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.

Pharmacological management of anticholinergic delirium - theory, evidence and practice.

The spectrum of anticholinergic delirium is a common complication following drug overdose. Patients with severe toxicity can have significant distress and behavioural problems that often require pharmacological management. Cholinesterase inhibitors, such as physostigmine, are effective but widespread use has been limited by concerns about safety, optimal dosing and variable supply. Case series support efficacy in reversal of anticholinergic delirium. However doses vary widely and higher doses commonly lead to cholinergic toxicity. Seizures are reported in up to 2.5% of patients and occasional cardiotoxic effects are also recorded. This article reviews the serendipitous path whereby physostigmine evolved into the preferred anticholinesterase antidote largely without any research to indicate the optimal dosing strategy. Adverse events observed in case series should be considered in the context of pharmacokinetic/pharmacodynamic studies of physostigmine which suggest a much longer latency before the maximal increase in brain acetylcholine than had been previously assumed. This would favour protocols that use lower doses and longer re-dosing intervals. We propose based on the evidence reviewed that the use of cholinesterase inhibitors should be considered in anticholinergic delirium that has not responded to non-pharmacological delirium management. The optimal risk/benefit would be with a titrated dose of 0.5 to 1 mg physostigmine (0.01-0.02 mg kg(-1) in children) with a minimum delay of 10-15 min before re-dosing. Slower onset and longer acting agents such as rivastigmine would also be logical but more research is needed to guide the appropriate dose in this setting.

Chinese herbal medicine-induced anticholinergic poisoning in Hong Kong.

OBJECTIVE: To study the epidemiology, causes, and clinical course of Chinese herbal medicine-induced anticholinergic poisoning in Hong Kong. DESIGN: Case series. SETTING: Hong Kong. PATIENTS: All case histories of Chinese herbal medicine-induced anticholinergic poisoning (with laboratory confirmation) recorded by the Hong Kong Poison Information Centre over a 93-month period were accessed for analysis. RESULTS: During the relevant period, 22 clusters of Chinese herbal medicine-induced anticholinergic poisoning involving 32 patients were retrieved. The commonest clinical features were mydriasis (n=32, 100%) and confusion (n=24, 75%). No gastro-intestinal decontamination was performed. None of these patients underwent intubation, defibrillation, cardioversion, pacing, fluid resuscitation, inotropic support or dialysis. Of the 32 patients, 17 (53%) were treated with physostigmine because of confusion, three of whom had previously received intravenous benzodiazepines. No patient could be effectively treated with benzodiazepines alone. There was no mortality, and all the patients were discharged within 3 days. None of them re-attended the emergency department within 1 week of discharge. The commonest cause was the substitution of flos campsis (Campsis grandiflora) by the flower of the Datura species (7 clusters [32%] in 10 patients). CONCLUSION: Mydriasis and confusion were the commonest clinical features of Chinese herbal medicine-induced anticholinergic poisoning in Hong Kong. Physostigmine was frequently used in the treatment; benzodiazepines appeared ineffective. The commonest cause was the substitution of flos campsis (Campsis grandiflora) by the flower of the Datura species.

Intoxication with a tropenol ester.

BACKGROUND: While the effects of medicinal products are investigated in depth before approval, often very little is known about the intermediates occurring during synthesis. The pharmacological properties of these intermediates can differ substantially from those of the end product. AIMS: To describe a work accident involving intoxication with such an intermediate, tropenol ester. CASE REPORT: A healthy 40-year-old chemical-technical operative erroneously used a scrubbing brush that had just been used to clear up tropenol ester, contaminating his work clothes. Presumably, contact was made with his skin when removing his work clothes later. Shortly thereafter, he developed signs of anticholinergic intoxication with mydriasis, dry mouth, abnormal coordination and later sleepiness and seizures. The patient received intensive medical treatment. Two weeks later, the anticholinergic symptoms had subsided. Qualitative analysis of a urine sample showed traces of tropenol ester. The substance is a muscarinic acetylcholine receptor antagonist. CONCLUSIONS: The clinical symptoms and biomonitoring suggest that intoxication with tropenol ester had occurred, which, as a tertiary amine, readily passes through the blood-brain barrier. The protracted course suggests high affinity for the receptor. Appropriate safety precautions must be taken when handling research substances and intermediates of unknown toxicity.

Wide complex tachycardia in a pediatric diphenhydramine overdose treated with sodium bicarbonate.

INTRODUCTION: Diphenhydramine is an antihistamine commonly implicated in overdose. It has many pharmacologic effects, including sodium channel blockade. Overdoses in toddlers causing QRS prolongation are only rarely reported and never with effective use of sodium bicarbonate. We report a diphenhydramine overdose in a toddler with multiple markers of sodium channel blockade effectively treated with sodium bicarbonate. METHODS: A 13-month-old infant girl was brought in by the emergency medical service for a witnessed tonic-clonic seizure. Two hours previously, the child had been found with an open bottle of 25-mg diphenhydramine tablets, 24 of which were missing. Midazolam was administered with seizure resolution. Examination revealed 4-mm reactive pupils; nystagmus; warm, dry, flushed skin; and altered mental status. Initial electrocardiograms revealed sinus tachycardia at a rate of 180 beats per minute, a prolonged QRS of 130 milliseconds (from a baseline of 65 milliseconds), and a positive terminal R wave in aVR, which later resolved after sodium bicarbonate treatment. The patient was discharged home the following day with no sequelae. RESULTS AND DISCUSSION: Diphenhydramine toxicity is a common poisoning in children. Toxicity typically presents with signs and symptoms of the anticholinergic toxidrome. Diphenhydramine also has sodium channel-blocking properties, and this can be shown in the form of prolonged QRS and a terminal R wave in aVR. QRS prolongation and aVR abnormalities from diphenhydramine ingestion in a toddler have been reported, but effective use of sodium bicarbonate has not. CONCLUSIONS: Electrocardiographic finding consistent with sodium channel blockade should be recognized as a complication of pediatric diphenhydramine overdose, and they seem responsive to hypertonic sodium bicarbonate.

Dilated pupils, dry mouth and dizziness - a case study.

A man, 44 years of age, presented with a 4 hour history of dizziness, blurred vision, dry mouth and dilated pupils. He was previously well and on no medications and there was no history of recent drug use, head injury or focal neurological symptoms. On questioning, the patient said that he had eaten lupini beans for lunch but that he hadn't had enough time to soak them for long enough before eating them. On examination his Glasgow Coma Score (GCS) was 15/15, heart rate 98 bpm, blood pressure 144/98, temperature 37.8°C and respiratory rate 18 breaths/minute. His skin was warm and dry with dry mucous membranes. His pupils were dilated at 6 mm and were nonreactive. Cardiovascular, respiratory, abdominal and neurological examinations were normal. He was unable to pass urine. Electrocardiogram showed normal sinus rhythm with a rate of 98 bpm.

Prolonged delirium after quetiapine overdose.

Quetiapine is an atypical antipsychotic agent increasingly used to treat schizophrenia and bipolar disorder in pediatric patients. Few published data exist concerning quetiapine's effects in therapeutic settings or short-term overdose in pediatric and adolescent populations. In this report, we describe a 15-year-old adolescent girl who experienced continued delirium 5 days after an overdose of quetiapine, trazodone, and clonidine. The patient initially presented with sedation and stable vital signs. After 3 days of gradual improvement, she experienced episodes of delirium coinciding with an increase in resting heart rate. On the basis of suspicion for quetiapine-associated antimuscarinic effects, the patient was administered intravenously with physostigmine on the fifth day after ingestion. Treatment resulted in a brief resolution of symptoms. Serum quetiapine levels measured 1 day and 5 days after ingestion were 3400 and 4800 ng/mL, respectively. The use of physostigmine and interpretation of serum levels are discussed further.

Clinical predictors of adverse cardiovascular events for acute pediatric drug exposures.

Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures.Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age <18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate <20 mEq/L; QTc ≥500 ms), for the primary/secondary outcomes.Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration <20 mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc ≥ 500 ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE.Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality.

Jimson weed abuse in an Oklahoma teen.

Jimson weed, a plant often abused by teenagers and young adults, grows wild throughout Oklahoma. It is best known for its hallucinogenic properties; however intoxication can lead to anticholinergic manifestations that are potentially dangerous. Over the past six years, sixty-three individuals in Oklahoma have been hospitalized for jimson weed intoxication, including this Oklahoma teen. Importance lies in proper identification, understanding, and management in persons presenting with jimson weed poisoning.

[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.

Safety and effectiveness of physostigmine: a 10-year retrospective review.

BACKGROUND: Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed. OBJECTIVES: To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium. METHODS: A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI's), and p values. RESULTS: Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non-diphenhydramine antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n = 3) had 100% response to physostigmine, whereas anticholinergic plants (n = 46/67; 68.7%, OR: 0.70; CI: 0.36-1.35), diphenhydramine (n = 43/56; 64.2%, OR: 1.30; CI: 0.63-2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30-7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED). DISCUSSION: Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6 h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED. CONCLUSIONS: In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2 mg.

Teenagers with Jimson weed (Datura stramonium) poisoning.

We report 2 cases of teenagers who were poisoned with Jimson weed (Datura stramonium) and presented to the emergency department with a severe acute anticholinergic toxidrome after ingestion of several hundred seeds. The patients presented with visual hallucinations, disorientation, incomprehensible and nonsensical speech, and dilated sluggish pupils. Both patients required restraints for combativeness until adequate sedation with lorazepam and haloperidol was achieved. Jimson weed is found in southern Canada and the United States and can cause acute anticholinergic poisoning and death in humans and animals. The treatment of choice for anticholinergic poisoning is mainly supportive care and gastrointestinal decontamination with activated charcoal. Jimson weed intoxication should be considered in cases of patients presenting with unexplained peripheral and central anticholinergic symptoms including delirium, agitation and seizures, especially among younger patients and partygoers. It is important that health care professionals recognize that Jimson weed is a toxic, indigenous, "wild" growing plant, subject to misuse and potentially serious intoxication requiring hospitalization.

Toxicological results in a fatal and two non-fatal cases of scopolamine-facilitated robberies.

The use of scopolamine as an incapacitating drug, in sexual crimes and robberies, has been known for many decades. However, blood concentrations and doses of scopolamine in those cases are largely unknown. Here we present the toxicological results of one fatal and two non-fatal cases in a series of scopolamine-facilitated robberies. In the fatal case, the concentration of scopolamine in heart blood was 0.30mg/L, about 3000 times higher than the average therapeutic level of 0.0001mg/L (for one dermal patch). In femoral blood, the concentration of scopolamine was much lower (0.0048mg/L), but still 50 times higher than therapeutic levels. The scopolamine concentration in the stomach was very high (20mg/kg) as compared to the heart blood and femoral blood, which explains the very high concentration in heart blood by postmortem leakage from the stomach. In the non-fatal case, the scopolamine concentration in serum, obtained 23h after the incident, was 0.00035mg/L. The estimated concentration of scopolamine at the time of the incident is 0.0035mg/L. In the other non-fatal case, scopolamine was detected in urine and in hair.

Adolescent with prolonged toxidrome.

A 13-year-old female was presented to the emergency department following an intentional ingestion. The patient developed significant toxicity including multiple, discreet tonic-clonic seizures. Despite appropriate resuscitation and antidotal management, the patient's symptoms persisted for more than 36 hours post-ingestion. An upright abdominal radiograph was performed revealing a radiopacity suggesting a pharmacobezoar. An esophagogastroduodenoscopy was performed with successful removal of a tennis ball-sized pharmacobezoar. The patient's symptoms subsequently subsided and she recovered fully with no neurologic deficits. Diphenhydramine has not been previously identified as a medication likely to form a pharmacobezoar and has not been shown to be radiopaque. Though bezoar formation is a rare clinical scenario, it is one that toxicologists must consider in patients with clinical courses that persist far beyond expected based on known toxicokinetic principles.

Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong.

In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989-2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data were obtained from Medline search, the Department of Health and the Drug and Poisons Information Bureau. In the New Territories East (where ~20% of the Hong Kong population lived), the incidence of herbal medicines induced anticholinergic poisoning during 1989-1993 was 0.09 per 100,000 population. There were no confirmed cases during 1994-1996. In the whole of Hong Kong, the incidence during 2000-June 2005 was 0.03 per 100,000 population. Contamination of Rhizoma Atractylodis (50%) and erroneous substitution (42%) were the main causes. The incidence during 2008-2012 was 0.06 per 100,000 population. Contamination of non-toxic herbs (50%) and erroneous substitution (41%) were the main causes. In Hong Kong, contamination of non-toxic herbs by tropane alkaloids and substitution of Flos Campsis by toxic Flos Daturae Metelis were the predominant causes of herbal medicines induced anticholinergic poisoning. Systematic studies along the supply chain are necessary to identify the likely sources of contamination. If erroneous substitution of Flos Campsis by Flos Daturae Metelis could be prevented, 40% of herbal medicines induced anticholinergic poisoning would not have occurred. Regular inspection of the retailer, continuing education for the staff in the herbal trade and repeated publicity measures will also be required. Pharmacovigilance of herbal medicines should help determine the incidence and causes of adverse reactions and monitor the effectiveness of preventive measures.

Anticholinergic poisoning associated with herbal tea.

An outbreak of cholinergic poisoning occurred in New York City during a 3-day period. Seven individuals from three families of South American origin were affected. Signs and symptoms of illness included dry skin, hyperthermia, tachycardia, dilated pupils, agitation, and hallucinations. Onset of illness in all cases was temporally associated with consumption of a tea that was labeled "Paraguay Tea" and was purchased from a grocery store specializing in South American foods. Paraguay tea, made from the leaves of the holly, Ilex paraguariensis, contains caffeine and theophylline and is a popular beverage in South America. Samples of the tea analyzed with gas chromatography contained belladonna alkaloids but neither caffeine nor theophylline. An investigation by the New York City Department of Health personnel determined that the tea was from a single lot, imported by one distributor, and sold at one grocery store. Unsold inventories of the tea were quarantined, and no further cases of anticholinergic poisoning were reported.

Acute anticholinergic poisoning in children.

We report two cases of unintentional poisoning with anticholinergic agents. The first patient, a 7-year-old girl, was prescribed four different medications by a general practitioner for treatment of abdominal colic and diarrhoea. All drugs had anticholinergic properties. The second patient, a 16-month-old boy, ingested his mother's cyproheptadine tablets. Both children presented with central and peripheral symptoms and signs compatible with acute anticholinergic syndrome. They recovered spontaneously following intravenous fluid replacement and close observation. Gastric lavage was also performed on the boy. Poisoning with cholinergic antagonists in children is a potentially serious hazard in Hong Kong. It may be avoided by careful prescribing on the part of general practitioners and safe storage of all medicinal products in the home environment.