Optimizing Oxygen Exposure with an Intact Cord During Preterm Resuscitation Using an Asphyxiated Model

Background: Optimal oxygen use during preterm resuscitation remains controversial. Meta-analysis has shown that preemies who do not achieve a heart rate (HR) of ≥100 bpm & SpO2 of ≥80% are at increased risk of mortality. In asphyxiated preterm neonates, the effect of supplemental O2 and delayed cord clamping (DCC) on transitional hemodynamics is not known. We hypothesized that in an asphyxiated lamb model, DCC for 5min with high supplemental O2 (HOX) will increase the likelihood of the composite outcome of HR≥ 100 bpm & SpO2 ≥80% by 5min, and improve hemodynamics compared to early cord clamping (ECC) and/or low supplemental O2 (LOX).

Methods: We studied the effect of initiating resuscitation in an asphyxiated preterm lambs with DCC and high FiO2 (DCCHOX – start at 0.6) and titrate based on target SpO2 as recommended by ILCOR. Comparative groups included DCC with low FiO2 (DCCLOX – start at 0.3 and titrate) and early cord clamping with high and low FiO2 (ECCHOX and ECCLOX). The primary composite outcome was HR ≥100 bpm and SpO2 ≥80% by 5min, we intend to compare gas exchange, oxygen load and hemodynamics during the first 5 min. Preterm lambs (126 -127d) with surfactant deficiency were randomly assigned to DCCHOX, DCCLOX, ECCHOX, and ECCLOX. Asphyxia was induced by cord occlusion until HR <90 bpm. In the DCC group, the cord was intact for 5 min and supplemental FiO2 was initiated at 0.6 (HOX) or at 0.3 (LOX) and titrated based on SpO2 after 2 min. The titration of FiO2 was proportional to difference between observed SpO2 and target SpO2 and was performed every min. Oxygen load (OL) was calculated as the sum of [VT*FiO2]/kg, (VT=tidal volume) for all breaths for 5 min.

Results: Twenty-two lambs were randomized (ECCLOX–6, ECCHOX–5, DCCLOX–6, DCCHOX–5, fig 1). Compared to ECCLOX (0%), only 20% of ECCHOX (p=0.3) and 33% of DCCLOX (p=0.4) achieved the primary outcome. With DCCHOX, 80% achieved the primary outcome (p=0.02). DCCHOX had significantly higher SpO2 (fig 1), higher systolic pulmonary blood flow (Qp) (fig 1), lower PaCO2 (fig 2), and a lower surge in systolic carotid blood flow (fig 1). ECCLOX had higher PaO2 compared to DCCLOX (fig 2) but had higher OL compared to all other groups (fig 2). There was no difference in oxidized to reduced glutathione ratio (fig 2).

Conclusion: In asphyxiated preterm lambs, resuscitation with DCCHOX achieved target SpO2 and HR by 5 min with reduced OL, increased Qp without a surge in carotid flow, and improved ventilation. DCCHOX strategy combines the benefits of high FiO2 (increased Qp without high OL/PaO2) and placental transfusion (dual sources of gas exchange and cardiac preload leading to stable cerebral hemodynamics) and warrants clinical studies.