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Torsade de Pointes Associated with Very-High-Dose Methadone

Mori J. Krantz, MD; Laurent Lewkowiez, MD; Helen Hays, MD; Mary Ann Woodroffe, BScN; Alastair D. Robertson, PhD; and Philip S. Mehler, MD
[+] Article and Author Information

From Denver Health Medical Center and The University of Colorado Health Sciences Center, Denver, Colorado; University of Alberta, Edmonton, Alberta, Canada.


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.


Ann Intern Med. 2002;137(6):501-504. doi:10.7326/0003-4819-137-6-200209170-00010
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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 A methadone derivative, levacetylmethadol, was withdrawn from the European market after being associated with torsade de pointes.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.

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Summary for Patients

Very High Doses of Methadone May Cause Abnormal Heart Rhythm

The summary below is from the full report titled “Torsade de Pointes Associated with Very-High-Dose Methadone.” It is in the 17 September 2002 issue of Annals of Internal Medicine (volume 137, pages 501-504). The authors are MJ Krantz, L Lewkowiez, H Hays, MA Woodroffe, AD Robertson, and PS Mehler.

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