Initiation of ventilation, surfactant treatment, and lung function after preterm birth

Sammanfattning: The thesis investigates lung function and the effects of rescue surfactant treatment in mechanically ventilated preterm human infants with respiratory distress syndrome (RDS), and the effects of ventilation at birth on the response to surfactant supplementation in preterm lambs. To assess lung function, the author recorded static pressure-volume (P-V) curves during passive deflation from total lung capacity (TLC) to ambient pressure and measured end-expiratory lung volume (FRC) during mechanical ventilation by tracer gas washout. Compared with air-ventilated infants, mechanically ventilated infants with early, severe RDS had a markedly reduced TLC, mainly because of a reduction in amplitude of the P-V curve (low inspiratory capacity, IC). In addition, dynamic compliance was lower than normal, the P-V curves were less steep at low pressures, and FRC was reduced. Rescue surfactant caused an immediate increase in deflation stability of the lungs resulting in a moderate increase in FRC at 5 cm H2O PEEP, but no significant change in TLC. Dynamic compliance was unchanged early after surfactant, but two measures of static compliance, viz. the volume change of the lungs between peak inspiratory pressure and zero pressure and the steepest slope of the P-V curve, increased significantly. In preterm lambs, delivered by caesarean section, manual ventilation with six large breaths at birth (inflation volumes approximately 30-40 mL/kg and plateau pressures 50-70 cm H2O) completely obliterated the lung mechanical effect of rescue surfactant given at 30 min of age. Compared with preterm lambs given prophylactic surfactant before the first breath, lambs given five lung inflations (8, 16, or 32 mL/kg) just before surfactant had a reduced lung mechanical response that correlated to the size of lung inflations at birth. There was also a negative correlation between the size of inflations at birth and alveolar expansion in histologic sections. Surfactant given before the first breath did not fully protect against the adverse effect of large lung inflations (16 mL/kg) if these were given immediately after surfactant. However, no negative effect was seen from large lung inflations given at 10 min of age or later. In summary, the main characteristic of severe RDS is a profound loss of lung volume, and this is not immediately corrected by rescue surfactant treatment. In preterm lambs, there is a short period early after birth, presumably before lung liquid has cleared, when the lung is sensitive to large inflations.