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

Abstract

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.

Role of nitric oxide in chick embryonic organogenesis and dysmorphogenesis

“…SNP, a NO donor, and L ‐NMMA, a NOS‐specific inhibitor, were used to characterize the production of NO in the developing embryo. In preliminary studies, stage 10–11 embryos were treated with varying concentrations of L ‐NMMA (0–25 m M ) and SNP (0–10 m M ), combined with sodium thiosulfate (0–50 m M ) to prevent cyanide toxicity, as described in animal and human studies (Vesey et al,1976; Hobel et al,1978; Schulz et al,1982; Schulz and Loeschcke,1985). Both L ‐NMMA and SNP/sodium thiosulfate were dissolved in HBSS.…”

Nitroprusside‐ and nitroglycerin‐induced hypotension: Effects on hemodynamics and on the microcirculation

“…Experiments with lac-labeled nitroprusside suggest that some cyanide is accumulated in the vessel walls. It appears possible to eliminate cyanide toxicity by simultaneously administering cyanide antidotes like sodium thiosulfate [10].…”

“…The acute toxicity of SNP results mainly from the in vivo release of 5 cyanide groups from each molecule of SNP. The cyanide groups are converted to thiocyanate by the hepatic enzyme rhodanase [10]. According to Barker, blood thiocyanate levels between 8 and 12 rag/100 ml can cause toxic effects.…”