Clinical application of 4% sodium citrate and heparin in the locking of central venous catheters (excluding dialysis catheters) in intensive care unit patients: A pragmatic randomized controlled trial

Abstract

Objectives The feasibility of utilizing 4% sodium citrate as an alternative locking solution for central venous catheters (CVCs) (excluding dialysis catheters) was assessed. Methods Using heparin saline and 4% sodium citrate as locking solution, then 152 patients in ICU undergoing infusion with central venous catheters, were randomly assigned to receive either 10 U/mL heparin saline or 4% sodium citrate. The used outcome indicators include: four indexes of blood coagulation at 10 minutes after locking and 7 d after the first locking, bleeding around the puncture site and subcutaneous hematoma rate, gastrointestinal bleeding rate, catheter indwelling time, catheter occlusion rate, catheter-related bloodstream infection (CRBSI) rate, rate of ionized calcium < 1.0 mmol/L. The main outcome indicator was the activated partial thromboplastin time (APTT) at 10 min after tube locking. The trial was approved by relevant authorities (Chinese Clinical Trial Registry, no: ChiCTR2200056615, registered on February 9, 2022, http://www.chictr.org.cn; Ethics Committee of People’s Hospital of Zhongjiang County, no: JLS-2021-034, approved at May 10, 2021, and no: JLS-2022-027, approved at May 30, 2022). Results Among the main outcome measures, the heparin group showed a significant increase in APTT compared to the sodium citrate group at 10 min after locking (LSMD = 8.15, 95%Cl 7.1 to 9.2, P < 0.001). Among the secondary outcome measures, the heparin group demonstrated a significant increase in prothrombin time (PT) compared to the sodium citrate group at 10 minutes after locking (LSMD = 0.86, 95%CI 0.12 to 1.61, P = 0.024). It is found that APTT (LSMD = 8.05, 95%CI 6.71 to 9.4, P < 0.001), PT (LSMD = 0.78, 95%CI 0.14 to 1.42, P = 0.017) and fibrinogen (FB) (LSMD = 1.15, 95%CI 0.23 to 2.08, P = 0.014) at 7 d after locking are increased in the heparin group compared to sodium citrate group. There was no significant difference in catheter indwelling time between the two groups (P = 0.456). The incidence of catheter blockage was lower in sodium citrate group (RR = 0.36, 95%CI 0.15 to 0.87, P = 0.024). No CRBSI occurred in the two groups. Among the safety evaluation indexes, the incidence of bleeding around the puncture site and subcutaneous hematoma was lower in sodium citrate group (RR = 0.1, 95%CI 0.01 to 0.77, P = 0.027). There was no significant difference in the incidence of calcium ion < 1.0 mmol/L between the two groups (P = 0.333). Conclusions In ICU patients using CVCs (excluding dialysis catheters) infusion, employing 4% sodium citrate as a locking liquid can reduce the risk of bleeding and catheter occlusion without any hypocalcemia.