Neuromuscular blockers in early acute respiratory distress syndrome.
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.)
Papazian
Laurent
L
Assistance Publique-Hôpitaux de Marseille Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 6236, Université de la Méditerranée Aix-Marseille II, Marseille, France. laurent.papazian@ap-hm.fr
Forel
Jean-Marie
JM
Gacouin
Arnaud
A
Penot-Ragon
Christine
C
Perrin
Gilles
G
Loundou
Anderson
A
Jaber
Samir
S
Arnal
Jean-Michel
JM
Perez
Didier
D
Seghboyan
Jean-Marie
JM
Constantin
Jean-Michel
JM
Courant
Pierre
P
Lefrant
Jean-Yves
JY
Guérin
Claude
C
Prat
Gwenaël
G
Morange
Sophie
S
Roch
Antoine
A
D001279:Atracurium / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009102:Multiple Organ Failure; D009466:Neuromuscular Blocking Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011030:Pneumothorax / Q000453:epidemiology; D016016:Proportional Hazards Models; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D016896:Treatment Outcome; D015300:Ventilator Weaning / Q000379:methods
D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C101584:cisatracurium