Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study

INTRODUCTION Liver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Ca(tot)/Ca(ion)) ratio ≥ 2.5, and to describe the feasibility of citrate CVVHD in liver failure patients. METHODS We conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run. RESULTS Accumulation of citrate in serum correlated with an increase in the Ca(tot)/Ca(ion) ratio. Although the critical upper threshold of Ca(tot)/Ca(ion) ratio ≥ 2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Ca(tot)/Ca(ion) ratio ≥ 2.5. In contrast, serum lactate ≥ 3.4 mmol/l and prothrombin time ≤ 26% predicted an increase in the Ca(tot)/Ca(ion) ratio ≥ 2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time). CONCLUSIONS Despite substantial accumulation of citrate in serum, CVVHD with regional citrate anticoagulation seems feasible in patients with severely impaired liver function. Citrate accumulation in serum is reflected by an increase in the Ca(tot)/Ca(ion) ratio. To identify patients at risk for citrate accumulation in terms of a Ca(tot)/Ca(ion) ratio ≥ 2.5, baseline serum lactate (threshold ≥ 3.4 mmol/l) and prothrombin time (threshold ≤ 26%) may be useful for risk prediction in daily clinical practice. Careful monitoring of electrolytes and acid-base status is mandatory to ensure patient safety.