Sildenafil in Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia: Friend or Foe?

Introduction: Sildenafil is a phosphodiesterase-5 inhibitor used to treat pulmonary hypertension, although its efficiency remains disputed in the neonatal population. We aimed to assess the clinical use of this drug in extremely premature infants diagnosed with pulmonary hypertension associated to bronchopulmonary dysplasia.

Study design: This is a retrospective study of 18 patients born at ≤ 32 weeks gestational age with pulmonary hypertension complicating moderate to severe bronchopulmonary dysplasia, which was diagnosed on echocardiography at 36 weeks corrected gestational age. Median corrected gestational age at starting sildenafil was 48 weeks (range 32-60). In 4 cases there was a period of > 2 weeks between the evidence of moderate-severe pulmonary hypertension and starting sildenafil. In all other cases it was started as soon as the diagnosis was suspected or confirmed.

Results: All infants tolerated the use of sildenafil. However, 5 babies (26.31%) died despite ongoing intensive care, and 5 babies (26.31%) died after having care redirected due to severe chronic lung disease (1 due to co-existing neurological abnormality), with on overall mortality of this study of 52.62%. Eight babies (42.1%) survived: 5 continued on sildenafil until hospital discharge, 1 continued on transfer to the paediatric intensive care unit and 2 stopped while inpatients. Upon follow up to 2 years of age, out of the 5 patients who continued upon hospital discharge, 4 stopped at 6, 7, 12 and 18 months respectively, with 1 child being lost to follow up. Two patients (10.52%) restarted sildenafil use later in childhood. Echocardiographic evidence of improvement was noted in 58% (11 cases), with no improvement in 6 cases (32%) and incorrect original diagnosis in 1 case (5%). One infant died less than a week from the initiation of treatment.

Conclusion: sildenafil use showed no clinical improvement of pulmonary hypertension complicating moderate to severe bronchopulmonary dysplasia in extremely premature infants.