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J R Soc Med. 2005 July; 98(7): 336.
PMCID: PMC1168929

Nicotinic antagonists and nerve gas poisoning

Whilst commending their article (March 2005 JRSM1), we disagree with Dr Sheridan and his co-workers that use of a non-depolarizing neuromuscular blocker (NDNMB) would ever 'normalize function at the neuromuscular junction' in the case of nerve agent or organophosphate poisoning. In this instance any dose of NDNMBs would effect neuromuscular blockade through nicotinic receptor occupancy, thus augmenting the dual block associated with excessive intrasynaptic acetylcholine.2 In addition, we suggest that shorter-acting drugs such as cisatracurium or vecuronium are preferable to pancuronium and gallamine, since the latter are vagolytic (leading to inadvertent underdosing of antidotal atropine) and less amenable to careful titration in an intensive-care setting.

It would seem more rational to accept that paralysis is inevitable after significant exposure to nerve agents (necessitating ventilation), but to give large doses of NDNMBs anyway, in order to saturate nicotinic receptor binding sites with the idea of possibly preventing acetylcholine mediated receptor damage at the neuromuscular junction. NDNMBs could continue to be given by infusion, until either oxime therapy had achieved significant acetylcholinesterase reactivation, or sufficient acetylcholinesterase had been synthesized de novo. This rationale may help shorten the paralysis that occurs during the 'intermediate phase' of recovery from nerve agent poisoning.

Needless to say, this is an area that requires more research but in which research is very controversial. The development of a novel, short-acting acetylcholine chelator or inactivator might provide a possible antidote in cases of nerve agent or organophosphate poisoning.

References

1. Sheridan RD, Smith AP, Turner SR, Tattersall JEH. Nicotinic antagonists in the treatment of nerve agent poisoning. J R Soc Med 2005;98 114-15 [PMC free article] [PubMed]
2. White SM. Chemical and biological weapons. Implications for anaesthesia and intensive care. Br J Anaesthesia 2002;89: 306-24 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press