This first systematic study on citrate pharmacokinetics and metabolism in critically ill patients confirms a major role of hepatic citrate metabolism by demonstrating reduced citrate clearance in cirrhotic patients. Pharmacokinetic data could provide a basis for the clinical use of citrate anticoagulation in critically ill patients. Provided dose adaptation and monitoring of ionized calcium, citrate anticoagulation seems feasible even in patients with decompensated cirrhosis. Metabolic consequences of citrate infusion were not different between groups in this study but may be more pronounced in prolonged infusion.

The removal of albumin bound substances has gained increasing interest in different diseases, especially in acute and chronic liver disease. Therefore, a new system, the fractionated plasma separation and adsorption (FPSA) system, was developed based on combined membrane and adsorbent blood purification techniques. The most important contribution to the FPSA system was the development of a new polysulfone hollow-fiber filter, which is characterized by a sieving coefficient of 0.89 for human serum albumin (HSA) but only of 0.17 for fibrinogen, and 0 (zero) for IgM immunoglobulins. Using a closed filtrate circuit connected to the new polysulfone filter which integrates 1 or 2 adsorption columns and also a high flux dialyzer adapted to a dialysis machine, the FPSA system opens excellent possibilities for the relatively specific removal of albumin bound substances from the blood such as albumin bound bilirubin or even tryptophan. In comparison to other systems (for example, the Molecular Adsorbent Recirculating System [MARS] and albumin dialysis systems), the FPSA system enables much higher elimination of strongly bound albumin substances. The first clinical investigations have recently started based on a modified dialysis machine designed with all necessary safety measures.

Alternative technologies for extracorporeal blood purification systems based on microadsorbents in suspension are discussed. Principally, microadsorbents offer higher efficiency and flexibility when compared to conventional column-based adsorption systems. Systems already clinically employed (e.g., BioLogic DT) or close to clinical application (e.g., the microspheres-based detoxification system, MDS) are described. The MDS technology, in particular, is characterized by efficiency and a high degree of flexibility with respect to both the use of different adsorbents as well as the combination with hemodialysis/hemofiltration therapy. It was designed for continuous use in intensive-care units, but enables also the removal of low-density lipoprotein, fibrinogen, autoimmune antibodies, immune complexes, and other pathophysiologically relevant substances. Alternative anticoagulation regimes and safety systems on fluorescence sensor technology have recently been developed for the MDS and are presented in this paper.

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