Thursday, December 4, 2008

APSAD Annual Scientific Conference 2008 - Australasian Professional Society on Alcohol and other Drugs.

November 23 - 26, 2008 Part I (Sunday 23 Nov).

This year's APSAD conference was a fine affair. I must have been to 15 or more of these in most State capitals, Cairns and Canberra. I missed last year’s Fest in Auckland but those who attended said it was excellent. Like national leaders’ meetings with their funny hats, shirts and coats, each APSAD conference is characterised by its own conference attaché bag. This natural-inspired over-the-shoulder model was one of the few I could imagine using in the future.

The venue was splendid, Darling Harbour being just an 8 minutes (downhill) walk from Town Hall station which made me into a commuter again. With medical practice responsibilities I was a part-time conference goer.=C 2 Thus these notes are incomplete and (as usual) opinionated.

The Sunday afternoon pre-conference session had been booked by the only drug company with a major stake in our field. Reckitt-Benckiser is manufacturer of buprenorphine which is the only registered alternative to methadone, the latter being a generic drug with small bread-and-butter profit lines in comparison. The sponsors began with the topics of pharmaceutical abuse and innovations in addiction management, then ending with two presentations on the potential cardiac complications of methadone before a panel discussion to which I had been invited (and generously funded).

Adrian Dunlop spoke eloquently about the past, present and future of addiction treatments.

Dr Eric Strain covered some historical details of non-medical use of pharmaceuticals in the US, giving some results on prevalence and consequences from household surveys over 25 years. Apparently most users obtained their supplies from one doctor; many from friends or relatives with less only ~1% or less from the internet. Australian figures may be quite different as people are entitled to attend more than one doctor on Medicare. Another speaker quipped that if Australia had a Bill of Rights, it would include being able to attend “as many doctors as you like”. Dr Strain touched on the gap between occasional use and dependent use, something some of us may still forget because of the selected referrals we receive. The other major differences between American street heroin users and those abusing pain killers is that the latter are more likely to be employed, white race and non-injectors. Dr Strain was too modest to mention his own research on buprenorphine abuse and perhaps too polite to mention the reported non-medical use of buprenorphine, including a naloxone combination product which became the drug of choice (mostly injected) by more than half those presenting for treatment in Wellington, New Zealand (see Robinson 1993).

Dr Nick Lintzeris gave some pointers about pharmaceutical abuse in Australia. His talk ending with a plea to put methadone treatment, including side effects, into context both globally, as well as for individual patients. In his rather frequent exposure during the conference, he reminded us that there are much more relevant issues for opioid therapy as patients get older such as testosterone levels, calcium leaching, osteoporosis, dental, viral and bowel problems.

Jason White detailed the rather sparse literature on cardiac complications in methadone recipients. He seemed persuaded that the connection between methadone and torsade is significant and that methadone treatment could be restricted or further regulated as a result. As a demonstration of patients on ‘normal’ methadone treatment coming to torsade, he cited Pearson and Woosley’s report of 59 FDA notifications from 1969 to 2002. While not fully documented, from the limited data 12 could have been on ‘standard’ MMT, 8 of whom were over 40 years of age. This leaves just 4 reported ‘standard’ MMT cases in the USA over a 33 year period in the age group we normally start on MMT. Justo’s more recent literature review found only 6 of 40 cases reported could have been on ‘standard’ MMT cases without other triggering factors (85% had one or more of these known causes of QT prolongation aside from high methadone doses).
QT prolongation on the cardiograph has long been know to occur in about a quarter of methadone patients yet its only serious consequence, ‘torsade de pointes’ tachycardia, hardly ever seems to occur in young patients (<40>40 years of age, electrolyte disturbance,20etc.

As our patient population on maintenance treatment gets older so we must be more vigilant about this and other eventualities. As with other related medical issues, close attention should be paid to cardiac status. This may include an ECG in those taking over 150mg, those prescribed other ‘at risk’ medications or those with HIV or personal/family history of unexplained syncope or fainting.

At this session I was delighted to finally learn the origin of the term ‘ether-a-go-go’ which is from the rhythmic dancing induced in the legs of doomed drosophila drones (flies) under the influence of ether in genetic experiments on channel blockers.

We were then shown a 15 minute video ‘interview’ with Colorado cardiologist Dr Mori Krantz detailing blow by blow the now supposedly conclusive case for methadone’s guilt beyond reasonable doubt in causing fatal arrhythmias. The final proof of any medical argument, we are told, involves randomisation of subjects and so the RCT by Wedam is proffered. This trial, a secondary analysis of ECG tracings obtained incidentally in a 1990s RCT, showed very high rates of QT prolongation in the first 4 months of MMT but no cases of torsade. On e of the panellists said to me privately that this appears to be rather persuasive of the safety of methadone rather than the opposite.

As above, hardly anyone has ever seen a case except in patients who are already stressed and in highly complex medical circumstances. I note that since his classic description of 17 non-fatal cases in 2002 (8 were pain management cases), Krantz has only reported two other individual cases of torsade, one of which was due to cocaine.

In the video, we are told that because one cannot diagnose an electrical disturbance after death, coroners are unable to detect whether the death was due to cardiac arrhythmia or respiratory depression from the drug. In fact many cases are very clear at autopsy as having the classic findings of post mortem sub-acute lung changes and high blood levels as to leave little doubt abou t the cause of death. So while Krantz’s proposition may be true for a certain minority, with a 20% mortality, there ought to be 4 times as many (80%) torsade survivors. Yet few if any of these ever seem to get to an emergency room (or ambulance) and have their potentially fatal problem diagnosed with a simple cardiograph tracing. Such reports are exceedingly scarce or non-existent. I called one of Australia’s busiest casualty departments to be told that their long-time medical director had never seen a case of methadone associated torsade. He also pointed out that for the past several years, modern cardiograph machines have given an automated print-out of QTc, making this information much more available that previously. This just might be the single most important cause of the ‘epidemic’ of electrical changes in the absence of actual symptomatic disease.

Further on in the presentation Krantz states the obvious it’s not to say that there is an epidemic of cardiac events in America”. Yet elsewhere he has written that large number of patients are at risk of developing torsade. Fanoe’s Copenhagen syncope study was put up as a written question in the video ‘interview’ (there was no interviewer as such) but Krantz failed to comment on it for some reason. Fanoe showed that out of 800 cases (with no torsade reported) that high rates of syncope (over 20% in most dose groups) in methadone patients was at least in part substantially explained by cardiac conduction problems such as torsade. This is hard to understand for a complication known to occur in less than 1% of patients). Krantz then alluded to Chugh’s Portland study suggesting that it lent support to his torsade theory, yet like so many of the other quoted references, this is another report which does not document any torsade cases. Perhaps I belabour the point. Where are all the bodies in this serial killing, Miss Marple?

[more about lives saved in another conference posting shortly]

Comments by Andrew Byrne ..

Dr Andrew Byrne MB BS (Syd) FAChAM (RACP)
Dependency Medicine,
75 Redfern Street, Redfern,
New South Wales, 2016, Australia
Email -
Tel (61 - 2) 9319 5524 Fax 9318 0631

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Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K. A Community-Based Evaluation of Sudden Death Associated with Therapeutic Levels of Methadone. American Journal of Medicine 2008 121: 66-71

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