Digoxin toxicity

Background

• Mechanism of action
  • Positive inotropic effect
    • Inhibits Na-K pump -> incr extracelluar K, incr intracellular Na -> incr intracellular Ca
  • Increases vagal tone
    • Can lead to bradyarrhythmias (esp in young)
  • Increases automaticity
    • Can lead to tachyarrhythmias (esp in elderly)
• Renally cleared
• Hemodialysis does not work
• Can also be found in nature: Foxglove, Oleander, certain toads

Risk Factors

• Electrolyte Imbalance
  • Hyperkalemia, Hypomagnesemia, Hypercalcemia
• Hypovolemia
• Renal insufficiency
• Cardiac Ischemia
• Hypothyroidism
• Meds
  • CCBs, amiodarone

Acute vs. Chronic

• Acute
  • Lower mortality
  • Bradycardia / AV block more common
  • Younger patients
  • Often don't need Fab
• Chronic
  • Higher mortality
  • Ventricular dysrhythmias more common
  • Older patients
  • Often need Fab therapy

Clinical Features

Cardiac

Digitalis effect

• Syncope
• Dysrhythmias
  • PVCs
  • Bradycardia
  • SVT w/ AV block
  • Junctional escape
  • Ventricular dysrhythmia, including bidirectional V-tach (esp in chronic toxicity)
• Digitalis Effect (seen with therapeutic levels; not indicative of toxicity)
  • T wave changes (flattening or inversion)
  • QT interval shortening
  • Scooped ST segments with depression in lateral leads
  • Increased U-wave amplitude

GI

• Often the earliest manifestation of toxicity
  • Nausea/vomiting
  • Abdominal Pain

Neuro

• Confusion
• Weakness
• Visual disturbances
  • Yellow halos
  • Scotomas
• Delirium

Differential Diagnosis

• Calcium channel blocker toxicity
• Beta blocker toxicity
• Clonidine toxicity
• Organophosphate toxicity
• Sick sinus syndrome

Diagnosis

Work-Up

• Digoxin level
  • Only useful prior to administration of Fab (otherwise becomes falsely elevated)
• Chemistry
• Urine output
• ECG (serial)

Evaluation

• Must use H&P and labs in combination; no single element excludes or confirms the diagnosis
• Digoxin level
  • Normal = 0.5-2 ng/mL (ideal = 0.7-1.1)
    • May have toxicity even with "therapeutic" levels (especially with chronic toxicity)
  • Measure at least 6hr after acute ingestion (if stable); immediately for chronic ingestion
    • If measure before this may be falsely elevated due to incomplete drug distribution
• Potassium level
  • Acute toxicity: Degree of Hyperkalemia correlates wwith degree of toxicity
  • Chronic toxicity: K+ may be normal/low (concomitant diuretic use) or high (renal failure)

Management

Calcium is theoretically contradindicated in Dig Toxicity (see Stone Heart)

• Digoxin Immune Fab
  • Indications
    • Ventricular dysrhythmias
    • Symptomatic bradycardias unresponsive to atropine
    • Hyerkalemia >5.0 mEq/L secondary to digitalis intoxicaiton
    • Coningestions of cardiotoxic drugs (beta-blockers, cyclic antidepressants)
    • Acute digoxin ingestion of greater than 10mg in adults or greater than 4mg in children
    • Acute digoxin ingestions with post distribution digoxin >10ng/mL (by 6 hours post ingestion)
    • Chronic digoxin ingestion leading to steady state serum digoxin concentrations of >4ng/ml
• Activated Charcoal
  • Questionable efficacy
  • Only an adjunctive tx; NOT an alternative to fab fragment therapy
  • Consider only if present within 1 hr of ingestion
  • 1g/kg (max 50g)

Dysrhythmias

• Digoxin Immune Fab is the agent of choice for all dysrhythmias!
• Cardioversion should only be used as a last resort (may precipitate V-Fib)
  • Consider lower energy settings (25-50J)
• Bradyarrhythmias (symptomatic)
  • Atropine 0.5mg IV
  • Pacing
• Ventricular dysrhythmias
  • Phenytoin
    • Enhances AV conduction
    • Phenytoin: 15-20mg/kg at 50mg/min
    • Fosphenytoin: 15-20mg PE/kg at 100-150mg/min
  • Lidocaine
    • Decreases ventricular automaticity
    • 1-3mg/kg over several minutes; follow by 1-4mg/min
  • Magnesium
    • Many patients have Hypomagnesemia and labs can be unreliable.
    • 2-4 g IV over 20-60 mins

Hyperkalemia

• Treat with Fab, not with usual meds
  • Once Fab is given hyperkalemia will rapidly correct
• If Fab unavailable and hyperkalemia is life-threatening then treat with:
  • Glucose-insulin
  • Sodium bicarb
  • Kayexelate
  • Dialysis
  • Calcium (controversial: some say dangerous, others say not)

Hypokalemia

• Chronic intoxication
  • Raise level to 3.5-4
• Acute intoxication
  • Do not treat (likely that potassium level is rapidly rising)

Hypomagnesemia

• Treat with 1-2g over 10-20 min
  • Monitor for resp depresion
  • Avoid in pts with:
    • Renal failure
    • Bradydysrhythmias/conduction blocks

Disposition

• Admit for signs of toxicity or history of large ingested dose; admit to ICU if Fab given
• Discharge after 12hr observation if asymptomatic after accidental overdose

See Also

• Digoxin Immune Fab
• Toxidromes
• Digoxin

External Links

• MDCalc - Corrected QT Interval