Opioid-Sparing Effects of Perioperative Ketamine With Inconsistent Analgesic Benefit in Orthopedic Surgery: A Systematic Review of Controlled Trials.

Effective postoperative pain management following orthopedic surgery remains a challenge, particularly in the context of increasing opioid-related morbidity. Multimodal analgesic strategies incorporate adjuvant therapies such as ketamine to reduce opioid requirements while maintaining adequate pain control. This systematic review evaluated the efficacy and safety of perioperative ketamine as an adjunct to opioid therapy for acute postoperative pain management in adults undergoing orthopedic procedures. A PRISMA-guided search of Ovid MEDLINE, Embase, Web of Science, and Cochrane CENTRAL identified randomized controlled trials published between January 2014 and September 2024. Eligible studies included patients aged 18-65 years undergoing orthopedic surgery who received perioperative ketamine compared to opioid-based regimens. Primary outcomes included postoperative opioid consumption and patient-reported pain scores, while secondary outcomes included adverse events. Risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Randomized Controlled Trials. Due to heterogeneity in ketamine dosing, administration, and outcome reporting, a qualitative synthesis was performed. Eleven randomized controlled trials met the inclusion criteria. Adjunctive ketamine reduced postoperative opioid consumption in five of 11 studies, with the most consistent effects observed within the first 24 hours postoperatively. Four studies reported statistically significant improvements in patient-reported pain scores, while others demonstrated no significant differences despite reduced opioid use. Ketamine showed a safety profile comparable to opioid-only regimens, with no consistent increase in adverse events; several studies reported reductions in opioid-related side effects such as pruritus and sedation. Perioperative ketamine may reduce postoperative opioid consumption without increasing adverse events, although its effect on pain intensity remains variable. These findings support its use as part of multimodal analgesia strategies aimed at minimizing opioid exposure, though further research is needed to standardize dosing protocols and evaluate long-term outcomes.