Continuous renal replacement therapy with regional citrate anticoagulation in patients with liver failure - A prospective observational study

Introduction: Regional citrate anticoagulation has been established as a safe alternative to heparin anticoagulation for continuous renal replacement therapy (CRRT). Since the metabolism of citrate is impaired in patients with liver failure it is unclear whether this therapeutic approach can be safely applied in this patient group as it may result in citrate intoxication with metabolic acidosis, decreased ionized calcium and increased total calcium. Methods: The study was designed as a prospective observational study. 24 critically ill patients (13 male, 11 female) with acute renal failure undergoing CRRT with regional citrate anticoagulation were included and assigned to two groups in accordance with their bilirubin levels either above or below 3 mg/dl. All patients were treated by continuous veno-venous hemodialysis (CVVHD) with a CRRT device designed for citrate anticoagulation (Multi Filtrate Fresenius Medical Care, Bad Homburg, Germany; using a high-flux filter (AV 1000S, Fresenius Medical Care) and a CVVHDF dose of 2 l/h. The filters were routinely replaced after 72 hours. 4% trisodium citrate solution was infused proximal to the extracorporeal circuit to obtain ionized calcium levels of 0.25 to 0.35 mmol/l for anticoagulation. Systemic calcium (0.1 molar) infusion was targeted to maintain systemic ionized calcium between 1.12 and 1.20 mmol/l. Calcium levels and blood gases were measured every 4 hours. Citrate therapy was discontinued when set goals for calcium levels and acid base metabolism could not be met, or total calcium exceeded 3 mmol/l. We compared the filter life span, parameters of acid base status, blood transfusion requirement, ionized systemic calcium, ionized calcium in the extracorporeal circuit (postfilter) and the demand of citrate and calcium in the two groups. Statistical analysis was performed using the Mann Whitney test. Results: The group with liver failure comprised 8 patients with a mean bilirubin level of 9.4 mg/dl, the other group of 17 patients with a mean bilirubin level of 0.7 mg/dl. A total of 98 filters were used in 60 episodes of therapy. In the group with liver failure, calcium demand increased in 3 cases, reflecting a problem with calcium metabolism while in the group with no liver failure, severe alkalosis with bicarbonate levels above 40 mmol/l occurred in one patient, necessitating termination of citrate therapy. No other complications occurred. The two groups showed no significant differences in the levels of ionized systemic calcium and calcium and citrate requirements. Although the ionized post-filter calcium levels differed significantly, the respective 95% confidence interval was well within the targeted range of 0.25 to 0.35 mg/dl, indicating that the difference was not relevant. Conclusion: With appropriate monitoring, regional citrate anticoagulation for CRRT is a safe treatment option, even in patients with liver failure.