Management of acute organophosphorus pesticide poisoning

Abstract

Organophosphorus pesticide self-poisoning is an important clinical problem in rural regions of the developing world, and kills an estimated 200,000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available. Medical management is difficult, with case fatality generally more than 15%. We describe the limited evidence that can guide therapy and the factors that should be considered when designing further clinical studies. 50 years after first use, we still do not know how the core treatments--atropine, oximes, and diazepam--should best be given. Important constraints in the collection of useful data have included the late recognition of great variability in activity and action of the individual pesticides, and the care needed cholinesterase assays for results to be comparable between studies. However, consensus suggests that early resuscitation with atropine, oxygen, respiratory support, and fluids is needed to improve oxygen delivery to tissues. The role of oximes is not completely clear; they might benefit only patients poisoned by specific pesticides or patients with moderate poisoning. Small studies suggest benefit from new treatments such as magnesium sulphate, but much larger trials are needed. Gastric lavage could have a role but should only be undertaken once the patient is stable. Randomised controlled trials are underway in rural Asia to assess the effectiveness of these therapies. However, some organophosphorus pesticides might prove very difficult to treat with current therapies, such that bans on particular pesticides could be the only method to substantially reduce the case fatality after poisoning. Improved medical management of organophosphorus poisoning should result in a reduction in worldwide deaths from suicide.

Figures

Figure 1

Management of a patient with severe organophosphorus poisoning in a Sri Lankan district hospital The absence of intensive-care beds and ventilators means that unconscious patients are frequently intubated and ventilated on the open ward. This figure is reproduced with permission from the corresponding author.

Figure 2

Use of butyrylcholinesterase recovery as a marker of organophosphorus pesticide elimination in (A) dimethoate and (B) fenthion poisoning Dimethoate is hydrophilic and rapidly excreted from the body. Plasma butyrylcholinesterase activity therefore begins to rise again within two days of ingestion. By contrast, fenthion is fat soluble and slowly redistributes into the blood after initial distribution into the fat. As a result, fenthion is detectable in the blood for many days and butyrylcholinesterase activity remains inhibited.

Figure 3

Chemical classes of organophosphorus pesticides Structures of organophosphorus pesticides from diethyl (A, B, C), dimethyl (D), and S-alkyl (E,F) classes. Most organophosphorus pesticides are thioates, with a double-bonded sulphur atom linked to the phosphate (A, C, F) that needs to be converted to the active oxon (eg, A to B). A few organophosphorus pesticides are oxons (eg, D, E) and do not need activation; they are able to inhibit acetylcholinesterase directly as soon as they are absorbed.

Figure 4

Variable response to oximes of acetylcholinesterase inhibited by different classes of organophosphorus pesticides Acetylcholinesterase was reactivated fully (A) quinalphos, a diethyl pesticide; partially (B) oxydemeton-methyl, a dimethyl pesticide, or not at all (C) profenofos, an S-alkyl pesticide by oximes after poisoning. The arrow shows the time of first dose of pralidoxime. Normal acetylcholinesterase activity is about 600 mU/μmol Hb. In-vitro acetylcholinesterase activity shows how much of the enzyme can be reactivated, i.e. how much of it has not yet aged (in these three cases, on admission when the first dose of pralidoxime was given, A: ∼85%, B: ∼50%, C: 5%, of the enzyme was not aged). All patients presented to hospital within 4 h.