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Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome*

Forel, Jean-Marie MD; Roch, Antoine MD, PhD; Marin, Valérie MD, PhD; Michelet, Pierre MD; Demory, Didier MD; Blache, Jean-Louis MD; Perrin, Gilles MD; Gainnier, Marc MD, PhD; Bongrand, Pierre MD, PhD; Papazian, Laurent MD, PhD

doi: 10.1097/01.CCM.0000239435.87433.0D
Clinical Investigations

Objective: To evaluate the effects of neuromuscular blocking agents (NMBAs) on pulmonary and systemic inflammation in patients with acute respiratory distress syndrome ventilated with a lung-protective strategy.

Design: Multiple-center, prospective, controlled, and randomized trial.

Setting: One medical and two medical–surgical intensive care units.

Patients: A total of 36 patients with acute respiratory distress syndrome (Pao2/Fio2 ratio of ≤200 at a positive end-expiratory pressure of ≥5 cm H2O) were included within 48 hrs of acute respiratory distress syndrome onset.

Interventions: Patients were randomized to receive conventional therapy plus placebo (n = 18) or conventional therapy plus NMBAs (n = 18) for 48 hrs. Both groups were ventilated with a lung-protective strategy (tidal volume between 4 and 8 mL/kg ideal body weight, plateau pressure of ≤30 cm H2O).

Measurements and Main Results: Bronchoalveolar lavages and blood samples were performed, before randomization and at 48 hrs, to determine the concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8. Pao2/Fio2 ratio was evaluated before randomization and at 24, 48, 72, 96, and 120 hrs. A decrease over time in IL-8 concentrations (p = .034) was observed in the pulmonary compartment of the NMBA group. At 48 hrs after randomization, pulmonary concentrations of IL-1β (p = .005), IL-6 (p = .038), and IL-8 (p = .017) were lower in the NMBA group as compared with the control group. A decrease over time in IL-6 (p = .05) and IL-8 (p = .003) serum concentrations was observed in the NMBA group. At 48 hrs after randomization, serum concentrations of IL-1β (p = .037) and IL-6 (p = .041) were lower in the NMBA group as compared with the control group. A sustained improvement in Pao2/Fio2 ratio was observed and was reinforced in the NMBA group (p < .001).

Conclusion: Early use of NMBAs decrease the proinflammatory response associated with acute respiratory distress syndrome and mechanical ventilation.

From Réanimation Médicale (JMF, AR, DD, MG, LP), Laboratoire d'Immunologie, UMR 600–CNRS FRE 2059 (VM, PB), and Département Anesthésie Réanimation (PM, GP), Assistance Publique Hôpitaux de Marseille, Hôpital Sainte Marguerite, Marseille, France; and the Département Anesthésie Réanimation, Institut Paoli–Calmettes, Marseille, France (JLB).

Supported, in part, by a grant from the Assistance Publique–Hôpitaux de Marseille, France.

© 2006 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins