AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The therapeutic properties of cardiac glycosides (eg, digoxin, a product of the foxglove plant) have been known since the days of the Roman Empire. The ancient Romans used red squill, a cardiac glycoside derived from the sea onion, as a diuretic and heart medicine. Cardiac glycosides are found in certain flowering plants such as oleander and lily-of-the-valley. Certain herbal dietary supplements also contain cardiac glycosides.

Physicians first studied digoxin in the 18th century. The syndrome of digoxin toxicity originally was described in 1785.

Pathophysiology

Digoxin's inotropic effect results from the inhibition of the sodium-potassium adenosine triphosphatase (NA⁺/K⁺ ATPase) pump. The subsequent rise in intracellular calcium (Ca⁺⁺) and sodium (NA⁺) coupled with the loss of intracellular potassium (K⁺) increases the force of myocardial muscle contraction (contractility), resulting in a net positive inotropic effect.

Digoxin also increases the automaticity of Purkinje fibers but slows conduction through the atrioventricular (AV) node. Cardiac dysrhythmias associated with an increase in automaticity and a decrease in conduction may result.

The relationship between digoxin toxicity and the serum digoxin level is complex; clinical toxicity results from the interactions between digitalis, various electrolyte abnormalities, and their combined effect on the Na⁺/K⁺ ATPase pump.

Cardiac glycoside toxicity from plants, such as oleander, foxglove, and lily-of-the-valley, is uncommon but potentially lethal. Case reports of toxicity from these sources implicate the preparation of extracts and teas as the usual culprit.

Frequency

United States

Approximately 0.4% of all hospital admissions, 1.1% of outpatients on digoxin, and 10-18% of nursing home patients develop toxicity.

The overall incidence of digoxin toxicity has decreased because of a number of factors including increased awareness of drug interactions, decreased use of digoxin to treat heart failure and arrhythmias, and the availability of accurate rapid radioimmunoassays to monitor drug levels.

International

Approximately 2.1% of inpatients on digoxin and 0.3% of all admissions develop toxicity.

Mortality/Morbidity

• Morbidity is usually 4.6-10%; however, morbidity is 50% if the digoxin level is greater than 6 ng/mL.
• Mortality varies with the population studied. Adult mortality depends on underlying comorbidity. In general, older people have a worse outcome than adults who, in turn, have a worse outcome than children.

Age

Advanced age (>80 y) is an independent risk factor and is associated with increased morbidity and mortality.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Constitutional symptoms (eg, weakness, fatigue)
• Cardiovascular
• • Palpitations
  • Syncope
  • Dyspnea
• Central nervous system
• • Confusion and somnolence
  • Dizziness without vertigo
  • Agitation, delirium, and hallucinations
  • Headache
  • Paresthesias and neuropathic pain
  • Seizures (extremely rare)
• Ocular
• • Disturbances of color vision with a tendency to yellow-green coloring
  • Blurred vision and diplopia
  • Halos and scotomas
  • Photophobia
• Gastrointestinal
• • Nausea, vomiting, anorexia, and diarrhea
  • Abdominal pain (uncommon)

Physical

Hemodynamic instability is related directly to the presence of a dysrhythmia or acute congestive heart failure (CHF).

• Cardiovascular findings on physical examination relate to the severity of CHF, dysrhythmias, or hemodynamic instability.
• • Digoxin toxicity may cause any dysrhythmia. Classically, dysrhythmias that are associated with increased automaticity and decreased AV conduction occur (ie, paroxysmal atrial tachycardia with 2:1 block, accelerated junctional rhythm, or bidirectional ventricular tachycardia [torsade de pointes]).
  • Premature ventricular contractions (PVCs) are the most common dysrhythmia. Bigeminy or trigeminy occurs frequently.
  • Sinus bradycardia and other bradyarrhythmias are very common. Slow atrial fibrillation with very little variation in the ventricular rate (regularization of the R-R interval) may occur.
  • First- and second-degree AV block, complete AV dissociation, and third-degree heart block are also very common.
  • Rapid atrial fibrillation or atrial flutter is rare.
  • Ventricular tachycardia is an especially serious finding.
  • Cardiac arrest from asystole or ventricular fibrillation is usually fatal.
• Gastrointestinal symptoms are common, but the abdominal examination is usually nonspecific.
• Neurological findings are related to changes in sensorium or mental status. Lateralizing findings usually indicate another disease process.
• Visual changes occur, but the pupils are spared, and objective findings are few.
• Drug-induced fever does not occur.

Causes

• Deteriorating renal function, dehydration, electrolyte disturbances, or drug interactions usually precipitates chronic toxicity.
• Acute overdose or accidental exposure to plants containing cardiac glycosides may cause acute toxicity.
• Hypokalemia, hypernatremia, or hypomagnesemia increases the toxic cardiovascular effects of digoxin because of their depressive effects on the NA⁺/K⁺ ATPase pump.
• • Digoxin toxicity does not cause hypokalemia, but hypokalemia can worsen digoxin toxicity.
  • Hyperkalemia is the usual electrolyte abnormality precipitated by digoxin toxicity, primarily in the acute setting. Hyperkalemia may be associated with acute renal failure that subsequently precipitates digoxin toxicity. Chronic digoxin toxicity does not usually cause hyperkalemia.
• Acidosis depresses the Na⁺/K⁺ ATPase pump and may cause digoxin toxicity.
• Myocardial ischemia suppresses the Na⁺/K⁺ ATPase pump and independently alters myocardial automaticity. Digoxin toxicity is more likely in this setting.
• Hypothyroid patients are prone to digoxin toxicity secondary to decreased renal excretion and a smaller volume of distribution.
• Bioavailability varies depending on the drug formulation.
• • Lanoxin has 25% less bioavailability than Lanoxicaps.
  • Toxicity may occur by increasing bioavailability.
  • Certain antibiotics that suppress intestinal flora may increase absorption of digoxin.
• Drug interactions are one of the most common causes of digoxin toxicity.
• • Some medications directly increase digoxin plasma levels; other medications alter renal excretion or induce electrolyte abnormalities.
  • Drugs that have been reported to cause digoxin toxicity include the following:
    • Amiloride - May reduce the inotropic response to digoxin
    • Amiodarone - Reduces renal and nonrenal clearance of digoxin and may have additive effects on the heart rate
    • Benzodiazepines (alprazolam, diazepam) - Have been associated with isolated reports of digoxin toxicity
    • Beta-blockers (propranolol, metoprolol, atenolol) - May have additive effects on the heart rate; carvedilol may increase digoxin blood levels in addition to potentiating its effects on the heart rate
    • Calcium channel blockers - Diltiazem and verapamil increase serum digoxin levels; not all calcium channel blockers share this effect.
    • Cyclosporine - May increase digoxin levels, possibly due to reduced renal excretion
    • Erythromycin, clarithromycin, and tetracyclines - May increase digoxin levels
    • Propafenone - Increases digoxin level; effects are variable.
    • Quinidine - Increases digoxin level substantially but clinical effect is variable; related drugs such as hydroxychloroquine or quinine may also affect levels.
    • Propylthiouracil - May increase digoxin levels by reducing thyroid hormone levels
    • Indomethacin
    • Spironolactone - May interfere with digoxin assays; may directly increase digoxin levels; may alter renal excretion.
    • Hydrochlorothiazide
    • Furosemide and other loop diuretics
    • Triamterene
    • Amphotericin B - May precipitate hypokalemia and subsequent digoxin toxicity
    • Succinylcholine - Increased risk of dysrhythmias has been reported.
  • Herb/nutraceutical - Avoid ephedra (risk of cardiac stimulation); avoid natural licorice (causes sodium and water retention and increases potassium loss).
• Clinical digoxin toxicity represents a complex interaction between digoxin and various electrolyte and renal abnormalities. A patient with normal digoxin levels (0.5-2 ng/mL) but renal insufficiency or severe hypokalemia may have more serious cardiotoxicity than a patient with high digoxin levels and no renal or electrolyte disturbances.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Arrhythmias
Dehydration
Syncope

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Initial digoxin level
• • In acute toxicity, repeat the digoxin level after 2-4 hours to guide therapy.
  • Digoxin levels do not necessarily correlate with toxicity, especially after acute ingestion.
  • Following acute ingestion, digoxin levels do not equilibrate quickly because of variable absorption and subsequent tissue distribution.
  • Toxicity is related to intracellular levels, not serum levels.
  • A digoxin level drawn within 4 hours of an acute ingestion may be incredibly high with no apparent clinical toxicity.
  • To best way to guide therapy is to follow the digoxin level and correlate it with serum potassium concentrations and the patient's clinical and ECG findings.
• Measure Na⁺, K⁺, Cl^-, CO^2-, Mg⁺⁺, Ca⁺⁺, BUN, and creatinine levels.
• Obtain cardiac markers if myocardial infarction is a clinical concern.
• False-negative assay results may occur in the setting of acute ingestion of nondigoxin cardiac glycosides, such as foxglove and oleander, even in the setting of profound clinical toxicity. This is caused by nonreactivity or minimal cross-reactivity with the digoxin radioimmunoassay.

Other Tests

• ECG
• • Digoxin effects on the baseline ECG include downward scooping of the ST segment and inverted T waves. These findings are not indicative of toxicity.
  • New QRS prolongation, varying degrees of AV block, and arrhythmias may signify digoxin toxicity. Comparison with previous ECGs is helpful.
  • Rhythm strips may be necessary to facilitate arrhythmia analysis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Oxygen, cardiac monitoring, IV access, and transport are usually the only requirements.
• Atropine is indicated for hemodynamically unstable bradyarrhythmias; lidocaine is indicated for ventricular tachycardia.

Emergency Department Care

Guide treatment of patients with digoxin toxicity by their signs and symptoms and the specific toxic effects. Treatment should not necessarily be driven by digoxin levels alone. Therapeutic options range from simply discontinuing digoxin therapy for patients who are stable with chronic toxicity to fab fragments, pacemaker, antiarrhythmic drugs, magnesium, and hemodialysis for acute severe ingestions.

• Initiate supportive therapy with oxygen, cardiac monitoring, and IV access.
• Activated charcoal is indicated for acute overdose or accidental ingestion. Cholestyramine binds enterohepatically-recycled digoxin and digitoxin, although no outcome studies have been performed.
• • Gastric lavage increases vagal tone and may precipitate or worsen arrhythmias. Consider pretreatment with atropine if gastric lavage is performed.
  • The availability of a digitalis-fab antibodies (Digibind) antidote usually renders gastric lavage unnecessary.
• Management of dysrhythmias varies, depending on the presence or absence of hemodynamic instability, the nature of the arrhythmia, the presence or absence of electrolyte disturbances, and the preferences of toxicology and/or cardiology consultants.
• • Bradyarrhythmias that are hemodynamically stable may be treated with observation and discontinuation of the drug. Ensure proper hydration to optimize renal clearance of excess drug. GI binding agents (eg, charcoal, cholestyramine) may be utilized to bind enterohepatically-recycled digitalis.
  • Hemodynamically stable supraventricular arrhythmias may be treated conservatively with observation and discontinuation of digoxin. In the setting of rate-related ischemia or hemodynamic instability, Digibind is the treatment of choice.
  • Hemodynamically unstable bradyarrhythmias respond best to Digibind. Atropine may be used for temporary adjuncts. Cardiac pacing has been used successfully, but it can lower the fibrillatory threshold and induce arrhythmias.
  • PVCs, bigeminy, or trigeminy may be observed unless the patient is hemodynamically unstable, in which case lidocaine may be effective.
  • Ventricular tachycardia responds best to Digibind. Lidocaine and Dilantin may be useful. Lidocaine may be given in boluses of 100 mg, according to advanced cardiac life support (ACLS) guidelines. If lidocaine is successful, begin a maintenance infusion at 1-4 mg/min. Phenytoin has been administered in boluses of 100 mg every 5-10 min up to a loading dose of 15 mg/kg. Avoid procainamide and bretylium.
  • Asystole and ventricular fibrillation are very serious findings. Digibind is indicated; however, its effect is limited by poor cardiac blood flow. Nevertheless, the use of digoxin-fab fragments is associated with a 50% survival rate.
• Cardioversion is relatively contraindicated because asystole or ventricular fibrillation may be precipitated.
  • Calcium channel blockers are contraindicated because they may increase digoxin levels.
  • Short-acting beta-blockers (eg, esmolol) may be helpful, but advanced or complete AV block may be precipitated.
• Consider magnesium therapy as a temporizing antiarrhythmic agent until fab fragments are available. It may be lifesaving when ventricular tachycardia or ventricular fibrillation is present.
• • After an initial bolus of 2 g intravenously, a maintenance infusion at 1-2 g/h is initiated.
  • Monitor magnesium levels approximately every 2 hours. The therapeutic goal is a level between 4 and 5 mEq/L.
• Correct electrolyte abnormalities, especially hypokalemia and hypomagnesemia. Dysrhythmias may be reversed with correction of electrolyte imbalances.
  • Treat hyperkalemia when K⁺ level is greater than 5.5 mEq/L.
  • Calcium is not recommended to treat hyperkalemia in this setting because ventricular tachycardia or ventricular fibrillation may be precipitated. This is based on the fact that intracellular calcium levels are already high in the setting of digoxin toxicity. However, anecdotal case reports and animal studies have been published that refute the dangers of calcium administration. Unless the patient is in extremis, other measures should be preferentially used to treat hyperkalemia.
  • Sodium bicarbonate and/or glucose and insulin are indicated.
  • Treatment with digoxin-fab fragments is indicated for hyperkalemia with K⁺ level greater than 5 mEq/L.
  • Kayexalate (0.5 g/kg PO) also is helpful in binding potassium and enterohepatically-recycled digitalis. However, digoxin-induced hyperkalemia reflects an extracellular shift, not an increase in total body potassium.
  • Caution is indicated when using Kayexalate concurrently with insulin/glucose/bicarbonate and/or Digibind because hypokalemia may be precipitated, which may worsen clinical toxicity.
• Digoxin-fab fragments (Digibind) are generally indicated for the following:
  • Dysrhythmias associated with hemodynamic instability.
  • Altered mental status attributed to digoxin toxicity.
  • Hyperkalemia with K⁺ greater than 5 mEq/L.
  • Serum digoxin level greater than 10 ng/mL in adults at steady state (ie, 6-8 h post acute ingestion or at baseline in the clinical setting of chronic toxicity).
  • Ingestion greater than 10 mg in adults (40 X 0.25 mg tablets) or greater than 0.3 mg/kg in children.

Consultations

• Medical toxicologist
• Cardiology
• Regional poison control center

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce toxic levels of digitalis, prevent complications, and reduce morbidity.

Drug Category: Antidote

For hemodynamic instability, refractory dysrhythmias, and severe or refractory hyperkalemia. Agent has reversed noncardiac digitalis-associated complications (eg, thrombocytopenia).

In chronic toxicity, plasma drug levels are > 6 ng/mL; in acute ingestion, do not base treatment on plasma drug levels alone.

Initially administering one-half doses is the best way in patients with chronic toxicity who are dependent on digoxin. This avoids completely reversing the clinical effects of digoxin and precipitating complications. Depending on the patient's status, additional antidote may be administered later. Agent is excreted renally. When administered to anephric patients, digitalis toxicity may recur within 7-14 days, as digoxin unbinds (recrudescence toxicity). Plasmapheresis may be performed or Digibind readministered in such situations.

Complications of therapy include allergic reactions (relatively rare and more common in patients with allergic histories), worsening CHF, tachyarrhythmias, and hypokalemia. Overall, incidence of complications is very low.

Digoxin levels drawn after administration may be exponentially higher because many assays for measuring digoxin measure total digoxin (including digoxin bound to Digibind). This may be misinterpreted as a therapeutic failure and worsening toxicity. Assays that measure only free digoxin are accurate and should reflect true posttreatment levels. Knowledge of your laboratory's digoxin assay is critically important in evaluating therapeutic effect.

Drug Category: Cardiovascular agents

May be useful for treatment of bradycardia associated with digoxin overdose.

Drug Category: GI decontaminant

Activated charcoal is useful in limiting the absorption of ingested digoxin. Most beneficial if administered within 4 h of ingestion.

Drug Category: Resin

Used in management of hypercholesterolemia and can bind drugs that are enterohepatically recycled. Upwards of 30% of a digoxin dose (higher in some individuals) and the majority of a digitoxin dose are enterohepatically recycled.

Drug Category: Electrolytes

Magnesium is useful as a temporizing antiarrhythmic agent until digoxin Fab fragments are available.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admission criteria
• • New cardiac dysrhythmias
  • Severe bradyarrhythmias
  • Advanced AV block
  • Acute prolongation of the QRS interval
  • Severe electrolyte abnormalities, especially hypokalemia or hyperkalemia
  • Dehydration
  • Inability to care for self
  • Suicidal ideation
• Admit patients with cardiac abnormalities to a monitored bed.
• ICU admission criteria include hemodynamic instability, refractory dysrhythmias, hyperkalemia, and renal failure. Admit patients receiving Digibind to ICU or critical care unit (CCU).

Further Outpatient Care

• Observe patients with acute ingestion on a cardiac monitor for 6 hours. In the absence of cardiac dysrhythmias, toxic digoxin levels, or hyperkalemia, patients may be discharged with appropriate follow-up care.
• Patients with chronic toxicity and noncardiac symptoms may be discharged if factors that led to the toxicity have been corrected (eg, electrolyte disorders, dehydration, drug-drug interactions) and proper care can be ensured. Discontinue use of the drug. Arrange follow-up care in the next 24 hours with a primary care provider.
• Intentional overdose requires psychiatric follow-up.

Transfer

• Transfer may be indicated if patient is unstable and the hospital has no ICU or CCU capabilities, no appropriate consultants (eg, toxicologist, cardiologist, intensivist), or when Digibind (if indicated) is not available. Treatment is best discussed with the regional poison control center and the patient's primary practitioner.

Deterrence/Prevention

• Digoxin toxicity may develop in patients with dehydration, worsening renal function, or new electrolyte disturbances. Drug interactions are an important causative factor. Careful patient monitoring, including drug levels, is required in these clinical settings.
• Advanced age decreases the volume of distribution and renal clearance. Elderly patients and those with chronic renal failure require lower maintenance doses.

Complications

• Refer to complications of Digibind therapy, as outlined in the Medication section.

Prognosis

• Morbidity and mortality rates increase if the patient has a new dysrhythmia, advanced AV block, or other significant ECG abnormality.

Patient Education

• Educate the patient to be aware of possible drug interactions when starting any new medication.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider the diagnosis in patients with dysrhythmias, electrolyte abnormalities, or renal insufficiency
• Cardioverting the digoxin-toxic patient with an unstable supraventricular arrhythmia
• Administration of intravenous calcium to treat hyperkalemia if digoxin toxicity is suspected or confirmed unless the patient is in extremis
• Failure to arrange psychiatric follow-up in cases of intentional overdose

Special Concerns

• Infants and children taking digoxin tolerate higher doses and plasma levels.
• • The pediatric volume of distribution is greater and the half-life of digoxin is less.
  • Pediatric myocardial cells may be less sensitive to the toxic effects of digoxin.
  • Decreased sensitivity to dysrhythmias by infants and children may contribute to increased tolerance to digoxin.
  • Infants and children manifest the same signs of toxicity as adults.
  • The treatment of toxicity in pediatric patients is the same as in adults.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Antman EM, Wenger TL, Butler VP, et al. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study. Circulation. Jun 1990;81(6):1744-52. [Medline].
• Benowitz N. Cardiac glycosides. In: Olson K, ed. Poisoning and Drug Overdose. 4th ed. 2004:155-7.
• Carter BL, Small RE, Garnett WR. Monitoring digoxin therapy in two long-term facilities. J Am Geriatr Soc. Jun 1981;29(6):263-8. [Medline].
• Colt HG, Shapiro AP. Drug-induced illness as a cause for admission to a community hospital. J Am Geriatr Soc. Apr 1989;37(4):323-6. [Medline].
• Doi SA, Landless PN. Digoxin in clinical practice: sorting out the facts. Br J Clin Pract. Sep-Oct 1995;49(5):257-61. [Medline].
• Eddleston M, Rajapakse S, Rajakanthan S, et al. Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial. Lancet. Mar 18 2000;355(9208):967-72. [Medline].
• Ellenhorn A. Digitalis. In: Ellenhorn's Medical Toxicology. 2nd ed. Lippincott Williams & Wilkins;1997:451-456.
• Fazio A. Fab fragments in the treatment of digoxin overdose: pediatric considerations. South Med J. Dec 1987;80(12):1553-6. [Medline].
• Fenton F, Smally AJ, Laut J. Hyperkalemia and digoxin toxicity in a patient with kidney failure. Ann Emerg Med. Oct 1996;28(4):440-1. [Medline].
• Fisch C, Knoebel SB. Recognition and therapy of digitalis toxicity. Prog Cardiovasc Dis. Jan 1970;13(1):71-96. [Medline].
• Fleisher G, Ludwig S. Textbook of Pediatric Emergency Medicine. Lippincott Williams & Wilkins;1993:768-9.
• Goodman LS, Gilman AG. The Pharmacologic Basis of Therapeutics. 7th ed. McGraw-Hill;1985:716-47.
• Green SM, Naftel J. Antiarrhythmic efficacy of magnesium in the setting of life-threatening digoxin toxicity. Am J Emerg Med. May 1989;7(3):347-8. [Medline].
• Hack JB, Woody JH, Lewis DE, et al. The effect of calcium chloride in treating hyperkalemia due to acute digoxin toxicity in a porcine model. J Toxicol Clin Toxicol. 2004;42(4):337-42. [Medline].
• Ibanez C, Carcas AJ, Frias J, Abad F. Activated charcoal increases digoxin elimination in patients. Int J Cardiol. Jan 27 1995;48(1):27-30. [Medline].
• Lacy CF, Armstrong LL, Goldman MP. Drug Information Handbook. 13th ed. 2005.
• Lip GY, Metcalfe MJ, Dunn FG. Diagnosis and treatment of digoxin toxicity. Postgrad Med J. May 1993;69(811):337-9. [Medline].
• Mahdyoon H, Battilana G, Rosman H, et al. The evolving pattern of digoxin intoxication: observations at a large urban hospital from 1980 to 1988. Am Heart J. Nov 1990;120(5):1189-94. [Medline].
• Ordog GJ, Benaron S, Bhasin V, et al. Serum digoxin levels and mortality in 5,100 patients. Ann Emerg Med. Jan 1987;16(1):32-9. [Medline].
• Pahor M, Guralnik JM, Gambassi G, et al. The impact of age on risk of adverse drug reactions to digoxin. For The Gruppo Italiano di Farmacovigilanza nell' Anziano. J Clin Epidemiol. Nov 1993;46(11):1305-14. [Medline].
• Park MK. Use of digoxin in infants and children, with specific emphasis on dosage. J Pediatr. Jun 1986;108(6):871-7. [Medline].
• Rosen P, Barkin R. Toxicologic problems: Common cardiac medications. In: Emergency Medicine: Concepts and Clinical Practice. 3rd ed. Mosby-Year Book;1992:2541.
• Steiner JF, Robbins LJ, Hammermeister KE, et al. Incidence of digoxin toxicity in outpatients. West J Med. Nov 1994;161(5):474-8. [Medline].
• Van Deusen SK, Birkhahn RH, Gaeta TJ. Treatment of hyperkalemia in a patient with unrecognized digitalis toxicity. J Toxicol Clin Toxicol. 2003;41(4):373-6. [Medline].
• Wofford JL, Hickey AR, Ettinger WH, Furberg CD. Lack of age-related differences in the clinical presentation of digoxin toxicity. Arch Intern Med. Nov 1992;152(11):2261-4. [Medline].

Article Last Updated: Jan 3, 2006