POTD: Digoxin toxicity

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Many of our patients are on digoxin, a potentially scary drug. Today we’re going to discuss what digoxin toxicity looks like, how to approach acute v. chronic toxicity, and digiFab/digiBind.

How does digoxin work?

  1. Inhibits cardiac Na/K antiporter → increased intracellular Na, decreased intracellular K

    1. Decreased intracellular K →  HYPERKALEMIA in dig overdose

  2. Increased intracellular Na → increased intracellular Ca

  3. Increased Ca →  INOTROPY

  4. Increased inotropy → reflex INCREASED VAGAL TONE

    1. In afib, this decreases conduction rate through AV node → slowed ventricular rate


Some pharmacology

  • Oral bioavailability = 40-90% 

  • Onset of action 2-6 hours after ingestion 

  • CANNOT be removed via hemodialysis

  • Renally excreted

  • Things that INCREASE digoxin levels:

    • Amiodarone, carvedilol, ranolazine, ticagrelor

    • Verapamil, tacrolimus, cyclosporine 

    • Macrolides (Azithromycin)

    • Azoles

  • Things that DECREASE digoxin levels:

    • Carbamazepine, fosphytoin, phenobarbital

    • Rifampin


Digoxin toxicity: Acute or Chronic

ACUTE - usually starts with GI sxs, and then later neuro sxs

CHRONIC - insidious onset neuro sxs

  • Precipitating factors:

    • Any AKI causes accumulation since digoxin is renally excreted

    • Drug interactions that INCREASE digoxin levels (above)

    • Tissue sensitivity to digoxin increased by: Hypo-K, hypo-Mg, hyper-Ca, MI, hypoxemia


Symptoms:

  • Arrhythmias:

    • Sinus bradycardia, high degree AV block

    • SVTs with AV block are CLASSIC

      • Afib with slow ventricular rate

      • Afib with junctional rhythm

      • Focal atrial tach with AV block

    • Junctional tachycardia

    • Ventricular arrhythmias usually in CHRONIC toxicity

      • Bidirectional v-tach strongly suggests digoxin

  • GI sxs: nausea, vomiting, abd pain, diarrhea

  • Neuro sxs: delirium, fatigue, visual changes (change in color perception, blurry vision, photophobia, blindness)

    • Rarely seizures


Some EKGs attached.

“Salvador dali mustache” = scooped ST segment with ST depression, flat/inverted T wave +/- prominent U wave, short QT

Checking digoxin levels:

  • PO digoxin requires 6+ hours to distribute into tissues 

  • ONLY POST-DISTRIBUTION levels actually reflect severity of intoxication

    • Used to calculate antiserum dose

  • ACUTE intox: check baseline digoxin then repeat another in 6 hours

  • CHRONIC intox: one digoxin level is fine assuming it was >6 hours after last dose

How much is too much?

  • Normal/therapeutic is 0.5-2 ng/ml

  • Scary levels:

    • ACUTE: > 10 ng/ml

    • CHRONIC: >4 ng/ml

  • However - serum digoxin doesn’t actually correlate that much with tissue levels or cynical toxicity 

  • After getting antidote, levels don’t mean anything

The antidote: digoxin specific antibody fragments (DSFab)

  • Indications:

    • Significant arrhythmias or HD instability

    • K > 5-5.5 if it’s caused by digoxin

  • Softer indications:

    • Acute ingestion > 10 mg

    • Moderate-severe GI sxs

    • Serum digoxin > 10-12 

    • Renal failure

    • AMS

  • Should consult toxicologist or poison control if not sure 

    • Poison control: 1-800-222-1222

  • Digibind or digifab available (2 diff brands)

    • Comes in vials of 40 mg antibody fragments, which neutralize 0.5 mg of digoxin

  • Dosage:

    • Chronic poisoning: (dig level x wt in kg) / 100, can start lower initially

    • Acute ingestion of known dose: (mg digoxin ingested) x 1.6

    • Acute toxicity unknown levels: 5 vials (HD stable) or 10 vials (unstable)

    • Chronic toxicity unknown levels: 3-6 vials and reeval

    • Or you can use MDCalc

The most important thing about digoxin toxicity is to recognize it!! Hopefully this helps!


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