Effects of Melatonin Treatment on Perioperative Sleep Quality: A Systematic Review and Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials

Purpose: Perioperative sleep disorders have attracted much attention due to their high prevalence and severe harm, and the current treatment methods are insufficient. Some randomized controlled trials (RCTs) have produced controversial results on whether melatonin can improve perioperative sleep quality. This review aimed to evaluate the effects of melatonin treatment on perioperative sleep quality.

Patients and methods: A systematic search of six databases was performed to identify RCTs investigating melatonin and perioperative sleep. The outcomes analyzed were subjective sleep quality, sleep latency (SL), total sleep time (TST), sleep efficiency (SE), the behavior of awakenings and daily naps, and the incidence of poor sleep quality. RevMan 5.4 and Stata 16 software was used for the meta-analysis and sensitivity analysis, and trial sequential analysis was conducted using TSA 0.9.5.10 Beta software. This study was registered in PROSPERO (registration number: CRD42022311378).

Results: 10 studies containing 725 participants were included. Melatonin improved postoperative subjective sleep quality (SMD: -0.30; 95% CI: [-0.47, -0.14]; P = 0.0004) but not preoperative sleep quality (MD: -2.76; 95% CI: [-10.44, 4.91]; P = 0.48). In the postoperative period, 6mg dose had the best efficacy (SMD: -0.31; 95% CI: [-0.57, -0.04]; P = 0.02). Melatonin increased postoperative TST (P = 0.02) and SE (P = 0.002) and decreased the incidence of postoperative poor sleep quality (P = 0.002) but had no effect on SL (P = 0.11), the number and duration of awakenings (P = 0.28; P=0.55), and the number and duration of daily naps (P = 0.26; P = 0.38). The trial sequential analysis showed that the accumulated Z value crossed both the traditional boundary value and the TSA boundary value, further confirming the stability of the result of the meta-analysis.

Conclusion: Melatonin treatment can improve postoperative sleep quality. A 6mg daily dose of melatonin may have a better beneficial effect, which needs further exploration. This study supports the application of melatonin for improving postoperative sleep quality.