Digoxin toxicity: Difference between revisions

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== Background ==
==Background==
===Mechanism of Action===
===Mechanism of Action===
{{Digoxin mechanism}}
{{Digoxin mechanism}}
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**Can lead to tachyarrhythmias (esp in elderly)
**Can lead to tachyarrhythmias (esp in elderly)


=== Risk Factors ===
===Risk Factors===
*Electrolyte Imbalance  
*Electrolyte Imbalance  
**[[Hypokalemia]], [[Hyperkalemia]], [[Hypomagnesemia]], [[Hypercalcemia]]  
**[[Hypokalemia]], [[Hyperkalemia]], [[Hypomagnesemia]], [[Hypercalcemia]]  
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*[[Hypothyroidism]]  
*[[Hypothyroidism]]  
*Meds  
*Meds  
**CCBs, amiodarone
**[[Calcium_channel_blockers|Calcium-Channel Blockers]], [[Amiodarone]]
 
===Environmental Exposures===
*Plants that contain cardiac glycosides:
**Oleander
**Foxglove
**Lily of the valley
**Milkweed


===Acute vs. Chronic===
===Acute vs. Chronic===
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| Age||Younger||Older
| Age||Younger||Older
|-
|-
| Therapy||Often don't need Fab||Often need Fab therapy
| Therapy||Often do not need Fab||Often need Fab therapy
|}
|}


== Clinical Features ==
==Clinical Features==
===Cardiac===
===Cardiac===
[[File:Digtox.jpg|thumb|Digitalis effect]]
[[File:Digtox.jpg|thumb|Digitalis effect]]
*[[Syncope]]
*[[Syncope]]
*Dysrhythmias
*[[Dysrhythmias]]
**PVCs (most common)
**[[PVCs]] (most common)
**[[Bradycardia]]
**[[Bradycardia]]
**SVT w/ AV block
**[[SVT]] with AV block
**Junctional escape
**Junctional escape
**Increased Automaticity: Atrial tachycardia, Regularized Atrial Fibrillation
**Increased Automaticity: [[atrial tachycardia]], regularized [[atrial fibrillation]]
**Ventricular dysrhythmia, including bidirectional V-tach (esp in chronic toxicity)
**[[Ventricular dysrhythmias]], including bidirectional V-tach (esp in chronic toxicity)
*Digitalis Effect (seen with therapeutic levels; not indicative of toxicity)
*[[Digitalis Effect]] (seen with therapeutic levels; not indicative of toxicity)
**T wave changes (flattening or inversion)
**T wave changes (flattening or inversion)
**QT interval shortening
**QT interval shortening
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*[[Confusion]]
*[[Confusion]]
*[[Weakness]]
*[[Weakness]]
*Visual disturbances
*[[Visual disturbances]]
**Yellow halos
**Yellow halos
**Scotomas
**Scotomas
*Delirium
*[[Delirium]]
 
===Metabolic===
*[[Hyperkalemia]] (acute poisoning)
*[[Hypokalemia]]
*[[Hypomagnesemia]]
**Worsens toxicity


==Differential Diagnosis==
==Differential Diagnosis==
*[[Calcium channel blocker toxicity]]
{{Symptomatic bradycardia}}
*[[Beta blocker toxicity]]
{{Tachycardia (wide) DDX}}
*[[Clonidine toxicity]]
*[[Organophosphate toxicity]]
*[[Sick sinus syndrome]]


==Diagnosis==
==Evaluation==
===Work-Up===
===Work-Up===
*Digoxin level
*Digoxin level
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*Urine output
*Urine output
*[[ECG]] (serial)
*[[ECG]] (serial)
**PVCs most common arrhythmia
**May see "regularized AF" on ECG where junctional escape rhythm takes over secondary to complete AV block
**Atach/Aflutter with slow conduction


===Evaluation===
===Evaluation===
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***Hypokalemia sensitizes myocardium to digoxin <ref>Shapiro W. Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication. Am J Cardiol. 1978; 41(5):852-9.</ref>
***Hypokalemia sensitizes myocardium to digoxin <ref>Shapiro W. Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication. Am J Cardiol. 1978; 41(5):852-9.</ref>


== Management ==
==Management==
''Calcium is theoretically contradindicated in Dig Toxicity (see [[Stone Heart]])''
''Calcium is theoretically contraindicated in Dig Toxicity (see [[Stone Heart]])''
*'''[[Digoxin Immune Fab]]'''
*'''[[Digoxin Immune Fab]]'''
**Indications
**Indications
*** Ventricular dysrhythmias: PVCs most common, Bidirectional VTach is rare
***Ventricular dysrhythmias: PVCs most common, Bidirectional VTach is rare
*** Symptomatic bradycardias unresponsive to atropine
***Symptomatic bradycardias unresponsive to atropine
*** Hyerkalemia >5.0 mEq/L secondary to digitalis intoxicaiton
***Hyperkalemia >5.0 mEq/L secondary to digitalis intoxication
*** Coningestions of cardiotoxic drugs (beta-blockers, cyclic antidepressants)
***Coingestions of cardiotoxic drugs (beta-blockers, cyclic antidepressants)
*** Acute digoxin ingestion of greater than 10mg in adults or greater than 4mg in children
***Acute digoxin ingestion of greater than 10 mg in adults or greater than 4 mg in children
*** Acute digoxin ingestions with post distribution digoxin >10ng/mL (by 6 hours post ingestion)
***Acute digoxin ingestion with post distribution digoxin >10 ng/mL (by 6 hours post ingestion)
*** Chronic digoxin ingestion leading to steady state serum digoxin concentrations of >4ng/ml  
***Chronic digoxin ingestion leading to steady state serum digoxin concentrations of >4 ng/ml  
*[[Activated Charcoal]]
*[[Activated Charcoal]]
**Questionable efficacy
**Questionable efficacy
**Only an adjunctive tx; NOT an alternative to fab fragment therapy
**Only an adjunctive treatment; NOT an alternative to fab fragment therapy
**Consider only if present within 1 hr of ingestion
**Consider only if present within 1 hr of ingestion
**1g/kg (max 50g)
**1 g/kg (max 50 g)


===Dysrhythmias===
===Dysrhythmias===
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**Consider lower energy settings (25-50J)  
**Consider lower energy settings (25-50J)  
*Bradyarrhythmias (symptomatic)
*Bradyarrhythmias (symptomatic)
**[[Atropine]] 0.5mg IV
**[[Atropine]] 0.5 mg IV
**[[Pacing]]
**[[Pacing]]
***Avoid transvenous if possible as myocardium is irritated
*Ventricular dysrhythmias
*Ventricular dysrhythmias
**[[Dilantin Load|Phenytoin]]
**[[Dilantin Load|Phenytoin]]
***Enhances AV conduction
***Enhances AV conduction
***Phenytoin: 15-20mg/kg at 50mg/min
***Phenytoin: 15-20 mg/kg at 50 mg/min
***Fosphenytoin: 15-20mg PE/kg at 100-150mg/min
***Fosphenytoin: 15-20 mg PE/kg at 100-150 mg/min
**[[Lidocaine]]
**[[Lidocaine]]
***Decreases ventricular automaticity
***Decreases ventricular automaticity
***1-3mg/kg over several minutes; follow by 1-4mg/min
***1-3 mg/kg over several minutes; follow by 1-4 mg/min
**[[Magnesium]]
**[[Magnesium]]
***Many patients have [[Hypomagnesemia]] and labs can be unreliable.
***Many patients have [[Hypomagnesemia]] and labs can be unreliable
***2-4 g IV over 20-60 mins
***2-4 g IV over 20-60 mins


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**Once Fab is given hyperkalemia will rapidly correct
**Once Fab is given hyperkalemia will rapidly correct
*If [[Fab]] unavailable and hyperkalemia is life-threatening then treat with:
*If [[Fab]] unavailable and hyperkalemia is life-threatening then treat with:
**Glucose-insulin
**[[Dextrose]]-[[insulin]]
**Sodium bicarb
**[[Sodium bicarb]]
**Kayexelate
**[[Kayexylate]]
**Dialysis
**[[Dialysis]]
**Calcium (controversial: some say dangerous, others say not)Theoretical concern for inducing "[[stone heart]]"
**[[Calcium]] (controversial: some say dangerous, others say not)
***Theoretical concern for inducing "[[stone heart]]"; Ca channels open and may lead to cardiac muscle tetany
***Chronic digoxin toxic patients likely have hyperkalemia from [[renal failure]], and calcium administration is likely safe in these patients<ref>Levine M, Nikkanen H, Pallin DJ. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg Med. 2011 Jan;40(1):41-6. doi: 10.1016/j.jemermed.2008.09.027. Epub 2009 Feb 6.</ref>
***Acutely toxic patients will not benefit from calcium, and priority must be placed on administering DigiFab


===[[Hypokalemia]]===
===[[Hypokalemia]]===
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===[[Hypomagnesemia]]===
===[[Hypomagnesemia]]===
*Treat with 1-2g over 10-20 min
*Treat with 1-2g over 10-20 min
**Monitor for resp depresion
**Monitor for respiratory depression
**Avoid in pts with:
**Avoid in patients with:
***Renal failure
***Renal failure
***Bradydysrhythmias/conduction blocks
***Bradydysrhythmias/conduction blocks
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*Admit for signs of toxicity or history of large ingested dose; admit to ICU if [[Fab]] given
*Admit for signs of toxicity or history of large ingested dose; admit to ICU if [[Fab]] given
*Discharge after 12hr observation if asymptomatic after accidental overdose
*Discharge after 12hr observation if asymptomatic after accidental overdose
*Of note<ref>Pharmacy Times. Feb 2016. Digoxin Overdose: Still No Role for Dialysis. https://www.pharmacytimes.com/contributor/craig-cocchio-pharmd/2016/02/digoxin-overdose-still-no-role-for-dialysis.</ref>:
**No routine role for hemodialysis
**Rechecking digoxin levels after Digifab is given is clinically useless, as both free and bound levels are measured


==See Also==
==See Also==
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{{#widget:YouTube|id=7iVe2HMHrX4}}
{{#widget:YouTube|id=7iVe2HMHrX4}}


== References ==
==References==
<references/>
<references/>
[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Drugs]]
[[Category:Pharmacology]]
[[Category:Tox]]
[[Category:Toxicology]]

Revision as of 18:48, 24 September 2019

Background

Mechanism of Action

  • Inhibits Na+/K+ ATPase in the myocardium[1]
    • Causes increase in intracellular sodium levels
    • Results in reversal of sodium-calcium exchanger
      • Normally imports three extracellular sodium ions into the cardiac myocyte in exchange for one intracellular calcium being exported
    • Sodium accumulates intracellularly and is exchanged for Calcium.
    • Causes an increase in the intracellular calcium concentration increasing contractility
      • Also a lengthening of phase 4 and phase 0 of the cardiac action potential which ultimately decreases heart rate
  • Summary
    • Inhibits NaK pump
      • Positive inotropy
    • Negative chronotropy/dromotropy
      • Indirect vagal stimulator

Adverse Effects

  • Increases vagal tone
    • Can lead to bradyarrhythmias (esp in young)
  • Increases automaticity
    • Can lead to tachyarrhythmias (esp in elderly)

Risk Factors

Environmental Exposures

  • Plants that contain cardiac glycosides:
    • Oleander
    • Foxglove
    • Lily of the valley
    • Milkweed

Acute vs. Chronic

Category Acute Chronic
Mortality Lower Higher
Arrythmias Bradycardia / AV block more common Ventricular dysrhythmias more common
Age Younger Older
Therapy Often do not need Fab Often need Fab therapy

Clinical Features

Cardiac

Digitalis effect

GI

Neuro

Metabolic

Differential Diagnosis

Symptomatic bradycardia

Wide-complex tachycardia

Assume any wide-complex tachycardia is ventricular tachycardia until proven otherwise (it is safer to incorrectly assume a ventricular dysrhythmia than supraventricular tachycardia with abberancy)

^Fixed or rate-related

Evaluation

Work-Up

  • Digoxin level
    • Only useful prior to administration of Fab (otherwise becomes falsely elevated)
  • Chemistry
  • Urine output
  • ECG (serial)
    • PVCs most common arrhythmia
    • May see "regularized AF" on ECG where junctional escape rhythm takes over secondary to complete AV block
    • Atach/Aflutter with slow conduction

Evaluation

  • Must use H&P and labs in combination; no single element excludes or confirms the diagnosis
  • Digoxin level
    • Normal = 0.5-2 ng/mL (ideal = 0.7-1.1)
      • May have toxicity even with "therapeutic" levels (especially with chronic toxicity)
    • Measure at least 6hr after acute ingestion (if stable); immediately for chronic ingestion
      • If measure before this may be falsely elevated due to incomplete drug distribution
  • Potassium level
    • Acute toxicity: Degree of Hyperkalemia correlates with degree of toxicity
      • Historical studies show K+ >5.5 mEq/L 100% mortality; K+ < 5 mEq/L 100% Survival [2]
    • Chronic toxicity: K+ may be normal/low (concomitant diuretic use), or high (renal failure)
      • Hypokalemia sensitizes myocardium to digoxin [3]

Management

Calcium is theoretically contraindicated in Dig Toxicity (see Stone Heart)

  • Digoxin Immune Fab
    • Indications
      • Ventricular dysrhythmias: PVCs most common, Bidirectional VTach is rare
      • Symptomatic bradycardias unresponsive to atropine
      • Hyperkalemia >5.0 mEq/L secondary to digitalis intoxication
      • Coingestions of cardiotoxic drugs (beta-blockers, cyclic antidepressants)
      • Acute digoxin ingestion of greater than 10 mg in adults or greater than 4 mg in children
      • Acute digoxin ingestion with post distribution digoxin >10 ng/mL (by 6 hours post ingestion)
      • Chronic digoxin ingestion leading to steady state serum digoxin concentrations of >4 ng/ml
  • Activated Charcoal
    • Questionable efficacy
    • Only an adjunctive treatment; NOT an alternative to fab fragment therapy
    • Consider only if present within 1 hr of ingestion
    • 1 g/kg (max 50 g)

Dysrhythmias

  • Digoxin Immune Fab is the agent of choice for all dysrhythmias!
  • Cardioversion should only be used as a last resort (may precipitate V-Fib)
    • Consider lower energy settings (25-50J)
  • Bradyarrhythmias (symptomatic)
    • Atropine 0.5 mg IV
    • Pacing
      • Avoid transvenous if possible as myocardium is irritated
  • Ventricular dysrhythmias
    • Phenytoin
      • Enhances AV conduction
      • Phenytoin: 15-20 mg/kg at 50 mg/min
      • Fosphenytoin: 15-20 mg PE/kg at 100-150 mg/min
    • Lidocaine
      • Decreases ventricular automaticity
      • 1-3 mg/kg over several minutes; follow by 1-4 mg/min
    • Magnesium
      • Many patients have Hypomagnesemia and labs can be unreliable
      • 2-4 g IV over 20-60 mins

Hyperkalemia

  • Treat with Fab, not with usual meds
    • Once Fab is given hyperkalemia will rapidly correct
  • If Fab unavailable and hyperkalemia is life-threatening then treat with:
    • Dextrose-insulin
    • Sodium bicarb
    • Kayexylate
    • Dialysis
    • Calcium (controversial: some say dangerous, others say not)
      • Theoretical concern for inducing "stone heart"; Ca channels open and may lead to cardiac muscle tetany
      • Chronic digoxin toxic patients likely have hyperkalemia from renal failure, and calcium administration is likely safe in these patients[4]
      • Acutely toxic patients will not benefit from calcium, and priority must be placed on administering DigiFab

Hypokalemia

  • Chronic intoxication
    • Raise level to 3.5-4
  • Acute intoxication
    • Do not treat (likely that potassium level is rapidly rising)

Hypomagnesemia

  • Treat with 1-2g over 10-20 min
    • Monitor for respiratory depression
    • Avoid in patients with:
      • Renal failure
      • Bradydysrhythmias/conduction blocks

Disposition

  • Admit for signs of toxicity or history of large ingested dose; admit to ICU if Fab given
  • Discharge after 12hr observation if asymptomatic after accidental overdose
  • Of note[5]:
    • No routine role for hemodialysis
    • Rechecking digoxin levels after Digifab is given is clinically useless, as both free and bound levels are measured

See Also

External Links

Video

{{#widget:YouTube|id=7iVe2HMHrX4}}

References

  1. Gheorghiade M. et al. Digoxin in the Management of Cardiovascular Disorders. Circulation. 2004; 109: 2959-2964
  2. Bismuth C et al. Hyperkalemia in acute digitalis poisoning: prognostic significance and therapeutic implications. Clin Toxicol. 1973; 6(2): 153–62.
  3. Shapiro W. Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication. Am J Cardiol. 1978; 41(5):852-9.
  4. Levine M, Nikkanen H, Pallin DJ. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg Med. 2011 Jan;40(1):41-6. doi: 10.1016/j.jemermed.2008.09.027. Epub 2009 Feb 6.
  5. Pharmacy Times. Feb 2016. Digoxin Overdose: Still No Role for Dialysis. https://www.pharmacytimes.com/contributor/craig-cocchio-pharmd/2016/02/digoxin-overdose-still-no-role-for-dialysis.