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DESCRIPTION
- A wide variety of prescription and over-the-counter medications produce anticholinergic toxicity.
- The diagnosis is established based on physical signs; however, duration of effect is influenced by the half-life of the drug.
FORMS AND USES
Some anticholinergic medications include oxyphenomium (Antrenyl), benztropine (Cogentin), biperiden (Akineton), orphenadrine (Disipal, Marflex, Norflex), trihexyphenidyl, anisotropine (Valpin), butylscopolamine (Buscapina, Buscopan), clidinium (Librax, Quarzan), dicyclomine (Bentyl), glycopyrrolate (Robinul), isopropa-mide (Darbid), mepenzolate (Cantil), methantheline (Banthine), oxyphencyclimine (Daricon), propantheline (Pro-Banthine), trospium (Spasmex), flavoxate (Urispas), oxybutynin (Ditropan), cyclopentolate (Cyclogel), homatropine, tropicamide (Mydriacyl), belladonnna, atropine, l-hyoscyamine, Bellafoline, scopolamine, hyoscine, ipratropium (Atrovent), and diphenidol (Vontrol).
TOXIC DOSE
Toxicity may develop if more than three to four times the maximum daily dose is exceeded for an anticholinergic compound.
PATHOPHYSIOLOGY
Each compound competitively antagonizes acetylcholine, primarily at the muscarinic acetylcholine receptor.
EPIDEMIOLOGY
- Poisoning is common.
- Toxic effects are mild following accidental pediatric ingestion, but severe effects may develop following misuse or abuse.
- Death is rare and is usually attributable to trauma sustained during delirium.
CAUSES
- Ingestion by toddlers is usually accidental.
- Adolescent and adult cases usually involve misuse or abuse.
- Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.
PREGNANCY AND LACTATION
- Dicyclomine and glycopyrrolate. US FDA Pregnancy Category B. Animal studies indicate no fetal risk and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in pregnant women do not.
- Most anticholinergic drugs. US FDA Pregnancy Category C. Studies have shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
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DIFFERENTIAL DIAGNOSIS
Toxicologic causes include sympathomimetic agents; the presentation may be similar (tachycardia, mydriasis, and delirium), but sympathomimetic agents usually cause perspiration and bowel sounds are usually present.
SIGNS AND SYMPTOMS
- A large ingestion can result in florid anticholinergic syndrome: tachycardia, dilated pupils, a flushed appearance, decreased bowel sounds, urinary retention, and, occasionally, seizures.
- A patient may not exhibit all of the signs and symptoms of anticholinergic toxicity; it is common for patients to exhibit varying degrees of anticholinergic syndrome and for signs to fluctuate over time.
Vital Signs
- Sinus tachycardia is common; in its absence, the diagnosis of anticholinergic toxicity should be questioned.
- Mild hyperthermia is common.
HEENT
- Dry mucous membranes and mydriasis are common; mydriasis often produces blurred vision.
- Unilateral mydriasis and anisocoria have occurred after instillation of an ophthalmic cycloplegic agent or other anticholinergic drug into one eye.
- Ophthalmic administration of an anticholinergic agent can produce systemic anticholinergic toxicity.
Dermatologic
Warm, dry, and flushed skin is common.
Cardiovascular
Dysrhythmias have been reported, but are rare.
Gastrointestinal
Ileus and decreased bowel sounds are common.
Fluids and Electrolytes
Dehydration is common.
Musculoskeletal
Psychomotor agitation can produce rhabdomyolysis.
Neurologic
- Agitation with altered mental status is common; seizures may occur.
- Toxic psychosis with anxiety, paranoia, and hallucinations is well reported.
- CNS depression with drowsiness and lethargy progressing to coma is less common.
- Dystonic reactions and movement disorders have been reported.
Genitourinary/Renal
Urinary retention is common.
PROCEDURES AND LABORATORY TESTS
Essential Tests
Minimally symptomatic patients may not require laboratory testing.
Recommended Tests
- Serum electrolytes, BUN, and creatinine are measured to assess dehydration and potential renal injury from myoglobin.
- Creatine kinase may be elevated if rhabdomyolysis occurs.
- Urinalysis is ordered to assess dehydration or myoglobin-induced renal injury.
- ECG, serum acetaminophen, and aspirin levels are used to detect occult overdose.
- Sinus tachycardia is common.
- Malignant dysrhythmia is rare.
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- In the agitated patient, treatment focuses on control of agitation and protection from self-harm.
- In the patient with CNS depression, treatment focuses on airway management.
- The dose and time of exposure must be determined for all substances involved.
DIRECTING PATIENT COURSE
The health-care professional should call the poison control center when:
- Seizure, hyperthermia, rhabdomyolysis, or other severe effects are present.
- The use of physostigmine is considered.
- Toxic effects are not consistent with anticholinergic toxicity.
- A 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.
- Toxic effects develop.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
Admission Considerations
Inpatient management is warranted for patients in need of observation for persistent agitation, altered mental status, seizure, hyperthermia, or continued sedation.
DECONTAMINATION
Out of Hospital
Ipecac should be administered to induce emesis within 1 hour of ingestion for the alert patient who is too small to have effective gastric lavage.
In Hospital
- Ipecac should be administered to induce emesis within 1 hour of ingestion for the alert patient who is too small to have effective gastric lavage.
- Aspiration of gastric contents through a nasogastric tube may be helpful shortly after ingestion of a liquid preparation.
- Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestions presenting within 1 hour of ingestion or if serious effects are present; lavage may be reasonable even 4 to 6 hours after ingestion due to gastrointestinal slowing.
- One dose of activated charcoal (1-2 g/kg) is 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 due to slowed absorption.
ANTIDOTES
Physostigmine is an antidote used for the diagnosis of anticholinergic poisoning.
Indications
- Physostigmine is a diagnostic agent that distinguishes altered mental status due to anticholinergic toxicity from other causes of agitation and hallucination.
- Positive response to test may avoid CT and lumbar puncture for evaluation of altered mental status.
Contraindications
- Known allergy to cholinergic agonist or sulfites
- Overdose of tricyclic antidepressant, or ECG findings suggestive of it (QRS widening, R wave in the ECG lead aVR)
- History of asthma, heart disease, diabetes, seizure disorder, or inflammation of iris or ciliary body
Method of Administration
- Patient is connected to a cardiac monitor, and atropine is available at the bedside.
- Physostigmine is administered by slow intravenous push over 5 minutes; adults, 0.5 to 2.0 mg; pediatric, 0.02 mg/kg up to 2.0 mg; it may be repeated once after 5 to 10 minutes if the patient's mental status does not improve.
Potential Adverse Effects
- These are more common with larger doses and faster rates of administration.
- Muscarinic effects include nausea, vomiting, diarrhea, sweating, bronchorrhea, bradycardia, and hypotension; cardiac dysrhythmia may occur.
- Nicotinic effects (weakness, fasciculation) also may occur.
- Seizures may occur.
ADJUNCTIVE TREATMENT
Agitation or Hallucinosis
- A benzodiazepine with which the provider has experience is administered.
- Diazepam. Adult dose is 5 to 10 mg intravenously; pediatric dose is 0.2 to 0.5 mg/kg intravenously; dose is repeated at 10-minute intervals, titrating to effect
- Lorazepam is an alternative. Adult dose is 1 to 2 mg intravenously; pediatric dose is 0.05 mg/kg, repeated at 10-minute intervals, and titrated to effect; the airway should be monitored closely.
- Repeated doses of physostigmine are not recommended for behavior control, because although physostigmine reverses behavioral effects, the symptoms usually recur within 30 to 60 minutes.
Seizure
- A patent airway must be ensured.
- A benzodiazepine is administered for initial control. If seizures persist or recur, another anticonvulsant such as phenobarbital may be added.
Dysrhythmias or Conduction Abnormalities
- Standard ACLS guidelines for control of dysrhythmia should be followed.
- Seizures are to be controlled and acidemia corrected.
- If QRS widening or dysrhythmia persists, sodium bicarbonate is administered, 1 to 2 mEq/kg as an intravenous bolus, repeated as needed for widened QRS; the pH should not exceed 7.55.
Not Recommended Therapies
Physostigmine should not be used when the diagnosis of anticholinergic toxicity is already apparent.
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PATIENT MONITORING
Vital signs, mental status, and fluid volume status should be followed until effects resolve.
EXPECTED COURSE AND PROGNOSIS
- Anticholinergic effects often persist for 24 to 48 hours; longer following a large exposure or continued gastrointestinal absorption due to anticholinergic effects.
- Hyperthermia and rhabdomyolysis can result from agitation that is improperly controlled, especially by the sole use of physical restraints.
DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department. Patients who have not developed altered mental status, seizures, or dysrhythmia during 6 to 12 hours of observation (4 to 6 hours of observation following last dose of benzodiazapine) may be discharged following gastrointestinal decontamination and psychiatric evaluation, if needed.
- From the hospital. The patient may be discharged after resolution of toxic effects and psychiatric evaluation, if needed.
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DIAGNOSIS
- The health-care provider should consider other causes of altered mental status.
- A minor improvement in mental status should not be attributed to physostigmine; the beneficial effect of physostigmine is usually obvious.
TREATMENT
The health-care professional should not use physostigmine as a therapeutic agent instead of diagnostic agent or when the ECG suggests type 1a antidysrhythmic toxicity (e.g., tricyclic antidepressants).
Section Outline:
ICD-9-CM 971.1Poisoning by drugs primarily affecting the autonomic nervous system: parasympatholytics (anticholinergics and antimuscarinics) and spasmolytics.
See Also: SECTION II, Seizures; SECTION III, Physostigmine chapter; and SECTION IV, Plants—Anticholinergic, Antihistamines—Nonsedating, Antihistamines—Over-the-Counter, Phenothiazines, and Antidepressants—Tricyclic chapters.
RECOMMENDED READING
Ellenhorn MJ. Antimuscarinic drugs. In: Ellen-horn's medical toxicology, 2nd ed. Baltimore: Williams & Wilkins, 1997:840-861.
Author: Edwin K. Kuffner
Reviewer: Richard C. Dart