Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults

Clinical Snapshot

Key Findings

• P Value: P = 0.65

• Effect Size: Risk difference -0.8 percentage points

• Primary Outcome: In-hospital death by day 28: ketamine 28.1% vs etomidate 29.1%

• Nnt Or Sensitivity: No significant difference - NNT not applicable. Ketamine associated with increased cardiovascular collapse risk (NNH = 20)

• Confidence Interval: 95% CI: -4.5 to 2.9 percentage points

Clinical Application

Both agents readily available in Australian EDs and ICUs. Choice should consider individual patient hemodynamic status and contraindications Both ketamine and etomidate are TGA-approved and PBS-listed. Results support current ANZCA guidelines allowing either agent based on clinical judgment. May influence local protocols favoring etomidate for hemodynamically unstable patients Critically ill adults requiring emergency or ICU intubation in tertiary care settings

Abstract

BACKGROUND: For critically ill adults undergoing tracheal intubation, observational studies suggest that the use of etomidate to induce anesthesia may increase the risk of death. Whether the use of ketamine rather than etomidate decreases the risk of death is uncertain. METHODS: In a randomized trial conducted in 14 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults who were undergoing tracheal intubation to receive ketamine or etomidate for the induction of anesthesia. The primary outcome was in-hospital death from any cause by day 28. The secondary outcome was cardiovascular collapse during intubation, defined by the occurrence of a systolic blood pressure below 65 mm Hg, receipt of a new or increased dose of vasopressors, or cardiac arrest. RESULTS: A total of 2365 patients underwent randomization and were included in the trial population; 1176 were assigned to the ketamine group and 1189 to the etomidate group. In-hospital death by day 28 occurred in 330 of 1173 patients (28.1%) in the ketamine group and in 345 of 1186 patients (29.1%) in the etomidate group (risk difference adjusted for trial site, -0.8 percentage points; 95% confidence interval [CI], -4.5 to 2.9; P = 0.65). Cardiovascular collapse during intubation occurred in 260 of 1176 patients (22.1%) in the ketamine group and in 202 of 1189 patients (17.0%) in the etomidate group (risk difference, 5.1 percentage points; 95% CI, 1.9 to 8.3). Prespecified safety outcomes were similar in the two groups. CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, the use of ketamine to induce anesthesia did not result in a significantly lower incidence of in-hospital death by day 28 than etomidate. (Funded by the Patient-Centered Outcomes Research Institute and others; RSI ClinicalTrials.gov number, NCT05277896.).

References

1. 1.Casey, J. D., Seitz, K. P., Driver, B. E., Gibbs, K. W., Ginde, A. A., Trent, S. A., Russell, D. W., Muhs, A. L., Prekker, M. E., Gaillard, J. P., Resnick-Ault, D., Stewart, L. J., Whitson, M. R., DeMasi, S. C., Robinson, A. E., Palakshappa, J. A., Aggarwal, N. R., Brainard, J. C., Douin, D. J., ... Semler, M. W. (2026). Ketamine or etomidate for tracheal intubation of critically ill adults. *New England Journal of Medicine*. https://doi.org/10.1016/j.chstcc.2025.100177