Sodium thiosulfate (STS) is typically given as an intravenous infusion during the last hour of a hemodialysis session, with doses usually ranging from 12.5 to 25 grams diluted in normal saline. The timing is deliberate: infusing STS while the dialyzer is still running allows the machine to help clear some of the drug’s acidic byproducts while still giving enough dwell time for a therapeutic effect. But the actual protocol varies considerably depending on the patient’s dialysis schedule, body weight, residual kidney function, and what condition is being treated, making STS one of the trickier drugs to dose in the dialysis unit.
Why STS Is Used in Dialysis Patients
The most common reason STS is administered during dialysis is calciphylaxis, a painful and often fatal condition in which small blood vessels in the skin and fat tissue become clogged with calcium deposits. The skin breaks down into necrotic wounds that are extremely difficult to heal and prone to infection. Calciphylaxis overwhelmingly affects people with advanced kidney disease, particularly those on dialysis, and it carries a one-year mortality rate that can exceed 50 percent in some case series.1JAMA Network Open. Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease: A Systematic Review and Meta-analysis Beyond calciphylaxis, vascular calcification itself is a major driver of heart disease and death in dialysis patients, and there is growing interest in using STS to slow or prevent calcium buildup in coronary arteries and other vessels.2PubMed Central. Sodium thiosulfate pharmacokinetics in hemodialysis patients and healthy volunteers
How STS Works Against Calcification
STS has two properties that make it useful against calcium-related disease. First, it acts as a calcium chelator, meaning it binds to calcium ions in the bloodstream and converts them into calcium thiosulfate, a compound that is far more soluble than the calcium phosphate crystals that lodge in vessel walls and soft tissue. By pulling calcium into a soluble form, STS helps the body clear it more easily. Second, STS is an antioxidant, which may reduce the oxidative stress and inflammation that contribute to calcification in the first place.3PubMed. Systematic review of sodium thiosulfate in treating calciphylaxis in chronic kidney disease patients Animal research has confirmed both of these actions, showing that STS can prevent vascular calcification in uremic models and may also protect against some of the downstream organ damage that calcification causes.4PubMed. Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification
The chelation effect is dose-dependent: more STS means more calcium gets swept up. But STS is also rapidly cleared by dialysis, which creates a fundamental tension. You want enough drug in the bloodstream long enough to do its job, but if the dialysis machine is running at full speed, it strips the drug out before it can work. This tension is at the heart of most practical dosing questions.
Standard Intravenous Protocol During Hemodialysis
The most widely described protocol involves dissolving 25 grams of STS in 100 to 200 mL of normal saline and infusing it intravenously during the last 30 to 60 minutes of a hemodialysis session, typically three times per week (matching the standard hemodialysis schedule). Some centers use a lower dose of 12.5 grams, particularly for smaller patients, those with a history of side effects, or as a starting dose before escalating.
The reason for timing the infusion at the end of the session rather than the beginning is straightforward. STS has a relatively small molecular size and is cleared efficiently by the dialyzer. If you infuse it at the start of a four-hour hemodialysis run, the machine removes most of it before the session ends, and the patient gets very little sustained exposure. By starting the infusion in the last hour, enough STS enters the bloodstream to begin chelating calcium, and the remaining dialysis time helps remove some of the acid that STS metabolism produces, without stripping away all of the drug.
Some protocols call for infusing STS after the dialysis session ends entirely, particularly when the goal is to maximize the amount of drug that stays in the body. The tradeoff here is that the patient has no dialysis support to buffer any acid load until the next session. In practice, both during-session and post-session approaches are used, and the choice often comes down to how well a given patient tolerates the metabolic effects.
Why Dosing Is Not One-Size-Fits-All
One of the more striking findings about STS dosing in dialysis is just how much the “right” dose depends on the specifics of a patient’s dialysis prescription. A simulation study found that, for a 70-kilogram adult with no remaining kidney function, the weekly STS dose needed to maintain a target blood level ranged from about 72 grams per week all the way up to 245 grams per week, depending on how often and how long the patient dialyzed.5PubMed Central. Simulation-based sodium thiosulfate dosing strategies for the treatment of calciphylaxis That is roughly a three-and-a-half-fold range driven largely by differences in hemodialysis frequency and session length. Blood flow rate and dialysate flow rate mattered less.
The practical implication is that a flat “25 grams three times a week” dose is going to be too much for some patients and not enough for others. Someone doing short daily hemodialysis sessions, for example, clears STS more frequently and may need a different per-session dose than someone on a conventional three-times-weekly schedule. Patients with some residual kidney function will also clear more STS between sessions. For this reason, experienced centers often start at a standard dose and adjust based on the patient’s acid-base response, wound healing progress, and tolerance of side effects.
Monitoring for Metabolic Acidosis
The most important safety concern with STS during dialysis is metabolic acidosis, specifically an elevated anion gap. When the body metabolizes STS, it generates sulfate and other acid equivalents. In a person with normal kidneys, these are handled without trouble. In someone on dialysis, the acid accumulates between sessions.
A study of 35 hemodialysis patients on STS found that almost all of them, 94 percent, developed an increase in their anion gap during treatment. On a 25-gram dose, the average increase was about 6.6 mmol/L, with some patients seeing jumps as high as 18 mmol/L. On the lower 12.5-gram dose, the average bump was smaller, around 2.6 mmol/L, and the difference between the two doses was statistically meaningful.6American Journal of Kidney Diseases. Sodium Thiosulfate and the Anion Gap in Patients Treated by Hemodialysis These changes were variable and sometimes severe, which means routine lab monitoring is not optional. In practice, clinicians typically check a basic metabolic panel before and after the first few STS infusions and periodically thereafter, watching especially for a dropping bicarbonate level and a widening anion gap.
Most patients experience only a mild, asymptomatic acidosis that corrects with their next dialysis session. But reports of severe, life-threatening acidosis do exist. In some cases, the severity of the acidosis has been out of proportion to what you would expect from the STS dose alone, raising the possibility that some patients metabolize STS into hydrogen sulfide more aggressively than others.7PubMed Central. Metabolic acidosis after sodium thiosulfate infusion and the role of hydrogen sulfide This individual variability is hard to predict in advance, so dose adjustment and close follow-up of acid-base status are standard recommendations, particularly after starting or escalating STS.8PubMed Central. Severe anion gap acidosis associated with intravenous sodium thiosulfate administration
Other side effects reported with STS infusions include nausea, vomiting, and hypotension, particularly if the drug is infused too quickly. Slowing the infusion rate or reducing the dose usually helps with these. The nausea can be significant enough that some patients have difficulty completing their prescribed course, which is a real-world problem given that calciphylaxis treatment often requires weeks to months of STS.
Peritoneal Dialysis Patients
Most of the literature on STS focuses on hemodialysis patients, but calciphylaxis also affects people on peritoneal dialysis (PD). Giving STS intravenously to a PD patient is possible, but it requires either placing a peripheral or central intravenous line or arranging infusions at a clinic, which undermines one of the main advantages of PD: independence from a dialysis center. This has led some centers to try giving STS directly into the peritoneal cavity, dissolved in dialysate.
The evidence on intraperitoneal STS is limited and mixed. A systematic review of PD patients receiving intraperitoneal STS found that doses ranged from 12.5 to 25 grams given three to four times per week, with dwell times from 12 hours to continuous use over several months. Wound healing was achieved in a majority of cases, but the adverse event profile was concerning: most patients eventually discontinued STS because of side effects, and some experienced chemical peritonitis, a serious complication involving inflammation of the peritoneal membrane. In the small case series reviewed, peritonitis led to death in a notable fraction of patients.9PubMed Central. Sodium Thiosulfate for Calciphylaxis Treatment in Patients on Peritoneal Dialysis: A Systematic Review
Not all the data is grim. A separate case series described intraperitoneal STS as a safe and convenient long-term option for selected patients, suggesting that individual technique, dosing, and monitoring protocols may matter as much as the route itself.10PubMed. Clinical experience with intraperitoneal sodium thiosulphate for calciphylaxis in peritoneal dialysis: A case series The overall picture is that intraperitoneal STS remains experimental, with small patient numbers and no randomized trials to guide practice. Some PD patients are switched to hemodialysis specifically to make STS administration simpler and safer.
Using STS to Slow Coronary Artery Calcification
Calciphylaxis gets the most attention, but a growing body of work is examining whether STS can slow the progressive coronary artery calcification (CAC) that affects a large proportion of long-term dialysis patients. This is a different goal: not treating an acute, life-threatening skin condition, but potentially preventing the gradual accumulation of calcium in heart arteries that drives cardiovascular events.
A meta-analysis pooling data from multiple studies found that three to six months of intravenous STS was associated with a meaningful reduction in CAC scores compared to usual care without STS. The effect was consistent across subgroups defined by age, sex, dialysis vintage, and study design.11PubMed Central. Influence of sodium thiosulfate on coronary artery calcification of patients on dialysis: a meta-analysis A randomized controlled trial found that intradialytic STS reduced arterial stiffness and stabilized vascular calcification in hemodialysis patients, while the control group saw their calcification scores climb.12PubMed. Effect of Sodium Thiosulfate on Arterial Stiffness in End-Stage Renal Disease Patients Undergoing Chronic Hemodialysis
An earlier pilot study painted a more nuanced picture. Although most individual patients showed some progression of calcification, the group as a whole did not show a significant increase in the mean rate of calcification, suggesting that STS may slow but not fully halt the process.13PubMed Central. Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy The administration protocol for CAC prevention is generally the same as for calciphylaxis: intravenous STS during hemodialysis sessions, though the dose and duration can vary by study.
This is where the evidence gets thin. Most of these studies are small, and there are no large-scale randomized trials proving that STS reduces hard cardiovascular endpoints like heart attacks or death. The CAC score improvements are promising and biologically plausible, but the field has not yet crossed the threshold from “this looks like it works on imaging” to “this saves lives.” Clinicians who use STS for CAC prevention tend to do so on an off-label, case-by-case basis, often in patients who already have severe or rapidly progressing calcification.
Preparing and Storing the Infusion
STS for intravenous use in the dialysis setting is typically compounded from a 25 percent solution (250 mg/mL). The standard approach is to draw up the prescribed dose and dilute it in 100 to 200 mL of 0.9 percent sodium chloride (normal saline), then infuse it over 30 to 60 minutes. Some centers use 250 mL bags for easier administration through the dialysis circuit’s venous port.
Stability testing has confirmed that STS solutions diluted in normal saline at concentrations between 16 and 72 mg/mL remain stable for at least 24 hours in polyolefin bags at room temperature, retaining more than 95 percent of their initial concentration with no visible changes in color, clarity, or precipitation.14Pharmaceutical Technology in Hospital Pharmacy. Physico-Chemical Stability of Sodium Thiosulfate Infusion Solutions in Polyolefin Bags at Room Temperature over a Period of 24 Hours This is useful information for dialysis units that batch-prepare doses or need to premix ahead of a patient’s arrival. If combined with sodium nitroprusside (a less common clinical scenario), the mixture is stable for up to 48 hours at room temperature when protected from light.15PubMed Central. Stability of Sodium Nitroprusside and Sodium Thiosulfate 1:10 Intravenous Admixture
One practical challenge in many dialysis facilities is that STS is not a drug routinely stocked by all pharmacies. It may need to be ordered from a compounding pharmacy, and insurance coverage can be inconsistent for what is, in many of its dialysis-related uses, an off-label medication. Dialysis nurses also need specific instructions on infusion timing, since administering STS at the wrong point in the session can significantly change both its effectiveness and its side-effect profile. Units that use STS regularly often develop written protocols specifying the dose, dilution, infusion rate, and lab monitoring schedule, which helps keep practice consistent across shifts and staff.
What a Typical STS Protocol Looks Like in Practice
Putting it all together, a common real-world STS protocol at a hemodialysis unit looks something like this:
- Starting dose: 12.5 grams diluted in 100 mL normal saline, infused over the last 30 to 60 minutes of a standard hemodialysis session.
- Escalation: If the first dose is tolerated without significant nausea, vomiting, or drop in bicarbonate, the dose is increased to 25 grams at the next session or after a few sessions.
- Frequency: Three times per week, matching the patient’s hemodialysis schedule.
- Monitoring: Basic metabolic panel checked before and after the first few infusions, then periodically (often weekly for the first month, then less frequently). Special attention to bicarbonate, anion gap, and potassium.
- Duration: For calciphylaxis, treatment continues until wounds are healed or the clinical team decides STS is not helping, often spanning weeks to several months. For vascular calcification, the optimal duration is not established.
- Adjustments: Dose reduced or infusion slowed if the patient develops nausea, hypotension, or a significant anion gap elevation. Some patients do well on a maintenance dose of 12.5 grams indefinitely.
There is no universally agreed-upon protocol because no large randomized trial has compared different dosing strategies head-to-head. Most of the guidance comes from case series, pharmacokinetic modeling, and expert consensus. This means there is real variation between centers, and patients transferring from one dialysis unit to another may find their STS protocol adjusted.
When STS Administration Goes Wrong
The cases that end up in the literature as warnings tend to share a few features. Most involve patients who received a full 25-gram dose without adequate metabolic monitoring in the days following infusion. The severe acidosis cases often present 12 to 48 hours after infusion, when the patient is between dialysis sessions and has no machine to help correct the acid buildup. By the time symptoms appear (confusion, rapid breathing, hemodynamic instability), the anion gap may be dangerously elevated.
The lesson from these reports is not that STS is too dangerous to use, but rather that the margin for error is narrower in dialysis patients than the drug’s “generally safe” reputation might suggest. The key protective steps are starting at the lower dose, checking labs early and often, and having a low threshold for backing off if the numbers trend the wrong direction. Patients themselves should know to report unusual fatigue, shortness of breath, or nausea between sessions, since these could signal acidosis building up before the next dialysis run.
One additional wrinkle is that STS-related acidosis does not always respond predictably to standard treatments like sodium bicarbonate supplementation. In cases where hydrogen sulfide production is thought to be driving the acidosis, simply adding more buffer may not be enough, and the definitive treatment is to stop STS and support the patient through the metabolic disturbance. This underscores why close communication between the nephrologist, the dialysis nursing team, and the patient is essential throughout the course of treatment.