Written by Clay Smith
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There was no difference in 28-day mortality in critically ill adult patients with ketamine vs. etomidate for rapid sequence induction (RSI), but ketamine increased the need for peri-intubation vasopressor support.
Watch the pendulum swing…
Etomidate causes early adrenal suppression. Ketamine may cause hypotension during induction. Observational studies have been back and forth on which is the better drug for RSI.
This was a multicenter RCT with 2,365 critically ill adult patients randomized to ketamine or etomidate for RSI. For the primary outcome of in-hospital 28-day mortality, there was no difference between the two groups: 28.1% (330/1173) ketamine vs. 29.1% (345/1,186) etomidate cohorts (–0.8% (95%CI −4.5 to 2.9, p = 0.65). But there was a big difference in the number of patients with cardiovascular (CV) collapse (SBP <65, new vasopressors, arrest) within 2 minutes of intubation: 22.1% (260/1,176) ketamine vs. 17% (202/1,189) etomidate cohort (difference 5.1% 95%CI 1.9 to 8.3), largely driven by new vasopressors. In subgroup analysis, CV collapse was even more pronounced in septic shock patients: 30.6% ketamine vs. 20.9% etomidate group (difference 9.7%; 95%CI 4.6 to 14.9).
No trauma patients were enrolled, so these were sepsis, respiratory, cardiac, and neuro patients. Also, the study was unblinded, which may have introduced bias.
How will this change my practice?
Ketamine usually increases heart rate and blood pressure during sedation. Its use has markedly increased over the course of my career for RSI. But in severely ill patients, observational studies have raised concern that ketamine may lower blood pressure. Now, we know it often increases need for vasopressors. On the other hand, the concern about adrenal suppression from etomidate appears to not impact 28-day mortality. We used etomidate almost exclusively in my early training. Then we gradually switched to ketamine. For me, the pendulum has swung back to etomidate for my sick medical patients.
Source
RSI Investigators and the Pragmatic Critical Care Research Group. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. N Engl J Med. 2025 Dec 9. doi: 10.1056/NEJMoa2511420. Epub ahead of print. PMID: 41369227.
