[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.

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.

[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.

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.

[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.

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

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.

[Leguminous plant causes poisoning with anticholinergic syndrome]. / Baljväxt orsakar förgiftning med antikolinergt syndrom.

In this case report we illustrate how incorrectly prepared and cooked seeds from white lupin - a common snack among people from parts of the Mediterranean and Middle East - caused an anticholinergic syndrome in a previously healthy man. The symptoms subsided without treatment and the patient was discharged from the hospital in good health. Anticholinergic syndrome results from inhibition of the parasympatic nervous system. The symptoms commonly include dry mouth, confusion, hallucinations, fever, tachycardia, and urine retention. The syndrome may most frequently be provoked by overdose of drugs such as prometazin, hyoscyamin, and biperidin or by ingestion of plants such as belladonna, datura and henbane. The aim of this report is to increase clinicians' awareness of white lupin's anticholinergic effects.

[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.

A 45-year-old woman with an anticholinergic toxidrome.

Intentional or accidental intoxications are common in the emergency department, but are not always sufficiently recognised. When intoxication is suspected, the causative agent or combination of agents often remain unclear, making these patients a diagnostic challenge. We present here a 45-year-old woman who was admitted due to altered consciousness. The clinical presentation fitted the anticholinergic toxidrome and an intoxication with venlafaxine (her known prescribed medication) was suspected. Plasma venlafaxine concentrations, however, were very low. After 24 hours the patient recovered completely. Further testing after discharge revealed high concentrations of promethazine, confirming the suspected diagnosis. This case illustrates the importance of knowledge of toxidromes and good collaboration with the hospital pharmacist. Because of the thorough testing the patient could receive proper treatment.

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.

Abuse of the over-the-counter antispasmodic butylscopolamine for the home synthesis of psychoactive scopolamine.

UNLABELLED: We report on two patients who ingested psychoactive scopolamine that was synthesized at home from butylscopolamine (Buscopan®), which is available as over-the-counter antispasmodic in nearly 100 countries worldwide. Patient 1 presented with severe central anticholinergic toxidrome, while patient 2 suffered from minor symptoms. An empty blister of Buscopan® was found in the patients' home, but initially was not suspected to be causative for the observed central anticholinergic symptoms, as Buscopan® is not able to pass the blood-brain barrier in its native form. Only later, the information by third parties and a Google search helped to identify homemade scopolamine derived from Buscopan® as the responsible agent in these two cases. Retrospectively, scopolamine could be detected in serum and urine of both patients, while it was absent in one control after ingestion of native Buscopan®. CONCLUSION: Over-the-counter drugs can be used to synthesize psychoactives with means that are available in every household. Such knowledge can spread via social media and internet discussion boards long before appearing in medical literature. While typical clinical presentation often enables clinicians to adequately identify and treat specific toxidromes, these sources of information need to be increasingly taken into account by medical professionals for identification of its causative agent. This potential of Buscopan® might gain importance as an easily accessible source of psychoactive scopolamine. WHAT IS KNOWN: • Substances with central anticholinergic effects are known for their hallucinogenic potential and may be used as psychoactives. What is New: • The over-the-counter antispasmodic butylscopolamine (Buscopan®) can be abused to synthesize anticholinergic, psychoactive scopolamine at home with means that are available in every household.

Serotonergic or Anticholinergic Toxidrome: Case Report of a 9-Year-Old Girl.

OBJECTIVE: The aim of this study was to report an acute onset of symptoms erroneously attributed to serotonin syndrome in a child who had been given both anticholinergic and serotonergic agents. CASE SUMMARY: A 9-year-old girl with chronic anxiety and gastrointestinal problems was prescribed oral sertraline 6.25 mg daily, as well as hyoscyamine, ondansetron, montelukast, and a course of nitazoxanide. She was also routinely given diphenhydramine and omeprazole. Three days after increasing sertraline to 12.5 mg, she presented to the emergency department with altered mental status, hallucinations, mydriasis, tachycardia, and pyrexia. She was admitted to the pediatric intensive care unit and subsequently treated unsuccessfully for serotonin syndrome, with blurred vision and clonus persisting at discharge 4 days after admittance. Upon follow-up with her outpatient clinic, all anticholinergic agents were discontinued, and symptoms slowly resolved. CONCLUSIONS: This case illustrates the importance of differential diagnosis between toxidromes and how clinical presentation can be altered by preexisting conditions as well as the use of medications that affect multiple neurotransmitter systems.

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.

[CENTRAL ANTICHOLINERGIC... SYNDROME?].

While reading special literature in diferent languages the authors noted surprising fact: the term and concept of "central anticholinergic syndrome" is well-known as common anaesthesia complication in German (abbr: ZAS) and partially Spanish sources, but in Russian, English or French literature is used only in toxicological context. Describing etiology, pathogenesis, symptoms, diagnosis and treatment of the complication manifesting with comatose, agitated or shivering forms, the authors analyzing the reasons for such a noticeably diferent approaches to the situation reaching 10% of all the general anaesthesia cases. Probably, ZAS isn't nosologically clearly defined syndrome, but just adverse appearance of one of the fundamental general anaesthesia mechanisms? Anyway, the problem of central cholinergic activity suppression, excessive by its amplitude and/or duration, exists all over the world. German concept of ZAS allows the anaesthesiologist to resolve it on pathogenically generalized basis, while in other professional communities various symptomatic approaches seem to be more common.

Multiple anticholinergic medication use and risk of hospital admission for confusion or dementia.

OBJECTIVES: To identify the association between use of multiple anticholinergic medications and risk of hospitalization for confusion or dementia. DESIGN: Retrospective cohort study conducted over 2 years between July 2010 and June 2012, using administrative claims data from the Australian Department of Veterans' Affairs. SETTING: Australia. PARTICIPANTS: Australian veterans dispensed at least one moderately or highly anticholinergic medication in the year before study start. MEASUREMENTS: Cumulative anticholinergic use on each day of the study period was determined. The association between hospitalization for confusion or dementia and number of anticholinergic medications used at the time of admission was compared against times during which participants were not taking anticholinergic medications. Sensitivity analyses were undertaken limiting the outcome to admissions for acute confusion and excluding individuals taking antipsychotics. RESULTS: Adjusted results showed a significantly greater risk of hospitalization for confusion or dementia when individuals were taking two or more anticholinergic medications. The adjusted incident rate ratios (IRRs) were 2.58 (95% confidence interval (CI) = 1.91-3.48) for those taking two anticholinergics and 3.87 (95% CI = 1.83-8.21) for those taking three or more. Sensitivity analyses in which participants taking antipsychotic medications were excluded and the outcome was limited to acute confusion also found similar risks for those taking two (IRR 1.82, 95% CI = 1.18-2.80) and three or more (IRR = 3.98 95% CI = 1.50-10.58) anticholinergic medications. CONCLUSION: Taking more anticholinergic medications is associated with greater risk of hospitalization for confusion or dementia. Strategies to reduce anticholinergic medication burden are likely to translate into significant health benefits.