Original Investigation 

Emergency Medicine

Ketamine, Etomidate, and Mortality in Emergency Department Intubations

Ian Ward A. Maia, Sérgio R. R. Decker, Lucas Oliveira J. e Silva, et al

JAMA Netw Open 2025;8;(12):e2548060. doi:10.1001/jamanetworkopen.2025.48060

Key Points

Question  Among critically ill adults undergoing rapid sequence intubation, is etomidate use associated with higher in-hospital mortality than ketamine?

Findings  In this cohort study using target trial emulation with inverse probability of treatment weighting and data from 18 Brazilian emergency departments, etomidate was associated with significantly higher risks of in-hospital mortality at 28 days (60.5% vs 54.4%) and 7 days (35.2% vs 30.1%) compared with ketamine.

Meaning  These findings suggest that etomidate may increase the risk of death and support reevaluating its role in emergency airway management for critically ill adults.

Abstract

Importance  The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial.

Objective  To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults.

Design, Setting, and Participants  This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded.

Exposure  Administration of etomidate or ketamine as the induction agent for RSI.

Main Outcomes and Measures  The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups.

Results  Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes.

Conclusions and Relevance  In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.