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Purpose: To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures (P L).Methods: A prospective randomised controlled study in patients with moderate to severe ARDS within 48 h of the onset of ARDS. All patients were monitored by means of an oesophageal catheter and followed up for 48 h. Moderate ARDS patients were randomised into two groups according to whether they were given a 48-h continuous infusion of cisatracurium besylate or not (control group). Severe ARDS patients did not undergo randomisation and all received cisatracurium besylate per protocol. The changes during the 48-h study period in oxygenation and in respiratory mechanics, including inspiratory and expiratory P L and driving pressure, were assessed and compared. Delta P L (∆P L) was defined as inspiratory P L minus expiratory P L.Results: Thirty patients were included, 24 with moderate ARDS and 6 with severe ARDS. NMBA infusion was associated with an improvement in oxygenation in both moderate and severe ARDS, accompanied by a decrease in both plateau pressure and total positive end-expiratory pressure. The mean inspiratory and expiratory P L were higher in the moderate ARDS group receiving NMBA than in the control group. In contrast, there was no change in either driving pressure or ∆P L related to NMBA administration.Conclusions: NMBA could exert beneficial effects in patients with moderate ARDS, at least in part, by limiting expiratory efforts. [ABSTRACT FROM AUTHOR]

Purpose: A specific biomarker of post-ARDS fibroproliferation could be useful in the identification of patients who could benefit from therapies aiming to modulate fibroproliferation such as corticosteroids.The aim of this prospective study was to determine the best threshold of the N-terminal-peptidetype III procollagen (NT-PCP-III) in non-resolving ARDS to validate this threshold according to the outcome. Methods: Concerning the best threshold of NT-PCP-III, all consecutive patients with a non-resolving ARDS were included if all the following criteria were fulfilled: moderate to severe ARDS lasting for at least 5 days, lung biopsy performed, serum and alveolar NT-PCP-III obtained within 1 week prior to biopsy, and no documented infection contra-indicating the corticosteroids. In the validation cohort part of the study, patients were included at day 7 if they presented a persistent moderate to severe ARDS. Results: Nineteen of 32 patients had fibroproliferatio nonbiopsy. Serum and alveolar NT-PCP-III were higher in patients with fibroproliferation. Using a threshold of 9 µg/L, alveolar NT-PCP-III had the highest accuracy for diagnosing fibroproliferation (sensitivity = 89.5 % and specificity = 92.3 %). Regarding the 51 patients included in the validation cohort, the mortality rate at day 60 was increased in patients presenting an alveolar NT-PCP-III level higher than 9 µg/L (69 vs. 17 %, p < 0.001). The mean alveolar level of NT-PCP-III on day 7 was 8.1-fold higher in nonsurvivors ( p = 0.03). Conclusions: The determination of NT-PCP-III on BAL done at day 7 in persistent ARDS is able to identify patients with fibroproliferation who could be included in a trial of corticosteroids or any other treatment that might help resolve lung fibroproliferation. [ABSTRACT FROM AUTHOR]

Introduction: Ventilator-associated pneumonia (VAP) may contribute to the mortality associated with acute respiratory distress syndrome (ARDS). We aimed to determine the incidence, outcome, and risk factors of bacterial VAP complicating severe ARDS in patients ventilated by using a strictly standardized lung-protective strategy.Methods: This prospective epidemiologic study was done in all the 339 patients with severe ARDS included in a multicenter randomized, placebo-controlled double-blind trial of cisatracurium besylate in severe ARDS patients. Patients with suspected VAP underwent bronchoalveolar lavage to confirm the diagnosis.Results: Ninety-eight (28.9%) patients had at least one episode of microbiologically documented bacterial VAP, including 41 (41.8%) who died in the ICU, compared with 74 (30.7%) of the 241 patients without VAP (P = 0.05). After adjustment, age and severity at baseline, but not VAP, were associated with ICU death. Cisatracurium besylate therapy within 2 days of ARDS onset decreased the risk of ICU death. Factors independently associated with an increased risk to develop a VAP were male sex and worse admission Glasgow Coma Scale score. Tracheostomy, enteral nutrition, and the use of a subglottic secretion-drainage device were protective.Conclusions: In patients with severe ARDS receiving lung-protective ventilation, VAP was associated with an increased crude ICU mortality which did not remain significant after adjustment. [ABSTRACT FROM AUTHOR]

Purpose: To compare characteristics, clinical evolution and outcome in adult patients with influenza A (H1N1) acute respiratory distress syndrome (ARDS) treated with or without extracorporeal membrane oxygenation (ECMO). Methods: A prospective observational study of patients treated in Marseille South Hospital from October 2009 to January 2010 for confirmed influenza A (H1N1)-related ARDS. Clinical features, pulmonary dysfunction and mortality were compared between patients treated with and without ECMO. Results: Of 18 patients admitted, 6 were treated with veno-venous and 3 with veno-arterial ECMO after median (interquartile, IQR) duration of mechanical ventilation of 10 (6-96) h. Six ECMO were initiated in a referral hospital by a mobile team, a median (IQR) of 3 (2-4) h after phone contact. Before ECMO, patients had severe respiratory failure with median (IQR) PaO to FiO ratio of 52 (50-60) mmHg and PaCO of 85 (69-91) mmHg. Patients treated with or without ECMO had the same hospital mortality rate (56%, 5/9). Duration of ECMO therapy was 9 (4-14) days in survivors and 5 (2-25) days in non-survivors. Early improvement of PaO to FiO ratio was greater in ECMO survivors than non-survivors after ECMO initiation [295 (151-439) versus 131 (106-144) mmHg, p < 0.05]. Haemorrhagic complications occurred in four patients under ECMO, but none required surgical treatment. Conclusions: ECMO may be an effective salvage treatment for patients with influenza A (H1N1)-related ARDS presenting rapid refractory respiratory failure, particularly when provided by a mobile team allowing early cannulation prior to transfer to a reference centre. [ABSTRACT FROM AUTHOR]

Background: In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. Methods: In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. Results: The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. Conclusions: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique–Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.) N Engl J Med 2010;363:1107-16. [ABSTRACT FROM AUTHOR]