Effect of sodium nitroprusside alone and in combination with sodium thiosulfate on the acid-base balance, and on thiocyanate and iron plasma levels in the rabbit.

An infusion of 7.5 mg/kg.h sodium nitroprusside (SNP) produced a fatal cyanide intoxication in conscious rabbits (n=6) after 60.8 +/- 6.7 min (chi +/- S.E.). When, however, the cyanide antidote sodium thiosulfate was infused simultaneously at a rate of 31.25 or 62.5 mg/kg.h, i.e. a molar SNP/thiosulfate ratio of 1:5 or 1:10 respectively, this high dose of SNP was well tolerated. In both concentrations, thiosulfate abolished the development of the severe metabolic acidosis that results from the infusion of toxic doses of SNP alone. In the presence of thiosulfate, the plasma level of thiocyanate rose linearly with the infusion time indicating a rapid detoxification of cyanide released in vivo from SNP, whereas at the end of the infusion of SNP alone no increase in plasma thiocyanate could be measured. No clear advantage of the higher thiosulfate dosage over the lower one could be established. The iron plasma level only rose during the first hour of SNP plus thiosulfate infusions reaching the iron binding capacity of plasma, and then remained stable throughout the experiment. This indicates that the iron plasma level is an unsuitable parameter for the control of SNP therapy. We suggest the simultaneous administration of SNP and thiosulfate at a molar ratio of 1:5 to make SNP a safer drug.