What are the signs and symptoms of Digoxin (digitalis glycoside) toxicity?

From the Guidelines

Digoxin toxicity is a life-threatening condition that requires immediate medical attention, and its management should be guided by the severity of symptoms and serum digoxin concentrations, with digoxin-specific antibody fragments being the treatment of choice for severe intoxication 1.

Signs and Symptoms of Digoxin Toxicity

Digoxin toxicity presents with a range of signs and symptoms affecting multiple body systems, including:

• Gastrointestinal disturbances such as nausea, vomiting, abdominal pain, and diarrhea
• Neurological symptoms like confusion, disorientation, headache, fatigue, weakness, and visual disturbances
• Cardiac manifestations including bradycardia, various arrhythmias, ventricular ectopy, and potentially life-threatening ventricular arrhythmias
• Hyperkalemia may occur in severe toxicity

Diagnosis and Management

If toxicity is suspected, digoxin levels should be measured, though symptoms can occur even within the therapeutic range of 0.8-2.0 ng/mL 1. Management includes:

• Discontinuation of digoxin
• Correction of electrolyte abnormalities, particularly potassium
• Administration of digoxin-specific antibody fragments (Digibind) in severe cases, with a clinical response rate as high as 80% to 90% 1
• Monitoring of potassium levels, as adverse events attributable to digoxin Fab therapy are rare but can include hypokalemia

Treatment of Severe Intoxication

For severe intoxication, characterized by serum digoxin concentrations exceeding 4 ng/mL and serious arrhythmias such as ventricular tachycardia, digoxin-specific Fab antibody is the treatment of choice, with doses lower than the full neutralizing dose being sufficient as long as cardiac arrest is not imminent 1. The dosage of digoxin Fab depends on the estimated amount of digoxin ingested, with each vial of 40 mg binding approximately 0.5 mg of digoxin 1. Repeat dosing may be necessary, particularly in the setting of chronic use.

From the FDA Drug Label

In recent controlled clinical trials, in patients with predominantly mild to moderate heart failure, the incidence of adverse experiences was comparable in patients taking digoxin and in those taking placebo. In a large mortality trial, the incidence of hospitalization for suspected digoxin toxicity was 2% in patients taking digoxin compared to 0. 9% in patients taking placebo. In this trial, the most common manifestations of digoxin toxicity included gastrointestinal and cardiac disturbances; CNS manifestations were less common. High doses of digoxin may produce a variety of rhythm disturbances, such as first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation. Digoxin produces PR prolongation and ST segment depression which should not by themselves be considered digoxin toxicity. Cardiac toxicity can also occur at therapeutic doses in patients who have conditions which may alter their sensitivity to digoxin Adults: Cardiac: Digoxin may cause anorexia, nausea, vomiting, and diarrhea Rarely, the use of digoxin has been associated with abdominal pain, intestinal ischemia, and hemorrhagic necrosis of the intestines. Gastrointestinal: Digoxin can produce visual disturbances (blurred or yellow vision), headache, weakness, dizziness, apathy, confusion, and mental disturbances (such as anxiety, depression, delirium, and hallucination) CNS: Gynecomastia has been occasionally observed following the prolonged use of digoxin. Thrombocytopenia and maculopapular rash and other skin reactions have been rarely observed. Other: The side effects of digoxin in infants and children differ from those seen in adults in several respects. Although digoxin may produce anorexia, nausea, vomiting, diarrhea, and CNS disturbances in young patients, these are rarely the initial symptoms of overdosage Rather, the earliest and most frequent manifestation of excessive dosing with digoxin in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia. In children, the use of digoxin may produce any arrhythmia The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin, until further evaluation proves otherwise.

The signs and symptoms of digoxin toxicity include:

• Cardiac disturbances:
  • First-degree, second-degree (Wenckebach), or third-degree heart block (including asystole)
  • Atrial tachycardia with block
  • AV dissociation
  • Accelerated junctional (nodal) rhythm
  • Unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy)
  • Ventricular tachycardia
  • Ventricular fibrillation
• Gastrointestinal disturbances:
  • Anorexia
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
  • Intestinal ischemia
  • Hemorrhagic necrosis of the intestines
• CNS manifestations:
  • Visual disturbances (blurred or yellow vision)
  • Headache
  • Weakness
  • Dizziness
  • Apathy
  • Confusion
  • Mental disturbances (such as anxiety, depression, delirium, and hallucination)
• Other:
  • Gynecomastia
  • Thrombocytopenia
  • Maculopapular rash and other skin reactions In infants and children, the earliest and most frequent manifestation of excessive dosing with digoxin is the appearance of cardiac arrhythmias, including sinus bradycardia 2.

From the Research

Digoxin Toxicity Signs and Symptoms

• Anorexia, nausea, vomiting, and neurological symptoms are common signs of digoxin toxicity 3
• Fatal arrhythmias can also be triggered by digoxin toxicity 3
• Ventricular arrhythmias are a significant concern in patients with elevated digoxin concentrations 4
• Other signs and symptoms of toxicity may include changes in heart rate and potassium concentration 4

Treatment of Digoxin Toxicity

• Digoxin-specific antibody fragments are safe and effective in severe toxicity 3
• The amount ingested and serum digoxin concentration can help determine the dose required, but are not essential 3
• A smaller initial loading dose of digoxin-specific antibody fragments may be sufficient, with further doses given as needed 5
• Monitoring should continue after treatment due to the risk of rebound toxicity 3

Clinical Outcomes of Digoxin Toxicity Treatment

• A study comparing treatment with digoxin-specific antibody fragments to supportive care found no significant difference in mortality or length of stay 4
• The study suggested that patients with chronic digoxin poisoning may derive little benefit from routine use of digoxin-specific antibody fragments 4
• Patients with multiple co-morbidities may require individualized treatment approaches 4