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

Abstract

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.

Pharmacokinetics of Intravenous Potassium Cyanide

“…found an apparent volume of distribution of 50% body weight, whilst Experiments [5][6][7][8] The analyses early in the course of these studies, appeared to confirm the findings of the earlier study and show first-order kinetics, but later the semilogarithmic plot deviated from a straight line and entered a second phase of much slower elimination (Figure 2). The second phase started at 75-80 min.…”

Dosing-Time Dependence of Lethal Toxicity Induced by Nitroprusside in Young Mice

“…The toxicity of SNP and its major metabolite, cyanide (CN -), was previously explored in nonchronobiological investigations in rodents and others mammals [37][38][39]. The subcutaneous administration of SNP to mice produced similar signs of toxicity described above, that were revealed by others authors when studying CN -toxicity in mice [39][40].…”

Stability of Sodium Nitroprusside and Sodium Thiosulfate 1:10 Intravenous Admixture

“…The physical compatibility of this mixture was also re-confirmed and is consistent with the previous literature. 5 A novel quantitative HPLC method for the determination of nitroprusside, thiosulfate, and thiocyanate in solution is also presented.…”

“…To combat cyanide toxicity, thiosulfate can be administered with nitroprusside, which has been demonstrated to have equal efficacy in the treatment of hypertensive crises 5 and cerebral vasospasm, 6 with no adverse events reported. A recent prospective randomized trial demonstrated equal blood pressure control between nicardipine and nitroprusside in neurosurgery patients.…”

“…Schulz et al demonstrated the efficacy of nitroprusside/thiosulfate admixture was maintained after 14 days of storage at room temperature, and reduced efficacy was associated with a visible color change. 5 …”