Sodium Thiosulfate Dosing for Calciphylaxis in Hemodialysis Patients
Start with 25 grams of sodium thiosulfate intravenously, administered three times per week immediately after each hemodialysis session, infused over 60 minutes for an initial treatment period of 3-6 months. 1, 2
Standard Dosing Protocol
The recommended starting dose is 25 grams per session (two 50 mL vials), diluted in 100 mL normal saline or 5% dextrose, infused over 60 minutes, given immediately after each hemodialysis session, three times weekly. 1
If concerned about adverse effects or patient tolerability, a lower starting dose of 12.5 grams per session can be considered, though this may reduce efficacy. 1
The standard treatment duration is 3-6 months, after which clinical response should be reassessed. 3, 1, 2
Dosing Rationale and Evidence Quality
The dosing recommendations come from multiple observational studies showing doses ranging from 12.5-25 grams per session, 2-3 times weekly. 3 While sodium thiosulfate has never been evaluated in a randomized controlled trial for calciphylaxis, and a recent meta-analysis did not find a consistent association with wound improvement or survival, it remains widely used due to individual case successes and lack of alternative therapies. 3
Research data support this dosing range, with one study using an initial dose of approximately 119.4 g/m²/week (roughly 25 grams three times weekly) with good outcomes. 4 Long-term use up to 52 months has been reported with acceptable safety profiles. 4, 5
Critical Monitoring Requirements
Monitor bone mineral density at baseline and 6 months, as significant hip bone density decline can occur with higher doses. 3, 1
Track serum electrolytes closely, particularly for anion gap metabolic acidosis, which can develop during treatment. 5
Assess for gastrointestinal disturbances (nausea, vomiting), which are dose-dependent and may require dose reduction. 3, 1
Document wound healing progress with regular photographic documentation. 2
Timing and Administration Details
Administer immediately after hemodialysis sessions to facilitate directly observed therapy and avoid premature drug removal. 1
The drug should be given post-dialysis because sodium thiosulfate has a markedly elevated half-life of 478 minutes in hemodialysis patients, with measurable quantities remaining more than 50 hours after treatment. 5
Infuse over 60 minutes to minimize acute adverse effects, particularly nausea. 1
Multimodal Treatment Considerations
While sodium thiosulfate is the primary pharmacologic intervention, calciphylaxis management requires additional measures:
Discontinue vitamin K antagonists (warfarin) immediately, as they increase calciphylaxis risk up to 11-fold. 3, 2
Consider reduced-dose apixaban as a safer anticoagulation alternative if needed. 3, 2
Optimize mineral metabolism by reducing calcium-containing phosphate binders and adjusting dialysate calcium to lower concentrations (1.5-2.0 mEq/L). 2
Implement aggressive pain control, as calciphylaxis lesions are extremely painful. 3, 2
Ensure meticulous wound care with careful debridement of necrotic tissue. 2
Common Pitfalls to Avoid
Do not delay treatment waiting for biopsy confirmation, as skin biopsy has poor sensitivity (20-80%) and may traumatize vulnerable tissue, triggering additional non-healing ulcers. 3, 2
Do not use lower doses than 25 grams without specific contraindications, as efficacy may be compromised. 1
Do not continue calcium-based phosphate binders or high dialysate calcium concentrations during treatment. 2
Duration and Reassessment
Continue treatment for 3-6 months initially, then reassess based on wound healing, pain control, and adverse effects. 3, 1
Some patients may require extended treatment beyond 6 months; long-term use up to 2 years has been reported with continued benefit. 6
If no improvement occurs after 3 months, consider parathyroidectomy if PTH >500 pg/mL. 2