Effect of bosentan therapy in persistent pulmonary hypertension of the newborn.

Background: Persistent pulmonary hypertension of the newborn (PPHN) contributes to neonatal hypoxemia and is associated with a high mortality. Some PPHN patients are unresponsive to inhaled nitric oxide (iNO). Bosentan, an oral endothelin-1 receptor antagonist, reduces pulmonary vascular resistance and hence may play a role in the treatment of PPHN.

Methods: A retrospective medical records review was performed in newborns who received oral bosentan as an adjunctive therapy for treatment of PPHN between January 2013 and February 2016 at the neonatal intensive care unit of Songklanagarind Hospital. The main outcomes were the effect of bosentan on oxygenation and hemodynamic status after commencement of treatment and the safety of bosentan.

Results: Forty neonates at a median (IQR) gestation of 38 (36.8-40) weeks and an initial median (IQR) oxygen index (OI) of 29.2 (13.4-40.1) received bosentan therapy. Oral bosentan was commenced at a median (IQR) age of 27 (14.5-40.2) hours and the mean (SD) duration of treatment was 6.2 (3.1) days. The OI, alveolar-arterial oxygen difference (AaDO) and oxygen saturation (SpO) improved significantly at 2 h after treatment (p = 0.002, p = 0.01 and p < 0.001, respectively). In 21 (52.5%) neonates who received iNO and bosentan, the median OI (IQR) was 34.2 (29.0-42.6) with a significant decrease of OI at 6 h (p = 0.005) after treatment. In 19 (47.5%) neonates who received bosentan alone, the median OI (IQR) was 13.0 (9.8-30.9) with a significant decrease of OI in 2 h (p = 0.01) after treatment. The blood pressures before and after bosentan treatment were not statistically significantly different. The mortality rate was 12.5% (5/40).

Conclusion: Oral bosentan may be a safe and effective treatment to improve oxygenation in neonates with PPHN. Bosentan can be used as an adjuvant therapy with iNO and can be an alternative therapy option in mild-to-moderate PPHN.