eMedicine Specialties > Cardiology > Arrhythmias

Digitalis Toxicity: Differential Diagnoses & Workup

Author: Vinod Patel, MD, Medical Director, Jefferson Family Medicine Center; Clinical Assistant Professor, Department of Family Medicine, State University of New York at Buffalo
Coauthor(s): Paul Arthur James, MD, IAFP Endowed Chair in Rural Medicine, Associate Professor of Family Medicine, Department of Family Medicine, University of Iowa College of Medicine
Contributor Information and Disclosures

Updated: Dec 22, 2008

Differential Diagnoses

Acute Renal Failure
Hypomagnesemia
Hypercalcemia
Hyponatremia
Hyperkalemia
Hypernatremia
Hypokalemia

Other Problems to Be Considered

Congestive heart failure
Arrhythmias
Pulmonary edema
Syncope
Drugs causing bradycardias such as calcium channel blockers or beta-blockers

Workup

Laboratory Studies

  • Plasma digoxin levels
    • The plasma digoxin level can be used to monitor both compliance and toxicity and can be used as a guide to appropriate dosing of medication.
    • Therapeutic levels vary; the lower limit ranges from 0.6-1.3 ng/mL, while the upper limit generally is agreed to be 2.6 ng/mL. Serum concentrations associated with toxicity overlap between therapeutic and toxic ranges because of the myriad of factors potentiating digoxin toxicity.
    • Because of the delayed onset of action of digoxin, at least 6 h must elapse between dosage and drawing a digoxin level specimen in order to prevent spuriously elevated levels. Strict adherence to levels without regard to clinical manifestations can result in inappropriate and costly intervention.
    • Other confounding variables include digoxin metabolites, drugs, and endogenous digoxin like factors. While most patients metabolize <20% of digoxin, 10% of the population metabolizes as much as 55% of digoxin to initially active metabolites. Not all routinely used radioimmunoassays (RIAs) measure each of these metabolites. Additionally, the antibodies used in digoxin immunoassay can cross-react with numerous compounds, including steroids and other drugs (eg, spironolactone). Finally, serum from neonates, pregnant women, patients with renal or hepatic failure, and patients with essential hypertension may cross-react with the digoxin antibody owing to endogenous digitalislike factors produced by these individuals. These substances may account for 50% of serum digoxin levels measured by RIAs in specific patients.
  • Electrolyte evaluation
    • Hyperkalemia: In acute toxicity, hyperkalemia is common owing to inactivation of the Na+/K+ -ATPase pump. It is a predictor of morbidity and mortality and also reflects the degree of poisoning.
    • Hypokalemia: Long-term digoxin users very often develop hypokalemia because of concurrent diuretic use. It should be corrected promptly and may help to improve cardiac glycoside-related arrhythmia.
    • Hypomagnesemia: Long-term digoxin users often have hypomagnesemia secondary to diuretic usage. Intracellular magnesium depletion may occur in long-term diuretic use despite normal serum magnesium level. Importantly, magnesium is a cofactor of the Na+/K+ -ATPase pump, and alterations of its concentration will affect the pump's actions.
  • Renal function: Obtain BUN and creatinine to assess renal function.

Other Tests

  • Electrocardiogram may be necessary to facilitate the diagnosis, the type of rhythm, and arrhythmia. The rhythm may be as follows:
    • Nonspecific
      • Premature ventricular contractions (PVCs), especially bigeminal and multiform
      • First-, second- (Wenckebach), and third-degree AV block
      • Sinus bradycardia
      • Sinus tachycardia
      • SA block or arrest
      • Atrial fibrillation with slower ventricular response
      • Atrial tachycardia
      • Junctional (escape) rhythm
      • AV dissociation
      • Ventricular bigeminy and trigeminy
      • Ventricular tachycardia
      • Torsade de pointes
      • Ventricular fibrillation
    • More specific, but not pathognomonic
      • Atrial fibrillation with slow, regular ventricular rate (ie, AV dissociation)
      • Nonparoxysmal junctional tachycardia (rate 70-130 beats per minutes [bpm])
      • Atrial tachycardia with block (atrial rate usually 150-200 bpm)
      • Bidirectional ventricular tachycardia

More on Digitalis Toxicity

Overview: Digitalis Toxicity
Differential Diagnoses & Workup: Digitalis Toxicity
Treatment & Medication: Digitalis Toxicity
Follow-up: Digitalis Toxicity
References
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References

  1. Mahdyoon H, Battilana G, Rosman H, Goldstein S, Gheorghiade M. 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].

  2. Barrueto F, Jortani SA, Valdes R, et al. Cardioactive steroid poisoning from an herbal cleansing preparation. Ann Emerg Med. Mar 2003;41(3):396-9. [Medline].

  3. Binder WD, Lewander WJ. Digoxin. In: Viccellio P, ed. Emergency Toxicology. Philadelphia, Pa: Lippincott-Raven; 1998:707-721.

  4. Dribben WH, Kirk MA. Digitalis glycosides. In: Tintinalli JE, Kelan G, Stapzcynsky JP, eds. Emergency Medicine: A Comprehensive Study Guide. 5th ed. New York, NY: McGraw-Hill; 1999:1139-42.

  5. Hoffman BF, Bigger T Jr. Digitalis and allied cardiac glycosides. In: Gilman AG, Rall TW, Nies AS, Taylor P, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY: Pergamon Press; 1990:814-39.

  6. Howland MA. Prescription medications, digoxin-specific antibody fragments. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Weis, eds. Goldfrank's Toxicologic Emergencies. 6th ed. Norwalk, Conn: Appleton & Lange; 1998:48:801-807.

  7. Lewin NA. Prescription medications, cardiac glycosides. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Weis, eds. Goldfrank's Toxicologic Emergencies. 6th ed. Appleton & Lange; 1998:791-800.

  8. Roberts DJ. Common cardiovascular drugs. In: Rosen P, ed. Emergency Medicine, Concepts and Clinical Practice. 2nd ed. St Louis, Mo: Mosby; 1992:1307-12.

  9. Smith TW, Antman EM, Friedman PL, et al. Digitalis glycosides: mechanisms and manifestations of toxicity. Part I. Prog Cardiovasc Dis. Mar-Apr 1984;26(5):413-58. [Medline].

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Further Reading

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Keywords

digitalis toxicity, atrial fibrillation, cardiac glycoside, congestive heart failure, CHF, digitoxin, digoxin, inotropic agent, inotropy, Digitalis purpurea, Thevetia peruviana, depletion of potassium stores, myocardial infarction, myocardial ischemia, hypothyroidism, hypercalcemia, renal insufficiency

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Contributor Information and Disclosures

Author

Vinod Patel, MD, Medical Director, Jefferson Family Medicine Center; Clinical Assistant Professor, Department of Family Medicine, State University of New York at Buffalo
Vinod Patel, MD is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, and North American Primary Care Research Group
Disclosure: Nothing to disclose.

Coauthor(s)

Paul Arthur James, MD, IAFP Endowed Chair in Rural Medicine, Associate Professor of Family Medicine, Department of Family Medicine, University of Iowa College of Medicine
Paul Arthur James, MD is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, North American Primary Care Research Group, Phi Beta Kappa, and Society of Teachers of Family Medicine
Disclosure: Nothing to disclose.

Medical Editor

Justin D Pearlman, MD, PhD, ME, MA, Director of Advanced Cardiovascular Imaging, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center
Justin D Pearlman, MD, PhD, ME, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Ronald J Oudiz, MD, FACP, FACC, Associate Professor of Medicine, Division of Cardiology, The David Geffen School of Medicine at UCLA; Director, Liu Center for Pulmonary Hypertension, LA Biomedical Research Institute at Harbor-UCLA Medical Center
Ronald J Oudiz, MD, FACP, FACC is a member of the following medical societies: American College of Cardiology, American College of Physicians, and American Heart Association
Disclosure: Actelion Grant/research funds Clinical Trials + honoraria; Encysive Grant/research funds Clinical Trials + honoraria; Gilead Grant/research funds Clinical Trials + honoraria; Pfizer Grant/research funds Clinical Trials + honoraria; United Therapeutics Grant/research funds Clinical Trials + honoraria; Lilly Grant/research funds Clinical Trials + honoraria; LungRx  Clinical Trials + honoraria

CME Editor

Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital
Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Chief Editor

Eric H Yang, MD, Assistant Professor of Medicine, Director of Coronary Care Unit, University of North Carolina at Chapel Hill School of Medicine
Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha
Disclosure: Up to Date Royalty Review panel membership

 
 
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