All Pharmacy Pearls

Introduction

Rapid sequence intubation is the most common method for emergency airway management and pairs a sedative induction agent with a neuromuscular blocker in rapid succession. Ketamine and etomidate are the most common induction agents because both can be used quickly and are often considered hemodynamically favorable.

Etomidate has historically been preferred, but ketamine has gained renewed interest. Etomidate causes reversible adrenal suppression even after a single dose, with higher adrenal insufficiency rates compared with ketamine. That concern becomes more important in septic or critically ill patients where adrenal function and vasopressor response matter.

Key Points

  • Ketamine provides dissociative anesthesia with analgesia, amnesia, and sympathetic stimulation.
  • Etomidate provides rapid sedation but no analgesia and inhibits cortisol synthesis through 11-beta-hydroxylase inhibition.
  • Recent observational data suggest possible mortality advantages with ketamine, but definitive randomized evidence is still pending.
  • Patient phenotype should drive induction choice: sepsis, shock, bronchospasm, adrenal risk, and adverse-effect tolerance all matter.

Pharmacology Snapshot

AgentRSI DosePractical Pearl
Ketamine1-2 mg/kg IV push; consider 0.5-1 mg/kg in elderly or hemodynamically unstable patients.NMDA antagonist with dissociative anesthesia, analgesia, and sympathetic stimulation. Useful in shock, bronchospasm, or reactive airway disease, but watch tachycardia, hypertension, hypersalivation, and emergence reactions.
Etomidate0.3 mg/kg IV push.GABA-A agonist with rapid onset and minimal immediate hemodynamic effect. Causes adrenal suppression even after one dose and should be used cautiously in sepsis or adrenal insufficiency risk.

Clinical Pearl

Ketamine and etomidate may both work for intubating conditions; the practical choice often turns on the patient after the tube is placed: shock trajectory, sepsis physiology, adrenal suppression risk, and adverse-effect profile.

Evidence Overview

SourceDesignPractical Takeaway
Jabre 200910Multicenter RCT, critically ill RSI patients.No significant difference in maximum SOFA score; adrenal insufficiency was higher with etomidate.
Sharda 20228Systematic review and meta-analysis.No significant mortality difference; ketamine was associated with higher post-intubation blood pressure.
Koroki 20245Bayesian meta-analysis, 13 studies.Estimated 84% probability that ketamine was superior to etomidate for mortality, with credible intervals crossing no effect.
Wunsch 20244Large retrospective cohort of critically ill patients.Etomidate was associated with higher in-hospital mortality compared with ketamine, independent of corticosteroid administration.
Maia 20253Retrospective cohort of ED intubations.Ketamine was associated with lower in-hospital mortality versus etomidate, consistent across subgroups.

Decision Points

Sepsis or adrenal risk

Favor ketamine when adrenal suppression could worsen the post-intubation course.

Bronchospasm

Ketamine’s bronchodilatory and sympathomimetic profile may be useful in reactive airway disease.

Tachycardia or hypertension

Account for ketamine’s sympathomimetic effects when elevated heart rate or blood pressure is already harmful.

Drug handling

Ketamine is controlled; etomidate is not. Both require clear RSI dose, route, and post-intubation sedation planning.

Pharmacist checkpoint

The induction agent is only the first dose. Make the post-intubation sedation, vasopressor, and adrenal-risk plan explicit before the airway team moves on.

Clinical Conclusions

Initial intubating conditions appear comparable. Ketamine and etomidate both remain viable RSI induction agents.

Etomidate’s adrenal effect is real. Avoid minimizing single-dose adrenal suppression in septic or critically ill patients.

Mortality evidence is evolving. Observational studies favor ketamine, but randomized data are still needed.

Use patient physiology to choose. Hemodynamic instability, sepsis, bronchospasm, tachycardia, and adverse-effect tolerance should guide the final choice.

Full Reference List

  1. DeMasi SC, et al. Protocol for the RSI Trial. medRxiv. 2025.
  2. Wollenman LC, et al. Ketamine vs etomidate and PTSD symptoms at 12 months. CHEST Crit Care. 2025;3(2).
  3. Maia IWA, et al. Ketamine, etomidate, and mortality in ED intubations. JAMA Netw Open. 2025;8(12):e2548060.
  4. Wunsch H, et al. Etomidate vs ketamine and mortality in critically ill patients. Am J Respir Crit Care Med. 2024;210(10):1243-1251.
  5. Koroki T, et al. Ketamine vs etomidate: A Bayesian meta-analysis. Crit Care. 2024;28(1):48.
  6. Kim J, et al. Ketamine vs etomidate for RSI in trauma patients. BMC Emerg Med. 2023;23(1):57.
  7. Engstrom K, et al. Pharmacotherapy optimization for RSI in the ED. Am J Emerg Med. 2023;70:19-29.
  8. Sharda SC, et al. Etomidate vs ketamine for RSI: Systematic review. Indian J Crit Care Med. 2022;26(1):108-113.
  9. Stanke L, et al. Hemodynamic effects of ketamine vs etomidate for prehospital RSI. Air Med J. 2021;40(5):312-316.
  10. Jabre P, et al. Etomidate vs ketamine for RSI: Multicenter RCT. Lancet. 2009;374(9686):293-300.
  11. Ketamine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health. Accessed February 2026.
  12. Etomidate. Lexi-Drugs. Lexicomp. Wolters Kluwer Health. Accessed February 2026.
Tags: Ketamine Etomidate RSI Emergency Medicine Pharmacy Friday Pearls