Review: Etomidate increased mortality and adrenal insufficiency in adults with sepsis

Pearl RG. — Tue, 19 Feb 2013 00:00:00 GMT

Question

Does etomidate increase risk for mortality and adrenal insufficiency (AI) when used for sedation during rapid-sequence intubation in patients with sepsis?

Review scope

Included studies compared etomidate with a control treatment in adults with sepsis or septic shock, and provided quantitative data for mortality (in-hospital or 28-d) or AI. Exclusion criteria included studies in pediatric patients and abstract reports. Outcomes were all-cause mortality and AI (≤ 9 µg/dL increase in serum cortisol level 30 or 60 min after administration of cosyntropin, 250 µg; or random cortisol level ≤ 15 µg/dL).

Review methods

MEDLINE, EMBASE/Excerpta Medica, {Cochrane Library, and acponline.org/journals}* (to Feb 2012); ClinicalTrials.gov; and reference lists were searched for randomized controlled trials (RCTs) and controlled observational studies. Investigators were contacted. 10 studies (n = 1623, mean or median age range 58 to 77 y, 22% to 72% men) met selection criteria: 2 RCTs (n = 198), {3 nonrandomized cohort analyses from RCTs}* (n = 860), 2 prospective cohort studies (n = 222), and 3 retrospective cohort studies (n = 343). 7 studies compared etomidate with other sedatives, 2 with midazolam, and 1 with ketamine. 4 studies scored ≥ 5 out of {8}* on the modified Jadad scale for methodological quality.

Main results

Meta-analysis of RCTs and cohort studies showed that etomidate increased risk for mortality and AI (Table).

Conclusion

Etomidate used for rapid-sequence intubation increased mortality and adrenal insufficiency compared with other sedatives, ketamine, or midazolam in patients with sepsis.Etomidate vs control treatment in patients with sepsis†OutcomesNumber of studies (n)Weighted event ratesRRI (95% CI)NNH (CI)EtomidateControl‡All-cause mortality (in-hospital or at 28 d)5 (865)43%36%20% (2 to 42)14 (7 to 139)All-cause mortality at 28 d3 (637)45%35%28% (6 to 54)11 (6 to 48)Adrenal insufficiency7 (1303)68%51%33% (22 to 46)6 (5 to 9)†Abbreviations defined in Glossary. Weighted event rates, RRI, NNH, and CI calculated from risk ratios in article and event rates provided by author and were based on a fixed-effect model.‡Other sedatives, midazolam, or ketamine.

Annals of Internal Medicine: Adrenal Disorders Topic Collection

Review: Etomidate increased mortality and adrenal insufficiency in adults with sepsis