No abstract

Long after resolution of the neonatal respiratory distress syndrome, deterioration of respiratory function in ventilated premature infants during severe nosocomial infections is commonly observed. Based on an increased oxygen demand and ventilatory support, impairment of the pulmonary surfactant system was hypothesized to occur. The clinical course of 10 premature neonates (764 +/- 57 g, 26.6 +/- 0.4 wk) with nosocomial infection mainly due to Staphylococcus epidermidis was divided into four periods in each individual patient: "before deterioration" (average 8 to 11 d of life), "deterioration" (11 to 17 d), "peak" (17 to 22 d), and "recovery" (22 to 24 d). A total of 810 airway specimens were obtained by small volume lavage (1 ml/kg bw), pooled to yield appropriate amounts for differential centrifugation into two distinct subfractions known as large surfactant aggregates (LA) and small surfactant aggregates (SA). "Before deterioration" the amount of phospholipids recovered was constant, and the two fractions were characterized by electron microscopic morphology and biochemical analysis. In the LA fraction lamellar body-like lipid structures were demonstrated, and the phospholipid composition was typical of pulmonary surfactant in premature neonates with a high content of phosphatidylcholine and phosphatidylinositol. With "deterioration" and "peak" the masses of total phospholipids and of phosphatidylcholine recovered were reduced (p < 0.05). At the same time the mass ratio of SA/LA for phosphatidylcholine decreased from 0.32 +/- 0.10 to 0.18 +/- 0.03, indicating a more pronounced decrease of the SA fraction (p < 0.05). The phospholipid composition in the LA fraction did not change during the course of nosocomial infection. In the SA fraction a decrease of phosphatidylcholine and a concomitant increase in lysophosphatidylcholine were observed at the "peak" of the infection. We concluded that, in ventilated premature neonates during nosocomial infection and respiratory deterioration, changes in phospholipid subfractions occur, possibly indicating impairment of pulmonary surfactant metabolism. These findings may be important when considering treatment of acute lung injury with nebulized exogenous surfactant.

Small volume bronchoalveolar lavages from 10 infants (26.6 ± 0.4 weeks gestational age) during postnatal nosocomial infection were fractioned by differential centrifugation into large (LA) and small (SA) surfactant aggregates. Before deterioration of the clinical status, the surface tension at minimum bubble radius (γ_min), as measured in a pulsating bubble surfactometer, was reduced to about 14 mN/m by LA and to about 22 mN/m by the corresponding SA. The γ_min of both LA and SA increased during clinical deterioration, was highest at the worst clinical state and returned during recovery to values in the range before deterioration. Respiratory support significantly correlated to γ_min at all times. In contrast, no correlation was observed for total protein or albumin content of the LA or SA fractions. The SA fraction was characterized by a 10-fold higher protein content than LA. These data demonstrate functional impairment of surfactant in subfractions during mechanical ventilation and nosocomial infection in preterm neonates that are not fully explained by inhibition with increasing amounts of total protein.

The function of pulmonary surfactant of a group of 14 preterm neonates (birth weight 907 ± 60 g) who suffered from severe respiratory distress syndrome (RDS) and who had received exogenous bovine lipid extracted surfactant on the first day of life was compared to that in a second group of 8 neonates (birth weight 940 ± 110 g) with mild RDS who had not received surfactant treatment. Mechanical respiratory support from day 2 on was the same in both groups. The minimal surface tension (γ_min) improved steadily, falling from about 30 mN/m initially to less than 20 mN/m before extubation. A consistent but loose correlation was found between γ_min and mechanical respiratory support necessary, as quantitated by the oxygenation index. Total protein was about 0.8 ± 0.2 mg/mg of phospholipids and did not change during the first week of life. There were no correlations between total protein and γ_min or the oxygenation index. The data suggest that inhibition of surfactant function by proteins leaked into the airspaces does not play a major role during recovery from RDS. Instead, endogenous remodelling of surfactant might be of greater relevance.