A Literature Search of QT Related Tachycardia in Methadone Maintenance Patients
Comments by Andrew Byrne
April 15, 2008
Surgery web page: http://www.redfernclinic.com/#news
Publication: Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D, 2006. Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction 101: 1333-1338.
The Addiction journal has a literature search of torsade arrhythmias in methadone maintenance patients. In 14 published reports, Dr Justo and colleagues found 40 documented cases, excluding those treated for chronic pain.
The median age was 41 years and 68% were male. The mean daily dose was 231mg. The corrected QT interval (QTc) around the time of the arrhythmia was 598 ± 75ms (~normal <450 male, <470 female). All patients reportedly survived the torsade episode(s).
In analysing the individual case reports, the authors found that 85% of subjects had one or more additional contributing factors over and above the use of methadone (mostly at very high doses). These factors included 22 patients (55%) taking drugs known to cause QT prolongation or to increase methadone levels; 16 (40%) with HIV infection; 14 (35%) had hypokalaemia; 11 (28%) had cirrhosis or renal failure and 9 (23%) had heart disease. Many had two or more of these additional risk factors. There were two cases of familial long QT syndrome, both women.
Justo and colleagues conclude that methadone may join a pharmacological category like amiodarone which causes significant QT prolongation but which is only rarely associated with torsades.
Erich Wedam’s RCT report (2007) and Janet Lipsky (1973) attest to frequent QTc prolongation in early methadone patients (23% and 34%). Yet no cases of torsades were reported and indeed tachycardia is either extremely rare or non-existent in such patients who form a quite different group to the torsade cases summarised in Addiction.
This is very reassuring information showing that the torsade arrhythmia does not seem to happen without warning in our usual patient group. Almost every case reported in the world literature was taking very high doses (in Krantz’s series it was 400mg daily) as well as usually also having one or more serious risk factors such as older age, HIV, co-medication, organ failure or heart disease. All of these are easy to recognise as long as the patients have regular and comprehensive medical assessments (including a cardiograph in appropriate cases). Personal or family history of syncope would be essential information.
According to Krantz’s experience in the field, the opioid treatment setting is an ideal venue for cardiac monitoring and preventive health strategies such as lipid studies, dietary advice, blood pressure, smoking cessation and harm reduction education which may help avoid infections including endocarditis (see ref below). Such attention to clinical detail will become even more relevant as our patients get older and as Krantz also points out, as maintenance treatments are used more in the community. He also mentions some tantalizing but as yet unproven information that there may be less coronary artery disease in those on long term opioids (also see Marmor, Maslansky et al).
It is hard to know how much attention front-line clinicians have been paying to the QT issue but one hopes that it does not detract from crucial issues such as treatment access and effectiveness.
References:
Krook AL, Waal H, Hansteen V. Routine ECG in methadone-assisted rehabilitation is wrong prioritization. Tidsskr Nor Laegeforen 2004 124: 2940–1 http://www.unboundmedicine.com/medline/ebm/record/15550974/abstract/.
Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MCP. QT-Interval Effects of Methadone, Levomethadyl, and Buprenorphine in a Randomized Trial. Arch Intern Med 2007 167;22:2469-2473.
Krantz MJ. Clinical Concepts- Cardiovascular Health in MMT Patients. Addiction Treatment Forum 2001 No 4 http://www.atforum.com/SiteRoot/pages/current_pastissues/fall2001.shtml.
Marmor M, Penn A, Widmer K, Levin R, Maslansky R. Coronary artery disease and opioid use. Am J Cardiol. 2004 93:1295-1297.
Amiodarone Review: http://www.eboncall.org/CATs/2611.htm.
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