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Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: An Observational Study.
Drugs Aging. 2019 01; 36(1):85-91.DA

Abstract

BACKGROUND

Delirium is a neuropsychiatric syndrome which occurs on average in one out of five hospitalized older patients. It is associated with a number of negative outcomes, including worsening of cognitive and functional status, increasing the burden on patients and caregivers, and elevated mortality. Medications with anticholinergic effect have been associated with the clinical severity of delirium symptoms in older medical inpatients, but this association is still debated.

OBJECTIVE

The aim was to assess the association 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 older patients admitted to the Acute Geriatric Unit (AGU) of the San Gerardo Hospital in Monza (Italy) between June 2014 and January 2015. Delirium was diagnosed on admission using the 4 'A's Test (4AT), a validated screening tool for delirium diagnosis, which has shown good sensitivity and specificity to detect this condition in elderly patients admitted to an AGU. Each patient's anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale, a ranking of anticholinergic medications to predict the risk of adverse effects on the central nervous system in older patients.

RESULTS

Of the 477 eligible for the analysis, 151 (31.7%) had delirium. According to the ACB scale, 377 patients (79.0%) received at least one anticholinergic drug. Apart from quetiapine, which has a strong anticholinergic effect, the most commonly prescribed anticholinergic medications had potential anticholinergic effects but unknown clinically relevant cognitive effects according to the ACB scale (score 1). Patients with delirium had a higher anticholinergic burden than those without delirium, with a dose-effect relationship between total ACB score and delirium, which was significant at univariate analysis. A plateau risk was found in patients who scored 0-2, but patients who scored 3 or more had about three or six times the risk of delirium than those not taking anticholinergic drugs. The dose-response relationship was maintained in the multivariate model adjusted for age and sex [odds ratio (OR) 5.88, 95% confidence interval (CI) 2.10-16.60, p = 0.00007], while there was only a non-significant trend in the models adjusted also for dementia and Mini Nutritional Assessment (OR 2.73, 95% CI 0.85-8.77, p = 0.12).

CONCLUSIONS

Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity. However, this effect was no longer evident in multivariable logistic regression analysis, after adjustment for dementia and malnutrition. Larger, multicenter studies are required to clarify the complex relationship between drugs, anticholinergic burden and delirium in various categories of hospitalized older patients, including those with dementia and malnutrition.

Authors+Show Affiliations

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Giuseppe La Masa 19, 20156, Milano, Italy. luca.pasina@marionegri.it.School of Medicine and Surgery, University Milano-Bicocca, Milano, Italy.Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Giuseppe La Masa 19, 20156, Milano, Italy.Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Giuseppe La Masa 19, 20156, Milano, Italy.School of Medicine and Surgery, University Milano-Bicocca, Milano, Italy.Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Giuseppe La Masa 19, 20156, Milano, Italy.Redaelli Geriatric Institute, Milano, Italy.School of Medicine and Surgery, University Milano-Bicocca, Milano, Italy.School of Medicine and Surgery, University Milano-Bicocca, Milano, Italy. Acute Geriatric Unit, San Gerardo Hospital, Monza, Italy.School of Medicine and Surgery, University Milano-Bicocca, Milano, Italy. Acute Geriatric Unit, San Gerardo Hospital, Monza, Italy.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

30484239

Citation

Pasina, Luca, et al. "Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: an Observational Study." Drugs & Aging, vol. 36, no. 1, 2019, pp. 85-91.
Pasina L, Colzani L, Cortesi L, et al. Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: An Observational Study. Drugs Aging. 2019;36(1):85-91.
Pasina, L., Colzani, L., Cortesi, L., Tettamanti, M., Zambon, A., Nobili, A., Mazzone, A., Mazzola, P., Annoni, G., & Bellelli, G. (2019). Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: An Observational Study. Drugs & Aging, 36(1), 85-91. https://doi.org/10.1007/s40266-018-0612-9
Pasina L, et al. Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: an Observational Study. Drugs Aging. 2019;36(1):85-91. PubMed PMID: 30484239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: An Observational Study. AU - Pasina,Luca, AU - Colzani,Lorenzo, AU - Cortesi,Laura, AU - Tettamanti,Mauro, AU - Zambon,Antonella, AU - Nobili,Alessandro, AU - Mazzone,Andrea, AU - Mazzola,Paolo, AU - Annoni,Giorgio, AU - Bellelli,Giuseppe, PY - 2018/11/30/pubmed PY - 2019/2/13/medline PY - 2018/11/29/entrez SP - 85 EP - 91 JF - Drugs & aging JO - Drugs Aging VL - 36 IS - 1 N2 - BACKGROUND: Delirium is a neuropsychiatric syndrome which occurs on average in one out of five hospitalized older patients. It is associated with a number of negative outcomes, including worsening of cognitive and functional status, increasing the burden on patients and caregivers, and elevated mortality. Medications with anticholinergic effect have been associated with the clinical severity of delirium symptoms in older medical inpatients, but this association is still debated. OBJECTIVE: The aim was to assess the association 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 older patients admitted to the Acute Geriatric Unit (AGU) of the San Gerardo Hospital in Monza (Italy) between June 2014 and January 2015. Delirium was diagnosed on admission using the 4 'A's Test (4AT), a validated screening tool for delirium diagnosis, which has shown good sensitivity and specificity to detect this condition in elderly patients admitted to an AGU. Each patient's anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale, a ranking of anticholinergic medications to predict the risk of adverse effects on the central nervous system in older patients. RESULTS: Of the 477 eligible for the analysis, 151 (31.7%) had delirium. According to the ACB scale, 377 patients (79.0%) received at least one anticholinergic drug. Apart from quetiapine, which has a strong anticholinergic effect, the most commonly prescribed anticholinergic medications had potential anticholinergic effects but unknown clinically relevant cognitive effects according to the ACB scale (score 1). Patients with delirium had a higher anticholinergic burden than those without delirium, with a dose-effect relationship between total ACB score and delirium, which was significant at univariate analysis. A plateau risk was found in patients who scored 0-2, but patients who scored 3 or more had about three or six times the risk of delirium than those not taking anticholinergic drugs. The dose-response relationship was maintained in the multivariate model adjusted for age and sex [odds ratio (OR) 5.88, 95% confidence interval (CI) 2.10-16.60, p = 0.00007], while there was only a non-significant trend in the models adjusted also for dementia and Mini Nutritional Assessment (OR 2.73, 95% CI 0.85-8.77, p = 0.12). CONCLUSIONS: Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity. However, this effect was no longer evident in multivariable logistic regression analysis, after adjustment for dementia and malnutrition. Larger, multicenter studies are required to clarify the complex relationship between drugs, anticholinergic burden and delirium in various categories of hospitalized older patients, including those with dementia and malnutrition. SN - 1179-1969 UR - https://www.unboundmedicine.com/medline/citation/30484239/Relation_Between_Delirium_and_Anticholinergic_Drug_Burden_in_a_Cohort_of_Hospitalized_Older_Patients:_An_Observational_Study_ L2 - https://dx.doi.org/10.1007/s40266-018-0612-9 DB - PRIME DP - Unbound Medicine ER -