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

N.H. Hillman*, L. Abugisisa, E. Royse, E. Fee, M.W. Kemp, B.W. Kramer, A.F. Schmidt, F. Salomone, M.W. Clarke, G.C. Musk, A.H. Jobe

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)726-732
Number of pages7
JournalPediatric Research
Volume88
Issue number5
DOIs
Publication statusPublished - 1 Nov 2020

Keywords

  • endotoxin
  • esterification
  • infants
  • maturation
  • mortality
  • pathways
  • premature lambs
  • pressure
  • prevention
  • pulmonary distribution
  • MORTALITY
  • PATHWAYS
  • PREMATURE LAMBS
  • ENDOTOXIN
  • ESTERIFICATION
  • PREVENTION
  • MATURATION
  • PRESSURE
  • INFANTS
  • PULMONARY DISTRIBUTION

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