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Ketamine vs etomidate for adult RSI: compare what the 2025 ED and ICU trial found, and where EMS sits outside it

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Ketamine vs etomidate for RSI now has one large randomized trial: the RSI trial, published in the New England Journal of Medicine in December 2025, included 2,365 critically ill adults intubated across six US EDs and eight ICUs. In-hospital death by 28 days didn’t differ, 28.1% with ketamine against 29.1% with etomidate. Cardiovascular collapse during intubation was more common with ketamine, 22.1% against 17.0%. No patient was intubated in the field, so the trial informs EMS practice without being EMS evidence. This page covers adults only. See adult RSI medications, agent by agent for where these two sit among the other four drugs.

Ketamine vs etomidate for RSI: what each source states
PointKetamineEtomidateSource
Labelled induction dose1 to 4.5 mg/kg IV; average 2 mg/kg0.2 to 0.6 mg/kg; usual 0.3 mg/kgFDA labels
StatPearls intubation dose2 mg/kg IV0.15 to 0.3 mg/kg IVStatPearls NBK459276
Onset and duration (label)within 30 seconds; 5 to 10 minutesusually within 1 minute; usually 3 to 5 minutesFDA labels
RSI trial dose options (nomogram)2.0, 1.5, or 1.0 mg/kg, clinician-selected0.3, 0.25, or 0.2 mg/kg, clinician-selectedCasey et al., 2025
RSI trial median dose given140 mg, 1.6 mg/kg of actual body weight20 mg, 0.28 mg/kg of actual body weightCasey et al., 2025
Adrenal effectDoes not impair cortisol productionInhibits 11-beta-hydroxylase; duration differs by source (below)Casey et al., 2025; StatPearls NBK459276; AMIDATE label

Labelled figures come from surgical anesthesia, not emergency intubation. The trial’s figures are what clinicians chose and gave, not a recommendation; the trial reported doses per kilogram of actual body weight, and its manuscript does not state which weight its nomogram used. The crew’s protocol sets the dose actually given.

The 2025 ketamine vs etomidate trial: who was in it and who was not

The trial included 2,365 critically ill adults, age 18 or older, intubated with an induction medication at 14 sites (6 EDs, 8 ICUs) across 6 US medical centers, from April 2022 to August 2025. An ED accounted for 55.7% of intubations and an ICU for 44.3%. Median age was 60; 46.7% had sepsis or septic shock, and 22.0% were already on vasopressors before induction. Design: pragmatic, 1:1, unblinded after randomization. Excluded: known pregnancy, prisoners, a primary trauma diagnosis, an immediate need too urgent for randomization, and clinician-judged necessity or contraindication for either drug.

Dosing ran on a nomogram of three tiers per drug, clinician-chosen. 99.2% of the ketamine group and 99.6% of the etomidate group received their assigned drug, and 99.7% in each also received a neuromuscular blocker. The trial reports its doses per kilogram of actual body weight, but its manuscript does not state what weight its nomogram used.

Compare the outcomes: mortality, blood pressure, and first pass

The trial found no difference in death and more cardiovascular collapse with ketamine. In-hospital death by 28 days occurred in 28.1% of the ketamine group and 29.1% of the etomidate group, a site-adjusted difference of −0.8 percentage points (95% CI, −4.5 to 2.9). Among the 1,101 patients with sepsis, mortality was 38.8% versus 38.2%.

The trial’s single prespecified secondary outcome, cardiovascular collapse during intubation, was defined as a systolic blood pressure under 65 mm Hg, a new or increased vasopressor, or cardiac arrest, from induction to 2 minutes after the tube. It occurred in 22.1% of the ketamine group versus 17.0% of the etomidate group, a difference of 5.1 percentage points (95% CI, 1.9 to 8.3).

First-attempt success: 85.7% ketamine, 86.7% etomidate. Ventricular tachycardia, a post hoc outcome, ran 1.0% versus 0.2%; vasopressors at 24 hours, 38.9% versus 42.3%.

The authors wrote that “the incidence of cardiovascular complications during intubation appeared to be higher with ketamine than with etomidate,” with effects that “appeared to be largest among patients with sepsis and shock.” Their caveat on secondary and subgroup results: the confidence intervals “were not adjusted for multiplicity and should not be used to infer definitive differences in treatment effects.”

Ketamine vs etomidate in the RSI trial: mortality and cardiovascular collapseA grouped bar chart on a 0 to 40 percent axis. In-hospital death by day 28: 28.1 percent with ketamine, 29.1 percent with etomidate. The trial’s secondary outcome, occurring from induction to two minutes after intubation: 22.1 percent with ketamine, 17.0 percent with etomidate. Population: critically ill adults intubated at 6 emergency departments and 8 intensive care units in the United States. Source: Casey et al., New England Journal of Medicine, 2025.KetamineEtomidateIn-hospital death by day 2828.1%29.1%Cardiovascular collapse during intubation22.1%17.0%010203040%Critically ill adults, 6 EDs and 8 ICUs, United States. Casey et al., NEJM 2025.
Percentages as reported. The trial enrolled no prehospital patients and excluded trauma.

Where the trial sits in the earlier ketamine vs etomidate evidence

Earlier evidence pointed both ways before this trial became the largest randomized comparison of the two agents. KETASED (Jabre et al., Lancet 2009), the only previous multicenter trial, enrolled 655 patients from French emergency medical services and emergency departments, 469 analysed; at 2 mg/kg ketamine versus 0.3 mg/kg etomidate, maximum organ-failure scores over 3 days didn’t differ significantly (mean difference 0.7 points, 95% CI 0.0 to 1.4), and adrenal insufficiency was more frequent with etomidate (odds ratio 6.7).

A 2025 meta-analysis of 7 randomized trials in adults (Greer et al., Critical Care Medicine) found that ketamine “probably increases hemodynamic instability in the peri-intubation period” (RR 1.29) but “probably decreases the need for initiation of continuous infusion vasopressors” (RR 0.75), and “results in less adrenal suppression” (RR 0.54), and “may have no effect on mortality” (RR 1.00, low certainty). An observational target-trial emulation across 18 Brazilian EDs (Maia et al., JAMA Network Open 2025), 1,810 adults, found higher weighted 28-day mortality with etomidate (RR 1.14) and more new hemodynamic instability with ketamine (24.2% versus 18.9%); the authors call for randomized trials. Sources disagree more on mortality than on peri-intubation instability, which more of them report with ketamine.

Which induction agent do sources favor for a hypotensive patient?

They split. StatPearls states that etomidate “does not affect systemic blood pressure” and “is usually preferable for patients with pre-existing hypotension and trauma.” The trial’s own authors note that ketamine “has been postulated to maintain hemodynamic stability,” and that “some experts specifically recommend ketamine for intubation of patients with sepsis or shock,” then report more collapse with ketamine in their own data. A 2025 meta-analysis that excluded pediatric-only studies (De Mucha and Thomas) found post-induction hypotension with ketamine no different from other agents overall (OR 1.10, 95% CI 0.78 to 1.56). No source here is ranked above another; protocol and medical direction decide.

How does etomidate cause adrenal suppression?

It inhibits 11-beta-hydroxylase, a key enzyme in cortisol synthesis, per StatPearls. How long that effect lasts is stated differently by source: the current AMIDATE label reports reduced cortisol and aldosterone “for approximately 6 to 8 hours,” while the trial’s introduction states that “a single dose decreases cortisol production for up to 72 hours.” KETASED and the Greer 2025 meta-analysis both found more adrenal suppression with etomidate, and the trial itself found no mortality difference, including in sepsis. None of that shows the adrenal effect is harmless; the sources simply report its duration differently.

What the trial cannot tell an EMS crew

The RSI trial ran entirely in hospitals, so three field situations sit outside it: every intubation happened in an ED or ICU, with that setting’s staffing, monitoring, and vasopressors; trauma was excluded outright, as the authors write, “the results may not apply to these patients”; and patients needing intubation too urgently to allow randomization were excluded too, leaving the crash airway outside the trial’s population.

The evidence closest to the field points more than one way. Stanke et al. (2021), 113 adults intubated by one regional prehospital service, found no difference in a 20% systolic drop, 16% etomidate versus 18% ketamine. Smida et al. (2026), the largest, a retrospective US registry study of 10,727 adults with at least one field intubation attempt by 703 EMS agencies, found etomidate linked to lower odds of collapse under a modified definition, though the authors flag “risk of bias from unknown or unmeasured confounders” and call for a randomized trial. A commentary on this trial by DeFilippo on NAEMSP’s blog concludes that ketamine “is still an excellent RSI medication, but it is not as blood pressure neutral as we once believed.” Which agent a service carries, and when each is used, is that service’s own protocol call.

Calculate both induction doses and verify the etomidate cap

Rapid Vent Calculator’s medications card computes both agents from the entered actual body weight under “INDUCTION AGENTS”: ketamine at 2 mg/kg and etomidate at 0.3 mg/kg. For an 80 kg adult, that’s 80 × 2 = 160 mg ketamine and 80 × 0.3 = 24 mg etomidate.

The calculator stops etomidate at 40 mg and shows “Common max 40 mg” once the raw multiplication passes that number, which happens only above about 133 kg. That cap is the calculator’s own behavior, not a labelled figure: the AMIDATE label runs 0.2 to 0.6 mg/kg with no milligram ceiling, StatPearls gives 0.15 to 0.3 mg/kg, and the trial’s median dose given was 20 mg (IQR 20 to 25). No label or guideline located sets a milligram maximum; it’s the app’s own limit, and the crew’s protocol governs the dose given. The app computes both doses for every patient entered; it doesn’t know the blood pressure, the shock state, or the protocol, and it never picks the agent. The ketamine dose gets its own page: the ketamine dose for intubation, source by source.

After induction: sedation, then the first vent settings

Both agents wear off in minutes: ketamine’s labelled surgical-anesthesia duration is 5 to 10 minutes, etomidate’s is 3 to 5. Rocuronium, a paralytic that can follow either one, runs far longer per its FDA label: 31 minutes at 0.6 mg/kg, 67 minutes at 1.2 mg/kg (medians), so the induction agent can wear off first. The ED-AWARENESS study found possible or definite awareness with paralysis in 2.6% of ventilated ED adults. Which drug class goes first is its own question: induction agent vs paralytic, in order. Sedation after the tube is scored on a scale rather than eyeballed, the RASS scale once the induction agent wears off. The trial’s own collapse window ran to 2 minutes after the tube, so that blood-pressure watch carries into the first ventilator minutes. From there the weight switches: tidal volume runs on ideal body weight, not the actual weight either induction dose used. Initial ventilator settings once the induction agent is in picks up from there.

Sources

  1. Casey JD, Seitz KP, Driver BE, et al.; RSI Investigators and the Pragmatic Critical Care Research Group. Ketamine or etomidate for tracheal intubation of critically ill adults. New England Journal of Medicine. 2026;394(16):1608-1620 (published online December 9, 2025). https://pubmed.ncbi.nlm.nih.gov/41369227/ (author manuscript: https://pmc.ncbi.nlm.nih.gov/articles/PMC12711137/)
  2. US Food and Drug Administration. AMIDATE (etomidate) injection prescribing information (Hospira, Inc.). DailyMed; revised April 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7ed5bf8-ba75-44dc-8f81-96b4ad5766be
  3. US Food and Drug Administration. Ketamine Hydrochloride Injection, USP (CIII) prescribing information (Civica, Inc.). DailyMed; revised June 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=58c86d9b-8694-4bd8-8254-f19ee3ad60b0
  4. Hendrix JM, Regunath H. Intubation Endotracheal Tube Medications. In: StatPearls. StatPearls Publishing; updated January 19, 2025. NCBI Bookshelf NBK459276. https://www.ncbi.nlm.nih.gov/books/NBK459276/
  5. Jabre P, Combes X, Lapostolle F, et al.; KETASED Collaborative Study Group. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374(9686):293-300. https://pubmed.ncbi.nlm.nih.gov/19573904/
  6. Greer A, Hewitt M, Khazaneh PT, et al. Ketamine versus etomidate for rapid sequence intubation: a systematic review and meta-analysis of randomized trials. Critical Care Medicine. 2025;53(2):e374-e383. https://pubmed.ncbi.nlm.nih.gov/39570063/
  7. Maia IWA, et al.; Brazilian Airway Registry Cooperation (BARCO) group. Ketamine, etomidate, and mortality in emergency department intubations. JAMA Network Open. 2025;8(12):e2548060. https://pmc.ncbi.nlm.nih.gov/articles/PMC12706683/
  8. de Mucha PV, Thomas S. Incidence of post-induction hypotension following emergency rapid sequence induction with ketamine: a systematic review and meta-analysis. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2025;33:71. https://pmc.ncbi.nlm.nih.gov/articles/PMC12044812/
  9. Stanke L, et al. Hemodynamic effects of ketamine versus etomidate for prehospital rapid sequence intubation. Air Medical Journal. 2021;40(5):312-316. https://pubmed.ncbi.nlm.nih.gov/34535237/
  10. Smida T, Crowe R, Scheidler J, Bardes J. A retrospective comparison of etomidate and ketamine for prehospital rapid sequence intubation. Air Medical Journal. 2026;45(5):477-483. https://pmc.ncbi.nlm.nih.gov/articles/PMC13482005/
  11. DeFilippo M. Understanding the RSI Trial and Its Implications for EMS Airway Management. NAEMSP Blog; December 16, 2025. https://naemsp.org/rsi_trial_ems_airway/
  12. US Food and Drug Administration. Rocuronium bromide injection prescribing information (Hospira, Inc.). DailyMed; revised June 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=309aeb1b-8022-4df7-8194-ae6529e3395c
  13. Pappal RD, Roberts BW, Mohr NM, et al. The ED-AWARENESS Study: A Prospective, Observational Cohort Study of Awareness With Paralysis in Mechanically Ventilated Patients Admitted From the Emergency Department. Annals of Emergency Medicine. 2021;77(5):532-544. https://pubmed.ncbi.nlm.nih.gov/33485698/
  14. Kuhl EA, Perera TB. Prehospital Mechanical Ventilation. In: StatPearls. StatPearls Publishing; updated March 8, 2024. NCBI Bookshelf NBK537072. https://www.ncbi.nlm.nih.gov/books/NBK537072/