Efficacy of High Frequency Oscillatory Ventilation and Co-Administered Inhaled Nitric Oxide and Intravenous Sildenafil in Treating Persistent Pulmonary Hypertension of Newborn in Congenital Diaphragmatic Hernia

Objective: To prospectively evaluate efficacy of co-administered intravenous sildenafil and inhaled nitric oxide (iNO) in treating severe persistent pulmonary hypertension of newborn (PPHN) in congenital diaphragmatic hernia (CDH) neonates on high frequency oscillatory ventilation (HFOV). Methods: Of 106-neonates, 41 with severe-PPHN on HFOV were treated with intravenous sildenafil and iNO (HSN). Twenty-nine with moderate- PPHN on conventional mechanical ventilation (CMV) and iNO (MNO), and 36 with no-PPHN on CMV and inotropes. Primary (60-days) outcomes analysed were survival, treatment failure, and adverse events. Secondary (60-days) outcomes were ventilation free days (VFD) at 60-days, neonatal intensive care unit free days (NICUFD) at 60-days. Variables are presented as true mean ± one standard deviation. Results: Survival in neonates on HSN was 76% versus 83% on MNO (p = 0.862). Overall survival was 80%. The treatment failure rate was 24% in neonates on HSN. In comparison treatment failure rates were 48% in MNO and 25% in CMV. Statistically, infants with adverse events were equivocal among the 3-groups. Infants treated preoperatively by HSN had less VFD at 60-days, 16 ± 9 versus 44 ± 21 MNO (p = 0.001). Few NICUFD at 60-days were observed in HSN 6 ± 5 versus 32 ± 15 MNO (p=0.001). Three-dimensional echocardiography revealed that biventricular dysfunction was the primary factor contributing to death in this cohort of CDH-neonates. Conclusions: Intravenous sildenafil and iNO achieved 76% survival in CDH-neonates with severe-PPHN on HFOV. Less VFD at 60-days and NICUFD at 60-days was observed in neonates treated with HSN.