title: Percutaneous exposure to the nerve agent VX: Efficacy of combined atropine, obidoxime and diazepam treatment.
abstract: The nerve agent VX is most likely to enter the body via liquid contamination of the skin. After percutaneous exposure, the slow uptake into the blood, and its slow elimination result in toxic levels in plasma for a period of several hours. Consequently, this has implications for the development of toxic signs and for treatment onset. In the present study, clinical signs, toxicokinetics and effects on respiration, electroencephalogram and heart rate were investigated in hairless guinea pigs after percutaneous exposure to 500 microg/kg VX. We found that full inhibition of AChE and partial inhibition of BuChE in blood were accompanied by the onset of clinical signs, reflected by a decline in respiratory minute volume, bronchoconstriction and a decrease in heart rate. Furthermore, we investigated the therapeutic efficacy of a single dose of atropine, obidoxime and diazepam, administered at appearance of first clinical signs, versus that of repetitive dosing of these drugs on the reappearance of signs. A single shot treatment extended the period to detrimental physiological decline and death for several hours, whereas repetitive administration remained effective as long as treatment was continued. In conclusion, percutaneous VX poisoning showed to be effectively treatable when diagnosed on time and when continued over the entire period of time during which VX, in case of ineffective decontamination, penetrates the skin.
authors.affiliation: TNO Defence, Security and Safety, BU CBRN Protection, 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: Herman P M
authors.initials: HP
authors.lastname: van Helden
mesh_terms: D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001285:Atropine / Q000008:administration & dosage / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs; D009768:Obidoxime Chloride / Q000008:administration & dosage / Q000627:therapeutic use*; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D012867:Skin / Q000187:drug effects*
chemical_list: D000931:Antidotes; D001285:Atropine; D002619:Chemical Warfare Agents; D003975:Diazepam; D009768:Obidoxime Chloride; D009946:Organothiophosphorus Compounds; C009680:VX-agent