Doctors treating critically ill patients in the emergency room may want to give the sedative etomidate, rather than ketamine, while placing a breathing tube, according to a randomized trial published Dec. 9 in New England Journal of Medicine.
The randomized trial of suppressive selection for intubation (RSI) is the first multicenter trial to demonstrate significant cardiovascular risks from high doses of ketamine (low blood pressure, arrhythmia), side effects that have not been well studied in the past.
“We know that patients are receiving 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 lead author Jonathan Casey, MD, associate professor of medicine in the Department of Allergy, Pulmonary and Critical Care at Vanderbilt University Medical Center.
“Studies like the RSI are extremely important for understanding the treatments that patients are already receiving and for ensuring that patients are receiving the treatments that will have the best results,” he said.
Casey led the trial, along with Brian Driver, MD, and Matthew Prekker, MD, MPH, of Hennepin Healthcare, and a team of patients, clinicians and researchers from six cities across the US
The RSI trial compared the use of ketamine and etomidate during tracheal intubation of 2,365 patients in 14 US emergency departments and intensive care units, including HCMC in Minneapolis. The trial found etomidate to be safe to use, meaning it did not increase the risk of death, and that etomidate significantly reduced the risk of dangerously low blood pressure during the procedure, compared to ketamine.
“Ketamine and etomidate have both been around for decades and are used countless times each year during emergency intubation,” Driver explained. “Despite their widespread use, no large, multicenter trial had ever directly compared the two to determine which medication leads to better patient outcomes until the RSI trial.”
“Our results show that etomidate is a safe option and that ketamine, in some cases, can cause significant drops in blood pressure during intubation,” he continues. “With this new evidence, many clinicians are likely to prefer etomidate when choosing a sedative for critically ill adults. This trial highlights the importance of studying not only new drugs or technologies, but also treatments that are already routinely used to understand which ones really benefit patients.”
Historically, etomidate was the most commonly used sedative, but it was found to impair cortisol production, raising concerns that it could increase the risk of death after intubation. Based on these concerns, some countries have taken etomidate off the market.
In many cases, ketamine has replaced etomidate as the primary sedative during emergency tracheal intubation. This was part of a movement by doctors and patients to use ketamine for a growing number of problems, including acute and chronic pain, depression and post-traumatic stress disorder, despite limited data on its effectiveness and safety.
Ketamine remains a valuable sedation drug for surgery and during mechanical ventilation, but may be used less frequently when there is a risk of low blood pressure.
Casey said the results of the RSI trial, showing that etomidate does not increase the risk of death and causes less hypotension than ketamine, may persuade countries that had taken etomidate off the market to make it available again. At the same time as the paper was released, the RSI trial was presented at the Critical Care Reviews conference in Melbourne, Australia – one of the countries where etomidate has been taken off the market.
For next steps, researchers are evaluating the effect of sedative medications on long-term patient-centered outcomes, such as PTSD symptoms at 12 months.
Finally, Hennepin Healthcare is also helping to lead a large, multicenter randomized trial (BREATHE) that is trying to understand whether using a smaller size breathing tube can prevent injury to patients’ vocal cords and long-term problems with breathing, speaking and swallowing.
The RSI trial was funded by the Patient-Centered Outcomes Research Institute (award number BPS-2022C3-30021) and the National Institutes of Health (award number K23HL153584).
