Anticholinergic Exposure, Drug Dose and Postoperative Delirium: Comparison of Dose-Related and Non-Dose-Related Anticholinergic Burden Scores in a Retrospective Cohort Study of Older Orthopaedic and Trauma Surgery Patients.

Purpose: Postoperative delirium (POD) is a common complication in older adult patients after surgery. A patient's preoperative anticholinergic (AC) burden is a potentially modifiable risk factor for POD. As the influence of the drug dose remains unknown, we aimed to compare three AC burden scores in relation to POD, two of which were dose-related.
Methods: This retrospective cohort study (03/22-10/22) included orthopaedic and trauma surgery patients > 65 years. POD was assessed using the four A's test (4AT), delirium diagnosis, and chart review. The AC burden was determined using the non-dose-related German Anticholinergic Burden score (GerACB), an extension of the dose-related Muscarinic Acetylcholinergic Receptor ANTagonist Exposure scale (extMARANTE), and the dose-related German Drug Burden Index (GerDBI). Multivariable logistic regression analysis determined the association between the preoperative AC burden and POD. Scores were compared using kappa statistics, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results: POD was observed in 71 of 385 patients (18.4%). For all three scores, a high AC burden was significantly associated with POD after adjusting for age, sex, dementia, preoperative physical status, and number of prescribed drugs (p < 0.001). The overall agreement among the burden classifications was substantial (no POD: κ = 0.645, POD: κ = 0.632). The GerACB had the lowest sensitivity with 23.9% (extMARANTE: 42.3%, GerDBI: 40.8%), but the highest PPV with 48.6% (extMARANTE: 38.5%, GerDBI: 43.3%).
Conclusion: Both dose-related and non-dose-related AC burden scores have limited sensitivity and modest PPV for screening a patient's medication for POD. However, given the additional effort required for dose consideration, the non-dose-related GerACB remains sufficient in clinical practice, with the lowest sensitivity but highest PPV.
Competing Interests: Declarations. Funding: Open Access funding enabled and organized by Projekt DEAL. Open access funding provided by the Stiftung Patient & Klinische Pharmazie, Munich, Germany. Conflicts of Interest: The project gertrud was partially funded by the Bavarian State Ministry of Health and Care within the Guideline for the Promotion of Innovative Medical Care Concepts (IMVR), grant notification dated 09.06.2021 (K1-2496-IMV-20-V4). A data sharing agreement without connection to the data of this manuscript was rewarded an allowance by Pipra AG, Zürich, Switzerland. T.S. received funding by the Munich Medical and Clinician Scientist Program, Faculty of Medicine, LMU Munich (MCSP ACS-11). The study sponsors were not involved in the study design, study execution, or data analysis. The authors have no other potential conflicts of interest to declare. Availability of Data and Material: The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics Approval: The study was approved by the Ethics Committee of LMU University Hospital Munich (No. 23-0041) and complied with the Declaration of Helsinki. Consent to Participate: The Ethics Committee of LMU University Hospital Munich waived the requirement to obtain any informed consent due to the retrospective design of the study. Consent for Publication: Not applicable Code Availability: Not applicable Author Contributions: The authors contributed to the paper as follows. Study conception: C.G., T.S., K.D., U.A., and D.S. Expert committee for anticholinergic dose values: C.R., V.S., and D.S. Data collection: C.G. and T.S. Data analysis: C.G., U.A., and D.S. Manuscript – original draft: C.G. All authors have read and approved the final version of the manuscript and agree to be accountable for the work.
(© 2024. The Author(s).)