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Ketamine vs Morphine for Acute Pain

March 4, 2024

Written by Samuel Rouleau

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A meta-analysis of 15 randomized trials found that ketamine had a quicker analgesic effect than morphine, but morphine exhibited sustained reduction in pain at 120 minutes.

A tale of two pain receptors
This meta-analysis included 15 randomized trials comparing the use of ketamine to morphine for acute pain in the ED. The primary outcome was pain quantified by the numeric rating scale (NRS). Among the studies, the dose of morphine was 0.1 mg/kg but ranged between 0.1 – 0.5 mg/kg for intravenous ketamine.

Those that received ketamine reported a lower NRS score at 30 minutes, though the mean difference in pain score was only 0.77. At 120 minutes, morphine had a lower NRS score than ketamine by 0.33. In two studies, ketamine was more likely to completely resolve pain at 15 minutes, though there was no difference between ketamine and morphine at 30, 60, 90, or 120 minutes. The meta-analysis found no difference between magnitude of pain reduction and the need for rescue analgesia between the two groups. The total adverse effects were low in both groups. There was a higher need for “intervention” in the morphine group, as 28 patients who received morphine required supplemental oxygen therapy compared to 8 in the ketamine group. There were no events of respiratory distress or cardiac arrest.

How will this change my practice?
Cards on the table, ketamine is one of my favorite medications. Unfortunately, I am underwhelmed by this meta-analysis.

  • I typically use opiates before ketamine. I use pain-dose ketamine early in patients who continue to have significant pain after opiates, are on a lot of outpatient opiates and I want to target a different pain receptor, or if there is concern for respiratory depression or hemodynamic instability.
  • I wonder if the quicker resolution of symptoms in the ketamine group would disappear if compared to fentanyl instead of morphine.
  • I was surprised by the heterogeneity in the ketamine dosing. For pain-dose ketamine, I stick with 0.1 – 0.3 mg/kg. Anything above 0.3 mg/kg makes me worried about potential dissociation.

Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: A meta-analysis of 15 randomized controlled trials. Am J Emerg Med. 2024;76:140-149. doi:10.1016/j.ajem.2023.11.056

What are your thoughts?