Anticholinergic load and delirium in end-of-life patients

Luca Pasina, Barbara Rizzi, Alessandro Nobili, Angela Recchia

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Delirium is a neuropsychiatric syndrome associated with negative outcomes, including worsening of cognitive and functional status and an increased burden on patients and caregivers. Medications with anticholinergic effect have been associated with delirium symptoms, but the relationship is still debated.

OBJECTIVE: To assess the relation between delirium and anticholinergic load according to the hypothesis that the cumulative anticholinergic burden increases the risk of delirium.

METHODS: This retrospective cross-sectional study was conducted in a sample of end-of-life patients in a hospice or living at home between February and August 2019. Delirium was diagnosed on admission using the 4 'A's Test (4AT) and each patient's anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale.

RESULTS: Of the 461 eligible for analysis, 124 (26.9%) had delirium. Anticholinergic medications were associated with an increased risk of delirium in univariate (OR (95% CI) 1.26 (1.16-1.38), p < 0.0001) and multivariate models adjusted for age, sex, dementia, tumors, Karnofsky Performance Status (KPS) score, days of palliative assistance, and setting (OR (95% CI) 1.16 (1.05-1.28), p < 0.0001). Patients with delirium had a greater anticholinergic burden than those without, with a dose-effect relationship between total ACB score and delirium. Patients who scored 4 or more had 2 or 3 times the risk of delirium than those not taking anticholinergic drugs. The dose-response relationship was maintained in the multivariate model.

CONCLUSIONS: Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity.

Original languageEnglish
Pages (from-to)1419-1424
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Issue number9
Publication statusPublished - Sep 2021


  • Aged
  • Aged, 80 and over
  • Cholinergic Antagonists/administration & dosage
  • Comorbidity
  • Cross-Sectional Studies
  • Delirium/epidemiology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Retrospective Studies
  • Sociodemographic Factors
  • Terminal Care


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