Perioperative ketamine or esketamine for acute postoperative pain after laparoscopic cholecystectomy: A systematic review and meta-analysis with meta-regression.

Abstract

<h4>Background</h4>This systematic review and meta-analysis investigated the effectiveness and safety of perioperative ketamine/esketamine in patients undergoing laparoscopic cholecystectomy (LC).<h4>Methods</h4>A literature search was conducted across Medline, Embase, Google Scholar, and clinicaltrials.gov until April 2025. Forty-eight randomized controlled trials (RCTs) comparing ketamine/esketamine with a control in LC patients and assessing postoperative pain scores were included. Statistical analysis was performed using R.<h4>Results</h4>This review included a total of 48 RCTs (n = 3508). Pooled analysis revealed that intervention significantly reduced postoperative pain at 4 (mean difference [MD]: -1.11, I² = 97.8%, p = 0.044, very low-certainty evidence) and 6 h (MD: -0.40, I² = 86.1%, p = 0.019, very low-certainty evidence), 24-h opioid consumption (MD: -4.10, I² = 98.3%, p = 0.024, very low-certainty evidence) and need for rescue analgesia (risk ratios [RR]: 0.64, I² = 36%, p = 0.006, very low-certainty evidence) compared to the control. According to subgroup analysis on the basis of regimen, esketamine significantly reduced postoperative pain at 1 (MD: -0.67, I² = 0%, p = 0.034) and 2 h (MD: -0.91, I² = 79.3%, p = 0.008). Ketamine significantly reduced 24-h opioid consumption (MD: -5.35, I² = 96%, p = 0.01) and the need for rescue analgesia (RR: 0.64, I² = 41.7%, p = 0.011). Safety analysis revealed the significantly increased risk of hallucinations, diplopia, and nystagmus with the intervention.<h4>Conclusion</h4>With a very low level of certainty, this meta-analysis demonstrated that ketamine/esketamine might help reduce acute postoperative pain and postoperative opioid needs in patients undergoing LC. Furthermore, ketamine may slightly increase the risk of some adverse events. However, dose-related meta-regression for adverse events was not performed due to inconsistent reporting across studies.<h4>Registration</h4>PROSPERO (CRD420251035913).

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