Torsade de Pointes due to Methadone Use in a Patient with HIV and Hepatitis C Coinfection. John J, Amley X, Bombino G, Gitelis C, Topi B, Hollander G, Ghosh J. Cardiol Res Pract. 2010; 2010: 524764
Dear Colleagues,
This case history is instructive although it is not novel. To call this torsade "due to methadone" in the title is highly misleading and contrary to the paper’s data.
The daily methadone dose was low at 40mg (and ‘recently increased’); the patient was aged 50 and was also prescribed three antiviral agents and two antibiotics for HIV. These factors made the patient easily identifiable as a high risk case for numerous medical complications including torsade de pointes tachycardia. Importantly, one of the HIV drugs used has been reported elsewhere to cause torsade (atazanavir, as reported by Dabiesingh; Ly and others). Hence older age, atazanavir and HIV are thus all known to be specific risk factors for developing QT problems. There is also some evidence that HCV may be an independent risk factor for QT prolongation (Norden). From the literature I have searched it seems that most HIV subjects with torsade de pointes are not taking methadone.
Unfortunately, details of this patient’s dependency management are scanty and it seems that there was limited if any addiction specialty input. Note that the patient survived and even 23 days after the methadone was ceased still had QT prolongation and was considered to be in need of a pacemaker (ICD). The reader is not informed, but methadone may have been substituted by another drug, such as morphine. Either way, it would seem to indicate that the methadone was NOT the cause of the electrical perturbations in this patient, despite the alarmist title.
The authors concede that a dose level of 40mg (increased two months before the episode following two years of no illicit drug use) is very unlikely to be a significant causative factor for QT prolongation. The methadone may even have delayed the onset of torsade, for example, by keeping the patient from other cardio-toxic drugs including alcohol, cocaine and amphetamine. It is paradoxical that this very patient was administered another QT prolonging drug, the anti-arrhythmic amiodarone during resuscitation. This drug is similar to methadone in that it can reportedly cause QT prolongation but rarely induces torsade.
These authors cite Adelaide author Athanasos but do so rather selectively. While he does indeed describe U-waves, of uncertain clinical significance, his study found no cardiologic consequences of low to medium doses of methadone, the latter findings appear to be ignored in the current paper. It is intriguing that these authors would repeat Krantz and colleagues’ controversial and unproven advice (Ann Int Med) about performing annual ECGs on methadone patients (see responses in Annals, 4 against, none in favour). This very case report is yet another example in which such serial ECGs were performed and yet torsade occurred regardless. It seems that in America performing a test is sometimes seen as a defence regardless of its utility or otherwise.
That this patient is alive at 50 after having such serious complications of IV drug use as HCV, HIV and hepatoma is indeed a credit to the methadone and medical care received at this institution bearing the name of one of the most innovative doctors of all time, Maimonides (see his treatises on haemorrhoids, digestion, chicken soup and cohabitation).
Reports of torsade in methadone patients are not usually published any more, probably because the details are similar to over 100 other such reports - it would be like describing a 'routine' case of appendicitis. Furthermore, there have apparently been no fatalities from confirmed torsade to date to my best knowledge, at least in the past 15 years (an American text states that it should have a mortality of zero). According to the Journal's web site these authors would have paid over US$500 to have this vignette made public.
If nothing more, the report should be a wake-up call to all who treat middle aged opioid dependent patients and remind us to take greatest care when anti-virals, anti-fungals, antibiotics, etc are being prescribed, especially by others who may not be familiar with the dependency side of their patient’s treatment. The size of the methadone dose appears to be of little relevance (Krantz’s original series had 6 of 9 subjects taking between 65mg and 125mg, mean 96mg daily; Pearson reports one case at 29mg daily).
Comments by Andrew Byrne ..
Link to article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021856/
Correction for Jones article summary: I stated in an early draft that there was no fetal loss but in fact there were two such events, both in the methadone group. This was promptly corrected on the web site and I apologise for the mistake. Dr Jones has also pointed out that the trend for greater attrition in the buprenorphine group did not reach statistical significance. To my mind the authors have still not justified their comment that buprenorphine is now a ‘first line option’. Just because they showed no difference in retention/attrition, this does not prove that the two treatments are equivalent therapeutically. I believe that both drugs are extremely useful in opioid dependency and that methadone remains the gold standard (O’Connor 2010 JAMA) although it does not suit everyone or every situation.
