Summary
Sodium nitroprusside (SNP) as a monoinfusion 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 µg/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 µg SNP/kg/min could within 5–10 h cause a life-threatening cyanide level in the blood. By contrast, mixed influsion 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.
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References
Aitken D, West D, Smith F et al. (1977) Cyanide toxicity following nitroprusside induced hypotension. Can Anaesth Soc J 24:651–660
Ansell M, Lewis FAS (1970) A review of cyanide concentrations found in human organs. J Forens Med 17:148–155
Asmus E, Garschagen H (1953) Über die Verwendung der Barbitursäure für die photometrische Bestimmung von Cyanid und Rhodanid. Z Anal Chem 138:414–422
Ballantyne B (1977) In vitro production of cyanide in normal human blood and the influence of thiocyanate and storage temperature. Clin Toxicol 11:173–193
Bennett NR, Abbott TR (1977) The use of sodium nitroprusside in children. Anaesthesia 32:456–463
Bogusz M, Moroz J, Karski J et al. (1979) Blood cyanide and thiocyanate concentrations after administration of sodium nitroprusside as hypotensive agent in neurosurgery. Clin Chem 25:60–63
Bonn R (1979) Determination of red blood cell cyanide after sodium nitroprusside infusion. Naunyn Schmiedebergs Arch Pharmacol 308s:87
Chakmakjian ZH, Bethune JE (1966) Sodium sulfate treatment of hypercalcemia. N Engl J Med 275:862–869
Davies DW, Kadar D, Steward DJ, Munro IR (1975) A sudden death associated with the use of sodium nitroprusside for induction of hypotension during anaesthesia. Can Anaesth Soc J 22:547–552
Dixon K (1962) Spectrophotometric determination of sodium thiosulfate in body fluids by use of an iodine-amylose complex. Clin Chim Acta 7:453–458
Eichler O (1950) Die Pharmakologie anorganischer Anionen. Handbook of experimental pharmacology, vol 10. Springer, Berlin Göttingen New York, pp 367–368, 649–661, 1095–1103
Elberg AJ, Gorman HM, Barker R, Strauss J (1979) Use of sodium nitroprusside in hypotension crisis in children. Cardiovasc Med 497–502
Gast JH, Arei K, Aldrich FL (1952) Quantitative studies on urinary thiosulfate excretion by healthy human subjects. J Biol Chem 196:875–884
Gettler AO, Baine JO (1938) The toxicology of cyanide. Am J Med Sci 195:182–198
Gilman A, Philips FS, Koelle ES (1946) The renal clearance of thiosulfate with observations on its volume distribution. Am J Physiol 146:348–357
Graham DL, Laman D, Theodore J, Robin ED (1977) Acute cyanide poisoning complicated by lactic acidosis and pulmonary edema. Arch Intern Med 137:1051–1055
Himwich WA, Saunders JP (1948) Enzymatic conversion of cyanide to thiocyanate. Am J Physiol 153:348–354
Höbel M, Kreye VAM, Raithelhuber A (1976) Sodium nitroprusside: its toxicity, metabolism, and organic distribution. Herz 1:130–136
Humphrey SH, Nash DA (1978) Lactic acidosis complicating sodium nitroprusside therapy. Ann Intern Med 88:58–59
Ivankovich A, Miletich DJ, Tinker JH (1978) Sodium nitroprusside: metabolism and general consideration. Int Anesthesiol Clin 16:1–29
Jack RD (1974) Toxicity of sodium nitroprusside. Br J Anaesth 46:952
Kreye VAW (1980) Sodium nitroprusside. In: Scriabine A (ed) Pharmacology of antihypertensive drugs. Ravens Press, New York, pp 373–396
Lang S (1895) Über die Entgiftung der Blausäure. Arch Exp Pathol Pharmacol 36:75–99
Lang K (1933) Die Rhodanbildung im Tierkörper. Biochem Z 259:243–256
Lawrence WS (1947) The toxicity of sodium cyanide at slow rates of infusion. Fed Proc 6:349
Lawson NW, Thompson DS, Nelson CL, Flacke JW, Seifen AB (1976) A dosage nomogram for sodium nitroprusside induced hypotension under anesthesia. Anesth Analg (Cleve) 55:574–581
MacRae WR, Owen M (1974) Severe metabolic acidosis following hypotension induced with sodium nitroprusside. Br J Anaesth 46:795–797
Mellino M, Phillips DF (1980) Severe lactic acidosis in a case of nitroprusside resistance. Cleve Clin Q 47:119–122
Merrifield AJ, Blundell MD (1974) Toxicity of sodium nitroprusside. Br J Anaesth 46:324
Michenfelder JD (1977) Cyanide release from sodium nitroprusside in the dog. Anesthesiology 46:196–201
Montoliu J, Botey A, Pons JM, Revert L (1979) Fatal hypotension in normal-dose nitroprusside therapy. Am Heart J 97:541–542
Naughton M (1974) Acute cyanide poisoning. Anaesth Intensive Care 4:351–356
Page IH, Corcoran AC, Dustan HP, Koppanyi T (1955) Cardiovascular actions of sodium nitroprusside in animals and hypertensive patients. Circulation 11:188–198
Posner MA, Rodman GH, Klick JM, Tobey RE (1977) Cyanide production during nitroprusside therapy in an oliguric patient. Anesth Analg 56:729–731
Rodkey FL, Collison HA (1977) Determination of cyanide and nitroprusside in blood and plasma. Clin Chem 23:1969–1975
Saunders JP, Himwich WA (1950) Properties of the transsulfurase responsible for conversion of cyanide to thiocyanate. Am J Physiol 163:404–409
Schulz V, Bonn R, Kindler J (1979) Kinetics of elimination of thiocyanate in 7 healthy subjects and in 8 subjects with renal failure. Klin Wochenschr 57:243–247
Schulz V, Döhring W, Rathsack P (1978) Thiocyanate intoxication with nitroprusside treatment for malignant hypertension. Klin Wochenschr 56:355–361
Skarzynski B, Szczepkowski TW, Weber M (1959) Thiosulfate metabolism in the animal organism. Nature 184:994–995
Szczepkowski TW, Skarzynski B, Weber M (1961) The metabolic state of thiosulfate. Nature 189:1007–1008
Tinker JH, Cucchiara RF (1978) Use of sodium nitroprusside during anaesthesia and surgery. Int Anesthesiol Clin 16:89–112
van Loenen AC, Hofs-Kemper W (1979) Stability and degradation of sodium nitroprusside. Pharmaceutisch Weekblad 114:424–436
Vesey CJ, Cole PV, Simpson PJ (1976) Cyanide and thiocyanate concentrations following sodium nitroprusside infusion in man. Br J Anaesth 48:651–660
Vesey CJ, Simpson PJ, Adams L, Cole PV (1979) Metabolism of sodium nitroprusside and cyanide in the dog. Br J Anaesth 51:89–97
Vesey CJ, Wilson J (1978) Red cell cyanide. J Pharm Pharmacol 30:20–26
WHO Expert Committee (1979) The selection of essential drugs. World Health Organisation, Geneva, Technical Report Series 641
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Schulz, V., Gross, R., Pasch, T. et al. Cyanide toxicity of sodium nitroprusside in therapeutic use with and without sodium thiosulphate. Klin Wochenschr 60, 1393–1400 (1982). https://doi.org/10.1007/BF01716244
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DOI: https://doi.org/10.1007/BF01716244