DESCRIPTION

Digoxin and digitoxin are medications used to treat heart disease.

FORMS AND USES

• Pharmaceutical preparations include deslanoside (Cedilanid-D), digoxin (Lanoxin, Lanoxicaps), digitoxin (Crystodigin, Purodigin), and powdered digitalis.
• Animal sources include several Bufo toad species, which contain bufogins, bufotoxin, and other toxins with cardiac glycoside activity.
• Other forms include numerous unregulated topical aphrodisiacs, including Love Stone and Rock Hard.
• Plants are discussed in SECTION IV, Plants—Cardiac Glycosides chapter.
• Digoxin and digitoxin are used to slow ventricular rate in cases of atrial fibrillation, atrial flutter, and supraventricular tachycardia.
• Digoxin and digitoxin are also used to maintain cardiac output in cases of congestive heart failure.
• Typical doses of digoxin for adults are 0.5 mg orally or 0.25 mg intravenously every 6 hours to 1 mg total dose, then 0.125 to 0.25 mg daily for maintenance.

TOXIC DOSE

Ingestion of greater than 10 mg digoxin by an adult or more than 4 mg by a child has been fatal.

PATHOPHYSIOLOGY

• Digoxin inhibits the cardiac Na⁺/K⁺ ATPase pump. This increases intracellular sodium, decreases calcium excretion, and produces increased intracellular calcium concentration, which augments contractility.
• Digoxin also increases vagal tone, decreasing baroreceptor sensitivity. This results in reduction of heart rate by decreasing myocardial and atrioventricular node conduction velocity and increasing atrioventricular node refractoriness.

EPIDEMIOLOGY

• Poisoning is common.
• Toxic effects following exposure are typically mild.
• Death occurs in patients with unrecognized digoxin toxicity.

CAUSES

• Poisoning usually results from suicidal ingestion.
• Child neglect or abuse should be considered in a patient under 1 year of age; suicide attempt in patients over 6 years of age.

RISK FACTORS

• Underlying cardiac disease may predispose to dysrhythmia.
• The elderly require smaller doses of digitalis and are more likely to have an underlying illness that predisposes to toxicity.

DRUG AND DISEASE INTERACTIONS

• Concurrent use of other drugs (beta-receptor blocker, calcium channel blocker) can cause bradycardia or conduction delay.
• Quinidine, quinine, verapamil, diltiazem, amiodarone, erythromycin, and tetracycline may increase digitalis levels.
• Nifedipine, spironolactone, triamterene, and amiloride decrease renal clearance of digoxin.
• Warfarin can increase digoxin levels.
• Renal failure decreases digitalis elimination.
• Hepatic failure decreases digitoxin elimination.
• Hypokalemia, hypercalcemia, hypomagnesemia, increased sympathetic nervous system activity, and hypothyroidism may exacerbate digitalis toxicity.

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.
• Digoxin is not contraindicated during breast-feeding.

Section Outline:

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

DIFFERENTIAL DIAGNOSIS

• Toxic causes of nausea, hypotension, and bradycardia include cardiotoxic plants, beta-receptor or calcium blockers, and type 1 antidysrhythmic agents.
• Nontoxic causes include gastroenteritis, small bowel obstruction, myocardial ischemia, hyperkalemia, or other electrolyte abnormalities.

SIGNS AND SYMPTOMS

• Early signs are nonspecific (malaise and nausea).
• As toxicity increases, interference with cardiac conduction predominates.

Vital Signs

Bradycardia, tachycardia, and hypotension may occur.

HEENT

Numerous types of visual complaints, including blurred vision, amblyopia, and colored visual halos, may occur.

Cardiovascular

Cardiac effects may include bradycardia, atrioventricular block, paroxysmal atrial tachycardia with block, intraventricular conduction delays, ventricular dysrhythmia, and congestive heart failure.

Gastrointestinal

Nausea, vomiting, anorexia, and abdominal pain are common and often precede cardiac effects.

Fluids and Electrolytes

• Hyperkalemia is common with acute overdose.
• Hypokalemia is associated with chronic toxicity or diuretic use.

Neurologic

Headache, weakness, drowsiness, hallucinations, and confusion may occur in severe cases.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Serum digoxin and digitoxin levels
  • Digoxin therapeutic range is 0.5 to 2 ng/ml.
  • Digitoxin therapeutic range is 18 to 22 ng/ml.
  • Hypokalemia can precipitate toxicity at therapeutic levels of digoxin or digitoxin.
• ECG
  • Nearly every possible dysrhythmia has been reported in cardiac glycoside toxicity.
  • Prolonged PR interval and shortened QTc interval are common.
  • Atrial or junctional tachydysrhythmia, sinus bradycardia, and atrioventricular block are characteristic.
  • Bidirectional ventricular tachycardia, paroxysmal atrial tachycardia with 2:1 block, and junctional tachycardia are highly suggestive of digoxin toxicity.
• Serum electrolytes, calcium, magnesium, BUN, and creatinine
  • Hyperkalemia in acute overdose is an indication for digoxin-specific antibodies.
  • Hypokalemia disposes patients to cardiac toxicity.
  • Hypercalcemia and hypomagnesemia may dispose patients to dysrhythmias.
  • Renal insufficiency impairs digoxin clearance.

Recommended Tests

• Liver function tests are ordered because decreased hepatic function increases digitoxin levels.
• Serum acetaminophen and aspirin levels in an overdose setting are ordered to detect occult ingestion.

Conditions that May Alter Laboratory Results

• Treatment with digoxin immune Fab antibodies. Serum digoxin levels will be elevated because both free and bound digoxin are measured by most laboratories.
• Digoxin-like immunoreactive substance (DLIS)
  • DLIS is an endogenous substance that may be detected by digoxin assays.
  • It is reported in neonates and, rarely, in pregnant women or patients with renal or hepatic failure.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Cardiovascular
  • Gastrointestinal
  • Fluids and Electrolytes
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Conditions that May Alter Laboratory Results

• Treatment focuses on supportive care and administration of digoxin immune Fab, if needed.
• 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:

• Cardiac dysrhythmia, altered mental status, or other serious effects are present.
• Toxic effects are not consistent with digitalis poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

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

• Ingestion of more than 2 to 3 mg of digoxin is possible.
• 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 treatment in an intensive care setting is warranted for symptomatic patients or those with new ECG abnormalities.

DECONTAMINATION

Out of Hospital

Emesis should be induced with ipecac within 1 hour of acute, single ingestion for alert pediatric or adult patients if health-care evaluation will be delayed.

In Hospital

• Emesis should be induced with ipecac within 1 hour of acute, single ingestion for pediatric patients too small to have effective gastric lavage.
• Gastric lavage should be administered in pediatric (tube size, 24-32 French) or adult patients (tube size 36-42 French) presenting within 1 hour of a large ingestion or if serious effects are present.
• 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.

ANTIDOTES

Digoxin Immune Fab Antibodies

• Indications
  • Any sign of cardiovascular instability, including hypotension, symptomatic bradycardia, and other potentially unstable dysrhythmias.
  • Rapid progression of toxicity, including gastrointestinal or cardiovascular symptoms.
  • Serum K⁺ is greater than 5.5 mEq/L.
  • Digoxin immune Fab may be effective even during cardiac arrest of short duration; survival rates of up to 50% have been reported.
• Dosage and method of administration
  • If the patient is critically ill in the setting of probable digoxin toxicity and the digoxin level is unknown, 10 to 20 vials should be administered empirically.
  • To determine the precise amount to administer and other factors to consider, see SECTION III, Digoxin Immune Fab chapter.

ADJUNCTIVE TREATMENT

• Potassium should be replaced if patient is hypokalemic.
• Digoxin immune Fab is the preferred treatment for all dysrhythmias.
• Lidocaine and phenytoin have been used successfully for managing ventricular dysrhythmias.
• Magnesium or phenytoin may be used for supraventricular tachydysrhythmias.
• Atropine may be used for bradydysrhythmias.
• Vasopressors may be helpful during initial stabilization of the patient or until digoxin immune Fab is available

Not Recommended Therapies

• Procainamide, quinidine, disopyramide, and propranolol may worsen atrioventricular nodal block.
• Calcium is contraindicated because of the risk of cardiac tetany.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • Digoxin Immune Fab Antibodies
• ADJUNCTIVE TREATMENT
  • Not Recommended Therapies

PATIENT MONITORING

• Continuous cardiac and hemodynamic monitoring should be instituted and serum potassium followed closely.
• Recovery is usually complete, but often complicated by patient's underlying disease.
• Sequelae of hypotension or hypoxia may develop.

EXPECTED COURSE AND PROGNOSIS

Improvement within 30 minutes of digoxin Fab treatment is expected if complications of shock, hypoxia, or a coingestant have not occurred.

DISCHARGE CRITERIA AND INSTRUCTIONS

• From the emergency department. Asymptomatic patients with nontoxic digoxin level, normal ECG, and normal electrolytes may be discharged following gastrointestinal decontamination, 6 hours of observation, and psychiatric evaluation, if needed.
• From the hospital. Patients may be discharged following gastrointestinal decontamination, resolution of cardiac effects, and psychiatric evaluation, if needed.

Section Outline:

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

DIAGNOSIS

• Symptoms of digitalis toxicity may be nonspecific, and a high index of suspicion is essential.
• Patients may exhibit digitalis toxicity at therapeutic digoxin levels.

TREATMENT

• Delay in treatment is dangerous because of acute deterioration.
• Hospital pharmacies are often inadequately stocked with digoxin immune Fab.
• Recurrence of digoxin toxicity after administration of digoxin immune Fab has occurred in patients with renal failure and in those given inadequate doses.

Section Outline:

• DIAGNOSIS
• TREATMENT

Poisoning by agents primarily affecting the cardiovascular system.

See Also: SECTION III, Digoxin Immune Fab chapter; and SECTION IV, Plants—Cardiac Glycosides chapter.

RECOMMENDED READING

Ellenhorn MJ. Digitalis. In: Ellenhorn's medical toxicology—diagnosis and treatment of human poisoning, 2nd ed. Baltimore: Williams & Wilkins, 1997:541-549.

POISINDEX Editorial Staff. Cardiac glycosides. In: Rumack BH, Sayre NK, Gelman CR, eds. POISINDEX system. Englewood, CO: Micromedex, Inc. (edition expires May 31, 1998).

Authors: Lada Kokan and Kennon Heard

Reviewer: Luke Yip