Sodium thiosulfate is an inorganic salt that is used in the treatment of cyanide poisoning and extravasation of chemotherapeutic agents.

Sodium thiosulfate Uses:

• Cyanide poisoning:
  • Treatment of acute, life-threatening conditions due to cyanide poisoning in combination with sodium nitrite.
• Off Label Uses in Adults:
  • Calciphylaxis;
  • Management of mechlorethamine extravasation;
  • Management of delayed calcium extravasation (calcinosis cutis);
  • Management of concentrated cisplatin (≥0.4 mg/mL) extravasation;
  • Management of bendamustine extravasation

Sodium thiosulfate Dose in Adults

Dose in the treatment of Cyanide poisoning: IV:

• When someone has cyanide poisoning, doctors might use sodium thiosulfate to help.
• They usually give it through a vein (IV).
• Before that, they'll give another medicine called sodium nitrite.
• After sodium nitrite, they give sodium thiosulfate right away.
• The dose of sodium thiosulfate is 12.5 grams, which is equal to 50 milliliters of a 25% solution.
• If the symptoms of cyanide poisoning come back, they might give another dose, but only half of the first one.
• Doctors need to watch the patient closely for 24 to 48 hours.
• If the symptoms come back again, they'll give both sodium nitrite and sodium thiosulfate again, but again at half the original doses.

Sodium thiosulfate dose in the treatment of Calciphylaxis (off-label): IV:

• In the treatment of calciphylaxis, which is sometimes done even though it's not officially approved for this use, the exact right dose of sodium thiosulfate isn't known for sure.
• For patients on dialysis, doctors often give 25 grams of sodium thiosulfate three times a week. They usually administer it during or after the dialysis session. This treatment continues until the symptoms of calciphylaxis go away completely.
• For patients who aren't on dialysis and still have normal or slightly reduced kidney function, they also get 25 grams of sodium thiosulfate three times a week.
• These doses and schedules are based on various studies and medical experience. It's essential for doctors to monitor patients closely and adjust the treatment plan as needed for the best results.

Dose in the management of extravasation (off-label):

In cases of extravasation, which is when certain medications leak into the surrounding tissues instead of staying in the vein, sodium thiosulfate is sometimes used to help manage the situation, even though it's not officially approved for this purpose.

• For Mechlorethamine administered under the skin (SubQ), doctors usually inject 2 milliliters of a 1/6 M (~4%) sodium thiosulfate solution into the area where the medication leaked for each milligram of Mechlorethamine suspected to have leaked.
• For concentrated Cisplatin, doctors inject 2 milliliters of a 1/6 M (~4%) sodium thiosulfate solution into the existing IV line for every 100 milligrams of Cisplatin that leaked. Additionally, they might also inject 1 milliliter of the same solution under the skin around the leak site, repeating this injection several times over the next few hours.
• For Bendamustine, the management is similar to Mechlorethamine, where sodium thiosulfate solution is used in the same manner for extravasation.

Sodium thiosulfate dose in the Management of delayed calcium extravasation (calcinosis cutis) (off-label):

• The initial dose of sodium thiosulfate is 12.5 grams, given over 30 minutes through an IV infusion.
• This dose may be increased gradually to 25 grams, three times per week.
• However, patients need careful monitoring for potential side effects such as non-anion gap acidosis, hypocalcemia (low calcium levels), and severe nausea.

Sodium thiosulfate Dose in Childrens

Sodium thiosulfate dose in Cyanide poisoning:

In cyanide poisoning cases involving infants, children, and adolescents, sodium thiosulfate is administered alongside sodium nitrite. Sodium nitrite is given first, followed immediately by sodium thiosulfate.

• The dose of sodium thiosulfate for this age group is based on weight, with a recommended dose of 250 milligrams per kilogram. This is usually given as 1 milliliter per kilogram or 30 to 40 milliliters per square meter of body surface area from a 25% solution. The maximum dose per administration is 12.5 grams, which is equivalent to 50 milliliters of a 25% solution.
• Patients should be closely monitored for 24 to 48 hours after administration. If symptoms of cyanide poisoning reappear, both sodium nitrite and sodium thiosulfate may be repeated at half of the original doses.

Sodium thiosulfate dose in the management of extravasation:

• For extravasation of Mechlorethamine, which is given under the skin (SubQ), the recommended dose for children and adolescents is to inject 2 milliliters of a 1/6 M (~4%) solution directly into the area where the medication leaked, for each milligram of Mechlorethamine suspected to have leaked.
• For concentrated Cisplatin extravasation in infants, children, and adolescents, doctors usually inject 2 milliliters of a 1/6 M (~4%) sodium thiosulfate solution into the existing IV line for every 100 milligrams of Cisplatin that leaked. Additionally, they might consider injecting 1 milliliter of the same solution under the skin around the leak site, using small subcutaneous injections, and repeating these injections several times over the next few hours.

Pregnancy Risk Factor C

• In terms of pregnancy risk, sodium thiosulfate falls into category C.
• This means that while animal studies haven't shown any teratogenic effects (effects on fetal development), there's limited data available for humans.
• However, it's crucial to note that medications classified as antidotes, like sodium thiosulfate, should be carefully considered in pregnant women.
• If there's a clear need for the medication due to a serious condition like cyanide poisoning, it should be used, without withholding it due to concerns about potential harm to the fetus.

Use during breastfeeding:

• Since it's not known whether sodium thiosulfate is present in breast milk, caution is advised when considering its use in breastfeeding women.
• However, because sodium thiosulfate may be crucial as an antidote in life-threatening situations, breastfeeding is not a contraindication to its use.
• Regarding the resumption of breastfeeding after administration, there's no clear guidance available.

Sodium thiosulfate Dose in Kidney Disease:

• While the manufacturer's labeling doesn't provide specific dosage adjustments, it's important to note that renal elimination plays a significant role in the clearance of sodium thiosulfate from the body. Consequently, in patients with renal impairment, there may be an increased risk of adverse effects.
• For the off-label use of sodium thiosulfate in calciphylaxis, no dosage adjustments are deemed necessary. However, for patients not on dialysis who have normal renal function or only mildly reduced glomerular filtration rate (GFR), healthcare providers may consider adjusting the dose based on the patient's appearance. This adjustment could help mitigate the risk of adverse effects associated with impaired renal function.

Sodium thiosulfate Dose in Liver disease:

• Since there haven't been studies specifically examining the effects of hepatic impairment on sodium thiosulfate metabolism and clearance, the manufacturer's labeling doesn't include any dosage adjustments for patients with liver issues.
• Therefore, caution should be exercised when administering sodium thiosulfate to individuals with hepatic impairment.

Side effects of Sodium thiosulfate:

• Cardiovascular:
  • Hypotension
• Central nervous system:
  • Disorientation
  • Flushing sensation
  • Headache
  • Salty taste
• Gastrointestinal:
  • Nausea, vomiting
• Hematologic & oncologic:
  • Prolonged bleeding time

Contraindications to Sodium thiosulfate:

• According to the manufacturer's labeling, there are no contraindications listed for the use of sodium thiosulfate.
• However, it's essential to consider individual patient factors and potential interactions with other medications or conditions when determining its suitability for use in specific cases.

Monitoring parameters:

Cyanide Poisoning:

• Duration of Monitoring: Monitor for at least 24-48 hours post-administration.
• Vital Signs: Monitor blood pressure and heart rate during and after infusion.
• Blood Parameters: Check hemoglobin/hematocrit levels.
• Gas Levels: Perform co-oximetry to assess blood oxygenation.
• Serum Lactate Levels: Monitor serum lactate levels to assess tissue perfusion.
• Venous-Arterial PO Gradient: Evaluate the venous-arterial oxygen partial pressure gradient.
• Methemoglobin and Oxyhemoglobin: Monitor serum levels for these substances, which can indicate cyanide poisoning.
• Pretreatment Cyanide Levels: Pretreatment cyanide levels may be helpful for diagnostic purposes.

Extravasation Management:

• Extravasation Site: Monitor and document the extravasation site for:
  • Pain
  • Blister formation
  • Skin sloughing
  • Arm/hand swelling/stiffness
• General Symptoms: Watch for fever, chills, or worsening pain, which could indicate complications.

Management of Delayed Calcium Extravasation (Calcinosis Cutis):

• Monitoring for Complications: Monitor for:
  • Non-anion gap acidosis
  • Hypocalcemia
  • Severe nausea, as these can be potential side effects of sodium thiosulfate treatment.

How to administer Sodium thiosulfate?

Cyanide Poisoning:

• Route: Administer by IV infusion.
• Infusion Rate: Over 10 to 30 minutes, immediately after sodium nitrite administration.
• Adjustment: Decrease the infusion rate if significant hypotension occurs.

Calciphylaxis (Off-label Use):

• Route: IV infusion.
• Infusion Rate: Over 30 to 60 minutes.

Extravasation Management (Off-label Use):

• General Steps:
  • Stop vesicant infusion immediately and disconnect IV line.
  • Gently aspirate extravasated solution from the IV line without flushing.
  • Remove the needle/cannula (temporarily keep it in place for cisplatin extravasation).
  • Elevate the extremity.
• Mechlorethamine Extravasation:
  • Route: Subcutaneous injection into the extravasation site.
  • Needle Size: Use ≤25-gauge needle; change needle with each injection.
• Cisplatin Extravasation:
  • Route: Inject into the existing IV line.
  • Additional Injection: Consider injecting 1 mL subcutaneously (clockwise) around the extravasation site using a new 25 or 27-gauge needle for each injection.
• Bendamustine Extravasation:
  • Route: Subcutaneous injection.
  • Management: Similar to mechlorethamine extravasation.

These guidelines outline the specific administration procedures for sodium thiosulfate in various clinical situations, ensuring safe and effective treatment.

Mechanism of action of Sodium thiosulfate:

Cyanide Toxicity:

• Role: Serves as a sulfur donor.
• Catalyzed Formation: Acts in the rhodanese-catalyzed formation of thiocyanate.
• Outcome: Thiocyanate is much less toxic than cyanide, helping to mitigate cyanide toxicity.

Extravasation Management:

• Neutralization: Sodium thiosulfate neutralizes the reactive species of mechlorethamine.
• Reduction of Tissue Injury: By reducing the formation of hydroxyl radicals, it helps prevent tissue injury caused by mechlorethamine extravasation.

These mechanisms illustrate how sodium thiosulfate functions in clinical settings, providing targeted actions to counteract specific toxic effects or mitigate damage caused by extravasation of certain medications.

Distribution:

• Volume of Distribution (V):
  • Thiosulfate: 0.15 L/kg
  • Thiocyanate: 0.25 L/kg

Elimination:

• Half-life:
  • Thiosulfate: Approximately 3 hours
  • Thiocyanate: 2.7 days (prolonged to ~9 days with renal impairment)

Excretion:

• Route: Primarily excreted in urine.
• Percentage Excretion: Approximately 20% to 50% of thiosulfate is excreted unchanged in urine.

International Brand Names of Sodium thiosulfate:

• Seacalphyx
• Krem Ochronny z Tiosiarczanem Sodu A
• Soft Mate Consept 2

Sodium thiosulfate Brand Names in Pakistan:

No Brands Available in Pakistan.