Introduction

  1. Rapid sequence intubation (RSI) is a process whereby an induction agent and a neuromuscular blocking agent are given in rapid succession to facilitate endotracheal intubation
  2. The selection of a specific sedative depends on multiple factors: the clinical scenario, which includes patient factors (includes cardiorespiratory and neurologic status, allergies, comorbidity) and the clinician's experience/training and institutional factors, as well as the characteristics of the sedative
  3. Etomidate remains the most commonly used induction agent; however, it is not without its own pharmacologic considerations such as the decrease in seizure threshold.

*Various formulations may appear; check your institution formulary.

Clinical Detail

Etomidate is a short-acting, hemodynamically neutral imidazole induction agent. The monograph below summarizes its key dosing and pharmacologic properties for rapid sequence intubation (RSI).

EtomidateDetail
Dose0.3 mg/kg IV
AdministrationIV push
Formulation*20 mg/10 mL; 40 mg/20 mL
PharmacokineticsOnset ~20 seconds; duration 4–10 minutes; metabolized by ester hydrolysis; ~75% renal excretion of metabolites
Adverse effectsInjection-site pain, nausea, vomiting, myoclonus
Drug interactionsNo major interactions
CompatibilityIncompatible with vitamin C and vecuronium
Clinical commentsHemodynamically neutral. A single induction dose causes transient inhibition of adrenal cortisol synthesis; the evidence section below summarizes the debated clinical significance of this effect.

Relative to the other agents commonly used for induction, etomidate is the most hemodynamically neutral. The table below compares the hemodynamic and endocrine effects of the agents most often selected for RSI.

DrugHemodynamic / endocrine effectComments
Etomidate↔ BP, ↔ CO, ↔ HR, ↓ cortisol, ↔ ICPProlonged inhibition of adrenal steroid synthesis after even a single dose in the critically ill
Ketamine↑ BP, ↑ HR, ↑ CO, ↔ cortisol, variable ICPCerebral perfusion pressure and ICP generally maintained with standard anesthetic management
Propofol↓ BP, ↔ HR, ↓ CO, ↔ cortisol, ↓ ICPHemodynamic compromise marked in elderly, ASA 3 or more, or hypovolemic patients with a standard induction dose

Evidence

The table summarizes the published evidence on etomidate and seizure / epileptiform activity, from the earliest reports through the most current 2026 literature. Sample sizes shown as “not reported in abstract” could not be confirmed against a primary-source abstract.

Author, yearDesign / sample sizeIntervention & comparisonOutcome
Perier et al, 2018Retrospective
N=97		Etomidate vs sodium thiopental for RSI in convulsive status epilepticusSeizure and/or status epilepticus recurred in 13 (56%) of the etomidate group vs 11 (44%) of the sodium thiopental group — no significant difference (adjusted OR 0.98).
Gabor, 2007Prospective randomized cross-over
N=30		Propofol 1 mg/kg vs etomidate 0.2 mg/kg for electroconvulsive therapyAfter etomidate induction, seizure durations recorded by EEG and EMG were longer than with propofol.
Zuckerbraun et al, 2006Pediatric ED
n=77 (etomidate RSI)		Etomidate for RSI in a pediatric emergency departmentNo relationship between seizures after etomidate administration and prior seizure history (p = 0.25).
Guldner, 2003Retrospective
N=105		Etomidate for RSI in a general ED populationThree patients vomited within 10 minutes of etomidate; no documented myoclonus, status epilepticus, or new-onset seizures.
Reddy, 1993Prospective randomized
N=67		Etomidate vs thiopental vs methohexital vs propofol for anesthesia inductionExcitatory movements (myoclonus, tremor, dystonia): etomidate 86.6%, thiopental 16.6%, methohexital 12.5%, propofol 5.5%. Multiple spikes appeared on EEG in 22.2% of etomidate patients.
Ebrahim, 1986Case series
N=12		Etomidate for induction in patients with intractable seizuresSubdural-electrode EEG: 9 of 12 patients showed an increase in epileptiform activity, marked in 6 of the 9.
Krieger, 1985Letter to editor
N not reported in abstract		Etomidate for induction or to activate a seizure focus25 patients had epileptiform activity associated with etomidate; 6/30 had generalized epileptiform activity on EEG.
Grant, 1983Letter (case series)
N not reported in abstract		Etomidate infusion for sedation in the ICUGeneralized and focal seizures after variable periods of etomidate; EEGs were not evaluated at the time of suspected activity. Infusions ran 6–28 hours at seizure onset.
Ghoneim, 1977Prospective randomized
N not reported in abstract		Etomidate vs thiopental for anesthesia induction28% etomidate vs 0% thiopental had myoclonic movements; 11% vs 1% had tonic movements. No epileptiform discharges in the 10 patients who had EEG monitoring.
Recent Evidence (2009–2026) — the etomidate-vs-ketamine question
Jabre et al, 2009
(KETASED RCT)		Multicenter RCT
N=655		Ketamine vs etomidate for RSI in acutely ill patientsNo significant difference in maximum SOFA score; adrenal insufficiency markedly more common with etomidate (OR 6.7). Ketamine a safe alternative, including in sepsis.
Kotani et al, 2023Meta-analysis
11 RCTs / 2704 pts		Etomidate vs other induction agents (mortality)Etomidate associated with increased mortality (RR 1.16, 95% CI 1.01–1.33; number needed to harm 31).
Andriazzi et al, 2026Meta-analysis
6 RCTs / 4108 pts		Ketamine vs etomidate for emergency intubation (incl. sepsis)No difference in 28-day mortality, including the sepsis subgroup. Ketamine increased post-intubation hypotension (RR 1.25); etomidate increased adrenal suppression.

Conclusions

  • Etomidate is a commonly used induction agent for RSI in emergency settings. It elicits myoclonus in a significant number of patients; however, whether that myoclonus reflects EEG-confirmed epileptiform activity remains uncertain. Depending on the origin and type of seizure, EEG may also struggle to differentiate non-seizure from seizure activity during myoclonic events.
  • Because of the low level of evidence specific to seizure risk, patients with a history of seizures should have an individualized risk-versus-benefit assessment to determine the best induction agent.
  • More recent evidence has shifted the broader induction debate toward the etomidate-versus-ketamine comparison. Signals on mortality are mixed — a 2023 meta-analysis suggested higher mortality with etomidate (RR 1.16), while a larger 2026 meta-analysis found no 28-day mortality difference — but the analyses consistently show etomidate causes more adrenal suppression and ketamine more post-intubation hypotension. Agent choice should weigh these trade-offs alongside the seizure considerations above.

References

  • Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2021, from http://www.micromedexsolutions.com/
  • Perier F. Seizure. 2018 Oct;61:170-176. PMID: 30176574.
  • Zuckerbraun NS. Acad Emerg Med. 2006 Jun;13(6):602-9. PMID: 16636355.
  • Grant IS, et al. Epileptiform seizures during prolonged etomidate sedation. Lancet 1983; 322(8348):511-2.
  • Guldner G, et al.. Acad Emerg Med 2003; 10:134-139.
  • Reddy RV, et al.. Anesth Analg 1993; 77:1008-11.
  • Ebrahim ZY, et al. . Anesth Analg 1986; 65:1004-6.
  • Krieger W, et al K. Seizures with etomidate anesthesia [letter]. Anesthesiol Analg. 1985; 64:1226-7.
  • Ghoneim MM, Anesth Analg 1977; 56:479-85.
  • Gabor G. Neuropsychopharmacol Hung 2007; 9(3):125-30.
  • Recent evidence added on review (2023–2026)
  • Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial (KETASED). Lancet. 2009;374(9686):293-300. doi:10.1016/S0140-6736(09)60949-1
  • Kotani Y, Piersanti G, Maiucci G, et al. Etomidate as an induction agent for endotracheal intubation in critically ill patients: a meta-analysis of randomized trials. J Crit Care. 2023;77:154317. doi:10.1016/j.jcrc.2023.154317
  • Koroki T, Kotani Y, Yaguchi T, et al. Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis. Crit Care. 2024;28(1):48. doi:10.1186/s13054-024-04831-4
  • Greer A, Hewitt M, Khazaneh PT, et al. Ketamine versus etomidate for rapid sequence intubation: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2025;53(2):e374-e383. doi:10.1097/CCM.0000000000006515
  • Daghmouri MA, Chaouch MA, Noomen M, et al. Etomidate versus ketamine for in-hospital rapid sequence intubation: a systematic review and meta-analysis. Eur J Emerg Med. 2025;32(3):160-170. doi:10.1097/MEJ.0000000000001237
  • Kim J, Jung K, Moon J, et al. Ketamine versus etomidate for rapid sequence intubation in patients with trauma: a retrospective study in a level 1 trauma center in Korea. BMC Emerg Med. 2023;23(1):57. doi:10.1186/s12873-023-00833-7
  • Andriazzi VH, Curcio RP, Novais MARA, et al. Etomidate versus ketamine for emergency intubation in critically ill patients: an updated meta-analysis and systematic review. J Intensive Care Med. 2026. doi:10.1177/08850666261460825
Tags: etomidate seizure induction rapid sequence intubation

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