DESCRIPTION

A syndrome of tachycardia, mydriasis, dry mucous membranes, decreased bowel sounds, urinary retention, hallucinations and warm, dry, and flushed skin caused by a blockade of the acetylcholine receptors.

PATHOPHYSIOLOGY

• Anticholinergic compounds competitively block acetylcholine at the postsynaptic muscarinic acetylcholine receptor. The result is decreased stimulation of the muscarinic acetylcholine receptor.
• Anticholinergic compounds do not have an effect on the postsynaptic nicotinic acetylcholine receptor.

Section Outline:

• DESCRIPTION
• PATHOPHYSIOLOGY

• Numerous agents antagonize the effects of acetylcholine at the postsynaptic muscarinic receptor; therefore, medication and occupational histories are important in determining the cause of this syndrome.
• Most patients will not exhibit all the classic anticholinergic symptoms simultaneously. Some agents may produce more subtle clinical syndromes in which some signs or symptoms are more prominent than others.
• Antimuscarinic effects may be remembered as "mad as a hatter" (altered mental status, hallucinations), "hot as hell" (hyperthermia), "dry as a bone" (dry mucous membranes), "blind as a bat" (mydriasis, blurred vision), "red as a beet" (flushed skin), and "seizing like a squirrel" (seizures).

DIFFERENTIAL DIAGNOSIS

Further information on each poison is available in SECTION IV, CHEMICAL AND BIOLOGICAL AGENTS.

Toxicologic Causes

• Antihistamines (most commonly diphenhydramine)
• Phenothiazines
• Anticholinergic plants
• Cyclic antidepressants
• Antispasmodic agents (clidinium, dicyclomine, flavoxate, hyoscine, oxybutynin, propantheline, scopolamine)
• Mucous membrane drying agents (glycopyrrolate)
• Mydriatic agents (atropine, cyclopentolate, homatropine, tropicamide)
• Bronchodilator agents (ipratropium)
• Skeletal muscle relaxants (cyclobenzaprine, orphenadrine)
• Anti-parkinsonian medications (benztropine, biperiden)

Other Compounds that Produce Similar Clinical Effects

• Sympathomimetic amines may produce tachycardia, dry mucous membranes, mydriasis, hyperthermia, delirium, and seizures. They generally cause diaphoresis, and bowel sounds are usually present.
• Hallucinogenic drugs or mushrooms may cause delirium and mydriasis.

SIGNS AND SYMPTOMS

Vital Signs

• Tachycardia is common due to the antimuscarinic blockade of the vagus nerve. Its absence should question the diagnosis of anticholinergic toxicity.
• Hyperthermia is usually mild unless environmental factors exacerbate the effect.
• Hypertension and tachypnea may be caused by psychomotor agitation.

HEENT

• Mydriasis and dry mucous membranes are common. Blurred vision occurs as a result of mydriasis.
• Isolated mydriasis and anisocoria have occurred after instillation of an ophthalmic mydriatic or other anticholinergic agent into one eye.
• Ophthalmic instillation can produce systemic anticholinergic toxicity.

Dermatologic

• Warm, dry, and flushed skin is common.
• Dry axillae in an agitated patient with psychomotor agitation suggests anticholinergic effects or severe dehydration.

Cardiovascular

• Tachycardia is common due to antimuscarinic effects that block vagal stimulation of the sinoatrial node.
• Hypertension may be related to psychomotor agitation.
• Hypotension can occur following seizures and may be associated with hypovolemia. Life-threatening dysrhythmias are rare.

Pulmonary

Bronchodilation may occur as a result of therapeutic use of antimuscarinic agents but is not a reliable marker of toxicity.

Gastrointestinal

• Ileus and decreased bowel sounds are common.
• Constipation is a common side effect of medications with anticholinergic effects.

Musculoskeletal

Psychomotor agitation may produce rhabdomyolysis.

Neurologic

• Agitation with altered mental status is common. Toxic psychosis with anxiety, paranoia, and hallucinations is well documented.
• CNS depression with drowsiness and lethargy progressing to coma is less common.
• Seizures may occur.
• Dystonic reactions and movement disorders also have been reported.

Genitourinary

Urinary retention with bladder distension is common.

Psychiatric/Psychological

Toxic psychosis with hallucinations is well documented.

PROCEDURES AND LABORATORY TESTS

Essential Tests

Testing may not be needed in minimally symptomatic patients.

Recommended Tests

• Serum electrolytes, BUN, creatinine to assess dehydration and potential renal injury from myoglobin.
• Creatine kinase may be elevated if rhabdomyolysis occurs.
• Urinalysis to assess dehydration or myoglobin-induced renal injury.
• ECG, serum acetaminophen and aspirin levels, urine toxicology screen to detect occult overdose. Sinus tachycardia is common. Malignant dysrhythmia is rare.
• Lumbar puncture, bacterial cultures, head CT, and other tests as indicated to assess altered mental status of unknown etiology.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
  • Toxicologic Causes
  • Other Compounds that Produce Similar Clinical Effects
• SIGNS AND SYMPTOMS
  • Vital Signs
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• In the agitated patient, focus treatment on control of agitation and protection from self-harm. In the patient with CNS depression, focus treatment on airway management.
• Supportive care should be provided while evaluating source of poisoning.
• Dosage and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

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

• the source of anticholinergic effects is unclear.
• coingestant, drug interaction, or underlying disease presents an unusual problem.

DECONTAMINATION

Out of Hospital

Ipecac should be administered to induce emesis within 1 hour of ingestion for an alert pediatric or adult patient if health-care evaluation will be delayed.

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.
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion 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 the gastrointestinal slowing effects of anticholinergic agents.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
• Irrigate eyes, skin, and mucous membranes with copious amounts of water following exposure to those areas.

ANTIDOTES

Antidotes should be administered for altered mental status: oxygen, thiamine, glucose, and naloxone.

Physostigmine

Physostigmine may be administered as a diagnostic agent to distinguish altered mental status due to anticholinergic toxicity from other causes of agitation and hallucination. A positive response to this test may obviate the need for a head CT and lumbar puncture for evaluation of altered mental status.

Contraindications

• Known allergy to cholinergic agonist or sulfites
• Tricyclic antidepressant overdose, or ECG findings suggestive of tricyclic antidepressant overdose (QRS widening, R wave in ECG lead aVR)
• History of asthma, heart disease, diabetes, seizure disorder, inflammation of iris or ciliary body

Method of Administration

• Place the patient on a cardiac monitor and have atropine available at the bedside.
• Adult dose is 0.5 to 2.0 mg slow push intravenously over 5 minutes. Repeat dose intravenously once after 5 to 10 minutes if needed.
• Pediatric dose is 0.02 mg/kg up to 2.0 mg slow push intravenously over 5 minutes. Repeat dose intravenously once after 5 to 10 minutes if needed.

Potential Adverse Effects

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

ADJUNCTIVE TREATMENT

• Treat psychomotor agitation with benzodiazepines. Tachycardia and hyperthermia may improve with both benzodiazepines and intravenous hydration.
• Support blood pressure and perfusion as clinically indicated.
• Hypertension usually resolves with sedation and rarely requires specific treatment.

Section Outline:

• DIRECTING PATIENT COURSE
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • Physostigmine
• ADJUNCTIVE TREATMENT

• The onset of anticholinergic syndrome is often gradual and may be delayed due to decreased gastrointestinal motility.
• The effects usually resolve over a period of 24 to 36 hours but may persist for days following large ingestions.

• The administration of physostigmine to patients with known exposure to an anticholinergic agent and presentation consistent with anticholinergic toxicity is not useful because the diagnosis is already known.
• The administration of repeat doses of physostigmine to control psychomotor agitation increases the likelihood of an adverse effect. Benzodiazepines are the preferred agents.

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

See Also: SECTION II, Hypertension, Hypotension, and Tachycardia chapters; SECTION III, Physostigmine chapter; and SECTION IV, Anticholinergic Compounds and Plants—Anticholinergic chapters.

RECOMMENDED READING

Ellenhorn MJ. Antimuscarinic drugs. In: Medical toxicology: diagnosis and treatment of human poisoning. Baltimore: Williams & Wilkins, 1997:840-861.

Author: Edwin K. Kuffner

Reviewer: Richard C. Dart