Authors: Dr. Mansoureh Fatahi , Dr. Saba Aghajani , Dr. Alireza Ebrahimi

Abstract

Background: Pain is a primary reason for emergency department (ED) visits and hospitalizations following injuries, and its inadequate management can lead to complications. Effective and safe pain control is crucial in traumatic patient management. While 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. This meta-analysis aimed to compare the efficacy and safety of morphine sulfate and ketamine in trauma patients experiencing musculoskeletal pain.

Methods and materials: This meta-analysis was registered in PROSPERO (CRD420251001307) and followed PRISMA guidelines. An extensive search was conducted across PubMed, Web of Science, Scopus, and Embase databases in March 2025 to identify randomized controlled trials (RCTs) comparing ketamine and morphine for pain 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 (IV) or intranasal (IN) ketamine to IV morphine sulfate in trauma patients with bone fractures or soft tissue injuries, reporting pain scores and side effects. Non-RCTs, observational studies, case reports, review articles, and studies with other comparison groups were excluded. Data on study characteristics, interventions, outcomes, and side effects were extracted using an Excel spreadsheet. Quality assessment was performed using the Cochrane Risk of Bias (RoB-2) tool. Data analysis involved calculating the standardized mean difference (SMD) and 95% confidence interval (CI) using a random-effect model. Heterogeneity was assessed with Cochrane’s Q statistic and Hedges’ g I2 estimation. Sensitivity analysis and visual/statistical assessments (funnel plots, Egger’s test) for publication bias were also performed.

Results: Out of 2020 initial articles, 12 RCTs published between 1996 and 2024, involving 1892 patients (968 ketamine, 924 morphine), were included. Morphine doses varied, primarily 0.1 mg/kg IV, while ketamine doses ranged from 0.1 to 0.5 mg/kg IV and 0.3 to 1.6 mg/kg IN. 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 minutes showed no statistically significant differences between the morphine and ketamine groups, with high heterogeneity observed at all time points (30 minutes: SMD -0.38, 95% CI -1.08 to 0.31, p=0.32, I2=94.5%; 60 minutes: SMD -0.42, 95% CI -1.3 to 0.46, p=0.41, I2=93.2%; 90 minutes: SMD -0.03, 95% CI -0.50 to 0.44, p=0.91, I2=74.8%; 120 minutes: SMD -0.44, 95% CI -2.46 to 1.58, p=0.70, I2=95.9%).

Regarding side effects, 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: This meta-analysis indicates that sub-dissociative ketamine and morphine provide comparable analgesia for acute musculoskeletal pain in emergency and trauma settings.

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 morphine was associated with a higher risk of neurological adverse events.

Keywords: Ketamine, Morphine sulfate, trauma, pain