Anticholinergic burden and revisit risk in frail patients with pharmacological sleepiness

Abstract

Objective

Drug-induced sleepiness is a frequent cause of emergency department (ED) visits for frail patients. The aim of this study was to assess the impact of anticholinergic burden on 90-day revisitation risk for frail patients who visit the ED due to drug-induced sleepiness.

Methods

This was a retrospective study in which patients treated at a fragility care area of an ED who sought consultation for drug-associated sleepiness from June 2020 to June 2021 were included. To evaluate the 90-day revisitation risk factors, a multivariate analysis was performed, including those factors with a p<0.200 from a previous univariate model. A Cox regression model was performed to assess the impact of a high burden on the time until 90-day ED revisitation.

Results

One hundred and forty-eight patients were included (mean age 80.7±12.3 years). The median number of drugs that patients were currently on at emergency admission was eight (range 2–19), while at hospital discharge it was nine (range 2–20), with the median number of central nervous system (CNS) depressant drugs on admission being three (range 1–6). Thirty-five (23.6%) patients revisited the ED 90 days after discharge for sleepiness or agitation. In the multivariate model, a significant association was observed between a high anticholinergic burden during treatment at discharge (OR 3.74, 95% CI 1.36 to 9.71), chronic kidney disease (OR 2.87, 95% CI 1.19 to 6.81), and the risk of 90-day revisitation. Patients with high anticholinergic burden had a shorter time to revisit than those with medium or low anticholinergic burden (HR 1.96, 95% CI 1.05 to 3.99).

Conclusions

Patients with pharmacological sleepiness and a high anticholinergic burden in their chronic treatment carry a greater risk of revisitation to EDs, and should be considered candidates for specific interventions after visiting these units.

WHAT IS ALREADY KNOWN ON THIS TOPIC.

• Sleepiness secondary to treatment is widely variable, and the risk of onset depends on multiple factors, including the different cognitive stages of patients, associated comorbidities and pharmacological treatment. Various studies have evaluated different risk factors associated with episodes of pharmacological sleepiness. However, the impact of anticholinergic burden associated with usual treatment on hospital readmission is unknown.

WHAT THIS STUDY ADDS

• The anticholinergic burden of pharmacological treatment has a direct impact on revisitation to the emergency department (ED) for patients who visit due to episodes of pharmacological sleepiness.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• The anticholinergic burden of chronic medication must be evaluated in those patients who visit the emergency services for drug-induced sleepiness, and treatment adjustments (deprescription or treatment modification) should be proposed at discharge to minimise its burden and prevent new episodes.

Introduction

Drug-induced sleepiness is a common cause of emergency department (ED) visits for frail patients.^{1 2} This adverse effect has relevant consequences after patient discharge, including predisposition to falls and accidents, decreased cognitive activity and abandonment of treatment. It is known that sleepiness secondary to treatment is widely variable and the risk of onset depends on multiple factors, including the different cognitive stages of patients, associated comorbidities and pharmacological treatment.³

Knowing the risk factors of this adverse event is essential for the development of interventions that optimise treatment to reduce new episodes, to improve the quality of life of patients and to avoid abandonment of treatment. Although some studies have evaluated different risk factors associated with episodes of pharmacological sleepiness,^{4 5} the impact of anticholinergic burden associated with usual treatment on revisitation episodes and hospital readmission for patients who visit after a first sleepiness episode is limited.

Hence, this study aims to evaluate the impact of anticholinergic burden on the frequency of 90-day revisitation in frail patients who visit the ED due to a sleepiness episode attributed to the treatment.

Methods

A retrospective cohort study was conducted in which patients who were attended at a fragility care area in an ED due to drug-associated sleepiness as a primary or secondary diagnosis from June 2020 to June 2021 were included. Patients with autolytic attempt were excluded. This study was performed in an ED of a tertiary hospital with 644 beds attending to approximately 140 000 emergencies per year in a health area with a reference population of 410 000 people, 24.1% being older than 65 years old.

Data on comorbidities were collected at the time of admission, and data were also collected on the patient’s destination at discharge, the number of drugs prescribed in the patient’s electronic prescription at admission, discharge from the ED and the anticholinergic burden of medication at discharge from the unit. This last factor was calculated using the anticholinergic Drug Burden Index (DBI) scale,⁶ identifying the patient as having a “high anticholinergic burden” for a score ≥1. Revisitation episodes related to new episodes of sleepiness or agitation during the 90 days after hospital discharge were recorded in the ED of the hospital itself or any other center included in the healthcare area.

To evaluate the risk factors for 90-day revisitation related to sleepiness or agitation, a multivariate analysis was performed, including those factors with a p<0.200 in the univariate model. This cut-off point was used to avoid the exclusion of covariates with a relevant weight in the final model.⁷

The variables evaluated included factors related to treatment at ED discharge (prescription of opioids, benzodiazepines, antidepressants, antipsychotics, polypharmacy (>9 medications) and high anticholinergic burden), patient comorbidities (hypertension, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease (glomerular filtration rate <60 mL/min), heart failure, dementia and active oncological disease) and destination after emergency discharge (home, nursing home and long stay health centre). Conversely, a Cox regression model was used to evaluate the impact of a high burden on the time to revisitation to the ED within 90 days after discharge caused by new episodes of sleepiness and agitation. This study was approved by the Hospital Bioethics Committee (IIBSP-COD-2022–40).

Results

One hundred and forty-eight patients were included (mean age 80.7 years, SD 12.3 years). The main demographic and clinical characteristics and destinations of the patients included are summarised in table 1. The median number of drugs at emergency admission was eight (2–19), while at hospital discharge it was nine (range 2–20). Of these patients, 81 (54.7%) had some type of dementia, with a moderate-severe dependence in 75 (50.7%).

Table 1.

Description of the characteristics and chronic conditions in the study population

	N=148 (%)
Age >80 years	96 (64.9%)
Female	87 (58.8%)
Comorbidities
Dementia	81 (54.7%)
Diabetes	42 (28.4%)
COPD	10 (6.8%)
Chronic renal failure (<50 mL/min)	29 (19.6%)
Cirrhosis	5 (3.4%)
Chronic heart failure	21 (14.2%)
Treatment at discharge
Polypharmacy (>9 drugs)	53 (35.8%)
Opioids	57 (38.5%)
Benzodiazepines	81 (54.7%)
Antipsychotics	121 (81.8%)
Antidepressants	83 (56.1%)
Antiepileptics	37 (25.0%)
Antiparkinsonians	30 (20.3%)
Destination
Home	78 (52.7%)
Nursing home	24 (16.2%)
Long stay health centre	46 (31.1%)

COPD, chronic obstructive pulmonary disease.

The median number of central nervous system (CNS) depressant drugs at admission was three (range 1–6). Antipsychotics (used by 81.8% of patients) and benzodiazepines (used by 54.7%) were the most commonly prescribed drugs at admission, followed by antidepressants (56.1%) and opioids (38.5%). At hospital discharge or in the subsequent 72 hours, the prescription of depressant drugs was modified in 97 (65.5%) patients. Ninety-nine (66.9%) patients showed a high anticholinergic DBI (DBI≥1) at admission, with 119 (80.4%) showing a high anticholinergic burden at discharge.

Thirty-five (23.6%) patients revisited the ED 90 days after discharge with sleepiness or agitation. Three risk factors (chronic kidney disease, diabetes and high anticholinergic burden) were included in the multivariate model (p<0.200) (table 2), which observes a significant association between a high anticholinergic burden in treatment at discharge (OR 3.74, 95% CI 1.36 to 9.71), chronic kidney disease (OR 2.87, 95% 1.19 to 6.81) and 90-day revisitation risk.

Table 2.

Results of the univariate model on factors associated with the risk of revisiting the emergency department after 90 days

	OR (95% CI)	P value
Age>80 years	0.82 (0.69 to 1.37)	0.722
Female	0.85 (0.43 to 1.72)	0.668
Comorbidities
Dementia	1.02 (0.51 to 3.08)	0.920
Diabetes	0.59 (0.28 to 1.26)	0.172
COPD	1.95 (0.46 to 8.20)	0.322
Chronic renal failure (<50 mL/min)	2.81 (1.20 to 6.56)	0.017
Polypharmacy (>9 drugs)	0.84 (0.41 to 1.70)	0.634
Opioids	0.77 (0.37 to 1.60)	0.501
Benzodiazepines	0.91 (0.46 to 1.81)	0.791
Antipsychotics	0.85 (0.43 to 1.72)	0.672
Antidepressants	0.97 (0.48 to 1.93)	0.936
Antiepileptics	0.80 (0.36 to 1.77)	0.583
Antiparkinsonians	1.62 (0.68 to 3.85)	0.727
High anticholinergic burden	3.58 (1.27 to 9.52)	0.009
Destination
Home	1.65 (0.81 to 3.35)	0.208
Nursing home	0.57 (0.21 to 1.51)	0.291
Long stay health centre	0.77 (0.36 to 1.67)	0.520

COPD, chronic obstructive pulmonary disease.

The effect of anticholinergic burden on the time to revisitation is shown in figure 1. Patients with high anticholinergic burden had a shorter time to revisit than those with medium or low anticholinergic burden (HR 1.96, 95% CI 1.05 to 3.99).

Figure 1.

Days until revisit to the emergency department for patients with and without high anticholinergic burden in their chronic treatment.

Discussion

According to the results of this study, the anticholinergic burden of pharmacological treatment shows a direct impact on revisit to the ED for patients who visit due to episodes of pharmacological sleepiness.

Sleepiness in frail patients is a common and often multifactorial phenomenon and may indicate an underlying sleep disorder, a chronic medical condition, an undiagnosed mood disorder or side effects of medication. It should be noted that polypharmacy is a common phenomenon in this patient profile,^{8 9} with a third of patients observed in this series on >9 drugs. The harmful effects of a high anticholinergic burden in older patients are widely known, and neurological disorders are among the most widely described negative effects.^{10 11} In fact, different scales for optimising chronic treatment in older patients, such as the Beers or STOPPFrail criteria, recommend limiting drugs with such effects in this population group.^{12 13} Despite this, many of the included patients showed a high anticholinergic burden in their chronic treatment, being similar to that in the other series described in the literature.^{14 15} In contrast, we observed that a significant percentage of older patients were being treated with other potentially inappropriate drugs, such as long-term benzodiazepines or opioids. However, according to the results of our series, these groups of drugs separately have not been associated with an increased revisit risk, with the association with other drugs with anticholinergic activity being a necessary condition for the increased risk. A complete review of chronic treatment in this group of patients who use emergency services due for this symptomatology is therefore necessary, with the objective of optimising the improvement of chronic pharmacotherapy by modifying various therapeutic groups.

The present study considered as inclusion criteria only those patients admitted for pharmacological drowsiness, although both drowsiness and agitation events were considered in revisit episodes. This consideration has made it possible to observe the negative effect of the modification and incorporation of new treatments that modify the anticholinergic burden or depressant effect of the CNS, highlighting the difficulty in changing treatment in elderly patients and the need for an expert multidisciplinary team to handle it.

The results of the study also highlight renal failure as a factor associated with ED revisit risk. It is known that patients with chronic renal failure have more emergency and hospital readmissions.^{16 17} Regarding pharmacological sleepiness, a large number of these drugs is partially or completely eliminated by the kidney, accumulating inside these patients and producing more adverse events.¹⁸ The adjustment of the dosage of the CNS depressant drugs in this group of patients should be one of the priorities at hospital discharge.

Another of the relevant findings of this study is that the number of patients with a high anticholinergic burden was higher on discharge from the ED than on admission. It should be noted that these patients often present with episodes of agitation during their stay in the ED, with their usual antipsychotic treatment increased in a significant number of cases. This practice should be monitored in the emergency rooms, and schemes that simplify treatment and reduce the patient’s anticholinergic burden should be proposed.

A limitation of this study is its unicentric character, as well as its not having analysed the effects of other factors related to the onset of sleepiness, such as physical activity or sleep hygiene. However, the study allows us to establish a score to identify a group of patients at high risk of revisitation that will require early and specific action. Neither were treatment modifications after hospital discharge considered, given the difficulty in obtaining them from private residential centres. Given the particularities in the medical care of these private centres, excluding the patients treated in them from the analysis could have led to a certain selection bias in the results obtained. On the other hand, our study covers an older population group, which limits the extrapolation of the results to young patients. However, both pharmacological sleepiness and polypharmacy mainly affect older patients, and therefore this group requires the most assistance in EDs.

Conclusions

Frail patients who visit the ED due to drug-induced sleepiness carry a high risk of 90-day revisitation. Patients with chronic kidney disease and a high anticholinergic burden in their treatment show an increased revisitation risk, and therefore are candidates for specific interventions coordinated with other care levels.

Data availability statement

Data are available upon reasonable request.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

This study involves human participants and was approved by This study was approved by the Hospital Santa Creu I Sant Pau Bioethics Committee (IIBSP-COD-2022-40).Retrospective study.