Role of perioperative ketamine on the incidence of rebound pain after regional nerve block in the adult surgical population: A systematic review and meta-analysis of randomised controlled trials.

Abstract

<h4>Background and aims</h4>Ketamine is being proposed for the prevention of rebound pain. This meta-analysis systematically reviews evidence from randomised controlled trials on the efficacy of ketamine (intravenous or perineural) in preventing rebound pain in adults undergoing surgery under regional nerve block.<h4>Methods</h4>A systematic search for randomised controlled trials evaluating ketamine/esketamine (perineural or intravenous) for preventing rebound pain was conducted across databases up to March 2025. Adults receiving regional nerve block with or without ketamine/esketamine were included. The primary outcome was the incidence of rebound pain. Secondary outcomes included onset time and severity of rebound pain, patient satisfaction, and adverse effects.<h4>Results</h4>Six trials enroling 890 patients were included. Ketamine/esketamine significantly reduced the incidence of rebound pain [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.32 to 0.59; <i>P</i> < 0.00001; <i>I</i>² = 39%]. The intravenous subgroup showed a significant reduction (OR 0.48, 95% CI 0.34 to 0.68; <i>P</i> < 0.00001; <i>I</i>² = 21%). The esketamine-versus-control subgroup also favoured active treatment (OR 0.37, 95% CI 0.22 to 0.64; <i>P</i> = 0.0004; <i>I</i>² = 51%). Hallucinations were significantly more frequent with active treatment (OR 12.73, 95% CI 2.98 to 54.41; <i>P</i> = 0.0006; <i>I</i>² = 0%).<h4>Conclusion</h4>Current evidence suggests that intravenous and perineural ketamine/esketamine reduce the incidence of rebound pain after a peripheral regional nerve block.

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