Oximes for acute organophosphate pesticide poisoning.
BACKGROUND
Acute organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the developing world. Standard treatment involves administration of intravenous atropine and oxime to counter acetylcholinesterase inhibition at the synapse. The usefulness of oximes, such as pralidoxime and obidoxime, has been challenged over the past 20 years by physicians in many parts of the world, who have failed to see benefit in their clinical practice.


OBJECTIVE
To find the clinical trial evidence for oximes producing clinical benefit in acute organophosphorus pesticide-poisoned patients.


METHODS
We carried out a systematic search to find randomised clinical trials (RCTs) of oximes in acute organophosphorus pesticide poisoning, using MEDLINE, EMBASE and Cochrane databases. All articles with the text words 'organophosphate' or 'oxime' together with 'poisoning' or 'overdose' were examined. (Search last updated November 2003.)


METHODS
Articles that could possibly be randomised clinical trials were retrieved to determine if this was the case.


METHODS
The published methodology of the possible RCTs located is not clear. One was found in abstract form only and two other published trials also had many gaps in the published methodology. We have attempted to contact the principal authors of all three trials but have been unable to obtain further information.


RESULTS
Two RCTs have been published, involving 182 patients treated with pralidoxime. These trials did not find benefit. However, the studies did not take into account a number of issues important for outcome and the methodology is unclear. Therefore, a generalised statement on effectiveness cannot be supported by the published results. In particular, characteristics at baseline were not evenly balanced, the dose of oxime was much lower than recommended in guidelines, there were substantial delays to treatment, and the type of organophosphate was not taken into account. The abstract of the third trial, a small possible RCT, is uninterpretable without further data.


CONCLUSIONS
Current evidence is insufficient to indicate whether oximes are harmful or beneficial in the management of acute organophosphorus pesticide poisoning. A much larger RCT is required to compare the World Health Organization recommended pralidoxime regimen (>30 mg/kg bolus followed by >8 mg/kg/hr infusion) with placebo. There are many theoretical and practical reasons why oximes may not be useful to patients with overwhelming self-poisoning. Such a study will need to be designed with pre-defined sub-group analysis to allow identification of patient sub-groups that may benefit from oximes.
Buckley
N A
NA
Dept. of Clinical Pharmacology, Australian National University Medical School, Canberra Hospital, PO Box 11, , Woden ACT 2606, Australia. nick.buckley@act.gov.au
Eddleston
M
M
Szinicz
L
L
D000931:Antidotes / Q000627:therapeutic use; D002801:Cholinesterase Reactivators / Q000627:therapeutic use; D006801:Humans; D062025:Organophosphate Poisoning; D010091:Oximes / Q000627:therapeutic use*; D010575:Pesticides / Q000506:poisoning*; D011041:Poisoning / Q000188:drug therapy; D011220:Pralidoxime Compounds / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D010575:Pesticides; D011220:Pralidoxime Compounds; C028797:pralidoxime