Anticholinergic Drug Burden and Postoperative Delirium: A Systematic Review and Meta-Analysis.

INTRODUCTION Postoperative delirium (POD) is an important postoperative neurocognitive complication, and cumulative anticholinergic drug burden (ADB) may increase its risk by impairing central cholinergic neurotransmission. This systematic review and meta-analysis aimed to clarify the overall association between ADB scores and POD risk in adult surgical patients.

Methods

We searched major databases and trial registries through February 2026 for studies that assessed ADB using validated scales and reported POD outcomes in adult surgical patients. Random-effects models pooled SMDs and ORs. Prespecified subgroup and sensitivity analyses explored heterogeneity and robustness. Risk of bias was assessed using NOS, and evidence certainty was rated using GRADE.

Results

Ten reports from nine independent cohorts comprising 10,457 participants were included. Patients with POD had higher ADB scores than those without POD (SMD = 0.31, 95% CI: 0.20-0.43). Each one-point increase in continuous ADB was associated with 22% higher odds of POD (OR = 1.22, 95% CI: 1.09-1.37). Both low-to-moderate and high burden were associated with increased POD risk. In scale-specific analyses, the association was significant for ACB. The association was attenuated in studies that excluded patients with cognitive impairment. Methodological quality ranged from moderate to high, and certainty of evidence was low.

Conclusions

Higher ADB is significantly associated with higher odds of POD, with a graded increase in risk across burden levels. Baseline cognitive impairment appears to amplify this association. These findings support preoperative ADB assessment and medication optimization in vulnerable surgical patients, while highlighting the need for prospective head-to-head comparisons of anticholinergic burden scales. REGISTRATION PROSPERO (CRD420261294941).