Hrev_master [Emergency Care Journal 2014; 10:2241] [page 59] Management of the patient with sepsis in emergency department: a new alternative protocol Manuel Monti,1 Lucia Stefanecchia,1 Igino Fusco Moffa,2 Luciano Fioriti,3 Manolo Filippucci,1 Giovanni Maria Vincentelli,4 Francesco Borgognoni1 1Emergency Department, Local Health Unit Umbria 1, Assisi; 2Prevention Department, Local Health Unit Umbria 1, Assisi; 3Medical Laboratory, Local Health Unit Umbria 1, Assisi; 4Emergency Department, San Giovanni Calibita - Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy Abstract Sepsis is a clinical syndrome induced from the host response to an infection. Severe sep- sis is the leading cause of death in critically ill patients. The introduction of the early goal- directed therapy (EGDT) has been able to reduce mortality in patients with severe sep- sis/septic shock. However, sepsis mortality rates remain high compared to other critical illnesses. Many studies have pointed out that the use of arterial line placement and the exe- cution of central venous pressure and central venous oxygen saturation measurements are the most difficult EGDT elements to carry out in community hospitals. For these reasons, the present independent review examines recent pathogenic, diagnostic, and therapeutic devel- opment in sepsis with particular relevance to the emergency practice, following the latest guidelines published in February 2013 and sev- eral recent studies. We propose a non-invasive alternative protocol which can replace the standard treatment with non-substantial changes in the patient outcome though over- coming the obstacles of a invasive method. Introduction The progression of sepsis towards an unfa- vorable outcome depends mainly on delayed diagnosis and treatment, on the virulence of the pathogen and on the immune status of the patient.1 Jones has recently defined sepsis as a complex puzzle, where the host response to the infection is characterized by different reac- tions such as inflammation, endothelial dys- function, alterations to the coagulation-fibri- nolysis system and others.2 The course of the disease can lead to severe sepsis, multiple organs failure, hypotension, and septic shock.3 The hospitalization rate of people with a principal diagnosis of septicemia or sepsis more than doubled from 2000 through 2008, increasing from 11.6 to 24.0 per 10,000 people with a prevalence of gram-negative infections.4 Patterns of infecting organisms were similar to those in previous studies, with predominant organisms being Staphylococcus aureus (20.5%), Pseudomonas species (19.9%), Enterobacteriacae (mainly E. coli, 16.0%), and fungi (19%).5 The early goal-directed therapy (EGDT) is often underused partly due to the difficulty in invasive procedures. The use of a non-invasive protocol to facilitate the implementation of EGDT may be an effective strategy to improve protocol adherence.6 The identification of sep- tic patients during the golden hour is very important, so the EGDT treatment is correlated to a favorable outcome (Figure 1).7 Diagnosis During the triage it is important to identify early signs of infections and hypotension/hypoperfusion through an accu- rate medical history and physical examination, using the standard ABCD protocol. At the end of the evaluation, a priority colour can be assigned to the patient (Figure 2). The first management steps for a patient attending the accident & emergency (A&E) department or hospitalized with a suspected sepsis are:1-8 i) recognition of the systemic inflammatory response syndrome (SIRS); identification of a single infective episode sure or probable (sepsis); evaluation of organs fail- ure (severe sepsis) or severe hypoperfusion (septic shock) (Figure 3). During the first medical assessment, it is necessary to perform:9 i) recording of a detailed medical history and complete physical examination; ii) detection of vital functions (blood pressure, heart rate, respiratory fre- quency, SpO2, body temperature); iii) blood tests: full blood count, kidney liver pancreas functional tests, coagulation, inflammatory markers, blood gas analysis including anion gap and lactate dosage, hemocultures if need- ed; iv) electrocardiogram; v) chest X-ray, abdomen ultrasound scan, rachicentesis and computed tomography scan of the head if clin- ically required); vi) start treatment, if required. The performance of blood cultures from 2 peripheral venous access for the identification of aerobic/anaerobic bacteria is very important (if such cultures do not cause a significant delay >45 min) and it is absolutely advisable to perform in the A&E, although we must con- sider some technical difficulties.1 In patients with central venous access it is required to per- form blood cultures of central and peripheral veins simultaneously, and reporting time and site of blood cultures.1 In presence of an uri- nary catheter or alterations of diuresis an uri- nalysis with urine culture must be performed. In presence of ulcers or wounds or evident cutaneous infection a skin swab for aerobic/anaerobic pathogens is required.1,8-10 Diagnostic procedures must be performed early in order to identify the source of infec- tion and the pathogen responsible, with removal of infected devices, if necessary.11 Treatment The initial treatment of a patient affected by sepsis has been described in the 2012 interna- tional guidelines, and it is based on the con- cept of bundle treatment. Bundle treatment refers to a series of therapeutic interventions administered for a disease, with a clear scien- tific evidence that they perform better in terms of outcome when compared to any of the single interventions.1 In the treatment of sepsis we can identify 2 types of bundle:1 i) the resuscita- tion bundle to be performed within 6 h and ii) the management bundle to be performed with- in 24 h. The goal of the resuscitation bundle is the stabilization of the vital signs [mean arte- rial pressure (MAP), central venous pressure (CVP), oxygen that reaches the superior vena cava (ScvO2), diuresis]. Several studies have complained about the lack of non-invasive methods to evaluate the efficacy of the resus- citation bundle.12-14 The pathogenesis of organ dysfunction is multifactorial and incompletely understood. Tissue hypoperfusion and hypoxia are domi- Emergency Care Journal 2014; volume 10:2241 Correspondence: Manuel Monti, Emergency Department, Local Health Unit Umbria 1, Via V. Muller 1, Assisi (PG), Italy. Tel. +39.334.6617176 - Fax: +39.075.5412205. E-mail: montimanuel@tiscali.it Key words: septic shock, non-invasive treatment, EGDT, clearance lactate. Received for publication: 17 January 2014. Accepted for publication: 7 May 2014. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright M. Monti et al., 2014 Licensee PAGEPress, Italy Emergency Care Journal 2014; 10:2241 doi:10.4081/ecj.2014.2241 Non co mmerc ial us e o nly [page 60] [Emergency Care Journal 2014; 10:2241] nant factors.15 In order to evaluate the hypoper- fusion it is necessary to start from the physical examination (consciousness, temperature, jugular status, pulmonary oedema, peripheral oedema, vital signs, diuresis) followed by inva- sive (CVP monitor) or non-invasive tests. Several groups have observed that CVP alone fails to reliably predict a hemodynamic response to volume expansion and some patients with high CVP will respond to volume expansion.16-18 However, internationally endorsed clinical guidelines recommend using CVP as the end point of fluid resuscitation. In our opinion, considering the complexity of the physiologic feedback and clinical picture, robust reflexes and homeostatic mechanisms, CVP can be considered as a parameter for assessing the volume status. However, the hemodynamic status of the patient should be considered before deciding any therapeutic procedure.1,19,20 Invasive measurement of CVP has a number of limitations, including the fact that it is influ- enced by the ventricular compliance, intratho- racic pressure, contraction of central veins, resulting in an approximate estimate of the haemodynamic status of the patient.21 In addi- tion, the use of invasive measurement needs experienced staff, which not always is present in the emergency department. Several authors have proposed the use of ultrasound to assess the diameter and the collapsibility of the infe- rior vena cava (IVC) as a parameter for the cal- culation of CVP.22,23 Its collapse index and CVP allow to classify a patient as empty when diam- eter of IVC is ≤15 mm and there is full collapse during inspiration corresponding to a CVP≤5 mmHG. A full patient, on the other hand, reports a diameter of IVC≥25 mm, no collapse during inspiration corresponding to CVP 15-20 mmHG (Table 1).22,23 Normal values are consid- ered as a IVC diameter of 20 mm with an inspi- ratory collapse of 50%.24-26 We believe that in the emergency depart- ment it is absolutely appropriate to use the ultrasound technique as an alternative to inva- sive procedures, which are difficult to perform for logistical and technical problems. Emergency physicians found point-of-care ultrasonographic data about cardiac contractil- ity, IVC diameter, and IVC collapsibility to be clinically useful in treating adult patients with sepsis.27 Another important issue to consider in a patient with sepsis is the tissue hypoxia.1 Hypoxia can be due to alterations to pre-load, post-load, myocardial contractility and O2 transport alterations. During hypoxia, cells in the tissues can extract more oxygen from the arterious blood, and this is particularly evident in the first phase of the sepsis. As a conse- quence, the amount of ScvO2 can be decreased (beginning of severe sepsis).24 When the alter- ations of the microcirculation are so severe that it is not anymore possible to extract an adequate level of oxygen from the blood, ScvO2 increases, marking the beginning of the septic shock.25 This means that, when cardiac output is low (and therefore it is a crucial clinical issue), cardiac output measurements are tech- nically poor in reflecting tissue oxygenation. It is possible to measure the venous oxygen sat- uration through a catheter in inferior or supe- rior vena cava with the exception of the coro- nary blood, resulting in an overestimation of the tissue oxygenation. It is however possible to monitor the myocardic hypoxia through the use of the Swan Graz in the pulmonary artery.26 A number of evidences has recently proved that it is possible to use the lactate clearance (a non-invasive method) instead of the ScvO2 to evaluate the efficacy of EGDT in A&E depart- ments.28-30 In 2010 Jones stated that the nor- malisation of the lactate clearance or of ScvO2 were comparable when monitoring their response to treatment, and that there was no difference between the two in terms of out- come when measuring the efficacy of the EGDT.31 The formula of the lactic acid clearance is the following: Initial lactate - Subsequent lactate 2h Initial lactate (%) A reduction of the clearance of the lactate >10% in 2 h is considered to be comparable to achieving or maintaining a ScvO2 >70%.32 We recommend the use of lactate clearance as the most appropriate and convenient method to choose during the early assessment of the sep- tic patient in the hospital when it is not practi- cal to insert a venous catheter. Review Table 1. Correlation between central venous pressure and inferior vena cava appearance. CVP (cm) 0-5 5-10 11-15 16-20 >20 IVC on inspiration Totally Collapses Collapses Collapses No collapses >50% <50% <50% change IVC diameter (cm) <1.5 1.5-2.5 1.5-2.5 >2.5 >2.5 IVC, inferior vena cava; CVP, central venous pressure. Figure 1. Efficacy of early goal-directed therapy in terms of mor- tality. Figure 2. Triage protocol of the patient with suspected sepsis, based on our experience and on scientific literature.1,7 Parameter: GCS. Ap-HT. Temperature, RR, O2 sat. Non co mmerc ial us e o nly [Emergency Care Journal 2014; 10:2241] [page 61] In conclusion, it is possible to develop a pro- tocol of evaluation and treatment of the septic patient using non-invasive techniques: ultra- sound (IVC, chest, heart) and clearance of the lactate (Figure 4). Conclusions The start of an early empiric treatment and of EGDT within 6 h is extremely important in patients with severe sepsis or septic shock. Monitoring the haemodynamic and perfusion status can now be achieved through the use of non-invasive techniques, very easy to use in A&E. References 1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sep- sis and septic shock: 2012. Crit Care Med 2013;41:580-637. 2. Jones AE, Trzeciak S, Dellinger RP. Arterial pressure optimization in the treatment of septic shock: a complex puzzle. Crit Care 2010;14:102. 3. Levy MM, Fink MP, Marshall JC, et al. SCCM/ESICM/ACCP/ATS/SIS International sepsis definitions conference 2001. Crit Care Med 2003;29:530-8. 4. Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence 2014;5:4-11. 5. Vincent JL, Rello J, Marshall J, et al. EPIC II group of investigators. 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