Background Recent studies have increasingly investigated the efficacy and safety of ketamine for the management of acute pain in emergency settings and compared it with standard treatments, such as morphine; however, the results remain inconsistent. This updated meta-analysis aimed to investigate the efficacy of low-dose ketamine compared to morphine on the severity of acute pain in emergency situations. Methods Web of Science, the Cochrane Library, PubMed, and Scopus were systematically searched from their establishment to June 2, 2025, to identify randomized controlled trials comparing the effect of ketamine with morphine on the severity of acute pain in emergency situations. We used a random-effects model to pool data. Results Twenty studies with 2559 participants were included. Compared to morphine, ketamine did not significantly change the numerical rating scale (NRS) score 15 min after administration (standardized mean difference (SMD) (SMD) -0.23, 95% confidence interval (CI) (-0.47, 0.00), I2 = 70.92%), 30 min after administration (SMD − 0.08, 95% CI (-0.23, 0.08), I2 = 55.94%), 45 min after administration (SMD 0.09, 95% CI (-0.16, 0.33), I2 = 69.76%), 60 min after administration (SMD 0.04, 95% CI (-0.16, 0.24), I2 = 74.54%), 90 min after administration (SMD − 0.09, 95% CI (-0.37, 0.19), I2 = 63.86%), and 120 min after administration (SMD − 0.01, 95% CI (-0.18, 0.16), I2 = 34.61%). Similarly, compared to morphine, ketamine did not significantly change the visual analogue scale (VAS) score 15 min, 30 min, and 60 min after administration. The two groups did not significantly differ in terms of complete resolution of pain at 30 min, 60 min, and 120 min after administration and the need for rescue analgesia. Ketamine did not increase the overall risk of adverse events (risk ratio (RR) 1.35, 95% CI (0.87, 2.09), I2 = 71.87%) and nausea (RR 0.99, 95% CI (0.68, 1.44), I2 = 24.94%), but significantly increased the risk of dizziness (RR 1.48, 95% CI (1.08, 2.03), I2 = 42.59%) and emergence phenomenon (RR 19.06, 95% CI (3.77, 96.47), I2 = 0.00%) compared to morphine. In subgroup analysis, intravenous ketamine and lower doses of ketamine (≤ 0.3 mg/kg) were more effective than intranasal ketamine and higher doses of ketamine (more than 0.3 mg/kg) in decreasing the severity of acute pain. Conclusion There is no significant difference in efficacy between ketamine and morphine in controlling the severity of acute pain, but ketamine faces greater safety issues compared to morphine.

The effect of low-dose ketamine compared to morphine on the severity of acute pain in emergency situations: a systematic review and meta-analysis

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2025年11月26日

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Jun Zhang,
Bin Ma

摘要

Background

Recent studies have increasingly investigated the efficacy and safety of ketamine for the management of acute pain in emergency settings and compared it with standard treatments, such as morphine; however, the results remain inconsistent. This updated meta-analysis aimed to investigate the efficacy of low-dose ketamine compared to morphine on the severity of acute pain in emergency situations.

Methods

Web of Science, the Cochrane Library, PubMed, and Scopus were systematically searched from their establishment to June 2, 2025, to identify randomized controlled trials comparing the effect of ketamine with morphine on the severity of acute pain in emergency situations. We used a random-effects model to pool data.

Results

Twenty studies with 2559 participants were included. Compared to morphine, ketamine did not significantly change the numerical rating scale (NRS) score 15 min after administration (standardized mean difference (SMD) (SMD) -0.23, 95% confidence interval (CI) (-0.47, 0.00), I² = 70.92%), 30 min after administration (SMD − 0.08, 95% CI (-0.23, 0.08), I² = 55.94%), 45 min after administration (SMD 0.09, 95% CI (-0.16, 0.33), I² = 69.76%), 60 min after administration (SMD 0.04, 95% CI (-0.16, 0.24), I² = 74.54%), 90 min after administration (SMD − 0.09, 95% CI (-0.37, 0.19), I² = 63.86%), and 120 min after administration (SMD − 0.01, 95% CI (-0.18, 0.16), I² = 34.61%). Similarly, compared to morphine, ketamine did not significantly change the visual analogue scale (VAS) score 15 min, 30 min, and 60 min after administration. The two groups did not significantly differ in terms of complete resolution of pain at 30 min, 60 min, and 120 min after administration and the need for rescue analgesia. Ketamine did not increase the overall risk of adverse events (risk ratio (RR) 1.35, 95% CI (0.87, 2.09), I² = 71.87%) and nausea (RR 0.99, 95% CI (0.68, 1.44), I² = 24.94%), but significantly increased the risk of dizziness (RR 1.48, 95% CI (1.08, 2.03), I² = 42.59%) and emergence phenomenon (RR 19.06, 95% CI (3.77, 96.47), I² = 0.00%) compared to morphine. In subgroup analysis, intravenous ketamine and lower doses of ketamine (≤ 0.3 mg/kg) were more effective than intranasal ketamine and higher doses of ketamine (more than 0.3 mg/kg) in decreasing the severity of acute pain.

Conclusion

There is no significant difference in efficacy between ketamine and morphine in controlling the severity of acute pain, but ketamine faces greater safety issues compared to morphine.