The Association of Serum Anticholinergic Activity With Delirium in Elderly Medical Patients

doi:10.1097/00019442-199802000-00005

The American Journal of Geriatric Psychiatry

Volume 6, Issue 1, Winter 1998, Pages 31-41

https://doi.org/10.1097/00019442-199802000-00005 Get rights and content

To investigate the hypothesis that elevated serum anticholinergic activity is independently associated with delirium in ill elderly persons, the authors performed a cross-sectional study of 67 acutely ill older medical inpatients. The presence of delirium was evaluated with the Confusion Assessment Method, and the presence of many delirium symptoms was measured by the Delirium Symptom Interview. Demographic data and clinical characteristics that may be important for the development of delirium were also collected. Logistic regression techniques demonstrated that elevated serum anticholinergic activity was independently associated with delirium. Among the subjects with delirium, a greater number of delirium symptoms was associated with higher serum anticholinergic activity.

Section snippets

METHODS

Between June 1 and September 15, 1995, patients age 75 years or greater admitted to the general-medical service of Boston's Beth Israel Deaconess Medical Center, East Campus, a 450-bed teaching hospital, were recruited for the present study. We identified potential participants through the hospital computerized database that includes the ages of all persons admitted to the hospital as well as the service to which they were admitted. Subjects were recruited consecutively, however because of

RESULTS

Delirium occurred in 30% of subjects. The characteristics of subjects with and without delirium are presented in Table 1. In the bivariate analysis, delirium was associated with higher serum anticholinergic activity quintile (P=0.003; Odds Ratio [OR]=1.95), ADL impairment (P=0.001; OR=1.50), previous cognitive impairment (P=0.036; OR=3.27), admission diagnosis of infection (P=0.015; OR=3.92), nursing home residency (P=0.002; OR=8.80), and elevated white blood-cell count (P=0.040; OR=1.16).

The

DISCUSSION

In this study of elderly medical inpatients, serum anticholinergic activity levels were independently associated with a diagnosis of delirium. Furthermore, the number of symptoms of delirium also increased with higher serum anticholinergic activity. Other variables that were associated with a greater likelihood of delirium in the adjusted analysis included impairment in ADLs, admission diagnosis of infection, and elevated white blood-cell count.

The hypothesis that an elevated serum

References (31)

P Trzepacz
The neuropathogenesis of delirium
Psychosomatics
(1994)
P Pompei et al.
Delirium in hospitalized older persons: outcomes and predictors
J Am Geriatr Soc
(1994)
MD Foreman
Confusion in hospitalized elderly: incidence, onset, and associated factors
Res Nurs Health
(1989)
R Hall et al.
Angel's trumpet psychosis: a central nervous system anticholinergic syndrome
Am J Psychiatry
(1977)
D Brizer et al.
Delirium induced by poisoning with anticholinergic agents
Am J Psychiatry
(1982)
LE Tune et al.
Association of postoperative delirium with raised serum levels of anticholinergic drugs
Lancet
(1981)
F Mondimore et al.
Post-ECT confusional states associated with elevated serum anticholinergic activity
Am J Psychiatry
(1983)
R Golinger et al.
Association of elevated plasma anticholinergic activity with delirium in surgical patients
Am J Psychiatry
(1987)
JR Mach et al.
Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study
J Am Geriatr Soc
(1995)
J Francis et al.
A prospective study of delirium in hospitalized elderly
JAMA
(1990)

JD Schor et al.

Risk factors for delirium in hospitalized elderly

JAMA

(1992)

Y Conwell et al.

Validation of a measure of physical illness burden at autopsy: The Cumulative Illness Rating Scale

J Am Geriatr Soc

(1993)

S Katz et al.

Studies of illness in the aged, the index of ADL: a standardized measure of biological and psychosocial function

JAMA

(1963)

Medical Economics Company, Inc.: Physicians' Desk Reference, 49th Edition. Montvale, NJ,...

LE Tune et al.

Anticholinergic side effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium

Am J Psychiatry

(1992)

Cited by (225)

Characteristics of providers who prescribed only anticholinergic medications for overactive bladder in 2020
2023, American Journal of Obstetrics and Gynecology
Pharmacologic therapy for overactive bladder typically includes either an anticholinergic or a beta-3 agonist. Based on research that has demonstrated increased risks of cognitive impairment and dementia associated with anticholinergic use, current guidelines support the use of beta-3 agonists rather than anticholinergics in older patients.
This study aimed to describe the characteristics of providers prescribing only anticholinergics to treat overactive bladder in patients aged ≥65 years.
The US Centers for Medicare and Medicaid Services publishes data on medications dispensed to Medicare beneficiaries. Data include the National Provider Identifier of the prescriber and the number of pills prescribed and dispensed for any given medication for beneficiaries aged ≥65 years. We obtained each provider’s National Provider Identifier, gender, degree, and primary specialty. National Provider Identifiers were linked to an additional Medicare database that includes graduation year. We included providers who prescribed pharmacologic therapy for overactive bladder in 2020 for patients aged ≥65 years. We calculated the percentage of providers who prescribed only anticholinergics (and did not prescribe beta-3 agonists) for overactive bladder and stratified by provider characteristics. Data are reported as adjusted risk ratios.
In 2020, 131,605 providers prescribed overactive bladder medications. Of those identified, 110,874 (84.2%) had complete demographic information available. Although only 7% of providers who prescribed medications for overactive bladder were urologists, prescriptions from urologists accounted for 29% of total prescriptions. Among providers prescribing medications for overactive bladder, 73% of female providers prescribed only anticholinergics, whereas 66% of male providers prescribed only anticholinergics (P<.001). The percentage of providers that prescribed only anticholinergics also varied by specialty (P<.001), with providers specialized in geriatric medicine being least likely to prescribe only anticholinergics (40%), followed by urologists (44%). Nurse practitioners (75%) and family medicine physicians (73%) were more likely to prescribe only anticholinergics. The percentage of providers who prescribed only anticholinergics was the highest for recent medical school graduates and decreased with time since graduation. Overall, 75% of providers within 10 years of graduation prescribed only anticholinergics, whereas only 64% of providers who were >40 years of age from graduation prescribed only anticholinergics (P<.001).
This study identified considerable differences in prescribing practices based on provider characteristics. Female physicians, nurse practitioners, physicians trained in family medicine, and those who recently graduated from medical school were the most likely to prescribe only anticholinergic medications and not prescribe any beta-3 agonist for the treatment of overactive bladder. This study identified differences in prescribing practices based on provider demographics that may guide educational outreach programs.
Neurological complications of steroids and of supportive care
2022, Neurological Complications of Systemic Cancer and Antineoplastic Therapy
Corticosteroids are commonly employed within oncology primarily as either part of a direct treatment regimen or more broadly a supportive care modality. However, despite the widespread and well-established benefits of corticosteroids in these roles, a myriad of side effects can develop in correlation with the chronicity and/or dosage required in use. In particular, neurological side effects can be pronounced, leading to a limitation in their cumulative use and a concern for the potential significant impact on patient quality of life. Neurologic complications also arise during the care of patients with cancer as a direct consequence of additional supportive care medications, including antiepileptics, analgesics, antiemetics, and antidepressants in particular, or during the management of tumor-associated CNS vascular damage, including ischemic infarction or hemorrhagic injury. Here, we review the spectrum of corticosteroid-induced neurologic complications as well as the neurologic complications that arise secondary to supportive care measures of patients within oncology.
The Association of Anticholinergic Drugs and Delirium in Nursing Home Patients With Dementia: Results From the SHELTER Study
2021, Journal of the American Medical Directors Association
Drugs with anticholinergic properties are associated with an increased prevalence of delirium, especially in older persons. The aim of this study was to evaluate the association between the use of this class of drugs in nursing home (NH) patients and prevalence of delirium, particularly in people with dementia.
Cross-sectional multicenter study.
3924 nursing home patients of 57 nursing homes in 7 European countries participating in the Services and Health for Elderly in Long TERmcare (SHELTER) project.
Descriptive statistics, calculation of percentage, and multivariable logistic analysis were applied to describe the relationship between anticholinergic drug use and prevalence of delirium in NH patients. The Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB) were used to calculate the anticholinergic load.
54% of patients with dementia and 60% without dementia received at least 1 anticholinergic drug according to the ACB. The prevalence of delirium was higher in the dementia group (21%) compared with the nondementia group (11%). Overall, anticholinergic burden according to the ACB and ARS was associated with delirium both in patients with and without dementia, with odds ratios ranging from 1.07 [95% confidence interval (CI) 0.94-1.21] to 1.26 (95% CI 1.11-1.44). These associations reached statistical significance only in the group of patients with dementia. Among patients with dementia, delirium prevalence increased only modestly with increasing anticholinergic burden according to the ACB, from 20% (with none or minimal anticholinergic burden) to 25% (with moderate burden) and 27% delirium (with strong burden scores).
The ACB scale is relatively capable to detect anticholinergic side effects, which are positively associated with prevalence of delirium in NH patients. Given the modest nature of this association, strong recommendations are currently not warranted, and more longitudinal studies are needed.
Biomarkers in delirium: A systematic review
2021, Journal of Psychosomatic Research
Delirium is a common neuropsychiatric disorder associated with prolonged hospital stays, and increased morbidity and mortality. Diagnosis is frequently missed due to varying disease presentation and lack of standardized testing. We examined biomarkers as diagnostic or prognostic indicators of delirium, and provide a rational basis for future studies.
Systematic review of literature published between Jan 2000 and June 2019. Searches included: PubMed; Web of Science; CINAHL; EMBASE; COCHRANE and Medline. Additional studies were identified by searching bibliographies of eligible articles.
2082 relevant papers were identified from all sources. Seventy-three met the inclusion criteria, all of which were observational. These assessed a range of fourteen biomarkers. All papers included were in the English language. Assessment methods varied between studies, including: DSM criteria; Confusion Assessment Method (CAM) or CAM-Intensive Care Unit (ICU). Delirium severity was measured using the Delirium Rating Scale (DRS). Delirium was secondary to post-operative dysfunction or acute medical conditions.
Evidence does not currently support the use of any one biomarker. However, certain markers were associated with promising results and may warrant evaluation in future studies. Heterogeneity across study methods may have contributed to inconclusive results, and more clarity may arise from standardization of methods of clinical assessment. Adjusting for comorbidities may improve understanding of the pathophysiology of delirium, in particular the role of confounders such as inflammation, cognitive disorders and surgical trauma. Future research may also benefit from inclusion of other diagnostic modalities such as EEG as well as analysis of genetic or epigenetic factors.
Therapeutic options for agitation in the intensive care unit
2020, Anaesthesia Critical Care and Pain Medicine
Agitation is common in the intensive care unit (ICU). There are numerous contributing factors, including pain, underlying disease, withdrawal syndrome, delirium and some medication. Agitation can compromise patient safety through accidental removal of tubes and catheters, prolong the duration of stay in the ICU, and may be related to various complications. This review aims to analyse evidence-based medical literature to improve management of agitation and to consider pharmacological strategies. The non-pharmacological approach is considered to reduce the risk of agitation. Pharmacological treatment of agitated patients is detailed and is based on a judicious choice of neuroleptics, benzodiazepines and α2 agonists, and on whether a withdrawal syndrome is identified. Specific management of agitation in elderly patients, brain-injured patients and patients with sleep deprivation are also discussed. This review proposes a practical approach for managing agitation in the ICU.
Anticholinergic drug exposure at intensive care unit admission affects the occurrence of delirium. A prospective cohort study
2020, European Journal of Internal Medicine
Anticholinergic drugs may increase the risk of delirium in non-critically ill patients, but it is unclear whether exposure to these drugs is also a risk factor for Intensive Care Unit (ICU) delirium. In this study the hypothesis was tested that anticholinergic drug exposure at ICU admission increases the risk to develop delirium during ICU stay, particularly in patients with advanced age and severe sepsis.
A prospective cohort study was performed in the mixed 32-bed medical-surgical ICU of the University Medical Center Utrecht, the Netherlands in the period from January 2011 till June 2013. Included were nonneurological patients that were consecutively admitted for more than 24 hours. The presence of delirium was evaluated each day using a validated algorithm based on the Confusion Assessment Method for the ICU (CAM-ICU), the initiation of delirium treatment as well as chart review by researchers. Anticholinergic drug exposure at ICU admission was assessed using the Anticholinergic Drug Scale (ADS). To evaluate the association between anticholinergic drug exposure at ICU admission and the risk of developing delirium, we performed multivariable competing risk Cox proportional hazard analysis corrected for confounding factors.
Approximately half (47%, n=513) of the 1090 included patients developed delirium during ICU admission. The absolute risk for delirium development increased with more anticholinergic drug exposure: 42% in patients with ADS score=0, 49% in patients with ADS score=1, and 53% in patients with ADS higher than 1. Taking competing events (death and discharge) and potential confounding factors into account, the subdistribution hazard ratio (SHR) was 1.13 (95% CI: 0.91-1.40) for ADS score=1 point and 1.35 (95% CI: 1.09-1.68) for ADS ≥2 compared with an ADS score=0 (no anticholinergic drug exposure). The effect was strongest during the first days of ICU admittance and was strongest in patients above 65 year without severe sepsis and/or septic shock (SHR 2.15, 95% CI 1.43-3.25).
Anticholinergic drug exposure at ICU admission increases the risk of delirium in critically ill patients. This effect was most pronounced in patients older than 65 years without severe sepsis and/or septic shock, and declining over time.

View all citing articles on Scopus

The authors are indebted to Sue Levkoff, Sc.D., for helpful advice; Xincha Cui, M.D., for assistance in database management; Susan Mitchell, M.D., M.P.H., for assistance in manuscript preparation; and the members of the phlebotomy department at the Beth Israel Deaconess Medical Center East Campus (formerly Boston's Beth Israel Hospital) for their assistance in sample acquisition.

Drs. Flacker and Cummings were supported in part by a Faculty Training Project in Geriatric Medicine and Dentistry from Bureau of Health Professions Grant 5-D31-AH-91000 and HHS grants AG08812, AG10829, and AG00294. The work was also supported in part by a grant from the Department of Veterans Affairs.

View full text

Regular ArticlesThe Association of Serum Anticholinergic Activity With Delirium in Elderly Medical Patients

Section snippets

METHODS

RESULTS

DISCUSSION

Psychosomatics

Delirium in hospitalized older persons: outcomes and predictors

J Am Geriatr Soc

Confusion in hospitalized elderly: incidence, onset, and associated factors

Res Nurs Health

Angel's trumpet psychosis: a central nervous system anticholinergic syndrome

Am J Psychiatry

Delirium induced by poisoning with anticholinergic agents

Am J Psychiatry

Association of postoperative delirium with raised serum levels of anticholinergic drugs

Lancet

Post-ECT confusional states associated with elevated serum anticholinergic activity

Am J Psychiatry

Association of elevated plasma anticholinergic activity with delirium in surgical patients

Am J Psychiatry

Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study

J Am Geriatr Soc

A prospective study of delirium in hospitalized elderly

JAMA

Risk factors for delirium in hospitalized elderly

JAMA

Validation of a measure of physical illness burden at autopsy: The Cumulative Illness Rating Scale

J Am Geriatr Soc

Studies of illness in the aged, the index of ADL: a standardized measure of biological and psychosocial function

JAMA

Anticholinergic side effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium

Am J Psychiatry

Regular Articles
The Association of Serum Anticholinergic Activity With Delirium in Elderly Medical Patients