Melatonin and melatonergic agents for the prevention of postoperative delirium: A meta-analysis of randomized placebo-controlled trials

Abstract

Summary: Studies on melatonin and melatonergic agents (MMA) for the prevention of postoperative delirium (POD) have produced inconsistent findings. We conducted a meta-analysis to assess the effect of perioperative MMA on the prevention for POD. This meta-analysis is registered in the PROSPERO (CRD42020164900). We searched PubMed, Embase, and Cochrane Library through August 1, 2020 to identify randomized placebo-controlled trials (RCTs) that assessed MMA for the prevention for POD in adult patients undergoing surgery. The primary outcome was POD. Relative risk (RR) with 95% confidence interval (CI) was pooled using a random-effects model. Nine RCTs with 1452 patients were included. The incidence of POD was 23.8% (173/726) and 24.4% (177/726) in the MMA and placebo groups, respectively. Compared with placebo, MMA did not reduce the occurrence of POD (9 trails, 1452 patients, RR 0.93, 95% CI 0.70–1.24), with modest heterogeneity (I2 = 40%). Sensitivity analyses suggested that MMA also did not reduce the occurrence of POD in elderly patients (age ≥65 years) (6 trails, 810 patients, RR 0.71, 95% CI 0.38–1.32), patients given melatonin (4 trails, 806 patients, RR 0.78, 95% CI 0.43–1.41) or ramelteon (4 trails, 345 patients, RR 0.89, 95% CI 0.44–1.78), and patients undergoing general anesthesia (4 trails, 681 patient, RR 1.02, 95% CI 0.82–1.28). Based on the current evidence, perioperative MMA may have no effect on the prevention of POD.

Keywords

• Melatonin
• Delirium
• Meta-analysis