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COMMENTARY
Year : 2014  |  Volume : 60  |  Issue : 1  |  Page : 31-32

The efficacy of pralidoxime in organophosphorus poisoning: A commentary


All Wales Therapeutics and Toxicology Centre, Cardiff and Vale University Health Board, Cardiff, United Kingdom

Date of Web Publication14-Mar-2014

Correspondence Address:
J M Coulson
All Wales Therapeutics and Toxicology Centre, Cardiff and Vale University Health Board, Cardiff
United Kingdom
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Coulson J M. The efficacy of pralidoxime in organophosphorus poisoning: A commentary. J Postgrad Med 2014;60:31-2

How to cite this URL:
Coulson J M. The efficacy of pralidoxime in organophosphorus poisoning: A commentary. J Postgrad Med [serial online] 2014 [cited 2017 Oct 22];60:31-2. Available from: http://www.jpgmonline.com/text.asp?2014/60/1/31/128804


Poisoning with organophosphorus pesticides is a significant global health problem [1] and is the principle cause of death through self-poisoning in India. [2] The organophosphates potentiate the action of acetylcholine through the inhibition of synaptic acetylcholinesterase. Standard treatment includes resuscitation and the administration of atropine and an oxime, such as pralidoxime.There is a lack of high quality evidence to support the efficacy of either antidote. Atropine is considered to be effective at antagonizing the features of excessive muscarinic stimulation. [3] The efficacy of pralidoxime is more contentious. The publication of a randomized control trial to compare the efficacy of pralidoximeand atropine with atropine alone by Banerjee and colleagues. [4] in this edition of the Journal of Postgraduate Medicine is a welcome contribution to this debate.

Theoretically, pralidoxime would be expected to be efficacious in the treatment of organophosphorus poisoning by reactivating nicotinic synapses, which are not antagonized by atropine, and so reduces the duration and severity of neuromuscular junction failure. Evidence from a recent meta-analysis does not, however, support this reasoning. [5] Banerjee et al. [4] found that the addition of pralidoxime to atropine therapy did not reduce either the mortality or the need for ventilator support. This finding must be interpreted with care since the power calculation was based on a non-inferiority margin of 10% rather than a superiority trial design.

The reason for a general apparent lack of efficacy of pralidoxime is unclear. The pharmacokinetic/pharmacodynamics relationship; differences in toxicity between organophosphorus formulations and base-line differences between treatment groups have all been cited as potential confounders.

Banerjee et al. [4] have rightly acknowledged the limitations of their research in that they were unable to investigate either the pharmacodynamics or the pharmacokinetic parameters. Eddleston et al. (2009) were, however, able to measure these parameters and found no evidence of benefit despite the clear red cell acetylcholinesterase reactivation. [3]

The dosing regimen of pralidoxime is controversial. [6],[7] Banerjee et al. [4] selected a dose lower than the dose recommended by the World Health Organization (WHO). The WHO regimen is, itself however, extrapolated from animal data rather than clinical trials. The authors note that the dose they selected is frequently used in rural India and that one of the study aims was to evaluate the efficacy of this regime.

Pawar et al. (2006) [7] found that a high dose regimen of pralidoxime reduced mortality and morbidity, although the study had several methodological limitations that weakened the general applicability of their findings to other clinical settings. [6] Further, Buckley et al. (2011) did not find any evidence to support the efficacy of a high dose regimen in preference to a lower dose during their meta-analysis. [5]

The organophosphates are not a homogenous group. There are marked differences in their toxokinetic and toxodynamic properties. The clinical syndrome produced by dimethoate appears to be distinct from chlorpyrifos and fenthion. [8] The effect of the type of agent ingested on pralidoxime efficacy is unclear. Eddleston et al. (2009) did not find a difference during the subgroup analysis. [3] Banerjee et al.[4] controlled for this variable by recording the type of agent ingested as stated in the clinical history. The distribution of the types of pesticide was consistent between the treatment arms, although the investigators were not able to confirm the identity of the compound chemically.

In conclusion, the future role of pralidoxime in the management of organophosphate-poisoned patients is unclear. There is little evidence to support the low-dose regimen in the rural setting. The apparent increased duration of hospitalization observed by Banerjee et al.[4] is a potential concern, although the study was not specifically designed to address this. Further trials of the risks/benefits of other oximes and the exploration of other pralidoxime are needed. For attempting to address this important issue, the work of Banerjee and colleagues. [4] is of significant importance.

 
 :: References Top

1.Jeyaratnam J. Acute pesticide poisoning: A major global health problem. World Health Stats Q 1990;43:139-44.  Back to cited text no. 1
    
2.Eddleston M. Patterns and problems of deliberate self-poisoning in the developing world. QJM 2000;93:715-31.  Back to cited text no. 2
[PUBMED]    
3.Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet 2008;371:597-607.  Back to cited text no. 3
    
4.Banerjee I, Tripathi SK, Sinha Roy A. Efficacy of pralidoxime in organophosphorus poisoning: Revisiting the controversy in Indian setting. J Postgrad Med 2014;60:27-30.  Back to cited text no. 4
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5.Buckley NA, Eddleston M, Li Y, Bevan M, Robertson J. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev 2011;2:CD005085.  Back to cited text no. 5
    
6.Eyer P, Buckley N. Pralidoxime for organophosphate poisoning. Lancet 2006;368:2110-1.  Back to cited text no. 6
    
7.Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: A randomised controlled trial. Lancet 2006;368:2136-41.  Back to cited text no. 7
    
8.Eddleston M, Eyer P, Worek F, Mohamed F, Senarathna L, von Meyer L, et al. Differences between organophosphorus insecticides in human self-poisoning: A prospective cohort study. Lancet 2005;366:1452-9.  Back to cited text no. 8
    




 

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Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
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