Introduction: Methadone exposure carries the risk of QT prolongation with associated torsade-de-pointes (TdP) and sudden death (SCD) in adults. Recent guidelines regarding screening ECGs exist despite the limited data regarding methadone use and its cardiac effects in children.
Hypothesis: Methadone use in children does not result in clinically significant cardiotoxicity.
Methods: A retrospective cohort study was performed from January 2014 to August 2016 at a tertiary children’s hospital evaluating measures of cardiotoxicity in all pediatric patients (< 18 yrs) on methadone. Measures of cardiotoxicity analyzed included prolongation of QTc interval, documented TdP, and SCD.
Results: A total of 118 patients (50% male) received methadone with a median age of 1.9 (IQR: 0.2 - 11.5) years and weight of 10.0 (IQR: 4.5 - 37.6) kgs. The primary indications included pain (57%), opioid withdrawal/sedation wean (41%), and opioid addiction (2%). ECGs were obtained prior to treatment in 60% of patients (n=71) with a mean QTc of 423 ± 26 msec and on treatment in 42% of patients (n= 49) with a mean QTc of 426 ± 29 msec (p= .19). The mean change in QTc observed after methadone initiation among patients with baseline and on treatment ECGs (n=35, 30%) was 8 ± 8 msec (421 ± 25 to 429 ± 32 msec, p=0.12). The mean change in QTc observed during treatment among patients with serial ECGs (n=30, 25%) was 24 ± 16 msec (428 ± 32 [first ECG on treatment] to 452 ± 29 msec [max QTc on treatment, p=0.004]). At baseline (n = 71), 23% of patients had an QTc ≥ 450 to 499 msec and 4% with QTc ≥ 500 msec. There was no significant change in risk on treatment stratified by QTc group (see Table). There were no arrhythmias or death documented while on therapy.
Conclusions: Methadone was not associated with clinically significant cardiotoxicity in children despite suboptimal ECG compliance to guidelines. Further data and compliance is warranted as a 20-43% of children receiving methadone had baseline or on-treatment QTc prolongation.