Exogenous surfactant improves ventilation efficiency and alveolar expansion in rats with meconium aspiration

The pathogenesis of neonatal meconium aspiration syndrome (MAS) may involve inactivation of endogenous surfactant, and data from clinical pilot studies indicate that treatment with exogenous surfactant may alleviate respiratory failure in babies with MAS. We studied ventilation efficiency after treatment with a modified porcine surfactant in experimental meconium aspiration. Adult rats were anesthetized and tracheotomized, and received via a tracheal cannula from 4 to 6 ml/kg body weight of a saline suspension of human meconium (25 mg [dry weight]/ml). After 30 min of ventilation with 100% oxygen, the animals were in respiratory failure, with dynamic lung-thorax compliance < 0.5 ml/cm H2O/kg and PaO2 < 8 kPa (60 mm Hg). Animals were then allocated to: (1) immediate treatment with surfactant (200 mg/kg); (2) treatment with surfactant (200 mg/kg 3 h later; or (3) a control group not receiving surfactant. All animals were ventilated for 6 h with variable FIO2 and peak inspiratory/positive end-expiratory pressure (PIP/PEEP). In the control group, six of 12 animals died of respiratory failure with hypoxemia and acidosis despite ventilation with 100% oxygen and high mean airway pressure (> 20 cm H2O). The lungs of all animals in this group showed severe atelectasis, influx of neutrophils, edema, and hyaline membranes. In contrast, animals allocated to immediate or late surfactant treatment had lower mortality (one of seven and two of eight, respectively), a reduction of oxygen supply by 30%, and a decrease in mean airway pressure of 3 to 4 cm H2O. This was associated with a > 50% increase in static lung volume at 40 cm H2O inflation and 10 cm H2O deflation pressure and improved alveolar expansion in histologic sections. Hyaline membranes tended to be less prominent in surfactant-treated animals than in controls. We conclude that both early and late treatment with surfactant is effective in this animal model of MAS.