Perioperative Ketamine or Esketamine for Acute Postoperative Pain after Laparoscopic Cholecystectomy: A Systematic Review and Meta-analysis with Meta-regression
Anaesth Crit Care Pain Med. 2026 Feb 5:101762. doi: 10.1016/j.accpm.2026.101762. Online ahead of print.
ABSTRACT
BACKGROUND: This systematic review and meta-analysis investigated the effectiveness and safety of perioperative ketamine/esketamine in patients undergoing laparoscopic cholecystectomy (LC).
METHODS: 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.
RESULTS: This review included a total of 48 RCTs (n = 3,508). 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 hours (MD: -0.40, I²=86.1%, p=0.019, very low-certainty evidence), 24-hours 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 hours (MD: -0.91, I²=79.3%, p = 0.008). Ketamine significantly reduced 24-hour 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.
CONCLUSION: 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.
REGISTRATION: PROSPERO (CRD420251035913).
PMID:41653984 | DOI:10.1016/j.accpm.2026.101762