Pharmacologic therapy of persistent pulmonary hypertension of the newborn.
Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition characterized by a failure of pulmonary vascular resistance to decrease adequately during the transition to extrauterine life. Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonary circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularly those with congenital diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-treated and control infants with PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack of specificity for the pulmonary circulation, and have received much less attention. Pharmacologic approaches, including pulmonary surfactants, prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate, and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary vascular pressures in humans and/or animals. A number of these agents are also effective when used in combination. For example, phosphodiesterase inhibitors have been reported to act synergistically with inhaled nitric oxide. Surfactants also appear to be useful in PPHN, particularly in patients with congenital diaphragmatic hernia, when used in combination with other therapies. Surfactant lavage and other novel therapies may also be effective in combination therapy of meconium aspiration syndrome. Further studies should be directed at defining the optimal therapies in specific clinical settings. Validation of multiple therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for rational, combined vasodilator strategies that are specific for the underlying pathophysiology in each patient.
Weinberger
B
B
Department of Pediatrics, Division of Neonatology, UMDNJ-Robert Wood Johnson Medical School, St. Peter's University Hospital, New Brunswick, NJ 08903, USA. barryw@pol.net
Weiss
K
K
Heck
D E
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Laskin
D L
DL
Laskin
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JD
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D011464:Epoprostenol / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D008471:Meconium Aspiration Syndrome / Q000188:drug therapy*; D009569:Nitric Oxide / Q000627:therapeutic use*; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011453:Prostaglandins / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011464:Epoprostenol