Effect of early adjunctive use of oral sildenafil and inhaled nitric oxide on the outcome of pulmonary hypertension in newborn infants. A feasibility study.

Introduction: Inhaled nitric oxide (iNO) is the standard therapy for infants with persistent pulmonary hypertension of the newborn (PPHN). Recently, sildenafil has been evaluated as an alternative or adjunctive pulmonary vasodilator.

Objective: To assess the effectiveness of adding sildenafil as an early adjunctive therapy together with iNO when treating newborns with PPHN and/or hypoxemic respiratory failure.

Methods: This is a randomized placebo trial on newborns with gestational age > 34 weeks, postnatal age < 48 hours, and diagnosed with PPHN (oxygen index (OI) ≥ 20). Newborns were randomized to two groups: Group A- received oral sildenafil and iNO, and group B- received placebo and iNO. Initial and follow up echocardiography were performed over 14 days period.

Results: A total of 24 newborns were recruited; 13 of them received sildenafil in addition to iNO and 11 received iNO and placebo. The most common causes of PPHN were meconium aspiration syndrome, pneumonia, and RDS. At the starting point, OI was marginally higher in the intervention group without statistical significance (29 vs 28). There were no differences between the two groups regarding surfactant administration, incidence of pneumothoraces, and the underlying causes of PPHN. Sildenafil or placebo treatment started within 12 hours after starting iNO (8 vs 6 hours).

Conclusion: Early use of oral sildenafil next to iNO in cases of PPHN was tolerated well by newborns and it did not show significant adverse effects. Further studies with a larger sample size is needed to assess its effecacy.