title: The potential role of bioscavenger in the medical management of nerve-agent poisoned casualties.
abstract: The provision of effective Medical Countermeasures (MedCM) for all agents and routes of exposure is a strategic goal of defence research and development. In the case of military autoinjector-based therapies for nerve agent poisoning, current treatment effectiveness is limited by the oxime reactivator being effective against only certain agents, by rapid clearance times of the drugs and because the doses may not be optimal for treatment of severe poisoning. Prolonged poisoning by nerve agents entering the body through the skin is also challenging. Since casualty handling timelines have reduced significantly in recent years, it may be sufficient for first aid therapy to provide protection for only a few hours until further medical treatment is available. Therefore, the traditional evaluation of first aid therapy in animal models of survival at 24 h may not be appropriate. At various echelons of medical care, further therapeutic interventions are possible. The current basis for the medical management of nerve-agent poisoned casualties is derived mainly from clinical experience with pesticide poisoning. Adjunct therapy with a bioscavenger (such as human butyrylcholinesterase (huBChE)), could have utility as a delayed intervention by reducing the toxic load. It has previously been demonstrated that huBChE is an effective post-exposure therapy against percutaneous VX poisoning. It is recommended that the scope of animal models of nerve agent MedCM are extended to cover evaluation of both first aid MedCM over significantly reduced timescales, and subsequent supportive therapeutic and medical management strategies over longer timescales. In addition to bioscavengers, these strategies could include repeated combined and individual therapy drugs to alleviate symptoms, other classes of drugs or ventilatory support. Crown Copyright©[2016] Published by Elsevier Ireland Ltd. This is an open access article under the Open Government Licence (OGL) (http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/).
authors.affiliation: Toxicology, Trauma and Medicine Group, Chemical, Biological & Radiological Division, Dstl Porton Down, Salisbury, SP4 0JQ, UK. Electronic address: hrice@dstl.gov.uk.
authors.forename: Helen
authors.initials: H
authors.lastname: Rice
authors.affiliation: Toxicology, Trauma and Medicine Group, Chemical, Biological & Radiological Division, Dstl Porton Down, Salisbury, SP4 0JQ, UK. Electronic address: tmann@dstl.gov.uk.
authors.forename: Tom M
authors.initials: TM
authors.lastname: Mann
authors.affiliation: Toxicology, Trauma and Medicine Group, Chemical, Biological & Radiological Division, Dstl Porton Down, Salisbury, SP4 0JQ, UK. Electronic address: sjarmstrong@dstl.gov.uk.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Armstrong
authors.affiliation: Toxicology, Trauma and Medicine Group, Chemical, Biological & Radiological Division, Dstl Porton Down, Salisbury, SP4 0JQ, UK. Electronic address: meprice1@dstl.gov.uk.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Price
authors.affiliation: Toxicology, Trauma and Medicine Group, Chemical, Biological & Radiological Division, Dstl Porton Down, Salisbury, SP4 0JQ, UK. Electronic address: acgreen@dstl.gov.uk.
authors.forename: A Chris
authors.initials: AC
authors.lastname: Green
authors.affiliation: Toxicology, Trauma and Medicine Group, Chemical, Biological & Radiological Division, Dstl Porton Down, Salisbury, SP4 0JQ, UK. Electronic address: jtattersall@dstl.gov.uk.
authors.forename: John E H
authors.initials: JEH
authors.lastname: Tattersall
mesh_terms: D000818:Animals; D001285:Atropine / Q000627:therapeutic use; D002091:Butyrylcholinesterase / Q000008:administration & dosage* / Q000097:blood; D002619:Chemical Warfare Agents / Q000506:poisoning; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D005392:First Aid; D006168:Guinea Pigs; D006801:Humans; D008887:Military Medicine; D000067397:Nerve Agents / Q000506:poisoning*; D062025:Organophosphate Poisoning / Q000628:therapy*; D009946:Organothiophosphorus Compounds / Q000506:poisoning
chemical_list: D001285:Atropine; D002091:Butyrylcholinesterase; D002619:Chemical Warfare Agents; D002801:Cholinesterase Reactivators; D000067397:Nerve Agents; D009946:Organothiophosphorus Compounds; C009680:VX-agent
keywords: Bioscavenger; Butyrylcholinesterase; Chemical casualty; Medical countermeasures; Nerve agent