Intravenous amiodarone for incessant tachyarrhythmias in children: a randomized, double-blind, antiarrhythmic drug trial.
BACKGROUND
Intravenous (IV) amiodarone has proven efficacy in adults. However, its use in children is based on limited retrospective data.


RESULTS
A double-blind, randomized, multicenter, dose-response study of the safety and efficacy of IV amiodarone was conducted in 61 children (30 days to 14.9 years; median, 1.6 years). Children with incessant tachyarrhythmias (supraventricular arrhythmias [n=26], junctional ectopic tachycardia [JET, n=31], or ventricular arrhythmias [n=4]) were randomized to 1 of 3 dosing regimens (low, medium, or high: load plus 47-hour maintenance) with up to 5 open-label rescue doses. The primary efficacy end point was time to success. Of 229 patients screened, 61 were enrolled during 13 months by 27 of 48 centers in 7 countries. Median time to success was significantly related to dose (28.2, 2.6, and 2.1 hours for the low-, medium-, and high-dose groups, respectively; P=0.028). There was no significant association with dose for any arrhythmia subgroup, including JET, but the subgroups were too small for an accurate assessment. Adverse events (AEs) were common (87%), leading to withdrawal of 10 patients. There were 5 deaths in the 30-day follow-up period (2 possibly related to the study drug). Dose-related AEs included hypotension (36%), vomiting (20%), bradycardia (20%), atrioventricular block (15%) and nausea (10%).


CONCLUSIONS
In children, the overall efficacy of IV amiodarone, as measured by time to success, was dose related but not significantly for any arrhythmia subgroup. AEs were common and appeared to be dose related. Although efficacious for critically ill patients, the dose-related risks of IV amiodarone should be taken into account when treating children with incessant arrhythmias. Prospective, placebo-controlled trials would be helpful in assessing antiarrhythmic drug efficacy in children, because their results may differ from retrospective series and adult studies.
Saul
J Philip
JP
Medical University of South Carolina, Charleston, SC 29425, USA. saulp@musc.edu
Scott
William A
WA
Brown
Stephen
S
Marantz
Pablo
P
Acevedo
Valeria
V
Etheridge
Susan P
SP
Perry
James C
JC
Triedman
John K
JK
Burriss
Susan W
SW
Cargo
Paul
P
Graepel
Jay
J
Koskelo
Eeva-Kaarina
EK
Wang
Rebecca
R
D000293:Adolescent; D000638:Amiodarone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D010599:Pharmacokinetics; D011336:Probability; D013610:Tachycardia / Q000150:complications / Q000188:drug therapy*; D013613:Tachycardia, Ectopic Junctional / Q000150:complications / Q000188:drug therapy; D013617:Tachycardia, Supraventricular / Q000150:complications / Q000188:drug therapy; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone