Pharmacologic therapy of persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn (PPHN) is a potentially li fe-threatening condition characterized by a failure of pulmonary vascular r esistance to decrease adequately during the transition to extrauterine life . Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonar y circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularl y those with congenital diaphragmatic hernias or meconium aspiration syndro me. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-tr eated and control infants with PPHN. Other therapeutic approaches to PPHN h ave been limited by a relative lack of specificity for the pulmonary circul ation, and have received much less attention. Pharmacologic approaches, inc luding pulmonary surfactants, prostacyclin, endothelin antagonists, Ca2+-ch annel blockers, magnesium sulfate, and tolazoline, have exhibited varying d egrees of efficacy in lowering pulmonary vascular pressures in humans and/o r animals. A number of these agents are also effective when used in combina tion. For example, phosphodiesterase inhibitors have been reported to act s ynergistically with inhaled nitric oxide. Surfactants also appear to be use ful 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 a spiration syndrome. Further studies should be directed at defining the opti mal therapies in specific clinical settings. Validation of multiple therape utic modalities for PPHN. including inhaled nitric oxide, will allow for ra tional, combined vasodilator strategies that are specific for the underlyin g pathophysiology in each patient. (C) 2001 Elsevier Science Inc. All right s reserved.