> As you infer, Matthew, trials for acute cyanide poisoning would be
> unpopular among volunteers. In countries with a license for
> hydroxocobalamin in cyanide poisoning it is also unethical NOT to use
> hydroxocobalamin as the alternatives are so unsatisfactory. However,
> there are a couple of trials which I find convincing, ( in as far as
> most toxicology trials are convincing. )
I was thinking more along the lines of studies in patients suffering either
from acute cyanide poisoning or smoke inhalation of the sort of severity in
which you would be considering use of B12- the ethics issue here would be
studies of low power (unless you had some way of getting the numbers)
without patient consent (because of unconsciousness). I'm not so sure about
it being unethical not to use B12- if you don't believe that a drug will
work in a particular patient you have no ethical imperative to use that
drug. Down to reading of the evidence again.
I'm not opposed to the use of B12 (not a particular area of interest for me,
so I'm happy to go along with consensus), just unconvinced by the evidence
cited so far- I've not seen human or animal studies (although I don't claim
to having great searching skills) looking at its administration half an hour
or more after toxic levels were achieved -as would usually happen with pre-
hospital administration- (as opposed to concurrent or preceding
administration) improving outcomes. My concern from the pathophysiology
viewpoint is that I understand cyanide as distributing to the tissues
extremely rapidly and having intracellular effects (disordered metabolism
and necrosis often, but of most relevance, apoptosis in the neocortex). It
may that altering the blood level once the cyanide has had time to get into
the tissues will have little or no effect as the damage has already
occurred.
My understanding is that there is still no good outcome evidence, so on that
basis, I'd reckon B12 is a safe, potentially useful but experimental drug.
Looking at other specialities, drugs are often restricted due to cost even
when proven efficacy (for example, how many of you are using Activated
Protein C? For those who do soft tissue clinics, how many have access to
glucuronic acid? How many A and Es keep COX2 inhibitors? Outside A and E
altogether, our rheumatologists are often told they can't have drugs on the
basis of cost.
I wonder if this is a worthwhile one for putting forwards to NICE for
consideration.
Matt Dunn
Warwick
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