Single-dose etomidate does not increase mortality in patients with sepsis: a systematic review and meta-analysis of randomized controlled trials and observational studies

Abstract

Background: The effect of single-dose etomidate on mortality in patients with sepsis remains controversial. We systematically reviewed the literature to investigate whether a single dose of etomidate for rapid sequence intubation increased mortality in patients with sepsis.

Methods: PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of single-dose etomidate on mortality in adults with sepsis. The primary outcome was all-cause mortality. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled relative risks (RRs) and 95% CIs.

Results: Eighteen studies (two RCTs and 16 observational studies) in 5,552 patients were included. Pooled analysis suggested that single-dose etomidate was not associated with increased mortality in patients with sepsis in both the RCTs (RR, 1.20; 95% CI, 0.84-1.72; P = .31; I(2) = 0%) and the observational studies (RR, 1.05; 95% CI, 0.97-1.13; P = .23; I(2) = 25%). When only adjusted RRs were pooled in five observational studies, RR for mortality was 1.05 (95% CI, 0.79-1.39; P = .748; I(2) = 71.3%). These findings also were consistent across all subgroup analyses for observational studies. Single-dose etomidate increased the risk of adrenal insufficiency in patients with sepsis (eight studies; RR, 1.42; 95% CI, 1.22-1.64; P < .00001).

Conclusions: Current evidence indicates that single-dose etomidate does not increase mortality in patients with sepsis. However, this finding largely relies on data from observational studies and is potentially subject to selection bias; hence, high-quality and adequately powered RCTs are warranted.