Antiarrhythmic Therapy

General Principles

• Majority of antiarrhythmic agents lack FDA approval for pediatric use; off-label administration standard.
• Initiate lowest recommended dose; titrate based on clinical response and medication tolerance.
• Correct underlying acid-base and electrolyte disturbances (potassium, calcium, magnesium) prior to administration to restore normal cardiac conduction.
• Close monitoring for proarrhythmia and treatment-related adverse effects mandatory.
• Pharmacokinetics differ significantly from adults; drug interactions require careful management.

Vaughan-Williams Classification

Categorizes agents based on primary electrophysiological mechanism of action.

Class	Mechanism of Action	Examples
I	Sodium channel blockade; slows depolarization
IA (Moderate)	Prolongs action potential	Procainamide, Quinidine, Disopyramide
IB (Weak)	Shortens repolarization	Lidocaine, Mexiletine, Phenytoin
IC (Strong)	Markedly slows conduction	Flecainide, Propafenone
II	Beta-adrenergic receptor blockade; suppresses sympathetic activity	Propranolol, Atenolol, Esmolol, Nadolol
III	Potassium channel blockade; prolongs action potential & refractoriness	Amiodarone, Sotalol, Dofetilide, Ibutilide
IV	Calcium channel blockade; slows AV node conduction	Verapamil, Diltiazem
V (Misc)	Variable mechanisms (AV node blockade, Na+/K+ ATPase inhibition)	Adenosine, Digoxin, Magnesium

Specific Pharmacologic Agents & Dosing Profiles

Class I: Sodium Channel Blockers

Procainamide (Class IA)

• Indication: Supraventricular tachycardia (SVT), Atrial fibrillation/flutter, Ventricular tachycardia (VT).
• Mechanism: Depresses myocardial excitability and conduction.
• Dose: IV load 10–15 mg/kg over 30–60 min; continuous infusion 20–80 mcg/kg/min (Max: 2000 mg/day).
• Caution: Monitor for hypotension during loading. Stop infusion if QRS widens >50%.

Lidocaine (Class IB)

• Indication: VT, Ventricular Fibrillation (VF).
• Mechanism: Local anesthetic depressing myocardial irritability; prevents ventricular depolarization.
• Dose: IV 1 mg/kg bolus (repeat q5 min x2); maintenance 20–50 mcg/kg/min.
• Caution: Avoid exceeding 20 mcg/kg/min in shock or hepatic disease.

Flecainide (Class IC)

• Indication: SVT, Atrial tachycardia, VT.
• Mechanism: Strong sodium channel blocker; cell membrane depression.
• Dose: 1–3 mg/kg/day PO divided TID (Max: 8 mg/kg/day).
• Caution: Negative inotropic effect. Strictly contraindicated in structural heart disease, severe heart failure, and AV block.

Class II: Beta-Blockers

Propranolol

• Indication: SVT, Long QT syndrome.
• Dose: PO 1–4 mg/kg/day divided Q6H. IV 0.01–0.15 mg/kg/dose slow push.
• Caution: Risk of bronchospasm, hypoglycemia, bradycardia.

Esmolol

• Indication: Rapid heart rate control.
• Mechanism: Rapid-acting selective $\beta$1-blocker.
• Onset/Half-life: Rapid onset (2–10 min); ultra-short half-life (2.7–4.8 min).
• Dose: IV load 100–500 mcg/kg; maintenance 25–100 mcg/kg/min (titrate up to 500 mcg/kg/min).

Class III: Potassium Channel Blockers

Amiodarone

• Indication: Refractory SVT, Junctional Ectopic Tachycardia (JET), VT, cardiac arrest.
• Mechanism: Prolongs action potential and refractoriness. Exhibits Class I, II, III, and IV properties.
• Half-life: Extremely prolonged (40–55 days chronic oral).
• Dose: IV load 5 mg/kg over 30–60 min (repeat up to 20 mg/kg); maintenance 5–15 mcg/kg/min.
• Drug Interactions: Significantly increases serum levels of digoxin, warfarin, flecainide, and phenytoin. Empiric 30-50% dose reduction of digoxin/warfarin required.

Sotalol

• Indication: SVT, VT, Atrial flutter.
• Mechanism: Combined nonselective $\beta$-blockade and Class III properties.
• Dose: >2 years: 30 mg/m2/dose Q8H. Requires age-based dose reduction nomograms for <2 years.
• Caution: Contraindicated in baseline prolonged QTc (>450 ms). Risk of Torsades de pointes.

Class IV: Calcium Channel Blockers

Verapamil

• Indication: SVT (excluding Wolff-Parkinson-White [WPW] syndrome).
• Dose: IV 0.1–0.3 mg/kg/dose over 2 min (Max: 5 mg/dose).
• Caution: Strictly contraindicated in infants <1 year. Causes severe apnea, profound bradycardia, hypotension, and cardiovascular collapse. Avoid in WPW due to accelerated antegrade accessory pathway conduction.

Class V: Miscellaneous

Adenosine

• Indication: Acute termination of narrow complex SVT (AVNRT, AVRT).
• Mechanism: Activates inward K+ rectifier current; inhibits calcium current. Direct AV nodal inhibition.
• Onset/Half-life: Very rapid; <10 seconds.
• Dose: Rapid IV push 0.1 mg/kg (Max: 6 mg). Repeat 0.2 mg/kg (Max: 12 mg).
• Caution: Contraindicated in asthma/bronchospastic disease. Must have DC cardioversion capability nearby.

Digoxin

• Indication: Heart failure, SVT, Atrial flutter/fibrillation.
• Mechanism: Inhibits Na+/K+ ATPase, increasing intracellular calcium (positive inotrope). Enhances vagal tone (decreases AV conduction).
• Dose: PO total load preterm 20-30 mcg/kg, term 25-35 mcg/kg. Maintenance 5-10 mcg/kg/day divided Q12H.
• Caution: Contraindicated in WPW syndrome (risk of VF). Toxicity presents as AV block, PR prolongation, arrhythmias, visual disturbances. Hypokalemia increases toxicity risk.

Clinical Management by Arrhythmia Type

Narrow QRS Tachycardias

• Acute Termination: Vagal maneuvers (ice bag to face in infants, Valsalva in older children). Adenosine rapid IV push. Synchronized DC cardioversion (0.5–2 J/kg) if hemodynamically unstable.
• Chronic Management (Non-WPW): Beta-blockers (propranolol, atenolol) form mainstay therapy. Digoxin effective in infants.
• Chronic Management (WPW): Beta-blockers preferred. Digoxin and calcium channel blockers strictly contraindicated due to risk of rapid antegrade accessory pathway conduction precipitating VF.
• Refractory SVT: Class IC (flecainide, propafenone) or Class III (amiodarone, sotalol) agents. Flecainide restricted to structurally normal hearts.
• Atrial Flutter/Fibrillation: Rate control via calcium channel blockers or beta-blockers. Rhythm control via procainamide, sotalol, or amiodarone. Consider anticoagulation.

Wide QRS Tachycardias (Ventricular Tachycardia)

• Hemodynamically Stable: Intravenous amiodarone, lidocaine, or procainamide. Correct underlying electrolyte imbalances (K, Ca, Mg).
• Hemodynamically Unstable: Immediate synchronized DC cardioversion. Amiodarone preferred during cardiac arrest.

Fetal Arrhythmia Management

Maternal transplacental administration required. Medication doses higher than standard adult arrhythmia management due to altered maternal pharmacokinetics (increased blood volume, altered gastric emptying, heightened renal clearance). Direct fetal intramuscular or umbilical vein injection reserved for severe, refractory hydropic cases.

• First-Line SVT (No Hydrops): Digoxin (Target maternal trough 1.5–2.0 mcg/mL).
• First-Line SVT (With/Without Hydrops): Flecainide (Maternal dose 50-100 mg Q8H). Highly successful conversion rate.
• Fetal Atrial Flutter: Sotalol (Maternal dose 80-160 mg BID). Superior conversion rate compared to digoxin/flecainide.
• Refractory Tachycardia/Severe Hydrops: Amiodarone (Load 1800-2400 mg/day for 48h; maintain 200-600 mg/day). Risk of fetal hypothyroidism.
• Fetal Ventricular Tachycardia: Maternal IV Magnesium (Max 48 hours), Lidocaine, or Propranolol.

Adverse Effects and Therapeutic Monitoring

Drug	Key Adverse Effects	Drug Interactions	Therapeutic Level
Amiodarone	Thyroid dysfunction, pulmonary fibrosis, hepatotoxicity, prolonged QTc, blue skin.	Increases levels of digoxin, warfarin, flecainide, phenytoin.	0.5–2.5 mg/L (correlation poor).
Flecainide	Proarrhythmia, negative inotropy, QRS widening.	Milk inhibits absorption in infants. Amiodarone increases toxicity.	0.2–1.0 mcg/mL.
Procainamide	SLE-like syndrome, QRS/QTc prolongation, hypotension.	Cimetidine/Amiodarone increase levels.	Procainamide: 4–10 mcg/mL. Combined (w/ NAPA): 10–30 mcg/mL.
Lidocaine	CNS toxicity (seizures, coma), paresthesias.	Cimetidine, propranolol increase toxicity.	1.5–5.0 mcg/mL.
Digoxin	AV block, PR prolongation, visual disturbances, vomiting.	Quinidine, amiodarone, verapamil increase levels.	0.8–2.0 ng/mL.
Sotalol	Torsades de pointes, severe bradycardia, QTc prolongation.	Avoid concurrent QT prolonging drugs.	N/A