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Efficacy of Inhaled Nitric Oxide and Intragastric Sildenafil in Treatment of Persistent Pulmonary Hypertension of Newborn (PPHN) on High Frequency Oscillatory Ventilation (HFOV)

Rajiv Parapurath*, Madan Samuel

Background: Optimizing management of Persistent Pulmonary Hypertension of Newborn (PPHN) continues following availability of oral and intravenous Phosphodiesterase-V inhibitors. Study queried whether High Frequency Oscillatory Ventilation (HFOV) coupled with pulmonary vasodilators improves outcomes in neonates with severe- PPHN.

Objective: To prospectively evaluate efficacy of inhaled Nitric Oxide (iNO) and intra Gastric Sildenafil (iGS) in neonates with severe-PPHN on HFOV and exogenous surfactant.

Methods: Eighty-four consecutive neonates with severe-PPHN on HFOV and exogenous surfactant were treated with iNO (n=40) or iGS (n=44). Primary (28 days) outcomes analysed were adverse events, failure rate and mortality. Secondary (24 months) outcomes were neurological impairment, sensorineural deafness and chronic lung disease. At age 2 years neurodevelopmental evaluation by Bayley Scales of Infant and Toddler Development (Bayley-III^UK) was performed.

Results: Adverse events (44%) occurred in iNO-(30%) versus (57%)-iGS (p=0.030). Failure rate (14%) was seen in iNO-0% versus 27%-iGS (p=0.001). Mortality rate (4%) was iNO-8% versus 0%-iGS (p=0.001). Neurological impairment (19%) ensued in iNO-32% versus 7%-iGS (p=0.001). Sensorineural deafness (4%) happened in iNO- 5% versus 2%-iGS (p=0.04). Chronic lung disease (5%) was observed in iNO-8% versus 2%-iGS (p=0.02). Normal neurological outcome occurred in 81%, iNO-68% versus 93%-iGS (p=0.010). Bayley-IIIUK scores at age 2-years were normal (108-116) in 81%, mild impairment (71-75) ensued in 10% and moderate to severe delay (57-62) occurred in 9%.

Conclusion: Intra-gastric sildenafil was as efficacious as inhaled nitric oxide in treating severe-PPHN in neonates on HFOV and exogenous surfactant. In 81% of children at age 2-years normal neurodevelopment followed, irrespective of adjuvant treatment modalities.