Ketamine Versus Morphine for Musculoskeletal Trauma Pain: A Meta-Analysis of Randomized Controlled Trials Publisher Pubmed



Fatahi M ; Ebrahimi A ; Aghajani S ; Arab Bafrani M ; Hamouda R ; Mayel M
Source: European Journal of Orthopaedic Surgery and Traumatology Published:2026

Abstract

Background: Pain is a primary reason for emergency department visits and hospitalizations following injuries, and its inadequate management can lead to complications. Effective and safe pain control is crucial in traumatic patient management. Opioids like morphine are commonly used for acute pain due to their effectiveness and rapid action. Ketamine has recently been explored for pain management in various settings. Our meta-analysis tried to evaluate the efficacy and safety of ketamine compared to morphine sulfate in trauma patients experiencing musculoskeletal discomfort. Methods and materials: The work was registered in PROSPERO (CRD420251001307) and observed PRISMA guidelines. An extensive search across PubMed, Web of Science, Scopus, and Embase databases in March 2025 was carried out to identify randomized controlled trials comparing ketamine and morphine for pain management in trauma patients. Two independent reviewers screened and evaluated articles, resolving conflicts with a third reviewer. Inclusion criteria focused on English-language RCTs comparing intravenous or intranasal ketamine to intravenous morphine sulfate in trauma patients with bone fractures or limb soft tissue injuries, reporting pain scores and side effects. Data on study characteristics, interventions, outcomes, and side effects were extracted using an Excel spreadsheet. Quality assessment was accomplished using the Cochrane Risk of Bias (RoB-2) tool. Data analysis involved calculating the standardized mean difference and 95% confidence interval using a random-effect model. Heterogeneity was evaluated with Cochrane’s Q statistic and Hedges’ g I2 estimation. Results: Out of 2020 initial articles, 12 trials published between 1996 and 2024, involving 1892 patients (968 ketamine, 924 morphine), were included. Pain scores were assessed at various intervals. A quality assessment revealed five studies with a high risk of bias, three with a low risk, and four with some concerns. Comparison of pain scores at 30, 60, 90, and 120 min showed no statistically significant differences between the morphine and ketamine groups, with high heterogeneity noticed at all time points (30 min: SMD − 0.38; 95% CI −1.08 to 0.31, p = 0.32, I2 = 94.5%; 60 min: SMD − 0.42; 95% CI −1.3 to 0.46, p = 0.41, I2 = 93.2%; 90 min: SMD − 0.03; 95% CI −0.50 to 0.44, p = 0.91, I2 = 74.8%; 120 min: SMD − 0.44; 95% CI −2.46 to 1.58, p = 0.70, I2 = 95.9%). Regarding side effects, there was a slightly difference in nausea/vomiting, favoring morphine (RR: 0.45; 95% CI 0.20 to 1.03; p = 0.057, I2 = 78.4%). Neurologic side effects were significantly higher in the ketamine group (RR: 2.38; 95% CI 1.23 to 4.63; p = 0.016, I2 = 72.5%). Overall side effects showed no meaningful difference (RR: 0.88; 95% CI 0.43 to 1.80; p = 0.71, I2 = 88.2%). Conclusion: Ketamine and morphine provide comparable analgesia for acute musculoskeletal pain in emergency and trauma units. None of the pooled differences in pain scores reached statistical or clinical significance across various time points, and all pooled mean differences remained below the minimal clinically important difference thresholds. While ketamine may offer a more rapid onset of action, its overall analgesic superiority over morphine was not demonstrated. Both agents were well-tolerated, although ketamine was linked to a higher risk of neurological complications. © The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature 2026.