Background/Aims: Cytokines are among the main target substances that have to be removed effectively in order to improve the patient’s health status in the treatment of sepsis, septic shock, and liver diseases. Although there are various medical devices commercially available, the success of their clinical use is limited. The aim of this in vitro study was to compare 3 different medical devices with respect to their clearance for the cytokines interleukin-6 (IL-6), IL-8, IL-1β, and tumor necrosis factor alpha. The medical devices that were tested are the whole blood adsorbent CytoSorb, the high cutoff filter EMiC2, and the hemofilter HemofeelCH 1.8. Methods: The study was carried out on the multiFiltrate machine with 1 L human plasma for 8 h. Samples for cytokine quantification were taken at defined time points from the plasma pool. Each experiment was conducted in triplicates, and clearance was calculated for all tested cytokines. Results: All 3 medical devices showed good cytokine removal. The highest clearance for all cytokines was achieved by hemoperfusion with Cytosorb. IL-8 and IL-6 clearance were higher with Hemofeel (continuous venovenous hemodiafiltration) than with EMiC2 (continuous venovenous hemodialysis) because the polymethyl methacrylate (PMMA)-based membrane Hemofeel is able to remove these 2 cytokines by adsorption. Protein and albumin loss was highest withCytosorb and lowest with EMiC2. Conclusion: The mechanisms of cytokine removal by blood purification include convection, diffusion, and adsorption. PMMA-based filters are able to combine all 3 mechanisms for certain cytokines. Cytosorb showed the best adsorption kinetics, while dialysis with polystyrene-based membranes offers the best biocompatibility because they do not show any unspecific adsorption of other plasma components.

Purpose: Extracorporeal blood purification systems based on combined membrane/adsorption technologies are used in acute liver failure to replace detoxification as well as to remove inflammatory mediators in sepsis patients. In addition to coating and chemical modification of the surface, pore size significantly controls the selectivity of adsorption materials. Methods: This study addresses the adsorption of albumin bound liver toxins, cytokines, and representative plasma compounds on three adsorbents which differ only in pore size distribution. All three adsorbents are based on hydrophobic poly(styrene-divinylbenzene) copolymer matrices and have mean pore sizes of 15, 30, and 100 nm. Results: The pores of adsorbents act as molecular sieves and prevent the entry of molecules that are larger than their molecular cut-off. The results of this study reveal that adsorbents based on styrene-divinylbenzene polymers with 15 nm pores are suitable for cytokine removal, and the same adsorbents with 30-40 nm pores are the best choice for the removal of albumin-bound toxins in the case of liver failure. Adsorbents with very large pores lack selectivity which leads to uncontrolled adsorption of all plasma proteins. Therefore, hydrophobic adsorbents with large pores offer inadequate plasma compatibility and do not fulfill the requirements for blood purification. Conclusions: Biocompatibility and efficiency of adsorbents used for blood purification can improved by fine tuning of adsorbent surface pore distributions.

Acylation of antimicrobial peptides mimics the structure of the natural lipopeptide polymyxin B, and increases antimicrobial and endotoxin-neutralizing activities. In this study, the antimicrobial properties of lactoferrin-based LF11 peptides as well as blood compatibility as a function of acyl chain length were investigated. Beyond the classical hemolysis test, the biocompatibility was determined with human leukocytes and platelets, and the influence of antimicrobial peptides (AMPs) on the plasmatic coagulation and the complement system was investigated. The results of this study show that the acylation of cationic peptides significantly reduces blood tolerance. With increasing acyl chain length, the cytotoxicity of LF11 peptides to human blood cells also increased. This study also shows that acylated cationic antimicrobial peptides are inactivated by the presence of heparin. In addition, it could be shown that the immobilization of LF11 peptides leads to a loss of their antimicrobial properties.

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.

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.