Cited by 2,432Respiratory Support and MechanismsIntensive Care Unit Cognitive DisordersAnesthesia and Sedative Agents

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Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

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Papazian, Laurent, Forel, Jean-Marie, Gacouin, Arnaud, Penot-Ragon, Christine, Perrin, Gilles, Loundou, Anderson, Jaber, Samir, Arnal, Jean-Michel, Perez, Didier, Seghboyan, Jean-Marie, Constantin, Jean-Michel, Courant, Pierre, Lefrant, Jean-Yves, Guérin, Claude, Prat, Gwenaël, Morange, Sophie, Roch, Antoine·2010·New England Journal of Medicine

DOI 10.1056/nejmoa1005372

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Abstract

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.)

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Authors: Papazian, L., Forel, J.-M., Gacouin, A., Penot-Ragon, C., Perrin, G., Loundou, A., Jaber, S., Arnal, J.-M., Perez, D., Seghboyan, J.-M., Constantin, J.-M., Courant, P., Lefrant, J.-Y., Guérin, C., Prat, G., Morange, S., & Roch, A.
Affiliations: Centre National de la Recherche Scientifique (FR)
Université de la Méditerranée Aix-Marseille II (FR)
Hôpital Pontchaillou (FR)
Hôpital Sainte-Marguerite (FR)
Assistance Publique Hôpitaux de Marseille (FR)
Hôpital Saint Eloi (FR)
Centre Hospitalier Universitaire de Besançon (FR)
CHU Ambroise Paré (BE)
Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
Centre Hospitalier Universitaire de Nîmes (FR)
Hôpital de la Croix-Rousse (FR)
Inserm (FR)
ORCID: Papazian, Laurent
Forel, Jean-Marie
Gacouin, Arnaud
Loundou, Anderson
Jaber, Samir
Arnal, Jean-Michel
Constantin, Jean-Michel
Lefrant, Jean-Yves
Guérin, Claude
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2010-09-16
Volume: 363
Issue: 12
Pages: 1107-1116
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1005372
OpenAlex: W2115186092
Cited by: 2,432
References: 29
Citations by year: 2026: 86 · 2025: 114 · 2024: 111 · 2023: 130 · 2022: 166 · 2021: 181 · 2020: 268 · 2019: 185 · 2018: 186 · 2017: 190 · 2016: 201 · 2015: 134 · 2014: 151 · 2013: 131 · 2012: 107
FWCI: 85.76
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Keywords: cisatracurium, acute respiratory distress syndrome, mechanical ventilation, 90-day mortality, ventilator-induced lung injury, muscle weakness, oxygenation, intensive care unit patients, mortality risk factors, PaO2/FiO2 ratio, plateau pressure
MeSH terms: Atracurium, Combined Modality Therapy, Double-Blind Method, Humans, Infusions, Intravenous, Middle Aged, Multiple Organ Failure, Neuromuscular Blocking Agents, Pneumothorax, Respiration, Artificial, Respiratory Distress Syndrome, Ventilator Weaning, Survival Rate, Proportional Hazards Models, Treatment Outcome

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Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

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