The role of hypoxia in organophosphorus nerve agent intoxication

Effectiveness of the standard therapy for organophosphorus (OP) anticholinesterase poisoning has been questioned because of the relative resistance of the cholinesterase (ChE) enzymes to reactivation by oximes (Harris et al., 1968). Because tissue hypoxia may be a significant lethal component of OP nerve agent intoxication, oxygen therapy should be beneficial. Although there have been no systematic investigations of the value of oxygen therapy in OP poisoning, it may improve the efficiency of ChE reactivation by the standard therapies of cholinolytics and oximes. Because tissue hypoxia may be generated by arterial hypoxemia due to respiratory failure, oxygen therapy should limit concomitant metabolic disturbances associated with anaerobiosis. This review addresses the interspecies variations and experimental model developments that should challenge neuroscientists to adopt an integrated, physiological approach to understanding the precise role of hypoxia in neurotoxicity. The significance of tissue hypoxia to protection and recovery of humans from OP nerve agent intoxication is also discussed.