Chemical and microbiological stability, anticoagulant efficacy and toxicity of 35 and 90 mM trisodium citrate solutions stored in plastic syringes

Objectives: Trisodium citrate represents an interesting alternative to heparin for the prevention of circuit clotting during extracorporeal procedures, but some protocols require not commercially available citrate concentrations. There is very little information available in the literature about the stability of diluted citrate solutions. This study is aimed to evaluate the long-term stability, efficacy and toxicity of 35 mM and 90 mM trisodium citrate solutions prepared by diluting commercially available sterile solution, stored in plastic syringes, and used as anticoagulant during the citrate bag changes in coupled plasma filtration adsorption (CPFA) technique in the COMPACT-2 clinical trial. Methods: The chemical stability of trisodium citrate solutions was evaluated by HPLC after 7, 14, 21 and 28 days of storage. The sterility tests were performed both immediately after preparation and after 28 days of storage. Results: After 28 days of storage, the concentration of trisodium citrate do not change in comparison to day 1, and both the solutions passed the sterility test. A preliminary test indicated that 35 mM solution is not enough to ensure an effective anticoagulant action on extracorporeal circuit, but the 90 mM solution was successfully used during a total of 7 CPFA treatments in 2 patients without clinical signs of toxicity. Conclusions: Both the 35 mM and 90 mM solutions are chemically and microbiologically stable for 28 days when stored at room temperature in 50 mL syringes protected by light. The 90 mM solution is effective and safe as regional anticoagulant in the CPFA protocol.