Karin Strobl

A Target-Orientated Algorithm for Regional Citrate-Calcium Anticoagulation in Extracorporeal Therapies

Background: Citrate anticoagulation offers several advantages in comparison to conventional anticoagulation. Most algorithms for regional citrate-calcium anticoagulation are based on citrate and calcium chloride infusion coupled in a fixed proportion to the blood flow without considering the hematocrit (Hct)/plasma flow or the filter clearance of citrate and calcium. Methods: The aim of this study was to develop an algorithm for optimized citrate anticoagulation in extracorporeal therapies such as dialysis. A mathematical model was developed to calculate the volume of citrate infusion required to achieve a desired ionized calcium (iCa) target level in the extracorporeal circuit and to restore the total calcium level to a physiological value. Results: The model was validated by correlation analyses for different blood Hct values and shows an excellent fit to the laboratory measurements. Conclusion: The results for both iCa target concentrations, namely those after citrate and calcium infusion, proved that the software algorithm adapts well to variable treatment parameters.

A target-oriented algorithm for citrate-calcium anticoagulation in clinical practice.

Background/Aims: Because of a high monitoring demand and an ensuing need for automation of regional citrate anticoagulation (RCA), a new semi-automated target-oriented algorithm was developed. The aim of this study was the evaluation of its functionality and safety. Methods: Fourteen haemodialysis patients were treated 5 times consecutively with RCA. Samples were drawn pre- and post-infusion once per hour. Electrolytes, blood cell counts, acid-base and coagulation parameters were analyzed. Results: Mean ionized calcium (Ca2+) values pre-filter were 0.23 and 0.33 mmol/l in the 0.2 and 0.3 mmol/l target groups, respectively. Extraction ratios for citrate and total calcium through the dialysis filter were constant during the entire treatment (83 and 68%, respectively). Citrate accumulation was avoided. Conclusion: The new algorithm enables safe and accurate RCA. By regulating Ca2+ pre-filter using the target-oriented algorithm, the degree of anticoagulation may be easily controlled.

In vitro investigations of citrate clearance with different dialysis filters.

Objective: In extracorporeal blood purification, citrate anticoagulation offers several substantial advantages over conventional heparin anticoagulation. However, there is still a lack of information on citrate kinetics, especially on the citrate clearance of conventional hemodialyzers. The aim of this study was to investigate the citrate clearance for different hemodialysis filters as a basis for the development of an intelligent citrate-calcium infusion algorithm. Materials and Methods: For our experiments, the Fresenius 4008H dialysis machine and the dialysis filters FX 60, F6 HPS, F8 HPS (Fresenius Medical Care, Bad Homburg, Germany), Polyflux 140H and 14L (Gambro Holding, Stockholm, Sweden), Xenium 130 (Baxter AG, Vienna, Austria) and APS-650 (ASAHI Kasei Kuraray Medical, Chiyoda-ku, Japan) were used. Clearance calculations were performed based on plasma/blood flow rate and the citrate concentrations at filter inlet and outlet. All experiments were carried out in vitro with fresh frozen plasma (FFP) or whole blood. Results: The results prove that citrate clearance is significantly higher with high-flux filters than with low-flux filters. Higher dialysate flow rates cause a more effective removal of citrate. The citrate clearance for low-flux and high-flux filters was 71 ± 7 and 86 ± 1% of the urea clearance, respectively. Conclusions: Citrate can efficiently be removed with standard hemodialysis. However, depending on the infused amounts as well as on the patient - especially in patients with impaired liver function - the use of a high-flux dialysis filter and a high dialysate flow rate should be considered to minimize the risk of citrate accumulation.

The role of ionized calcium and magnesium in regional citrate anticoagulation and its impact on inflammatory parameters

Introduction Regional anticoagulation with citrate has been found to be superior to heparin in terms of biocompatibility, and numerous protocols for regional citrate anticoagulation have been published, while a consensus on the target concentration of ionized calcium (Ca2+) in the extracorporeal circuit has not been reached so far. Methods The aim of this in vitro study was to assess the impact of different citrate concentrations on coagulation as well as on complement activation and cytokine secretion and to investigate the impact of ionized magnesium (Mg2+) on these parameters. Results We found that citrate effectively reduced coagulation, complement activation, and cytokine secretion in a dose-dependent manner and that a target Ca2+ concentration of 0.2–0.25 mM was required for efficient anticoagulation. Mg2+ triggered complement activation as well as interleukin (IL)-1β secretion in lipopolysaccharide (LPS)-stimulated whole blood in a dose-dependent manner and independently of Ca2+. Additionally, it was found to reduce activated clotting time (ACT) in samples with low Ca2+ levels, but not at physiological Ca2+. Conclusions Taken together, our data support the notion that regional citrate anticoagulation results in decreased release of inflammatory mediators in the extracorporeal circuit, requiring the depletion of both, Ca2+ and Mg2+.

Influence of citrate concentration on the activation of blood cells in an in vitro dialysis setup

Background Regional citrate anticoagulation has been associated with enhanced biocompatibility in hemodialysis, but the optimal dose of citrate remains to be established. Here, we compared parameters related to cellular activation during in vitro dialysis, using two doses of citrate. Methods Human whole blood, anticoagulated with either 3 mM or 4 mM of citrate, was recirculated in an in vitro miniaturized dialysis setup. Complement (C3a-desArg), soluble platelet factor 4 (PF4), thromboxane B2 (TXB2), myeloperoxidase (MPO), as well as platelet- and red blood cell-derived extracellular vesicles (EV) were quantified during recirculation. Dialyzer fibers were examined by scanning electron microscopy after recirculation to assess the activation of clotting and the deposition of blood cells. Results Increases in markers of platelet and leukocyte activation, PF4, TXB2, and MPO were comparable between both citrate groups. Complement activation tended to be lower at higher citrate concentration, but the difference between the two citrate groups did not reach significance. A strong increase in EVs, particularly platelet-derived EVs, was observed during in vitro dialysis for both citrate groups, which was significantly less pronounced in the high citrate group at the end of the experiment. Assessment of dialyzer clotting scores after analysis of individual fibers by scanning electron microscopy revealed significantly lower scores in the high citrate group. Conclusions Our data indicate that an increase in the citrate concentration from 3 mM to 4 mM further dampens cellular activation, thereby improving biocompatibility. A concentration of 4 mM citrate might therefore be optimal for use in clinical practice.