Efficacy and Safety of Esketamine in Patients Undergoing Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Laparoscopic cholecystectomy is the gold standard for gallbladder disease but is often associated with significant postoperative pain. Opioid analgesia is effective and is the mainstay of treatment. However, opioids are limited by multiple adverse effects such as nausea and respiratory depression. Esketamine is an NMDA receptor antagonist that has emerged as a potential analgesic adjunct. This systematic review and meta-analysis aims to evaluate the efficacy and safety of perioperative esketamine for patients undergoing laparoscopic cholecystectomy. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing perioperative esketamine with control regimens in adults undergoing laparoscopic cholecystectomy. Five databases were searched from inception to 25 August 2025. Random-effects meta-analyses were performed for pain, hemodynamic, recovery, and safety outcomes. Results: Six randomized controlled trials including 569 patients were eligible. Esketamine was associated with lower pain scores at rest and during movement, although neither were statistically significant. No significant clinical differences were observed in mean arterial pressure or heart rate changes during surgery or after surgery. However, esketamine significantly shortened wake-up time (MD = −3.55 min, 95% CI [−6.09 to −1.02]), improved postoperative sleep quality (MD = −5.78, 95% CI [−6.80 to −4.76]), and reduced PONV (RR = 0.47, 95% CI [0.24 to 0.92]) and respiratory depression (RR = 0.18, 95% CI [0.03 to 0.98]). Conclusions: Esketamine improved selected recovery and safety outcomes but did not significantly reduce hemodynamic parameters, postoperative pain or rescue analgesia. Larger high-quality trials are needed to confirm its role in laparoscopic cholecystectomy.