Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

A)

1) Deadly nightshade

1) Chinese herbal medicine

1) Datura Fastuosa (Chinese herbal medicine)

1) Daturae Folium (dried leaves and flowering tops)
2) Hindu datura
3) Metel
4) Unmatal
5) Yangjinhua (Chinese herbal from dried flowers)

1) Angel's Trumpet
2) Brugmansia suaveolens

1) Jamestown weed
2) Jimson weed
3) Thorn Apple
4) Stink weed

1) Chinese herbal medicine

1) Black henbane

1) Blue Bonnet
2) Texas blue bonnet
3) Lupine
4) CESTRUM NOCTURNUM
5) ANTICHOLINERGIC PLANTS
6) LYCIUM HALIMOFOLIUM
7) YANGJINHUA (CHINESE HERBAL MEDICINE from DRIED FLOWERS)

Available Forms Sources

A)

1) DATURA STRAMONIUM: Each seed weighs about 1 mg and contains about 0.4% belladonna alkaloid (Goldfrank & Melinek, 1979).

a) Young Datura plants contain mainly scopolamine, the older ones have mostly hyoscyamine.
b) The table below shows the relationship between plant part and the amount of alkaloid present in that part (Frohne & Pfander, 1984).

PART	AMOUNT OF ALKALOID (%)
Flowers	0.61
Fruit	0.66
Leaves	0.38
Pericarp	0.05
Roots	0.23
Seeds	0.58
Shoots	0.16

2) DATURA METEL L

a) ALKALOID CONTENT by plant part (Duke, 1985)

PART	ALKALOID CONTENT (%)
Fruit	0.12
Leaves	0.2 to 0.5
Roots	0.1 to 0.2
Seed	0.2 to 0.5

3) HYOSCYAMUS NIGER

a) This plant is in the Solanaceae family. Its roots, leaves and fruits contain alkaloids like atropine, hyoscyamine, and scopolamine (Doneray et al, 2007). ALKALOID content by plant part are listed below (Frohne & Pfander, 1984)

PART	ALKALOID CONTENT (%)
Leaves	0.17
Roots	0.08
Seeds	0.30

4) ATROPA BELLADONNA

a) ALKALOID CONTENT BY PLANT PART (Frohne & Pfander, 1984)

PART	ALKALOID CONTENT (%)
Flowers	0.4
Fruits (Berries)	0.65
Leaves	0.5
Roots	0.85
Seeds	0.8

5) A few drops of the juice from the berries (or urine from a patient) may be instilled into a rabbit's eye to test for dilatation of the pupils (Frohne & Pfander, 1984).

a) A few drops of the diluted juice from the berries or solution made from mashed seeds may be mixed with water and tested with long-wave (365 nm) UV light. The glycoside scopolin, which accompanies the alkaloids, will fluoresce light blue (Frohne & Pfander, 1984).

B)

1) ALKALOID by PLANT (Frohne & Pfander, 1984; Chan, 1995; Duke, 1985).

PLANT	PART	ALKALOID
Datura stramonium	Leaves	Hyoscyamine
	Roots	Hyoscyamine & Hyoscine
	Seeds	Hysocyamine
Datura metel L	All	Scopolamine, Hyoscyamine, Atropine, Others
Hyoscyamus niger	All	Hyoscyamine & Hyoscine
Atropa belladonna	All	Hyoscyamine, Scopolamine
Lycium halimifolium	All	Atropine Hyoscyamine
Cestrum nocturnum	All	Atropine (possibly)

C)

1) CHINESE HERBAL MEDICINES (Chan, 1995)

1) YANGJINHUA: Used to treat bronchial asthma, bronchitis, pain, seizures, psychosis and flu symptoms
2) DATURA METEL L: Primarily used in Southern China
3) DATURA innoxia Mill: Primarily used in Northern China

2) DATURA STRAMONIUM

a) Extracts of D. stramonium and other Datura species have been applied to the skin or oral mucosa to treat inflammation and trauma (Pereira & Nishioka, 1994). Historically, D. stramonium has been used by the American Indians as a folk medicine and in religious activities (CDC, 1995).
b) MISUSE - Datura stramonium (Jimson weed) is readily found in southern Canada and the United States and has been intentionally misused for its euphoric and hallucinogenic effects. Reports of exposure have mostly occurred in teenagers and young adults. The plant forms a pod in the fall that contains multiple small white seeds that mature into black seeds. All parts of the Jimson weed are considered poisonous and contain the belladonna alkaloids atropine, L-hyoscyamine, and L-scopolamine; however the seeds are most often implicated in poisoning (Spina & Taddei, 2007; Nelson et al, 2007). The seeds contain the highest concentration of belladonna alkaloids with symptoms generally occurring within one hour of exposure (Spina & Taddei, 2007).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: The anticholinergic toxidrome refers to a set of signs and symptoms that occur with toxicity from antagonists of the muscarinic cholinergic receptors. It can occur after poisoning from naturally occurring alkaloids found in many plants. This class of plants is occasionally abused (mostly by adolescents) for its hallucinogenic effects.
B) TOXICOLOGY: Is due to extensive antagonism of the central and peripheral muscarinic acetylcholine receptors.
C) EPIDEMIOLOGY: Poisoning is common, but rarely severe. Effects have resulted primarily from ingestion of flowers, seeds, roots or extracts. There are rare reports of fatalities from consumption of seeds or tea brewed from Datura species.
D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Somnolence, anticholinergic effects of mydriasis, flushing, fever, dry mouth, decreased bowel sounds, and tachycardia are characteristic. Mild hypertension, nausea and vomiting are also common. Agitation, confusion, and hallucinations may develop with moderate poisoning.
2) SEVERE TOXICITY: Severe effects may include agitated delirium, psychosis, hallucinations, seizures, hyperthermia, and coma. Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, coma or seizures.

0.2.3)

A) WITH POISONING/EXPOSURE

1) Sinus tachycardia and mild hyperthermia are common. Hypertension may occur inconsistently.

0.2.4)

A) WITH POISONING/EXPOSURE

1) MYDRIASIS and loss of accommodation for near vision is a common finding.

0.2.5)

A) WITH POISONING/EXPOSURE

1) Sinus tachycardia, particularly in children and young adults, and either hypertension or hypotension may occur, but are inconsistent findings.

0.2.6)

A) WITH POISONING/EXPOSURE

1) Dyspnea, tachypnea, and apnea have been infrequently reported.

0.2.7)

A) WITH POISONING/EXPOSURE

1) Anxiety, delirium, disorientation, hallucinations, hyperactivity, and seizures may occur. Severe poisoning may produce coma.

0.2.8)

A) WITH POISONING/EXPOSURE

1) Dry mouth and decreased gastrointestinal motility with loss of bowel sounds are common. Swallowing will be difficult and speech may sound unintelligible because of oral dryness.

0.2.9)

A) WITH POISONING/EXPOSURE

1) Elevated liver enzymes have been reported.

0.2.10)

A) WITH POISONING/EXPOSURE

1) Urinary retention may occur and necessitate catheterization. Urinary incontinence has been reported.

0.2.14)

A) WITH POISONING/EXPOSURE

1) Skin is commonly dry and flushed, particularly the face and neck.

0.2.20)

A) Use during pregnancy may increase risk of respiratory abnormalities, hypospadias, and eye or ear malformations, but causal relationship is unclear.

Laboratory Monitoring

A)

B)

C)

D)

E)

F)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) The vast majority of plant poisonings that produce the anticholinergic toxidrome require only supportive care; administer activated charcoal if patient presents shortly after ingestion; sedate with benzodiazepines for agitation and delirium. Hypertension and tachycardia are generally mild and well tolerated, and do not require specific treatment. Physostigmine can be used to establish the diagnosis; it may help avoid an invasive, costly work-up, but should only be given in a setting where intensive monitoring and resuscitation is possible, and should NOT be given if the history or ECG (QRS widening) suggests tricyclic antidepressant poisoning.

B) MANAGEMENT OF SEVERE TOXICITY

1) Orotracheal intubation for airway protection should be performed early. Patients may benefit from gastric lavage if they present soon after a large ingestion; administer activated charcoal. GI decontamination should be performed only in patients who can protect their airway or who are intubated. Severe delirium may develop and require large doses of benzodiazepines for sedation. Seizures (may progress to status epilepticus) may require aggressive use of benzodiazepines, propofol and/or barbiturates. Monitor core temperature and treat hyperthermia with aggressive benzodiazepine sedation to control agitation, and external cooling. Clinical manifestations may be prolonged due to prolonged absorption in the setting of an anticholinergic ileus.

C) DECONTAMINATION

1) PREHOSPITAL: Decontamination is not recommended because of potential for somnolence and seizures. For dermal exposure, wash skin thoroughly.
2) HOSPITAL: Activated charcoal if recent, substantial ingestion, and patient able to protect airway. Consider gastric lavage in recent, life threatening ingestion, protect airway prior to procedure.

D) AIRWAY MANAGEMENT

1) Perform early in patients with severe intoxication (i.e., seizures, severe delirium or hyperthermia).

E) ANTIDOTE

1) Physostigmine is indicated to reverse the CNS effects caused by clinical or toxic dosages of agents capable of producing anticholinergic syndrome; however, long lasting reversal of anticholinergic signs and symptoms is generally not achieved because of the relatively short duration of action of physostigmine (45 to 60 minutes). It is most often used diagnostically to distinguish anticholinergic delirium from other causes of altered mental status. CAUTION: If tricyclic antidepressants are coingested, physostigmine may precipitate seizures and dysrhythmias. DOSES: ADULT: 2 mg IV at a slow controlled rate, no more than 1 mg/min. May repeat doses at intervals of 10 to 30 min if severe symptoms recur. For patients with prolonged anticholinergic delirium consider a continuous infusion, start at 2 mg/hr and titrate to effect. CHILD: 0.02 mg/kg by slow IV injection, at a rate no more than 0.5 mg/minute. Repeat dosage at 5 to 10 minute intervals as long as the toxic effect persists and there is no sign of cholinergic effects. MAXIMUM DOSAGE: 2 mg total.

F) SEIZURE

1) Intravenous benzodiazepines; add propofol or barbiturates if seizures persist or recur.

G) BODY TEMPERATURE ABOVE NORMAL

1) Control agitation with benzodiazepines, initiate aggressive external cooling measures (i.e., remove patient's clothing, cover with a damp sheet or spray skin with water and direct fan at the patient’s skin to enhance evaporation).

H) DELIRIUM

1) Sedate patient with benzodiazepines as necessary. Large doses may be required.

I) ENHANCED ELIMINATION

1) Hemodialysis and hemoperfusion are of no value in this setting because of the large volume of distribution.

J) PATIENT DISPOSITION

1) HOME CRITERIA: Asymptomatic children (other than mild drowsiness or stimulation) with acute inadvertent ingestion may be monitored at home.
2) OBSERVATION CRITERIA: Patients with deliberate ingestions and symptomatic patients should be sent to a health care facility for observation for 6 to 8 hours.
3) ADMISSION CRITERIA: Patients with significant persistent central nervous system toxicity (i.e., hallucinations, somnolence, delirium, coma), or persistent tachycardia should be admitted. Patients with coma, seizures or delirium should be admitted to an intensive care setting.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (i.e., seizures, severe delirium, coma), or in whom the diagnosis is not clear.

K) PITFALLS

1) Physostigmine is generally not advised for long term management as anticholinergic effects generally recur 30 to 45 minutes after physostigmine administration. Anticholinergic toxicity may be prolonged secondary to decreased gastrointestinal motility leading to prolonged absorption.

L) PHARMACOKINETICS

1) While the exact pharmacokinetics will vary with the particular poison, the majority of poisons that cause anticholinergic symptoms will have a rapid onset and long duration of effect.

M) DIFFERENTIAL DIAGNOSIS

1) Anticholinergic poisoning from other substances, sympathomimetic poisoning (should have less mydriasis, usually no visual hallucinations, usually have moist skin), CNS infection, or ethanol/benzodiazepine/barbiturate withdrawal.

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

1) MILD TO MODERATE TOXICITY: Somnolence, anticholinergic effects of mydriasis, flushing, fever, dry mouth, decreased bowel sounds, and tachycardia are characteristic. Mild hypertension, nausea and vomiting are also common. Agitation, confusion, and hallucinations may develop with moderate poisoning.
2) SEVERE TOXICITY: Severe effects may include agitated delirium, psychosis, hallucinations, seizures, hyperthermia, and coma. Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, coma or seizures.

Vital Signs

3.3.1)

A) WITH POISONING/EXPOSURE

1) Sinus tachycardia and mild hyperthermia are common. Hypertension may occur inconsistently.

3.3.3)

A) WITH POISONING/EXPOSURE

1) HYPERTHERMIA has been reported (Nikolaou et al, 2011; Coremans et al, 1994; Hanna et al, 1992; Pereira & Nishioka, 1994; Rauber-Luthy et al, 1999; Groszek et al, 2000; Ertekin et al, 2005) and may be life-threatening, particularly in children in warm climates. About 18.1% of patients in one study had elevated temperatures (O'Grady et al, 1983).
2) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 10 (8.2%) patients developed fever or hyperthermia. Hypothermia occurred in five or fewer cases (Forrester, 2006).
3) DATURA INOXIA: Hyperpyrexia was reported in 10 of 15 patients (67%) who ingested wasp honey or honeycomb. Wasp honeycomb can be found in rural areas near Datura inoxia, a plant whose leaves, fruits, and flowers contain atropine and scopolamine. It is believed that the wasps may have transported the atropine or scopolamine from the Datura plant to the honeycomb, leading to an accumulation of the anticholinergic agents in the honey (Ramirez et al, 1999).

3.3.4)

A) WITH POISONING/EXPOSURE

1) HYPERTENSION

1) Hypertension has been inconsistently reported (Rosen & Lechner, 1962).
2) Hypertension has been reported following Datura stramonium ingestion (Martinez et al, 2001; Guharoy & Barajas, 1991; Vanderhoff & Mosser, 1992; CDC, 1995), D candida ingestion (Finlay, 1998), Brugmansia species ingestion (Isbister et al, 2003), ocular exposure to D. suaveolens (Havelius & Asman, 2002), and ingestion of mandragora officinarum (Nikolaou et al, 2011).
3) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 9 (7.4%) patients developed hypertension (Forrester, 2006).

3.3.5)

A) WITH POISONING/EXPOSURE

1) TACHYCARDIA

a) Sinus tachycardia is a common anticholinergic finding, particularly in children and young adults (Nikolaou et al, 2011; Pekdemir et al, 2004; Parissis et al, 2003; Mrvos et al, 2001; Belton & Gibbons, 1979; CDC, 1995) (O'Grady et al, 1983) (Guharoy & Barajas, 1991; Vanderhoff & Mosser, 1992; Chang et al, 1999; Francis & Clarke, 1999; Tsiodras et al, 1999).
b) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 50 (41%) patients developed tachycardia (Forrester, 2006).

Heent

3.4.1)

A) WITH POISONING/EXPOSURE

1) MYDRIASIS and loss of accommodation for near vision is a common finding.

3.4.3)

A) WITH POISONING/EXPOSURE

1) MYDRIASIS and CYCLOPLEGIA are common following ingestion (Nikolaou et al, 2011; Ertekin et al, 2005; Pekdemir et al, 2004; Parissis et al, 2003; Martinez et al, 2001; Mrvos et al, 2001; Vanderhoff & Mosser, 1992; Shenoy, 1994; Hanna et al, 1992; Pereira & Nishioka, 1994; CDC, 1995; Finlay, 1998; Francis & Clarke, 1999; Tsiodras et al, 1999; Schumacher, 1965) and have been reported after smoking Datura stramonium extract (Guharoy & Barajas, 1991). This may persist for some days after acute poisoning (Jennings, 1935). Blurred vision also occurs (Eichner et al, 1967; Bryson et al, 1978; Chang et al, 1999).

a) INCIDENCE (DATURA STRAMONIUM): In a retrospective study of 122 jimsonweed exposures, 42 (34.4%) patients developed mydriasis. In addition, blurred vision and miosis occurred in five or fewer cases (Forrester, 2006).
b) INCIDENCE (BRUGMANSIA): Mydriasis was reported in 100% of 33 patients with Brugmansia poisoning, mean duration was 29 hours (standard deviation 13 hours) (Isbister et al, 2003).
c) INCIDENCE (DATURA INOXIA): Mydriasis was reported in 5 of 15 patients (33%) who ingested wasp honey or honeycomb. Wasp honeycomb can be found in rural areas near Datura inoxia, a plant whose leaves, fruits, and flowers contain atropine and scopolamine. It is believed that the wasps may have transported the atropine or scopolamine from the Datura plant to the honeycomb, leading to an accumulation of the anticholinergic agents in the honey (Ramirez et al, 1999).
d) INCIDENCE (ATROPA BELLADONNA): In a retrospective series of children with atropa belladonna poisoning, mydriasis was noted in 31 out of 43 patients (72%) with mild to moderate poisoning and 3 out of 6 (50%) patients with severe poisoning (Caksen et al, 2003).

2) ANISOCORIA has occurred after ocular contact with Jimson weed leaves or seeds (Savitt et al, 1986).

a) CASE SERIES (ANISOCORIA): Unilateral mydriasis (anisocoria) was reported in 7 patients following inadvertent ocular instillation of the sap from Angel's trumpet (Datura suaveolens). Three patients also experienced ipsilateral cycloplegia. The cycloplegia and mydriasis spontaneously resolved in all patients within one week postexposure (Havelius & Asman, 2002).
b) CASE REPORT (BRUGMANSIA SUAVEOLENS and DATURA SUAVEOLENS): Similar symptoms were reported in a young girl after touching an Angel's Trumpet (Brugmansia suaveolens or Datura suaveolens) and then touching her eye; anisocoria completely resolved within 48 hours (Andreola et al, 2008).

3) NYSTAGMUS (SURAMA): Rotary nystagmus was seen in a 25-year-old and a 16-year-old who ingested Surama herbal cigarettes containing 92.5% Datura stramonium leaf (Ballantyne et al, 1976).

3.4.6)

A) WITH POISONING/EXPOSURE

1) DRYNESS of the throat and mucous membranes have been reported after ingestion of anticholinergic plants, after application of an extract to the oral mucosa and after smoking of an extract (Michalodimitrakis & Koutselinis, 1984; CDC, 1995; Guharoy & Barajas, 1991; Pereira & Nishioka, 1994; Eshov & Krenzelok, 1995; Chang et al, 1999). Thirst is a common symptom.

Cardiovascular

3.5.1)

A) WITH POISONING/EXPOSURE

1) Sinus tachycardia, particularly in children and young adults, and either hypertension or hypotension may occur, but are inconsistent findings.

3.5.2)

A) HYPERTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypertension has been inconsistently reported (Rosen & Lechner, 1962).
b) Hypertension has been reported following Datura stramonium ingestion (Martinez et al, 2001; Guharoy & Barajas, 1991; Vanderhoff & Mosser, 1992; CDC, 1995), D candida ingestion (Finlay, 1998), Brugmansia species ingestion (Isbister et al, 2003), ingestion of Burdock root tea (which contains high levels of an atropine-like alkaloid) (Bryson et al, 1978), ocular exposure to D. suaveolens (Havelius & Asman, 2002), and ingestion of Mandragora officinarum (Nikolaou et al, 2011).
c) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 9 (7.4%) patients developed hypertension (Forrester, 2006).
d) MANDRAGORA OFFICINARUM: An adult developed symptoms of anticholinergic poisoning including tachycardia (heart rate of 110/beats/min) and hypertension (155/95 mmHg) 4 hours after ingesting 5 mandragora officinarum berries as an aphrodisiac. All symptoms resolved after the administration of physostigmine and the patient recovered completely (Nikolaou et al, 2011).

B) SINUS TACHYCARDIA

1) WITH POISONING/EXPOSURE

a) Sinus tachycardia is a common anticholinergic finding, particularly in children and young adults (Nikolaou et al, 2011; Pekdemir et al, 2004; Parissis et al, 2003; Mrvos et al, 2001; Belton & Gibbons, 1979; CDC, 1995) O'Grady et al, 1983; (Guharoy & Barajas, 1991; Vanderhoff & Mosser, 1992; Chang et al, 1999; Francis & Clarke, 1999; Tsiodras et al, 1999).

1) INCIDENCE: In a series of 33 patients with Brugmansia poisoning, 11 (33%) were tachycardic. In the 24 patients in whom the time of ingestion was determined, tachycardia was more common in patients presenting within 5 hours of exposure (7 of 8, 88%) compared with those presenting more than 5 hours after exposure (5 of 16, 31%) (Isbister et al, 2003).
2) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 50 (41%) patients developed tachycardia (Forrester, 2006).

b) Sinus tachycardia with occasional ventricular ectopy were reported in an 82-year-old who had ingested a nickel-sized piece of D. innoxia (Hanna et al, 1992)
c) Sinus tachycardia, as well as other anticholinergic effects, occurred in 3 children after ingestion of an Atropa belladonna plant. All three children recovered following gastric decontamination and treatment with physostigmine (Eshov & Krenzelok, 1995).
d) INCIDENCE: In a retrospective study, involving 49 children with deadly nightshade (Atropa belladonna) poisoning, tachycardia appeared to be less common in children with severe intoxication (33.3%; n=6) as compared with children who developed mild/moderate intoxication (93%; n=43). The absence of tachycardia in children with deadly nightshade poisoning may suggest more severe intoxication (Caksen et al, 2003).
e) DATURA STRAMONIUM: A 4-year-old boy ingested an unknown amount of datura stramonium weed (jimson weed) which contained 0.2% to 0.5% atropine alkaloid, and developed impaired consciousness, mydriasis, excitement, hallucinations, ataxia, and a tachycardia of up to 130 beats/min. Symptoms occurred approximately 3 hours after ingestion with a slow recovery over 2 days (Schumacher, 1965).
f) MANDRAGORA OFFICINARUM: An adult developed symptoms of anticholinergic poisoning including tachycardia (heart rate of 110/beats/min) and hypertension 4 hours after ingesting 5 mandragora officinarum berries as an aphrodisiac (Nikolaou et al, 2011).

C) CONDUCTION DISORDER OF THE HEART

1) WITH POISONING/EXPOSURE

a) CASE REPORT (DATURA SUAVEOLENS): A 20-year-old woman on methadone maintenance ingested a tea containing Datura suaveolens, and developed coma, severe hyperthermia (42.9 C), seizures, tachycardia to 200 beats/minute, hypotension and eventually ventricular tachycardia and fibrillation unresponsive to resuscitation including cooling, fluids, electrolyte replacement, vasopressors, physostigmine, and defibrillation. She died 4 hours postingestion; it is unclear if other drugs may have been involved (Rauber-Luthy et al, 1999).

Respiratory

3.6.1)

A) WITH POISONING/EXPOSURE

1) Dyspnea, tachypnea, and apnea have been infrequently reported.

3.6.2)

A) HYPERVENTILATION

1) WITH POISONING/EXPOSURE

a) Ingestion of 435 mg of scopolamine by a 76-year-old caused respiratory difficulties (Smith et al, 1991).
b) DATURA STRAMONIUM: Tachypnea, with or without respiratory difficulty has been reported after ingestion of D. stramonium seeds (Guharoy, 1991 & Barajas) (Vanderhoff & Mosser, 1992).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) CASE REPORT (DATURA STRAMONIUM): A 12-year-old boy developed respiratory failure secondary to acute respiratory distress syndrome after ingesting Datura stramonium seeds, and died, 4 days later, from refractory hypoxemia (Thabet et al, 1999).

Neurologic

3.7.1)

A) WITH POISONING/EXPOSURE

1) Anxiety, delirium, disorientation, hallucinations, hyperactivity, and seizures may occur. Severe poisoning may produce coma.

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) ANTICHOLINERGIC DELIRIUM WITH DISORIENTATION/AGITATION

1) Anticholinergic delirium with disorientation, hallucinations (visual, auditory, tactile) anxiety, agitation and combativeness is common, especially after recreational use or in young children (Rakotomavo et al, 2014; Berdai et al, 2012; Spina & Taddei, 2007; Mrvos et al, 2001; Kurzbaum et al, 2001; Al-Habeeb et al, 1999; Groszek et al, 2000; CDC, 1995; Coremans et al, 1994; Hanna et al, 1992; Vanderhoff & Mosser, 1992; Schumacher, 1965; Finlay, 1998).
2) INCIDENCE (BRUGMANSIA): In a series of 33 patients with Brugmansia poisoning, 29 (88%) developed delirium with a mean duration of 18 hours (standard deviation 12 hours)(Isbister et al, 2003).
3) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 61 (50%) patients developed hallucination or delusion; 48 (39.3%) patients developed agitation or irritability (Forrester, 2006).
4) CASE SERIES (DATURA SUAVEOLENS): 3 of 5 adolescent males, who ingested Datura suaveolens-Coca Cola mixture, presented with extreme agitation and combativeness approximately 1 hour later. The patients recovered following supportive care (Francis & Clarke, 1999). Similar symptoms were reported in 2 teenagers who ingested Jimson weed (D. stramonium) and alcohol. Restraints were necessary in one patient until adequately sedated (Spina & Taddei, 2007).
5) DATURA INOXIA: Agitation and hallucinations were reported in 2 patients who ingested large amounts of wasp honeycomb. Both patients subsequently died from heatstroke as a result of the anticholinergic effects combined with high environmental temperatures and excessive physical activity (Ramirez et al, 1999). Wasp honeycomb can be found in rural areas near Datura inoxia, a plant whose leaves, fruits, and flowers contain atropine and scopolamine. It is believed that the wasps may have transported the atropine or scopolamine from the Datura plant to the honeycomb, leading to an accumulation of the anticholinergic agents in the honey.
6) Toxic psychosis, consisting of hallucinations, disorientation, agitation, combativeness, and anxiety, occurred in three adolescents who had ingested tea containing Angel's trumpet (Gopel et al, 2002).
7) CASE REPORT (DATURA STRAMONUM)/LATE ONSET OF SYMPTOMS: A 5-year-old boy developed a sudden onset of difficulty speaking and a decreased level of consciousness due to the ingestion of Datura stramonium 2 days previously. Upon admission, he developed blurred vision, hallucinations and difficulty speaking (slurred speech) and walking. Diagnostic and laboratory studies were normal and a toxicology screen was negative. By the second day of admission, the child became more alert and was able to recognize his mother and his gait and speech normalized. Upon further questioning the mother stated that child had been playing in the yard and the child admitted to eating the seeds and the flowers of the Datura stramonium plant (brought to the hospital for identification). All symptoms resolved within 48 hours of admission with supportive care (Ozkaya et al, 2015).
8) CASE REPORT (DATURA STRAMONIUM): Agitation, disorientation and hallucinogenic delirium developed in a 5 year-old boy following the ingestion of an unknown amount of herbal tea containing datura stramonium (ie, the leaves and flowers). His physical exam and laboratory studies were essentially normal with bilateral mydriasis unreactive to light. The child was treated with diazepam to treat his agitation and his vital signs remained stable. The following day his restlessness and delirium had improved. Bilateral mydriasis persisted until time of discharge at 48 hours. His 4-year-old brother also drank the same tea but developed lethargy and coma requiring airway management and mechanical ventilation. Both children recovered completely with no permanent sequelae (Rakotomavo et al, 2014).
9) CASE REPORT (MANDRAGORA OFFICINARUM): An adult developed symptoms of anticholinergic poisoning including early symptoms (approximately an hour after ingestion) of agitation, aggression, and hallucinations after ingesting mandragora officinarum berries as an aphrodisiac. All symptoms resolved after the administration of physostigmine; the patient recovered completely (Nikolaou et al, 2011).
10) CASE REPORT (ATROPA BELLADONNA): A 37-year-old woman presented to the ED with visual hallucinations, incoherent speech, and agitation approximately 30 minutes after ingestion of an herbal flu remedy inadvertently containing Atropa belladonna roots. The patient recovered following supportive care (Duenas-Laita et al, 2000).
11) CASE REPORT (DATURA SPECIES): A 49-year-old woman presented to the hospital with complaints of confusion and visual and auditory hallucinations that developed approximately 2 hours after using an oral preparation concocted with a Datura species of plant, which was intended as a treatment for gingivitis and was reportedly not swallowed. The patient recovered spontaneously within 12 hours (Pereira & Nishioka, 1994).
12) APHONIA occurred in a 72-year-old woman within 15 minutes of ingesting a liquid extract of a white flower, which was later determined to be Datura candida (Finlay, 1998).
13) CASE REPORT (DATURA INNOXIA MILLER): A 48-year-old man presented to the ED with difficulty in walking, confusion, agitation, disorientation, and hallucinations approximately 2 hours after drinking 6 glasses of lime tea and taking 500 mg of paracetamol. It was subsequently revealed that the packages of lime tea that he had consumed also contained Datura inoxia Miller. The patient gradually recovered with supportive care and was discharged 12 hours later without sequelae (Pekdemir et al, 2004).

B) DROWSY

1) WITH POISONING/EXPOSURE

a) DATURA STRAMONIUM: Lethargy, drowsiness and headache have resulted from D. stramonium and Atropa belladonna (deadly nightshade) ingestion (Caksen et al, 2003; CDC, 1995; Coremans et al, 1994)
b) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 16 (13.1%) patients developed drowsiness or lethargy (Forrester, 2006).

C) COMA

1) WITH POISONING/EXPOSURE

a) Severe poisoning may produce coma (Rakotomavo et al, 2014; Caksen et al, 2003; Hall et al, 1977; Theus et al, 1994). Electroencephalograms have shown slow wave activity and bizarre rhythmical bursts of high-voltage short wave activity (Mikolich et al, 1975).
b) CASE REPORT (DATURA SAUVEOLANS): Coma occurred in one of 14 people who ingested vegetable soup containing Datura sauveolans. The patient gradually regained consciousness following administration of physostigmine (Chang et al, 1999).
c) CASE REPORT (DATURA STRAMONIUM): Coma developed in a 4-year-old boy following the ingestion of an unknown amount of herbal tea containing datura stramonium (ie, the leaves and flowers). Physical exam was positive for bilateral mydriasis and bilateral Babinski signs. The child required intubation and mechanical ventilation. Activated charcoal via a nasogastric tube was given. After 12 hours, the child was extubated and slowly his consciousness improved. He was discharged after 72 hours. His 5-year-old brother also drank the same tea but developed agitation and hallucinogenic delirium. Both children recovered completely with no permanent sequelae (Rakotomavo et al, 2014).
d) CASE REPORT (DATURA STRAMONIUM): Coma occurred in a 15-year-old boy following acute Datura stramonium intoxication. The patient recovered following supportive care (Martinez et al, 2001).
e) CASE REPORT (DATURA STRAMONIUM): A 20-year-old man presented in a comatose state. He had bilateral mydriasis and abnormal corneal reflexes with decorticate posturing and positive Babinski signs. His Glasgow coma scale score was 5. It was revealed that the patient had ingested an unknown quantity of Datura stramonium seeds. Administration of physostigmine resulted in responsiveness of the patient and resolution of his neurological signs and symptoms 3 hours later (Parissis et al, 2003).
f) CASE REPORT (DATURA STRAMONIUM): An 8-year-old girl presented as comatose (Glasgow Coma Scale (GCS) score of 5) following suspected ingestion of Datura stramonium leaves. The patient was hyperthermic (38.9 degrees C), with xerostomia and mydriasis. Laboratory analysis revealed elevated transaminase concentrations (AST 370 Units/L, ALT 304 Units/L), an elevated creatine kinase concentration (CK) (5739 Units/L), and an LDH concentration of 1014 Units/L. On hospital day 2, the patient's neurological status improved (GCS 10), however, her liver enzyme and CK concentrations continued to increase (ALT, AST, CK, and LDH of 1829 Units/liter, 2052 Units/liter, 6970 Units/liter, and 1087 Units/liter, respectively). With supportive care, the patient's condition improved with normalization of laboratory values by hospital day 10 (Ertekin et al, 2005).

D) HYPERREFLEXIA

1) WITH POISONING/EXPOSURE

a) Bilateral, dorsiflexor Babinski responses and decerebrate posturing have been reported (Parissis et al, 2003; Mikolich et al, 1975). Hyperreflexia may occur (Rosen & Lechner, 1962).

E) SEIZURE

1) WITH POISONING/EXPOSURE

a) First hyperactivity, then seizures may rarely occur (Smidt et al, 1978; Thabet et al, 1999).
b) DATURA SUAVEOLENS: Tonic-clonic seizures were reported in a 20-year-old woman following ingestion of a tea containing Datura suaveolens (Rauber-Luthy et al, 1999).
c) DATURA STRAMONIUM/INCIDENCE: In a retrospective study of 122 jimsonweed exposures, seizures developed in five or fewer cases (Forrester, 2006).

F) AMNESIA

1) WITH POISONING/EXPOSURE

a) Amnesia may occur during the delirious and confusional state in severe cases of intoxication (Gopel et al, 2002; Smidt et al, 1978; Coremans et al, 1994; Vanderhoff & Mosser, 1992).

G) PARALYSIS

1) WITH POISONING/EXPOSURE

a) Partial paralysis, loss of coordination, muscular weakness, and loss of sensation occurred after approximately 435 mg of scopolamine, PO in a 76-year-old (Smith et al, 1991).

H) DISTURBANCE IN SPEECH

1) WITH POISONING/EXPOSURE

a) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 9 (7.4%) patients developed slurred speech (Forrester, 2006). A teenager developed incomprehensible and nonsensical speech after ingesting jimson weed and alcohol (Spina & Taddei, 2007).
b) ATROPA BELLADONNA: In a retrospective study, involving 49 children with deadly nightshade (Atropa belladonna) poisoning, incoherent speech appeared to be more common in children with severe intoxication (100%; n=6) as compared with children who developed mild/moderate intoxication (41.8%; n=43). The results of the study indicate that the presence of incoherent speech in children with deadly nightshade poisoning may be an indicator to the severity of intoxication (Caksen et al, 2003).

I) ACUTE CONFUSION

1) WITH POISONING/EXPOSURE

a) INCIDENCE (JIMSONWEED): In a retrospective study of 122 jimsonweed exposures, 42 (34.4%) patients developed confusion (Forrester, 2006).

Gastrointestinal

3.8.1)

A) WITH POISONING/EXPOSURE

1) Dry mouth and decreased gastrointestinal motility with loss of bowel sounds are common. Swallowing will be difficult and speech may sound unintelligible because of oral dryness.

3.8.2)

A) DRUG-INDUCED ILEUS

1) WITH POISONING/EXPOSURE

a) ATONIA: Decreased gastrointestinal motility is common (CDC, 1995). Jimson seeds have been recovered from the stomach between 16 and 36 hours following ingestion (Levy, 1976).

B) APTYALISM

1) WITH POISONING/EXPOSURE

a) INCIDENCE (ATROPA BELLADONNA): In a retrospective series of children with atropa belladonna poisoning, dry mouth was noted in 19 out of 43 patients (44%) with mild to moderate poisoning and 1 out of 6 (17%) patients with severe poisoning (Caksen et al, 2003).
b) CASE REPORT (MANDRAGORA OFFICINARUM): An adult developed symptoms of anticholinergic poisoning (ie, dry mouth and skin, mydriasis, and hyperthermia) 4 hours after ingesting 5 mandragora officinarum berries as an aphrodisiac (Nikolaou et al, 2011).
c) CASE REPORT (DATURA STRAMONIUM): Dry mouth was reported in an 8-year-old child following suspected ingestion of Datura stramonium leaves (Ertekin et al, 2005).

C) NAUSEA AND VOMITING

1) WITH POISONING/EXPOSURE

a) CASE REPORT (MANDRAGORA OFFICINARUM): An adult developed nausea and vomiting and abdominal pain one hour after ingesting 5 mandragora officinarum berries (Nikolaou et al, 2011).
b) CASE SERIES (DATURA STRAMONIUM): In a retrospective study of 122 jimsonweed exposures, 10 (8.2%) patients developed vomiting (Forrester, 2006).

Hepatic

3.9.1)

A) WITH POISONING/EXPOSURE

1) Elevated liver enzymes have been reported.

3.9.2)

A) LIVER ENZYMES ABNORMAL

1) WITH POISONING/EXPOSURE

a) Elevation of SGOT and LDH has been reported (Caksen et al, 2003; Levy, 1977; Mikolich et al, 1975).
b) CASE REPORT (DATURA STRAMONIUM): Elevated liver enzyme concentrations (peak AST and ALT concentrations of 1829 and 2052 Units/liter, respectively) and an elevated LDH concentration (peak of 1087 Units/liter) were reported in an 8-year-old girl following a suspected ingestion of Datura stramonium leaves. The patient also developed hyperthermia, xerostomia, mydriasis, and rhabdomyolysis (peak creatine kinase concentration of 6970 Units/liter). With supportive care, the patient recovered with normalization of laboratory values by hospital day 10 (Ertekin et al, 2005).

Genitourinary

3.10.1)

A) WITH POISONING/EXPOSURE

1) Urinary retention may occur and necessitate catheterization. Urinary incontinence has been reported.

3.10.2)

A) RETENTION OF URINE

1) WITH POISONING/EXPOSURE

a) Urinary retention and bladder distention may occur and necessitate catheterization (Nikolaou et al, 2011; Isbister et al, 2003; Goldfrank & Melinek, 1979; Ballantyne et al, 1976; Shervette et al, 1979; Chang et al, 1999).
b) CASE REPORT (MANDRAGORA OFFICINARUM): An adult developed symptoms of anticholinergic poisoning including urinary retention 4 hours after ingesting 5 mandragora officinarum berries as an aphrodisiac. Catheterization was necessary. All symptoms resolved after the administration of physostigmine; the patient recovered completely (Nikolaou et al, 2011)

B) URINARY INCONTINENCE

1) WITH POISONING/EXPOSURE

a) Urinary incontinence has been reported in a case of D. stramonium tea ingestion (Coremans et al, 1994)

Acid-Base

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Metabolic acidosis was a rare effect in a retrospective series of 122 jimsonweed exposures reported to a poison center (Forrester, 2006).

Hematologic

3.13.2)

A) PROTHROMBIN TIME ABNORMAL

1) WITH POISONING/EXPOSURE

a) PROTHROMBIN TIME: Prolongation has been reported, but is not common and has not been associated with clinical bleeding (Ertekin et al, 2005; Caksen et al, 2003; Mikolich et al, 1975).

Dermatologic

3.14.1)

A) WITH POISONING/EXPOSURE

1) Skin is commonly dry and flushed, particularly the face and neck.

3.14.2)

A) ANHIDROSIS

1) WITH POISONING/EXPOSURE

a) Skin is commonly dry and warm as a result of the decreased activity of the sweat glands and flushing (Klein-Schwartz & Oderda, 1984; Jennings, 1935; Pereira & Nishioka, 1994; Eshov & Krenzelok, 1995; Groszek et al, 2000).
b) CASE REPORT (MANDRAGORA OFFICINARUM): An adult developed symptoms of anticholinergic poisoning (ie, dry mouth and skin, mydriasis, and hyperthermia) 4 hours after ingesting 5 mandragora officinarum berries as an aphrodisiac. All symptoms resolved after the administration of physostigmine; the patient recovered completely (Nikolaou et al, 2011).

B) FLUSHING

1) WITH POISONING/EXPOSURE

a) INCIDENCE (ATROPA BELLADONNA): In a series of children with atropa belladonna poisoning, flushing was noted in 32 out of 43 patients (74%) with mild to moderate poisoning and 2 out of 6 (33%) patients with severe poisoning (Caksen et al, 2003).
b) DATURA INOXIA: Facial flushing was reported in 10 of 15 patients (67%) who ingested wasp honey or honeycomb. Wasp honeycomb can be found in rural areas near Datura inoxia, a plant whose leaves, fruits, and flowers contain atropine and scopolamine. It is believed that the wasps may have transported the atropine or scopolamine from the Datura plant to the honeycomb, leading to an accumulation of the anticholinergic agents in the honey (Ramirez et al, 1999).

Musculoskeletal

3.15.2)

A) RHABDOMYOLYSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT (DATURA STRAMONIUM): Rhabdomyolysis with a peak creatine kinase concentration of 6970 Units/liter was reported in an 8-year-old child following a suspected ingestion of Datura stramonium leaves. The patient also developed hyperthermia, xerostomia, mydriasis, and coma (Glasgow Coma Scale score of 5), as well as elevated hepatic enzyme concentrations (peak AST and ALT concentrations of 1829 and 2052 Units/liter, respectively) and an elevated LDH concentration (peak of 1087 Units/liter). With supportive care, the patient gradually recovered with normalization of laboratory values by hospital day 10 (Ertekin et al, 2005).

Endocrine

3.16.2)

A) HYPERGLYCEMIA

1) WITH POISONING/EXPOSURE

a) ATROPA BELLADONNA: In a retrospective study, involving 49 children with deadly nightshade (Atropa belladonna) poisoning, hyperglycemia appeared to be less common in children with severe intoxication (0%; n=6) as compared with children who developed mild/moderate intoxication (39.5%; n=43) (Caksen et al, 2003).
b) DATURA INNOXIA MILLER: Hyperglycemia (blood glucose 280 mg/dL) was reported in a 48-year-old man who consumed 6 glasses of lime tea, mixed with Datura innoxia Miller, and 500 mg of paracetamol (Pekdemir et al, 2004).

Reproductive

3.20.1)

A) Use during pregnancy may increase risk of respiratory abnormalities, hypospadias, and eye or ear malformations, but causal relationship is unclear.

3.20.3)

A) PREGNANCY CATEGORY

BELLADONNNA	C
Reference: Briggs et al, 1998

B) FETAL DEVELOPMENT

1) Use during pregnancy may increase risk of respiratory abnormalities, hypospadias, and eye or ear malformations, but causal relationship is unclear (Briggs et al, 1998).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs (including temperature) and mental status.
B) Some plant alkaloids that cause severe symptoms are detected by chromatography, but this is rarely useful in guiding management.
C) No specific lab work is needed in most patients.
D) Monitor creatinine phosphokinase in patients with prolonged agitation, seizures or coma.
E) Monitor renal function and urine output in patients with rhabdomyolysis.
F) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity (ie, agitation, delirium, hallucinations, seizures, coma, hypotension).

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) No specific lab work (ie, CBC, electrolytes) is needed unless otherwise clinically indicated.
2) Monitor creatinine phosphokinase in patients with prolonged agitation, seizures, or coma.

4.1.3)

A) Monitor renal function and urine output in patients with rhabdomyolysis.

4.1.4)

A) OTHER

1) MONITORING

a) Monitor vital signs (including temperature) and mental status.
b) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity (i.e., agitation, delirium, hallucinations, seizures, coma, hypotension).

2) OTHER

a) Shaking the seeds of Datura stramonium with water may produce a light green fluorescence when seen under long wavelength (365 nm) UV light (Frohne & Pfander, 1984).

Methods

A)

1) DATURA FEROX: High performance liquid chromatography, coupled with a photodiode array (PDA) detector and a Z spray mass selective detector (ZMD), was used to analyze 3 viscera samples (stomach and its contents, liver, and kidney) in a man who died following a suspected heart attack. The HPLC method identified the presence atropine and scopolamine in the samples. A more detailed inspection of the stomach contents revealed the presence of several brown to black kidney-shaped seeds, subsequently identified as Datura ferox seeds.

a) Using the PDA detector, the limit of detection was 1 mcg/mL for both atropine and scopolamine, and the limit of quantitation was 10 mcg/mL for both atropine and scopolamine. Using the ZMD detector, the limits of detection for atropine and scopolamine were 10 pg/mL and 100 pg/mL, respectively, and the limits of quantitation were 100 ng/mL and 1 ng/mL, respectively (Steenkamp et al, 2004).

2) MANDRAGORA OFFICINARUM (BERRIES): Gas chromatography/electron impact mass spectrometry were used to detect the tropane alkaloids, hyoscyamine and scopolamine, in mandragora berries. The mass spectra of hyoscyamine, scopalmine, and methaqualone have a base peak of m/z 124, 94, and 235, respectively. The limit of detection of this method (recovery of greater than or equal to 85%) for both hyoscyamine and scopolamine in blood was 5.0 mcg/L (Nikolaou et al, 2011).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with significant persistent central nervous system toxicity (i.e., hallucinations, somnolence, delirium, coma), or persistent tachycardia should be admitted. Patients with coma, seizures or delirium should be admitted to an intensive care setting.

6.3.1.2) HOME CRITERIA/ORAL

A) Asymptomatic children (other than mild drowsiness or stimulation) with acute inadvertent ingestion may be monitored at home.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (i.e., seizures, severe delirium, coma), or in whom the diagnosis is not clear.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with deliberate ingestions and symptomatic patients should be sent to a health care facility for observation for 6 to 8 hours.

Monitoring

A)

B)

C)

D)

E)

F)

Oral Exposure

6.5.1)

A) Prehospital gastrointestinal decontamination is not recommended because of the potential for somnolence and seizures. For dermal exposure, wash skin thoroughly.

6.5.2)

A) SUMMARY

1) Decreased gastrointestinal motility is common and gastric decontamination may be useful late in an exposure. Jimson seeds have been recovered from the stomach between 16 and 36 hours following ingestion (Levy, 1976).
2) Consider gastric decontamination even in symptomatic patients presenting 12 to 24 hours following ingestion, due to the decrease in gut motility.

B) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

C) A retrospective study, involving 17 patients who ingested D. stramonium seeds, showed that the group with successful removal of D. stramonium seeds via nasogastric lavage (n=14) did not have significantly different ICU admission rates or length of hospital stays as compared with the group who did not have the D. stramonium seeds lavaged (n=3). However, because of study limitations, including the small sample size of patients, further investigation may be warranted (Salen et al, 2003).

6.5.3)

A) PHYSOSTIGMINE

1) PHYSOSTIGMINE/INDICATIONS

a) Physostigmine is indicated to reverse the CNS effects caused by clinical or toxic dosages of agents capable of producing anticholinergic syndrome; however, long lasting reversal of anticholinergic signs and symptoms is generally not achieved because of the relatively short duration of action of physostigmine (45 to 60 minutes) (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008). It is most often used diagnostically to distinguish anticholinergic delirium from other causes of altered mental status (Frascogna, 2007; Shannon, 1998).
b) Physostigmine should not be used in patients with suspected tricyclic antidepressant overdose, or an ECG suggestive of tricyclic antidepressant overdose (eg, QRS widening). In the setting of tricyclic antidepressant overdose, use of physostigmine has precipitated seizures and intractable cardiac arrest (Stewart, 1979; Newton, 1975; Pentel & Peterson, 1980; Frascogna, 2007).

2) DOSE

a) ADULT: BOLUS: 2 mg IV at slow controlled rate, no more than 1 mg/min. May repeat doses at intervals of 10 to 30 min, if severe symptoms recur (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008). INFUSION: For patients with prolonged anticholinergic delirium, a continuous infusion of physostigmine may be considered. Starting dose is 2 mg/hr, titrate to effect (Eyer et al, 2008)
b) CHILD: 0.02 mg/kg by slow IV injection, at a rate no more than 0.5 mg/minute. Repeat dosage at 5 to 10 minute intervals as long as the toxic effect persists and there is no sign of cholinergic effects. MAXIMUM DOSAGE: 2 mg total (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
c) AVAILABILITY: Physostigmine salicylate is available in 2 mL ampules, each mL containing 1 mg of physostigmine salicylate in a vehicle containing sodium metabisulfite 0.1%, benzyl alcohol 2%, and water (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).

3) CAUTIONS

a) Relative contraindications to the use of physostigmine are asthma, gangrene, diabetes, cardiovascular disease, intestinal or urogenital tract mechanical obstruction, peripheral vascular disease, cardiac conduction defects, atrioventricular block, and in patients receiving choline esters and depolarizing neuromuscular blocking agents (decamethonium, succinylcholine). It may cause anaphylactic symptoms and life-threatening or less severe asthmatic episodes in patients with sulfite sensitivity (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
b) Too rapid IV administration of physostigmine has resulted in bradycardia, hypersalivation leading to respiratory difficulties, and possible seizures (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).

4) ATROPINE FOR PHYSOSTIGMINE TOXICITY

a) Atropine should be available to reverse life-threatening physostigmine-induced, toxic cholinergic effects (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008; Frascogna, 2007). Atropine may be given at half the dose of previously given physostigmine dose (Daunderer, 1980).

5) CLINICAL OUTCOME USING PHYSOSTIGMINE - A retrospective study was performed that examined the administration of physostigmine, following Datura stramonium poisoning, and its effect on ICU admissions and length of hospital stays. Seventeen patients, who presented with anticholinergic toxicity following ingestion of D. stramonium seeds, were included in the study. Physostigmine and benzodiazepines were administered to 3 of the 17 patients and benzodiazepines, as sole therapy, were administered to 14 of the 17 patients. The 3 patients in the physostigmine group required the ICU and 79% of the benzodiazepines only group also required the ICU, indicating that the use of physostigmine did not result in significantly decreased intensive care use. The average length of hospital stay was also not significantly different between the two groups. The average length of stay for the physostigmine group was 42 hours and the average length of stay for the benzodiazepines only group was 28 hours (p = 0.45). However, because of the small sample size and the lack of randomization within the study, further investigation is warranted (Salen et al, 2003).
6) CLINICAL OUTCOME IN CHILDREN NOT RECEIVING PHYSOSTIGMINE - In a retrospective study conducted from 1998 to 2003 in Turkey, the clinical outcome of 23 children (ages 2 to 10 years) with hyoscyamus niger intoxication and typical atropine toxicity were reviewed. Each patient received gastric lavage and activated charcoal. Patients with agitation/seizures were treated with diazepam. Most patients (n=16) were discharged within one day, and no child required intubation or developed permanent sequelae. The authors reported that hyoscyamus niger symptoms were self-terminating in most cases, and supportive care was successful without the use of physostigmine (Note: physostigmine is unavailable in Turkey) (Doneray et al, 2007).

B) MONITORING OF PATIENT

1) Monitor vital signs (including temperature) and mental status.
2) Most plant products that cause severe symptoms are detected by thin layer chromatography, but this is rarely useful in guiding management.
3) No specific lab work is needed in most patients.
4) Monitor creatinine phosphokinase in patients with prolonged agitation, seizures or coma.
5) Monitor renal function and urine output in patients with rhabdomyolysis.
6) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity (i.e., agitation, delirium, seizures, coma, hypotension).

C) TACHYARRHYTHMIA

1) Sinus tachydysrhythmias do NOT need to be routinely treated unless the patient demonstrates signs/symptoms of hemodynamic instability. Sedating agitated patients with benzodiazepines may diminish tachycardia. Severe tachydysrhythmias may respond to physostigmine or IV beta-blockers (short-acting titratable agents preferred).

D) VENTRICULAR ARRHYTHMIA

1) QRS widening or ventricular tachycardia may respond to sodium bicarbonate. A reasonable starting dose is 1 to 2 mEq/kg IV bolus. Repeat as needed; endpoints include cessation of dysrhythmias, normalization of QRS complexes and a blood pH of 7.45 to 7.55. Monitor ECG continuously and monitor serum electrolytes and venous blood gases.
2) Consider lidocaine if sodium bicarbonate is not successful.
3) LIDOCAINE/DOSE

a) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.

1) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).

b) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

4) LIDOCAINE/MAJOR ADVERSE REACTIONS

a) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

5) LIDOCAINE/MONITORING PARAMETERS

a) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

6) Severe dysrhythmias may respond to physostigmine.

E) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

F) DELIRIUM

1) SEDATION - Sedation with benzodiazepines may control tachycardia associated with agitation and hallucinations.
2) TACHYCARDIA SUMMARY

a) Evaluate patient to be sure that tachycardia is not a physiologic response to dehydration, anemia, hypotension, fever, sepsis, or hypoxia. Sinus tachycardia does not generally require treatment unless hemodynamic compromise develops.
b) If therapy is required, a short acting, cardioselective agent such as esmolol is generally preferred (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
c) ESMOLOL/ADULT LOADING DOSE

1) Infuse 500 micrograms/kilogram (0.5 mg/kg) IV over 1 minute (Neumar et al, 2010).

d) ESMOLOL/ADULT MAINTENANCE DOSE

1) Follow loading dose with infusion of 50 mcg/kg per minute (0.05 mg/kg per minute) (Neumar et al, 2010).
2) EVALUATION OF RESPONSE: If response is inadequate, infuse second loading bolus of 0.5 mg/kg over 1 minute and increase the maintenance infusion to 100 mcg/kg (0.1 mg/kg) per minute. Reevaluate therapeutic effect, increase in the same manner if required to a maximum infusion rate of 300 mcg/kg (0.3 mg/kg) per minute (Neumar et al, 2010).
3) The manufacturer recommends that a maximum of 3 loading doses be used (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
4) END POINT OF THERAPY: As the desired heart rate or blood pressure is approached, omit loading dose and adjust maintenance infusion as required (Prod Info BREVIBLOC(TM) intravenous injection, 2012).

e) CAUTION

1) Esmolol is a short acting beta-adrenergic blocking agent with negative inotropic effects. Esmolol should be avoided in patients with asthma, obstructive airway disease, decompensated heart failure and pre-excited atrial fibrillation (wide complex irregular tachycardia) or atrial flutter (Neumar et al, 2010).

3) PHYSOSTIGMINE - If severe, physostigmine should be used as above (Klein-Schwartz & Oderda, 1984).

G) HYPERTENSIVE EPISODE

1) Monitor vital signs regularly. For mild/moderate hypertension without evidence of end organ damage, pharmacologic intervention is generally not necessary. Sedative agents such as benzodiazepines may be helpful in treating hypertension and tachycardia in agitated patients, especially if a sympathomimetic agent is involved in the poisoning.
2) For hypertensive emergencies (severe hypertension with evidence of end organ injury (CNS, cardiac, renal), or emergent need to lower mean arterial pressure 20% to 25% within one hour), sodium nitroprusside is preferred. Nitroglycerin and phentolamine are possible alternatives.
3) SODIUM NITROPRUSSIDE/INDICATIONS

a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.

4) SODIUM NITROPRUSSIDE/DOSE

a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).

5) SODIUM NITROPRUSSIDE/SOLUTION PREPARATION

a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

6) SODIUM NITROPRUSSIDE/MAJOR ADVERSE REACTIONS

a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

7) SODIUM NITROPRUSSIDE/MONITORING PARAMETERS

a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

8) NITROGLYCERIN/INDICATIONS

a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).

9) NITROGLYCERIN/ADULT DOSE

a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).

10) NITROGLYCERIN/PEDIATRIC DOSE

a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).

H) BODY TEMPERATURE ABOVE REFERENCE RANGE

1) Hyperthermia should be managed with external cooling and sedation with benzodiazepines. Avoid phenothiazines.

I) RHABDOMYOLYSIS

1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
6) MANNITOL/INDICATIONS

a) Osmotic diuretic used in the management of rhabdomyolysis and myoglobinuria (Zimmerman & Shen, 2013).

7) RHABDOMYOLYSIS/MYOGLOBINURIA

a) ADULT: TEST DOSE: (for patients with marked oliguria or those with inadequate renal function) 0.2 g/kg IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase within 2 to 3 hours. The patient should be reevaluated if there is inadequate response following the second test dose (Prod Info MANNITOL intravenous injection, 2009). TREATMENT DOSE: 50 to 100 g IV as a 15% to 25% solution may be used. The rate should be adjusted to maintain urinary output at 30 to 50 mL/hour (Prod Info mannitol IV injection, urologic irrigation, 2006) OR 300 to 400 mg/kg or up to 100 g IV administered as a single dose (Prod Info MANNITOL intravenous injection, 2009).
b) PEDIATRIC: Dosing has not been established in patients less than 12 years of age(Prod Info Mannitol intravenous injection, 2009). TEST DOSE (for patients with marked oliguria or those with inadequate renal function): 0.2 g/kg or 6 g/m(2) body surface area IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase; TREATMENT DOSE: 0.25 to 2 g/kg or 60 g/m(2) body surface area IV as a 15% to 20% solution over 2 to 6 hours; do not repeat dose for persistent oliguria (Prod Info MANNITOL intravenous injection, 2009).

8) ADVERSE EFFECTS

a) Fluid and electrolyte imbalance, in particular sodium and potassium; expansion of the extracellular fluid volume leading to pulmonary edema or CHF exacerbations(Prod Info MANNITOL intravenous injection, 2009).

9) PRECAUTION

a) Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia; do not add to whole blood for transfusions(Prod Info Mannitol intravenous injection, 2009); enhanced neuromuscular blockade observed with tubocurarine(Miller et al, 1976).

10) MONITORING PARAMETERS

a) Renal function, urine output, fluid balance, serum potassium, serum sodium, and serum osmolality (Prod Info Mannitol intravenous injection, 2009).

J) EXPERIMENTAL THERAPY

1) TACRINE - There is one case report describing the use of tacrine hydrochloride, 30 milligrams intravenously, to reverse central anticholinergic effects in a 15-year-old male after ingestion of a Datura/cola mixture (Francis & Clarke, 1999). Experience with this antidote for anticholinergic poisoning is limited.
2) DONEPEZIL - Donepezil administration was successful in resolving severe agitation and progressive delirium and coma in a 53-year-old male following an intentional ingestion of 1 gram of amitriptyline, an anticholinergic agent. Because physostigmine was not available, donepezil was given as an alternative acetylcholinesterase inhibitor. Although donepezil has a longer half life than physostigmine in cerebral tissue, the clinical efficacy of donepezil for the treatment of delirium due to an anticholinergic overdose, needs further investigation (Noyan et al, 2003).

Enhanced Elimination

A)

1) Hemodialysis and hemoperfusion are of no value in this setting because of the large volume of distribution.

Abstracts

Case Reports

A)

1) (HYOSCYAMUS NIGER): An adult couple arrived at the emergency room 2.5 hours after having ingested a meal containing a "parsnip" from their garden. The "parsnip" was identified as a root of Hyoscyamus niger (Henbane). They were experiencing symptoms of dry mouth, dilated pupils, thirst, purposeless movements (picking at air), intermittent mental confusion and delirium, hallucinations, and warm, flushed skin. The heart rate was 120 beats/minute, and the blood pressures were 148/102 and 162/90 mmHg. One patient had vomited spontaneously prior to admission. ECG showed sinus tachycardia. The patients were treated symptomatically, with gradual slowing of the heat rate, and regaining normal sensorium within 11 hours. The patients were discharged with only mild headaches about 25 hours postingestion (Spoerke, 1987).
2) CHRONIC DATURA ABUSE

a) A 32-year-old man, living in a rural area of Jharkhand, India, with undiagnosed paranoid schizophrenia was brought to an outpatient clinic by his father due to long-term (6 years) aggressive behavior. The patient had been ingesting Datura seeds on a regular basis for the past 3 years, usually ingesting 3 to 4 seeds throughout the day with a maximum intake of 6 seeds daily. He reported taking the seeds to reach an altered state of consciousness which he reported helped him to relieve his poor feelings of himself. Ten days prior to presentation, the patient had not ingested any datura seeds. He showed no signs of withdrawal or toxicity. His physical and laboratory examinations were normal. A mental status examination showed preserved affect, delusion of control, delusion of persecution and delusion of reference. He had evidence of poor judgment and insight and was diagnosed with paranoid schizophrenia. He was started on antipsychotic (haloperidol) therapy with clinical improvement of his psychotic symptoms (Khanra et al, 2015).

Range Of Toxicity

Summary

A)

Minimum Lethal Exposure

A)

1) CASE REPORTS

a) DATURA STRAMONIUM (JIMSON WEED)

1) A 2-year-old died after ingesting 100 seeds of Datura stramonium (Brundage, 1929).
2) Two fatalities from consumption of an unspecified amount of tea brewed from D. stramonium roots have been reported (CDC, 1995). Ethanol had also been consumed by these adolescents, aged 16 and 17 years. A postmortem blood level in one case detected atropine (55 ng/mL) and ethanol (0.03 g/dL), a blood alcohol level far below that considered to indicate intoxication. Two other adolescents who had consumed small amounts of the tea only experienced hallucinations.
3) A 12-year-old boy developed respiratory failure secondary to acute respiratory distress syndrome after ingesting Datura stramonium seeds, and died, 4 days later, from refractory hypoxemia (Thabet et al, 1999).

b) DATURA SUAVEOLENS

1) A 20-year-old woman, undergoing methadone therapy, became comatose 1 to 2 hours after ingesting a tea containing Angel's trumpet (Datura suaveolens). The patient also developed seizures, hyperthermia, hypotension, and ventricular tachycardia progressing to ventricular fibrillation. Despite aggressive supportive measures, the patient died approximately 4 hours after ingestion (Rauber-Luthy et al, 1999).

Maximum Tolerated Exposure

A)

1) The onset is rapid and the symptoms are easily recognizable.
2) ALKALOID CONTENT - Of plants will vary from year to year due to variation in factors that effect growth (i.e., available moisture, spring temperatures, etc.) making it difficult to associate symptoms with ingestion of a specific amount of plant material.
3) POTENTIAL SYMPTOMS BY AMOUNT OF ALKALOID INGESTED -

a) The figures below should be used as estimates for adults only, and are for the amount of alkaloid ingested, not amount of plant ingested (Schreiber, 1979).

ALKALOID AMOUNT (mg)	POTENTIAL SYMPTOM INITIATION
0.5	Dryness of mouth
0.75	Mydriasis
1.25	Flushing, Tachycardia, Tachypnea
4.0	Restlessness, ataxia
4.75	Xerostomia, Tachycardia over 130 bpm, Psychological Disturbances
9.0+	Coma, Seizures, Potential Death

4) Some species may have very high levels of alkaloids. As an example, Datura candida and Datura suaveolens flowers may have scopolamine content as high as 65 percent (Frohne & Pfander, 1984).
5) A wine made from D. Suaveolens contained 29 mg of scopolamine per milliliter (Smith et al, 1991).
6) The particular actions seem may vary by the part of the plant ingested and the time of year. As an example, the seeds and unripe fruit of Atropa belladonna contain primarily L-hyoscyamine, but the contents of the ripe fruits is almost entirely the racemic atropine which has only half the activity on the peripheral nervous system (Frohne & Pfander, 1984).

B)

1) DATURA STRAMONIUM (JIMSON WEED)

a) SEED INGESTION: Toxicity has been reported from a few seeds ingested by an adolescent (Guharoy & Barajas, 1991) and from 30 to 50 seeds ingested by individuals ranging in age from 14 to 21 years (CDC, 1995). Teenagers have developed moderate symptoms after ingesting 2 grams (described as 1 teaspoon) to 25 grams (described as one handful) of Jimson seed (Levy, 1977).
b) ONSET: The onset of symptoms has been reported as 30 to 105 minutes after ingestion, lasting 18 to 216 hours (Duke, 1985). In a young boy, symptoms (ie, hallucinations, slurred speech, abnormal gait) developed 48 hours after ingesting the seeds and flowers (amount unknown) of a Datura stramonium plant (Ozkaya et al, 2015).
c) CASE REPORTS

1) CASE REPORT (DATURA STRAMONUM)/LATE ONSET OF SYMPTOMS: A 5-year-old boy developed a sudden onset of difficulty speaking and a decreased level of consciousness due to the ingestion of Datura stramonium 2 days previously. Upon admission, he developed blurred vision, hallucinations and difficulty speaking (slurred speech) and walking. Diagnostic and laboratory studies were normal and a toxicology screen was negative. By the second day of admission, the child became more alert and was able to recognize his mother and his gait and speech normalized. Upon further questioning the mother stated that child had been playing in the yard and the child admitted to eating the seeds and the flowers of the Datura stramonium plant (brought to the hospital for identification). All symptoms resolved within 48 hours of admission with supportive care (Ozkaya et al, 2015).
2) HERBAL TEA INGESTION/PEDIATRICS: Agitation, disorientation and hallucinogenic delirium developed in a 5 year-old boy following the ingestion of an unknown amount of herbal tea containing datura stramonium (ie, the leaves and flowers). His physical exam and laboratory studies were essentially normal with bilateral mydriasis unreactive to light. The child was treated with diazepam for agitation. His vital signs remained stable. The following day his restlessness and delirium had improved. Bilateral mydriasis persisted until his time of discharge at 48 hours. His 4-year-old brother also drank the same tea (amount unknown) but developed lethargy and coma requiring airway management and mechanical ventilation. Both children recovered completely with no permanent sequelae (Rakotomavo et al, 2014).
3) SEEDS: Twelve hours after ingesting several Datura stramonium seeds, a 16-year-old was admitted to a hospital for visual hallucinations, agitation, nausea, mydriasis, tachycardia, tachypnea with mild respiratory distress, hypertension and elevated temperature. Supportive treatment, ipecac-induced vomiting (no particulates retrieved), IV fluids, and diazepam were given. Symptoms resolved except for mydriasis 24 hours after admission.
4) SEEDS: Symptoms developed in a 17-year-old 3 to 4 hours after ingesting an unknown quantity of seeds. Chief signs/symptoms included hypertension, tachypnea, tachycardia, mydriasis, cycloplegia, agitation, delusions, combativeness and amnesia. The patient's status returned to normal 36 hours after ingestion (Vanderhoff & Mosser, 1992).
5) HERBAL TEA INGESTION/TEENS: Unspecified amounts of tea produced toxicity in 6 persons, aged 15 to 17 years. Supportive treatment, physostigmine, and activated charcoal were administered to 4 individuals, with discharge the day after ingestion (CDC, 1995).
6) SMOKING, EXTRACT: The smoking of one cigarette which had an extract of D. stramonium from the boiled plant produced anticholinergic signs and symptoms in 3 males, aged 14 and 15 years (Guharoy & Barajas, 1991). Symptoms resolved 24 hours after hospitalization. The onset of symptoms was not reported.
7) EXTRACT, ORAL APPLICATION: Use of a D. stramonium extract-containing mouthrinse and toothpaste for the treatment of gingivitis resulted in symptoms within 2 hours, lasting approximately 24 hours (Pereira & Nishioka, 1994).

2) DATURA INNOXIA

a) CASE REPORTS

1) ROOT, INGESTION: An 82-year-old man developed symptoms 45 minutes after ingesting a nickel-sized root portion which had been mistaken for horseradish (Hanna et al, 1992).

3) DATURA SUAVEOLENS

a) OCULAR EXPOSURE: Unilateral mydriasis and blurred vision developed in an adult shortly after cutting a plant identified as D. suaveolens (Angels trumpet). No generalized anticholinergic signs or symptoms were reported. Mydriasis was reproduced within 15 minutes of application of 1 drop of the plant's juice to another human eye. Mydriasis lasted 6 days. No other effects were reported (Voltz et al, 1992).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) FATALITY

a) CASE REPORT (DATURA STRAMONIUM): The postmortem whole blood concentrations of hyoscyamine and scopolamine, in a 19-year-old man who died following ingestion of an unknown amount of Datura stramonium seeds, were 1.1 mcg/mL and 0.2 mcg/mL, respectively (Boumba et al, 2004).

2) SURVIVAL

a) CASE REPORT (MANDRAGORA OFFICINARUM): An adult developed symptoms of anticholinergic poisoning 4 hours after ingesting 5 mandragora officinarum berries. Hyoscyamine and scopolamine were detected at concentrations of 539.8 and 32.7 mcg/mL, respectively in the urine, which was collected shortly after admission. Tropane alkaloids were not detected in blood. No other toxic substances were detected. The berries were identified as Mandragora; analysis detected hyoscyamine and scopolamine at concentrations of 25.6 and 0.7 mcg/g, respectively. All symptoms resolved after the administration of physostigmine (Nikolaou et al, 2011).

Pharmacology Toxicology

Pharmacologic Mechanism

A)

B)

C)

Physicochemical

Animal Toxicology

Clinical Effects

11.1.2)

A) Symptoms include muscle tremors, nervousness, excitability, and sudden death. Rumen atony and anorexia often limit toxicity in cattle (Nelson et al, 1982).

11.1.4)

A) DATURA STRAMONIUM - Poisoning symptoms include intermittent hyperesthesia, tachypnea, reduced drinking, tremors, drowsiness, recombency, and changes in locomotion (El Dirdiri et al, 1981).

11.1.5)

A) A horse died of acute gastric dilatation and rupture following ingestion of feed contaminated with Datura species seeds (Schulman & Bolton, 1998).
B) A horse developed dry oral mucosa, bilateral mydriasis, and a paralytic ileus after ingesting a feed supplement contaminated with Datura species seeds. The horse, not responding to aggressive supportive treatment, was euthanased (Schulman & Bolton, 1998).

11.1.9)

A) DATURA STRAMONIUM - Poisoning symptoms include ataxia, inability to stand, tachypnea, reduced drinking, and trembling (El Dirdiri et al, 1981).

11.1.10)

A) TERATOGENICITY -

1) CONGENITAL ARTHROGRYPOSIS -

a) Congenital arthrogryposis was seen in 25 pigs farrowed in a lot that was surrounded on three sides by growths of Datura stramonium. The sows had some signs of intoxication during pregnancy, such as incoordination (Leipold et al, 1973).
b) Keeler (1981) tried to produce arthrogryposis in newborn hampshire pigs by feeding the mothers 1.2 g/kg or 1.7 g/kg. The doses were large enough to produce toxicity in the sows, but congenital arthrogryposis was not seen in the offspring.

Range Of Toxicity

11.3.2)

A) DATURA STRAMONIUM - JIMSON WEED

1) CATTLE

a) Cattle receiving 0.06 to 0.09% total body weight per day may become toxic. In an animal that weighs 450 kilograms, this is approximately 272 to 408 grams of seeds per day (Nelson et al, 1982).
b) Other studies indicated that 170 to 255 grams of Jimson weed seed per day did not produce toxicity (Nelson et al, 1982).
c) In one experiment, it was shown that cattle may show signs of toxicity at levels of 881 seeds/kg of feed (Nelson et al, 1982).

2) GOAT

a) Ingestion of the fruits or leaves at 2.5 or 10 grams per kilogram per day killed the animals within 136 days (El Dirdiri et al, 1981).

3) SWINE

a) Doses of 2.2 to 2.7 mg/kg/day of Jimson weed seed may produce toxic signs and symptoms (Nelson et al, 1982).

4) SHEEP

a) Ingestion of the fruits or leaves of Jimson weed at 10 grams per kilogram per day killed the animals within 38 days (El Dirdiri et al, 1981).

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FeedBack

PLANTS-ANTICHOLINERGIC

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Musculoskeletal

Endocrine

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Monitoring Parameters Levels

Methods

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Patient Disposition

Monitoring

Oral Exposure

Enhanced Elimination

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Pharmacologic Mechanism

Clinical Effects

Range Of Toxicity

General Bibliography