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Trisodium Citrate Dihydrate

Also known as: sodium citrate dihydrate, sodium citrate, anhydrous sodium citrate, trisodium citrate, citrate phosphate dextrose, Trisodium Citrate Dihydrate

Overview

Trisodium citrate dihydrate is the dihydrate salt form of trisodium citrate, a sodium salt of citric acid. While citric acid is naturally found in citrus fruits, trisodium citrate dihydrate is synthetically produced. It is widely utilized in medical and food applications due to its properties as an anticoagulant, buffering agent, and food additive. In medical settings, its primary use is as an anticoagulant in blood collection and storage solutions, and notably as a catheter lock solution to prevent infections and thrombosis in medical devices. Its mechanism of action involves chelating calcium ions, which are crucial for blood coagulation, thereby effectively preventing clot formation. It is highly water-soluble and maintains stability in aqueous solutions. Research on trisodium citrate dihydrate, particularly in clinical contexts for anticoagulation and catheter lock solutions, is well-established, with a moderate to high level of maturity. High-quality evidence, including randomized controlled trials and meta-analyses, supports its efficacy and safety, especially as an alternative to heparin for catheter locks.

Benefits

Trisodium citrate dihydrate offers significant benefits primarily as an anticoagulant. Its main effect is to prevent blood clotting by chelating calcium ions, which are essential for the coagulation cascade. In a meta-analysis of 17 randomized controlled trials (RCTs) involving over 128,000 catheter-days, citrate lock solutions demonstrated a statistically significant reduction in catheter-related bloodstream infections (CRBSI) compared to heparin, particularly when used in combination with antibiotics or at low concentrations. This indicates a clinically meaningful improvement in infection control, especially for patients requiring long-term catheterization, such as those undergoing hemodialysis. While its primary benefits are in anticoagulation and infection prevention, there is some evidence suggesting an improvement in antioxidant status in blood preservation solutions, though its effects on oxidative stress markers are limited. The benefits are observed throughout the period of catheter use, as citrate lock solutions are regularly applied to maintain catheter patency and reduce infection risk.

How it works

Trisodium citrate dihydrate primarily functions by chelating calcium ions. Calcium ions are essential cofactors in the blood coagulation cascade, playing a critical role in various steps of clot formation. By binding to these calcium ions, trisodium citrate dihydrate effectively removes them from circulation, thereby inhibiting the coagulation process and preventing clot formation. When used as a catheter lock solution, it acts locally within the catheter lumen, preventing coagulation without inducing systemic anticoagulation effects. Its interaction with the body's systems is localized, ensuring that its anticoagulant action is confined to the specific area of application, such as a medical device or blood collection tube. The minimal systemic absorption at clinical concentrations further contributes to its safety profile.

Side effects

Trisodium citrate dihydrate is generally considered safe and well-tolerated, particularly when used as a catheter lock solution or anticoagulant in blood collection. Common side effects are minimal, with local irritation being possible but uncommon. Uncommon side effects (1-5% incidence) may include rare metabolic disturbances if significant systemic absorption occurs. Rare side effects (less than 1% incidence) can involve hypocalcemia, but this typically only occurs with excessive systemic exposure. Regarding drug interactions, there is a potential for additive anticoagulant effects if trisodium citrate dihydrate is combined with systemic anticoagulants, necessitating careful monitoring. Contraindications include hypersensitivity to citrate or sodium salts. Caution is advised in patients with pre-existing electrolyte imbalances. For special populations, it is considered safe for use in hemodialysis patients, although dosage and concentration adjustments may be necessary in individuals with renal impairment to prevent potential complications.

Dosage

The recommended dosage of trisodium citrate dihydrate varies depending on its specific application. For catheter lock solutions, low-concentration citrate solutions, such as 4% trisodium citrate dihydrate, have demonstrated efficacy in reducing catheter-related bloodstream infections (CRBSI). While concentrations can vary, clinical use generally favors lower concentrations, as high concentrations (e.g., above 30%) may be associated with toxicity. When used as a lock solution, it is typically applied after catheter use, with the dwell time varying according to specific clinical protocols. It is primarily used in aqueous solutions for catheter locks, and pharmaceutical-grade purity is required for medical applications. Systemic absorption is minimal when used as intended, ensuring localized action. No specific cofactors are required for its mechanism of action, as it directly chelates calcium.

FAQs

Is trisodium citrate dihydrate safe as a catheter lock?

Yes, meta-analyses confirm it is safe and effective as a catheter lock solution, showing a reduction in infections compared to heparin, especially at low concentrations.

Does it cause systemic anticoagulation?

When used as a catheter lock solution, systemic absorption is minimal, meaning it does not cause significant systemic anticoagulation effects.

Can it replace heparin?

Evidence supports its use as a safe and effective alternative to heparin for catheter locks, particularly when combined with antibiotics or used at low concentrations.

How quickly does it work?

It acts immediately upon contact by chelating calcium ions, thereby preventing blood coagulation.

Are there risks of hypocalcemia?

The risk of hypocalcemia is rare and primarily occurs only if there is excessive systemic exposure, which is uncommon with proper use.

Research Sources

https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1530619/full – This meta-analysis of 17 RCTs (over 128,000 catheter-days) compared citrate lock solutions to heparin, finding significantly lower CRBSI incidence with citrate, especially low-concentration citrate with antibiotics. The study highlights citrate's effectiveness in infection control, though it notes heterogeneity and variability in citrate concentrations as limitations.
https://archive.hshsl.umaryland.edu/bitstreams/341a0430-d95f-486b-bd67-7599e397e0ff/download – This systematic review and expert interviews explored the clinical use of citrate in cardiac surgery and blood preservation. It found that citrate phosphate dextrose solutions can improve antioxidant status in blood, although their effect on oxidative stress markers is limited. Expert opinions supported its clinical utility and safety.
https://pubchem.ncbi.nlm.nih.gov/compound/Trisodium-Citrate-Dihydrate – This source provides comprehensive chemical and pharmacological data for Trisodium Citrate Dihydrate. It confirms its chemical identity, lists various synonyms, and details its role as an anticoagulant through calcium chelation, supporting its established clinical safety and efficacy.