Anticholinergic load and delirium in end-of-life patients.
Anticholinergic drugs
Delirium
Elderly
End-of-life
Journal
European journal of clinical pharmacology
ISSN: 1432-1041
Titre abrégé: Eur J Clin Pharmacol
Pays: Germany
ID NLM: 1256165
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
04
12
2020
accepted:
12
03
2021
pubmed:
19
3
2021
medline:
21
12
2021
entrez:
18
3
2021
Statut:
ppublish
Résumé
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. To assess the relation between delirium and anticholinergic load according to the hypothesis that the cumulative anticholinergic burden increases the risk of delirium. 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. 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. Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity.
Sections du résumé
BACKGROUND
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
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
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
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
CONCLUSIONS
Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity.
Identifiants
pubmed: 33733683
doi: 10.1007/s00228-021-03125-w
pii: 10.1007/s00228-021-03125-w
doi:
Substances chimiques
Cholinergic Antagonists
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1419-1424Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Witlox J, Eurelings LS, de Jonghe JF et al (2010) Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 304:443e451
doi: 10.1001/jama.2010.1013
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, Arlington
doi: 10.1176/appi.books.9780890425596
Davis DH, Muniz-Terrera G, Keage HA, Stephan BC, Fleming J, Ince PG et al (2017) Association of delirium with cognitive decline in late life: a neuropathologic study of 3 population-based cohort studies. JAMA Psychiatry. 74(3):244–251
doi: 10.1001/jamapsychiatry.2016.3423
Kennedy M, Enander RA, Tadiri SP, Wolfe RE, Shapiro NI, Marcantonio ER (2014) Delirium risk prediction, healthcare use and mortality of elderly adults in the emergency department. J Am Geriatr Soc 62:462–469
doi: 10.1111/jgs.12692
Inouye SK, Westendorp RG, Saczynski JS (2014) Delirium in elderly people. Lancet. 383(9920):911–922
doi: 10.1016/S0140-6736(13)60688-1
Marcantonio ER (2017) Delirium in hospitalized older adults. N Engl J Med. 377(15):1456–1466
doi: 10.1056/NEJMcp1605501
Collamati A, Martone AM, Poscia A et al (2016) Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence. Aging Clin Exp Res 28:25e35
doi: 10.1007/s40520-015-0359-7
Maldonado JR (2008) Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment. Crit Care Clin 24:789e856 ix
Hshieh TT, Fong TG, Marcantonio ER, Inouye SK (2008) Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci MedSci 63:764e772
Tune LE (2001) Anticholinergic effects of medication in elderly patients. J Clin Psychiatry. 62(suppl 21):11–14
pubmed: 11584981
Han L, McCusker J, Cole M, Abrahamowicz M, Primeau F, Élie M (2001) Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med. 161(8):1099–1105
doi: 10.1001/archinte.161.8.1099
Naja M, Zmudka J, Hannat S, Liabeuf S, Serot JM, Jouanny P (2016) In geriatric patients, delirium symptoms are related to the anticholinergic burden. Geriatr Gerontol Int. 16(4):424–431
doi: 10.1111/ggi.12485
Fox C, Smith T, Maidment I, Chan WY, Bua N, Myint PK, Boustani M, Kwok CS, Glover M, Koopmans I, Campbell N (2014) Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review. Age Ageing. 43(5):604–615
doi: 10.1093/ageing/afu096
Tune LE, Egeli S (1999) Acetylcholine and delirium. Dement Geriatr Cogn Disord. 10(5):342–344
doi: 10.1159/000017167
Campbell N, Boustani M, Limbil T, Ott C, Fox C, Maidment I, Schubert CC, Munger S, Fick D, Miller D, Gulati R (2009) The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging. 4:225–233
pubmed: 19554093
pmcid: 2697587
Welsh TJ, van der Wardt V, Ojo G, Gordon AL, Gladman JRF (2018) Anticholinergic drug burden tools/scales and adverse outcomes in different clinical settings: a systematic review of reviews. Drugs Aging. 35:523–538. https://doi.org/10.1007/s40266-018-0549-z
doi: 10.1007/s40266-018-0549-z
pubmed: 29736815
Egberts A, Moreno-Gonzalez R, Alan H, Ziere G, Mattace-Raso FUS (2020) Anticholinergic drug burden and delirium: a systematic review [published online ahead of print, 2020 Jul 20]. J Am Med Dir Assoc S1525-8610(20)30349-2
Pasina L, Recchia A, Agosti P, Nobili A, Rizzi B (2018) Prevalence of preventive and symptomatic drug treatments in hospice care: an Italian observational study. Am J Hosp Palliat Care. 36:216–221. https://doi.org/10.1177/1049909118794926
doi: 10.1177/1049909118794926
pubmed: 30114944
Pasina L, Recchia A, Nobili A, Rizzi B Prevalence of preventive and symptomatic medications among end-of-life patients living at home: an Italian observational study. Eur Geriatr Med
Blass DM, Black BS, Phillips H, Finucane T, Baker A, Loreck D, Rabins PV (2008) Medication use in nursing home residents with advanced dementia. Int J Geriatr Psychiatry 23(5):490–496
doi: 10.1002/gps.1921
Agar M, Currow D, Plummer J, Seidel R, Carnahan R, Abernethy AP (2009) Changes in anticholinergic load from regular prescribed medications in palliative care as death approaches. Palliat Med 23:257–265
doi: 10.1177/0269216309102528
Boustani M, Campbell N, Munger S, Maidment I, Fox C (2008) Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 4(3):311–320. https://doi.org/10.2217/1745509X.4.3.311
doi: 10.2217/1745509X.4.3.311
Bellelli G, Morandi A, Davis DH et al (2014) Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing 43:496–502
doi: 10.1093/ageing/afu021
Hsu WH, Wen YW, Chen LK, Hsiao FY (2017) Comparative associations between measures of anti-cholinergic burden and adverse clinical outcomes. Ann Fam Med. 15(6):561–569
doi: 10.1370/afm.2131
Rudolph JL, Salow MJ, Angelini MC, McGlinchey R (2008) The anticholinergic risk scale and anticholinergic adverse effects in older person. Arch Intern Med 168(5):508–513
doi: 10.1001/archinternmed.2007.106
Zimmerman KM, Salow M, Skarf LM, Kostas T, Paquin A, Simone MJ, Rudolph J (2014) Increasing anticholinergic burden and delirium in palliative care inpatients. Palliat Med. 28(4):335–341
doi: 10.1177/0269216314522105
Hein C, Forgues A, Piau A, Sommet A, Vellas B, Nourhashémi F (2014) Impact of polypharmacy on occurrence of delirium in elderly emergency patients. J Am Med Dir Assoc 15(11):850.e11-5
doi: 10.1016/j.jamda.2014.08.012
Viktil KK, Blix HS, Moger TA, Reikvam A (2007) Polypharmacy as commonly defined is an indicator of limited value in the assessment of drug-related problems. Br J Clin Pharmacol. 63(2):187–195
doi: 10.1111/j.1365-2125.2006.02744.x
Mazzola P, Ward L, Zazzetta S, Broggini V, Anzuini A, Valcarcel B, Brathwaite JS, Pasinetti GM, Bellelli G, Annoni G (2017) Association between preoperative malnutrition and postoperative delirium after hip fracture surgery in older adults. J Am Geriatr Soc. 65(6):1222–1228
doi: 10.1111/jgs.14764