outlet: UAB press release 

Sedative choice could improve patient outcomes in patients who have been intubated.  

Etomidate proves more effective for sedative use in patient intubations

• Read this story and more at https://www.uab.edu/news/
• The UAB News Studio is available for live or taped interviews with UAB experts.

BIRMINGHAM, Ala. – Intubations are a common medical practice in which doctors insert a tube into the trachea to hold the airway open for patients who cannot breathe effectively due to illness or trauma-related injuries. Results in a recent multisite trial, in which the University of Alabama at Birmingham was a trial site, revealed doctors may want to consider utilizing etomidate, rather than ketamine, during intubation procedures.

outlet: First10 EM blog 

Some topics just get people excited. The drugs we use during intubation – well, people are going to have an opinion. Etomidate was popular while I trained, but was actually hard to find in the emergency department. Then came worries of adrenal suppression. Was etomidate just changing biochemical outcomes, or was it actually changing patient outcomes? Was etomidate increasing mortality? That debate drove many into the arms of ketamine, but the data has always been questionable. We finally have high quality data, in the form of the RSI trial, but has high quality data ever been the deciding factor in a heated debate?

outlet: Em docs blog 

Spoon Feed —
There was no difference in 28-day mortality in critically ill adult patients with ketamine vs. etomidate for rapid sequence induction (RSI), but ketamine increased the need for peri-intubation vasopressor support.

Source
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. doi: 10.1056/NEJMoa2511420. Epub ahead of print. PMID: 41369227.

Key takeaways:

• In the ketamine group, 28.1% died in the hospital by day 28 vs. 29.1% in the etomidate group.
• More patients assigned ketamine vs. etomidate had a greater than 30 mm Hg reduction in systolic blood pressure.

Perspective from Robert Glatter, MD, FACEP, FAAEM

In-hospital mortality by day 28 did not significantly differ based on use of ketamine or etomidate to induce anesthesia in critically ill adults undergoing intubation, according to results published in The New England Journal of Medicine.

outlet: Drugs.com  

WEDNESDAY, Dec. 17, 2025 — Use of ketamine to induce anesthesia does not result in lower in-hospital death by day 28 compared with etomidate among critically ill adults undergoing tracheal intubation, according to a study published online Dec. 9 in the New England Journal of Medicine.

Jonathan D. Casey, M.D., from the Vanderbilt Health in Nashville, Tennessee, and colleagues conducted a randomized trial in 14 emergency departments and intensive care units in the United States involving critically ill adults who were undergoing tracheal intubation. Participants were randomly assigned to receive ketamine or etomidate for induction of anesthesia (1,176 and 1,189 participants, respectively).

outlet: ACP Hospitalist website 

Critically ill patients randomized to ketamine for anesthesia during tracheal intubation had similar inpatient mortality and higher risk of cardiovascular collapse during intubation than those who received etomidate, according to a new multicenter trial.

outlet: Healthday News Story 

No reduction seen in in-hospital death by day 28 with use of ketamine rather than etomidate to induce anesthesia in critically ill adults undergoing tracheal intubation

4250 Newsletter subscribers and 5000 Paper of the Day subscribers, all of whom were notified of the RSI trial results 

outlet: Critical Care Review newsletter 

outlet: American Association for Respiratory Care blog 

A new study published in The New England Journal of Medicine suggests that etomidate may be a better sedative for patients undergoing endotracheal intubation than ketamine.

The finding comes from investigators at Vanderbilt Health and elsewhere who conducted a randomized trial involving 2,365 patients in 14 U.S. emergency departments and ICUs. About half of the patients were intubated using ketamine, and the other half were intubated using etomidate.

The use of etomidate significantly decreased the risk of dangerously low blood pressures during the procedure when compared with ketamine without any impact on the risk of death.

Spoon Feed
There was no difference in 28-day mortality in critically ill adult patients with ketamine vs. etomidate for rapid sequence induction (RSI), but ketamine increased the need for peri-intubation vasopressor support.

Watch the pendulum swing…
Etomidate causes early adrenal suppression. Ketamine may cause hypotension during induction. Observational studies have been back and forth on which is the better drug for RSI.

This was a multicenter RCT with 2,365 critically ill adult patients randomized to ketamine or etomidate for RSI. For the primary outcome of in-hospital 28-day mortality, there was no difference between the two groups: 28.1% (330/1173) ketamine vs. 29.1% (345/1,186) etomidate cohorts (–0.8% (95%CI −4.5 to 2.9, p = 0.65). But there was a big difference in the number of patients with cardiovascular (CV) collapse (SBP <65, new vasopressors, arrest) within 2 minutes of intubation: 22.1% (260/1,176) ketamine vs. 17% (202/1,189) etomidate cohort (difference 5.1% 95%CI 1.9 to 8.3), largely driven by new vasopressors. In subgroup analysis, CV collapse was even more pronounced in septic shock patients: 30.6% ketamine vs. 20.9% etomidate group (difference 9.7%; 95%CI 4.6 to 14.9).

Outlet: JournalFeed

outlet: The Bottom Line website 

Clinical Question

• Among adults with non‑traumatic critical illness undergoing emergency tracheal intubation in the ED or ICU, how does induction with ketamine (1–2 mg/kg IV, dosed by actual body weight) versus etomidate (0.2–0.3 mg/kg IV, dosed by actual body weight) affect 28‑day mortality?

outlet: Pharmacy – Emergency Medicine Deep Dive Podcast 

In this episode, we dive into the RSI Trial, a groundbreaking study comparing ketamine and etomidate for rapid sequence intubation in critically ill adults. While the trial found no difference in 28-day mortality between the two drugs, it revealed that ketamine was linked to more episodes of cardiovascular collapse, largely due to increased vasopressor use. We unpack the clinical debate around this finding, exploring whether it reflects true hemodynamic instability or the effects of ketamine’s stronger analgesia. Tune in as we explore what this means for critical care practice and challenge the assumption that ketamine is always the safer choice.

Outlet: The World’s Okayest Medic Podcast 

outlet: HCMC press release 

Doctors treating seriously ill patients in an emergency setting may want to give the sedative etomidate, rather than ketamine, while placing a breathing tube, according to a randomized trial published Dec. 9 in the New England Journal of Medicine.

The Randomized Trial of Sedative Choice for Intubation (RSI) is the first multicenter trial to demonstrate significant cardiovascular risks of high doses of ketamine (low blood pressure, arrhythmia), side effects that have not been well studied in the past.

Outlet: Clinical Advisor 

In critically ill adults undergoing emergency tracheal intubation, etomidate did not increase the risk of in-hospital death and resulted in fewer episodes of cardiovascular collapse compared with ketamine, according to findings published in the New England Journal of Medicine. Cardiovascular collapse is a peri-procedural outcome defined as severe hypotension, new or increased vasopressors, cardiac arrest, or death. The occurrence of cardiovascular collapse during tracheal intubation of critically ill adults increases patients’ risk of in-hospital mortality.

 

outlet: Wake Forest press release 

It’s the first study to demonstrate cardiovascular risks of high doses of ketamine (low blood pressure, arrhythmia), side effects that have not been well studied in the past.Share:Share on FacebookShare on BskyShare on XShare on LinkedInShare via Email

Doctors treating seriously ill patients in an emergency setting may want to give the sedative etomidate, rather than ketamine, while placing a breathing tube, according to a randomized trial published Dec. 10 in the New England Journal of Medicine.

The Randomized Trial of Sedative Choice for Intubation (RSI) is the first multicenter trial to demonstrate significant cardiovascular risks of high doses of ketamine (low blood pressure, arrhythmia), side effects that have not been well studied in the past.

Outlet: VUMC Press Release

outlet: Emcrit

The RSI trial was just published, comparing ketamine versus etomidate. Unless you’re living under a rock, you’ve probably already heard about it. So I’m not going to recap the trial, I’ll get right into the key bits.

Outlet: Respiratory Therapy News Story 

Results of a clinical trial comparing sedation of intubated patients using ketamine or etomidate found greater risks and fewer benefits when using ketamine.

— Large randomized trial weighs survival and cardiovascular complications

outlet: Sedative Choice May Boost Breathing Tube Outcomes

Outlet: News Medical Life Sciences 

To support seriously ill patients with a breathing machine, doctors must place a breathing tube. Before intubation, doctors give a medicine to make patients unconscious, most commonly ketamine or etomidate. Whether ketamine improves survival compared with etomidate was not known. The RSI trial compared ketamine with etomidate in 2,365 patients across 14 emergency departments and ICUs in the United States. The study showed similar survival with both drugs, but ketamine was associated with more cardiovascular collapse during intubation.

When critically ill patients need a breathing machine, a breathing tube is placed through the mouth and into the windpipe. Before placing the breathing tube, doctors give a medication to induce unconsciousness. In the United States, ketamine and etomidate are the two most commonly used medications for this purpose, but prior studies raised concern that etomidate might worsen outcomes. The RSI trial evaluated whether using ketamine instead of etomidate improves survival or reduces complications during emergency tracheal intubation.

Importance

Among critically ill adults undergoing tracheal intubation, complications during the procedure—including severe low blood pressure and cardiac arrest—can lead to organ injury and death. Before the RSI Trial, it was uncertain whether choosing ketamine rather than etomidate reduces mortality for critically ill adults undergoing emergency intubation.

Objective

To determine the effect of ketamine compared with etomidate for induction of anesthesia on in-hospital death by day 28 among critically ill adults undergoing tracheal intubation in emergency departments and intensive care units.

Interventions

In a randomized trial conducted in 14 emergency departments and ICUs in the United States, critically ill adults undergoing tracheal intubation were randomly assigned to receive ketamine or etomidate for induction of anesthesia. The primary outcome was in-hospital death from any cause by day 28. The secondary outcome was cardiovascular collapse during intubation, defined as systolic blood pressure <65 mm Hg, receipt of a new or increased dose of vasopressors, or cardiac arrest.

Results

Among 2,365 patients included in the trial population, 28-day in-hospital mortality occurred in 330 of 1,173 (28.1%) in the ketamine group and 345 of 1,186 (29.1%) in the etomidate group (adjusted risk difference, –0.8 percentage points; 95% CI, –4.5 to 2.9; P = 0.65). Cardiovascular collapse during intubation occurred in 260 of 1,176 (22.1%) in the ketamine group and 202 of 1,189 (17.0%) in the etomidate group (risk difference, 5.1 percentage points; 95% CI, 1.9 to 8.3). Prespecified safety outcomes were similar in the two groups.

Conclusions and Relevance

Among critically ill adults undergoing tracheal intubation, induction with ketamine did not result in a lower incidence of death by day 28 compared with etomidate, and was associated with a higher incidence of cardiovascular collapse during intubation.

ClinicalTrials.gov Identifier: NCT05277896
Manuscript Title: Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults
Journal: New England Journal of Medicine
PMID: 41369227

outlet: EmCrit podcast 

Just off embargo: The RSI Trial

Ketamine vs. Etomidate for the induction of critically ill patients for RSI

I am lucky enough to be joined by lead authors:

Jonathan Casey

and

Brian Driver