Objective To compare the efficacy and safety of etomidate versus ketamine as induction agents for rapid sequence intubation in critically ill adults, focusing on 28-day mortality and post-intubation hypotension. Data Sources PubMed, Embase, and the Cochrane Library were systematically searched from inception to January 2026. Reference lists of included studies were also manually screened. Study Selection We included randomized controlled trials (RCTs) comparing single-dose intravenous ketamine versus etomidate for emergency rapid sequence intubation in critically ill adults (≥ 18 years) in non-operating room settings (eg, intensive care unit or emergency department). Data Extraction Two investigators independently screened records, extracted data using a standardized form and assessed the risk of bias using the RoB 2 tool. The certainty of evidence was evaluated using the GRADE framework. Data Synthesis Six RCTs comprising 4108 randomized patients (2046 assigned to ketamine and 2062 to etomidate) were included. For the primary outcome, the pooled analysis evaluated 4102 patients and showed no statistically significant difference in 28-day mortality between the ketamine and etomidate groups (28.7% vs 29.9%; relative risk RR 0.96; 95% CI, 0.87-1.05; I 2 = 13.8%). In a prespecified subgroup analysis of patients with sepsis (n = 1546), mortality also did not differ significantly (RR 1.04; 95% CI, 0.91-1.19). However, ketamine was associated with a statistically significant increase in the incidence of post-intubation hypotension (14.2% vs 11.3%; RR 1.25; 95% CI, 1.01-1.53; I 2 = 0%). Conversely, ketamine significantly reduced the risk of adrenal suppression compared to etomidate (5.3% vs 14.7%; RR 0.36; 95% CI, 0.17-0.75). No significant differences were observed regarding peri-intubation cardiac arrest or first-attempt intubation success. Conclusions For emergency intubation in critically ill adults, including those with sepsis, 28-day mortality is similar between etomidate and ketamine. However, ketamine may increase post-intubation hypotension, whereas etomidate may increase adrenal suppression.
Andriazzi et al. (Tue,) studied this question.