Effect of Melatonin on Postoperative Pain and Perioperative Opioid Use: A Meta‐analysis and Trial Sequential Analysis

We performed this meta-analysis in order to assess the effect of melatonin on postoperative pain and perioperative opioid consumption.We systematically searched PubMed, EMBASE, and the Cochrane Library until October 2019 for studies concerning the effect of melatonin vs. placebo on postoperative pain. We also searched for grey literature in ClnicalTrials.gov and grey literature databases, including OpenGrey and Grey Literature Report. We performed a meta-analysis of postoperative pain scores, perioperative opioid use, the number of patients with analgesic requirements, the time to the first analgesic requirement, length of hospital stay, and common reported adverse events of melatonin.According to the inclusion and exclusion criteria, 15 studies with a total of 1,102 patients were included in the final analysis. Melatonin was significantly associated with decreased VAS score (24 hours postoperatively) compared to placebo (trial sequential analysis = conclusive; mean difference [MD] -0.86; 95% confidence interval [CI] -1.38, -0.34; P = 0.001). Patients randomly assigned to melatonin were administered less postoperative opioids than patients in the control groups (trial sequential analysis = inconclusive; MD -3.33 mg; 95% CI -5.28, -1.38; P = 0.0008). The need for analgesic requirements was significantly decreased in the melatonin group. Patients who received melatonin had a significantly longer time to the first analgesic requirement. Compared to the placebo group, there were no significant differences in terms of length of hospital stay, dizziness, headache, paresthesia, and nausea.Given the low quality of evidence, minor degree of VAS score reduction, and inconclusive trial sequential analysis of postoperative opioid consumption, this meta-analysis neither supports nor opposes the effect of melatonin on postoperative pain.