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Ketamine vs Etomidate RCT- Which Causes Higher SOFA Score? 

December 4, 2023

Written by Jason Lesnick

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This single center RCT found no difference in maximum Sequential Organ Failure Assessment (SOFA) score between critically ill adult ED patients receiving ketamine vs etomidate for rapid sequence intubation (RSI).

Etomidate for everyone or keep on keepin’ on with ketamine   
This study was a single center, parallel-group, partially blinded (ED team aware of what medication the patient received but ICU was not) RCT that compared ketamine with etomidate for RSI from September 2013 through November 2015. The authors enrolled and randomized 143 patients to either 1 dose of ketamine (2 mg/kg) or etomidate (0.3 mg/kg). 

For the first 103 patients enrolled, the primary outcome was mortality at hospital discharge or at 30 days; however, the outcome was changed to maximum SOFA score while obtaining FDA approval for the Exception from Informed Consent. The authors note that maximum SOFA score has been shown to correlate well with mortality. The study was powered to identify a 2-point between-group-difference (which has previously been considered clinically relevant and used in prior trials), and based on their calculations required 126 patients with complete outcomes. 

73 patients were randomized to etomidate and 70 to ketamine, 14 patients withdrew from the trial, and complete data are available for 129 patients; median age 50 years, 36% women. The median max SOFA score in the ketamine group was 6.5 (IQR 5-9) and 7 (IQR 5-9) in the etomidate group. There was no significant difference between the two groups with a median difference of -0.2 (95%CI -1.4 to 1.1; p = 0.79). Secondary outcomes included first attempt success, incidence of hypotension in the ED, vasopressor-free days, ventilator-free days, ICU free days, and thirty day mortality. None of these had statistically significant differences. 

The authors concluded that based on this study and their review of previous literature, there is not clear evidence that either etomidate or ketamine is superior to the other for use in emergency tracheal intubation.

How will this change my practice?
This reaffirms my practice that based on the currently available evidence either ketamine or etomidate are reasonable options in ED patients who require RSI. I look forward to the results of the currently enrolling study “The Randomized Trial of Sedative Choice for Intubation”.

Editor’s note: This study concluded 8 years ago. Why did they sit on these data for 8 years? Also, 30-day mortality was 11% in the ketamine group and 21% in the etomidate group – with rounding, a difference of -9% (-21 to 3). Although this did not reach statistical significance, it’s concerning. I use ketamine and will continue to do so until I see results of a larger trial. ~Clay Smith

The Effect of Ketamine Versus Etomidate for Rapid Sequence Intubation on Maximum Sequential Organ Failure Assessment Score: A Randomized Clinical Trial. The Journal of Emergency Medicine, Volume 65, Issue 5, 2023, Pages e371-e382, ISSN 0736-4679, https://doi.org/10.1016/j.jemermed.2023.06.009. 

What are your thoughts?