Recent developments in the pathophysiology and treatment of persistent pulmonary hypertension of the newborn☆,☆☆,★,★★
Section snippets
FETAL AND TRANSITIONAL PULMONARY VASOREGULATION
The fetal circulation is characterized by high pulmonary vascular resistance; pulmonary blood flow accounts for less than 10% of combined ventricular output in the late-gestation ovine fetus.5 Mechanisms responsible for maintaining high fetal pulmonary vascular resistance and causing sustained pulmonary vasodilation at birth are incompletely understood; however, studies in fetal and transitional pulmonary vasoregulation have led to increased understanding of the normal physiologic control of
CLINICAL TRIALS OF INHALED NO IN INFANTS WITH PPHN
Recent studies have demonstrated that inhaled NO causes marked improvement in oxygenation in many newborn infants with PPHN. Roberts et al.33 reported that brief (30 minutes) inhalation of NO at 80 ppm improved oxygenation in patients with PPHN, but this response was sustained in only one patient after NO was discontinued. In another report, rapid improvement in oxygenation in neonates with severe PPHN was demonstrated with the use of doses of 20 ppm NO for 4 hours, after which the dose was
MANAGEMENT STRATEGIES IN PPHN
Increasing clinical experience with inhaled NO in PPHN has led to improved understanding of the potential role of this potent and selective pulmonary vasodilator. Although consensus on diagnostic criteria is lacking,38 for the purposes of this discussion PPHN is defined as severe neonatal hyoxemic respiratory failure associated with extrapulmonary right-to-left shunting of blood across the foramen ovale or patent ductus arteriosus or both. Patients with idiopathic PPHN have severe pulmonary
NITRIC OXIDE IN THE PREMATURE INFANT'S PULMONARY CIRCULATION
The fetus is characterized by both structural and functional pulmonary immaturity, including surfactant deficiency. Pulmonary immaturity and hyaline membrane disease lead to respiratory failure after premature delivery, and exogenous surfactant therapy can decrease the severity of the respiratory insufficiency.69 However, exogenous surfactant therapy results in suboptimal responses in up to 50% of human neonates thought to have HMD,70 which suggests that other problems of prematurity (e.g.,
TOXICITY
The clinical studies described above were designed to investigate the hemodynamic effects of inhaled NO within ”nontoxic“ concentrations, but concerns remain regarding potential toxic effects, including methemoglobinemia and lung injury caused by NO2, peroxynitrite, and hydroxyl radical formation.81, 82 Although little evidence exists for NO toxicity at low concentrations in adult animals,83, 84, 85 further studies in the neonatal lung are needed. Of particular concern are the potential effects
SUMMARY
Successful management of severe PPHN depends on the application of appropriate strategies to manage the cardiopulmonary interactions that characterize this syndrome. Manifestations of PPHN often involve dysfunctional pulmonary vasoregulation, with suprasystemic pulmonary vascular resistance causing extrapulmonary shunting, pulmonary parenchymal disease causing intrapulmonary shunting, and systemic hemodynamic deterioration. Inhaled NO can cause marked improvement in oxygenation when optimal
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Persistent Pulmonary Hypertension
2018, Avery's Diseases of the Newborn: Tenth EditionPersistent Pulmonary Hypertension
2017, Avery's Diseases of the Newborn, Tenth EditionDevelopmental Biology of the Pulmonary Vasculature
2017, Fetal and Neonatal Physiology, 2-Volume SetPharmacologic Therapies II: Inhaled Nitric Oxide
2017, Assisted Ventilation of the Neonate: An Evidence-Based Approach to Newborn Respiratory Care: Sixth EditionNeonatology for Anesthesiologists
2016, Smith's Anesthesia for Infants and Children, Ninth EditionDevelopmental Physiology of the Pulmonary Circulation
2014, The Lung: Development, Aging and the Environment: Second Edition
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From the Department of Pediatrics, Divisions of Neonatology and Pulmonary Medicine, Children's Hospital and the University of Colorado School of Medicine, Denver, Colorado
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Reprint requests: John P. Kinsella, MD, Division of Neonatology, Box B-070, Children's Hospital, 1056 E. 19th Ave., Denver, CO 80218-1088.
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THE JOURNAL OF PEDIATRICS 1995;126:853-64
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0022-3476/95/$3.00 + 0 9/18/64030