Respiratory distress syndrome--new therapeutic approaches to a complex pathophysiology.

In this review I have emphasized the complicated events that occur during the course of RDS. RDS is initiated by an inadequate pool size of functional surfactant within a structurally and functionally immature lung. Obstetric and delivery room management apparently can significantly influence surfactant function and, therefore, the incidence of RDS, possibly by affecting the permeability properties of the pulmonary vascular endothelium and alveolar epithelium. The course and severity of RDS will be further influenced by neonatal care and other occurrences such as the presence or absence of a PDA. Many details of the biochemical and physiologic events that result in RDS have not been defined, so we are currently unable to quantitatively understand how all the various factors interact during the course of RDS to give the characteristic clinical course of the disease. Variations in the magnitude and timing of these interactions will likely explain the variable manifestations of respiratory failure in the tiny infant. Within the context of the pathophysiology of RDS, surfactant replacement therapy and HFV represent two new and very different approaches to treatment. Initial clinical trials of surfactant replacement therapy in infants with RDS are encouraging, and experience with animal models indicates that such an approach will work. Replacement therapy also makes sense if one considers what is known about surfactant metabolism during RDS. However, no standard, tested, and safe preparation of surfactant is available. If past experience is any guide, it may not be easy to develop an acceptable product for general use. HFV offers an opportunity to ventilate infants with relatively high mean airway pressures but without the use of high peak airway pressures. Early clinical trials suggest the technique will benefit some infants, however no ventilators for HFV are available for clinical use. In light of the low mortality from respiratory failure in RDS and a morbidity from RDS resulting mostly from the other diseases of prematurity, these new therapeutic approaches need to be thoroughly tested and understood before general clinical use.