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Digoxin, Poisoning, Emergency Medicine

Basics

Description

- Acute digitalis effects (elevated levels in children and intentional overdose): - Inhibits sodium-potassium ATPase pump in cell membranes - Allows more calcium ions to enter cell and cardiac cells to contract more strongly - Increases K+ extracellularly - Increases vagal tone - Slows atrioventricular (AV) node conduction (vagotonic) - Increases automaticity and conduction system refractory period - Bradydysrhythmias

- Digoxin/digitoxin pharmaceuticals - Plants and animals containing cardiac glycosides: - Foxglove - Oleander (white and yellow) - Lily of the valley - Dogbane - Red squill - Cane toad, Colorado River toad

- Cardiovascular: - Dysrhythmias: - Paroxysmal atrial tachycardia (PAT) with AV block - Bidirectional ventricular tachycardia (VT) is pathognomonic - Premature ventricular contractions (PVCs) most common - Nonparoxysmal accelerated junctional tachycardia - VT - Ventricular fibrillation - Atrial fibrillation/flutter - Bigeminy - Bradycardia - Nonparoxysmal atrial tachycardia - AV blocks - Sinus arrhythmia - Premature atrial contraction

- CHF exacerbation - Hypotension - Shock - Cardiovascular collapse - Syncope

- CNS: - Mental status changes: - Agitation - Lethargy - Psychosis

- Cardiac arrest resuscitation: - Defibrillate for ventricular fibrillation, pulseless VT. - Standard advanced cardiac life support (ACLS) protocol - Administer digoxin-specific antibody Fab fragments (Digibind), up to 5-20 vials IV push (IVP). - MgSO4, 2 g IVP - Continue resuscitation for 30 min after digoxin-specific antibody Fab fragments.

- 1st choice: Digoxin-specific antibody Fab fragments (Digibind, DigiFab) - Indications: - SDC ≥15 ng/mL at any time or ≥10 ng/mL at steady state (6 hr) - Ingestion of >10 mg in adults or 0.2 mg/kg or 4 mg in children - Hyperkalemia >5-5.5 mEq/L - Hemodynamically unstable or life-threatening dysrhythmias - VT, ventricular fibrillation - Atrial tachycardia - Variable AV block - Bradycardia with no response to atropine - Hypotension

- For bradydysrhythmias: - Pacing for symptomatic bradydysrhythmia - MgSO4 for ventricular dysrhythmias with torsades de pointes - Quinidine, procainamide contraindicated

  • Acute digitalis effects (elevated levels in children and intentional overdose):Inhibits sodium-potassium ATPase pump in cell membranesAllows more calcium ions to enter cell and cardiac cells to contract more stronglyIncreases K+ extracellularlyIncreases vagal toneSlows atrioventricular (AV) node conduction (vagotonic)Increases automaticity and conduction system refractory periodBradydysrhythmias
  • Chronic digitalis effects (therapeutic to toxic levels in elderly patients):Inhibits sodium-potassium ATPase pump in cell membranesIncreases intracellular calciumIncreases vagal toneBradydysrhythmiasIncreases automaticityUsually hypokalemic secondary to diuretic useTachydysrhythmias

Etiology

  • Digoxin/digitoxin pharmaceuticals
  • Plants and animals containing cardiac glycosides:FoxgloveOleander (white and yellow)Lily of the valleyDogbaneRed squillCane toad, Colorado River toad

Diagnosis

Signs and Symptoms

  • Toxicity onset: 2 hr after PO ingestion and 15 min following IV
  • Toxicity:Occurs with normal digoxin levels (chronic)May be absent with elevated digoxin levels (acute)
  • Cardiovascular:Dysrhythmias:Paroxysmal atrial tachycardia (PAT) with AV blockBidirectional ventricular tachycardia (VT) is pathognomonicPremature ventricular contractions (PVCs) most commonNonparoxysmal accelerated junctional tachycardiaVTVentricular fibrillationAtrial fibrillation/flutterBigeminyBradycardiaNonparoxysmal atrial tachycardiaAV blocksSinus arrhythmiaPremature atrial contractionCHF exacerbationHypotensionShockCardiovascular collapseSyncope
  • CNS:Mental status changes:AgitationLethargyPsychosis
  • Visual perception:BlurredScotomaGreen to yellow haloPhotophobiaColor perception changes
  • GI:Anorexia, nausea, vomiting, abdominal pain

History

  • Accidental adult or pediatric overdose of a known amount
  • Intentional acute overdose in a patient not taking digoxin chronically
  • Intentional acute or chronic overdose in a patient taking digoxin chronically
  • Unintentional chronic ingestion of digoxin in which renal clearance decreases or the dose chronically increases
  • Unintentional toxicity from recent antibiotic use (esp. macrolides) that alter GI flora, primarily by decreasing Eubacterium lentum, increasing absorption

Physical Exam

  • Altered mental status
  • Bradycardia
  • Tachycardia
  • Irregular rhythm
  • Hypotension

Essential Workup

  • ECG:
  • Digoxin level:Normal range: 0.5-2 ng/mLDistribution after oral intake not complete until 6 hr; therefore, >6-hr level is most accurate steady state concentration.False elevations possible with spironolactone use, pregnancy, hyperbilirubinemia, chronic renal failure, liver failure, CHFMay be falsely elevated after digoxin-specific Fab fragments given

Diagnosis Tests & Interpretation

Lab

  • Electrolytes, BUN, creatinine, glucose:Hypokalemia contributes to digitalis toxicity.Hyperkalemia seen in acute toxicity and correlates with acute digitalis mortality better than digoxin serum levels.Follow K+ serially
  • Calcium, magnesium

Serum digoxin concentration (SDC) should not be obtained after digoxin-specific antibody Fab fragments have been administered because it will be inaccurate.

Differential Diagnosis

  • Overdoses:Calcium channel blockersβ-BlockersQuinidine, procainamideClonidineOrganophosphatesAntidysrhythmicsOther antihypertensives
  • Primary cardiac dysrhythmias
  • Acute gastroenteritis

Treatment

Pre-Hospital

  • Establish IV access
  • Continuous cardiac monitoring
  • Apply pads for potential cardioversion
  • If cardioversion is necessary for tachydysrhythmias, use low levels (50 J)
  • May precipitate refractory tachydysrhythmias

Initial Stabilization/Therapy

ABCs:

  • IV, oxygen, monitor:IV fluid bolus if hypovolemic
  • Administer naloxone, thiamine, dextrose for altered mental status.

Ed Treatment/Procedures

  • Cardiac arrest resuscitation:Defibrillate for ventricular fibrillation, pulseless VT.Standard advanced cardiac life support (ACLS) protocolAdminister digoxin-specific antibody Fab fragments (Digibind), up to 5-20 vials IV push (IVP).MgSO4, 2 g IVPContinue resuscitation for 30 min after digoxin-specific antibody Fab fragments.
  • General measures:Activated charcoal if acute ingestionReplenish magnesium.Treat hyperkalemia with insulin, dextrose, bicarbonate, sodium polystyrene sulfonate.Calcium can probably be used to treat hyperkalemia, but because other safer alternatives exist it is not recommended, unless life-saving membrane stabilization is needed secondary to hyperkalemia, in the unstable patient.If the patient has hyperkalemia from digoxin toxicity treatment with digoxin-specific Fab fragments are indicated 1st in the hemodynamically stable patient.

DYSRHYTHMIA MANAGEMENT

  • 1st choice: Digoxin-specific antibody Fab fragments (Digibind, DigiFab)Indications:SDC ≥15 ng/mL at any time or ≥10 ng/mL at steady state (6 hr)Ingestion of >10 mg in adults or 0.2 mg/kg or 4 mg in childrenHyperkalemia >5-5.5 mEq/LHemodynamically unstable or life-threatening dysrhythmiasVT, ventricular fibrillationAtrial tachycardiaVariable AV blockBradycardia with no response to atropineHypotensionOnset: 20-30 minDigoxin levels may increase, decrease, or stay in therapeutic range after therapy owing to Fab digoxin complexes and redistribution.Renal clearance of drug-antibody complexes:Too large to be removed by dialysis2nd dose if rebound toxicityComplications:Exacerbation of CHFHypokalemiaAtrial fibrillation with rapid ventricular response
  • If digoxin-specific antibody Fab fragments not immediately available initiate the following:Lidocaine:For ventricular dysrhythmias without AV blockNot harmful but not very effectiveFor bradydysrhythmias:Pacing for symptomatic bradydysrhythmiaMgSO4 for ventricular dysrhythmias with torsades de pointesQuinidine, procainamide contraindicated
  • Cardioversion is last resort for severe, life-threatening tachydysrhythmia:Start at low energy 10-50 J, then increase to high levels if ineffective.Safe if digoxin level <2 ng/mL

Medication

  • Activated charcoal slurry:
  • Digoxin-specific antibody Fab fragments:40-mg vial neutralizes 0.5 mg of digoxin.If amount ingested known:Number of vials needed to treat equals [amount ingested (mg)/0.5 (mg/vial)]If steady serum level known:Number of vials needed equals [SDC (ng/mL) — weight (kg)]/100If neither amount ingested nor serum level known:Acute toxicity: 5-10 vials adults or childrenChronic toxicity: 1-2 vials in adults or childrenBolus digoxin-specific antibody Fab fragments for cardiac arrestAdditional doses as needed
  • Standard treatment for hyperkalemia and bradycardia (calcium only if necessary)
  • Dosage is based on weight and serum concentration. There is no change in the setting of renal or hepatic dysfunction.
  • Recrudescence of toxicity has been reported in patients with concomitant renal failure. Redosing of digoxin-specific antibody Fab fragments should be used again when indicated.
  • Weight-based dosing for children is the same as it is for adults.
  • On some occasions, accidental dose ingested by a child is known and the number of vials is indicated by the amount of digoxin bound by each vial. See dosing.

Digoxin-specific Fab fragments are pregnancy class C.

Follow-Up

Disposition

Admission Criteria

  • ICU:Unstable cardiovascular status in acute or chronic toxicity
  • Telemetry:Asymptomatic or mildly symptomatic dysrhythmiaHigh risk for developing toxicity

Discharge Criteria

Acute/chronic ingestion:

  • Digoxin level <2 ng/mL
  • Asymptomatic for 6 hr and no ECG abnormalities

Followup Recommendations

Psychiatric referral for stable patients who are suicidal

Pearls and Pitfalls

When it is known that the patient is on digoxin and presents with cardiovascular instability, and/or hyperkalemia, treatment should begin with the antidote: Digoxin-specific Fab fragments.

Additional Reading

  • Erickson CP, Olson KR. Case files of the medical toxicology fellowship of the California poison control system-San Francisco: calcium plus digoxin-more taboo than toxic? J Med Toxicol. 2008;4(1):33-39.
  • Levine M, Nikkanen H, Pallin DJ. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg Med. 2011;40(1):41-46.

Codes

ICD9

972.1 Poisoning by cardiotonic glycosides and drugs of similar action

ICD10

  • T46.0X1A Poisoning by cardi-stim glycos/drug simlar act, acc, init
  • T46.0X4A Poisoning by cardi-stim glycos/drug simlar act, undet, init

SNOMED

  • 10385009 Poisoning by digoxin
  • 291992008 Accidental digoxin poisoning
  • 291994009 Digoxin poisoning of undetermined intent