Effect of perioperative opioid-sparing multimodal analgesia on early postoperative sleep disturbance in adults undergoing elective non-cardiac, non-obstetric surgery under general anaesthesia: protocol for a systematic review and meta-analysis

Abstract: Early postoperative sleep disturbance is common after adult non-cardiac surgery under general anaesthesia and has been consistently associated with worse pain control, increased risk of postoperative delirium, impaired functional recovery and prolonged hospital stay, which imposes a significant burden on both patients and healthcare systems. Opioid-sparing multimodal analgesia is increasingly recommended within enhanced recovery after surgery pathways because it can effectively reduce opioid exposure while maintaining adequate analgesia; however, its specific effect on early postoperative sleep outcomes has not been systematically synthesised to date, leaving a critical gap in evidence-based perioperative care.

Methods and analysis: We will conduct a systematic review and meta-analysis of randomised controlled trials enrolling adults aged 18 years or older undergoing elective non-cardiac, non-obstetric surgery under general anaesthesia. Eligible studies must evaluate a perioperative opioid-sparing multimodal analgesic strategy, with multimodality defined at the level of the overall perioperative analgesic regimen. A single investigational adjunct may be eligible when it has a perioperative analgesic role and is incorporated into a common background analgesic regimen, such that the intervention arm as a whole constitutes multimodal analgesia. Eligible comparators will include opioid-dominant analgesia, placebo, no additional intervention or a common or otherwise comparable background analgesic regimen without the opioid-sparing component of interest. The coprimary outcomes will be subjective sleep quality during the night of surgery or, if unavailable, during the night of postoperative day 1 (POD1), and the incidence of early postoperative sleep disturbance within 3 days after surgery (including the night of surgery). Secondary outcomes will include objective sleep parameters (eg, total sleep time and sleep efficiency), postoperative opioid consumption (converted to intravenous morphine milligram equivalents where possible), pain scores, patient-reported quality of recovery assessed using validated instruments, postoperative nausea and vomiting, delirium, length of hospital stay and intervention-related adverse events. We will search MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials and Web of Science Core Collection from inception to 30 April 2026 as the initial search cut-off date without language restrictions. The searches will be updated before the final analysis of the systematic review. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform will also be searched for ongoing or unpublished trials, and the reference lists of included studies and relevant systematic reviews will be screened for additional eligible studies. Two reviewers will independently screen studies, extract data and assess risk of bias (ROB) using the Cochrane RoB 2 tool. Random-effects pairwise meta-analyses will be performed where studies are clinically and methodologically comparable, and the certainty of evidence for the coprimary outcomes will be appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.