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 Feb:76:140-149. doi: 10.1016/j.ajem.2023.11.056. Epub 2023 Dec 3.


Objective: To compare the effectiveness and safety of ketamine and morphine in adult patients with acute pain in emergency department (ED) by using a meta-analysis method.

Methods: This study was based on the Cochrane methodology for conducting a meta-analysis. Only randomized controlled trials (RCTs) were eligible for this study, with an experimental group that received low-dose ketamine and a control group that received morphine. The participants were adults who had acute pain in the ED. The primary outcome measures were the numeric rating scale (NRS) and visual analog scale (VAS). The secondary outcome measures were the complete resolution of pain, NRS reduction ≥3 points, NRS reduction ≥50% or 60%, change of NRS score, change of VAS score, rescue analgesia, satisfaction and adverse events. Subgroup analysis was performed for studies with intravenous and intranasal administration of ketamine. The Review Manager Database was used to analyze the included studies.

Results: 15 RCTs involving 1768 patients were included. The ketamine group had lower NRS scores than morphine group at 30 min (MD, -0.77 [95% CI, -0.93 to -0.61]; p < 0.00001), while the morphine had better analgesic effects at 120 min after treatment (MD, 0.33 [95% CI, 0.15 to 051]; p = 0.0003). The subjects of complete resolution of pain in the ketamine group performed better than those in the morphine group at 15 min (RR 3.18, 95% CI 1.75 to 5.78; p = 0.0001). Compared with the morphine group, the ketamine group had a lower incidence of adverse events requiring intervention (RR, 0.34 [95% CI, 0.18 to 0.66]; p = 0.001). Subgroup analysis of intravenous ketamine showed that ketamine had lower VAS score than the morphine group at 30 min. However, also on the 30-min VAS score, intranasal ketamine analgesia was less effective than morphine.

Conclusions: Ketamine had better analgesic effects in the early stages after treatment, while morphine maintained more durable effects. Compared with morphine, ketamine had a lower incidence of adverse events requiring intervention. The results of subgroup analysis showed that intravenous administration of ketamine was more effective than intranasal administration.

Keywords: Acute pain; Ketamine; Meta-analysis; Morphine.

Publication types

  • Meta-Analysis

MeSH terms

  • Acute Pain* / drug therapy
  • Adult
  • Analgesics / therapeutic use
  • Analgesics, Opioid
  • Double-Blind Method
  • Emergency Service, Hospital
  • Humans
  • Ketamine*
  • Morphine
  • Randomized Controlled Trials as Topic


  • Ketamine
  • Morphine
  • Analgesics, Opioid
  • Analgesics