[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.

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.

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.

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.

Postoperative Anticholinergic Poisoning: Concealed Complications of a Commonly Used Medication.

BACKGROUND: Scopolamine is a potent anticholinergic compound used commonly for the prevention of postoperative nausea and vomiting. Scopolamine can cause atypical anticholinergic syndromes due to its prominent central antimuscarinic effects. CASE REPORT: A 47-year-old female presented to the emergency department (ED) 20 h after hospital discharge for a right-knee meniscectomy, with altered mental status (AMS) and dystonic extremity movements that began 12 h after her procedure. Her vital signs were normal and physical examination revealed mydriasis, visual hallucinations, hyperreflexia, and dystonic movements. Laboratory data, lumbar puncture, and computed tomography were unrevealing. The sustained AMS prompted a re-evaluation that revealed urinary overflow with 500 mL of retained urine discovered on ultrasound and a scopolamine patch hidden behind her ear. Her mental status improved shortly after patch removal and physostigmine, with complete resolution after 24 h with discharge diagnosis of scopolamine-induced anticholinergic toxicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although therapeutically dosed scopolamine transdermal patches rarely cause complications, incomplete toxidromes can be insidiously common in polypharmacy settings. Providers should thoroughly evaluate the skin of intoxicated patients for additional adherent medications that may result in a delay in ED diagnosis and curative therapies. Our case, as well as rare case reports of therapeutic scopolamine-induced anticholinergic toxicity, demonstrates that peripheral anticholinergic effects, such as tachycardia, dry mucous membranes, and hyperpyrexia are often not present, and incremental doses of physostigmine may be required to reverse scopolamine's long duration of action. This further complicates identification of the anticholinergic toxidrome and diagnosis.

[Malignant hyperthermia syndrome in the intensive care unit : Differential diagnosis and acute measures]. / Maligne hypertherme Syndrome auf der Intensivstation : Differenzialdiagnostik und Akutmaßnamen.

Malignant hyperthermia is a life-threatening disease caused by derangement of the autonomic nerve system and hypermetabolism of the peripheral musculature. Commonly body core temperatures of more than 40 °C will be found in this disease which is caused mostly by psychopharmacological drugs like antidepressants, neuroleptics but also antibiotics, pain killers, anti-Parkinson drugs, and volatile anesthetics. The inducers of malignant hyperthermia interact with postsynaptic receptors (serotonin, anticholinergics) or muscular intracellular structures responsible for calcium utilization (volatile anesthetics, succinylcholine). Rarely malignant hyperthermia is a consequence of mental stress or vigorous exercise and or heat. Malignant hyperthermic syndromes lead to a severe dysbalance of the autonomic nerve system accompanied by rhabdomyolysis, disseminated intravascular coagulopathy, and finally multi-organ failure. Accordingly, medical management is primarily directed to stabilize vital functions, withdrawal of the causing drug, and if possible antagonizing toxic substances. The leading symptom hyperthermia needs to be treated physically with available cooling systems.

Central anticholinergic syndrome vs. idiosyncratic reaction triggered by a small IV dose of atropine.

A 58-year-old male was scheduled to undergo radical gastrectomy for cancer under general anesthesia. The patient developed agitation and irregular breathing after receiving a single dose of atropine (0.5 mg) to treat bradycardia immediately prior to induction of anesthesia. Within 5 min after the atropine injection, the patient became unresponsive with facial flushing and diaphoresis. When a drop in oxygen saturation was observed, a laryngeal mask airway was inserted after administering a small bolus dose of propofol (80 mg) and the patient was ventilated with 100% oxygen. Physostigmine was not administered because of the relatively low dose of atropine and the fact that his symptoms were not totally consistent with central anticholinergic syndrome (CAS). The differential diagnosis at the time also included an acute cardiovascular event and an idiosyncratic reaction to atropine. The patient fully recovered within 80 min from this highly unusual reaction to a single 0.5 mg IV dose of atropine.

Anticholinesterase Therapy Worsening Head Drop and Limb Weakness Due to a Novel DOK7 Mutation.

Dok-7 myasthenia is an autosomal recessive congenital myasthenic syndrome due to DOK7 mutations. Anticholinesterase therapy is ineffective and may worsen the weakness in patients with Dok-7 myasthenia or few other forms of congenital myasthenic syndromes. We describe a 31-year-old man previously diagnosed with seronegative myasthenia gravis. Repetitive stimulation of the right spinal accessory nerve showed 51% decrement. Needle electromyography revealed myopathic changes in clinically affected muscles. Muscle biopsy was normal. The patient was referred to us for worsening weakness after taking pyridostigmine. We searched for DOK7 mutations and identified compound heterozygous mutations of a common c.1124_1127dupTGCC mutation and a novel splice site mutation, c.772+2_+4delinsCCGGGCAGGCGGGCA. Discontinuation of pyridostigmine improved weakness. He further regained strength with oral albuterol therapy and decrement was reduced to 25%. Worsening of symptoms with anticholinesterase therapy in patients with "seronegative myasthenia gravis" should prompt clinicians to consider a possibility of congenital myasthenic syndromes to avoid unnecessary use of immunosuppressive therapy. Patients with Dok-7 myasthenia respond well to oral albuterol treatment.

Intoxicación por Datura stramonium: serie de tres casos / Datura stramonium poisoning: series of three cases

Se presenta una serie de tres casos de pacientes menores de edad con intoxicación por ingesta de semillas de Datura stramonium, ocurridos durante el mes de mayo en la provincia de Mendoza. Pacientes de sexo masculino, ente 15 y 3 años de edad. Uno de ellos asociado con ingesta intencional de semillas y otros dos por intoxicación accidental al ingerir las semillas jugando con el fruto de la planta. La recolección de semillas se realizó en zona rural periurbana, y todos los casos fueron llevados a la consulta por familiares directos, ante la presencia de desorientación, ataxia y disartria. Los tres pacientes desarrollaron síndrome anticolinérgico, con delirio y alucinaciones, requiriendo internación y tratamiento sintomático, con buena evolución y recuperación completa entre las 24 y 72 horas. Se resalta el riesgo que representa la presencia de este vegetal tóxico, no sólo por su fácil disponibilidad, sino por las bajas dosis letales de sus alcaloides y la falta de diagnóstico etiológico por parte de los servicios de urgencia.

A series of three cases of pediatric patients with poisoning by ingestion of seeds of Datura stramonium, which occurred during the month of May in the province of Mendoza is presented. Male patients, among 15 and 3 years old. One associated with intentional ingestion of seeds and other two by accidentally ingesting seeds while playing with the fruit of the poisonous plant. Seed collection was conducted in rural and peri-urban areas, and all patients were brought to the office by relatives, due to the presence of dysarthria disorientation and ataxia. The three patients developed anticholinergic syndrome with delirium and hallucinations, requiring hospitalization and symptomatic treatment. All cases had favorable outcome and complete recovery within 24 to 72 hours. It is highlighted the risk posed by the presence of this toxic plant, not only for its easy availability, but low lethal doses of its alkaloids and lack of etiological diagnosis by emergency services.

Medication misadventures in older adults: literature from 2013.

The objective of this paper is to review articles published in 2013 examining drug-related problems in the elderly and comment on their potential impact on clinical practice. To identify articles, we did a systematic search of the English-language literature restricted to those aged 65 + from January 2013 to December 2013 using Medline and Google Scholar and a combination of the following search terms: drug-related problems, medication-related problems, medication errors, suboptimal prescribing, inappropriate prescribing, underutilization, polypharmacy, medication monitoring, medication dispensing, medication administration, medication adherence, adverse drug events, and adverse drug withdrawal events. A manual search of major general medicine and clinical pharmacology journals was also conducted to identify additional articles. A total of 51 articles were identified of which 20 were chosen to highlight. Three were annotated and critiqued and the additional 17 articles were summarized in an appendix. One article reported the results of a randomized controlled trial that showed that a pharmacist intervention successfully reduced suboptimal prescribing in older hospital patients. Another paper from this group previously reported data from the same study showing that the intervention also reduced medication related readmissions to the hospital. An observational study compared the use of two thiazide diuretics in older outpatients. They found that chlorthalidone was more likely to cause hypokalemia than hydrochlorothiazide. Finally, in a randomized controlled trial a pharmacist intervention resulted in the reduction of anticholinergic burden but did result in an improvement in cognition. These studies highlight that medication errors and adverse drug events continue to be important issues for health care professionals caring for older adults.