Hillman Noah H, Abugisisa Leenah, Royse Emily, Fee Erin, Kemp Matthew W, Kramer Boris W, Schmidt Augusto F, Salomone Fabrizio, Clarke Michael W, Musk Gabrielle C, Jobe Alan H
Division of Neonatology, Cardinal Glennon Children's Hospital, Saint Louis University, Saint Louis, MO, 63104, USA.
School of Women's and Infants' Health, University of Western Australia, Perth, WA, 6009, Australia.
Pediatr Res. 2020 Nov;88(5):726-732. doi: 10.1038/s41390-020-0809-6. Epub 2020 Feb 17.
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.
Preterm lambs received either (1) protective tidal volume (V) ventilation with surfactant from birth or (2) injurious V 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 for 6 h.
Plasma Bud levels were proportional to the dose received and decreased throughout ventilation. In both protective and injurious V 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.
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.
在早产羊中，将0.25毫克/千克布地奈德（Bud）添加到表面活性剂中可降低机械通气对肺部和全身的影响，以及降低早产儿支气管肺发育不良（BPD）的发生率和严重程度。我们推测，表面活性剂中较低浓度的布地奈德在减少全身皮质类固醇暴露的同时将减少损伤。
早产羔羊出生后要么接受（1）使用表面活性剂的保护性潮气量（V）通气，要么接受（2）15分钟的损伤性V通气，然后进行表面活性剂治疗。羔羊被进一步分为接受与（i）生理盐水、（ii）0.25毫克/千克布地奈德、（iii）0.1毫克/千克布地奈德或（iv）0.04毫克/千克布地奈德混合的表面活性剂。然后所有羔羊均接受6小时的保护性V通气。
血浆布地奈德水平与所接受的剂量成正比，并在整个通气过程中下降。在保护性和损伤性V通气中，6小时时肺内残留的布地奈德均<4%。0.1毫克/千克布地奈德也出现了0.25毫克/千克布地奈德在生理和损伤标志物方面的一些改善，而0.04毫克/千克布地奈德的作用微乎其微。
较低剂量的布地奈德在减轻机械通气引起的肺部和全身炎症方面效果较差。血浆布地奈德水平与给药剂量成正比，且大部分布地奈德离开了肺部。
