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IntroductionRegional 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.MethodsThe 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.ResultsWe 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+.ConclusionsTaken 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+.

Aims Regional citrate-calcium anticoagulation is becoming more and more attractive for extracorporeal treatments in the clinical routine. Methods A prediction and simulation tool for the safe application of RCA during extracorporeal treatments was introduced. The model predicts the course of the ionized calcium level in the patient and the current anticoagulation status in the extracorporeal circuit based on the actual settings of the dialysis machine. Results The simulation tool delivers areas in which the blood and dialysate flow can be adjusted to reach the desired target values for RCA and predicts the time course of several parameters during treatment.

Background and Aims Extracorporeal cytokine removal may be desirable. We sought to assess extracorporeal blood purification (EBP) techniques for cytokine removal in experimental animal studies. Methods We conducted a targeted, systematic search and identified 17 articles. We analyzed cytokine clearance, sieving coefficient (SC), ultrafiltrate (UF) concentration, and percentage removal. As this review concerns technical appraisal of EBP techniques, we made no attempts to appraise the methodology of the studies included. Results are in descriptive terms only. Results Applying predicted clearance for 80 kg human, high volume hemofiltration (HVHF) techniques and plasmafiltration (PF) showed the highest rates of cytokine removal. High cutoff (HCO)/HF and PF techniques showed modest ability to clear cytokines using low to medium flows. Standard hemofiltration had little efficacy. At higher flows, HCO/HF achieved clearances between 30 and 70 ml/min for IL-6 and IL-10. There was essentially no removal of tumor necrosis factor (TNF)-alpha outside of PF. Conclusions Experimental animal studies indicate that HVHF (especially with HCO filters) and plasmafiltration have the potential to achieve appreciable IL-6 and IL-10 clearances. However, only PF can remove TNF-alpha reliably.

Introduction Lipopolysaccharides (LPS) are extremely strong stimulators of inflammatory reactions, act at very low concentrations, and are involved in the pathogenesis of sepsis and septic shock. Because of its toxicity, the efficient removal of endotoxin from patients’ blood is very important in clinical medicine. The purpose of this study was to determine the endotoxin adsorption capacities of commercial endotoxin adsorbers for endotoxin removal in buffer solution, protein solution, serum and heparinized plasma; some of these were also characterized in whole blood. The tested LPS adsorbers were Toraymyxin® PMX-20R, Alteco® LPS Adsorber, DEAE-Sepharose, Polymyxin B-Agarose, and EndoTrap® red. Methods The adsorber materials were tested in buffer and protein solutions spiked with fluorescently labeled LPS (100 ng/ml). Additionally, batch tests with LPS-spiked serum, heparinized plasma and whole blood were performed with an LPS concentration of 5 ng/ml. Additionally, the washing solutions of the two tested Polymyxin B (PMB)-based adsorbers were analyzed for PMB release to determine if the resulting LPS inactivation was caused by PMB leakage. Results The results show that DEAE-Sepharose was most effective in LPS adsorption. Of the other tested endotoxin removal materials, only the PMB-based adsorbers were able to reduce the LPS activity. However, we were able to show that the reduction in LPS activity was caused by desorbed PMB, which inactivates endotoxins. Conclusions None of the adsorbents that were tested in this study showed promising results for potential use in extracorporeal blood purification.

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.

Plasma sorption processes have so far been performed with filters and appropriate adsorption columns. In this paper, we introduce a newly developed plasma sorption system, which is based on the high adsorption capacity of microspheres in a recirculation system. The technology has been applied successfully in vitro to eliminate endotoxins, low density lipoproteins (LDL) and barbiturates from human plasma