Pediatr Drugs 2006; 8 (3): 179-188 REVIEW ARTICLE 1174-5878/06/0003-0179/$39.95/0  2006 Adis Data Information BV. All rights reserved. Persistent Pulmonary Hypertension of the Newborn Pathogenesis, Etiology, and Management Enrique M. Ostrea Jr, 1,2 Esterlita T. Villanueva-Uy, 3,4,5 Girija Natarajan 6 and Herbert G. Uy 3,5 1 Wayne State University, Detroit, Michigan, USA 2 Hutzel Women’s Hospital and Children’s Hospital of Michigan, Detroit, Michigan, USA 3 Philippine General Hospital, Manila, Philippines 4 University of the Philippines National Institutes of Health, Manila, Philippines 5 University of the Philippines College of Medicine, Manila, Philippines 6 Wayne State University Neonatology Program, Detroit, Michigan, USA Contents Abstract ............................................................................................................... 179 1. Pathogenesis ....................................................................................................... 180 2. Etiology ............................................................................................................ 180 3. Diagnosis ........................................................................................................... 181 4. Treatment .......................................................................................................... 182 4.1 Surfactant Therapy .............................................................................................. 182 4.2 Mechanical Ventilation .......................................................................................... 182 4.3 Pulmonary Vasodilators .......................................................................................... 183 4.4 Phosphodiesterase Inhibitors ..................................................................................... 184 4.5 Nitric Oxide .................................................................................................... 184 4.6 Extracorporeal Membrane Oxygenation .......................................................................... 185 5. Conclusion ......................................................................................................... 185 Persistent pulmonary hypertension of the newborn (PPHN) is characterized by severe hypoxemia shortly after Abstract birth, absence of cyanotic congenital heart disease, marked pulmonary hypertension, and vasoreactivity with extrapulmonary right-to-left shunting of blood across the ductus arteriosus and/or foramen ovale. In utero, a number of factors determine the normally high vascular resistance in the fetal pulmonary circulation, which results in a higher pulmonary compared with systemic vascular pressure. However, abnormal conditions may arise antenatally, during, or soon after birth resulting in the failure of the pulmonary vascular resistance to normally decrease as the circulation evolves from a fetal to a postnatal state. This results in cyanosis due to right-to-left shunting of blood across normally existing cardiovascular channels (foramen ovale or ductus arteriosus) secondary to high pulmonary versus systemic pressure. The diagnosis is made by characteristic lability in oxygenation of the infant, echocardiographic evidence of increased pulmonary pressure, with demonstrable shunts across the ductus arteriosus or foramen ovale, and the absence of cyanotic heart disease lesions. Management of the disease includes treatment of underlying causes, sedation and analgesia, maintenance of adequate systemic blood pressure, and ventilator and pharmacologic measures to increase pulmonary vasodilata- tion, decrease pulmonary vascular resistance, increase blood and tissue oxygenation, and normalize blood pH. Inhaled nitric oxide has been one of the latest measures to successfully treat PPHN and significantly reduce the need for extracorporeal membrane oxygenation.