Oral and Transdermal Rivastigmine for the Treatment of Anticholinergic Delirium: A Case Report.

BACKGROUND: Anticholinergic toxicity is a common cause of delirium in emergency department patients. The standard antidotal treatment for anticholinergic toxicity is physostigmine. Physostigmine functions as a reversible acetylcholinesterase inhibitor that readily crosses the blood-brain barrier. Rivastigmine is another member of this class currently approved for the treatment of Alzheimer's disease and Parkinson's disease. Rivastigmine also crosses the blood-brain barrier and has been found to be effective in the management of anticholinergic toxicity in limited case reports. CASE REPORT: A 61-year-old women presented to the emergency department via emergency medical services with altered mental status and a Glasgow Coma Scale score of 8 out of 15. She was found down near multiple medication bottles, including diphenhydramine and dicyclomine. Her physical examination was consistent with anticholinergic toxicity with mydriasis, obtundation, and warm flushed skin. In addition to standard resuscitation, she received two doses of rivastigmine 3 mg via nasogastric tube. After the second dose she was alert and oriented. She was admitted to the intensive care unit and had a rivastigmine patch applied. She was deemed back to her baseline 27 h after presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although the standard antidotal treatment for anticholinergic toxicity is physostigmine, there is a national shortage of this medication. In the absence of this standard antidote, it is reasonable for emergency physicians to use rivastigmine as an alternative treatment. This can be delivered orally or via nasogastric tube with dosing each hour until resolution of symptoms. Alternatively, in consultation with toxicology, it may be reasonable to use transdermal rivastigmine, as it provides consistent drug absorption for 24 h.

[Central anticholinergic, neuroleptic malignant and serotonin syndromes : Important differential diagnoses in postoperative impairment of consciousness]. / Zentrales anticholinerges, malignes neuroleptisches und Serotoninsyndrom : Wichtige Differenzialdiagnosen bei postoperativen Bewusstseinsstörungen.

Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2 mg (0.04 mg/kg body weight, BW) administered over 5 min. For serotonin syndrome an initial dose of 12 mg cyproheptadine followed by 2 mg every 2 h is recommended (maximum 32 mg/day or 0.5 mg/kgBW day-1) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120 mg dantrolene (1-2.5 mg/kgBW maximum 10 mg/kgBW day-1) is the recommended treatment.

Anticholinergic syndrome: blurred vision and headache.

A young woman presented with blurred vision due to anticholinergic syndrome. We highlight the importance of considering this condition in the context of multiple medications and increased anticholinergic burden. The documented pupil abnormality gives an opportunity to review the syndrome of the reverse (inverse) Argyll Robertson pupil (preserved pupil light response with loss of accommodation). We review other situations in which the reverse Argyll Robertson pupil may occur and its possible mechanism in this case.

Central anticholinergic syndrome secondary to atropine eye drops: A case study.

Atropine eye drops are frequently used in the treatment of keratitis and during ophthalmic surgery. We described a rare complication of central anticholinergic syndrome secondary to atropine eye drops.

Unintentional cetirizine overdose causing anticholinergic syndrome.

The incidence of anticholinergic syndrome due to second generation antihistamines is infrequently reported. Largely due to their decreased affinity for central nervous system (CNS) receptors, second generation antihistamines are rarely associated with anticholinergic symptoms, though toxicity is still possible particularly when taken in excess. We report a case of a six year old boy who presented with agitation, hallucinations, fixed and dilated pupils, tachycardia, and hyperthermia consistent with anticholinergic toxicity several hours after accidental overdose of a second generation antihistamine, cetirizine. Early identification of this rare phenomenon is important not only for appropriate emergency management but also for avoidance of potentially invasive and unnecessary tests which may further increase patient morbidity.

Anticholinergic syndrome after atropine overdose in a supposedly homeopathic solution: a case report.

BACKGROUND: A 53-year-old male with no pre-existing conditions and no permanent medication presented to our emergency department with an anticholinergic syndrome including confusion, anxiety, ataxia and dysarthria after ingestion of a homeopathic solution containing Atropa belladonna extract supposedly in a D4 dilution. METHODS: Atropine sulphate was quantitatively analysed in serum and the homeopathic preparation via liquid chromatography/mass spectrometry. RESULTS: Analysis revealed concentrations of approximately 3 mg/mL atropine sulphate in the homeopathic solution and a serum level of 5.7 ng/mL (±1.4) in the patient's blood proving a 600-fold overdose of atropine due to a production error of the homeopathic dilution. The patient was observed and recovered without further intervention. CONCLUSION: Rare but possibly dangerous manufacturing errors should be considered when faced with symptoms occurring after ingestion of homeopathic or holistic remedies.

A comparison of anticholinergic burden in older patients with and without cancer.

Aim: To compare anticholinergic burden (ACB) in older patients with and without cancer and evaluate the effects of ACB on geriatric syndromes. Methods: A total of 291 patients from the geriatric clinic and 301 patients from the oncology clinic were evaluated. ACB <2 was categorized as low ACB and ACB ≥2 was categorized as high ACB. A comprehensive geriatric assessment was performed on patients from the geriatric clinic. Results: ACB scores were significantly higher in patients without cancer compared with those with cancer (p < 0.005). Number of falls and Geriatric Depression Scale 15 scores were higher and Mini-Nutritional Assessment and Barthel/Lawton activities of daily living scores were lower in geriatric patients with high ACB scores compared with those with low ACB scores (p < 0.005). Conclusion: It is crucial to understand the potential effects of ACB for rational drug use and optimum cancer management in older patients with cancer.

Lay abstract The elderly population is increasing rapidly worldwide, and most cancer patients are over the age of 65. In this age group, preexisting medical conditions other than cancer lead to the use of multiple drugs, which is defined as polypharmacy. Additionally, the anticholinergic burden (ACB) of the drugs affects cancer treatment in the elderly. This study investigated the frequency of polypharmacy and ACB in elderly patients with and without cancer and their relationship with geriatric syndromes such as depression, falls, nutritional and cognitive impairments. We found that ACB was higher in older patients without cancer than those with cancer and is related to increased falls, depressive symptoms, and impaired nutritional and functional status in older patients. Given the prevalence of cancer among older adults, it is crucial to understand the potential effects of the ACB for rational drug use and optimum cancer management in older patients with cancer.

The Use of Physostigmine in the Diagnosis and Treatment of Anticholinergic Toxicity After Olanzapine Overdose: Literature Review and Case Report.

BACKGROUND: Second-generation antipsychotic agents are commonly used by clinicians for the treatment of various psychiatric and medical conditions. Despite their presumed safety, an overdose with olanzapine may lead to the development of anticholinergic toxicity. The anticholinergic toxidrome is characterized by both central and peripheral physical findings. Central anticholinergic syndrome, a term used to describe the symptoms that arise from reduced cholinergic activity in the central nervous system, is characterized primarily by signs and symptoms consistent with hyperactive delirium. Signs of peripheral anticholinergia include mydriasis and blurred vision, tremors, ataxia, fever/hyperthermia, flushed and dry skin, dry oral mucosa, decreased bowel sounds, constipation, and urinary retention, among other symptoms. In extreme cases, central anticholinergic syndrome can be associated with seizures, coma, respiratory failure, and cardiovascular collapse. OBJECTIVE: To provide scientific evidence regarding the efficacy and safety of physostigmine use in cases of anticholinergic toxicity. METHODS: We conducted a comprehensive review of the published literature on the symptoms, diagnosis, and treatment of anticholinergic toxicity. RESULTS: Currently the recommended treatment for olanzapine overdose, as is the case of most severe anticholinergic toxicity cases, involves supportive care, along with cardiac, neurological, and respiratory status monitoring. In addition, we detail the symptoms characteristic of anticholinergic toxicity, using the case of a patient experiencing central anticholinergic syndrome after an overdose with olanzapine. CONCLUSION: Physostigmine, a tertiary acetylcholinesterase inhibitor, can be used to assist in the both the diagnosis and management of severe anticholinergic toxicity associated with an olanzapine overdose, which might be applicable to the antimuscarinic toxidrome associated with the ingestion of agents with significant anticholinergic activity.

Association between anticholinergic burden and hospital readmission in older patients: a prospective analysis.

OBJECTIVE: Despite known adverse effects of anticholinergic (AC) medication, little work has been devoted to the impact of high anticholinergic burden on the rate of hospital readmission. The purpose of this study was to analyze prospectively the link between high AC burden and the rate of all-cause thirty-day hospital readmission in older people. STUDY DESIGN: This was a prospective non-interventional study conducted from January to August 2019 in one acute-care geriatric ward. All hospital stays of patients aged at least 75 years who were discharged to their home were included in the analysis. AC burden was determined from discharge prescriptions using the Anticholinergic Drug Scale (ADS) and the Anticholinergic Risk Scale (ARS), and defined as high if ≥3. RESULTS: The analysis concerned 350 hospital stays. Median patient age was 88 years (interquartile interval 84-91). In a multivariate analysis, the risk of hospital readmission within 30 days was not increased for patients with high AC burden (ADS≥3): odds ratio 1.16 [95% confidence interval 0.56-2.37], compared to a patient whose anticholinergic burden was not high. CONCLUSION: Unlike retrospective studies on this issue, the findings of our prospective analysis do not support a higher risk of hospital admission within 30 days for older people with high AC burden as assessed from their discharge prescriptions.

[Botulism: A case report and literature review]. / Botulisme : à propos d'un cas et revue de la littérature.

INTRODUCTION: Botulism is a rare syndrome resulting from the action of a neurotoxin produced by Clostridium botulinum, that it is potentially life threatening if diagnosis is delayed. CASE REPORT: We report a 26-year-old woman who presented an acute onset of bilateral cranial neuropathies associated with an anticholinergic syndrome in the absence fever leading to consider and confirm the diagnosis of botulism. At the end of follow-up, 7 weeks later, the outcome was favorable with an almost complete neurologic recovery. CONCLUSION: Although botulism is uncommon, better awareness of its manifestations and high clinical suspicion should shorten diagnostic delay that makes the use of specific antitoxin ineffective. An acute onset of a bilateral oculomotor palsy, a fixed pupillary dilation and descending weakness in the absence of fever is typical of botulism. Outcome is usually favorable with a slow but full neurological recovery.

[Analytical investigation of a suspected case of drug-facilitated crime]. / Säker och känslig analysmetodik viktig vid misstänkta fall av ofrivillig drogning.

Sometimes it is suspected that people have been involuntary exposed to drugs, usually by spiked drinks. A young woman was transported to an emergency department by ambulance. Her clinical symptoms (decreased consciousness, mydriasis, confusion, hallucinations and urine retention) indicated anticholinergic syndrome that was effectively treated with the antidote physostigmine. A urine sample tested negative for common narcotic drugs and alcohol, but an extended toxicological analysis of the urine revealed the presence of the alkaloid scopolamine. Scopolamine occurs naturally in Solanaceae plants and is used in some medications. The woman reported that the symptoms had appeared soon after she was offered tea by a male acquaintance. The analytical results along with the woman's story indicated that she had been subjected to a drug-facilitated crime. The results further demonstrate that in suspected cases of involuntary drug exposure, testing should cover a wide panel of relevant drugs, otherwise poisoning may be missed.

Unknowing ingestion of Brugmansia suaveolens leaves presenting with signs of anticholinergic toxicity: a case report.

BACKGROUND: Brugmansia suaveolens is the commonest species under the Solanacea ("Angels Trumpet" in English; "Attana" in Sinhalese) plant family in Sri Lanka. It contains alkaloids like scopolamine, atropine and hyoscyamine which can cause an anticholinergic toxindrome. There have been a few reported cases of accidental ingestion of Brugmansia seeds among children, seeds being the most toxic part, but no such reported cases of Brugmansia leaves poisoning among adults. CASE PRESENTATION: A 60-year-old-female Sinhalese presented with acute confusion, delirium, and agitation. She had ingested a herbal drink made from leaves of an unknown plant from her garden prior to onset of symptoms. She had urinary retention, mydriasis and sinus tachycardia. She was managed supportively with activated charcoal and hydration and the delirium completely resolved within 15 hours. The presented unkown plant leaves were identified as Brugmansia suaveolens. CONCLUSION: Although seeds are the most toxic plant part in most cases of Brugmansia poisoning, leaves also have a significant degree of toxicity. It is important that medical professionals promptly recognize the features of anticholinergic syndrome, and have a high index to suspect Brugmansia poisoning and start prompt treatment. It is also important to improve awareness of toxic plants among the general community to prevent toxicities and fatalities.

An Evaluation of Longitudinal Measures of Anticholinergic Exposure for Application in Retrospective Administrative Data Analyses.

INTRODUCTION: As continuous exposure to anticholinergics has been associated with adverse outcomes, accurately measuring exposure is important. However, no gold standard measure is available, and the performance of existing measures has not been compared. Our objective was to compare the properties of the Cumulative Anticholinergic Burden (CAB) measure against two existing measures of anticholinergic exposure and to assess their compatibility for use in observational studies based on claims data. METHODS: The average daily dose, cumulative dose and CAB measures were evaluated on: the applicability for use with anticholinergic burden scales, the ability to consider duration and/or accumulation of exposure, and consideration of anticholinergic dose, potency, and residual effect. To calculate each measure empirically, Truven MarketScan claims data from 2012 to 2015 were analyzed. Cumulative anticholinergic exposure over 1-year post-enrollment was calculated for each measure using Anticholinergic Cognitive Burden scale scores. Median [interquartile range (IQR)] and ranges of measure scores, and Spearman's correlation coefficients between measures, were estimated. Due to the differing methods of calculation, the absolute values of each score cannot be compared. RESULTS: The properties of the different measures varied, with only the CAB considering both dose and theoretical potency. The cohort included 99,742 individuals (mean age = 73.1 years; 54.9% female). Among individuals prescribed anticholinergics (n = 55,969), 1-year median (IQR) scores based on average daily dose, cumulative dose and CAB measures were 0.9 (0.3-1.5), 16.9 (7.3-33.9) and 203 (68-500), respectively. Measures were highly inter-correlated (r2 = 0.74-0.83). CONCLUSIONS: Considering both potency and dose, the CAB may prove a more comprehensive measure of anticholinergic burden; however, additional research is necessary to demonstrate whether it has any association with relevant health-related outcomes. FUNDING: Astellas Pharma Global Development, Inc.

Development of an Anticholinergic Burden Scale specific for Korean older adults.

AIM: The aim of this study was to develop the Korean Anticholinergic Burden Scale through assessment of previously developed tools, a literature review and a modified Delphi process. METHODS: We carried out a systematic review to identify previously published anticholinergic burden tools. A composite medication list was made by extracting medications and their quantitative grading from the existing tools, after excluding the medications not distributed in Korea and topical agents. We also added medications available in Korea that had not been rated. For medications with conflicting anticholinergic scores or no anticholinergic score, we determined the final score from 0 ("no anticholinergic effect") to 3 ("strong anticholinergic effect") with a literature review and expert consensus through a two-round Delphi process. RESULTS: A composite list of 655 medications with anticholinergic scores was extracted from 10 existing tools. A total of 38 medications available in Korea were added to the list. A total of 494 medications were deemed suitable for a Korean-specific scale. We confirmed the anticholinergic scores of 352 medications from existing scales, and 142 underwent the Delphi process. The final scores graded by experts showed high reliability among experts with an intra-class correlation of 0.98 (95% confidence interval 0.97-0.98). Finally, 56 medications were categorized as strong anticholinergics, 23 as moderate, 59 as weak and 356 as having no anticholinergic activity. CONCLUSIONS: This newly created consensus-driven anticholinergic burden scale designed specifically for the Korean healthcare system might be a practical tool for assessing anticholinergic burden in older adults with polypharmacy in routine medication reviews and in research. Geriatr Gerontol Int 2019; 19: 628-634.

Carga anticolinérgica en pacientes mayores de 65 años con tratamiento farmacológico ambulatorio en una población colombiana / Anticholinergic load in patients older 65 years with ambulatory pharmacological treatment in a Colombian population

RESUMEN Introducción: los fármacos con potencial efecto anticolinérgico son prescritos frecuentemente en la población mayor de 65 años. Existen varias escalas para calcular la carga anticolinérgica: Anticholinergic Drug Scale, Anticholinergic Risk Scale y Anticholinergic Cognitive Burden. Objetivo: caracterizar la carga anticolinérgica en pacientes mayores de 65 años con polifarmacia que son formulados ambulatoriamente. Métodos: estudio de corte transversal, retrospectivo con información de prescripción registrada desde abril hasta septiembre de 2016. Se utilizó la base de datos transaccional de prescripción de una EPS nacional registrada en la plataforma tecnológica de un PBM (Pharmacy Benefit Management). Se analizaron los medicamentos con propiedades anticolinérgicas y carga anticolinérgica. Resultados: fueron 115.713 los pacientes formulados, con una edad media de 74 años. Los grupos terapéuticos más asociados con carga anticolinérgica moderada fueron, en un 6,5 %, dimenhidrinato, amantadina, biperideno y quetiapina. Un 13,1 % con carga anticolinérgica alta donde se encuentran el butil bromuro de hioscina y la amitriptilina. Discusión: el manejo de las patologías en los pacientes adultos mayores es compleja y se llega hasta el punto de requerir prescripción de múltiples medicamentos; por lo cual, se hace fundamental evaluar la necesidad del uso de estos, además de verificar su pertinencia y las posibles interacciones farmacológicas de alta significancia clínica, para evitar la presencia de eventos adversos. Por esto se han desarrollado escalas que permiten mejorar el resultado terapéutico especialmente en fármacos con carga anticolinérgica.

SUMMARY Background: Drugs with potential anticholinergic effect are usually prescribed to the population over 65 years. There are several scales created to calculate anticholinergic burden: Anticholinergic Drug Scale, Anticholinergic Risk Scale, and Anticholinergic Cognitive Burden. Objective: To characterize the anticholinergic burden in patients older than 65 years with polypharmacy who are prescribed in ambulatory settings. Methods: Retrospective cross-sectional study with information registered from April to September 2016. The database of prescription records of a health management organization (HMO), with national registries in the Pharmacy Benefit Management (PBM) technology platform, was used. Medicines were analyzed by its anticholinergic properties and anticholinergic burden. Results: There were 115,713 patients with a median age of 74 years. The medicines with moderate anticholinergic burden were dimenhydrinate, amantadine, biperidene and quetiapine in 6.5 %, and with high anticholinergic burden hyoscine butylbromide and amitryptiline in 13.1 %. Discussion: The medical attention of diseases of the elderly is complex and requires the prescription of multiple medications. It is important to evaluate the medicines and verify their relevance and possible pharmacological interactions, to avoid the presence of adverse events. For this reason, scales have been developed, they allow improving therapeutic results, and especially in medicines with anticholinergic burden and systems of clinical alerts that promotes correct formulation.

Anticholinergic toxicity in a one-year-old male following ingestion of Lupinus mutabilis seeds: case report

ABSTRACT CONTEXT: The seeds from Lupinus mutabilis Sweet, also called "chocho", are an important part of the diet in several countries in South America. Prior to consumption, processing is required to remove toxic alkaloids. These alkaloids are known to have pharmacological properties as antiarrhythmics, antimuscarinics and hypoglycemics. CASE REPORT: We report a case in which a one-year-old male initially presented with altered mental status and respiratory distress and subsequently developed symptoms of anticholinergic toxicity, after ingesting a large amount of chocho seeds. CONCLUSION: In spite of going through a difficult clinical condition, the subject evolved favorably through receiving supportive treatment. The seeds from Lupinus mutabilis provide nutritional benefits when consumed, but people need to know their risks when these seeds are consumed without proper preparation.

Anticholinergic Medication Burden in Pediatric Prolonged Critical Illness: A Potentially Modifiable Risk Factor for Delirium.

OBJECTIVES: It is important to describe and understand the prevalence and risk factors for the syndrome of delirium in critical illness. Since anticholinergic medication may contribute to the development of delirium in the PICU, we have sought to quantify anticholinergic medication exposure in patients with prolonged admission. We have used Anticholinergic Drug Scale scores to quantify the magnitude or extent of this burden. DESIGN: Retrospective cohort study, January 2011 to December 2015. SETTING: Single academic medical center PICU. PATIENTS: Children under 18 years old with a PICU admission of 15 days or longer, requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily Anticholinergic Drug Scale scores for the first 15 days of admission, in each of 88 subjects (total of 1,320 PICU days), were collected and assessed in relation to demographic data, severity of illness, and medication use. Median (interquartile range) of daily Anticholinergic Drug Scale score was 5 (interquartile range, 3-7). Anticholinergic Drug Scale score was not associated with age, sex, medical history, presenting Severity of Illness score, PICU length of stay, ventilator hours, or hospital mortality. Medications most frequently associated with high Anticholinergic Drug Scale score were low potency anticholinergic drugs such as morphine, midazolam, vancomycin, steroids, and furosemide, with the exception of ranitidine (Anticholinergic Drug Scale score 2). Patients receiving high doses of midazolam infusion had significantly higher Anticholinergic Drug Scale scores compared with those receiving lower or no midazolam dosing. CONCLUSIONS: A high number of medications with anticholinergic effects are administered to PICU patients receiving prolonged mechanical ventilation. These exposures are much higher than those reported in adult intensive care patients. Since anticholinergic drug exposure is associated with delirium, further study of this exposure in PICU patients is needed.

[Hypertensive crisis and anticholinergic toxidrome secondary to accidental consumption of datura stramonium in two children]. / Poussée tensionnelle et toxidrome anticholinergique secondaire à une consommation accidentelle de datura stramonium chez l'enfant, à propos de 2 cas.

OBJECTIVE: To identify a hypertensive clinical form of atropine or anticholinergic toxidrome secondary to accidental consumption of Datura seeds. PATIENTS AND METHODS: We report two cases of Datura intoxication in two children who presented marked anticholinergic syndrome whose diagnosis was made by the anamnesis and the clinic. RESULT: Patient 1: A 5-year-old boy, returns home agitated with balance disorders. He was admitted to pediatric resuscitation unit. His Glasgow score was 11/15. The child made inconsistent remarks. The neurological examination revealed mydriasis. Hemodynamically, the blood pressure was 145/91mmHg, the heart rate was 145 bpm. The rest of the examination noted a temperature of 37.5°, a bladder globe. Standard biological tests were normal. ECG found sinus tachycardia. Urine analysis revealed a positive alkaloid reaction with the presence of atropine. The evolution was favorable after 48hours. Patient 2: 45-month-old boy admitted to a state of severe agitation of toxic origin. The clinical examination showed a central and peripheral anticholinergic symptomatology with severe hallucinations, severe hypertension, and a heart rate at 190 bpm. The rest of the examination found erythema in the thorax and upper limbs, bilateral mydriasis. The toxicological report confirmed the presence of alkaloids. The evolution was favorable. CONCLUSION: Hypertension crisis and other anticholinergic clinical signs of Datura stramonium intoxication achieve favorable outcomes in children.