Pulmonary hypertension in bronchopulmonary dysplasia

Abstract

Pulmonary hypertension (PH) is a common complication of neonatal respiratory diseases including bronchopulmonary dysplasia (BPD), and recent studies have increased awareness that PH worsens the clinical course, morbidity and mortality of BPD. Recent evidence indicates that up to 18% of all extremely low birth weight infants will develop some degree of PH during their hospitalization, and the incidence rises to 25–40% of infants with established BPD. Risk factors are not yet well understood, but new evidence shows that fetal growth restriction is a significant predictor of PH. Echocardiography remains the primary method for evaluation for BPD-associated PH, and the development of standardized screening timelines and techniques for identification of infants with BPD-associated PH remains an important ongoing topic of investigation. The use of pulmonary vasodilator medications such as nitric oxide, sildenafil, and others in the BPD population is steadily growing, but additional studies are needed regarding their long-term safety and efficacy.

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

“…33 In addition, lack of an accepted algorithm for PH surveillance likely contributes to considerable heterogeneity in the diagnosis and assessment of PH among infants with BPD. 10,33 Although some authors suggest that PH should be confirmed with cardiac catheterization before initiating sildenafil therapy, .95% of our cohort did not undergo catheterization, suggesting that clinicians are relying on echocardiography in the diagnosis of PH. Because of the poor correlation between standard echocardiography and cardiac catheterization, 35 clinicians are left to balance the limitations of echocardiography with the risks associated with cardiac catheterization.…”

“…4 Inhaled nitric oxide (iNO) improves pulmonary artery pressures acutely during cardiac catheterization, 9 but the economic burden and cumbersome mode of administration of iNO limit its use in chronic treatment. 10 A pragmatic therapeutic option for patients with BPD-PH is oral sildenafil, a selective type 5 phosphodiesterase inhibitor. 11,12 In adults with PH, sildenafil has improved survival rates, exhibited low toxicity, and is available as an enteral preparation that is more practical for long-term, outpatient therapy.…”

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

“…In pulmonary hypertension associated with existing BPD, small retrospective case series have demonstrated benefit from sildenafil with regard to echocardiographic assessments of pulmonary hypertension [3,112,113], but not always associated with clinical improvement [112]. One retrospective study with long term follow up of 22 infants showed that sildenafil was well tolerated with long term improvement in pulmonary hypertension, although 20% of the study population died [114].…”

“…Affected infants have a poor prognosis with a mortality of 47% within two years following the diagnosis of pulmonary hypertension [2]. Between 25 and 40% of premature infants with BPD have concomitant pulmonary hypertension [3].…”

Sildenafil for pulmonary hypertension complicating bronchopulmonary dysplasia

“…Enteral sildenafil increased circulating cGMP and allowed two of three infants to wean without rebound PAH. Subsequently, the use of sildenafil has expanded to include primary PPHN secondary to meconium aspiration and congenital diaphragmatic hernia, pulmonary hypertension accompanying BPD and postoperative PAH, as well as other applications [9][10][11]. However, the evidence for use of sildenafil in treatment of PAH secondary to BPD is limited to one retrospective case series.…”