Emergent Management of Digitalis Toxicity 

In considering the emergent management of digoxin toxicity, keep in mind that the relationship between digoxin toxicity and the serum digoxin level is complex. Clinical toxicity results from the interactions between digitalis, various electrolyte abnormalities, and their combined effect on the sodium-potassium adenosine triphosphatase (Na⁺/K⁺ ATPase) pump.^[1]

Infants and children taking digoxin tolerate higher doses and plasma levels. The pediatric volume of distribution is greater and the half-life of digoxin is less. Pediatric myocardial cells may be less sensitive to the toxic effects of digoxin; decreased sensitivity to dysrhythmias by infants and children may contribute to increased tolerance to digoxin.

Consultations

Consultations with the following can be beneficial:

• Medical toxicologist
• Cardiology
• Regional poison control center

Prehospital care

Oxygen, cardiac monitoring, intravenous (IV) access, and transport are usually the only requirements. Atropine is indicated for hemodynamically unstable bradyarrhythmias; lidocaine is indicated for ventricular tachycardia.

Infants and children manifest the same signs of toxicity as adults, and the treatment of toxicity in pediatric patients is the same as in adults.^[2]

Guide treatment of patients with digoxin toxicity by their signs and symptoms and the specific toxic effects. Treatment should not necessarily be driven by digoxin levels alone. Therapeutic options range from simply discontinuing digoxin therapy for patients who are stable with chronic toxicity to fab fragments, pacemaker, antiarrhythmic drugs, magnesium, and hemodialysis for acute severe ingestions.

Initiate supportive therapy with oxygen, cardiac monitoring, and IV access. Activated charcoal is indicated for acute overdose or accidental ingestion. Cholestyramine binds enterohepatically-recycled digoxin and digitoxin, although no outcome studies have been performed.

Gastric lavage increases vagal tone and may precipitate or worsen arrhythmias. Consider pretreatment with atropine if gastric lavage is performed. The availability of a digitalis-fab antibodies (Digibind) antidote usually renders gastric lavage unnecessary.

Arrhythmias

Management of dysrhythmias varies, depending on the presence or absence of hemodynamic instability, the nature of the arrhythmia, the presence or absence of electrolyte disturbances, and the preferences of toxicology and/or cardiology consultants. (See the image below.)

Bradyarrhythmias that are hemodynamically stable may be treated with observation and discontinuation of the drug. Ensure proper hydration to optimize renal clearance of excess drug. Gastrointestinal (GI) binding agents (eg, charcoal, cholestyramine) may be utilized to bind enterohepatically-recycled digitalis.

Hemodynamically stable supraventricular arrhythmias may be treated conservatively with observation and discontinuation of digoxin. In the setting of rate-related ischemia or hemodynamic instability, Digibind is the treatment of choice.

Short-acting beta blockers (eg, esmolol) may be helpful for supraventricular tachyarrhythmias with rapid ventricular rates, but advanced or complete atrioventricular (AV) block may be precipitated. Calcium channel blockers are contraindicated because they may increase digoxin levels.

Hemodynamically unstable bradyarrhythmias respond best to Digibind. Atropine may be used for temporary adjuncts because it improves AV nodal conduction. Cardiac pacing has been used successfully, but it can lower the fibrillatory threshold and induce arrhythmias.

Premature ventricular contractions (PVCs), bigeminy, or trigeminy may be observed unless the patient is hemodynamically unstable, in which case lidocaine may be effective.

Ventricular tachycardia responds best to Digibind. Lidocaine and phenytoin may be useful because they depress the enhanced ventricular automaticity without significantly slowing AV conduction. Phenytoin may reverse digitalis-induced prolongation of AV nodal conduction. Phenytoin has been shown to dissociate the inotropic and dysrhythmic action of digitalis, thus suppressing digitalis-induced tachydysrhythmias without diminishing the contractile effects. In addition, phenytoin can terminate supraventricular dysrhythmias induced by digitalis, whereas lidocaine has not been as effective.

Lidocaine may be given in boluses of 100 mg, according to advanced cardiac life support (ACLS) guidelines. If lidocaine is successful, begin a maintenance infusion at 1-4 mg/min. Phenytoin has been administered in boluses of 100 mg every 5-10 minutes up to a loading dose of 15 mg/kg. Avoid procainamide and bretylium.

Asystole and ventricular fibrillation are very ominous findings. Digibind is indicated; however, its effect is limited by poor cardiac blood flow. Nevertheless, the use of digoxin-fab fragments has been associated with a 50% survival rate in isolated case reports.

Quinidine, procainamide, and bretylium are contraindicated. Quinidine and procainamide worsen AV, sinoatrial (SA), and His-Purkinje conductivity. Additionally, quinidine reduces digoxin tissue binding and renal clearance, thereby increasing digoxin levels. Bretylium can precipitate ventricular dysrhythmia.

Cardioversion is relatively contraindicated because asystole or ventricular fibrillation may be precipitated.

Electrolytes

Consider magnesium therapy as a temporizing antiarrhythmic agent until fab fragments are available. It may be life saving when ventricular tachycardia or ventricular fibrillation is present. IV magnesium sulfate, 2 g over 5 minutes, has been shown to terminate digoxin-toxic cardiac arrhythmias in patients with and without overt disease. Aside from successful replacement of intracellular magnesium, it also may act as an indirect antagonist of digoxin at the supraphysiologic level. After an initial bolus of 2 g intravenously, a maintenance infusion at 1-2 g/h is initiated. Monitor magnesium levels approximately every 2 hours. The therapeutic goal is a level between 4 and 5 mEq/L.

Correct electrolyte abnormalities, especially hypokalemia and hypomagnesemia. Dysrhythmias may be reversed with correction of electrolyte imbalances. Treat hyperkalemia when the K⁺ level is greater than 5.5 mEq/L.

Calcium is not recommended to treat hyperkalemia in this setting, because ventricular tachycardia or ventricular fibrillation may be precipitated. This is based on the fact that intracellular calcium levels are already high in the setting of digoxin toxicity. However, anecdotal case reports and animal studies have been published that refute the dangers of calcium administration. Unless the patient is in extremis, other measures should be preferentially used to treat hyperkalemia.

Sodium bicarbonate and/or glucose and insulin are indicated. Treatment with digoxin-fab fragments is indicated for hyperkalemia with K⁺ level greater than 5 mEq/L.

Kayexalate (0.5 g/kg PO) also is helpful in binding potassium and enterohepatically recycled digitalis. However, digoxin-induced hyperkalemia reflects an extracellular shift, not an increase in total body potassium.

Caution is indicated when using Kayexalate concurrently with insulin/glucose/bicarbonate and/or Digibind, because hypokalemia may be precipitated, which may worsen clinical toxicity.

Digibind

Digoxin-fab fragments (Digibind) are generally indicated for the following:

• Dysrhythmias associated with hemodynamic instability
• Altered mental status attributed to digoxin toxicity
• Hyperkalemia with K⁺ greater than 5 mEq/L
• Serum digoxin level greater than 10 ng/mL in adults at steady state (ie, 6-8 h post acute ingestion or at baseline in the clinical setting of chronic toxicity)
• Ingestion greater than 10 mg in adults (40 x 0.25 mg tablets) or greater than 0.3 mg/kg in children

Admission criteria include the following:

• New cardiac dysrhythmias
• Severe bradyarrhythmias
• Advanced AV block
• Acute prolongation of the QRS interval
• Severe electrolyte abnormalities, especially hypokalemia or hyperkalemia
• Dehydration
• Inability to care for self
• Suicidal ideation

Admit patients with cardiac abnormalities to a monitored bed. Intensive care unit (ICU) admission criteria include the following:

• Hemodynamic instability
• Refractory dysrhythmias
• Hyperkalemia
• Renal failure

Admit patients receiving Digibind to the ICU or critical care unit (CCU).

Transfer

Transfer may be indicated if patient is unstable and the hospital has no ICU or CCU capabilities or no appropriate consultants (eg, toxicologist, cardiologist, intensivist) or when Digibind (if indicated) is not available. Treatment is best discussed with the regional poison control center and the patient's primary practitioner.

Observe patients with acute ingestion on a cardiac monitor for 6 hours. In the absence of cardiac dysrhythmias, toxic digoxin levels, or hyperkalemia, patients may be discharged with appropriate follow-up care.

Patients with chronic toxicity and noncardiac symptoms may be discharged if factors that led to the toxicity have been corrected (eg, electrolyte disorders, dehydration, drug-drug interactions) and proper care can be ensured. Discontinue use of the drug. Arrange follow-up care in the next 24 hours with a primary care provider. Intentional overdose requires psychiatric follow-up.