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Emergency and Acute Medicine – Digoxin Poisoning
Basics
Description
Acute digitalis toxicity, typically seen with elevated levels in children or intentional overdose, occurs through inhibition of the sodium–potassium ATPase pump in cell membranes. This allows increased intracellular calcium, leading to stronger myocardial contraction, increased extracellular potassium, enhanced vagal tone, slowed atrioventricular (AV) node conduction (vagotonic effect), increased automaticity, prolonged refractory periods, and predominantly bradydysrhythmias.
Chronic digitalis toxicity, usually occurring in elderly patients at therapeutic to toxic levels, also involves sodium–potassium ATPase inhibition with increased intracellular calcium and vagal tone. These patients commonly develop bradydysrhythmias, increased automaticity, tachydysrhythmias, and are often hypokalemic due to concurrent diuretic use.
Etiology
Sources include digoxin and digitoxin pharmaceuticals as well as plants and animals containing cardiac glycosides such as foxglove, oleander (white and yellow), lily of the valley, dogbane, red squill, cane toad, and Colorado River toad.
Diagnosis
Signs and symptoms
Toxicity typically begins about 2 hours after oral ingestion and as early as 15 minutes after intravenous administration. Toxicity may occur at normal digoxin levels in chronic exposure and may be absent despite elevated levels in acute overdose.
Cardiovascular manifestations include a wide range of dysrhythmias: premature ventricular contractions (most common), paroxysmal atrial tachycardia with AV block, nonparoxysmal accelerated junctional tachycardia, atrial fibrillation or flutter, bigeminy, sinus arrhythmia, AV blocks, bradycardia, ventricular tachycardia, ventricular fibrillation, and the pathognomonic bidirectional ventricular tachycardia. Other findings include hypotension, syncope, shock, cardiovascular collapse, and exacerbation of congestive heart failure.
Central nervous system findings include agitation, lethargy, psychosis, and characteristic visual disturbances such as blurred vision, scotomas, photophobia, and green-to-yellow halos.
Gastrointestinal symptoms include anorexia, nausea, vomiting, and abdominal pain.
History may reveal accidental pediatric or adult overdose, intentional acute or chronic overdose, unintentional chronic toxicity due to declining renal clearance or dose escalation, or recent antibiotic use—especially macrolides—that alter gastrointestinal flora and increase digoxin absorption by reducing Eubacterium lentum.
Physical examination
Common findings include altered mental status, bradycardia or tachycardia, irregular rhythm, and hypotension.
Essential workup
Electrocardiography is required to evaluate for dysrhythmias. Serum digoxin level should be obtained, recognizing that steady-state levels are most accurate when measured more than 6 hours after oral ingestion. False elevations may occur with spironolactone use, pregnancy, hyperbilirubinemia, chronic renal failure, liver failure, or congestive heart failure. Levels may be falsely elevated after administration of digoxin-specific Fab fragments.
Diagnosis tests and interpretation
Laboratory studies
Electrolytes, blood urea nitrogen, creatinine, and glucose should be assessed. Hypokalemia predisposes to toxicity, whereas hyperkalemia in acute poisoning correlates more strongly with mortality than digoxin serum levels and should be followed serially. Calcium and magnesium levels should also be measured.
Serum digoxin concentration should not be obtained after digoxin-specific Fab fragments are administered, as results will be inaccurate.
Differential diagnosis
Consider overdoses involving calcium channel blockers, β-blockers, clonidine, organophosphates, quinidine, procainamide, other antidysrhythmics or antihypertensives, primary cardiac dysrhythmias, and acute gastroenteritis.
Treatment
Prehospital care
Establish intravenous access, initiate continuous cardiac monitoring, and apply defibrillation pads. If cardioversion is required for tachydysrhythmias, use low-energy shocks (around 50 J), as higher energy may precipitate refractory arrhythmias.
Initial stabilization
Follow airway, breathing, and circulation principles. Provide oxygen, intravenous fluids if hypovolemic, and administer naloxone, thiamine, and dextrose for altered mental status when indicated.
Emergency department treatment and procedures
Cardiac arrest should be managed according to standard advanced cardiac life support protocols, including defibrillation for ventricular fibrillation or pulseless ventricular tachycardia. Administer digoxin-specific antibody Fab fragments promptly, typically 5–20 vials intravenously as indicated. Magnesium sulfate 2 g IV may be given, and resuscitation should continue for at least 30 minutes after Fab administration.
Supportive care includes activated charcoal for acute ingestion, magnesium repletion, and treatment of hyperkalemia with insulin, dextrose, bicarbonate, or sodium polystyrene sulfonate. Calcium is generally avoided unless life-saving membrane stabilization is required in unstable patients. In hemodynamically stable patients with hyperkalemia from digoxin toxicity, digoxin-specific Fab fragments are the first-line therapy.
Dysrhythmia management
First-line therapy is digoxin-specific antibody Fab fragments (Digibind or DigiFab). Indications include serum digoxin concentration ≥15 ng/mL at any time or ≥10 ng/mL at steady state, ingestion of more than 10 mg in adults or 0.2 mg/kg (or 4 mg) in children, hyperkalemia >5–5.5 mEq/L, hemodynamic instability, or life-threatening dysrhythmias such as ventricular tachycardia, ventricular fibrillation, atrial tachycardia with variable AV block, atropine-resistant bradycardia, or hypotension.
If Fab fragments are unavailable, lidocaine may be used for ventricular dysrhythmias without AV block, atropine or pacing for symptomatic bradycardia, and magnesium sulfate for torsades de pointes. Quinidine and procainamide are contraindicated. Electrical cardioversion is a last resort and should begin at low energy (10–50 J).
Medication
Activated charcoal may be administered at 1 g/kg if within 1 hour of ingestion. Each 40-mg vial of digoxin-specific Fab fragments neutralizes approximately 0.5 mg of digoxin. Dosing may be calculated based on amount ingested, serum concentration, or given empirically (acute toxicity: 5–10 vials; chronic toxicity: 1–2 vials). Additional doses may be required for rebound toxicity. Standard therapies for hyperkalemia and bradycardia should be used, with calcium reserved only when absolutely necessary.
Special populations
In older adults, dosing of Fab fragments is based on weight and serum concentration and does not change with renal or hepatic dysfunction, though rebound toxicity may occur in renal failure. Pediatric dosing follows the same weight-based principles as adults. Digoxin-specific Fab fragments are pregnancy category C.
Follow-up and disposition
Admission criteria
Patients with unstable cardiovascular status from acute or chronic toxicity require intensive care admission. Telemetry admission is appropriate for asymptomatic or mildly symptomatic patients with dysrhythmias or high risk for progression.
Discharge criteria
Patients may be discharged if digoxin levels are below 2 ng/mL, they remain asymptomatic for at least 6 hours, and no ECG abnormalities are present.
Follow-up recommendations
Psychiatric referral is recommended for patients with intentional overdose.
Pearls and pitfalls
In patients known to be taking digoxin who present with cardiovascular instability or hyperkalemia, treatment should begin immediately with digoxin-specific Fab fragments rather than waiting for confirmatory testing.
Basics
Description
Acute digitalis toxicity, typically seen with elevated levels in children or intentional overdose, occurs through inhibition of the sodium–potassium ATPase pump in cell membranes. This allows increased intracellular calcium, leading to stronger myocardial contraction, increased extracellular potassium, enhanced vagal tone, slowed atrioventricular (AV) node conduction (vagotonic effect), increased automaticity, prolonged refractory periods, and predominantly bradydysrhythmias.
Chronic digitalis toxicity, usually occurring in elderly patients at therapeutic to toxic levels, also involves sodium–potassium ATPase inhibition with increased intracellular calcium and vagal tone. These patients commonly develop bradydysrhythmias, increased automaticity, tachydysrhythmias, and are often hypokalemic due to concurrent diuretic use.
Etiology
Sources include digoxin and digitoxin pharmaceuticals as well as plants and animals containing cardiac glycosides such as foxglove, oleander (white and yellow), lily of the valley, dogbane, red squill, cane toad, and Colorado River toad.
Diagnosis
Signs and symptoms
Toxicity typically begins about 2 hours after oral ingestion and as early as 15 minutes after intravenous administration. Toxicity may occur at normal digoxin levels in chronic exposure and may be absent despite elevated levels in acute overdose.
Cardiovascular manifestations include a wide range of dysrhythmias: premature ventricular contractions (most common), paroxysmal atrial tachycardia with AV block, nonparoxysmal accelerated junctional tachycardia, atrial fibrillation or flutter, bigeminy, sinus arrhythmia, AV blocks, bradycardia, ventricular tachycardia, ventricular fibrillation, and the pathognomonic bidirectional ventricular tachycardia. Other findings include hypotension, syncope, shock, cardiovascular collapse, and exacerbation of congestive heart failure.
Central nervous system findings include agitation, lethargy, psychosis, and characteristic visual disturbances such as blurred vision, scotomas, photophobia, and green-to-yellow halos.
Gastrointestinal symptoms include anorexia, nausea, vomiting, and abdominal pain.
History may reveal accidental pediatric or adult overdose, intentional acute or chronic overdose, unintentional chronic toxicity due to declining renal clearance or dose escalation, or recent antibiotic use—especially macrolides—that alter gastrointestinal flora and increase digoxin absorption by reducing Eubacterium lentum.
Physical examination
Common findings include altered mental status, bradycardia or tachycardia, irregular rhythm, and hypotension.
Essential workup
Electrocardiography is required to evaluate for dysrhythmias. Serum digoxin level should be obtained, recognizing that steady-state levels are most accurate when measured more than 6 hours after oral ingestion. False elevations may occur with spironolactone use, pregnancy, hyperbilirubinemia, chronic renal failure, liver failure, or congestive heart failure. Levels may be falsely elevated after administration of digoxin-specific Fab fragments.
Diagnosis tests and interpretation
Laboratory studies
Electrolytes, blood urea nitrogen, creatinine, and glucose should be assessed. Hypokalemia predisposes to toxicity, whereas hyperkalemia in acute poisoning correlates more strongly with mortality than digoxin serum levels and should be followed serially. Calcium and magnesium levels should also be measured.
Serum digoxin concentration should not be obtained after digoxin-specific Fab fragments are administered, as results will be inaccurate.
Differential diagnosis
Consider overdoses involving calcium channel blockers, β-blockers, clonidine, organophosphates, quinidine, procainamide, other antidysrhythmics or antihypertensives, primary cardiac dysrhythmias, and acute gastroenteritis.
Treatment
Prehospital care
Establish intravenous access, initiate continuous cardiac monitoring, and apply defibrillation pads. If cardioversion is required for tachydysrhythmias, use low-energy shocks (around 50 J), as higher energy may precipitate refractory arrhythmias.
Initial stabilization
Follow airway, breathing, and circulation principles. Provide oxygen, intravenous fluids if hypovolemic, and administer naloxone, thiamine, and dextrose for altered mental status when indicated.
Emergency department treatment and procedures
Cardiac arrest should be managed according to standard advanced cardiac life support protocols, including defibrillation for ventricular fibrillation or pulseless ventricular tachycardia. Administer digoxin-specific antibody Fab fragments promptly, typically 5–20 vials intravenously as indicated. Magnesium sulfate 2 g IV may be given, and resuscitation should continue for at least 30 minutes after Fab administration.
Supportive care includes activated charcoal for acute ingestion, magnesium repletion, and treatment of hyperkalemia with insulin, dextrose, bicarbonate, or sodium polystyrene sulfonate. Calcium is generally avoided unless life-saving membrane stabilization is required in unstable patients. In hemodynamically stable patients with hyperkalemia from digoxin toxicity, digoxin-specific Fab fragments are the first-line therapy.
Dysrhythmia management
First-line therapy is digoxin-specific antibody Fab fragments (Digibind or DigiFab). Indications include serum digoxin concentration ≥15 ng/mL at any time or ≥10 ng/mL at steady state, ingestion of more than 10 mg in adults or 0.2 mg/kg (or 4 mg) in children, hyperkalemia >5–5.5 mEq/L, hemodynamic instability, or life-threatening dysrhythmias such as ventricular tachycardia, ventricular fibrillation, atrial tachycardia with variable AV block, atropine-resistant bradycardia, or hypotension.
If Fab fragments are unavailable, lidocaine may be used for ventricular dysrhythmias without AV block, atropine or pacing for symptomatic bradycardia, and magnesium sulfate for torsades de pointes. Quinidine and procainamide are contraindicated. Electrical cardioversion is a last resort and should begin at low energy (10–50 J).
Medication
Activated charcoal may be administered at 1 g/kg if within 1 hour of ingestion. Each 40-mg vial of digoxin-specific Fab fragments neutralizes approximately 0.5 mg of digoxin. Dosing may be calculated based on amount ingested, serum concentration, or given empirically (acute toxicity: 5–10 vials; chronic toxicity: 1–2 vials). Additional doses may be required for rebound toxicity. Standard therapies for hyperkalemia and bradycardia should be used, with calcium reserved only when absolutely necessary.
Special populations
In older adults, dosing of Fab fragments is based on weight and serum concentration and does not change with renal or hepatic dysfunction, though rebound toxicity may occur in renal failure. Pediatric dosing follows the same weight-based principles as adults. Digoxin-specific Fab fragments are pregnancy category C.
Follow-up and disposition
Admission criteria
Patients with unstable cardiovascular status from acute or chronic toxicity require intensive care admission. Telemetry admission is appropriate for asymptomatic or mildly symptomatic patients with dysrhythmias or high risk for progression.
Discharge criteria
Patients may be discharged if digoxin levels are below 2 ng/mL, they remain asymptomatic for at least 6 hours, and no ECG abnormalities are present.
Follow-up recommendations
Psychiatric referral is recommended for patients with intentional overdose.
Pearls and pitfalls
In patients known to be taking digoxin who present with cardiovascular instability or hyperkalemia, treatment should begin immediately with digoxin-specific Fab fragments rather than waiting for confirmatory testing.
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