Journal
CRITICAL CARE MEDICINE
Volume 34, Issue 11, Pages 2749-2757Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.CCM.0000239435.87433.0D
Keywords
acute respiratory distress syndrome; neuromuscular blocking agents; cytokines; inflammation mediators; mechanical ventilation; oxygenation
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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 (Pao(2)/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-alpha, interleukin (IL)-1 beta, IL-6, and IL-8. Pao(2)/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-1 beta (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-1 beta (p =.037) and IL-6 (p =.041) were lower in the NMBA group as compared with the control group. A sustained improvement in Pao(2)/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.
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