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Regional citrate anticoagulation has emerged as a promising method in critically ill patients at high risk of bleeding. However, in patients with liver failure, citrate accumulation may lead to acid-base and electrolyte imbalances, notably of calcium. The aim of this study was to evaluate the feasibility and safety of regional citrate anticoagulation during liver support using a molecular adsorbent recirculating system as well as its effects on electrolyte and acid-base balance in patients with liver failure.Prospective observational study.University hospital.Twenty critically ill patients supported by molecular adsorbent recirculating system resulting from liver failure between January 2007 and May 2009.The median duration of molecular adsorbent recirculating system treatment was 20 hrs (interquartile range, 18−22 hrs). Two of 77 molecular adsorbent recirculating system treatments (2%) were prematurely discontinued as a result of filter clotting and bleeding, respectively. The median citrate infusion rate, necessary to maintain the postfilter ionized calcium between 0.2 and 0.4 mmol/L, was 3.1 mmol/L (interquartile range, 2.3–4 mmol/L) blood flow. The median calcium chloride substitution rate was 0.9 mmol/L (0.3–1.7 mmol/L) dialysate. Total serum calcium remained stable during molecular adsorbent recirculating system treatments. There was a statistically significant increase of the ratio of total calcium to systemic ionized calcium (2.04 ± 0.32 mmol/L to 2.17 ± 0.35; p = .01), which reflected citrate accumulation resulting from liver failure. Under close monitoring, no clinically relevant electrolytes or acid-base disorders were observed.Our results suggest that regional citrate anticoagulation is a safe and feasible method to maintain adequate circuit lifespan without increasing the risk of hemorrhagic complications while maintaining a normal acid-base as well as electrolyte balance in patients with liver failure supported by molecular adsorbent recirculating system.