Treatment with neuromuscular blocking agents and the risk of in-hospital mortality among mechanically ventilated patients with severe sepsis

OBJECTIVES:: Recent trials suggest that treatment with neuromuscular blocking agents may improve survival in patients requiring mechanical ventilation for acute respiratory distress syndrome. We examined the association between receipt of a neuromuscular blocking agent and in-hospital mortality among mechanically ventilated patients with severe sepsis. DESIGN:: A pharmacoepidemiologic cohort study of patients with sepsis and a respiratory infection who had been admitted to intensive care and placed on mechanical ventilation within the first 2 days of hospitalization. We used propensity score matching and instrumental variable methods to compare the outcomes of patients treated with neuromuscular blocking agents within the first 2 hospital days to those who were not. Sensitivity analysis was used to model the effects of a hypothetical unmeasured confounder. SETTING:: Three hundred thirty-nine U.S. hospitals that participated in the Premier Perspective database between 2004 and 2006. PATIENTS:: Seven thousand eight hundred sixty-four patients met inclusion criteria, including 1,818 (23%) who were treated with a neuromuscular blocking agent by hospital day 2. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Patients who received neuromuscular blocking agents were younger (mean age, 62 vs 68), more likely to be treated with vasopressors (69% vs 65%) and had a lower in-hospital mortality rate (31.9% vs 38.3%, p < 0.001). In 3,518 patients matched on the propensity for treatment, receipt of a neuromuscular blocking agent was associated with a reduced risk of in-hospital mortality (risk ratio, 0.88; 95% CI, 0.80, 0.96). An analysis using the hospital neuromuscular blocking agent-prescribing rate as an instrumental variable found receipt of a neuromuscular blocking agent associated with a 4.3% (95% CI,-11.5%, 1.5%) reduction in in-hospital mortality. CONCLUSIONS:: Among mechanically ventilated patients with severe sepsis and respiratory infection, early treatment with a neuromuscular blocking agent is associated with lower in-hospital mortality.