A perioperative bivalirudin anticoagulation protocol for neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation

Introduction: There is little published data regarding bivalirudin anticoagulation for surgical neonates on extracorporeal membrane oxygenation (ECMO). This study described our perioperative anticoagulation protocol and evaluated the relationship of bivalirudin dose to activated partial thrombin time (aPTT) and thromboelastography reaction time (TEG-R) monitoring assays. Materials and methods: Neonates with congenital diaphragmatic hernia (CDH) on ECMO and single-agent bivalirudin anticoagulation at our institution from 2016 to 2018 were included. Bivalirudin infusion rates, laboratory results, transfusions, and clinical events during the initial (cannulation to repair) and postoperative (up to 60 h post-repair) periods were recorded. Results: Forty-two neonates met inclusion criteria. Bivalirudin was started at 0.16 mg/kg/h and titrated in 10–20% increments to target aPTT of 70–85 s and TEG-R of 9–12 min. All patients achieved target anticoagulation levels within the first 12 h on doses ranging from 0.12–0.36 mg/kg/h. Postoperatively, bivalirudin increased to median 0.16 (range 0.08–0.40), 0.22 (0.08–0.60), and 0.39 (0.08–0.80) mg/kg/h by 6, 24, and 60 h, respectively. On multivariable regression, no significant association of aPTT (p = 0.09) or TEG-R (p = 0.22) with bivalirudin dose was seen. Hemoglobin decrease ≥2 g/dL in 24 h occurred in 39%, but there were no reoperations, deaths, or circuit changes for thrombosis. Conclusions: This standardized perioperative bivalirudin protocol achieved target anticoagulation level quickly. Postoperative bleeding was managed without significant morbidity. Consistent dose-response relationships between bivalirudin and aPTT or TEG-R were not seen, but gradually increasing doses were needed to maintain therapeutic anticoagulation.