We often receive questions on why we do not recommend, in our catalogue and on our website, the determination of cyanide levels on patients receiving nitroprusside. We do not recommend blood cyanide levels on these patients for two reasons.

First of all, at low infusion rates (less than 2 ug/kg/min) the cyanide released by nitroprusside is completely metabolized, by the liver, to thiocyanate. At infusion rates greater than 2 ug/kg/min, cyanide concentrations could accumulate, leading to cyanide toxicity. However, these same doses are not problematic if nitroprusside is infused along with the appropriate dose of sodium thiosulfate. Patients receiving the nitroprusside – thiosulfate mixture rapidly convert cyanide to thiocyanate. Under the condition of concurrent thiosulfate administration, which is now considered standard therapy, quantification of cyanide concentrations is not necessary because toxicity is averted.

Secondly, the nitroprusside molecule, which contains five cyanide (CN) groups and a nitroso (NO) group, avidly binds to hemoglobin. At equilibrium, the amount of CN that is bound to the red blood cells is approximately 20 times that due to ingestion of cyanide salts or exposure to hydrogen cyanide gas. Since the analytical method for measuring CN measures all of the cyanide bound to the erythrocyte, the blood concentrations are almost always elevated. However, the reference range for cyanide toxicity is based on exposure to cyanide salts and is meaningless for exposure to nitroprusside. For example, in poisoning with sodium cyanide, patients are comatose at levels greater than 2 ug/mL, and levels greater than 5 ug/mL are lethal. Patients receiving nitroprusside therapy, however, may have blood CN concentrations as high as 40 to 100 ug/mL without symptoms of toxicity. Thus, the measurement of blood cyanide concentrations would be misleading and may lead to inappropriate cessation of therapy.

Although cyanide concentrations are not recommended, for patients on long term nitroprusside therapy, the measurement of thiocyanate is recommended (on an every other day schedule). Studies have shown that, in patients with normal renal function, thiocyanate toxicity can occur after 7-14 days of continuous nitroprusside infusion at a rate > 2 ug/ kg/min. Patients with renal impairment can develop toxicity in 3-6 days at similar infusion rates. (Thiocyanate toxicity has clinical features often indistinguishable from cyanide toxicity but without metabolic acidosis).

As always, if your office has any questions about this topic, or any other topic, please call Warde Medical Laboratory at 800-876-6522.