CHAPTER 3-78: THIOSULFATE, SODIUM

INTRODUCTION

1. Pharmacology. Sodium thiosulfate is a sulfur donor that promotes the conversion of cyanide to the less toxic thiocyanate by the sulfur transferase enzyme rhodanese. Unlike nitrites, thiosulfate is essentially nontoxic and may be given empirically in suspected cyanide poisoning. Animal studies suggest enhanced antidotal efficacy when hydroxocobalamin is used with thiosulfate. Sodium thiosulfate has poor oral bioavailability. Following IV injection, sodium thiosulfate is extensively distributed into the extracellular fluids and excreted unchanged in the urine, with a reported half-life of 0.65 hours.

2. Indications

   1. May be given alone or in combination with nitrites or hydroxocobalamin to patients with acute cyanide poisoning; may also be used as empiric treatment of possible cyanide poisoning associated with smoke inhalation.

   2. Prophylaxis during nitroprusside infusions.

   3. Extravasation of mechlorethamine and cisplatin (infiltrate locally Antineoplastic Agents).

   4. Cisplatin overdose: sodium thiosulfate binds to free platinum to form a nontoxic thiosulfate-cisplatin complex, limiting damage to renal tubules.

   5. Other reported uses: bromate salt ingestion (unproven); reduced calcium urolithiasis via formation of calcium thiosulfate, which is more soluble than other urinary calcium salts, and prophylaxis for cisplatin-induced nephrotoxicity.

3. Contraindications. No known contraindications.

4. Adverse effects

   1. Intravenous (IV) infusion may produce a burning sensation, muscle cramping and twitching, and nausea and vomiting.

   2. Severe anion gap acidosis was reported following daily IV infusion of 25 g of sodium thiosulfate (>3 days) in a patient with nondialysis chronic kidney disease.

   3. Use in pregnancy. FDA Category C (indeterminate). This does not preclude its acute, short-term use in a seriously symptomatic patient (Introduction).

5. Drug or laboratory interactions. Thiosulfate falsely lowers measured cyanide concentrations in several methods. Sodium thiosulfate and hydroxocobalamin are chemically incompatible and should not be administered in the same IV line.

6. Dosage and method of administration

   1. For cyanide poisoning. Administer 12.5 g (50 mL of 25% solution) IV over 10 minutes or at 2.5–5 mL/min. The pediatric dose is 400 mg/kg (1.6 mL/kg of 25% solution) up to 50 mL. Half the initial dose may be given after 30–60 minutes if needed.

   2. For prophylaxis during nitroprusside infusions. The addition of 10 mg of thiosulfate for each milligram of nitroprusside in the IV solution has been reported to be effective and physically compatible.

   3. For cisplatin overdose. Administer (ideally within 1–2 hours of the overdose) 4 g/m² of sodium thiosulfate by IV bolus over 15 minutes, followed by an infusion of 12 g/m² over 6 hours. Although no optimal dosing regimen has been established, it is recommended to continue maintenance dosing until urinary platinum levels are below 1 mcg/mL.

7. Formulations

   1. Parenteral. As a component of the cyanide antidote kit (Nithiodote^®), thiosulfate sodium, 25% solution, one 50-mL (12.5 g) vial per kit. Also available separately in vials containing 10% (100 mg/mL) in 10 mL or 25% (250 mg/mL) in 50 mL.

   2. Suggested minimum stocking levels to treat a 100-kg adult for the first 8 hours and 24 hours: two Nithiodote^® kits, containing two 12.5-g vials of sodium thiosulfate or the equivalent ...