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Rapid and complete bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning in minipigs after intraosseous administration

Lookup NU author(s): Professor Simon ThomasORCiD, Dr Robert Jefferson, Dr Michael Dunn, Dr Daniel Vidler, Professor Peter Blain

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Abstract

TUDY OBJECTIVE: Management of chemical weapon casualties includes the timely administration of antidotes without contamination of rescuers. Personal protective equipment makes intravenous access difficult but does not prevent intraosseous drug administration. We therefore measured the systemic bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning when administered by the intraosseous, intravenous, and intramuscular routes in a small study of Göttingen minipigs. METHODS: Animals were randomly allocated to sequentially receive atropine (0.12 mg/kg by rapid injection), pralidoxime (25 mg/kg by injection during 2 minutes), and hydroxocobalamin (75 mg/kg during 10 minutes) by the intravenous or intraosseous route, or atropine and pralidoxime by the intramuscular route. Plasma concentrations were measured for 6 hours to characterize the antidote concentration-time profiles for each route. RESULTS: Maximum plasma concentrations of atropine and pralidoxime occurred within 2 minutes when administered by the intraosseous route compared with 8 minutes by the intramuscular route. Maximum plasma hydroxocobalamin concentration occurred at the end of the infusion when administered by the intraosseous route. The mean area under the concentration-time curve by the intraosseous route was similar to the intravenous route for all 3 drugs and similar to the intramuscular route for atropine and pralidoxime. CONCLUSION: This study showed rapid and substantial antidote bioavailability after intraosseous administration that appeared similar to that of the intravenous route. The intraosseous route of antidote administration should be considered when intravenous access is difficult


Publication metadata

Author(s): Murray DM, Eddleston M, Thomas S, Jefferson RD, Thompson A, Dunn M, Vidler DS, Clutton E, Blain PG

Publication type: Article

Publication status: Published

Journal: Annals of Emergency Medicine

Year: 2012

Volume: 60

Issue: 4

Pages: 424-430

Print publication date: 01/10/2012

ISSN (print): 0196-0644

ISSN (electronic): 1097-6760

Publisher: Mosby, Inc.

URL: http://dx.doi.org/10.1016/j.annemergmed.2012.05.013

DOI: 10.1016/j.annemergmed.2012.05.013


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