Torsade de Pointes Associated with Very-High-Dose Methadone

  1. Mori J. Krantz, MD;
  2. Laurent Lewkowiez, MD;
  3. Helen Hays, MD;
  4. Mary Ann Woodroffe, BScN;
  5. Alastair D. Robertson, PhD; and
  6. Philip S. Mehler, MD
  1. From Denver Health Medical Center and The University of Colorado Health Sciences Center, Denver, Colorado; University of Alberta, Edmonton, Alberta, Canada.

    Abstract

    Background: Methadone is an effective treatment for opioid dependency and chronic pain. A methadone derivative, levacetylmethadol, was withdrawn from the European market after being associated with torsade de pointes. To date, no association between methadone and this arrhythmia has been described.

    Objective: To evaluate a series of methadone-treated patients experiencing torsade de pointes.

    Design: Retrospective case series.

    Setting: Methadone maintenance treatment programs in the United States and a pain management center in Canada.

    Patients: 17 methadone-treated patients who developed torsade de pointes.

    Measurements: Chart review for concomitant arrhythmia risk factors and quantification of corrected QT interval (QTc).

    Results: The mean daily methadone dose was 397 ± 283 mg, and the mean QTc interval was 615 ± 77 msec. Fourteen patients had a predisposing risk factor for arrhythmia. A cardiac defibrillator or pacemaker was placed in 14 patients; all 17 patients survived.

    Conclusions: This series raises concern that very-high-dose methadone may be associated with torsade de pointes. Given the likely expansion of methadone treatment into primary care, further investigation of these findings is warranted.

    Article and Author Information

    • Acknowledgments: The authors thank Lisa Kosmiski, Fred Masoudi, William Baker, and Edward Havranek for manuscript review and Megan Marx, DeeAnn Rivera, and Jon Lee for assistance with data collection.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Mori J. Krantz, MD, Division of Cardiology, Denver Health Medical Center, Mail Code 0960, 777 Bannock Street, Denver, CO 80204-4507.

    • Current Author Addresses: Drs. Krantz and Lewkowiez: Denver Health Medical Center, 777 Bannock Street, Mailcode 0960, Denver, CO 80204.

    • Dr. Hays and Ms. Woodroffe: 210 Meadowlark Place Professional Centre, 8708 155 Street, Edmonton, Alberta T5R 1W2, Canada.

    • Dr. Robertson: University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box B-130, Denver, CO 80262.

    • Dr. Mehler: Denver Health Medical Center, 660 Bannock Street, Mailcode 1914, Denver, CO 80204.

    • Author Contributions: Conception and design: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, P.S. Mehler.

    • Analysis and interpretation of the data: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

    • Drafting of the article: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

    • Critical revision of the article for important intellectual content: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

    • Final approval of the article: M.J. Krantz, L. Lewkowiez, H. Hays, M.A. Woodroffe, A.D. Robertson, P.S. Mehler.

    • Provision of study materials or patients: M.J. Krantz, H. Hays, M.A. Woodroffe.

    • Statistical expertise: M.J. Krantz, A.D. Robertson.

    • Administrative, technical, or logistic support: M.J. Krantz, P.S. Mehler.

    • Collection and assembly of data: M.J. Krantz, P.S. Mehler.

    Summary for Patients

    • Summaries for Patients:Very High Doses of Methadone May Cause Abnormal Heart Rhythm Ann Intern Med September 17, 2002 137:I-42
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    1. Ann Intern Med September 17, 2002 vol. 137 no. 6 501-504
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