Can digoxin cause arrhythmias?

Can Digoxin Cause Arrhythmia?

Yes, digoxin can cause a wide range of cardiac arrhythmias, particularly at high doses or in the presence of predisposing conditions such as hypokalemia, hypomagnesemia, or renal impairment. 1, 2

Types of Arrhythmias Caused by Digoxin

In Adults

High doses of digoxin may produce a variety of rhythm disturbances, including: 2

• Conduction disturbances: First-degree, second-degree (Wenckebach), or third-degree heart block (including asystole) 2
• Supraventricular arrhythmias: Atrial tachycardia with block, AV dissociation, accelerated junctional (nodal) rhythm 2
• Ventricular arrhythmias: Unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy), ventricular tachycardia, and ventricular fibrillation 2

Important distinction: Digoxin produces PR prolongation and ST segment depression at therapeutic doses, which should not by themselves be considered digoxin toxicity 2

In Pediatric Patients

The arrhythmia profile differs significantly in children: 2

• Cardiac arrhythmias are the earliest and most frequent manifestation of excessive dosing in infants and children, rather than gastrointestinal or CNS symptoms 2
• Most common: Conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia 2
• Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even without first-degree heart block 2
• Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin until proven otherwise 2

Risk Factors That Increase Arrhythmia Risk

Electrolyte Abnormalities

Hypokalemia is a major contributing factor to digitalis toxicity and arrhythmias: 2, 3

• Toxicity may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexists 1, 2
• In pediatric patients, odds of arrhythmia are 138% higher when potassium levels are abnormal (<3.5 mmol/L or >6.0 mmol/L) during digoxin administration 4
• Cardiac arrhythmias compatible with digoxin toxicity can develop in the presence of stable, normal serum digoxin concentrations when hypokalemia and intracellular potassium loss occur 3

Serum Digoxin Levels

Overt digitalis toxicity is commonly associated with serum digoxin levels greater than 2 ng/mL: 1, 5

• However, levels previously considered therapeutic (up to 2 ng/mL) may exert deleterious cardiovascular effects long-term, including increased risk of death due to arrhythmias or MI 1
• Target therapeutic serum concentration should be 0.5-0.9 ng/mL to minimize arrhythmia risk while maintaining efficacy 6, 5

Patient-Specific Risk Factors

Higher risk populations include: 1, 2, 7

• Elderly patients: Low lean body mass and impaired renal function elevate serum digoxin levels 1, 2
• Renal impairment: Reduced clearance increases toxicity risk 2, 7
• Pre-existing conduction disorders: Therapeutic doses may cause heart block in patients with sinoatrial or AV conduction disorders 2
• Post-MI patients: Digoxin should be used with caution or not at all, particularly with ongoing ischemia 1

Drug Interactions

Concomitant medications that increase serum digoxin concentrations and arrhythmia risk include: 1, 5, 2

• Amiodarone, verapamil, quinidine 1, 5, 2
• Clarithromycin, erythromycin, itraconazole 1, 5, 2
• Cyclosporine 1, 5, 2

The dose of digoxin should be reduced if treatment with these drugs is initiated 1

Special Contraindications Related to Arrhythmia Risk

Absolute Contraindications

Digoxin is potentially harmful and contraindicated in: 1, 6

• Patients with AVRT or atrial fibrillation and pre-excitation on resting ECG (manifest accessory pathway) 1
• Digoxin shortens the refractory period of the accessory pathway, such that atrial fibrillation may induce ventricular fibrillation 1
• Second- or third-degree heart block without a permanent pacemaker 6
• Pre-excitation syndromes (Wolff-Parkinson-White) 6

Relative Contraindications

Use with extreme caution in: 1, 6

• Suspected sick sinus syndrome 6
• Previous digoxin intolerance 6
• Acute myocardial infarction with ongoing ischemia 1

Monitoring to Prevent Arrhythmias

Mandatory Serial Monitoring

Serial monitoring of serum electrolytes (especially potassium and magnesium) and renal function is mandatory, as digoxin can cause arrhythmias particularly with hypokalemia: 1, 6

• Check potassium and magnesium levels regularly 1
• Monitor renal function (serum creatinine) periodically 2
• Target serum digoxin concentration: 0.5-0.9 ng/mL 6, 5

Clinical Monitoring

Regular monitoring should include: 6, 8

• Heart rate and rhythm assessment 6, 8
• Signs of toxicity: nausea, vomiting, visual disturbances, altered mental status, weakness, and cardiac arrhythmias 8
• Withhold digoxin when pulse rate is less than 60 beats per minute or if there is significant sinus or atrioventricular block 5

Clinical Context and Incidence

Despite these risks, when administered with attention to dose and factors that alter disposition, digoxin is well tolerated by most patients with heart failure: 1

• In a large mortality trial, the incidence of hospitalization for suspected digoxin toxicity was 2% in patients taking digoxin compared to 0.9% in patients taking placebo 2
• The incidence and severity of digoxin toxicity has decreased substantially in recent years, likely due to lower dosing strategies and better monitoring 2, 9
• In recent controlled clinical trials with predominantly mild to moderate heart failure, the incidence of adverse experiences was comparable between digoxin and placebo groups 2

However, cardiac arrhythmias remain the most common serious adverse effect, accounting for about one-half of all digoxin-related adverse reactions 1