Outlet: EM-RAP 

Ketamine or etomidate for tracheal intubation of critically ill adults Casey JD, Seitz KP, Driver BE, et al. N Engl J Med. Published online December 9, 2025. doi:10.1056/NEJMoa2511420

SUMMARY:

• Many articles have compared etomidate vs ketamine as induction agents for rapid sequence intubation (RSI), and the retrospective and prospective trial data have shown mixed results. A major concern is etomidate’s effects on the adrenal glands. Laboratory testing has indicated that etomidate affects markers of adrenal function, even when administered as a single dose; however, real effects on clinical outcomes have been much more difficult to demonstrate. We have recently covered a massive retrospective study on the topic, which reported a 3% absolute increase in mortality with etomidate use in a 40,000-patient outcome cohort, but this finding was almost certainly influenced by unmeasured but highly relevant confounders.

outlet: Medscape Perspective Commentary  

Robert D. Glatter, MD: Hi, and welcome. I’m Dr Robert Glatter, medical advisor for Medscape Emergency Medicine. Today, I’ll be speaking with Dr Ken Milne, an emergency physician at Strathroy Middlesex General Hospital in Ontario, Canada, and the founder of the well-known podcast, The Skeptics’ Guide to Emergency Medicine, about the results of the Randomized Trial of Sedative Choice for Intubation (RSI), published on December 9, 2025, in The New England Journal of Medicine. RSI compared the safety and efficacy of two common induction agents, etomidate and ketamine, in various clinical settings and under different physiologic conditions.

Outlet: Pharmacy to Dose: The Critical Care Podcast  

Youtube: https://youtu.be/uWx3tYZ_mfs    
Apple: https://podcasts.apple.com/us/podcast/pharmacy-to-dose-the-critical-care-podcast/id1479298456?i=1000746033779   
Spotify: https://open.spotify.com/episode/5R9a9Es0lggximB2iC6Gw0?si=ca7eca2d4edf455f   

Outlet: The Skeptics Guide to Emergency Medicine Podcast 

Reference:  Casey et al. RSI Investigators and the Pragmatic Critical Care Research Group. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. NEJM. 2025 Dec

Guest Skeptic: Dr. Scott Weingart is an ED Intensivist from New York. He did fellowships in Trauma, Surgical Critical Care, and ECMO. Scott is best known for talking to himself about Resuscitation and Critical Care on the podcast EMCrit, which has been downloaded more than 50 million times.

outlet: Emergency Medicine Education blog 

There remains significant controversy regarding the optimal induction agent for rapid sequence intubation (RSI), particularly when comparing etomidate and ketamine. Concerns surrounding etomidate center on its potential to cause transient adrenal suppression, which has raised questions about possible harm in critically ill patients. However, it is unclear whether this theoretical risk translates into meaningful clinical outcomes, especially given that these patients often present with existing or impending multi-organ dysfunction. In this context, attributing adverse outcomes to a single induction dose, without robust control or randomization, may overstate its clinical impact.

Despite these ongoing debates, recent evidence has helped clarify this issue. By the end of 2025, two notable studies were published comparing etomidate and ketamine for RSI in critically ill patients.

outlet: St. Emlyn’s Emergency Medicine blog 

For as long as I can remember, emergency and critical care clinicians have debated the optimal induction agent for tracheal intubation in the critically ill. When I started my anaesthetic placements, I used only two drugs for an RSI, Thiopentone and Suxamethonium. Anything else was considered ‘fancy’ amongst the older anaesthetists. The cool kids were using Etomidate/Sux as an alternative, and as I wanted to move with the times, that became my go-to regimen for many years. That changed when Ketamine became the standard here in Virchester, and these days it’s rare that I use anything else, to be honest. I even still occasionally use Etomidate in selected cases (mostly cardioversions), but the logic behind that is not clear (even to me).

Outlet: ECC Podcast 

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.

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: 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: 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.

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: 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: 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

We start our Critical Care Reviews Down Under coverage with RSI talking with the first author of the “Ketamine versus Etomidate for Adults Receiving Emergency Endotrachael Intubation”, Jonathan Casey! We will pick up the rest of our CCR Down Under Coverage after the holiday break!

outlet: ICU-Ed and Todd-Cast podcast 

Outlet: Hennepin airway podcast 

outlet: Flightbridge ED podcast