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. We hypothesized that 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 min and 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 h. Results Plasma Bud levels were proportional to the dose received and decreased throughout ventilation. In both protective and injurious V T ventilation, <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. Conclusions 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.

中文翻译：

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布地奈德与表面活性剂的剂量影响早产羔羊正常和有害通气后的肺部和全身炎症

背景 在表面活性剂中添加 0.25 mg/kg 布地奈德 (Bud) 可降低早产羊对机械通气的肺部和全身反应，以及早产儿支气管肺发育不良 (BPD) 的发生率和严重程度。我们假设表面活性剂中较低的布地奈德浓度会减少损伤，同时减少全身皮质类固醇的暴露。方法 早产羔羊接受（1）出生时使用表面活性剂的保护性潮气量（VT）通气或（2）损伤性 VT 通气 15 分钟，然后进行表面活性剂处理。羔羊被进一步分配给与 (i) 盐水、(ii) Bud 0.25 mg/kg、(iii) Bud 0.1 mg/kg 或 (iv) Bud 0.04 mg/kg 混合的表面活性剂。然后用保护性 VT 为所有羔羊通风 6 小时。结果 血浆芽水平与接受的剂量成正比，并在整个通气过程中降低。在保护性和损伤性 VT 通气中，<4% 的芽在 6 小时时仍留在肺中。Bud 0.25 mg/kg 对生理学和损伤标志物的一些改善也发现在 0.1 mg/kg 中，而 0.04 mg/kg 的影响很小。结论 较低剂量的 Bud 在减少机械通气引起的肺部和全身炎症方面效果较差。血浆芽水平与给药剂量成正比，大部分离开肺。