Development of a Treatment Agent for Mass Casualty Smoke-Cyanide Exposure

Abstract

Smoke inhalation is the major cause of death in fire victims. Combined cyanide and carbon monoxide poisoning is frequent in smoke inhalation victims, and mortality correlates more closely with cyanide levels than carbon monoxide exposure levels. There is currently no available treatment for mass casualty cyanide exposure, since treatment of individual victims requires administration of intravenous antidotes, and some antidote agents are contraindicated in smoke inhalation. We are developing a novel cyanide antidote, cobinamide, which could be administered intravenously or intramuscularly in mass casualty cyanide poisoning scenarios. Because cyanide antidotes cannot be tested for efficacy in humans, animal studies must be performed to demonstrate effectiveness of this agent in combined smoke-cyanide inhalation for FDA approval.METHODS: Six ventilator-supported New Zealand white rabbits were exposed to cold smoke breaths until toxic carbon monoxide levels were achieved (~30%), concurrent with intravenous cyanide infusion (0.167mg NaCN in 0.9% NaCl/min for 60 minutes). Animals were monitored with continuous gas exchange, hemodynamics, blood gases, cyanide levels, and diffuse optical spectroscopy, providing tissue oxy-and deoxyhemoglobin and cytochrome c oxidase measures in vivo. Intravenous cobinamide was administered in treatment arm animals and compared to control responses.RESULTS: Intravenous cobinamide reversed cyanide toxicity in these animals in the face of smoke induced carbon monoxide exposure, without evident adverse effects.CONCLUSIONS: Intravenous cobinamide shows promise as a potential antidote for cyanide poisoning in smoke inhalation victims, and an intramuscular formulation could potentially be administered in mass casualty exposure scenarios. Further validation and safety studies will be required for FDA approval of this promising agent.CLINICAL IMPLICATIONS: Treatment of fire smoke inhalation victims.DISCLOSURE: The following authors have nothing to disclose: Sasan Sani, Jangwoen Lee, Rene Patino, David Mukai, David Yoon, Sari Mahon, Gerry Boss, Steve Patterson, Matthew BrennerNo Product/Research Disclosure InformationBeckman Laser Institute, Irvine, CA. Language: en