Use of intranasal insulin on postoperative delirium: A systematic review and meta-analysis of randomised controlled trials

Background and Aims: Postoperative delirium remains a major concern among adult patients undergoing surgery. Intranasal insulin is believed to reduce postoperative delirium in adults. However, its efficacy and safety profile remain unclear. The primary objective was to examine the effects of intranasal insulin on the incidence of postoperative delirium. Secondary outcomes include serum concentration of Tissue Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP), haemostasis model assessment - insulin (HOMA-IR), and serum glucose. Methods: All randomised controlled trials (RCTs) were searched in the databases of CENTRAL, EMBASE, and MEDLINE until January 2025. Case reports, case series, letters to the editor, and conference abstracts were excluded. We used Revman Version 5.4 to calculate the fixed-effects and random-effects models to report the primary and secondary outcomes by using the odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (CI). This review included a Grading of Recommendations Assessment, Development and Evaluation analysis on the quality of evidence for all measured outcomes. Results: Seven studies with a total of 739 patients were included in this systematic review. In comparison to intranasal saline, intranasal insulin significantly reduced the incidence of postoperative delirium among adults undergoing surgery (OR: 0.37, 95% CI: 0.22, 0.63). Its administration was also associated with a statistical decrease in the serum concentration of TNF-α (MD: -3.10, 95% CI: -4.42, -1.78), serum concentration of IL-6 (MD: -3.86, 95% CI: -5.92, -1.80), and serum concentration of CRP (MD: -1.71, 95% CI: -3.38, -0.04). However, no statistical differences were observed in the HOMA-IR and serum glucose. Conclusions: This meta-analysis highlighted the promising application of intranasal insulin in reducing the incidence of postoperative delirium, serum concentration of TNF-α, IL-6, and CRP in adult patients undergoing surgery. However, a high degree of heterogeneity and limited sample size warrant future adequately powered studies to confirm our findings.