Belladonna Alkaloid Intoxication: the 10-Year Experience of a Large Tertiary Care Pediatric Hospital

American Journal of Therapeutics 23, e74–e77 (2016)

Belladonna Alkaloid Intoxication: The 10-Year Experience of a Large Tertiary Care Pediatric Hospital

Miguel Glatstein, MD,1,2* Fatoumah Alabdulrazzaq, MD,3 and Dennis Scolnik, MB, ChB3,4

The belladonna alkaloids can be isolated from a number of plants, which contain hallucinogens that represent a serious danger to infants, children, and adolescents. Roots, leaves, and fruits of the plant contain the alkaloids atropine, hyoscyamine, and scopolamine, which can lead to an anticholinergic toxidrome; however, not all characteristics of the toxidrome are necessarily present in each case of poisoning. A retrospective chart review of all children seen following anticholinergic ingestions, between April 2001 and November 2010, at the Hospital for Sick Children in Toronto. Ten children, with a mean age of 15.5 years (range, 15–18 years), were identified; 5 had used jimsonweed and the others had a variety of tablets containing atropine. All 10 presented with severe anticholinergic symptoms and 2 with suicide attempts. Treatments included charcoal, benzodiazepines, haloperidol, and physostigmine, and 2 patients were intubated. Ingestion and subsequent severe anticholinergic toxidrome occurred exclusively in adolescents. It is important to educate this age group regarding the toxicity and potential risks associated with the recreational use of these plants and substances. Physostigmine canhelpinboththediagnosisandmanagementofpatientsintoxicatedwiththesesubstances.

Keywords: Atropa belladonna, anticholinergic toxidrome, physostigmine, belladonna alkaloids

INTRODUCTION membranes, tachycardia, decreased bowel sounds, dif- ficulty swallowing and speaking, hyperthermia, hyper- 3 The belladonna alkaloids, including the tropane alka- tension, seizures, loss of consciousness, and coma. loids atropine, hyoscyamine, and scopolamine, are Other manifestations include confusion, agitation, and found in a number of plants.1 Consumption of any part combative behavior. Not all the characteristics of anti- of the plant can result in a severe anticholinergic toxi- cholinergic toxidrome are necessarily present in each 4 drome2 consisting of mydriasis, blurred vision, photo- poisoning, but the clinical picture is often dominated phobia, dry mouth, dry skin, extreme thirst, dry mucous by a toxic psychosis with hallucinations, disturbances of orientation, and psychomotor agitation, aggression, or anxiety.5 Children have a special susceptibility, and

1 even small amounts can produce central nervous sys- Division of Pediatric Emergency Medicine, Department of Pediat- 5 rics, Dana-Dwek Children Hospital, Tel Aviv University, Tel Aviv, tem manifestations ; however, it is mainly adolescents Israel; 2Division of Clinical Pharmacology and Toxicology, Ichilov who experiment recreationally with these plants for Hospital, Tel Aviv University, Tel Aviv, Israel; and 3Division of their hallucinogenic and euphoric effects. Pediatric Emergency Medicine, Department of Pediatrics, and Although Atropa belladonna, also known as deadly 4Division of Clinical Pharmacology and Toxicology, The Hospital nightshade, is perhaps the most well-known example in for Sick Children, University of Toronto, Ontario, Canada. this group of plants, Datura is another plant that contains The authors have no conflicts of interest to declare. tropane alkaloids, primarily in its seeds and flowers. It *Address for correspondence: Division of Pediatric Emergency has been used in some cultures for centuries, both as Medicine, Department of Pediatrics, Dana-Dwek Children Hospi- a poison and as a hallucinogen.6 There are 9 species, tal, Sackler School of Medicine, Tel Aviv University, 6 Weizman St, Tel Aviv 64239, Israel. E-mail: [email protected] one of which is jimsonweed (Datura stramonium), also called locoweed. Jimsonweed grows wild in warm and

moist areas of the world, and in southern Canada and the Institutional Research Ethics Board at the Hospital for United States, where it is also used as an ornamental Sick Children, Toronto, University of Toronto, Canada. plant. It has been used to treat “madness,” epilepsy, and depression in addition to being used as a hallucinogenic. Ingestion of any part of the plant can result in RESULTS severe anticholinergic toxicity.7 Jimsonweed parties are becoming more common, so that multiple teenagers are The medical records of 10 patients meeting inclusion usually involved when exposure occurs.8 criteria were reviewed. Toxicological examination was The manifestations of jimsonweed poisoning include obtained in all patients. Ages ranged from 15 to 18 years the classic anticholinergic symptoms, and death can (Table 1). In most cases, hospitalization occurred within occur from central nervous system depression, circula- the first 12 hours after ingestion. Also, in most of the tory collapse, and hypotension.9 Coingestion of other cases, the patients or their parents do not know the central nervous system depressants can increase the ingested amount of the belladonna alkaloids. The com- toxicity of jimsonweed. monest presentations were changes in the level of Angel’s trumpet, also known as devil’s weed, thorn consciousness,9 visual hallucinations,9 aggression,6 psy- apple, tolguacha, Jamestown weed, stinkweed, Datura, chomotor agitation,5 and mumbling speech.3 Symptoms or moonflower,10 is another plant that has increasingly subsided within 24 hours except for 1 patient in whom been used for its hallucinogenic effect, mainly because it agitation persisted for 2 days. Physical examination is cheap and easily available.11 Confusingly, moon- showed dilated pupils,7 dry mucous membranes,1 and flower is also a name given to several plants, such as skin redness.1 There were no accidental ingestions: 8 were Datura inoxia, which was responsible for the anticholin- for recreational purposes and 2 were suicide attempts. ergic poisoning of more than a dozen adolescents in one The teenagers received different treatments (Table 1), series.12 including charcoal, fluids, midazolam, and haloperidol. We have reviewed all anticholinergic intoxications The 2 patients who attempted suicide were treated with at our institution over a 10-years period and describe midazolam and the antidote physostigmine. the clinical manifestations and treatments used. DISCUSSION MATERIALS AND METHODS All 10 of our patients, with ingestions leading to anticho- We performed a retrospective chart review of all patients linergic toxidromes, were significantly ill adolescents aged ,18 years with confirmed anticholinergic intoxica- who needed, at the very least, treatment and a period tion seen from April 2001 to July 2010 at the Hospital for of observation in the emergency department. Although Sick Children, Toronto, Ontario, Canada. Charts were 8 patients presented after recreational experimentation, identified using the specific ICD 10 codes T44.3 [“Other 2 were attempted suicides. parasympatholytics (anticholinergics and antimuscar- Five patients presented after the use of jimsonweed, inics) and spasmolytics, not elsewhere classified”]and Datura stramonium, which has been known to produce X 69 (intentional self-poisoning by and exposure to other hallucinogenic effects for centuries. It is easily obtained and unspecified chemicals and noxious substances- and abused by adolescents, especially because the plants-jimsonweed poisoning). Inclusion criteria for the Internet has provided a widespread and popular vehi- study were presentation to the emergency department or cle for the rapid and facile sharing of information. admission to an inpatient unit or the intensive care unit, Many herbal hallucinogens are now widely available of a pediatric patient with intoxication involving anticho- via unregulated Web sites that sell these products linergic seeds, tablets, or teas. No exclusion criteria, other purely for recreational use.13 than age limit, were used. Data were extracted by Belladonna alkaloids need to be considered, along 2 independent investigators using a structured form. with drugs such as amphetamine, cocaine, phencycli- Clinical outcomes, such as the extent and duration of dine (PCP), in any patient presenting with delirium or clinical manifestations, treatments employed, clinical psychosis. Other causes of altered mental status and responses, and outcomes were collected and analyzed. hallucinations include hypoglycemia, which must be Concomitant medications and other toxic exposures urgently excluded, encephalitis, meningitis, intracere- were recorded. Encephalopathy was accepted when at bral hemorrhage, thyrotoxicosis, sepsis, psychiatric least 2 of the following symptoms were present1: altered illness, withdrawal, and other toxic exposures.14 Diag- states of consciousness,2 altered cognition or personality, nosis can be difficult because of the wide range of signs and3 seizures. The study was approved by the and symptoms associated with anticholinergic toxicity

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Table 1. Characteristics of pediatric patients with anticholinergic intoxication over 10 years at The Hospital for Sick Children (N 5 10).

Age Anticholinergic Clinical Treatment in emergency Cause of Patient (yr) ingested manifestations Disposition department ingestion

1 18 Jimsonweed Agitation 3 days hospitalization Charcoal Social Hallucinations Tachycardia Benzodiazepines Mydriasis Slurred speech 2 17 Tablets Agitation Discharged from Benzodiazepines Social Hallucinationsemergency department Physostigmine Hyperthermia 3 15 Tablets Drowsiness 2 days hospitalization Charcoal Social Fluids 4 17 Jimsonweed Hallucinations 3 days hospitalization Benzodiazepines Social Tachycardia Incoherent speech Dry mouth Redness Hyperthermia 5 16 Jimsonweed Hallucinations Not reported Charcoal Social Tachycardia Incoherent speech Disorientation Fluids Dilated pupils 6 15 Tablets Hallucinations ICU admission Benzodiazepines Suicidal Tachycardia Drowsiness Intubation 7 15 Jimsonweed Hallucinations 3 days hospitalization Haloperidol Social Flushed face Drowsiness Mydriasis 8 16 Jimsonweed Agitation ICU admission Benzodiazepines Unknown Hallucinations Tachycardia Mydriasis Hyperthermia 9 16 Tablets Agitation ICU admission Midazolam Social Hallucinations Tachycardia Mydriasis Hyperthermia 10 15 Tablets Agitation 3 days hospitalization Midazolam Suicidal Hallucinations Tachycardia Physostigmine Mydriasis Hyperthermia

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and the difficulties associated with obtaining an accu- substances. For this reason, it is very important for rate history in recreational drug ingestions.12 individuals to become educated on the toxicities and Not all the characteristics of anticholinergic toxi- potential risks associated with the recreational use of drome are necessarily present in each case.2 Clinical these plants. manifestations are caused by central or peripheral nervous system effects or both. The central effects are dose and agent dependent, and it may present in infants as REFERENCES ataxia, seizure, or coma, making diagnosis difficult when the history of ingestion is not so clear15 and when 1. Marc B, Martis A, Moreau C, et al. Acute Datura stramo- fever is present. No clinical laboratory tests are rou- nium poisoning in an emergency department [in French]. – tinely available to detect or prove anticholinergic toxic- Presse Med. 2007;36:1399 1403. ity, and the diagnosis is generally based on history, 2. 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