Management of Digoxin Toxicity

A 78-year-old woman is brought in by EMS after her husband called 911 for increased confusion associated with intractable vomiting. On arrival to the emergency department (ED), the patient is altered with a heart rate of 48 and a blood pressure of 68 over palpation.  EMS was able to insert a peripheral IV line and provide initial fluid resuscitation. The patients medication list includes Metformin, Furosemide, Diltiazem, Digoxin, and baby aspirin.  The cardiac monitor displays a bradycardic irregularly irregular rhythm.  As you jump into resuscitating this patient, you wonder:

  • Is this digoxin toxicity? 
  • Do I need to start pressors?
  • If the patient’s bradycardia does not respond to Atropine, what should I do next?
  • What other tests need to be considered immediately?

What is Digoxin?

  • Digoxin is a cardioactive glycoside that was derived from the foxglove plant Digitalis Purpurea. 
  • Digoxin was first approved by the FDA in 1954 for the treatment of atrial flutter (Aflutter), atrial fibrillation (Afib) and heart failure (HF).

What kind of patients are on Digoxin?

  • Digoxin has shown beneficial effects on patients with heart failure with reduced ejected fraction, usually <40% (Fu 2020)
  • It has also been used for rate control in AFib and Aflutter that is refractory to traditional medication
Mechanism of Action of Digitalis Reilly EF, Stawicki SP. High‑yield toxicology

Pathogenesis of Digoxin Toxicity (Smith 1988, David 2020): 

    • Digoxin has a narrow therapeutic index
    • Primarily works on the Na+/K+ pump of the cardiac myocyte
      • Digoxin inhibits the Na+/K+ pump
      • Leads to an increased Intracellular Na+ and decreased Intracellular K+
      • It is the Na+/K+ in the skeletal muscles that cause hyperkalemia (Kashani 2005) as skeletal muscle is the largest reservoir for potassium in the body
    • Increased intracellular Na+ prevents the Na+/Ca2+ channel leading to increased intracellular Ca2+
    • Intracellular calcium within the cardiac myocytes results in increased inotropy
    • This will cause increased irritability of cardiac myocytes leading to tachy/brady dysrhythmias (Smith 1988, Ershad 2020)

Factors Contributing to Digoxin Toxicity (Gheorghiade 2004):

    • Increased drug in the body
      • Intentional/Unintentional overdose
      • Ingestion of plants or animals containing cardiac glycosides
        • Digitalis, foxglove, red quill, lily of the valley, oleander, yellow oleander, pong pong, cerbera manghas, dogbane, aconite, bufo toads, Colorado river toad
    • Decreased elimination
      • Renal insufficiency: prolongs the half-life and increases volume of distribution
    • Metabolic disturbances
      • Hypokalemia: can sensitize myocardium to digoxin, diuretics 
      • Hypomagnesemia: can sensitize myocardium to digoxin and increases activity of cardiac glycosides
      • Hypernatremia
      • Hypercalcemia: predisposes patient to toxicity
      • Acid-base disturbance: can cause electrolytes changes
      • Polypharmacy: Diuretics, medication that affects the renal function

Serum Levels (Heart Failure Society of America 2010):

    • Ideal therapeutic levels should be maintained between 0.8-2.0 ng/ml 
      • May take up to 7 days to reach steady state (Oncu 2018) 
    • Consider toxicity when levels start approaching >2 ng/ml 

Acute Symptomatology:

      • GI: Nausea and vomiting usually in the first 2-4 hours
      • CNS: Lethargy and confusion
      • Cardiac: AV blocks, PVCs, Bradydysrhythmias, ventricular arrythmias
      • Hyperkalemia

Chronic Symptomatology:

      • Features are similar to acute intoxication
      • Visual disturbances: green-yellow visual disturbances
      • Low K+ levels may be secondary to concomitant use of diuretics (Kashani 2005)
Figure 2 ECG changes in Digoxin effect (Burns 2021)

ECG features demonstrating Digoxin Effect

      • Shortened Atrial and Ventricular refractory periods leading to ECG morphology
      • A classic ECG sign in digoxin effect is an ST segment depression in a concave manner (Ma 2001)
      • Scooped ST (Dali) or Hockey stick
      • Digoxin Effect does not imply Digoxin Toxicity

ECG features in Digoxin Toxicity: 

      • Digoxin can cause a large variety of EKG abnormalities (Richter 2009)
      • PVCs is the most common arrythmia (Kashani 2005)
      • Biphasic T wave: a prominent U followed by a flattened T
      • Shortened QT interval
      • Sinus Bradycardia

        ECG changes in the setting of Digoxin effect (Burns 2021)
      • Slow Afib (not Afib with RVR)
      • AV blocks
          • Digoxin primarily affects the level of the AV node, decreasing conduction there and increasing the refractory period
          • With higher concentrations, Type I AV blocks may progress to a Type II Mobitz I pattern
          • Mobitz II is highly unlikely to occur as it originates below the AV node
          • A higher degree AV block in AFib will produce a junctional rhythm which can produce a regularized R-R pattern leading to a regular AFib pattern (figure 4).
    • Ventricular Tachycardia
          • Impulses from the lower AV node will go down the left and right bundle branches leading to a Bidirectional Ventricular Tachycardia (Richter 2009) (figure 5).
Regular Afib in the setting of digoxin toxicity (Burns 2021)

Management of digoxin toxicity:

  • Acute
    • ECG, cardiac monitor, IV access
    • BMP and Serum Digoxin level
      • Evaluate for elevated digoxin levels in acute toxicity
        • For acute ingestions obtain levels on presentation and 6 hours after known ingestion
      • Evaluate for hyperkalemia in acute toxicity as there is correlation with severity
    • Digibind is your treatment of choice in hyperkalemia in the setting of Digoxin Toxicity
    • If hyperkalemia is present treat with Insulin, albuterol, and Calcium or follow your institution’s hyperkalemia protocol
      • These are temporizing measures at best
      • Theoretical idea of stone heart has been disproven (Levine, 2011)
    • Evaluate for life threatening arrythmias
    • Give antidote if indicated

Indications for antidote (Ershad 2020):

      • Any life-threatening digoxin related dysrhythmia
      • Refractory hyperkalemia
      • Digoxin level >15 at any time 
      • Digoxin level >10, 6 hours following ingestion
      • Acute ingestion of >10mg in adults
      • Acute ingestion of >4mg (>0.1 mg/kg) in peds
      • Chronic elevation of digoxin concentration with AMS, cardiac dysrhythmia, or severe GI symptoms
      • Do not wait for digoxin level if clinical presentation of digoxin toxicity is the likely cause
    • Consider Atropine 0.5 mg IV in bradydysrhythmia or high degree AV block
    • Transvenous pacer wires may cause myocardial irritability (Kashani 2005)
    • ECMO
      • Not well studied, not indicated for removal of digoxin (Mowry 2015)
  • Chronic
  • Serum digoxin Level can be misleading
    • It does not have to be >2 to have toxic effects
    • Patients may be symptomatic at therapeutic levels
  • Check Electrolyte levels
    • Potassium may be low secondary to concomitant use of diuretics which can potentiate toxic effect
    • Replete magnesium levels as hypomagnesemia can potentiate digoxin toxicity
  • Always check renal function
  • Give antidote if indicated
  • Consult your local poison control
  • Activated charcoal is an adjunctive treatment.  Consider if known ingestion time was < 1hr ago
    • 1g/kg to a max of 50g

Contraindications for antidote:

      • No absolute contraindications
      • Caution in:
        • Sinus node disease
        • Patients with WPW as it could increase anterograde conduction leading to ventricular fibrillation
        • ESRD
        • Known hypersensitivity to digoxin or other digitalis derived products

Antidote (Digibind) Equation (Pincus 2016):

  • Each vial contains 38 mg of antidote (Digibind) which will bind to 50 mcg of digoxin (Ershad 2020)
      • If the quantity is known but not the dose
        • number of vials required = 1.6 x (Ingested dose in milligrams)
      • If the level of digoxin is known
        • Number of vials required = (Serum Digoxin Level) x (Weight in kilograms)/100
      • Pediatrics dose is 5 vials
      • Acute ingestion 
        • 5 vials if patient is hemodynamically stable
        • 10 vials if patient hemodynamically unstable
        • 20 vials if patient is cardiac arrest
      • Chronic ingestion
    • Adults 3-6 vials
    • Pediatrics 1-2 vials
      • Pregnancy
        • It is acceptable to give in pregnancy when necessary (pregnancy category C)

Take Home Points

  • Although the overall prevalence of digoxin toxicity seems to be decreasing, one must think of this toxicity when facing a patient with bradycardia and “something else”
  • Obtain a 12 lead EKG, serum electrolytes and serum digoxin level initially
  • Digoxin toxicity may mimic several different EKG patterns
  • “Scooped” ST segments signify that the patient is taking digoxin (“dig effect”) and is not an indication of digoxin toxicity
  • Simple doses to remember for Digibind
    • 5 vials in hemodynamically stable patients
    • 10 vials in unstable patients
    • 20 vials in the setting of cardiac arrest
    • Of note: consult your pharmacy to see how many vials are available at your local hospital

Authors: Santiago Lopez, MD PGY3 Good Samaritan Hospital, Katrina D’Amore, DO Good Samaritan Hospital, John Kashani DO, FACMT St. Joseph’s University Medical Center

Post Peer Reviewed By: Anand Swaminathan, MD (@EMSwami) and Salim R. Rezaie, MD (Twitter: @srrezaie)

Cite this article as: Anand Swaminathan, "Management of Digoxin Toxicity", REBEL EM blog, February 21, 2022. Available at: https://rebelem.com/management-of-digoxin-toxicity/.
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Anand Swaminathan

Clinical Assistant Professor of Emergency Medicine at St. Joe's Regional Medical Center (Paterson, NJ)
REBEL EM Associate Editor and Author

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