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JAMA Oct 2021Death rattle, defined as noisy breathing caused by the presence of mucus in the respiratory tract, is relatively common among dying patients. Although clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Death rattle, defined as noisy breathing caused by the presence of mucus in the respiratory tract, is relatively common among dying patients. Although clinical guidelines recommend anticholinergic drugs to reduce the death rattle after nonpharmacological measures fail, evidence regarding their efficacy is lacking. Given that anticholinergics only decrease mucus production, it is unknown whether prophylactic application may be more appropriate.
OBJECTIVE
To determine whether administration of prophylactic scopolamine butylbromide reduces the death rattle.
DESIGN, SETTING, AND PARTICIPANTS
A multicenter, randomized, double-blind, placebo-controlled trial was performed in 6 hospices in the Netherlands. Patients with a life expectancy of 3 or more days who were admitted to the participating hospices were asked to give advance informed consent from April 10, 2017, through December 31, 2019. When the dying phase was recognized, patients fulfilling the eligibility criteria were randomized. Of the 229 patients who provided advance informed consent, 162 were ultimately randomized. The date of final follow-up was January 31, 2020.
INTERVENTIONS
Administration of subcutaneous scopolamine butylbromide, 20 mg four times a day (n = 79), or placebo (n = 78).
MAIN OUTCOMES AND MEASURES
The primary outcome was the occurrence of a grade 2 or higher death rattle as defined by Back (range, 0-3; 0, no rattle; 3, rattle audible standing in the door opening) measured at 2 consecutive time points with a 4-hour interval. Secondary outcomes included the time between recognizing the dying phase and the onset of a death rattle and anticholinergic adverse events.
RESULTS
Among 162 patients who were randomized, 157 patients (97%; median age, 76 years [IQR, 66-84 years]; 56% women) were included in the primary analyses. A death rattle occurred in 10 patients (13%) in the scopolamine group compared with 21 patients (27%) in the placebo group (difference, 14%; 95% CI, 2%-27%, P = .02). Regarding secondary outcomes, an analysis of the time to death rattle yielded a subdistribution hazard ratio (HR) of 0.44 (95% CI, 0.20-0.92; P = .03; cumulative incidence at 48 hours: 8% in the scopolamine group vs 17% in the placebo group). In the scopolamine vs placebo groups, restlessness occurred in 22 of 79 patients (28%) vs 18 of 78 (23%), dry mouth in 8 of 79 (10%) vs 12 of 78 (15%), and urinary retention in 6 of 26 (23%) vs 3 of 18 (17%), respectively.
CONCLUSIONS AND RELEVANCE
Among patients near the end of life, prophylactic subcutaneous scopolamine butylbromide, compared with placebo, significantly reduced the occurrence of the death rattle.
TRIAL REGISTRATION
trialregister.nl Identifier: NTR6264.
Topics: Aged; Aged, 80 and over; Butylscopolammonium Bromide; Cholinergic Antagonists; Confidence Intervals; Death; Double-Blind Method; Drug Administration Schedule; Female; Hospice Care; Humans; Incidence; Informed Consent; Injections, Subcutaneous; Life Expectancy; Male; Middle Aged; Netherlands; Placebos; Proportional Hazards Models; Respiratory Sounds; Treatment Outcome
PubMed: 34609452
DOI: 10.1001/jama.2021.14785 -
Journal of UOEH 2019Constipation is very common and can be caused by adverse drug reactions as a result of many drugs. While the adverse effects of several medications such as opioids and... (Review)
Review
Constipation is very common and can be caused by adverse drug reactions as a result of many drugs. While the adverse effects of several medications such as opioids and anticholinergic agents are well established and well known, other commonly prescribed drugs, such as hypnotics, are less well understood. This review presents the results of an analysis of the relationship between constipation and drugs.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents, Tricyclic; Calcium Channel Blockers; Cholinergic Antagonists; Constipation; Diuretics; Histamine Antagonists; Humans; Hypnotics and Sedatives; Opioid-Induced Constipation; Parasympatholytics
PubMed: 31292358
DOI: 10.7888/juoeh.41.145 -
Neuro-degenerative Diseases 2015In this article, we review the downregulation of acetylcholinergic activity in schizophrenia and discuss the similarity and difference between Alzheimer's disease (AD)... (Review)
Review
In this article, we review the downregulation of acetylcholinergic activity in schizophrenia and discuss the similarity and difference between Alzheimer's disease (AD) and schizophrenia in terms of acetylcholine (ACh) and anticholinergic activity (AA); then, we propose the use of cognition-enhancing therapy for schizophrenia. As ACh regulates an inflammatory system, when the cholinergic system is downregulated to a critical level, the inflammatory system is activated. We consider the possibility that AA appears endogenously in AD and accelerates AD pathology. This hypothesis can also be applied to schizophrenia. In fact, even before the onset of the disorder, in the prodromal phase of schizophrenia, cognitive dysfunction exists, and antibodies against astrocyte muscarinic-1 and muscarinic-2 receptors are present in the serum of patients with the paranoid type of schizophrenia. Then we noted that the prodromal phase in schizophrenia might correspond to the mild stage in AD and the acute phase to moderate stage concerning AA. We also think that we should enhance cognition in schizophrenia even in the prodromal phase because as mentioned above, downregulation of ACh is prominent in schizophrenia even in the prodromal phase.
Topics: Animals; Cholinergic Antagonists; Humans; Schizophrenia
PubMed: 26138495
DOI: 10.1159/000381523 -
Skin Therapy Letter Mar 2019Hyperhidrosis is a condition characterized by excessive sweat production beyond which is physiologically necessary for thermal regulation. Affecting over 4.8% of the... (Review)
Review
Hyperhidrosis is a condition characterized by excessive sweat production beyond which is physiologically necessary for thermal regulation. Affecting over 4.8% of the United States population, studies have shown that severe primary hyperhidrosis interferes with daily activities and can be considered intolerable, negatively impacting a patient’s quality of life. Glycopyrronium tosylate is a topical anticholinergic agent that reduces sweat production by blocking the activation of acetylcholine receptors in peripheral sweat glands. In clinical trials, topical glycopyrronium tosylate, a pre-moistened cloth containing 2.4% glycopyrronium solution, was shown to be an effective, safe and non-invasive treatment for patients suffering from primary hyperhidrosis. This review examines the clinical trials of topical glycopyrronium tosylate and its role in primary hyperhidrosis. Glycopyrronium tosylate was recently US FDA-approved (as of June 2018) to manage patients with primary axillary hyperhidrosis.
Topics: Administration, Cutaneous; Cholinergic Antagonists; Clinical Trials as Topic; Glycopyrrolate; Humans; Hyperhidrosis
PubMed: 30970203
DOI: No ID Found -
Journal of Neurochemistry Sep 2021The cholinergic system is a complex neurotransmitter system with functional involvement at multiple levels of the nervous system including the cerebral cortex, spinal... (Review)
Review
The cholinergic system is a complex neurotransmitter system with functional involvement at multiple levels of the nervous system including the cerebral cortex, spinal cord, autonomic nervous system, and neuromuscular junction. Anticholinergic medications are among the most prescribed medications, making up one-third to one-half of all medications prescribed for seniors. Recent evidence has linked long-term use of anticholinergic medications and dementia. Emerging evidence implicates the cholinergic system in the regulation of cerebral vasculature as well as neuroinflammation, suggesting that anticholinergic medications may contribute to absolute risk and progression of neurodegenerative diseases. In this review, we explore the involvement of the cholinergic system in various neurodegenerative diseases and the possible detrimental effects of anticholinergic medications on the onset and progression of these disorders. We identified references by searching the PubMed and Cochrane database between January 1990 and September 2019 for English-language animal and human studies including randomized clinical trials (RCTs), meta-analyses, systematic reviews, and observational studies. In addition, we conducted a manual search of reference lists from retrieved studies. Long-term anticholinergic medication exposure may have detrimental consequences beyond well-documented short-term cognitive effects, through a variety of mechanisms either directly impacting cholinergic neurotransmission or through receptors expressed on the vasculature or immune cells, providing a pathophysiological framework for complex interactions across the entire neuroaxis.
Topics: Animals; Brain; Cholinergic Antagonists; Cholinergic Neurons; Humans; Tardive Dyskinesia
PubMed: 33222198
DOI: 10.1111/jnc.15244 -
Journal of Pain and Symptom Management Feb 2023Children with severe neurological impairment and polypharmacy are exposed to anticholinergic (AC) medications that may have anticholinergic side effects, but this is...
CONTEXT
Children with severe neurological impairment and polypharmacy are exposed to anticholinergic (AC) medications that may have anticholinergic side effects, but this is understudied. Anticholinergic Cognitive Burden (ACB) scores measure total anticholinergic burden for a medication regimen, and scores ≥3 have been associated with increased morbidity and mortality in adults.
OBJECTIVE
We assessed the relationship between ACB scores and parent-reported anticholinergic symptoms in children.
METHODS
Cross-sectional study of patients one to 18 years-old with ICD-defined severe neurological impairment and polypharmacy. At routine clinical visits, total ACB scores were computed for all medications. Parent-reported AC symptoms (constipation, drowsiness, difficulty concentrating, dry mouth, or urinary problems) were assessed. Multivariable logistic regression was used to test the association between total ACB scores ≥3 for scheduled medications and the presence of AC symptoms, adjusted for age and recent acute healthcare utilization.
RESULTS
Among 123 unique patients, 87% were prescribed AC medications. Common AC medication classes included: systemic antihistamines (64%), anxiolytics (53%), antidepressants (30%), H2 blockers (22%), and muscle relaxants (20%). Total ACB scores ≥3 were observed in 44% for scheduled medications and in 63% of patients for scheduled plus PRN medications. Total ACB scores ≥3 were significantly associated with an increased odds of ≥1 anticholinergic symptoms for scheduled medications (OR: 3.1; 95% CI: 1.4, 6.7) and for scheduled plus PRN medications (OR: 2.9; 95% CI: 1.3, 6.4).
CONCLUSION
If replicated in larger populations, the association between elevated total ACB scores and anticholinergic side effects in children should prompt clinicians to consider deprescribing potentially unneeded anticholinergic medications.
Topics: Humans; Child; Infant; Child, Preschool; Adolescent; Cholinergic Antagonists; Cross-Sectional Studies; Delivery of Health Care
PubMed: 36332769
DOI: 10.1016/j.jpainsymman.2022.10.013 -
Journal of Parkinson's Disease 2022Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications.
BACKGROUND
Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications.
OBJECTIVE
To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients.
METHODS
We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Drug Burden Index-Anticholinergic component (DBI-Ach). Correlations between scales were assessed with weighted kappa coefficients.
RESULTS
Between 31.5 to 46.3% of PD patients were taking medications with anticholinergic properties. Among the scales applied, the ACB produced the highest prevalence of medications with anticholinergic properties (46.3%). Considering only medications with definite anticholinergic activity (scores of 2 or 3 on ACB, ADS, or ARS), the most common anticholinergic drug classes were antiparkinsonian (8.2%), antipsychotic (6.4%), and urological (3.3%) medications. Cholinesterase inhibitors and medications with anticholinergic properties were co-prescribed to 5.4% of the total cohort. The most highly correlated scales were ACB and ADS (κ= 0.71), ACB and ARS (κ= 0.67), and ADS and ARS (κ= 0.55).
CONCLUSION
A high proportion of PD patients (20%) were either taking antiparkinsonian, urological, or antipsychotic anticholinergic medications or were co-prescribed anticholinergic medications and cholinesterase inhibitors. By virtue of its detection of a high prevalence of anticholinergic medication usage and its high correlation with other scales, our data support use of the ACB scale to assess anticholinergic burden in PD patients.
Topics: Antipsychotic Agents; Cholinergic Antagonists; Cholinesterase Inhibitors; Humans; Outpatients; Parkinson Disease
PubMed: 34806617
DOI: 10.3233/JPD-212769 -
Medicina (Kaunas, Lithuania) Oct 2021: Anticholinergic drug use in the pharmacotherapy of elderly persons is common despite the increased risk of side effects. We examined the prevalence of anticholinergic...
: Anticholinergic drug use in the pharmacotherapy of elderly persons is common despite the increased risk of side effects. We examined the prevalence of anticholinergic drug use and total anticholinergic drug burden among patients admitted to an acute care geriatric ward in Poland. : Cross-sectional study of 329 subjects hospitalized at the geriatric ward. Patient condition was assessed with a comprehensive geriatric assessment. The Anticholinergic Cognitive Burden (ACB) scale was used to estimate the total anticholinergic load. : Mean patient age was 79.61 ± 6.82 years. 40.73% of them were burdened with at least one anticholinergic drug. The clinically significant anticholinergic burden was observed in 13.98% of subjects. Patients with dementia, risk of falls, and severe disability had significantly higher total ACB scores compared to other groups. The receiver operating characteristics (ROC) curve revealed that the total ACB score ≥ 1 was significantly associated with dementia and the risk of falls. Total ACB score ≥ 2 was significantly associated with severe disability. : Patients admitted to an acute care geriatric ward had an anticholinergic cognitive burden score comparable to other patient populations. We found associations at both low and elevated levels of anticholinergic burden with dementia and risk of falls. At elevated anticholinergic burden levels, we found associations with severe disability. Despite recommendations against the use of anticholinergics in older adults these medications are still commonly prescribed. Further study is necessary to define the characteristics of anticholinergic medication most closely associated with negative outcomes in elderly populations.
Topics: Aged; Aged, 80 and over; Cholinergic Antagonists; Cross-Sectional Studies; Dementia; Hospitals; Humans; Inpatients
PubMed: 34684152
DOI: 10.3390/medicina57101115 -
BMC Geriatrics Mar 2023As people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy is the associated increase in anticholinergic exposure to older adults. In addition, several studies suggest an association between anticholinergic burden and declining physical function in older adults.
OBJECTIVE/PURPOSE
This systematic review aimed to synthesise data from published studies regarding the association between anticholinergic burden and mobility. The studies were critically appraised for the strength of their evidence.
METHODS
A systematic literature search was conducted across five electronic databases, EMBASE, CINAHL, PSYCHINFO, Cochrane CENTRAL and MEDLINE, from inception to December 2021, to identify studies on the association of anticholinergic burden with mobility. The search was performed following a strategy that converted concepts in the PECO elements into search terms, focusing on terms most likely to be found in the title and abstracts of the studies. For observational studies, the risk of bias was assessed using the Newcastle Ottawa Scale, and the Cochrane risk of bias tool was used for randomised trials. The GRADE criteria was used to rate confidence in evidence and conclusions. For the meta-analyses, we explored the heterogeneity using the Q test and I test and the publication bias using the funnel plot and Egger's regression test. The meta-analyses were performed using Jeffreys's Amazing Statistics Program (JASP).
RESULTS
Sixteen studies satisfied the inclusion criteria from an initial 496 studies. Fifteen studies identified a significant negative association of anticholinergic burden with mobility measures. One study did not find an association between anticholinergic intervention and mobility measures. Five studies included in the meta-analyses showed that anticholinergic burden significantly decreased walking speed (0.079 m/s ± 0.035 MD ± SE,95% CI: 0.010 to 0.149, p = 0.026), whilst a meta-analysis of four studies showed that anticholinergic burden significantly decreased physical function as measured by three variations of the Instrumental Activities of Daily Living (IADL) instrument 0.27 ± 0.12 (SMD ± SE,95% CI: 0.03 to 0.52), p = 0.027. The results of both meta-analyses had an I statistic of 99% for study heterogeneity. Egger's test did not reveal publication bias.
CONCLUSION
There is consensus in published literature suggesting a clear association between anticholinergic burden and mobility. Consideration of cognitive anticholinergic effects may be important in interpreting results regarding the association of anticholinergic burden and mobility as anticholinergic drugs may affect mobility through cognitive effects.
Topics: Humans; Aged; Activities of Daily Living; Cholinergic Antagonists; Walking Speed; Polypharmacy; Quality of Life
PubMed: 36949391
DOI: 10.1186/s12877-023-03820-6 -
The Cochrane Database of Systematic... Sep 2021
Topics: Cholinergic Antagonists; Dementia; Humans; Pharmaceutical Preparations; Uncertainty
PubMed: 34494256
DOI: 10.1002/14651858.ED000154