Effect of melatonin and melatonin agonists on postoperative sleep quality in adult patients: a protocol for systematic review and meta-analysis with trial sequential analysis.

Introduction The circadian rhythm of melatonin secretion is disturbed after general anaesthesia, leading to postoperative sleep disturbance. Small studies investigating the preventive effect of melatonin administration on postoperative sleep disturbance have not reached any conclusions. Therefore, we will conduct a systematic review and meta-analysis to obtain conclusive results. Methods and analysis We prepared this protocol following the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines. We will conduct a search for randomised controlled trials that evaluated the effect of melatonin and melatonin agonists on postoperative sleep quality in adult patients undergoing general anaesthesia or regional anaesthesia with sedation. We will exclude patients undergoing regional anaesthesia without sedation. Relevant studies will be searched in the following eight databases: MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and four preregistration sites from inception to 1 January 2021. No language restrictions will be applied. Two authors will independently scan and select eligible studies and perform data extraction and assessment of the risk of bias. The Visual Analogue Scale scores for sleep quality will be combined as the mean difference with a 95% CI using a random-effect model; we will use I2 to assess heterogeneity. We will evaluate the quality of trials using the Cochrane methodology and assess the quality of evidence using the Grading of Recommendation Assessment, Development and Evaluation approach. If appropriate, trial sequential analysis will be performed. Ethics and dissemination No ethical approval is required for this meta-analysis, as it does not include individual patient data. We will disseminate the results of this meta-analysis in a peer-reviewed journal. PROSPERO registration number CRD42020180167.