Effects of budesonide and surfactant in preterm fetal sheep

Background: Mechanical ventilation causes lung injury and systemic inflammatory responses in preterm sheep, and is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Budesonide added to surfactant decreased BPD by 20% in infants. Objective: Determine the effects of budesonide and surfactant on injury from high tidal volume (VT) ventilation in preterm lambs. Methods: Ewes at 125 {plus minus} 1 day GA had fetal surgery to expose fetal head and chest with placental circulation intact. Lambs were randomized to either 1) mechanical ventilation with escalating VT to target 15 mL/kg by 15 min or 2) continuous positive airway pressure (CPAP) of 5 cmH2O. After the 15 min intervention, lambs were given surfactant 100 mg/kg with A) saline, B) budesonide 0.25 mg/kg, or C) budesonide 1 mg/kg. The fetuses were returned to the uterus for 24 hours, then delivered and ventilated for 30 min to assess lung function. Results: Budesonide levels were low in lung and plasma. CPAP groups had improved oxygenatio...