UMEM Educational Pearls

Etomidate is often a go-to agent for RSI because it is considered relatively hemodynamically neutral. However, lab studies have shown an association with transient adrenal suppression, and some observational studies and meta-analyses have suggested that patients intubated with etomidate face higher risk of cardiovascular collapse and in-hospital mortality than those intubated with ketamine.

The RSI trial was a pragmatic open-label multi-center randomized control trial conducted in 6 EDs and 8 ICUs across the US and compared induction with ketamine 1-2mg/kg versus etomidate 0.2-0.3mg/kg for RSI of critically ill adults (excluding trauma patients). They found no significant difference in overall 28 day hospital mortality across the cohort. They found an increased risk of cardiovascular collapse during intubation in the ketamine group. This increased risk was more pronounced in patients with sepsis or septic shock and patients with APACHE II ?20.

Some details:

• Cardiovascular collapse during intubation was defined as systolic BP <65mmHg, new or increased vasopressors, or cardiac arrest within 2 minutes of induction
• The prevalence of 28 day hospital mortality was 28.1% in the ketamine group vs 29.1% in the etomidate group, with an absolute difference -0.8%, 95% CI ?4.5% to 2.9%; P=0.65
• The prevalence of peri-intubation cardiovascular collapse was 22.1% in the ketamine group vs 17.0% in the etomidate group, absolute risk difference 5.1%; 95% CI, 1.9% to 8.3%. 
  • Among patients with sepsis or septic shock, 30.6% vs 20.9%, absolute risk difference 9.7%; 95% CI, 4.6% to 14.9%. 
  • Among patients with APACHE II ?20, 31.4% vs 20.7%, absolute risk difference 10.7%, 95% CI 5.5% to 16.0%.
• Both ketamine and etomidate were dosed using actual body weight, whereas data is more supportive of using ideal body weight for ketamine. The dose used for ketamine was also on the higher end of that recommended for critically ill patients. There was no investigation of how the impact of the dose of either drug on the outcomes assessed.

Overall - this was a well conducted randomized control trial that  - at the very least - suggests that etomidate is likely as safe (if not safer) than ketamine with respect to 28d mortality and peri-intubation cardiovascular collapse, even among patients with critical illness or septic shock.

References

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. 2025 Dec 9:10.1056/NEJMoa2511420. doi: 10.1056/NEJMoa2511420. Epub ahead of print. PMID: 41369227; PMCID: PMC12711137.