Treatment of anticholinesterase poisoning: supportive care, atropine and oximes
THE CONTEXT
Treatment combines termination of exposure, respiratory and circulatory support, control of convulsions and appropriate antidotes.
Immediate and supportive measures
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Terminate further exposure, provide fresh air, and wash exposed skin and mucous membranes with soap and water. Gastric lavage is used according to need.
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Maintain a patent airway and provide positive pressure respiration if breathing is failing.
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Maintain blood pressure and hydration, and control convulsions with judicious use of diazepam.
Atropine
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Atropine is highly effective against muscarinic symptoms; higher doses are needed to antagonize central effects.
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Atropine does not reverse peripheral muscular paralysis because this is a nicotinic effect.
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Both carbamate and organophosphate anticholinesterase poisoning require prompt atropine administration.
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The described regimen is atropine 2 mg intravenously every 10 minutes until dryness of the mouth or other signs of atropinization appear. Up to 200 mg in a day has been administered, and maintenance treatment may be required for 1–2 weeks.
Oximes and pralidoxime
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Oximes restore neuromuscular transmission in organophosphate anticholinesterase poisoning. Their reactive hydroxyl groups accelerate reactivation of phosphorylated cholinesterase by more than a million times.
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Pralidoxime's positively charged quaternary nitrogen attaches to the enzyme's unoccupied anionic site. Its oxime end reacts with phosphorus at the esteratic site, and the resulting oxime-phosphonate diffuses away, leaving reactivated cholinesterase.
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Pralidoxime is ineffective and contraindicated in carbamate poisoning. The anionic site is unavailable for attachment, pralidoxime does not reactivate carbamylated enzyme, and it has weak anticholinesterase activity of its own.