Effect of Anticholinergic Drug Burden on Postoperative Delirium in Elderly Patients: A Nested Case–Control Study

TL;DR

Higher preoperative use of anticholinergic drugs increases the risk of postoperative delirium in elderly patients, especially when the drug burden score is 3 or higher.

Contribution

This study demonstrates that anticholinergic drug burden is an independent predictor of postoperative delirium in elderly patients.

Findings

Each 1-point increase in ACB score raises delirium odds by 10%.

Patients with ACB scores ≥3 had a 77% higher risk of postoperative delirium.

Kaplan-Meier analysis showed higher cumulative delirium incidence in the ACB ≥3 group.

Abstract

Postoperative delirium (POD) is a common complication in elderly patients. This study aimed to investigate the association between preoperative anticholinergic drug burden and POD in elderly patients.

This nested case–control study included patients aged ≥ 65 years who underwent general anesthesia between April 2020 and April 2022 at multiple hospitals in China. POD occurring within 7 days postoperatively was assessed using the 3‐Minute Diagnostic Interview for Confusion Assessment Method. Preoperative anticholinergic drug burden was quantified using the Anticholinergic Cognitive Burden (ACB) scale. Univariate and multivariate logistic regression models with random effects were used to determine the association between ACB scores and POD occurrence. Kaplan–Meier survival analysis with log‐rank tests was plotted to compare the cumulative POD incidence across groups. Subgroup analyses were performed to explore the relationship between ACB scores and POD occurrence within specific populations.

Among 10,296 patients, 1131 (11.0%) developed POD. The study employed a 5:1 matched case–control design and included 1125 cases and 5296 matched controls. Univariate (odds ratio [OR]: 1.230; 95% confidence interval [CI]: 1.119–1.353, p < 0.001) and multivariate (adjusted OR: 1.118; 95% CI: 1.006–1.243, p = 0.037) analyses demonstrated a significant association between higher anticholinergic drug burden and increased POD risk. When analyzed categorically (ACB score 0 as reference), adjusted ORs were 1.100 (95% CI: 0.919–1.317; p = 0.296) for ACB = 1, 1.213 (95% CI: 0.831–1.771; p = 0.318) for ACB = 2, and 1.963 (95% CI: 1.253–3.076; p = 0.003) for ACB ≥ 3. Kaplan–Meier analysis demonstrated a significantly higher cumulative incidence of POD in the ACB ≥ 3 group (log‐rank p < 0.001), with divergence starting on postoperative day 3.

A higher preoperative anticholinergic drug burden is associated with an increased risk of POD in elderly patients, particularly when the ACB scores are ≥ 3.

This nested cohort study, nested within a multicentre prospective dataset of 6421 elective non‐cardiac surgery patients aged ≥ 65 years, tested whether pre‐operative anticholinergic burden predicts incident post‐operative delirium. Multivariable conditional logistic regression analysis revealed that each 1‐point increment in the Anticholinergic Cognitive Burden (ACB) score independently raised delirium odds by 10%; patients accumulating an ACB score ≥ 3 experienced a 77% higher delirium risk.

Figures