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Patients undergoing major orthopedic surgery have typically suffered moderate to severe pain after their procedure.1 Though the recent use of peripheral nerve blocks has helped blunt that pain, they typically wear off in 24 hours, and patients are forced to resort to intravenous and oral opioids to help them recover. In the setting of an opioid crisis in the United States, helping to decrease the need for narcotics in a vulnerable patient population might be of great interest to clinicians. And it would appear that help might be on the way: low-dose ketamine.

In our recent systematic review, we searched for RCTs of low-dose ketamine, an older intravenous anesthetic, in adult patients undergoing orthopaedic procedures that are quite painful: joint replacement, back surgery, trauma, and arthroscopic reconstruction.2 Our meta-analysis included 20 trials with 1271 patients, and showed that low-dose/microdose ketamine reduced total opioid/narcotic use at 24 and 48 hours when compared to placebo. Pain scores using the Visual Analogue Scale (VAS) were also lower at those time points. And though heterogeneity continues to be an issue with reviews of ketamine, sensitivity analyses substantially decreased the heterogeneity while still demonstrating a positive benefit from the drug. The overall GRADE of the evidence was “Moderate”.

Of note, there have been concerns over ketamine causing unwanted side effects like hallucinations and nausea, but our analysis showed no statistical difference between the drug versus placebo. Although ketamine might play a role in decreasing the incidence of chronic pain after these procedures, there are insufficient studies at present to provide a definitive answer.

Low dose ketamine in patients undergoing total joint replacement, back surgery, and arthroscopic reconstruction appears to demonstrate a significant reduction in narcotic use and pain scores with few side effects. A recommended dose would be 0.5 mg/kg as a bolus before incisions, +/- an infusion of 2-5 mcg/kg/min, to be stopped at wound closure.

Access the article:

Low dose ketamine in painful orthopedic surgery: a systematic review and meta-analysis. BJA 2019; 123: 326-35.

J. Mark Riddell is a physician and graduate of the MSc in Evidence-Based Health Care programme at the University of Oxford, and an anesthesiologist at Southern New Hampshire Medical Center in Nashua, NH, USA.

Competing Interests: The review was undertaken as part of the MSc in EBHC.


  1. Gebershagen HJ, Aduckathil S, van Wijck AJM, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology 2013; 118: 934-44.
  2. Riddell JM, Trummel JM, Onakpoya IJ. Low dose ketamine in painful orthopedic surgery: a systematic review and meta-analysis. BJA 2019; 123: 326-35.