Cyanide toxicity of sodium nitroprusside in therapeutic use with and without sodium thiosulphate

Sodium nitroprusside (SNP) as a mono-infusion was administered to 51 patients for periods of a few hours. A further group of 19 patients received SNP for periods of several days as a combination solution of SNP mixed with sodium thiosulphate. The concentrations of cyanide and of thiocyanate in the blood of all patients were measured. In seven of the patients the level of thiosulphate was also measured. Infusion of SNP on its own at levels exceeding 2 microgram/kg/min led to the rising of cyanide levels in the blood being proportional to dosage. Infusion of SNP mixed with thiosulphate showed no such accumulation of cyanide in any patient, irrespective of dosage level and duration. The efficacy at lowering blood pressure was fully maintained in the mixed infusion. The elimination half-life for thiosulphate was 16.5 min. Pharmacokinetic calculation of the rise in cyanide level showed that mono-infusions of 5-10 micrograms SNP/kg/min could within 5-10 h cause a life-threatening cyanide level in the blood. By contrast, mixed infusion of SNP together with thiosulphate, for which light-opaque syringes and tubing must be used, is a procedure free of danger and should become the technique of choice when therapeutically administering SNP in order to lower blood pressure.