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Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis*

Chan, Chee Man MD, MPH; Mitchell, Anthony L. MD; Shorr, Andrew F. MD, MPH

doi: 10.1097/CCM.0b013e31825fec26
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Objective: To evaluate the effects of single-dose etomidate on the adrenal axis and mortality in patients with severe sepsis and septic shock.

Design: A systematic review of randomized controlled trials and observational studies with meta-analysis.

Setting: Literature search of EMBASE, Medline, Cochrane Database, and Evidence-Based Medical Reviews.

Subjects: Sepsis patients who received etomidate for rapid sequence intubation.

Interventions: None.

Measurements and Main Results: We conducted a systematic review of randomized controlled trials and observational studies with meta-analysis assessing the effects of etomidate on adrenal insufficiency and all-cause mortality published between January 1950 and February 2012. We only examined studies including septic patients. All-cause mortality served as our primary end point, whereas the prevalence of adrenal insufficiency was our secondary end point. Adrenal insufficiency was determined using a cosyntropin stimulation test in all studies. We used a random effects model for analysis; heterogeneity was assessed with the I2 statistic. Publication bias was evaluated with Begg’s test. Five studies were identified that assessed mortality in those who received etomidate. A total of 865 subjects were included. Subjects who received etomidate were more likely to die (pooled relative risk 1.20; 95% confidence interval 1.02–1.42; Q statistic, 4.20; I2 statistic, 4.9%). Seven studies addressed the development of adrenal suppression associated with the administration of etomidate; 1,303 subjects were included. Etomidate administration increased the likelihood of developing adrenal insufficiency (pooled relative risk 1.33; 95% confidence interval 1.22–1.46; Q statistic, 10.7; I2 statistic, 43.9%).

Conclusions: Administration of etomidate for rapid sequence intubation is associated with higher rates of adrenal insufficiency and mortality in patients with sepsis.

From the Pulmonary & Critical Care Medicine (CMC, AFS), Washington Hospital Center, Washington, DC; and Emergency & Critical Care Medicine (ALM), University of Maryland Medical Center, R. Adams Cowley Shock Trauma Center, Baltimore, MD.

*See also p. 3086.

Dr. Chan participated in the conception, literature review process, data abstraction, data analysis, and drafting of this manuscript. Dr. Mitchell participated in the literature review process, data abstraction process, and drafting of this manuscript. Dr. Shorr assisted in the conception, data analysis, and drafting of this manuscript.

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The authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail chee262@hotmail.com

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins