Effect of perioperative esketamine administration for postoperative sleep disturbance following general anaesthesia: protocol for a planned systematic review and meta-analysis of randomised controlled trials

INTRODUCTION: Postoperative sleep disturbance (PSD) is a common complication following major surgery, occurring in 15%-72% of patients. PSD poses a significant threat to both postoperative recovery and long-term outcome, leading to elevated risks of cognitive decline, pain sensitivity and cardiovascular events in patients. The current pharmacological treatments for PSD are typically reactive, administered only after symptoms have manifested, highlighting a critical unmet need for effective prophylactic strategies during the perioperative period. Recently, an increasing number of studies have demonstrated the effect of esketamine on preventing PSD, but their findings are inconsistent. This protocol outlines a systematic review and meta-analysis to examine the effect of perioperative esketamine on the prevention of PSD. METHODS AND ANALYSIS: A comprehensive search will be conducted in MEDLINE (via Ovid), EMBASE (via Ovid), the Cochrane Central Register of Controlled Trials (via Ovid), PubMed and Web of Science by two authors independently. The search terms will comprise indexed and free-text terms to encompass the concepts of esketamine and PSD. The primary outcome is the incidence of PSD at postoperative days 1, 3 and 7. Two authors will independently conduct study screening, data extraction and risk of bias assessment with the Cochrane Collaboration's tool. RevMan V.5.4.1 and Stata V.17.0 software will be used to conduct the statistical analysis. Subgroup analysis, sensitivity analysis and assessment of publication bias will be performed to verify the strength of our conclusions. Finally, the Grading of Recommendations Assessment, Development and Evaluation approach will be used to recommend evidence quality. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. The findings will be presented at national or international conferences and submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD420251232636.