INDEX

    Cardiac Glycosides Overdose

    Cardiovascular, Toxicology

    Last Updated Oct 20, 2020
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    Context

    • Digoxin (Lanoxin®) is a synthetic cardiac glycoside used in treatment of congestive heart failure, atrial fibrillation and flutter.
    • Natural cardiac glycosides include various plants (foxglove, lily-of-the-valley, oleander), and certain toad venoms (Bufo spp).

    Signs and Symptoms

    • Toxicity can occur with acute or chronic exposures.
    • Chronic toxicity is more common in elderly patients with unrecognized impaired renal function or drug interactions that affect digoxin clearance.
    • Acute toxicity occurs with intentional overdose, exposure to cardiac glycoside-containing plants or remedies, or iatrogenic errors.

    Cardiac

    • Common: Bradycardia (can be severe), all degrees of heart block, almost any type of atrial or ventricular dysrhythmia.
    • Less common: Asystole and/or cardiac arrest.

    Non-cardiac

    • Common: Nausea and vomiting, confusion, disorientation.
    • Uncommon: Visual disturbances.

    Laboratory abnormalities

    • Common: Hyperkalemia (classic in acute toxicity), hypokalemia (chronic toxicity).
    • Uncommon: Hypomagnesemia (chronic toxicity).

    ECG changes

    • Almost any type of atrial or ventricular dysrhythmia can be seen.
    • Bradycardia (can be severe).
    • Any degree of heart block.
    • Junctional or ventricular tachycardia, ectopy.
    • Premature ventricular contractions are common.
    • Accelerated junctional rhythm with or without high-degree AV block.

    Typical course

    • 60-85% of pharmaceutical digoxin is absorbed following ingestion.
    • Peak effects occur within 6-12 hours post ingestion.
    • In overdose, cardiac toxicity may occur within 30 minutes.
    • Not removed by extracorporeal means.

    Mechanism of Toxicity

    • Inhibits cardiac and skeletal muscle Na-K-ATPase pumps resulting in increased intracellular sodium which increases activity of Na-Ca pump and intracellular calcium, leading to enhanced myocardial contractility and automaticity.
    • At toxic levels, increased automaticity contributes to tachydysrhythmias.
    • Inhibition of Na-K-ATPase also results in hyperkalemia.
    • Hypokalemia may be seen in chronic overdose
    • Death is usually due to asystolic cardiac arrest.

    Toxic Dose

    • Toxic dose is not well established.
    • “Therapeutic” digoxin levels range from 0.64-1.28 nmol/L (0.5-1.0 ng/mL); however, cardiotoxicity has been reported within therapeutic range, particularly in patients on chronic therapy and in patients with underlying cardiovascular disease.
    • Ingestion of > 10 mg by an adult or > 4 mg by a child may be fatal.
    • In patients with heart disease on chronic digoxin therapy, acute ingestion of < 2 mg may produce toxicity.

    Diagnostic Process

    • Serum levels do not correlate well with toxic effects:
      • interpret with clinical presentation and laboratory data.
    • Levels drawn < 6-8 hours post-ingestion are higher than post-distribution phase levels and do not correlate with clinical effects.
    • Early levels should be repeated within 2-4 hours if patient is showing no evidence of clinical toxicity (particularly if time of ingestion is unknown).
    • Many other cardiac glycosides cross-react with standard digoxin immunoassay; correlate with clinical effects.

    Clinical Pitfalls

    • Relying on digoxin levels to confirm diagnosis.
    • The presence of concomitant cardiac medications contributing to the clinical picture.

    Recommended Treatment

    • Consult BC Drug and Poison Information Centre (DPIC) for case discussion.
      • 604-682-5050, 1-800-567-8911, dpic.org.
    • Administer activated charcoal in recent, acute ingestion. Repeat doses of activated charcoal have not been shown to affect outcome.
    • Monitor vital signs, ECG, serum electrolytes, renal function.
    • Monitor specific free serum digoxin levels (usually NOT available). Note: Serum total digoxin levels measured by standard immunoassays after administration of digoxin-specific antibodies are unreliable and cannot be used to monitor therapy.
    • Antidotal therapy: Digoxin-specific antibodies, Fab fragments (DigiFab®). Rapidly reverses toxic cardiac and extracardiac effects of acute or chronic digoxin toxicity in most patients
        • Indications
          • Any potential digoxin-related life-threatening dysrhythmia OR
          • Serum digoxin level > 12.8 nmol/L (10 ng/mL) measured > 6 hours post-ingestion in an acute ingestion, OR
          • Acute ingestion of > 10 mg in an adult (4 mg in a child), OR
          • Serum potassium > 5.5 mmol/L in an acute ingestion.
        • Dosing of antidote is based on serum digoxin level, or the amount ingested.
        • Other cardiac glycoside poisonings.
          • DigiFab ® can be used to reverse the effects of non-pharmaceutical cardiac glycosides.
        • Empiric dosing of 10 vials (5 in children) in the following situations:
          • Strong suspicion of digoxin toxicity in the absence of serum levels.
          • Non-pharmaceutical glucoside exposure.
    • Non-antidotal therapy (if antidote is not immediately available)
      • Atropine for bradycardia and varying degrees of heart block:
        • 0.5 – 1 mg  q 15 minutes up to maximum of 3 mg.
      • Magnesium may be beneficial even in patients with normal levels:
        • MgSO4 2 grams IV over 15 minutes.
      • External transvenous pacing in patients with severe bradycardia and/or slow ventricular rate due to refractory AV block (caution: insertion of transvenous pacemakers may worsen some dysrhythmias).
      • Cardioversion may precipitate serious dysrhythmias.
    • Avoid
      • Beta-blockers, procainamide, amiodarone – may worsen AV block.
    • Hyperkalemia
      • Usually responds to antidotal therapy.
      • If antidote not immediately available, treatment with intravenous insulin/dextrose, and/or sodium bicarbonate may be useful.
        • Humulin R 10 Units IV + 50 CC D50W.
        • NaHCO3 1 – 2 ampules (1 ml/kg).
      • Theoretical risk with IV calcium as may precipitate dysrhythmias; however, case reports of inadvertent calcium administration resulted in no adverse effects.
    • Hypokalemia (usually in chronic toxicity)
      • Replace and monitor closely as administration of antidote may result in rapid drop in serum potassium.
    • Hemodialysis is not useful to remove digoxin but may be required to treat renal failure, or life-threatening hyperkalemia unresponsive to other therapeutic measures.
    • Monitoring
      • Clinical symptoms and dysrhythmias generally resolve within 60-90 minutes following antidote administration. Persistent symptoms and/or arrhythmias should prompt investigations for alternative diagnoses.

    Criteria For Hospital Admission

    • Dysrhythmias, hypotension or severe electrolyte disturbances will require admission to a monitored setting (telemetry, CCU, ICU).

    Criteria For Transfer To Another Facility

    Criteria For Safe Discharge Home

    • Asymptomatic patients should be monitored for at least 12 hours after ingestion as toxicity can be delayed.
    • Patients should be monitored a minimum of 2-3 days following cardiac glycoside toxicity.
    • Psychiatric consultation should be sought if the overdose was intentional.

    Quality Of Evidence?

    Justification

    Case reports and case series.

    Low

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