Does melatonin administration reduce the incidence of postoperative delirium in adults? Systematic review and meta-analysis

Abstract

Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent.

Objective: This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD.

Design: A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool.

Outcome measures: The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented.

Results: Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01).

Conclusion: This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial.

Prospero registration number: CRD42021285019.

Keywords: adult anaesthesia; clinical pharmacology; neurology; psychiatry; surgery; therapeutics.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart for study selection process. N=number of articles. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.

Figure 2

Forest plot displaying ORs and 95% CIs of effect of melatonin or melatonergic agent on incidence of postoperative delirium per study. Overall OR generated using a random-effects meta-analysis.