Double relief: A systematic review and meta-analysis of intravenous ketamine and morphine combination for acute trauma analgesia

Background and Aims: Acute trauma pain often remains inadequately treated despite opioid therapy. Low-dose ketamine has emerged as a promising adjunct analgesic that may enhance morphine effectiveness while reducing opioid requirements. This systematic review assessed the efficacy and safety of morphine combined with low-dose ketamine versus morphine alone for acute trauma analgesia. Material and Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, comprehensive searches were conducted across six databases (2006–2024) for studies comparing morphine–ketamine combination versus morphine monotherapy in acute trauma patients. Six eligible randomized controlled trials (RCTs) ( n = 708) were included. Meta-analysis was performed using RevMan 5.4 software with random-effects modeling. Results: Six RCTs involving 708 patients from emergency departments and prehospital settings were analyzed. Morphine–ketamine combination demonstrated superior analgesic efficacy with significantly lower final pain scores (mean difference (MD): –0.26; 95% confidence interval (CI): –0.40 to –0.12; P = 0.0003). Subgroup analysis by ketamine dose indicated the most pronounced and statistically significant pain reduction at 0.3 mg/kg (MD: –0.30; 95% CI: –0.48 to –0.12; P = 0.001), while lower doses showed similar trends. Significant pain reduction occurred at 30 min after sensitivity analysis (MD: −0.64, P < 0.00001) and sustained through 60 min (MD: −0.32, P < 0.0001). The combination reduced total morphine consumption by 2.93 mg ( P = 0.07). Overall, adverse events increased (odds ratio: 2.37, P = 0.05), but specific events—nausea, vomiting, and hallucinations—showed no significant differences between groups. No serious adverse events occurred. Conclusion: Low-dose ketamine as a morphine adjunct improves acute trauma pain control, shows a trend toward reduced opioid requirements, and maintains an acceptable safety profile, supporting its clinical implementation in emergency settings.