Surfactant metabolism in the newborn : The impact of ventilation strategy and lung disease

Developmental deficiency in pulmonary surfactant leads to respiratory distress syndrome (RDS) in preterm infants, but all newborns may have impaired surfactant metabolism secondary to lung disease or ventilator induced lung injury. Exogenous surfactant treatment is usually administered in conjunction with mechanical ventilation. If instead surfactant administration is followed by nasal continuous positive airway pressure (nCPAP), the treatment response appears to be more sustained. The aims of the thesis were to (1) distinguish normal and abnormal surfactant turnover in term and preterm infants using a novel stable isotope technique, (2) determine if high frequency oscillatory ventilation (HFOV) decreases surfactant production in preterm infants with RDS, (3) systematically examine stable isotope methodology for in vivo studies of surfactant metabolism (4) follow-up the implementation of INSURE, i.e. surfactant administration during a brief intubation, and (5) experimentally test the hypothesis, that surfactant administration followed by spontaneous breathing improves the treatment response. After an intravenous infusion of stable isotope (13C) labeled precursors for surfactant phospholipid, the 13C-enrichment over time was measured in serial tracheal aspirates using gas chromatography/mass spectrometry. Term infants without lung disease had significantly faster endogenous surfactant turnover compared to preterm infants with RDS. Term infants with severe respiratory failure exhibited disrupted surfactant metabolism and decreased amounts of surfactant phospholipids in tracheal aspirates, suggesting delayed maturity of the surfactant system or impairment from the underlying disease. HFOV versus conventional ventilation did not affect the surfactant metabolic indices in preterm infants with RDS. The method yielded reproducible data and similar surfactant metabolic indices regardless of mass spectrometry instrumentation and the surfactant phospholipid pool being analysed. Fractional catabolic rate, which is tracer independent, is suggested to be the primary measure of surfactant turnover. A retrospective, 10-year follow-up of all inborn infants with RDS (n=420, gestational age >=27 to