Methodology: 4/5
Usefulness: 4/5
N Engl J Med. 2025 Dec 9. doi: 10.1056/NEJMoa2511420.
Question and Methods: This multi-center, open label RCT of 2359 patients compared 28-day mortality in patients randomized to receiving ketamine or etomidate for their sedation prior to rapid sequence intubation in the ED and ICU.
Findings: There was no significant difference in 28-day mortality between the Ketamine and Etomidate groups (ARR 0.8, 95% CI −4.5 to 2.9; P=0.65). The secondary composite outcome of “peri-intubation hemodynamic collapse” was statistically significant (ARR 5.1, 95% CI 1.9 to 8.3) but primarily powered by new or increased vasopressors post induction (21.3% vs 15.9%).
Limitations: Major limitations are the lack of blinding and study power to detect a 5% difference in mortality.
Interpretation: This study did not demonstrate any meaningful difference in sedation choice during RSI. The mortality theorized secondary to adrenal suppression was not demonstrated in this study. Differences in pre-sedation vasopressor use and “high dose” ketamine for critically ill patients are likely driving the secondary outcome and therefore significant difference should be interpreted with caution.
For a more in-depth summary on the usage of ketamine and etomidate, read on here.
Summary by:Dr. Mathieu Mckinnon
JC Supervisor: Dr. Jeffrey Perry
