Written informed consent was acquired from the patient or his legal representative.Patients and randomizationAdult critically ill patients with acute renal failure requiring CVVH were eligible for inclusion. Exclusion criteria were (recent) bleeding or a suspicion of bleeding necessitating transfusion, selleck chemicals llc need of therapeutic anticoagulation or (suspected) heparin-induced thrombocytopenia. CVVH was initiated when, after resuscitation of the circulation, oliguria persisted and was accompanied by a steep rise in serum creatinine, or at a non-declining rise in creatinine in non-oliguric patients. Randomization was computer-based. When inclusion and exclusion criteria were checked in the patient data management system (MetaVision?, IMDSoft, Tel Aviv, Israel), the system automatically randomized the patients.

Study protocolPatients were randomized to one of two groups. In group 1, postdilutional CVVH was initiated at a filtrate flow of 4 L/h (blood flow 220 ml/min), which was converted to 2 L/h (blood flow 150 ml/min) after 60 minutes. In group 2, postdilutional CVVH was initiated at a filtrate flow of 2 L/h and converted to 4 L/h after 60 minutes. The cross-over design was chosen to detect differences in plasma and ultrafiltrate anti-Xa activity in case of elimination of anti-Xa activity by filtration. The 4 L/h dose is our default starting dose in the unit, which is normally reduced to 2 L/h if uremic toxins are low and circulation has stabilized.We used a 1.9 m2 cellulose triacetate hollow fiber membrane (UF 205, Nipro, Osaka, Japan), bicarbonate buffered replacement fluids heated to 39��C, and the Aquarius device (Edwards LifeSciences, S.

A., Saint-Prex, Switzerland). Nadroparin (Sanofi-Synthelabo, Maassluis, the Netherlands) was added to the one-liter priming solution (2850 IU). Patients received an intravenous bolus of 2850 IU nadroparin at initiation of CVVH, or 3800 IU when body weight exceeded 100 kg, followed by a continuous infusion in the extracorporeal circuit before the filter of 380 or 456 IU/h, respectively.After baseline sampling of arterial blood, samples of ultrafiltrate, arterial blood and postfilter blood were taken one hour after the start of CVVH, and at 15 minutes, 6 hours, 12 hours and 24 hours after the conversion from 4 to 2 L/h or from 2 to 4 L/h to measure antithrombin (at baseline only), anti-Xa activity, PTT, aPTT, platelet count, ETP, prothrombin fragments 1 and 2 (F1+2), thrombin-antithrombin complexes (TAT) and D-dimers.

Postfilter samples were taken directly after the filter, before infusion of the replacement fluid. Results of postfilter measurements are actual values, not corrected for hemoconcentration, unless indicated differently. Circuits were disconnected Entinostat at high prefilter or transmembrane pressure (both more than 300 mmHg), if vascular access failed, routinely after 72 hours or for clinical reasons (renal recovery, transport).