Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes.
OBJECTIVE
To investigate the relationship between the daily dose of the synthetic opioid methadone and the corrected QT (QTc) interval in a series of methadone-treated patients who developed torsade de pointes.


METHODS
Retrospective case series analysis.


METHODS
Outpatient pain management center and methadone maintenance treatment programs.


METHODS
Seventeen patients who developed torsade de pointes while receiving very high daily doses of methadone.


RESULTS
The QTc intervals were calculated for each patient. The relationship between daily methadone dose and QTc interval was assessed and adjusted for clinical characteristics that may have independently prolonged cardiac repolarization. The mean QTc interval was 615 +/- 77 msec. Multiple linear regression indicated that only the daily methadone dose was predictive of the QTc interval (r = +0.51, p = 0.03). All other variables examined, such as age, sex, presence of hypokalemia or structural heart disease, and presence of QT-prolonging drugs, were not predictive of the QTc interval (minimum p = 0.28).


CONCLUSIONS
In this series, the daily methadone dose correlated positively with the QTc interval. This finding supports the possibility that methadone contributed to the development of arrhythmia.
Krantz
Mori J
MJ
Division of Cardiology, Denver Health Medical Center, University of Colorado Health Sciences Center, Denver, Colorado 80204-4507, USA. Mkrantz@dhha.org
Kutinsky
Ilana B
IB
Robertson
Alastair D
AD
Mehler
Philip S
PS
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000209:etiology; D008133:Long QT Syndrome / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy; D012189:Retrospective Studies; D016171:Torsades de Pointes / Q000097:blood / Q000139:chemically induced*
D008691:Methadone