Non-cholinergic intervention of sarin nerve agent poisoning

The protective effects of selected anesthetic regimens on sarin (GB) were investigated in domestic swine. At 30% oxygen, the toxicity of this agent in isoflurane anesthetized animals (LD50 = 10.1 μg/kg) was similar to literature sited values in awake swine (LD50 = 11.8 μg/kg) and slightly higher than that of both ketamine (LD50 = 15.6 μg/kg) and propofol (LD50 = 15.3 μg/kg) anesthetized swine. Use of 100% oxygen in ketamine anesthetized animals resulted in three-fold protective effects compared to 30% oxygen. Use of 100% oxygen in both isoflurane and propofol anesthetized animals, compared to 30% resulted in profound protection against GB poisoning (>33×). There were no differences in the severity of the poisoning or recovery time in animals treated over dose ranges of 10-350 μg/kg (isoflurane) or 15-500 μg/kg GB (propofol). Survivors of high GB challenges that were revived from propofol anesthetic exhibited no signs of cognitive impairment seven days later. Protective treatments did not attenuate cholinesterase (ChE) inhibition; survivors of otherwise supralethal GB concentrations exhibited very low blood ChE activities. This work indicates that propofol has protective effects against GB, and that oxygen tension may have an important role in treating nerve agent casualties. More importantly, it demonstrates that non-cholinergic protective mechanisms exist that may be exploited in the future development of medical countermeasures against organophosphorous nerve agents.

► Anesthetics and oxygen tension significantly affect the toxicity of nerve agents. ► Propofol and 100% oxygen can protect against >33× LD50 of sarin. ► Protection by propofol and oxygen was not the result of cholinesterase activation.