title: Timing of decontamination and treatment in case of percutaneous VX poisoning: a mini review.
abstract: Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to improve treatment efficacy compared to a single injection treatment. Because of the effectiveness of continuous treatment, it was investigated to what extent a subchronic pretreatment with carbamate (pyridostigmine or physostigmine combined with either procyclidine or scopolamine) would protect against percutaneous VX exposure. Inclusion of scopolamine in the pretreatment prevented seizures in all animals, but none of the pretreatments affected survival time or the onset time of cholinergic signs. These results indicate that percutaneous poisoning with VX requires additional conventional treatment in addition to the current pretreatment regimen. Decontamination of VX-exposed skin is one of the most important countermeasures to mitigate the effects of the exposure. To evaluate the window of opportunity for decontamination, the fielded skin decontaminant Reactive Skin Decontaminant Lotion (RSDL) was tested at different times in hairless guinea pigs percutaneously challenged with 4× LD50 VX in IPA. The results showed that RSDL decontamination at 15 min after exposure could not prevent progressive blood cholinesterase inhibition and therefore would still require additional treatment. A similar decontamination regimen with RSDL at 90 min showed that it still might effectively increase the time window of opportunity for treatment. In conclusion, the delay in absorption presents a window of opportunity for decontamination and treatment. The continuous release of VX from the skin presents a significant challenge for efficacious therapy, which should ideally consist of thorough decontamination and continuous treatment.
authors.affiliation: TNO Earth Environmental and Life Sciences, CBRN Protection, PO Box 45, 2280 AA Rijswijk, The Netherlands. Marloes.joosen@tno.nl
authors.forename: Marloes J A
authors.initials: MJ
authors.lastname: Joosen
authors.forename: Marcel J
authors.initials: MJ
authors.lastname: van der Schans
authors.forename: Willem C
authors.initials: WC
authors.lastname: Kuijpers
authors.forename: Herman P M
authors.initials: HP
authors.lastname: van Helden
authors.forename: Daan
authors.initials: D
authors.lastname: Noort
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000506:poisoning; D003666:Decontamination / Q000379:methods*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D062025:Organophosphate Poisoning / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy*; D009946:Organothiophosphorus Compounds / Q000493:pharmacokinetics / Q000506:poisoning*; D011352:Procyclidine / Q000008:administration & dosage; D011729:Pyridostigmine Bromide / Q000008:administration & dosage; D012601:Scopolamine / Q000008:administration & dosage; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D009946:Organothiophosphorus Compounds; D011352:Procyclidine; D011729:Pyridostigmine Bromide; D012601:Scopolamine; C009680:VX-agent