Doctors in emergency settings may want to use etomidate instead of ketamine when intubating critically ill patients, according to a recent randomized trial published in the New England Journal of Medicine. The study, known as the Randomized Trial of Sedative Choice for Intubation (RSI), is the first multicenter trial to highlight significant cardiovascular risks associated with high doses of ketamine, such as low blood pressure and arrhythmia—side effects that have not been thoroughly examined before.
"We know that patients receive treatments every day in hospitals around the world that have never been evaluated in a rigorous study and may be ineffective or even harmful," said Jonathan Casey, MD, associate professor at Vanderbilt University Medical Center and lead author of the study. "Studies like RSI are critically important to understand the treatments that patients are already receiving and to ensure that patients receive the treatments that will result in the best outcomes."
Casey led the research alongside Brian Driver, MD, and Matthew Prekker, MD, MPH, from Hennepin Healthcare. The team included clinicians and researchers from six U.S. cities. The RSI trial compared ketamine and etomidate during tracheal intubation on 2,365 patients across 14 emergency departments and intensive care units nationwide.
The findings indicated that etomidate did not increase mortality risk but significantly reduced occurrences of dangerously low blood pressure during intubation compared to ketamine. "Ketamine and etomidate have both been around for decades and are used countless times each year during emergency intubations," said Driver. "Despite their widespread use, no large, multi-center trial had ever directly compared the two to determine which medication leads to better outcomes for patients until the RSI trial." He added: "Our results show that etomidate is a safe option and that ketamine, in some situations, can trigger significant drops in blood pressure during intubation. With this new evidence, many clinicians are likely to favor etomidate when choosing a sedative for critically ill adults. This trial highlights the importance of studying not only new drugs or technologies but also the treatments already in routine use so we can understand which ones truly benefit patients."
Etomidate was previously more commonly used but concerns over its impact on cortisol production led some countries to withdraw it from clinical practice. As a result, ketamine became more widely used for emergency tracheal intubation despite limited data on its safety profile.
While ketamine remains valuable for sedation during certain procedures or mechanical ventilation, experts suggest it may be less suitable when there is a risk of hypotension.
Casey noted that these results might prompt countries which removed etomidate from their markets to reconsider its availability: “showing that etomidate does not increase the risk of death and causes less hypotension than ketamine may convince countries...to make it available again.” The findings were also presented at the Critical Care Reviews conference in Melbourne—a country where etomidate has been withdrawn.
Researchers plan further studies on how sedative medications affect long-term patient outcomes such as symptoms related to post-traumatic stress disorder one year after treatment. Additionally, Hennepin Healthcare is co-leading another multicenter randomized trial called BREATHE focused on whether using smaller breathing tubes can reduce injury to vocal cords as well as long-term complications with breathing or swallowing.
Funding for this research came from awards by the Patient-Centered Outcomes Research Institute (BPS-2022C3-30021) and National Institutes of Health (K23HL153584).
