Supplementary materials: Are treatment effects consistent with hypothesized mechanisms of action proposed for postoperative delirium interventions? Reanalysis of systematic reviews

This is peer-reviewed supplementary material for the article 'Are treatment effects consistent with hypothesised mechanisms of action proposed for postoperative delirium interventions? Reanalysis of systematic reviews' published in the Journal of Comparative Effectiveness Research.

Summary: Aim: Postoperative delirium (POD) is associated with increased morbidity and is poorly understood. The aim of this review was to identify putative mechanisms through re-analysis of randomized trials on treatment or prevention of POD. Materials & methods: A systematic review was performed to identify systematic reviews of treatments for POD. Constituent randomized controlled trials were identified, and interventions were grouped according to hypothesized mechanisms of action. Effects were meta-analyzed by hypothesized mechanism and timing of intervention. Results: A total of 116 randomized controlled trials described 47 individual interventions for POD, with nine mechanisms identified. The largest effects were observed for postoperative inflammation reduction, and preoperative reinforcement of sleep–wake cycle. Conclusion: This approach identifies treatments focused on mechanisms of action that may be front runners for future trials and interventions.