DESCRIPTION

Edrophonium chloride (Tensilon, Enlon, Reversol) is a parenteral cholinergic agonist mediator used primarily in the diagnosis of myasthenia gravis.

FORMS AND USES

• The initial dose for the differential diagnosis of myasthenia gravis is 1 to 2 mg intravenously over 15 to 30 seconds.
  • If no reaction occurs after 45 seconds, the remainder of the 10-mg total dose is injected.
  • In geriatric patients the maximum dose is reduced to 5 to 7 mg.
• In children over 75 pounds, the test dose is 1 mg and total dose is up to 5 mg in increments of 1 mg.
• In children under 75 pounds, the dose is 0.2 mg/kg intramuscularly.
• Adequacy of current myasthenia treatment.
  • The dose is 1 to 2 mg intravenously 1 hour after ingestion of the treatment drug.
  • The response is myasthenic in the undertreated patient, adequate in the controlled patient, and cholinergic in the overtreated patient.
• Differentiation of myasthenic crisis from therapeutic cholinergic excess.
  • A test dose of 1 mg is administered intravenously over 15 to 30 seconds.
  • If symptoms do not worsen, an additional 1 mg is given.
  • If symptoms improve, no further dose is given.
• It is also used as an antagonist to nondepolarizing neuromuscular blockers.
• The bite of some neurotoxic snakes are treated with edrophonium.

PATHOPHYSIOLOGY

• Edrophonium reversibly binds acetylcholinesterase in peripheral and CNS synapses, thereby potentiating the effect of acetylcholine.
• Onset is in 30 to 60 seconds, and duration of action is 10 to 30 minutes.
• Nicotinic effects are manifested as muscle weakness and fasciculation.
• Muscarinic effects are manifested as the SLUDGE syndrome (salivation, lacrimation, urination, defecation/diaphoresis, gastrointestinal cramping, and emesis).

EPIDEMIOLOGY

Toxic effects are common but are typically mild.

CAUSES

• Poisoning may be caused by rapid injection of edrophonium or by waiting an insufficient period of time to determine the response to previous dose(s).
• Poisoning may also be caused by idiopathic hypersensitivity to anticholinesterase agents.

RISK FACTORS

• Geriatric patients are more susceptible to adverse cardiac effects.
• Dysrhythmia is more common in patients with heart disease.

DRUG AND DISEASE INTERACTIONS

• Edrophonium may cause synergistic cholinergic effects in patients already taking therapeutic anticholinesterases (neostigmine, pyridostigmine, physostigmine).
• Synergistic cholinergic effects may occur with organophosphate insecticides.
• The probability of dysrhythmia is increased with digoxin, calcium channel blockers, and beta-blockers.
• Quinidine may antagonize edrophonium effects and mask diagnostic response in myasthenia gravis.
• Procainamide may antagonize effects on skeletal muscle.

PREGNANCY AND LACTATION

US FDA Pregnancy Category C. 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.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

Toxic causes of small pupils with signs of cholinergic excess include organophosphate or carbamate insecticides and other therapeutic cholinesterase inhibitors (neostigmine, pyridostigmine, physostigmine).

SIGNS AND SYMPTOMS

Vital Signs

Bradycardia and tachypnea may occur.

HEENT

Increased salivation and lacrimation, diplopia, and pupillary constriction may occur.

Dermatologic

Diaphoresis is common.

Cardiovascular

Bradycardia, hypotension, atrioventricular block, atrial fibrillation, atrial flutter, ventricular tachycardia, and asystole may occur.

Pulmonary

Increased pulmonary secretions, laryngospasm, bronchiolar constriction, and, in severe cases, respiratory paralysis may occur.

Gastrointestinal

Nausea, vomiting, diarrhea, abdominal cramps, and increased intestinal secretions may occur.

Renal

Urinary frequency may occur.

Musculoskeletal

Weakness and fasciculation may occur.

Neurologic

Seizures, dysarthria, dysphonia, and dysphagia may occur.

PROCEDURES AND LABORATORY TESTS

• Essential tests. ECG and continuous cardiac monitoring should be performed; bradycardia, atrioventricular block, atrial fibrillation, atrial flutter, ventricular tachycardia, and asystole may develop.
• Recommended tests. Other tests are recommended only as indicated by patient course.
• Not recommended tests. Serum levels are not clinically useful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS

Treatment should focus on airway management, cardiac toxicity, seizure management, and atropine administration.

DIRECTING PATIENT COURSE

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

• Bronchospasm, apnea, hypotension, or other severe effects are present.
• Toxic effects are not consistent with edrophonium toxicity.
• Coingestant, drug interaction, or underlying disease presents an unusual challenge.

Patients should be referred to a health-care facility when:

• Any toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual challenge.

Admission Considerations

Inpatient treatment is warranted when the patient develops shock, seizure, airway compromise, or persistent dysrhythmia or has an underlying medical condition that warrants prolonged observation.

DECONTAMINATION

Decontamination is not helpful because of the intravenous route of administration.

ANTIDOTES

Atropine

• Indications. Clinically significant muscarinic symptoms: salivation, lacrimation, urination, defecation, emesis, diaphoresis, bradycardia, hypotension, and asystole.
• Contraindications. No absolute contraindications.
• Method of administration
  • Adult
    • The dose is 0.5 mg up to 2 mg intravenously, then 0.5 mg every 3 to 10 minutes as needed.
  • Pediatric
    • The dose is 0.01 to 0.05 mg/kg intravenously, then 0.01 to 0.05 mg/kg every 3 to 10 minutes as needed, up to 5 mg.
• Adverse effects. Anticholinergic syndrome

Pralidoxime

Indications. Severe or prolonged nicotinic symptoms (profound muscle weakness, respiratory depression, coma, seizures). For details of administration, see SECTION III, Pralidoxime chapter.

ADJUNCTIVE TREATMENT

Hypotension

• Patient should be administered 10 to 20 ml/kg 0.9% NaCl and placed in the Trendelenburg position.
• Further fluid therapy should be guided by central pressure monitoring to avoid volume overload.
• If hypotension is unresponsive, a vasopressor should be administered.
  • Dopamine
    • The dose is 2 to 5 µg/kg/min, titrated to effect.
    • Infusion rates above 20 µg/kg/min should be avoided.
  • Norepinephrine
    • The dose is 0.1 to 0.2 µg/kg/min, titrated to effect.
  • High rates of infusion may cause tissue ischemia.

Seizures

A benzodiazepine should be administered for initial control.

• Diazepam
  • Adult dose is 5 to 10 mg initially, repeated every 10 minutes if needed.
  • Pediatric dose is 0.2 to 0.5 mg/kg initially, repeated every 10 minutes if needed.
• Lorazepam
  • Adult dose is 2 to 4 mg by intravenous push over 2 to 5 minutes, repeated every 10 minutes if needed.
  • Pediatric dose is 0.1 mg/kg by intravenous push over 2 to 5 minutes, not to exceed 4 mg/dose, repeated every 10 minutes if needed.
• The airway should be monitored closely.

Tracheostomy and Mechanical Ventilation

Required rarely for respiratory paralysis and secretions resistant to treatment.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
• ANTIDOTES
  • Atropine
  • Pralidoxime
• ADJUNCTIVE TREATMENT
  • Hypotension
  • Seizures
  • Tracheostomy and Mechanical Ventilation

PATIENT MONITORING

Cardiac and respiratory monitoring should be performed until dysrhythmias resolve and patient is stable.

EXPECTED COURSE AND PROGNOSIS

• Direct effects resolve within 10 to 30 minutes if uncomplicated unless complications of hypoxia or seizure intercede.
• Secretions and respiratory paralysis resolve over a longer period.
• Chronic renal failure may prolong duration of adverse events.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patient may be discharged after resolution of toxic effects, depending on the underlying medical condition and the reason for use of edrophonium.
• From the hospital. Patient may be discharged after resolution of airway compromise and as general medical condition allows.

Section Outline:

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

DIAGNOSIS

• Myasthenia gravis may produce respiratory paralysis misinterpreted as secondary to edrophonium.
• Reversal of nondepolarizing neuromuscular blockers may wear off prematurely because of the short duration of action for edrophonium.
• Edrophonium should not be given to patients already in cholinergic excess.
• When given to reverse neuromuscular blockade, the effect of each dose should be assessed before giving additional edrophonium.

TREATMENT

Atropine may not be immediately available.

Section Outline:

• DIAGNOSIS
• TREATMENT

Poisoning by drugs primarily affecting autonomic nervous system: parasympathomimetics (cholinergics).

See Also: SECTION II, Hypotension and Seizure (Unexplained) chapters; and SECTION III, Pralidoxime chapter.

RECOMMENDED READING

Gilman AG, Rall TW, Nies AS, et al., eds. Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York: Pergamon, 1990.

Youngberg JA. Cardiac arrest following treatment of paroxysmal atrial tachycardia with edrophonium. Anesthesiol 1979;50:234-235.

Author: Steven A. Seifert

Reviewer: Richard C. Dart