Assessment of melatonergics in prevention of delirium in critically ill patients A protocol for systematic review and meta-analysis

Background: Delirium is a commonly occurred complication in the critically ill. Melatonin is an endogenous hormone exerting multiple biological effects, mainly in regulating diurnal rhythms, also in inflammatory process and immune response. We aimed to assess the efficacy of exogenous melatonergics in prevention of delirium. Methods: PubMed, Cochrane Library, and Embase will be searched to identify randomized controlled trials published from 1960 to April 2019. Critically ill adult patients administrated with melatonergics will be included. The primary outcome measure will be the incidence of delirium. The secondary outcome measure will be the length of stay in intensive care unit. The pooled effects of dichotomous outcomes will be analyzed as risk ratio, and that of continuous outcomes will be analyzed using weighted mean difference. Subgroup and sensitivity analyses will be conducted. Funnel plots and/or Egger test will be done for the examination of publication bias. The quality of evidence resulting from this study will be evaluated using the GRADE methodology. Trial sequential analysis (TSA) will be done to test whether the evidence in our meta-analysis is reliable and conclusive. Result: The evidence to date of the melatonergics in prevention of delirium will be systematically reviewed and meta-analyzed with the GRADE level reported and TSA examined. Conclusion: The stronger evidence for the efficacy of melatonergics in prevention of delirium in critically ill patients will be provided for intensive care physicians. PROSPERO registration number: CRD42019138863.