INDICES> pralidoxime (PAM) (2)

["Janet McNeece" <Jmcneece@mail.rah.sa.gov.au>]

Indices: pralidoxime (PAM) (2)

Dear Sir
There is a useful review of the treatment of organophosphorus 
poisoning (including the use of pralidoxime) in the QJM 2002; 95 
(5): 275-83,  authors Eddleston M, Szinicz L,  Eyer P, Buckley N.  
This review was performed by a group of toxicologists from various 
countries.  I have attached the conclusion below for your interest 
however, I have heard from my colleague that she has obtained a 
full copy of this paper from the journal web site (free) so this may 
be worth a try.

If you cannot easily get a copy of the reference this is a copy of the 
conclusion.

Detailed observational clinical studies suggest that oximes 
encourage acetylcholinesterase A ChE regeneration.  Animal data 
consistently show a markedly positive effect of oximes on survival.  
Physicians in India, China and Vietnam have recently reported 
improved outcomes in uncontrolled studies with high doses of 
pralidoxime.  However, no clinical trials have formally assessed the 
efficacy of high-dose pralidoxime.


Two small randomized controlled trials have looked at either lower 
doses; 1g bolus doses of pralidoxime or 12g given by infusion over 
3-4 days.  Increased mortality was found with patients receiving the 
infusion of pralidoxime without a loading dose compared to either 
placebo or a loading dose alone.  The authors of these studies 
have stated that pralidoxime should not be used for 
organophosphorus poisoning.  However, we do not believe that the 
results of these randomized controlled trials can be used to make 
such a generalised comment and the effectiveness of pralidoxime 
in our view is still undecided.


Although the studies are methodologically weak, it is quite 
possible that their conclusions are correct.  There are many factors 
present in self-poisoning cases in South Asia that would reduce 
the effectiveness of pralidoxime.  A  study from Sri Lanka showed 
that around 70% of organophosphorus poisoned patients had 
ingested dimethylated compounds; this situation may well be 
similar in other parts of the tropics and since many patients 
present more than 12 hours after the poisoning, it may be too late 
for oximes.  In addition, the suicidal dose is often large and the 
pesticide persistent for several days, resulting in repeated inhibition 
of any newly reactivated AChE.
We believe that a large high-quality randomized controlled trial 
comparing the current WHO-recommended regimen with placebo is 
required to definitively assess the value of pralidoxime in acute 
organophosphorus poisoning.  Such a trial may well confirm the 
Vellore group's findings.
Randomization should be stratifies according to baseline severity, 
time to presentation, and class of  organophosphorus pesticide 
taken (diethyl or dimethyl), with predefined sub-group hypotheses.  
Because of the importance of aging in determining the usefulness 
of oximes, red blood cell acetylcholinesterase activity and the 
potential for ex-vivo reactivation will have to be measured for such a 
study to be fully interpretable.  Only after such a study has been 
completed will it be possible to determine whether 
orgonophosphorus- poisoned patients benefit from oxime therapy. 


Hope this is useful


Janet McNeece
Senior Pharmacist
Medicines Information
Royal Adelaide Hospital
South Australia

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