Comparison of the Effects of Glycopyrrolate and Atropine on Postoperative Delirium in Older Adult Patients Undergoing Laparoscopic Colorectal Surgery: A Randomized Controlled Trial

Background: Postoperative delirium (POD) is a common complication that hinders recovery in older patients. This study aimed to compare the effects of glycopyrrolate and atropine, used to counteract the peripheral effects of neostigmine, on POD incidence in older patients undergoing laparoscopic colorectal surgery. Methods: This single-centre, double-blind, randomized controlled trial recruited patients (aged 65– 80 years) undergoing laparoscopic colorectal surgery. Patients were randomized to receive either glycopyrrolate (0.04 mg kg − 1 neostigmine and 0.008 mg kg − 1 glycopyrrolate) or atropine (0.04 mg kg − 1 neostigmine and 0.016 mg kg − 1 atropine) during emergence from anaesthesia. The primary outcome was the incidence of POD within the first 3 postoperative days, assessed using the 3-minute Diagnostic Interview for Confusion Assessment Method. Secondary outcomes included comparing the hemodynamic effects of glycopyrrolate and atropine and examining POD biomarkers. Results: Among 121 patients, the glycopyrrolate group had a significantly lower incidence of POD compared with the atropine group (11.7% vs 27.9%; relative risk, 0.42; 95% confidence interval, 0.19– 0.94; p = 0.045). Glycopyrrolate better maintained baseline heart rate and mean arterial pressure. No significant differences were observed in plasma levels of neurofilament light chain, neuron-specific enolase, and Tau protein between groups at different time points. Conclusion: The combination of glycopyrrolate and neostigmine was associated with a lower incidence of POD than atropine in older adults undergoing laparoscopic colorectal surgery. Registration: Chinese Clinical Trial Registry, ChiCTR2300072798. Keywords: postoperative delirium, glycopyrrolate, atropine, older adult patients, colorectal surgery