Authors: Lama Alzimami , Mohammed AlAdhab , Muath Almuhanna , Rawan Alkhammas , Afnan K. Alturki , Khadijah I. Basheikh , Yousef Abdullatif Aljohar , Norah Almulhim , Wedad Almutairi , Raha Alotaibi , Aishah Alhadi , Amal Alzahrani , Abdulaziz Alabdulaali

Abstract

Background: Laparoscopic cholecystectomy (LC) is frequently associated with early postoperative pain and opioid-related adverse effects. We evaluated the efficacy and safety of perioperative low-dose esketamine in adults undergoing LC.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, PubMed, the Cochrane Library, Embase, and Web of Science were searched from inception to February 2026 for randomized controlled trials comparing esketamine with placebo or a standard anesthetic regimen. Random-effects meta-analyses generated mean differences, standardized mean differences, or risk ratios with 95% confidence intervals (CIs).

Results: Nine trials involving 699 participants were included. Esketamine reduced pain within 2 hours (MD-0.67; 95% CI -0.90 to -0.45) and reduced pain at rest and with movement through 72 hours, although several later estimates were highly heterogeneous. Intraoperative remifentanil consumption (SMD -0.74; 95% CI -1.31 to -0.18) and propofol consumption (SMD -0.55; 95% CI -0.98 to -0.11) were lower. Awakening time, postanesthesia care unit stay, and anesthesia duration did not differ significantly. No clear increase was observed in common adverse events, including nausea, vomiting, hallucinations, or agitation.

Conclusion: Perioperative low-dose esketamine modestly reduced postoperative pain and anesthetic requirements without a clear increase in common adverse events. However, the average early pain reduction was below a commonly used 1-point minimal clinically important difference, and substantial heterogeneity and imprecision limit confidence in the clinical importance and generalizability of these findings (PROSPERO: CRD420251251995).

Keywords: Esketamine, laparoscopic cholecystectomy, postoperative pain, opioid sparing, meta-analysis.