Effects of Esketamine on Postoperative Sleep Quality: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose: Postoperative sleep disturbances are common and deleteriously affect patient recovery, yet effective pharmacologic interventions remain limited. Esketamine has demonstrated analgesic and antidepressant properties, but its effect on postoperative sleep quality is unclear. To assess the impact of perioperative esketamine on subjective sleep quality in adult surgical patients. Patients and Methods: Randomized controlled trials (RCTs) comparing esketamine with placebo, standard care, or other sedatives were retrieved from PubMed, Embase, and the Cochrane Library up to September 1, 2025. The primary outcome was postoperative subjective sleep quality, measured by validated scales. Secondary outcomes included incidence of sleep disturbance, pain scores, anxiety, depression, and quality of recovery (QoR-15). Subgroup analyses were prespecified by dose, timing, and dexmedetomidine co-administration. Among 21 included RCTs, 15 studies with 6880 participants reported postoperative subjective sleep quality. Results: The baseline sleep scores were comparable between esketamine and control groups. On postoperative day 1, esketamine significantly improved sleep quality (SMD = − 0.40, 95% CI [− 0.59, − 0.20], I 2 = 72%, p < 0.0001). Subgroup analyses indicated that higher doses (> 0.25 mg/kg) and intraoperative administration yielded larger effects. Esketamine also significantly decreased the incidence of postoperative sleep disturbance, reduced pain scores, and improved QoR-15. No significant effects were found for anxiety or depression outcomes. Conclusion: Perioperative esketamine significantly enhances subjective sleep quality, reduces sleep disturbance incidence, and also confers analgesic and recovery benefits. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/ , identifier, CRD420251138011. Keywords: esketamine, postoperative sleep quality, sleep disturbance, systematic review, meta-analysis