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

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. 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. 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). 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.