DESCRIPTION

• A syndrome of salivation, lacrimation, urination, defecation, vomiting, diarrhea, and increased bronchial secretions caused by overstimulation of acetylcholine receptors.
• Altered mental status, fasciculation, weakness, and seizure occur in severe cases.

PATHOPHYSIOLOGY

• Cholinergic compounds inhibit the activity of the enzyme acetylcholinesterase, which results in the accumulation of acetylcholine and the overstimulation of the acetylcholine receptor. There are two types of cholinergic effects, depending on the set of automatic nervous system receptors affected.
  • Nicotinic effects are manifested by muscle weakness, fasciculation, hypertension, and tachycardia.
  • Muscarinic effects involve pupillary constriction, bronchoconstriction, secretory functions, and bradycardia.
• Carbamate compounds (insecticides, physostigmine, neostigmine, pyridostigmine, edrophonium) are reversible inhibitors of acetylcholinesterase, and organophosphates are irreversible inhibitors of acetylcholinesterase.
• Organophosphate and carbamates bind to the acetylcholinesterase enzyme located in the synaptic junctions. The binding inactivates the acetylcholinesterase, preventing the breakdown of acetylcholine. Carbamates spontaneously disassociate from the acetylcholinesterase. The organophosphate-acetylcholinesterase bond eventually becomes permanent and inactivates the acetylcholinesterase. Natural recovery involves the synthesis of new acetylcholinesterase.

Section Outline:

• DESCRIPTION
• PATHOPHYSIOLOGY

• Numerous agents increase the concentration of acetylcholine in the synapse; therefore, medication and occupational histories are important in determining the cause of this syndrome.
• Organophosphates and carbamates often produce muscarinic symptoms that are clinically apparent. Other agents may produce more subtle clinical syndromes in which some symptoms or signs are more prominent than others.
• Muscarinic effects are manifested by the DUMBELS syndrome (Diaphoresis and diarrhea, Urination, Miosis, Bradycardia and bronchospasm, Emesis and excess of Lacrimation and salivation, and Seizures).
• Absence of symptoms or signs at presentation does not rule out potentially fatal ingestion.

DIFFERENTIAL DIAGNOSIS

Toxicologic Causes

• Further information on each poison is available in SECTION IV, CHEMICAL AND BIOLOGICAL AGENTS.
• Carbachol, methacholine, and arecholine are direct-acting parasympathomimetics, mimicking the action of acetylcholine.
• Arecoline produces both nicotinic and muscarinic effects associated with an elevation of acetylcholine in the CNS.
• Bethanechol produces primarily muscarinic effects.
• Pilocarpine used in the treatment of closed-angle glaucoma may produce systemic cholinergic effects.
• Numerous mushroom species produce cholinergic effects; both nicotinic and muscarinic effects occur, but muscarinic effects predominate.

Other Compounds that Produce Similar Clinical Effects

• Sympathomimetic amines may produce sweating, tachycardia, and hypertension.
• Nicotine overdose may be clinically indistinguishable from effects of agents that inhibit acetylcholinesterase.
• Beta-blockers, calcium channel blockers, and digoxin may produce bradycardia, atrioventricular (AV) block, and hypotension, mimicking some cholinergic effects.
• Muscle weakness and fasciculation of nicotinic agents may be mistaken for conditions that result in impaired neuromuscular transmission such as snake or scorpion envenomations, heavy metal poisoning, botulism, and Eaton-Lambert syndrome.
• Pulmonary irritants may produce nausea, vomiting, and bronchorrhea; these effects can usually be differentiated by the patient's medical history.
• Botulism is associated with descending muscle weakness or paralysis.

SIGNS AND SYMPTOMS

The examiner should check for unusual odors.

Vital Signs

• Bradycardia and hypotension are muscarinic effects.
• Ventricular dysrhythmias may result in hypotension.
• Tachycardia and hypertension are nicotinic effects.
• Tachypnea is common secondary to bronchorrea.

HEENT

• Miosis, excessive salivation, and lacrimation are common.
• Blurred vision, fasciculation of periorbital muscles, and eye pain may occur.

Dermatologic

Profuse diaphoresis is common.

Cardiovascular

• Cardiac depression or cardiovascular collapse may occur.
• Atrial fibrillation, atrioventricular blocks, and asystole may occur.

Pulmonary

Bronchospasm, bronchorrhea, and pulmonary edema are common.

Gastrointestinal

Nausea, vomiting, abdominal pain, diarrhea, and involuntary defecation occur.

Neurologic/Musculoskeletal

• Muscle fasciculation, weakness, and paralysis may occur.
• Seizures may occur.

Genitourinary

Urinary incontinence is common, especially in severe cases.

Other

Unusual odors may be perceived by the health-care professional; some organophosphate insecticides have a garlic-like odor.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Red blood cell cholinesterase and plasma cholinesterase are both decreased when toxic effects of organophosphate or carbamate insecticide are present. Serum cholinesterase is often more readily available at most laboratories.
• Serum electrolytes, glucose, BUN, and creatinine are measured to detect other causes of dysrhythmia or decreased kidney function.
• ECG and continuous cardiac monitoring assess other potential causes of dysrhythmia and blood pressure abnormalities.

Recommended Tests

• Serum acetaminophen and aspirin levels in overdose setting are ordered to detect occult ingestion.
• Arterial blood gases are ordered to detect acidosis or hypoxia.
• Blood levels of specific agents are rarely useful during the acute episode. Blood levels may be useful during forensic investigations.
• Abused drugs, especially cocaine, may contain contaminants such as organophosphate insecticides.
• Head CT, lumbar puncture, bacterial cultures, and other tests are ordered as indicated in patients with altered mental status of unknown etiology.
• Chest radiography is used to assess pulmonary edema if clinically indicated.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
  • Toxicologic Causes
  • Other Compounds that Produce Similar Clinical Effects
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Neurologic/Musculoskeletal
  • Genitourinary
  • Other
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• The health-care provider should provide supportive care while evaluating the source of poisoning and while treating with atropine and pralidoxime, if indicated.
• Dose 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 cholinergic effects is unclear.
• coingestant, drug interaction, or underlying disease present unusual problems.

DECONTAMINATION

• Out of hospital. Emesis should not be induced.
• In hospital
  • Gastric lavage in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients is used for substantial ingestion presenting within 1 hour of ingestion or if serious effects are present.
  • Endotracheal intubation before lavage should be considered if CNS depression, hydrocarbon carriers, or bethanechol is involved.
  • One dose of activated charcoal (1-2 g/kg) is administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

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

Atropine Sulfate

Treats the muscarinic effects by acting as a competitive inhibitor of acetylcholine at the acetylcholine receptor. Atropine is indicated for patients with severe bronchorrhea and/or bradycardia.

• Method of administration
  • Adult dose is 1 to 4 mg intravenously initially, then every 1 to 10 minutes as needed to control bronchorrhea or to treat bradycardia.
  • Pediatric dose is 0.01 to 0.04 mg/kg intravenously initially, then every 1 to 10 minutes to control bronchorrhea or to treat bradycardia.
  • In severe cases (both adult and pediatric), the atropine requirement may exceed tens or hundreds of milligrams over the first 24 hours.

Pralidoxime (2-PAM)

Treats both nicotinic and muscarinic effects by removing organophosphate or carbamates from the cholinesterase binding site.

• Method of administration
  • Adult dose is 1 to 2 g intravenously over 15 to 30 minutes. Repeat doses of 1 to 2 g intravenously every 2 to 4 hours or a continuous intravenous infusion at 500 mg/h is commonly required for organophosphates.
  • Pediatric dose is 20 to 40 mg/kg intravenously over 15 to 30 minutes. Repeat doses of 20 to 40 mg/kg intravenously every 2 to 4 hours or an intravenous infusion of 10 mg/kg is commonly required for organophosphates.

ADJUNCTIVE TREATMENT

• Hypoxia and electrolytes should be corrected as clinically indicated.
• Tachycardia or bradycardia should be treated if clinically indicated.
• Hypertension should be treated if clinically indicated; short-acting and easily reversible agents should be used because most hypertensive effects of drugs are transient and may be followed by hypotension.

Section Outline:

• DIRECTING PATIENT COURSE
• DECONTAMINATION
• ANTIDOTES
  • Atropine Sulfate
  • Pralidoxime (2-PAM)
• ADJUNCTIVE TREATMENT

• Onset is often rapid, but may be delayed after dermal exposure.
• Effects peak in the first day, but may persist for days or weeks if not treated.

The most common problem in treatment is the failure to administer adequate amounts of atropine, allowing respiratory effects to interfere with oxygenation.

Poisoning by drugs primarily affecting the autonomic nervous system.

See Also: SECTION II, Bradycardia Toxidrome, Hypotension, and Tachycardia chapters; SECTION III, Atropine and Pralidoxime chapters; and SECTION IV, Carbamate Insecticide, Nicotine, and Organophosphate Insecticide chapters.

RECOMMENDED READING

Aaron CK, Howland MA. Insecticides: organophosphates and carbamates. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Steven A. Seifert

Reviewer: Richard C. Dart