Regional Citrate Anticoagulation versus No Anticoagulation for CKRT in Patients with Liver Failure with Increased Bleeding Risk

Abstract

Background The opinions on the efficacy and safety of no anticoagulation versus regional citrate anticoagulation for continuous KRT (CKRT) were controversial in patients with severe liver failure with a higher bleeding risk. We performed a randomized controlled trial to assess no anticoagulation versus regional citrate anticoagulation for CKRT in these patients. Methods Adult patients with liver failure with a higher bleeding risk who required CKRT were considered candidates. The included participants were randomized to receive regional citrate anticoagulation or no-anticoagulation CKRT. The primary end point was filter failure. Results Of the included participants, 44 and 45 were randomized to receive regional citrate anticoagulation and no-anticoagulation CKRT, respectively. The no-anticoagulation group had a significantly higher filter failure rate (25 [56%] versus 12 [27%], P = 0.003), which was confirmed by cumulative incidence function analysis and sensitive analysis including only the first CKRT sessions. In the cumulative incidence function analysis, the cumulative filter failure rates at 24, 48, and 72 hours of the no-anticoagulation and regional citrate anticoagulation groups were 31%, 58%, and 76% and 11%, 23%, and 35%, respectively. Participants in the regional citrate anticoagulation group had significantly higher incidences of Ca2+ tot/Ca2+ ion >2.5 (7% versus 57%, P < 0.001), hypocalcemia (51% versus 82%, P = 0.002), and severe hypocalcemia (13% versus 77%, P < 0.001). However, most (73%) of the increased Ca2+ tot/Ca2+ ion ratios were normalized after the upregulation of the calcium substitution rate. In the regional citrate anticoagulation group, there was no significant additional increase in the systemic citrate concentration after 6 hours. Conclusions For patients with liver failure with a higher bleeding risk who required CKRT, regional citrate anticoagulation resulted in significantly longer filter lifespan than no anticoagulation. However, regional citrate anticoagulation in patients with liver failure was associated with a significantly higher risk of hypocalcemia, severe hypocalcemia, and Ca2+ tot/Ca2+ ion >2.5. Clinical Trial registry name and registration number RCA for CRRT in Liver Failure and High Risk Bleeding Patients, NCT03791190.