8 September 2009

Torsade rarity: Annals responses argue ECG ineffective and unnecessary before MMT.

Krantz et al, Annals of Internal Medicine March 17: letters in reply, Aug 4 2009.


Dear Readers,

Each of four responses to this item was strongly critical of the position or Krantz et al. regarding cardiac safety in methadone patients. Apart from my own small contribution, there were considered responses from physicians and alumni of Johns Hopkins, Harvard and Rockefeller University as well as the medical director of a network of private addiction clinics treating 5000 methadone patients in California. There was no letter in support of Krantz et al and their “guidelines”.

Despite my written requests to Drs Krantz, Stimmel, Haigney and Martin, there is still no indication from these authors on the proposed means whereby regular ECG tracings would or could prevent torsade tachycardia from occurring in MMT patients. It would seem incumbent on Dr Krantz and colleagues to explain just how they anticipate the published recommendations might reduce cardiac side effects, and further, what might be the downside of the recommendation in terms of barriers to methadone treatment for those who want and need it both in developed and developing countries.

Krantz has written that cardiac safety in methadone treatment is a ‘national priority’ and that torsade is ‘potentially fatal’. Yet in 40 years there has still not been one confirmed death due to this complication in a methadone patient I can find in the literature. Out of ~100 case reports the great majority had complex medical scenarios including HIV, existing heart disease, metabolic disturbance and/or taking exceedingly high doses (mean 400mg daily in Krantz’s original report). These would only represent a small minority of those being assessed in addiction clinics around the world.

It is difficult to accept these guidelines in their present form when the main authors simply deflect criticism from senior colleagues rather than responding to it - see their response to the four letters.

Two original panel members declined to be associated with the publication and its recommendations. Their names were on the original internet version published around 1 Dec 2008 and now withdrawn. To my knowledge their dissenting views have not been published although the Annals editors took the rather unusual step of writing their own rapid response pointing out some of the facts following my initial communications: http://www.annals.org/cgi/eletters/0000605-200903170-00103v1 (‘Putting the cart before the horse’). They also published a balanced and well considered editorial in the same hard-copy edition by Gourevitch.

I am still persuaded by the advice given by Dr Mori Krantz consistently from 2002 up until his Annals article this year that ECG is unnecessary before starting methadone treatment unless there is a specific indication (*see his quotes below). This is parallel with the views of other respected authors such as Krook, Athanasos, Gourevitch, Kreek, Bart and others.

We need a high level of awareness for numerous diseases and complications in older addiction patients. Cardiac conduction disturbance is just one of many such areas that we need to deal with. Although cardiac problems are dwarfed in scope by many other problems such as blood borne infections and hormonal imbalance, they should not be overlooked in known high risk groups.

In our own practice we generally order an electrocardiogram when the methadone dose exceeds 150mg daily and/or when there are other risk factors such as HIV, older age or other drug prescription known to affect methadone metabolism or cardiac conduction.

Comments by Andrew Byrne .. http://www.redfernclinic.com/c/

Original article: http://www.annals.org/cgi/content/full/0000605-200903170-00103v1

Krantz on cardiac health in MMT patients (2001): http://www.atforum.com/SiteRoot/pages/current_pastissues/fall2001.shtml#anchor1222388

Krook AL, Waal H, Hansteen V. Routine ECG in methadone-assisted rehabilitation is wrong prioritization. Tidsskr Nor Laegeforen 2004 124;22:2940-1

Athanasos P, Farquharson AL, Compton P, Psaltis P, Hay J. Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. J Addict Dis. 2008 27(3):31-5

Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients - a cross-sectional study. Addiction 2007 102;2:289-300

Gourevitch MN. First Do No Harm ... Reduction? Annals of Internal Medicine 2009 150;417-8

*Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368;9535:556-557 (quotes herewith from page 557)
“… we do not believe that routine ECG screening is warranted for heroin addicts entering treatment.”
“… we believe that the decision for ECG screening should not only be informed by the patient’s arrhythmia risk factors but also by the dose of methadone received.”

Possibly the last word: 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#anchor1222388