Ibutilide therapy in the conversion of atrial flutter in neonatesDeepa Prasad, MD,* Christopher Snyder, MD,† Ravi Ashwath, MD†

From the *Department of Pediatrics, and †Division of Pediatric Cardiology, UH Rainbow Babies and Children’s Hospital,Case Western Reserve University, Cleveland, Ohio.

OverviewAtrial flutter (AFL) is an uncommon arrhythmia in the fetaland neonatal period, and without appropriate treatment, itcan lead to hydrops fetalis and even death. Treatment forneonatal AFL includes medications, transesophageal over-drive pacing, or synchronized direct current cardioversion(DCC). Ibutilide is an accepted pharmacological method ofcardioversion in adults and younger children, but there are nodocumented uses of it in neonates. We report the successfulcardioversion of AFL with slow intravenous (IV) infusion of0.01 mg/kg of ibutilide in 2 neonatal patients.

IntroductionThe overall incidence of supraventricular tachycardia isabout 1.2% of all children and 0.3% of all neonates.1

Synchronized DCC is an extremely effective method ofconverting AFL to normal sinus rhythm (NSR) in neonates,with success rates of greater than 85%.3–5 Various antiar-rhythmic agents have been tried in the past for conversion;however, the efficacy is variable and serious adverse effectshave been reported such as torsades de pointes, ventriculartachycardia, hypothyroidism, atrioventricular block, andhepatotoxicity.5,7–10 In spite of this, pharmacological car-dioversion may have some advantages over synchronizedDCC in the neonate: there is no need for intubation and it isless invasive.

The use of ibutilide in the conversion of AFL in neonateshas yet to be reported in the literature. We report 2 neonateswith AFL, who were successfully converted with ibutilideinfusion at 0.01 mg/kg over 15 minutes without majoradverse events.

Case 1A 32 weeks’ gestation female infant delivered via cesareansection secondary to fetal tachycardia developed respiratory

KEYWORDS Atrial flutter; Ibutilide; Neonate; Pharmacological cardioversionABBREVIATIONS AFL¼ atrial flutter; DCC¼ direct current cardioversion;

IV ¼ intravenous; NSR ¼ normal sinus rhythm; QTc ¼ corrected QT

interval (Heart Rhythm 2013;10:1231–1233)

Address reprint requests and correspondence: Dr Ravi Ashwath,Division of Pediatric Cardiology, UH Rainbow Babies and Children’sHospital, Case Western Reserve University, 11100 Euclid Avenue,Cleveland, OH 44106. E-mail address: Ravi.Ashwath@uhhospitals.org.

1547-5271/$-see front matter B 2013 Heart Rhythm Society. All rights reserved.

distress, requiring intubation and surfactant administration.Her initial electrocardiogram revealed AFLwith atrial rates of400 beats/min with 2:1 atrioventricular response (Figure 1A).An echocardiogram revealed a structurally normal heart withnormal cardiac function. The patient received 2 IV infusionsof 0.01 mg/kg of ibutilide over 15 minutes, administered 5minutes apart, which first produced 4:1 block (Figure 1B)followed by conversion to NSR with 2:1 block and correctedQT interval (QTc) prolongation (max 550 ms; Figure 1C),which lasted for 10 minutes. No ventricular arrhythmias wererecorded. An hour after the discontinuation of ibutilideinfusion, the patient’s electrocardiogram revealed NSR withQTc normalization. She experienced no recurrence of AFL atfollow-up, and the QTc remained normal on subsequentelectrocardiograms.

Case 2A 37 weeks’ gestation male infant was delivered via cesareansection owing to fetal tachycardia, with a history of fetaltachycardia for the preceding 2 weeks that had failed toconvert to NSR despite maternal therapy with digoxin. Thefetal echocardiogram showed normal intracardiac anatomywith AFL and atrial rates of 440 beats/min and 2:1ventricular response. At birth, his ventricular rate was 220beats/min and he was otherwise hemodynamically stable.Baseline electrocardiogram showed a typical AFL with atrialrates of 428 beats/min with 2:1 ventricular response(Figure 2A). Postnatal echocardiogram revealed normalcardiac anatomy and function.

Digoxin loading was tried initially, but was againineffective. After the failed digoxin trial, the decision wasmade to attempt conversion with an ibutilide infusion. Thispatient received 2 IV infusions of 0.01 mg/kg of ibutilideover 15 minutes, administered 5 minutes apart. During thefirst infusion, transient QTc prolongation (max 550 ms) wasnoted, which resolved spontaneously in less than 10 minutes.During the second infusion, AFL was successfully convertedto NSR. No ventricular arrhythmias were recorded.He experienced no recurrence of AFL at follow-up, andthe QTc remained normal on subsequent electrocardiograms.

DiscussionThe first successful DCC of neonatal AFL was reported in1965.2 This method of converting neonates and children

http://dx.doi.org/10.1016/j.hrthm.2013.04.023

Figure 1 A: Electrocardiogram (ECG) illustrating typical atrial flutter with an atrial rate of 400 beats/min and 2:1 atrioventricular (AV) conduction. B: ECGobtained after initial ibutilide infusion, illustrating 4:1 block and prolongation of atrial cycle length (CL) to 180 ms without a change in the P-wave morphology.C: ECG after the second dose of ibutilide, illustrating normal sinus rhythm with 2:1 block and corrected QT interval prolongation.

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from AFL to NSR is an extremely effective treatment, withsuccess rates of greater than 85%.3–5 Transesophagealpacing has also been used in neonates and children but hasbeen reported to have lower success rates (32%–73%).5,11,12

Various antiarrhythmic agents such as digoxin, quinidine,procainamide, flecainide, sotalol, propranolol, and amiodar-one have also been used alone or in combination, but withvariable success rates.3–6 Although synchronized DCC has ahigher efficacy, at times medications may be preferredbecause they generally do not require sedation and/or

Figure 2 Electrocardiogram of the neonate showing typical atrial flutterwith an atrial rate of 428 beats/min and 2:1 atrioventricular node conduction.CL ¼ cycle length.

intubation and are less invasive. The downside is that manyantiarrhythmic agents have numerous side effects and mayeven be proarrhythmogenic, so careful monitoring isrequired during their administration.

Ibutilide is a pure class III antiarrhythmic agent that actsby activating the slow inward sodium current, resulting inprolongation of the action potential duration.13 In addition toits primary method of action, it has been shown to prolongrefractoriness of the atrioventricular node, His-Purkinjesystem, and accessory pathway14 and it blocks the delayedrectifier Kþ current.15 The drug is eliminated mainly in urine,and it has a half-life of approximately 6 hours (range 2–12hours). The recommended dose for IV administration inpatients weighing less than 60 kg is 0.01 mg/kg, withadministration of a second dose when necessary.16,17 Anumber of studies have previously demonstrated that ibuti-lide has a greater efficacy and conversion rate than mostother agents in the conversion of AFL in adult patients18–20

but carries a risk of adverse events such as torsades depointes and other ventricular arrhythmias.18,21 Because ofthese risks, it is important to ensure that patients have normalelectrolyte levels prior to administering ibutilide and thatequipment for cardioversion is immediately available.

The safety and efficacy of ibutilide in children has yet tobe established but, in a single study, the conversion rate was83% in children aged 6 months to 18 years of age.22 The

1233Prasad et al Ibutilide in Atrial Flutter Conversion in Neonates

medication was well tolerated with few adverse events (1%risk of torsades de pointes and 1% risk of nonsustainedventricular arrhythmia).

In a study of adult patients who received ibutilideinfusion, the authors were able to significantly decrease theincidence of torsades de pointes and other ventriculararrhythmias with prophylactic use of magnesium, therebyenhancing the safety of ibutilide.23 On the basis of this, onemight consider pretreatment of these neonates with magne-sium sulfate (25–50 mg/kg/dose) prior to administeringibutilide and/or administer the medication at a slower rate.Currently, no guidelines exist for infusion rates of ibutilide inneonates and children. Our recommendation is to perform alarger study in neonates to assess whether slower infusionrates and/or pretreatment with magnesium would decreaseQTc prolongation without altering the efficacy.

ConclusionsSynchronized DCC is currently the most effective method toconvert AFL in neonates. Pacing and several pharmacolog-ical agents have been tried but have variable success rates.We report the successful conversion of AFL to NSR in 2neonates without lasting side effects. Ibutilide could prove tobe an acceptable and safe alternative to synchronized DCC.

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