Anticholinergic Medications and Risk of Community-acquired Pneumonia in Elderly Adults: A Population-based Case–control Study

Kathleen J. Paul, MD, MPH; Rod L. Walker, MS; Sascha Dublin, MD, PhD

Disclosures

J Am Geriatr Soc. 2015;63(3):476-485. 

In This Article

Abstract and Introduction

Abstract

Objectives To determine whether use of anticholinergics is associated with risk of community-acquired pneumonia in older adults.

Design Population-based case–control study.

Setting An integrated healthcare delivery system in Washington State.

Participants Data from a nested case–control study of community-dwelling immunocompetent adults aged 65 to 94 were analyzed. Pneumonia cases (n = 1,039) were ascertained according to International Classification of Diseases, Ninth Revision, codes from 2000 to 2003 and validated using chart review. Controls (n = 2,022) were matched 2:1 to cases according to age, sex, and year.

Measurements Anticholinergic medication exposure was ascertained using prescription data; acute use was defined as one or more prescription fills 90 days or less before the index date (date of pneumonia diagnosis), past use was defined as one or more prescription fills within the prior year but none within 90 days, and chronic use was defined as three or more prescription fills within the prior year. The reference group was those with no fills in the prior year. Conditional logistic regression was used to analyze the association between anticholinergic use and pneumonia, adjusted for comorbidities.

Results Acute use of anticholinergics was observed in 59% of cases and 35% of controls (adjusted odds ratio (aOR) = 2.55, 95% confidence interval (CI) = 2.08–3.13) and past use in 17% of cases and 23% of controls (aOR = 1.19, 95% CI = 0.92–1.53). Chronic use of anticholinergics was observed in 53% of cases and 36% of controls (aOR 2.07, 95% CI = 1.68–2.54). Results were not different for high- and low-potency anticholinergic medications.

Conclusion In older adults, anticholinergic medication use is associated with pneumonia risk, adding to substantial evidence suggesting that these medications are high risk.

Introduction

Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in older adults; respiratory illness, including pneumonia and influenza, was the eighth leading cause of death in the United States in 2011.[1] There is increasing interest in whether medication use contributes to risk of CAP in older adults in addition to well-established risk factors such as chronic obstructive pulmonary disease (COPD), congestive heart failures (CHF), and asthma. Prescription opiates[2] and antipsychotics[3,4] have been associated with greater risk of pneumonia in elderly adults, whereas other commonly prescribed classes of medications, including benzodiazepines, statins, and proton pump inhibitors, have demonstrated inconsistent associations across studies.[2,5–9] No prior studies have addressed whether oral anticholinergic medications affect the risk of pneumonia in this population.

Anticholinergic medications are frequently prescribed for common conditions that affect older adults such as urinary incontinence, depression, pain, and insomnia. Providers tend to be well aware of the anticholinergic effects of medications such as tricyclic antidepressants and bladder antispasmodics but not necessarily aware of anticholinergic properties of selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, and pain medications.[10] The American Geriatrics Society 2012 revised Beers criteria define most tricyclic antidepressants, first-generation antihistamines, antipsychotics, and antispasmodics as potentially inappropriate medications in elderly adults but do not make recommendations on other classes of anticholinergics commonly used in this population.[11] Anticholinergic medications act on muscarinic acetylcholine receptors centrally and peripherally, with side effects including dry mouth, dry eyes, vision changes, constipation, urinary retention, sedation, confusion, and delirium. Evidence is accumulating to suggest that anticholinergics may also contribute to more-chronic functional decline, including fatigue, weakness, falls, and cognitive deficits.[10,12]

Specifically relevant to the development of pneumonia, central effects of anticholinergic medications including sedation and altered mental status may contribute to risk of aspiration events.[13] Sedation and altered mental status could also contribute to poor pulmonary hygiene and atelectasis in the context of a viral respiratory infection, increasing the risk of developing postviral pneumonia.

The objective of the current study was to determine whether acute or chronic use of anticholinergic medications was related to risk of CAP in older adults and whether anticholinergic potency further affected risk. It was hypothesized that use of anticholinergic medications would increase the risk of pneumonia in this population in addition to their known adverse effects and that high-potency anticholinergics would be associated with greater risk than low-potency anticholinergics.

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