Volume I:
First Thirty Minutes
- Section 1
  Acute Care Algorithm/ Treatment Plans/ Acronyms
- Section 2
  Universal Approach
  - CALS Universal Approach To Emergency Advanced Life Support
- Section 3
  Steps 1-6
- Section 4
  Preliminary Impression/Focused Clinical Pathways
Volume II:
Resuscitation Procedures
Volume III:
Definitive Care

Cardiovascular 14: Digitalis Toxicity Portal

Introduction: Digitalis toxicity is a common adverse drug reaction. Digoxin, the form of cardiac glycoside primarily prescribed in clinical medicine, is most often used to treat supraventricular tachyarrhythmias and CHF.

Signs and Symptoms of Digitalis Toxicity¹

GI symptoms—including anorexia, nausea, or vomiting—are mediated by the effects of excess digitalis on the chemoreceptors of the medulla in the brain.
Neurologic symptoms—including headache, fatigue, confusion, delirium, seizures, or visual color disturbance—are mediated by the effects of excess digitalis on the chemoreceptors of the medulla of the brain.
Cardiac arrhythmias associated with digitalis toxicity are variable and may be hard to differentiate from rhythm disturbances caused by underlying heart disease, but most commonly the rhythm disturbances include ventricular ectopic rhythms, bradycardia with varying degrees of AV block, and atrial arrhythmias. Rhythms that especially suggest digitalis toxicity include paroxysmal atrial tachycardia with block, non-paroxysmal accelerated junctional tachycardia, bi-directional VT, new onset ventricular bigeminy, and regularized AF. Digitalis-induced cardiac arrhythmias are a result of disturbances of impulse formation and conduction within different cardiac tissues resulting from digitalis altering the refractory period, impulse transmission, and automaticity of the conduction tissue along with rhythm changes mediated by sympathetic activity and increased vagal tone.

Treatment of Digitalis Intoxication

The treatment of digitalis overdose in cases of chronic digitalis use is primarily dictated by the degree of cardiac toxicity and the hemodynamic stability demonstrated by the patient. If the patient is hemodynamically stable and displaying the common arrhythmias—such as PVCs, first-degree AV block, or AF with a slow ventricular rate—appropriate treatment consists of temporary withdrawal of the drug, ECG monitoring, and later dose adjustment to prevent recurrent problems. If the rhythm disturbance is unstable or causing hemodynamic compromise, then active intervention is indicated to the degree necessary to stabilize the patient's rhythm, until which time the excess digitalis dissipates.

In serious digitalis toxicity, specific treatment considerations include:

With acute digitalis overdose (within 1 hour), consider active treatment to remove the excess digitalis with activated charcoal (AC) 1 g/kg PO. Avoid the use of naso- or- orogastric tubes as vagal stimulation may induce arrhythmias.
Hypokalemia is commonly observed in patients with digitalis-induced ectopic tachyarrhythmias. These arrhythmias are frequently improved by giving potassium plus volume replacement, but hyperkalemia must be avoided.¹ Give potassium therapy with caution when heart block is present, since elevating the serum potassium concentration may further impair atrial ventricular conduction.²
Hypomagnesemia is frequently associated with hypokalemia and digitalis toxicity. Either rule out hypomagnesemia or give magnesium sulfate IV along with potassium IV for digitalis toxicity and cardiac arrhythmias.
Digoxin-specific antibody therapy (Digibind or Digoxin Immune FAB [antigen binding fragments])^3,4,5 is available and effective for acute or severe symptomatic digitalis toxicity. FAB fragments bind to free digoxin, creating an inactive compound that is excreted by the kidneys. The effect of FAB fragments begins within minutes of IV dose and results in complete removal of the effects of digitalis within 30 minutes. Although expensive, FAB fragments may be lifesaving in certain circumstances. Indications for the use of FAB fragments in digitalis toxicity include:
1. Refractory VT
2. Refractory VF
3. High-grade AV block
4. Shock or fulminant CHF
5. Cardiac arrest
6. Hyperkalemia (serum potassium > 5)³
7. Steady state serum levels of digitalis > 10 ng/mL in adults³
8. PEDS: Steady state serum levels > 5 ng/mL in children and infants⁵
9. Acute ingestion of > 10 mg of digoxin in adults or (PEDS) > 0.3 mg/kg in infants, or > 4 mg in previously healthy children^3,5
Dosage of FAB fragments: Each 38 mg vial of FAB fragments will bind 0.5 mg of digoxin or digitoxin.³ Dosing tables are available from a regional poison control center or are present on the drug insert sheets that come with the Digibind (FAB fragments).

Dosage calculations of FAB fragments may be determined as follows:

In acute ingestion of known amounts of digoxin, the number of vials of FAB fragments to give equals number of mg of digitalis ingested X 0.8 divided by 0.5 mg digitalis bound/vial.³ (ie, number of vials = mg digitalis X 0.8 divided by 0.5).

If the serum digoxin level is known in the case of chronic digitalis ingestion, the number of vials of FAB fragments to give equals the serum digoxin level times the patient's weight in kg divided by 100.³

If there is an unknown quantity of digoxin ingested acutely, give 10 vials of FAB fragments³ or 5 vials for a child.⁶

Another alternative is to give half the calculated dose and observe for response at the end of the infusion. Resolution of signs, symptoms, and arrhythmias warrants further observation; continued signs of toxicity require further FAB administration. ^{7, 8}

Give FAB fragments IV over a 30-minute time interval through a 0.22 μm filter, except in cases where the patient is in impending cardiac arrest or is in cardiac arrest, and then give as an IV bolus.³

Side effects of FAB fragments include³:

Exacerbations of CHF with the loss of digitalis effect
Rapid ventricular rate in AF
Hypokalemia that may appear many hours after the ingestion of the FAB fragments

Treatment of digitalis-induced bradycardia/heart block

Digitalis-induced bradycardia is often mediated through the vagus nerve, so atropine (0.5 mg IV) is the initial treatment. (Repeat as needed.) The use of transvenous pacemakers for treating bradycardia or heart block associated with digitalis toxicity must be used with great caution; digitalis-toxic patients are susceptible to pacemaker-induced ventricular rhythm disturbances.

Treatment of digitalis-induced ventricular premature beats and non-sustained VT
- The initial management of ventricular ectopy consists of appropriate IV replacement of potassium, magnesium, and volume, if needed.
- Give lidocaine first 1 to 1.5 mg/kg IV; repeat 0.5 mg/kg every 2 to 3 minutes up to 3 mg/kg. Follow with 2 to 4 mg/kg drip.⁹
- Phenytoin is a not listed by the manufacturer for the treatment of digitalis toxicity but has been found to be useful in some cases when lidocaine is not effective. Give phenytoin 100 mg IV every 5 minutes by slow infusion; repeat until the arrhythmia is controlled up to maximum of 20 mg/kg.⁹
Treatment of digitalis-induced sustained VT without shock or cardiac arrest
- VT that is not associated with shock or cardiac arrest needs to be treated with combination therapy using anti-arrhythmic medication plus FAB fragments.
- Initial drug therapy consists of lidocaine 1 to 1.5 mg/kg IV; repeat 0.5 mg/kg every 2 to 3 minutes up to 3 mg/kg. Follow with IV drip 2 to 4 mg/min.⁹
- The FAB fragments should become effective within 30 to 60 minutes, and then the lidocaine may be stopped.³
Treatment of digitalis-induced unstable VT
- Treat VT associated with hemodynamic compromise or shock with immediate cardioversion plus 10 to 20 vials of FAB fragments IV given rapidly plus anti-arrhythmic therapy.
- For the cardioversion, start with 25 to 50 J. Use this lower energy because digitalis-toxic patients tend to have adverse reactions to direct current (DC) counter-shock. If the patient does not respond to the initial counter-shock of 25 to 50 J, then immediately re-shock with 200 J. For a third attempt, go up to 300 J.¹⁰
- Use lidocaine IV (as delineated for VT).
Treatment of digitalis-induced VF or pulseless VT

VF and pulseless ventricular tachycardia due to digitalis toxicity initially requires following ACLS guidelines of electrical defibrillization, intubation, oxygenation, and administration of epinephrine.

Further therapy consists of:

Giving lidocaine (bolus 1.5 mg/kg IV push followed by 0.5 mg/kg every 8 to 10 minutes up to 3 mg/kg).
Give FAB fragments 20 vials IV push.
Re-attempt defibrillation every minute until achieving cardioversion.

Use of beta-adrenergic blocking drugs with digitalis toxicity

Beta blocking drugs have been used for digitalis-induced arrhythmias because beta blockers tend to decrease the heart automaticity. Nevertheless, beta blockers decrease conduction and myocardial contractility, so use with great caution, if at all.1,⁹

Use of IA anti-arrhythmic drugs (quinidine, procainamide) with digitalis toxicity is not suggested as good clinical practice.⁹

DC counter-shock of digitalis-toxic patients

Use DC counter-shock in digitalis-toxic patients with great caution. DC counter-shock may cause severe irreversible arrhythmias. Use lower energy settings to decrease risk.¹⁰

Magnesium sulfate used to be recommended for the treatment of digitalis-induced ventricular arrhythmias.9 ECC/AHA recommendations now suggest that magnesium only be given when the patient has a magnesium deficiency or displays torsades de pointes.¹¹

References

Braunwald E. WB Saunders Company. Heart Disease, a Textbook of Cardiovascular Medicine. 1984:2:523-26.
Fisch C, et al. Potassium and the monophasic action potential, electrocardiogram, conduction and arrhythmias. Progr Cardiovasc Dis. 1966:8:387.
Physicians’ Desk Reference. 2002:56:1514-5.
Smith TW, et al. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Experience in 26 cases. N Engl J Med. 1982:307:1357-62.
American Heart Association. Advanced Cardiac Life Support. 1997:11-12 to 14.
Levine M, O’Connor A. Dosing regimen for digoxin-specific antibody (Fab) fragments in patients with digoxin toxicity. http://www.uptodate.com/contents/dosing-regimen-for-digoxin-specific-antibody-fab-fragments-in-patients-with-digoxin-toxicity/contributors. Updated October 14, 2010. Accessed July 7, 2011.
Ford M, et al. Clinical Toxicology, 1st Edition. New York: WB Saunders; 2001.
Bateman D. Digoxin-specific antibody fragments: how much and when? Toxicol Rev. 2004;23:135-43.
Wyugaarden JB, et al. Cecil Textbook of Medicine. 1992:19:204-205.
Lown B, et al. Cardioversion and digitalis drugs: Changed threshold to electric shock in digitalized animals. Circ Res. 1965:17:519.
Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation Supplement. 2000; 102: (8):I-123-I124.

Cardiovascular 14: Digitalis Toxicity Portal

References

Edition 13-October 2011