Ketamine vs Etomidate – Hypotension At Induction

Written by Clay Smith

Spoon Feed
Ketamine was associated with a greater risk of peri-intubation hypotension than etomidate.

Why does this matter?
Ketamine has magical powers causing catecholamine release and usually raises heart rate and BP. However, it may cause myocardial depression. Etomidate is also known to be hemodynamically neutral yet is known to cause adrenal suppression for about 24 hours, which is of questionable clinical significance. What if ketamine was compared with etomidate in regard to hypotension?

Ketamine raises BP, right?
This was a retrospective look at National Emergency Airway Registry (NEAR) data comparing the hemodynamic effects in non-hypertensive patients over 14 years old in 738 intubations with ketamine and 6,068 with etomidate. To my surprise, ketamine was more likely to cause peri-intubation hypotension (defined as <100 systolic) than etomidate; 18.3% vs 12.4%, respectively (5.9% difference, 95%CI 2.9 to 8.8%). More patients needed intervention for peri-intubation hypotension with ketamine as well. Patients receiving ketamine were more likely to have a difficult airway and have video over direct laryngoscopy. Yet even with logistic regression and adjustment, the increased risk of peri-intubation hypotension remained. Low-dose ketamine (≤1mg/kg) was not found to be associated with hypotension. Results could have been confounded if doctors chose ketamine for use in sicker, more unstable patients.

Three take home points the authors emphasized:

  1. Ketamine may not be superior for hemodynamics in unstable patients.

  2. Optimize pre-induction resuscitation no matter what drug you choose.

  3. Use lower dose ketamine in very unstable patients.

Source
Ketamine versus Etomidate and Peri-Intubation Hypotension: A National Emergency Airway Registry Study. Acad Emerg Med. 2020 Jun 26. doi: 10.1111/acem.14063. Online ahead of print.

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Another Spoonful (added 5/2/2021)
Written by Clay Smith

Scott Weingart, with the EMCrit podcast, covers this paper. Scott notes in the podcast, “The perfect RCT has already been done,” that answers the question of whether ketamine is as hemodynamically stable as etomidate. His conclusion, based on the 2009 Jafre, et al KetaSED RCT is that, “Ketamine is at least as stable as etomidate.” Scott mentions that these retrospective NEAR registry studies are unhelpful, since higher quality RCT-data already exists. He thinks the KetaSED RCT is, “Almost pristine for the question.” While I agree that the results of KetaSED are somewhat reassuring, I wouldn’t go as far as to say it is the perfect RCT to answer this question. The primary outcome of KetaSED is maximum SOFA score during the first 3 days in the ICU; power calculations and sample size are driven by this outcome. Although the difference in BP pre- and post-intubation is recorded, KetaSED isn’t powered to determine non-inferiority for this outcome. In fact, ketamine drops SBP and DBP more than etomidate, though the difference is not statistically significant. See figure and red box below. At the end of the day, I still reach for ketamine in almost all patients for induction, especially the ones who are unstable. But I don’t think that KetaSED has provided definitive data to settle this question. If anything, KetaSED raises the same concerns as these NEAR registry studies (JF posts 8/3/20 and 8/4/20) – namely, ketamine appears to be associated with a drop in BP in some super-sick patients. The only definitive answer would come from an RCT designed and powered to detect noninferiority in the change in BP pre- and post-intubation comparing etomidate and ketamine. That would be pristine!

From KetaSED

3 thoughts on “Ketamine vs Etomidate – Hypotension At Induction”

    1. claybartonsmith@gmail.com

      That is true. But the authors expressed some uncertainty and said, “it seems prudent that patients who remain frankly unstable or in shock despite attempts to optimize before intubation, should receive lower induction doses.”

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