Background – Optimal oxygenation of preterm infants during resuscitation continues to be controversial. Meta-analysis has shown that preterm infants who do not achieve a SpO2 of ≥80% and a heart rate (HR) of ≥100 bpm are at increased risk of mortality. Translational and clinical studies demonstrate improvement in HR and SpO2 following ventilation with an intact cord. In asphyxiated preterm neonates, the combined effect of supplemental O2 and deferred cord clamping (DCC) on transitional hemodynamics is not known. We hypothesized that in asphyxiated preterm lambs, DCC for 5 min combined with high supplemental O2 (HOX) will increase the likelihood of composite outcome of HR≥ 100 bpm and SpO2 ≥80% by 5min and stabilize carotid and pulmonary blood flows compared to early cord clamping (ECC) and/or low supplemental O2 (LOX). Currently the International Liaison Committee on Resuscitation (ILCOR) recommends ECC with LOX (0.3 initial FiO2) for preterm infants.
Objective – 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.
Methods - 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, table 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 peak pulmonary blood flow (Qp) (fig 2), lower PaCO2 (fig 3), and a lower surge in peak carotid blood flow (fig 4). ECCLOX had higher PaO2 compared to DCCLOX (fig 5) but had higher OL compared to all other groups (fig 6).
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.
