Reducing Bleeding Complications in Neonates After CDH Repair on ECMO

Research study background

Neonates with severe congenital diaphragmatic hernia (CDH) almost always require extracorporeal membrane oxygenation (ECMO) support. However, undergoing CDH repair while on ECMO significantly increases the risk of postoperative bleeding complications, which carry a high mortality rate.

Prior to 2019, heparin was the standard anticoagulant at Children’s Hospital Colorado for neonates with CDH on ECMO. However, its longer half-life and variable pharmacokinetics limited its safety in critically ill surgical neonates. Bivalirudin, a direct thrombin inhibitor with a shorter half-life and more predictable, adjustable dosing, has since emerged as a promising off-label alternative. In 2019, Children’s Colorado began transitioning from heparin to bivalirudin for neonatal ECMO following CDH repair. By 2021, bivalirudin was exclusively used for these patients.

In this retrospective study, neonatology and pediatric surgery experts Chris Derderian, MD, Jason Gein, MD and Caroline Credille, CPNP-AC compared heparin and bivalirudin for bleeding complications after CDH repair on ECMO to determine how often patients required a reoperation. They also analyzed intracranial hemorrhage (ICH) incidence, ECMO circuit changes, blood transfusion volume, ECMO duration and survival to discharge. For the study, severe CDH was defined as a prenatal observed-to-expected lung-to-head ratio of less than 25% and/or percent predicted lung volume less than 15%.

A review of data on 62 neonates who underwent CDH repair at Children’s Colorado between 2008 and 2023 found that 44 neonates received heparin after surgical repair and 18 received bivalirudin. Of those on bivalirudin, eight were initially managed with heparin during ECMO until repair. Neither group experienced a bleeding event leading up to repair. After surgery, 17 neonates in the heparin group and one in the bivalirudin group experienced bleeding and required a reoperation. Additionally, ICH was diagnosed in four neonates in the heparin group, but none in the bivalirudin group. Cardiopulmonary arrest was the leading cause of death in the heparin group, while intractable pulmonary hypertension accounted for the most deaths in the bivalirudin group.

Compared to the heparin group, neonates in the bivalirudin group required about half the total blood product volume while on ECMO. The bivalirudin group also had a significantly shorter time from ECMO cannulation to CDH repair, reflecting changes in the anticoagulation strategy and CDH repair timing management approach at Children’s Colorado. There were no deaths from postoperative bleeding, thrombosis or hemorrhage in the bivalirudin group. Yet, the benefits observed from bivalirudin did not result in better outcomes; IHC hemorrhage rates, circuit changes, ECMO duration or overall survival were similar among both groups. Study authors noted this is likely due to the small bivalirudin cohort.

Relevance to future research

This study, while limited, is among the first to show that bivalirudin reduces bleeding complications in these neonates compared to heparin, aligning with its known benefits in ECMO, and several centers around the country are beginning to replicate this analysis at their institutions. These findings highlight bivalirudin’s potential to improve bleeding and thrombosis management in neonates with severe CDH on ECMO, but further large-scale studies comparing the two anticoagulants are needed. The team is also evaluating which ECMO circuits work best with bivalirudin to determine if this approach could expand to other pediatric populations.