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Treatment With Neuromuscular Blocking Agents and the Risk of In-Hospital Mortality Among Mechanically Ventilated Patients With Severe Sepsis*

Steingrub, Jay S. MD1,2; Lagu, Tara MD, MPH2,3,4; Rothberg, Michael B. MD, MPH5; Nathanson, Brian H. PhD6; Raghunathan, Karthik MD, MPH7; Lindenauer, Peter K. MD, MSc2,3,4

Critical Care Medicine:
doi: 10.1097/CCM.0b013e31829eb7c9
Clinical Investigations
Abstract

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.

Author Information

1Division of Pulmonary and Critical Care Medicine, Baystate Medical Center, Springfield, MA.

2Department of Medicine, Tufts University School of Medicine, Boston, MA.

3Center for Quality of Care Research, Baystate Medical Center, Springfield, MA.

4Division of General Medicine, Baystate Medical Center, Springfield, MA.

5Department of Medicine, Medicine Institute, Cleveland Clinic, Cleveland, OH.

6OptiStatim, LLC, Longmeadow, MA.

7Department of Anesthesiology, Duke University Medical Center Anesthesiology Service, Durham VA Medical Center, Durham, NC.

* See also p. 208.

Drs. Steingrub, Lagu, Rothberg, and Lindenauer were involved in the conception, hypothesis delineation, and design of the study. Drs. Steingrub, Lagu, Rothberg, Nathanson, Raghunathan, and Lindenauer were involved in the acquisition of the data or the analysis and interpretation of such information. Drs. Steingrub, Lagu, Rothberg, Nathanson, Raghunathan, and Lindenauer were involved in writing the article or substantially involved in its revision prior to submission.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Presented, in part, at the minisymposium, “Lung Injury in the Intensive Care Unit: Mechanisms, Therapies, Physiology, and Outcomes,” 2011 ATS Annual Meeting, Denver, CO.

Dr. Steingrub received grant support from the National Heart, Lung, and Blood Institute (Acute Respiratory Distress Syndrome Network). Dr. Nathanson’s company, OptiStatim, LLC, has a paid consulting agreement with Baystate Medical Center. Dr. Raghunathan received grant support for research from the Department of Anesthesiology, Duke University Medical Center. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Peter K. Lindenauer, MD, MSc, Center for Quality of Care Research, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199. E-mail: peter.lindenauer@bhs.org

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins