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.).
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Anesthesiology | |
| Intensivist/Critical Care |  |
This study evaluated the 28-day mortality impact of ketamine vs etomidate in RSI where they found no difference; however, ketamine caused more CVS instability. Strengths: Well powered multicenter trial. Evaluated primary as well as various secondary outcomes. Weakness: Unblinded trial with risk of bias. Criticism: 1. more CVS instability in ketamine group that is against conventional belief and happened despite relatively fewer cardiac unstable patients in that group than in the etomidate group; 2. more hemodynamic imbalances (extremes) seen in the etomidate group after 2 min study period and more use of vasopressor and inotropes in that group compared with ketamine; and 3. although mortality is statistically similar, it trended as less in the ketamine group despite having higher immediate hemodynamic insults. Will a higher number benefit here? Final Impression: Good trial that turned the consensus on ketamine but the cardiovascular impact is an eye-opener.
Important information that anyone undertaking tracheal intubation of critically ill adults in the the ED should read. This large RCT showed no difference in 28-day mortality between ketamine and etomidate, although it was not powered to detect small differences, such as the 0.8% difference observed in the point estimates. Cardiovascular collapse during intubation was more common with ketamine (22% v 17%). The difference in this composite outcome was mainly seen in greater use of vasopressors with ketamine, so the clinical importance of this difference can be debated.
The RSI trial showed no statistical difference in 28-day mortality between etomidate or ketamine when used in RSI for emergent intubation. Interestingly, there were hemodynamic issues related to ketamine that were unexpected and counter to traditional teaching. However, it's also possible that the study was underpowered to detect small differences (the study was powered to detect a difference of ~5%). However, that would require a much larger study that may not be feasible. Other safety measures such as "Ongoing receipt of vasopressors at 24 hours" had a point estimate that showed ketamine to be better, although statistically not significant (it potentially could be with a larger study). Regardless, this is the largest RCT evaluating this question and at this point should not leave doubt that etomidate is a viable option compared with ketamine for RSI.
TRANSLATED FROM SPANISH BY AI: Ketamine is a common drug used globally by some specialists (anesthesia, ICU); however, there are areas of the world where it is not routinely used in emergency rooms to intubate critically ill patients. // ORIGINAL COMMENT: La Ketamina es un medicamento común utilizado a nivel global por algunos especialistas (anestesia, UCI), sin embargo, hay zonas del globo, que en las salas de urgencia no se utiliza de forma habitual para intubar a pacientes críticos
