Cyanide Antidotes and Methods of Their Administration in Dogs:

Abstract

To test the efficacies of various antidotes to cyanide (CN) poisoning, the lethal dose of CN in dogs was estimated during constant infusion of KCN at a rate of 0.1 mg/kg per min. Arterial blood pressure, right ventricular pressure, heart rate, electrocardiogram, blood-gas and pH values, and whole blood and tissue CN concentrations were measured. The lethal dose in animals whose lungs were ventilated with room air was 2.4 .+-. 0.2 mg/kg (mean .+-. SE), while the whole-blood CN concentration was 438 .+-. 40 .mu.g/dl and the gracilis muscle concentration was 2.0 .+-. 0.3 .mu.g/100 g. A low dose of vitamin B12a (100 mg/kg), an infusion of thiosulfate (12 mg/kg per h) or ventilation with 100% O2 increased the amount of CN needed to cause death. A bolus injection of nitrite (5 mg/kg), thiosulfate (150 mg/kg), or cysteine (450 mg/kg) increased the protection from lethality even further. Protection against CN administration for the total 150-min period of observation was provided by a bolus injection plus a constant infusion of nitrite (5 mg/kg bolus plus 5 mg/kg per h), thiosulfate (30 mg/kg bolus plus 60 mg/kg per h), or vitamin B12a (50 mg/kg bolus plus 100 mg/kg per h). Nitrite infusion produced high levels of methemoglobin 7.2 .+-. 1.1 g/dl, while vitamin B12a infusion and cysteine injection at the stated doses did not prevent CN-induced circulatory failure. Thiosulfate may be the most effective and safest prophylactic agent against CN toxicity in dogs. Use as an antidote for nitroprusside and Laetrile-induced cyanide toxicity is discussed.