Severe hypoxia produced by concomitant intoxication with sublethal doses of carbon monoxide and cyanide

It has long been known that a number of tissue hypoxicants are generated in the fire scenario. However, until recently few investigators have undertaken to correlate smoke inhalation deaths with the simultaneous exposure to histotoxic hypoxicants. Carbon monoxide and hydrogen cyanide are two histotoxic hypoxicants that are generated in nearly every fire. Prior studies performed in our laboratory have demonstrated that death can result from concomitant exposure to otherwise sublethal concentrations of carbon monoxide and cyanide. Since most smoke inhalation victims exhibit acid/base anomalies, we sought to investigate whether the death associated with simultaneous exposure to these two hypoxicants, at concentrations widely held to be nonlethal, could be explained by acid/base imbalances. Male ICR mice were exposed to 0.35% carbon monoxide immediately after having been injected ip with potassium cyanide solution, or were challenged with either agent alone. Animals challenged with cyanide or carbon monoxide alone demonstrated significant hypoxia. However, animals challenged with both agents demonstrated much greater hypoxia than could be explained by an additive effect alone. Controls demonstrated no alteration in acid/base homeostasis. Blood pH perturbations were found to be due to severe lactic acidosis coupled with inadequate respiratory compensation. Thus, it appears that the synergistic lethal effect of simultaneous administration of carbon monoxide and cyanide are related to a precipitous decrease in blood pH, the tissue hypoxia and its resulting complications.