Diferencia entre revisiones de «Digoxin toxicity»

(Major update: DigiFab dosing formulas, empiric vial dosing, bidirectional VT, calcium controversy, hyperkalemia significance, drug interactions, avoid cardioversion, references with PMIDs)
(Remove refs with incorrect PMIDs (verified against PubMed))
 
(No se muestran 2 ediciones intermedias del mismo usuario)
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==Background==
==Background==
*Digoxin (digitalis) is a cardiac glycoside used for [[atrial fibrillation]] rate control and [[heart failure]]
*Digoxin (digitalis) is a cardiac glycoside used for [[atrial fibrillation]] rate control and [[heart failure]]
*'''Narrow therapeutic index''' (therapeutic level: '''0.5-2.0 ng/mL''')
*Narrow therapeutic index (therapeutic level: 0.5-2.0 ng/mL)
*Mechanism of action: inhibits Na/K-ATPase → increased intracellular calcium → increased contractility
*Mechanism of action: inhibits Na/K-ATPase → increased intracellular calcium → increased contractility
*Also increases vagal tone (AV nodal blockade)
*Also increases vagal tone (AV nodal blockade)
*Toxicity occurs from:
*Toxicity occurs from:
**'''Acute ingestion''' (intentional overdose, accidental)
**Acute ingestion (intentional overdose, accidental)
**'''Chronic accumulation''' (most common — renal insufficiency, drug interactions, dehydration)
**Chronic accumulation (most common — renal insufficiency, drug interactions, dehydration)
*'''Drug interactions that increase digoxin levels''':
*Drug interactions that increase digoxin levels:
**'''Amiodarone''' (increases level by ~50%), verapamil, diltiazem, quinidine
**Amiodarone (increases level by ~50%), verapamil, diltiazem, quinidine
**Macrolide antibiotics (erythromycin, clarithromycin)
**Macrolide antibiotics (erythromycin, clarithromycin)
**Cyclosporine, itraconazole
**Cyclosporine, itraconazole
*'''Conditions that increase sensitivity to digoxin''':
*Conditions that increase sensitivity to digoxin:
**'''Hypokalemia''' (most important — K and digoxin compete for same binding site)
**Hypokalemia (most important — K and digoxin compete for same binding site)
**Hypomagnesemia, hypercalcemia, hypothyroidism, [[renal failure]]
**Hypomagnesemia, hypercalcemia, hypothyroidism, [[renal failure]]
*Mortality without antidote: up to 20-30% in significant poisoning
*Mortality without antidote: up to 20-30% in significant poisoning
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==Clinical Features==
==Clinical Features==
===GI (Often Earliest)===
===GI (Often Earliest)===
*'''Nausea, vomiting, anorexia''' (most common symptoms)
*Nausea, vomiting, anorexia (most common symptoms)
*Abdominal pain, diarrhea
*Abdominal pain, diarrhea


===Cardiac (Most Dangerous)===
===Cardiac (Most Dangerous)===
*'''Almost ANY dysrhythmia can occur'''
*Almost ANY dysrhythmia can occur
*Classic: '''increased automaticity + decreased conduction'''
*Classic: increased automaticity + decreased conduction
*Most common arrhythmia: '''PVCs'''
*Most common arrhythmia: PVCs
*Highly suggestive rhythms:
*Highly suggestive rhythms:
**'''Bidirectional ventricular tachycardia''' (nearly pathognomonic)
**Bidirectional ventricular tachycardia (nearly pathognomonic)<ref>Smith TW. Digitalis: Mechanisms of action and clinical use. N Engl J Med. 1988;318(6):358-365. PMID 3277052</ref>
**'''Atrial tachycardia with AV block''' (PAT with block)
**Atrial tachycardia with AV block (PAT with block)
**'''Accelerated junctional rhythm'''
**Accelerated junctional rhythm
**'''Regularized atrial fibrillation''' (AF with complete heart block + junctional escape)
**Regularized atrial fibrillation (AF with complete heart block + junctional escape)
*Sinus [[bradycardia]], AV block (1st, 2nd, 3rd degree)
*Sinus [[bradycardia]], AV block (1st, 2nd, 3rd degree)
*'''Ventricular fibrillation''' / '''asystole''' (in severe toxicity)
*Ventricular fibrillation / asystole (in severe toxicity)


===Neurologic===
===Neurologic===
*'''Visual disturbances''': xanthopsia (yellow-green halo vision), blurred vision, photophobia
*Visual disturbances: xanthopsia (yellow-green halo vision), blurred vision, photophobia
*Confusion, delirium, weakness, fatigue
*Confusion, delirium, weakness, fatigue
*Drowsiness
*Drowsiness


===Metabolic===
===Metabolic===
*'''Hyperkalemia''' in acute toxicity (Na/K-ATPase inhibition → K moves extracellularly)
*Hyperkalemia in acute toxicity (Na/K-ATPase inhibition → K moves extracellularly)
**'''K >5.0 in acute digoxin poisoning is a marker of severe toxicity'''
**K >5.0 in acute digoxin poisoning is a marker of severe toxicity
**In chronic toxicity, K is often low (from concurrent diuretic use)
**In chronic toxicity, K is often low (from concurrent diuretic use)


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==Evaluation==
==Evaluation==
*'''ECG''' (look for dysrhythmias, ST changes)
*ECG (look for dysrhythmias, ST changes)
**'''Digitalis effect''' (scooped ST depression, "Salvador Dali mustache") ≠ toxicity
**'''Digitalis effect''' (scooped ST depression, "Salvador Dali mustache") ≠ toxicity
**Digitalis '''toxicity''' = arrhythmias
**Digitalis toxicity = arrhythmias
*'''Digoxin level''':
*Digoxin level:
**Therapeutic: 0.5-2.0 ng/mL
**Therapeutic: 0.5-2.0 ng/mL
**'''Draw level ≥6 hours''' after last dose (allows tissue distribution)
**Draw level ≥6 hours after last dose (allows tissue distribution)
**Level >2.0 suggests toxicity but '''clinical correlation is essential'''
**Level >2.0 suggests toxicity but clinical correlation is essential
**Level may be falsely elevated after Digibind (measures bound + unbound)
**Level may be falsely elevated after Digibind (measures bound + unbound)
*'''BMP''': '''potassium''' (critical — hypokalemia worsens toxicity), creatinine, magnesium, calcium
*BMP: potassium (critical — hypokalemia worsens toxicity), creatinine, magnesium, calcium
*'''Magnesium level''' (hypomagnesemia increases digoxin sensitivity)
*Magnesium level (hypomagnesemia increases digoxin sensitivity)


==Management==
==Management==
===Digoxin-Specific Antibody Fragments (DigiFab/Digibind)===
===Digoxin-Specific Antibody Fragments (DigiFab/Digibind)===
*'''Definitive antidote''' — highly effective
*Definitive antidote — highly effective
*'''Indications for empiric dosing''':
*Indications for empiric dosing:
**'''Life-threatening arrhythmias''' (VT, VF, symptomatic bradycardia, high-grade AV block)
**'''Life-threatening arrhythmias''' (VT, VF, symptomatic bradycardia, high-grade AV block)
**'''Hyperkalemia >5.0 mEq/L''' in acute poisoning
**Hyperkalemia >5.0 mEq/L in acute poisoning
**'''Hemodynamic instability'''
**Hemodynamic instability
**'''Digoxin level >10 ng/mL''' (acute) or >4 ng/mL (chronic) with symptoms
**Digoxin level >10 ng/mL (acute) or >4 ng/mL (chronic) with symptoms
*'''Dosing''':
*Dosing:
**If '''amount ingested known''': # vials = (body load in mg × 0.8) / 0.5
**If amount ingested known: # vials = (body load in mg × 0.8) / 0.5
**If '''level known''': # vials = (level ng/mL × weight kg) / 100
**If level known: # vials = (level ng/mL × weight kg) / 100
**'''Empiric dosing''': '''10-20 vials''' for acute life-threatening toxicity; '''3-6 vials''' for chronic toxicity
**'''Empiric dosing''': '''10-20 vials''' for acute life-threatening toxicity; '''3-6 vials''' for chronic toxicity
**Onset: '''30-60 minutes'''
**Onset: 30-60 minutes
*Each vial binds ~0.5 mg digoxin
*Each vial binds ~0.5 mg digoxin
*Post-Digibind: total digoxin level rises (bound to antibody) but '''free digoxin decreases'''
*Post-Digibind: total digoxin level rises (bound to antibody) but free digoxin decreases


===Supportive Measures===
===Supportive Measures===
*'''Correct hypokalemia''' to >4.0 mEq/L (in chronic toxicity)
*Correct hypokalemia to >4.0 mEq/L (in chronic toxicity)
*'''Correct hypomagnesemia''': magnesium sulfate 2g IV
*Correct hypomagnesemia: magnesium sulfate 2g IV
*'''Calcium''': '''CONTROVERSIAL in digoxin toxicity'''
*Calcium: CONTROVERSIAL in digoxin toxicity
**Traditional teaching: avoid calcium (risk of "stone heart")
**Traditional teaching: avoid calcium (risk of "stone heart")
**Recent evidence suggests risk may be overstated, but '''use with extreme caution'''
**Recent evidence suggests risk may be overstated, but '''use with extreme caution'''
**If hyperkalemic arrest, may give calcium but '''administer Digibind simultaneously'''
**If hyperkalemic arrest, may give calcium but administer Digibind simultaneously
*'''Atropine''' for symptomatic bradycardia: 0.5-1 mg IV (may repeat)
*Atropine for symptomatic bradycardia: 0.5-1 mg IV (may repeat)
*'''Activated charcoal''' if acute ingestion within 1-2 hours and protected airway
*Activated charcoal if acute ingestion within 1-2 hours and protected airway
*'''Avoid electrical cardioversion''' if possible (may precipitate VF in digitalis toxicity)
*Avoid electrical cardioversion if possible (may precipitate VF in digitalis toxicity)
*If cardioversion unavoidable: use '''lowest effective energy'''
*If cardioversion unavoidable: use lowest effective energy


===What to Avoid===
===What to Avoid===
*'''No calcium''' (controversial — may worsen toxicity)
*No calcium (controversial — may worsen toxicity)
*'''No Class IA antiarrhythmics''' (procainamide, quinidine — worsen conduction)
*No Class IA antiarrhythmics (procainamide, quinidine — worsen conduction)
*'''Minimize cardioversion'''
*Minimize cardioversion
*'''No beta-blockers''' (worsen bradycardia/AV block)
*No beta-blockers (worsen bradycardia/AV block)


===Refractory Cases===
===Refractory Cases===
*'''Lidocaine''' (for ventricular arrhythmias not responsive to Digibind)
*Lidocaine (for ventricular arrhythmias not responsive to Digibind)
*'''Phenytoin''' (can improve conduction through AV node; historical use)
*Phenytoin (can improve conduction through AV node; historical use)
*'''Temporary pacing''' for complete heart block refractory to atropine and Digibind
*Temporary pacing for complete heart block refractory to atropine and Digibind
*Consider '''hemodialysis''' — does NOT effectively remove digoxin (highly protein/tissue bound) but may help if Digibind unavailable
*Consider hemodialysis — does NOT effectively remove digoxin (highly protein/tissue bound) but may help if Digibind unavailable


==Disposition==
==Disposition==
*'''Admit all symptomatic patients''' to monitored bed or ICU
*Admit all symptomatic patients to monitored bed or ICU
*'''ICU''' for arrhythmias, hemodynamic instability, or Digibind administration
*ICU for arrhythmias, hemodynamic instability, or Digibind administration
*Continuous telemetry for minimum '''12-24 hours'''
*Continuous telemetry for minimum 12-24 hours
*'''Serial digoxin levels''' are NOT useful post-Digibind (measures total, not free)
*Serial digoxin levels are NOT useful post-Digibind (measures total, not free)
*'''Poison control: 1-800-222-1222'''
*Poison control: 1-800-222-1222


==See Also==
==See Also==

Revisión actual - 10:25 22 mar 2026

Background

  • Digoxin (digitalis) is a cardiac glycoside used for atrial fibrillation rate control and heart failure
  • Narrow therapeutic index (therapeutic level: 0.5-2.0 ng/mL)
  • Mechanism of action: inhibits Na/K-ATPase → increased intracellular calcium → increased contractility
  • Also increases vagal tone (AV nodal blockade)
  • Toxicity occurs from:
    • Acute ingestion (intentional overdose, accidental)
    • Chronic accumulation (most common — renal insufficiency, drug interactions, dehydration)
  • Drug interactions that increase digoxin levels:
    • Amiodarone (increases level by ~50%), verapamil, diltiazem, quinidine
    • Macrolide antibiotics (erythromycin, clarithromycin)
    • Cyclosporine, itraconazole
  • Conditions that increase sensitivity to digoxin:
    • Hypokalemia (most important — K and digoxin compete for same binding site)
    • Hypomagnesemia, hypercalcemia, hypothyroidism, renal failure
  • Mortality without antidote: up to 20-30% in significant poisoning

Clinical Features

GI (Often Earliest)

  • Nausea, vomiting, anorexia (most common symptoms)
  • Abdominal pain, diarrhea

Cardiac (Most Dangerous)

  • Almost ANY dysrhythmia can occur
  • Classic: increased automaticity + decreased conduction
  • Most common arrhythmia: PVCs
  • Highly suggestive rhythms:
    • Bidirectional ventricular tachycardia (nearly pathognomonic)[1]
    • Atrial tachycardia with AV block (PAT with block)
    • Accelerated junctional rhythm
    • Regularized atrial fibrillation (AF with complete heart block + junctional escape)
  • Sinus bradycardia, AV block (1st, 2nd, 3rd degree)
  • Ventricular fibrillation / asystole (in severe toxicity)

Neurologic

  • Visual disturbances: xanthopsia (yellow-green halo vision), blurred vision, photophobia
  • Confusion, delirium, weakness, fatigue
  • Drowsiness

Metabolic

  • Hyperkalemia in acute toxicity (Na/K-ATPase inhibition → K moves extracellularly)
    • K >5.0 in acute digoxin poisoning is a marker of severe toxicity
    • In chronic toxicity, K is often low (from concurrent diuretic use)

Differential Diagnosis

Evaluation

  • ECG (look for dysrhythmias, ST changes)
    • Digitalis effect (scooped ST depression, "Salvador Dali mustache") ≠ toxicity
    • Digitalis toxicity = arrhythmias
  • Digoxin level:
    • Therapeutic: 0.5-2.0 ng/mL
    • Draw level ≥6 hours after last dose (allows tissue distribution)
    • Level >2.0 suggests toxicity but clinical correlation is essential
    • Level may be falsely elevated after Digibind (measures bound + unbound)
  • BMP: potassium (critical — hypokalemia worsens toxicity), creatinine, magnesium, calcium
  • Magnesium level (hypomagnesemia increases digoxin sensitivity)

Management

Digoxin-Specific Antibody Fragments (DigiFab/Digibind)

  • Definitive antidote — highly effective
  • Indications for empiric dosing:
    • Life-threatening arrhythmias (VT, VF, symptomatic bradycardia, high-grade AV block)
    • Hyperkalemia >5.0 mEq/L in acute poisoning
    • Hemodynamic instability
    • Digoxin level >10 ng/mL (acute) or >4 ng/mL (chronic) with symptoms
  • Dosing:
    • If amount ingested known: # vials = (body load in mg × 0.8) / 0.5
    • If level known: # vials = (level ng/mL × weight kg) / 100
    • Empiric dosing: 10-20 vials for acute life-threatening toxicity; 3-6 vials for chronic toxicity
    • Onset: 30-60 minutes
  • Each vial binds ~0.5 mg digoxin
  • Post-Digibind: total digoxin level rises (bound to antibody) but free digoxin decreases

Supportive Measures

  • Correct hypokalemia to >4.0 mEq/L (in chronic toxicity)
  • Correct hypomagnesemia: magnesium sulfate 2g IV
  • Calcium: CONTROVERSIAL in digoxin toxicity
    • Traditional teaching: avoid calcium (risk of "stone heart")
    • Recent evidence suggests risk may be overstated, but use with extreme caution
    • If hyperkalemic arrest, may give calcium but administer Digibind simultaneously
  • Atropine for symptomatic bradycardia: 0.5-1 mg IV (may repeat)
  • Activated charcoal if acute ingestion within 1-2 hours and protected airway
  • Avoid electrical cardioversion if possible (may precipitate VF in digitalis toxicity)
  • If cardioversion unavoidable: use lowest effective energy

What to Avoid

  • No calcium (controversial — may worsen toxicity)
  • No Class IA antiarrhythmics (procainamide, quinidine — worsen conduction)
  • Minimize cardioversion
  • No beta-blockers (worsen bradycardia/AV block)

Refractory Cases

  • Lidocaine (for ventricular arrhythmias not responsive to Digibind)
  • Phenytoin (can improve conduction through AV node; historical use)
  • Temporary pacing for complete heart block refractory to atropine and Digibind
  • Consider hemodialysis — does NOT effectively remove digoxin (highly protein/tissue bound) but may help if Digibind unavailable

Disposition

  • Admit all symptomatic patients to monitored bed or ICU
  • ICU for arrhythmias, hemodynamic instability, or Digibind administration
  • Continuous telemetry for minimum 12-24 hours
  • Serial digoxin levels are NOT useful post-Digibind (measures total, not free)
  • Poison control: 1-800-222-1222

See Also

References

  • Hauptman PJ, Kelly RA. Digitalis. Circulation. 1999;99(9):1265-1270. PMID 10069797
  • Hack JB, Lewin NA. Cardioactive steroids. In: Goldfrank's Toxicologic Emergencies. 10th ed. McGraw-Hill. 2015.
  • Chan BS, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol. 2014;52(8):824-836. PMID 25089630
  • Levine M, et al. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg Med. 2011;40(1):41-46. PMID 18814997
  1. ↑ Smith TW. Digitalis: Mechanisms of action and clinical use. N Engl J Med. 1988;318(6):358-365. PMID 3277052
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