Etomidate Versus Ketamine for Emergency Intubation in Critically Ill Patients: An Updated Meta-Analysis and Systematic Review

ObjectiveTo 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 SourcesPubMed, Embase, and the Cochrane Library were systematically searched from inception to January 2026. Reference lists of included studies were also manually screened. Study SelectionWe 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 (e.g., intensive care unit or emergency department). Data ExtractionTwo 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 SynthesisSix RCTs comprising 4,108 patients (2,046 assigned to ketamine and 2,062 to etomidate) were included. The pooled analysis showed no statistically significant difference in 28-day mortality between the ketamine and etomidate groups (39.0% vs. 40.3%; relative risk [RR] 0.96; 95% CI, 0.89-1.03; p=0.29; I{superscript 2}=11%). In a prespecified subgroup analysis of patients with sepsis (n=1,546), mortality also did not differ significantly (RR 0.94; 95% CI, 0.86-1.03). 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; p=0.04; I{superscript 2}=0%). No significant differences were observed regarding peri-intubation cardiac arrest, first-attempt intubation success, or ventilator- and intensive care unit-free days. ConclusionsThere is no statistical difference in 28-day mortality between etomidate and ketamine for emergency intubation in critically ill adults, including those with sepsis. The higher incidence of post-intubation hypotension with ketamine suggests etomidate presents a more favorable hemodynamic safety profile in this setting. Key pointsO_ST_ABSQuestionC_ST_ABSDoes the choice between etomidate and ketamine for emergency intubation in critically ill patients impact 28-day mortality? FindingsIn this systematic review and meta-analysis of randomized controlled trials, there was no statistically significant difference in 28-day mortality between patients induced with ketamine (39.0%) and those induced with etomidate (40.3%). MeaningThe use of etomidate versus ketamine for rapid sequence intubation does not alter 28-day mortality, indicating that the choice of induction agent should be individualized.