In this episode, I’ll discuss some possible negative effects of using low-dose ketamine to achieve an opioid-sparing effect in critically ill patients.
Using a low-dose ketamine infusion has been recommended by recent sedation guidelines for the purpose of reducing opioid consumption. This is however a surrogate outcome that may or may not be associated with any clinically meaningful benefit.
The 2018 PADIS Guidelines published by the Society of Critical Care Medicine gave a positive recommendation for the use of ketamine saying:
We suggest using low-dose ketamine (0.5 mg/kg IVP x 1 followed by 1-2 μg/kg/min infusion) as an adjunct to opioid therapy when seeking to reduce opioid consumption in postsurgical adults admitted to the ICU.
This was a conditional recommendation based on very low levels of evidence. Its inclusion in the guidelines was based on some systematic reviews in non-ICU patients and a single randomized controlled trial of 93 surgical ICU patients that the panel described as “generally positive”.
Back in episode 957 I discussed a review article from the from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology that was neutral on the use of ketamine for analogosedation in ICU patients, essentially saying that you could either use it or not.
Now a group of authors have published a small single center randomized, double-blind, controlled trial looking at the Effect of Low-Dose Ketamine Infusion in the Intensive Care Unit on Postoperative Opioid Consumption and Traumatic Memories After Hospital Discharge. In this study, 118 ICU patients were randomized to receive adjunctive ketamine 1.5 µg/kg/min or placebo.
The authors found that low-dose ketamine was associated with a statistically significant reduction in ICU opioid use of 15%. The benefit was probably greatest in patients with intraabdominal surgery. However the authors also conducted a telephone interview after ICU discharge with some of the patients and were able to analyze long term data for 45 patients in total. In these interviews, low-dose ketamine use was significantly associated with frightening and delusional memories of critical illness and ICU treatment in 65% of patients vs only 41% with placebo.
While this is a tiny, single-center study that should be replicated before drawing definitive conclusions, it does give extra weight to the opinions of the review discussed in episode 957 that low dose ketamine might not deserve a guideline recommendation suggesting it be used routinely as an adjunct for analgosedation in all ICU patients.
The article in this episode is a selection from my Hospital Pharmacy Academy’s weekly literature digest. Have you ever felt like your physician colleagues are one step ahead of you with new literature developments? Every week, Academy members are provided a summary curated and explained by me of the top hospital pharmacy-related articles published that week from over 20 major journals and sources to save you time and keep you up to date with the literature. To get immediate access, go to pharmacyjoe.com/academy.
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