Post‐Exposure Therapy Administered 30 Minutes After an LD50 Dose of Soman in Guinea Pigs without Carbamate Pretreatment

Abstract

Exposure to soman (GD), a chemical warfare agent (CWA), causes cholinesterase inhibition, seizure, convulsions, cardiorespiratory dysfunction, and death. Current US military management of CWA poisoning involves carbamate pretreatment and post‐exposure oxime/cholinolytic therapy. However, CWAs pose a potential threat to civilian populations without access to pretreatment programs. We used unanesthetized guinea pigs, instrumented to record CNS and cardiorespiratory activities, to determine a post‐exposure therapeutic window within which effects of GD poisoning could be mitigated without carbamate pretreatment. An LD99 dose of GD was followed by a therapy delay of up to 30 min. The therapy mix included im scopolamine (0.25 mg/kg), methylatropine (2 mg/kg), the oxime MMB4 (26.1 mg/kg), physostigmine (0.075 mg/kg), and ip Phenobarbital (25 mg/kg). After GD, all animals showed periods of hypersecretion, dystonia/tremor, seizure, bradycardia, and bradypnea. After therapy, cardiorespiratory parameters returned to control levels and seizures ceased within 10 min with no recurrence. 88% of animals survived >24 hrs. Of those, one was asymptomatic at 24 hrs, and the rest showed only mild dystonia. In conclusion, our therapy mix, even following 30 min of poisoning without pretreatment, effectively eliminated the most life‐threatening signs of GD intoxication. Funded by Defense Threat Reduction Agency.