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.