Systematic review finds ketamine offers no pain advantage over opioids in prehospital trauma care settings

BACKGROUND: Effective prehospital analgesia is vital in trauma care. Although opioids are first line, they carry risks of adverse events. Ketamine has emerged as a promising alternative, offering potent analgesia, dissociation, and a favorable hemodynamic profile suited to resource-limited, time-sensitive prehospital care. OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the analgesic effectiveness and physiologic effects of ketamine compared with opioid-based analgesia in adult patients with traumatic injuries treated in the prehospital setting. METHODS: CINHAL Plus (EBSCO), OVID, and Cochrane Central were searched (2013-2024) using MESH terms such as ``ketamine,'' ``prehospital,'' and ``trauma.'' Included studies involved adults with traumatic injuries treated by prehospital clinicians with ketamine. Comparators included opioid monotherapy and ketamine-opioid combinations. Primary outcomes were pain scores, hemodynamic parameters, and adverse events. Risk of bias was assessed using established tools for randomized and nonrandomized studies, and certainty of evidence was evaluated using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations). Meta-analyses were conducted using a quality-effects model incorporating study-level risk of bias. RESULTS: Eighteen studies met inclusion criteria; three were suitable for meta-analysis comparison of ketamine and opioid monotherapy. Ketamine was not associated with a significant difference in pain reduction compared with opioids (weighted mean difference [WMD] 0.00; 95% confidence interval [CI] -0.77-0.78). Heart rate increased modestly with ketamine (WMD 3.19 beats/min, 95% CI 1.48-4.90), whereas systolic blood pressure showed no difference as compared with opioids (WMD 1.53 mm Hg, 95% CI -2.68-5.75). No difference in respiratory rate was observed (WMD -0.07 breaths/min, 95% CI -0.84-0.70). Adverse events were infrequent and were primarily mild, with emergence reactions most common. CONCLUSIONS: Ketamine provides analgesia consistent with similar effectiveness to opioids in prehospital trauma care, with comparable physiological effects and low reported rates of serious adverse events.