DESCRIPTION

This chapter covers plants that have anticholinergic properties when ingested in sufficient amounts; for certain species, this amount can be quite small.

FORMS AND USES

• Datura species (jimsonweed, devil's apple, thorn apple, stinkweed, loco seeds, locoweed, Jamestown weed) contain hyoscyamine, scopolamine, and atropine.
• Atropa belladonna (belladonna, deadly nightshade) contains hyoscyamine, hyoscine, and atropine.
• Hyoscyamus niger (henbane, black henbane) contains hyoscyamine, hyoscine, and atropine.
• Brugmansia species (angel's trumpet) have anticholinergic properties similar to those of Datura species.
• Lycium halimifolium (matrimony vine) contains atropine, scopolamine, and hyoscyamine.
• Cestrum nocturnum and C. diurnum (night-blooming jessamine and day-blooming jessamine) contain solanine and various anticholinergic alkaloids.
• Mandragora officinarum contains hyoscyamine, scopolamine, and mandragorine.
• Several other plant species also cause anticholinergic effects.

TOXIC DOSE

Toxicity is difficult to estimate because concentration of toxin varies by species, with additional variation within each species. A few seeds or leaves of jimsonweed are usually sufficient to cause anticholinergic effects.

PATHOPHYSIOLOGY

• Plant parts contain tropane alkaloids (hyoscyamine, hyoscine, scopolamine, mandragorine, and atropine).
• These are anticholinergic compounds that competitively block muscarinic acetylcholine receptors.

EPIDEMIOLOGY

• Poisoning is common.
• Mild to moderate toxicity is common following accidental pediatric ingestion.
• Abuse commonly occurs by ingestion of plant material, ingestion of tea brewed from the plant, or inhalation of smoked plant material; toxicity also may follow ingestion of herbal preparations containing the plants.
• Death is rare and usually due to trauma sustained during delirium.

CAUSES

• Pediatric exposures are usually accidental.
• Exposures in teenagers and adults usually involve abuse or ingestion of herbal preparations.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES

DIFFERENTIAL DIAGNOSIS

• Toxic causes of anticholinergic effects include atropine, some mushrooms, and antihistamines. Due to pupillary dilation and tachycardia, sympathomimetic plants (e.g., ephedra) also may be confused with anticholinergic toxicity.
• Other drugs or conditions that produce hallucinations and delirium may be confused initially with anticholinergic syndrome (e.g., LSD, mescaline, peyote, phencyclidine).

SIGNS AND SYMPTOMS

• Anticholinergic compounds usually produce prompt onset of anticholinergic signs combined with delirium and hallucinations.
• Liquid preparations such as teas or herbal extracts often produce more acute onset and severe effects.
• Ingestion of plant parts may allow delay before toxicity develops.

VITAL SIGNS

Hyperthermia, tachycardia, and hypertension are common.

HEENT

• Dry mucous membranes, pupil dilation, and blurred vision are common.
• Isolated pupil dilation may occur following accidental contact secondary to rubbing eyes after handling an anticholinergic plant.

Dermatologic

Skin is commonly warm, dry, and flushed.

Cardiovascular

Tachycardia and hypertension are common.

Pulmonary

Smoke from burning of anticholinergic plants can cause respiratory irritation as well as systemic anticholinergic toxicity.

Gastrointestinal

Anticholinergic toxicity typically produces decreased gastrointestinal motility and bowel sounds; however, plants also may contain toxins that cause vomiting and diarrhea.

Renal

Acute renal injury may occur with rhabdomyolysis.

Fluids and Electrolytes

Dehydration is common secondary to increased insensible losses and decreased oral fluid intake caused by delirium.

Musculoskeletal

Agitation can produce rhabdomyolysis.

Neurologic

• Agitation, altered mental status, delirium, and hallucinations are common.
• Seizures occur infrequently.

PROCEDURES AND LABORATORY TESTS

Essential Tests

There are no essential tests for minimally symptomatic patients.

Recommended Tests

• Serum electrolytes, BUN, and creatinine are used to assess dehydration or kidney injury from rhabdomyolysis.
• Serum creatine kinase becomes elevated if rhabdomyolysis occurs.
• ECG should be monitored for patients with marked tachycardia; sinus tachycardia is common.
• Urinalysis should be performed to detect dehydration and myoglobin (positive dipstick for blood, but no red blood cells on microscopic analysis).

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
• VITAL SIGNS
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on control of agitation and protecting the patient from self-harm.
• Dose and time of exposure should be determined for all substances involved.
• Physostigmine may be helpful in ruling out other causes of altered mental status.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• Seizure or other severe effects develop.
• Use of physostigmine is considered.
• Toxic effects are not consistent with anticholinergic toxicity.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Undesired effects develop (hallucinations, blurred vision, seizure).
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted if patient is in need of observation for agitation, delirium, or dysrhythmia, or if sedation is needed.

DECONTAMINATION

Out of Hospital

Emesis should be induced with ipecac within 1 hour of ingestion for alert pediatric or adult patients, especially if plant parts are involved.

In Hospital

• Emesis should be induced with ipecac within 1 hour of ingestion for alert patients who have ingested plant parts.
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present; lavage may be reasonable even several hours after ingestion due to gastrointestinal slowing.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred; one repeat dose of activated charcoal may be helpful 4 to 6 hours following the first dose if a patient continues to exhibit signs of anticholinergic toxicity.
• Skin and mucous membranes should be washed copiously with water following mucous membrane or dermal exposure.

ANTIDOTES

Physostigmine is a specific antagonist to anticholinergic effects; however, it is used only to diagnose anticholinergic toxicity.

Indications

• Physostigmine is a diagnostic agent to distinguish altered mental status due to anticholinergic toxicity from other causes of agitation and hallucination.
• A positive response to a physostigmine test (clearing of delusion or hallucination) indicates an anticholinergic effect. Head CT and lumbar puncture may become unnecessary because the cause of altered mental status is known.

Contraindications

• A known allergy to a cholinergic agonist or to sulfites precludes the use of physostigmine.
• A tricyclic antidepressant overdose, or ECG findings suggestive of such an overdose (QRS widening, R-wave in ECG lead aVR), contraindicates use of physostigmine.
• Patients with a history of asthma, heart disease, diabetes, seizure disorder, or inflammation of the iris or ciliary body should not receive physostigmine.

Method of Administration

• Clinician should place the patient on a cardiac monitor and have atropine available at the bedside.
• Physostigmine should be given by slow intravenous push over 5 minutes.
  • Adult dose is 0.5 to 2.0 mg.
  • Pediatric dose is 0.02 mg/kg, up to 2.0 mg.
  • Dose may be repeated once after 10 minutes if needed.
• Physostigmine effect typically wanes after 30 minutes.

Potential Adverse Effects

• Adverse effects are more common with larger doses and faster rates of administration.
• Muscarinic effects include vomiting, diarrhea, sweating, bronchorrhea, bradycardia, and hypotension; cardiac dysrhythmia may occur.
• Nicotinic effects (weakness, fasciculation) also may occur.
• Seizures occur rarely.

ADJUNCTIVE TREATMENT

Agitation or Hallucinosis

A benzodiazepine with which the provider has experience should be administered. Airway must be monitored closely.

Diazepam

• Adult dose is 5 to 10 mg intravenously.
• Pediatric dose is 0.2 to 0.5 mg/kg intravenously.
• Dose may be repeated at 10-minute intervals and titrated to effect.

Lorazepam

• Adult dose is 1 to 2 mg intravenously.
• Pediatric dose is 0.05 mg/kg intravenously.
• Dose may be repeated at 10-minute intervals and titrated to effect.

Seizure

• A patent airway must be assured.
• A benzodiazepine should be administered for initial control (see SECTION II, Seizures chapter, for further details).
• If seizures persist or recur, another anticonvulsant such as phenobarbital can be added.

Dysrhythmias or Conduction Abnormalities

Standard advanced cardiac life support guidelines should be followed.

Not Recommended Therapies

Physostigmine should not be used once the diagnosis is apparent.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • Indications
  • Contraindications
  • Method of Administration
  • Potential Adverse Effects
• ADJUNCTIVE TREATMENT
  • Agitation or Hallucinosis
  • Seizure
  • Dysrhythmias or Conduction Abnormalities
  • Not Recommended Therapies

PATIENT MONITORING

Vital signs, mental status, and volume status should be monitored until effects resolve.

EXPECTED COURSE AND PROGNOSIS

• Anticholinergic effects often persist for 24 to 48 hours and can last even longer following large exposure and if there is persistent gastrointestinal absorption.
• Hyperthermia and rhabdomyolysis can result from agitation that is improperly controlled (i.e., by the use of physical restraints alone).

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Asymptomatic patients may be discharged following decontamination and 4 to 6 hours of observation after the last dose of benzodiazepine; psychiatric evaluation should be obtained if needed.
• From the hospital. Patients may be discharged after resolution of toxic effects and psychiatric evaluation, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

DIAGNOSIS

• Minor partial improvement in mental status should not be attributed to physostigmine.
  • The beneficial effect of physostigmine is usually obvious.
  • Minor improvement may indicate that the patient has a component of anticholinergic toxicity, but life-threatening causes must be ruled out.
• Time should not be wasted attempting to identify the plant; instead, the patient should be treated symptomatically.

TREATMENT

• Physostigmine should not be used when the ECG suggests type 1a antidysrhythmic toxicity (widening of QRS or QTc, or R wave in lead aVR).
• It is important to maintain urinary output at 1 to 2 cc/kg/h; patients are usually dehydrated and may have rhabdomyolysis.

Section Outline:

• DIAGNOSIS
• TREATMENT

Poisoning by drugs primarily affecting the autonomic nervous system: parasympatholytics (anticholinergics and antimuscarinics) and spasmolytics.

See Also: SECTION II, Seizures; and SECTION III, Physostigmine chapter.

RECOMMENDED READING

Centers for Disease Control. Jimson weed poisoning: Texas, New York, and California, 1994. MMWR 1995;44:41-44.

Chan TYK. Anticholinergic poisoning due to Chinese herbal medicines. Vet Hum Toxicol 1995;37:156-157.

Author: Edwin K. Kuffner

Reviewer: Richard C. Dart