In the Literature

Summary of "Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults"

Summary published May 18, 2026

Summary by John "JW" Beard, MD

The New England Journal of Medicine | April 2026

Casey JD, Seitz KP, Driver BE, Gibbs KW, Ginde AA, Trent SA, Russell DW, Muhs AL, Prekker ME, Gaillard JP, Resnick-Ault D, Stewart LJ, Whitson MR, DeMasi SC, Robinson AE, Palakshappa JA, Aggarwal NR, Brainard JC, Douin DJ, Marvi TK, Scott BK, Alber SM, Lyle C, Gandotra S, Van Schaik GW, Lacy AJ, Sherlin KC, Erickson HL, Cain JM, Redman B, Beach LL, Gould B, McIntosh J, Lewis AA, Lloyd BD, Israel TL, Imhoff B, Wang L, Spicer AB, Churpek MM, Rice TW, Self WH, Han JH, Semler MW; RSI Investigators and the Pragmatic Critical Care Research Group. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. N Engl J Med. 2026 Apr 23;394(16):1608-1620. doi: 10.1056/NEJMoa2511420. Epub 2025 Dec 9. PMID: 41369227; PMCID: PMC12711137.

doi: https://doi.org/10.1056/nejmoa2511420

  • The choice of induction agent during emergency tracheal intubation of critically ill adults has important patient safety implications, including the risks of death and peri-intubation hemodynamic instability.
  • Previous observational studies have suggested that using etomidate for tracheal intubation of critically ill patients may increase the risk of death, but rigorous data from randomized controlled trials are lacking.
  • This multicenter randomized controlled trial evaluated whether ketamine reduces mortality compared with etomidate.
  • 2365 critically ill adults in U.S. EDs and ICUs were assigned to receive ketamine or etomidate during tracheal intubation. The primary outcome was 28-day in-hospital mortality; the secondary outcome was cardiovascular collapse during intubation.
  • There was no significant difference in 28-day mortality between ketamine and etomidate (28.1% vs. 29.1%; risk difference −0.8%, 95% CI −4.5 to 2.9, P=0.65).
  • Mortality findings were consistent across subgroups, including patients with sepsis.
  • Ketamine was associated with a higher incidence of cardiovascular collapse during intubation compared to etomidate (22.1% vs. 17.0%; risk difference 5.1%, 95% CI 1.9 to 8.3), including increased hypotension and vasopressor use, particularly in sicker patients.
  • Additional findings demonstrated that ketamine administration was associated with lower peri-intubation systolic blood pressure (median difference −6 mm Hg, 95% CI −9 to −1) and higher rates of hypotension (SBP <80 mm Hg: risk difference 3.8%, 95% CI 1.1 to 6.5), while other clinical outcomes were similar between groups.
  • These results do not support ketamine as a mortality-reducing alternative and challenge the perception that it provides superior hemodynamic stability.
  • For anesthesia professionals, induction agent selection should focus on hemodynamic risk. Etomidate may offer greater cardiovascular stability, especially in patients with shock or sepsis, while ketamine may increase peri-intubation instability.
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