Automated regional citrate anticoagulation based on online monitoring of ionized calcium concentration: Proof of concept.

Abstract

Regional citrate anticoagulation (RCA), a complex and effective technique, is recommended as the anticoagulation of choice for continuous renal replacement therapy. One of its key objectives is to keep the ionized calcium in the targeted range. In this study, we aimed to develop an automated RCA based on online monitoring of the ionized calcium concentration and closed-loop feedback. We constructed calcium-selective electrodes with liquid inner contact, which measured a potentiometric signal as the output. We tested the responses, stability, and selectivity of the electrodes in flowing fluid containing calcium chloride. We compared the measurement accuracy between the electrodes and an i-STAT system in vivo. Moreover, we established closed-loop feedback using a proportional-integral-derivative controller model. We performed simulated automated RCA both in vivo and in vitro. The electrode gave a Nernstian response to the variation of ionized calcium concentration. It showed high stability and a relatively short response time. Changes in the fluid flow rate, solution PH, and addition of metal ions including Mg2+ and K+ did not interfere with the measurements of ionized calcium. These measurements in whole blood by the electrode were very close to those assessed by the i-STAT system. The feedback control system responded quickly to an abnormal ionized calcium concentration and regulated the infusion rates of calcium or citrate to maintain the concentration of ionized calcium within the targeted range. We successfully trialed automated RCA, which may help simplify the complexities of RCA in the future.