp-9, tnfa and mip-2, and a significant decrease in il-10. during the repair phase, tissue injury was partially reverted, balf proteins and levels of tnfa decreased, but mmps and mip-2 persisted elevated. mortality during the repair phase was 50%. survivors showed lower levels of collagen and higher levels of mmp-2 (995 ± 143 vs. 446 ± 70 units, p \ .05) and mip-2 (721 ± 196 vs. 135 ± 13 pg/mg protein, p \ .05).blockade of mmp-2, but not mip-2, delayed wound closure in both murine and human alveolar cells cultured in presence of balf from ventilated mice or patients respectively.conclusions. vili is partially reversible by decreasing airway pressures and increasing peep. mmp-2 promotes epithelial repair.grant acknowledgment. universidad de oviedo (unov-09-becdoc), ficyt (cof-08-20). introduction. critically ill survivors present significant long-term brain-related morbidity. excessive end-inspiratory stretch during mechanical ventilation (mv), even in healthy lungs, may promote alterations in the local and the systemic inflammatory cascade. the effects of ventilator-induced systemic inflammation on brain structures are unknown. to characterize the role of the ventilatory pattern (high vs. low tidal volume (vt)) in the development of local or systemic inflammatory response and regional neuronal brain activation in rats. brains were processed for c-fos immunohistochemistry, as a cellular marker for activated neurons, in the following regions: thalamus, cerebral cortex, amygdala, hippocampus, hypothalamus, and caudal striatum. data were analyzed using one-way anova (p \ 0.05). results. map and lung compliance remained stable and in the normal range in both groups. pao 2 decreased and paco 2 increased at 3 h in lvt. mv animals presented high levels of systemic and lung inflammatory mediators compared with baseline levels. hvt significanly increased tnfa and il-6 in plasma when compared with lvt group. in the lungs mv increased il-6, il-10, il-1b and mip-2 proteins, irrespective of the vt level (lvt or hvt). mcp-1 only increased in hvt lungs, while tnfa lung levels are similar in ventilated and non-ventilated animals. a significant increase in the number of c-fos immunopositive neurons was only found in retrosplenial cortex and thalamus in hvt animals as a sign of neuronal activation of those areas. none of these two areas were activated in lvt or in control animals. mechanical ventilation produced a moderated systemic and lung inflammation in the context of a preserved lung function. high tidal volume ventilation promoted differential neuronal activation in the brain compared with lvt animals. these findings suggest a novel cross-talking mechanism between lung and brain in the context of experimental acute lung injury.grant acknowledgment. mec bfu2006-07124/bfi, fundació parc taulí. jl-a is senior researcher program i3 isciii, and ciberes. (2).in an ex vivo perfused human lung preparation injured by e. coli endotoxin, allogeneic human mscs or the conditioned medium restored normal fluid balance (3).objectives. we wished to evaluate the potential for mscs to modulate inflammation and enhance repair after ventilator induced lung injury (vili). adult male sprague-dawley rats were anaesthetised, orotracheally intubated and subjected to injurious mechanical ventilation. following the development of vili, animals were recovered and extubated. thereafter the animals received two intravenous injections of mscs (2.5 million cells) or vehicle immediately post injury and at 24 h. the extent of the inflammatory response and recovery from vili, as measured by systemic oxygenation, respiratory static compliance, lung wet:dry ratio and lung lavage inflammatory cell infiltration, was assessed at 48 h. mscs reduced inflammation and enhanced repair following vili. msc treatment improved respiratory static compliance, reduced total lung water as assessed by wet:dry ratio, and decreased bronchoalveolar lavage total inflammatory cell and neutrophil counts, from 73,772 cells/ml to 11,828 cells/ml (ci 4.827-119.060) (fig. 1 ). there was a trend towards better oxygenation in the msc group.conclusions. these findings demonstrate the potential of mscs to modulate inflammation and enhance repair following vili. further analysis of our work, including bal cytokine assay and histological assessment of injury, will provide insight into the utility of mscs to enhance repair in the lung. to determine the role of vagus nerve signaling in vili and establish whether stimulation of the vagus reflex can mitigate lung injury from high volume ventilation.methods. first we demonstrate that disruption of the cap reflex by bilateral vagotomy results in worsening lung injury in a mouse model of high-volume-induced lung injury. in a clinically relevant rat model of injurious ventilation following hemorrhagic shock/resuscitation (hs; model of lung ischemia/reperfusion injury), we then tested the hypothesis that electrical and pharmacological stimulation of the vagus nerve can attenuate injurious effects of vili. finally, to determine the molecular mechanisms by which stimulation of the cholinergic response mitigates vili, we exposed human bronchial epithelial cells (beas2b) to cyclic stretch (30 cycles/min, 25 pka) in the presence of specific agonist or antagonist of the 7 subunit of the acetylcholine nicotine receptor. vagotomy exacerbates lung injury from high volume ventilation in mice as demonstrated by increased wet-to-dry ratio, infiltration of neutrophils in bronchoalveolar lavage fluid and lung tissues, and increased tissue levels of interleukin-6. vagotomy exacerbated while vagus stimulation attenuates lung injury in rats after ischemia reperfusion injury ventilated with either high or low volume strategies. treatment of both mice and rats with the vagus mimetic drug, semapimod, resulted in decreased lung injury. vagotomy also increased pulmonary apoptosis whilst vagus stimulation (electrical and pharmacological) attenuated vili-induced apoptosis. in vitro studies suggest that vagus-dependent effects on inflammation and apoptosis are mediated via the a7nachrc-dependent effects on cyclic stretch-dependent singling pathways c-jun n-terminal kinase (jnk) and fas (tnf receptor superfamily, member 6).conclusions. stimulation of the cholinergic anti-inflammatory reflex may represent a promising alternative for the treatment of vili.introduction. so far, histological data on critical illness myopathy (cim) primarily refers to muscle biopsies taken during protracted critical illness (after weeks), repeatedly describing pronounced type-ii muscle fibre atrophy.objectives. we speculate that type-ii fibre atrophy develops during early critical illness in patients with non-excitable muscle membrane which predicts cim. (1) methods. due to their elevated risk for cim, critically ill patients with sofa scores c8 on 3 of 5 consecutive days within the first 8 days after icu admission were eligible for inclusion into this prospective, observational study. preexisting iddm or neuromuscular disorder, pregnancy, bmi c 35 kg/m 2 , age \ 18 years, or pretreatment[4 days on other icu constituted exclusion criteria. surgical muscle biopsies were taken from vastus lateralis muscles between day 5 and 8 after first sofa c 8 and postprocessed according to standard procedures (isopentane, liquid nitrogen, atpase/toluidineblue staining). we assessed muscle membrane excitability after direct muscle stimulation, abnormal muscle membrane excitabilty indicating cim (1). after quantifying fibre-type specific median cross sectional areas (csa) with imagej-software, we compared fibre-type specific csa in patients with and without non-excitable muscle membrane. nonparametric tests (mann-whitney u) were used for statistical analyses, results expressed as median and (25th/75th) percentiles for continuous variables. . 33 patients were enrolled and subsequently biopsied. 29 patients were evaluated for muscle membrane excitability, of whom 62% (n = 18) showed non-excitable muscle membrane. reliable csa quantification was obtainable for 27 patients.type-ii but not type-i muscle fibre csa during early critical illness was significantly decreased in patients with non-excitable muscle membrane (2,839 lm 2 compared to 4,285 lm 2 for type-ii, p = 0.028; 3,504 lm 2 compared to 3,683 lm 2 for type-i, p = 0.197; n = 23). furthermore, non-excitable muscle membrane was associated with significantly lower mrc scores after end of sedation (3.00 (2.94/3.41) vs. 3.75 (3.31/4.75) , p = 0.023, n = 20). in patients showing non-excitable muscle membrane after direct muscle stimulation we could observe selective type-ii fibre atrophy as early as within the first 10 days after icu admission (day 5-8 after 1st sofa c 8). our findings demonstrate that nonexcitable muscle membrane indeed is associated with a histomorphological correlate previously linked to cim. these results highlight the need to focus on early critically illness in order to investigate pathophysiological aspects of cim. bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. little is known on the innate immune response to bacteria among extremely premature infants. objectives. identify innate immune defect in premature infants as risk factor for the development of neonatal sepsis. methods. we compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. levels of surface expression of innate immune receptors (cd14, tlr2, tlr4, and md-2) for gram-positive and gramnegative bacteria were measured in cord blood leukocytes at the time of birth. the cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes were also measured in the presence or absence of interferon-c. results. leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. these innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 h with interferon-c. conclusions. premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. maturation of the innate immune response to bacteria can be induced by interferon-c ex vivo and represents a promising strategy to prevent neonatal sepsis. the anaphylotoxin c5a impairs neutrophil phagocytosis in animals 1 and humans 2 with sepsis. although dependency on the phosphoinositol 3-kinase delta (pi3kd) pathway has been identified 2,3 , greater understanding of the mechanism will allow novel therapeutic options. objectives. to test the hypotheses that c5a mediates its effect on phagocytosis by impairing rhoa activation, and that similar defects will be found in neutrophils from critically ill patients. methods. the mechanism was dissected using an in vitro model of c5a-mediated neutrophil dysfunction, treating healthy human donor neutrophils with c5a at concentrations found in sepsis (100 nm). phagocytosis was assessed by zymosan particle uptake. neutrophils exposed to zymosan were assayed for rhoa activity, a key mediator of actin polymerisation in phagocytosis 4 . phagocytosis by neutrophils from critically ill patients was investigated, looking for correlations with a marker of c5a exposure (cd88, the main c5a receptor) 2 , an examination of the rhoa and actin polymerisation response to zymosan, and the ability of gm-csf to restore phagocytosis ex-vivo. results. c5a inhibited phagocytosis of zymosan by healthy donor neutrophils (reducing from 67 to 27%, p \ 0.0001) and also impaired rhoa activation (figure) . blocking pi3kd, using inhibitor ic87114, prevented the inhibition of rhoa by c5a, and prevented the reduction in phagocytosis. treatment with gm-csf restored phagocytosis and rhoa activation (fig. 1 ). neutrophils from patients with critical illness showed a strong correlation between phagocytosis and surface cd88 expression (r = 0.80, p \ 0.001), consistent with our previous findings 2 . patient neutrophils failed to up regulate rhoa or polymerise actin in response to zymosan, in marked contrast to cells from healthy donors (p = 0.002 and p = 0.006 respectively). ex-vivo gm-csf was able to improve phagocytosis by patient neutrophils from 32 to 69%, p \ 0.001. conclusions. these data demonstrate that c5a inhibits rhoa activity through pi3kd, inhibiting phagocytosis. gm-csf is able to reverse this inhibition. similar effects are seen in neutrophils from critically ill patients, providing new avenues for therapeutic intervention in critical illness. host infection triggers an innate immune response leading to a systemic inflammatory response, often followed by an immune dysfunction which impairs the lung defence mechanisms in mice and increases susceptibility to secondary p. aeruginosa pneumonia. activation of the toll-like receptor (tlr)-dependent signalling pathways influences the magnitude of the initial pro-inflammatory phase of sepsis. contribution of tlr signaling to the subsequent development of post-infective immunosuppression has been poorly studied.objectives. to investigate the relative contribution of tlr2 and tlr4 in lung defence towards p. aeruginosa in the setting of sepsis-induced immune dysfunction. we used wild-type (wt) c57bl6/j mice and littermates deficient for tlr2 (tlr2 ko), tlr4 (tlr4 ko) or both tlr2 and tlr4 (tlr2 9 4 ko). these animals were subjected to a sublethal polymicrobial sepsis (cecal ligature and puncture, clp) followed by a secondary p. aeruginosa pneumonia at day 8 post-clp 1 . we evaluated 8-day survival and the lung response 4 and 24 h after instillation through lung histology, quantification of protein level, cell recruitment and myeloperoxydase (mpo) activity. lung expression of tlr2, tlr4 and tlr5 was assessed through quantitative rt-pcr. bacterial lung clearance was evaluated through quantitative culture of bronchoalveolar lavage fluid (balf). bacteremic dissemination was assessed through quantitative blood cultures. finally, we measured cytokines in the balf and in the whole lung. post-septic wt and tlr4 ko mice displayed high susceptibility (mortality rate 80%) towards secondary pneumonia. in contrast, post-septic tlr2-deficient mice (either tlr2 ko or tlr2 9 4 ko), survived the secondary pulmonary infection (mortality rate \20%). in wt mice, clp increased lung expression of tlr2, but neither of tlr4 nor tlr5. tlr2 ko mice displayed improvement in lung bacterial clearance and reduction in bacteremic dissemination as compared to wt mice. with regard to pulmonary inflammation, tlr2 ko mice displayed decreased alveolar damage. furthermore wt and tlr2 ko mice displayed differences in the pulmonary release of cytokines. thus tlr2 ko mice exhibited increased production of tnf-a and ifn-c and a decreased production of il-10.conclusions. in a model of polymicrobial sepsis followed by p. aeruginosa pneumonia, tlr2 deficiency improves survival by promoting efficient bacterial clearance and decreasing pulmonary inflammation. tlr2-dependent mechanisms that specifically contribute to lung defence in the setting of sepsis-induced immune dysfunction are currently investigated. infection is a serious complication in critically ill patients, who can be in a state of secondary immunodeficiency due to a severe illness. apart from common nosocomial pathogens, highly unusual microorganisms may be found in these patients, i.e. pathogens whose cultivation requires specific conditions, and/or agents which are difficult to cultivate. molecular biology-based methods (pathogen-specific probes with real-time pcr detection, or universal system pcr detection with subsequent sequenation) make diagnosis faster and more accurate.objectives. i) to assess an agreement of investigation results using classical microbiology techniques and molecular biology-based methods; ii)to evaluate the clinical effect of the diagnoses based on the frequency of changes in antibiotic therapy as a direct result of molecular detection of ''pathogens'' (mpd) and to assess the effect of this change by evaluating a 3-day trend of inflammatory parameter concentrations i.e. of procalcitonin (pct) and c-reactive protein (crp). a total of 408 samples (blood, bal, tracheal aspirate, urine, cerebrospinal fluid and secretions from abdomen drains and thoracic punctures) were taken from 152 icu patients (aged 21-87). these were investigated simultaneously, both by classical microbiology and microbial methods, using the system of pathogen-specific probes with real time pcr for 30 agents. each sample was tested simultaneously with the universal pcr detection system for bacteria and fungi with the subsequent sequenation.results. an agreement between the two compared examination methods was found in 46% of samples and disagreement in 24% of the samples. 5% of the results were classified as ''not possible to interpret''. in 25% of the samples, mbm detected the presence of other agents, which were not confirmed by cultivation. in 50% of cases, the mdp results did not contribute to the decision to change the atb. in 45% of cases, a modification of atb treatment followed; a change, reduction or stopping the administration of the drug. in 5% of cases, atb was changed without any direct connection to the results. in 64% of patients who underwent the change in atb treatment, a decrease in inflammatory parameters occurred (pct and crp), however, in 16% there was an increase. the remaining 20% are divided equally between those ''without any change'' and ''data not available''.conclusions. the advantage of septic-state diagnostics using molecular biology techniques, as opposed to classical microbiology methods, is the fast availability of the examination results (4-24 h) , and its high sensitivity and specificity. proving the presence of agents in biological material does not necessarily signify its pathogenicity. however, in combination with a thorough assessment of the clinical progression, including laboratory indicators of inflammation, it is of considerable benefit in decisions about the efficacy of antibiotic therapy. common antibiotics and the number of patients on high or low intensity crrt recruited were: ciprofloxacin (5, 2) , meropenem (13, 12), piperacillin-tazobactam (4, 7) , vancomycin (13, 13). the clearance of individual antibiotics varied approximately 3-and 50fold within a single crrt regimen for high and low flow rates, clearance, estimated using ccrt extraction ratios for the two flow rates, differed significantly: meropenem (32 vs. 21 ml/min; p = 0.0123) and vancomycin (14 vs. 7 ml/min; p = 0.0187). using dialysate clearances, significant differences for vancomycin (28 vs. 22 (1) objectives. to perform a meta-analysis on incidence and outcome of intra-abdominal hypertension (iah) in different icu populations, the evolution of iap over time and the correlation with organ failure and fluid balance (fb)methods. pts admitted to icu with iap measurements (gastric or bladder) were included. data from existing databases were collected on 2,645 pts from 24 centers (10 countries [1] . recently, it was demonstrated that 10% hes 200/0.5 induces increased inflammation and leads to more tubular damage compared to 6% hes 130/0.42 in an ex-vivo kidney perfusion model [2] . we investigated whether different hes solutions lead to disturbed cell proliferation or to increased apoptosis in murine kidney cells. we performed a large cohort study on prospectively collected data over a 12year period (1997) (1998) (1999) (2000) (2001) (2002) (2003) (2004) (2005) (2006) (2007) (2008) . data were extracted from the cub-réa network 1 , a french regional database in which 35 icus from paris and its suburb prospectively record data using standardized coding methods. cancer patients with septic shock were selected through keywords including the malignancy status on one hand (''hematological malignancy'', ''cancer'', ''cancer with metastasis''), and ''septic shock'' or the combination of ''septicemia'' and ''shock'' on the other hand. extracted variables included demographic characteristics, type of malignancy, requirements for organ failure supports (vasopressor therapy, mechanical ventilation, renal replacement therapy) and severity-of-illness score (saps2 1, 2, 3, 4, 5 however, some studies have suggested little effect on morbidity or mortality. 6, 7 clarification of any differences would improve pre-operative risk assessment, providing more information for the clinician and patient. it would also aid resource planning in the critical care unit. we hypothesized a proportional increase in the extremes of bmi occurring over the 13-year study period. we analysed data collected prospectively between april 1996 and april 2009 on patients undergoing cardiac surgery in our unit using the patient analysis and tracking system (pats ò ) database. the patients were grouped according to bmi. for each group we calculated organ specific complication rates, re-operation and readmission rates, itu and postoperative length of stay and overall mortality. we studied the change in mean bmi of patients over the 13 year period. in comparison with normal bmi range (18.5-24.9), patients with bmi range \18.5 had significantly increased rates of peri-operative myocardial infarction (mi) ( conclusions. both the high and low extremes of bmi range show significant increases in complication rates compared to normal bmi patients undergoing cardiac surgery. the bmi group 40-44.9 shows significant increase in re-operation, readmission and mortality rates.there is a year on rear increase in the bmi group [40. this suggests a greater demand for resources particularly in the intensive care unit as the population with a higher morbidity and mortality increases. we would welcome an opportunity to present a detailed analysis of our findings. with advances in critical care medicine, more patients are surviving intensive care units stays. patients admitted to critical care may experience morbidity that affects their life after discharge 1 . in addition to any physical morbidity, treatment in critical care may also be stressful and psychologically traumatic for patients 2 .objectives. to describe the psychological outcome of patients surviving icu admission at 6 months. a second end-point was to find possible relationships between patients' background and intensive care variables, post-traumatic stress and depression disorders.methods. retrospective analysis of data from icu follow-up clinic. data were collected in questionnaires (ptss-14 and beck inventory) during an interview at 6 months after discharge of icu in the last 5 years. statistics analysis: pearson's chi-square or fisher's exact test, significance for p \ 0.05. . 770 patients were interviewed, mean age was 50 ± 19, 67% were male and 49.5% were trauma victims. mean icu length of stay was 10 ± 10 days and sapsii score 45 ± 16. 55.8% of patients had less than 4 years of education. concerning previous health status 49.3% were healthy and 5.2% were dependent for daily living activities. 34.5% were retired. more than 60% had new complaints after discharge. only 39.6% of the previously professionally active patients resumed their work and only 49% of the retired were able to maintain their normal activity. almost 40% of patients had new psychiatrics symptoms and only 8.7% were being followed by psychiatry: 17% were on benzodiazepines and 9.5% on anti-depressants. 11.4% of the patients had symptoms suggestive of diagnosis of post-traumatic stress disorder (ptsd) having a ptss-14 superior to 49. regarding beck inventory, 38% were considered to have a depression, with 20.9% having moderate to severe depression. after the interview 21% were oriented to a psychiatric consultation. 72% of depressive patients had new symptoms (p \ 0.01). of the previously active patients who did not resume normal activities, a significant (p \ 0.01) part was depressed (73.8%). the same is true for the retired patients (59.2%), p = 0.002. longer hospital and icu lengths of stay were related with development of depression (p = 0.048 and p = 0.028, respectively). patients with higher sapsii were more prone to develop ptsd. women had more ptsd than men (p = 0.003). patients in risk of ptsd and depression were younger (p = 0.011; p = 0.009, respectively). as with depression these patients also had more new complains and did not return to work. introduction. mild hypothermia improves outcome after cardiopulmonary resuscitation (cpr). modes of action for it are manifold, though one way might be reduction of basal metabolic rate (bmr). therapeutic hypothermia was able to reduce bmr in patients with traumatic brain injury and critically ill patients with fever.objectives. in the present study we investigated the metabolic effect of therapeutic hypothermia in patients after successful cpr.methods. 25 patients after cpr were treated with therapeutic hypothermia (33°c) for 24 h and subsequently rewarmed with a rate of 0.4°c per hour until 36°c was reached. all patients received standardized sedoanalgetic medication and neuromuscular blockers. indirect calorimetry was performed at 33, 34.5 and 36°c, as well as between 36.5 and 37.5°c and 48-72 h after cpr. for statistical analysis repeated measures anova, linear and logistic regression were used. a linear relation between bmr and temperature was detected (297 kj/m 2 /1.5°c; p \ 0.0001). therapeutic hypothermia (33°c) was associated with a reduction of bmr by 22 ± 6% compared to 36°c. in this regard no difference was found between patients with good and bad neurological outcome (good outcome vs. bad outcome: 24 ± 4 vs. 19 ± 7%; p = 0.479). concerning substrate oxidation rates only fat oxidation rate showed a temperature dependency (10 g/day/1.5°c; p \ 0.0001). in contrast to protein oxidation rate (good outcome vs. bad outcome: 45 ± 51 vs. 49 ± 70 g/day; p = 0.751) patients with good neurological outcome had a significantly higher fat oxidation rate (good outcome vs. bad outcome: 144 ± 57 vs. 110 ± 47 g/day; p = 0.039) and a significantly lower glucose oxidation rate (good outcome vs. bad outcome: 21 ± 77 vs. 74 ± 99 g/day; p = 0.029) as compared to patients with bad neurological outcome.conclusions. in patients after cpr mild therapeutic hypothermia (33°c) was associated with a reduction of bmr by 22%. a linear relation between temperature and bmr was detected. fat oxidation rate was temperature dependent in contrast to protein and glucose oxidation rate. a significant difference in glucose and fat oxidation rates was found between patients with good and bad neurological outcome. objectives. our goal was to determine whether its institution after resumption of spontaneous circulation (rosc) improves survival and neurological recovery in an experimental model of cardiac arrest in rabbits.methods. ventricular fibrillation was induced in anesthetized rabbits. after 5-min of untreated fibrillation, cardiopulmonary resuscitation was attempted using external massage, electric shocks and intravenous epinephrine. after rosc, rabbits randomly underwent either normothermic life support (control group with conventional ventilation until weaning) or hypothermic support with rapid cooling (tlv group). in this last group, a 32°c hypothermia was induced by 20-min of tlv using a perfluorocarbon. subsequently, the perfluorocarbon was removed from the lungs and rabbits were conventionally ventilated with maintenance of hypothermia during 3 h. rabbits were further warmed and weaned from ventilation. in both groups, hemodynamic and biochemical parameters were monitored, as well as survival and neurological recovery. after 7 days, survivors were finally euthanized for post-mortem analyses. neurological dysfunction was assessed by a 0-100% scoring system evaluating reflexes, postural reactions and behaviour (0%: no dysfunction; 100%: brain death).results. ten rabbits were randomized to the control group and 10 to the tlv one. defibrillation was obtained using 1.4 ± 0.3 and 1.5 ± 0.3 electric shocks, respectively. subsequent rosc was observed after 2.3 ± 0.3 and 2.4 ± 0.3 min, respectively. oesophageal and tympanic temperatures were rapidly reduced in the tlv group, achieving 32.5 ± 0.2 and 32.5 ± 0.3°c within 30-min versus 37.5 ± 0.5 and 37.1 ± 0.3°c in control, respectively. in the tlv group, rabbits returned to normothermia within 2-3 h after the hypothermic episode. throughout follow-up, no significant difference in blood pressure was observed between both groups (e.g., 82 ± 3 and 82 ± 5 mmhg in control vs. tlv at 1 h after cardiac arrest, respectively) whereas heart rate was decreased throughout hypothermia in tlv vs. control (e.g., 174 ± 6 vs. 221 ± 7 beats/min at 1 h following cardiac arrest, respectively). lactates's concentration and epinephrine dosages were not significantly different between groups. importantly, neurological dysfunction was significantly attenuated in tlv vs. control (e.g., 5 ± 3 vs. 32 ± 9% after 48 h). in control, 5/10 (50%) rabbits survived throughout the follow-up and the others died or should be euthanized earlier following severe disability. in the tlv group, survival was significantly increased as 9/10 rabbits survived to the entire follow-up (90%).conclusion. ultra-fast cooling induced by tlv after rosc improves survival and neurological recovery following 5-min of experimental cardiac arrest in rabbits.grant acknowledgment. (ca) . th involves at least 12 h of induced hypothermia (33-34°c), mechanical ventilation and sedation. th may affect sedation through changes in pharmacology. still, no clinical studies have investigated the use of sedation during th. objective. to compare the efficacy of two sedation protocols for patients treated with th. methods. open, randomised, controlled, population based study of patients treated with th (33-34 c for 24 h) after ca in two norwegian university hospitals. patients were randomised to sedation with remifentanil + propofol (rp) or fentanyl + midazolam (fm). baseline characteristics (age, sex, bmi, saps-ii) and cardiovascular variables during study drug infusion (blood pressure, heart rate, use of fluids, vasopressors and inotropic drugs) were recorded. the primary end point was defined as time from stop of sedation to extubation. results. sixty patients were randomised. one patient was withdrawn by next of kin. baseline characteristics were similar in the two groups. for two patients in the rp group, and one in the fm group, study drugs were stopped shortly after allocation due to cardiovascular instability. the rp group had lower heart rates and more patients needed noradrenaline infusions than the fm group (57.3(14.4) (mean(sd)) vs. 66.2(15) beats/min, p = 0.05, and 21 vs. 10 patients, p = 0.004, respectively). other circulatory variables were similar. reasons to not stop sedation or not extubate after stop of sedation were; cessation of icu treatment (n = 15), need for mechanical ventilation (n = 10), inadequate awakening (n = 6), seizures after stop (n = 4), and other (n = 4). sedation was stopped according to protocol in 35 of 59 patients. median (range) time from stop of sedation to extubation for the 17 patients who could be extubated according to protocol was 0.25 (0-0.72) vs. 12.7 (0. 5-26.4) h in the rp and fm group, respectively, p = 0.002. ''cerebral performance category'' on day 13-15 was similar in the two groups. conclusions. time to extubation after cessation of sedation was significantly shorter in patients sedated with rp compared to fm. however, the benefit from a short time to extubation is limited by that only one-third of the patents can be extubated according to protocol. the rp group had lower heart rates and needed more noradrenaline. no major differences were observed for outcome.grant acknowledgment. ntnu. increased blood glucose variability during therapeutic hypo-thermia and neurological recovery after cardiac arrest key: cord-355038-o2hr5mox authors: nan title: proceedings of réanimation 2020, the french intensive care society international congress date: 2020-02-11 journal: ann intensive care doi: 10.1186/s13613-020-0623-7 sha: doc_id: 355038 cord_uid: o2hr5mox nan rationale: expiratory muscles has recently been stated as the «neglected component» in mechanically ventilated patient. several authors stated these muscles importance in cough capacity, contractile efficiency of the diaphragm or reduction of hyperinflation. however, few studies reported potential factors leading to expiratory muscle weakness and its importance on weaning success or survival after mechanical ventilation. patients and methods: this study is a secondary analysis of our previously described cohort of 124 patients ventilated for at least 24 h assessed for respiratory muscles function. maximal expiratory pressure (mep) measurement was carried out during spontaneous breathing trial using a manometer with an unidirectional valve. mep diagnostic accuracy to predict icu-aw (icu acquired weakness), weaning success and sursvival within 30 days were assessed using expiratory muscle strength as absolute values (cmh 2 o), as %predicted values and as %lower limit of normal. results: due to the paucity of data reporting threshold value for expiratory muscle weakness, we considered our median value (47 cmh 2 o (iqr 44)) as the threshold value for expiratory muscle weakness group (mep ≤ 47 cmh 2 o) and normal expiratory muscle group (mep > 47 cmh 2 o). patients with low mep received more catecholamines (p = 0.04) and a higher duration of mechanical ventilation (p = 0.001). inversely, higher body mass index was associated with higher mep. patients with low mep presented more icu-aw compared to normal mep patients (64% vs. 35%; p = 0.003). no other outcomes were different between groups. mep was statistically able to predict icu-aw but area under (auc) receiving operating curves showed weak predictive ability (auc: 0.66 (95% ic 0.55-0.77; p < 0.01) for a threshold value ≤ 49 cmh 2 o. expiratory muscle weakness was unable to predict critical outcomes when adjusting mep to the %predicted or lower limit of normal. discussion: possible explanation is that contrary to inspiratory muscle weakness, cough inefficacy after weaning from mechanical ventilation could be managed with cough supplementation techniques (i.e. mechanical in-exsufflation). conclusion: in our cohort, mep was not associated with mechanical ventilation weaning or death. despite our results, different clinical techniques for quantifying expiratory muscle weakness may provide more beneficial results. compliance with ethics regulations: yes rationale: venoarterial extracorporeal membrane oxygenation (va-ecmo) is used to support tissue perfusion during extracorporeal cardiopulmonary resuscitation (e-cpr). shock, resuscitation and the extracorporeal circuit may trigger a capillary leakage and a vasoplegic shock. currently, in these situations, high doses of norepinephrine (ne) are required. because high ne doses may have significant cardiovascular side effects, alternative options to support arterial blood pressure are needed. in recent years, several approaches to decrease the administration of high ne doses have been tested, one of them is the administration of vasopressin (avp). randomized trials have shown that avp infusion increases arterial pressure and systemic vascular resistance, decreases catecholamine requirements in patients with or at high risk of vasoplegic syndrome and attenuates vascular dysfunction. currently, no data are available for the study of the effects of avp in shock state in post refractory cardiac arrest. patients and methods: 20 pigs were randomized into two groups, in order to receive avp or ne. a refractory cardiac arrest of ischemic origin was surgically created and va-ecmo was started after a 30 min period of cardio-pulmonary resuscitation. then, resuscitation lasted 6 h in each randomization group. the evolution of the consequences of the shock was evaluated by lactatemia and microcirculation (sdf and nirs) at baseline hour, h0 (when ecmo starts), h3 and h6. renal and hepatic functions were assessed. results: experimental conditions were met for 16 animals (avp, n = 8; ne, n = 8). the groups were comparable on the shock impact and its severity. no significant differences were found between populations for ecmo flow and map. there was a significant difference on fluid volume resuscitation amount (14000 [11.250-15.250 ] ml in the ne group versus 3500 ml in the avp group, p < 0.05) (fig. 1 ). no significant difference between the ne and avp groups for lactate clearance between h0 and h6 (25.6 [− 7.31 to 35.34]% vs 47.84 [13.42-82.73 ]%, p = 0.686). we did not find any significant for sublingual microcirculation indices and nirs values. renal and liver function evolution were similar in the two groups during the protocol. conclusion: avp administration in refractory cardiac arrest resuscitated by va-ecmo when compared to ne is associated with less fluid volume for similar global and regional hemodynamic effects. compliance with ethics regulations: yes. patients and methods: a single-center prospective study. patients younger than 6 months with severe bronchiolitis and supported by niv or hfnc were included. niv/hfnc was discontinued according to the local practices and no protocol existed. exceptt the principal investigator, the attending team was blinded to the study. weaning failure was defined as the need to reinstate niv/hfnc in the 48 h after discontinuation. ethical approval was not necessary for this study in accordance with the french data protection autority methodology reference number mr-004. results: a total of 95 patients (median age 47 days, 53 (56%) males) were included. respectively, 72 (76%) and 23 patients (24%) were supported by niv and hfnc at admission (fig. 1) . regarding the mode of niv, a bilevel mode was used in 46 patients (48%) (fig. 1 ). in patients supported by hfnc, the ventilatory support was discontinued progressively by decreasing air flow in 9 patients (39%) while it was stopped abruptly in 5 (22%). in patients supported by niv, the respiratory support was stopped abruptly in 5 (19%) of them while hfnc was used as a weaning method for 17 (65%) patients. a total of 22 (23%) patients experienced a weaning failure. patients supported by niv/ hfnc who experienced a prompt weaning had a lower pediatric intensive care unit (picu) length of stay as compared to patients in whom hfnc was used as a weaning method (78 ± 27 h versus 112 ± 112 h, p = 0.01). however, the hospital length of stay was similar according to the weaning method (6 ± 3 days versus 7 ± 3 days for prompt and progressive methods respectively, p = 0.07). the duration of the weaning process did not differ according to the bed-availability in picu. in patients with severe bronchiolitis, a prompt weaning from niv/hfnc was associated with a lower length of stay in picu. however, the hospital length of stay was similar according to the weaning method. we suggest that a prompt weaning should be preferred in order to reduce the risk of picu related complications. compliance with ethics regulations: yes. information and incitation to open a twitter account and to follow critical care journal feeds) or group 3 (control group). ict were interrogated on their recent medical literature knowledge at 3 and 6 month on 5 trials published in pre-selected journals. results: during the study period, on the 969 french ict contacted, 77 agree to participate: 16 were already on twitter, 31 were randomized to twitter incitation and 30 to control group. at 3 month, there were 62 who answered electronic questionnaire. self-declaration of article knowledge was not different between 3 groups (p = 0.85). knowledge of primary outcome of each trial was not significantly better in 3 groups (p = 0.09). in per-protocol analysis of ict on twitter or not, knowledge of article and primary outcome were also not significantly different (respectively p = 0.57 and p = 0.17). short incitation to open a twitter account and follow major medical journals with specific focus on cardiac arrest did not improve knowledge of medical literature by intensive care trainees at 3 month. further trials are needed to better imply intensive care trainees in scientific medical literature. compliance with ethics regulations: yes. 1-1.1] ; p = .07) as independently associated with in-hospital mortality ( fig. 1 ). discussion: triple therapy is the recommended first-line treatment of caps. however, herein, it was not significantly associated with better survival in critically ill, thrombotic aps patients. for the subgroup of "definite/probable caps" patients, double and triple regimens were associated with survival. but the bivariable analyses including the day-0 saps ii showed that survival was linked to in-icu anticoagulation and corticosteroids-not ivig or plasmapheresis. our findings indicate that corticosteroids should probably be added to in-icu anticoagulation to treat "definite/probable caps". frequent fever and elevated c-reactive protein in all thrombotic aps patients suggest a marked inflammatory state that could explain corticosteroid efficacy. neither plasmapheresis nor ivig impacted the prognosis of "definite/ probable caps", but that finding could be explained by a lack of power compared to caps registry data. conclusion: in-icu anticoagulation was the only aps-specific treatment independently associated with survival for all patients. doublebut not triple-therapy was independently associated with better survival of "definite/probable caps" patients. in these patients, double therapy should be used as first-line therapy while the role of triple therapy requires further evaluation. compliance with ethics regulations: yes. motor deficiency 0 (0%) 2 (11%) 4 (15%) 0.021 cognitive impairment 0 (0%) 2 (11%) 7 (26%) 0.001 intra-individual relationships between δpdi and tfdi for mechanically ventilated (mv) patients (a) and healthy subjects (c). relationships between δpdi and tfdi when breathing cycles were averaged for all participants during each condition for mv patients (b) and healthy subjects (d). − 25%: initial settings minus 25% inspiratory help, + 25%: initial settings plus 25% more inspiratory help, pep 0: zero positive end-expiratory pressure, sbt: spontaneous breathing trial. healthy subjects performed spontaneousbreathing (sb) and ventilation against inspiratory threshold at 10, 20, 30, 40 and 50% of maximal inspiratorypressure (mip) groups. airway closure occurrence increased with bmi (22%, 38% and 58%, p = 0.04). when present, airway opening pressure was 9.6 cmh2o (8. 5-13.2) and similar between the 3 groups. with increasing bmi, total peep increased from 6.0 to 9.0 cmh2o between groups (p = 0.02). all values of esophageal pressure increased with bmi. endexpiratory esophageal pressure was strongly correlated with bmi (rho = 0.71, p < 0.001), as illustrated in fig. 1 . consequently end-expiratory transpulmonary pressure decreased from − 2.7 to − 9.3 cm h2o with increasing bmi (p = 0.008). the ratio of eelv to predicted functional residual capacity was negatively correlated with end-expiratory pressure (rho = − 0.39, p = 0.01), but not with bmi. driving pressure and elastance of the respiratory system, chest wall and lung were similar across all ranges of bmi. likewise, eelv was similar between groups. conclusion: in ards, increasing bmi is associated with increased occurrence of airway closure and increased values of esophageal pressure. conversely, chest wall elastance is not influenced by bmi, as well as lung elastance. including bmi in interpreting respiratory mechanics in ards patients can provide additional information for the clinical management. compliance with ethics regulations: yes. rationale: low tidal volume is the cornerstone of protective ventilation inthe initial phase of ards (1) . whether such low tidal volume can still be achieved when the patient is allowed to breathe spontaneously under pressure support ventilation (psv) is unknown. in moderate-tosevere ards patients receiving neuromuscular blockade, we assessed the tidal volume and its potential association with the outcome during the "transition period" following neuromuscular blockade. patients and methods: retrospective observational study in two university intensive care units. patients fulfilling moderate-to-severe ards criteria less than 72 h after intubation and receiving neuromuscular blockers were included upon entry in the "transition period". we defined the "transition period" as the 72 h following neuromuscular blockers cessation. ventilatory and hemodynamic parameters were recorded every 3 h during the "transition period". primary outcome was the association between mean tidal volume under pressure support ventilation (psv) during the "transition period" and the 28-day mortality after adjustment for confounding factors. data are reported as median [1st-3rd quartile] or number (percentage). results: one hundred nine patients were included, with a pao2/fio2 ratio of 100 mmhg at intubation and 194 mmhg at inclusion and a sofa score at 7 [4.5-10] . patients had been ventilated 2 days [1-3.8 ] before inclusion. during the "transition period", 88 patients (80.7%) were switched to psv. the median duration of psv was 42 h . the mean tidal volume under psv was significantly lower in survivors than in non survivors at day 28 (7.1 ml/kg [6.3-7 .9] vs. 7.8 ml/kg [6.8-9.4 ] respectively, p = 0.007). by multivariate analysis (cox proportional hazards regression model), mean tidal volume during psv remained independently associated with the 28-day mortality after adjusting for sofa score and immunosuppression. patients with a mean tidal volume above 8 ml/kg under psv during the "transition period" had a lower cumulative probability of survival at day 28 as compared with others (log rank test, p = 0.008) (fig. 1) . conclusion: in patients with moderate-to-severe ards, a higher tidal volume under psv within the 72 h following neuromuscular blockers cessation is independently associated with the 28-day mortality.compliance with ethics regulations: yes. kaplan-meier estimate of the cumulative probability of survival according to the mean tidal volume (vt)-lower of higher than 8 ml/ kg-under pressure support ventilation (psv) during the "transition period" transfusion is associated with adverse events, and equipoise remains on the optimal transfusion strategy in oncologic patients in surgical setting. patients and methods: this is a retrospective, single center study. all adults admitted to the intensive care unit (icu) after oncologic surgery from january 2017 to december 2018 were eligible. the following types of surgery for cancer or metastasis resection with a high risk of bleeding were eligible: thoracic, abdominal, neurosurgery, gynecologic, urologic, otorhinolaryngology or spinal surgery. the primary outcome was a composite outcome including post-operative complications (respiratory, cardiac, renal, thromboembolic, infectious and/or hemorrhagic) and/or hospital mortality. results: of the 287 patients included, 142 patients (49.5%) had anemia (based on the who definition: hemoglobin level 10-11.9 g/dl for female; hemoglobin level 10-12.9 g/dl for male), 69 patients (24%) had moderate anemia (hemoglobin level: 8-9.9 g/dl) and 32 patients (12.5%) severe anemia (hemoglobin level < 8 g/dl). fifty-six patients (19.6%) received at least one rbc transfusion during their hospital stay. patients exposed to moderate and severe anemia required more often renal replacement therapy (rrt) for acute kidney injury (aki) (1.1% vs. 10 .9%; p = 0.003), had more surgery-related infections (7.6% vs. 22.8%; p = 0.004). patients who received rbc had more often aki with rrt (0.9% vs. 19.6%; p < 0.001), thromboembolic events (2.2% vs. 8.9%; p = 0.039), sepsis (4.3% vs. 16.1%; p = 0.004), pneumonia (4.8% vs. 14.3%; p = 0.024), surgical site infections (8.7% vs. 30.4; p < 0.001) and second surgery for infection (3% vs. 16.1%; p = 0.001). the multivariate analysis found an association between moderate and severe anemia (moderate anemia: or 15.03 [2.73-282.3] ; severe anemia: or 16.65 [2.71-325.7 ]; p = 0.011) and severe post-operative complications (fig. a) . there was also an association between rbc transfusion and severe post-operative complications ]; p < 0.001) (fig. b) . conclusion: anemia was frequent in oncologic surgical patients. anemia, including moderate anemia, was independently associated to patient outcomes; however, rbc transfusion also negatively impacts on patients' prognosis. our study highlights the need for further research to identify the optimal hemoglobin threshold for rbc transfusion in surgical oncologic patients. compliance with ethics regulations: yes. rationale: right ventricular (rv) failure is a common complication in moderate to severe acute respiratory distress syndrome (ards). rv failure is exacerbated by hypercapnic acidosis and overdistension induced by mechanical ventilation. veno-venous extracorporeal co2 removal (ecco2r) might allow ultraprotective mechanical ventilation strategy with a low tidal volume (vt) and plateau pressure (pplat). this study investigated if ecco2r therapy could have beneficial effects on rv function. patients and methods: this prospective monocentric pilot study was conducted in a french icu from january 2017 to march 2019. patients with moderate to severe ards with pao2/fio2 ratio between 80 to 150 mmhg were enrolled. ventilation parameters, arterial blood gases, echocardiographic parameters performed by transthoracic echocardiography (tte), low-flow ecco2r system operational characteristics, outcomes and adverse events were collected during the protocol. primary end point was evolution of rv echocardiographic parameters with ultraprotective ventilation strategy at 4 ml/kg pbw during the 24-h following the start of ecco2r. results: eighteen patients were included. efficacy of ecco2r allowed an ultraprotective strategy in all patients. we observed a significant improvement of rv systolic function parameters assessed by tte (fig. 1 ). tricuspid annular plane systolic excursion (tapse) increased significantly under ultraprotective ventilation compared to baseline (from 22.8 to 25.4 mm; p < 0.05). systolic excursion velocity (s') also increased after 1-day protocol (from 13.8 m/s to 15.1 m/s; p < 0.05). a significant improvement of aortic velocity time integral (vtiao) under ultraprotective ventilation settings was observed. there were no significant differences in the values of systolic pulmonary arterial pressure (spap). when patients were separated in two groups according to baseline paco2 level above or under 50 mmhg, we showed the deleterious effect of hypercapnia on rv function, and observed in both groups a beneficial impact of an ultraprotective ventilation strategy on tapse. no severe adverse events directly related to ecco2r were observed in our small cohort. conclusion: the low-flow ecco2r allows ultraprotective ventilation strategy and improve rv function in moderate to severe ards patients. similarly to prone positioning, ecco2r could become a strategy that enables to reconcile lung protective approach with rv protective approach in ards patients. large-scale clinical studies, including patients with severe rv dysfunction, will be required to confirm these results and to assess the overall benefits, in particular the best timing of beginning ecco2r in ards patients. compliance with ethics regulations: yes. rationale: bronchoalveolar lavage (bal) is usually deemed to allow the diagnosis of a large array of pulmonary diseases and is usually considered as well tolerated in intensive care unit (icu) patients. however, recent data suggest that the diagnostic yield of bal could be rather low (1) , and may question its innocuity (2) . the present study aimed at assessing the benefit-to-risk balance of bal in icu patients. patients and methods: the study was approved by the appropriate ethics committee and registered with clinicaltrials.gov (nct03098888). in 16 icus, from april 2017 to october 2018, we prospectively collected adverse events (ae) during or within 24 h after bal and assessed the bal input for decision-making in consecutive adult patients. aes were categorized in 5 grades of increasing severity. the occurrence of a clinical ae at least of grade 3, i.e. sufficiently severe to need therapeutic action (s), including modification (s) in respiratory support, defined poor bal tolerance. the bal input for decision-making was declared satisfactory if it allowed to interrupt or initiate one or several treatments. results: we included 483 bal in 483 patients (age 63 yrs ; female gender: 162 [33.5%]; simplified acute physiology score ii: 48 ; immunosuppression 244 [50.5%], chronic pulmonary disease [163/483 (33.7%)]). bal was performed either in non-intubated patients receiving standard o2 therapy (n = 56 [11.6%]), or noninvasive ventilation (n = 4 [0.8%]), or high-flow nasal cannula o2 therapy (45 [9.3%]), or in patients under invasive mechanical ventilation (n = 378 [78.3%]). a total of 710 aes were observed in 415 (85.9%) patients. sixty-seven (13.9%) patients reached the grade 3 of ae or higher. the main predictor of poor bal tolerance identified by logistic regression was the association of a bal performed by a non-experienced physician (non-pulmonologist, or intensivist with less than 10 years in the specialty or less than 50 bal performed) in non-intubated patients (or: 31.8 [95% confidence interval 11. 6-87.6] ; p < 0.0001). ordinal regression also showed that when bal was performed by a non-experienced physician in a non-intubated patient, this was associated with an increased risk of ae of any grade (or: 12.66 [6.27-25.57 ]). a satisfactory bal input for decision-making was observed in 227 (47.0%) cases and was not predictable using logistic regression. conclusion: adverse events related to bal in icu patients are frequent, and sometimes serious. our findings call for an extreme caution when envisaging a bal in icu patients and for a mandatory accompaniment of the less experienced physicians. compliance with ethics regulations: yes. meningitis is a rare complication of critically ill patients with severe pneumococcal community-acquired pneumonia paul jaubert, julien charpentier, jean-daniel chiche, frédéric pene, alain cariou, guillaume savary, marine paul, jean-paul mira, mathieu jozwiak cochin, paris, france; 2 mignot, versailles, france correspondence: paul jaubert (paul.jaubert@gmail.com) ann. intensive care 2020, 10 (suppl 1): rationale: severe pneumococcal community-acquired pneumonia (pcap) is a frequent infection requiring intensive care unit (icu) admission. pneumococcal meningitis associated with pcap has been reported and could worsen the prognosis of patients. however, this complication is difficult to predict and lumbar puncture is not systematically performed, regardless the severity of pcap. thus, we investigated the characteristics of patients with pcap associated with pneumococcal meningitis. patients and methods: we retrospectively included all patients admitted for pcap in our icu between 2006 (inception of our electronic medical sheet) and the end of 2018. community-acquired pneumonia was defined according to the criteria of the american thoracic society. we excluded all patients admitted in icu with initial suspicion of meningitis. variables regarding epidemiology, clinical and microbiological characteristics, management and prognosis of these patients were collected and analyzed. results: among the 264 patients admitted for pcap (62 ± 17 years old, saps ii 55 ± 22, 59% of men), 59% of the patients required mechanical ventilation and 29% vasopressors infusion. the icu mortality was 16%. s. pneumoniae was documented by a positive antigen test in 81% of the patient and/or by a positive sputum smear, tracheal aspirate or distal protected airway specimen in 54% of the patients, and/or by pleural aspirate in 5% of the patients and/or by positive blood culture in 32% (n = 84) of the patients. a lumbar puncture was performed in 39% (n = 33) of the patients with bacteriemia and in 30% (n = 54) of the patients without bacteriemia, with a median delay of 12 h [interquartile range: after the onset of antibiotherapy. alllumbar punctures (n = 87) were performed for neurological signs: 50% of coma, 46% of confusion and 1% of seizures. when a lumbar puncture was performed, meningitis was diagnosed in 24% (n = 8) of the patients with bacteriemia and in 2% (n = 1) of the patients without bacteriemia (p < 0.05). the icu mortality (22% vs. 16%, respectively), age (58 ± 19 vs. 63 ± 17 years old, respectively), saps ii (65 ± 27 vs. 54 ± 22, respectively) or icu length of stay (17 ± 24 vs. 11 ± 16 days, respectively) were not different between patients with and without meningitis (each p = ns). conclusion: meningitis is a rare complication of pcap and is more frequent in patients with bacteriemia. suprisingly, meningitis is not associated with higher icu mortality. further analyses are ongoing to identify independent risk factors of meningitis in patients with pcap. compliance with ethics regulations: yes. rationale: shock is the clinical expression of a circulatory failure that results in inadequate cellular oxygen utilization. whereas the host response to septic shock has been extensively described, knowledge of the pathogenesis of non-septic shocks remains limited. we aimed to characterize the systemic host response in shock related to non-septic conditions (nssh) as compared with septic shock (ssh). patients and methods: we performed a prospective study in two intensive care units (icus) in patients admitted for ssh (n = 931) or nssh (n = 1338). immune responses were determined upon icu admission by measuring 17 plasma biomarkers reflecting host response pathways implicated in the pathogenesis of critical illness (in 573 ssh and 287 nssh patients), and by applying genome-wide blood mrna expression profiling (in 267 ssh and 136 nssh patients). results: compared with nssh, patients with ssh had more chronic comorbidities, greater disease severity (apache iv score 89 vs. 71 , p < 0.001) and worse outcomes resulting in higher mortality rates up to one year after icu admission (53.8% vs. 38.8%, p < 0.001). plasma biomarker analysis revealed severely disturbed host responses in both ssh and nssh patients. however, ssh patients displayed more prominent inflammatory responses, endothelial cell activation, loss of vascular integrity and a more pro-coagulant state relative to nssh patients. blood leukocyte genomic responses were more than 80% common between ssh and nssh patients relative to health (fig. 1a) , comprising overexpression of innate pro-and anti-inflammatory pathways, and underexpression of lymphocyte and antigen-presentation gene sets. direct comparison of ssh to nssh patients matched for severity (fig. 1b) showed overexpression of genes involved in mitochondrial dysfunction and specific metabolic pathways, and underexpression of lymphocyte, nf-κb and cytokine pathways. conclusion: patients with ssh and nssh present with largely similar host response aberrations at icu admission; however, patients with septic shock show more dysregulated inflammatory and vascular host responses, as well as specific leukocyte transcriptome alterations consistent with greatermetabolic reprogrammingand more severe immune suppression. compliance with ethics regulations: yes. rationale: aki is associated with short and long term mortality and morbidity. although recovery has been demonstrated to be associated with outcome of critically ill patients, interpretation of available data is limited by time dependent nature of recovery and by competing risks. our objective was to describe renal recovery, pattern of recovery according to adqi definitions and risk factor of this later. monocenter retrospective cohort study. adult patients admitted in our icu from july 2018 to december 2018 were included. aki was defined according to kdigo criteria and recovery according to adqi definition. incidence of recovery at each time point was depicted using competing risk survival analysis. risk of transition between aki and no-aki was assessed by a semi-markov model. last, a trajectoire analysis was performed to depict most frequent recovery patterns. results are reported as n (%) or median (iqr). results: 350 patients were included with a median age of 57 (45-72). median sofa score at admission was 4 [2] [3] [4] [5] [6] [7] . at icu admission, 85 patients (24.2%) had an aki stage 1, 44 patients (12.6%) an aki stage 2 and 37 patients (10.6%) an aki stage 3. according to adqi criteria, aki was defined as rapidly reversed in 42 patients (25.3% of aki patients), persistent aki in 16 patients (9.7%) and as acute kidney disease (akd) in 64 patients (38.6%), remaining patients couldn't be classified (n = 44). risk of recovery was of 9% per day until day 7 then 15% per day (fig. 1a) . fine and gray model, taking into account death as competing risk, identified 3 risk factors negatively associated with renal recovery, namely sofa score (shr = 0.94 per point; 95% ic = [0.89-0.99]), preexisting hypertension (shr = 0.56; 95% ic = [0.32-0.98]) and aki severity (stage 3 vs. stage 1 shr = 0.17; 95% ic = [0.06-0.56]). risk of de novo aki was maximal during the first 7 days and ranged from 25 to 36% per day. trajectoire model identified 3 clusters of patients ( fig. 1b) , closely associated with patients' outcome: a) low patients' severity and no or mild aki (n = 251; hospital mortality: 8%); b) moderate to severe aki but little associated organ dysfunction (n = 70, hospital mortality: 12.9%); c) severe aki and multiple organ failure (n = 29; hospital mortality: 89.7%). conclusion: this study, assessing aki recovery patterns, is the first to our knowledge using adqi definition. despite the high rate of early recovery and of rapidly reversed aki, up to 40% of aki patients had not recovered at day 7 and could therefore be classified has having akd. compliance with ethics regulations: yes. rationale: sepsis is the most frequent cause of acute kidney injury (aki). the "acute disease quality initiative workgroup" recently proposed new definitions for aki, classifying it as transient or persistent. we aimed to determine the incidence, attributable mortality and host response characteristics of transient and persistent aki in patients with sepsis. patients and methods: we performed a prospective observational study comprising consecutive admissions for sepsis in 2 intensive care units (icus) in the netherlands, stratified according to the presence and evolution of aki. attributable mortality fraction (excess risk for dying with persistent aki relative to transient aki) was determined using a logistic regression model adjusting for confounding variables. in a subset of 866 sepsis patients, 16 plasma biomarkers indicative of major pathways involved in sepsis pathogenesis were measured. in a second subset of 392 patients, whole-genome blood-leukocyte transcriptomes were analyzed. results: 1545 sepsis patients were included. aki occurred in 37.7% (n = 577), of which 18.4% (n = 106) was transient and 81.6% (n = 471) persistent. patients with persistent aki had higher disease severity scores on admission than patients with transient aki or without aki and more frequently had severe (injury of failure) rifle aki-stages on admission (n = 322, 68.4%) than transient aki patients (n = 33, 31.1%, p < .001). persistent aki, but not transient aki, was associated with increased mortality by day-30 (adjusted or 2.42, 95% ci 1.28-4.58; p = .006) ( figure) and up to 1-year (adjusted or 2.10, 95% ci 1.12-3.92;p = .020). the attributable mortality of persistent relative to transient aki by day-30 was 14.0% (95% ci 3.7-24.2%). persistent aki was associated with enhanced and sustained inflammatory and procoagulant responses during the first 4 days, and a more severe loss of vascular integrity compared with transient aki. baseline blood gene expression showed minimal differences with respect to the presence or evolution of aki. conclusion: persistent aki is associated with higher sepsis severity, sustained inflammatory and procoagulant responses, and loss of vascular integrity as compared with transient aki, and independently contributes to sepsis mortality. compliance with ethics regulations: yes. rationale: to address the paucity of data on the epidemiology of patients admitted to intensive care units (icus) with in-hospital cardiac arrest (ihca), we examined key features, mortality and trends in mortality in a large cohort of patients admitted in 33 french icus over the past 18 years. patients and methods: from 1997 to 2015 database of the collège des utilisateurs de bases de données en réanimation (cub-réa), we determined temporal trends in the characteristics of ihca, patients' outcomes and predictors of icu mortality. results: of the 376 325 icu admissions, 33 126 (8.8%) were cardiac arrests and 15 324 were ihca (4.1%). during the study period, the age of ihca patients increased by 0.7 years (p = 0.04) and patients presented more comorbidities (chronic heart disease, chronic kidney disease and cancer). patients were also more critically ill over the period as reflected by the increase of saps-ii by 2.3% (p < 0.001). paradoxically, in-hospital management became lighter through the time with reduced respiratory support (p < 0.001), renal support (p < 0.001) and use of vasoactive drugs (p < 0.001). crude in-icu mortality decreased from 78% to 62.5% over the past eighteen years (p < 0.001), fig. 1 rationale: in surgery, prophylaxis antibiotic aims at preventing the occurrence of post-operative infections. for adults, it is currently recommended to only use prophylactic antibiotic therapy during the time of the intervention. but in pediatric cardiac surgery, there is no consensus around the optimal duration of use of antibiotic prophylaxis. the protocol was modified in 2018 in the icu and its time reduced to 24 h. we aimed to determine whether 24 h of post-sternotomy antibiotic prophylaxis was not less effective than 48 h treatment to help prevent care-associated infections. patients and methods: after agreement of the ethics committee of our institution, we performed a retrospective non inferiority study, with an inferiority margin to 10%. the primary objective is to compare the incidence of care-related infections between a second-generation cephalosporin (c2g) antibiotic prophylaxis during 48 h and a 24-h protocols. the secondary objectives are to determine the infection's incidence, to identify the risk factors for nosocomial infections and to compare the incidence of multidrug-resistant infections. results: between january 2013 and july 2019, 402 children underwent cardiac surgeries with sternal opening. 299 received 48 h of c2g antibiotic prophylaxis and 103 received 24 h of c2g treatment. five previously infected children have been excluded. both groups were demographically and surgically similar. the median age was 7 months (range a few hours of life to 14.5 years old) and the median weight was 6.7 kg. in the intent-to-treat analysis, incidence of care-related infections is at 10.03% in the c2g-48 h group and 10.68% in the c2g-24 h group. a multivariate analysis shows that the shorter 24-h time antibiotic prophylaxis is not inferior regarding infection prevention compared to 48 h of antibiotic prophylaxis, p = 0.046. as in the per protocole analysis, the c2g-48 h group rate was 9.1% and 6.6% for the g2g-24 h group. conclusion: it demonstrates that shortening the antibiotic prophylaxis treatment time to 24 h does not affect or increase the rate of infections after a pediatric sternotomy surgery compared to 48-h protocole. prophylaxis in pediatric cardiac surgery should be short-lived. a multicenter prospective study would allow a consensus and confirm this decision. compliance with ethics regulations: yes. rationale: the use of "big data" is getting increasingly popular in the medical field, especially in intensive care where large amounts of data are continuously generated. however, big data can be misleading when essential clinical data are missing. the adequate adjustment for potential confounding factors (e.g., severity of respiratory distress) should be the key procedure in the big data analyses; however, it is challenging to capture the clinical severity within large electronic databases. bronchiolitis is one main reason for admission to pediatric intensive care unit (picu). the modified wood's clinical asthma score (mwcas) is widely used to assess the severity of bronchiolitis. the objective of the study is to build an automated mwcas (a-mwcas) to continuously assess the severity of respiratory distress in critically ill children. this retrospective study included all infants < 2 years old with a clinical diagnosis of bronchiolitis, ventilated with non-invasive neurally adjusted ventilatory assist, in a canadian picu, between october 2016 and june 2018. we developed an algorithm, using python 3.7, which was directly connected to the electronic medical record. the components of the score were collected using structured query language (sql) queries and processed to derive the a-mwcas. for validation, the a-mwcas score was compared to the mwcas manually computed by a clinical expert (m-mwcas) . results: sixty-four infants were included in the study, for which 256 of a-mwcas and m-mwcas were generated respectively. the cohen's kappa coefficient was applied to estimate the agreement between the two scores which was 0.71 (95% confidence interval) ( table 1 ) which corresponds to 78.5% of complete agreement. 17.5% of the a-mwcas scores were within ± 0.5 of the m-mwcas. the kappa coefficient for the each score component were: 0.91 for the oxygen saturation, 0.79 for the expiratory wheezing, 0.91 for the inspiratory breath sounds, 0.89 for the use of accessories muscles and 0.51 for the mental status, respectively. discussion: the largest discrepancy was observed in the mental status, which clinical evaluation is relatively subjective and varies among care team members (doctor, nurse, respiratory therapist…). the automated score likely decreases this variability by consistently using the same source (respiratory therapist), but its validity should be confirmed in a prospective study. the a-mwcas provides a valid estimation of the mwcas that is fast and robust. after external prospective validation, it may help to add some clinical sense within large electronic databases, with improved assessment of the respiratory distress. compliance with ethics regulations: yes. rationale: in paediatric intensive care units (picu), survival rates have dramatically improved. this has been accompanied by increased morbidity, including psychological morbidity. these new impairments, that can affect the survivors and their families have been conceptualized under the frame of post-intensive care syndrome (pics) and picsfamily. the aim of this study was to explore the experience of critically ill children parent's during the stay in picu, and its impact on the family. patients and methods: we planned a prospective, single centre study for 3 months. we collected qualitative written data from parents whose child had been admitted to the picu for the first time, for at least two nights. results: fifty-seven questionnaires were analysed from thirty-seven admissions. picu admissions were mostly unplanned. among parents 40% experienced very painful memories during admission and 61% have feared for their child's life. during the stay, noise has bothered 30% of parents, and many have described difficulties to rest at night. 81% had the sensation that their child was suffering, mostly from pain, tiredness, anxiety or fear. during picu stay, 75% of parents had to stop working, and siblings schooling was impacted in 25% of cases, 77% of parents considered themselves to be useful for their child and 81% have participated to nursing care. more than 70% were satisfied about information given and communication, 77% appreciated empathy and support from care givers. parents received support from family, friends, and also from other parents of hospitalized children. parents expressed relief (46%) and serenity (38%) to leave picu, 58% of them were in demand to meet picu staff again after discharge. conclusion: picu parent's experience is tough, and the impact on family is clear. these are known risks factors for pics. on a very positive note, parents seemed to be satisfied by family-centred care, and were able to preserve their parental role. however, there is still room for improvement of practices. compliance with ethics regulations: yes. the gut has been suspected to be involved in multiple organs dysfunction syndrome (mods) in the intensive care unit (icu). studies suggested a link between gastrointestinal dysfunction (gid) and outcomes. but these studies included very few patients and most of them were retrospective. patients and methods: this study is a secondary analysis of data from a previous study that included patients from 44 french icus. gid is defined as the association of vomiting and constipation or diarrhea during the first week after icu admission. patients included were treated with vasopressors and mechanical ventilation. the first goal was to determine if gid is a risk factor of 28-day mortality in this population. secondary goals were to assess the impact of gid on nosocomial infections. results: among 2410 included patients, 238 (9.9%) had gid. by day-28, 76 (32%) of the 238 patients with gid and 780 (36%) of the 2172 patients without gid had died (odds ratio 0.84 [0.96-1.01]; p = 0.25). multivariable regression model did not show any association between gastrointestinal dysfunction and increased risk of 28-day mortality in patients (odds ratio 0.76 [0.56-1.04], p = 0.083). gastrointestinal dysfunction was strongly associated with other secondary outcomes ( table 1 ). patients with gid had longer ventilation duration, icu length of stay and hospital length of stay. they also had more nosocomial infections, in particularly ventilator-associated pneumonia. this association still existed in a multivariable regression model for prediction of nosocomial infection including the same variables than the previous model (odds ratio 1.68 [1.19-2.37 ], p = 0.0028). no association with day-90 mortality was observed. conclusion: gastrointestinal dysfunction was not a risk factor of day-28 mortality but was associated with an increased risk of nosocomial infection and an increased length of stay. this study is observational and no causality link can be done. however, our data suggest further studies on strategies aimed to limit gid. compliance with ethics regulations: yes. rationale: acute cholangitis (ac), a bacterial infection related to an obstruction of the biliary tree, may be responsible for life-threatening organ failure. however, little is known about the outcome and the predictive factors of mortality of critically ill patients admitted in icu for acute cholangitis. we aimed to describe characteristics of patients admitted in icu for ac and to analyze predictive factors of in-hospital mortality including the time to biliary drainage procedure. patients and methods: retrospective study of all cases of acute cholangitis admitted in 11 french icus (5 tertiary hospitals and 6 non-ter1 [5.3; 54.8 ] µg/l. 63% of patients (n = 252) have positive blood culture, mostly gram negative bacilli (86%) and 14% producing extended spectrum beta lactamase enterobacteriaecae. at icu admission, persisting obstruction was frequent (79%) and therapeutic endoscopic retrograde cholangiopancreatography was performed in 76% of them. in a multivariable analysis, at icu admission, several factors were significantly associated with in-hospital mortality: sofa score (or = 1.14 [95% ic 1.05; 1.24] by point, p = 0.001), arterial lactate (or = 1.21 [1.08; 1.36 ] by 1 mmol/l, p < 0.001), total serum bilirubin (or = 1.26 [1.12; 1.41] by 50 umol/l, p < 0.001), obstruction nonrelated to gallstones (p < 0.05) and ac complications (liver abcess and/or pancreatitis) (or = 2.74 [1.45; 5 .17] p = 0.002). in addition, time > 48 h between icu admission and biliary drainage was associated to in-hospital mortality (adjusted or = 2.73 [1.30; 6.22 ] p = 0.02). conclusion: acute cholangitis is responsible for high mortality in icu. organ failure severity, causes and local complications of cholangitis are predictive factors of mortality as well as delayed biliary drainage. compliance with ethics regulations: yes. the united kingdom) were included (n = 152). predictors of one-year mortality were retrospectively screened and tested on a single center training cohort. a predictive score was developed and tested on an independent multicenter cohort. results: four independent pre-transplantation risk factors were associated with one-year mortality after transplantation in the training cohort: age ≥ 53 years (or = 5.79, 95% ci = 1.05-32.04, p = 0.044), pre-transplantation arterial lactate level ≥ 4mml/l (or = 9.99, 95% ci = 1.62-61.46, p = 0.013), mechanical ventilation with pao2/ fio2 ≤ 200 mmhg (or = 8.60, 95% ci = 1.30-56.88, p = 0.026) and pretransplantation leukocyte count ≤ 10g/l (or = 12.91, 95% ci = 2.26-73.87, p = 0.004). a simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for aclf-3 model (tam) score. a cut-off at 2 points distinguished a high-risk group (score > 2) from a low-risk group (score ≤ 2) with one-year survival of 8.3% vs. 83.9% respectively (p < 0.001). the model and its simplified version were validated on the independent multicenter cohort. there was a significant difference between the high-risk and low-risk group with one-year survival of 10% vs. 71.9% respectively (p < 0.001). conclusion: liver transplantation can be an effective treatment for critically ill cirrhotic patients with hepatic and extra hepatic organ failure provided patients are carefully selected and that they are transplanted at the optimal time in the intensive care. the tam score can help stratify post-transplantation survival and assist clinicians in the transplantation decision-making process at the bedside of aclf-3 patients. compliance with ethics regulations: yes. rationale: trans-thoracic echocardiography (tte) is commonly used in the initial management of patients with shock in icu. there is little published evidence for any mortality benefit. we compared the effect of echocardiography protocol versus standard care for survival and clinical outcomes. patients and methods: this randomized controlled trial included selected shocked patients (systolic blood pressure < 90 mm hg and signs of organ hypoperfusion) randomized to early tte plus standard care versus standard care without tte. the primary outcome measure was survivalto 28 days. secondary outcome measures included initial treatment and vasopressor weaning. results: 202 consecutive subjects with circulatory shock (low systolic arterial blood pressure (sap) and signs of organ hypoperfusion) at the time of icu admission are included in the study. in the tte group: fluid prescription during the first 24 h was significantly lower rationale: both the negative prognostic value and reversibility of left ventricular (lv) diastolic dysfunction in septic patients remain debated. the excess of mortality in septic shock patients with hyperdynamic profile has only been reported by small-size studies. accordingly, the primary objective of the prodiasys study was to assess the impact of lv diastolic dysfunction (and its severity) and of lv hyperkinesia echocardiographically identified during the initial phase of septic shock on 28-day survival. the secondary objective was to assess the potential link between lv diastolic dysfunction, cumulative water balance (on day 4), and outcome. patients and methods: this was a multicenter, prospective, observational, cohort study. patients older than 18 years hospitalized in icu for septic shock (sepsis-3 definition) were eligible. exclusion criteria were administration of inotropes, severe left valvular disease, constrictive pericarditis and moribund patients. in each patient, echocardiography was first performed within 12 h after the diagnosis of septic shock and then daily until day 3, after vasopressor discontinuation, at icu discharge and on day 28 or at hospital discharge, whichever occurred first. vital and biological parameters usually monitored for septic shock management were collected at each echocardiographic assessment. vital status was collected on day 28. associations between lv diastolic dysfunction or lv hyperkinesia and day-28 mortality were analyzed using a chi2 test. adjusted analyses were performed using logistic regression models, including variables known to be linked with the prognosis of septic shock (e.g., severity scores, delay of antibiotherapy). the relationship between the grade (i to iii) of lv diastolic dysfunction and 28-day survival were analyzed using a logistic regression model. the relationship between the presence of lv diastolic dysfunction and cumulated water balance on day 4 were analyzed using a linear regression model adjusted on the body weight on admission. the relationship between the grade of lv diastolic dysfunction and cumulated water balance on day 4 were analyzed using a linear regression model. diaphragm dysfunction and weaning induced pulmonary edema are two frequent causes of weaning failure but their coexistence and interaction have been poorly investigated. we hypothesized that diaphragm dysfunction may not induce a sufficient decrease in intra-thoracic pressure to increase venous return and generate a weaning induced pulmonary edema. we therefore investigated whether weaning induced pulmonary edema and diaphragm dysfunction are or not associated and evaluated the effect of diaphragm dysfunction on cardiac function and lung aeration during a spontaneous breathing trial (sbt). patients and methods: patients with readiness to wean criteria who had failed a first sbt were eligible. before and after a second sbt, diaphragm function was assessed by measuring the change in tracheal pressure induced by a bilateral phrenic nerve stimulation (ptr, stim), cardiac function (cardiac output, systolic pulmonary arterial pressure) was evaluated with echocardiography and lung aeration was estimated from the lung ultrasound score (lus). plasma protein concentration and hemoglobin were also sampled before and after the sbt. diaphragm dysfunction was defined by ptr, stim < − 7 cmh2o and weaning induced pulmonary edema was diagnosed in case of sbt failure associated with 1) increase in plasma protein concentration or hemoglobin > 5% during the spontaneous breathing trial and/or 2) early (e) over late peak diastolic velocity ratio > 0.95 or e over peak diastolic velocity ratio > 8.5. results: fifty-three patients were included and 31/53 (58%) failed the sbt. diaphragm dysfunction was present in 20/24 (83%) of patients with weaning induced pulmonary edema, in 11/22 (50%) patients with sbt success and in 2/7 (29%) patients with other causes of sbt failure (p < 0.01). during the sbt, diaphragm dysfunction induced a significant increase in systolic pulmonary arterial pressure but no change in cardiac output. patients with diaphragm dysfunction had a higher lus as compared to their counterparts (10 ± 9 vs. 3 ± 4, respectively, p < 0.01). conclusion: diaphragm dysfunction induces a loss of lung recruitment and a significant increase in systolic pulmonary arterial pressure during the sbt. coexistence of diaphragm dysfunction and weaning induced pulmonary edema is common in case of sbt failure but weaning induced pulmonary edema appears more likely to be involved than diaphragm dysfunction. compliance with ethics regulations: yes. rationale: diaphragmatic weakness in the intensive care unit (icu) is associated with poor outcome. prolonged mechanical ventilation is associated either with a decrease (atrophy) or an increase (supposed injury) in diaphragmatic thickness, both associated with prolonged weaning. shear wave elastography is a non-invasive technique that measures diaphragm shear modulus (sm), a surrogate of its mechanical properties. the aim of this study was to describe the diaphragm shear modulus during the icu stay and to describe its relation with diaphragm thickness. patients and methods: this prospective and monocentric study included all consecutive critically ill patients. ultrasound examination of the diaphragm (aixplorer; supersonic-imagine, aix-en-provence, france) was obtained by two investigatorsevery other day until icu discharge. demographics, diaphragm thickness, sm and outcomes were collected. a mixed model regression was used to study the relation between sm and diaphragm thickness. results: we enrolled 102 patients from 2017 december 1st to 2018 june 1st, 88 being invasively mechanically ventilated during the stay. diaphragm ultrasound evaluation was feasible in 94/102 (96%) patients. the duration of mechanical ventilation during the icu stay was 7 [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] days with 3 [1] [2] [3] [4] [5] days spent on controlled mechanical ventilation. sm was 14.3 ± 4.3 kpa and diaphragm end-expiratory thickness was 0.20 ± 0.05 cm upon icu admission. increase and decrease ≥ 10% during icu stay occured in 37 and 49 percent of the patients respectively for diaphragmatic thickness, and in 51 and 41 percent of the patients respectively for diaphragmatic sm. diaphragm thickness over time was inversely correlated with diaphragm sm and with time spent under mechanical ventilation (table) . diaphragm sm over time was correlated with time spent under pressure support ventilation or under spontaneous breathing (compared to controlled ventilation) and with time spent under deep sedation. diaphragm sm was inversely correlated with age, sepsis, exposition to steroids (table) . no association was found between diaphragm sm and outcomes. discussion: our results are in line with the myotrauma concept, suggesting alteration in diaphragm mechanical properties associated with increased diaphragm thickness in critically ill patients. we hypothesize that this observation most likely reflects muscle injury and tissue infiltration with edema and inflammatory cells. conclusion: shear wave ultrasound elastography suggests that in critically ill patients, the increase in diaphragmatic mass is associated with an alteration in diaphragm mechanical properties as measured by sm. compliance with ethics regulations: yes. rationale: diaphragm dysfunction and intensive care unit (icu) acquired weakness (icu-aw) are associated with poor outcomes in the icu but their long term impact on prognosis and health-related quality of life (hrqol) is poorly established. this study sought to determine whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and icu-aw has a particular impact on two-year survival and hrqol. patients and methods: we used a previous cohort study conducted in our institution to follow up mechanically ventilated patients in whom diaphragm and limb muscle functions were investigated at the time of liberation from mechanical ventilation. diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < 11 cmh2o and icu-acquired weakness was defined by medical research council (mrc) score < 48. hrqol was evaluated with the sf-36 questionnaire. results: sixty-nine of the 76 patients enrolled in the original study were included in the survival analysis and 40 were interviewed. overall two-year survival was 67% (46/69): 62% (28/45) in patients with diaphragm dysfunction, 71% (17/24) in patients without diaphragm dysfunction, 46% (11/24) in patients with icu-acquired weakness and 76% (34/45) in patients without icu-acquired weakness. patients with concomitant diaphragm dysfunction and icu-acquired weakness had a poorer outcome with a 2-year survival rate of 36% (5/14) compared to patients without diaphragm function and icu-acquired weakness (79% (11/14) (p < 0.01)). hrqol was not influenced by the presence of icu-acquired weakness, diaphragm dysfunction or their coexistence. conclusion: icu-acquired weakness but not diaphragm dysfunction has a strong negative impact on two-year survival of critically ill patients. the presence of diaphragm dysfunction appears more likely to be a determinant of early prognosis and does not appear to have a significant impact on long-term survival. compliance with ethics regulations: yes. rationale: influenza can lead to severe condition with acute respiratory failure and acute respiratory distress syndrome due to a massive pulmonary inflammatory in response to the viral invasion. lung bacteriobiota has been described to be associated with pulmonary inflammation in chronic respiratory diseases such as chronic obstructive pulmonary disease or cystic fibrosis. lung mycobiota has been poorly investigated despite the well-known role for fungi in numerous respiratory diseases. the aim of our study was to assess the prognostic value of lung bacteriobiota and mycobiota among critically ill influenza patients. patients and methods: we prospectively included influenza patients admitted to icu. sputum were stored a -80 °c. bacterial and fungal dna were extracted thanks to qiaamp ® powerfecal ® pro dna kit. 16s rrna gene v3-v4 regions and its2 regions were amplified by pcr and sequenced on illumina miseq ® . taxonomic assignation was obtained by dada2 pipeline and microbiota analysis were performed according to day-28 mortality by the mean of phyloseq package on r 3.6.0 software. results: thirty-nine patients were admitted to icu for influenza with 23 sputa available and finally 18 dna samples available after extraction. bacteriobiota alpha diversity was significantly lower among non-survivors than survivors when expressed by the mean of shannon index, simpson index or evenness (respectively p = 0.01, p = 0.02, p = 0.01). area under the curve to predict day-28 mortality was 0.91, 95ci [0.77; 1.00] for shannon index, 0.8995ci [0.74; 1.00] for simpson index and 0.91 95ci [0.77; 1.00] for evenness. β-diversity analysis also demonstrated significant differences between survivors and non-survivors (adjusted permutational multivariate anova, p = 0.01). nonsurvivors had a higher abundance of staphylococcus, haemophilus, streptococcus and moraxella. none of the fungal alpha-diversity index nor beta-diversity were significantively different between survivors and non-survivors. non-survivors had a higher proportion of candida albicans and malassezia but not of aspergillus. conclusion: the lung bacteriobiota profile, but not the mycobiota one, of critically ill influenza patients is associated with day-28 mortality and may be used to identify subjects with a poor prognosis at the time of admission. compliance with ethics regulations: yes. that takes into account the interaction between multiple cellular pathways. the pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. results: 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. severe influenza was associated with upregulation in several neutrophilrelated pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (net) formation. the degree of upregulation in neutrophil-related pathways was significantly higher in severely infected patients compared to moderately infected patients. severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation, cd4+ t-cell co-stimulation, cd8+ t cell and natural killer (nk) cells effector functions. apoptosis pathways were also downregulated in severe influenza patients compared to moderate and healthy controls. conclusion: these findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection. compliance with ethics regulations: yes. rationale: herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ards). however, few is known about herpes simplex virus (hsv) and cytomegalovirus (cmv) reactivation occurring in patients with severe ards under venovenous extracorporeal membrane oxygenation (ecmo). we tried to determine the frequency of herpesviridae reactivation and its impact on patients'prognosis during ecmo for severe ards. patients and methods: we conducted an observational, retrospective study in a medical icu (ards and ecmo referee center) between 2011 and 2017. patients with a severe ards requiring a venovenous ecmo for 2 days or more were included. hsv and/or cmv reactivation occurring after ecmo insertion was screened for these patients. patients with immunosuppression, antiviral therapy against hsv and/ or cmv prior to inclusion, or hsv/cmv reactivation known at the time of ecmo insertion were excluded. hsv reactivation was defined by a positive qualitative throat sample (virocult ® ) pcr or positive bronchoalveolar lavage (bal) pcr. cmv reactivation was defined by a positive quantitative blood or bal pcr. results: during a five-year period, 123 non-immunocompromised patients with a severe ards necessitating a veno-venous ecmo were included. sixty-seven (54%) experienced hsv and/or cmv reactivation during ecmo course (20 viral co-infection, 40 hsv alone and 7 cmv alone). hsv reactivation occurred earlier than cmv after the beginning of mv (10 (6-15) vs. 19 (13-29) days; p < 0.01) and after ecmo implementation (4 (2-8) vs. 14 (10-20) days; p < 0.01). in univariate analysis, hsv/cmv reactivation was associated with a longer duration of mechanical ventilation (34 (22-52.5) vs. 17.5 (9-28) days; p < 0.01), a longer duration of .5) vs. 9 (5-14) days;p < 0.01), and a prolonged vs. 16 (9-30) days; p < 0.01) and hospital stay (44 (29-63.5) vs. 24 (11-43) days; p < 0.01). however, in multivariate analysis, viral reactivation remained associated with prolonged mv only. when comparing patients having cmv (alone or combined with hsv) vs. hsv reactivation alone, cmv positive patients had a longer mechanical ventilation duration and fewer ventilator-free days at day-28 and a longer icu and hospital length of stay. conclusion: herpesviridae reactivation is frequent among patients with sevre ards under veno-venous ecmo and is associated with a longer duration of mechanical ventilation. cmv seems to have a proper negative role on pulmonary fiunction as compared to hsv alone. hsv and cmv deserve to be researched in severe ards patients under ecmo. compliance with ethics regulations: yes. charlotte vandueren 1 , benjamin zuber 2 , eve garrigues 3 , antoine gros 4 , nicolas epaillard 5 , guillaume voiriot 6 , yacine tandjaoui rationale: respiratory syncytial virus (rsv) is a common cause of pediatric bronchiolitis and influenza-like illness in adults. its involvement in severe infections in adults remains unclear. the captif study aimed at comparing characteristics and prognosis of icu patients infected with rsv and influenza, assuming that, based on the limited evidence, the mortality of rsv infection would be lower than the influenza related one. patients and methods: multicenter franco-belgian retrospective study. adults admitted to 18 icus between 1/nov/2011 and 30/ apr/2017 with respiratory rsv infection were included and matched 1:1 to influenza patients on center and icu admission date. patients' characteristics, clinical presentation, and outcome were compared between groups using univariate and multivariable analyses. results: we report here the results for the first 470 cases among 650 included patients. mean age was 65.5 (16.7) years and saps-2 score was 42 (17), not different between groups. compared to influenza patients, rsv patients more frequently had chronic respiratory failure (61% vs 39%, p < 0.001) or immune suppression (36 vs 26%, p = 0.03). frequencies of cardiac, renal and hepatic chronic diseases were similar. almost all patients had respiratory symptoms (> 95%), extrarespiratory symptoms were more frequent in influenza patients (9 vs 15%, = 0.04). rsv patients more frequently had bronchospasm (51 vs 36%, p = 0.001). clinical presentation such as ards (20%), shock (30%) and pulmonary coinfection (32%) were similar, however sofa score was higher in rsv patients (4.6 (3.4) vs 5.6 (4), p = 0.004). the p/f ratio was around 210 mmhg in both groups, paco 2 was higher in rsv patients (55 vs 47 mmhg, < 0.001). respiratory assistance at diagnosis tended to differ (p = 0.06), rsv patients receiving more non invasive ventilation (29 vs 19%) and less high flow oxygen therapy (10 vs 14%) but invasive ventilation was required similarly (36 vs 33%). during icu stay, ards was more frequent in rsv patients (21 vs 30%, p = 0.03), accordingly prone position (1.3 vs 4.3%) and ecmo (2.5 vs 9.1%) were more frequently needed. length of mechanical ventilation (2 days (0-8) ) and icu los (5 days (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) ) were not different. icu mortality was similar in rsv and influenza patients (18.4% and 21.3%), the multivariate analysis did not find an association between type of virus and mortality. conclusion: rsv infection is frequent in adult icu patients. it presents more frequently than influenza as an acute on chronic respiratory failure with bronchospasm. despite difference in case mix and clinical presentation, vrs severity and burden appear similar to influenza justifying effort to prevent and treat it. compliance with ethics regulations: yes. rationale: mortality in acute stroke patients requiring mechanical ventilation ranges from 60 to 90% at 1 year. studies evaluating indicators of outcome in these patients have limitations, including singlecenter, retrospective designs and no adjustment for withholding/ withdrawal of life-sustaining treatments (wlst). our objective was to identify factors associated with 1-year survival in acute stroke patients requiring mechanical ventilation. patients and methods: retrospective analysis of a prospective multicenter database between 1997 and 2016. icu stroke patients entered in the database and requiring mechanical ventilation within 24 h were included. were excluded patients with stroke of traumatic origin, subdural hematoma or venous cerebral thrombosis. factors associated with 1-year survival were identified using a cox model stratified on inclusion center, adjusted on wflst occurring during the first 48 h. data are presented as median [q1-q3] or percentages. cox model results are presented as hazard ratios (hr) and 95% confidence intervals (ci). results: we identified 419 patients from 14 icus, aged 68 [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] years and 60% males. on admission, the glasgow coma score (gcs) was 4 [3] [4] [5] [6] [7] [8] and the saps 2 score was 58 . types of strokes were ischemic (46%), hemorrhagic (42%) and subarachnoid hemorrhage (sah) (12%). ischemic stroke patients received thrombolysis or thromboaspiration in 35/191 (18%) cases, and hemorrhagic stroke/ sah patients received neurosurgery or embolization in 35/228 (15%) cases. reasons for endotracheal intubation were coma (72%), acute respiratory failure (12%), seizures (8%), cardiac arrest (5%) and elective procedure (3%). sixty-five (16%) patients received a decision of wflst in the first 48 h. one-year survival year was 23%. variables independently associated with 1-year survival were stroke type (ischemic as reference, hemorrhagic hr 0. (fig. 1) . inclusion period (1996 inclusion period ( -2002 inclusion period ( /2003 inclusion period ( -2009 inclusion period ( /2010 inclusion period ( -2016 or having a stroke unit on site was not associated with 1-year survival. conclusion: in acute stroke patients requiring mechanical ventilation, the reason for intubation and the opportunity to receive a specific stroke therapy are independently associated with long-term survival. these variables should be integrated in the decision process regarding initiation of mv in acute stroke patients. compliance with ethics regulations: yes. rationale: international guidelines recommend targeted temperature management (ttm) between 32° and 36 °c for out-of-hospital cardiac arrest (ca) patients. however, it is unknown if this treatment is effective whatever the severity of the insult. we aimed to examine the association between ttm and long-term neurological outcome according to the risk evaluated at time of admission in intensive care unit (icu) using a dedicated and validated score. patients and methods: we used data prospectively collected in the sudden death expert center (sdec) registry (great paris area, france) between may 2011 and december 2017 and in the resuscitation outcome consortium-continuous chest compression (roc-ccc) between june 2011 and may 2015. we used a modified version of the cardiac arrest hospital prognosis (mcahp) score to assess the risk of poor outcome at icu admission in each of 2 datasets. we finally studied the association between ttm use and long-term neurological prognosis according to mcahp score at icu admission divided into tertiles of severity in each of the 2 datasets. results: there were 2723 patients analyzed in the french dataset and 4202 in the north-american dataset. the mcahp identified 3 categories: low risk (score < 80 points, 40% of unfavourable outcome), medium risk (80 ≤ score < 105, 80% of unfavourable outcome) and high-risk group (score > 105, 95% of unfavourable outcome). according to the mcahp score at icu admission, ttm was associated with a better long-term neurological prognosis in patients with low risk (aor = 1.62 [1.15-2.30 rationale: acute ischaemic stroke is associated with a high risk of mortality, morbidity and healthcare-related costs. over the last decades new treatments, such as thrombolysis and thrombectomy, have been introduced. because of their further improvement, complications have been decreasing. this also led to extending indications for treatment to patients who were previously not eligible. the impact of this evolution on long-term outcome and cost-effectiveness has mainly been assessed in clinical trials and simulation studies. patients and methods: this single-centre retrospective study included 564 patients treated for stroke between january 2017 and february 2019. functional outcome at 90 days was assessed by the modified rankin scale (mrs). cost data were retrieved from individual invoices of 538 patients. undiscounted total healthcare costs were calculated for the index hospital stay, capped at 90 days. contribution of 6 cost categories to total costs was analysed. mrs at 90 days was used as a proxy for utilities to define quality-adjusted life years (qalys). multivariate analysis was done for gender, age, charlson comorbidity index, pre-stroke mrs, stroke severity (nihss) and treatment modality (thrombectomy, thrombolysis, thrombectomy + thrombolysis, no intervention). incremental cost-effectiveness ratios (icers), associated to each treatment modality, were calculated. results: no intervention was done in 328 patients (61.0%). 93 patients (17.3%) required thrombolysis, 64 (11.9%) thrombectomy and 53 (9.9%) the combination. total costs were mean 15,787 eur 177) . hospitalisation costs (mean 11,275 eur, iqr 2066-12,428) represented 71% of total costs, compared with drug costs (341 eur, iqr 118-330), procedural costs (3283 eur, iqr 652-2981), honoraria (290 eur, iqr 111-395), lab (123 eur, iqr 22-116) and imaging (475 eur, iqr 334-539). mean total costs differed between treatment modalities: 12,553 (iqr 3080-12,947) eur for no intervention, 11,820 197) eur for thrombolysis, 26, 103 (iqr 12, 893) eur for thrombectomy and 30,301 (iqr 12, 488 ) eur for the combination (p < 0.0001). drivers for total costs were treatment modality (p < 0.017) and nihss-stroke severity (p < 0.0001). utility scores were 0.65 rationale: emergency endotracheal intubation (eti) in the intensive care unit (icu) often concerns hypoxemic patients with hemodynamic instability. a cardiovascular collapse (cvc) after eti is a life-threatening complication. 2018 french guidelines suggested systematic fluid loading prior to eti. our study aimed to predict cvc after eti, while using echocardiography, and to evaluate the impact of fluid loading. patients and methods: a prospective study of 70 consecutive intubations was performed from june 2017 to november 2018 in three icus. patients were selected if mean blood pressure measurements ≥ 60 mmhg before eti. cvc was defined as mean blood pressure < 60 mmhg within 15 min following eti. four echocardiographic examinations were performed: 1-30 min before and 2-30 min after eti (or when a cvc occurred); 3-after passive leg raising; 4-3 h following eti. patients were classified as fluid responders when the left ventricular outflow tract velocity-time integral increased by at least 10% compared with baseline. results: 269 echocardiographic examinations were performed. cvc occurred in 32/70 procedures (46%). in cvc group, mean dose of diprivan, used for fast sequence induction, was higher (2.8 ± 1 mg/kg vs 1.3 ± 0.7 mg/kg, p = 0.02). in the cvc group, fluid responsiveness was considered in 44% patients and left ventricular (lv) systolic dysfunction 13%. lv diastolic dysfunction did not concern any patient in the cvc group. systolic blood pressure (sbp) < 120 mmhg was the sole independent risk factor for cvc occurrence in multivariate analysis: or 5.9 ci 95% 1.7-21.2, p = 0.02. fluid responsiveness independent risk factors for cvc patients was sbp < 120 mmhg (or 8.7, ci 95% 1. rationale: the autonomic nervous system is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of autonomic nervous system activity and a relation between hrv and outcome has been proposed in various types of patients. we attempted to evaluate the best determinants of such variation in survival prediction using a physiological data-warehousing program (reastoc clinicaltrials identifier nct 02893462). patients and methods: physiological tracings were recorded at 125 hz from the standard monitoring system (intelliview philips mp70) using the synapse software (ltsi inserm umr 1099), for a 2 h period, during the 24 h following icu admission. all measurements were recorded while patients were laying in bed, with the head at 30° and without any medical intervention. physiological data were associated with metadata collection by a dedicated research assistant. hrv was derived using kubios hrv, in either temporal ( (sdnn), (rmssd) and triangular index (ti)), frequency ( (lf), (hf)), non-linear domains (poincaré plotting) and entropy. results: 540 consecutive patients were recorded between may 2014 and april 2019. a lower lf/hf (< 0.9) and sd2/sd1 (< 1.3) ratios on admission were associated with a higher icu mortality. multivariate analysis enabled to develop a mortality predictive model (bicus) associating spo2/fio2 and hrv parameters (lf/hf and shannon entropy) with an auc = 0.73 (p < 0.0001) for a bicus value > 1 (fig. 1) . conclusion: hrv measured on admission enables to predict prognosis in the icu, independently of the admission diagnosis, treatment and mv requirements. bicus may help predict prognosis on a real time basis, using parameters derived from standard routine monitoring. compliance with ethics regulations: yes. rationale: stroke, in the context of type 2 diabetes (t2d) is associated with a worse outcome than in non-diabetic conditions, reflected by an increased ischemic volume and more intracerebral hemorrhage. an unbalanced diet is one of major risk for developing t2d. we aimed at creating a reproducible mouse model of stroke in impaired glucose tolerance condition induced by high fat diet. patients and methods: adult c57bl6mice (28 male and 28 female) were fed for 2 months with either high fat diet (hfd, 43% lipids, 21% proteins, 35% carbohydrates) or a normal diet (nd, 8.4% lipids, 19.3% proteins, 72.4% carbohydrates) . we used a model of middle cerebral artery occlusion (mcao) by a monofilament for 90 min. oral glucose tolerance test and insulin tolerance test were used for evaluating the pre-diabetic state. mice were euthanized 20 h after reperfusion. systemic inflammation, cerebral infarct volume and hemorrhagic transformation were determined. results: hfd was associated with an increased glycaemia following the oral glucose tolerance test. plasma leptinlevels in stroke conditions were significantly higher in hfd vs nd group. the hfd group presented a significant increase of infarct volume (hfd: 51.86 ± 4.46 mm 3 vs nd: 33.23 ± 4.29 mm 3 p = 0.016) and hemorrhagic transformation (hfd: 2.67 ± 0.66 vs nd: 0.73 ± 0.28 p = 0.012) (fig. 1 ) compared to nd group. discussion: in humans, one of the mechanisms leading to insulin resistance is low-grade inflammation. hfd increases gut permeability, which leads microbiota dysbiosis, thereby promoting metabolic endotoxaemia and a low-grade inflammation state. experimental mouse models available for diabetes studies use leptin receptor deficient mice which develop t2d or destruction of pancreatic beta cells by streptozotocine injection (t1d). studies using diet-induced insulin resistance models generally feed the mice for 12 weeks or more. however, metabolic disorders could appear earlier such as increase inflammatory markers. in our model, a short exposition to hfd (8 weeks) leads to an increase of the pro-inflammatory markers as plasma leptin and a more severe stroke status (infarct and hemorrhagic transformation). conclusion: two months of hfd in adult mice altered hyperglycemia control. this metabolic disorder was associated with significantly higher leptin production, increased infarct volume and hemorrhagic complications than in normal-fed mice. this new model is particularly relevant to study stroke under pre-diabetic conditions induced by hfd. compliance with ethics regulations: yes. eight weeks of hfd increase ischemic volume and hemorrhagic transformation. (a)-infarct volume (v) 24 h after reperfusion, all value are mean ± sem, hfd: v = 51.66 ± 4.46 mm 3 , n = 14, nd: v = 33.23 ± 4.26 mm 3 , n = 7, *p = 0.016 (b)-hemorrhage transformation (ht) score 24 h after mcao. all value are mean ± sem hfd: ht score = 2.67 ± 0.66, n = 15, nd: ht score = 0.73 +/+ 0.28, n = 15 *p = 0.012 rationale: cardiac arrest (ca), as massive ischemia reperfusion (ir), is an universal health issue. medication taken at the time of the ca could have prognosis consequences. no medication has proven its benefit on ca prognosis. pharmacological pre-or postconditioning aims to reduce ir injury but with disappointing results. metformin (met) is a worldwide-prescribed antidiabetic drug, and several clinical reports plead for a potential protective effect in various settings of sterile and non sterile inflammation, including ir. our hypothesis is that met act as a preconditioning drug against ca-induced ir. patients and methods: retrospective single academic medical center survival study (french west indies) on resuscitated ca in icu (institutional ethical committee approval). data were extracted from medical charts, pmsi, and laboratory dbsynergy ™ software. anonymized data were entered on a excel ™ and transferred to ibm ® -spss ® software (v 24.0.0.0) for analysis. univariate study (chi-2, fisher exact tests, student-t test, mann-whitney u-test if required) was followed by a multivariate model (odd ratio or and 95% ic: kaplan-meier estimator and non parametric logrank test-mantel cox model). assuming an overall in-hospital mortality for ca in icu of 80% with an expected mortality decrease of 15% by met, the number of patients to be included is 510. results: the inclusion period was 2012 to 2018, with 555 included patients (202 diabetic patients among whom 62 took met). the d28 mortality was 67% in met+ patients (n = 62) versus 82% in nomet patients (n = 493), p < 0.01. comparing alive (n = 115) versus deceased (n = 440) at d28 in univariate then multivariate analysis, asystole on the first ekg, number of iterative cardiac arrest,sofa, no-flow, lactate, low-flow and sapsii appear as independent criteria associated with d28mortality.conversely, met intake showed up as a protective criterion (or 0.477, ci95 0.237-0.957). the survival curve, including strata of low-flow duration at the cut-off 20 min, is reported on the fig. 1 . among diabetic patients (n = 202), the mortality of patients in the met+ (n = 62) was 67% versus 80% in the nomet (n = 140), p = 0.04. conclusion: in diabetic patients suffering of massive ir related to resuscitated ca, a current treatment by met is associated with a better survival. these results support a protective effect of met and are important to initiate prospective evaluations, because of millions diabetic people around the world and the potential benefit of met. the potential benefit in non diabetic patients and in sterile as well as non sterile inflammation should be addressed. compliance with ethics regulations: yes. rationale: during systemic inflammation, the accumulation of misfolded proteins in the endoplasmic reticulum (er) induces er stress (ers). in animal models, the inhibition of ers reduces inflammatory response and organ failure. cardiopulmonary bypass (cpb) induces a significant systemic inflammatory response but ers expression has never been described in cardiac surgery patients. our objective was to describe the variations of the glucose related protein of 78 kda (grp78), the final effector of the ers, during cpb. patients and methods: we conducted a prospective monocenter study including patients undergoing cardiac surgery with cpb. two samples (paxgene ® tube + edta tube) were taken at three times: before cpb, 2 h after the end of cpb (h2-cpb) and 24 h after (h24-cpb). after rna isolation and reverse transcription, we performed a quantitative polymerase chain reaction to evaluate the expression of gene encoding for grp78 and determined the plasma level of grp78 using enzyme-linked immunosorbent assay. our main objective was to study the variation of grp78 between pre-cpb and h2-cpb samples. our secondary objectives were to evaluate the association of ers with morbi-mortality: organ failure at 24 h (catecholamines and/or invasive ventilation and/or acute renal failure), troponinemia and pao2/fio2 ratio (lung damage control). fig. 1 ). we found an inverse correlation between grp78 plasma level and troponinemia at h2 (r = − 0.31; 95% ci[− 0.56; − 0.10]; p = 0.037) and a correlation between the pao2/fio2 ratio and grp78 plasma level at h2 (r = 0.37; 95% ci[0.10; 0.59]; p = 0.0064). we showed a significant relationship between the variation in plasma concentration of grp78 and post-operative organ failure after cpb. further studies are needed to better understand the molecular mechanisms of ers in acute inflammatory organ failure in humans. compliance with ethics regulations: yes. patients and methods: in a retrospective monocentric study (01/2013-01/2017) conducted in cardio-vascular surgical intensive care unit (icu) in henri mondor teaching hospital, all consecutive adult patients who underwent peripheral va-ecmo were included, with exclusion of those dying in the first 24 h. diagnosis of acute mesenteric ischemia was performed using digestive endoscopy, abdominal ct-scan or fist-line laparotomy. significative results in the univariate analysis were analyzed in a multivariate analysis using logistic regression. results: 150 va-ecmo were implanted. median age was 58 (48-69) years and median . va-ecmo was implanted after a cardiotomy in 43% of the cases and for a medical reason in 57% of the cases including 26% of refractory cardiac arrest. patients characteristics are reported in the table. acute mesenteric ischemia was suspected in 38 patients, with a delay of 4 (2-7) days after ecmo implantation. digestive endoscopy was performed in 33 patients, ctscan in five patients and first-line laparotomy in three patients. acute mesenteric ischemia was confirmed in 14 patients, i.e. an incidence of 9%. laparotomy was performed in six of the 14 patients, two having a stage i colitis ischemitis with stable conditions and 6 being considered too severe to undergo futile surgery. overall mortality was 56%. all the patients with acute mesenteric ischemia died in the icu. independent risk factors of developing acute mesenteric ischemia were renal replacement therapy , p = 0.02)) and onset of a second shock state within the first 5 days of icu stay (or 7.8 (95% ic 1.5-41.3, p = 0.02)). conversely, early enteral nutrition was negatively associated with acute mesenteric ischemia (or 0.15 (95% ic 0.03-0.69), p 0.02). conclusion: acute mesenteric ischemia is a relatively frequent condition among patients under va-ecmo for cardiogenic shock. its extremely poor prognosis requires low threshold of suspicion. compliance with ethics regulations: yes. (1). it allows the computation of trans-pulmonary pressure (2) and can be used to set positive end-expiratory pressure (peep) (3.4) . prone position(pp) can reduce mortality in patients with acute respiratory distress syndrome (ards), but peep selection in pp is controversial. in human ards end-expiratory pes at zero flow (peept,es) was not different between supine (sp) and pp at same peep (5). as no study measured ppl in sp and pp in ards we aimed at comparing peept,es and end-expiratory ppl at zero flow (peept,ppl) in this condition. our hypothesis was that peept,es was close to dorsal peept,ppl (peept,ppldorsal) in sp and to ventral peept,ppl (peept,pplventral) in pp. in eight female pigs of 40 kgs intubated, sedated, paralyzed and mechanically ventilated, ards was induced by repeated saline lavage until pao2/fio2 < 100 mmhg under fio2 1 and peep 5cmh2o. pes was measured by nutrivent catheter. ppl was measured by custom-made pouch sensors inserted surgically into the right anterior and posterior sixth intercostal space. ppl sensors were filled with air. after ards induction animals were randomly assigned to sp or pp. in each position, a recruitment manoeuver was performed and peep decreased from 20 to 5 cmh2o by steps of 5cmh2o lasting 10 min each, then the animals were crossed over into the alternate position where the same procedure was done. at the end of each step nonstressed volume and correct position (baydur maneuver) were determined for pes and ppl sensors, then a 3-s end-expiratory occlusion was performed and pes and ppl recorded. linear mixed model was used to compare the value of pes and ppl at each peep and position. results: box-and-whisker plots of pes and ppl in sp and pp are shown in fig. 1 . there is marked dorsal-to-ventral gradient in ppl at each peep in sp, which is reverted in pp at peep 10 and 15 only. there was no interaction between pressures and peep or position. with increasing peep pes increased significantly from peep 5 in sp and pp. peept,pplventral was significantly lower than peept,es in sp but not in pp. (medtronic) , carescape 860 (ge)) were set in pressure support 0 cmh2o, peep 4 cmh2o, fio2 21% and equipped with the same double limb ventilator circuit (intersurgical) without any humidification device. asl 5000 bench model was set with 3 inspiratory/expiratory resistance (r) and compliance (c) combinations: r13/12-c54, r12/14-c39 and r22/18-c59 mimicking normal, ards and copd conditions, respectively (1) . inspiratory effort generated by asl 5000 consisted of 30 consecutive breaths obtained from the esophageal pressure in a real patient at the time of a spontaneous breathing trial. for each icu ventilator and rc combination, two steps were performed: in the first, atc was not activated and ventilator attached to asl 5000 without ett (atc-ett-); in the second, atc was set on at 100% compensation for an ett 8 mm id and such an ett (shiley hi contour, covidien) joined icu ventilator to asl 5000 (atc+ ett+). the null hypothesis is that vtatc+ ett+ minus vtatc-ett-is 0. primary end point was the breath by breath paired difference betwen atc+ ett+ and atc-ett-. it was tested to zero for each ventilator in each rc condition. results: median vt was 213 ml. table 1 displays mean (± sd) difference in vt (ml) between atc+ ett+ and atc-ett-: a negative value means that atc under delivers and a positive value that atc over delivers vt for a given patient's inspiratory effort and rc. in four ventilators (c6, s1, elisa 800 and 980) atc almost systematically under delivered vt. in several instances under compensation was greater than 10% median vt. by contrast atc performed better with the other three ventilators (evita xl, v500 and carescape 860). conclusion: atc tended to under deliver vt. furthermore, there were marked differences between icu ventilators the clinician should be aware of when using the atc option. compliance with ethics regulations: na. rationale: during the last decades, identification of factors associated with ventilation-induced lung injury has led to improved survival in patients with ards. the mechanical power of ventilation is the total energy transmitted from the ventilator to the respiratory system per unit of time and comprises three different components: elastic related to peep, elastic related to tidal volume and resistive. this integrative variable has been recently proposed as an useful predictor of ventilationinduced lung injury and death among ventilated patients. our goal was to determine the respective impact of the total mechanical power and its three components on the outcome of patients with ards. patients and methods: we performed a post hoc analysis of a randomized, controlled study of patients with ards with a pao2/fio2 ratio < 150. themechanical power at inclusion and averaged on the first 2 days after inclusion (total and its three different components) was computed according to the following equation: powerrs (j/ min) = 0.098 respiratory rate tidal volume [peep (1) + ½ driving pressure (2) + (peak pressure-plateau pressure) (3)], where the (1), (2) and (3) parts correspond respectively to the elastic related to peep, elastic related to tidal volume and resistive components. the association between each of these four types of mechanical power evaluated during the first 2 days after inclusion and mortality at d90 was assessed one after the other through multiple logistic regression, allowing control for potential confounding variables at inclusion (age, igs score without age, group of randomization, pao2/fio2, arterial ph). results: data from 339 patients were analyzed, among which 115 (33.9%) died before d90. there was no difference concerning the mechanical power at inclusion between survivors and non survivors (either total or its three components). among the four different types of mechanical power tested during the first 2 days after inclusion, the elastic component related to tidal volume was the only one that was independently associated with mortality at d90 (or 1.030; 95% ci 1.003-1.058; p = 0.03) (figure) . conclusion: our study shows that only the elastic component of the mechanical power related to tidal volume independently predicted mortality at d90 among patients with ards, whereas the total mechanical power, its elastic component related to peep and its resistive component did not. further studies are needed to better define how the mechanical power of ventilation could be useful to synthetize the risk of ventilation-induced lung injury. compliance with ethics regulations: yes. probability of death at d90 as a factor of mean value (on d1-d2) of the elastic component related to tidal volume of the mechanical power. to examine the effect of early-stage mechanical ventilation (mv) on diaphragmatic contractility. in the 2nd step, if a diaphragmatic dysfunction was detected, we assessed its influence on the weaning from ventilator. patients and methods: we measured prospectively the ultrasounddiaphragmatic thickening fraction (dtf) between 2 groups: a study group versus a control group (n = 30 for each). the study group included all adult patients receiving mv, in whom, the dtf was measured within a minimum of 48 h and a maximum of 5 days of mv. for the control group, were enrolled after their approval for participation, adult volunteers in spontaneous ventilation (sv). patients with factors affecting the diaphragmatic contractility (neuromuscular disease, severe obesity, and neuromuscular blockers…) were excluded. the ultrasound measurements were obtained at the zone of apposition of the right hemithorax. teleinspiratory and telexpiratory diameters (tid/ ted) were taken on the 3 medio-axillary lines: posterior, median and anterior. the dtf was calculated as following: dtf = (tid-ted/ted) x 100. at the 1st step, the dtfs were compared and at the 2nd step: the relationship between dtf and weaning was analysed. results: our 2 groups were comparable in corpulence and co morbidities. the sv group was younger (35 vs. 47 years, p < 0.05) with a predominant female composition. the diaphragmatic exploration concluded that in the mv group, the mean tid tended to be higher but without significant difference (29.1 + 7 versus 26.1 + 5 mm, p = 0.09), the mean ted was significantly higher (20.9 + 6 versus 17.6 + 3.2 mm, p = 0.01) and dtf was significantly lower (39.9 + 12.5% versus 49 + 20.5%, p = 0.043). the ventilation mode had no effect on dtf (40.2 + 13% for control volume vs. 38.6 + 9% for psv mode, p = 0.8). fourteen among 30 ventilated patients had a successful weaning with a mean duration of 6 days. a negative correlation was found close to significance between dtf and weaning duration (rho = − 0.464 and p = 0.08). a dtf value > 33% wasassociated with weaning success (or = 2, 95% ci = [1.07-3.7] and p = 0.058) with sensitivity = 85.7%, specificity = 50%, ppv = 60% and npv = 80%. conclusion: the diaphragmatic contractile function was altered from the first days of mv. weaning duration seemed to be negatively correlated with dtf, and a dtf at the first 5 days of mv greater than 33% was predictive of weaning success. compliance with ethics regulations: yes. rationale: mechanical ventilation is a life-saving treatment that is however associated with lung injury and/or diaphragm dysfunction. the optimal ventilator settings to provide lung protective ventilation while maintaining safe diaphragm activity are difficult to determine. a noninvasive and bedside evaluation of the diaphragm activity could be helpful in this context. the present study investigated whether changes in diaphragm shear modulus (i.e. stiffness, δsmdi) assessed by ultrasound shear wave elastography (swe) may be used as a surrogate of changes in transdiaphragmatic pressure (δpdi) in mechanically ventilated patients. patients and methods: patients had to be ventilated for at least 24 h without contraindications for the placement of an oeso-gastric catheter. pdi was monitored continuously and smdi was measured at the zone of apposition of the right hemi-diaphragm, at 2 hz sampling rate. measurements were performed twice under initial ventilator settings and at the end of a weaning trial. pearson correlation coefficients (r) were computed to determine within-individual correlations between pdi and smdi and changes in pdi and in smdi occurring between initial ventilator settings and the end of the sbt were compared by a paired test. results: twenty-five patients were enrolled and 8 displayed a significant correlation between δsmdi and δpdi (mean r = 0.73, range = 0.62-0.88, all p < 0.05) (fig. 1a ). compared to their counterparts, patients with significant within correlations had a lower respiratory rate (16.8 ± 4.7 vs 23.9 ± 6.2breath/min. respectively; p < 0.01) and a significant increase in δsmdi (7.3 ± 5.5 kpa vs 13.4 ± 9.0 kpa. p < 0.01) between initial ventilator settings and the sbt. patients without δsmdi-δpdi correlation only displayed an increase in δpdi (7.9 ± 5.9 vs 14.9 ± 7.9 cmh 2 o, p < 0.01) at the end of the sbt with no concomitant significant increase in δsmdi (7.6 ± 3.8 kpa vs 7.9 ± 5.3 kpa, p > 0.05). (fig. 1b) . conclusion: smdi obtained by swe appears as a promising technique to assess diaphragm activity in mechanically ventilated patients but technological improvements are necessary to increase swe sampling rate before enabling its generalization in the icu. compliance with ethics regulations: yes. rationale: end-inspiratory (eip) and end-expiratory (eep) pauses are commonly used during volume assist control ventilation to assess plateau pressure and total positive end-expiratory pressure (peeptot). they can also be used during assisted ventilation (av) for muscle pressure assessment. it requires ventilators able to perform eip during av. plateau pressure (pplat) usually increases in av during eip due to "hidden" inspiratory effort. pressure muscular index (pmi) is equal to pplat minus the sum of peeptot (measured during an eep) and set pressure support (ps); it theoretically reflects patient's effort without esophageal pressure (pes) monitoring. pes is the gold standard method to assess inspiratory muscle pressure (pmus, difference of pes drop at neural end-inspiration and correction factor for chest wall elastance and tidal volume). we aimed to illustrate the feasibility of measuring pmi using a standard icu ventilator at the bedside and study the correlation between pmus and pmi. patients and methods: measurements were recorded in 4 icu patients. pes was measured using an nasogastric probe (equipped with an esophageal balloon) inserted for advanced monitoring (severe acute respiratory distress syndrome-ards) or for a study protocol (difficult weaning after copd exacerbation). recorded eip, eep and pes were used for post hoc analyses. results reported as ranges and median [iqr] . correlation between pmus and pmi tested with spearman correlation test. results: 25 out of 28 eip and eep duos could be analyzed (2-esophageal spasm/1-calibration error). ventilator mode was pressure support ventilation (ps 0-12 cmh2o). cmh2o, pmus = 3.5 [1.7-9 .5] cmh2o, pmi = 4.5 [2.4-7.8 ]. for all recordings, spearman r coefficient between pmus and pmi was 0.438 (p = 0.028). conclusion: muscular effort can be assessed in av using eip and eep using icu ventilators. however, recordings can be influenced by expiratory muscles contraction. patient's ability to follow directions during the maneuvers is an important factor to obtain reliable values. there seem to be a correlation in our small sample between muscular pressure assessed without and with pes. compliance with ethics regulations: yes. rationale: severe pneumonia can culminate in acute respiratory distress syndrome (ards). an uncontrolled inflammatory response is a key feature favoring transition towards ards. however, the underlying mechanisms remain poorly understood. in this context, the contribution of "innate t cells" (itc) -a family of non-peptide reactive t cells comprising nkt cells, mucosal associated invariant t (mait) cells and γδt cells-has never been explored. itc have emerged as key players in orchestration of the host response during infections and inflammation processes. for these reasons, these cells are already seen as potential therapeutic targets in other medical fields (especially oncology). here, we hypothesized that a tight regulation of their functions could be paramount to control the inflammatory response and to prevent ards development. patients and methods: to explore this, we combined a murinemodel of influenza a virus (iav) infection mimicking ardssymptoms and a clinical study recruiting patients admitted in icu for severe pneumonia. using flow-cytometry approaches, we investigated (1) the abundance and dynamics of itc in various compartments, (2) their pattern of activation/regulation markers (respectively cd69 and pd-1) and (3) their cytokine production. results: during experimental iav pneumonia, itc were transiently recruited into the airways. unlike γδt and nkt, mait cells phenotype was largely changed, displaying a progressive cd69 overexpression and increased il-17a production. during the resolution phase, up to 90% of pulmonary maits expressed pd-1 (versus < 10% in controls), which can suggest emergence of regulatory functions. last, using gene-targeted mice, we suggested that mait cells confer a protective effect during pneumonia. in the ongoing clinical study, the proportion of circulating mait cells in patients was markedly decreased compared to controls (1.0 ± 1.0% versus 5.7 ± 2.8% of t cells), but not for nkt or γδt cells. notably, some patients with severe ards presented detectable levels of maits in their respiratory fluids. in addition, circulating mait cells in patients overexpressed cd69 and pd-1 (56.5% and 55% respectively), but with a reduced proportion able to produce il-17 and ifnγ, compared to healthy controls. lastly, proportion of activated (cd69 +) mait cells significantly decreased with clinical improvement. conclusion: this translational approach combining in vivo animal experiments and clinical samples with ex vivo experiments indicates a preferential modulation in mait cells functions during severe pneumonia. these data justify an in-depth analysis of mait cells activation mechanisms and functions in this context, in order to further explore a potential use as a disease-progression marker and -in a long term perspective-as a potential therapeutic target. compliance with ethics regulations: yes. representative flow-cytometry dot-plots of mait cells labelling using fluorophore-conjugated mr1 tetramers loaded with 5-op-ru from lungs of an infected mouse (a) and blood sample of a patient with pneumonia (b). c: frequency of mait cells, proportion of cd69 and pd-1 + mait cells in bronchoalveolar lavage during experimental murine pneumonia. d: blood frequency of mait cells in patients with pneumonia compared with healthy controls (as % of total t cells) rationale: immune paralysis following hyperinflammatory states increases the risk of secondary infections and death. reversing t-cells exhaustion using recombinant il7 or immune checkpoints inhibitors may improve the prognosis of patients with sepsis admitted to the icu. however, there is an unmet need to better characterize the state of t-cells exhaustion in these patients, its reproducibility and its correlation with the outcomes before implementing immunotherapy in the therapeutic armamentarium against sepsis. patients and methods: prospective observational cohort study performed in two tertiary-care icus in a university hospital. peripheral blood mononuclear cells were collected at day 1 in 80 adult patients with sepsis admitted to the icu. the level of cd4+ and cd8+ t-cells exhaustion was quantified using multi-color flux cytometry targeting the following exhaustion markers: pd-1, 2b4 and cd160. cd4+ regulatory t-cells (cd3+ cd4+ cd25hi cd127lo cells) were also assessed. results: the 80 patients included in the study could be split in five clusters according to their dominant pattern of exhaustion markers on cd8+ t-cell (i.e. no markers, pd-1+, 2b4+, 2b4+ cd160+ and 2b4+ pd-1+) and independently of their underlying morbidities. no patients harbored a fully exhausted triple-positive pattern. by multivariate analysis, saps2 gravity score at day 1 (p = 0.007), a dominant 2b4 and/or pd-1 cd8+ pattern (p = 0.04) and lung sepsis (p = 0.02) where associated with the risk of death at day 28, whereas hemoglobin level was associated with survival (p = 0.04). no cd4+ or cd8+ exhaustion pattern independently predicted the risk of secondary infections. neither the level of cd4+ regulatory t-cells nor the dominant cd4+ exhaustion pattern was associated with the outcomes. rationale: there is growing use of multiplex polymerase chain reaction (mpcr) for respiratory virus testing in patients with communityacquired pneumonia (cap). data on one-year outcomes in patients with severe cap of bacterial, viral and unidentified etiology are scarce. patients and methods: a single-center retrospective study was performed in 123 intensive care unit (icu) patients with known one-year survival status who had undergone respiratory virus testing for cap by mpcr. one year after icu admission, mortality rates and functional status were compared in patients with cap of bacterial, viral or unidentified etiology. results: there were 19 (15.4%) patients in the bacterial group, 37 (30.1%) in the viral group and 67 (54.5%) with unidentified etiology. one-year mortality was 57.9% (n = 11/19), 27% (n = 10/37) and 28.4% (n = 19/67), respectively (p = 0.046). in multivariate analysis, one-year mortality was higher in the bacterial group than in the viral group (hr 2.92, 95% ic 1.71-7.28, p = 0.02), had a trend to be higher in the bacterial group compared to the unidentified etiology group (hr 2.07, 95% ic 0.96-4.45, p = 0.06) and was not different between the viral and unidentified etiology groups (hr 0.71, 95% ic 0.30-1.65, p = 0.43). severe dyspnea (mmrc score = 4 or death), major adverse respiratory events (new homecare ventilatory support or death) and severe autonomy deficiencies (adl katz score ≤ 2 ordeath) were observed in 52/104 (50.0%), 65/104 (62.5%) and 47/104 (45.2%) patients, respectively, with no difference between groups. conclusion: cap of bacterial origin was associated with a poorer prognosis than viral or unidentified etiology. impaired functional status was observed in a substantial proportion at one-year, irrespective of the causative microorganisms involved. compliance with ethics regulations: yes. interest of unyvero multiplex pcr (curetis) for bal rapid microbiologic and antibiotic susceptibility documentations in immunocompromised patients under antibiotic therapy jean-luc baudel 1 , jacques tankovic 2 , redouane dahoumane 2 , salah gallah 2 , laurent benzerara 2 , jean-remy lavillegrand 1 , razach abdallah 1 , geoffroy hariri 1 , naike bige 1 , hafid ait-oufella 1 , nicolas veziris 2 , eric maury 1 , bertrand guidet 1 rationale: our aim was to evaluate the interest of the unyvero rapid (4.5 h) multiplex pcr assay (performed on bronchoalveolar lavage [bal] samples) for the management of immunocompromised patients already treated with antibiotics and diagnosed with pneumonia (according to clinical and radiological findings). we thus performed an observational study that compared the results (and the length of time to obtain them) of routine microbiological evaluation and unyvero assay. patients and methods: from july 2018 to january 2019 and from april to august 2019, we examined bal samples from immunocompromised patients (coming from hematology, oncology, hepatology, gastroenterology, internal medicine, and neurology units) diagnosed with pneumonia (based on clinical and radiological findings), and already receiving antibiotic treatment. the following data were collected: age, gender, saps2 score, lung ct scan (92%) or x-ray (8%) results, duration and content of prior antibiotic therapy, direct examination, culture, antibiogram and unyvero results, secondary confirmation of pneumonia or not, possible changes in antibiotic therapy that could have been made after obtention of unyvero results. informed consent was obtained from all patients. results: 40 bal samples were analyzed in 38 immunocompromised patients (m/f ratio 2.17, saps2 51.5 ± 6.8) mostly with hematologic (76%) or oncologic (13%) diseases. the patients received either corticosteroids (47%), or chemotherapy (37%), or immunotherapy (8%). 40% of the patients were under mechanical ventilation, 15% under optiflow. 32% presented a shock, 22% had aplasia or neutropenia, 24% were allografted, 16% were autografted. the duration of prior antibiotic therapy at the time of bal were 9.3 ± 5.6 days. direct examination was positive in 22.5% of the cases, culture (both above and under the classical threshold of 104 cfu/ml) in 60%, unyvero in 47.5%. a retrospective analysis of all the cases confirmed the initial diagnosis of pneumonia in only 50% of the cases. compared to culture, the sensitivity of unyvero was 81%, its specificity 94%. unyvero could permit to rapidly deescalate antibiotic therapy in 42% of the cases and to rapidly stop it in 32%. the unyvero assay on bal samples is useful in this specific population for rapid obtention of microbiological results and also for confirmation of the negativity of cultures and thus permits a better management of antibiotic therapy, leading to a reduction of antibiotic resistance selection pressure in the icu. compliance with ethics regulations: yes. do not underestimate rsv pneumonia among critically ill patients erwan begot 1 , suzanne champion 1 , charline sazio 1 , benjamin clouzeau 1 , alexandre boyer 1 , hoang-nam bui 1 , marie-edith lafon 2 , camille ciccone 2 , julia dina 3 , didier gruson 1 , renaud prével 1 1 chu bordeaux, medical intensive care unit, bordeaux, france; 2 chu bordeaux, virology laboratory, bordeaux, france; 3 national reference center for measles mumps and rubella, chu de caen, caen, france correspondence: erwan begot (erwan.begot@chu-bordeaux.fr) ann. intensive care 2020, 10 (suppl 1):f-019 rationale: respiratory syncitial virus (rsv) is a well-known cause of respiratory failure among neonates but its pathogenicity in adults is now emerging as a potential cause of viral pneumonia. data are limited with conflicting results regarding rsv pneumonia severity in adults. data are lacking about critically ill rsv patients' characteristics and outcomes. the aim of this study is to compare rsv patients' characteristics, care and outcomes to influenza patients' ones. patients and methods: patients diagnosed with rsv and influenza pneumonia admitted to our medical icu were included. data were retrospectively recorded. quantitative data are expressed by median and interquartile range and compared by use of mann-whitney test. qualitative data are expressed by number and percentages and compared by use of fischer exact t-test. rsv strains were prospectively collected. results: eighteen critically ill patients with rsv pneumonia and 95 with influenza pneumonia were included. rsv and influenza patients had the same characteristics at admission except for age (respectively 71yo [62; 81] and acute respiratory distress syndrome rates (respectively 7/18 (39%) vs 47/95 (49%), p = 0.44). they received similar treatment as suggested by oro-tracheal intubation rates (respectively 6/18 (33%) vs 52/95 (54%), p: 0.12) and antibiotics prescription (respectively 16/18 (89%) vs 88/95 (93%), p: 0.63). rsv and influenza patients also had the same rates of bacterial co-infections (4/18 (22%) vs 28 (29%), p: 0.78). invasive aspergillosis remained a rare event but also occurred among rsv patients (1/18 (6%) vs 3/95 (3%), p: 0.51). acute coronary syndromes were as frequent in both groups (respectively 2/18 (12%) vs 9/95 (10%), p = 1.00). day-28 mortality was similar between rsv and influenza patients (respectively 3/18 (19%) rationale: respiratory distress from seawater drowning is commonly considered multifactorial. etiologies are debatable and include heart failure, infection and acute respiratory distress syndrome (ards). documented bacterial infections seems mostly related to the site of drowning. data in this regard are scarce with prospective studies lacking. the objective of our study was to describe prospectively the characteristics and determinants of respiratory distress from seawater drowning. patients and methods: all patients admitted for seawater drowning to seven intensive care units (icu) on the french riviera in the summers of 2017 and 2018 were prospectively included. recorded data included clinical features on examination, personal history, chest x-rays, echocardiography and biological results obtained within the first 48 h. a paired student's t-test was used to study statistical differences between quantitative variables on admission and during early evaluation (i.e. first 48 h). results: forty-eight patients were admitted to seven centers of which 45 (94%) were diagnosed as having ards, 31 (65%) early pneumonia and 4 (8%) acute cardiogenic pulmonary edema. twenty-one (44%) respiratory samples were collected but bacterial culture was positive in only 5 cases. multidrug-resistant bacteria were not observed, and amoxicillin-clavulanate as first-line treatment was effective in all cases. echocardiography performed in 38 (75%) patients was normal and unable to identify specific patient profiles. the median clinical pulmonary infection score (cpis) on admission was 6 (iqr, 5-7) and decreased rapidly and significantly (p < 0.0001) within 24 h to 3 (iqr, 2-3) (fig. 1) . conclusion: data from this multicenter cohort suggest that respiratory distress following seawater drowning can mimic bacterial pneumonia during the first 24 h with subsequent rapid clinical improvement in patients admitted to the icu. probabilistic antibacterial therapy should therefore be limited to the most severe patients. isolate ards is often the only etiology found and is resolutive within 24 h. this prospective cohort is the largest of its kind and gives a better insight into the limited impact of cardiogenic and infectious processes on sea drowning-related respiratory distress. compliance with ethics regulations: yes. rationale: patients treated with "extracorporeal membrane oxygenation" (ecmo) are at a higher risk of developing nosocomial infections and they are consequently often treated with beta-lactams. french guidelines recommend obtaining beta-lactam trough concentrations above four times the minimal inhibitory concentration (mic) of the causative bacteria. the ecmo device may alter the pharmacokinetics of these medications, which may result in underexposure to beta-lactam antibiotics. patients and methods: this observational, prospective, multicenter, case-control study was performed in the intensive care units of two tertiary care hospitals in france. ecmo patients with sepsis treated with piperacillin-tazobactam were enrolled. control patients were matched according to sofa score and creatinine clearance. the pharmacokinetics of piperacillin was described based on a population pharmacokinetic model, allowing to calculate the time spent above 4 × the mic breakpoint for pseudomonas aeruginosa susceptibility after the first dose and at steady state between two piperacillin infusions. results: forty-two patients were included. the median age was 60 years [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] , the sofa score was 11 [9] [10] [11] [12] [13] [14] , and median creatinine clearance was 47 ml/min . there was no significant difference in the time above 4 x mic in patients treated with ecmo and controls during the first administration (p = 0.184) and at steady state (p = 0.309). there was no significant difference between the trough at steady state (p = 0.535), with 18/42 patients (43%) exhibiting concentrations of piperacillin lower than 4 x mic. ecmo support was not associated with a steady state trough concentration below 4 x mic (or = 0.5 [0.1-2.1], p = 0.378). the only variable independently associated with this risk was a creatinine clearance ≥ 40 ml/min, (or = 4.3 [1.1-17.7 ], p = 0.043). conclusion: ecmo support has no significant impact on piperacillin exposure. intensive care unit patients with sepsis are, however, frequently underexposed with piperacillin, which suggest that therapeutic drug monitoring should be strongly recommended for severe infections. impact of a visual support dedicated to prognosis of patients on symptoms of stress of family members rationale: family members commonly have inaccurate expectations of patient's prognosis. adding to classic oral information a visual support, depicting day by day the evolution of the condition of the patient, improves the concordance in prognosis estimate between physicians and family members. the objective of this study was to evaluate the impact of this support on symptoms of anxiety/depression of family members. patients and methods: we conducted a bi-center prospective beforeafter study. all consecutive patients admitted in the two icus were eligible. in the before period (3 months), family members received classic oral information. in the after period (3 months) , in addition to classic oral information, the visual support ( fig. 1) was available for family members in the patient's room from the day of admission until discharge from the icu. at day 5 and 90 from admission, symptoms of anxiety/depression of referent family member were evaluated by hospital anxiety and depression scale (hads). results: 140 patients and their referent family members were included (77 in period before and 63 after). characteristics of patients of the two groups were similar regarding age, reason for admission, saps ii at admission and sofa score at day 5. also characteristics of referent family members were comparable in terms of age, sex ratio, type of relationship with the patient and number of visits since admission. at day 5, total had score was 17 [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] in the group before without the support and 15 [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] in the group after with the support (p = 0.43). the prevalence of symptoms of anxiety (had-a score > 7) and depression (had-d score > 7) was similar in the two groups (respectively 66.2% and 49.4% in the group before, and 68.3% and 36.5% in the group after (ns)). at day 90, total had score was 11 in the group before [7-16] and 9 [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] in the group after (p = 0.38). by multivariate analysis the following factors were significantly associated with total had score > 12 at day 5: age of patient ]), number of visits of referent ) and previous or current treatment of referent for anxiety or depression .06]). conclusion: in this study, the use of a visual support dedicated to prognosis of patients did not modify the level of stress of family members. compliance with ethics regulations: yes. rationale: the use of sedation and opioids at the end of life is a topic of considerable ethical debate. incidence of discomfort during the end-of-life of icu patients and impact of sedation on discomfort are poorly known. patients and methods: post-hoc analysis of an observational prospective multicenter study comparing terminal weaning vs. immediate extubation for end-of-life in icu patients, aimed at assessing the incidence of discomfort events according to levels of sedation. discomforts including gasps, significant bronchial obstruction or high behavioral pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. level of sedation was assessed using the richmond agitation sedation scale (rass). results: among the 450 patients included in the original study, 226 (50%) experienced discomfort after mechanical ventilation withdrawal. patients with discomfort received lower doses of midazolam and equivalent morphine, and less frequently had deep sedation (rass -5) than patients without discomfort (59% vs 79%, p < 0.001). after multivariate logistic regression, immediate extubation was the only factor associated with discomfort whereas deep sedation and administrations of vasoactive drugs were two factors independently associated with no discomfort. death occurred less rapidly in patient with discomfort than in those without discomfort (7.3 h [1.9-25.0] vs 1.6 [0.3-6.0], p < 0.0001) (figure) . long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others. discussion: despite the theoretically expected anticipatory titrated doses of opioids and benzodiazepines to alleviate any discomfort after withdrawal of mechanical ventilation, half of the patients did not receive sedation or opiate when the decision to withdraw mechanical ventilation was taken. a major point that could interfere with the continuous deep sedation practice until death is the fear of potentially hastening death, and there is much controversy regarding its proper use in end-of-life care. conclusion: discomfort was frequent during end-of-life of icu patients and was mainly associated with terminal extubation and less profound sedation. compliance with ethics regulations: yes. rationale: bereavement in intensive care unit (icu) is associated with psychiatric disorders on relatives called post-intensive care syndrome family (pics-f). no isolated intervention (such as condolence letter) has shown a positive effect on these disorders, despite a well acceptance by relatives. we thought that a more integrated bereavement program should be considered. the goal of this study is to evaluate a combined psychologist-physician post-death meeting (pdm) in a bereavement program to evaluate needs and adhesion of relatives, and the effect on symptoms of anxiety and depression. patients and methods: monocentric, prospective study focused on relatives of patient admitted > 48 h and deceased in icu. during patient's stay, relatives' presence was allowed on a 24 h-basis and they could meet a clinician psychologist. formal meeting between relatives and the staff was realized at patient's admission and after important decision-making treatment. two weeks after patient's death, the psychologist called relatives to offer emotional support and to invite to a pdm. pdm occurs 3 weeks after patient's death with the psychologist and the physician in charge of the patient. the objectives of the meeting were to provide emotional support, to answer medical question, and to detect symptoms of anxiety and/or depression with the hospital anxiety and depression scale (hads). we hypothesized that pmd would be able to alleviate pics-f at 3 months. we aimed to enroll 70 families to detect a 20% lowering of hads. results: the rate of pdm acceptance was lower than expected. after 53 inclusions, only 12 relatives accepted the pdm, whereas the phone call was well perceived (86%). main association with acceptance of pmd was a short duration of icu stay (4.3 days [2-5.3] vs 7.3 days [3.7-10.9] p = 0.027) and icu admission for acute respiratory failure (66.7% vs 19.5%, p = 0.003) ( table 1) . we found no relation between the number of in icu meeting (psychologist of medical staff) and pmd acceptance. for relatives who accept pmd we found a high proportion of symptoms of anxiety and depression (92% and 83%) with a hads at 28.5 [22-34.5] (median, iqr). no evaluation was performed at 3 months. conclusion: post death contact appears well perceived by relatives but pmd quite useless. this result may be explained by the inclusion of only late death (> 48 h) where psychologist and medical staff had the opportunity to support relatives. further study should focus on early death (< 48 h). compliance with ethics regulations: yes. rationale: pediatric intensivists frequently question themselves on the issue of limitation or termination of life-sustaining treatments (llst) carried out on children. such a decision comes under the claeys-leonetti law which forbids doctors from applying unreasonable treatment however, every so often, parents oppose themselves to a collegial llst decision that the medical and paramedical team had taken. such cases can even end up in court. in order to sort out this problem, this study focused on the factors that underlie the disagreement and the solution brought forward by pediatricians whenever parents demand to persue treatments although considered as unreasonable obstinacy. patients and methods: we carried out a qualitative study involving three multipurpose pediatric critical care unit. all pediatricians operating within these units were contacted. those who volonteered were met individually for a semi-directed interview. every interview was recorded and entitled to a complete hand-written retranscription. the interviews were analysed following the phenomenological interpretive analysis method and were subject to dual listing. results: 16 pediatricians out of 30 took part in the study. 8/16 claimed they would increase treatments or carry out cardiopulmonary resuscitation acts if asked to do so by parents, even if this went against the initial collegial decision. 8/16 claimed they would persue treatments although not beyond the current level. 2/16 said they would oppose themselves to parents concerning blood transfusion for comfort reasons. several key factors were identified as leading a doctor to the non-application of a llst decision: the certainty regarding the child's death on a short or mid-term basis (16/16), the litigiousness risk (14/16), the apprehension of mediatic pressure (14/16), the fear of a violent reaction from parents (13/16), other self-interest positions within the medical team (12/16), empathy towards parents (11/16), the uncertainty concerning the neurological prognosis (5/16), the lapse of time needed to fully accept the application in force of a decision (5/16). 12 pediatricians out of 16 admitted their own-suffering when confronted to the situation. conclusion: this study points out that pediatricians tend to follow parents' position when confronted to parental opposition. in such situations, pediatricians go against their own decision in order to safeguard the parental alliance even if it leads to unreasonable obstinacy, thus conflicting with medical deontological code obligations. compliance with ethics regulations: yes. rationale: end-of-life management strategies are clearly a worldwide issue of major importance that intensivists have to deal with on a daily basis. advance directives may be the solution sought to guide physicians to take such difficult decisions. yet, health care directives are not legislated in tunisia. the objective of this project was to draw a general descriptive overview to assess patients' wishes in tunisia. patients and methods: data were collected from a 39-item-questionnaire based on the french intensive care society's form for advance directives which was filled by 101 people of general population in tunisia, including doctors and paramedics, from may to mid-september 2019. all people included were 18 or older and well informed of the form's utility. results: a total of 101 participants were included. the mean age was 34.6 ± 13.5 years with extremes of 18 and 76 and a sex ratio of 1.7. fourty-one (36.6%) were either doctors or nurses and 3 (3%) did suffer from a severe medical condition. among all the participants, 30 (29.7%) thought that end-of-life decisions were up to the doctor. for the rest, they willingly chose to be hospitalized in an icu, to undergo cardiopulmonary rescuscitation and to have ventilation support with orotracheal intubation or tracheostomy respectively in 63 (87.5%), 60 (83.3%) and 67 (93.1%) of the cases. only 4 (5.6%) refused temporary dialysis. when asked about sequelae they can live with, participants accepted hemiplegia in 63.9% and paraplegia in58.3% of the cases. on the contrary, 68 (94.4%) refused to live in permanent coma and 55 (79.9%) disagreed to undergo tracheostomy and ventilation for life. moreover, 31 (43.1%) found that serious un aesthetic sequelae was a fatal consequence they could not survive. as well, only 7 (9.7%) consented to live with deep intellectual deficiency. regarding palliative care, 53 (73.6%) participants wished to be profoundly sedated until death, 65 (90.3%) prefered to die home over 2 (2.8%) in hospital. sixtytwo (84.9%) desired to see a representative of their religion. furthermore, 65 (89%) were for organ donnation. gender, being a health care professional and age under 30 versus equal or over30 were not significant in dependent factors (p > 0.05). conclusion: it is our duty ashealth care professionals to spread advance directives awareness and education. nevertheless, the law should keep the pace with ethics evolution. compliance with ethics regulations: yes. rationale: adapted organ support techniques are needed to enhance reliability of preclinical animal experiments in the intensive care setting (guillon, annals of intensive care-2019). a few renal replacement therapy (rrt) models have already been developed in rats, mostly hemodialysis in chronic kidney disease models or hemofiltration techniques in sepsis experiments. mounting evidence from clinical (gaudry, nejm-2016) and histopathological studies suggest that rrt for acute kidney injury (aki) could impair renal recovery by acting as a 'second hit' leading to a maladaptive repair of tubular epithelium. we aimed to study this hypothesis in a hemodialysis model in rats with septic aki. patients and methods: on day 1, sprague-dawley rats were injected with lipopolysaccharide or placebo (nacl 0.9%) intraperitoneally. on day 2, anesthetized rats underwent femoral artery catheterization for hemodynamic parameters monitoring. at the same time, one femoral vein and one carotid artery were catheterized for arterio-venous sterile extracorporeal circulation with or without passing through a miniature sterile polyester sulfone hemodialyzer (20 cm2 surface, 50 kda pores, microkros ® ) filled with dialyzate liquid in the outer compartment (table 1) . vessels were ligated after the procedure and rats allowed to awaken. on day 3, rats were sacrificed. results: all rats injected with lipopolysaccharides o127:b8 10 mg/kg survived at day 2. anesthesia was much challenging: ketamine + xylazine and tiletamine-zolazepam + xylazine required induction and maintenance intraperitoneal injections. these medications induced important hemodynamic parameters fluctuations and high mortality. isoflurane gas inhalation enabled better stability, less hypothermia and quick awakening. adequate temperature was controlled with a heating pad during the procedure and an incubator after. supine position was maintained. the whole circuit was anticoagulated with 1 ml of heparinized saline 100 ui/ml, since clots occurred in the absence of anticoagulation and bleeding when higher dosing was used. circuit (< 1.5 ml including dialyzer) was filled with saline solution before initiation, and total restitution of blood at the end of the experiment prevented any blood transfusion requirement. hematocrit was determined at beginning (50%) and end of experiment (40%). a peristaltic pump provided a blood flow rate of 1.0 ml/min, (higher rate was not tolerated) for 2 h. of note, rats who underwent sham procedure (vessels ligature only) survived and did not display aki. circulation of a counterflow dialysate in the dialyzer is planned but has not been performed yet. conclusion: this hemodialysis system for rats is feasible at a reasonable price and might help research involving rrt in either ckd or aki. compliance with ethics regulations: yes. there were no significant relationship between rri and past medical history or severity score. we observed a significant negative correlation between rri and diastolic arterial pressure (p = 0.004) and heart rate (p = 0.004) as it could be expected by rri formula. an increased rri was associated with higher potassium (p = 0.019) and higher creatinine levels (p = 0.042). although not significant, we found a higher rate of subsequent rrt in the high rri group (23% vs 6%, p = 0.146). over the first 3 days, fluid balance was significantly different between groups (2217 ml vs -1314 ml respectively for low and high rri group, p = 0.017). since standard of care were similar, this suggests different fluid volume status between the two groups. in the low rri group, the cause of aki could predominantly be prerenal since positive fluid balance was not explained by more severe aki with refractory oliguria as shown by the low rrt rate. nevertheless, we did not observed any relationship between rri and the evolution of serum urea or creatinine levels, nor with the presumed aetiology of aki. conclusion: when focussing on the first rri measurement once stage 2 aki was reached, rri ≤ 0.7 seems to be in favour of prerenal and transient renal dysfunction even if this is not supported by creatinine serum evolution. compliance with ethics regulations: yes. rationale: critically ill patients are at higher risk of bleeding but also dialysis filter clotting (inflammatory state). intermittent hemodialysis with calcium-free citrate-containing (0.8 mmol/l) dialysate (cafcit-ihd) recently emerged as a new safe and simple alternative to continuous renal replacement therapy allowing heparin-free extended dialysis sessions (> 5 h). in this study, we aimed to answer to two issues still unresolved: (i) can citrate contained in the dialysate accumulate and lead to citrate intoxication in patients with liver disorders, and (ii) can citrate be avoided using citrate-and calcium-free dialysate (ccf-ihd)? patients and methods: monocentric retrospective study. among the 450 sessions performed with cafcit-ihd, the 20 ihd sessions (18 critically ill patients) with citrate measurement available before and after the dialysis filter were reviewed. estimation of the liver clearance was performed using the picco lemon ® system (pulsion). in addition, 8 sessions performed using ccf-ihd were reviewed. results: all the patients had liver disorders (post-liver transplantation period n = 2; cirrhosis with child > a6). among the eighteen cafcit-ihd patients, fifteen (75%) and six (30%) received mechanical ventilation or vasopressive drugs, respectively. the median time of the dialysis session was 5 h [2] [3] [4] [5] , with hourly ultrafiltration rate of 400 ml (one premature termination not related to dysfunctional catheter). in all patients, ionized calcium (ica) decreased below 0.40 mmol/l after the filter, whereas post-filter calcium reinjection according to ionic dialysance led to a stable pre-filter (i.e. patient) ica. median citrate concentrations were all below 0.8 mmol/l after the filter (minimal concentration to obtain anticoagulation 3 mmol/l) and all except one below the normal value (< 125 µmol/l) before the filter. during all the sessions, ionized to total calcium ratio was below 2.1 and the strong ionized gap decreased. when available (n = 7), no correlation could be identified between serum citrate concentration and liver clearance. last, in 8 ccf-ihd sessions performed in critically ill patients, no premature termination occurred (median time of the sessions 5 h) and post-filter ica also decreased below 0.45 mmol/l. no citrate accumulation could be identified in critically ill patients (even with liver disorders) and receiving extended dialysis sessions (5 h or more) using calcium-free citrate containing-ihd. interestingly, we demonstrated that citrate is not required to obtain optimal regional anticoagulation (i.e. post-filter ica < 0.45 mmol/l), and a citrate-and calcium-free dialysate could be a safe alternative. compliance with ethics regulations: yes. rationale: ventilator induced diaphragmatic dysfunction is highly prevalent in adult critical care and associated with worse outcomes. specificities in pediatric respiratory physiology suggest that critically ill children may be at high risk of developing this complication, but no study has described the evolution of diaphragmatic function in critically ill children undergoing mechanical ventilation. this study aims to validate a method to quantify diaphragmatic function in mechanically ventilated children. in this prospective single-center observational study, 10 children between 1 week and 18 years old intubated for elective ent surgery and without pre-existing neuromuscular disease or recent muscle paralysis were recruited. immediately after intubation, diaphragmatic function was evaluated using brief airway occlusion maneuvers during which airway pressure at the endotracheal tube (paw) and electrical activity of the diaphragm (eadi) were simultaneously measured for 5 consecutive spontaneous breaths, while the endotracheal tube was occluded with a specific valve. occlusion maneuvers were repeated 3 times. in order to account for central respiratory drive and sedation use, we recorded the neuromechanical efficiency ratio (nme, paw/eadi), in addition to the maximal inspiratory force (mif). in order to determine the optimal measure of nme during an occlusion, the variability over the three occlusion maneuvers of different variables (first breath, last breath, breath with maximal paw deflection, breath with maximal nme value, and median nme value) was assessed using coefficients of variation and repeatability coefficients. results: patients had a median age of 4.9 years (interquartile range 3.9-5.5), a median weight of 18 kg (14-23), and 5 were male (50%). the median evolution of paw, eadi, and nme ratio over the 5 occluded breaths are represented on fig. 1 . nme values corresponding to the last breath and the breath with maximal paw deflection were the least variable, with median coefficient of variation of 23% and 23% and repeatability coefficients of 3.44 and 3.44, respectively. conclusion: brief airway occlusions can be used to assess diaphragmatic function in intubated children through both mif and nme ratio, and the latter should ideally be computed on the last breath or the breath with the largest pressure deflection to improve repeatability and decrease variation. compliance with ethics regulations: yes. epidemiology is poorly understood due to the rare use of validated diagnostic tools. the main objective of the study was to determine, by systematically calculating the wat-1 score, the incidence of ws in our surgical picu. the secondary objective was to analyze the risk factors, consequences and management modalities of ws. patients and methods: following institutional review board approval, we conducted a prospective monocentric study between july 2018 and january 2019. all consecutive mechanically ventilated children admitted in our surgical picu with sedation/analgesia by continuous intra-venous (iv) benzodiazepines (bzd) and/or opioids for at least 48 h were included. as soon as sedation was decreased and during 72 h following their total discontinuation, wat-1 score was assessed twice a day. ws was defined by a wat-1 score > 3. the search for risk factors and consequences associated with ws was performed by univariate analysis (mann-whitney and chi2 test). ethical standards were satisfied and the lack of opposition from patients and their parents was systematically checked. results: the incidence of ws was 50% among the 46 patients of our cohort including 54% of children admitted postoperatively and 35% after severe traumatic brain injury (tbi). significant results are reported in table 1 . our results show that even for sedation time less than 5 days, children could develop ws (11/23 patients). on the other hand, age, severity (pelod 2 score), number of previous surgeries and severe tbi were not associated with ws. our study also demonstrated that cessation of sedation and prevention of ws was not uniform in our unit. the high incidence of withdrawal syndrome in our study, even in children sedated for less than 5 days, and its consequences require thinking about prevention. we suggest a systematic monitoring of the occurrence of this adverse event using a validated score, from 3 days of continuous iv sedation/analgesia. compliance with ethics regulations: yes. rationale: severe traumatic brain injury (tbi) is a major healthcare problem. amplitude and duration of intracranial hypertension is highly associated with patient outcome. the intracranial pressure (icp) is therefore one key parameter to monitor in the acute phase. when icp is monitored with an external ventricular drain, the pressure recorded by the monitor does not always correspond to the real icp, depending on the status (open/closed) of the 3-way tap. misleading values could therefore be sent to the patient medical record. our hypothesis is that a machine-learning algorithm will be able to identify automatically and in real time the reliable and non-reliable values of the icp signal. we retrospectively studied pediatric patients having an external ventricular drain between july 2018 and july 2019, in a single pediatric intensive care unit. the icp signals were extracted from a high-frequency database (128 hz) and pre-processed adequately. to train the algorithms, an annotated database was manually created with two classes: reliable icp vs. non-reliable icp (drain system opened to allow cerebrospinal fluid removal). eleven signal characteristics were compared between the two classes (mann-whitney test), and significantly differing variables were tested in the algorithms. we compared the performance of two machine-learning algorithms: the k-nearest neighbors (knn) and the support vector machine (svm). using 10-fold cross-validation method, 75% of the data was used to train the algorithms and 25% was used for testing. the best classifier was further validated by simulating a real-time icp analysis, using a 15 s sliding-window approach with 50% overlap. the study was approved by the localresearch ethics committee. results: sixteen patients were included in the study. the training database created from 14 patients, contained 320 segments (of 15 s duration) per class and per patient. eight signal variables were identified and kept to define the segments. the knn algorithm, with k = 3, led to the best performance, with a mean of 98% (mean ± sd: 98% ± 0.29%). the knn was then visually validated on icp signals from the remaining two patients ( figure) . by simulating a real-time icp extraction, our algorithm was able to efficiently identify the reliable icp segments, and to display a mean value only for valid segments. university hospital picu (paris). all consecutive children (1 month-18 years) admitted for acute encephalitis were included and diagnosis was confirmed using the 2013 consensus conference criteria's. data regarding clinical, biological and radiological presentations were collected as well as data on the therapeutics used and outcomes at discharge and at the last medical consultation. results: 106 patients were included with a mean age of 6.2 years (range 0.1 to 17 years old). infectious causes were identified in 45% (n = 48), autoimmune causes in 8% (n = 8) and acute demyelinating encephalomyelitis in 4% (n = 4) of cases. etiology remained undetermined in 43% of cases (n = 46). the most common pathogens were, in order of frequency, influenzae virus, mycoplasma pneumoniae and epstein-bar virus. the main clinical features were fever (88% n = 93); epileptic seizures (80% n = 85) and coma (46% n = 49). regarding therapeutics, 52% of patients required mechanical ventilation and 20% of patients required hemodynamic support. 47% received corticosteroids, 17% intravenous immunoglobulins and 12% plasmatic exchanges. the use of these specific treatments was heterogeneous, especially in infectious and undetermined encephalitis, where respectively 48% and 38% received boluses of corticoids. the mean length of stay in picu was 10.7 days (range 1-155 days). the mortality rate was 10% and the overall rate of sequelae at discharge was 76% and 61% at distance, with 21% considered as severe (gose-ped score > 5). the use of mechanical ventilation and young age at diagnosis were risk factors associated with poor prognosis at discharge. the etiology of acute encephalitis remains indeterminate in more than 40% cases with a clear predominance of infectious causes when an etiology is found. this is a severe pathology responsible for significant mortality and morbidity requiring long-term follow-up. compliance with ethics regulations: yes. rationale: preserving neurological outcome of children under extracorporeal membrane oxygenation (ecmo) remains challenging. acute brain injury (abi) is a frequent complication of ecmo that could be prevented by continuous neuromonitoring. cerebral near infrared spectroscopy (nirs) is routinely used for detecting cerebral complications of cardiac surgery. in adults and infants under prolonged ecmo, cerebral hypoxia is associated with poor neurological outcome. the aim of this study was to assess the value of an impaired cerebral oxygenation on mortality and occurrence of an abi in children under ecmo. patients and methods: children under 18 years old were included in this observational retrospective monocentric study if they needed veno-venous (v-v) or veno-arterial (v-a) ecmo for respiratory and/ or circulatory failure and had concomittant nirs monitoring. cerebral desaturation was defined as a rsco 2 value under 50% or under 20% from the baseline; cerebral hyperoxia was defined as a rsco 2 value above 80%. proportion of time in cerebral desaturation and hyperoxia were recorded. neurological lesions were identified on imaging (mri or scan) by blinded radiologist and classified as major or minor. abi was defined as any hemorragic or ischemic lesion on cerebral imaging, including brain death. results: 63 patients were included. ecmo duration was 9 [5; 13] days. the mortality rate was 32 (50.8%), and the proportion of abi was 34 (54%) including 5 brain deaths, 10 (15.9%) major lesions, and 19 (30.2%) minor lesions. mean rsco 2 was 73 ± 9% in the right hemisphere, and 75 ± 9% in the left hemisphere. there was no significant difference in cerebral hypoxia between survivors and non survivors, and between patients with and without an abi. cerebral hyperoxia was associated with a better survival (p = 0.03 in the right hemisphere, and p = 0.02 in the left hemisphere). in v-v ecmo and at the right conclusion: in our study, cerebral hypoxia was not associated with poor neurological outcome, but cerebral hyperoxia seems to be protective especially in v-v ecmo. this is the first study assessing the value of cerebral oxymetry in all age ranges pediatric ecmo. in this population, multimodal monitoring might be better than nirs alone to predict neurological impairment. further prospective studies are needed to assess first the feasibility, then the impact of such a monitoring. compliance with ethics regulations: yes. cerebral autoregulation impairment is associated with acute neurological events during pediatric extracorporeal membrane rationale: children supported by extracorporeal membrane oxygenation (ecmo) present a high risk of adverse neurological complications. as some animal studies have shown, cerebral autoregulation (ca) impairment after exposure to ecmo, may be a key factor. our main objective was to investigate the feasibility of ca continuous monitoring during ecmo treatment. the second objective was to analyze the relationship between ca impairment and neurological outcome. patients and methods: an observational prospective study including children treated by ecmo in 2 centers was conducted. a correlation coefficient between the variations of regional cerebral oxygen saturation (rsco 2 ) and the variations of mean arterial blood pressure(map) was calculated as an index of ca (cerebral oxygenation reactivity index, cox) during ecmo. a cox > 0.3 was considered as indicative for dysautoregulation. cox values were averaged inside 2 mmhg-map bins, allowing determining optimal map (mapopt) and lower (lla) and upper (ula) limits of autoregulation in 8-h periods. neurological outcome was assessed by the onset of an acute neurologic event (ane) defined by occurrence of hemorrhagic or ischemic stroke and/ or clinical or electrical seizure and/or brain death during the ecmo treatment. rationale: myocardial ischemia reperfusion (ir) injury is the leading cause of perioperative morbi-mortality. protective effect of pharmacologic preconditioning such as anesthetic preconditioning (apc) with sevoflurane (sev) has been widely demonstrated in animal and human models. apc seems to protect myocardial cells from apoptosis, a programmed process of cell death tightly controlled by bcl-2 family proteins. however, the involved mechanisms in apc have yet to be characterized. we hypothesized that apc protects against myocardial apoptotic cell death by regulating bcl-2 anti-apoptotic members. to study the sev-induced apc mechanisms against myocardial ir, we used a validated in vitro model reproducing ir injury. rat cardiomyoblast cells h9c2 were cultivated in 0.1% o2 hypoxia in the presence of ischemia-mimicking medium. after 90 min of ischemia, the reperfusion injuries are induced by replacing the culture medium with a krebs-henseleit normoxic medium for 60 min. apc was performed by adding sev directly into the culture medium at an initial concentration of 20 mm, prior to ischemia, for 60 min. we then used another preconditioning agent, metformin (met), to explore the same signaling pathways. apoptotic cell death was measured by caspase activity assay and western blotting (expression of cleaved caspase 3) under ir and apc conditions. results: our model faithfully reproduced the protective effect of apc which results in a significant decreased apoptosis under ir (50% reduction of the caspase 3 enzymatic activity, correlated with a decrease of caspase 3 cleavage). we showed that sev induces overexpression of the anti-apoptotic protein bcl-xl, which is responsible for the protective effect of apc. furthermore, these observations were confirmed in vivo in mouse heart lysates. we demonstrated that bcl-xl overexpression was due to the activation of the protein kinase akt. interestingly, we were able to show that preconditioning with met reproduces the protective effect of sev by inducing an akt-dependent bcl-xl overexpression. indeed, sev and met, which are both complex 1 inhibitors of mitochondrial respiratory chain, seem to share a common reactive oxygenated species-dependent protective mechanism responsible for bcl-xl protein regulation. rationale: despite early endovascular treatment with successful recanalization, 50% of acute ischemic stroke (ais) patients experience a poor functional outcome after a large vessel occlusion. sepsis is frequent at the acute phase of stroke and is associated with poorer short and long term outcomes. we aimed to investigate the cerebral consequences of sepsis after recanalized ais and explore possible mechanisms involved. patients and methods: male c57bl6 mice were randomly assigned to a 2x2 factorial plan to one of the 4 following groups: 1) a 60-minute middle cerebral artery (t-mcao) transient occlusion under inhaled general anesthesia, followed 5 min after recanalization by intraperitoneal (i.p.) sepsis (lps, 10 µg/g diluted in 100µl of nacl0.9%), (tmcao/ lps group); 2) t-mcao followed by i.p. placebo (100µl of nacl0.9%) (tmcao/placebo group); 3) sham operation (cervicotomy without carotid catheterization) followed by i.p. lps. (sham/lps group); 4) sham operation followed by i.p. placebo, (sham/placebo group). in all groups, animals received subcutaneous fluid resuscitation (200µl nacl 0.9%) immediately after the procedure and 1 h later. twenty-four hours after recanalization, animals were scored for sepsis features and neurological deficit (on the modified neurological severity scale), (mnss) before sacrifice. the primary outcome measurement was a composite of death and hemorrhagic transformation at 24 h. secondary outcome measurements included neurological deficit, sepsis features, neutrophil activation reflected by plasmatic myeloperoxydase (mpo) levels, stroke volume, and microglial activation in brain parenchyma (infarct core, perilesional area, controlateral hemisphere). results: t-mcao/lps animals had higher mnss (1.7 fold, p = 0.02) and sepsis (6 fold, p = 0.0018) scores at 24 h with increased plasma mpo levels at 1 h (2.8 fold, p < 0.01) and 24 h (5.9 fold, p < 0.0001), as well as, lower temperature (3.0 °c reduction, p = 0.01) and glycemia (0.9 g/l reduction, p = 0.01) as compared to tmcao/placebo animals. t-mcao/lps animals had a higher risk of unfavorable outcome at 24 h (4-group comparison: p = 0.03; 2x2 analysis: t-mcao/lps, 6/12 − 50%vs. t-mcao/placebo 1/17-6%-, p < 0.01), whereas stroke volumes were not significantly different between groups. detailed results are presented in table 1 . compared to t-mcao/placebo group, t-mcao/ lps animals had 1.3 fold increase (p = 0.05) in the mean number of microglial cells in the hemisphere controlateral to t-mcao, whereas no significant difference was observed in infarct core or peri-infarct parenchyma. conclusion: early sepsis after experimental ais worsens outcome and neurological deficit, without impacting stroke volume. early sepsisinduced systemic activation of neutrophils and increased microglial activation in the hemisphere contralateral to ischemia may have an important role on neurological outcomes observed in this setting. compliance with ethics regulations: yes. rationale: extracellular vesicles (evs) regulate diverse cellular and biological processes via facilitating intercellular cross-talk. several studies have suggested an association between lung injury and the generation of evs derived from platelets, neutrophils, monocytes, lymphocytes, red blood cells, endothelial cells, and epithelial cells. every year more than 25,000 patients require cardiac surgery with cardiopulmonary bypass (cpb). this cpb allows a substitution of the heart pump function and an oxygenation of the blood permitting a stop of the mechanical ventilation (mv). stopping mv during cpb is responsible for lung damage, leading to postoperative systemic inflammation while maintaining mv with positive expiratory pressure (peep) diminished the occurrence of atelectasis and the postoperative inflammatory response. in addition, this surgery is marked by immune dysfunction, leading to real immunosuppression of patients in postoperative care. a link between pulmonary injury and postoperative immunosuppression has been established, however, the mechanisms underlying this association are not fully known and evs may have a role in this post-operative immunosuppression. the purpose of this study is to investigate whether lung injury induced during cardiac surgery with cpb lead to the emergence of evs. the effect of mv during cpb on the production of these evs has also been studied. patients and methods: patients were prospectively divided into two groups: without mv during cpb and dead space mv with positive end-expiratory pressure during cpb. pao 2 (arterial oxygen tension)/ fio 2 (inspired oxygen fraction) ratio, biological markers of lung injury (cxcl10, ccl2, tnf-α, il-1β, il-10, rage, il-8) and blood cell count were collected before, 24 h and 7 days after surgery. the quantification of plasma evs was performed using turnable resistive pulse sensing and characterization of evs was performed using flow cytometry before, 24 h and 7 days after surgery. rationale: the benefit of prone positioning (pp) during moderate to severe acute respiratory distress syndrome (ards) may be related to its impact on the inflammatory response to ventilator-induced lung injuries. [11c]-pk11195 is a positron emission tomography (pet) radiotracer that allows the non-invasive quantification of macrophages. we aimed to evaluate the effects of pp on [11c]-pk11195 lung uptake in animals with experimental ards. patients and methods: experimental ards (by hydrochloric acid) was induced in 10 pigs in supine position (sp), to obtain a pao 2 / fio 2 < 300 mmhg. animals were under general anesthesia, neuromuscular blockade, and ventilated with a 6 ml kg −1 tidal volume, and 5 cmh 2 o of positive end-expiratory pressure (peep). immediately after experimental ards, animals were randomized to be prone positioned, or to remain in sp. pet and computerized tomography (ct) were acquired 4 h after randomization (h4). [11c]-pk11195 uptake was measured on the whole lungs, and by dividing the lungs into 8 regions or slices-of-interest (soi) along the ventro-dorsal axis, and was quantified by the standardized uptake value (suv), corrected for lung tissue density. results: pp was performed in 6 animals, and sp in 4. after ards induction, pao 2 /fio 2 was 107 [iqr, [1.2-1.7] in sp animals (p = 0.61). in pp animals, [11c]-pk11195 suv was significantly lower in ventral soi, compared to sp, and significantly increased in dorsal soi ( fig. 1 , *: p < 0.01 between groups in a given soi). in univariate analysis, [11c]-pk11195 regional suv was positively associated with regional ct-measured peep-related increase in gas volume, and negatively with peep-related lung recruitment, but not with regional tidal volume. conclusion: during experimental ards, pp redistributed lung macrophage recruitment estimated by [11c]-pk11195 uptake from ventral lung regions to dorsal regions, without affecting global macrophage influx. the intensity of macrophage recruitment was associated with peep-related lung inflation. compliance with ethics regulations: yes. rationale: acute respiratory distress syndrome (ards) is a pleiomorphic disease characterized by a severe respiratory failure associated with an increased mortality. nowadays, predicting clinical outcome of patients suffering from ards remains difficult. therefore, identifying new biomarkers to predict patient outcome, to evaluate response to therapy and to identify new potential pathways of interest are highly needed. exosomes are extracellular vesicles involved in cell-cell communication by transferring micrornas (mirnas) from donor to recipient cells. thus, exosomal mirnas can significantly affect biological pathways within recipient cells resulting in alterations of cellular function and the development of a pathological state. as biomarkers are highly needed in the particular field of ards, we realized a monocentric and prospective study to identify a new potential biomarker of interest. therefore, a prospective plasma sampling at the diagnosis of moderate to severe ards according to the definition of "berlin" has been performed. we analysed mirna content of exosomes from plasma ards patients compared to healthy subjects (hs) in order to identify new potential predictive biomarkers in ards. during one-year period, patients hospitalized in the icu of chu sart tilman suffering from infectious moderate-to-severe ards have been included. the ethical committee review boards of the hospital approved the research protocol (b707201422832, ref: 2014/302), and informed consents were obtained. exosomes were isolated from plasma samples of 10 ards patients and 10 hs with standard ultracentrifugation protocol. exosomal mirna content was analyzed using small rna sequencing method, and diseases/biological processes associated to altered mirs were determined by bioinformatic analysis. results: for the first time, exosomal mirna expression modifications were studied in patients with moderate-to-severe infectious ards. we identified a new signature statistically significant composed of three up-regulated mirnas (mir-122, mir-23a and mir-126) and one downregulated (mir-let-7b). conclusion: we identified potential biomarkers for ards from plasma exosomes. our findings may thus lead to predict ards outcome but also a better understanding about the roles of these mirs in the pathogenesis of ards and thus open new avenues for therapeutic approaches. in particular, exploit and develop the pro-fibrotic pathway induced by down-expression of mir-let-7b. but also confirm in the future the current interest about mir-126 in its ability to restore pulmonary integrity after trauma. compliance with ethics regulations: yes. rationale: diabetic ketoacidosis (dka) is a life-threatening emergency. microvascular hyporeactivity was reported in these patients and was completely reversibly when ph was corrected with treatment: aggressive rehydration, electrolyte replacement and insulin therapy (1) . red blood cell (rbc), a component of the microcirculation, showed alterations oftheir shape in diabetic patients (2) but no data were available concerning the time course of the rbc deformability during treatment for dka. we aimed to assess the rbc deformability during dka treatment in icu patients. patients and methods: after approval by the ethics committee, rbcs deformability was assessed, in all icu patients admitted for dka and without infection, by ektacytometry technique (laser-assisted optical rotational red cell analyzer-lorrca): at icu admission, +8 h, +24 h and at the end of the icu stay (36-48 h). elongation index (ei) was defined as (l − w)/(l + w), where l is the length and w is the width. at 37 °c, ei values were determined in the function of shear stress (ss) in a range of 0.5-50 pa, based upon the laser diffraction pattern changes. a higher ei indicates greater rbc deformation. rbc deformability from patients with dka was compared at icu admission to healthy volunteers (v) and to diabetic patients followed in consultation (d). we also studied the evolution of deformability during treatment. results: 15 icu dka patients compared to 31 d and 20 v were studied. as expected, glycemia and glycated hemoglobin were significantly higher in dka compared to d (respectively: glycemia: 549 (444-872) vs 139 (92-181) mg/dl and 11.7% (9.4-13.4) vs 7.8 (7.3-8.2); all p < 0.001). dka patients received 6279 (5482-8308) ml of fluids and 2.24 ui/ kg bw (1.71-2.42 ) of insulin during their first 24 h of icu stay. rbcs deformability from dka patients was significantly more altered at icu admission compared to others groups ( fig. 1 ) and these alterations persists despite treatment. no correlations were observed between these alterations and quantity of fluids or insulin received, glycemia, glycated hemoglobin, ph, natremia, age or length of diabetes history. conclusion: in contrast of reversible microvascular hyporeactivity, rbc deformability from dka patients was already altered at icu admission and remains altered despite treatment. these alterations could contribute to the blood flow abnormalities observed in these patients. compliance with ethics regulations: yes. rationale: sepsis remains the first cause of acute circulatory failure in the emergency department (ed). standardized fluid resuscitation may not be adapted in certain patients, especially those with early sepsisinduced cardiac dysfunction in whom excessive fluid administration could be deleterious. information on early hemodynamic profile of septic patients in the ed are scarce. accordingly, we aimed at describing hemodynamic profiles encountered in septic patients assessed shortly after their ed admission using focused echocardiography. patients and methods: we prospectively enrolled adult patients with sepsis (qsofa score ≥ 2) from january 2017 to july 2019 in the ed (nct02974790). focused echocardiography were performed by emergency physicians previously trained to ecmu 1 level. each patient was evaluated according to a standardized protocol based on a limited number of simple binary clinical questions. investigators interpreted on-line the echocardiographic examination, determined the hemodynamic profile based on simple yet robust criteria (hypovolemia, left ventricular [lv] or right ventricular [rv] failure, vasoplegia with hyperdynamic state, tamponade, severe mitral or aortic regurgitation, or apparently normal profile), and recorded any substantial change in planned therapeutic management (surviving sepsis campaign 2016). data were digitally stored and validated off-line by an expert in critical care echocardiography. results: focused echocardiography were performed in 81 patients (mean age: 70 ± 15 years; men: 58%; source of infection: pulmonary 37%, urinary 25%, abdominal 25%) after a median fluid loading of 500 ml (iqr: 500-1500 ml). according to sepsis-3 definition, 44 patients had sepsis and 37 sustained septic shock. mean sofa score was 5.3 ± 2.9 (hemodynamic failure 85%, respiratory failure 72%, renal failure 67%), mean lactate reached 4.7 ± 4.3 mmol/l, icu admission involved 38% of patients and overall 28-day mortality reached 35%. hemodynamic profile was hypovolemia in 54 patients (67%), vasoplegia in 26 patients (32%), cardiac failure in 21 patients (26%) (lv failure: n = 15; rv failure: n = 6) and without relevant hemodynamic abnormality in 9 patients (11%). ongoing therapy was altered based on early echocardiographic assessment in 26% of cases. mortality rate was not significantly different between groups (p = 0.46). conclusion: although hypovolemia was predominantly identified in patients presenting to the ed with sepsis during hemodynamic assessment, early ventricular dysfunction involved one-quarter of patients. these results suggest that early focused echocardiographic assessment promises to help the front-line physician tailoring the therapeutic management of septic patients in ed, especially regarding fluid resuscitation. compliance with ethics regulations: yes. right ventricular failure in septic shock characterization, incidence and impact on fluid-responsiveness guillaume geri 1 , amélie prigent 2 , xavier repessé 2 , marine goudelin 3 , gwenael prat 4 , bruno evrard 3 , cyril charron 1 , philippe vignon 3 , antoine vieillard-baron 1 1 ambroise paré hospital, boulogne-billancourt, france; 2 ambroise paré hospital, medical icu, aphp, boulogne-billancourt, france; 3 chu limoges, limoges, france; 4 chu brest, brest, france correspondence: guillaume geri (guillaume.geri@aphp.fr) ann. intensive care 2020, 10 (suppl 1):f-049 rationale: right ventricular (rv) failure was defined by rv dilatation with systemic congestion. tricuspid annular plane systolic excursion (tapse) could be of limited value. we report the incidence of rv failure in patients with septic shock, its potential impact on the response to fluids, as well as tapse values. patients and methods: ancillary study of the hemopred prospective multicenter study including patients under mechanical ventilation with circulatory failure. 282 with septic shock were analyzed. patients were classified in 3 groups based on central venous pressure (cvp) and rv size (rv/lv end-diastolic area, eda). in group 1, patients had no rv dilatation (rv/lveda < 0.6). in group 2, patients had rv dilatation (rv/ lveda ≥ 0.6) with a cvp < 8 mmhg (no venous congestion). rv failure was defined in group 3 by rv dilatation and a cvp ≥ 8 mmhg. passive leg raising (plr) was performed. results: 41% of patients were in group 1, 17% in group 2 and 42% in group 3. in group 2 and 3, rv/lv eda was higher than in group 1, 0.7 [0.7; 0.9] versus 0.5 [0.4; 0.5]. cvp was 12 [10; 14.5] mmhg in group 3. a correlation between rv size and cvp was only observed in group 3. higher rv size was associated with a lower response to plr (figure) . a large overlap of tapse values was observed between the 3 groups. 36.5% of patients with rv failure had an abnormal tapse. conclusion: rv failure is frequent in septic shock and alters fluid responsiveness. tapse was not accurate enough to diagnose rv failure. compliance with ethics regulations: yes. rationale: weaning-induced pulmonary oedema (wipo) is a leading cause of weaning failure in high-risk patients (heart failure, copd, obesity). we hypothesized that hypervolemia associated with positive fluid balance facilitates wipo in high-risk patients. patients and methods: in this prospective, observational, singlecenter study, patients with copd and/or heart failure with reduced ejection fraction (< 40%) were studied. exclusion criteria were nonsinus rhythm, severe mitral valve disease and inability to obtain adequate echocardiographic views. echocardiography was performed immediately before and during spontaneous breathing trial (sbt, 30-min t-tube). patients who failed sbt were treated according to echocardiographic results before undergoing a second sbt. fluid balance and body weight were collected at each sbt. shows interesting performance to predict fluid responsiveness in spontaneously breathing patients. nevertheless, measurement sites of inferior vena cava (ivc) diameters remain controversial for that purpose. the aim of the study was to test the accuracy of different measurement sites of civc to predict fluid responsiveness in spontaneously breathingpatients. this study is a post hoc analysis of two prospective cohorts. we included spontaneously breathing patients without mechanical ventilation presenting with sepsis-related acute circulatory failure and considered for volume expansion (ve). we assessed hemodynamic status at baseline and after a fluid challenge (fc) induced by a 30 min-infusion of 500 ml-gelatin 4%. the ivc diameters were measured off-line with ultrasonography using the bi-dimensional mode on a subcostal long-axis view. the civc was calculated as [ (expiratory-inspiratory)/expiratory] diameters during standardized (civc-st) and unstandardized breathing (civc-ns) conditions. breathing standardization consisted of a deep inspiration with concomitant control of buccal pressures and passive exhalation. patients were referred to be responders to fc (i.e. fluid responsive) when the stroke volume increased by ≥ 10%. results: among the 81 patients included in the study, 41 (51%) were responders to fc. the accuracy of civc-st and civc-ns before fc to predict fluid responsiveness differed significantly by measurement sites (interaction p value < 0.0001 and < 0.001, respectively). measuring ivc diameters 4 cm from the junction of the ivc and the right atrium provided the best accuracy to predict fluid responsiveness ( fig. 1 ). at 4 cm caudal to the right atrium, civc-st was significantly better than civcns to predict fluid responsiveness: area under roc curve 0.98 (95% ci 0.97-1.0) versus 0.84 (95% ci 0.78-0.94), p < 0.001. at 4 cm, a civcst ≥ 44% and a civc-ns ≥ 33% predicted fluid responsiveness with sensitivity of 93% and 66%, and specificity of 98% and 92%, respectively. conclusion: accuracy of civc to predict fluid responsiveness in spontaneously breathing patients depends on both measurement sites of ivc diameters and breathing conditions. measuring ivc diameters during a standardized inspiration maneuver at 4 cm caudal to the right atrium is the most relevant mean to optimize civc performance to guide ve. compliance with ethics regulations: yes. rationale: intermittent hemodialysis (ihd) is increasingly used in patients admitted to intensive care unit (icu) with acute kidney injury (aki) requiring renal replacement therapy (rrt). however, this technique is associated with nearly 20% of episodes of perdialytic hemodynamic instability (hi), a common cause of increased morbidity and mortality. at the same time, trans-thoracic echocardiography (tte) has become widely used in intensive care units and is now one of the hemodynamic monitoring methods used daily in the icu setting. patients and methods: search for one or more pre-dialysis tte criteria predictive of perdialytic hi, defined by a systolic blood pressure (sbp) lesser than 90 mmhg or a suddain decrease in sbp of more than 40 mmhg. prospective, observational study of standard care in a medical icu. collection of demographic, clinical and pre-dialysis echocardiographic data from included patients. results: twenty-five patients with a total of 98 sessions of ihd between november 2017 and november 2018 were included in the study. tte was performed for each patient before each ihd session. hi occurred in 31 hemodialysis sessions. in univariate analysis, the existence of prior heart disease (38% vs 0%, p = 0.04), a greater diameter of the left atrium (4.2 vs 3.6 cm, p = 0.0001), a lower cardiac output (5.8 vs 6.6 l/min, p = 0.04), a right dysfunction assessed by lowered tapse and s-wave (16 vs 24 mm, p < 0.0001 and 12.8 vs 15.7 cm/s, p = 0.002, respectively) and an increase in paps (45 vs 34 mmhg, p = 0.003) were significantly associated with the occurrence of perdialytic hi (fig. 1 rationale: several transthoracic echocardiography (tte) parameters of left (lv) and right ventricular (rv) systolic function are available. we compared the ability of these different parameters to track changes in lv or rv systolic function and to detect lv or rv systolic dysfunction in critically-ill patients. in 20 patients (15 mechanically ventilated and 2 with atrial fibrillation), tte examinations were performed before and after i) infusion of 500-ml of saline (n = 10), ii) changes in norepinephrine (n = 8), iii) or in dobutamine (n = 2) dosage. for the lv systolic function, we compared the mitral annular plane systolic excursion (mapse), the systolic (s') peak velocity of the lateral mitral annulus and the global longitudinal strain (glslv) to the lv ejection fraction (lvef), considered as the gold standard. for the rv systolic function, we compared the tricuspid annular plane systolic excursion (tapse), the systolic peak (s) velocity of the tricuspid annulus and the global longitudinal strain (glsrv) to the rv fractional area change (fac), considered as the gold standard. results: after pooling all values, lvef (55 ± 12% at baseline) was better correlated to glslv (r 2 = 0.71) than to mapse (r 2 = 0.25) and s' wave (r 2 = 0.13) (each p < 0.05). the concordance rate between changes (in %) in lvef and in the other parameters of lv systolic function was 87% for glslv, 72% for mapse and 67% for s' wave. both mapse and s' wave could not reliably detect moderate (30% ≤ lvef ≤ 40%) or severe (lvef < 30%) lv dysfunction. conversely, a glslv > − 12% predicted moderate lv dysfunction with a sensitivity of 100% (95% ic: 29-100%) and a specificity of 89% (95% ic: 71-98%) and a glslv > − 9.5% predicted severe lv dysfunction with a sensitivity of 100% (95% ic: 16-100%) and a specificity of 96% (95% ic: 82-100%). after pooling all values, fac (32 ± 11% at baseline) was better correlated to glsrv (r 2 = 0.57) than to tapse (r 2 = 0.31) and s wave (r 2 = 0.24) (each p < 0.05). the concordance rate between changes (in %) in fac and in the other parameters of rv systolic function was 81% for glsrv, 72% for tapse and 50% for s wave.both tapse and s wave could detect rv dysfunction (fac ≤ 35%) with moderate reliability only. conversely, a glsrv > − 12% detected rv dysfunction with a sensitivity of 56% (95% ic: 30-80%) and a specificity of 100% (95% ic: 77-100%). in critically-ill patients, glslv and glsrv seem to be the best tte parameters of lv and rv systolic function. enrolments are still ongoing, which may allow further analysis. compliance with ethics regulations: yes. rationale: passive leg raising (plr), pulse pressure variation (ppv), and the 15-second end-expiratory occlusion test (eexpo) are frequently used to assess preload responsiveness. however, there are conditions in which they are not valid or feasible, which may preclude their applicability in the daily clinical practice. the aim of this study was to estimate the prevalence of such conditions in critically ill patients with acute circulatory failure. between january and april 2019, all patients of a 25-bed medical icu were daily screened and those with acute circulatory failure, defined by norepinephrine infusion or fluid therapy > 1l during the previous 24 h, were included. in each of them, we screened the criteria of validity/feasibility of ppv, plr and eexpo. results: eighty-four patients (78% with septic shock, 8% with cardiogenic shock, 8% with hypovolemic shock, 6% with non-septic vasoplegic shock) were enrolled in the study. among them, norepinephrine infusion was ongoing at the time of enrolment in 95% of the patients whilst 69% were under mechanical ventilation, and 30% with acute respiratory distress syndrome. plr was not applicable in 37% of cases. this was mainly due to venous compression stocking (17% of cases), intra-abdominal hypertension (11% of cases), and either an absence of cardiac output monitoring or impossibility to perform echocardiography (9% of cases). among the 58 intubated patients, ppv was applicable in 16% of cases, including cases with high ppv under conditions generating false negatives (low tidal volume or lung compliance) or low ppv values under conditions generating false positives (spontaneous breathing, cardiac arrythmias). however, ppv was not interpretable in 84% of cases. this was mainly due to low tidal volume ventilation (27% of cases), spontaneous breathing activity (12% of cases), while the remaining non-interpretable cases (51%) had more than one reason. in the 58 intubated patients, eexpo was not applicable in 21% of cases. this was due to impossibility for patients to sustain a 15-s hold of mechanical ventilation in 58% of cases, and either an absence of cardiac output monitoring or the impossibility to perform echocardiography in 42% of cases. plr and eexpo were both valid and feasible in 35% of the patients, and the three tests were all feasible in only 4% of patients. rationale: comorbid association between chronic respiratory diseases and sleep apnea syndrome (sas) revealed frequent with systematic search in icu following icu stay. this association carries prognosis impact depending whether specific treatment is implemented or not. nosas and stop bang scores are proposed for screening of sas in general population. the aim of the present study is to report the prevalence of sas in icu patients admitted for hypercapnic respiratory failure and compare association of nosas and stop bang score with sas severity. the study was conducted between january 2016 and september 2018. patients consecutively admitted in the icu for hypercapnic respiratory failure had calculation of a no sas and stop bang scores at admission. in survivors nocturnal polygraphic records was performed 3 to 4 weeks following icu discharge. the association between the number of apnea-hypopnea episodes, bmi, and clinical variables suggestive of sas, was tested by poisson regression model. results: during the study-period, 65 patients (mean age: 69 ± 9 years, ph 7.29 ± 0.03, paco 2 75 ± 16) were admitted for hypercapnic respiratory failure. non invasive ventilation was used in 85% and death occurred in six patients. polygraphic records were performed in 45 (9 lost to follow-up) mean apnea-hypopnea index was 40 ± 15 with a minimum of 7 and a maximum of 62. poisson logistic regression showed that no sas (p = 0.006) but not stop bang (p = 0.1) was associated with the level of apnea-hypopnea index. rationale: patients with severe acute exacerbations of chronic obstructive pulmonary disease (copd) may benefit from high-flow nasal oxygen regarding its physiological effects and good tolerance. bronchodilator vibrating mesh nebulization through high-flow nasal oxygen circuit has been described to induce similar effect to standard facial mask jet nebulization in stable copd patients. we aim to evaluate whether vibrating mesh nebulization of salbutamol through highflow nasal oxygen circuit is efficient in unstable patients with copd. patients and methods: we conducted a monocenter non-randomized physiological prospective cross-over study, between january and september 2019, including icu patients with severe acute exacerbation of copd and respiratory acidosis treated by salbutamol nebulization. spirometry and airway resistances records were performed after a 3-h wash-out period without bronchodilator, before and after vibrating mesh nebulization of 5 mg salbutamol through high-flow nasal oxygen circuit. the primary endpoint was forced expiratory volume in 1 s after salbutamol nebulization. secondary endpoints included other spirometry parameters, clinical parameters, dyspnea assessed by a borg scale. results: fourteen consecutive patients were included, forced expiratory volume in 1 s increased significantly after salbutamol nebulization through high-flow nasal oxygen (91 ± 111 ml, p = 0.005), as well as forced vital capacity (190 ml ± 193, p = 0.005). airway resistances were not significantly changed after nebulization (− 0.73 ± 1.67, p = 0.08) as well as peak expiratory flow (+ 231 ml ± 439, p = 0.09). no difference was observed on borg scale (p = 0.06) and respiratory rate (p = 0.18) after salbutamol nebulization, while heart rate increased significantly (p = 0.01). discussion: salbutamol nebulization using vibrating mesh nebuliser placed on high-flow nasal oxygen circuit induces a significant but moderate bronchodilation in patients with severe acute exacerbation of copd. moreover, improvement of forced vital capacity after salbutamol nebulization suggests a reduction of dynamic hyperinflation. conclusion: salbutamol vibrating mesh nebulization through highflow nasal oxygen circuit increases significantly forced expiratory volume in 1 s. compliance with ethics regulations: yes. t-piece versus sub-therapeutic pressure support for weaning from invasive mechanical ventilation in patients with chronic obstructive pulmonary disease: a comparative prospective study amira jamoussi, fatma jarraya, samia ayed, takoua merhabene, jalila ben khelil, mohamed besbes abderrahmen mami hospital, tunis, tunisia correspondence: amira jamoussi (dr.amira.jamoussi@gmail.com) ann. intensive care 2020, 10 (suppl 1):f-058 rationale: the best weaning strategy for patients with chronic obstructive pulmonary disease (copd) remains unknown. the spontaneous breathing trial (sbt) represents a crucial step of weaning, but the choice between the t-piece (sv-tube) or the sub-therapeutic setting of the level of pressure support without positive expiratory pressure (psv) is still a matter of debate. we aimed to compare the success of extubation between two groups of copd patients according to the sbt type (vs-tube vs psv). patients and methods: it was a prospective and comparative study, from april 2017 to march 2019, at the abderrahmen mami hospital's intensive care unit (icu). copd patients who underwent invasive mechanical ventilation (mv) for at least 24 h and met the criteria for weaning were included and randomized to sv-tube or psv. a multivariate analysis was performed to determine the association between the sbt modality and the success of extubation (no re-intubation during the 48 h following extubation). results: during the two years' study, 32 patients were included. the mean age was 66 ± 10 years, the sex-ratio was 4.33. weaning process was simple in 16 patients (50%), difficult in 10 patients (31%) and prolonged in 6 patients (19%). fifteen and 17 patients were respectively randomized to the sv-tube and psv groups. the mean duration of mv before randomization was comparable between the 2 groups (sv-tube 6.87 ± 4.3 days vs psv 6.06 ± 4.8 days, p = 0.622). mean weaning time (days) was 3.73 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] for the sv-tube group and 4.35 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] for the psv group. the mean total mv duration (days) was higher in the sv-tube group than in the psv group (15.13 vs 7.65, p = 0.105). the number of re-intubated patients within 48 h following extubation was higher in the psv group (7/17 vs 1/15, p = 0.024) as well as the overall reintubation rate (64.7% vs 20%, p = 0.011). in multivariate analysis, the sbt's trial was independently associated to the success of extubation (or = 0.081, ic [0.008-0.865], p = 0.037) in favor of sv-tube' modality. the median length of stay in intensive care was 16 days [10; 26]. the mortality was higher in the psv group (7/17 vs 2/15, p = 0.08). extubation failure was a factor associated with mortality (or = 8.333, ci [1.392, 49 .872], p = 0.02). conclusion: ventilation weaning was easy in 50% of intubated copd patients. sv-tube as sbt modality was associated to success of extubation in patients with copd. mortality in intensive care was significantly higher in re-intubated patients. compliance with ethics regulations: yes. rationale: non-invasive ventilation has become the mainstay in hypercapnic respiratory failure. delaying intubation and invasive ventilation is associated with a worse outcome in these patients. although a predictive score of niv failure has been validated for hypoxemic respiratory failure no such score exists in hypercapnic respiratory failure. the aim of our study is to compare the performance of two scores in the predictive niv failure hypercapnic respiratory failure. patients and methods: consecutive patients admitted between january 2017 and july 2019 for hypercapnic respiratory failure, were included. hacor score and rox score were calculated in each patient at admission. in patients ventilated non-invasively, the outcome (niv success or failure) was noted. the area under curve (auc) and operative characteristics were computed for both scores. results: during the study-period, 107 out of 133 patients admitted for hypercapnic respiratory failure received niv as the primary ventilatory mode. these patients were mainly men (77/30), had a mean age of 66.7 ± 10 years and had the following pulmonary disease: copd exacerbation 50.5%, obesity-hypoventilation syndrome 18.7%, bronchiectasis 15.9%, and other diseases: 8.4%. niv failure occurred in 39 patients (36.4%) and icu mortality in 18.7%. mean hacor score and rox score were 5.8 ± 3.6 and 18.3 ± 2, respectively. the auc under roc was higher for hacor than rox (0.91 and 0.76 respectively) ( fig. 1 ). the hacor score (cut-off 6) had a sensitivity of 0.93 and specificity of 0.85. conclusion: hacor score seems more accurate in predicting niv failure in hypercapnic respiratory failure. further prospective validation is needed. compliance with ethics regulations: na. rationale: published data on outcomes in respiratory weaning centers are limited and seem to depend on the organisation of healthcare systems and patient case-mix. the weaning center of our university hospital (post intensive care rehabilitation unit) admits for weaning and rehabilitation patients from medical and surgical intensive care units without severe neurological pathologies. the aim of this study was to describe patient's characteristics and outcome (weaning outcomes and survival) and to compare in subgroups according to the initial medical, surgical or cardiac surgical context. patients and methods: we conducted a monocentric retrospective observational study between 01/02/2016 and 30/06/2018. «successful outcome» was defined by the association of survival and weaning from invasive ventilation. factors associated with evolution were investigated by uni-and multivariate analysis. survival after discharge was analysed according to the initial context and according to the type of ventilation at discharge. results: among 215 patients included, 167 (77.6%) had a successful outcome with high use of non-invasive ventilation (niv) (37%). respiratory history (p = 0.02), female gender (p < 0.001), igs2 score at admission to the srpr (p = 0.001) and non-cardiac surgical setting (p < 0.012) were associated with an adverse course. the 6-month survival rate was 84% in discharged patients. the outcome was not different in the tree subgroups. niv rate at discharge was high in the subgroup of cardiac surgery patients. a multidisciplinary and personalised approach by a specialized weaning unit can provide a successful service model for patients who require liberation from prolonged invasive mechanical ventilation. compliance with ethics regulations: yes. rationale: high-dose insulin euglycemic therapy (hiet) is recommended as first line therapy for calcium channel blockers (ccbs) poisoning because of its inotropic effect. our first objective was to study its hemodynamic impact. we performed a retrospective cohort study of all consecutive patients admitted for ccbs poisoning treated with hiet, in one icu at the university hospital of lille between january 2013 and july 2018. the hemodynamic impact was studied through mean arterial pressure (map), vasoactive-inotropic score (vis) and map/vis ratio during the 24 h following hiet initiation. metabolic parameters were also collected. results: 104 patients admitted for ccbs poisoning. 43 patients treated with hiet in icu (7 patients without circulatory shock, 5 patients with shock after hiet and 31 patients with shock at baseline before hiet). among shocked patients at baseline (n = 31), no hemodynamic improvement was found except an increased map/vis ratio at h24 (p < 0.05). on the contrary, an initial worsening of vis (137 [ rationale: ketamine is used in the induction and maintenance of general anesthesia. recently, there were concerns regarding its liver toxicity. we conducted a study to investigate the link between ketamine use and liver dysfunction (ld) in intensive care unit (icu) patients. patients and methods: data were extracted from the [anonymized] study, a randomized controlled trial designed to evaluate the effect of cisatracurium on 90-day mortality rate in moderate and severe acute respiratory distress syndrome (ards) patients. the main endpoint was the occurrence of a ld defined as a total serum bilirubin superior or equal to 33 micromol/l. a matched case-control cohort was created: cases, receiving at least 1 day of continuous ketamine infusion, were paired 1 for 1 with controls according to treatment with cisatracurium, hepatic and cardiovascular sofa sub-score, total serum bilirubin level at the time of inclusion, age, sex, ards from septic origin, shock anytime after inclusion. an analysis was also made on the whole cohort comparing the patients receiving at least 1 day of continuous ketamine infusion to all patients who did not fulfill this criterion. results: 66 cases were identified and matched to 66 controls. in the ketamine group, the median ketamine duration was 5 (3-8) days, and median total cumulative dose 18.6 (9.6-42.5) g. the occurrence of ld was higher in the ketamine group than in the matched control group (53.8% versus 28.6%, p = 0.002, fig. 1 ). the hazard ratio (hr) for ld in the ketamine group was 2.03 (95% ci 1.15-3.59, p = 0.015). there was an increased risk of ld of 5.9% per day of exposure to ketamine (hr 1.06, 95% ci 1.02-1.1 p = 0.003) and of 0.8% per gram of ketamine infused (hr 1.01, 95% ci 1.00-1.01, p = 0.006), with a risk starting to be statistically significant after 4 days and 18gr. in multivariate analysis on the whole cohort, ketamine exposure (hr 2.49, 95% ci 1.40-4.44, p = 0.02), cumulative dose in gram (hr: 1.02, 95% ic: 1.01-1.04, p = 0.002) and ketamine exposure in days (hr: 1.16, 95% ic: 1.07-1.25, p < 0.001) remained independent risk factors for ld occurrence. conclusion: ketamine use in critically ill patients treated for ards is associated to a higher risk of liver dysfunction, assessed by total serum bilirubin. this risk is dose-dependent and increases with duration of treatment. the prescription of high doses or prolonged treatment with ketamine should probably be avoided in critically ill patients. compliance with ethics regulations: yes. rationale: ciguatera is one of the most common cases of marine poisoning associated with fish consumption in the world. the incidence of this intoxication is largely unreported. in martinique, the incidence of this intoxication seems constantly increasing. during the last 3 years, numerous cases of large collective poisonings have been reported in martinique, especially during summer. the spectrum of clinical manifestations is large including gastrointestinal, neurological andcardiovascular symptoms. ciguatoxin, the toxin responsible for ciguatera fish poisoning is considered as a sodium channel agonist with cholinergic and adrenergic activity. it is rarely fatal and management of poisoned patients is essentially based on supportive care. the objective of this study was to describe the clinical characteristics and complications of ciguatera poisoning in martinique, focusing on the cardiovascular ones. observational, retrospective, single-center study covering six-year period from october 2012 to september 2018, including all patients admitted to the emergency department of the university hospital of martinique (chu), and all patients who were declared to the regional health agency (ars) for ciguatera intoxication. results: one hundred and forty-nine patients (149) who were ciguatera-affected were included. the incidence rate found was to be 0.67 cases per 10.000 patient-years in martinique over the period. about 90% of patients had gastrointestinal symptoms such as nausea, vomiting, diarrhea, or abdominal pain; 83% neurological disorders and 42% cardiovascular symptoms including, bradycardia, hypotension and interventricular block. ingestion of carangue fish was related to a major risk of chronic signs. conclusion: the incidence of ciguatera in martinique is increasing, with 0.67 cases/10.000 patient-years. the clinical presentation is defined mainly by digestive signs, followed by peripheral neurological disorders and cardiovascular symptoms. ciguatera fish poisoning in martinique presents similar clinical presentation to that of the other caribbean islands. there is no specific treatment. acute ciguatera poisoning is responsible for significant cardiovascular complications. physicians should be aware of the potential cardiovascular risk of ciguatera poisoning. compliance with ethics regulations: yes. rationale: pesticides have represented the most incriminated products in severe acute poisonings, in the developing countries, due to the availability of these products. organophosphate poisoning accounts for 3 million poisonings/year worldwide. organophosphate (op) pesticides are used mainly as insecticides in agriculture. the moroccan anti-poison and pharmacovigilance centrer shows that op poisoning are responsible for 13% of all poisonings combined. the aim of our study: epidemiological, clinical, management and prognostic factors. patients and methods: a retrospective study was conducted on patients with op poisoning admitted to our nine-bed medical intensive care unit between january 2018 and december 2018. inclusion criteria were: all patients over 16 years of age and the exlusion criteria were: pesticide poisoning other than op, alcohol poisoning, drug poisoning, scorpionic poisoning and snake bites. statistical analysis was performed with spss software. results: forty patients were admitted for acute op poisoning. in morocco, organophosphores are available over-the-counter in several forms: rodentocides, malathion, cockroach trap, baygon insecticide ( fig. 1 ). the average age was 26 years with a female prévalence of 74.1%. the intoxications were mostly intentional (85%). the symptomatology was determined by the three syndromes: central syndrome in 50%, muscarinic syndrome in 69%, nicotinic syndrome in 10%. rhythm disorders in 8%, and cardiovascular collapse in 9%. the symptomatic treatment was applied to all patients, antidotic treatment was administered in 80% of patients. the average length of hospitalization was 06 days. conclusion: acute op poisoning is a real public health problem. its associated symptomatic treatment (respiratory and neurological resuscitation) and antidotic treatment. the mortality remains high in our context, therefore, we must attach great importance to the prevention. compliance with ethics regulations: yes. (1). over an 8-month period, health officials in guadeloupe and martinique reported more than 12.000 such cases. assault of these brown algae represents not only an environmental and economic disaster, but also a threat for human health. after 48 h on seashore, large amounts of toxic gas are produced by matter decomposition, including hydrogen sulfide (h2s) and ammoniac (nh3). the acute effects on humans after exposure to high concentrations of h2s are well described and of increasing severity with concentration, leading to potentially fatal hypoxic pulmonary, neurological and cardiovascular injuries (table 1) ; however, the association of long-term exposure to sargassum and health events is unknown. although less documented, long term exposures may result in conjunctiva and upper airways irritation, headaches, vestibular syndrome, memory loss, and modification of learning abilities. in the absence of any available antidote, management of h2s intoxication relies on supportive care and prevention using individual protection. the objective of this study was to evaluate the clinical characteristics and consequences of long-term exposure to sargassum among the local population. we conducted a prospective observational cohort study including all patients admitted to the emergency department at the university hospital of martinique from march 2018 to december 2018 due to exposure to sargassum. patients were managed according to the protocol established by the research group on sargassum in martinique. we assessed the patients exposure to sargassum and air pollutants using 14 monitor located near of the patient's residence. demographics and clinical data (including cardiovascular, neurological and respiratory events) were collected. data are presented as mean ± sd or %.comparisons were performed using univariate analysis. results: in 8 months, 160 patients were included (age: 48 ± 20 years, 54 m/146 w, past history: hypertension (n = 25), diabetes (n = 29), asthma (14). patients arrived with referral letter from their general practitioner (80%) and presented headaches (76%), developed gastrointestinal disturbances (79%), dizziness (54%), skin lesions (30%), cough (44%) and conjunctivitis (33%). not all patients were clinically symptomatic. in the patients presented in june (14%), symptoms more frequently occurred in the workplace or at home (p < 0.05). initial lung function tests were normal (50%). three patients were admitted in intensive care unit. conclusion: our study indicates that the magnitude of health effects following long-term exposure to sargassum may be larger than previously recognized. efforts to limit long-term exposure are mandatory. compliance with ethics regulations: yes. rationale: liver consequences of out-of-hospital cardiac arrest (ohca) have been poorly studied. the aim of this study was to describe the characteristics of ohca-induced acute liver dysfunction and its association with outcomes. we analyzed all consecutive ohca patients admitted to two academic centers between 2007 and 2017. patients treated with vitamin k antagonist were not included. acute hepatocellular insufficiency (ahi), liver failure (lf) and hypoxic hepatitis (hh) were defined as a prothrombin (pt) ratio < 50%, a hepatic sofa sub-score > 2 and an increase in transaminases > 20 times the normal values, respectively. indocyanine green (icg) clearance was used as the reference measure of liver function in a subset of patients. multivariate logistic regression was used to identify potential risk factors for day 28 mortality. rationale: neuron-specific-enolase (nse) is commonly used as a biomarker reflecting the extent of brain injury in different settings. in post-cardiac arrest patients, previous clinical studies reported that an increase in nse was predictive of a poor outcome but did not specifically focused on neurological outcome. in this prospective study, we aimed to determine the nse performance for prediction of severe brain damage in post-cardiac arrest patients. patients and methods: all consecutive patients admitted in our icu after cardiac arrest between january 2017 and february 2019 that were still comatose at h48 and had at least one measurement of serum nse were included. blood samples for nse measurement were serially collected at 48 (h48) and 72 h (h72) after cardiac arrest and serum nse levels were measured within 4 h. we used the following criteria for the definition of severe brain damage (primary endpoint): cerebral performance categories (cpc) 3 or 4 level at discharge, brain death or withdrawal of life-sustaining treatments (wlst) based on neurological status. we also assessed the predictive value of serum nse using allcause mortality as a secondary endpoint. results: during the study period, 155 patients were available for the analysis. they were mostly male (66.9%), with an age of 60.6 years. among these patients, 83 (50.3%) had a good neurologic outcome (cpc 1-2) and 68 patients were classified as having a severe brain damage (52 wlst based on neurological status, 11 brain deaths and 5 survivors with . in univariate analysis, patients with severe brain damage less frequently received bystander cpr, had longer duration of no-flow, less initial shockable rhythm, more post-resuscitation shock and higher nse values: mean at h48 were 217.3 versus 26.2; and 270.1 versus 21.4 at h72 (p < 0.001). nse levels at h48 and h72 were strong predictors of severe brain damage (auc of 0.948 and 0.972 respectively, figure 1 ) and also predicted all-cause mortality (auc of 0.896 and 0.931 respectively). to predict severe brain damage with 100% specificity, best nse cutoff values at h48 and h72 were 52.3 and 53.2 µg/l, with a sensitivity of 77.6 and 82.9% respectively. conclusion: a high serum nse measured at h48 and h72 after cardiac arrest accurately predicted severe brain damage with a high specificity. our results support the use of nse for neuroprognostication after cardiac arrest, in combination with other predictors. compliance with ethics regulations: yes. rationale: the psychological care of patients, their relatives and of healthcare workers is a major issue in the intensive care unit (icu). psychologists may provide emotional support during trying times. the intervention of a psychologist may alleviate long term mental health issues such as post-traumatic stress disorder. the main objective of our study was to describe the availability of psychologists in french-speaking icus. patients and methods: internet survey conducted between march and may 2019 using surveymonkey (san mateo, usa). survey consisting of 20 questions sent to subscribers of the srlf mailing list via mailchimp software (atlanta, usa). frequencies and percentages were determined for categorical variables and median and interquartile range for continuous variables. the icus with or without psychologist were compared using nonparametric fisher exact test. stata 14 used (lakeway drive, te, usa). results: 263 responses were obtained from 197 unique icus in france (n = 182), belgium (n = 6), switzerland (n = 5), algeria (n = 2), morocco (n = 1) and tunisia (n = 1). 164 (82%) icus were part of public hospitals, 33 (18%) of private facilities. 187 (94%) icus cared for adult patients, 10 (6%) for children. the median number of beds was 20 [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] . 79 (40%) icus were open to visitors 24/7, 46 (23%), to visitors > 8 h/day and 72 (37%) to visitors < 8 h/day. psychological consults were established in 89 (45%) wards (2 icus did not answer). pediatric icus employed more psychologists than adult icus (p = 0.006). comparison of icus based on the presence or not of a psychologist appears in table 1 . in icus where a consulting psychologist is available, their effective availability is 0.5 [0.2-1] full time equivalent. consults are delivered to: patients (100%), families (100%) or healthcare workers (60%). out of the 106 icus without a psychological consult, responders from 5 (2.5%) icus believe that a psychological consult is undesirable. out of the 106 icus without psychological consult, 24 (22%) responders cannot obtain a psychological consult, whatever the circumstances, 41 (39%) can require an outside psychological consult when needed, while 41 (39%) can require assistance from a psychologist working in another unit (several answers possible for each respondent). conclusion: psychologists consult in only half of adult icus but in almost all pediatric icus. 22% of icus are unable to provide a psychological consult. psychological consults are delivered in similar proportions to patients, their family and to a lesser extent to healthcare workers. responders from 2.5% icus without an established psychological consult believe that the availability of a psychologist is undesirable. compliance with ethics regulations: na. rationale: comfort of patients in intensive care unit (icu) is now a real concern for the healthcare teams. perceived patient discomfort assessment is a daily practice for our staff. the primary objective of our study was to assess whether the overall discomfort score reported by patients hospitalized in a separate intermediate care unit differs from that reported by patients hospitalized in icu. a tailored multicomponent program consisting of assessment of icu-related self-perceived discomforts with a 18-item questionnaire, immediate and monthly feedback to healthcare teams and site-specific tailored interventions, was applied in our department, located in a general hospital, and comprising a 12-bed icu and a separate 6-bed intermediate care unit rationale: the transition period surrounding the discharge from icu to hospital ward is a critical period in the course of the patient. handoff of complex patients is at high risk for communication failures between providers, inaccurate cares and icu readmission. a transition program including a post icu follow-up has been proposed to improve handoff quality. post icu consults by icu team represent, also, an opportunity for improving feedback on the quality of icu cares. the goal of the present study is to assess the feasibility and the impact of a systematic early post-icu consult (epicuc) program on handoff quality in a 14 bed mixed icu. patients and methods: before the development of the epicuc program, standardized handoffs were already applied including identified day and hour of discharge and both verbally communicate and written medical and nurse information for receiving team. from 1st march to 30th october 2019, all patients who were discharged to the ward of our hospital were candidates for epicuc. epicuc were performed by icu staff (at least one icu physician) within the 3 days following discharge. the epicuc consisted of a face-to-face discussion with the receiver team to assess the accuracy, completeness and understanding of passing information and of a patient visit. a standardized form was used for collecting data. the impact of epicuc on handoff quality was assessed by the number of communication failures and the number of patients in whom epicuc resulted in a management change. personal feeling of epicuc providers on its usefulness was assessed by a 0-10 rating scale. results: among the 209 candidates for epicuc, 4 were dead and 74 already discharged alive from hospital at epicuc time. epicuc were performed in 131 patients (63%) within 4 ± 3 days after icu discharge. 85 epicuc (65%) were performed by both, nurse and icu physician. 111 (85%) patients and 84 receiver teams (64%) were available at epi-cuc time. epicuc duration was 11 ± 4 min. a communication failure was identified in 38 epicuc (29%), either a rectification of passing information (n = 30; 23%) and/or a change in patient management (n = 19; 15%). the usefulness of the epicuc was rated at 4 ± 3 and 5 ± 3 by icu physicians and nurses, respectively. conclusion: the time spent for epicuc appears reasonable. epi-cuc identified a communication failure in one-third of handoffs and allowed care readjustment in one quarter of patients. factors associated with handoff failures will be presented during the congress. compliance with ethics regulations: yes. rationale: surviving a critical illness is a challenging condition for patients and relatives. the psychological aspects are directly affected by physical status and performance. patients can feel depressed or anxious facing difficulties during recovery time. the aim of this study was to correlate patients' perceptions of his health status and his clinical performance measured after icu discharge. patients and methods: this is a prospective pilot study of an icu follow-up clinic conducted in a single center from january 2018 to july 2019. this clinic is multidisciplinary and includes two visits at 3 and 6 months after icu discharge. patients with more than 5 days of icu los were eligible. all patients at 3 and 6-m visit were evaluated with sf-36, 6mwt, mrc and time-up-and-go test. we conducted an analysis comparing clinical performance data and qualitative data between 3 and 6 months after icu discharge. the investigation included 90 patients who had at least 5 days of icu length of stay. 50 patients attended the consult at 3-m and 28 patients attended the consult both times. the median age (iqr) was 63 (54-71) and 56% were men. 48%, 30% and 22% of patients had medical, scheduled surgical and emergency surgical admission causes respectively, with median (iqr) saps iii score 53 (44-73). 38%, 14% and 80% of patients had sepsis, delirium and mechanical ventilation as a support. the physical status was progressively increased overtime likewise the physical capacity assessed by sf-36 score with p-value 0.007 between 3 and 6-m. however, no significant difference between the subjective dimension of sf-36, which analyses the perception of the patient about his physical capacity, assessed at 3-m and at 6-m was demonstrated (p 0.35). in this pilot-phase of following a cohort of critically ill patients, the natural physical improvement does not seem to change the patient's perception of their performances. this paradigm rouses a different perspective that should take into account when setting up rehabilitation programs. compliance with ethics regulations: yes. post-traumatic stress disorder after discharge from an acute medical unit basma lahmer 1 , naoufel madani 1,2 , jihane belayachi 1,2 , redouane abouqal rationale: post-traumatic stress disorder (ptsd) occurs after exposure to a traumatic event and comprises of symptoms of repeated re-experiencing of the said event, avoidance of reminders, emotional numbing and persistent hyperarousal. in individuals exposed to "medical stress", various studies found evidence of ptsd occurring after the onset, diagnosis, or treatment of physical illness. our study aims to determine ptsd's risk factors in patients of an acute medical unit (amu) after their discharge. patients and methods: it was a prospective, analytical study conducted over a period of 2 months at an acute medical unit. we collected sociodemographic and clinical data, patients' medical history, and evaluated the symptoms of anxiety and depression during their stay using the hospital anxiety and depression scale (hads). the prevalence of severe ptsd symptoms was assessed with the impact of events scale-revised (ies-r) at 6 weeks and 3 months using a cutoff of 33. associations between ptsd as evaluated by ies-r at 3 months and patients' characteristics, including hads scores at admission were investigated using unadjusted linear regression, for univariate and multivariate regression analysis. statistical analyses were carried out using spss for windows (spss, inc., chicago, il, usa). we included 141 patients in our study with a mean age of 49.74 ± 17.8. in our population, 20.8% of patients scored higher than a 33 ies-r cutoff at 6 weeks compared to 17.6% at 3 months. the mean hads-anxiety score is 7.8 ± 6 and that of the hads-depression score is 7.1 ± 6.3. on one hand, higher hads-anxiety score during the stay in the amu was linked to higher ies-r scores at 3 months β: rationale: objective of critical care includes restoration of functional capacities. prompt identification of muscle acquired weakness (icu-aw) is crucial to target efficient rehabilitation. in published literature, data of quadriceps strength (qs) cannot be compared because of insufficient standardization of measurement protocols. we recently validated a highly standardized protocol of qs measurement. in order to build basic and comparable knowledge and to identify the weakest patients, this study aimed to describe qs of critically ill (ci) patients during their short-term evolution, and to compare them to surgical (s) and healthy (h) subjects. patients and methods: this observational study included ci patients who spent at least 2 days in icu, patients scheduled for elective colorectal surgery (s) and young healthy volunteers (h). maximal isometric qs was assessed using a handheld dynamometer (microfet2 ® ) and expressed in newton/kg (n/kg). dominant leg was tested in supine position using a highly standardized procedure. ci and s patients were tested at t0 (as soon as collaborative in icu) and 1 month after discharge (m1 rationale: the post intensive care syndrome (pics) gathers various disabilities, associated with a substantial healthcare use. however, patients' comorbidities and active medical conditions prior to intensive care unit (icu) admission may partly drive healthcare use after icu discharge. to delineate the relative contribution of critical illness and pics per se to post-critical illness increased healthcare use, as opposed to pre-existing comorbidities, we conducted a population-based evaluation of patients' healthcare use trajectories. patients and methods: using discharge databases in a 2.5-million-people region in france, we retrieved, over three years, all adult patients admitted in icu for septic shock or acute respiratory distress syndrome (ards), intubated at least 5 days and discharged alive from hospital. healthcare use (days spent in healthcare facilities) was analyzed two years before and two years after icu admission. healthcare trajectories were next explored at individual level: patients were assembled according to their individual pre-icu healthcare use trajectory by clusterization with the k-means method. results: eight-hundred and eighty-two (882) patients were included. median duration of mechanical ventilation was 11 days (interquartile ranges [iqr] 8; 20), mean saps2 was 49, and median hospital length of stay was 42 days (iqr 29; 64). prior to icu admission, we observed, at the scale of the whole study population, a progressive increase in healthcare use. however, clusterization of individual according to pre-icu healthcare trajectories identified patients with elevated and increasing healthcare use (n = 126), and two main groups with low (n = 476) or no (n = 251) pre-icu healthcare use. patients with high healthcare use had significantly more comorbidities than those with low healthcare use. in icu, however, saps2, duration of mechanical ventilation and length of stay were not different across the groups. interestingly, analysis of post-icu healthcare trajectories for each group revealed that patients with low or no pre-icu healthcare (which represented 83% of the population) switched to a persistent and elevated healthcare use during the two years post-icu. conclusion: for 83% of ards/septic shock survivors, critical illness appears to have a pivotal role in healthcare trajectories, with a switch from a low and stable healthcare use prior to icu, to a sustained higher healthcare recourse two-years after icu discharge. this underpins the hypothesis of long-term critical illness and pics-related quantifiable consequences in healthcare use, measurable at a population level. compliance with ethics regulations: yes. (1) to describe the pre-hospital grading protocol developed by the northern french alps emergency network (trenau) for children, (2) to evaluate its quality to detect the most severe trauma patients and (3) to assess the accuracy of this procedure to perform an adequate triage. patients and methods: our regional trauma system included 13 hospitals categorized as level i, ii or iii pediatric trauma centers. eachpatient was graded a, b or c by an emergency physician, according to the seriousness of their injuries at presentation on scene. the triage was performed according to this grading and the categorization of centers. this study is a registry analysis of an 8-year period (2009 to 2017). results: a total of 1142 children (mean age 10 years, 65% were boys) with severe trauma were included in the cohort. fifty-seven, 22% and 21% of patients were admitted to a level i, ii and iii, respectively. road accident was the main mechanism of injury (35% of patients). thirtysix percent of patients had a severe trauma, defined as an injury severity score (iss) higher than 15. one quarter of patients had at least 2 severe lesions and one-third of patients had a trauma brain injury. the pre-hospital gradation was closely related with injury severity score (iss) and intra-hospital mortality rate. the triage protocol had a sensitivity of 78% and a specificity of 33% to predict adequate admission of patients with iss more than 15. using a specific trauma score (including occurrence of death, an admission in intensive care unit and the need for urgent surgery), sensitivity and specificity reached 91 and 41%, respectively. fourty-six percent of patients were not graded at the scene (non-graded group). undertriage rate was significantly reduced in the graded group compared with the non-graded group, (22% versus 45%), without significant modification of the overtriage rate (43% versus 45%). overall, mortality at discharge from hospital was 2%, but 33% in grade a patients. conclusion: implementation of a regional pediatric trauma system with a specific pre-hospital triage procedure was effective in detecting severe pediatric trauma patients and in lowering the rate of prehospital undertriage. compliance with ethics regulations: yes. rationale: critically ill children suffer from pathophysiological changes, leading to large between-subject variability in drug clearance. since piperacillin is eliminated mainly via the kidney, changes in renal function go along with a modified elimination, and possible subtherapeutic or toxic drug concentrations. we aimed to determine the most accurate glomerular filtration rate (gfr) estimation formula for assessing piperacillin clearance in critically-ill children. patients and methods: all children hospitalized in pediatric intensive care unit and receiving piperacillin were included. piperacillin was quantified by high performance liquid chromatography. pharmacokinetics were described using the non-linear mixed effect modeling software monolix. in the initial pharmacokinetics model, gfr was estimated according to the schwartz 1976 formula. in the study, gfr was estimated with 11 additional formulas, developed with plasma creatinine and/or cystatin c. biases, precisions, spearman's rank correlation coefficient and normalized prediction distribution error (npde) were used to assess the models. results: we included 20 children with a median (range) postnatal age of 1.9 (0.1-19) years, body weight of 12.5 (3.5-69) kg and estimated gfr according to the schwartz 1976 formula of 160.5 (38-315) ml min-1.1.73 m 2 . piperacillin concentrations were best predicted with the model using the creatinine clearance. the correlations were most accurate: r2 = 0.7 between the population-predicted and the observed concentrations, r2 = 0.0004 and r2 = 0.04 for the npde versus population-predicted concentrations and time, respectively. concerning the individual predicted concentrations, bias and precision were respectively − 4.1 mg l −1 and 14.7 mg l −1 . gfr estimations based on serum creatinine were higher than those based on cystatin c (p = 0.02). conclusion: in summary, the 12-h creatinine clearance is the best predictor of piperacillin clearance and this could be investigated for drugs with renal elimination. as a whole, literature and our findings strongly suggest using creatinine clearance to also estimate gfr in critically ill children. the gap between the gfr estimations is large depending on the formulas, with higher estimations with equations based on serum creatinine. compliance with ethics regulations: yes. rationale: acute pancreatitis (ap) incidence have increased dramatically over the past years. new guidelines in 2018 were recently published in order to standardize the definition and management of ap. the aim of this study is to describe the management of children that were diagnosed with ap from the pediatric intensive care unit (picu) in two french hospitals. patients and methods: this retrospective cohort study included children aged under 18 years old, who were admitted to the picu of robert-debré hospital and trousseau from 2006 to 2018 with a discharge diagnosis of ap. data collected included management, severity and outcomes. we have also obtained data on clinical, biological and radiological presentation. results: sixty patients were included, the median age was 8 years (5-14) and 75% had a co-morbidity mainly hematologic (26/60). most of the ap were moderate (52%) or severe (45%). hemodynamic failure was the main reason for picu admission requiring a median fluid resuscitation 56 ml/kg complemented by a median intravenous fluid therapy of 4 ml/kg/h (2-5) during the first 24 h. twenty patients (37%) required mechanical ventilation. fasting has been instituted in 59 patients (98%) for a median of 4 days (1-6), whereas 54 patients (90%) received parenteral nutrition, only 18 patients (30%) received enteral nutrition. antibiotic therapy was given to 53 patients (88%) including 13% for curative therapy. the median length of stay in picu was 4 days (2) (3) (4) (5) (6) . the mortality rate was 13%. conclusion: this is the first french study which precisely described the management of patients with ap in picu. it highlighted the differences withthe new international guidelines. this study could improve the management of pa in picu and open research perspectives. compliance with ethics regulations: yes. rationale: apheresis and therapeutic plasma exchange (tpe) for children diseases has been poorly investigated in mostly small-uncontrolled studies. the purpose of this study is to describe indications and safety of tpe in children. patients and methods: in this single center and retrospective study, we included 94 patients who underwent tpe with an age < 18 years old in the pediatric center of necker-enfants-malades hospital from january 2005 to december 2014. data were retrospectively collected in an electronic case report form via a web-based data collection system. results: 78 patients with a median age of 9.8 years [range 0.53; 17.93] were selected. they achieved a total number of 731 procedures. indications were antibody-mediated rejection (n = 33; 42%) or desensitization therapy (n = 5; 6%) for solid organ or hematopoietic transplantations; microangiopathy (n = 17; 22%); renal diseases (n = 6; 8%) and pediatric inflammatory diseases (n = 16; 21%); or hyperviscosity syndrome (n = 1; 1%). each patient had an average of 6 procedures for the first session [range 1; 19] with a median volume of 1834 ml [range 500; 5000 ml] corresponding to a median (rang) total plasma volume (tpv) equivalent of 1.39 l/m2 [0.58-2.1]. within 15 days since the beginning of sessions, 72 patients (92%) present a total of 311 adverse events (aes) potentially related to tpe. there was a median (range) of 5 aes/patients [0-24]. there was no association between aes and diseases, severity of patients, venous access, plasma substitute and body weight. few of aes (n = 23 for 72 patients) were potentially life-threatening and concerned mostly critically ill children. allergic reactions represented only 20 aes for 14 patients (grade i n = 18; grade ii n = 1; grade iii n = 1). at the 12 months endpoint, 15 (19%) patients died and 10 (13%) patients had severe persistent disease. no death had been related to the tpe process. we describe one of the largest retrospective pediatric cohort updated to the last international recommendations. tpe in children is performed for specific and potentially refractory disease. it is feasible without a major risk of life threatening adverse events. compliance with ethics regulations: yes. yacine benhocine university hospital nedir mohamed, tizi-ouzou, algeria correspondence: yacine benhocine (yacine001@yahoo.fr) ann. intensive care 2020, 10 (suppl 1):f-080 rationale: although analysis of literature data shows that implantable chamber catheters (iccs) are less at risk of infectious complications than other central venous catheters, these complications can be serious, which may differ from ongoing treatments such as chemotherapy, and may lead to the removal of the implanted device. the literature on preventing these infections is quite disparate, as practices. purpose: to evaluate the incidence of infections, to identify responsible germs and to measure the impact of preventive measures. patients and methods: prospective, descriptive, mono-centric study, from january 2012 to january 2019. all patients under the age of 15 who have benefited from an implantable chamber catheter, whose insertion procedure is as follows: local anesthesia, surgical asepsis (polyvidone iodine) in an operating room, double disinfection, no antibiotic prophylaxis, routes used: subclavian (89%), internal jugular (11%) by anatomic registration. the main criteria of judgment are: the incidence of local and general infections, their time of onset, responsible microorganisms. statistical analysis used the statistical package for the social sciences software. results: 4480 patients were included, the average incidence density of early infection is 0.61/1000 day-catheters. the time of onset of infection is essentially between the 2nd and 3rd week post-exposure, of which 20% is general infection. ablation involved 52% of infected catheters. the causative organisms are mainly gram-positive cocci (67.99%), gram-negative bacilli are less involved (23.33%), with a significant number of candida infections (8%). discussion: higher incidence of data from the literature. to remedy this requires the implementation of additional hygiene measures: antiseptic showers preoperatively, chlorhexidine??, and practice changes: echo guidance, antibiotic prophylaxis or locks? second generation catheters? our practices are disparate especially since the recommendations specifically concerning the prevention of infectious risk associated with internationally published iccs are rare. conclusion: at the end of this work, our perspectives are to: update the procedure, highlight risk factors on which it is possible to act, the adhesion of the different staff to the protocols. compliance with ethics regulations: yes. rationale: the 2014 sepsis and septic shock pediatric guidelines advise to treat patients using care bundles. in the first hour, the «resuscitation bundle» contains an appropriate fluid resuscitation, a broad-spectrum antibiotics administration after blood cultures, and initiation of inotrope if needed. the objectives were to evaluate the resuscitation bundle compliance in a cohort of septic children with cardiovascular dysfunction, and to analyze the effect on severity and outcome in pediatric intensive care unit (picu). patients and methods: retrospective analysis of the diabact iii study. this study analyzed the care course of children with severe community-acquired bacterial infection, hospitalized in picus in france's west departments, between august 2009 and january 2014. children with severe sepsis and cardiovascular dysfunction were retrospectively included. results: we included 92 children of whom 6 (6.5%) had compliant bundled care. the severity scores at picu's admission were similar between groups (p = 0.55 for the prism score and 0.58 for the pelod 2). there was the same proportion of fluid-refractory shock (p = 0.65), mechanical ventilation (p = 1.0), neurological dysfunction (p = 1.0) and cardiac arrest (p = 0.39). in the «resuscitation bundle compliant» group, 33.3% died versus 15.1% in the other group (p = 0.46). we highlighted a severity bias: the sickest patients were more likely to receive compliant bundled care. conclusion: in our cohort, the resuscitation bundle's compliance was low. we did not show some effect on morbidity nor mortality. however, this study helps understand the factors associated with resuscitation bundle's compliance. rationale: nosocomial infections with extended-spectrum β-lactamase (esbl) producing gram-negative bacilli (gnb) are an important cause of hospital morbidity and mortality. the objective of this study was to determine the incidence and risk factors of nosocomial esbl-producing gnb infections in a paediatric intensive care unit (picu). patients and methods: a prospective surveillance study was performed from january 2015 through march 2019 in a picu. all patients hospitalized for more than 48 h were included. centers for disease control and prevention criteria were applied for the diagnosis of nosocomial infection. results: during the study period, 1783 patients (median age: 12 ± 434 days) were included. the average length of stay was 9 ± 11 days with a total of 15,980 days of hospitalization. newborns accounted for 61.8% of patients. sixty-two per cent of patients were colonized with multi drug resistant gram-negative rods, on admission or during their stay in the picu. one hundred and nineteen bacterial infectious episodes were registered (7.4/1000 patient days). one hundred infectious episodes were caused by a gnb and 44 (36.9%) by esbls producing gnb with an incidence of 2.7/1000 patient days (bloodstream infections: 21 episodes, ventilator acquired pneumonia: 16 episodes). esbls producing gnb infection had a specific incidence of 10.9 per 1000 catheter-days, and 2.3 per 1000 mechanical ventilation-days. fifty-nine percent of patients infected with esbls producing gnb had a prior digestive colonization with a multidrug-resistant gnb. forty-one episodes (93%) occurred in patients with central venous catheters. klebsiella pneumoniae was the most frequently isolated bacteria (45.4%). mortality in the esbls producing gnb group was high (29.5%). associated factors of nosocomial esbls producing gnb infection were mechanical vrntilation (p < 0.001), central venous catheterization (p < 0.001) and colonization with multiple drug-resistant gram-negative bacteria (p < 0.001). conclusion: nosocomial esbl-producing gnb infection had an incidence of 2.7 per 1000 patient days in our unit and seems to increase the mortality rate. factors associated with this infection were identified. marie lemerle 1 , aline schmidt 2 , valérie thepot-seegers 3 , achille kouatchet 1 , valérie moal 4 , mélina raimbault 5 , corentin orvain 2 , jean-francois augusto 6 , julien demiselle 1 1 chu angers, médecine intensive réanimation, angers, france; 2 chu angers, maladie du sang, angers, france; 3 chu angers-ico, angers, france; 4 chu angers, pharmacie, angers, france; 5 chu angers, labora-toire de biochimie, angers, france; 6 chu angers, néphrologie dialyse transplantation, angers, france correspondence: marie lemerle (marielemerle@yahoo.fr) ann. intensive care 2020, 10 (suppl 1):f-083 rationale: acute kidney injury (aki) is associated with high morbidity and mortality in the setting of tumor lysis syndrome (tls). thus, strategies aimed at preventing aki occurrence represent a major goal to improve prognosis of patients with tls. the role of hyperphosphatemia as a risk factor of tls has been poorly analyzed. the aim of this study was to study the association between hyperphosphatemia and aki, and to determine whether a cut-off value of phosphatemia or phosphatemia's variation was associated with aki development during tls. patients and methods: in this retrospective and monocentric study, we included all patients with tls and whithout aki at admission, admitted to hematology, nephrology and intensive care units of the university hospital of angers between 01/01/2007 and 31/12/2017. results: one hundred and thirty tls episodes were identified in 120 patients. aki developed during 56 episodes of tls (43%). hospital mortality was much higher in aki patients (26.8% versus 10.8%, p = 0.018). phosphate maximal values (2.2 ± 0.7 versus 1.9 ± 0.3) and ldh maximal values (4337.5 ± 4511.9 versus 2437.7 ± 2937.0) were higher in tls with aki, before aki occurrence (p = 0.006 and p = 0.009, respectively). we found no association between the other biological parameters of tls and aki (serum calcium, uric acid and potassium). after adjustment for cofounders, there was a strong association between a rise in phosphate level of 0.1 mmol/l (hr 1.31 ic 95% [1.19-1.42 ], p < 0.0001), exposure to platinum salts (hr 3.66 ic 95% [1.74-7.71 ], p = 0.0006) and increasing maximal ldh value (hr per 1000ui/l increase 1.10 ic 95% [1.03-1.17], p = 0.030) with aki. conclusion: this study highlights the utmost importance of serum phosphate in the setting of tls: phosphate is an early relevant biomarker for the risk of aki development. further studies are needed to assess whether aggressive prophylactic treatment to control serum phosphate concentration, such as renal replacement therapy before aki onset, constitutes a valuable approach. compliance with ethics regulations: yes. retrospective cohort of patients admitted to the medical icu of university affiliated hospital after carts treatment between august 2018 and august 2019. results: of the 20 patients treated by carts in the haematology department, 7 (35%) were subsequently admitted to icu. median age was 66 [50.5-68.5] years, and 5 (71.4%) were female. carts were indicated for r/r lymphoma. the median time between carts injection and icu admission was 5 [3.5-5.75 ] days. all patients had cytokine release syndrome (crs), and 6 (85.7%) developed car-related encephalopathy syndrome (cres). median sofa score and saps 2 were 4 [2-4.5] and 45 [40.5-49 .5], respectively. four (57.1%) patients had hypotension treated by fluid bolus (n = 3) or vasopressors (n = 2), and 2 (28.6%) had acuterespiratory failure requiring oxygen therapy (n = 1) or mechanical ventilation (n = 1). six (85.7%) patients had neurological symptoms (impaired consciousness n = 4, confusion n = 2, transient aphasia n = 1), of whom one developed refractory convulsive status epilepticus afterwards. all patients received broad spectrum antibiotics, of whom 2 (28.6%) had documented infections. six (85.7%) patients received interleukin-6 inhibitor (single dose n = 2, multiple doses n = 4), and 5 (71.4%) received intravenous dexamethasone. one patient died in the icu from septic shock. median icu and hospital length of stays were 4 [4] [5] [6] [7] [8] [9] [10] [11] [12] and 24 [21.5-28.75] days, respectively. two (28.6%) patients died from relapsing malignancy before hospital discharge. three months after icu admission, four (57.1%) patients were alive in complete remission. conclusion: more than 30% of patients treated with carts required icu admission for the management of a crs or a cres. early icu admission, close collaboration between haematologists and intensivists, and prompt administration of appropriate therapy (il-6 inhibitor and/or dexamethasone) and supportive care resulted in a good prognosis. compliance with ethics regulations: yes. rationale: tisagenlecleucel (ctl019) is a chimeric antigen receptor t cell therapy that reprograms autologous t cells to target cd19 + leukemia cells, approved in the us since august 2017 and in the eu since august 2018 for children and young adult (< 25 years old) with relapsed/refractory b-cell acute lymphoblastic leukemia (b-all). this study reports the experience of picu management of ctl019 toxicity in patients treated in robert-debré university hospitals. patients and methods: all patients (age < 18 years old) treated by tisagenlecleucel infusions between march 1, 2016 and september 15, 2019, included in sponsored-clinical trials or treated within the french compassionate program or with the commercial product, were retrospectively analyzed. results: twenty-four patients were infused and 8 patients (33%) were managed in picu for 11 stays. (2 stays: n = 1 and 3 stays: n = 1). median age at picu admission was 11.5 years old [10.9; 13.2] with a median delay after car-t cells infusions of 5 days [4.5; 6] . the median length of stay in picu was 2 days [1.5; 3] with a max at 25 days. cytokine release syndrome (crs) was the main indication of picu hospitalization (37.5%, n = 9) with grade 2 (n = 5) and grade 3 (n = 4) according to american society for transplantation and cellular therapy (astct) consensus grading system and treated by corticosteroid (n = .9) and tocilizumab (n = 5, only one infusion). norepinephrine was the only vasopressor used. the median vaso-inotrope score (vis) for grade 3 was 20 [17.5; 22 .5] with a maximum at 30. neurologic toxicity was observed in 2 patients with a grade 4 (status epilepticus) and grade 3 (focal edema on neuroimaging with depressed level of consciousness) according to immune effector cell-associated neurotoxicity syndrome (icans) grading system from astct consensus. the status epilepticus was managed with anti-epileptic drugs without mechanical ventilation. the focal edema was related to hhv6 and toxoplasmosis encephalitis. evolution was positive with foscavir and ganciclovir and 14 days of mechanical ventilation. one patient was hospitalized for septic shock secondary to gram-negative central line bloodstream infection in aplasia, with a vis score at 20. evolution was favorable with antibiotics and central line removal. no death in picu from severe tisagenlecleucel toxicity was observed since the beginning of the car-t cells program. conclusion: toxicity profile of tisagenlecleucel required frequent and early picu hospitalization after infusions for severe crs and icans management. compliance with ethics regulations: yes. rationale: car-t cell (chimeric antigen receptor t) therapy is a promising treatment in refractory acute lymphoid leukemia (all) and diffuse large b cell lymphoma (dlbcl). the main complication consists in a cytokine release syndrome (crs) leading to an inflammatory state that can be very severe with life-threatening organ failure. neurological toxicity is also reported. we aim to describe car-t cells-related complications in icu patients. patients and methods: this is a single-center prospective study conducted between july 2017 and august 2019. all the patients who have received car-t cells and who required icu admission were included. crs grading was defined according to the most recent classification of the asbmt and neurological toxicity was assessed with the cartox scale. each admission is considered independent and therefore corresponds to one patient. results: 48 admissions, representing 41 patients (27 men and 14 women), were considered. the median age was 56 years . twothirds of the patients have been diagnosed with dlbcl (n = 34, 71%) and one-third with all (n = 14, 29%), 31 months [23-59] ago. they had received 4 lines [3] [4] of chemotherapy and had a high tumor burden (65% of lymphomas classified stage iv). the majority of the patients was admitted because of hemodynamic failure (n = 23, 48%) or respiratory failure (n = 9, 19%), 5 days [3] [4] [5] [6] [7] after car-t cells infusion. sofa at admission was 4 [2] [3] [4] [5] [6] . all the patients presented at least one complication ( figure) , the most common being crs (n = 39, 81%) with a median grade of 2 [1] [2] . neurological toxicity was reported in 17 (35%) patients (worst grade at 3 [2] [3] [4] ). documented bacterial infection involved 29% of the patients and consisted in catheter-related infections for half of the cases. in the icu patients were managed with fluid resuscitation (n = 27, 56%) during the first day, vasopressors (n = 14, 29%) and broad spectrum antibiotics (98%). a single patient required mechanical ventilation and two patients underwent dialysis. tocilizumab (anti-il6 receptor) was given to 34 patients (87% of crs) in a median time of 5.5 h [2.1-21.5 ] after icu admission. 30 patients (61%) received corticosteroids. the median icu length of stay was 4.5 days [3] [4] [5] [6] . 3 patients (6%) died in the icu and hospital mortality was 14%. the 5-fluorouracil (5-fu)-induced hyperammonemic encephalopathy is a rare but serious 5-fu adverse drug reaction, which could require the admission of patients in intensive care unit (icu). given the paucity of data regarding this 5-fu adverse drug reaction, we performed a retrospective national survey from the french pharmacovigilance database to better characterize 5-fu-induced hyperammonemic encephalopathy and its management. patients and methods: since the inception of the french pharmacovigilance database, we identified all patients that experienced 5-fu-induced encephalopathy. variables regarding epidemiology, characteristics, management and prognosis of these patients were collected and analyzed. results: from 1985 from to 2018 years-old, 43% of women) were included. overall mortality was 17% (n = 5) and 57% (n = 17) of patients were admitted in icu. the 5-fu-induced hyperammonemic encephalopathy started 2 [1] [2] [3] [4] days after the onset of 5-fu infusion. the most common neurological disorders were consciousness impairment, confusion and seizures. abnormalities in ct scan, mri, electroencephalogram and lumbar puncture were found in 9%, 65%, 77% and 16% of the whole population respectively, similar in icu and non-icu patients. ammonemia was dosed in 50% of the whole population and in 65% of icu patients. hyperammonemia tended to be higher in icu than in non-icu patients (250[133-522] vs. 139[68-220] µmol/l, respectively, p = ns) and in patients with the lowest glasgow outcome scale, but was not different between survivors and non-survivors. among icu patients, 70% required mechanical ventilation and 47% anti-epileptic drugs administration. besides 5-fu discontinuation, lactulose intake, renal replacement therapy or ammonium chelators were used to decrease hyperammonemia in 17%, 27% and 7% of patients respectively. a complete neurological recovery was observed in up to 70% of icu and non-icu patients within a delay of 5[2-10] days. a dihydropyrimidine deshydrogenase (dpd) deficiency was found in 21% of tested patients. a 5-fu rechallenge was considered in 47% (n = 14) of patients with complete neurological recovery, including a patient with a partial dpd deficiency, within a delay of 19[18-28] days after recovery. a 5-fu-induced hyperammonemic encephalopathy relapse was observed in 57% of patients with 5-fu rechallenge. no relapse was observed when 5-fu rechallenge was performed with a decreased 5-fu dosage. conclusion: we report the first national survey and the largest cohort of patients with 5-fu-induced hyperammonemic encephalopathy so far. this serious 5-fu adverse drug reaction must be known by intensivists, since more than half of patients are admitted in icu and specific treatments are available. compliance with ethics regulations: yes. immune related adverse events: a retrospective look into the future of oncology in the intensive care unit adrien joseph 1 , annabelle stoclin 2 , antoine vieillard-baron 3 , guillaume geri 3 , jean-marie michot 4 rationale: immune checkpoint inhibitors (ici) represent a paradigmatic shift in oncology. with their new position as a mainstay in cancer treatment, new toxicities called immune related adverse events (iraes) have emerged. patients and methods: retrospective study including patients admitted in the icu within 60 days after treatment with an ici in 3 french hospitals. patients were classified into 3 groups according to the reason for admission: irae, intercurrent adverse event (intae) or event related to tumor progression (tumprog). results: 84 patients were admitted during the course of an ici treatment, including 21 irae, 25 intae and 38 tumprog, with a significant increase between 2013 (n = 1) and 2018 (n = 24 patients, p for trend < 0.001). irae included 5 pneumonitis, 4 colitis, 4 diabetes complications, 2 hypophysitis, nephritis, myocarditis and cardiac disorders, hepatitis or allergic reaction and 1 meningitis. the immune related nature of the complication was known before admission in only 4 (18%) cases. mean age was 61 (± 14) years and 73% had a performance status of 0-1. primary tumors were melanomas (14, 67%), non-small cell lung cancers (4, 19%) , urothelial carcinomas (2, 10%) and hodgkin lymphomas (1, 5%) . ici at the time of admission included anti-ctla4 (5, 24%), anti-pd1/pdl1 (10, 48%) and anti-ctla4/anti-pd1 combination in 6 (29%) patients. mean duration of stay in the icu was 6.5 (± 9) days. three patients required vasopressor therapy alone, 2 with mechanical ventilation and one with extracorporeal membrane oxygenation. three patients required non-invasive ventilation and 2 renal replacement therapy alone. six required only endocrine or electrolytic equilibration and 4 others did not receive any form of organ support. icu mortality was 14%. compared with other admissions, anti-ctla4 or anti-ctla4/anti-pd1 combination treatments were associated with irae diagnosis (or = 6.1 [1.1-43.4] , p = 0.021 for anti-ctla4 and 5.7 [1.2-31.4] for anti-ctla4/anti-pd1, p = 0.014) and so was the diagnosis of melanoma (5.7 [1.8-20.1] , p = 0.001). there was no difference in terms of icu and post-icu survival between irae (median post-icu survival 14 months [7-na]), intae (20.9 [9.5-na]) and ). six patients admitted for an irae were rechallenged with the same ici after icu discharge and 3 achieved complete response. conclusion: we conducted the first study describing patients admitted in the icu for iraes. their specific and heterogeneous profile, along with the expected increase in the number of admissions, underlines the need for an in-depth knowledge for icu physicians in order to take part in the multidisciplinary care required by these patients. compliance with ethics regulations: yes. rationale: patients with advanced-stage non-small-cell lung cancer have high mortality rates in the intensive care unit (icu). in this context, acute respiratory failure due to cancer involvement is the worst situation. in the last two decades, targeted therapies have changed the prognostic of patients with lung cancer outside the icu. unlike cytotoxic chemotherapy, the fast efficacy of targeted therapies led some intensivists to use them as rescue therapy for icu patients. we sought to investigate the outcomes of patients with lung cancer involvement responsible for acute respiratory failure and who received tyrosine kinase inhibitor during icu stay. patients and methods: we performed a national multicentric retrospective study with the participation of the grrroh (groupe de recherche en réanimation respiratoire en onco-hématologie). all patients with non-small-cell lung cancer admitted to the icu for acute respiratory failure between 2009 and 2019 were included in the study if a tyrosine kinase inhibitor was initiated during icu stay. cases were identified using hospital-pharmacies records. we collected demographic and clinical data in icu charts. vital status was assessed at the time of study completion (august 2019). the primary outcome was overall survival 90 days after icu admission. results: twenty-nine patients (age: 60 ± 14 years old) admitted to a total of 14 icus throughout france were included. seventeen patients (59%) were nonsmoker. the most frequent histological type was adenocarcinoma (n = 20, 69%) and a majority had metastatic cancer (n = 21, 72%). epithelial growth factor receptor mutation was the most common oncologic driver identified (n = 15, 52%). during the icu stay, 16 (55%) patients required invasive mechanical ventilation, 12 (41%) catecholamine infusion, 3 (10%) renal replacement therapy and one (3%) extracorporeal membrane oxygenation. in addition to tyrosine kinase inhibitor, 20 (69%) patients received steroids (beyond 0.5 mg/kg/day) and 3 (10%) cytotoxic chemotherapy during icu stay. seventeen patients (59%) were discharged alive from icu and 9 (31%) were still alive after 90 days (see kaplan-meier curve figure) . moreover, 5 patients (17%) were alive one year after icu discharge. conclusion: despite a small sample size this study showed that, in the context of lung cancer involvement responsible for acute respiratory failure, the use of tyrosine kinase inhibitor should not be refrained in patients with severe condition in icu. compliance with ethics regulations: yes. rationale: acute respiratory failure is the leading reason for intensive care unit (icu) admission in immunocompromised patients and the need for invasive mechanical ventilation has become a major clinical end-point in randomized controlled trials (rct). however, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. this study explores how this outcome varies across icus. patients and methods: hierarchical models and permutation procedures for testing multiple random effects were applied on both data from observational cohort (the trial-oh study: 703 patients, 17 icus) and randomized controlled trial (the high trial: 776 patients, 31 icus) to characterize icu variation in intubation risk across centers. results: the crude intubation rate varied across icus from 29% to 80% in the observational cohort and from 0 to 86% in the rct. this center effect on the mean icu intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p-value = 0.013, median or 1.48 [1.30-1.72 ]; rct: p-value:0.004, median or 1.51 [1.36-1.68 ]). two icu-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to icu admission) and could partly explain this center effect. in the rct that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. conclusion: invasive mechanical ventilation has become an important endpoint in immunocompromised patients with acute respiratory failure. however, we found significant variation in intubation risk across icu in both an observational cohort and a randomized controlled trial. our results highlight the need to take into account center effect in analysis because it could be an important confounder. reasons for heterogeneity are various (case-mix differences, center practices). this gives opportunities to future improvement in care management and study design. compliance with ethics regulations: yes. rationale: influenza virus (iv) infection is a major cause of ards that has been the focus of attention since the pandemic 2009 h1n1 (h1n1pdm2009) iv. although iv-mediated damage of the airway has beenextensively studied emphasizing specificity compared to other causes of ards, the impact of iv infection on the prognosis of ards patients, compared to the other causes of ards, has been few assessed. patients and methods: systematic detection of iv in times of epidemic using rt-pcr in respiratory specimen is routine practice in our icu along with prospective data collection of patients admitted to our icu for ards with pao 2 /fio 2 ratio ≤ 150 mmhg. all patients received lung-protective ventilation, the sequential organ failure assessment (sofa) score was calculated on the first 3 days of mechanical ventilation. the primary endpoint compared the 28-day survival from the diagnosis of ards between patients with and without iv infection. results: from october, 2009 to may, 2019, 509 patients (pts) [median saps ii score = 59 (33-67); age 58 years (47-68); pao 2 / fio 2 ≤ 100 mmhg, n = 308 (61%)] were admitted to our icu for ards with pao 2 /fio 2 ratio ≤ 150 mm/hg, including 100 pts (20%) with iv infection (h1n1pdm2009 iv a, n = 45; h3n2 a virus, n = 45; b virus, n = 10; associated bacteria, n = 46). other main causes of ards were bacterial pneumonia without iv (39%), aspiration (15%), non-pulmonary sepsis (18%). 221 (42%) received prone positioning, and 47 (9%) extra-corporeal membrane oxygenation. the overall mortality rate at day-28 for the entire population was 33% (22 pts (22%) with iv infection versus 148 pts (36%) without iv infection, p = 0.007). kaplan-meier survival curves showed that survival was significantly higher in patients with iv infection than in those without iv infection. iv infection remained independently associated with a better prognosis at day-28 when entered as dichotomous variable (iv infection, yes/no) (adjusted hazard ratio (hr) = 0.60, 95% ci 0.37-0.98, p = 0.04) and when iv infection only was distinguished from other causes of ards including mixed infection iv plus bacteria (adjusted hr = 0.37, 95% ci 0.19-0.72, p = 0.003). of note, within the first 3 days of mechanical ventilation, non-pulmonary sofa scores were significantly lower in iv patients although similar pulmonary sofa scores. conclusion: our results suggest that patients with iv related ards have less severe non-pulmonary organ dysfunctions than those with ards from other and a lower mortality at day-28 despite similar ards severity. compliance with ethics regulations: yes. rationale: acute respiratory distress syndrome (ards) remains frequent in intensive care unit (icu) with 20% to 40% mortality. according to joint theater trauma system, ards occurs among 30% of war casualties: direct lung trauma, blast lesions, burn, massive transfusion and systemic inflammatory response syndrome lead to ards development. however, there is no data reporting ards among french evacuated casualties from forward environment. our study's aim is to describe ards incidence and its severity concerning medical evacuations from war theater. patients and methods: this is an observational retrospective multicentric study analyzing all evacuated patient from war theater and admitted in icu. all patients developing ards according to berlin definition have been included. study has been approved by local ethic committee. primary study endpoint was ards developing. second study endpoints were ards severity, duration of invasive ventilation, ards treatments, icu length of stay and mortality. results: 141 patients have been admitted in icu between 2003 and 2018. 5 have been excluded. a total of 136 patients have been analyzed. 84% (n = 48) were military aged 30 (25-36) years. 42% (n = 57) developed ards. we found 57% (n = 32) war casualties, 30% (n = 17) trauma not related to war and 14% (n = 8) medical patients. among severe trauma, median iss was 34 (27-44), ais thorax 3 (2) (3) (4) , and 71% benefited from surgery on forward environment and 37% (n = 18) received massive transfusion. 22% (n = 13) suffered from mild ards, 42% (n = 24) moderate ards and 36% (n = 20) severe ards. evacuation time was 26 (24-48) h. at admission in icu, pao 2 /fio 2 ratio was 241 (144-296) (fig. 1 ). all patients were intubated. ards treatments used were curarization (76%, n = 43), prone position (16%, n = 9), inhaled nitric oxide (noi) (10%, n = 6), almitrine (7%, n = 7) and extracorporeal life support (ecls) (4%, n = 2). invasive ventilation duration was 13 (7-27) days, length of stay 18 (9-33) days, and 3-month mortality 21% (n = 12). conclusion: according to our study, ards among french evacuated patients from war theaters remains frequent: it occurs on 42% among icu admitted patients. 36% suffer from severe ards with 21% global mortality. those datas are consistent with us studies. also, we wonder if we must adapt our treatment capacities on forward environment for the most severe patients. in us army, a specialized team (acute lung rescue team) is trained to care the most hypoxemic war casualties with more treatment options as noi, ecls. compliance with ethics regulations: yes. rationale : we recently reported that septic shock patients with pneumonia exhibit a high risk of icu-acquired pneumonia, suggesting that a primary pulmonary insult may drive profound alterations in lung defence towards secondary infections (1) . given their importance in lung immune surveillance, alveolar macrophages (am) are likely to play a pivotal role in this setting. the objective of this experimental study is to address the impact of primary pulmonary or non-pulmonary infectious insults on lung immunity. patients and methods: we established relevant double-hit experimental models that mimic common clinical situations. c57bl/6 j mice were first subjected either to polymicrobial peritonitis induced by caecal ligation and puncture (clp), or to bacterial pneumonia induced by intra-tracheal instillation of staphylococcus aureus or escherichia coli. respective control mice were subjected to sham laparotomy or intratracheal instillation of phosphate-buffered saline. seven days later, mice that survived the primary insult were subjected to intra-tracheal instillation of pseudomonas aeruginosa (pao1 strain). we assessed survival and pulmonary bacterial clearance of post-septic animals subjected to p. aeruginosa pneumonia, as well as the distribution and functional changes in alveolar macrophages. results: when compared to sham-operated mice, post-clp animals exhibited increased susceptibility to secondary p. aeruginosa pneumonia as demonstrated by defective lung bacterial clearance and increased mortality rate (50% vs. 0%, p < 0.05). in contrast, all postpneumonia mice survived and even exhibited improved bacterial clearance as compared to their control counterparts. when addressing whole-lung immune cell distribution at the time of second hit (day 7), amounts of am were decreased in post-clp mice while preserved or even increased in post-pneumonia mice. antigen-presenting functions of am appeared similar in all conditions. percentages of apoptotic (annexinv + ) and necrotic (7-aad + ) am were comparable at day 1 and day 7 after the first hit. interestingly, both ly6c high and ly6c low monocytes were sustainably increased in the lungs of post-clp mice, while only transiently expanded following pneumonia, suggesting that differences in am counts could be related to modulated turnover from precursor monocytes. conclusion: using clinically relevant double-hit experimental models, a primary pulmonary infection conferred resistance to secondary bacterial pneumonia. ongoing investigations are aimed at addressing the antibacterial am functions, as well as the turnover-driving mechanisms.compliance with ethics regulations: yes. rationale: little is known on the role of exit-site signs in predicting intravascular catheter infections. the current study aimed to describe the association between local signs at the exit-site and catheter-related bloodstream infection (crbsi), which factors substantially influenced local signs and which clinical conditions may predict crb-sis if inflammation at insertion site is present. patients and methods: we used individual data from 4 multicenter randomized-controlled trials in intensive care units (icus) that evaluated various prevention strategies regarding colonization and crbsi in central venous and arterial catheters. we used univariate and multivariate logistic regression stratifying by center in order to identify variables associated with redness, pain, non-purulent discharge, purulent discharge and ≥ 1 local sign and subsequently evaluate the association between crbsi and local signs. moreover, weevaluated the role of thedifferent local signs for developing crbsi in subgroups of clinically relevant conditions. results: a total of 6976 patients, 14,590 catheters (101,182 catheterdays) and 114 crbsi (0.8%) from 25 icus withdescribed local signs were included. redness, pain, non-purulent discharge, purulent discharge and ≥ 1 local signs at removal were observed in 1633 (11.2%), 59 (0.4%), 251 (1.7%), 102 (0.7%) and 1938 (13.3%) episodes, respectively. the sensitivity of ≥ 1 local sign for crbsi was by 40.4%, whereas the highest specificities were observed for pain (99.6%) and purulent discharge (98.4%). positive predictive value (ppv) was low for redness (2%), pain (3%), non-purulent discharge (3%) and ≥ 1 local sign (2%), but increased for purulent discharge (12.7%). negative predictive values were high for all local signs. after adjusting on confounders, crbsi was associated with redness, non-purulent discharge, purulent discharge and ≥ 1 local sign (fig. 1 ). conditions independently associated with ≥ 1 local sign were age ≤ 75 years old (or 1.23, 95% ci 1.07-1.40, p < 0.01), sofa score (sofa < 8 or 1.45, 95% ci 1.23-1.71, p < 0.01), non-immunosuppression (or 1.38, 95% ci 1.12-1.68, p < 0.01), catheter maintenance > 7 days (or 3.36, 95% ci 3.03-3.73, p < 0.01) and insertion site (or for subclavian site 1.63, 95% ci 1.37-1.93, p < 0.01). however, the presence of ≥ 1 local sign was more predictive for crbsi in the first 7 days of catheter maintenance (or 6.30, 95% ci 3.53-11.24 vs. > 7 catheter-days or 2.61, 95% ci 1.58-4.32, p heterogeneity = 0.02). conclusion: this post hoc analysis showed that local signs were related to crbsis in the icu. local signs were independently associated with specific patient's and catheter's conditions. in the first 7 days of catheter maintenance, local signs were predictive for crbsi. compliance with ethics regulations: yes. rationale: pneumococcal meningitis (pm) is the leading cause of bacterial meningitis in adult patients requiring icu admission and is associated with a high case fatality rate (cfr), ranging from 15 to more than 33% (1) (2) (3) . patients with pm may develop sepsis or septic shock that may impact management and outcomes. we aim to describe the epidemiology and outcomes of pm associated with sepsis in adult patients in france. we analysed the occurrence of pm with sepsis from 2010 to 2015 in adult patients, using the national french hospital database pmsi (programme de médicalisation des systèmes d'information). for all analyses, only the first hospital admission was considered. cases were identified using a combination of a diagnosis code for pm plus a diagnosis code for sepsis (either a code for organ failure or a procedure code for organ support). data recorded included comorbidities (4), characteristics of the hospital stay, severity of the patients including major intracranial complications and characteristics of the infection. costs and endpoints were determined at the end of all the hospital stays related to the first admission for pm with sepsis. standardized incidence, hospital mortality, and cfr were estimated. temporal trends were assessed using cochran armitage tests of trends and linear trend analyses. results: a total of 1236 pm with sepsis aged ≥ 18 years were hospitalized in france during 2010-2015. the incidence of pm decreased from 3.7 to 2.6 per 1 m inhabitants (p < 0.02) (fig. 1) . most of them came from home (94%), were admitted in an academic institution (93%) and benefited from icu (93%). their median age was 62 [51; 73] years. twothird of them had at least one comorbidity. the initial neurological presentations included coma (58%), focal signs (15%), seizures (12%) and brain stem involvements (16%). the saps ii score was 57 [44; 69] points. the main neurological complications were cerebrovascular complications (6%), cerebral abscess (4%) and hydrocephaly (2%). pm was associated with pneumococcal septicaemia or pneumococcal pneumonia in 30% and 23% of cases respectively. the length of icu and hospital stays were 10 [4; 21] and 22 [10; 41] days respectively and only icu length of stay decreased over time (p < 0.01). the prognosis was poor since only 27.6% of the patients were discharged to home. indeed, 42.6% of them died and 18% were transferred to rehabilitation units. no temporal trends could be observed for these outcomes. the average hospital costs per case were 21, 717€ [13.198; 34.232] . conclusion: pm with sepsis in adult in france remained a real burden associated with a high mortality rate, and disability. compliance with ethics regulations: na. rationale: mucormycosis is an emerging fungal infection, especially in patients with hematological malignancies. although this infection may lead to multi organ failure, no study has been dedicated to critically ill patients with hematological malignancy. the primary objective was to assess outcome in this setting. the secondary objective was to assess prognostic factors. patients and methods: this retrospective cohort study was performed in 5 icus. critically ill adult patients with hematological malignancies and mucormycosis were included between 2002 and 2018. mucormycosiswas classified as "probable"or "proven" regarding eortc criteria. variables are reported as median [iqr] or number (%). adjusted analysis was performed using cox model. results: twenty-six patients were included with a median age of 38 years [iqr, . acute leukemia was the most frequent underlying disease (n = 13, 50%). nine patients (35%) were allogeneic stem cell transplantation (sct) recipients. nineteen patients (73%) had neutropenia and 16 patients (62%) had received steroids. the main reason for admission was acute respiratory failure (n = 14, 54%) followed by shock (n = 5, 19%). the median sofa score at admission was 7 [iqr, 5-8] points. only 3 patients (11%) had received prior anti-fungal prophylaxis effective against mucorales. mucormycosis was "proven" in 14 patients and "probable" in 12 patients. diagnosis was made by histopathologic examination in 14 patients, direct microscopy or culture in 5, and polymerase chain reaction in 7. rhizopus and mucor were the most frequent documented species. seven patients (27%) had concurrent aspergillus infection. mucormycosis was diagnosed 1 day [− 4 to + 6] after icu admission. ten patients (38%) had pulmonary involvement whereas five patients (19%) had rhino-cerebral involvement. infection was disseminated in eight patients (31%). twenty-two patients (85%) were treated with liposomal amphotericin b. twelve patients (46%) received antifungal combination including posaconazole in 7. eight patients (31%) underwent curative surgery. multiple organ failure was frequent, 21 patients (81%) requiring invasive mechanical ventilation (imv), 19 (69%) vasopressors, and 9 (35%) renal replacement therapy. icu and hospital mortality rates were 77% and 88%, respectively. only two patients were alive at day 90. three variables were associated with mortality in a cox model including allogeneic sct .32]; figure), sofa score (hr 1.19 [95% ic 1.02-1.39]) and dual therapy (hr 3.02 [95% ic 1.18-7.72]) (fig. 1) . conclusion: mucormycosis is associated with a high mortality rate in patients with hematological malignancies, especially in allogeneic sct recipients. futility of icu management in these patients is to be considered and strategies aiming to improve these patients' outcome are urgently needed. compliance with ethics regulations: yes. rationale: sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. several mediators, alone or in combination, were proposed to characterize individual response, but none was proven to have good external validity. the aim of this work was to establish whether some combinations are linked to clinical phenotypes in patients with presumed sepsis, using the data collected in the captain multicenter cohort which methods and first results were previously published (parlato, icm 2018). patients and methods: 279 patients were prospectively included at the time of sepsis criteria, 188 (67%) of whom with a secondary confirmed infection. community acquired pneumonia was causal in 70% of infections. saps2 score = 55 points [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] , age = 65 years , male sex = 64%. 203 patients were followed for more than 3 days, in whom usual icu clinical and biological parameters were collected, as well as 29 plasma biomarkers and 10 leucocyte associated rnas. patients were clinically classified according to their acute severity (sofa score, serum lactate), confirmed initial infection, outcome (secondary infection occurrence, icu survival). non-supervised principal component analysis of the maximal values of biomarkers assessed on first 2 days of sepsis, and varimax rotation technique of the selected components using sas software. results: 203 patients, med sofa day1 = 5 pts, med serum lactates day 1 = 1.5 meq/l, bacterial infection = 141 (69%), enterobacteriaceae infection = 45 (22%), vap and/or bacteremia after day 5 = 30 (15%), alive at icu d/c = 146 (72%). five components explain 57% of the variance of the biomarkers. the first component (26% of the variance) was not linked to the clinical predetermined phenotypes. the second component (11% of the variance) was principally made of hla-dr rna, cd74 rna and cx3cr1 rna, and linked to a lower initial severity (r = − 0.32, p = 0.0001), a less frequent confirmation of initial infection (p = 0.0001), a lower occurrence of pneumonia or bacteremia (p = 0.02) or death (p = 0.008). conclusion: in our cohort, using non supervised analysis, we could separate a biomarker association linked to lower initial severity, lower rate of a bacterial cause to sepsis, and better outcome. the markers found are among those which are regularly considered as describers of the peripheral alteration of the immune system observed during sepsis (pachot, ccm 2005; friggeri, cc 2016; peronnet icm 2017) . compliance with ethics regulations: yes. (1) compared a standard of care to a procalcitonin (pct) oriented use of antimicrobials for sepsis in 8 icus. serial blood samples were biobanked in 4/87 icus (455/621 patients enrolled for pro-adrenomedullin (proadm) and pct concentrations). patients and methods: the aim of the study was to evaluate the respective impact of serial pct and proadm measurements in predicting relapse or superinfection and death on day 28*. relapse was defined as the growth of one or more of the initial causative bacterial strains (i.e., same genus, species) from a second sample taken from the same infection site at 48 h or more after stopping of antibiotics, combined with clinical signs or symptoms of infection. superinfection was defined as the isolation from the same or another site of one or more pathogens different from that identified during the first infectious episode, together with clinical signs or symptoms of infection [4] [5] [6] [7] [8] [9] [10] [11] points at amission, medical admission: 427 (95%), immunocompromised: 81 (18%), on mechanical ventilation 306 (67%), pct and proadm at inclusion were 2 [0. 6-9.3] ng/ml and 1.5 [0.4-2.7 ] nm/l respectively. 173 (38%) patients developed a first episode of recurrence or supereinfection after a median delay of 11 days [8] [9] [10] [11] [12] [13] [14] [15] [16] and 98 (22%) died before d28. the hr maximization process proposed an optimal cut point of 1 ng/ml for pct and 2 nm/l for pro adm to predict d28 death. in the multivariate cox model, both pct and proadm were associated with death but not with relapse or superinfection (table 1) . conclusion: conclusion: both serial measurements of pct and proadm are independent predictors of death in patients treated for sepsis in icu. our study confirmed the use of 2 nm/l as a good prognosis cut point for proadm. 1. compliance with ethics regulations: yes. rationale: the performance of serum (1-3)-β-d-glucan (bdg) and its evolution to predict the occurrence of invasive fungal infection (ifi) in a high risk non immunocompromized population remains to be determined (1). in a post hoc analysis of the empiricus randomized clinical trial (2), we aimed to assess the prognostic value of repeated measures of bdg on the occurrence of invasive fungal infections. patients and methods: non-neutropenic, non-transplanted, critically ill patients with icu-acquired sepsis, multiple candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between july 2012 and february 2015 in 19 french icus were included. bdg were collected in icu at day 0, 3, 7, 14 and 28 after inclusion. a value time 0 of more than 80 pg/ ml, 250 pg/ml and an increase by more than 24% from the previous measurement (threshold of measurement error) were assessed at baseline and overtime. for that purpose, we conducted cause specific hazard models with death as a competing risk. we also planned subgroup analyses on the placebo and the micafungin groups. cumulative risk (cumrisk) of ifi at day 28 were derived from models. [4.7; 5.2] ). neither a bdg > 250 pg/ml, nor an increase by 24% of bdg over time were associated with the occurrence of ifi. similar results were found in the placebo subgroup. conclusion: among high risk patients, a first measurement of bdg over 80 pg/ml was highly associated with the occurrence of ifi. neither a cut-off of 250 pg/ml, nor repeated measurements of bdg over time seemed to be useful to predict the occurrence of ifi. the cumulative risk of ifi in the placebo group if bdg > 80 pg/ml is 25.39% questioning about the potential interest of empirical therapy in this subgroup. compliance with ethics regulations: yes. rationale: since the 2016 sepsis-3 conference, the distinction between sepsis and septic shock is based on blood lactate value. septic shock may be encountered in the pre-hospital setting. in order to reduce the mortality, the precocity of treatments implementation has been emphasized, particularly early antibiotic administration. prior antibiotic administration, and blood culture drawing must be performed. the aim of this survey was to clarify the capabilities of french prehospital emergency service (pems) to measure blood lactate and to draw blood culture prior to hospital admission for septic shock. patients and methods: we performed an electronic survey of 26 auto-questions addressed to the deputy chair of the french pems in 2018. results: sixty pems (60%) participated in the survey. twenty-five percent are able to measure blood lactate and 45% are able to draw blood culture in the prehospital setting. ninety-five percent declared lactate measurement is helpful in assessing severity. ninety percent claimed that the lactate value influences the hospital facility, emergency department vs. intensive care unit. twenty-eight percent believe that the impossibility to draw blood culture precludes prehospital antibiotic administration. sixty-three percent estimate that a protocol for septic shock management would be beneficial. conclusion: few french pems are able to measure lactate and draw blood culture in the prehospital setting. the impact of blood lactate measurement and blood culture drawing by pems on septic shock outcome requires further studies. compliance with ethics regulations: yes. rationale: head injury is a common cause of morbidity and mortality in the first four decades of life, accounting for approximately 200,000 annual hospital admissions in the united kingdom. the majority of patients recover without intervention, however some may develop a long-term disability or even die. the early detection of pathology is therefore absolutely critical in determining patients' prognosis, helping to provide appropriate timely management. the national institute for health and care excellence (nice) adult head injury guidelines, recommend that head injuries with specific risk factors should have a ct scan within 1 h of risk factors being identified. furthermore the provisional report should be made available within 1 h of the scan. this audit assessed the compliance of staff to the nice adult head injury guidelines. patients and methods: the previous 40 adult ct head scans, requested due to head injury, from the emergency department (ed) at london north west healthcare nhs trust were analysed for compliance to the nice guidelines. the standards measured were: (1) time from request of scan to completion of scan should be within 1 h; (2) time from completion of scan to publication of provisional report should be within 1 h. the locally agreed target for both standards was 100%. results: on review of the 40 ct scans, 32 (80%) were completed within 1 h of request. from the 8 scans (20%) not completed within the hour, 4 were due to porter unavailability, 1 due to an uncooperative patient and the remaining 3 reasons were not clear from documentation. following completion of the scan, 38 scans (95%) were provisionally reported within 1 h. conclusion: this study highlighted a good compliance by hospital staff in ensuring patients with head injuries are managed appropriately, following detection of risk factors indicating a ct head scan. having said that, the locally agreed targets were just short of being met. one factor resulting in delayed scans was porter availability. an intervention recently introduced is the use of the "e-portering" application, which will endeavour to save time for referrers requesting porters and allow patient tracking. it is also worth educating porters, via email bulletins, on the importance of priority scans, such as ct head following injury. furthermore, the findings of the audit were relayed to the radiology department to help improve reporting times and to the ed to re-emphasize prompt requesting of ct head scans when clinically indicated. compliance with ethics regulations: yes. rationale: continuous insufflation of oxygen (cio) performed with specific endotracheal tube during cardiopulmonary resuscitation (cpr) is as effective as intermittent ventilation on endotracheal tube. experimental data suggest that cio improves the efficacy of external cardiac massage and reduces gastric dilatation. as endotracheal intubation is a cause of cpr interruption and requires skilled staff, a specific device has been developed to perform cio without intubation. this device has been implemented progressively in our fire department since 2015. we evaluated this practice. patients and methods: longitudinal study comparing the patients with out-of-hospital cardiac arrest managed by our fire department with cio or bag-valve ventilation between january 2015 and april 2019. patients who received mechanical chest compression were excluded. the main outcome was hospital survival. secondary outcomes were the return of spontaneous circulation (rosc) and cpr quality. univariate and multivariate analysis was performed in the whole cohort and in the sub-groups of patient with shockable and non-shockable rhythms to take into account factors associated with survival (shockable rhythm, witness, age). results: among the 793 patients included, 262 have been ventilated with cio and 531 with valve-bag. the mortality was similar in the two groups (cio: 85.1% valve-bag: 88.1% p 0.23). mortality and rosc were not associated with cio in the multivariate analysis (odds ratio or 1.19 95%-confidence interval ci95 [0.75-1.9] and 0.97 [0.59-1.6], respectively). cpr quality was better with cio than with valve-bag regarding cpr fraction (ratio of duration of chest compressions on total duration of cpr, 84 versus 76% p < 0.0001) and adequacy to the guidelines of the rhythm and depth of chest compressions (70% vs 50% p < 0.0001 and 47% vs 38% p < 0.0001, respectively). in both subgroups of patients, cpr quality was still better with cio than with valve-bag. in the subgroup of patients with shockable rhythm, univariate analysis showed a lower mortality among the 59 patients with cio than among the 140 patients with valve-bag (57.6% vs 82.9% p < 0.001) but this difference was not confirmed by the multivariate analysis (or 0.4 ci95 [0.10-1.03], p 0.06). conclusion: cio without intubation is associated with an improvement of cpr quality but neither with mortality nor return of spontaneous circulation in case of out-of-hospital cardiac arrest. compliance with ethics regulations: yes. rationale: cardiovascular accidents are a leading cause of death. a cardiopulmonary resuscitation (cpr) of quality has well shown that can reduce the mortality; despite this, survival rate has not changed significantly during last years. the aim of this study is to test a new wearable glove to provide lay people with instructions during out-ofhospital cpr. patients and methods: we performed a blinded, controlled trial on an electronic mannequin ambuman to test the performance of adult volunteers, non-healthcare professionals performing a simulated cpr both, without and with glove, following the glove instructions. the group without glove, also called "no-glove" is intended as control group. each compression performed on the electronic mannequin ambuman was recorded by a connected laptop computer, drawing a depth frequency curve over the time. primary outcome was to compare the accuracy of the two simulated cpr sessions in terms of depth and frequency of chest compressions performed by the same lay volunteers. secondary outcome was to compare the decay of performance and percentage of time in which the candidate performed accurate cpr. finally, the participants were asked if the glove was useful for cpr maneuvers. the difference between the two groups in regard to change in chest compression depth over time due to fatigue, defined as decay were also analyzed. results: 571 chest compressions were included: 293 in control group, 278 in glove group (table 1) . mean depth of compression in the control group was 55.17 mm versus 52.11 mm in the glove-group (p = 0.000016). compressions with an appropriate depth were not statistically different (81.9% vs 73.6%, p = 0.017). mean frequency of compressions in the group with glove was 117.67 rpm vs 103.02 rpm in the control group (p < 0.00001). the percentage of compression cycles with an appropriate rate (> 100 rpm) was 92.4% in the group with the glove versus 71% in the control group, with an observed difference of 21.4% between the two groups, which was statistically significant (p < 0.0001,ci = 95%). a mean reduction over time of compressions depth of 5.3 mm (sd 10.28) was observed in the control group versus a mean reduction of 0.83 mm in the group wearing the glove (sd 9.91), but this mean difference in the decay of compressions delivery was not statistically significant (f-ratio = 5.680, ss = 579.61, df = 1, ms = 579.61, p = 0.018). conclusion: the visual and acoustic feedbacks provided by the device were useful in dictating the correct rhythm for non-healthcare professionals, translating in a significantly more accurate cpr. compliance with ethics regulations: yes. rationale: neuroprognostication after cardiac arrest (ca) is a crucial issue and current guidelines recommend delayed multimodal approach. we aimed to describe reasons for death in a prospective cohort of ca patients and evaluate the diagnostic accuracy of early combined neurological prognostication tools such as automated pupillometry (ap), continuous amplitude electroencephalography (aeeg) and cardiac arrest hospital prognosis (cahp) score performed 24 h after return of spontaneous circulation (rosc). we set up a monocentric prospective cohort of adult ca patients admitted in icu after sustained rosc and collected data according to utstein style recommendations. reasons for death were described under recently proposed classification: withdrawal of life-sustaining therapies (wlst) for neurological reasons, wlst due to comorbidities, refractory shock or recurrence of sudden ca or respiratory failure. for patients who kept abnormal neurologic state after rosc with glasgow coma scale < 15, we analysed accuracy of early neuroprognostication tools (ap, aeeg and cahp score) to predict poor neurological outcome, i.e. cerebral performance category (cpc) > 2 at hospital discharge. results: 144 patients were admitted after sustained rosc from ca during the period (31.08.2018 to 10.07.2019). in-hospital mortality was 51%. neurological wlst was the first reason for death (62%). exhaustive early neuroprognostication with ap, aeeg and cahp score was available for 75 patients. among them, poor neurological outcome at hospital discharge (cpc > 2) was observed for 39 patients (52% (fig. 1) . this strategy would falsely misclassificate 4% of patients in a good neurologic outcome category. other survivors (24%) should then be investigated with further classical delayed neuroprognostication tools. compliance with ethics regulations: yes. rationale: management delay is one of the determining factors in the assessment of emergency department quality of care. asking for a specialized advice seems to increase the time of delay. our study aimed at measuring the delays in obtaining specialized advice and identify their major causes. patients and methods: we conducted a prospective study over the period of 1 month. we included all adult patients presenting to the emergency department who required specialized advice. data of all patients was collected. waiting times and influencing factors were studied. results: a total of 75 patients were included. the main reason for calling for a specialized advice was to ask for a department transfer in 68% of cases. the time of the day when specialized advice was solicited (n (%)): in the morning 51 (68); in the afternoon 17 (23); in the evening 9 (12). the main solicited specialties were (n (%)): visceral surgery 18 (24), trauma medicine 15 (20), cardiology 10 (13), urology 5 (7), and pulmonology 5 (7). the average waiting time between calling for and getting the specialized advice was 176 ± 115 min. seventy-five percent of the specialized advice was obtained within 1 h. the causes of the delay were (n (%)): physician busy in the operating room 22 (39), unreachable physician 9 (12), physician in the outpatient clinics 7 (10). the impact of the waiting time was (n (%)): conflict 20 (27), worsening patient state 4 (5). the average time between calling for the specialized advice and reaching a management decision was 210 ± 127 min. conclusion: the increasing length of stay of patients in the ed is strongly correlated to the delay in obtaining specialized advice. the implementation of a strategy to reduce the waiting time is necessary to avoid overcrowding the emergency departments and provide optimal care. compliance with ethics regulations: yes. rationale: hypnoanalgesia has been used since few years to reduce icu-patients physical and psychological discomfort during invasive procedures. however, feasibility of overall well-being management of intubated patients with hypnosis has not been described. patients and methods: we report here the hypnotic accompaniment of a 16-year old patient without significant medical history hospitalized in our icu for a severe gbs during 3 months. the gbs was diagnosed by electrophysiological study and immunologic markers. patient had nearly complete paralysis of all extremities, but no facial or bulbar muscles. he received mechanical ventilation during 87 days, including weaning time. tracheotomy was performed at day 15. sedative drugs were stopped 2 days after intubation. hypnosis sessions were startedvery early after intubation by one of our trained intensivist. eight hypnotic sessions of hypnoanalgesia or hypnotherapy were performed after approval of the patient and his parents. time distribution is reported in fig. 1 . first and second sessions were performed in order to induce relaxation and reduce anxiety. following sessions were dedicated to: 1) decrease pain intensity (initially neuropathic, then induced by physiotherapy), 2) attenuate the negative perception of paralysis, 3) reduce the discomfort of tracheotomy 4) promote the belief in healing 5) facilitate swallowing exercises. furthermore the patient was quickly trained to use self-hypnosis in order to dissociate him from pain, anxiety and icu pollutions. results: feasibility of hypnosis was judged satisfactory by the operating physician, despite mechanical ventilation. after extubation, final debriefing with the patient indicates that the most efficient sessions were those focused on anxiety disorders (using the suggestion of a safe place) and suggestions of mobility (using a mangas metaphor). the patient reported very positive perception of hypnosis use. he explained that self-hypnosis was effective to reduce many discomfort. he used it frequently (generally twice a day) for a puff of anxiety or before enoxaparin injection. our observation suggests that hypnosis seems feasible in icu-awake patients and may be an interesting way to improve their icu lived experience in combination with validated measures. further investigations are needed to evaluate its effects on post-traumaticstress disorder. compliance with ethics regulations: yes. rationale: there is little medical reference for hypnosis in the intensive care field. closed specialties such as anesthesia, emergency medicine can help and refer to hypnosis for certain technical procedures. objective: to propose landmarks for a successful implementation of hypnosis by intensivists within the intensive care unit. patients and methods: this monocentric prospective observational study was performed from february 2018 to june 2019 in the 15-bed medical icu of brest university hospital. collected data were: characteristics of patients and hypnosis sessions performed, demographic data, physiological parameters (heart and respiratory rates) and objective and subjective evaluation of hypnosis sessions quality. results: 60 patients were included (mean age 55.4 ± 19 years, saps ii 34.5 ± 14 points). 100 hypnosis sessions were performed, of which 1/3 under mechanical ventilation. patterns of hypnosis sessions were: anxiety/comfort (53%), during a technical procedure (38%): toe, cvc placement, thoracic drainage, upper digestive or bronchial endoscopy), initiation of noninvasive ventilation or before intubation. most of time, the hypnotic trance was permitted by formal hypnosis techniques with travel and nature themes suggestion. efficacy was qualitatively assessed and rated as "total effectiveness" for 60% of sessions. qualitative evaluation by hypnotherapist, technical operator and observers was respectively 7.25 ± 1.5, 9.25 ± 0.5 and 9 ± 1/10. heart rate decreased from 93 ± 17 to 88 ± 13 bpm and respiratory rate/min decreased from 22 ± 7 to 17.7 ± 5 rpm during sessions. discussion: after a meeting, the healthcare team carried out a brainstorming to propose hypnosis in our unit. several difficulties were observed to explain implementation failures such as: finding competent patient, respiratory assistance, difficult communication, noisy environment, many nursing care, unexpected emergencies, etc.…). this experience allowed writing a vademecum to perform hypnosis in intensive care. our aims are to get more trained caregivers and to integrate hypnosis during our postresuscitation consultation, especially for post-traumatic stress. conclusion: hypnotic tools can facilitate technical procedures and improve patients' and caregivers' quality of life within the icu. compliance with ethics regulations: yes. effect of a musical intervention during central venous catheterization in an intensive care unit: the music cat prospective randomized pilot study sophie jacquier, brice sauvage, gregoire muller, thierry boulain, mai-anh nay chr, orléans, france correspondence: sophie jacquier (sophie.jacquier@chr-orleans.fr) ann. intensive care 2020, 10 (suppl 1):f-112 rationale: evaluate the effect of a musical intervention on patient anxiety during a central venous access or a dialysis catheter implantation in an intensive care unit. patients and methods: the music cat study was a prospective, single-centre, controlled, open-label, two-arm randomized trial, conducted from february 2018 to february 2019. central venous catheterization with musical intervention was compared to standard care, i.e., the usual procedure of central venous catheterization without listening to music. eligible patients had to be able to hear, understand explanations and consent. randomisation was stratified according to ventilation type (mechanical ventilation or not) and catheter site (superior vena cava or femoral vein). the music care ® (paris, france) application was used to make the patients listen to music through headphones. each patient chose his/her musical topic on a digital tablet, just before the catheterization. the primary outcome was the change in anxiety visual analogic scale (vas) between the beginning and the end of the catheterization procedure (t0-tf anxiety vas). secondary outcomes included the patient's pain vas at the end of the procedure (tf pain vas). results: 31 patients were included in the standard care group versus 36 in the musical intervention group. main reasons for admission were the need of central catheter for chemotherapy (27, 40%), and sepsis and/or shock in both groups (26, 39%). catheters were inserted in the internal jugular vein in most cases (56, 82%) and about one-third were tunnelled in both groups. there was no between-group difference regarding median t0-tf anxiety vas: 0 [iqr:− 3 to 0] in the standard care group versus − 1 [− 3 to 0] in the music intervention group (p = 0.20) (fig. 1) , with no significant interaction between the variables of stratification or the operator experience and the intervention. the median tf pain vas was not statistically different between groups: 0 [0 to 4.1] in standard care group and 0 [0 to 2] in music intervention group (p = 0.60), with no significant interaction between the variables of stratification or the operator experience and the intervention. conclusion: in this first randomized pilot study of musical intervention for central venous catheterization in awake patients in the intensive care unit, the musical intervention did not reduce patients' anxiety as compared to usual care. as the study may have been underpowered, larger size trials are needed. compliance with ethics regulations: yes. rationale: sleep is markedly altered in icu-patients under mechanical ventilation and may be due to noise, light, patient-care activities, patient-ventilator asynchronies, or the result of acute brain dysfunction induced by sedative drugs. to our knowledge, sleep has never been studied at icu admission before any sedation. our study aimed at assessing sleep quality of non-intubated sedation-free patients admitted to icu for acute respiratory failure. patients and methods: observational study performed in a single centre of a teaching hospital. patients admitted to icu for acute respiratory failure (respiratory rate ≥ 25 breaths/min and pao 2 / fio 2 < 300 mm hg under high-flow nasal oxygen) could be enrolled. patients with hypercapnia, central nervous disease, intubated early after admission and those with a do-not-intubate order were excluded. sleep was evaluated by complete polysomnography (psg) that started in the afternoon following admission and was continuously performed until the next morning. results: over a 3-year period 128 patients were screened and 44 patients were included. among them, 10 patients were excluded for the following reasons: 1 patient was intubated shortly after psg initiation, 1 psg was lost, and 8 eeg recordings (18%) were stopped before midnight (electrodes turned off or loss of signal). therefore, 34 patients in whom psg was complete during the nocturnal period were retained in the analysis (27 rationale: convulsive status epilepticus (cse) is a common neurological emergency associated with high mortality and morbidity rates. there are strong experimental data suggesting a potential impact of secondary brain insults (sbi) on outcome after cse. however, there is no clinical proof to support this hypothesis. our objective was to evaluate the association between sbi (mean arterial blood pressure, arterial partial pressure of carbon dioxide, arterial partial pressure of oxygen, temperature, natremia, and glycemia) at day 1 and neurological outcomes 90 days after cse. patients and methods: this was a post hoc analysis of the hyber-natus multicenter open-label clinical trial randomized 270 critically ill patients with cse requiring mechanical ventilation to either therapeutic hypothermia (32-34 °c for 24 h) plus standard care or standard care alone. 265 patients still alive at day 2 after inclusion were enrolled from march 2011 to january 2015 in 11 french medico-surgical icus. the primary outcome was favourable outcome 90 days after cse defined as a glasgow outcome scale score of 5. results: median age was of 57 years . a previous history of epilepsy was noted in 130 (49%) patients. most episodes (173/265, 65%) occurred out-of-hospital, and 230 (87%) were witnessed from their onset. cse was refractory in 86 (32%) patients and total seizure duration was 67 min (35-120). a favorable 90-day outcome occurred in 126 (48%) patients. maximal glycemia value and hyperglycemia > 9.9 mmol/l at day 1 were the only sbi variables associated with outcome in univariate analysis. by multivariate analysis, age > 65 years (or, 0.46; 95% ic, 0.26-0.83; p = 0.01), refractory cse (or, 0.50; 95% ic, 0.26-0.96; p = 0.04), and primary brain insult (or, 0.50; 95% ic, 0.25-0.99; p = 0.047) were associated with an increased risk of poor outcome, and a bystander-witnessed onset of cse (or, 2.49; 95% ic, 1.05-5.59; p = 0.04) was associated with a decreased risk of poor outcome. conclusion: in our population, secondary brain insults were not associated with outcome in critically ill patients with convulsive status epilepticus; whereas age, bystander-witnessed onset of status epilepticus, refractory status epilepticus and primary brain insult were identified as strong predictors of 90-day functional impairment. further studies are warranted to confirm our findings. compliance with ethics regulations: yes. rationale: acute stroke (as) is a leading cause of morbidity and mortality worldwide. however, data on the prognosis andfunctional outcome of patients with as requiring icu management is limited. our purpose was to identify factors associated with good outcome (defined by a modified rankin score (mrs) of 0-2) 6 months after icu admission. patients and methods: retrospective cohort of patients admitted to the medical icu of a university-affiliated hospital between january 2014 and december 2018 and coded for acute stroke using the icd-10 criteria. patients with traumatic stroke and isolated subarachnoid hemorrhage were excluded. results: we identified 323 patients. median age was 67 [54.5-77] years and 173 (53.6%) were males. main reasons for icu admission were coma (87%), hemodynamic instability (28.2%), acute respiratory failure (26%), and cardiac arrest (5.3%). glasgow coma score at icu admission was 6 [4] [5] [6] [7] [8] [9] [10] and points. types of stroke were hemorrhagic in 248 (76.8%) patients and ischemic in 75 (23.2%). mechanical ventilation was required in 257 patients (79.6%). seizures occurred in 11.8% of the patients and convulsive status epilepticus in 3.1%. pneumonia was diagnosed in 60 (18.6%) patients (aspiration pneumonia n = 20, ventilator associated pneumonia n = 40). thrombolysis or thromboaspiration were performed in 18 (24%) patients with ischemic stroke. surgical evacuation of expanding hematoma was performed in 21 (6.5%) patients, 19 (5.9%) had craniectomy, and 61 (18.9%) had external shunt for hydrocephalus. icu and hospital mortality were 58.8% and 61%, respectively. six months after icu admission, 44 (13.6%) patients had a good outcome (mrs 0-2), 42 (13.1%) had significant disability (mrs 3-5), and 200 (61.9%) were deceased (lost follow-up n = 37, 11.5%). on multivariable analysis, age (or 0.95 per year (0.91-0.99), p = 0.01), saps 2 (or 0.95 per point (0.90-0.99), p = 0.03), and hemorrhagic stroke (or 0.27 (0.08-0.9), p = 0.03) reduced the likelihood of good outcome (mrs 0-2) 6 months after icu admission. conclusion: in our study, prognosis of acute stroke requiring icu admission was poor and a good functional outcome occurred in less than 15% of the patients at 6 months. age, severity at icu admission, and type of stroke predicted outcome. compliance with ethics regulations: yes. rationale: in intensive care units, severe spontaneous hemorrhagic brain injuries have a poor prognosis for mortality and functional outcomes. affected patients face particular ethical issues regarding the difficulty of anticipating their eventual recovery. in this context, prognostic scores can help clinicians in patients/relatives counseling and therapeutic decisions. the previous reviews pointed out many prognostic tools for intracranial hemorrhage and subarachnoid hemorrhage but did not focus on injuries explicitly severe nor assessed the methodological limitations of the models. our systematic review aimed to assess methodologically prognostic tools for functional outcomes in severe spontaneous haemorrhagic brain, with particular attention to their clinical utilities. patients and methods: following prisma recommendations, we queried medline, embase, web of science, and the cochrane by february 19, 2019. we included multivariate prognostic models explicitly developed or validated on adults with severe intracranial or subarachnoid haemorrhage. we evaluated the articles following the charms recommendations (checklist for critical appraisal and data extraction for systematic reviews of prediction modelling studies) and the tri-pod statements (transparent reporting of a multivariable prediction model for individual prognosis. results: our review confirmed the multiple publications of prognostic scores, as we found 71 articles aiming to develop or validate prognostic tools. relying on guidelines, we discarded 52 articles due to the lack of prognostic capacities, validation, or predictor selection. 8 articles developed and validated a prognostic tool and 19 externally validated existing models (fig. 1) . no score was of good methodological quality in intracranial hemorrhage. we highlighted two prognostic scores in subarachnoid hemorrhages: the sahit predicting unfavorable outcome or mortality at 6 months and the fresh predicting unfavorable outcome at 12 months. conclusion: although prognostic studies on haemorrhagic brain injuries abound in the literature, they generally lack of methodological robustness or show incomplete reporting. with the numerous published scores, we believe that it is time to stop developing new scores. ongoing validation, recalibration, and impact studies would keep improving existing good tools. the use of "patient-centered" approaches could also enhance them, and be more appropriate to inform patients and families about their long-term potential recovery. these considerations should drive future research in the modern era of neurocritical care prognosis. compliance with ethics regulations: na. rationale: respiratory pattern analysis by a visual examination is an important part of clinical assessment but is dependent on caregiver expertise and is subjective. furthermore, there is no easy medical device used in picu to measure tidal volume (vt) and minute ventilation (mv) in spontaneous breathing patients. the clinical research unit in critical care of chusj and ets have developed a non-invasive computerized 3d video analyzing system (retract system) to detect and perform a video analysis of respiratory status in children. the aim of this study is to test the reliability of the retract system to monitor respiratory distress in critically ill children. the retract system is detailed in reference 1. in summary, cameras reproduce in 3d the thorax and abdomen of a subject. the respiratory status (respiratory rate (rr), tidal volume (vt), minute ventilation (mv)) assessed by the retract system was compared on a bench test (high-fidelity mannequin) and in critically ill children, to the ventilator measurements and clinician expert evaluation (gold standard). bland-altman plots were used for comparison. results: we observed a significant agreement, on mannequin, between retract system and gold standard method in estimating vt, rr and mv, i.e. 95% of the paired differences were within the limits of agreement in bland-altman plots, as illustrated in fig. 1 . in critically ill children (n = 2), the correlation between the pairs of measures was also high (r > 0.95, p < 0.001) and thecoefficient of determination with a high fit (0.90 < r2 < 0.99, p < 0.0001). for good correlation, the retract system needed to have a visual access to thorax and abdomen in a quiet subject. the retract system measurements of vt, rr and mv for respiratory distress monitoring in patients seems reliable. more testing are required to validate this method in usual practice and to develop the retractions signs video analysis. compliance with ethics regulations: yes. rationale: severe bronchiolitis requires hospitalization in paediatric intensive care unit (picu). non-invasive ventilation (niv) has been demonstrated to treat them since twenty years, its use is well defined but there is no consensus for the weaning. this study evaluated the application of a nurse-driven niv weaning protocol in hospitalized infants with severe bronchiolitis and verified its safety. this was a retrospective monocentric study in a picu of robert debré hospital-paris, france. in the epidemic period of bronchiolitis between 2015 and 2017, all patients under one year old with severe bronchiolitis and requiring niv were included. two groups were compared: one group using the nurse-driven niv weaning protocol and one group without using this protocol. occurrences of complications, duration of ventilatory support and length of stay (los) in picu and total los were compared. results: 191 patients were included in the study, 115 in the no-protocol group, and 72 in the protocol group. the nurse-driven protocol was using at the rate of 90% (n = 72/80 in the protocol group (p = 0.522). picu los were 3.5 days [3] [4] [5] in the no-protocol group versus 4 days [3-5.5 ] in the protocol group (p = 0.383), hospital los was 10 days [7] [8] [9] [10] [11] [12] [13] [14] in the no-protocol group versus 10 days [7] [8] [9] [10] [11] [12] in the protocol group (p = 0.447) (fig. 1) . the use of this first nurse-driven niv weaning protocol was feasible and simple with a very good application rate. its utilization was safe. the occurrence of complications did not increase by the use of this protocol. it would allow an optimal niv weaning without prolonging the ventilatory support duration nor picu los or hospital los. the professional practices appeared to be coordinated and the nurses appeared to be more autonomous. compliance with ethics regulations: yes. no-protocol and protocol groups comparison: cpap duration (1), ventilatory support duration (2), picu los (3), hospital los (4) rationale: first-line management of severe acute bronchiolitis in infants is mainly based on non-invasive ventilation (niv) and high-flow nasal cannula (hfnc) therapy. however, pediatric data regarding weaning from niv/hfnc are lacking. this study aims to identify the weaning practices from niv/hfnc in children with severe bronchiolitis. the weaniv-survey is a cross-sectional survey. a questionnaire was sent to french-speaking physicians with key roles in pediatric intensive care units. results: a total of 73% (24/33) of french university hospital were represented in the study. only 9% of pediatric centers used a protocol for weaning from niv/hfnc and nurses were considered as key-actors of the weaning process for half of participants. continuous positive airway pressure (cpap) was the mode of ventilation mainly used as the first-line therapy in clinical practice. the main criteriaconsidered toinitiate weaning process were: noor slight respiratory distress, a fio 2 < 40%, a respiratory rate < 50/min and no significant apnea. three strategies to discontinue niv/hfnc were identified: 1/gradual decrease of ventilatory parameters (pressure or flow), 2/abrupt discontinuation and 3/gradual increase in off-ventilation time. abrupt weaning strategy was the most commonly used, no matter the mode of ventilation. a significant level of respiratory distress, the presence of apneas, an increase in oxygen requirement, and a respiratory rate > 60/ min were identified as weaning failure criteria by most pediatric intensive care physicians. conclusion: in most centers, the weaning process does not follow any protocol. abrupt weaning seems to be commonly used as weaning strategy in children with severe bronchiolitis supported by niv/hfnc. based on the study findings, we suggest that criteria for weaning initiation and for weaning failure must be defined and weaning protocols generated. compliance with ethics regulations: yes. complications secondary to prone positioning occured for 6 patients (12.2%). conclusion: this first study, which evaluate prone positioning efficacy in severe p-ards shows evidence that prone positioning improves oxygenation parameters and survival rate. these results highlight the necessity to develop a multicentric prospective randomized study to confirm these conclusions. compliance with ethics regulations: yes. (4 vs 2) and vasoactive-inotropic score (vis) (205 vs 50) were significantly higher in the non-survivor group. cannulation was veno-venous (14%) or veno-arterial (67%) and 8 patients (19%) were finally not initiated on ecmo. we observed an increase of patients cannulated in our picu over time (fig. 1 ). there was no significant difference in mortality between patients transported on ecmo after cannulation in our picu and those who were transported to be cannulated in a referral ecmo center. the median time between the decision and the cannulation was 3.25 h and the median time taken in charge by picu transport team was approximately 1 h. these periods were not significantly different between cannulation on site or in an ecmo center and between survivors and not-survivors. conclusion: in our study, multiple organ dysfunction, particularly hematologic and acuterenal failures, seems to be a risk factor of mortality. the delay between decision and management is similar whatever the cannulation site. specific ecmo mobile team and picu transport team seem to be essential, fast and trained to transfer these patients. it would be interesting to compare our cohort with children requiring ecmo already hospitalized in a referral ecmo center. compliance with ethics regulations: yes. rationale: life expectancy in patients with metastatic breast cancer (mbc) has substantially improved over the last decade. life threatening complications result from advanced diseases, infection and treatment-related toxicity. only few studies have assessed outcomes in this setting. we performed a hospital-wide study to investigate how icu resources are needed in patients with mbc. patients and methods: all patients with mbc managed at our hospital between 2010 and 2019 were retrospectively included. the primary outcome was overall survival (os). factors associated with icu mortality were identified using a multivariable cox proportional hazard model with sensitivity analysis. results are expressed as median [interquartile ranges] unless stated otherwise. results: among the 1128 patients managed at our hospital, 68 (6%, including 1 male) were admitted to the icu (8 [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] patients per year). age was 55 [49-67] years. patients were receiving their 2nd [1st-3rd] line of treatment and had 3 [2] [3] metastatic sites. sofa score at admission was 3 [1] [2] [3] [4] [5] [6] [7] [8] . main reason for icu admission was sepsis (n = 23, 34%), acute respiratory failure (n = 22, 32%), coma (n = 9, 13%) and metabolic disorder (n = 7, 10%). invasive mechanical ventilation was required for 18 patients (26%) and renal replacement therapy for 10 (15%). sixteen (24%) patients died in icu. following icu discharge, median os was 6.4 months (95% ci [1.7-17.9 ]) and 22/52 (42.3%) patients died within 3 months. an antineoplastic treatment was resumed for 33/52 (62%) patients alive after icu discharge. factors independently associated with mortality were performance status ≥ 2 (hr 1.85, 95% ic [1.01-3.40] ) and sofa score at day 1 (hr 1.19 per point, 95% ic [1.11-1.27] ). after sensitivity analysis, the number of treatment lines at icu admission was not associated with mortality. conclusion: icu admission is required in the course of the mbc disease for 6% of the patients. determinants of short term outcomes rely on performance status and disease severity but not on the characteristics of the underlying disease. ongoing analyses will assess whether icu survivors reach life expectancy of patients never admitted to the icu. compliance with ethics regulations: yes. hubert gheerbrant 1 , jean-françois timsit 2 , nicolas terzi 1 , stephane ruckly 3 , mathieu laramas 1 , matteo giaj levra 1 , emmanuelle jacquet 1 , loic falque 1 , denis moro-sibilot 1 , anne-claire toffart 1 1 chu grenoble alpes, grenoble, france; 2 aphp, paris, france; 3 outcom-erea, bobigny, france correspondence: hubert gheerbrant (hgheerbrant@chu-grenoble.fr) ann. intensive care 2020, 10 (suppl 1):p-002 rationale: the prognosis of critically ill cancer patients admitted in intensive care unit (icu), remains an issue. our objective was to assess the factors associated with 3-and 6-month survival of icu cancer survivors. patients and methods: based on the french outcomerea ™ database, we included solid cancer patients discharged alive, between december 2005 and november 2013, from the medical icu of the university hospital in grenoble, france. patient characteristics and outcome at 3 and 6 months following icu discharge were extracted from available database. results: of the 361 cancer patients with unscheduled admissions, 253 (70%) were discharged alive from icu. the main primary cancer sites were digestive (31%) and thoracic (26%). the 3-and 6-month mortality rates were 33% and 41%, respectively. factors independently associated with 6-month mortality included ecog performance status (ecog-ps) of [3] [4] 3. 1.60-9.43). interestingly, cancer chemotherapy prior to icu admission was independently associated with lower 3-month mortality (or, 0.38; 95% ic: 0.2-0.75). among patients with an ecog-ps 0-1 at admission, 70% (n = 66) and 61% (n = 57) displayed an ecog-ps 0-2 at 3 and 6 months, respectively. at 3 months, 74 (55%) patients received anticancer treatment, 13 (8%) were given exclusive palliative care. discussion: factors associated with 6-month mortality are almost the same as those known to be associated with icu mortality. we highlighted that most patients recovered an ecog-ps of 0-2 at 3 and 6 months, in particular those with a good ecog-ps at icu admission, and could benefit from an anticancer treatment following icu discharge. conclusion: these results should be taken into account when deciding upon icu admission. it is of paramount importance to have an evaluation of both patient's general condition and anticancer treatment opportunities following icu discharge. compliance with ethics regulations: yes. rationale: the decision to urgently initiate medical anti-cancer treatment in cancer patients admitted to intensive care unit for cancerrelated organ failure is an issue. we currently lack criteria to select patients who may benefit from the treatment initiation. the purpose of our exploratory study was therefore to evaluate the characteristics of patients whose medical anti-cancer treatment is initiated in icu and to identify prognostic factors for in-hospital mortality. in these patients. patients and methods: we analyzed retrospectively, over a period of 11 years (1/1/2007 to 31/12/2017), cancer patients over 18-year old admitted to our icu bordet and in whose anti-cancer medicaltreatment was initiated during in-icu stay. to identify prognostic factors for in-hospital mortality, we carried out a multivariate analysis of the factors influencing this mortality, considered as a binary. we also analyzed the long term survival of patients alive after their hospital stay (from the day of going out of hospital). results: overall, 147 patients were included, 78 men (53%) and 69 women (47%), with a median age of 58 years (18-86). of these, 79 patients (54%) had a solid tumor and 68 (46%) had a hematological tumor. in-icu mortality is 23% (95% ci 17-31%) and in-hospital mortality 32% (95% ci 25-40%). the prognostic factors for in-hospital mortality were age (mean 61 vs 54 in those who survived), the sofa score (median 6 vs 2), the saps ii score (mean 41 vs 31), the charlson score (mean 8 vs. 6.5), the number of organ failure (mean 2.5 vs 1.4) and the presence of a therapeutic limitation (ntbr stated within 24 h: 68% vs 16%). survival at 1 year of patients who survived the hospital stay was 37% and median survival time was estimated to be 0.5 year (95% ci 0.4-0.9). in patients with a solid tumor, 1-year survival was 17% and 61% in those with a hematological tumor (p < 0.001). conclusion: we observed, in selected cancer patients admitted to the icu for a cancer-related complication, that the initiation of an anti-cancer medical treatment is feasible and can lead to interesting results, particularly in patients with a hematological tumor. compliance with ethics regulations: yes. rationale: considerable progress in the management of onco-hematology (oh) malignancies led to an increase in the number of patients proposed for intensive care unit (icu) admission. several guidelines offer decision models for icu transfer of these patients. we aimed to describe prognosis, adequacy of icu admission and denial in oncohematology patients. we included all oh patients proposed for icu admission in a tunisian medical icu, between january 2016 and july 2019. from an admission proposal registry, were collected patient underlying condition, functional status, malignancy and predicted prognosis, acute critical illness and its reversibility, adequacy of icu rationale: cancer patients frequently need intensive care support for a life-threatening condition due to the underlying neoplasm or an adverse therapy-related event. however, there are poor data on their characteristics and outcomes in the intensive care setting. the aim of the present study was to describe clinical characteristics and to identify factors associated with in-icu mortality in critically ill cancer patients. patients and methods: it is a retrospective study conducted in the medical icu of farhat hached teaching hospital between january 2007 and december 2018. all cancer patients with complete records were included. baseline characteristics, clinical parameters, severity of illness, primary tumor location and outcomes were collected. univariate and multivariate regression analyses were carried out to identify factors independently associated to poor prognosis. rationale: prognostic impact of underlying malignancy seems limited in most studies assessing outcome of critically ill cancer patients [1] . however, only limited number of characteristics, namely disease progression status and preexisting stem cell transplantation, were usually assessed [1] . primary objective of this study was to assess influence of hematological malignancy aggressiveness on hospital outcome. secondary objective was to assess influence hematological malignancy aggressiveness on type of infection. patients and methods: post-hoc analysis of prospective multicenter cohort performed in 17 hospitals in france and belgium and including critically ill adults with underlying hematological malignancy admitted in icu from jan 2010 to may 2011. a cox model was used to adjust for confounding variables then a propensity score matching on characteristics associated with underlying malignancy aggressiveness was performed. results: of the 1011 included patients, 300 (29.7%) had low grade malignancy (lg), the most frequent being myeloma (n = 126), chronic lymphocytic leukemia (n = 76), and myelodysplasia (n = 46). patients with lg malignancy were older, underwent more frequently autologous stem cell transplantation (sct) and had less frequently altered performans status. they had more severe organ failure at icu admission (sofa score 6 [4] [5] [6] [7] [8] [9] vs. 5 [3] [4] [5] [6] [7] [8] , p = 0.03). before adjustment, mortality was 36% (n = 108) and 39.9% (n = 284) respectively in patients with and without lg malignancy (p = 0.27). after adjustment for confounder using a cox model, a higher mortality was associated with nonlow grade malignancy (or 1.49; 95% ic 1.17-1.9). a propensity score then allowed a 1:1 matching upon variable associated with malignancy aggressiveness. after matching unadjusted mortality was 36% (n = 108) in patients with lg malignancy and 48.8% (n = 146) in patients with high grade malignancy (p = 0.002) (figure) . in the matched cohort and after adjustment for confounder, high grade malignancies were associated with lower mortality (or 1.42; 95% ic 1.10-1.84). risk of fungal infection was unchanged by underlying malignancy before adjustment (6% vs. 8.6% of patients with and without lg malignancy; p = 0.26) or after adjustment (hr 1.29; 95% ic 0.71-2.41). conclusion: despite anti-cancer advances, aggressiveness of hematological malignancies is associated with overall icu outcome. lowgrade malignancies displaying a better prognosis than non-low grade. aggressiveness of the underlying malignancy is not associated with risk of fungal infection. compliance with ethics regulations: yes. rationale: guillain-barré syndrome is the most common cause of acute flaccid paralysis and is associated with pulmonary embolism due to the mobility limitation. the aim of this study is to describe the incidence, the severity of pulmonory embolism in patients admitted to an intensive care unit (icu) for guillain-barre syndrome (gbs). patients and methods: twenty-eight adults patients with confirmed diagnosis of gbs were admitted to the icu in our university hospital center over a 10-year period and they were all included. prevalence, risk factors and course of vte were analyzed in icu patients with various forms and severity of gbs. results: during the study period, 23 adult gbs patients were included. five (17.9%) developped pulmonary embolism. the mean age was51.2 ± 16.7 years and the sex ratio was 0.86. the comparaison betewen the 2 groups with and without pe showed that factors associated with the development of this complication were: respiratory failure requiring mecanical ventilation (p = 0.03), infectious complications (p < 0.001), blood pressure lability (p = 0.029), the delay of icu admission (p = 0.02), the delay to treatment initiation (p = 0.036), the sofa score (p = 0.03) and the presence of quadriplegia (p = 0.031). conclusion: pulmonary embolism is a frequent complication in patients with gbs. factors associated with this complication were: respiratory failure requiring mecanical ventilation, infectious complications, the delay of icu admission, the delay to treatment initiation, a high sofa score and the presence of quadriplegia. preventive measures in this category of patients have to be improved. rationale: acute respiratory distress syndrome (ards) is a life-threatening pathology associated with very high morbidity and mortality (35-45%) in intensive care units (icu) and with even higher mortality among the severly burned patients worldwide (36 à 80%). the aim of our study was to describe in tunisia burn patients with ards and to identify prognosis factors. patients and methods: we conducted a descriptive retrospective study between 01-01-2017 to 31-12-2018, in burns icu, in ben arous, in tunisia. all burns who presented an ards, according to the berlin 2012 definition, during their stay in the icu, were included. when clinical or gasometric data was uncomplete, these patients were excluded. results: during the study period, 691 patients were admitted to our burn unit including 246 ventilated patients. fifty patients presented an ards: fifteen patients were excluded for lack of information, and 35 patients were retained. the sex ratio was 2.5. patients had a mean age of 36 ± 12 years, an average burned area of 44% ± 22%, an average unit of burn skin score (ubs score) of 94 ± 77 and an average sequential organ failure assessment score (sofa score) of 4. none of the patients had a history of cardiovascular or pulmonary diseases. the average time of onset of ards was 5 ± 4 days. ards was mild in 1 case, moderate in 11 and severe in 23. the etiology of ards was pulmonary in 25 cases (71%) and extra-pulmonary in 10 (29%). the pulmonary ards had as cause pneumonia isolated in 15 patients, an isolated pulmonary burn in 6 patients and a combination of pneumonia and lung burns in 4 patients. extra-pulmonary ards were all due to sepsis and mainly to bacteremia. septic shock was associated with ards in 20 patients (57%). the treatment was a conventional treatment based on protective ventilation, curarization and prone positioning in addition to the etiological treatment. the average length of stay in icu was 9 days and mortality was 85% in these patients. conclusion: mortality from ards in burns in tunisia, is important especially in those with pulmonary burns as well as those with sepsis. the introduction of new treatments, such as extracorporeal membrane oxygenation, remains essential to improve the prognosis of burn patients. compliance with ethics regulations: yes. rationale: aspiration pneumonia (ap) is common in intensive care unit (icu). the incidence of ap among adults hospitalized with pneumonia ranges between 5 and 53.2%. usually one or more risk factors are identified to be involved in ap. the aim of this study was to determine the risk factors and predictors of mortality on patients with ap. patients and methods: we retrospectively included patients aged more than 18 years and who were hospitalized in our icu for ap. patients were excluded if they had history of tuberculosis, if they have bronchiectasis or metastatic brain tumor. results: a total of 102 patients were included. history of diabetes, hypertension, epilepsy and ischemic stroke were found respectively in 22.2%, 21.5%, 16.7%, and 7.8% of cases. the reason of icu admission were coma (35%), acute respiratory failure (33%), poisoning (27%) and cardiac arrest (5%). the incidence of acute respiratory distress syndrome (ards) was 17%. the most common organism isolated was staphylococcus aureus (4 cases). risk factors for ap were epilepsy (20%), swallowing disorders (18%), ischemic stroke (12%), copd (9%) and degenerative neurological disease (5%). the mortality rate was 17.6%. the median duration of mechanical ventilation was 12 days [iqr 10-23]. in multivariate logistic regression analysis; saps ii score (or = 1.05, 95% ic [1.001-1.1], p = 0.046) and ards (or = 44.04, 95% ic [3.91-495 .57], p = 0.002) were independently associated with mortality. conclusion: risk factors for aspiration pneumonia were epilepsy, swallowing disorders and ischemic stroke. ards and saps ii score were independent predictive factors of mortality. compliance with ethics regulations: yes. undetermined. the aim of this study was to evaluate the impact of hyperoxia on morbidity and mortality. patients and methods: this was a prospective study performed in the icu of abderrahmen mami hospital during a 4-month period. all patients admitted in icu during the study-period were included. those who didn't need oxygen therapy or in end of life stage were excluded. arterial blood gases were analyzed daily and each day with at least one value of oxygen arterial saturation (sao2) > 92% was considered as a day with hyperoxia. for each patient included, the number of times and days spent in hyperoxia was recorded as well as complications during the icu stay and the outcome. results: during the study-period, 140 patients were included but only 112 were eligible. mean age was 58 ± 18 years. acute on chronic respiratory failure was the most frequent reason of admission (67%). non-invasive ventilation was required for 18% of patients and invasive mechanical ventilation was necessary in 65% of cases. overall mortality was 32%. hyperoxia was observed in 96% of cases, with an average of 10 ± 10 times during the icu stay and 6 ± 6 days. a statistically significant association was observed between a long duration of hyperoxia and the occurrence of ventilator acquired pneumonia (p < 10-3), ventilator acquired bronchitis (p = 0.001), acute respiratory distress syndrome (p < 10-3), atelectasis (p < 10-3), septic shock (p < 10-3), rythm disorders (p = 0.003), reintubation (p < 10-3) and tracheostomy (p = 0.038). on multivariate analysis, independent factors of mortality were: simplified acute physiology score ii, cardiac failure, need for invasive mechanical ventilation and septic shock. hyperoxia was not independently associated with mortality. conclusion: hyperoxia is frequent in icu. it is significantly associated with icu complications but not independently associated with mortality. compliance with ethics regulations: yes. experience of the practice of prone position in patientswith acute respiratory distress syndrome in intensive care (chu oran) nabil ghomari, soumia benbernou, djebli houria faculté de medecine d'oran, oran, algeria correspondence: nabil ghomari (nabilghomari@hotmail.fr) ann. intensive care 2020, 10 (suppl 1):p-013 rationale: mechanical ventilation (mv) in the prone position (pp) and low tidal volume have become recommendations with a high level of scientific evidence in recent years. the pp has been practiced for 7 years in the chu oran emergency resuscitation service. we wanted to report the service experience in the practice of pp in patients with ards. patients and methods: retrospective study performed in patients with severe hypoxia ards with spo2 < 88% under fio2 > 80% or pao2/fio2 < 150 during the period march 2011 to december 2018. results: 38 patients received ventilation in pp. ards was secondary to thoracic trauma in 42% of patients, septic shock in 32% and aspiration pneumonitis in 26%. analysis of the success factors and improvement of oxygenation found that lobar ards, the delay < 72 h and a duration of pp ≥ 18 h were statistically significant. conclusion: the pp must be integrated into the arsenal of care of the patients in ards especially in our country where we do not have all the therapeutic options. compliance with ethics regulations: yes. julien goutay, nicolas cousin, thibault duburcq, erika parmentier-decrucq chu de lille, pôle de réanimation, hôpital salengro, lille, france correspondence: julien goutay (julien.goutay@gmail.com) ann. intensive care 2020, 10 (suppl 1):p-014 rationale: in veno-venous extracorporeal membrane oxygenation (vv-ecmo) therapy, blood flow is the main determinant of arterial oxygenation and should be 60-80 ml/kg/min in adults. this flow rate is determined by several factors including the size of the inflow cannula. the impact on clinical outcomes of arterial cannula's size in veno-arterial ecmo (va-ecmo) has already been studied, and showed no difference for survival to discharge, weaning success rate and initial flow rate between a small cannula group and a larger one. our first objective was to describe the impact of inlet cannula size on the assistance flow rate in patients treated with vv-ecmo. secondary objectives were to analyze its impact on ecmo weaning, mechanical ventilation characteristics and mortality. patients and methods: we retrospectively reviewed all cases of respiratory failure treated with vv-ecmo admitted in the medical intensive care unit (icu) of lille's teaching hospital from january 1st, 2013 through march 31st, 2019. inlet cannula size was collected and divided into two groups: the "small cannula" group had inlet cannula less than or equal to 23fr, while "large cannula" were larger than 23fr. primary endpoint was the initial flow rate according to the inlet cannula size, and its changes during the first 48 h of assistance. secondary endpoints were the analysis of predictive factors associated with the choice of a larger inlet cannula, and the impact of its size on clinical outcomes such as successful ecmo weaning. results: 74 patients treated with vv-ecmo were admitted in our hospital. eleven (15%) were cannulated with a large inlet device. mean initial ecmo flow rate was statistically higher in the "large cannula" group than in the "small cannula" one: 5.8 l/min (± 0.7) versus 4.7 (± 0.8) respectively, p < 0.0001. the difference was also significant during the first 48 h of assistance. we found no difference between the two groups on clinical outcomes such as ecmo weaning time. in univariate analysis, weight was heavier in the "large cannula" group [94 (± 26) kg] than "small cannula" [81 (± 20)], p < 0.05. conclusion: ecmo initial flow rate was higher in a "large inlet cannula" group (internal diameter more than 23 fr) compared with a "small cannula" group. we found no correlation with cannula-related haemorrhagic or thrombotic complications. inlet cannula size did not influence ecmo weaning, and duration time, but this may be a lack of statistical power. further prospective studies should confirm this results. compliance with ethics regulations: yes. rationale: burn patients are at risk of multidrug-resistant (mdr) bacterial infections with high mortality rate. therefore, monitoring the emergence of mdr pathogens in these vulnerable patients is important. this study aimed to assess digestive colonization with carbapenemase-producing gram-negative bacilli (cp-gnb) in patients admitted to the burn intensive care unit. patients and methods: our study was prospective and conducted over a one-year period (january 2018 to december 2018). every admitted patient was subjected to the screening. a double swab set was used to collect rectal swab specimens. one swab was used for mdr screening by disk diffusion method on selective media; the other for multiplex real-time pcr (cepheid's genexpert ® ) allowing detection of the most common carbapenemase-encoding genes (ceg) (blaoxa-48, blakpc, blandm, blavim and blaimp). results: among the 125 studied patients, 71 (56.8%) were detected positive at admission for cp-gnb by the genexpert ® carba-r assay. eleven patients, initially not colonized, acquired positive faecal carriage subsequently during their hospital stay. forty-two colonized patients (59.1%) developed cp-gnb infection during their hospitalization. the ceg blandm quantitatively dominated by far with 54 detections; either alone (15 cases) or associated with other ceg (39 cases). the second most frequent gene was blaoxa-48. it was detected alone eight times and in association with other ceg 38 times. forty-three patients carried blavim gene, usually in association with other ceg (93%). however, only one patient carried blakpc gene. the parallel screening by classical microbiology methods (disk diffusion on selective media) detected the presence of cp-gnb in all molecular positive samples. conclusion: our study describes the characterization of carbapenemase in burn patients and highlights their alarming spread. this emphasizes the importance of an active surveillance program by early detection of cp-gnb carriers and an isolation policy to limit the mdr infections expansion. compliance with ethics regulations: yes. rationale: invasive fungal infections are increasingly observed in the icus especially in burn units. inthe absence of simple and accessible techniques for early microbiological diagnosis, the use of antifungal treatment is increasing. little is known about the extent of the problem of antifungal prescription in burn icus. we aimed to evaluate the antifungal prescription in major burn patients. patients and methods: during the study period (2018-2019), all prescriptions of antifungals were analysed. analysis concerned demographics, clinical circumstances, as well as the basis of antifungal prescribing (targeted vs. empiric). among the 691 patients admitted in this period, 58 patients were treated with antifungals (sex ratio: 1.4; mean age: 38 ± 19 years, with low associated comorbidity). the tbsa was 34.25% [19.5-53.25 ], ubs was 57 [32. [75] [76] [77] [78] [79] [80] [81] [82] [83] [84] [85] [86] [87] [88] [89] [90] [91] . most of the patients (87.9%) were transferred from another hospital structure within 62 ± 96 h. antifungal treatment was started at the average of the seventh day post wound injury, more often on an empiric basis. sofa score at the beginning of the treatment was 11 ± 3.9. lymphopenia was present in 32% and thrombopenia was present in 41%. index of colonisation was positif only in 4 cases. the average candida score was 2.72 ± 1.15. microbiological results were tardily collected, within 3 weeks, in 27%. fungal urine infections were found in 9 cases. candidemia and catheter-related infections were considered only in 2 cases. the risk factors of fungal infection as described in literature were found in most of the patients including mechanical ventilation (84.4%), length period of stay (16 days [8.75-29.5]), central venous line (100%), severe sepsis or septic shock (100%), large-spectrum antibiotherapy for more than 3 days (100%). conclusion: the management of antifungal infections in major burn patients is still challenging. antifungal prescription is based on clinical presumption. the empirical prescription reflects the lack of efficient laboratory support and late microbiological results prompting physicians to rely on clinical informations. the management of fungal infections is based on the improvement of mycological investigations. compliance with ethics regulations: na. rationale: invasive candidiasis is a widespread and alarming infection in intensive care units (icu) patients. its diagnosis is often difficult because of the lack of specificity of clinical signs and the low sensitivity of blood cultures. while the candida albicans species remain the most common cause of bloodstream infections, non-albicans are emerging. these infections are serious, associated with high mortality rate and requiring early diagnosis and appropriate treatment. in tunisia, few data are available. we aimed to determine the epidemiological profile of a series of candidemia in icu, the risk factors associated with the occurrence of candidemia and to describe the modalities of the mycological diagnosis of candidemia and their etiological profile. patients and methods: a retrospective longitudinal descriptive study conducted in the parasitology-mycology laboratory with the collaboration of the medical icu of la rabta hospital-tunis over a 12-year period from january 1, 2006 to december 31, 2017. all hospitalized icu patients with at least one candida-positive blood culture were included. results: forty-three patients among 2585 hospitalized patients during the study period had at least one candidemia infection. the main risk factors for development of candidemia infection include invasive procedures, a prior use of antibiotics and parenteral nutrition. c. albicans was the most common species, detected in 41.9% of patients. nonalbicans candida species were prominent (58.1%), represented by c parapsilosis, followed by c. tropicalis and c. krusei then c. glabrata and finally c. lusitaniae. all the isolates tested were sensitive to the common antifungal agents. the mortality rate of our patients was high (76.7%), and the detection of the albicans species in blood cultures was the only prognostic factor identified (or = 9.38 [0.83-105.23], p = 0.06). conclusion: candidemia in the medical icu patients is common and is associated with high mortality rate. despite the progress of biological tools, the diagnosis is difficult and needs to take into account the risk factors of the patients as well as scores based on clinical and microbiological parameters. a better identification of risk patients may help to early initiate empirical antifungal treatment. compliance with ethics regulations: yes. necrotizing soft-tissue infections in the intensive care unit: a retrospective hospital-based study kais regaieg, sabrine nakaa, arnaud mailloux, madjid boukari, johana cohen, dany goldgran-toledano groupe hospitalier intercommunal le raincy-montfermeil, montfermeil, france correspondence: kais regaieg (kais.regaieg@gmail.com) ann. intensive care 2020, 10 (suppl 1):p-018 rationale: the objective of our study is to describe the epidemiological and clinical characteristics of necrotizing soft-tissue infections (nsti) and to improve therapeutic management. we conducted a retrospective observational study that included patients admitted in the intensive care unit (icu) of general hospital between september 2014 and aout 2019 with a primary or secondary diagnosis of nsti. we collected demographic and clinical data, cultured pathogens, lengths of stay, and in-icu mortality. results: during the study period, a total of 20 patients admitted to the icu were diagnosed with nsti (0.3% of the total number of patients). the mean of age was 69 years. the sex ratio (m/w) was 0.6. ten patients (50%) were directly admitted to the icu, others were transferred from medical or surgical wards. the mean of saps ii was 61.6 (26.6). the main indication to admission in icu was shock (50%). the most common comorbidity was diabetes (50%). the other co-morbidities associated with nsti were cardiovascular diseases (33%), obesity (25%) and carelessness (25%). the sites most commonly affected were extremities in 15 patients (75%) and abdomen/ano-genital in 4 patients (20%). in icu, a total of 17 patients (85%) were mechanically ventilated [ (median duration: 4.70 days (8.63)], 15 patients (75%) were given vasopressors, and 4 patients (20%) underwent renal-remplacement. all patients underwent one or more chirurgical intervention. 17 patients (85%) underwent radical necrosectomy. in 3 cases, an amputation was necessary. polymicrobian infection was seen in 10 patients (50%). in 8 patients (40%), we used vacuum assited closure therapy, which in 3 patients was followed by definitive reconstruction by split skin grafts. the mortality in icu was 50%. the mean stay in icu was 12 days . the mean duration of hospitalization of the patients who survived was 75 days (15-180). on the basis of a univariate analysis, higher saps ii score and lactate levels were associated with increased mortality (p < 0.01). conclusion: ntsi is rare in icu but it's a life-threatening and disabling disease with a high mortality requiring a multidisciplinary management. early diagnosis and adequate treatment are necessary to improve clinical outcome and must be known by everyone. more studies are needed to estimate the interest and delay of new strategies such as negative pressure therapy. compliance with ethics regulations: yes. rationale: nosocomial infections remain a major cause of mortality and morbidity in burn patients. providing information about the main causative bacterial agents and determination of their susceptibility to antibiotics may improve empiric therapy and early detection of emerging antimicrobial resistance. the aim of our study was to investigate the species distribution and antibiotic susceptibility of isolated strains from a burn intensive care unit (icu). patients and methods: this study was performed retrospectively on all bacteriological samples taken from the burn icu at the trauma and burn center in tunisia during a seven year period (from january 2012 to december 2018). all isolated microorganisms were identified on the basis of standard microbiological techniques. antibiotic susceptibility testing was carried out by the agar disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. minimum inhibitory concentration of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may 2017. results: during the study period, the most frequent identified species were pseudomonas aeruginosa (15.7%), staphylococcus aureus (15%), klebsiella pneumoniae (12.6%) and acinetobacter baumannii (12%). these strains have been mainly isolated from blood cultures (37%) and skin samples (26.6%). pseudomonas aeruginosa resistance to ceftazidime increased from 9.2% in 2012 to 53.5% in 2018 and resistance to imipenem and ciprofloxacin was 63.3% and 42.9%, respectively. four strains were resistant to colistin. rationale: community-acquired peritonitis is a heterogeneous condition characterized by peritoneum inflammation in response to a bacteria injury. the aim of our study is to describe the epidemiological, clinical, bacteriological, etiological, therapeutic characteristics of community peritonitis, and to evaluate the prognostic factors. patients and methods: this is a retrospective descriptive and analytical study spanning three years (between january 2015 and december 2017) involving 114 cases of community peritonitis, hospitalized in the surgical emergency resuscitation department p33 ibn rochd casablanca university hospital. our study included adult patients with community-acquired peritonitis who underwent medical and surgical management. the studied parameters are the demographic data, the clinical and paraclinical signs, the care taken and the evolution of the patients. the study showed that the mean age was 54.2 ± 17.2 years, with a sex ratio of 2.17. patients medical history included tobacco (31.60%), extra-abdominal signs [hemodynamic failure (45%), renal failure (n = 39, 50%), hematological disorders (n = 80, 70%) and respiratory disorders (n = 38, 60%)]. therapeutic management was based on perioperative resuscitation, treatment of organ failure, probabilistic antibiotic therapy and median laparotomy surgery. the main etiologies of community peritonitis were: digestive perforation (76.3%), purulent effusion (50%), intestinal necrosis (16.7%), cholecystitis (3.5%). intraoperative bacteriological specimens yielded the following bacteriological profile: predominance of ngb (85.9%) dominated by e. coli (46.8%) followed by klebsiella pneumoniae and enterobacter cloacae (28.2%) the mean hospital stay was 5.4 ± 5.5 days. the mortality rate was 55.3%. conclusion: improvement in the prognosis of community-acquired peritonitis can only be achieved by constant assessment of very early diagnosis and initiation of appropriate resuscitation and antibiotic therapy associated with a complete surgery carefully codified according to guidelines. compliance with ethics regulations: yes. rationale: klebsiella pneumoniae carbapenemase (kpc)-producing bacteria are a group of emerging highly drug-resistant gram-negative bacilli causing infections associated with significant morbidity and mortality. the aim of our study is to point out the incidence of bloodstream infections (bsi) caused by kpc in icu patients, its clinical presentation and course. patients and methods: we conducted a retrospective descriptive study. all patients hospitalized in the icu of our hospital who developed bsi caused by kpc from january 01, 2016 to december 31, 2017 were included. results: during the study period, 20 patients were included. the mean age was 45.7 ± 22.5 years ranging from 8 to 91 years. sex ratio (m/f) was 3. trauma was the major cause of hospitalization in 12 cases (60%). the most common past medical diseases were arterial hypertension in 7 patients (35%). length of hospital stay prior to icu admission was 4 ± 7.2 days. at infection onset, mean saps ii was 49 ± 13.2, mean sofa was 10.4 ± 4.8 and mean apache ii was 19.8 ± 6.7. during icu hospitalization, all patients required invasive mechanical ventilation during 27.2 ± 13.2 days, had a central venous catheter (cvc) and an indwelling urinary catheter in place, 15 patients (63.9%) had tracheotomy, 12 (60%) underwent surgery, 9 (45%) presented acute kidney failure and 4 (20%) needed hemodialysis. before the isolation of kpc, all patients presented infections. antibiotics prescript were: colistin in 14 patients (70%), carbapenems in 12 patients (60%), amoxicillin/clavulanic acid in 11 patients (55%), cephalosporins in 9 patients (45%), fluoroquinolones in 6 patients (30%), tigecycline in 5 patients (25%), aminosids in 4 patients (20%), rifampicin in 4 patients (20%), fosfomycin in 3 patients (15%), glycopeptides in 2 patients (10%). the delay for kpc-bsi onset was 17.7 ± 7.5 days. the most common infection sources responsible of kpc-bsi were: cvc in 6 patients (30%) and pneumonia in 5 patients (25%). kpc infection was responsible of septic shock in 18 patients (50%). resistance rates were: gentamycin (65%), amikacin (20%), colistin (15%), fosfomycin (10%) and tigecycline (10%). antibiotics used to treat kpc bloodstream infection were resumed in table 1 . the mean length of icu stay was 36.1 ± 16.8 days. out of the 20 included patients, 7 patients died (the mortality rate was 35%). death was related to kpc infection in 5 patients. conclusion: the high prevalence of kpc-bsi in icu patients dictates the importance of implementation of infection control measures and strict antibiotic policies. compliance with ethics regulations: not applicable. we identified 103 episodes of nosocomial infections in 56 patients, representing a cumulative incidence rate of 41.17 per 100 exposed patients. the incidence density was 30.43 infections per 1000 days of hospitalization. the prevalence of pneumonia was 38.83%, followed by urinary tract infections 21.35%, central venous catheterization infections 15.53%, bacteriemia16.3%, meningitis 6.7% and surgical site infections 1.9%. the incidence rate of intubation-related pneumonia was 24.47/1000 day of exposure. the incidence rate of bladder-related urinary tract infection was 9.7/1000 day of exposure. the incidence rate of positive culture of the central venous catheter was 7.05/1000 day of exposure. the incidence rate of bacteremia related to stay was 9.2/1000 day of exposure. the mortality rate was 26.5% with a significant difference between infected and uninfected patients (p = 0.041). microorganisms were gram negative bacteria in 80% of cases. conclusion: epidemiological surveillance of healthcare-associated infections is needed to establish prevention plans. compliance with ethics regulations: not applicable. in the prehospital setting, early identification of septic shock (ss) with high risk of mortality is essential to guide hospital orientation (emergency department (ed) or intensive care unit (icu)) prior to early treatment initiation. in this context, the severity assessment is most of the time restricted to clinical tools. in this study, we describe the association between prehospital shock index (si) and mortality at day 28 of patients with ss initially cared for in the prehospital setting by a mobile intensive care unit (micu in this study, we reported an association between prehospital si and mortality of patients with prehospital ss. a si > 0.9 is a simple tool to assess severity and to optimize prehospital triage between ed and icu of patients with ss initially cared for in the prehospital setting by a micu. the association of si with biomarkers may be helpful to improve the screening for ss and decision making of ss in the prehospital setting. compliance with ethics regulations: yes. the failure rate and complications were comparable between the 2 groups, but the ultrasound-guided internal jugular catheter appears to be faster to insert and requires fewer punctures, so it could be an alternative to the femoral one in emergency situations. rationale: neuromyelitis optica (nmo) is a rare but severe disease. the prognosis of treated nmo attacks remains unclear. we evaluated our practice, the early evolution and the prognosis of nmo patients. patients and methods: an observational study was performed on patients with nmo attacks presenting with visual or medullar symptoms admitted for plasma exchange (pe) therapy from january 2017 to august 2019. treatment efficiency was defined as a negative shift of the visual or motor disability score (edss). nonparametric mann-whitney and fisher exact tests were used for statistical analysis as required. results: twenty-four patients had 110 pe sessions. characteristics of the cohort are described in table 1 . 5 (20.8%) died from complications of nmo attacks. treatment had an effect in 15 (85.2%) patients. the shift in the ambulatory and visual edss was respectively − 0.4 + 2.3 and − 1.7 + 1.7. the 5 non-survivor patients had all aqp4 antibodies (p < 0.05). residual edss was higher in the non-survivor group (8.7 + 1.0 vs 6.1 + 1.7, p < 0.01). pulse steroids were administered in 1 (20%) patient in the non-survivor group vs 15 (78%) patients in the survivor group (p < 0.05). twelve (80%) patients previously given pulse steroid therapy responded to pe. discussion: we assessed the handling of nmo attacks and identified our flaws. we concluded that pulse steroid therapy should not be withheld or replaced by lower dosage. we also need to find a way to make attacks identified by physicians earlier to shorten the delay between its onset and patient's admission in a specialized care unit. we observed that the mean improvement is modest during the early phase of our treatment. but a modest improvement in the edss can have a great impact in the patient's quality of life and even survival. conclusion: nmo attacks remain a threatening disease despite aggressive treatment. shortening the delay of treatment and ensure adequate pulse steroid therapy coupled to pe could be a way to improve the prognosis. compliance with ethics regulations: yes. rationale: acute kidney injury in trauma patients is a problem that has been little studied in the intensive care unit (icu). its occurrence has been shown to be associated with high morbidity and mortality. we aim to determine the outcome of icu trauma patients with acute kidney injury (aki), including the incidence of death in the icu, of nonreversible renal impairment and icu complications. patients and methods: this is a prospective study, conducted in the department of emergencies and icu, including trauma patients with a minimum icu stay of 7 days. renal failure was defined based on the new kdigo classification. predictors of mortality and poor outcome were identified using univariate and then multivariate analysis. results: one hundred and fifty patients were admitted during the study period for the management of post-traumatic injuries, among which 98 patients were included. the incidence of aki in the studied population was 47% (46 cases) with 26 (56%) diagnosed with stage one, ten (22%) with stage two and ten (22%) with stage three. the overall mortality of patients with post-traumatic aki was 34.8% (16 patients) with a mean icu lengh of stay (los) at 22 ± 18 days and of days on ventilator at 17 ± 15. eight patients (17.4%) needed renal replacement therapy and thirty-four had non-reversible renal impairement (74%). during icu stay, eight patients (17%) were diagnosed with pulmonary embolism. on univariate analysis, the following variables were associated to mortality in patients with post-tramatic aki including; age, hemodynamic instability on the day of diagnosis and bilirubin levels on the day of aki diagnosis. besides, according to our analysis, the use of renal replacement therapy and the non-reversibility of renal impairment during icu stay were also associated to icu mortality. among these factors, the non-reversibility of renal impairment in the icu was a predictor of mortality on multivariate analysis (p = 0.009, or = 29, . in this cohort, the following variables were predictive of non-reversible renal impairment during icu stay; including age (with a best cut-off of 55 years old), medical history of hypertension, higher iss and diuretics' administration. on multivariate analysis, the age (p = 0.004, or = 0.9, ci 0.80-0.97) and use of diuretics (p = 0.003, or = 33, ci 3.1-359) were associated to non-reversible aki in the icu. conclusion: our study confirms that post-traumatic aki in the icu is associated to high morbidity and mortality. the identification of outcome predictors could be valuable to guide the management of aki. compliance with ethics regulations: yes. rationale: the occurrence of acute kidney injury (aki) in trauma patients is a problem that has been little studied to date. its presence has been shown to be associated with an increased risk of morbidity and mortality in affected individuals. to determine the incidence of post-traumatic aki and identify its predictive risk factors that could be eventually prevented. patients and methods: this is a 10-month long prospective cohortstudy, conducted in the department of emergencies and intensive care unit (icu) of a university hospital, including trauma patients with a minimum icu stay of 7 days. renal failure was defined based on the new kdigo classification. predictors of aki were identified using univariate and then multivariate analysis. results: one hundred thirty patients were admitted during the study period for the management of post-traumatic injuries, among which 86 patients were included. the incidence of aki in the studied population was 53% (46 cases) with 26 (56%) diagnosed with stage one, ten (22%) with stage two and ten (22%) with stage three. on univariate analysis, older age and medical history of diabetes or hypertension were predictors of aki. injury assessment found traumatic brain injury (ais > 3), glasgow (gcs) on admission, and the diagnosis of fat embolism to be associated to post-traumatic aki. moreover, hemodynamic instability on admission and during icu stay, shock-index on admission, the amount of fluid administered the use of vasoactive drugs, sepsis, hyperbilirubinemia, p/f ratio and acute respiratory distress syndrome (ards) were also associated to post-traumatic aki. among these factors, ards (p = 0.001, or = 9, ci 6-100), fat embolism (p = 0.028, or = 2, ci 1. ) without preload-dependence, and 2 were unclassified. multivariate analysis (using variables collected prior to hypotension) identified the following variables as risk factors for the occurrence of hypotension associated with preload-dependence: preload-dependence before hypotension (odds ratio = 4.01, p < 0.001), fluid removal rate by crrt (or = 0.71 per 1 increase in sd, p < 0.001), and lactate levels (or = 1.32 per 1 increase in sd, p < 0.001). in this single center study, preload dependence-associated hypotension was slightly more frequent than hypotension without preload dependence in icu patients undergoing crrt. testing for preload dependence to adjust fluid removal could help prevent hypotension incidence during crrt. rationale: few studies report the relation between functionnal brain alterations during and after icu stay and abnormalities of cbf displayed on tcd. using vti as hemodynamic parameter is unusual for evaluation of cbf. the purpose of this preliminary study was to compare the values of vti of healthy controls (c) versus icu (p) with usual parameters (i.e. diastolic (vd) and mean velocities (vm), resistance (ir) and pulsatility index (ip)). rationale: accurate diagnosis of the level of consciousness is a challenge and different states such as coma, vegetative state (vs) or minimally conscious state (mcs) are often confused while they convey meaningful prognostic information. this distinction rely on the coma recovery scale-revised (crs-r) gold-standard. however, this clinical scale is imperfect since unresponsive patients can exhibit genuine signs of consciousness using advance neuroimaging techniques. expanding the range of behaviors indexing consciousness at bedside is thus of decisive importance. patients and methods: we designed and proposed a new clinical sign of mcs, the habituation to auditory startle reflex (asr), based on the blink response to repeated sounds: either inhibition of the automatic asr response (extinguishable) or nohabituation (inextinguishable response). we prospectively tested this new sing in patients suffering from disorders of consciousness after severe brain injury and first compared its diagnostic performances with the current gold-standard (crs-r) using standard discrimination metrics (auc, sensitivity, specificity, likelihood ratios) and their 95% confidence interval. we then investigated the correlates of this new sign on two validated neuroimaging diagnostic procedures (multivariate eeg-based classification of the state of consciousness and fdg-pet metabolic index of the best preserved hemisphere) using an anova with the state of consciousness and the asr response as independent variable. rationale: although continuous electroencephalography (ceeg) is commonly recommended in neurocritical care patients, implementation of this monitoring in routine is facing the need for a specific training of professionals. we evaluated the effectiveness of a training program for the basic interpretation of ceeg to critical care staffs in a prospective multicentre study. patients and methods: after completion of a pre-test, participants (physicians and nurses) recruited in 6 french intensive care units (icu) received a face-to-face eeg learning course, followed by additional e-learning sessions at day-1 (post-course), day-15, day-30 and day-90, based on training tests followed by illustrated and commented answers. each test was designed in order to evaluate knowledge and skills through correct recognition of 10 predefined eeg sequences covering the most common normal and abnormal patterns. the primary objective was to achieve a success rate of more than 80% of correct answers at day-90 in at least 75% of participants. results: among 250 participants, 108 (43.2%) completed the full training program and 77 of these 108 (71.3%) full-training participants achieved at least 80% of correct answers at day-90. paired comparisons between scores obtained at each evaluation demonstrated a statistically significant increase over time. at day 90, rates of correct answers were greater than 80% for all predefined usual eeg sequences, excepted for the recognition of periodic and burst-suppression patterns and reactivity, which were identified in only 42.6% (95% ci 36.4-48.8) and 60.2% (54.1-66.3) and 70.4 (64.7-76.1) tests, respectively. discussion: this multicentric prospective study, which evaluated a training program for the basics of electroencephalography offered to critical care teams, provides interesting information about the training process and its impact on learners according to their different characteristics. we believe that participants reflect the heterogeneity of the various use of ceeg in the critical care setting. participants came from university and non-university icus, and whereas some of them used to monitor patients with ceeg, others were in an implementation process when the last monitored neurocritical care patients with intermittent eeg. in accordance with previous studies, we focused to the entire medical and nursing icu staffs. conclusion: a 3-months training program aiming to teach the basic interpretation of continuous eeg in the intensive care units was associated with a significant attrition in participation over time. however, participants who received the full training program were capable to accurately recognize the vast majority of eeg patterns that are encountered in critically ill patients. compliance with ethics regulations: yes. mourad goulmane oran hospital and university center, oran, algeria correspondence: mourad goulmane (goulmane.mourad@univ-oran1. dz) ann. intensive care 2020, 10(suppl 1):p-043 rationale: cerebral venous thrombosis (cvt) is a rare but very serious disease with various clinical and etiological aspects. unlike ischemic arterial accidents, epidemiological studies are limited. the aim of our work was to study the clinical, etiological and evolutionary features of cvt in the algerian population from a sample of 28 patients. patients and methods: this is a retrospective observational study conducted in the neurology department of the chu d'oran between january 2016 and december 2017. in a clinical context suggestive of cvt, the diagnosis of certainty was provided by brain mri coupled with mra. all subjects benefited from a complete etiological assessment. the anticoagulant treatment was based on the low molecular weight heparin relayed by the anti-vitamin k. the duration of the follow-up was 12 months. results: the mean age was 38.26 ± 13.59 years, the sex ratio was 6 (24f/4h), the onset was subacute in 55% of cases. the main early signs were headache (88.8%), visual disturbances (50%), epileptic seizures (44.4%) and motor deficit (44.4%). thrombosis predominated in the upper sagittal sinus and lateral sinuses; parenchymal lesions were associated in 2/3 of the cases. gynecologic obstetric causes were by far the most frequent. the evolution was favorable in 83.3% of the cases. discussion: cvt is characterized by its clinical polymorphism, its predominance in young women, and its most often favorable evolution. the causes are multiple and often intricate requiring the realization of a systematic etiological assessment even if the cause seems obvious. the treatment of choice remains early anticoagulation, based on heparinotherapy even in case of hemorrhagic softening. the characteristics of cvt in the algerian population are distinguished by a high frequency of gynecological obstetric causes. awareness campaigns for women of childbearing age are useful. compliance with ethics regulations: not applicable. rationale: the ct-dragon score was developed to predict longterm functional outcome after acute stroke in the anterior circulation treated by thrombolysis. its implementation in clinical practice is hampered by the plethora of variables included. in addition, the score has not been validated in important subgroups such as stroke patients undergoing thrombectomy. given these limitations, the current study was designed to evaluate the use of a simplified score based on machine learning, as a possible alternative. this single-centre retrospective study included 564 patients treated for stroke, in the anterior and posterior cerebral circulation, between 01-2017 and 02-2019. at 90 days, favourable (modified rankin scale (mrs): 0-2) and miserable outcome (mrs: 5-6) were predicted by ct-dragon. machine learning selected the aim was to describe the adherence rates to gold 2017 guidelines in critically ill copd patients and to identify predictors of low adherence. patients and methods: a prospective cohort study conducted from december 2017 to april 2019 in a 9-bed medical intensive care unit of farhat hached hospital. all adult patients admitted for aecopd during the period of the study were included. demographic and clinical data were recorded. adherence to gold 2017 was evaluated. univariate and multivariate regression analyses were carried out to identify factors independently associated to non-adherence to gold 2017 guidelines. results: seventy-seven patients were recruited. patients' characteristics were : mean age, 65.5 ± 9 years; male 71 (92.2%); median duration of the disease, 6 [13-14] years; mmrc scale ≥ 2, 67 (88.2%); health insurance coverage rate, 57 (75%); pulmonologist follow up, 34 (59,6%); frequent exacerbator (≥3 exacerbations in the last year), 26 (34.2%); median exacerbations episodes, 2 [1] [2] [3] . long-term oxygen use and home mechanical ventilation were respectively used in 10 (13.2%) and 5 (6.6%). eight (10.5%), 14 (18.4%) and 54 (71.1%) belonged to copd groups b, c and d, respectively. pharmacological treatment included: saba-ics combination, 25 (32.9%), laba-ics, 10 (13.2%), laba-lama, 10 (13.2%) and lama-laba-ics, 9 (11.8%). overall adherence to 2017 gold guidelines treatment recommendations for the different stages of copd was 22 (28.9%). two patients (2.6%) were over treated and 52 (68.4%) were undertreated. inappropriate treatment rate was 6 (75%) in gold b, 12 (85.7%) in gold c and 36 (66.7%) in gold d. univariate analysis identified two factors associated with non-adherence to gold 2017: the absence of pulmonologist follow-up (50% vs. 9.1%; p = 0.01) and the low income (35.2% vs. 9.1%; p = 0.021). in multivariate analysis only the lack of pulmonologist follow-up was identified as an independent risk factor associated with gold guidelines discrepancies (or, 10; 95% ci [2.1-47.0]; p = 0.04). there is a lack of adherence to gold 2017 guideline treatment recommendations in tunisian copd patients. this may lead to severe exacerbations. discrepancies were due to the poor access of severe copd patients to an appropriate pulmonologist follow-up. compliance with ethics regulations: yes. the operating theaters concerned were: the otolaryngology block, ophthalmology, vascular and thoracic surgery, and gynecological surgery. all patients over 18 years of age were enrolled using the clinical parameters of difficult intubation (arne score > 11), which will benefit from orotracheal intubation. the main judgment criteria were: first-pass success rate, intubation time, which is defined as the time between inserting the slide into the patient's mouth and obtaining the capnography curve, the cormack-lehane score and the pogo score (percentage of opening of the glottis). statistical analysis used spss software. results: a total of 62 patients were included. no cases of failure with this device were observed, the duration of intubation was on average 21.5 s (only 3 cases required more than 1 min). the cormack-lehane score 1 and 2 involved 55 patients (88.7%), and the pogo score greater than 50% involved 51 patients (82.25%). one case required the features of the simplified score. discrimination, calibration and misclassification of both models were tested. results: 32% had proximal anterior stroke, 2% proximal posterior stroke and 50% lacunar infarcts in either circulation. in 16% no thrombus was objectivated. 13% of patients were treated with thrombectomy, 17% received thrombolysis and 9% underwent both thrombolysis and thrombectomy. 61% only received anti-platelet therapy. the area under the receiver-operating-characteristic curve (auc-roc) for ct-dragon was 0.78 (95% ci 0.74-0.81) for favourable and 0.78 (95% ci 0.72-0.83) for miserable outcome. r2 ofct-dragon was 0.30 and 0.22 for favourable (lack of fit, p = 0.75) and miserable (lack of fit, p = 0.8) outcome respectively. misclassification rate was 29% for favourable and 13% for miserable outcome with ct-dragon. selection of predictors from the ct-dragon was done by logistic regression, bootstrap forest and decision tree analysis. nih stroke scale, pre-stroke mrs and age were identified as the strongest contributors to favourable and miserable outcome, and included in the simplified score. auc-roc was 0.83 (95ci% 0.79-0.86) and 0.83 (95ci% 0.77-0.87) for the prediction of favourable and miserable outcome respectively. r2 was 0.42 and 0.29 for the prediction of favourable (lack of fit p = 0.34) and miserable (lack of fit p = 1.0) outcome respectively. misclassification rate was 26% for favourable and 14% for miserable outcome with the simplified score. the simplified score had better discriminative power than ct-dragon for both outcomes (both p < 0.005). the ct-dragon score revealed acceptable discrimination in our cohort of both anterior and posterior circulation strokes, receiving a variety of treatment modalities. the simplified score had a better discrimination, while maintaining comparable and good specificity and misclassification rate for miserable outcome. the simplified score needs further validation in a prospective, multi-centre study. compliance with ethics regulations: yes. rationale: the 2017 gold report represents a major revision to gold strategy guidelines. it brings new recommendations regarding diagnosis, severity assessment, and both pharmacologic and non-pharmacologic treatment of copd. however, adherence to evidence-based therapeutic guidelines is often poor in low-income developing countries and represents a significant barrier to optimal management. the setting up of an lma-fastrach (desaturation). a case of glottic edema has been noted. discussion: this study shows a very high success rate with this technique (95.16% in the first trial and 4.83% in the second trial), in the context of a predictable difficult intubation. the video-airtraq allows a very good visualization of laryngeal structures, a shortening of the duration of intubation, and is rarely responsible for immediate or secondary complications. all the data in the literature go in the same direction. conclusion: at the end of this work, our perspectives are to update the difficult intubation procedure, integrating the video-airtraq into our algorithm, as well as into our difficult intubation trolley. to take into consideration the cost of this device to eventually generalize it to all our structures. compliance with ethics regulations: yes. ) and 15 beds of continuous monitoring. the activity of the cp is organized in a medical visit in the morning and in conducting projects in the afternoon. the activity is presented using a 2-years balance sheet results: the activity of pharmaceutical interventions (pi) or answers to requests from teams is shown in table 1 . the solicitations doubled the second year. the cp is involved in the conduct of internal or polar projects (set up of cooperative sedation, nutrition…), the good use of health products (relay iv/po, infusion, crushed tablets and compatibility with gastric probe, drug incompatibilities, proton pump inhibitors…), the efficiency of the drug circuit (link with the pharmacy, reflection on the improvement of the circuit, regular meetings with nurses), medico-economic analysis of health products spending and the formalization of actions by protocolisation. he is also very involved in clinical research: patient screening, clinical study setup: blipic study (beta-lactam's dosing in pneumonia in icu in patients treated by continuous renal replacement therapy; clinicaltrials nct03897582) or in candiarea project (invasive infections to candida and preemptive treatment guided by biomarkers; in progress). a satisfaction survey submitted at 6 months to nurses (12 answers/60) or to doctors/ residents (13/25) reported cp competence in the accompaniment of teams (> 80%) [in medico-economical, contribution of knowledge, vigilance reflex…], relevance of information transmitted (> 85%) [administration of drugs, dosage adjustments, …] and his relationship adapted to the units (> 90%) [communication, availability] . the development of clinical pharmacy in icu involves mastery of the specificities of icu by the cp, requiring a learning period and relationships adapted to clinical situations and teams. many health products projects specific to critical care are coordinated by the cp and made possible by medical and paramedical involvement. the cp appears as a vector of good use both in medical (reasoned prescription) and paramedical (good practices) with increasing solicitation of teams since his arrival. this reception has been facilitated by an innovative approach of clinical pharmacy deployment in our icu on an impulse of the clinical pole compliance with ethics regulations: yes. predicting models such as the news has been developed in the emergency department, but it has only been fewly evaluated in the icu. heart rate variability (hrv) reflects the autonomic nervous system response in various pathological situations and may vary according to patients' physiological status. the rox index, which reflects the acute respiratory failure severity, seems to be a good predictor of high-flow nasal canula failure. the aim of this study was to evaluate the potential value of news, hrv and irox (inversed rox) as poor outcome predictors, using artificial intelligence and machine learning. a retrospective analysis of a prospective datawarehousing project (reastoc clinicaltrials identifier nct 02893462) on icu patients who did not require invasive ventilation. physiological parameters were collected on admission, within a 24-h delay. news, hrv (in time, frequency, and non-linear domains), and irox were computed and integrated into the prediction model. analysis was performed using medcalc and matlab machine-learning work-package. results: one hundred and twelve patients were included. patients who died in the icu (n = 8) had highest news as compared with icu survivors (9.0 [5.0-11.6] vs. 6.0 [5.0-7.0] respectively; p = 0.03). the irox was higher (18. 4 [15.7-19 .8] vs. 9.0 [5.8-20.9], p = 0.008) and most hrv parameters also depicted higher values for icu survivors. considering a composite icu prognostic outcome parameter (mortality and/or need for any form of respiratory assistance and/or an icu los > median los), there was also a difference for news, hrv and irox (p < 0.0001). the best value to predict icu mortality for news was 8 (auc = 0.73, p = 0.005), irox > 9.5 (auc = 0.76, p = 0.03) and hrv (shannon entropy) > 2.9 (auc = 0.74, p = 0.04). the best model to predict the need fo respiratory assistance combines irox and hrv (sd1/sd2; auc = 0.63, p = 0.0001). adding shannon entropy on this model predicts either the need for respiratory assistance and icu survival (respectively auc 0.62, p = 0.006 and auc 0.72, p = 0.005). in icu spontaneously breathing patients, news, irox and hrv are different in between survivors and patients who died. the best model to predict the need for respiratory assistance combines irox and hrv (sd1/sd2). compliance with ethics regulations: yes. rationale: sepsis is known for its important mortality in critically ill patients. the last guidelines defined sepsis as life threatening organ dysfunction. it rejected the concept of systemic inflammatory response syndrome (sirs) associated to suspected or confirmed infection, and considered the concept of dysregulated response to infection. actual guidelines recommend the quick sequential organ failure assessment score (qsofa) to identify patients with sepsis especially when outside intensive care unit. thus, outcomes have mainly to judge the value of sirs in the sepsis-3 era. the purpose of our study was to compare whereas qsofa score or the sirs criterion are superior to predict in-hospital mortality, shock and mechanical ventilation use in sepsis. our study includes patients in whom the sepsis-3 definition is met. therefore, this inclusion was retrospectively performed throughout emergency department (ed) admission cases for clinically suspected infection. we collected 93 patients admitted to ed for sepsis. mean age was 65 years ± 14 with bornes of 24 and 92. men were 57% of the patients. death occurs in 29.6% of patients, sepstic shock in 25% and the use of mechanical ventilation in 5.6%. qsofa ≥ 2 has a significant association with in-hospital mortality (p < 0.001) but not sirs ≥ 2 (0.208). neither qsofa ≥ 2 nor sirs ≥ 2 has association with the use of mechanical ventilation (p = 0.104 vs. p = 1). whereas, both have a significant association for prediction of septic shock. the absolute sensitivity and negative predictive value in our study can be explained by the small size of our sample. this needs confirmation with literature data about the fact that sirs criterion are superior in term of sensitivity and npv than qsofa to predict septic shock. despite the weak odds ratio (or) of sirs before that of qsofa and the poor specificity and positive predictive value (ppv), we can conclude that sirs according to its sensitivity and npv, seems to persist useful in the sepsis-3 era as a reliable prognostic tool in the ed. this may need more large studies for confirmation. conclusion: despite sirs has no significant association with mortality in sepsis, it has largely higher sensitivity and superior npv to predict septic shock than qsofa in ed. compliance with ethics regulations: yes. our study aimed to determine the predictive factors of mortality in our patients. retrospective study over 2 years in the intensive care unit of the hospital 20 august. all patients with septic shock were included. a p value < 0.05 was considered significant. results: 81 patients were collected. the age ranged from 11 to 94 years old. the average duration of hospitalization in pre-intensive care was 5 days. the reasons for admission: (febrile respiratory distress: 31% of cases, polytrauma: 14% and 23% for sepsis), the most frequent infections: pulmonary (33%) and blood (32%). 38% received prior antibiotic therapy and 35% were immunocompromised. the overall mortality was 48%. the analytical study of the data shows that the age, the length of stay before admission in intensive care and that in intensive care, fever, hypothermia, slimming, hypotension, collapse, failures (respiratory, hematological, renal, hepatic and neurological) and the use of catecholamines are correlated with mortality, whereas sex, chest pain, tachycardia or bradycardia and mottling are not predictive of mortality. conclusion: despite improved techniques for the diagnosis and treatment of patients with septic shock, mortality remains high, especially in the presence of certain risk factors, hence the value of prevention in immunocompromised patients and the reduction in their length of stay in a hospital setting. compliance with ethics regulations: yes. conclusion: p. mirabilis is among the leading bacteria responsible for nosocomial infections in icu. they are emerging highly drug resistant pathogens whose incidence is rapidly increasing in icu. so that, it early identification with in vitro testing is of paramount importance to the success of infectioncontrol efforts. compliance with ethics regulations: not applicable. rationale: influenza is a potential lethal disease causing dozens of thousands excess deaths per year both in europe and in the united states. besides hygiene procedures, vaccination is a cornerstone of influenza prevention and guidelines recommend for vaccination among health workers (hw), especially if they are in close contact with frail people. despite these recommendations, the vaccination coverage is low among health workers both in europe and in the us. the relevance of a mandatory vaccination for health workers is currently a hot topic but data are scarce regarding intensive care unit health workers' opinion. patients and methods: health workers from 2 medical, 6 surgical and 2 polyvalent icus received a link to the electronic record of the survey. results: among the 10 icus, 1637 icu health workers (hw) (medical: 185 and paramedical: 1452) were questioned. three hundred and forty-one icu (21%) answered, 107 (58%) medical health workers (mhw) and 234 (16%) paramedical health workers (phw) (p < 0.0001). among mhw 94/107 (88%) were vaccinated vs only 119/234 (51%) phw (p < 0.0001). discrepancies exist between medical and paramedical icu health workers' opinions and beliefs about vaccination for influenza and its acceptance. medical health workers were more prone to consider influenza as a potentially lethal disease occurring not only among frail people but also in healthy people, to consider the vaccine efficient and safe. to agree with "vaccination for influenza is mostly related with gain for pharmaceutical industry" (or: 11 [2.3-50] ) and to disagree with "the risk of guillain-barré syndrome is higher after an episode of influenza than after vaccination for influenza" (or: 4.2 [1.2-14] ) were independently associated to the disagreement with a mandatory vaccination for icu hw. conclusion: vaccination for influenza should be strongly recommended as a tool of individual protection for icu health workers as for general population. as confidence in vaccine efficacy and concerns about vaccine side-effects impact the vaccination rate, objective information should be provided to icu health workers about the efficacy and the side effects of vaccination for influenza. compliance with ethics regulations: yes. rationale: intra-abdominal infections are a major cause of morbidity and mortality. sfar recommendations on this topic were published in february 2015. the purpose of this work was to evaluate whether our antibiotic therapy was adequate for these recommendations and whether they were adapted to our unit. the secondary objectives were to look for different risk factors for mortality, to evaluate the impact of inappropriate antibiotic therapy, to evaluate the relevance of carbapenem prescription. this is a single-center retrospective observational study of secondary peritonitis in the tourcoing intensive care unit. for each peritonitis, the epidemiological data and the co-morbidities of the patients were collected. bacteriology and anti-infectious therapies were described to determine the rates of adaptation of our antibiotic therapy and that recommended by sfar. the adequacy of our treatments to the recommendations was also quantifiable. the description of the stay, the occurrence of a death was specified. results: 131 peritonitis were included. the rate of adaptation of the sfar antibiotic therapy was 80%. the rate of adaptation of our antibiotic therapy was 73% and its adequacy rate of 24%. the main differences in prescriptions concerned over-prescription of antifungals, molecule against gram positive bacillus and a sub-prescription of aminoglycosides and beta-lactams, in particular carbapenems. the different mortality risk factors found were sofa score > 8 (or 5.4 95% ci 2.15-13.7), the charlson score > 3 (or 5.2 95% ci 1.52-17.9), the hollow organ perforation (or 4.2 95% ci 1.63-10.59). a comparison of the appropriate or not antibiotic groups did not reveal a significant difference in mortality, number of surgical revision and length of stay. in 55% of nosocomial peritonitis, antibiotic therapy with carbapenem was recommended. after recovery of microbiological data, it was only necessary for 7.7% of cases. conclusion: our work showed a low rate of compliance with sfar recommendations. these recommendations are applicable to our service by providing a particular reflection for fungal infections. our study does not show a correlation between mortality and inadequate antibiotic therapy, surgery remaining the major treatment. compliance with ethics regulations:yes. rationale: acinetobacter baumannii is a gram-negative opportunistic bacteria that has gained several drug resistance mechanisms over the last decades. analysis of a. baumanii's resistance profile helps to establish a prompt control and a prevention program. the aim of this study was to evaluate the epidemiology and antimicrobial resistance of a. baumannii isolates in a trauma and burn center in tunisia. patients and methods: retrospectively, we studied all strains of acinetobacter baumannii isolated over a 7-year period (from january 2012 to december 2018). conventional methods were used for identification. antimicrobial susceptibility testing was performed with the disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. data were analyzed using the sir-system. minimum inhibitory concentration (mic) of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may 2017. results: during the study period, 1248 non-repetitive strains of acinetobacter baumannii were isolated representing 9.9% of all isolates, 14% of gram-negative bacilli (gnb) and 40.6% of non-fermenting gnb. in our center, infections due to a. baumannii were endemic with epidemic peaks. a. baumannii was mainly isolated from burn intensive care unit (67%) and anesthesiology department (22.6%). the most frequent sites of isolation were blood cultures (34.3%), catheters (20%), respiratory specimens (12.5%) and skin samples (10% sampling duration is also reduced, improving workflow. evaluators consider that bronchosampler rationalizes the cumbersome sampling process and that the closed system design reduces the risk of losing sample or sample contamination. the set-up, the suction capacity, the sampling quality and quantity have all been evaluated better or far better than that usually observed with usual sampling techniques and devices. finally, 36 (75%) of users prefer bronchosampler to commonly used method. conclusion: this satisfaction survey shows that with its simple but revolutionary design, bronchosampler brings a real effective benefit in sampling procedure enabling the clinician to perform it alone, and 39 (81%) of the survey evaluators consider that bronchosampler should replace their current practice. compliance with ethics regulations: yes. rationale: the possibility of having a sensitive, specific and prognostic biological marker for bacterial infections is a considerable challenge. a step was taken with the discovery of pracalcitonin. patients and methods: this is a prospective observational cohort study of 120 patients in the medical resuscitation department of the university hospital of casablanca during the 6-month period, including patients in whom the pct was dosed. the data collected allowed us to form two groups according to the pct value: pct+ group with pct > 2 ng/ml and pct− group with pct < 2 ng/ml. the statistical analysis of these different data was carried out using epi info software version 3.5.3. results: 60% of our patients had a bacterial infection and 40% did not have one. we also distinguished community infections (42% of i+ patients) and nosocomial infections (58% of i+ patients). we found that the highest rates of pct were in nosocomial infections and the lowest pct rates were found in community-acquired infections. then, in each type of organ involvement we tried to vary the pct thresholds to 0.5-2 and 10 ng/ml in order to find the best threshold for which pct allowed to diagnose bacterial infection, justifying our choice of departure. we concluded that the best pct cut-off value in general was 2 ng/ml, because it gave us the best sensitivity/specificity ratio (67% and 50% respectively) with a positive predictive value of 65% and a negative predictive value of 52%. the link between pct and bacterial infection was moderate (yule q-factor at 0.34). by analyzing the different therapeutic aspects, we showed that 71% of our patients had been treated with atb before the pct assay and that the broadest spectrum antibiotics available to our service were used in patients with pct levels the highest. finally, concerning the evolution, the higher the rate of pct, the higher the death rate, especially since 100% of patients with pct > 10 ng/ml died. conclusion: procalcitonin is considered to be one of the best markers of systemic bacterial infection. indeed, its elevation is earlier than that of crp and its specificity is better compared to il-6 and il-8. the rate of procalcitonin remains low in the presence of viral infection. procalcitonin is also a prognostic marker, its elevation is correlated with the severity of the infection, and its decrease is a good indicator of the effectiveness of antibiotic therapy. compliance with ethics regulations: not applicable. rationale: due to induction immunosuppression infection is the most common cause of mortality within the first year after lung transplantation (ltx). the management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. we sent by email a survey to 180 ltx centers around the world dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy. we considered perioperative period as the period of the transplant surgery (per operative) and the postsurgery time before any infection occurrence (postoperative). after general questions on local practices, we asked each center for colonization definition and their diagnostic methods for microbial screening in recipients and donors. the clinical cases were related to specific issues concerning the management of antibiotic therapy in different clinical situations, including no prior colonization, prior colonization with sensitive or multi-drug resistant (mdr) microorganisms including prior colonization with mdr bacteria not sensitive to beta-lactams. the invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center between june and september 2018. we received a total of 99 responses from 24 countries, mostly from western europe (n = 46) and the usa (n = 34), (fig. 1) . systematic screening for bronchial colonization before ltx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. definition of colonization was very heterogeneous and the delay between the last bacterial isolation in pre-transplant and the ltx to consider if the therapy should target these bacteria varied between 1 week and more than 1 year. in recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin/tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. for these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). in recipients with pre-transplant colonization, antibiotics were adapted to the susceptibility of the most resistant strain isolated in pre-transplant samples and given for at least 14 days (67%). conclusion: practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. the antibiotic duration reported was longer for colonized recipients. compliance with ethics regulations: not applicable. the vancomycin was therefore considered as justified or not and appropriate or not. occurrence of nephrotoxicity and supratherapeutic exposure in this study group was compared to critically ill children control group. results: thirty one children receiving 43 vancomycin lines of treatment whose 13 (26%) observed a risk of acute kidney injury (aki) (n = 8) and an aki (n = 5) during the vancomycin treatment period were included. there was a trend to inversed relationship between plasmatic concentrations of vancomycin and estimated creatinine clearance (r2 = 0.2019). seven patients observed a nephrotoxicity related to vancomycin, they had a higher plasmatic concentration of vancomycin (p = 0.0009). seven patients (22%) had a supratherapeutic exposure to vancomycin. nephrotoxicity and supratherapeutic exposure were higher in children with or combined liver-kidney transplantation than in comparative critically ill children group. we found 1 blood stream infection due to the central catheter and 7 blood stream infections probably due to the central catheter. one hundred thirtyfive bacteria were identified of which 108 (80%) were staphylococcus coagulase negative. nineteen (44%) lines of vancomycin were appropriate and 31 (72%) were justified. conclusion: vancomycin could have been avoided in one third of children with liver or combined liver-kidney transplantation during the early phase of postoperative stage. vancomycin is associated with a risk of both nephrotoxicity and supratherapeuric exposure. vancomycin should be used with caution, appropriate indications and dosing in this vulnerable population. compliance with ethics regulations: yes. rationale: early bacterial infection is a major and severe complication occurring within the first month after pediatric liver transplantation (lt). the rise of antimicrobial resistance, especially extended-spectrum beta lactamase producing enterobacteriaceae (esbl-pe), is henceforth a concern for these patients. this study aimed to assess the epidemiology of early bacterial infections, including those caused by multidrugresistant (mdr) pathogens, and to identify the risk factors for infection. rationale: the number of cancer patients admitted to emergencies is clearly increasing and digestive oncology is the leading cause of consultation. the aim of this work is to identify the epidemiological factors, the therapeutic modalities as well as the predictive factors of mortality and to compare them with the data of the literature. patients and methods: 81 patients admitted to visceral emergencies for an urgent syndrome revealing or complicating a primary or secondary digestive cancer, and who required immediatemedical and/or surgical intervention and who had stayed at the surgical resuscitation level in our hospital center for a duration of 2 years. several data were entered on excel and analyzed using the spss version 20 software.-epidemiological, concerning age and sex; -clinics including risk factors, history, general condition of the patient and clinical examination data; -para-clinical, interesting biological assessments, and morphological examinations-medical and surgical therapeutics; -postoperative follow-up-treatment results. the three most frequent sites were rated in order of increasing frequency: colo-rectum (49%), pancreas (17%), and stomach (12%). the age group most found was age over 60 years with 48% of cases, 12% of patients had under 40 years. this series includes 46 men and 35 women with a sex ratio of 1, 31. the installation method was mostly gradual with 62% of cases. our patients have consulted for urgent clinical presentations mainly occlusive syndrome noted in 47% of patients. abdominal ct was the first examination performed, followed by abdominal ultrasonography in 73% and 22%, respectively. the therapeutic management was medico-surgical. the surgery done in 96% of patients, 74% for palliative indication: 40% were operated for an ostomy discharge, 24% for a digestive bypass, 24% for a palliative resection and 12% for a stoma feeding. postoperative outcomes were 44% morbidity and 43% mortality. the main cause of death was septic shock in 80% of cases, thanks to multivariate statistical analysis three factors were deduced significantly related to mortality: the asa score: p = 0.004; or = 2.520; ic: [1.33; 4.74 icu and hospital mortality rates were 60% (n = 21) and 65.7% (n = 23), respectively. ten patients were alive 6 months after with a median rankin score at 0 [0-1]. more than half of the patients without stupor had a favorable neurological outcome (fig. 1) . in univariate analysis, mechanical ventilation and stupor were correlated with mortality, whereas dic and apl were not. by multivariate analysis stupor was the only factor significantly associated with a higher mortality (hr: 8.56 [2.4-30.4] ). conclusion: intracranial hemorrhage is associated with a high mortality rate in al patients, stupor at the onset of intracranial bleeding being independently associated with poor outcome. up to one third of patients will nevertheless survive and experience a favorable neurological outcome. compliance with ethics regulations: yes. neurological outcome assessing by modified rankin scale according to stupor or coma at intracranial hemorrhage diagnosis (blank reflect missing data) rationale: sinusoidal obstruction syndrome (sos, previously known as veno-occlusive disease) is a complication of high dose chemotherapy, frequently occurring during bone marrow transplantation (bmt). severe sos is associated with a high mortality rate, related to multi-organ failure (mof). defibrotide being the only available option for prevention and treatment. prognosis of patients with sos requiring intensive care unit (icu) admission remains unknown. the primary objective was to assess the outcome of these patients. secondary objective was to assess risk factors associated with hospital mortality. patients and methods: retrospective study conducted between january 2007 and july 2019 in 12 french icus. critically ill adult patients with sos (according to ebmt classification) who received defibrotide were included. results are reported as median [iqr] or number (%). adjusted analysis was performed using cox model. results: seventy-one patients were included with a median age of 47 years . underlying hematologic diseases were acute myeloid leukemia (41%), lymphoma (21%),myelodysplasia/myeloproliferative neoplasm (18%) or acute lymphoid leukemia (15%). sos occurred during myeloablative allogeneic bmt (34%), reduced conditioning allogeneic bmt (41%), autologous bmt (11%) or chemotherapy (14%, including gemtuzumab ozogamycin in 7 patients). median sofa score at icu admission was 11 ]. ebmt prognostic score was often "very severe" (69%). main reasons for icu admission were respiratory failure (n = 26), acute renal injury (n = 17), shock (n = 11), liver failure (n = 8), coma (n = 6) and monitoring (n = 3). median bilirubin level at icu admission was 51 µmol/l [iqr 36-90] and platelets count 24 g/l . mechanical ventilation (mv), vasopressors, and renal replacement therapy (rrt) were required in 59% (n = 42), 52% (n = 37) and 49% (n = 34) of patients, respectively. sixteen patients receiving defibrotide experienced bleeding events. icu and hospital mortality rates were 39% and 54% respectively, mainly related to organ dysfunction. in univariate analysis, delayed defibrotide initiation, bilirubin level, organ supports, sofa, and ebmt scores were associated with hospital mortality. cox model identified older age (hr 1.02, 95% ci 1.00-1.04), mv (hr 1.99, 95% ci 1.00-3.99), rrt (hr 2.55, 95% ci 1.32-4.91), as associated with mortality. prophylactic defibrotide was correlated with a better outcome (hr 0.35, 95% ci 0.13-0.92). similar results were observed after adjustment for center effect. conclusion: when organ support is required, icu management is associated with high mortality. organ support (namely rrt and mv) and older age were associated with poor outcome. prophylactic defibrotide was associated with survival either due to selection process or to efficacy in this setting. additional studies are needed to confirm these results. compliance with ethics regulations: yes. rationale: prognosis of critically ill immunocompromised patients (ciip) has improved over time. neutropenia is common and is found in one third of these patients. prognostic impact of neutropenia remains controversial and little data focus on ciip admitted in a context of acute respiratory failure (arf). primary objective was to assess prognostic impact of neutropenia on outcome of these patients. secondary objective was to assess etiology of arf according to neutropenia. patients and methods: retrospective analysis of prospective multicenter multinational dataset. adults immunocompromized patients with arf were included. adjusted analyses included (1) a hierarchical model with center as random effect; (2) propensity score (ps) matched cohort; and (3) adjusted analysis in the matched cohort. results: overall, 1481 patients were included in this study. median age was 64 [iqr 55-72] and 613 patients (39.7%) were of female gender. median sofa score was 7 [4] [5] [6] [7] [8] [9] [10] and ps was 1 [0] [1] [2] [3] . main immune defect were hematological malignancy in 533 patients (36%), solid tumor in 473 (32%), systemic disease in 155 (10.5%), and other immunosuppressive drugs in 117 (8%). neutropenia at admission was observed in 165 patients (11%). initial oxygenation strategy was oxygen in 755 patients (51%), high flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs. 42% in non-neutropenic patients; p = 0.006). after adjustment for confounder in a mixed model, neutropenia was no longer associated with outcome (or 1.40, 95% ci 0.93-2.11). after ps matching, 148 neutropenic and non-neutropenic patients were compared. hospital mortality was similar in both groups (52% vs. 46% respectively; p = 0.35). after adjustment for variables associated with mortality, neutropenia was not associated with hospital mortality (or 1.04, 95% ci 0.63-1.72). arf etiologies were distributed similarly in both neutropenic and non-neutropenic patients (fig. 1) , main etiologies being bacterial pneumonia (49% vs. 46%), invasive fungal infection (11% vs. 10%), pneumocystis jiroveci pneumonia (2% vs. 0.7%), and undetermined etiology (8% vs. 10%) (p = 0.815). conclusion: neutropenia at icu admission is not associated with hospital mortality in this cohort of ciip admitted for arf. surprisingly, arf etiology did not differ despite the multiplicity of observed immune defects. compliance with ethics regulations: yes. rationale: hepatic dysfunction (hd) is commonly observed in patients with hematologic malignancies and associated with an increased mortality in allogeneic hematopoietic stem cell transplantation patients. we aimed to assess incidence, risk factors and prognostic impact of hd in a large multicenter cohort study of critically ill patients with hematologic malignancies. patients and methods: this research was a post hoc analysis of a franco-belgian multicenter prospective study assessing the prognosis of patients with hematologic malignancies admitted to intensive care unit (icu) between january 2010 and may 2011. hd was defined as serum total bilirubin ≥ 33 µmol/l at icu admission. for patients with hd, a review of medical hospital records was performed by an expert panel to assess management of hd by attending physicians. results: among the 1011 patients with hematologic malignancies admitted to icu, 893 were included in the study, mainly patients with non-hodgkin lymphoma (31.5%) or acute myeloid leukemia (27.1%). hd at icu admission occurred in 183 patients (20.7%). factors independently associated with hd were the use of cyclosporine (or = 3.357, 95% ci 1.926-5.851, p < 0.0001) and antimicrobial treatment (or = 1.578, 95% ci 1.038-2.401, p = 0.033) before icu admission, abdominal symptoms at icu admission (or = 2.182, 95% ci 1.461-3.258, p < 0.0001), ascites (or = 2.562, 95% ci 1.059-6.196, p = 0.037), hepatic charlson comorbidity (or = 2.228, 95% ci 1.057-4.696, p = 0.035), increased creatinine at icu admission (or = 1.001, 95% ci 1-1.003, p = 0.02), neutropenia (or = 1.465, 95% ci 1.001-2.144, p = 0.049) and myeloma (or = 0.378, 95% ci 0.188-0.761, p = 0.006). hospital mortality was 56.3% and 36.3% in patients with hd and patients with no hd respectively (p < 0.0001). hd appeared as an independent factor of hospital mortality after adjustment with other organ failure (oradj = 1.861, 95% ci 1.275-2.717, p = 0.001). factors independently associated with hospital mortality among patients with hd at icu admission are reported in table 1 . etiologic diagnoses for hd by physicians were undetermined for 125 patients (72.2%) including 92 (53.2%) for whom the existence of hd has not even been mentioned in the medical record. investigations were performed in 29% and only 19% of patients received a specific treatment for hd. conclusion: hd at icu admission is common, underestimated, poorly investigated, and impairs outcome in critically ill patients with hematologic malignancies. hd should be considered and managed as other organ dysfunctions. it raises the importance of an early severity assessment of hd and a development of diagnosis strategies to get therapeutic options, in close collaboration between hematologists and intensivists. compliance with ethics regulations: yes. rationale: acute respiratory failure (arf) is the main cause for admission to the icu for patients with hematological malignancies (hm). viral pneumonia is poorly described in this population. respiratory viruses pcr is a rapid and sensitive diagnostic tool. thoracic ct allows to guide the diagnosis but is also poorly described. the primary objective was to describe ct features suggesting viral pathogenicity. secondaryobjectives were to assess risk factors associated with the use of invasive mechanical ventilation (imv) and icu mortality. rationale: high-dose methotrexate (hd-mtx) is commonly used in the treatment of solid tumours and hematological malignancies. severe toxicities are frequent, leading to organ dysfunction, multiple organ failure and death. outcome of these patients when critical illness occurs is poorly studied. this study aims to describe mtx-induced toxicities and to assess outcome in critically ill patients. in this retrospective study conducted in the icu of one university hospital between january 2002 and december 2018, all the patients who were given hd-mtx (single dose greater than 500 mg/m 2 ) in the icu were included. results are presented as median [interquartile range] and number (percent). results: 33 patients (24 men and 9 women) aged 48 years [34-63], were included. b-cell lymphoma had been diagnosed in 31 patients (burkitt, n = 14; diffuse large b cell lymphoma with cns (central nervous system) involvement, n = 9; primary cns lymphoma, n = 5) and t-cell lymphoma in two patients. patients were mainly admitted for coma (n = 14; 42%) or acute kidney injury (n = 8; 24%). mtx was administered at a median dose of 6.1 g [5-14] . fourteen patients had concomitant medication interacting with mtx. median mtx clearance was 4 days [4] [5] . frequent mtx-related complication were mucositis (n = 21, 64%), diarrhea (n = 14, 44%) or hepatic failure (n = 15, 45%). during icu stay, 11 patients experienced acute kidney injury (kdigo stage 2.5 [2] [3] ). two patients received carboxypeptidase and three underwent dialysis. overall, 19 patients (57%) required mechanical ventilation, 10 (30%) vasopressors. hospital mortality was 33% (n = 11). cox model identified mtx concentration 24 h after administration higher than 4.6 µmol/l as associated with hospital mortality (hr 6.7, 95% ci 1.6-27.3) (fig. 1) . conclusion: to our knowledge this is the first study assessing characteristics and outcome of critically ill patients receiving hd-mtx. mtx concentration at h24 was associated with hospital mortality. despite underlying malignancy, icu support of these patients was associated with a meaningful survival. compliance with ethics regulations: yes. rationale: high-dose methotrexate (1 g/m 2 ; hdmtx) is the cornerstone of chemotherapy in acute lymphoblastic leukemia (all) and several high-grade non-hodgkin lymphoma (hnhl). despite standardized prevention, acute kidney injury (aki) and other life-threatening complications still occur. given the cost of glucarpidase, an enzyme that metabolizes mtx in few minutes, and the complexity of hematological patients admitted to the icu, a better comprehensive view of the factors that predict hdmtx toxicity, as well as the role of glucarpidase as rescue therapy in patients with organ failure, is mandatory. patients and methods: retrospective monocenter study including all the adult patients referred for all or hnhl in a french university hospital, and who received hdmtx. aki was defined according to the kdigo classification. univariate analysis (fischer exact or mann-withney tests) followed by multivariate analysis (stepwise logistic regression) were used to identify before hdmtx the clinical and biological predictive factors of aki. outcomes following glucarpidase were also addressed. results: from dec-2011 to sept-2018, 468 patients received hdmtx (median dose 3 g/m 2 ; all n = 126, hnhl n = 342), totalizing 1264 hdmtx pulses. sixty-nine patients (14.7%) developed aki after a median time of 2 days (stage 1 n = 35, stage 2 n = 18, stage 3 n = 16 including one requiring dialysis in the first week). by multivariate analysis, only age, body mass index and a diagnosis of all were significantly and independently associated with the risk to develop aki. mtx exposure (maximal serum concentration at h24-48) was also associated with aki (auc 0.85, p < 0.01). glucarpidase was used in 42 patients (9%) that differed by a higher age and bmi, and a lower basal egfr. glucarpidase was followed by a rapid renal improvement but serum creatinine did not return to baseline (120 vs. 92 micromol/l). thirty patients with aki or delayed mtx elimination did not receive glucarpidase but none required renal replacement therapy and egfr was only slightly but not significantly reduced at the end of follow-up. extra-renal adverse-events (rbc and platelets transfusions, neutropenia, hepatitis, severe diarrhea, mucitis) were more frequent in patients that developed aki. eighteen patients were admitted to the icu, including 9 and 6 that required mechanical ventilation or vasopressor drugs, respectively. conclusion: few actionable factors predict the development of aki after hdmtx, suggesting additional genetic factors. aki was reversed by glucarpidase but progression toward ckd was the rule. further studies will have to identify patients that will actually beneficiate from glucarpidase. compliance with ethics regulations: yes. khaoula ben ismail, sana khedher, ameni khaled, nassereddine foudhaili, mohamed salem usi digestif-service de gastroenterologie-eps charles nicolles.tunis-tunisie., tunisia, tunisia correspondence: khaoula ben ismail (khaoula87@hotmail.fr) ann. intensive care 2020, 10(suppl 1):p-085 rationale: infection is common and accounts for major morbidity and mortality in cirrhosis. patients with cirrhosis are immunocompromised and have increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. we aimed to evaluate the impact of infection on hepatic encephalopathy. patients and methods: this is a prospective study, conducted over a period of 3 years from january 2016 to december 2018. consecutive patients with approved decompensated cirrhosis admitted to our department are included. all clinical and biological data were collected from the medical records. univariate and multivariate analysis were used to identify the impact of infection on hepatic encephalopathy. results: a total of 110 patients diagnosed with decompensated cirrhosis were enrolled in this study. mean of age was 62 years (18-88). sex ratio was 1.2. hcv (39%) was the main etiology of cirrhosis. the reasons of hospitalization were: oedema with ascitic syndrome (44% of cases), digestive bleeding (21% of cases), fever (16% of cases), and encephalopathy (36% of cases). patients with infection seemed to have a high incidence of hepatic encephalopathy with 64% versus 36% when the patients are none infections. the results also showed that in those with hepatic encephalopathy, an effective antibiotic treatment accelerates significantly wakefulness under 48 h with a rate of 76% vs. 24% (p < 0.03) . in addition, the infection does not influence mortality or length of stay compared to other complications such as digestive bleeding. conclusion: we found that infection caused more episodic hepatic encephalopathy than other complication and an effective antibiotherapy accelerate wakefulness. compliance with ethics regulations: yes. rationale: hepatic encephalopathy (he) is a common cause of hospitalization in patients with cirrhosis. pharmacologic treatment for acute (overt) he has remained the same for decades. to compare polyethylene glycol electrolyte solution (peg) and lactulose treatments in patients with cirrhosis admitted to the hospital for he. we hypothesized that rapid catharsis of the gut using peg may resolve he more effectively than lactulose. patients and methods: this is a prospective study, conducted over a period of 3 years. from janury 2016 to december 2018, we have been interested in cirrhotic patients with hepatic encephalopathy. all clinical and biological data were collected from the medical records. univariate and multivariate analysis were used to identify the difference beteween peg and lactulose in the treatement of hepatic encephalopathy. results: a total of 110 patients diagnosed with decompation of cirrhosis were enrolled in this study. mean of age was 62 years (18-88). sex ratio was 1.2. hcv (39%) was the main etiology of cirrhosis. the hospitalization reasons were: edematous-ascitic syndrome in 44%, gastro-intestinal bleeding 21%, fever in 16%, and encephalopathy was present in 36% of cases. a total of 40 patients were randomized to each treatment arm. baseline clinical features at admission were similar in the groups. twelve of 20 patients in the standard therapy arm (55%) had an improvement of 1 or more in hesa score, thus meeting the primary outcome measure, compared with 17 of 20 evaluated patients receiving peg (85%) (p < 0.01). the mean ± sd hesa score at 24 h for patients receiving standard therapy changed from 2.3 ± 0.9 to 1.6 ± 0.9 compared with a change from 2.3 ± 0.9 to 0.9 ± 1.0 for the peg-treated groups (p = 0.002). the median time for he resolution was 2 days for standard therapy and 1 day for peg (p = 0.01). adverse events were uncommon, and none wasdefinitely study related. conclusion: we found that peg led to more rapid he resolution than standard therapy, suggesting that peg may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute he. compliance with ethics regulations: yes. acute pancreatitis and pregnancy janati adnane, lina berrada obstetric intensive care unit, casablanca, morocco correspondence: janati adnane (adnanejanati@gmail.com) ann. intensive care 2020, 10(suppl 1):p-087 rationale: the association of acute pancreatitis and pregnancy is rare but not negligible, it often cause a diagnostic problem given the gravidal context that can lead to serious repercussions. the objective of our study is to assess the particularities in the diagnosis, management and prognosis of acute pancreatitis during pregnancy patients and methods: this is a retrospective study about cases of acute pancreatitis occurred during pregnancy over a 3-year period (2017-2019) at the obstetric intensive care unit of the meriem maternity hospital in the chu ibn rochd casablanca. a retrospective analysis of the medical files of these patients was carried out, considering epidemiological and etiological criteria, the treatments administered and maternal/fetal fate. we found 10 cases during this period, with an incidence of 1/3000. the average age of onset was 28 years, 90% of cases occurred in the 3 rd trimester. epigastric pain and vomiting were the common symptomatology. ultrasound showed biliary lithiasis in 70% of cases with increased pancreas size in 30% of cases. maternal mortality was zero. uncomplicated benign forms are the most common (80%). severe hypokalemia was found in 40% of patients. neonatal morbidity was marked by six premature deliveries. among them, a newborn died at day-1 of life discussion: the association of acute pancreatitis and pregnancy is rare, more frequent during the 3 rd trimester, it mainly affects the young woman. lithiasic biliary pathology remains by far the most frequent etiology. the diagnosis is clinical most often represented by epigastralgia with vomiting and biological via lipasemia and amylasemia dosage. uncomplicated benign forms are the most common. hydroelectrolytic disorders are often found. abdominal ultrasound allows the etiological diagnosis. the treatment is above all symptomatic whose objective is the digestive rest, the correction of the hydroelectrolyte disorders but first of all relieve the pain. conclusion: acute pancreatitis is a rare event in pregnant women, but can have a maternal and fetal prognosis. it must be systematically evoked in front of the acute abdominal pains of the pregnant woman because the confirmation of the diagnosis is easy and the maternal results depend mainly on therapeutic management. prematurity remains the predominant factor in neonatal morbidity. compliance with ethics regulations: not applicable. rationale: aclf is a clinical concept defined in patients with chronic liver disease who presented organ failure(s) secondary to an acute decompensated event. liver transplantation in this indication showed good results in selected patients. the aim of this prospective study was to evaluate the outcome and the factors associated with a favorable selection to liver transplantation in this population. patients and methods: all consecutive patients admitted to the icu with cirrhosis and aclf, were recruited. patient with age < 18 years or with fulminant hepatitis were excluded. results: between july 2017 and february 2019, 155 cirrhotic patients were admitted to icu. mean age was 55.6 ± 11.3 years (71.6% male). cirrhosis was due to alcohol in 78.1% of the patients. aclf grading at admission was: 44.5% aclf3 (n = 60), 21.3% aclf2 (n = 33), 14.8% aclf1 (n = 23), and 19.4% aclf0 (n = 30). of the 155 patients, 46.5% (n = 72) were considered to be eligible for a transplant project and were assessed for liver transplantation. the main reasons were alcohol abuse (66.3%, n = 55), death within 7 days after admission (32.5%, n = 27) and rapid improvement of the liver disease. of the eligible patients, 50% were transplanted with a mean time between admission to icu and liver transplantation of 68.9 ± 105.1 days. twelve patients died on the waiting list (24% of the listed patients), mainly of septic shock. among those who were assessed for liver transplantation but not listed (n = 21), 76.2% died before the listing (n = 16) and 23.8% were not listed because of severe comorbidities (n = 5). the global mortality rate was 56.8% (n = 88). the 28 and 90 days rate mortality were respectively 42.9% and 56.2%. the overall 3-month patient survival was respectively 97% and 26% in the transplant and non-transplant group (p < 0.001) for the entire cohort. among eligible patients, factors associated with the absence of liver transplantation, in the multivariate analyses, were mechanical ventilation (hr 8.95, 95% ci rationale: body composition is known to be a prognostic factor in cirrhotic patients. however, the link between this and the prognosis of patients in intensive care unit (icu) is unknown. the computed tomography offer accurate estimations of muscle mass by analysing a cross-section usually going through the third lumbar vertebrae. this retrospective study aimed to assess the feasibility of body composition (bc) analysis in cirrhotic patients with septic shock, using computed tomography (ct) and evaluate the impact of bc (muscle mass, subcutaneous and visceral fat) on outcome. patients and methods: this retrospective study included 36 cirrhotic patients with septic shock hospitalized in icu who underwent an abdomino pelvic ct scan within 48 h of admission. we collected the surface areas of muscle mass and adipose tissue on the ct scans. we compared bc data with mortality and with the number of organ failures. the average age was 60 years . the average child and meld scores were respectively 10.8 [8-14] and 28.7 . the prevalence of sarcopenia was 50%. it was not associated with a higher mortality rate at day 28 (p = 0.31) or with a higher number of organ failures at day 28 (p = 0.55). we observed a higher subcutaneous adiposity index in patients who died at day 28 (p = 0.03) and in patients with renal insufficiency at admission (p = 0.019). there was a trend (p = 0.057) towards more visceral fat in patients who died in icu. the assessment by ct of body composition reveal evaluation of bc using ct is feasible and reproducible and may constitute a promising tool to evaluate in cirrhosis critically ill patients. visceral fat mass seems associated with poor outcome in cirrhotic patients with septic shock compliance with ethics regulations: yes. rachid jabi, mohammed bouziane chu mohammed vi, oujda, morocco correspondence: rachid jabi (jabirachid@gmail.com) ann. intensive care 2020, 10(suppl 1):p-090 rationale: the infection of the necrosis constitutes a pejorative element in the management of the necrotico-haemorrhagic pancreatitis, in the absence of the drainage the mortality approaches 100%. the morbidity and mortality of surgery can be avoided with minimally invasive treatments. purpose: to compare the morbidity and mortality of the two groups of post-ercp pancreatitis and the other etiologies. patients and methods: a retrospective study over 4 years between 2016 and 2019 and a comparison between pancreatitis secondary to post-ercp and other etiologies of pancreatitis. a p value of 0.05 is considered significant. the surgical treatment used in 10 cases of superinfection post ercp against seven cases of other etiologies of pancreatitis. high mortality in post-ercp pancreatic arm 88% vs. 50% (p = 0.09). high morbidity in the operated group 66% vs. 28% (p = 0.04) represented mainly digestive haemorrhages. duration of stay was significantly longer in the operated group 36 vs. 12 days (p = 0.04). thrombocytopenia and beta-lactamase-producing enterobacteria have further complicated management in the post-ercp infected pancreatitis arm. the antibiotic resistance of infected pancreatitis in post-ercp patients is 86.65% for ciprofloxacin, 19.17% for imipenem and 65% for amikacin. conclusion: pancreatitis the most common adverse effect of ercp with significant morbidity and mortality. the collaboration between the intensive care unit gastroenterologist and the surgeon improves management since the risk factors are mainly related to the patient and can not be modified. compliance with ethics regulations: yes. gautier nitel, aghiles hamroun, anne bignon, gilles lebuffe chru lille, lille, france correspondence: gautier nitel (gautier.nitel@gmail.com) ann. intensive care 2020, 10(suppl 1):p-091 rationale: liver transplantation (lt) has been recently experiencing an expansion of its indications, allowing patients with potentially more co-morbidities to access to transplantation. in our era of graft shortage, we should focus on the identification of the best lt candidates. the aim of our work is to study the determinants of early morbidity and mortality after lt from three angles: occurrence of a major cardiovascular event (mace) or acute renal failure (kdigo stage 2-3 aki) in the first 30 days postoperative, and death in the year following lt. retrospective study investigating the occurrence of mace or aki (kdigo 2-3) within 30 days post-operative and mortality at 1 year after lt, including patients who received a first lt between january 2014 and december 2017 in our center. analysis of risk factors by a multivariate step-by-step analysis. statistical significance for p < 0.05. data presented in odds ratio (or) rationale: infectious complications are frequently reported in critically ill patients supported by veno-arterial extracorporeal membrane oxygenation (va-ecmo) for refractory cardiogenic shock, but their diagnosis is challenging. no study has specifically studied bloodstream infection (bsi) in this population and some recommendations suggest performing systematic blood culture (bc). in our unit, systematic bc are daily sampled. we investigated the interest of systematic bc to detect bsi under va-ecmo. patients and methods: in a retrospective analysis (2013-2017), and after exclusion of patients dying within 24 h, all adult patients from cardio-vascular intensive care unit supported by va-ecmo were included. systematic daily and "on demand" bc (at the physician's discretion) performed from va-ecmo implantation to 5 days after withdrawal were analyzed. bsi was defined as at least one bc positive to a pathogen (except for contaminants bsi which required at least two positive bc with the same bacteria in 48 h). multivariable logistic regression was performed to identify risk factors for positivity of systematic bc. rationale: fungal infections are constantly increasing in hospitals. indeed, the increase in these infections and especially candida yeast infections is almost parallel to the increase in the widespread use of a wide range of implanted medical devices such as catheters. for this reason, we have been investigating, isolating and identifying candida yeast colonizing vascular catheters and studying the epidemiological and clinical characteristics of patients with colonized catheters. patients and methods: it is a prospective, transversal study conducted at the intensive care and neurosurgery services of the sétif university hospital, evaluating the fungal colonization of vascular catheters. these are collected from hospitalized patients for a period of 5 months. a culture of the distal end of the catheter is performed directly after its ablation. the results obtained showed that among the 30 samples taken, six are colonized by the yeasts, the incidence is 20%. six yeast of candida spp were isolated, 50% of them were candida albicans species, 33.33% candida parapsilosis and 16.66% were candida glabrata. conclusion: it appears that colonization of catheters occurs most frequently in patients with the following characteristics: extreme ages of life, male sex, antibiotic therapy and length of hospitalization or prolonged catheterization. compliance with ethics regulations: yes. rationale: the threat of emergent extensively drug-resistant bacteria (exdr) dissemination worldwide is real. it has become a global public health issue. in fact, glycopeptides-resistant enterococcus faecium (gre) and carbapenemase-producing enterobacteriaceae (cpe) are the lead microorganisms in the high resistant bacteria category. the aim of our study was to characterize the molecular mechanisms and to determinate the antimicrobial susceptibility profiles of gre and cpe isolated from burn patients. patients and methods: prospectively, we studied all cpe and gre strains isolated from burn patients between january and december 2018. all isolated microorganisms were identified on the basis of conventional microbiological techniques. antibiotic susceptibility testing was carried out by the agar disc diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. molecular characterization was performed by multiplex real-time pcr (cepheid, genexpert ® ) allowing detection of the most prevalent carbapenemase encoding genes (blavim, blandm, blaimp, (blaoxa-48 and blakpc) as well as the genes vana and vanb of gre. results: during the study period, 53 exdr were isolated from 42 burn patients. the most frequent sites of isolation were blood cultures (34%) and skin samples (30.2%). cpe represented 86.8% of isolated exdr (46 strains). among them, the most frequently identified species was klebsiella pneumoniae (73.9%) followed by enterobacter cloacae (13%). twenty-four cpe (52.2%) expressed the blandm gene. the blaoxa-48 gene was found in 12 strains (26.1%) and ten strains (21.7%) carried both genes. of the 46 cpe, 89.1% revealed ertapenem mic > 1 mg/l whereas most strains were susceptible to imipinem and meropenem with 79.5% and 60.9% of susceptibility, respectively. the antibiotics showing the highest resistance rates were cefotaxime (78.3%), piperacillin-tazobactam (97.8%), ciprofloxacin (78.3%) and amikacin (42.9%). the most active agents were colistin and fosfomycin with 6.5% of resistance for each. seven strains of gre were isolated (13.2% of exdr). all of them expressed the vana gene, with vancomycin mic > 256 mg/l. however, teicoplanin mics ranged from 16 to 64 mg/l. all gre strains were beta-lactam resistant and highly resistant to aminosides. linezolid and tigecycline were the only active antibiotics. the dissemination of these extensively drug-resistant bacteria must be contained by implementation of strict isolation methods and better hygienic procedures in order to limit their economical and health consequences. compliance with ethics regulations: yes. rationale: stenotrophomonas maltophilia has emerged as an important pathogen that induces nosocomial infections. it is a non-fermentative, gram-negative bacillus that causes severe infectious diseases, particularly bacteremia in the hospital setting. morbidity and mortality due to stenotrophomonas maltophilia seems to be high, particularly in critically ill patient. the aim of this study was to describe the clinical features, management and outcome of patients with stenotrophomonas maltophilia infections. patients and methods: this was a retrospective analysis of prospectively collected data of patients hospitalized in intensive care unit (icu) between january 2010 and december 2018. collected data were: age, gender, comorbidities, severity scores on admission, prior infections, use of antibiotics, use of invasive devices (urinary tract catheter, or mechanical ventilation), microbiological data, and antimicrobial therapy and outcome. results: during the study period, 27 patients with stenotrophomonas maltophilia infection were included, with a mean age of 51 ± 17 years. the simplified acute physiology score ii and acute physiology and chronic health evaluation ii on admission were respectively 35 ± 15 and 20 ± 8. bacteremia caused by stenotrophomonas maltophilia was observed in 25 patients (92%) and ventilator acquired pneumonia in two patients (8%). twenty four episodes were classified as primary bacteraemia and only one as secondary bacteraemia due to urinary infection. four patients (15%) developed septic shock. mean sofa on the day of stenotrophomonas maltophilia infection was 6 ± 2. prior antibiotic use was observed in 85% including an antipseudomonal agent in 26% of cases. infection due to stenotrophomonas maltophilia was considered in 26 cases. empiric antibiotic therapy was administered to 13 patients (48%) and had included an appropriate agent in only five cases (38%). after adapting antibiotics, monotherapy was the choice for six (25%) patients while a combination of two antibiotics was indicated in the 20 others (75%). the most used antibiotic was the colistin in 11 episodes (46%). intensive care mortality was 37%. univariate comparison between dead and survivors showed a significant difference in prior nosocomial infection and respiratory comorbidities. no independent risk factor of mortality was found in multivariate analysis. rationale: thrombocytopenia is a frequent disorder in critically ill patients, and several studies have reported its correlation with poor prognosis. considering the major role of platelets in hemostasis, a significant drop in platelet count is an alarming sign in septic patients. the aim of this study was to show the relationship between thrombocytopenia and platelet level changes and mortality in septic patients. patients with criteria for septic shock (based on the third international consensus definitions for sepsis and septic shock) at admission or at any time during hospitalization were included in a prospective study conducted for a period of 8 months (january 1-august 31, 2018) in a medical surgical intensive care unit. patients hospitalized for less than 24 h were excluded. thrombocytopenia was defined as a platelet count less than 150.000/mm 3 , and recovery was defined as returning to levels more than 150.000/mm 3 after presenting thrombocytopenia. we assessed the platelet count during the hospitalization and its outcomes. we included 82 patients. the mean ± sd age was 56.54 ± 18.45 years. sex ratio was 1.92. thrombocytopenia during sepsis (group 1) was found in 46 patients (56%) with a mortality rate at 85%. the mortality rate among patients not showing thrombocytopenia (group 2) was significantly lower 26% (p = 0.01). the receiver operating characteristic showed that in (group 1), a drop in the platelet count (from admission to septic shock day) more than 45% was associated with poor outcome (sensibility = 56%, specificity = 88%, auc = 0.82). among the (group1), 30% showed recovered platelet counts. the mortality was significantly higher in the patients with uncovered thrombocytopenia (90% vs. 28%, p = 0.001). conclusion: thrombocytopenia was shown to be an indicatorof poor prognosis in our study. in addition, drops of > 45% and failure to recover the platelet counts were further determinants of unfavorable outcomes. compliance with ethics regulations: yes. mehdi gaddas 1 , sarra dhraief 1 , karim mechri 1 , imen jami 2 , amenallah messaadi 2 , lamia thabet 1 rationale: pseudomonas aeruginosa is known as an opportunistic pathogen frequently causing serious infections. multidrug resistance in this bacterium is increasing worldwide and poses a major problem in the treatment of infections due to this microorganism. analysis of resistance profile to antibiotics of p. aeruginosa helps to establish a prompt control and prevention program. the aim of this study was to evaluate epidemiological profile and antimicrobial resistance of p. aeruginosa isolates in a trauma and burn center. patients and methods: retrospectively, we studied all p. aeruginosa isolates over a 7-year period (from january 2012 to december 2018). conventional methods were used for identification. antimicrobial susceptibility testing was performed with disk diffusion method and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. data were analyzed using the sirsystem. minimum inhibitory concentration of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may 2017. results: during study period, 1499 non-repetitive strains of p. aeruginosa were isolated, representing 12% of all isolates. in our center, infections due to p. aeruginosa were endemic with epidemic peaks. p. aeruginosa was mainly isolated from burn intensive care unit (73.4%) and anesthesiology department (11.1%). the most frequent sites of isolation were skin samples (35.1%), blood cultures (19.7%), catheters (12.5%) and urines (10.3%). the survey of antibiotic susceptibility showed high percentage of resistance to the different antibiotics: 33.8% of strains were resistant to ceftazidime, 65% to ticarcillin, 57.5% to pipercaillin-tazobactam, 57% to imipenem, 56.8% to ciprofloxacin and 68% to gentamicin. resistance to colistin was rare. it concerned only four strains, isolated from burn patients. the survey of antibiotic susceptibility evolution have shown a global increase of resistance to commonly prescribed antibiotics between 2012 and 2018: from 48% to 57.2% to imipenem, from 47.5 to 61.8% to ticarcillin-clavulanate, from 7.3% to 49% to ceftazidime and from 59.2 to 65% to gentamicin. whereas ciprofloxacin resistance rate have decreased from 60.9 to 55%. antibiotic resistant strains were mainly isolated from burn intensive care unit, with 66% of resistance to imipenem and 40.2% to ceftazidime. the dissemination of multidrug-resistant strains of p. aeruginosa in our center must be contained by the implementation of strict isolation methods and better hygienic procedures. compliance with ethics regulations: yes. acinetobacter baumanii: therapeutic impasse sabah benhamza, mohamed lazraq, abdelhak bensaid, youssef miloudi, najib el harrar réanimation de l'hôpital du 20 août, casablanca, morocco correspondence: sabah benhamza (benhamzasabah5@gmail.com) ann. intensive care 2020, 10(suppl 1):p-098 rationale: acinetobacter baumanii (ab) is frequently responsible for nosocomial infection in the intensive care units, and its resistance to antibiotics continues to increase. the objective of our study is to determine the epidemiological profile and antibiotic sensitivity of isolated bacteria in the intensive care unit august 20, in order to optimize the probabilistic antibiotherapy of bacteremia in intensive care. patients and methods: this is a retrospective study performed in the intensive care unit of the hospital august 20, 1953, spread over a period of 3 years from january 2016 to january 2019. results: the incidence of ab infection in our department was 4.77% for all patients admitted to intensive care. the average age was 45 years ± 20, male predominance (sex ratio 2.42). the average time to onset of infection was 11 days. during the study period, 41 ab strains were isolated, 70% of which were pulmonary, 20% blood, and 8% urinary. resistance to c3g reached 96% in 2016, 98% in 2017 and 99% in 2018. for imipenem resistance was 81% in 2016, 85% in 2017, 76% in 2018. for amikacin, resistance was 41% in 2016, 43% in 2017, and 35% in 2018. for fluoroquinolones resistance was 75% in 2016, 68% in 2017 and 74% in 2018. cotrimoxazole resistance was around 30% in the last 3 years conclusion: the resistance of ab to antibiotics has reached very alarming levels, especially for carbapenems. this requires resuscitators to change their antibiotic prescription behavior and to invest in the prevention of nosocomial infections. compliance with ethics regulations: yes. this is a prospective observational study conducted at the ed during the period of 1 year. data of all patients admitted with suspected infection of any cause were collected. poor outcomes were defined as death and transfer to an icu within 48 h. results: during the study period, a total of 200 patients with a mean age of 68 ± 11 were included. 55% were male. within 48 h of management in the ed, 10% of patients were transferred to the icu and 5% died. independent predictors of icu-transfer and death included low systolic blood pressure, fever and tachycardia. a prediction model containing these independent predictors had a good predictive accuracy with an area under the curve of 0.89 (95% ci 0.8403-0.9296). sensitivity was 63%, specificity 93%, positive predictive value 72% and negative predictive value 90%. conclusion: assessing readily available clinical variables at arrival to the ed can aid in predicting poor outcomes. [3] [4] [5] [6] [7] [8] . the most common co-morbidities were chronic respiratory failure (crf, n = 11) and hypertension (n = 11). respiratory distress (n = 19) and coma (n = 18) were the major indications for iv. us diaphragmatic exploration was performed at a median delay of iv at 4 days [2] [3] [4] [5] [6] [7] . 95% of patients received sedation and 27.5% received neuromuscular blockers. the ventilator mode was control volume in 35 patients via endotracheal tube (n = 33) and tracheostomy cannula (n = 7). no major incident was detected during the turning of patients. both tid and ted decreased from the sp to the pp (fig. 1) : tid (mm) (28 in sp vs. 24.5 in pp, p = 0.001), ted (mm) (18.7 in sp vs. 18 in pp, p = 0.037). the observed dtf was lower in the pp but without significance (37.4 vs. 42.05%, p = 0.36). no difference was showed when the comparison between sp-dtf and pp-dtf was adjusted on the ventilator mode, obesity, neuromuscular blockers and crf. the positioning in pp in ventilated patients reduces both tele-inspiratory and tele-expiratory diameters of the diaphragm but not altered its contractile function. compliance with ethics regulations: yes. significance was considered at p < 0.05. results: results are presented in the table below. discussion: nebuliser type influences the efficiency of aerosol delivery, with the vmn delivering a significantly higher % aerosol dose than the jn at the two circuit positions (p = 0.0037 on inspiratory limb; p = 0.0004 at the dry side of humidifier). in agreement with previous reports using bias flow, for both nebulisers, the location within the circuit has a significant effect, with the nebuliser on the dry side of the humidifier delivering more aerosol than on the inspiratory limb (p = 0.0100 for vmn; p = 0.0127 for jn). conclusion: for a mechanically ventilated adult tracheotomy patient, the type of nebuliser and the location of the nebuliser within the circuit influences aerosol delivery. rationale: automatic tube compensation (atc) is a mode available in most icu ventilators. it compensates for the resistive pressure into endotracheal tube/tracheostomy canula by continuously providing a pressure assistance based on internal diameter of a new endotracheal tube/tracheostomy tube. its use in icu is unclear. we designed a survey to further explore this. patients and methods: the survey was endorsed by the acute respiratory failure section and the clinicaltrials group of the european society of intensive care medicine (esicm). the pool was sent out via an email on june 27 2019 to the esicm members worldwide. the following closed questions were: country, years in icu, kind of icu, kind of hospitals, kind of respirators, atc use (never, always or in some patients), reasons to or not to use atc, ventilatory mode in which atc was used. the database was frozen on august 1 st 2019 after two reminders. we used the gross national income per capita (usd) provided by the world bank2016 to transform the respondent's country into a geographical-economical variable with 3 levels: high-europe, high-noneurope and middle (1) . atc use was coded as yes or no. the primary end-point was atc rate of use and the hypothesis was that less than 50% of the respondents do use it. variables were expressed as counts. groups were compared by chi square test. a logistic regression analysis was performed to explore the contributing factors to atc use. we received 644 responses without any doublons, of which six were empty, from 72 countries. four-hundred and nine respondents used atc always or in some patients (64% atc rate of use). this rate was not different between economical-geographical regions, icu, hospitals and years in icu. for those respondents who did not use atc the reasons were: atc mode not available in icu ventilators (41.9%), atc not helpful mode (36.7%), atc not known (18.8%) and atc provides too much pressure assistance (5.7%). for those respondents who used atc the reasons were: helpful in weaning (68.2%), set by default (30.5%) and physiological benefit (1.2%). they used atc during spontaneous breathing trial (30.4%), with any assisted mode (27.9%) and with specific modes (11.7%). we found no risk factor for atc use in the logistic regression model (fig. 1) . the atc rate of use was unexpectedly high in this survey. this may result from respondents selection bias or from an a priori underestimation of its use. compliance with ethics regulations: yes. rationale: during pressure support ventilation (psv), adjusting the level of assistance mainly aims at maintaining the patient's respiratory effort within a normal range. however, respiratory effort measurement is impeded in clinical routine by the need of esophageal pressure recording. in this study, we evaluated the accuracy of assessing the respiratory effort from the flow and airway pressure signals using several machine learning algorithms based on the equation of motion of the respiratory system. patients and methods: using the asl5000 simulator (ingmar medical) connected to a pb980 ventilator (medtronic) set in psv, we simulated a massive number of different respiratory cycles. each simulated cycle represented a unique combination of compliance and resistance of the respiratory system, duration and intensity of the muscle pressure (pmus), positive end-expiratory pressure (peep) and pressure support levels. using least squares regression methods, the flow waveform was fitted according to the equation of motion of the respiratory system to determine the compliance and resistance of the respiratory system, and the pmus. the hypothesis used (alone or in combination) to constrain the system were: linearity of pmus at the onset of the inspiratory effort, nullity of pmus at the end of insufflation, and nullity of pmus during expiration. thus, nine methods were built and tested. calculated and actual peak pmus values were compared using the bland-altman method. the nine methods of pmus assessment were evaluated using 34 550 different simulated cycles. by limiting the analysis to selected cycles with a predefined applicability criterion (intrinsic peep less than 1 cmh 2 o), a limited inspiratory effort (peak pmus less than 15 cmh 2 o) and a high quality of fitting (r 2 > 0.99), the method using the three hypothesis together to constrain the system was characterized by a bias of 0.34 cmh 2 o and limits of agreement of -0.44 and 1.12 cmh 2 o. however, when widening the analysis to all the simulated conditions, no method allowed an accurate estimation of the peak pmus : the best one exhibited a bias of -3.38 cmh 2 o and limits of agreement of − 15.18 and 8.42 cmh 2 o. conclusion: among the nine machine learning methods tested, some provided an accurate estimate of the respiratory effort in selected cycles but none allowed such accuracy across all simulated conditions. this incites to assess automated methods using a more complex physiological and physical model. compliance with ethics regulations: not applicable. rationale: there is a growing interest in esophageal pressure monitoring in mechanically ventilated patients. esophageal pressure can be measured with a specific nasogastric catheter equipped with esophageal balloon and connected to a pressure transducer. it is used as a surrogate for pleural pressure and may be considered as a corner stone in advanced care of ventilated patients to better assess lung and chest wall mechanics and easily detect patient-ventilator asynchronies. however, this promising technique is still seldom used in clinical practice. trained icu nurses may perform oesophageal pressure measurements which may help facilitate its implementation in the usual patient care. this study aimed at assessing whether a specific educational program to train nurses to perform esophageal pressure monitoring allowed reliable measurements. this was a prospective monocenter study performed in an academic icu. written informed consent was obtained from the nurses before inclusion in the study. the specific educational program consisted of a 30-min online theoretical course, a 1-h group theoretical teaching and a 30-min simulation training on a mannequin. then each participating nurse performed three esophageal pressure measurements (using nutrivent ® catheters and an icu monitor connected to arterial line pressure transducers system) on three different mechanically ventilated paralysed patients under supervision. a knowledge assessment was performed with a short written mcq test. the skill evaluation was by two trained experts. concretely the trained nurses performed an esophageal pressure measurement without assistance. their ability to control the esophageal balloon position by an occlusion test, to measure the inspiratory and expiratory airway and transpulmonary pressures and to calculate of respiratory system, lung and chest wall compliances was assessed at the bedside using a standardized evaluation form. we present here the preliminary results of the first nine included nurses. the written knowledge assessment was considered as rationale: several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation. we conducted this study to compare t-piece and pressure support ventilation (psv) (8 cmh 2 0 and peep0) in the process of weaning of mechanical ventilation in burns. patients and methods: it was a prospective randomized trial in burn icu in tunisia during 9 months. mechanically ventilated patients who met standard weaning criteria were included [1] . patients were randomized into two groups: group1 under t-piece and group 2 under psv. duration of the test: 30-120 min. the tolerance of the vs test should be judged on clinical criteria. stopping the test if occurred: agitation, tachypnea > 35 cycles/ min, tachycardia > 140 / min, spo 2 < 90%. successful withdrawal was defined as the ability to maintain spontaneous respiration for 48 h after extubation. results: thirty patients were included, randomized into two groups. the mean age was 29 ± 11 years with a ratio sex of 4. the average tbsa was 31 ± 18%. the cause of mechanical ventilation was essentially a face neck burned (79%). the following table shows the weaning outcome of both modalities. eighty percent of succeeded extubation for both groups (n = 12/15). the cause of failure of extubation was secretion retention and clutter in majority of cases followed by neurological and cardiac distress. the duration of mechanical ventilation does not influence the outcome of the weaning test (p < 0.005), with a mean of duration of 16 ± 10 days. conclusion: our study did not show any difference between the two weaning modalities in the matter of outcome of extubation. the choice of weaning test of mechanical ventilation is to be judged by the clinician according of the state of his patient. compliance with ethics regulations: not applicable. rationale: when expiratory tidal flow does not go up after increasing expiratory driving pressure expiratory flow limitation (efl) occurs. it is thought that efl heralds airway closure (ac). we investigated the role of chest wall elastance (ecw) in both efl and ac in acute respiratory distress syndrome (ards) patients. our hypothesis was that the lower the ecw to lung elastance (el) ratio the higher the likelihood of efl and ac. patients and methods: twenty-five moderate to severe ards patients were prospectively included in two centers. mechanical ventilation was delivered in volume-controlled mode with tidal volume 6 ml/kg predicted body weight at positive end-expiratory pressure 5 cmh 2 o in semi-recumbent position. airway (paw) and esophageal (pes) pressures and flow were continuously recorded during 2 min by a data logger (biopac 150). then, end-expiratory and end-inspiratory occlusions were performed for 5 s, then respiratory system was slowly inflated at constant flow. finally, patient was allowed to breathe out freely to atmosphere by using a three-way stop lock by-passing expiratory valve. ac and airway opening pressure (aop) were determined according to chen et al. (1) . efl was assessed by the atmospheric method (2) . dynamic elastance of chest wall (edyn,cw) and lung (edyn,l) were obtained from least square linear regression method over 10 consecutive breaths. static elastance (est,cw and est,l) were determined by classic formulas and also by taking into account aop (est,cw_aop and est,l_aop, respectively). the performance of ecw/el ratio to predict efl and ac was assessed by the area under receiver operating characteristic (aucroc) curve. results: efl was observed in 9 patients (36%) and ac in 14 (56%). median aop was 8.2 cmh2o (95% ci 7. 6-12.8) . aucrocs for ecw/el ratios to detect efl and ac are shown in table 1 . edyn,cw/edyn,l ratio was better to detect efl than est,cw/est,l ratio with edyn,cw/edyn,l ≤ 0.16 100% sensitivity and 84% specificity. correction for aop made the performance of est,cw/est,l ratio as good as that of the edyn ratio. ac was poorly predicted by edyn and est ratios but its prediction greatly improved with aop correction. however, with the est,cw/ est,l_aop the critical ratio was 1.81 (sensitivity 75%, specificity 100%) and 0.60 (sensitivity and specificity 100%) for predicting efl and ac, respectively. conclusion: efl and ac are frequent in ards at peep 5 cmh 2 o. edyn,cw/edyn,l ratio lower than 1 best predicted efl occurrence. once ac is taken into account est,cw/est,l ratio greater than 1 accurately predicts ac. efl and ac are two distinct phenomena. compliance with ethics regulations: yes. rationale: anesthesia outside the operatingroom (aoor) in a pediatric environment was giving increasingly increasing indications and a lot of progress because of its interest in carrying out diagnostic and/or therapeutic explorations: 20% of the acts of anesthesia are performed outside the operating room. the objective of our study is: to clarify the importance and the frequency of the practice of the ahbo, to define its particularities, as well as an evaluation of the ratio: benefit/risk in order to reduce the morbidity and mortality. patients and methods: we report in this study the experience of the service of the resuscitation mother-child on the gestures of aoor. this is a prospective observational study, spread over a period of 2 months: from 1/09/17 to 31/10/17, dealing with 251 acts performed for endoscopic digestive and bronchial procedures, cures in dermatology and radiotherapy, and medical imaging (ct and mri). results: of the 251 procedures performed: 91 were performed for ct, 66 for mri, 7 for arteriography and 50 for endoscopic digestive procedures, 14 for bronchoscopies, 6 for radiotherapy treatments, 17 for laser treatments in dermatology. anesthesia techniques use intravenous induction in 70% of cases using: hypnotics (propofol, midazolam, ketamine), morphine (remifentanyl, fentanyl), inhalation induction in 30% of cases (sevoflurane, halothane) and curare for 7 cases of bronchoscopy (rocuronium). this anesthesia was marked by the occurrence of accidents in order of frequency: cardiac in 15% of cases (tachycardia, hypotension and rhythm disorders), and then respiratory in 10% of cases. the most serious accidents were admitted in reality and are represented by 8 cases, of which 3 required an intubation (bronchoscopy), a case of cardiorespiratory arrest recovered, 2 cases of severe hypoxia associated with bradycardia and which required the ventilation with the mask (radiotherapy), and 2 cases of bronchospasm requiring the deepening of the anesthesia (absence of tci). a good knowledge of the patient and the intervention, and difficulties specific to each specialty is necessary, as well as a preanesthetic consultation. the aoor must obey the same safety rules as in the operating theater and that in terms of: equipment, monitoring (integrate the capnograph to respiratory monitoring whenever deep sedation and when the continuous control of vas is difficult), anesthetic technique (tcbi) and post-procedure wakefulness management that must meet the same requirements as the sspi, especially for prolonged sedation. compliance with ethics regulations: yes. umbilical vein catheterization through wharton's jelly: a possibility for a fast and safe way to deliver treatments in the delivery room? suzanne borrhomée hôpital rené dubos, france correspondence: suzanne borrhomée (suzanne.borrhomee@gmail. com) ann. intensive care 2020, 10(suppl 1):p-108 rationale: a fast and safe venous access can be a critical issue in the delivery room during neonatal cardiopulmonary resuscitation, or before endotracheal intubation. here, we describe a new method to inject drugs using the umbilical vein, directly punctured through wharton's jelly. this method was performed in 10 newborns between november 2016 and may 2018. umbilical vein was identified and punctured easily and a reflux was obtained in all patients. the first step was antisepsis, and then the umbilical vein was punctured. the puncture was made approximately 2 to 3 cm above the navel. after checking for blood reflux, the nurse injected the treatment. the cannula was left in the vein during the injection and removed as soon as the intervention was over (intubation was performed, or the heart rate had increased). results: here, we report ten cases of emergency injection in the delivery room using this method: -four cases of cardiopulmonary resuscitation using this method to deliver epinephrine. cardiac massage was performed on all patients.-six cases of intubations in the delivery room using this method to administer the premedication. in all patients, the umbilical vein was identified easily. the equipment was the one usually used for venous injection in our unit and was manipulated and handled with ease. venous access was obtained in a matter of seconds, and blood reflux was observed in all patients. the treatments were efficient in all but two patients, which was imputable to the method in one patient. discussion: although this method has been known in our nicu for several years, there has been no publication regarding this method in neonates. inserting an umbilical vein catheter in the delivery room has been validated for resuscitation but this technique is lengthy and requires some sterility conditions that makes it even longer, and thus non-fitting for an emergency tracheal intubation. our method is fast and can be performed easily with no specific training. the whole manipulation procedure, from the beginning of the puncture to the end of the flush-out takes 15 to 20 s. we only identified few specific risks related to this method, mostly infectious, and the risk of drug diffusion. we describe a new route for administration of drugs in the delivery room that was successfully used in 9 nine neonates. umbilical vein needle catheterization is not only safe and efficient, but is also fast and easy to perform without any special training. compliance with ethics regulations: yes. rationale: liver transplantation (lt) is the only option for children with end stage liver disease. recent advances in surgical procedure and immunosuppression have permitted a better patient and long term graft survival. however, acute cellular rejection remains a frequent complication occuring in 20 to 50% of the cases according to different studies. it is more likely to occur during the 4 first weeks post lt. many predictive factors of acute rejection have been described in litterature and results differ from one study to another. pediatric studies regarding this topic are few. the aim of this work is to study acute cellular rejection prevalence in the 30 days following lt and to determine predictive factors. rationale: sedation practices for pediatric magnetic resonance imaging (mri) are highly heterogenous. the main challenge is to keep children immobile while being alone in a traumatizing environment for a long time. clinicians have to ensure hemodynamic and respiratory stability in this isolated environment while minimizing sedation neurologic adverse effects. in this series, we report the potential usefulness, feasibility, efficacy and safety of dexmedetomidine sedation for pediatric mri. patients and methods: a single center retrospective review of six children sedated with dexmedetomidine for mri in an emergency context. all children were hospitalized in the pediatric intensive care unit of a university hospital at the time of mri. results: data on six patients aged 8 months to 4 years is reported. five patients received dexmedetomidine by intravenous route (bolus of 1-2 µg/kg over 10 min, followed by a continuous infusion of 1 µg/ kg/h). one child received dexmedetomidine by intranasal route (4 µg/ kg with atomization device). one child experienced bradycardia that did not require any intervention. very few movements were recorded during the mris for which images were rated as good quality. conclusion: dexmedetomidine seems a promisingly useful sedation agent for pediatric mri, thanks to its efficient sedative properties and good tolerability without respiratory compromise. compliance with ethics regulations: yes. rationale: computational models, or virtual patients, could be used to teach cardiorespiratory physiology and ventilation, determine optimal ventilation management as well as forecast the effect of various ventilatory support strategies. currently, there is no virtual patient specifically designed for modelling children cardiorespiratory system. thus, our research team has developed a cardiorespiratory simulator for children called "simulresp©". according to summers et al., the quality of a physiologic model is evaluated by three specific criteria: qualitatively, which relates to the model's ability to provide directionally appropriate predictions; quantitatively in steady states and in dynamics, which is the ability of the model to provide accurate predictions in steady state situations as well as dynamic transitions. the purpose of this study was to evaluate the quality ofsimulresp© according to these criteria. this study consisted in a prospective evaluation of the simulresp©'s predictions with simulated healthy subjects. the tests were performed with patients from 8 to 18 years old (8, 10, 12, 14, 16, 18 years), with different characteristics; gender (m, f) and weight (10th, 50th and 90th percentile). blood gas values (ph, pco 2 , po 2 and spo 2 ) were simulated for several virtual healthy patients with different characteristics. this study was conducted for both spontaneously breathing and mechanically ventilated patients. simulresp©'s quality and reliability were evaluated in terms of accuracy, robustness, repeatability and reproducibility. results: simulresp©'s validation procedures are ongoing. we intend simulresp© to be accurate when simulating healthy spontaneously breathing patients. but we hypothezised that simulresp© would not be able to simulate accurate blood gas values of mechanically ventilated patients conclusion: simulresp© is a promising computational model that will serve to perform calibration and validation procedures of clinical decision support systems and help clinican to determine optimal respiratory support strategies at bedside. further calibration procedures are yet required. compliance with ethics regulations: yes. the isthmic surgical tracheostomy, which was performed in the operating room by otolaryngologist under general anesthesia. the cutaneous incision was transversal in all cases.the choice of the cannula was adapted to the age, and the decanulation was carried out according to the evolution of the underlying disease. complications associated with tracheotomy are diverse, and common complications are such as careassociated pneumonia (22.5%), tracheostomy tube obstruction (7.5%), accidental decannulation (2.5%), pneumothorax (2.5%) and cases of tracheal stenosis (2.5%). the mortality rate amounted to 27.5%, where in most cases was due to the poor prognosis of the underlying diseases. the main factors of evolution are the patient's previous condition, cranial trauma, guillain-barré syndrome, tracheostomy time, prolonged tracheal intubation and the presence of complications. conclusion: regardless of the indication, the tracheotomy is an act of survival whose usefulness and effectiveness are certain. rationale: aspiration pneumonia (ap) is a frequently suspected complication of drug overdose requiring mechanical ventilation (mv) and admission to intensive care unit (icu). in the absence of reliable biomarkers for distinguishing between aspiration pneumonia and aspiration pneumonitis, antibiotic therapy is frequently prescribed. latest studies suggest that a care protocol could better select patients requiring antibiotic therapy. the objective was to determine the impact of a care protocol on the antibiotic prescription among patient admitted to icu for toxic coma with mv. we conducted a prospective observational cohort study in four icu. we included all patients admitted for toxic coma with mv. in the university-affiliated icu, a care protocol was applied. in the three others icu, physicians declared that they did not follow formalized conduct within the service and did as usual. results: we included 43 patients in care protocol group and 42 in control group. the mean saps ii was 43.3 (± 15.3) with a mean glasgow coma scale score at 4.9 (± 2.1) before intubation. within the total population, 40 patients (47%) had a pulmonary bacteriologic sample (pbs), mostly because purulent tracheobronchial aspirate and new infiltrates on the chest x-ray (respectively 36.4% and 29.4% of the population with a bacteriological sample). among the patients with a bacteriological sample, 34 (85%) were culture positive. the incidence of probabilistic antibiotherapy did not differ between the care protocol group (n = 16) and the control group (n = 16) . there was no difference for the incidence of pbs (20 in each group). the others secondary outcomes did not differ either (table 1) . conclusion: our study does not show that a care protocol allows a reduction of antibiotic prescription among patient admitted to icu for toxic coma with mv. our incidence of antibiotic prescription is lower than the previous studies. the absence of difference can be explain by two reasons: some of the physicians of the control group had been trained in the university-affiliated icu in the last years and may follow a management approach similar to that of the control group; despite our precautions, the existence of the study could have modify the practices in the control group. compliance with ethics regulations: yes. rationale: pancreatic surgery is associated with high morbidity, mostly due to infectious complications, so that many centers introduce post-operative antibiotics for all patients. such systematic prescriptions are not consensual and often rely on local practices. the aims of the study were to describe the occurrence of surgical site infection (ssi) and the antibiotic (atb) prescription after pancreatic surgery, and to determine the risk factors of post-operative surgical site infection, in order to better define the clinical indications for the prescription of antibiotics after major pancreatic surgery. patients and methods: all patients undergoing a scheduled major pancreatic surgery from january 2007 to november 2018 were included in the study. patients were classified in four groups according to the occurrence of a surgical site infection and to the post-operative antibiotic prescription as follows (ssi+/atb+; ssi-/atb+; ssi+/atb-, ssi-/ atb-). in addition, risk factors (fever and pre-operative biliary prosthesis) associated with the occurrence of a surgical site infection and with the antibiotic prescription, were analyzed using a logistic regression model. results: data from 149 patients (115 pancreaticoduodenectomies and 34 splenopancreatectomies) were analyzed and classified as presented in the table. thirty patients (20.1%) experienced a surgical site infection and 42 (28.2%) received post-operative antibiotics. we did not find any difference on post-operative antibiotic prescriptions (26.7% versus 28.6%, p = 0.9) between patients who developed a surgical site infection and those who did not. amongst the 107 patients who were not prescribed antibiotics post-operatively, 85 (79.4%) did not develop a surgical site infection while 22 (20.6%) did. in-icu mortality did not differ between infected and non-infected patients (7 versus 2%, p = 0.13). post-operative fever was different between ssi+ and ssi-(73.3 versus 34.2%, p < 0.001), while the prevalence of pre-operative biliary prosthesis was similar (37.9 versus 26.7%, p = 0.3). amongst patients who did not develop a surgical site infection, antibiotic prescription was not associated with fever (p = 1), but associated with a higher prevalence of preoperative biliary prosthesis (15.6 versus 52.9%, p = 0.0001). conclusion: non-systematic antibiotic prescription after major pancreatic surgery allowed to appropriately spare antibiotics in 85 (56%) patients at the cost of under prescription in 22 (14.8%) patients. these results suggest that systematic post-operative antibiotic prescription could be excessive. fever appears to be a relevant clinical sign for individual-based prescription, whereas the presence of a biliary prosthesis does not. compliance with ethics regulations: yes. (2, 3) . however, there is little evidence to support those recommendations (1) . we aimed to describe care paths of pm with sepsis in french hospitals and to assess outcomes depending on their hospital trajectory. we conducted a retrospective analysis of the french medico administrative (pmsi) database of consecutive patients with pm and sepsis admitted to french hospitals, between 2010 and 2015. only the first hospital admission was considered. cases were identified using a combination of a diagnosis code for pm plus a diagnosis code for organ failure or a procedure code for organ support. hospital trajectories were determined from the first admission to death or discharge, taking into account all potential transfers. costs and endpoints were determined at the end of patients' trajectories. five groups of patients were defined, according to care pathways: direct icu admission (1sticu); secondary icu admission, after initial admission to another unit including wards (ward2ndicu) rationale: new-onset atrial fibrillation (af) is a common complication in patients with sepsis and is associated with increased mortality and morbidity rates. this condition results from a complex chain of events in response to infection, involving immunologic, humoral and cellular process and sympathetic overactivity. landiolol, the new injectable beta-blocker, with high beta1 selectivity and minimal impact on arterial blood pressure, may have beneficial effects in such a context. in this study, we aimed to investigate whether landiolol decrease the newonset of atrial fibrillation in a mice model of endotoxin-induced sepsis. patients and methods: thirty c57bl/6 male mice were randomly allocated to the following groups: sham (administration of 500 µl of isotonic saline intraperitoneally-ip), septic (administration of 500 µl of isotonic saline with 20 mg/kg of lipopolysaccharide-lps-of e. coli o55:b5 ip) and septic + landiolol (administration of isotonic saline with 20 mg/kg of lps and, two hours later 25 mg/kg of landiolol ip). four hours later, an attempt of af occurrence was triggered by a transesophageal electric pacing at fixed rate (as previously reported) in all mice previously anesthetized by isoflurane 2%. ekg was continuously recorded. results: ten mice per group (mean weight: 22 ± 2 g) have been included and analyzed. among the sham group the mean heart rate was at 362 bpm versus 502 bpm in the septic group. among the septic + landiolol group the mean heart rate was at 465 bpm (p < 0,001). after transesophageal stimulation, none mice in the sham group had af, seven mice (70%) in the septic group had an af, and 2 mice (20%) in the septic + landiolol group had an af. landiolol decreased the incidence of new-onset, sepsis-induced atrial fibrillation in mice (p = 0.025). conclusion: landiolol seems to have a protective effect against sepsis-induced af in mice. however, the mechanisms, including sympathetic activation and inflammasome pathways, should be investigated before drawn definitive conclusion regarding to efficiency of landiolol to prevent new-onset af during sepsis. compliance with ethics regulations: yes. 20-25 mg/l at 24 or 48 h, proportion of patients with a vancomycin serum concentration < 10 mg/l, previously associated with resistance emergence and assessment of mortality and test of cure. results: a serum vancomycin concentration between 20-25 mg/l was reported in 43 out of 179 included patients (24%). a serum vancomycin concentration < 20 ml/l and > 25 mg/l were reported in 89 patients (51%) and 44 patients (25%), respectively. vancomycin serum concentrations during follow-up are shown in fig. 1 . in multivariate regression analysis, a longer time between admission and initiation of vancomycin was the only parameter associated with a serum vancomycin out of this target, while acute kidney injury (aki) was associated with a lower incidence of subtherapeutic concentration. acute kidney injury rate was significantly higher in patients with a serum vancomycin concentration > 25 mg/l. discussion: an adequate therapeutic target of serum vancomycin concentration was reached in 25% patients with nearly 50% < 20 mg/l, which was similar to previous studies. aki and rrt requirement were higher in patients with serum vancomycin concentration > 25 mg/l, whereas it is hardly to know whether it is a cause or a consequence. conclusion: these findings highlight the importance of a larger loading dose, vancomycin monitoring and measured creatinin clearance to improve vancomycin dosing protocol. compliance with ethics regulations: yes. rationale: suicide is a global phenomenon and one of the leading causes of death in the world. tunisia ranks second in the suicide rate in the maghreb, with 5.5 cases of suicide per 100,000 inhabitants. the aim of this study was to reconstruct the state of suicidal subjects before the act in order to identify their psychiatric profile. patients and methods: a 3-year prospective observational singlecenter (6-bed intensive care unit) study including all patients hospitalized for suicide attempt (sa). psychiatric evaluation of patients and contact with their families were done before intensive care unit discharge. results: seventy-one patients were enrolled with female predominance (sex ratio 0.42). mean age was 30 ± 13 years. familial or personal history of mental illness were found in 8 (11%) and 30 cases (42%) respectively. personal mental disorders were depression (17%), bipolar disorder (10%), schizophrenia (8%) and border line personality disorder (7%). twenty-five per cent had prior sa. sixty-three per cent were single, 30% married and 7% divorced. the common methods of suicide included drug (52%), chloralose (34%) and pesticide (13%) poisoning. mean igs ii and apache ii scores were 30 ± 19 and 14 ± 9 respectively. on admission, 59% of all patients were in coma, 11% had shock and 48% developed aspiration pneumonia. mechanically ventilation was done in 59% of all cases with mean duration of 3 days. the mean length of stay in intensive care unit was 4 days. mortality rate was 7%. psychiatric evaluation and contact with families deduced that the main precipitating factors for suicide were traumatic events. in fact: relationship problems (familial, marital or breakups), school failure and mourning were found in 66%, 6% and 1% of all cases respectively. reactional sa accounted for 61%. rationale: poisoning is a worldwide problem, associated with high morbidity and moratlity. in tunisia, the rate of fatal poisoning has been increasing in the last years, with emergence of new toxic substances. regardless of the toxic, fatal poisining is considered as a non natural death, that requires medico-legal investigation, to assess whether it is suicidial, crimnal or accidental death. this study aimes to determine the epidemiological characteristics of the cases of fatal poisoning in south, to identify the toxics used in oder to deduce the preventive measures. patients and methods: we conducted a retrospective study of all cases of fatal poisoning recorded in the forensic department of habib bourguiba university hospital in sfax, tunisia, over a 12-years period (2006) (2007) (2008) (2009) (2010) (2011) (2012) (2013) (2014) (2015) (2016) (2017) . results: during the study period, 88 cases of fatal poisoning were autopsied. the number of victims recorded per year varied between 1 and 16 cases with an average of 8 cases per year. the average age was 30 years with extrems ranging from 7 months to 85 years. nearly half (46.5%) were younger than 40 years. a male predominance was noted with a sex-ratio of 1.04. the majority of victims were single, loweducated and from rural origin. personal antecedent of psychiatric pathology was found in 9.1% of cases. psychotic disorders (schizophrenia) and depression were the most common pathologies. in our study we noticed that death occured every weekday without significant difference between days. however, the frequency of fatal poisoning was slightly higher in cold seassons (53.9%). in 71.6% of cases, victims were found dead at home. accidental fatal poisoning was the most common (56%). no criminal cases have been observed. we noted a male predominance in accidental forms and a female predominance in suicidal forms. carbon monoxide poisoning was the most common (35 cases) followed by the organophosphorus poisoning which was noted in 15 cases. conclusion: decreasing the mortality rate from poison ingestion requires increasing public awareness about poisons and improving emergency service equipment and health personnel training. compliance with ethics regulations: yes. severe acute poisoning by organophosphate pesticides: report of 18 cases at the oran hospital and university center mourad goulmane hospital and university center of oran, oran, algeria correspondence: mourad goulmane (goulmane.mourad@univ-oran1. dz) ann.intensive care 2020, 10(suppl 1):p-126 rationale: organophosphate pesticides are synthetic organic pesticides widely used in agriculture mainly as an insecticide, nemacid or acaricide. these are the agricultural products, the most incriminated in poisoning in our context. the objective of this work was to determine the clinical, paraclinical, and progressive characteristics of this poisoning in a resuscitation environment. patients and methods: retrospective study of cases admitted to intensive care (january 2016-december 2018). inclusion criteria were clinical, para-clinical, therapeutic and progressive. results: 18 cases were identified: 16 women and 2 men, mean age = 26.3 ± 10 years. the suicide attempt was the main reason for the intoxication (16 cases). the glasgow coma score averaged 11 ± 4. the central syndrome was present in 80% of our patients, followed by muscarinic syndrome 75% and nicotinic syndrome in 58% of cases. therapeutic management consisted of mechanical ventilation in 50% of cases, the use of vasoactive drugs in 20% of cases and the administration of antidotal treatment in 100% of cases. the overall mortality was 16.66%. conclusion: organophosphate pesticides intoxication is a real health problem in algeria. it is a serious condition dominated by the respiratory and neurological distress that causes most deaths. it concerns in our context especially young women who ingest the product for the purpose of autolysis. the diagnosis is based on the clinical and dosage of cholinesterase activity in the plasma. treatment combines symptomatic measures that rely primarily on respiratory and neurological resuscitation to antidotal treatment. the clinical course in this type of intoxication is generally favorable under treatment with regression of signs in a few days. mortality is high in our context, so it should be considered a diagnostic and therapeutic emergency. the commercial availability of these products is worrisome, justifying the use of a broad prevention program to inform the public and authorities of the danger of organophosphate pesticides compliance with ethics regulations: not applicable. . the clinical examination revealed that five patients met the criteria for serious intoxication with the following signs: coma in four patients requiring the use of mechanical ventilation, seizures (n = 1), rhabdomyolysis (n = 3), shock (n = 1), toxic takotsubo (n = 1) and hepatocellular failure (n = 1) leading to patient's death. the use of mechanical ventilation was necessary in 4 patients. the analysis of the severity factors did not show a statistically significant association between severity, age (p = 0.6), sex (p = 1) and chronic consumption of psychoactive substances (p = 0.52). on the other hand, we did not find a statistically significant association between serious intoxication, the number of tablets ingested (p = 0.7), the apacheii score (p = 0.11) and the average length of stay (p = 0.11). conclusion: ecstasy acute poisoning is becoming more common in our country and can potentially be very serious regardless of age, sex, medical history or number of tablets ingested. on the other hand, the concentration of nmda could be the only factor to be taken into consideration upon admission. compliance with ethics regulations: yes. quarter of early trauma-related mortality, in some series. early identification of poor outcome predictors could be valuable to guide the most appropriate care. we aim to determine factors associated to mortality in patients with severe non-penetrating chest trauma admitted to the icu. patients and methods: this is a prospective cohort study, including all patients with isolated severe blunt chest trauma (abbreviated injury scale ais > 3) admitted to the intensive care unit of a university hospital, over a one-year period. the primary objective was to analyse risk factors associated to death and poor outcome using univariate and multivariate analysis. results: one hundred-thirty patients were admitted to the icu for blunt chest trauma among them 72 were diagnosed with severe isolated chest trauma and were included. the mean age was at 33 ± 18, mean iss at 36 ± 15 and mean tts at 7 ± 3. twenty-eight (39%) patients were diagnosed with acute respiratory distress syndrome, 31 (43%) with post-traumatic acute kidney injury and fourteen (19%) with post-traumatic pulmonary embolism. the mean length of icu stay (los) was at 17 ± 13 days and mean number of days on ventilator was at 10 ± 9 days. thirty-two (44%) patients underwent elective tracheostomy for prolonged intubation. thirty-seven patients (51%) developed infections, among them thirty (42%) were diagnosed with pulmonary infection and seven (9%) with non-thoracic infections. overall mortality had an incidence of 16.7% (12 patients rationale: early hyperglycaemia in traumatic brain injury (tbi) is a part of the stress response. it is an important indicator of severity and a reliable predictor of prognosis. we aimed to describe the epidemiological, clinical and paraclinical characteristics and to assess the prognostic impact of this hyperglycaemia on the tbi. we conducted a retrospective study in the intensive care unit (icu) of our hospital between 2009 and 2012. were included all patients with tbi and blood glucose > 8 mmol/l at the first 24 h post-trauma. results: during the study period, 694 patients were hospitalized in our icu with tbi. early hyperglycemia (> 8 mmol / l) was found in 380 patients (54.7%). in univariate analysis, glycaemia > 8.5 mmol/l (= 154 mg/dl) at admission was significantly associated with mortality (p = 0.015). we observed that glycaemia > 7.3 mmol/l at h12, > 7.2 mmol/l at h24, > 6.7 mmol/l at h36 and > 6.5 mmol/l at h48 was significantly associated with mortality (p = 0.07; p < 0.0001; p = 0.001 and p = 0.0008, respectively). the risk factors significantly associated with mortality were age > 32 years (p < 0.0001), saps ii > 40 (p < 0.0001), initial shock (p < 0.0001), glasgow coma scale (gcs) < 7/15 (p < 0.0001), coma period > 7 days (p = 0.023). the ct scan lesions statistically associated with mortality were: subdural hematoma (p < 0.0001), cerebral oedema (p < 0.0001), intra cerebral haemorrhage (p = 0.023), cortical contusion (p = 0.001), contusion of cerebral trunk (p = 0.011), contusion of the corpus callosum (p = 0.003), thalamus contusion (p = 0.004). in multivariate analysis, independent risk factors statistically associated with mortality were age > 32 years old (or = 2.92 ic [1.52-5.78 ]; (p = 0.001)), glycaemia > 8.5 mmol/l at admission (or = 2.25 ic [1.16-4.39 ]; (p = 0.017)),gcs < 7/15 (or = 3.40 ic [1.8-6.24 ]; p < 0.001), intracerebral hematoma (or = 3.2 ic [1.10-10.18 ]; p = 0.049). we recommend a mandatory control of the blood glucose levels during a tbi with a target between 6.5 and 7.5 mmol/l in the acute phase. compliance with ethics regulations: not applicable. the fat embolism syndrome (fes) is a set of clinical, biological and radiological signs resulting in the obstruction of microcirculation by micro-droplets of insoluble fats.the clinical signs of the fes are not very specific, the diagnosis is difficult and the risk of misunderstanding this syndrome is very real.the fes appears after a trauma, often few days later. however, it sometimes occurs without previous trauma; and it is particularly difficult to recognize in these cases. the aim of this work is to define the epidemiological profile, the clinical and para-clinical features of this syndrome and its therapeutic management. rationale: sedative and analgesic treatment administered to critically ill patients with mechanical ventilation need to beregularly assessed to ovoid complications of oversedation mainly in elderly patients. our objective is to evaluate our sedation practice in the elderlyin our unit patients and methods: it was a prospective observational study, including elderly patients over 65 years of age without acute brain injury requiring sedation more than 48 h of hospitalization in the intensive care unit of our university hospital between april 2018 and december 2018. thirty patients were included. the aged was 73.3 years, the sex ratio was 1.7. respiratory distress was the most common reason for hospitalization 53%. the most accepted diagnoses were the decompensation of copd in 34% of cases and septic shock in 23% of cases. the saps ii averaged 58 ± 12 points, sofa averaged 10 ± 2.4 points. renal failure was found in 21 patients (70%), hepatic impairment was noted in 7 patients (23%), hypoproteinemia was marked in 17 patients (57%). midazolam was used in 90% of patients. it was in combination with fentanyl in 63% of cases and remifentanyl in 30% of cases. the median ramsay score 5.7 ± 0.6 on the first day of sedation and 5.3 ± 0.7 on the second day of sedation. the median rass scale was − 4.7 ± 0.6 on the first day of sedation and − 4.4 ± 0.8 on the second day of sedation. the median bps scale 3.6 ± 1.4 on the first day of sedation and 3.6 ± 1.2 on the second day of sedation. the mean wake up time was 6 ± 3, 38 days. neuromyopathy of resuscitation was suspected in seven patients (20%), withdrawal syndrome was observed in two patients (7%) and acute cognitive dysfunction in two patients (7%). the median duration of sedation was 4.2 days ± 1.9 days, the median duration of mechanical ventilation was 11.1 ± 6.3 days, the median length of stay was 14.3 ± 9.8 days. ventilator-associated pneumonia was diagnosis among 79% of patients. the mortality in intensive care was 37%. conclusion: sedation analgesia in the elderly person should be adapted according to age, ideal weight and renal and hepatic function by decreasing the initial doses. it should be evaluated by the recommended scores by setting a sedation objective according to the pathology. compliance with ethics regulations: not applicable. rationale: more than 2500 original articles are newly indexed in pub-med every day. journal club (jc) is one way to cope with this abyssal amount of medical information. we aimed at (1) describing journals and articles analyzed during our jc sessions (2), reporting the proportion of published articles being analyzed during jc sessions and (3) assessing the clinical impact on our daily practices for each journal. patients and methods: a retrospective analysis of prospectively collected data over a 12-year period from 2007 to 2019 in a universityaffiliated icu. jc sessions were scheduled weekly and participants were free to choose and expose orally an article recently published in any medical journal (general, icu or non-icu specialized). clinical impact of a journal was retrospectively and independently assessed by two attending intensivists (dc, hm) and was defined by the ratio of articles considered as having a direct impact on our daily practices over the number of articles of the same journal read during the same period. results: from august 2007 to august 2019, 313 jc sessions were held and 1712 articles-mostly original (n = 1657/1712; 97%)-from 93 journals were analyzed, accounting for 0.01% of the 11869960 articles (0.02% of the 10982188 original articles) referenced in pubmed during the same period. median number of articles exposed per session was 6 [4] [5] [6] [7] . median number of doctors attending each session was 7 [6] [7] [8] (attendings: 2 [2] [3] , fellows: 1 [1] [2] , residents: 3 [2] [3] ). general, icu and non-icu specialized journals accounted for 32%, 47% and 21% of the exposed articles, respectively. most of the reported articles dealt with intensive care (n = 1177, 69%) especially infectious diseases (n = 286/1177; 24%), hemodynamics (n = 123/1177; 10%) or icu-organization (n = 111/1177; 9%). compared to general and non-icu specialized journals, the proportion of read-over-published articles was higher for icu-specialized journals (0.18% vs. 0.13% vs. 2.61%, respectively; p < 0.0001). among original articles, only 93 (5.9%) [interventional (n = 61/93; 66%); observational (n = 32/93; 34%) studies] were considered as having a clinical impact on our daily practices. compared to icu and non-icu specialized journals, general journals had a higher clinical impact (4.3% vs. 4.9% vs. 9 .1%, respectively; p = 0.001). data regarding the 3 most read general, icu and non-icu specialized journals are detailed in table 1 . in a french university-affiliated icu with regular jc sessions, the proportion of read-over-published articles and the clinical impact of medical journals appear minor. in the ocean of medical literature, general medical journals appear more worth reading by intensivists than icu-specialized journals. compliance with ethics regulations: yes. rationale: the world's population is aging and the 80 and over's age group is growing fast (+ 3.8% per year). this aging population is impacting intensive care units with exponential rates of elderly patients (14.4% in 2011, 18% in 2017) , associated with significant mortality (from 15% to 50%). the evolution and the prognostic factors of these elderly patients in intensive care are therefore a public health issue for optimal management. patients and methods: we included all patients aged 80 and over who were operated and admitted to surgical resuscitation in our center, with a duration of stay greater than 24 h, from april 2016 to july 2018. the data collected were: general characteristics of this population, mortality in intensive care, at day 30 and at 6 months and the prognostic factors guiding their evolution in intensive care and at 6 months. results: of the 102 patients included in our study, mortality was 31.4% in intensive care, 42.2% at day 30 and 60.8% at 6 months. the prognostic factors in the intensive care unit were the average dose of noradrenaline at day 1 (threshold at 0.65 mg/h), the sofa score at day 1 (threshold at 6 points) and the igs2 score (threshold at 66 points). the prognostic factors at 6 months were ventilatory autonomy on day 1 (spontaneous ventilation, non-invasive ventilation, invasive ventilation), the reason for admission to intensive care (acute respiratory distress or septic shock) and the fragility score (clinical failure scale with a threshold at 4). conclusion: the mortality of patients aged 80 and over is influenced by prognostic factors easily obtained daily at patient's bed. these prognostic factors could be an aid for the resuscitation teams to evaluate the relevance of the care undertaken in elderly or even very elderly patients admitted in an acute situation. compliance with ethics regulations: not applicable. assessing patient safety culture perception in the intensive care unit in tunisia oussama jaoued, chaoueh sabrina, sik ali habiba, wael chemli, gharbi rim, fekih hassen mohamed, elatrous souheil hôpital taher sfar, mahdia, tunisia correspondence: oussama jaoued (oussamajaoued@gmail.com) ann. intensive care 2020, 10(suppl 1):p-143 rationale: in tunisia health care system, patient safety has become a priority of quality assessment. the aim of our study was to describe the safety culture perception of the intensive care unit staff. patients and methods: the safety attitude questionnaire (saq-icu) was distributed to all intensive care unit staff by email. the questionnaire explores 6 safety culture domains: "team work", "safety climate", "job satisfaction", "stress recognition", "perception of the hospital and intensive care unit management" and "work condition". results: eighty participants responded to the questionnaire, 61% of them were women. participants were doctors in 62.5%. the coordination between physicians and nurses was very good only in 21%. thirtynine participants thought that the workload was high and 41% like their work. medical errors are handled appropriately in 26% of cases and it was difficult to discuss errors in 19% of cases. the hospital is a good place to work in 5% of participants, 28% of participants were less effective at work when there were tired. the hospital did a good effort of training new personal in 18% of cases. the number of medical staff was lower than expected in 82% of cases. half of participants would feel safe being treated as patients in their respective units. all domains explored by saq-icu could be improved according to attendants. conclusion: safety culture perception among intensive care unit staff had several deficiencies, mainly the working conditions, the ignorance of medical error reporting procedures and the lack of communication. rationale: the simplified acute physiology score ii (saps ii) is an icu scoring system used to predict the mortality risk in patients presenting at the icu. however the majority of critically ill patients present initially at the ed and their transfer to the icu may be delayed for hours. therefore, the ability to accurately assess mortality risk at ed may have a great impact. the purpose of this study was to evaluate the performance of saps ii in predicting early and late mortality in ed patients. patients and methods: this prospective study was conducted at the ed during a 6-month period. data for adult ed patients were evaluated. saps ii score was used to predict early and late mortality rates at 48-h and 30-day respectively. discrimination was evaluated by calculating the area under the receiver operating characteristic curve (auroc). results: during the study period 200 patients were enrolled. the mean age was 65 ± 10 years, 52% of the patients were men. the mean saps ii was 30. the early mortality rate was 20% and late mortality rate was 15%. saps ii was efficient in predicting early mortality, with an auroc of 0.84 (95% ci 0.79-0.89). however, it demonstrated no value in predicting late mortality with an auroc of 0.44 (95% ci 0.39-0.49) conclusion: in this study, saps ii score was accurate in predicting early mortality, however this tool appears less suitable for predicting late mortality. compliance with ethics regulations: yes. oussama jaoued, chaoueh sabrina, sik ali habiba, yosri ben ali, fekih hassen mohamed, elatrous souheil hôpital taher sfar, mahdia, tunisia correspondence: oussama jaoued (oussamajaoued@gmail.com) ann. intensive care 2020, 10(suppl 1):p-145 rationale: the aging of the population increased the number of hospitalizations in icu. the aim of our study was to determine the impact of hospitalization of patients over the age of 80 on morbi-mortality and consumption of care (omega score). patients and methods: this is a retrospective study carried out in the icu in the hospital of taher sfar in mahdia over a period of 17 years. all patients hospitalized in the icu were included in this study. two groups of patients were individualized: g1: patients over 80 years old, g2: patients under 80 years old. results: during the study period, 4053 patients (3664 < 80 years old and 389 ≥ 80 years old) with a mean age 56 ± 20 years and with a mean sapsii 32 ± 19 were included. the common reason for hospitalization was acute respiratory failure in 53% of cases. comparing the two groups, the severity score sapsii was higher among patients older than 80 years (43 ± 16 vs 30 ± 18, p < 0.001). the use of mechanical ventilation was more common in the first group (67% vs. 55%, p < 0.001). the incidence of nosocomial infections was similar in both groups (12% in the group g2 and 14% in group g1, p = 0.2) and the use of renal replacement therapy was also similar in tow groups (7% in the g2 group and 6% in the g2 group, p = 0.3). the duration of mechanical ventilation and length of stay were similar between the two groups. workload evaluated by the omega score was higher in the first group (57 rationale: icu outcome depends on quality of pre-icu care. we aimed to assess the chain of care of deteriorating ward patients (dwp), through evaluation of preadmission severity and delays before admission, and association with outcome. patients and methods: retrospective observational study in a single center (750 beds general hospital) for 1 year-may 15th of 2018 to 2019. all adult patients admitted in the icu from the wards were included, except for scheduled surgery, or unexpected event in the operative theater. preadmission severity was assessed through levels of national early warning score 2 (news2): group 1 with news2 inferior to 5, group 2 with news2 between 5 and 7, and group 3 with news2 superior to 7. these scores were established from vital signs during the 48 h before icu admission. patterns of patients, including sofa and saps2, knaus index, charlson comorbidity score, cause of admission and technics used in the icu, length of stay in the icu and in the hospital, limitations of life-supporting care, and mortality at 30 and 90 days after icu stay. satistical analysis was performed through chi 2 and fisher tests on qualitative parameters, and with kruskal-wallis, student and mann-whitney tests for quantitave data. results: sixty-eight patients were studied: 23 in group 1, 21 in group 2 and 24 in group 3. most patients (all except 9) had not respiratory rate monitoring before icu admission. icu mortality was associated with rising preadmission severity (group 1: 8.7%; group 2: 38.1%; group 3: 45.8%). base patterns (charlson comorbidity score, knaus index) did not differ between the 3 groups, and 61.8% of patients presented with sepsis. main causes of admission were respiratory (45.5%), hemodynamic (25%) or neurologic (17.7%) failures. all patients admitted after cardiac arrest resuscitation (8 patients) belonged to group 3. acute severity scores (sofa and saps2) followed preadmission severity. limitation or withdrawing of life support in the icu was higher in group 3 (62.5%) than in groups 2 (30%) and 1 (8.7%) . median delay between first news2 equal or superior to 5 and icu admission was 14 h, and 9 h between news2 equal or superior to 7. diffrences in delays were not associated with outcome. discussion: our study outlines weaknesses in the chain of care of dwp. emphasis should be put on respiratory rate monitoring and better assessment of severity. rationale: access to critical care is controversial in older patients for 2 reasons: lack of available icu-beds and speculation on induced costs. in contrast, admission of young patients aged 40 or under is infrequently questioned even though they develop catastrophic multiple-organ failure requiring full care. in addition, emotive reaction triggered in staff by these patients often represents a heavy psychological burden when icu-stay is < 48 h. information on the epidemiology, clinical information and induced costs regarding such patients is lacking. patients and methods: this study retrospectively assessed the records of patients aged 40 or under, and admitted from january 2008 to august 2019. cost-related expenses charged to care-payers were obtained from our medical information department. data (number, percentages or medians) were reported and discussed by comparison with those of nonagenarians during the same period. results: of 10,948 icu-admissions, 1347 were aged 40 or under (13%), 117 of whom (8.7%) died within the icu, with 41 (35%) dying within 48 h of admission despite full intensive care. the latter represent our study population (0.4% of the screened population). the median age was 32.8 years , male gender was prevalent (61%). half the patients (n = 20, 48%) were referred from the emergency department, 11 (26.8%) from hematology, 3 from oncology (7.3%), 6 from medical intermediate care units (14.6%), and one from digestive surgery (2.4%). the first diagnosis at admission was septic shock (n = 17, 41.4%), followed by post-anoxic encephalopathy (n = 13, 31.7%), coma (n = 5, 12.2%), acute respiratory failure (n = 4, 9.8%) and cardiogenic shock (n = 2, 4.9%). sapsii was 71 . all patients were ventilated and infused norepinephrine. two patients underwent ecmo, and 2 others mars. mean (± sem) retribution per stay was 13,475 ± 3565 €, and mean retribution per "day of stay" 6737 €. discussion: full care of these icu-patients, with early mortality has a financial impact similar to that of nonagenarians at 13,160 ± 11,070 €; the cost per "day of stay" is therefore on average 100% higher than that of nonagerians (mean length of stay: 6.3 days), and, in our experience, 50% higher than that of average patients. conclusion: icu-patients aged 40 or under represent a small percentage of admissions and display half our overall mortality: one third of them die within 48 h of admission with a not insignificant financial impact for cost-payers. septic shock is the first cause of referral, followed by unexpected cardiac arrest. compliance with ethics regulations: yes. rationale: severity scores in patients with sepsis are useful for triaging and predicting mortality. mortality in emergency department sepsis (meds) score is validated in patients with sepsis in the emergency department. curb-65 is validated in patients with communityacquired pneumonia but not in sepsis. curb-65 is a simple bedside tool that has many common elements with new sepsis identification score-q sofa. the study aimed to assess the accuracy of curb-65 score in predicting icu admittance and mortality compared to meds score. patients and methods: this prospective study was conducted at the ed during a 6-month period. we enrolled all adult patients with sepsis admitted to the ed. meds and the curb-65 scores were calculated at admission. patients were studied using curb-65 score and their icu admission and in-hospital mortality were ascertained. results: a total of 120 patients were enrolled. the mean age was 60 ± 10 years. 60% of the patients were men. 30% of patients had a curb-65 score ≥ 3 points with a mean meds score of 13%. among these patients, 40% were admitted to icu and 30% died. the curb-65 score,was efficient in predicting both icu admittance and in-hospital mortality with an auroc of 0.84 (95% ci 0.79-0.89) and 0.73 (95% ci 0.67-0.79), respectively. conclusion: a higher curb-65 score was correlated with higher rates of icu admittance and mortality in patients with sepsis due to any cause. compliance with ethics regulations: yes. abderrahim achouri, hadil mhadhbi, khedija zaouche, hamida maghraoui, radhia boubaker, kamel majed university hospital center rabta of tunis, tunis, tunisia correspondence: abderrahim achouri (achouryabderrahim@gmail. com) ann. intensive care 2020, 10(suppl 1):p-150 rationale: sepsis is a major cause of mortality. in other hand, preexistent chronic diseases seem to worsen outcomes among critically ill patients. the acknowledgement of this fact may motivate studies in this type of situations in order to improve survival in sepsis. on that purpose, our study tried to check the impact of chronic pre-existent illnesses on outcomes in this type of emergency patients. patients and methods: we have included patients in whom the sepsis-3 definition was met throughout emergency department admission cases for infection. in this study, considered outcomes were in-hospital mortality, shock occurence and the use of mechanical ventilation. results: we collected 93 patients admitted to ed for sepsis. mean age was 65 years ± 14 with bornes of 24 and 92. men were 57% of the patients. cormorbidities were: insulin dependent diabetes mellitus in 11.1% of patients, non insulin dependent diabetes mellitus in 42.6%, chronic obstructive lung disease in 20.4%, chronic renal failure in 19.4% with 12% in chronic replacement therapy from total patients, coronary artery disease in 16.7%, with stent in 8.3% and 3.7% with aortic coronary graft from total patients, arterial hypertension in 50%, chronic heart failure in 20.4%, atrial fibrillation in 10.2%,. death occurs in 29.6% of total patients, septic shock in 25% and the use of mechanical ventilation in 5.6%. we did not find any association between comorbidity and the use of mechanical ventilation, but association with in-hospital mortality was found in pre-existent coronary artery disease (p = 0.001) and in patients with coronary artery stent (p = 0.011). odds ratio (or) was respectively 5.2 (95% ic = [1.8-15 .0]) and 5.6 (95% ic = [1.3-24.1] ). we found significant association between chronic heart failure and shock (p = 0.013) with or = 3.4 (95% ic = [1. 3-9.1] ). discussion: the small size of our sample may enlimit the contibution of other comorbidities on outcomes in sepsis such chronic renal failure, especially with renal replacement therapy and diabetes mellitus. whereas, we can conclude that cardiac diseases have the most important impact on outcomes in sepsis. outcomes in sepsis can be affected by comorbidities, especially cardiac diseases. therefore, that needs large studies to check it. compliance with ethics regulations: yes. micafungin population pk analysis in critically ill patients receiving continuous veno-venous hemofiltration or continuous veno-venous hemodiafiltration nicolas garbez 1 , litaty mbatchi 1 , steven c. wallis 2 , laurent muller 1 , jeffrey lipman 2 , jason a. roberts 2 , jean-yves lefrant 1 , claire roger 1 1 chu nîmes, nîmes, france; 2 university of queensland, brisbane, australia correspondence: nicolas garbez (nicolas.garbez@umontpellier.fr) ann. intensive care 2020, 10(suppl 1):p-151 rationale: to compare the population pharmacokinetics (pk) of micafungin in critically ill patients receiving continuous veno-venous hemofiltration (cvvh, 30 ml/kg/h) to those receiving equidoses of hemodiafiltration (cvvhdf, 15 ml/kg/h + 15 ml/kg/h). critically ill patients in septic shock undergoing continuous renal replacement therapy (crrt) and receiving 100 mg micafungin once daily were eligible for inclusion. total micafungin plasma concentrations were analyzed using pmetrics ® . probability of target attainment (pta) was calculated from monte carlo simulations using 24-hour area under curve/minimum inhibitory concentration (auc0-24/mic) cut-offs 285 (c. parapsilosis), 3000 (all candida species) and 5000 (c. non parapsilosis). daily dosing regimens of 100, 150 and 200 mg were simulated for the first 2 days of treatment. results: eight patients were included in the study. micafungin concentrations were best described by a two-compartmental pk model. no covariate, including crrt modality (cvvh and cvvhdf), was retained in the final model, confirmed by internal validation. the mean parameter estimates (standarddeviation) were 0.96 (0.32) l/h for clearance, 14.84 (5.33) l for the volume of the central compartment, 0.36 (0.33) 1/h and 0.53 (0.24) 1/h for rate constants. the standard 100 mg daily dosing was unable to reach 90% of pta for all candida species except c. albicans on the second day of therapy (fig. 1) . conclusion: there was no difference in micafungin pk between equidoses of cvvh and cvvhdf. a dose escalation to 200 mg is suggested to achieve the pk/pd target of candida species with mics exceeding 0.016 mg/l in this population. these "off-label" dosing regimens should be further investigated in clinical trials knowing the favourable toxicity profile and the post-antifungal effect of micafungin in order to ensure efficacy and to prevent the emergence of resistance due to an inadequate initial antifungal dosing regimen. compliance with ethics regulations: yes. rationale: sepsis is an important cause of morbidity and mortality in hospitalized patients. recognizing and responding to patients who experience clinical deterioration remains challenging in daily practice. our purpose was to assess the ability of the quick sequential organ failure assessment (qsofa) score to identify, among patients reviewed by an intensivist, those at risk of adverse outcomes. patients and methods: retrospective cohort of patients with suspected infection reviewed by an intensivist in a university-affiliated hospital between january 2018 and june 2018. outcomes of interest were hospital mortality and a combined criterion of hospital mortality or icu stay of 3 days or more. results: during the study period, 1163 patients were reviewed by an intensivist, of whom 459 (39.6%) had suspected infection according to the sepsis-3 criteria. at the time of review, 192 (41.8%) patients with suspected infection were qsofa positive (≥2) and 267 (58.2%) were qsofa negative (0-1). following the review, 240 (52.5%) patients were admitted to the icu, among whom 202 (79.5%) had a prolonged stay (≥3 days). in-hospital mortality was 27.9%, and 79.9% of the patients met the combined criterion of in-hospital mortality or prolonged icu stay. qsofa positive patients required more frequently mechanical ventilation (52.9% vs. 36.6%, p = 0.01) and vasopressor support (50.5% vs. 28.8%, p < 0.001) than qsofa negative patients. moreover, qsofa positive patients had higher hospital mortality than qsofa negative patients (34.5% vs. 23.2%, p = 0.02). for the prediction of in-hospital mortality, a positive qsofa had a predictive positive value (ppv) of 34%, and a negative predictive value (npv) of 77%. for the prediction of in-hospital mortality or prolonged icu stay, a positive qsofa had a ppv of 83% and a npv of 24%. conclusion: hospitalized patients with suspected infection for whom a review by an intensivist was requested, are at high risk of hospital mortality. although the accuracy of qsofa for identifying patients at risk of adverse outcomes is limited, its integration in a multimodal risk assessment approach may help distinguish the subset of patients who will benefit from an escalation of care. compliance with ethicsregulations: yes. rationale: according to the sepsis-3 consensus, sepsis is identified as an increase of at least 2 points in the sepsis-related organ failure assessment (sofa) score in patients who presented infection. the quick sofa or qsofa is considered as a predictive tool of sepsis and mortality when it is equal to 2 points or more. systemic inflammatory response syndrome (sirs) criteria are of limited utility because of their low sensitivity. hyperlactatemia, as known is a determinant of tissue hypoperfusion. our objective was to evaluate the prognostic value of sofa > 2, sirs > 2, qsofa > 2 and lactate level > 2 mmol/l in infected patients. nine-month prospective cohort study. patients aged 18 years or older who had a proven or suspected infection were included. sofa score, sris criteria, sofa q and lactate levels were determined within the first 24 h of infection. the primary endpoint was hospital mortality at 30 days. the predictive power of the studied parameters was determined using using the area under the receiver operating characteristic curve (auroc). results: a cohort of 71 cases was studied with mean age at 49.5 years. bacterial pneumonia was the most common infection site (66%). in the first 24 h of onset of infection the medians [iqr 25-75] of the sofa, sris, and sofa scores and lactate levels were respectively 6 [3] [4] [5] [6] [7] [8] [9] , 3 [2] [3] , 1 [1-2] and 2.04 [0.65-3.4] . the progression to severe septic status was observed in 34 patients (48%) and norepinephrine was introduced in 32 cases. median length of stay was 11 days [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] and mortality was 53%. overall, the accuracy in predicting mortality of the 4 studied parameters was poor. an increase of sofa score by at least 2 points had greater accuracy with auroc = 0.762 [0.647-0.877], sensitivity = 74% and specificity = 79%. conclusion: in infected patients, the sofa score had greater prognostic accuracy than the sirs criteria, the qsofa score or the lactate level. these results suggest that sirs, qsofa, and high lactate level may be useful in screening for sepsis, but this utility is limited in predicting mortality. compliance with ethics regulations: yes. rationale: quick sequential organ failure assessement (qsofa) has been validated for patients with presumed sepsis and others in general emergency department (ed) population. however, it has not been validated in specific subgroups of patients with a high mortality. the aim of this study is to evaluate the ability of qscore to predict prognosis in patients with decompensated liver cirrhosis. patients and methods: this is a retrospective study, conducted over a period of 3 years from january 2016 to december 2018. consecutive patients with decompensated cirrhosis, admitted in our department are included. data of all patients were collected and the qsofa score was calculated at admission. the main study endpoints were length of stay, complications and in-hospital mortality. results: a total of 110 patients diagnosed with decompensated cirrhosis were enrolled. mean of age was 62 years (18-88). sex ratio was 1.2. hcv (39%) was the main etiology of cirrhosis. the reasons of hospitalization were: oedema with ascitic syndrome in 44% of cases, digestive haemorrhage (21% of cases), fevers (16% of cases), and hepatic encephalopathy was present in 36% of cases. the mean duration of stay was 10 days ± 7. in-hospital mortality rate was 20% and mean score qsofa was 1.2.the qsofa score was significantly correlated with length of stay (p = 0.02) and complications(p = 0.04) but not with in-hospital mortality (p = 0.99). conclusion: the qsofa score was not useful for predicting in hospital mortality in patients with decompensated liver cirrhosis but it was significantly correlated to the length of stay and complications. compliance with ethics regulations: yes. angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study clara vigneron 1 , aldéric lécluse 2 , thomas ronzière 3 , sonia alamowitch 4 , olivier fain 1 , nicolas javaud 5 1 médecine interne, centre de référence associé sur les angioedèmes à kinines (créak), hôpital saint-antoine, aphp, paris, france; 2 neurologie, chu angers, angers, france; 3 neurologie, chu pontchaillou, rennes, france; 4 neurologie, hôpital saint-antoine, aphp, paris, france; 5 urgences, centre de référence associé sur les angioedèmes à kinines (créak), hôpital louis mourier, aphp, colombes, france correspondence: clara vigneron (claravigneron@hotmail.fr) ann. intensive care 2020, 10(suppl 1):p-156 rationale: bradykinin-mediated angioedema is a complication associated with thrombolysis for acute ischemic stroke. risk factors are unknow and management is discussed. the aim of this study was to clarify risk factors associated with bradykinin-mediated angioedema after thrombolysis for acute ischemic stroke. patients and methods: in a case-control study conducted at a french reference center for bradykinin angioedema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angioedema, were compared to controls treated with thrombolysis treatment without angioedema. two matched control subjects were analyzed for each case. results: 53 thrombolysis-related angioedema were matched to 106 control subjects. the sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). the upper airways were involved in 37 (70%) cases. three patients required mechanical ventilation. patients with bradykinin-mediated angioedema were more frequently women (33 (62%) vs. 44 (42%); p = 0.01), had higher frequency of prior ischemic stroke (12 (23%) vs 9 (8%); p = 0.01), hypertension (46 (87%) vs. 70 (66%); p = 0.005), were more frequently treated with angiotensinconverting enzyme inhibitor (37 (70%) vs. 28 (26%); p < 0.001) and were more frequently hospitalized in intensive care unit (11 (21%) vs. 5 (5%); p = 0.004). in multivariate analysis, factors associated with thrombolysisrelated angioedema were female sex (odds ratio [or], 3.04; 95% confident interval [ci], 1.32-7.01; p = 0.009) and treatment with angiotensin-converting enzyme inhibitors ([or], 6.08; 95% [ci], 2.17-17.07; p < 0.001). discussion: because of theretrospective case-control design and the lack of the total number of thrombolysis for ischemic stroke, the incidence of this complication could not be evaluated in our study. previous studies reported an incidence of 2.1 to 7.9% of angioedema in patients treated with a thrombolytic therapy for acute ischemic stroke. our case-control study permits for the first time to analyse more cases to evaluate associated risk factors of this rare complication. conclusion: this case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykininangioedema associated with thrombolysis for ischemic stroke. compliance with ethics regulations: yes. rationale: patients with inflammatory bowel disease (ibd), frequently treated by immunosuppressive drugs, are more susceptible to be admitted to the intensive care unit (icu). however, outcome and predictive factors of mortality are little known. therefore, we aimed to assess the outcome and prognostic factors for critically ill ibd patients. patients and methods: we retrospectively studied data of consecutive ibd (i.e. crohn's disease and ulcerative colitis) patients admitted in 3 icus between 2007 and 2017. in-icu and one-year mortalities were estimated and predictive factors of in-icu mortality were identified by univariate and multivariate analysis. results: seventy-six patients (male: 62%, median age: 52.7 [42. 1-66.5] years, charlson index: 2 [3.0-5.0]) entered the study. ibd type was largely represented by crohn's disease (67.1%) and its localization was mostly extensive: l3 (58.8% of crohn's disease) or e3 (92% of ulcerative colitis) according to the montreal classification. twenty-seven patients (35.5%) were treated with corticosteroids and 37 (50%) with immunosuppressive therapy (azathioprine: 26.3% and anti-tnfα: 20%). reasons for admission were shock/sepsis (61.8%) and acute respiratory failure (19.7%). icu diagnoses were infection (75%), ibd flare-up (48.7%) or both (32.9%), and pulmonary embolism (5.3%). at admission, sofa score was 5 [2.0-8.0] and . fifty-three patients (56.6%) required mechanical ventilation, 29 (38.2%) vasoactive drugs, and 8 (10.5%) renal replacement therapy. twenty-three patients underwent emergency surgery (30.2%) and six urgent endoscopic treatment (7.9%). in-icu and one-year mortality rate were 7.9% and 18.4%, respectively. prognostic factors of in-icu mortality were sofa score (hr 1.31, 95% ci [1.17-1.47 ], p < 0.01) and azathioprine treatment before icu admission (hr 4.13, 95% ci [1.56-10 .90], p < 0.01) (fig. 1) . previous immunosuppressive treatment with anti-tnf did not alter the prognosis and even the type of ibd. conclusion: our study showed that more than 90% of ibd critically ill patients were discharged alive from the icu and a majority of them survived after one-year (81.6%). we also found that sofa score and previous azathioprine immunosuppressive treatment worsened icu outcome. higher severity of the acute event affected short-term prognosis and should be taken into account for best icu triage and management. intensivists should pay particular attention to patients treated by azathioprine. compliance with ethics regulations: yes. fig. 1 outcome of ibd patients admitted to the icu according to precious treatment with azathioprine status all aps patients with any new thrombotic manifestation(s) admitted to 24 icus. results: one hundred and thirty-four patients (male/female ratio: 0.4; mean age at admission: 45.4 ± 15.0 years), who experienced 152 caps episodes, required icu admission. the numbers of definite, probable or no-caps episodes (fig. 1) , respectively, were: 11 (7.2%), 60 (39.5%) and 81 (53.5%). no histopathological proof of microvascular thrombosis was the most frequent reason for not being classified as definite caps. overall, 35/152 (23.0%) episodes were fatal, with comparable rates for definite/probable caps and no caps (23% vs. 28.8% respectively, p = 0.4). the kaplan-meier curve of estimated probability of survival showed no between-group survival difference (log-rank test p = 0.5). discussion: our results suggest that the caps criteria do not sufficiently encompass all the parameters responsible for thrombotic aps patients' disease severity in the icu. the absence of items referring to organ dysfunction/failure in the caps criteria probably limited their ability to predict mortality. albeit useful for the retrospective classification and comparison of patients, the caps criteria may be too stringent and not yet ready-to-use for the management of icu patients. for physicians outside expert aps centres, the absence of caps criteria could be misleading and lead to rejection of the diagnosis for near-caps patients, thereby preventing them from receiving the appropriate aggressive treatment they indeed require. we think that, when confronted with a critically-ill thrombotic aps patient, caps criteria should be interpreted with caution and should not be the only elements taken into account to decide the intensity of the therapeutic management. rationale: 75% of resuscitation patients develop anemia during their stay, it can worsen the prognosis, prolong the length of stay and lead to transfusions that can be the cause of complications. the objective of our work is to specify the incidence of anemia in our unit, its etiologies and its therapeutic management. patients and methods: we conducted a descriptive and analytical retrospective study within the surgical emergency resuscitation department of ibn rochd university hospital of casablanca, over a period of 4 years from 2015 to 2018. we included all anemic patients. statistical analysis was performed with spss statistics 20. p < 0.05 was considered significant. results: we included 361 patients with an estimated incidence of 27%, the average age was 39 years, the sex ratio h / f was 1.93. 47% of admissions were for traumatic pathology and 30% postoperative digestive surgery. 13% had hypotension at admission and the mean temperature was 38.2% .the onset of anemia and its depth were related to length of stay with 99.18% of patients who were anemic beyond the 12th day of hospitalization with a hemoglobin level that became < 8.5 g / dl beyond the 40th day. 60% of the patients had a normochromic normocytic anemia becoming microcytic with the lengthening of the duration of stay. ferritinemia dosed in 1% of patients and was normal. 48% of our patients had exclusive parenteral nutrition while 26% had an enteral / parenteral combination. 91% were transfused in red blood cells (rbc) and 45% of patients were transfused more than once. 32% received between 3 and 4 rbc units. in 11 patients who received 26 transfusion episodes costing 875 euros, the transfusion was inappropriate. the total cost of the transfusion was estimated at around 33,000 euros. 30% were supplemented with oral iron with an increase in hemoglobin in 6% of them. 52% of the patients came out of the intensive care unit with a hemoglobin level < 10 g/dl/l. the mortality rate of our patients was 14% with as predictive factors in multivariate analysis, hyperthermia, coagulopathy, the transfusion appears as a factor of good prognosis. the prevention of blood spoliation and the fight against inflammation and nosocomial infection remain the pillars of the management of anemia in intensive care but in view of our results and the protective role of transfusion it would be interesting to see again the transfusion thresholds in our context. compliance with ethics regulations: yes. (fig. 1 ). discussion: we described a series of 11 patients with severe acute viral myopericarditises associated with anti-rnapol3 autoantibodies, an association that has never been reported previously. the fortuitous association of these autoantibodies with acute myopericarditis is highly unlikely. acute myocarditis is a very rare disease with a reported incidence of 22/100,000 inhabitants. anti-rnapol3-antibody detection is also very rare: 4.6% positive tests (including the 11 patients in this series) out of 1114 samples during a 5-year period in our immunology laboratory. this 63% proportion of patients with proven influenza-virus infections suggest that such severe infections could trigger anti-rnapol3 autoantibody production. however, influenza is a common disease and anti-rnapol3 autoantibodies are very rare. furthermore, no anti-rnapol3 autoantibodies were detected in the 20 patients with severe influenza-related ards. last, anti-rnapol3 autoantibodies remained detectable several months after the viral infection had been cured. conclusion: this previously unknown association between severe acute viral myopericarditis and anti-rnapol3 autoantibodies is probably not fortuitous. anti-rnapol3 antibody detection in acute myopericarditis patients could imply individual susceptibility to severe viral infection. further studies are needed to investigate the pathophysiological mechanisms involved in this entity and potential specific therapeutic strategies. fig. 1 relative frequencies of digestive manifestations in 173 critically ill tma patients rationale: arrhythmia-induced cardiomyopathy has been recognized for several decades, but most severe forms, i.e. cardiogenic shock and refractory cardiogenic shock requiring mechanical circulatory support, were rarely described in adults. in this retrospective study, we described patients admitted in our tertiary care center for non-ischemic acute cardiac dysfunction (or worsening of previously known cardiac dysfunction) and recent onset supraventricular arrhythmia who developed cardiogenic shock requiring veno-arterial ecmo (va-ecmo). results: in a 10 years period, 35 patients had va-ecmo for acute non ischemic cardiac dysfunction and recent onset supraventricular arrhythmia (table 1 ). fourteen (40%) patients had known nonischemic cardiomyopathy and 10 (29%) known paroxystic atrial fibrillation. cardiogenic shock was the first manifestation of the disease in 21 patients. atrial fibrillation was the main cause of arrythmia (77% of cases). at ecmo implantation, sofa score was 10 [7-13], inotropic score 29 , lvef 10% [10-15] and lactate level was 8 [4] [5] [6] [7] [8] [9] [10] [11] mmol/l. twelve patients had sustained successful reduction after amiodarone and/or electric shock, all were weaned from ecmo and 11 survived without transplantation nor long term assist device. among the 21 patients with failure of reduction, 7 underwent an atrio-ventricular ablation while on ecmo and 1 had atrial tachycardia ablation; all were weaned from ecmo and 7 survived. among the remaining 13 patients without reduction and without ablation procedure, only the 6 patients who were bridged to heart transplantation or left ventricular assist device survived. in univariate analysis, factors associated with unfavorable outcome were previously known heart disease, heart rate, renal replacement therapy, nt-probnp level, failure of rhythm reduction after amiodarone load and/or electric shock. among the 18 patients who recovered and survived (11 with successful reduction and 7 with successful ablation), lvef increased from 10 [10-15]% before ecmo implantation to 50 [45-55]% at long term follow-up. discussion: this is the largest cohort of arrhythmia induced cardiomyopathies on va-ecmo and the first description of atrio-ventricular node ablation with favorable outcome in this setting. conclusion: arrhythmia induced cardiomyopathy is probably underrecognized and should be considered in any patient with nonischemic acute cardiac dysfunction and recent onset supraventricular arrhythmia. recovery is possible in the most severely ill patients on va-ecmo, even with severe left ventricular dilation. aggressive rate control by av-node ablation may be warranted in case of failure of reduction, and may allow recovery and favorable outcome. compliance with ethics regulations: yes. rationale: diagnosis of sepsis is a major challenge in intensive care units and is associated with a high morbidity and mortality. sepsis identification is even more difficult in patients with extracorporeal membrane oxygenation (ecmo) because of many confounding factors. the primary objective was to study the ability of c-reactive protein (crp) and procalcitonin (pct) values measured at ecmo support initiation (day 0) to predict the occurrence of early sepsis in patients undergoing venoarterial ecmo (va-ecmo) or venovenous ecmo (vv-ecmo). the secondary objectives were to study the association between these biomarkers and mortality rate during ecmo support and in-hospital mortality rate. furthermore, we investigated the relationship between early sepsis and mortality. patients and methods: we performed a retrospective, monocentric study in the cardiovascular intensive care unit of the university hospitals of lille, france. between november 1, 2014 and december 31, 2017, we included patients over 18 years old, who underwent an ecmo support for a medical or surgical indication, and for whom biomarkers (crp and pct) levels were available for at least the first 2 days of admission. biomarkers and blood cultures were daily assessed for the first ecmo support days. early sepsis was defined by sepsis diagnosis in the first 7 days after circulatory assistance initiation. in-hospital mortality rate was censored at 28 days. after univariate analysis, a cox multivariate regression model was used to assess if the association between biomarkers levels and early sepsis or mortality rate was independent. a kaplan-meier survival plot was used to describe the association between early sepsis and mortality. results: among 100 patients included, 68 underwent va-ecmo and 32 underwent vv-ecmo. an early sepsis diagnosis was made in 17.6% of va-ecmo patients and in 100% of vv-ecmo patients. pct and crp levels on day 0 were significantly associated with early sepsis diagnosis (fig. 1 rationale: fluids are one of the most prescribed drug in intensive care, particularly among patient with circulatory failure. yet, very little is known about their pharmacodynamic properties and this topic has been left largely unexplored. several factors may impact the haemodynamic efficacy of fluids among which the infusion rate. the aim of this study was to investigate the influence of the rate of fluid administration on the fluid pharmacodynamics, in particular by studying mean systemic pressure (pms). we conducted a prospective observational study in 14 patients with septic shock to compare two volume expansion strategies. a fluid bolus, 500 ml of normal saline were administered and several haemodynamic variables were recorded continuously: cardiac output (co), arterial pressure (ap), mean systemic pressure (pms, estimated from ci, pvc and map). infusion rate was left at the discretion of the attending physician. a "slow" and a "fast" groups were determined based on the median of the infusion duration. fluids effect was measured by the area under the curve (auc), maximal effect (emax) and time to maximal effect (tmax) for each haemodynamic variable. the effects of fluid on psm disappeared in one hour on average. compared to patients of the "slow" group, those of the "fast" group had a shorter tmax and a higher emax for pms (p = 0.046 and 0.02 respectively). the auc for pms was identical between group, while in case of similar effect of infusion rates, it should be larger in the "slow" group. regarding co, tmax was also shorter in the "fast" than in the "slow" group (p = 0.048). the decreasing slope from maximal effect was comparable between groups, for pms as for co. the effect of a 500 ml fluid bolus with normal saline in septic shock patients vanished within one hour. a faster infusion rate increased the maximal and total effect of the fluid bolus and shortened the delay to reach the maximal effect. rationale: significant hypotension following spinal anesthesia is a common issue in everyday clinical practice. toavoid this potentially harming situation, an empirical fluid administration is usually performed before the procedure. inferior vena cava (ivc) ultrasound has been demonstrated effective in guiding fluid therapy in critical care patients. the purpose of this study was to evaluate the ivc ultrasound guided volemic status optimization in order to decrease post-spinal hypotension rate. patients and methods: in this prospective, controlled, randomised study, 474 consecutive patients were recruited and 429 patients were randomly assigned to a control group, consisting of pre-anesthesia empirical fluid administration (itt), an ivc ultrasound group in which fluid management was based on an ivc ultrasound evaluation, and a passive leg raising test (plrt) group in which volume optimization was performed following the above mentioned test. primary outcome was the hypotension rate reduction after spinal anaesthesia following fluid optimization therapy between the groups. secondary outcomes were the total fluid amount administered, the total vasoactive drug amount used and the time needed to realize the whole anaesthetic procedure in all three groups. results: 11% reduction in hypotension rate (95% ci 1-24%, p = 0.086) was observed between the echocardiography group and the control group, and there was a reduction of hypotension rate by 9% (ci 95% 3-21%, p = 0.154) between the echocardiography group and the plrt group. the total fluid amount administered was significantly greater in the ultrasound group than in the control group (593 ml; sd 369 ml, versus 453 ml; sd 458 ml, p = 0.01498). the total amine consumption was 36% in control group, 16% in ivc group and 22% in plrt group. an increased of total study time was observed for the echocardiography group 48 min (sd 10 min) in comparison with the control group 46 min (sd 27 min) and ptlr group 40 min (sd 13 min), (p < 0.001). the study showed a faint but positive trend toward the use of ivc-ultrasound to identify patients in spontaneous breathing needing fluid optimization before spinal anesthesia compliance with ethics regulations: yes. rationale: we performed a systematic review and a meta-analysis of studies investigating the ability of the end-expiratory occlusion (eexpo) test to predict preload responsiveness, through the changes in cardiac output (co) or its surrogates, in adult patients. this meta-analysis was prospectively registered on prospero (crd-42019138265). we screened pubmed, embase and cochrane database to identify all original articles published between 1960 and 2019 evaluating the ability of the eexpo test to predict a significant increase in co or surrogate, compared to the one induced by a subsequent volume expansion or by passive leg raising (plr). the meta-analysis determined the pooled area under the receiver operating characteristics curve (auroc) of eexpo testinduced changes in co to detect preload responsiveness, as well as pooled sensitivity and specificity and the best diagnostic threshold. subgroup analysis and sensitivity analysis were planned to investigate potential sources of heterogeneity. results: thirteen studies (530 patients) were identified and included in the analysis. nine studies were performed in the intensive care unit and four in the operating room. preload responsiveness was defined according to co changes induced by fluid administration in 12 studies (fluid-induced increase in co ≥10% or ≥15%) and according to co changes induced by plr in one study. the duration of the respiratory hold ranged between 12 and 30 s. for the eexpo test-induced changes in co, the pooled sensitivity and specificity were 87 [82-91]% and 91 [87-94]%, respectively, while the pooled auroc curve was 0.95 ± 0.01 (fig. 1) . the corresponding best diagnostic threshold was 5.1 ± 0.2%. when changes in co were monitored through pulse contour analysis compared to other methods the accuracy of the test was significantly higher ( (1). continuing (decrease to 30% of peak level) or modification (decrease < 30%) of antibiotic therapy was guided by a serum pct assay from the third day of treatmentand every 48 h until antibiotic was stopped. this last was stopped when pct levels had decreased of 80% from the initial value. results: a total of 106 patients had been diagnosed as sepsis (n = 79, 75%) and septic shoc (n = 27, 25%). mean age was 32 years ± 14. an average ubs and absi score of 40% and 6. the average length of stay in icu was 13 days. patients were assigned into two groups: group a (favorable evolution, n = 76); group b (unfavorable evolution, n = 30). the therapeutic attitude according to the kinetics of the pct are presented in the table 1 . we found a significant difference between patients with unfavorable evolution compared to those with a favorable evolution (in whom we stopped antibiotics) (p < 0.005), in terms of hemodynamic state, pct concentration and renal clearance. pctguided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in our patients. the average duration of antibiotic was 5.6 ± 3 days. conclusion: pct measurement may help with the decision to initiate antibiotic therapy in low risk acuity of infection and allows more judicious antibiotic use by reducing antibiotic exposure. compliance with ethics regulations: not applicable. rationale: reducing the risk of severe hypoxemia during endotracheal-intubation (eti) is a major concern in intensive care unit but little attention was paid to co 2 variations during this period. we conducted a prospective observational study to describe transcutaneous co 2 (ptcco 2 ) throughout intubation in patients who received preoxygenation with standardoxygen therapy (sot), non-invasive ventilation (niv), or high flow nasal cannula oxygen therapy (hfncot). patients and methods: patients over 18 years undergoing eti in icu were continuously monitored for ptcco 2 during intubation and the following 3 h under mechanical ventilation (mv). haemodynamics and respiratory parameters were also recorded as well as arterial partial pressure of co 2 (paco 2 ) to evaluate reliability of the transcutaneous measure. results: two hundred and two patients were included in the study. we found a strong correlation between ptcco 2 recorded at preoxygenation and the last paco 2 available before intubation (r = 0.87, p < 0.0001). in 75% of patients ptcco 2 values recorded at initiation of mv were out of 35-45 mmhg ranges. ptcco 2 recorded at eti, at initiation of mv, 30 min and 1 h of mv were significantly higher than ptcco 2 during preoxygenation (p < 0.05 by anova). variations of ptcco 2 were significantly different according to the preoxygenation method (p < 0.001 for interaction in anova). lastly, a decrease in ptcco 2 higher than 5 mmhg within half an hour after the beginning of mv was independently associated with postintubation hypotension (pih) (odds ratio = 2.14, 95% confident interval 1.03-4.44, p = 0.04). conclusion: ptcco 2 is a valuable tool to record paco 2 variation in patients requiring invasive mechanical ventilation and could be useful to prevent pih. compliance with ethics regulations: yes. rationale: intubation in intensive care unit (icu) is a critical procedure which leads to serious adverse event in 20 to 40% of cases. several recent trials were conducted to help physicians to choose medications, devices and modality of intubation. especially, videolaryngoscope (vl) led to several publications in the last few years, with increasing tools marketed and spread use (difficult airway management, routineintubation). we designed an online survey to take a picture of intubation process and devices availability in france. toolbox. it was positioned as a first line laryngoscope for every intubation in critically ill patients to reinforce the vl skill training. present study was performed using prospectively collected data from a continuous quality improvement database about airway management in a 20-beds french teaching hospital medical icu. all consecutive intubation procedure performed with vl from september 2018 to june 2019 were included. "first attempt success" group and "first attempt failure" group were compared by univariate and multivariate analysis in order to analyze the first attempt intubation success rate according to the level of operators' expertise, identify factors associated with first pass intubation failure and describe the intubation related complications. results: we enrolled 202 consecutive endotracheal intubations. overall first attempt success rate was 126 (62%). comorbidities, junior operator, the presence of cardiac arrest and coma were associated with a lower first attempt success rate. the first attempt success rate was less than 50% in novice operators (1-5 previous experiences with vl, independently of airway expertise with direct laryngoscopies) and 87% in expert operators (greater than 15 previous experiences with vl) (fig. 1 rationale: tracheostomy in intensive care unit (icu) has many advantages. but only patient comfort and shorter icu and hospital stay were demonstrated. the timing of this procedure is still debated. the aim of this study was to determine the impact of early tracheostomy on prognosis. we performed a retrospective study in a medical icu (6 beds unit) from january 2013 to november 2018. the technique of tracheostomy was exclusively surgical in the operating room made by the surgeon. the primary endpoint was mortality in icu. the secondary outcomes were post-tracheostomy incidence of ventilator acquired pneumonia, duration of mechanical ventilation and length of stay in icu. these criteria were assessed in relation to timing of the tracheostomy defined as early when performed before day 10 of mechanical ventilation. results: forty-two patients were enrolled during the study period. mean age of patients was 55 ± 19 years. median length of stay in icu was of 49 days. mortality rate was of 60%. comparing the two groups, early vs late tracheostomy, no difference was found with respect to mortality (62% vs. 59%, p = 0.84), vap occurrence (12% vs. 35%, p = 0.21), post-tracheostomy duration of mechanical ventilation (52 ± 81d vs. 28 ± 31d, p = 0.17), or length of stay in icu (64 ± 78d vs. 61 ± 40d, p = 0.84). in multivariate analysis, the only factor independently related to mortality was the sofa score patient on tracheostomy day with p = 0.041 and or = 1.88 (ci95% [1.023-3.464] ). conclusion: tracheostomy in the intensive care unit remains a justified alternative despite the discordant data in the literature. in our study, the delay of the procedure didn't interfere with the evolution. however, the patient severity as attested by sofa score at the day of tracheostomy, was the only independent prognostic factor. those results should be confirmed by other large prospective studies. compliance with ethics regulations: not applicable. sabah benhamza, mohamed lazraq, youssef miloudi, abdelhak bensaid, najib el harrar réanimation de l'hôpital du 20 août, casablanca, morocco correspondence: sabah benhamza (benhamzasabah5@gmail.com) ann. intensive care 2020, 10(suppl 1):p-187 rationale: many unknowns remain as to the place of tracheostomy in intensive care. reluctance to perform a tracheotomy is numerous, especially when pre-exists chronic respiratory failure, but some data suggest benefits. we report in this work our experience in tracheotomy in the intensive care unit of the 20 august hospital, casablanca. patients and methods: this is a retrospective descreptive study over 2 years (january 2016 to january 2018) including all patients that have been tracheostomized in the intensive care unit of the 20 august hospital 1953. results: during the study period, 50 patients were tracheostomized with a prevalence of 9.4% in 2 years, the predominance was male (sex ratio 2.3). the average age was 44 ± 18 years old. the indication for tracheostomy was prolonged ventilation in 76% of cases, extubation failure in 20% of cases, and intubation failure in 8% of cases. tracheostomy was performed on average on the 12th day of intubation. all patients were tracheostomized in the operating room by ent surgeons. the main complications attributable to tracheotomy were hemorrhage of the tracheostomy orifice in 2 patients (4%) immediately resumed, 2 cases of subcutaneous emphysema (4%), 1 case of pneumothorax (2%), 3 cases of orifice infection (6%). no patient died of a tracheostomy related cause. the tracheotomy in intensive care is still a subject of debate especially concerning the time of its realization. however it seems to reduce the duration of mechanical ventilation, facilitates the care and also the ventilatory weaning. compliance with ethics regulations: yes. rationale: hfnco is a frequently used device providing heated and humidified high flow oxygen with several advantages: decreased work of breathing, decreased dead space, increased end expiratory lung volume (eelv), more stable fio 2 . the increase in eelv is relying of the positive expiratory effect generated by the device. the level of generated pep seems however to largely depend on whether the mouth is open or not. this study was aimed to assess the impact of mouth opening on eelv increase induced by hfnco using electric impedance tomography. patients and methods: the following hfnco trial was proposed to healthy subjects who used hfnco on a regular basis for patients care. oxygen flow was set successively during 10 min periods at 0, 35 and 70 l/min (optiflowtm; fisher & paykel healthcare, auckland, nz). these three conditions were tested in semi recumbent and supine position chosen at random. measurement started in supine position with no flow (baseline) and each period was separated from the following by a wash out period on 2 min during which the subject could breath normally with no supplemental oxygen. electric impedance tomography (pulmovista ® 500, dräger medical gmbh, lündbeck, germany) was performed applying a 16 electrodes belt placed between the 4th and 5th intercostal space, including a reference electrode located on the abdomen. as no spirometer was used, the data of eelv computed on the eit device were expressed as percentage of variation of the value measured in supine or semi recumbent position with no flow. demographic data were expressed as median and extreme values. comparisons were performed using u mann whitney test. 6[19.4-29.6] accepted to participate to the study. when subjects received hfnco with open mouth (whatever position) no modification of eelv was observed (table 1) . conversely, a significant increase in eelv was noted with closed mouth, whatever position. in the semi recumbent position the increase in eelv was even more important with 70l/min. conclusion: electrical impedance tomography illustrates the impact of mouth closure on eelv increase among healthy subjects receiving hfnco. compliance with ethics regulations: yes. rationale: in stable copd patients, nasal high flow oxygen (nhf) use can be associated with reduction in respiratory rate (rr) and minute ventilation (mv). in thesepatients, paco 2 remains stable or decreases under nhf. this suggests a possible dead space reduction related to a washout effect of nhf. the aim of this study was to assess the physiological effects of nhf in hypercapnic patients with acute copd exacerbation. patients and methods: crossover study in hypercapnic patients suffering from acute copd exacerbation and treated with intermittent non-invasive ventilation (niv). nhf 40l/min or standard oxygenotherapy (stand o2) were randomly administered during 1 h between niv treatments. rr, tidal volumes (vt), mv and corrected mv (cormv = mv x paco2/40) variations were recorded during the last 10 min of each study period using a respiratory inductive plethysmography vest. blood gas analysis was performed at the end of each oxygen administration period. visual analogic dyspnea score (vas) quoted from 0 to 10 was assessed by the patient after 30 and 60 min. results given as median [iqr] . wilcoxon tests were used to compare data between stand o2 and nhf. results: twelve patients were included and data could be recorded in 10 ( (fig. 1 ). dyspnea scores were not different between the 2 modalities. conclusion: in case of acute copd exacerbation, using nhf between niv treatments was associated with paco 2 and rr decrease. mv concomitantly decreased suggesting a deadspace volume reduction related to a washout effect of nhf. corrected mv decreased in all the patients except one. these results suggest that nhf could be used to deliver oxygen between niv treatments to copd patients suffering from acute exacerbation and could contribute reducing paco 2 . compliance with ethics regulations: yes. rationale: the role of atypical micro-organisms in acute exacerbation of chronic obstructive pulmonary disease (copd) that require mechanical ventilation is poorly none. the aim of this study was to determine the role of atypical pathogens in severe acute exacerbation of copd. patients and methods: in this prospective study we included all patients admitted for acute exacerbation of copd requiring mechanical ventilation. atypical pathogens (chlamydophila pneumoniae and mycoplasma pneumoniae) were searched by serological diagnosis and by culture of sputum samples. in this study we included 58 patients aged 65 ± 13 years. sixty-eight percent of sputum culture were considered significant. six cultures were positive with 6 different microorganisms. neither chlamydophila pneumoniae nor mycoplasma pneumoniae were found. the prevalence of chlamydophila pneumoniae was 56.9% (positive igg serum). the demographic characteristics was similar between patients with and without positive culture. the rate of noninvasive ventilation (niv) failure was 18% in positive serology group versus 44% in negative serology group (p = 0.032). the mortality was similar in both groups. in multivariate logistic regression analysis only positive serology (or = 4.326; 95% ic [1.110-16.790 ], p = 0.034) was an independent factor of niv failure. conclusion: a positive serology of chlamydophila pneumoniae was a predictive factor of niv failure without an impact on the morbidity and mortality of copd patient treated with mechanical ventilation. compliance with ethics regulations: yes. rationale: emergency departments (ed) receive a growing up number of patients with acute exacerbation of chronic obstructive pulmonary disease (copd) .non-invasive ventilation (niv) could be a good alternative to achieve a respiratory support, avoiding as much as possible the complications of invasive ventilation. the study aimed to assess the clinical outcomes of using niv in acute exacerbation of copd at ed and to identify whether clinical variables present at admission are predictive of niv failure. we conducted a prospective study conducted at the ed over a period of one year. data of all patients admitted for acute exacerbation of copd for all causes and requiring non-invasive ventilation were collected. niv failure was defined as need for endotracheal intubation or death. results: during the study period, a total of 70 patients with a mean age of 65 years (± 12) were included. acute exacerbation of copd was due to bronchitis in 46%, to pneumonia in 30% of cases. 18% of patients had no apparent etiology of acute exacerbation of copd. bilevel positive airway pressure was performed on all patients, during a mean period of 10 h (± 6). clinical niv success was observed in 50 patients (71%). the predictors of niv failure were advanced age, tachycardia, and hypercapnia. conclusion: the efficiency of niv in the management of acute exacerbations of copd at ed is well documented. this is further supported by our study which showed a clinical success in 71% of patients with acute exacerbation of copd. compliance with ethics regulations: yes. rationale: non invasive ventilation (niv) is often performed in elderly patients with acute respiratory failure (arf) at emergency department (ed). this technique may be subject to many difficulties, due to the presence of frequent co-morbidities. the aim of this study was to identify the predictive factors of niv failure in elderly patients with arf at ed. patients and methods: this was a retrospective study conducted at ed on 1 year and 4 months including patients aged more than 65 years and who required the use of niv for an arf. all data were collected and analyzed using the spss 22 software. patients were divided into two groups: niv failure and niv success. niv failure was defined by inhospital mortality, requirement of intubation or hospitalization at intensive care unit. results: during the study period, a total of 75 elderly patients that required niv for arf were included. median age was 74 years (min = 65, max = 88) and sex ratio was 2.57. the median charlson index was 5 (min = 3, max = 9). the etiological diagnoses of arf were acute decompensation of chronic obstructive pulmonary disease (72%), acute heart failure (61%), pneumonia (37%) and pulmonary embolism (1%). the arf was hypercapnic in 71% of cases and nonhypercapnic in 39%. niv failure concerned 32%. predictive factors of niv failure were clinical signs of right heart dysfunction (p < 0.05), c reactive protein (p = 0.004), initial ph (p = 0.044) and kidney dysfunction (p < 0.05). conclusion: in our study, niv failure in elderly patients with arf at ed was influenced by clinical signs of right heart dysfunction, c reactive protein, initial ph and kidney dysfunction. these clinical and biological factors could be useful to identify the most critical elderly patients and to better guide therapeutic decisions. compliance with ethics regulations: yes. rationale: the interest of ecco2r in the management of very severe acute asthma exacerbations is still unclear. since it could help to control respiratory acidosis and /or to limit dynamic hyperinflation, its clinical benefits are uncertain, even in mechanically ventilated patients. the rexecor observatory is a prospective ecco2r cohort in the great paris area. tencases of severe asthma treated by ecco2r were retrospectively reviewed. mainly, arterial blood gases (abg), duration of ecco2r and imv were collected and in-icu mortality were assessed. data are reported as median (iqr). results: ten patients (7 men, age: 58 (ic: 41-61) years, bmi: 24.7 (ic: 19.3-25.9) kg/m 2 , fev-1: 1.76 (ic: 1.27-2.57) l, (68 (ic: 60-73) %), saps2: 26.5 (ic: 23.5-39.7) points) were included. one patient suffered from cardiac arrest before admission and one had pneumothorax at icu admission. nine patients were under imv (started on the day of admission for 8). before ecco2r, 10 patients received systemic corticosteroids, 8 paralyzing agents, 1 epinephrine and 10 salbutamol. two patients suffered from pneumonia. ecco2r was started 2 (ic: 1-3.75) days after intubation. venous vascular access was achieved via the right internal jugular route in 8 patients and via the femoral route in 2. the hemolung device was used in 4 patients, the ila activve in 5 and the prismalung in 1. abg before and after 1 day of ecco2r are reported in table 1 . duration of ecco2r was 8 (ic: 5.25-11) days and 3 patients were weaned from imv under ecco2r. for the remaining 6 patients, duration of imv after ecco2r was 21 (ic: 6-34.5) days. icu stay was 28.5 (ic: 15-48.75) days. the only one niv patient was not intubated. ecco2r as stopped in 3 patients because of complications (one hemolysis, one internal bleeding and one membrane clotting). one patient died in icu after limitation of life-sustaining therapy decision. we report a preferential use of ecco2r in imv patients, contrasting with a marginal use in only one niv patient to prevent intubation. the mortality rate was low, in line with previous case series of severe acute asthma with ecmo or ecco2r support. more studies are needed (1) to better delineate the pathophysiological benefits of ecco2r in asthma patients and (2) to confirm strong clinical benefits. compliance with ethics regulations: not applicable. rationale: acute exacerbations of chronic obstructive pulmonary disease (aecopd) are the most important events characterizing respiratory illness progression. their management often needs noninvasive or invasive ventilation (iv). data of literature confirm that the mortality of aecopd requiring iv is high but are discordant about prognostic factors. the aim of our study was to describe the epidemiologic and clinical features of patients admitted for aecopd requiring iv, the treatment and the evolution in intensive care unit in order to deduce the independent factors of mortality. patients and methods: a 4-year retrospective analytic observational single-center study including patients hospitalized for aecopd requiring iv. results: fifty-eight patients were enrolled. mean age was 68 ± 9 years with sex-ratio of 4.8. eighty one percent were smokers and 55% were classified gold stage 3. history of intensive care hospitalization and prior iv were found in 43% and 34% of all cases respectively. mean apache ii score was 21 ± 9. the predominant precipitating factor for aecopd was respiratory tract infection (65% of all cases). twenty two percent of all patients presented septic shock. iv was initiated on admission in 40% of all cases and after noninvasive ventilation failure in 60% of all cases. forty-eight per cent of all patients developed septic shock as evolutionary complication. mortality rate was 62%. in univariate analysis: male gender (p = 0.022), duration of respiratory disease progression (p = 0.04), annual exacerbations frequency (p < 10 −3 ), gold 3 stage (p = 0.008), prior iv (p < 10 −3 ), duration of symptoms before hospitalization (p = 0.03), apache ii score (p = 0.04), ph (p = 0.004), shock on admission (p = 0.01) and septic shock as evolutionary complication (p = 0.01) were predictors of mortality in our study. besides; shock on admission (p = 0.001) and as evolutionary complication (p = 0.017) were the two independent prognostic factors in multivariate analysis. conclusion: vital and functional prognosis of aecopd requiring iv depends on the severity of the underlying respiratory illness, the severity of the exacerbation and the quality of an early management. this emphasizes the importance of controlling modifiable risk factors including smoking cessation, basic treatment improvement and early appropriate treatment of these exacerbations. compliance with ethics regulations: yes. medical background, biological parameters, death-rate and outcome of patients have been compared. results: in total, 37 patients have been included in the "hlh" population. death-rate in intensive care unit was 59% in the "hlh" group compared to 51% in the "not hlh" group (p = 0.48). we used more extrarenal cleansing in the "hlh" group (67% vs. 30%, p < 0.02), the duration of assisted ventilation was longer (17.5 days vs. 7.5 days, p < 0.02), as well as the duration of extrarenal cleansing (5.1 days vs. 1.6 days, p < 0.05) and those of amines (9.9 days vs. 4.5 days, p = 0.008). the average time of hospitalization was significantly longer in the "hlh" group (17.9 days vs. 9.17 days, p < 0.01). the secondary hlh to sepsis in intensive care unit, not well known and understudied, seems to have a different profile and a more serious outcome but no change in death-ratehas been found considering the pairing with the sofa. further studies are needed to plan a better therapeutic strategy within this population. compliance with ethics regulations: not applicable. serum and peritoneal exudate concentrations after high doses of ß-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study lisa leon, philippe guerci, elise pape, nathalie thilly, amandine luc, adeline germain, anne-lise butin-druoton, marie-reine losser, julien birckener, julien scala bertola, emmanuel novy chru nancy, vandoeuvre les nancy, france correspondence: lisa leon (lisaleon1307@gmail.com) ann. intensive care 2020, 10(suppl 1):p-198 rationale: critically ill patients with severe intra-abdominal infections (iais) requiring urgent surgery may undergo several pharmacokinetic alterations that can lead to ß-lactam under dosage. the aim of this study is to measure serum and peritoneal exudate concentrations of ß-lactams after high doses and optimal administration schemes. patients and methods: this observational prospective study included critically ill patients with suspicion of iai who required surgery and a ß-lactam antibiotic as empirical therapy. serum and peritoneal exudate concentrations were measured during surgery and after a 24 h steady-state period. the pharmacokinetic/pharmacodynamic (pk/ pd) target was to obtain ß-lactam concentrations of 100% ƒt>4x mic (minimum inhibitory concentration) based on a worst-case scenario (highest ecoff value) before bacterial documentation (a priori) and redefined on the mic of the isolated bacteria (a posteriori). results: forty-eight patients were included with a median [iqr] age of 64 [53-74] and a saps ii score of 40 . septic shock occurred in 23% of cases. the main diagnosis was secondary nosocomial peritonitis. piperacillin/tazobactam was the most administered ß-lactam antibiotic (75%). prior to bacterial documentation, 16 patients (33.3%) achieved the a priori pk/pd target. iai was documented in 34 patients (70%). enterobacteriaceae were the most isolated bacteria. based on the mic (n = 23) of isolated bacteria, 78% of the patients achieved the pk/pd target (100% ƒt>4xmic). in the fig. 1 we presented serum ß-lactams pk/pd target attainment and observed total concentrations of piperacillin-tazobactam at each timepoint in serum and peritoneal exudate. in critically ill patients with severe iais, high doses of ß-lactams ensured 100% ƒt>4xmic in 78% of critically ill patients with severe iais within the first 24 h. a personalized ß-lactam therapeutic scheme with a pk/pd target based on local ecology should be warranted. compliance with ethics regulations: yes. rationale: intensive care unit acquired bloodstream infections (icu-bsi) are frequent, and associated with high morbidity and mortality rates. the objective of our study was to describe the epidemiology and the prognosis of icu-bsi in our icu (cayenne general hospital). secondary objectives were to search for factors associated to icu-bsi caused by esbl-pe, and those associated with mortality at 28 days. patients and methods: we retrospectively studied icu-bsi in the medical-surgical intensive care unit of the cayenne general hospital, during 78 months (january 2013 to june 2019). we assessed survival at 28 days from the diagnosis of icu-bsi. results: icu-bsi was diagnosed in 9.5% of admissions giving a density incidence of 10.3 icu-bsi/1000 days. the median delay to the first rationale: necrotizing soft tissue infections (nsti) are a heterogenous group of severe infections. among them, group a streptococcal (gas) infection represent a subgroup that could benefit from specific therapies targeting the toxinic pathway, such as intravenous immunoglobulins or clindamycin. nevertheless, previous trials evaluating these treatments suffered from a low rate of gas infection among the study population. early identification of patients at high risk of gas infection would allow for assessing targeted treatment strategies. patients and methods: we conducted a secondary analysis of a previously published cohort of 224 patients admitted to our tertiary center for surgically proven nsti between 2006 and 2017. admission characteristics and microbiological documentation based on surgical samples, blood cultures or subcutaneous puncture were recorded. we compared patients with a documented gas infection to all other patients regarding admission characteristics. a generalized linear regression model was used to identify admission characteristics associated with a subsequent documentation of gas infection. results: among 224 patients, 60 (27%) had a gas infection, which was monomicrobial in 39 (17%) cases. admission characteristics associated with gas infections by univariate analysis were nsaid treatment before admission (19 (31.7%) for gas infections vs 27 (16.7%) for others, p = 0.004) and leukocytosis as a continuous variable (17,200 /mm 3 [12,350-22,500] vs. 13,600 [9000-21,000], p = 0.016). those inversely correlated with gas infections were immunodeficiency (6 (10%) vs. 52 (31.7%), p = 0.002), and an abdominoperineal topography (1 (1.7%) vs. 37 (22.7%), p > 0.001). after multivariate analysis only immunodeficiency (or = 0.29 [0.10-0.74], p = 0.015) and an abdominoperineal infection (or = 0.06 [0.00-0.30], p = 0.007) remained associated with the absence of gas infection. using these criteria allowed for identifying subgroups of patients with increased likelihood of gas infections: from 27% overall (n = 224) to 32% for non-abdominoperineal infections (n = 186), 33% for patients without immunodeficiency (n = 166) and 38% for both non abdominoperineal infections in patients without immunodeficiency (n = 138). a sensitivity analysis for monomicrobial gas infections yielded similar results with the addition of younger age and non-nosocomial infections as predictors. conclusion: upon admission, the absence of immunodeficiency and of an abdominoperineal infection in nsti patients were covariables associated with gas infection. compliance with ethics regulations: yes. rationale: sickle-cell disease is the most common genetic disorder in the world. a complication of this disease is the acute chest syndrome (acs) which is associated with a high risk of death. respiratory tract infections are often mixed up and the introduction of betalactam antibiotics is recommended. glomerular hyperfiltration is common and responsible of a high risk of underdosing. this study compares cefotaxim continuous infusion to intermittent bolus in adult patients with acs. patients and methods: this observational retrospective monocentric study included acs admitted in intensive care unit and treated by cefotaxim with at least one plasmatic dosing between may 2016 and august 2019. results: thirty patients received bolus administration while the 30 others received continuous infusion. we observed 5 patients (16%) and 28 patients (93%) with a cefotaxim trough level ≥ 2 mg/l in the bolus and continuous group, respectively (p < 0.001). the median residual concentration was 0 mg/l [0-0] and 10.5 mg/l [7. 4-13.3] in the bolus and continuous group, respectively (p < 0.001). there was no toxic effect induced by overdosing of cefotaxim. conclusion: compared to intermittent bolus infusion, continuous cefotaxim administration maximizes the pharmacokinetics parameters by obtaining a plasmatic concentration 5 times above the minimal inhibitory concentration of usual germs associated with acs. continuous infusion of time-dependant antibiotics seems to decrease the risk of underdosing in patients with sickle cell disease. compliance with ethics regulations: not applicable. (n = 10, 22%), followed by esophageal varices rupture (n = 7, 15%), ulcer bleeding (n = 8, 17%) and diverticular hemorrhage (n = 7, 15%). infectious diseases were diagnosed in three patients (7%), including one clostridium colitis, one erosive gastritis with helicobacter pylori and one esophageal candidiasis. conclusion: gib is associated with a high mortality rate in immunocompromised patients, especially in patients with hematological malignancies. specific malignant lesions were the main etiology and may be difficult to treat. comparison with critically ill non-immunocompromised patients with gib will help physicians to provide specific therapeutic strategies in this population. compliance with ethics regulations: yes. risk factors for delayed defecation and impact on outcome in critically ill patients: a multicenter prospective non-interventional study benoît painvin 1,* , arnaud gacouin 2 , antoine roquilly 3 , claire dahyot-fizelier 4 , sigsimond lasocki 5 , chloe rousseau 6 , denis frasca 7 , philippe seguin 8 1 anesthésie-réanimation/chu rennes, rennes, france; 2 réanimation médicale/chu rennes, rennes, france; 3 réanimation chirurgicale/ chu nantes, nantes, france; 4 réanimation chirurgicale/chu poitiers, poitiers, france; 5 anesthésie-réanimation/chu angers, angers, france; 6 centre investigation clinique/chu rennes, rennes, france; 7 anesthésie-réanimation/chu poitiers, poitiers, france; 8 réanimation chirurgicale/chu rennes, rennes, france correspondence: benoît painvin (painvinbe@gmail.com) ann. intensive care 2020, 10(suppl 1):p-211 rationale: delayed defecation is very common in intensive care units (icu) and it increases length of mechanical ventilation (mv), icu length of stay (los) and possibly mortality. the objective of this prospective multicenter study was to determine risks factors for constipation in icu and to evaluate their impact on mortality. patients and methods: it was a prospective multicenter non-interventional trial performed in 5 university icus in france from january 2017 to october 2017. all patients ≥ 18 years old who had an expected los of 3 days and mechanically ventilated for at least 2 days were eligible. defecation was defined as the time of the first stool passage. results: 396 patients were included in the analysis. a stool passage was observed in 84% of the patients during their icu stay with a mean delay of 7 ± 3 days. in multivariate analysis, risk factors for delayed passage of stool were non-invasive ventilation use and time spent under invasive ventilation whereas alcoholism, laxative treatment (before and after icu admission) and nutrition ≤ 48 h favoured passage of stool (table 1) . no relations between constipation and mortality were found. conclusion: we highlighted new and important independent factors for constipation in critically ill patients leading to a better prevention of this phenomenon.. compliance with ethics regulations: yes. rationale: community peritonitis is a frequent medical-surgical emergency of the adult, acquired by the patient in a non-hospital setting. careful multidisciplinary care is essential, involving surgeons, anesthetists, microbiologists and radiologists. the objective of our study is to determine the bacteriological aspects of intra-abdominal sepsis, to describe their sensitivity profiles and to propose treatment regimens for the management of community peritonitis. we conducted a descriptive retrospective study spanning a period of two years from january 2017 to january 2019 involving 312 cases of community abdominal sepsis operated in the operating room of surgical emergencies of our hospital. we included in our study adult patients admitted for suspected or confirmed abdominal sepsis who had undergone bacteriological examinations on the abdominal collections. samples taken are sent directly to the bacteriology laboratory for bacteriological analysis of the results. the studies showed the mean age is 45.36 years old, with a sex ratio of 2.76. we found 215 positive results mainly of peritoneal origin with a percentage of 59.53% peritonitis, dominate by intestinal peritonitis 41.40% followed by the appendicular origin 33.59% then peritonitis by perforation of ulcer. the most incriminated organism in intraabdominal sepsis is e. coli with a percentage of 44.33% of the total germs found, followed by streptococcus spp 11.14%, enterococci 5.32%, non-fermenting bgn composed mainly of pseudomonas aeruginosa 5.66%, staphylococci 4.66% and acinetobacter baumanii 3.33%. note also the presence of bacteroides fragilis is 1%. e. coli had a very low sensitivity profile for amoxicillin/clavulanic acid (59.4%), unlike ceftriaxone, gentamicin, amikacin and ertapenem, which had a sensitivity of 77.44%, respectively. 90.22%, 100%, 90.22%. conclusion: knowledge of the bacterial ecology of intraabdominal sepsis is important in the choice of probabilistic antibiotherapy, pending bacteriological findings. no data are yet available about nutritional management and risk of malnutrition in tunisian medical intensive care units (icu). the purpose of this study was to describe nutritional management in medical intensive care patients and to evaluate the risk of malnutrition. patients and methods: we conducted a prospective observational cross-sectional study in medical icus all around the tunisian country on the 18th september 2018. all participant units received a questionary form about routine nutritional management and data of all patients hospitalized in icu on the study day. collected data were: demographic characteristics, reason for admission, severity scores and subjective evaluation of nutritional status on admission, type and volume of nutritional support on the study day and the day before, nutritional status, nutric score and biological data on the study day, reasons for nutritional interruption and other supports prescribed. results: thirteen icu all around tunisia participated to the study. no icu had a nutrition team and only one had a written nutrition protocol. four icus evaluated systematically the nutritional status on admission. all icus were aware and practiced early enteral nutrition in patients unable to maintain oral intake with a systematic supplementation of oligoelements and minerals. neither target energy nor protein intake were calculated. on the study day, 89 patients were hospitalized with an occupation rate of 58%. mean age was 51 ± 28 years. mean body mass index was 22 ± 9 and 69% of patients were judged well nourished. enteral nutrition support was prescribed on admission in 66% of cases with a mean caloric intake of 1100 ± 614 kcal/day. the mean caloric target on the study day was 1721 ± 637 kcal/day with a mean caloric intake of 1677 ± 594 kcal/day and a mean caloric gap of 44 ± 43 kcal/day. the mean nutric score and body mass index on the study day were 3 ± 2 and 24 ± 6 respectively. twenty patients were judged malnourished by the nutric score and twenty two by clinical evaluation. a good correlation was found between nutric score and clinical evaluation of nutritional status (k = 0.773). conclusion: tunisian icus don't have nutrition team or nutritional written protocol. early enteral feeding and supplementation is common. a good correlation exists between nutric score and clinical nutrition status evaluation. compliance with ethics regulations: yes. rationale: whether more intensive glycemic control (gc) is beneficial or harmful forcritically ill patient has been debated over the last decades. gc has been shown hard to achieve safely and effectively in intensive care. the associated increased hypoglycemia and glycemic variability is associated with worsened outcomes. however, modelbased risk-based dosing approach have recently shown potential benefits, improving significantly gc safety and performances. the stochastic targeted (star) gc framework is a model-based controller using a unique risk-based dosing approach. star identifies modelbased patient-specific insulin sensitivity and assesses its potential variability over the next hours. these predictions are used to assess hypoglycemic risks associated with a specific insulin and/or nutrition intervention to reach a specific target band. this study analyzes preliminary clinical trial results of star in a belgian icu compared to the local standard protocol (sp). the mean age in our series was 54.09 years with a male predominance (sex ratio = 2.14). the main revealing symptoms were epigastralgia, weight loss and vomiting. subtotal gastrectomy was performed in 40.9% of cases and total gastrectomy in 45.45% of cases. curative resection could only be performed in 86.36% of cases. operative mortality was 31.81% and morbidity was 22.71%. the main factor influencing operative mortality was age greater than 70 years. in univariate analysis the main prognostic factors; tumor size, degree of parietal invasion, presence of ganglionic invasion, presence of more than 3 ganglia invaded, presence of metastases, locally advanced tumor, tumor stage and curative nature of resection. patient-related factors such as age associated blemishes and biological factors have a significant influence on the patient's prognosis. the prognosis of gastrectomies, although it has improved overall, remains mediocre. the only way to improve the prognosis remains the early diagnosis with an effective surgical management and the introduction of an adapted resuscitation. compliance with ethics regulations: yes. efficacy of multiple second line agents in refractory status epilepticus in a pediatric intensive care unit lea savary, claire le reun chu tours, tours, france correspondence: lea savary (lea.savary@hotmail.com) ann. intensive care 2020, 10(suppl 1):p-216 rationale: convulsive status epilepticus (cse) is the most common neurological emergency in children. refractory status epilepticus (rse) occurs whenseizures are not controlled with first-and secondline agents. in adults, rse requires pharmacological induced coma. in pediatric patients, association of second line treatment is often used to avoid general anesthesia although there is currently no data on the efficacy of this association. we performed a monocentric retrospective study to assess the efficacy of multiple second line agents in pediatric rse. all children admitted to clocheville hospital (tours) between january 2013 and december 2017 with a diagnosis of rse were included. our population was divided into two groups: need of general anesthesia (midazolam+) or not (midazolam-). results: 55 children were included (30 in group midazolam+, 25 in group midazolam−) during the study period. among the 48 patients with multiple second line agents, 52% did not need general anesthesia (n = 25). in group midazolam+, cse was 20% longer in patients treated with multiple second line agents ( rationale: drowning is an acute respiratory failure resulting from immersion or submersion in a liquid. patients and methods: we report 8 cases of drowning collated in the pediatric reanimation department during a period from 2010 to 2016. the aim of our retrospective study was to analyze and compare the different epidemiological, clinical, parcalinical, therapeutic and evolutionary of drowning in our study. results: our study contains 6 boys and 2 girls, with a sex ratio (m/f) of 3, in an age between 9 months and 8 years. for cases studied, no one was classified stage i, 37.5% classified stage ii, 25% stage iii, and 37.5% stage iv. all cases collected by ou service were victim of accidental drowning, 87.5% were secondary to the lack of parental supervision. among 8 cases, 6 had respiratory complications, 4 cases of hydroelectrolytic disorders, 1 case with infectious complications, 3 cases of neurological and cases of cardiac or hypothermic complication. in our study, 5 cases recovered well and 3 cases died. the survival of the drowned person depends on the speed and efficiency of the intervention, which in thefirst place is prehospital, thus ensuring the first actions at the scene of the accident, which will have repercussions on the hospital care. this has an equal share in the improvement of the victim's prognosis. compliance with ethics regulations: not applicable. epidemiology of severe pediatric trauma following winter sport accidents in the northern french alps emilien maisonneuve 1 , nadia roumeliotis 2 , pierre bouzat 1 , guillaume mortamet 1 1 chu grenoble, grenoble, france; 2 chu sainte-justine, montréal, canada correspondence: emilien maisonneuve (emilienmaisonneuve@orange. fr) ann. intensive care 2020, 10(suppl 1):p-218 rationale: this study describes the epidemiology of severe injuries related to winter sports (skiing, snowboarding and sledding) in children, and assesses potential preventive actions. we did a single-center retrospective study in our pediatric intensive care unit in the french alps. we include all patients less than 15 years old, admitted to the intensive care unit following a skiing, snowboarding or sledding accident from 2011 to 2018. results: we included 186 patients (mean age 10.5 years and 68% were male); of which 136 (73%), 21 (11%) and 29 (16%) had skiing, snowboarding and sledding accidents, respectively. the average iss (injury severity score) was 16. the major lesions were head (n = 94 patients, 51%) and intra-abdominal (n = 56 patients, 30%) injuries. compared to skiing and snowboarding, sledding accidents affected younger children (7 vs. 11 years, p < 0.001); most of whom did not wear a helmet (90% vs. 8%, p < 0.001). severity scores were similar amongst winter sports (iss = 17 for skiing, 11 for snowboarding and 17 for sledding accident, p = 0.02). rationale: best strategies for the management of severe pediatric traumatic brain injury (tbi) are still not clearly established and wide variations among professional practices have been reported in the literature. unfortunately, these variations in practice have an impact on the patient's outcome. the objectives of this work were to assess the adequacy of professional practices to the guidelines for the management of severe head injury 2019 and to assess the level of agreement of respondents in the absence of guideline. patients and methods: a practice survey was conducted in frenchspeaking hospitals in canada, belgium, switzerland and france from april 1st to june 30th, 2019. the survey was conducted as a progressive clinical case with 70 questions based on guidelines 2012 and the literature from 2012 to 2019. the questions related to the assessment and management of tbi during the acute and intensive care phase. results: seventy-eight questionnaires were included. the adherence to guidelines 2019 was good, with 11 items out of 15 obtaining an adherence rate of more than 60% regardless of the annual number of tbi managed by the centre. there was strong agreement among clinicians on the intracranial pressure (pic) (> 80%) and cerebral perfusion pressure (> 70%) thresholds used according to age. guidelines for indication of pic monitoring were almost perfectly followed in the case of glasgow score < 8 and abnormal brain ct scan (n = 73, 93%). on the other hand, the natremia and glycemia thresholds and the role of transcranial doppler were not consistent. strong adherence to recent recommendations was achieved: seizure prophylaxis with levitracetam (n = 21/33, 64%) and capnia threshold (n = 52, 67%). assessment of o 2 pressure in brain tissue (n = 12, 16%) and autoregulation (n = 35; 45%) was not a common practice. conclusion: overall, practices for the management of tbi appear to be standardised. variations persist in areas where there is a lack of literature and guidelines in paediatrics, so clinicians seem to refer to adult guidelines. compliance with ethics regulations: yes. choubeila guetteche chu constantine, constantine, algeria correspondence: choubeila guetteche (cguetteche@gmail.com) ann. intensive care 2020, 10(suppl 1):p-220 rationale: ingesting a coin cell is a common household accident in children, which can have serious consequences. the goal is to determine prognostic factors to improve management and reduce complications. patients and methods: we conducted a retrospective study including children under 15 admitted in pediatric intensive care between january 2014 and may 2019 for ingestion of button cells, with epidemiological, clinical and paraclinical data collection. results: twenty-six children 17 boys (65%), and 9 girls (35%) were included, with an average age of 28 months (10-120), increased incidence in recent years. clinical signs indicative were dysphasia with hyper-sialorrhea in 24 cases, cervical pain in one case, respiratory distress in one case, the cell was located in the upper third of the esophagus in 18 cases, third average in 6 cases, third inferior in 2 cases, the mean time before extraction was 20 h. complications: 2 cases of mediastinitis, 2 cases of oesotracheal fistula, a case of perforation. conclusion: the young age of the child, the diameter of the battery, and especially the time of care are risk factors for the occurrence of complications, the prevention passes through the education of the general public and creation of channel of taking into account fast charge. compliance with ethics regulations: not applicable. yacine benhocine university hospital center nedir mohamed, tizi-ouzou, algeria correspondence: yacine benhocine (yacine001@yahoo.fr) ann. intensive care 2020, 10(suppl 1):p-221 rationale: inhalation of foreign bodies is a common and serious accident in children, especially between 1 and 3 years old. at this age, children use their mouth to explore their environment. asphyxia is the immediate risk and respiratory sequelae may appear secondarily. the severity of this incident has been considerably reduced due to the progress of the instrumentation and anesthesia which condition the smooth running of the therapeutic act. aim: to evaluate the anesthetic modalities of the extraction of the foreign bodies of the airways in children, in order to optimize our care with a maximum of security. a prospective, mono-centric, descriptive study from january 2011 to november 2013 of 128 patients treated for inhalation of foreign bodies in the airways. study population wasdefined by: age, sex, hospitalization context, physical and radiological examination data, anestheticmanagement. results: the average age of the patients was 39.4 months, the male predominated (81%), and the hospitalization context was polymorphic. general anesthesia was necessary in all cases, sevoflurane mainly for narcosis; the combination of an opioid in 70.8% of cases and a curare in 8.6%. spontaneous ventilation is desirable, but 79% was manually broken down intermittently between extraction attempts. cases of desaturation, bronchospasm, bradycardia, and pneumothorax have been reported. 86.71% had a good evolution. discussion: the results of the epidemiological data are consistent with those of the literature. the penetration syndrome is very revealing. the chest x-ray is the key examination, the diagnosis is often based on indirect signs. in case of asphyxia by foreign body enclosed above or between the vocal cords, laryngoscopy and oxygenation is the first step to perform. in other cases, a rigid bronchoscopy is performed under general anesthesia; inhalation induction with sevoflurane is the technique of choice for many experienced authors. controlled ventilation is used in the majority of cases because spontaneous ventilation is not often not possible. the heterogeneity of anesthetic practices accounts for the multiplicity of clinical situations. conclusion: the inhalation of a foreign body is a diagnostic and therapeutic emergency. extraction of the foreign body takes place under general anesthesia, which is difficult and at risk. compliance with ethics regulations: yes. non-invasive neurally adjusted ventilatory assist (nava) in infants with bronchiolitis: a retrospective cohort study alex lepage-farrell, sally al omar, atsushi kawaguchi, sandrine essouri, philippe jouvet, guillaume emeriaud chu sainte justine, université de montréal, montréal, canada correspondence: alex lepage-farrell (alex.lepage-farrell@umontreal.ca) ann. intensive care 2020, 10(suppl 1):p-222 rationale: bronchiolitis is one main reason for admission to pediatric intensive care unit. most infants are successfully managed with nasal cpap or high-flow nasal cannula, but about a third of these patients are not sufficiently supported and require an alternative support. non-invasive neurally adjusted ventilatory assist (niv-nava) improves patient-ventilator interactions and could therefore improve the effectiveness of non-invasive support. our hypothesis is that niv-nava is feasible in infants with bronchiolitis and that it reduces the respiratory effort. patients and methods: we retrospectively studied all patients under 2 years of age with a clinical diagnosis of bronchiolitis ventilated with niv-nava in our pediatric intensive care unit, between october 2016 and june 2018. patients characteristics, respiratory and physiologic parameters, including diaphragmatic electrical activity (edi) were extracted from an electronic medical database (data collected every 30 s). respiratory effort was estimated using the modified wood clinical score for asthma (mwcas) and the inspiratory peak edi, and 2-h periods before and after niv-nava initiation were compared (wilcoxon rank test). the study was approved by the local research ethics committee. results: during the study period, 205 patients were admitted with bronchiolitis; 64 infants (36 boys) with a median (25th-75th percentile) age of 52 (32-92) days were treated with niv-nava after a failure of other non-invasive support methods, and all were included. twentyfive subjects (39%) had at least one comorbidity. the interfaces used were predominantly face masks (92%). the maximum ventilatory settings were nava level of 1.0 (0.8-1.0), peep of 7 (7-8) cmh 2 o, fio 2 of 60% (39-100) and maximal pressure of 20 (20-22) cmh 2 o. total duration of non-invasive ventilation was 70 (53-133) hours, including 48 (29-76) hours in niv-nava. as detailed in the table 1 , mwcas significantly decreased after niv-nava initiation, from 3.0 (2.5-3.5) to 2.5 (2.0-3.0), p < 0.01. a decrease in inspiratory peak edi was also observed, which was particularly clinically relevant in infants with high baseline edi (> 20mcv). capillary blood ph and pco2 also significantly improved after niv-nava introduction. six patients (9%) needed escalation to endotracheal intubation. conclusion: this study confirms the feasibility of niv-nava in infants with bronchiolitis after failure of first line non-invasive support, with a low failure rate. niv-nava initiation was followed by a decrease in respiratory effort and an improvement in blood gases. this observational study supports the needs for prospective interventional trial. compliance with ethics regulations: yes. rationale: the use of blood transfusion is frequent in pediatric intensive care units and has increased significantly since 2002. considered as therapeutic, it requires an assessment of the benefit / risk balance before making the transfusion decision. the aim of our study is to describe the transfusion practices in the pediatric resuscitation department of the ehs canastel, algeria. patients and methods: a retrospective observational study over a 6-month period from january 2018 of any blood transfusion performed in hospitalized patients, in the pediatric intensive care unit. we studied : the age, the sex, the history of blood transfusion, the indication of transfusion, the haemodynamic and respiratory parameters, the transfusional accidents, the length of stay in intensive care, the evolution after a blood transfusion. results: these included 45 transfusion patients out of 135 hospitalizations during the 6-month period, mean age was 38 months.all patients had no transfusion history, 30% of patients had their anemia admission and 70% developed it during their stay. the reason for hospitalization was respiratory distress in 40%, convulsive condition in 30%, polytrauma in 10%, and head trauma in 20%. the indication of the transfusion was placed on a hb inferior or equal to 7 g / dl in 50% of cases, in 30% on an hb superior to 7 g / dl in addition to the clinical criteria of intolerance to anemia; in 20% of the cases no clinical or biological criteria found, the nature of the blood products was of the red cell in 77% of the cases and of the plasma concentrate in 13/100 of the cases and pfc in 10%. 33% received a+, 6% of a-, 15% of b+, 35% of o+ and 9% of o-. 20% of the patients had a transfusion-like reaction at 5 min after the start of the transfusion; 51% of the patients were under artificial ventilation and 29% were under hemodynamic support, 13% under diuretic.the average length of stay was 33 days; the favorable outcome was 35% of the patients after the transfusion with an increase in the hb level beginning, 29% of the patients had complications of their pathology and the death in 33% of the cases. conclusion: current transfusion practices in children often do not reflect the implementation of our current knowledge of the need for transfusion. hence the need to review the protocols and practice other transfusion alternatives to avoid complications and improve the quality of care. compliance with ethics regulations: not applicable. rationale: bacterial multi drug resistance is medical actuality nowadays, because of its morbidity and mortality especially in intensive care, it constitutes a real problem in our hospitals. we conducted a retrospective descriptive study, to identify bacterial drug resistance profile of patients with cross infections in the department of intensive care in 20 august hospital. this study included patients hospitalized between 1st january and 31st december 2017. the data was collected from medical records of this unit as from the register of the bacteriology service of ibn rochd university hospital. results: 468 patients were hospitalized in the resuscitation service, of which 98 had nosocomial infection, an incidence of 20.9%. the mean age of the patients was 51 years with male predominance (sex ratio 2.5), the average stay in intensive care was 17 days. the site of infection was pulmonary in 34% of cases, blood in 20% of cases, urinary in 18% of cases, central catheter in 13%, neuro-meningeal in 5.5% of cases. the germs isolated were: acinetobacter baumanii in 30.5% of cases, pseudomonas aeroginosa in 17.8% of cases, klebsiella pneumonia in 12.9% of cases, enterococcus feacalis in 9.4% of cases, e.coli in 8.1% of cases and staphylococcus aureus in 7% of cases. acinteobacter baumanii showed resistance rates of up to 90% for the impenem and 77% for amikacin. regarding pseudomonas, it was resistant to impenem in 57% of cases and in 46% of cases to amikacin. compared to klebsiella, resistance to imipenem was 52% and 2% for amikacin. the mortality rate of infected patients was 59% conclusion: in the light of this work, we found that important emergence of multidrug resistance bacteria in intensive care unit is related to not only the immunocompomised state of patients but also to daily bad practices of health professionals such as the misuse of antibiotics. compliance with ethics regulations: yes. overnight culture of escherichia coli, klebsiella pneumoniae, staphylococcus aureus and pseudomonas aeruginosa, was also sequenced. results: twenty-four samples and the pc were analyzed. amplicon sequence analyses found similar results with the two primer pairs in 58% of cases. cultured pathogen was found in 89% (8/9) for human primer pair and in 44% (4/9) for earth primer pair. for each eta, ngs revealed bacteria unknown as pathogen globally identified as oropharyngeal flora in conventional microbiology (table 1) . alpha diversity decreased for all vap patients overtime, average shannon 2.5 (2; 2.8) versus 2 (1.6; 2.6), and was higher in upper respiratory tract (os) versus lower respiratory tract (eta): average shannon 2.5 (1.7; 2.7) vs. 1.8 (0.7; 2.6) (ns). conclusion: this pilot study highlights the impact of 16s rdna amplification procedures (especially oligonucleotide sequences) used on the results in microbiome research. concordance between ngs and bacterial culture, as well as similar evolution of the alpha diversity than previously described (1), enables us to validate our methodology using the "gut primers" pair 515f-806r. these findings allow furthers major studies on the pulmonary microbiome of icu ventilated patients including comparison according to the occurrence of a vap or not. compliance with ethics regulations: yes. rationale: in the field of intensive care only few studies have explored bacterial microbiota whereas virome remained hardly considered. it appears essential to describe both evolution in mechanically-ventilated patients to improve the pathophysiological understanding of ventilator-associated pneumonia (vap) development. to date no study had been simultaneously conducted on lower respiratory tract with a single nucleic acid extraction before metagenomics analysis of bacterial microbiota and virome. we conducted a preliminary study to validate our methodology based on a common automated extraction of nucleic acids. patients and methods: twelve mechanically ventilated patients were selected: five who developped (vap) and seven controls (c) who did not. endotracheal aspirate (eta) were collected between intubation and day 12 (or dvap for vap patients). conventional bacterial microbiology and multiplex respiratory viruses pcr were also performed. total nucleic acids were extracted using nuclisens easymag extractor. for the bacterial microbiota, region v4 of the 16s rrna genes was amplified. for the virome, the nextera dna xt kit (illumina) and rna seq trio kit (nugen) protocols were used to prepare viral dna and rna libraries. libraries underwent paired-end sequencing on the illumina miseq (bacteria) or nextseq-500 (virus) platform. after bioinformatics analysis we compared the performance of metagenomics analysis with conventional bacterial culture and other common viral detection methods. results: for culturable bacteria, concordance between conventional microbiology and sequencing was found in 89% (8/9 table 1 . our preliminary results confirm the feasability of exploring both bacterial microbiota and virome on the same sample using a common extraction method. data from metagenomics were highly concordant with conventionnal detection methods for known pathogenic viruses and bacteria in lower tract respiratory sample and enables identification of other microorganisms. this is the first step for a large cohort study that aims to compare evolution of global lung microbiome in patients at risk of vap and assess how bacteria and virus interplay. compliance with ethics regulations: yes. references 1. clancy department of medical and toxicological critical care, lariboisière hospital one microorganism was isolated in 82.1% and two in 17.9% of cases. the main isolated microorganism were enterobacteriaceae in 67.7% of patients. they were esbl-producers in 27.6% of cases. initial antibiotic therapy was appropriate in 65.1% of cases. factors independently associated with esbl-pe as the causative microorganism of icu-bsi were esbl-pe carriage prior to icu-bsi the sensitivity of esbl-pe carriage to predict esbl-pe as the causative microorganism of icu-bsi was 64.9%, and specificity was 81.2%. mortality at 28 days was 20.6% in the general population in multivariable analysis, there was no parameter which was independently associated to mortality at day 28 from the occurrence of icu-bsi. conclusion: icu-bsi complicates 9.5% of admission to icu and was associated with 25% in-hospital mortality assessing and applying individualized treatment for group a streptococcal necrotizing soft-tissue infection is possible service de réanimation médicale intensive care decompressive craniectomy in traumatic brain injury: about 147 cases karama bouchaala sex ratio of 8.8. the mean (sd) length of stay in icu was 22.9 ± 21.8 days. the mean glasgow coma score (gcs) (sd) was 7.2 ± 3.6 and gcs ≤ 8 in 68.1%. sofa score > 5 was found in 71 patients (48.3%) and sapsii score ≥ 30 in 121 patients (82.3%). the cerebral ctscan at admission showed acute subdural hematoma (asdh) in (84.4%), cerebral oedema (65.3%) and cerebral contusions (83%) teaching: fresenius medical care; patent or product inventor: gml czech republic banydeen rishika: no conflict of interest baptiste amandine: no conflict of interest baptiste olivier: no conflict of interest barbar saber davide: no disclosure barbier françois: no disclosure barbierlouise: trainings, teaching: ethicon, astellas; invitation to national or international congresses: sandoz, astellas barnerias christine: no disclosure baron aurore: no disclosure baron elodie: no conflict of interest barr att -due andreas: no disclosure barrau stephanie: no disclosure barraud damien: no disclosure barraud helene: no disclosure barrois brigitte: no conflict of interest baruchel andré: no disclosure bastide marie anaïs: no conflict of interest baudel jean-luc: no conflict of interest baudin florent: invitation to national or international congresses: dr baudin has received speaking fees from maquet critical care (epnv teaching: drager; invitation to national or international congresses: msd; hill rom beganton frankie: no conflict of interest begot erwan: no disclosure beinse guillaume: research support/scientific studies: association pour la recherche contre le cancer ion and fresenius kabi bensaid abdelhak: no disclosure bensardi fatimazahra: no disclosure benyamina mourad: no disclosure benzerara laurent: patent or product inventor: aphp benzerdjeb nazim: research support/scientific studies: amarape, icap; consultancy, expert: alphasights, msd; trainings, teaching: msd beqiri erta: no disclosure béranger agathe: no conflict of interest berard emilie: no conflict of interest berdai adnane: no disclosure berger patrick: no disclosure bernal william: no disclosure bernardin gilles: no disclosure berrada lina: no conflict of interest berthaud romain: no conflict of interest berthet guillaume: no conflict of interest berti enora: no conflict of interest bertoli sarah: no disclosure bertrand pierre-marie no conflict of interest besbes lamia: no disclosure besbes mohamed: no conflict of interest besch camille: invitation to national or international congresses: abbvie no conflict of interest boisseau chloé: no disclosure boissel nicolas: no disclosure boissier florence: no conflict of interest boivin alexandra: no conflict of interest bonacorsi stéphane: no conflict of interest bongiovanni filippo: no conflict of interest bonnardel eline: no conflict of interest bonnefoy-cudraz eric: no disclosure bonnet sixtine: no conflict of interest bonnevie tristan: research support/scientific studies invitation to national or international congresses: fresenius kabi and fresenius medi-calcare bucur petru: no disclosure buetti niccolo: research support/scientific studies: swiss national science foundation research grant and bangerter rhyner foundation supporting my postdoc bui hoang-nam: no disclosure burelli gabrielle: no conflict of interest burgel pierre-régis: no disclosure burghi g: no conflict of interest bustarret olivier: no conflict of interest butin-druoton anne-lise: invitation to national or international congresses expert: astra-zeneca; invitation to national or international congresses expert: hamilton medical; invitation to national or international congresses: hamilton medical chemli wael: no conflict of interest chenouard alexis: no conflict of interest cherkab rachid: no conflict of interest chevret sylvie: no disclosure chhun stephanie: no conflict of interest chiche jean-daniel: no disclosure chicoisneau maxence: no conflict of interest chlilek abdelaziz: no disclosure chocron richard: consultancy, expert: aspen chommeloux juliette: no conflict of interest chomton maryline: no conflict of interest chosidow olivier: no disclosure chouchana laurent expert: biotest; invitation to national or international congresses: sanofi research support/scientific studies: fresenius medical care; consultancy, expert: fresenius medical care; invitation to national or international congresses: xenios novalung, heilbronn, germany dachraoui fahmi: no disclosure dahoumane redouane: no conflict of interest dahyot-fizelier claire: no disclosure daix thomas: no conflict of interest daly foued: no conflict of interest damonti lauro: no conflict of interest dantan etienne: no conflict of interest darmon michaël: research support/scientific studies: msd no disclosure das vincent: no disclosure daubin cedric: no conflict of interest daubin delphine: no conflict of interest daudon michel: no disclosure daufresne pierre: no conflict of interest dauger stéphane: no conflict of interest daviet florence: invitation to national or international congresses: sandosz de courson hugues: no conflict of interest de jong audrey: trainings, teaching: baxter, medtronic; invitation to national or international congresses teaching: cardiosleep delhaes laurence: no disclosure delignette marie-charlotte: no conflict of interest dellamonica jean: trainings, teaching: medtronic; invitation to national or international congresses: msd, general electrics delpierre clément: no conflict of interest delville marianne: no conflict of interest demailly zoé: research support/scientific studies: srlf demarest elsa: no disclosure demaret pierre: no conflict of interest demiselle julien: no conflict of interest demondion pierre: no conflict of interest demoule alexandre: research support/scientific studies: drager, philips; consultancy, expert: baxter, respinor, lungpacer; trainings, teaching: fisher & paykel, hamilton, baxter; invitation to national or international congresses: fisher & paykel denis manon: no conflict ofinterest depeyre fanny: invitation to national or international congresses: pfizer deplante yvon: no conflict of interest dequin pierre-françois: research support/scientific studies: medimmune combioxin ferring pharmaceuticals a/s asahi kasei pharma america corporation derauglaudre lucie: no conflict of interest derbel karim: no disclosure derkaoui ali: no disclosure dervin krystel: no conflict of interest desaive thomas: no conflict of interest desguerre isabelle: research support/scientific studies: ptc inc, avexis; consultancy, expert: avexis, ptc inc, biogene; trainings, teaching: roche, ptc inc, avexis; invitation to national or international congresses: sarepta, biogen, avexis, biomarin desnos cyrielle: no conflict of interest desroys du roure françois: no conflict of interest detollenaere charles: no conflict of interest devaquet jérôme: invitation to national or international congresses expert: lungpacer; invitation to national or international congresses: lungpacer dreyfuss didier: research support/scientific studies: grant from french ministry of health drouot xavier: no disclosure du cheyron damien: no conflict of interest dubé bruno-pierre: consultancy, expert: novartis, gsk dubert marie: no conflict of interest dubost baptiste: no conflict of interest dubost jean-louis: no conflict of interest duburcq thibault: no conflict of interest duchemann boris: consultancy, expert: bms, msd, roche; invitation to national or international congresses no conflict of interest frérou aurélien: no conflict of interest fritz caroline: no disclosure fromentin mélanie: research support/scientific studies: msd; invitation to national or international congresses: msd frouin antoine: no conflict of interest frugier alexandre: no disclosure gaboriau louise: no conflict of interest gaci rostane: invitation to national or international congresses: bard gacouin arnaud: no disclosure gaddas mehdi: no conflict of interest gaillard arnaud: trainings, teaching: zoll medical gaimard sophie: no conflict of interest gainnier marc: no conflict of interest galbois arnaud: no conflict of interest galerneau louis-marie: invitation to national or international congresses: agir à domicile galicier lionel: consultancy, expert: novartis, eusapharma; trainings, teaching: baxalta, pfizer; invitation to national or international congresses no conflict of interest ichaï philippe: no conflict of interest imen sioud: no conflict of interest ioos vincent: no disclosure iserin franck: no disclosure issa nahema: no conflict of interest jaber samir: consultancy, expert: drager, fisher-paykel; medtronic; baxter xenios fresenius; invitation to national or international congresses: drager no conflict of interest jacq gwenaëlle: no conflict of interest jacquet emmanuelle: research support/scientific studies: unicancer (esme and storm studies invitation to national or international congresses: pfizer université laval-qc-ca labbe vincent: no disclosure labro laura: no disclosure lacaille florence: no conflict of interest lacampagne alain: no disclosure lacan claire: no conflict of interest lacherade jean-claude: no conflict of interest ladjemi maha-zohra: no conflict of interest lafon charles: no conflict of interest lafon marie-edith: no disclosure lafon thomas: no conflict of interest lagache laurie: invitation to national or international congresses advertising documents: philips; trainings, teaching: novartis, gsk, astra zeneca, boeringher; invitation to national or international congresses: chiesi, astra zeneca, sos oxygene, novartis, boeringher lamoth frédéric: consultancy, expert: gilead, msd, basilea; invitation to national or international congresses: msd expert: norgine; trainings, teaching: fujifilm, boston scientific lebreton guillaume: no disclosure lebrun-vignes benedicte: research support/ scientific studies: novartis; consultancy, expert: ansm lebuffe gilles: no disclosure leclerc maxime: no conflictof interest lécluse aldéric: research support/scientific studies: pgrx avc study; consultancy, expert: bms-pfizer, boerhinger ingelheim, bayer; invitation to national or international congresses: bms-pfizer, boerhinger ingelheim ledoux didier: no disclosure lefebvre francois: no conflict of interest macloughlin ronan: research support/scientific studies: aerogen ltd no conflict of interest mari arnaud: no conflict of interest marie damien: no conflict of interest marijon eloi: no disclosure mariotte eric: consultancy, expert: sanofi-aventis marjanovic nicolas: no disclosure marjanovic zora: no disclosure maroni arielle: no conflict of interest marot benoit: no conflict of interest marque sophie: no conflict of interest marti teaching: zambon, chiesi; invitation to national or international congresses no conflict of interest matusik elodie: no conflict of interest mauchien benedicte: no conflict of interest maury eric: research support/scientific studies: doran international, drager; trainings, teaching: vygon maxime virginie: no conflict of interest mayaux julien: invitation to national or international congresses stock shareholder: tanderev; patent or product inventor: tanderev mercat alain: research support/scientific studies: fisher-paykel, general electric; consultancy, expert: faron pharmaceuticals no disclosure merhabene takoua: no conflict of interest merle jean-claude: no disclosure mesotten dieter: no conflict of interest messaadi amenallah: no conflict of interest messika jonathan: invitation to national or international congresses: cslbehring; fisher&paykel metaxa victoria: no disclosure metogo mbengono junette arlette: no conflict of interest meunier anne: no conflict of interest meurice jean-claude: no disclosure meybeck agnes: consultancy, expert: janssen, gilead; invitation to national or international congresses teaching: msd no conflict of interest morimont philippe: no conflict of interest moro-sibilot denis: no disclosure mortamet guillaume: no conflict of interest mosbah nabil: no conflict of interest moschietto sebastien: no conflict of interest moucadel virginie: research support/scientific studies: biomérieux moulaire rigollet valérie: no disclosure mouliade charlotte: no conflict of interest moulin florence: no disclosure mounir yousfi: no conflict of interest mourabit karima: no disclosure mourvillier bruno: trainings, teaching: msd research support/scientific studies: aerogen; advertising documents: aerogen; patent or product inventor: aerogen musiari michele: no conflict of interest n'guyen quang-thang: no conflict of interest n'guyen tran: no disclosure nabil mosbah: no disclosure naccache lionel: no disclosure naimi skander: no conflict of interest nakaa sabrine: no disclosure nallet-amate megan: no conflict of interest natalis eloïse: no disclosure naudin jérôme: invitation to national or international congresses: novartis nay mai-anh: no conflict of interest nemlaghi safaa: no conflict of interest neofytos dionysios: research support/scientific studies: msd; consultancy, expert: msd, gilead, pfizer; invitation to national or international congresses: gilead, pfizer nesseler nicolas: no conflict of interest neviere remi: no disclosure nguyen alexandre: no disclosure nguyen khoa thao: no conflict of interest nicolau-travers marie-laure: no disclosure niérat marie cécile: no conflict of interest nieszkowska ania: no disclosure nigeon olivier: no conflict of interest nitel gautier: no conflict of interest nodea elena madalina: no conflict of interest noel marine: no conflict of interest nogier marie-béatrice: no disclosure noorah zaid: no disclosure nouira wiem: no conflict of interest noumeir rita: stock shareholder: softmedical noury norbert: no conflict of interest novy emmanuel: research support/scientific studies: msd; invitation to national or international congresses: pfizer expert: air liquide medical system ollivier veronique: no conflict of interest onimus thierry: no conflict of interest oppenheimer anne: invitation to national or international congresses: gedeon richter orkisz maciej: no conflict of interest orliaguet gilles: research support/scientific studies research support/scientific studies: oxynov; patent or product inventor: oxynov patrier juliette: no conflict of interest paugam catherine: no disclosure paul marine: no conflict of interest paul-bellon rachel: no disclosure paulo nicolas: no conflict of interest pavot arthur: invitation to national or international congresses: fresenius medical care france pehlivan jonathan: no conflict of interest peigne vincent: invitation to national or international congresses: air liquide péju edwige: no conflict of interest pene frédéric: consultancy, expert: alexion pépin-lehalleur adrien: invitation to national or international congresses: chiesi pere morgane: no conflict of interest pereira bruno: no disclosure perez didier: no disclosure perez pierre: no disclosure perez yonatan: no conflict of interest perier françois: no disclosure perin nicolas: no conflict of interest biomerieux robin emmanuel: no conflict of interest robin nicolas: no disclosure robineau olivier: no disclosure roch antoine: no disclosure roche anne: no conflict of interest roger claire: consultancy, expert: pfizer, fre-senius medical care; invitation to national or international congresses: msd,pfizer rolle amélie: no conflict of interest rondeau eric: no disclosure ronzière thomas: no disclosure roquilly antoine: no disclosure rosselli sylvène: no disclosure rouby jean-jacques: no disclosure rouis sana: no conflict of interest rouleau stéphane: no conflict of interest roulet sylvie: no disclosure roulland charlotte: no disclosure roumeliotis nadia: no conflict of interest rousse natacha: no disclosure rousseau anne-françoise: invitation to national or international congresses no disclosure sagnier anne: no disclosure saillard colombe: trainings,teaching: amgen, novartis; invitation to national or international congresses no conflict of interest schmidt aline: no disclosure schmidt matthieu: consultancy no disclosure schultz marcus: no conflict of interest schwebel carole: invitation to national or international congresses: pfizer scicluna brendon: no disclosure sculier jean-paul: no conflict of interest see perrine: no conflict of interest seghboyan jean-marie: no disclosure seguin amelie: no conflict of interest seguin philippe: consultancy, expert: lfb; invitation to national or international congresses: astellas sejourne caroline: no conflict of interest sellami walid: no conflict of interest sendid boualem: research support/scientific studies: allfun project, fp7 european commission; invitation to national or international congresses: pfizer senhadji lahcen: no conflict of interest serbouti rita: research support/scientific studies: fresenius medical care; consultancy, expert: fresenius medical care; trainings, teaching: fresenius medical care; invitation to national or international congresses: fresenius medical care serfaty lawrence: no disclosure série mathieu: no conflict of interest shaw geoffrey m.: no conflict of interest shi rui: no conflict of interest shimi abdelkrim: no disclosure shojaei maryam: no disclosure si-tahar mustapha: consultancy, expert: cynbiose respiratory; stock shareholder: cynbiose respiratory siami shidasp: no conflict of interest silva daniel: research support/scientific studies: fresenius medical care france; consultancy, expert: fresenius medical care france; invitation to national or international congresses: xenios novalung, heilbronn no conflict of interest sirault bruno: no disclosure sirodot michel: no disclosure slama michel: no disclosure slim amine: no disclosure smielewski peter: no disclosure soares marcio: stock shareholder: epimed solutions teaching: gilead; invitation to national or international congresses: pfizer spagnoletti marco: no conflict of interest steckelmacher claire: no disclosure stockx luc: research support/scientific studies: phenox, medtronic; consultancy no conflict of interest voiriot guillaume: research support/scientific studies: biomérieux, sos oxygène, janssen; consultancy, expert: biomérieux; invitation to national or international congresses: biomérieux von kietzell matthias: invitation to national or international congresses expert: aguettant; invitation to national or international congresses: vifor yacoubi wejden: no conflict of interest yager hélène: no conflict of interest yahya yosra: no conflict of interest yakini khalid: no disclosure yakouben karima: no disclosure yonis hodane: invitation to national or international congresses: lvl medical et pfizer younan romy: no conflict of interest youssoufa atika: no disclosure zacharia mahi: no disclosure zafrani lara: research support/scientific studies: jazz pharmaceuticals zambon olivier: no disclosure zaouak nadia: no conflict of interest zaouche khedija: no conflict of interest zarrougui wafa: no conflict of interest ze minkande jacqueline: no disclosure zeghdoud dalila: no disclosure zerbib yoann: no conflict of interest zerhouni amel: no conflict of interest zerhouni amine: no conflict of interest zerimech farid: no conflict of interest zerouali khalid: no disclosure zheng yi: no conflict of interest zimmerli stefan: research support/scientific studies: msd, pfizer, gilead; consultancy, expert: msd, pfizer; trainings, teaching: gilead; invitation to national or international congresses springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations 6 farhat hached hospital, sousse, tunisia; 7 yassminet regional hospital, ben arous, tunisia; 8 habib bougatfa regional hospital, bizerte, tunisia; 9 larabta hospital, tunis, tunisia; 10 carthagene private hospital, tunis, tunisia; 11 regional hospital of zaghouan, zaghouan, tunisia; 12 regional hospital of tozeur, tozeur, tunisia; 13 habib thameur hospital, tunis, tunisia correspondence: samia ayed (samia.ayed@yahoo.fr) ann. intensive care 2020, 10(suppl 1):p-213 geoffroy hariri, kyann hodjat-panah, laurene blum, jean-rémi lavillegrand, idriss razach, naike bige, jean-luc baudel, bertrand guidet, eric maury, hafid ait-oufella médecine intensive-réanimation, hôpital saint-antoine, paris, france correspondence: geoffroy hariri (geoffroyhariri@hotmail.com) ann. intensive care 2020, 10(suppl 1):p-158 rationale: hemolytic anemia (ha) is a common condition in intensive care unit but its diagnosis remains challenging. free hemoglobin (and heme) degradation leads to co release that can bind to hemoglobin to form carboxyhemoglobin (hbco). we hypothesized that hbco concentration could be used as a reliable diagnosis tool for ha. patients and methods: we performed a monocentric retrospective study in a 18-bed intensive care unit at st antoine hospital, paris, between 2012 and 2018. all patients hospitalized for ha with arterial hbco dosage at admission were included. arterial hbco was measured in routine in our department with an il system 1303 ph/ blood gas analyzer. demographic and biological data were collected. a group control of patients with non-hemolytic anemia (hb < 9 g/ dl) (nha) was also included. finally, we analyzed patients outcome according to hbco changes during icu stay. results: between 2012 and 2018, 98 patients with ha were included. 100 nha patients were included in the control group. patients with ha were younger than patients with nha (47 [32; 63] vs. 69 [59; 78] years old, p = 0.001) but admission sofa was not different between groups (6 [3; 7] , vs. 6 [4; 9] , p = ns). among patients with ha, 55% had thrombotic microangiopathy, 25% had autoimmune hemolytic anemia and 20% had sickle cell disease. at icu admission, ha patients had higher hbco level than patients with nha (3.31 [2.3; 3.9] vs. 1.34 [0.9; 1.7] %; p < 0.0001). hbco was a reliable biomarker of hemolysis (auc 0.92 (0.88; 0.96) p < 0.0001). an hbco level threshold at 2.05% identify hemolysis with a sensitivity 87 (79-92) % and a specificity 88 (82-93) %. in ha group, hbco was negatively correlated to hb level (r = 0.41; p < 0.0001). in ha patients, changes of hbco level during icu management were associated with outcome, decreasing in survivors (2.7 [2; 3.4] vs. 3.1 [2.2; 4.2] ; p = 0.018) but not in non-survivors (2.8 [1.9; 3.3] vs. 2.6 [1.3; 3 .5] %; p = 0.57). conclusion: carboxyhemoglobin is a reliable diagnosis and prognosis biomarker for hemolytic anemia in icu compliance with ethics regulations: yes. rationale: thrombocytopenia is the most commonly hemostatic disorder encountered in intensive care, present in 41 to 66% of patients. the mortality associated with this thrombocytopenia, the numerous pathological contexts associated with resuscitation and the lack of a recommended management strategy led to the establishment of these guidelines. the aim of our study was to determine the incidence, causes and risk factors associated with the occurrence of thrombocytopenia, as well as the impact of thrombocytopenia on the mortality and length of stay in the icu ibn medical resuscitation unit. rochd de casablanca, over a period of 12 months. patients and methods: this was a prospective study, carried out in the medical resuscitation department of ibn rochd university hospital in casablanca over a period of 12 months. there were two groups: ''sick'' group with thrombocytopenia with a platelets count < 150,000/ mm 3 , and a ''control'' group without thrombocytopenia. patients with previous platelet disorders, hematologic malignancies, and patients undergoing chemotherapy were excluded. of the 317 patients included, 107 episodes of thrombocytopenia were identified, anoverall incidence of 33.75%. sepsis was incriminated 65 times (60.7%), followed by ards in 12 patients (11.2%), massive filling in 10 patients (9.3%), disseminated intravascular coagulation in 9 patients (8.4%), and massive transfusion in 6 patients (5.6%). the drug origin was incriminated in 2 patients (1.8%). it was due to quinolones and imipenem. the mortality rate was 54 deaths (50.4%) which was inversely proportional to the lowest platelet count in the thrombocytopenia group, compared to 61 deaths (30%) in the control group. the mean duration of stay in the thrombocytopenia group was 11 ± 10 days with extremes ranging from 3 to 124 days. conclusion: thrombocytopenia was a common abnormality in the intensive care system, it occured in many pathological situations and was a factor of morbidity and excess mortality. the most common etiology in this study was sepsis. the diagnostic and therapeutic approach depended on the particular clinical context in which thrombocytopenia occurs. its onset may constitute a hematological emergency, particularly when there is a major mucocutaneous and / or visceral hemorrhagic syndrome, which necessitates a rapid etiological diagnosis, and the establishment of an effective treatment, both symptomatic and specific. compliance with ethics regulations: not applicable. marc pineton de chambrun 1 , romaric larcher 2 , frédéric pene 3 , laurent argaud 4 , alexandre demoule 5 , rémi coudroy 6 , elie azoulay 7 , yacine tandjaoui-lambiotte 8 , stanislas faguer 9 , alain combes 1 , charles-edouard luyt 1 , zahir amoura 10 1 sorbonne université, aphp, hôpital la pitié-salpêtrière, institut de cardiométabolisme et nutrition (ican), service de médecine intensive-réanimation, paris, paris, france; 2 rationale: catastrophic antiphospholipid syndrome (caps), the most severe manifestation of antiphospholipid syndrome (aps), is characterised by simultaneous thromboses in multiple organs. diagnosing caps can be challenging but its early recognition and management is crucial for a favourable outcome. this study was undertaken to evaluate the frequencies, distributions and ability to predict mortality of "definite/probable" or "no-caps" categories of thrombotic aps patients requiring admission to the intensive care unit (icu rationale: septic acute kidney injury (s-aki) is a frequent complication in critically ill patients and is associated with high morbidity and mortality. it is well known that chronic kidney disease increases the risk of pulmonary embolism (pe), but few studies have investigated the relationship between acute kidney injury (aki) and pe occurrence in septic patients. the aim of this study is to determine whether patients with aki are at increased risk of developing pe. patients and methods: were included, in a prospective study conducted over 6 months (january 01-june 30, 2018) in a medical surgical intensive care unit, all the patients older than 18 years with septic shock at admission or during hospitalization. two groups were compared: patients with kidney injury (aki+ group) and patients without kidney injury (aki− group). we studied the occurrence of pe in these two groups. results: we included 75 patients. the mean (sd) age was 56.43( ± 18) years. sex ratio was 1.91. thirty one (41.3%) patients developed pe. the occurrence of pe was significantly higher in (aki + group) [27 patients (51%) vs. 4 patients (17%); p = 0.006]. the incidence of pe according to kidney injury severity was 2 patients (10%) kdigo i, 5 patients (50%) kdigo ii, 20 patients (86%) kdigo iii. in the aki+ group, pe was significantly associated with increased sofa score at admission (10 points vs. 6 points; p = 0.02), lower platelets count (95,000 vs. 145,000; p = 0.032), higher lacatatemia at septic shock day [6.20 vs. 4 .9 mmol/l; p = 0.003] and higher c reactive protein level [223 mg/l vs. 150 mg/l; p = 0.005]. in a multivariate analysis the pe risk factors in (aki+ group) were thrombopenia (odds ratio = 1.01; ci [1.01-1.02], p = 0.01) and c-reactive protein value (odds ratio = 1.016; ci[1.005-1.027], p = 0.001). discussion: the increased risk for pe with aki may be due to endothelial involvement, vascular injury and the related changes found in procoagulant proteins (increased levels of fibrinogen, factor vii, factor viii, von willebrand factor, and plasminogen activator inhibitor-1). in our study, lower platelet and higher c reactive protein level were found in patients with pe, suggesting the participation of disseminated intravascular coagulation. these factors may contribute to increase pe risk. conclusion: the risk of pe is higher in septic patients with aki than in those with normal kidney function. therefore, because of paucity of evidence, larger studies are needed to understand pe pathway in septic aki and to establish efficient prophylaxis protocols. compliance with ethics regulations: yes. and 33 of these patients (33.3%) required intensive care. the lasted were 16 males (48%) and a majority (72%) were younger than 65 years of age. in intensive care patients, only 6 (18.8%) had nosocomial infection, majority were community acquired infections (81.2%) with 16 (48%) pneumoniae, 4 (12.5%) profound abscess, 2 pyelonephritis (6.2%), 1 (3%) meningitidis. 27 patients(87%) required mechanical ventilation for 8 days (95% ci 4-12), length of stay in icu was 15 days (95% ci 7-22) and mortality rate was 55%. conclusion: hmkp infections lead young patients in intensive care unit in one third of case with a majority of pneumoniae requiring mechanical ventilation and with a high rate of mortality. furthers studies are needed to investigate the role of this particular strain in severity. compliance with ethics regulations: yes. rationale: infections secondary to snakebite occur in a number of patients, and are potentially life-threatening. bothrops lanceolatus bites in martinique average thirty cases per year and may result in severe thrombotic and infectious complications. we aimed to investigate the infectious complications related to bothrops lanceolatus bite. patients and methods: a retrospective single-center observational study over seven years (2011) (2012) (2013) (2014) (2015) (2016) (2017) (2018) was carried out, including all patients admitted to the hospital due to bothrops lanceolatus bite. clinical and biological data were reported using the dx care, x-plore et cyberlab softwares of the emergency medicine and analyzed. one hundred and seventy snake-bitten patients (121 males and 49 females) were included. thirty-nine patients (23%) presented grade 3 or 4 envenoming. twenty patients (12%) developed wound infections. the isolated bacteria were aeromonas hydrophila (3 cases), morganella morganii (2 cases), group a streptococuss, and group b streptococcus (one case each). patients were treated empirically with third-generation cephalosporin (or amoxicillin/clavulanate), aminoglycoside and metronidazole combinations. outcome was favorable. the main factor significantly associated with the occurrence of infection following snakebite was the severity of envenoming (p < 0.05). our findings clearly point towards the frequent onset of infectious complications in b. lanceolatusbitten patients presenting with grade 3 and 4 envenoming. conclusion: infectious bite-related complications of bothrops lanceolatus account for approximately 10% of the cases, with a strong predominance for grade iii and iv. thus, based on the bacteria identified in the wounds; we suggest that empiric antibiotic therapy including third-generation cephalosporin should be administered to those patients on hospital admission. compliance with ethics regulations: yes. rationale: endocrine abnormalities have been reported with varying frequencies, following traumatic brain injury (tbi). few studies have examined the clinical features and outcomes of isolated acute thyrotropic hormone deficiencies after tbi. theaim of the study was to evaluate the early changes in thyrotropic hormone levels after traumatic brain injury (tbi) and to evaluate whether hormone changes are related to outcome patients and methods: we conducted a 12 months long prospective cohort, including all patients admitted to a university hospital icu with moderate to severe traumatic brain injury (tbi), defined as a glasgow coma scale below twelve (gcs < 12). blood samples for basal hormone values of thyroid-stimulating hormone (tsh) and free thyroxine (ft4) were obtained on days 1, 3, 7 and 10. tsh serum concentrations were considered normal at > 0.27 mu/l; ft4 at > 12 pmol/l. a thyrotropic insufficiency was defined as low ft4 and low tsh plasma levels. all patients were screened with a brain mri. patients were also monitored for neurological deterioration, including cognitive decline, convulsive seizures, increase in cerebral edema and brain herniation that were simultaneous to the diagnosis. results: during our study period's, 465 trauma patients were admitted to our icu and 134 met the inclusion criteria. on admission, our patients had a mean age at 36.8 ± 19, a mean injury severity score (iss) at 35 ± 11, a mean abbreviated injury severity (ais) of the head at 4.5 ± 0.7 and a mean gcs at 7 ± 3. of the 134 patients a thyrotropic insufficiency was diagnosed in 26 patients (20%) during the first 10 days. the median delay to thyrotropic insufficiency diagnosis was 3 days. in three of 26 (11%), the thyrotropic insufficiency was nonrecovering during the patient's icu stay and was transient for the rest. none of the patients with acute thyrotropic insufficiency had direct hypothalamic or pituitary lesions on the brain mri. factors associated to the occurrence of acute thyrotropic insufficiency were: the ais of the head (4.8 ± 0.4 vs. 4 ± 0.7, p = 0.001), cerebral contusions (95% vs. 65%, p = 0.008), subarachnoid haemorrhage (85% vs. 60%, p = 0.037) and subdural haematoma (57% vs. 30%, p = 0.012). thyrotropic insufficiency was associated to neurological deterioration (p = 0.001) on the day of diagnosis but did not affect icu mortality (12% vs. 11%, p = 0.6). in this study, low pituitary-thyrotropic axis hormone levels were found in the acute phase of tbi and were associated to neurological deterioration but with no perceived effect on icu mortality. compliance with ethics regulations: yes. rationale: acute diabetes insipidus following head injury and its effect on patients outcome have not been sufficiently evaluated in large prospective studies. the aim of this study was to determine the incidence of acute cdi, delay of onset predictive factors and its impact on tbi patients. we conducted a prospective cohort, including all patients admitted to icu with moderate to severe tbi, defined as a glasgow coma scale (gcs) below twelve. for each tbi patient plasma sodium was measured daily, and if abnormally high, urine specific gravity and osmolality were measured. cdi was diagnosed using the seckl and dunger criteria. acute cdi was defined as cdi diagnosed in the first week following injury. all patients were screened with a brain mri. results: during our study's period, 451 trauma patients were admitted to our icu, 158 presented with moderate to severe tbi and were included. on admission, our patients had a mean age at 36.8 ± 19, a mean injury severity score (iss) at 35 ± 11, a mean abbreviated injury severity (ais) of the head at 4.5 ± 0.7 and a mean gcs at 7 ± 3. twenty-three percents (37 patients) of the patients developed hypernatremia and 15% (24 patients) were diagnosed with acute cdi. in 16 of 24 (66%), the cdi was nonrecovering. the median delay to develop transient cdi was 28 h and for non-recoviring cdi was 68 h (p = 0.045). none of the patients with acute cdi had direct hypothalamic or pituitary lesions. factors associated to the occurrence of acute cdi were: younger age (29 ± 19 vs 38 ± 19, p = 0.039), neuro-surgery (22% vs. 9%, p < 0.001), hemorrhagic shock (24% vs. 7%), p < 0.001), cerebral edema (25% vs. 10%), p < 0.019), and fractures to the base of the skull (20% vs. 8%, p = 0.022). patients who developed cdi had a significantly higher mortality than those who did not (15 of 24 (62%) vs. 17 of 134 (12%), p < 0.001). there were no difference in terms of mortality between non-recovering and transient cdi (68% vs. 50%, p = 0.1), similarly the onset of cdi did not affect mortality (32 h vs. 35 h, p = 0.5). patients with acute cdi had poor glasgow outcome scale (2 ± 1.5 vs. 3.4 ± 1.3, p < 0.001) and longer icu los (23 ± 14 vs. 12 ± 11, p = 0.001). conclusion: acute cdi is associated with higher mortality and poor outcome. therefore it is essential to diagnose and treat it promptly and correctly. compliance with ethics regulations: yes. acute glucocorticoid deficiency following traumatic brain injury mariem dlela, rania ammar zayani, abir bouattour, najeh baccouche, mounir bouaziz habib bourguiba hospital, sfax, tunisia correspondence: mariem dlela (mariem241090@gmail.com) ann. intensive care 2020, 10(suppl 1):p-203rationale: published data demonstrates that long-term hypopituitarism could be common after traumatic brain injury (tbi).however, few studies focused on radiological, clinical, and repetitive endocrine assessment in the acute phase. the aim of the study was to evaluate the early changes in the adrenal axis following (tbi) and to evaluate whether hormone changes affect patient's outcome. we conducted a prospective study, including all patients admitted to a university hospital icu with moderate to severe traumatic brain injury (tbi), defined as a glasgow coma scale below twelve (gcs < 12). each patient underwent sequential measurement of plasma cortisol (pc) on days 1, 3, 7 and 10 after tbi. we defined adrenal insufficiency as pc less than 100 ng/ml. patients who received glucocorticosteroid therapy were excluded. outcome was measured by incidence of death, and glasgow outcome scale (gos) on day thirty. souhila sadat, dalila zeghdoud, dalila bougdal, kamel guenane ehs salim zemirli, alger, algeria correspondence: souhila sadat (sadatsouhila@hotmail.fr) ann. intensive care 2020, 10(suppl 1):p-205rationale: the renewed interest in the pathophysiology of severe traumatic brain injury (tcg), allowed the understanding of the pathophysiological mechanisms leading to neuronal death.the non-invasive, easy, patient-based technical dtc allows evaluation of cerebral blood flow. purpose of the study: to determine the contribution of transcranial doppler (dtp) in the prevention of post-traumatic ischemia. patients and methods: a monocentric, observational, prospective study over a period of 2 years, including 100 tcg in the monitoring of cerebral blood flow (dsc) was provided by the dtc. we collected the following data: age, gender, lesion mechanism, lesion association, glasgow score at admission, time to perform the initial scan, time to perform the initial doppler, various abnormalities found at the initial dtp, the analysis of the level of map according to each situation of cerebral blood flow, the proposed therapies, the time to obtain a correct dtc. (59%), the statistical analysis showed no difference between the delay in setting up a hypohemia and the presence of a correct cerebral blood flow (p = 1.000), the statistical analysis of the map in the dtc group hypohemia compared to the correct dtc group objectified the absence significant difference between the two groups. the realization of dtp allowed therapeutic prioritization, the introduction of norepinephrine was in 100% of cases, osmotherapy in 100% of cases, optimization of sedation in 29.34% of cases, the introduction of penthotal in 13.54% of cases and the completion of decompressive in 8.82% of cases. statistical analysis of mortality showed a significant difference in mortality (p = 0.07) in the hypohemic dtc group compared with the correct doppler . conclusion: ttc is an essential monitoring tool of cerebral hemodynamics, which may in prove the neurologic outiome of tcg. compliance with ethics regulations: yes. rationale: hyponatremia is a frequent electrolyte disturbance in hospitalized patients. it is particularly common in brain-injured patients with significantly elevated morbidity and mortality. the aim was to study the prevalence of hyponatremia in the acute phase of post-traumatic cerebral aggression, its degree of severity, its predictive factors as well as its prognostic impact in the population of post-traumatic brain injury. patients and methods: this is a retrospective study, carried out over a period of 4 years about all traumatized head patients who developed hyponatremia during the first 36 h of their stay. the descriptive part treated all patients who developed hyponatremia by detailing its different stages of severity.the analytical part treated the patients who developed a hypo-osmolar hyponatremia with a threshold of 130 mmol/l retained to define the severity. during the study period, the incidence of hyponatremia in head trauma patients was 30.8%. the occurrence of hyponatremia was associated only with the occurrence of early seizures (p = 0.006).severe hyponatraemia was associated with paroxysmal occurrence (p = 0.002), mass effect (p = 0.01), and hemostasis disorders. the multivariate study revealed that severe hyponatremia was associated with the glasgow score (p < 0.001) and pupillary changes (p = 0.048). on the other hand, it is the initial variation in serum sodium that was associated with both the severity of the initial neurological examination; glasgow (p < 0.001), saps2 (p = 0.001), pts (p = 0.049) and prism scores (p = 0.007), haemodynamic instability (p = 0.07) and neurovegetative disorders (p = 0.04). lesional features have also been found.regarding the prognosis, the occurrence of initial hyponatremia had a protective effect: a more favorable gos score p = 0.051 and a lower mortality (p = 0.045). a poor neurologic prognosis as well as a high mortality were associated with the most severe hyponatraemia and particularly with the initial variation of the sodium level (p = 0.002;). the mortality was 24.9%. it was also particularly related to the initial change in sodium levels (p < 0.001, 0.002). we concluded that there is no association between post traumatic early hyponatremia and the severity of the initial clinical presentation. however, the depth of hyponatremia and especially the initial change in sodium levels have been associated with more severe clinical pictures and a more limited prognosis. compliance with ethics regulations: yes. rationale: post-traumatic epilepsy (pte) is one of the complications described in the aftermath of headtrauma. its incidence is variable in the literature because of its clinical polymorphism. objectives of the study was to analyze the epidemiological profile (clinico-biological, radiological, therapeutic and evolutionary) of the patients having presented pte and to determine the risk factors for this pathology by comparing them with the rest of the traumatized brain patients. patients and methods: our study was retrospective. it was conducted in the intensive care unit (icu) of our university hospital between 2009 and 2012. were included in our study all patients admitted to the service with brain injury and a glycaemia above 8 mmol/l during the first 24 h post-trauma. results: the incidence of pte was 4.6%. (32 among 694) the average age was 29.5 ± 17.1 years. the sex ratio was 5.4. the average of gcs was 7.6 ± 3.6. three (9.4%) patients had initial motor impairment. seizures were observed in 3 (9.3%) patients during the first 24 h of hospitalization. the mean delay of occurrence of pte was 17 ± 17.7 months. pte was diagnosed before the end of the first post-traumatic year in 13 patients (54% of cases). the most commonly observed brain lesions were cortical brain contusions ( rationale: electrolytic disorders are common in neuro-resuscitation, especially dysnatremias and dyskalemias. hyponatremias are the most frequent, including the 2 main etiologies: the syndrome of inappropriate secretion of antidiuretic hormone (siadh) and the "cerebral salt wasting" syndrome (csw). diabetes insipude of central origin secondary to a lack of dha secretion is the second most common disorder. patients and methods: it is a prospective study, analysing all the brains injured admitted to the a1 intensive care unit of chu hassan in fez, morocco. study spread over a 5-month period from 01/08/2018 to 31/12/2018. the objective of the study is to detect the most frequent hydro-electrolytic disorders and to evaluate the therapeutic effectiveness of the service protocols. results: all these brains injured have caused he disorders over a period of time varying between d2 and d5: *18 cases of hyponatremia (30%)/12 cases of hypernatremia (19%), *19 cases of hypokaliemia (32%)/ 11 cases of hyperkaliemia (18%), *25 cases of hyperchloremia, or 41%/ 5 cases of hypochloremia (8%). *6 cases of diabetes insipidus, or 9.8%. *7 cases without he disorder (11.4%). the treatment for these disorders was: *for hypona; it reached 118 mmol/l, initially corrected by a 24-hour water restriction, followed by an increase in the basic ration and furosemide boluses according to the ecv, even sodium loads for a single case of salt loss syndrome, while the main etiology remains the siadh. *for hyperna, it has reached 178 mmol/l, evaluated by the extracellular volume, corrected by enteral tap water after calculation of the hydric deficit. if hperna is associated with polyuria greater than 2 cc/kg/h; we speak of: *insipude diabetes, with polyuria up to 5 cc/kg/h, compensated with potassium-containing solutions and blood ionogram monitored every 6 h. desmopressin was used in titration, by bolus of 0.5 µg, with a diuresis objective between 1 and 1.5 ml/kg/h. *for hypokalemia, up to 2.2 g/dl, observed mainly in the acute phase of brain aggression, corrected by increase in br for a k between 2.5 and 3 g/l, and by potassium loads if k below 2.5 g/l. the evolution: 5 deaths or 8.2% (2 cases of uncorrected diabetes insipidus), the restriction of disorders were corrected. conclusion: a knowledge of the hydroelectrolytic disorders encountered in this context is essential, as well as the implementation of a diagnostic and therapeutic protocol, which will reduce the time required to correct these disorders. compliance with ethics regulations: yes. .0] u/h). however, workload was increased under star (12 vs. 7 measurements per day), as expected from measurement interval difference between star (3-hourly) and the sp (4-hourly). conclusion: this unique patient-specific risk-based dosing approach gc framework was successful in controlling all patients safely and effectively. these preliminary results are encouraging and show gc can be achieved safely and effectively at lower target bands. in turns, these improved gc outcomes could improve patient outcomes. compliance with ethics regulations: yes. rationale: although its incidence has declined in recent years, gastric cancer remains common worldwide and is the leading cause of gastrectomy. his treatment is mainly surgical, but his prognosis remains poor. many studies on survival and prognostic factors have been carried out in foreign series. patients and methods: this is a retrospective study covering a period of three years from january 2014 to december 2016 interesting patients who had a gastrectomy and hospitalized in emergency resuscitation department surgical uhc ibnou rochd from casablanca. the statistical analysis of the different clinical, paraclinical and therapeutic data was carried out thanks to an exploitation sheet. rationale: gram-negative bloodstream infections (gnbsi) require timely appropriate antimicrobial therapy in intensive care units (icu) patients. conventional techniques usually take 24-72 h for antimicrobial susceptibility testing (ast). innovative approaches (accelerate pheno ™ system) provide pathogen identification in ~2 h and ast including minimal inhibitory concentrations (mics) in ~7 h. we report, in icu patients with gnbsi, results of implementation of the accelerate pheno ™ in our laboratory. we prospectively screened all gnbsi episodes reported in adult icu patients between september 2018 and september 2019. to allow integration into the laboratory workflow, the accelerate pheno ™ was run on blood bottles positive before 10 am (day 0), in parallel with routine procedures: maldi-tof identification after short incubation on solid media (day 0), β lacta (bio-rad ® ) test (day 0) and disk diffusion method for ast (day+1). for each episode, antimicrobial regimen was reassessed by a multidisciplinary team of bacteriologists, infectious diseases and icu physicians by the end of day 0. we measured: (i) concordance of accelerate pheno ™ results with conventional techniques, (ii) number of antibiotic adaptations on day 0 and (iii) number of patients within the therapeutic range (free fraction over 4 x mic and below concentration at risk of adverse events), based on real-time measurement of beta-lactams concentrations. results: of 67 patients reported with gnbsi over the study period, 26 were included. mean age was of 60 ± 16.5 years, 15/26 were males. main sources of gnbsi were pulmonary (n = 8) and digestive (n = 7). bacterial identification of the accelerate pheno ™ was concordant with standard techniques in 22 (85%): enterobacteriacae (n = 18), pseudomonas aeruginosa (n = 4). overall categorical agreement for ast was of 96% (15 errors including 6 very major errors). by the end of day 0, the antibiotic regimen was de-escalated in 7 (27%) patients, which was appropriate in 6 (23%). in 2 cases, de-escalation was possible, but not fulfilled by icu physicians. twenty patients had beta-lactams concentrations measurements: 12 were in the therapeutic range, 2 below and 6 over. conclusion: accelerate pheno ™ provided rapid and accurate results for most microorganisms isolated in blood cultures of icu patients with gnbsi. however, in a laboratory with routine maldi-tof early identification and β lacta test performed on day 0, the impact on early adaptation of the antibiotic regimen was evident in around 1 patient over 4. compliance with ethics regulations: not applicable. jean-luc baudel 1 , jacques tankovic 1 , redouane dahoumane 1 , jean-remy lavillegrand 2 , razach abdallah 2 , geoffroy hariri 2 , naike bige 2 , hafid ait-oufella 2 , nicolas veziris 1 , eric maury 2 , bertrand guidet 2 1 service bactériologie, hôpital saint-antoine, paris, france; 2 service réanimation médicale, hôpital saint-antoine, paris, france correspondence: jean-luc baudel (jean-luc.baudel@aphp.fr) ann. intensive care 2020, 10(suppl 1):p-226 rationale: evaluation of the accurateness of the accelerate phenotest bc kit for rapid analysis (1.5 h for microorganism identification and 5 additional hours for antibiotic susceptibility testing) of positive blood cultures from icu and hematology patients. patients and methods: from february to august 2019, we included patients from the icu and hematology units with positive blood cultures. the following informations were collected : gender, age, duration of prior antibiotherapy, source of the infection, results obtained by conventional microbiological methods and by phenotest (data obtained and time to obtention of results). informed consent was obtained from all patients. results: 33 blood cultures were analyzed in 31 patients (m/f ratio 1.07, age 59.3±, 16 from the icu and 15 from hematology). 57% of the patients were receiving antibiotics at the time of blood culture collection (mean duration : 7.9 days). the source of infection was unknown in 59% of cases, urinary in 21%, catheter-related in 10%, ascites in 6%, pneumonia in 4%. in 17 cases (51%), there was a perfect match between phenotest and conventional results (identification and antibiotic susceptibility testing). in 5 cases (15%), the bacterium responsible was not present in the phenotest panel. in 3 cases (9%), phenotest identification was correct, but some discrepancies were observed regarding antibiogram. in 4 cases (12%) phenotest identification was again correct but no antibiogram was available. in 2 cases (6%), where two bacteria were present, phenotest could not identify one of them. in 2 cases, phenotest did not provide bacterial identification because too few bacteria were present in the blood culture bottle. conclusion: the phenotest panel covered 85% of the bacteria implicated in this study. when the bacterium responsible was present in the panel, the results given by the phenotest correlated in 70% of cases with those of conventional methods. some rare discrepancies were observed regarding antibiotic susceptibility testing that have to be analyzed further. in the remaining 30% of cases, where too few bacteria or two different bacteria were present in the blood culture bottle, technical limitations did not permit to correctly identify microorganism(s) present or to obtain an antibiogram. compliance with ethics regulations: yes. mélanie fromentin, antoine bridier-nahmias, constance vuillard, jean-damien ricard, damien roux inserm umr 1137 iame infection antimicrobials modelling evolution, paris, france correspondence: mélanie fromentin (mel.fromentin@wanadoo.fr) ann. intensive care 2020, 10(suppl 1):p-227 rationale: studying human lower respiratory tract microbiota by using ngs (new generation sequencing) method is complex because of many unexpected biases due to dna extraction and amplification procedures. lung microbiota evolution under mechanical ventilation evolution may be highly informative to evaluate the actual risk of vap (ventilator-associated pneumonia) development. before starting a large study on the lung microbiome of ventilated icu patients, a methodological study was mandatory. patients and methods: five control and three vap patients were selected. endotrachealaspirate (eta) and oropharyngeal swab (os) were collected at icu admission for control patients and, 6 days before and on the day of vap diagnosis for vap patients. after automated extraction of total dna, hypervariable region v4 of the 16s rdna genes was amplified with two different pairs of primers 515f-806r: oligonucleotides from the earth microbiome project (earth primer pair) and from the gut microbiome project (gut primer pair), followed by sequencing on illumina miseq plateform. after bioinformatics analysis with mothur ® software, we compared the performance of ngs alongsideconventional bacterial culture. differences in alpha diversity (microbial diversity in a sample), expressed as the shannon index, across respiratory tract site (upper or lower) and across time (before and at vap time) has been investigated. a positive control (pc), rationale: colistin is used as a last-line treatment to combat multidrug-resistant (mdr) gram-negative bacilli (gnb). worryingly, colistin resistance in klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter baumannii is increasingly reported worldwide. we hereby report the prevalence of colistin resistance among gnb isolated from burn patients in tunisia. the study was carried out on 225 strains of gnb isolated from microbiological samples of burn patients hospitalized in the intensive care unit between october 2017 and december 2018. identification was performed by conventional methods. antimicrobial susceptibility was tested by disk diffusion method and the results were interpreted according to ca-sfm guidelines. minimum inhibitory concentration (mic) of colistin was determined using the eucast broth micro-dilution method (umic, biocentric ® ) results: pseudomonas aeruginosa was the most frequently isolated bacteria (111 strains), followed by acinetobacter baumannii (99 strains) and klebsiella pneumoniae (15 strains). the most common sites of isolation were blood cultures (45%), catheters (22%) and skin samples (21%). most of p. aeruginosa isolates were multidrug-resistant with high levels of resistance to imipenem (71.7%), ceftazidime (63%) and ciprofloxacin (74.5%). however, all of them were susceptible to colistin. in fact, mics of colistin against all p.aeruginosa isolates were less than or equal to 0.5 mg/l. a. baumannii strains had high resistance rates to beta-lactams : 100% to ceftazidime and 94% to imipenem. only one strain was resistant to colistin with a mic equal to 32 mg/l. all k. pneumoniae isolates were resistant to extended-spectrum cephalosporins. one third of these strains were resistant to imipenem and more than half (58.3%) were resistant to amikacin. two strains were resistant to colistin with high mics (> 64 mg/l). both were carbapenemase-producers, carrying oxa-48 and ndm carbapenemase encoding genes. conclusion: these data suggest that colistin-resistant or pan-drug resistant gnb clinical isolates are still relatively rare. however, they have important global public health implications because of the therapeutic problems they present, especially for vulnerable populations such as severely burned patients. hence the need to test colistin regularly in the laboratory and to set up a monitoring program for mdr pathogens. compliance with ethics regulations: yes. rationale: descending necrotizing mediastinitis (dnm) are medicosurgical emergencies whose forecast is closely related to the precocity of the therapeutic assumption. the purpose of our work is to profile these patients as well as the therapeutic and evolutionary aspects. patients and methods: retrospective study over 5 years in the intensive care unit of the hospital 20 august. all patients with dnm on cervicofacial cellulitis were included. results: 12 cases were collected, 17% of cellulitis, incidence of 2.4 patients / year. average age 39, sex ratio of 1.4. smoking, chronic alcoholism and diabetes are the most common antecedents. the favoring factors were: (poor dental conditions: 100% of cases, non steroidien anti-inflammatory drugs: 33%, diabetes: 25%). in 67% of cases the front door was dental. average time taken to take care of 10 days. c-reactive protein and procalcitonin were positive in all patients. in 33% the chest x-ray was normal. all patients received tri-antibiotic therapy. intubation were difficult in all patients, we used nasofibroscope in 25% of cases and a rescue tracheotomy in one patient. only one patient had a cervico-thoracic surgical approach; for all the others she was cervical alone. streptococcus was the most isolated germ. the complications were (septic shock: 33%, ards: 8%). the average hospital stay was 7 days with a mortality rate of 42%. conclusion: dnms are poorly prognostic. the best treatment remains prevention by better management of dental abscesses and tonsillar phlegmons. rationale: the initial, empirical antibiotic therapy of ventilator-associated pneumonia (vap) is often based on timing of its occurrence in relation to the onset of mechanical ventilation. this is due to reported differences between causal pathogens associated with early-onset (e-vap < 5-7 days of mechanical ventilation) compared to late-onset vap (l-vap ≥ 5-7 days of mv). e-vap is most often reported to be due to antibiotic-sensitive pathogens while l-vap is frequently attributed to antibiotic-resistant pathogens. however, there is emerging evidence that the isolated microorganisms may be similar regardless of onset time. the aim of our study was to compare the clinical outcomes of critically ill patients developing e-vap and l-vap and to compare the causative pathogens of the two groups. patients and methods: all the patients with the diagnosis of vap admitted between january 2014 and december 2018 were retrospectively included. vap was suspected on the basis of clinical and chest x-ray findings. the identification of the causative organisms was performed with endotracheal aspirate (eta) cultures. results: ninety patients developed vap. e-vap was observed in 30 patients (33,3%), whereas 60 patients (66,6%) developed l-vap. among patients with early-onset vap, 53% received antibiotics prior to the development of pneumonia, compared to 88% with late-onset vap (p = 0.001). otherwise, no differences (sociodemographic factors, antecedents, severity score, length of stay, length of mv) between the two groups were observed. the most common pathogens associated with e-vap were enterobacter species (26.6%), pseudomonas aeruginosa (23.3%) and oxacillin-resistant staphylococcus aureus (orsa 13,3%). enterobacter species (36.6%), acinetobacter baumannii (26.6%) and pseudomonas aeruginosa (25%) were the most common pathogens associated with l-vap. no difference was noted in the contribution of multidrug resistant bacteria mdr (50% vs. 70%). hospital mortality was significantly greater for patients with l-vap caused by mdr (73%) compared to patients with e-vap (50%) (p = 0.04). conclusion: this classification is no longer helpful for empirical antibiotic therapy, since both early-onset and late-onset vap were caused by mdr bacteria. this justifies the need of intensive care unit-specific knowledge of causal agents associated with vap to reduce the rate of administration of inadequate antimicrobial therapy. compliance with ethicsregulations: yes.