Sodium thiosulfate disposition in humans: relation to sodium nitroprusside toxicity

Thiosulfate concentrations and pharmacokinetics were studied in relation to sodium nitroprusside before, during, and after anesthesia. Normal thiosulfate concentrations were 1.13 +/- 0.11 mg/dl and 0.28 +/- 0.02 mg/dl in plasma and urine, respectively. Cholecystectomy patients had similar concentrations during surgery, with bile thiosulfate concentration of 13.72 +/- 2.95 mg/dl. Fasting patients and children had significantly higher plasma and urine thiosulfate concentrations. Over 99% of endogenous filtered thiosulfate was reabsorbed by the kidney in the average case. Coronary bypass patients had decreased plasma thiosulfate levels and increased excretion postoperatively. Disappearance of injected thiosulfate was biphasic; the distribution phase was dependent on the initial rate of injection, and the elimination phase depended on extracellular fluid turnover and renal excretion. Cholecystectomy patients on diuretics had a markedly increased rate of excretion, 56% within 100 min, versus normal subjects who excreted less than 50% in up to 18 h. In children, plasma thiosulfate did not change significantly, while blood cyanide concentration increased significantly during sodium nitroprusside administration and surgery. Thiosulfate did not change during recovery while cyanide decreased. Normal production of thiosulfate in humans may be limited; hence, continuous thiosulfate infusion may be required during sodium nitroprusside administration.