Regional citrate anticoagulation for renal replacement therapy during venovenous ECMO: A randomized crossover pilot study

Background: Regional citrate anticoagulation (RCA) is suggested as the preferred anticoagulation strategy during continuous renal replacement therapy (CRRT), as it prolongs circuit lifespan while minimizing bleeding complications. However, evidence on its use in CRRT circuits during extracorporeal membrane oxygenation (ECMO) is limited. In patients receiving ECMO, systemic anticoagulation with unfractionated heparin (UFH) is routinely administered to maintain circuit patency and is often relied upon to anticoagulate the CRRT circuit, limiting the use of regional citrate anticoagulation. The aim of this study is to evaluate whether adding regional citrate anticoagulation (RCA) to systemic unfractionated heparin (UFH) reduces CRRT circuits clotting in patients undergoing venovenous extracorporeal membrane oxygenation (VV ECMO). Results: Patients were randomized to receive alternating CRRT circuits anticoagulated with either systemic UFH alone or regional citrate anticoagulation added to systemic UFH (RCA + UFH), according to a predefined crossover sequence. Each circuit was maintained for up to 72 h or until clotting occurred. Coagulation parameters, CRRT pressures, and thromboelastography (TEG) data were collected.A total of 66 CRRT circuits from 18 patients were analyzed (33 RCA + UFH; 33 UFH). No clotting events occurred in the RCA + UFH circuits, whereas 6 events were observed with UFH alone (0% vs 19%; p < 0.001). Cox proportional hazards analysis showed significantly longer circuit survival with RCA + UFH compared to UFH alone (p = 0.029). Platelet counts increased during RCA + UFH but declined during UFH alone (median change +6 vs -7 ×10³/μL; p < 0.001), with a significantly more favorable overall trend under RCA + UFH (effect estimate +13 × 10³/μL, 95% CI 8-19). D-dimer levels increased significantly during UFH alone, whereas a lower increase was observed with RCA + UFH (effect estimate -782 μg/L, 95% CI -1525 to -39).Thromboelastography performed at the circuit level showed significantly prolonged R-times with RCA + UFH compared with UFH alone (median R-time 90 vs. 30 min; p < 0.001). No clinically relevant RCA-related metabolic complications were observed, including no episodes of severe hypernatremia, metabolic alkalosis, or citrate accumulation. Conclusions: In patients undergoing VV ECMO, adding regional citrate anticoagulation to systemic unfractionated heparin reduced CRRT circuit clotting, prevented platelet consumption. This technique was feasible, safe, and may improve CRRT efficiency in this high-risk population. Clinical trial: ClinicalTrials.gov Identifier NCT05148026.