Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn

Abstract

Rapid evaluation of a neonate who is cyanotic and in respiratory distress is essential for achieving a good outcome. Persistent pulmonary hypertension of the newborn (PPHN) can be a primary cause or a contributing factor to respiratory failure, particularly in neonates born at 34 weeks or more of gestation. PPHN represents a failure of normal postnatal adaptation that occurs at birth in the pulmonary circulation. Rapid advances in therapy in recent years have led to a remarkable decrease in mortality for the affected infants. Infants who survive PPHN are at significant risk for long-term hearing and neurodevelopmental impairments, however. This review focuses on the diagnosis, recent advances in management, and recommendations for the long-term follow-up of infants who have PPHN.

Figures

Figure 1

The mechanism of endothelium-dependent pulmonary vasodilation at birth. NO and PGI2 are released in response to birth related stimuli. NO and PGI2 increase the cGMP and cAMP levels in the smooth muscle cell. Type 5 and Type 3 phosphodiesterases (PDE) degrade these cyclic nucleotides. A decrease in intra-cellular Ca2+ levels leads to relaxation of vascular smooth muscle. NO levels are decreased by asymmetric dimethyl arginine (ADMA), superoxide (O2−) and endothelin (ET-1). Non steroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase (COX). PGIS=PGI2 synthase. (Adapted from Figure 1, Berger S & Konduri GG: Pulmonary hypertension in children. Pediatr Clin North Am 2006; 53:961-987).

Figure 2

Lung diseases associated with PPHN in 299 infants enrolled in the early inhaled nitric oxide study in term and near term neonates (6). Meconium aspiration syndrome (MAS) was the most frequent diagnosis, followed by primary PPHN, respiratory distress syndrome (RDS) and pneumonia and/or sepsis. Infants with congenital diaphragmatic hernia were excluded from this study.

Figure 3

Chest X-ray obtained in an infant with primary PPHN on the left (A) shows absence of parenchymal lung disease. Chest X-ray on the right (B) was obtained in an infant with suspected RDS who did not improve with surfactant therapy. Echocardiography demonstrated total anomalous pulmonary venous return to inferior vena cava.

Figure 4

Effect of inhaled NO on the pulmonary circulation. Inhaled NO reaches healthy alveoli, shown on the left and diffuses to the adjacent pulmonary arteries to cause vasodilation. As NO reaches the lumen of pulmonary artery, it is inactivated by hemoglobin (Hb) limiting its effect to the pulmonary circulation. NO does not reach the atelectatic alveoli shown to the right, maintaining constriction of the adjacent pulmonary arteries. Increased perfusion of the ventilated segments of the lung improves VQ match and oxygenation in parenchymal lung disease.

Figure 5

Relationship of the severity of respiratory failure, defined by oxygenation index (OI) at the time of initiation of inhaled NO therapy and the ECMO rates observed in these babies. Data are from six randomized trials in term/near term neonates for babies assigned to the iNO arm in these trials (, , , , & 89). The trials are labeled by first author and are shown in the order of highest to lowest OI. NINOS=neonatal inhaled nitric oxide study group. The ECMO rate correlates with the severity of respiratory failure at the time of iNO initiation.