The Relationship Between Acute-Phase Circuit Occlusion and Blood Calcium Concentration in an Ex Vivo Continuous Renal Replacement Therapy Model.

Background and objective Continuous renal replacement therapy (CRRT) is a blood purification therapy modality for the treatment of renal failure in critically ill hospitalized patients with multiorgan dysfunction, effectively preventing uremia and multiple organ failure while improving renal function. However, the perfusion of patient blood through extracorporeal circulation often results in unexpected early occlusion of the CRRT circuit or hemofilter, leading to frequent interruptions in CRRT and wastage of medical resources. Moreover, clinical research on such circuit occlusions is limited. In Japan, CRRT circuits require long-term perfusion, often lasting 24 hours or more, indicating the need for a model capable of inducing occlusion at any arbitrary time; this model can evaluate various aspects, including causes and underlying mechanisms, and contribute to the development of an occlusion prediction method. Hence, we hypothesized the need for a model for inducing occlusion at arbitrary time points. Consequently, we strove to develop an ex vivo circuit occlusion model involving the injection of calcium into circulating citrated animal blood to evaluate the relationship between the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time. Methods We developed a circuit occlusion model using a commercially available CRRT circuit, polysulfone membrane hemofilter, heating extension tube, and thermostatic water bath, along with commercially available citrated bovine whole blood. The circuit was filled with blood over a 10-min duration using a roller pump and was occluded after a specific period by varying the flow rate of calcium injected into bovine whole blood. Additionally, continuous injection of 1 mEq/mL calcium chloride into the circuit was maintained while bovine whole blood circulated. Measurements were performed at each calcium injection flow rate (2, 3, and 4 mL/h), with each measurement performed five times. The group that did not receive calcium injection was used as the control (0 mL/h: Con), and the experiment was performed three times. Groups were defined as "0, 2, 3, and 4" for each calcium injection flow rate. The relationship among the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time was evaluated. Furthermore, blood tests and blood viscoelastic tests were performed at arbitrary times. Results The circuit occlusion time varied with each calcium injection flow rate, and a significant difference was observed between each group (p<0.05). Circuit pressure gradually changed at four min before occlusion when calcium was injected at 2, 3, and 4 mL/h, with a more rapid change at one min before occlusion. We measured circuit pressure at four and one min before occlusion (-4 min, and -1 min, respectively), and at the time of circuit occlusion (0 min) in the Con and 4 mL/h groups. Significant differences were observed in AP between -4 min and 0 min and -1 min and 0 min at a calcium flow rate of 4 mL/h. Additionally, significant differences were seen in prefilter and return pressures between -4 min and 0 min, -4 min and -1 min, and -1 min and 0 min at a calcium flow rate of 4 mL/h (p<0.05). Conclusions Our proposed model accurately estimated the occlusion time based on changes in circuit pressure. This model can be used to create various experimental systems depending on the desired occlusion time.