High doses of methadone can cause sudden death from acute ventricular tachyarrythmias... or at least that is the impression that some research seems to imply. This is known by some cynics as "Krantz Syndrome" after the author of one of the most influential pieces of research on the subject (click here for abstract).
Krantz's postulate is that some people have naturally prolonged QT intervals on their ECG, which is associated with "Torsade des Pointes" arrythmias. In his study, methadone patients further increased the QT interval, but his patients were complex medical subjects, most of whom were being treated for intractable pain and not regular addiction patients at all. In his first report of 17 cases from US and Canadian pain centres, none of whom died, 15 had pre-existing risk factors for arrhythmias. Also, the mean dose was a ‘stratospheric’ 400mg. Other researchers have confirmed the findings, again in very high doses of methadone not normally used in addiction work. Krantz himself concluded that routine ECG examinations in normal addiction patients was not indicated.
However, the BNF and the new guidelines suggest that in methadone maintenance where the dose of methadone rises above 100mg daily, an ECG should be performed. What you do with patients whose QT is prolonged (>440 msec in males or >470 msec in females) is not stated - but clearly other drugs that can also affect either the QT interval or methadone metabolism, should be avoided.
I suspect that this advice will be officially debunked in the future, but for the time being, that is the advice. You have been told!
