Hrev_master [page 69] [Emergency Care Journal 2014; 10:3754] Ventimask in exacerbation of chronic obstructive pulmonary disease and mild acidosis before starting with bilevel positive airway pressure Andrea Bellone,1 Luca Motta,1 Massimiliano Etteri,1 Anna Maria Bianchi,1 Anna Cappelletti,1 Ilaria Bossi,1 Massimo Guanziroli,1 Paolo Pina,1 Livio Colombo2 1Emergency Department, Sant’Anna Hospital, San Fermo della Battaglia (CO); 2Emergency Department, San Paolo Hospital, Milan, Italy Abstract Patients with chronic obstructive pulmonary disease (COPD) during an episode of acute or acute on chronic respiratory failure due to infection present a special problem with regard to the relief of hypoxia. In a prospective, randomized, multicenter controlled trial, we evaluated the efficacy of oxygen delivery by Ventimask compared with Venturi mask in patients affected by exacerbation of COPD and mild acidosis before starting with non-invasive bilevel-positive airway pressure (PAP). The study involved 80 patients with exacerbation of COPD divided in two groups: Group A=40 patients randomized to Ventimask plus stan- dard therapy and Group B=40 patients ran- domised to Ventury mask plus standard thera- py. The primary endpoint was to evaluate the efficacy of oxygen therapy with Ventimask compared with Venturi mask in terms of avoid- ing the need for non-invasive bilevel-PAP dur- ing the 1st h and reducing PaCO2 retention. Twenty-five patients (62%) started with bilevel-PAP in Group A and 28 (70%) in Group B (not significant). There were no significant changes in arterial blood gases values between the two groups. In Group A, pH and PaCO2 were 7.32±0.11 and 68.5±13.6 mmHg at admission, and 7.33±0.05 and 64.8±4.9 mmHg after 1 h (not significant). In Group B, pH and PaCO2 were, respectively, 7.32±0.11 and 65.7±13.6 mmHg at admission, and 7.33±0.03 and 64.0±5.5 mmHg after 1 h (not significant). Our conclusion did not show any significant differ- ences between the two oxygen masks delivery in terms of preventing the need of bilevel-PAP and reducing PaCO2, despite the trend towards a reduction of the utilization of non-invasive positive pressure ventilation was in favor of Ventimask. Introduction Patients with chronic obstructive pulmonary disease (COPD) during an episode of acute or acute on chronic respiratory failure due to infection present a special problem with regard to the relief of hypoxia. Oxygen therapy to correct the hypoxemia becomes necessary, but it may sometimes lead to a reduction in ventilation and may worsen the inequality of ventilation/perfusion ratio caused by release of hypoxic vasoconstriction.1 Various attempts to overcome this adverse effect, namely a danger- ous rise in the arterial carbon dioxide tension (PaCO2), include oxygen by nasal probes or catheter or simple disposable masks based on the Venturi principle which allow for fixed con- centrations of oxygen. Ventimask (Flexicare Medical Ltd, Mountain Ash, Wales, UK) is a fixed mask that permits a better adhesion to the face compared with a Venturi mask. In addition, it could decrease a surplus gas through flushing out of expired CO2 thus limit- ing CO2 rebreathing.2 Our aim was to evaluate the new mask of oxygen delivery with regard to the pathophysiologic effects. Materials and Methods In a prospective, randomized, controlled trial, we studied 80 consecutive patients admitted to two different Emergency Departments (Sant’Anna Hospital, Como, and San Paolo Hospital, Milan) after an episode of acute hyper- capnic respiratory failure due to exacerbation of COPD. pH ranged from 7.32 to 7.35. Inclusion criteria were: i) exacerbation of COPD (where diagnosis of COPD is made on the basis of history, symptoms and/or FEV1/FVC <50% of predicted values);3,4 ii) age >18 years old; iii) dyspnea at rest with respira- tory rate >25 breath/min or signs of respiratory distress; iv) PaCO2> 45 mmHg; v) pH between 7.32-7.35. Exclusion criteria were: i) diagnosis of other causes of severe acute respiratory fail- ure; ii) unstable angina or acute myocardial infarction; iii) severe respiratory acidosis (pH<7.3); iv) hemodynamic instability; v) severe arrhythmias; vi) Kelly score >3; vii) res- piratory arrest or need of immediate endotra- cheal intubation (ETI); viii) pregnancy. In order to assess patients with acute dysp- nea, we are used to perform multi-area ultra- sound (lung, heart and compressive ultra- sound of legs) for ruling out other causes of acute respiratory failure such as acute cardio- genic pulmonary edema or thromboembolic pulmonary disease. Study design Between January 2010 and December 2013, 80 patients affected by an acute or acute on chronic respiratory failure caused by exacerba- tion of COPD who met the above mentioned inclusion criteria and gave their consent were randomized into two groups: Group A was treated with standard therapy plus Ventimask with an inspiratory fraction of oxygen (FiO2) between 28 to 35% set in order to maintain peripheral oxygen saturation (SpO2) from 88% to 92 % for 1 h;5 Group B was treated with stan- dard therapy plus Venturi mask with FiO2 from 28 to 35% set in order to maintain SpO2 from 88% to 92 % for 1 h. The initial pharmacological therapy in both groups followed COPD treatment guidelines [inhaled bronchodilators (four puff of albuterol every 20 min) plus steroid iv (metilprednisolone 60 mg iv)].4 Arterial blood analysis was sampled at the emergency room (ER) at time 0 and 60 min after the beginning of oxygen therapy. Arterial blood pressure, visual electrocardiography and SpO2 were monitorized continuously. When patients entered the ER, arterial blood gases at time 0 were performed after 5 min of wash out (without oxygen). Indication for starting bilevel-positive airway pressure (PAP) during exacerbation of COPD were: PaCO2> 45 mmHg and pH<7.35 despite 1 h of pharmaco- logic therapy. Indication for ETI were: respira- tory arrest, intolerance to mask, need to pro- tect airways, increase PaCO2 >20% in spite of non-invasive ventilation (NIV). Randomization The randomization was realized by using opaque sealed envelopes. Each center received a number of envelopes corresponding to the Emergency Care Journal 2014; volume 10:3754 Correspondence: Andrea Bellone, Emergency Department, Sant’Anna Hospital, via Ravona 1, 22020 San Fermo della Battaglia, Italy. Tel. +39.02.48703668 - Fax: +39.031.5855853. E-mail: andreabellone@libero.it Key-words: Ventimask, chronic obstructive pul- monary disease, exacerbation, mild acidosis, bilevel positive airway pressure. Received for publication: 14 April 2014. Revision received: 2 July 2014. Accepted for publication: 7 July 2014. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright A. Bellone et al., 2014 Licensee PAGEPress, Italy Emergency Care Journal 2014; 10:3754 doi:10.4081/ecj.2014.3754 Non co mmerc ial us e o nly [Emergency Care Journal 2014; 10:3754] [page 70] number of patients to enrol (for each center the randomization was organized in groups 1:1 to each technique). The study involved 80 patients divided into two well balanced groups of treatment. We hypothesized that 25% of patients randomized to standard therapy (Ventury mask) could reach the primary end-point (the need of NIV) during the first hour and that the intervention treatment (Ventimask) could reduce the pro- portion of 2/3, corresponding to 8.3%. Based on 80% power to detect a significant difference with alpha error ≤0.05 two-tailed, 39 patients (78 in all) were required for each study arm. The study population for the statistical analy- sis was formed by all randomized subjects who did not withdraw the study consent before the application of the technique. Results The baseline characteristics of the patients are shown in Table 1. Age of patients was sim- ilar in the two groups and did not influence the need of bilevel-PAP. Twenty-five patients (62%) started with bilevel-PAP in group A and 28 (70%) in group B (not significant) because they did not improve gas exchange after 1 h of oxygen and pharma- cologic therapy (Table 2). Our results did not show any significant changes of arterial blood gases values between the two groups and after 1 h. In Group A, pH and PaCO2 were 7.32±0.11 and 68.5±13.6 mmHg, at admission, and 7.33±0.05 and 64.8±4.9 mmhg after 1 h. In Group B, pH and PaCO2 were 7.32±0.11 and 65.7±13.6 mmHg at admission, and 7.33±0.03 and 64.0±5.5 mmHg after 1 h (Table 3). Respiratory rate decreased significantly in both groups after 1 h (P<0.01), whereas SpO2 increased significantly (P<0.01). There were not any significant differences in both groups with regard to FiO2. Discussion In individuals with COPD who receive sup- plemental oxygen, carbon dioxide accumula- tion may occur through three main mecha- nisms. First, ventilation/perfusion matching: under- ventilated lung usually has a low oxygen content which leads to localized vasoconstriction limit- ing blood flow to that lung tissue. Supplemental oxygen abolishes this constriction, leading to poor ventilation/perfusion matching. This redis- tribution of blood to areas of the lung with poor ventilation reduces the amount of carbon diox- ide eliminated from the system.6 Second, the Haldane effect: most carbon dioxide is carried by the blood as bicarbonate, and deoxygenated hemoglobin promotes the production of bicarbonate. Increasing the amount of oxygen in the blood by administer- ing supplemental oxygen reduces the amount of deoxygenated hemoglobin, and thus reduces the capacity of blood to carry carbon dioxide.7 Third, respiratory homeostasis: in healthy individuals, a rise in carbon dioxide causes an increase in the drive to breathe. However, in some COPD patients, this response has been blunted, leaving low oxygen levels as the main stimulus of respiration (hypoxic drive). Hence, giving supplemental oxygen reduces their stimulus to breathe, causing hypoventilation, and allowing carbon dioxide to accumulate in the body.8 To allow for more precise control of the rise of PaO2, mainly in patients with exac- erbation of COPD, the Venturi principle deter- mining fixed concentrations of 24-28-35 and more oxygen was adopted. Simultaneously this avoided rebreathing by the high air flow enter- ing the mask.9 Patients with acute on chronic respiratory failure due to exacerbation of COPD and a mild respiratory acidosis are at risk for both hypoxemia and worsening hyper- capnia. In these patients, the minimal safe goal of oxygen therapy can be accepted as the achievement of a SpO2 of 90-92%.9,10 At the same time, patients have to be submitted to pharmacological therapy by inhaled bron- Article Table 1. Baseline characteristics of the patients. Group A Group B P Baseline characteristics Age (years) 74.8±6.9 76.8±6.6 0.98 Male/female ratio 22/18 24/16 Condition (n) APACHE II score 17.4±2.6 18.9±4.6 0.23 History (n) Chronic heart failure 6 (15) 4 (10) 0.50 Hypertension 16 (44.4) 16 (44.4) 0.99 Diabetes 10 (25.0) 14 (38.8) 0.72 Values in brackets are expressed as percentage. Table 2. Patients’ outcomes. Group A Group B P ETI (n)° 3 (7.5) 2 (5) ns In-hospital death (n)° 1 (2.5) 0 (0) ns Length of hospital stay (days)# 13 (7-19) 14 (6-20) ns bilevel-PAP (n)° 25 (62) 28 (70) ns ETI, endotracheal intubation; PAP, positive airway pressure; ns, not significant. °Values in brackets are expressed as percentage; #values in brackets are expressed as range. Table 3. Physiologic measurements at baseline and after 1 hour. Group A Group B P Baseline Respiratory rate (breaths/min) 32.9±4.5 34.8±4.4 0.21 Arterial pH 7.32±0.11 7.32±0.11 0.55 PaCO2 (mmHg) 68.5±13.6 65.7±13.6 0.26 PaO2/FiO2 ratio 183±64 189±53 0.27 Bicarbonate (mEq) 34±4 33±6 0.76 Heart rate (beats/m) 90±20 93±23 0.71 Baseline 1 h Baseline 1 h Group A Group B Baseline vs 1 h Respiratory rate (breaths/min) 32.9±4 26.3±5 34.8±4 27.2±4 <0.01 <0.01 Arterial pH 7.32±0.1 7.33±0.5 7.32±0.1 7.33±0.3 ns ns PaCO2 (mmHg) 68.5±13 64.8±5 65.7±13 64.0±5 ns ns PaO2/FiO2 ratio 183±64 217±78 189±53 221±60 <0.01 <0.01 SpO2 (%) 83.6±4 92.1±3 85.1±7 92.0±2 <0.01 <0.01 SD, standard deviation; ns, not significant. Values are expressed as mean±standard deviation. Non co mmerc ial us e o nly [page 71] [Emergency Care Journal 2014; 10:3754] chodilators and steroid iv. When the topic and systemic pharmachological therapy do not improve pH and PaCO2 after 1 h, patients have to start with bilevel-PAP. Approximately 20% of patients who are acidotic at the time of arrival in ER will correct their pH completely into the normal range just with standard medical ther- apy, including, most importantly, properly con- trolled oxygen therapy. Therefore, the delay before starting NIV within 1 h of pharmacolog- ical treatment is reasonable.11 A limit of our study was that we did not take into consideration the pharmacologic treat- ments and oxygen administration to the patients at home and during the transport to the ER. Conclusions The aim of our study was to evaluate the efficacy of a new mask of oxygen delivery, Ventimask, that might relief arterial hypox- emia without worsening PaCO2 but reducing the need of bilevel-PAP in patients with exac- erbation of COPD and mild acidosis. Our results showed that both modalities of oxygen delivery are effective in relieving hypoxemia without any significant change in PaCO2, but they were unable to prevent the need to begin NIV. 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