What are the signs of digoxin (digitalis glycoside) toxicity?

Signs of Digoxin Toxicity

Digoxin toxicity presents with a characteristic triad of cardiac arrhythmias, gastrointestinal symptoms, and neurological manifestations, with diagnosis confirmed by serum digoxin levels typically >2 ng/mL, though toxicity can occur even within therapeutic range. 1

Cardiac Manifestations

The cardiac signs are the most critical and potentially life-threatening:

• Enhanced automaticity with conduction block is the hallmark pattern—look for ectopic atrial, junctional, or ventricular beats combined with atrioventricular block 1
• Bidirectional or fascicular ventricular tachycardia is highly specific for digoxin toxicity and should immediately raise suspicion 1
• Conduction disturbances include first-degree, second-degree (Wenckebach), or third-degree heart block, which may progress to asystole 2
• Atrial tachycardia with block, accelerated junctional rhythm, and ventricular ectopy (especially bigeminy or trigeminy) are common 2
• Severe overdose causes hyperkalemia and cardiac standstill 1
• PR prolongation and ST segment depression occur but should not by themselves be considered toxicity 2

Gastrointestinal Manifestations

These are often the earliest symptoms in adults:

• Anorexia, nausea, and vomiting are the most common GI symptoms 1, 2
• Diarrhea and abdominal pain occur frequently 2
• Rarely, intestinal ischemia and hemorrhagic necrosis of the intestines can develop 2

Neurological Manifestations

CNS symptoms are less common but diagnostically important:

• Visual disturbances are classic—blurred vision, yellow-green color vision (xanthopsia), photopsia, and "snowy" vision 1, 2
• Confusion and altered mental status may be the sole presenting feature, especially in elderly patients 1, 3
• Headache, weakness, dizziness, and apathy are frequent 2
• Psychiatric symptoms including anxiety, depression, delirium, and hallucinations can occur 2

Diagnostic Considerations

The diagnosis requires the combination of characteristic arrhythmias, ancillary symptoms, and elevated serum concentrations 1:

• Overt toxicity is commonly associated with serum digoxin levels >2 ng/mL 4, 1
• Toxicity can occur even when serum concentration is within therapeutic range (0.5-1.2 ng/mL), particularly in vulnerable patients 1, 5
• The therapeutic window is narrow, with toxic effects typically occurring at concentrations >2.8 ng/mL 6

Critical Risk Factors

These conditions significantly increase susceptibility to toxicity even at lower serum levels:

• Hypokalemia and hypomagnesemia are the most important electrolyte risk factors 1
• Renal dysfunction and advanced age (>70 years) dramatically increase risk 1
• Hypothyroidism potentiates toxicity 1
• Drug interactions with amiodarone, verapamil, clarithromycin, erythromycin, itraconazole, cyclosporine, and propafenone increase digoxin levels 4, 1

Special Considerations in Pediatric Patients

The presentation differs significantly in children:

• Cardiac arrhythmias, including sinus bradycardia, are the earliest and most frequent manifestation in infants and children, not GI symptoms 2
• Conduction disturbances or supraventricular tachyarrhythmias (atrial tachycardia with or without block, junctional tachycardia) are most common 2
• Any arrhythmia in a child taking digoxin should be assumed to be digoxin-induced until proven otherwise 2

Common Pitfalls

• Do not dismiss symptoms in elderly patients with "therapeutic" digoxin levels—toxicity frequently occurs within the therapeutic range in this population 1, 3
• Altered mental status may be the sole manifestation of toxicity, particularly in elderly patients with chronic lung disease 3
• Many extracardiac symptoms (nausea, tiredness, dizziness) are nonspecific and also occur in patients with renal impairment at low digoxin levels, potentially leading to misdiagnosis 7
• In patients with impaired kidney function, extracardiac symptoms have limited diagnostic value for distinguishing toxicity from underlying illness 7