Increased Resistance to Nitroprusside-induced Cyanide Toxicity in Anuric Dogs

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Abstract
Sodium nitroprusside (SNP) is frequently used to decrease afterload in patients who have vasoconstriction with low cardiac output. Often, these patients are concomitantly oliguric or anuric, conditions suggested to be likely to increase the risk of SNP-induced cyanide (CN) toxicity. Previously, it was determined in normal dogs that SNP, 0.5 mg/kg per h, was tolerated for 48 h without CN toxicity, whereas 0.75 mg/kg per h resulted in toxicity and death. In the present study, dogs rendered anuric by bilateral ureteral ligation were again maintained for 48 h or until death in a simulated intensive-care situation, and were given various doses of SNP. CN toxicity, as evidenced by near-linear increases in blood CN, metabolic acidosis and increases of mixed venous blood PO2 [partial pressure of O2] with time, did not occur in animals given SNP at either 0.5 or 0.75 mg/kg per h (n = 8), and was the cause of death in only 2 of 7 dogs given SNP, 1.0 mg/kg per h. In all 5 dogs given SNP 1.25 mg/kg per h, cyanide toxicity developed, with death occurring at an average of 21 h. Comparisons between the anuric dogs studied herein and the normal dogs studied previously with SNP, 1.0 mg/kg per h, indicated that CN levels were significantly higher in the normal dogs at 36 h and that thiocyanate (SCN) levels were significantly lower in the normal dogs at 24 and 36 h. The observed resistance to SNP-induced CN toxicity in anuric dogs was probably secondary to decreased sulfate and thiosulfate excretion, resulting in greater availability of thiosulfate donor, which in turn enabled greater rates of detoxification of CN to SCN to be catalyzed by hepatic rhodanase. Anuria per se evidently does not increase the risk of SNP-induced CN toxicity, probably because of increased availability of endogenous sulfur donor. Based on this study in dogs, SNP dosage limits in anuric or oliguric patients would not be arbitrarily decreased because of the possibility of cyanide toxicity.