QTc interval screening for cardiac risk in methadone treatment of opioid
dependence. Pani PP et al. Cochrane Database CD008939
Trends in reporting methadone-associated cardiac arrhythmia, 1997-2011:
an analysis of registry data. Kao D et al. Ann Intern Med 2013
Opioid addiction agonist therapy and the QT prolongation phenomenon:
state of the science and evolving research questions. Wedam EF, Haigney MC.
Addiction 2013
False sense of safety by daily QTc interval monitoring during methadone
IVPCA titration in a patient with chronic pain. Miranda-Grajales H et al. J
Pain Res 2013 [full citations below]
Dear Reader,
Before commenting on these four recent items, here is my summary of the
state of play: “While
distressing and serious, torsade de pointes tachycardia is a very rare event in
methadone patients. This arrhythmia is
highly treatable with a low or zero mortality rate judging from the cases
reported in the literature since 2002 (n~100).
Torsade de pointes appears to affect the older patient population
(>40 years), is more common in women and generally when higher doses of
methadone (>120mg daily) are combined with other drugs such as certain
antibiotics and anti-virals.”
These four recent items related to cardiac complications in patients
prescribed methadone. While the Cochrane
review finds insufficient evidence to advise any interventions on this subject,
the other three papers are disappointingly thin on facts and high on the ‘fog’ factor despite the clarity now appearing after a
decade of clinical experience since Krantz’s seminal report of 17 cases in 2002. [Cochrane abstract: http://www.ncbi.nlm.nih.gov/pubmed/23787716?dopt=Abstract
]
Kao, Krantz (senior and corresponding author) and colleagues purport to
present an ‘analysis’ of FDA adverse event reports. Their torsade figures include reports which
were not primarily due to methadone (43% not primary suspect) and further, it
also comprises reports of QT prolongation without a break-down of these two
very different syndromes. Hence to
arrive at the actual number of torsade reports where methadone was the primary
suspect one needs to discount 361 by 43% and then take account of the
proportion of torsade cases (figure not given here but was about 70% in Pearson’s paper).
This makes about 2 reports of torsade tachycardia per month in
America. About half would have been
dependency cases (FDA information). See
my own more detailed description and conclusions [ http://methadone-research.blogspot.com.au/2013/07/can-adverse-event-reports-inform.html
]. [Abstract can be accessed here: http://www.ncbi.nlm.nih.gov/pubmed/23689766?dopt=Abstract
]
In an ‘Addiction’ editorial Wedam and Haigney write
discomforting and confusing words about the so-called “QT prolongation phenomenon”. Why
call it a ‘phenomenon’ any more than a fever in an infant with an
infection? But it serves to spice up the
‘mystery’ which scientific discourse is meant to
dispel. Many commentators and public health
authorities have called for more substantial research on this subject,
preferably national surveys. Yet now
that such research it to hand from Norway and France (sudden deaths in Norway
and torsade reports in France, all very reassuring and consistent) many writers
seem to ignore its outcomes. Wedam and
Haigney cite the Norway article by Anchersen but then states that Americans
must be different to Europeans!! Their
citations do not (and cannot) justify such a position, making the contention no
more than a ruse to confuse.
This ‘Addiction’ editorial continues a long history of
apparent antagonism to methadone treatment.
Their titles would seem to support this while few of the items would
appear to be productive issues aimed at improving patient care or public health
goals. Topics included cravings from
additional methadone, memory problems, injecting of methadone, benzodiazepine
abuse, deaths, and more. [full Addiction article available on line: http://onlinelibrary.wiley.com/doi/10.1111/add.12123/full
]
The third item is a chronic pain case report of such an extraordinary
nature that it can have little or no relevance to regular clinical
practice. Veteran author Dr Cruciani
(senior and corresponding author) and colleagues surprisingly publish a
detailed day-to-day report of a complex pain patient who was clinically
overdosed with methadone given parenterally along with pethidine and other
opioids. The most telling features
relative to cardiac safety would include: the lowest QTc values (317, 416ms)
were found on the days after the highest methadone doses (334, 363mg). One slightly prolonged reading (451ms)
occurred two days after methadone was ceased altogether. These findings are consistent with the
literature in which normal QTc levels were commonly found in patients who had
torsade de pointes away from the tachycardia episode (and also large diurnal
variations in QTc values). A single ECG
tracing is almost certainly a waste of time for routine purposes in low or
perhaps even high-risk patients. And
despite all the prolonged QT levels this patient still did NOT develop any
arrhythmia.
While torsade de pointes is extremely uncommon, it
will still be seen occasionally in dependency and pain practice. The arrhythmia needs to be considered in
someone with fainting, fitting, palpitations, shortness of breath or
occasionally, chest pain. Treatment
involves the use of urgent paramedic treatment and transfer to cardiac intensive
care for monitoring. Some patients will
need intravenous magnesium, temporary pacemaker and/or cardioversion. Withdrawal or replacement of the suspected
drugs and/or reduction in doses may be useful.
There is no single agreed protocol for this condition but its treatment
should be directed by cardiac experts, just as dependency should be directed by
dependency experts and pain by pain management experts. It is crucial not to
avoid appropriate doses of methadone as the risk of inadequate doses is very
substantial, including death, whereas there he never been a reported confirmed
death due to torsade de pointes.
As Pani et al. point out there is no proven
preventive strategy but it would seem prudent to order a cardiograph on
patients who are prescribed high dose methadone (>150mg), especially if
there are any other risk factors.
Comments by Andrew Byrne ..
Full citations for these articles:
Pani PP, Trogu E, Maremmani I, Pacini M. QTc interval screening for
cardiac risk in methadone treatment of opioid dependence. Cochrane Database
Syst Rev. 2013 Jun 20;6:CD008939
Kao D, Bucher Bartelson B, Khatri V, Dart R, Mehler PS, Katz D, Krantz
MJ. Trends in reporting methadone-associated cardiac arrhythmia, 1997-2011: an
analysis of registry data. Ann Intern Med. 2013 21;158(10):735-40
Wedam EF, Haigney MC. Opioid addiction agonist therapy and the QT
prolongation phenomenon: state of the science and evolving research questions.
Addiction 2013 108;6:1015-1017
False sense of safety by daily QTc interval monitoring during methadone
IVPCA titration in a patient with chronic pain. Miranda-Grajales H, Hao J,
Cruciani RA. J Pain Res 2013 6:375-8
