47 - Persistent Pulmonary Hypertension

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) represents the failure of the pulmonary circulation to undergo the normal fall in pulmonary vascular resistance (PVR) at birth in order to accommodate the marked rise in pulmonary blood flow that enables the successful transition to postnatal life. PPHN is characterized by severe hypoxemia secondary to sustained elevation of PVR resulting in right-to-left extrapulmonary shunting of deoxygenated blood. PPHN is associated with diverse cardiopulmonary disorders and high early mortality rate for infants with severe disease, especially in the setting of genetic causes of developmental lung disease. Surviving infants with PPHN have an increased risk of long-term comorbidities. PPHN physiology can be categorized by (1) maladaptation: pulmonary vessels have normal structure and number but have abnormal vasoreactivity; (2) excessive muscularization: increased smooth muscle cell thickness and increased distal extension of muscle to vessels that are usually not muscularized; and (3) underdevelopment: lung hypoplasia associated with decreased pulmonary artery number. Treatment involves adequate lung recruitment, optimization of cardiac output and left ventricular function, and pulmonary vasodilators such as inhaled nitric oxide. Infants who fail to respond to conventional therapy should be evaluated for lethal genetic lung disorders, including alveolar capillary dysplasia (ACD), TBX4, TTF-1, ABCA3, surfactant protein diseases, and others.