Citrate is predominantly metabolized in the hepatic citric acid cycle and clearance is almost independent of sellectchem renal function and urinary excretion [6,7]. Metabolism of citrate leads to the release of Caion into the systemic circulation. Citrate also contributes to the supply of alkaline plasma buffer bases, because 3 g bicarbonate are produced out of 1 g citrate [8,9]. In liver failure, citrate metabolism is impaired with the risk of citrate accumulation [10]. This impairment can result in a drop of Caion due to complex binding between citrate and Caion requiring more calcium chloride substitution at the venous line of the extracorporeal circuit. Finally, this binding leads to an increase in the concentration of total calcium (Catot), defined as the sum of Caion, protein, and citrate-bound calcium.

In consequence, an increase in the Catot/Caion ratio might be observed. A serum Catot/Caion ratio ��2.5 is assumed to be a critical threshold for the prediction of citrate accumulation [11]. In addition, metabolic acidosis with an enlarged anion gap due to reduced citric acid cycle production of bicarbonate out of citrate and accumulation of negative loaded citrate ions might be observed as a complication of CVVHD using citrate for regional anticoagulation [12].Considering these potential side effects, patients with overt hepatic impairment have been excluded in most of the previous studies on citrate anticoagulation. Consequently, data on the feasibility of citrate CVVHD in liver failure patients are scarce. The aim of our study was therefore to characterize predictors for citrate accumulation in terms of a Catot/Caion ratio ��2.

5 and to investigate the feasibility of citrate anticoagulation in patients with markedly impaired liver function. Secondary endpoints were the direct measurement of serum citrate levels and their correlation to Catot, Caion, the Catot/Caion ratio, pH, and anion gap as well as the evaluation of the time course of electrolytes and acid-base status during CVVHD treatment. Additionally, we analyzed the filter lifetime.Materials and methodsPatientsTwenty-eight ICU patients aged 18 to 75 years suffering from decompensated liver cirrhosis (25 patients) or acute liver failure (three patients) who required renal replacement therapy due to secondary acute renal failure were included in the study.

Forty-three CVVHD runs with a maximum of two runs per patient were performed in these 28 patients. Patients were consecutively enrolled between October 2009 and October 2011. The diagnosis of liver cirrhosis was confirmed either by histology and/or by ultrasound, computed tomography or magnetic resonance Carfilzomib tomography and typical clinical criteria such as ascites, hepatorenal syndrome or presence of esophageal varices. Presence of acute liver failure was defined as an abrupt loss of liver function without pre-existing liver disease.