Dose of budesonide with surfactant affects lung and systemic inflammation after normal and injurious ventilation in preterm lambs

BACKGROUND: The addition of budesonide (Bud) 0.25 mg/kg to surfactant decreased the lung and systemic responses to mechanical ventilation in preterm sheep, and the rates and severity of bronchopulmonary dysplasia (BPD) in preterm infants. HYPOTHESIS: Lower budesonide concentrations in surfactant will decrease injury while decreasing systemic corticosteroid exposure. METHODS: Preterm lambs received either: 1) protective tidal volume (V(T)) ventilation with surfactant from birth or 2) injurious V(T) ventilation for 15 minutes then surfactant treatment. Lambs were further assigned to surfactant mixed with: i) Saline, ii) Bud 0.25 mg/kg, iii) Bud 0.1 mg/kg, or iv) Bud 0.04 mg/kg. All lambs were then ventilated with protective V(T) for 6 hours. RESULTS: Plasma Bud levels were proportional to the dose received, and decreased throughout ventilation. In both protective and injurious V(T) ventilation, less than 4% of Bud remained in the lung at 6 h. Some of the improvements in physiology and markers of injury with Bud 0.25 mg/kg were also found with 0.1 mg/kg, whereas 0.04 mg/kg had only minimal effects. CONCLUSION: Lower doses of Bud were less effective at decreasing lung and systemic inflammation from mechanical ventilation. The plasma Bud levels were proportional to dose given and the majority left the lung.