Neuromuscular blockers and ARDS: Thou shalt not breathe, move, or die!

Background\ud In patients undergoing mechanical ventilation for Acute Respiratory Distress Syndrome (ARDS), neuromuscular blocking agents (NMBAs) may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness.\ud \ud Methods\ud Objective\ud To identify if 48 hour therapy with the NMBA cisatracurium early in the course of ARDS reduces adjusted 90-day in-hospital mortality rate.\ud \ud Design\ud Multicenter, double blind, randomized clinical trial.\ud \ud Setting\ud Twenty multidisciplinary intensive care units in France\ud \ud Subjects\ud Patients presenting with onset of severe ARDS within the previous 48 hours. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen 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.\ud \ud Intervention\ud After enrollment, 340 patients were randomized to receive either cisatracurium besylate (n = 178) or placebo (n = 162). All patients were sedated to a Ramsay sedation score of 6 using sulfentanil and midazolam prior to intervention. A dose of 15 mg cisatracurium besylate or placebo was then administered, followed by a continuous infusion of 37.5 mg/hour for 48 hours. Patients were not monitored for depth of paralysis.\ud \ud Outcomes\ud 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.\ud \ud Results\ud The crude 90-day mortality was 31.6% (95% confidence interval [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). The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% CI, 0.48 to 0.98; P = 0.04), after adjustment for the baseline PaO2:FIO2 ratio, plateau pressure and the Simplified Acute Physiology II score. 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.\ud \ud Conclusions\ud In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time o the ventilator without increasing muscle weakness.\ud \ud Trial Registration\ud NCT0029965