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Toxicity, Digitalis: Treatment & Medication
Updated: Dec 1, 2008
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Treatment
Prehospital Care
- Oxygen, cardiac monitoring, IV access, and transport are usually the only requirements.
- Atropine is indicated for hemodynamically unstable bradyarrhythmias; lidocaine is indicated for ventricular tachycardia.
Emergency Department Care
Guide treatment of patients with digoxin toxicity by their signs and symptoms and the specific toxic effects. Treatment should not necessarily be driven by digoxin levels alone. Therapeutic options range from simply discontinuing digoxin therapy for patients who are stable with chronic toxicity to fab fragments, pacemaker, antiarrhythmic drugs, magnesium, and hemodialysis for acute severe ingestions.
- Initiate supportive therapy with oxygen, cardiac monitoring, and IV access.
- Activated charcoal is indicated for acute overdose or accidental ingestion. Cholestyramine binds enterohepatically-recycled digoxin and digitoxin, although no outcome studies have been performed.
- Gastric lavage increases vagal tone and may precipitate or worsen arrhythmias. Consider pretreatment with atropine if gastric lavage is performed.
- The availability of a digitalis-fab antibodies (Digibind) antidote usually renders gastric lavage unnecessary.
- Management of dysrhythmias varies, depending on the presence or absence of hemodynamic instability, the nature of the arrhythmia, the presence or absence of electrolyte disturbances, and the preferences of toxicology and/or cardiology consultants.
- Bradyarrhythmias that are hemodynamically stable may be treated with observation and discontinuation of the drug. Ensure proper hydration to optimize renal clearance of excess drug. GI binding agents (eg, charcoal, cholestyramine) may be utilized to bind enterohepatically-recycled digitalis.
- Hemodynamically stable supraventricular arrhythmias may be treated conservatively with observation and discontinuation of digoxin. In the setting of rate-related ischemia or hemodynamic instability, Digibind is the treatment of choice.
- Short-acting beta-blockers (eg, esmolol) may be helpful for supraventricular tachyarrhythmias with rapid ventricular rates, but advanced or complete AV block may be precipitated. Calcium channel blockers are contraindicated because they may increase digoxin levels.
- Hemodynamically unstable bradyarrhythmias respond best to Digibind. Atropine may be used for temporary adjuncts because it improves AV nodal conduction. Cardiac pacing has been used successfully, but it can lower the fibrillatory threshold and induce arrhythmias.
- PVCs, bigeminy, or trigeminy may be observed unless the patient is hemodynamically unstable, in which case lidocaine may be effective.
- Ventricular tachycardia responds best to Digibind. Lidocaine and phenytoin may be useful because they depress the enhanced ventricular automaticity without significantly slowing AV conduction. Phenytoin may reverse digitalis-induced prolongation of AV nodal conduction. Phenytoin has been shown to dissociate the inotropic and dysrhythmic action of digitalis, thus suppressing digitalis-induced tachydysrhythmias without diminishing the contractile effects. In addition, phenytoin can terminate supraventricular dysrhythmias induced by digitalis, whereas lidocaine has not been as effective. Lidocaine may be given in boluses of 100 mg, according to advanced cardiac life support (ACLS) guidelines. If lidocaine is successful, begin a maintenance infusion at 1-4 mg/min. Phenytoin has been administered in boluses of 100 mg every 5-10 minutes up to a loading dose of 15 mg/kg. Avoid procainamide and bretylium.
- Asystole and ventricular fibrillation are very ominous findings. Digibind is indicated; however, its effect is limited by poor cardiac blood flow. Nevertheless, the use of digoxin-fab fragments has been associated with a 50% survival rate in isolated case reports.
- Quinidine, procainamide and bretylium are contraindicated. Both quinidine and procainamide worsen AV, SA, and His-Purkinje conductivity. Additionally, quinidine reduces digoxin tissue binding and renal clearance, thereby increasing digoxin levels. Bretylium can precipitate ventricular dysrhythmia.
- Cardioversion is relatively contraindicated because asystole or ventricular fibrillation may be precipitated.
- Consider magnesium therapy as a temporizing antiarrhythmic agent until fab fragments are available. It may be lifesaving when ventricular tachycardia or ventricular fibrillation is present. Intravenous magnesium sulfate, 2 g over 5 minutes, has been shown to terminate digoxin-toxic cardiac arrhythmias in patients with and without overt disease. Aside from successful replacement of intracellular magnesium, it also may act as an indirect antagonist of digoxin at the supraphysiologic level.
- After an initial bolus of 2 g intravenously, a maintenance infusion at 1-2 g/h is initiated.
- Monitor magnesium levels approximately every 2 hours. The therapeutic goal is a level between 4 and 5 mEq/L.
- Correct electrolyte abnormalities, especially hypokalemia and hypomagnesemia. Dysrhythmias may be reversed with correction of electrolyte imbalances.
- Treat hyperkalemia when K+ level is greater than 5.5 mEq/L.
- Calcium is not recommended to treat hyperkalemia in this setting because ventricular tachycardia or ventricular fibrillation may be precipitated. This is based on the fact that intracellular calcium levels are already high in the setting of digoxin toxicity. However, anecdotal case reports and animal studies have been published that refute the dangers of calcium administration. Unless the patient is in extremis, other measures should be preferentially used to treat hyperkalemia.
- Sodium bicarbonate and/or glucose and insulin are indicated.
- Treatment with digoxin-fab fragments is indicated for hyperkalemia with K+ level greater than 5 mEq/L.
- Kayexalate (0.5 g/kg PO) also is helpful in binding potassium and enterohepatically-recycled digitalis. However, digoxin-induced hyperkalemia reflects an extracellular shift, not an increase in total body potassium.
- Caution is indicated when using Kayexalate concurrently with insulin/glucose/bicarbonate and/or Digibind because hypokalemia may be precipitated, which may worsen clinical toxicity.
- Digoxin-fab fragments (Digibind) are generally indicated for the following:
- Dysrhythmias associated with hemodynamic instability.
- Altered mental status attributed to digoxin toxicity.
- Hyperkalemia with K+ greater than 5 mEq/L.
- Serum digoxin level greater than 10 ng/mL in adults at steady state (ie, 6-8 h post acute ingestion or at baseline in the clinical setting of chronic toxicity).
- Ingestion greater than 10 mg in adults (40 X 0.25 mg tablets) or greater than 0.3 mg/kg in children.
Consultations
Medication
The goals of pharmacotherapy are to reduce toxic levels of digitalis, prevent complications, and reduce morbidity.
Antidote
For hemodynamic instability, refractory dysrhythmias, and severe or refractory hyperkalemia. Agent has reversed noncardiac digitalis-associated complications (eg, thrombocytopenia).
In chronic toxicity, plasma drug levels are >6 ng/mL; in acute ingestion, do not base treatment on plasma drug levels alone.
Initially administering one-half doses is the best way in patients with chronic toxicity who are dependent on digoxin. This avoids completely reversing the clinical effects of digoxin and precipitating complications. Depending on the patient's status, additional antidote may be administered later. Agent is excreted renally. When administered to anephric patients, digitalis toxicity may recur within 7-14 days, as digoxin unbinds (recrudescence toxicity). Plasmapheresis may be performed or Digibind readministered in such situations.
Complications of therapy include allergic reactions (relatively rare and more common in patients with allergic histories), worsening CHF, tachyarrhythmias, and hypokalemia. Overall, incidence of complications is very low.Digoxin levels drawn after administration may be exponentially higher because many assays for measuring digoxin measure total digoxin (including digoxin bound to Digibind). This may be misinterpreted as a therapeutic failure and worsening toxicity. Assays that measure only free digoxin are accurate and should reflect true posttreatment levels. Knowledge of your laboratory's digoxin assay is critically important in evaluating therapeutic effect.
Digoxin-Fab fragments (Digibind)
Composed of digoxin-specific antibody fragments prepared from the IgG of sheep immunized with digoxin. The smaller Fab fragment avidly binds digoxin but is minimally immunogenic in humans and is excreted renally. Each vial of the drug contains 40 mg of Digoxin-specific antibody fragments.
Adult
Chronic toxicity:
Number of vials = digoxin level (ng/mL) X weight (kg)/100 (eg, a 50-kg patient with a digoxin level of 5 ng/mL would be given 2.5 vials)
Acute overdose:
Number of vials = total amount ingested (mg) X 0.8/0.5 (eg, a patient who overdosed on 30 X 0.25 mg tablets would receive 30 X 0.25 X 0.8/0.5 vials, or 12 vials)
Substitute 1 for 0.8 from the above equation if ingestion is digitoxin instead of digoxin
Unknown acute ingestion or unknown drug level:
If amount ingested is unknown or digoxin level unavailable, rapidly administer 10 vials, which usually is adequate to reverse toxicity; a repeat dose with 10 vials is indicated if there is no or only partial clinical response
In the setting of chronic toxicity where the drug level is not immediately available, administer 6 vials
Administer calculated dose IV over 30 min; effects should occur within 30 min
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged monitoring for digitalis toxicity is recommended in patients with renal failure; caution when interpreting lab results during therapy (encountering elevated serum digoxin levels is common)
Cardiovascular agents
Cardiovascular agents may be useful for treatment of bradycardia associated with digoxin overdose.
Atropine (Atropair)
Enhances sinus node automaticity by blocking acetylcholine effects at AV node, decreasing refractory time and speeding conduction through AV node.
Adult
0.4 mg IV, may repeat q1-2h
Pediatric
0.01-0.03 mg/kg IV
Coadministration with other anticholinergics have additive effects; pharmacologic effects of atenolol and digoxin may increase with atropine; antipsychotic effects of phenothiazines may decrease with this medication; TCAs may increase effects
Documented hypersensitivity; thyrotoxicosis, narrow-angle glaucoma, and tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in Down syndrome and/or children with brain damage to prevent hyperreactive response; caution in coronary heart disease, congestive heart failure, cardiac arrhythmias, and hypertension; caution in peritonitis, ulcerative colitis, hepatic disease, and hiatal hernia with reflux esophagitis; in prostatic hypertrophy, prostatism can have dysuria and may require catheterization
GI decontaminant
Activated charcoal is useful in limiting the absorption of ingested digoxin. Most beneficial if administered within 4 h of ingestion.
Activated charcoal (Liqui-Char)
Prevents absorption by adsorbing drug in intestine. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Theoretically, by constantly bathing the GI tract with charcoal, intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine. Supplied as an aqueous mixture or in combination with a cathartic (usually sorbitol 70%). Does not dissolve in water.
For maximum effect, administer within 30 min of ingesting poison.
Adult
1 g/kg PO; may repeat in 2-4 h at one-half original dose
Pediatric
<2 years: 1-2 g/kg PO without cathartic
>2 years: 1-2 g/kg PO
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases absorptive properties)
Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; unprotected airway and absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administering activated charcoal; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black; protect airway in patients with depressed level of consciousness; if using multiple dose charcoal, monitor for presence of bowel sounds to minimize risk of charcoal ileus and vomiting with subsequent pulmonary aspiration
Resin
Resin is used in management of hypercholesterolemia and can bind drugs that are enterohepatically recycled. Upwards of 30% of a digoxin dose (higher in some individuals) and the majority of a digitoxin dose are enterohepatically recycled.
Cholestyramine (Questran)
Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic re-uptake of intestinal bile salts. Shown to decrease digoxin levels following therapeutic dosing and acute or chronic digitalis toxicity. However, agent may not change ultimate outcome because of prolonged administration time necessary.
Adult
4 g PO q6h, in a slurry or with a cathartic (ie, sorbitol)
Pediatric
Not established
Inhibits absorption of numerous drugs, including warfarin, vitamin K, thyroid hormone, amiodarone, NSAIDs, methotrexate, digitalis glycosides, glipizide, chlorothiazide, propranolol, phenobarbital, phenylbutazone, folic acid, phenytoin, imipramine, niacin, methyldopa, tetracyclines, clofibrate, hydrocortisone, penicillin G
Documented hypersensitivity; complete biliary obstruction; intestinal obstruction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in constipation and phenylketonuria
Electrolytes
Magnesium is useful as a temporizing antiarrhythmic agent until digoxin Fab fragments are available.
Magnesium
Possesses antiarrhythmic properties that are beneficial with treatment of digoxin toxicity. May be a lifesaving adjunct in treatment of digoxin-induced ventricular tachycardia or ventricular fibrillation.
Adult
2 g IV bolus over 2 min, followed by 1-2 g/h infusion
Monitor levels q2h; therapeutic goal is 4-5 mEq/L
Pediatric
Not established
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine
Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Monitor for signs of magnesium toxicity manifested by neuromuscular dysfunction (eg, depressed or absent deep tendon reflexes) or respiratory compromise
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| Differential Diagnoses & Workup: Toxicity, Digitalis |
 Treatment & Medication: Toxicity, Digitalis |
| Follow-up: Toxicity, Digitalis |
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Further Reading
Keywords
digitalis toxicity, digoxin toxicity, cardiac glycoside toxicity, foxglove plant, digoxin poisoning, acute digoxin overdose, digoxin overdose, acute ingestion of digoxin, cardiac glycoside overdose
