Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults

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.).

Figure 1.. In-Hospital Death by Trial Group.

The percentage of patients without in-hospital death (primary outcome) is displayed for the ketamine group (red) and the etomidate group (blue) from randomization until 28 days after randomization. The incidence of in-hospital death by 28 days did not differ significantly between the ketamine group (28.1%) and the etomidate group (29.1%) (absolute risk difference adjusted for trial site, −0.8 percentage points; 95% CI, − 4.5 to 2.9; P=0.65 using a generalized linear mixed-effects model with a random effect for trial site).

Figure 2.. Subgroup Analyses of the Primary Outcome.

Shown are the absolute risk differences and 95% confidence intervals adjusted for trial site for the primary outcome (in-hospital death by 28 days) in the ketamine group as compared with the etomidate group in each prespecified subgroup. Differences between the ketamine group and the etomidate group were calculated with the use of a generalized linear mixed-effects model with a random effect for trial site and fixed effects for trial group, the proposed effect modifier, and the interaction between the trial group and the proposed effect modifier without adjustment for covariates. Differences of less than 0 indicate a lower likelihood of death with the use of ketamine. Sepsis or septic shock at enrollment is defined according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Chronic corticosteroid receipt is defined as receiving corticosteroids for at least 3 consecutive weeks prior to enrollment. Acute neurologic condition is defined as intracranial bleeding, meningitis, encephalitis, or stroke. Active cardiac condition is defined as cardiac arrest, cardiogenic shock, congestive heart failure, cardiogenic pulmonary edema, pulmonary hypertension, or myocardial infarction. APACHE II is the Acute Physiology and Chronic Health Evaluation II score, which ranges from 0 to 71, with higher scores indicating a greater severity of illness. The widths of the confidence intervals were not adjusted for multiplicity and should not be used to infer definitive differences in treatment effects between the two groups.