Prophylaxis and Treatment of Cyanide Intoxication Cyanide - Mechanism of Prophylaxis.

One treatment for cyanide poisoning involves administration of the combination sodium thiosulfate and sodium nitrate. To understand better the action of thiosulfate on cyanide toxicity, a study was made of the pharmacokinetics of cyanide distribution and metabolism in the absence and presence of thiosulfate. Fasted mongrel dogs were anesthetized with sodium pentobarbital and both jugular veins were catheterized. Thiosulfate did not alter the kinetics of distribution or elimination of thiocyanate. A pharmacokinetic model of thiocyanate distribution and elimination was developed based on thiocyanate plasma concentration that were measured after i.v. administration. Thiosulfate was shown to not affect the model parameters for thiocyanate. The thiocyanate model was coupled with a model for cyanide and the blood levels of cyanide and thiocyanate measured after administration of cyanide was used to determine values for the cyanide model parameters. This kinetic analysis showed that: (1) thiosulfate increased the rate of conversion of cyanide to thiocyanate by a factor of 36.5 and (2) the apparent volume of distribution of cyanide was reduced by thiosulfate. The mechanism of thiosulfate protection appeared to be due to an initial burst of formation of thiocyanate formation and thus limited the amount of cyanide distributed peripherally.