Neonatal and Postneonatal Pulmonary Hypertension

Abstract

During transition at birth with ventilation of the lungs, pulmonary vascular resistance (PVR) decreases from high fetal values, leading to an 8 to 10-fold increase in pulmonary blood flow (Qp). In some infants, this transition does not occur, resulting in pulmonary hypertension (PH). In infants, PH can present as: (a) primary PH in term neonates (idiopathic), (b) PH secondary to lung disease or hypoplasia in term infants, (c) acute PH in preterm infants with respiratory distress syndrome (RDS), (d) chronic PH with bronchopulmonary dysplasia (BPD) in preterm infants and (e) post-neonatal PH. A hemodynamically significant patent ductus arteriosus (PDA) can exacerbate PH in preterm infants due to increased Qp. Pulmonary vein stenosis (PVS) can complicate BPD with PH. Diagnosis of PH is based on clinical features, echocardiography and, in some intractable cases, cardiac catheterization. Therapy of PH includes oxygen, invasive or non-invasive ventilation, correction of acidosis, surfactant and selective and non-selective pulmonary vasodilators such as inhaled nitric oxide and sildenafil, respectively. Early closure of a hemodynamically significant PDA has the potential to limit pulmonary vascular remodeling associated with BPD and PH. The role of thiamine in pathogenesis of PH is also discussed with the recent increase in thiamine-responsive acute pulmonary hypertension in early infancy. Recognition and prompt therapy of PH can prevent right ventricular dysfunction, uncoupling and failure.

Controversies in neonatology: The efficacy of inhaled nitric oxide in preterm infants with persistent pulmonary hypertension

“…In our study, the median maximum dose for iNO was observed to be 20 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) among positive responders, compared to 40 in negative responders. Inhaled nitric oxide has a good safety profile used at 20ppm, while lower doses may be equally as effective as higher doses.…”

“…Preterm infants<28 weeks of gestation have 50-70% moderate-to-large ductal shunt that can increase pulmonary blood pressure and flow and decrease lung compliance stated as 72.7% in our study. On the other hand the presence of an open ductus can regulate extreme elevations in pulmonary arterial pressure as a pop-off valve (22,23).…”

Perinatal origins of bronchopulmonary dysplasia—deciphering normal and impaired lung development cell by cell

“…During the fetal development, gas exchange is provided by placenta and fetal pulmonary vascular resistance (PVR) is high. Perinatal transition is normally marked by a significant decrease in PVR, resulting in up to tenfold increase in pulmonary blood flow [ 93 – 95 ]. However, in some instances this change in vascular resistance does not occur, resulting in PH.…”

“…Late onset of PH in BPD patients (3–4 months of age) is now well described and justifies continuous screening for PH in premature infants with BPD [ 96 ]. Current therapies are based on the underlying pathophysiology of neonatal PH and include maintaining adequate oxygen saturation, correction of acidosis, surfactant therapy, and the use of pulmonary vasodilators, such as inhaled nitric oxide and sildenafil [ 94 , 95 ].…”

Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs

“…Persistent pulmonary hypertension of the newborn (PPHN) [ 7 ] is a disorder characterized by elevated pulmonary vascular resistance (PVR), extra-pulmonary right-to-left shunting and hypoxemia. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator approved by the Food and Drug Administration in term infants with PPHN and acts by increasing cGMP in pulmonary arterial smooth muscle cells (PASMC).…”