Cyanide Release from Sodium Nitroprusside in the Dog

Abstract

Dogs (39, including 8 from a previous study) were given during a 1 h infusion of either low (< 1.0 mg/kg) or high doses (> 1.0 mg/kg) of sodium nitroprusside in the presence or absence of circulating methemoglobin. In animals given low doses, the metabolic effects were relatively mild and consistent with those accounted for by a reduction in arterial pressure to 40 torr. In animals given high doses (with the same arterial pressure) metabolic alterations were significantly magnified and O2 extraction was decreased. Animals pretreated with methemoglobin and given high doses of nitroprusside (at the same arterial pressure) showed no toxic effect. In separate studies, blood and tissue levels of cyanide were measured in dogs given high doses of nitroprusside (2.5-3.5 mg/kg) in the presence or absence of methemoglobin. In dogs given methemoglobin, 60% of the administered cyanide (as nitroprusside) was recovered in the blood (as cyanmethemoglobin) after a 1 h infusion. Thereafter, blood cyanide levels declined over 3 h to 25% of peak levels, presumably by conversion to thiocyanate, since tissue levels of cyanide were negligible. In dogs not given methemoglobin blood cyanide levels qualitatively followed a similar pattern but quantitatively were a 4th to a 3rd those of pretreated dogs, and tissue levels of cyanide became elevated. In the dog, nitroprusside, acutely administered, probably causes cyanide toxicity at doses exceeding 1.0-1.5 mg/kg. The release of cyanide from nitroprusside in blood appears to be rapid and in large quantities. Detoxification (presumably by conversion of cyanide to thiocyanate) seems to be fairly rapid but insufficient to prevent toxicity. Protection is probably provided by methemoglobin.