Antiarrhythmic drug treatment in children: evidence-based recommendations

Evidence-based dosing guidance on antiarrhythmic drugs (AAD) treatment is available for several drugs in paediatric subpopulations. Further, intravenous antiarrhythmic therapy may lead to severe adverse events in this population, so caution is recommended [1].

Dr Nico Blom (Leiden University Medical Center, the Netherlands) discussed the available evidence and clinical experience on AAD therapy in children [1]. His overview focussed on supraventricular tachycardia (SVT), as this condition is the most common in children (0.14% incidence). Most SVT events occur in the first year of life, with 90-95% of children having a normal heart. The most common SVT types are atrioventricular re-entrant (AVRT) and atrioventricular nodal re-entry tachycardia (AVNRT). Rare chronic SVT forms include focal (FAT) and multifocal atrial tachycardia (MAT), congenital and postoperative junctional ectopic tachycardia (JET). Postoperative atrial flutter usually occurs in older children and young adults.

Dr Blom further indicated that acute management of SVT by intravenous injection of AAD (after failure of Valsalva and adenosine) could comprise of esmolol (500 µg/kg loading dose over 2 minutes, 50-200 µg/kg/min maintenance), flecainide (1-2 mg/kg over 10 minutes), or amiodarone (5 mg/kg over 30-60 minutes in case of poor cardiac function). Verapamil is never used in infants of <1-2 years, based on case reports in the 1980s.

A randomised, double-blind trial evaluating amiodarone in children enrolled 61 patients (median age 1.6 years) suffering from incessant SVT, postoperative JET or VT and randomised them to either 1, 5, or 10 mg/kg amiodarone followed by 2, 5, or 10 mg/kg/day [2]. Five study patients died (2 possibly related) and there was a high rate of adverse events, leading to drug withdrawal in 10 patients. The 5 and 10 mg/kg doses were equally effective with 5 mg/kg having less side effects. Dr Blom suggested his institutional ICU-approach for postoperative JET, a slow bolus of 5 mg/kg over 60 minutes followed by continuous infusion of 10-20 mg/kg/day [1].

For maintenance therapy of SVT (AVRT), the most commonly used drugs in newborns and infants are: first-line beta-blockers or digoxin, second-line Class Ic (i.e. flecainide, propafenone) or sotalol, third-line amiodarone, and fourth-line exotic combinations (e.g. sotalol/flecainide, amiodarone/flecainide) [1,3]. In the first months, SVT in infants can be difficult to control but eventually often resolves. Duration of therapy in symptom- and recurrence-free patients is approximately 6 months, followed by a stop between 6 and 12 months of age (one drug at a time). Maintenance therapy in older children consists of first-line beta-blockers and second-line sotalol, flecainide, or verapamil. Optimal starting and target oral sotalol dosing for SVT in children was evaluated as 2 and 4 mg/kg/day in neonates (<1 month), 3 and 6 mg/kg/day in infants and children <6 years, and 2 and 4 mg/kg/day in children >6 years [4]. For flecainide, an average dose of 4.5 mg/kg/day was shown to be safe and effective for children <1 year [5].

Focal AT, MAT, and congenital JET in infants are difficult to control with AAD and associated with Takotsubo cardiomyopathy. Ivabradine was introduced as an emerging drug for difficult chronic SVT mechanisms based on abnormal automaticity in infants and young children.

Dr Blom warned, “The most common errors in paediatrics are dosing errors, most likely leading to a 10-fold or greater overdose by calculation errors (commas!), which usually occur when children are admitted to hospital, not when children are dosed by their parents.”

In summary, for acute AAD management in infants, amiodarone is mostly used in haemodynamically unstable and postoperative children, but esmolol is a safe alternative. Intravenous AAD must be used with caution and ECMO stand-by is advised. For chronic AAD management in children, propranolol and digoxin were similarly efficacious. In most infants, AAD drugs can be stopped in the first year of life. Solatol and Class Ic drugs are most popular for different SVT forms, while amiodarone is only used as third-line treatment. Ivabradine is emerging for incessant FAT, MAT, and especially JET.

1. 
   
   1. Blom N. Anti-arrhythmic drug treatment in children: evidence and experience. EHRA 2021 Congress, 23-25 April.
   2. Saul JP, et al. Circulation 2005:112(22):3470-3477.
   3. Sanatani S, et al. Circ EP 2012:5:984-991.
   4. Läer S, et al. JACC 2005:46(7):1322-1330.
   5. Cunningham T, et al. Ped cardiol 2017:38(8):1633-1638.

 

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Posted on 16 June 20216 September 2023