Digoxin Toxicity

Aka: Digoxin Toxicity, Digitalis Toxicity, Digibind, Digoxin-Immune Fab, Cardiac Glycoside Overdose, Digoxin Poisoning, Digoxin Overdose

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II. Epidemiology

  1. Digoxin Toxicity was common with standard dose Digoxin (Incidence 7-20%)
    1. Lower doses used since in the U.S. has resulted in decreased toxicity

III. Causes

  1. Digoxin (Digitalis)
  2. Other Cardiac Glycosides (e.g. herbal products)
    1. Aconite (Monkshood)
      1. Used in Traditional Chinese Medicine
      2. Effects Sodium channels with risk of ventricular Arrhythmia (including Ventricular Tachycardia)
    2. Almendra de quema grasa
    3. Asclepias sp. (milkweed)
    4. Cerbera odollam (Suicide tree, pong-pong)
      1. Therapeutic dose is 1/32 of an almond
    5. Colorado River Toad
    6. Foxglove
      1. Purple foxglove (Digitalis purpurea)
      2. Woolly foxglove (Digitalis lanata)
    7. Lily-of-the-valley (Convallaria majalis)
    8. Ouabain (Strophanthus gratus)
    9. Oleander
      1. Common oleander (Nerium oleander)
      2. Yellow oleander (Thevetia peruviana) has lethal levels of cardiac glycosides in 1-2 nuts

IV. Risk Factors

  1. Hyperkalemia (associated with increased mortality)
  2. Hypokalemia
  3. Hypomagnesemia
  4. Hypercalcemia
  5. Medication use interfering with Digoxin excretion
    1. Quinidine
    2. Verapamil
    3. Amiodarone

V. Symptoms

  1. Anorexia
  2. Nausea
  3. Vomiting
  4. Somnolence
  5. Muscle Weakness
  6. Diarrhea
  7. Yellow Vision (xanthopsia)

VI. Signs

  1. Hypotension
  2. Bradycardia

VII. Labs

  1. Serum Digoxin Level
    1. Obtain at baseline and again in 6 hours after ingestion (in acute ingestion)
    2. Non-Digoxin cardiac glycosides will also raise this level (but unpredictably)
    3. Toxic level >2.5 mg/ml
      1. Does not always correlate with toxicity
      2. Toxicity may occur at low levels and not at high ones

VIII. Diagnostics: Electrocardiogram

  1. Dysrhythmia
    1. Bradycardia
    2. Wide Complex (prolonged QRS, esp. if concurrent Hyperkalemia)
    3. Premature beats
    4. Bigeminy
    5. Paroxysmal Atrial Tachycardia with 2:1 AV Block
    6. Atrial Fibrillation
    7. Nodal rhythm
    8. Ventricular Tachycardia
  2. T Wave Inversion
  3. Sagging or "scooped out" ST Depression
  4. PR Interval increased or prolonged (first degree AV Block)

IX. Differential Diagnosis

  1. See Unknown Ingestion
  2. Bradycardia and Hypotension
    1. Beta Blocker Overdose
    2. Calcium Channel Blocker Overdose
    3. Clonidine Overdose (and similar Clonidine effect such as with afrin)
    4. Digoxin

X. Management

  1. Stop Digoxin
  2. Consider Activated Charcoal in acute ingestions within prior 1 hour
  3. Correct Hypokalemia and Hyperkalemia (and other Electrolyte abnormalities)
    1. Use caution if Heart Block is present
    2. Hyperkalemia is associated with increased mortality
  4. Treat associated Arrhythmias appropriately
    1. Follow ACLS protocol
    2. Atropine may be used prn Bradycardia (esp. when Anti-Digoxin Antibodies are not available)
  5. Rehydrate to improve Renal Function and correct Hypotension refractory to Anti-Digoxin Antibodies
    1. Improved Renal Function will lower Digoxin levels
  6. Avoid potentially harmful interventions
    1. Calcium infusion (e.g. Calcium Chloride or Calcium Gluconate)
      1. "Stone heart" theoretical concern that intracellular Calcium is already high in Digoxin Toxicity
      2. However original theory was from the 1950s and recent studies fail to find significant effect
      3. May still be needed in severe Hyperkalemia
      4. Levine (2011) J Emerg Med 40(1):41-6 +PMID:19201134 [PubMed]
    2. Catecholamines
    3. Electrical Cardioversion or Transcutaneous Pacing
      1. Digoxin Toxicity results in a hyperexcitable Myocardium at risk for malignant Arrhythmia (VF, VT)
      2. Safe if Digoxin Level is under 2 ng/ml
      3. Use lowest possible energy if needed (start at 10-20 J and increase in 10-20 J increments)
  7. Facilitate Digitalis neutralization and elimination
    1. Anti-Digoxin antibodies (see below)
    2. Dialysis (consider in refractory toxicity)
  8. Measures for refractory cardiovascular collapse
    1. Extracorporeal Membrane Oxygenation (VA-ECMO)

XI. Management: Anti-Digoxin Antibodies

  1. DigiFab (or DigitalisAntibody Fragment Therarapy, preferred over Digibind)
    1. Mechanism
      1. Binds free Digoxin and complexes are renally excreted
    2. Indications
      1. Digoxin Toxicity (Dysrhythmia, Serum Potassium >5.5, Altered Mental Status)
      2. Acute Digoxin ingestion >10 mg in adults and >4 mg (or 0.1 mg/kg) in children
      3. Chronic Digoxin Toxicity with significant Dysrhythmia or Hyperkalemia
    3. Dosing
      1. General
        1. One vial or 40 mg binds 0.5 mg Digoxin
        2. Administer by slow IV push
      2. Acute toxicity
        1. Known ingestion acute dose: 1.6 x (Digoxin mg ingested)
        2. Stable: 5 vials of DigiFab in adults or children (repeat as needed)
        3. Hemodynamically unstable: 10 to 20 vials DigiFab in adults (10 vials in children)
          1. Do not wait for Digoxin level in life threatening known Poisoning
        4. Reevaluate in 30 minutes
      3. Chronic toxicity
        1. Empiric dose: 3 to 6 vials for adults (1-2 vials for children)
        2. Calculated dose
          1. Based on serum Digoxin level taken 6 hours after last dose
          2. Number of vials = (Digoxin level ng/ml) x WtKg/100
    4. Adverse effects
      1. Postural Hypotension
      2. Hypokalemia
      3. Allergic Reactions (less common than with Digibind)
    5. Efficacy
      1. Only partial benefit in chronic toxicity (lowers level but does not correct Hyperkalemia or Bradycardia)
      2. Chan (2016) Clin Toxicol 54(6):488-94 +PMID: 27118413 [PubMed]
    6. References
      1. Watts and Lovecchio (2016) Crit Dec Emerg Med 30(12): 24
  2. Digibind (40 mg/vial)
    1. Replaced by DigiFab (due to fewer Hypersensitivity Reaction)
    2. Indications
      1. Massive Digoxin Overdose
      2. Refractory Digitalis Toxicity
    3. Calculate vials needed based on Digoxin level
    4. Vials = (Digoxin Level in ng/ml) x (WtKg)/100
      1. Typical Digoxin Poisoning requires 5-10 vials

XII. References

  1. Hendrickson, Swadron and Nordt in Herbert (2020) 20(2): 6-7
  2. Orman and Hayes in Herbert (2017) EM:Rap 17(4): 6-7
  3. Vega (2024) Am Fam Physician 109(2): 143-53 [PubMed]

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