Optimization of Therapeutic Strategies for Organophosphate Poisoning

The National Preparedness Vision requires the U.S. be prepared to prevent, protect against, respond to, and recover from all hazards associated with a chemical attack. Results of this study demonstrate that we cannot protect service members and first responders as required following a nerve agent attack. The research presented herein aimed to construct a physiologically based pharmacokinetic model to determine optimal therapeutic strategies for organophosphate (nerve agent) poisoning. The constructed model integrated organophosphates and two antidotes, atropine and oximes. Model results reasonably mirrored literature data and anecdotal observations of organophosphate poisoning. Results suggest a symptoms-based dosing strategy of atropine and a time-based dosing strategy of oximes. For patients severely poisoned with organophosphorus nerve agents, model results support documented claims of oxime's inefficacy and tendency to heighten the severity of poisoning. The results strongly indicate that military personnel attacked with nerve agents are at a significant health risk if they employ their prescribed treatment as current doctrine dictates. Results presented herein suggest that oxime use be discontinued as currently prescribed within the context of nerve agent exposure; its use will not alter the effects of nerve agent exposure and may increase the adverse effects.