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Sodium thiosulfate is a safe and effective antidote that detoxifies cyanide by donating a sulfur moiety to form thiocyanate. Thiocyanate is much less toxic than cyanide and is renally eliminated. Sodium thiosulfate works synergistically with nitrites and hydroxocobalamin in the detoxification of cyanide. Because sodium thiosulfate does not compromise hemoglobin oxygen saturation, it can be used without nitrites in circumstances where the formation of methemoglobin would be detrimental, as in patients who have elevated concentrations of carboxyhemoglobin or preexistent methemoglobinemia from smoke inhalation from fires. Sodium thiosulfate is used prophylactically with nitroprusside to prevent cyanide toxicity. Sodium thiosulfate is also used to treat calciphylaxis (calcific uremic arteriolopathy) by forming the very water-soluble calcium thiosulfate.4,21
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In 1933 Chen et al.6 noted that preexposure treatment with intravenous (IV) sodium thiosulfate protected dogs against three minimum lethal doses of sodium cyanide, and even more remarkable was the synergistic effects obtained by combining sodium thiosulfate with either inhaled amyl nitrite or IV sodium nitrite, which protected the dogs against 10 to 18 minimum lethal doses of cyanide.5,6
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The chemical formula of sodium thiosulfate is Na2S2O3. The molecular weight of sodium thiosulfate is 248 Da including the pentahydrate. It is a pentahydrate that is highly water soluble. Sodium hyposulfite is a synonym.
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The sulfur provided by sodium thiosulfate binds to cyanide with the help of rhodanese (cyanide sulfur transferase) and mercaptopyruvate sulfur transferase.6,27,29 This sulfur, a sulfane sulfur (a divalent sulfur bound to one other sulfur), is the only type of sulfur that reacts with cyanide to produce thiocyanate, which is minimally toxic and renally eliminated. In many different animal models, sodium thiosulfate protects against several minimum lethal doses of cyanide.14,17 The addition of rhodanese increases the efficacy of sodium thiosulfate, but the use of rhodanese is impractical in the clinical setting.17,28 The cationic site on rhodanese is crucial to cleaving the sulfur–sulfur bond of thiosulfate and forming a sulfur–rhodanese complex that readily reacts with cyanide.29
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Rhodanese is probably not solely responsible for sulfur–sulfur bond cleavage, as rhodanese is largely a mitochondrial enzyme found in the liver and skeletal muscle, and sodium thiosulfate is a divalent ion that poorly crosses membranes.11,17,22,27,29 An additional theory proposes that both mercaptopyruvate sulfurtransferase and rhodanese are involved in the formation of sulfane sulfur in the liver from sodium thiosulfate, and that serum albumin then carries the sulfane sulfur from the liver to other organs. When cyanide is present, albumin delivers this sulfur to cyanide, forming thiocyanate.15,27–29
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Sodium thiosulfate is a large divalent anion. Canine studies suggest that sodium thiosulfate rapidly distributes into the extracellular space and then slowly into the cell, perhaps with a carrier facilitating entry into the mitochondria.13,22 When administered prior to cyanide, thiosulfate converted ...