Cardiac complication black box
warnings on the anti-emetic droperidol have done nothing
to improve patient outcomes, but have merely robbed
surgeons of the best tool for treating post-operative
nausea.
That's the conclusion of new research
in the journal Anesthesiology.
FDA'S
TIDE TURNS
After years of being accused of dilatoriness in posting
warnings about drug adverse effects, the FDA is now
being criticized for overreacting with excessively harsh
warnings. Last month, the American Journal of Psychiatry
carried research which argued that FDA black box
warnings on SSRI antidepressants have actually increased
adolescent suicides, the very problem they were meant
to address.
In the current study, Mayo Clinic
researchers looked at the records of nearly 300,000
surgical patients who passed through their system before
and after the droperidol warning led them to abandon
the drug. They found that droperidol use was in no way
associated with the serious cardiac complication known
as torsade de points — the supposed side effect
that led the FDA to recommend against it based on 10
cases over 30 years.
Of 139,932 patients treated prior
to the black box warning, 1.66% met one of three endpoints
- QT prolongation, torsade de points or death within
48 hours of surgery — but not one of the case reviews
showed a clear case of torsade de points, even though
nearly 17,000 had taken droperidol.
Of 151,256 patients treated after
the warning, 1.46% met one of the three endpoints, including
two documented cases of torsade de points. One conclusion
that may be safely drawn from this is that there is
no evidence of a link between droperidol and torsade
de points, the authors suggest. Another conclusion is
that torsade de points is too rare a complication to
justify dropping such a useful drug as droperidol.
TRIGGER
HAPPY?
In the US, says Dr Gregory Nutall, lead author of the
Mayo research, a black box warning is a death sentence.
"If you use it, and anything at all goes wrong, you're
likely to find yourself in court with somebody waving
this warning under your nose. Usage fell to zero after
the warning."
Droperidol has its defenders for
good reason. It's cheap, well-understood and was safely
used for decades. While the FDA agonized publicly for
months before slapping black box labels on antidepressants,
their approach to droperidol was a lot more cursory.
The drugs that replaced droperidol
after the FDA intervened were principally the 5-HT3
antagonists, of which the best known is ondansetron.
"They aren't bad drugs. They're effective at preventing
post-operative nausea," says Dr Nutall. "But they do
less for the patient who already has it." Physicians
need choices so they can give non-responders different
drugs, he says, rather than upping the dosage of drugs
that aren't working.
Ironically, the 5-HT3 antagonists
class is also listed in drug reference works as having
QT interval prolonging effects with possible associated
torsade de points. Of the two patients who developed
torsade de points in the Mayo study, one had taken ondansetron.
Neither had taken droperidol.
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