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Safety and efficacy of nitric oxide in chronic lung disease

Abstract

Background: Therapies for neonatal chronic lung disease (CLD) of prematurity have had limited success.

Aims: To determine whether inhaled nitric oxide (INO) administered to very low birthweight infants with developing CLD might improve oxygenation without adverse effects.

Methods: Subjects were 10–30 days of age, birth weight <1250 g, with developing or established CLD, and requiring mechanical ventilation with mean airway pressure ≥7 cm H2O and Fio2 ≥0.40. We monitored changes in oxygenation and Fio2 requirement during treatment with INO (initial dose 20 ppm). Tracheal aspirate samples obtained before, during, and after treatment were analysed for interleukin 1β (IL-1β), IL-8, 8-epi-prostaglandin F (8-epi-PGF), laminin, and endothelin 1 (ET-1) to assess any potential effects of INO on markers of inflammation peroxidation, basement membrane injury, or vasoactivity.

Results: Thirty three patients met entry criteria. Mean gestational age was 25 (SD 2) weeks; birth weight was 736 (190 g); age of study infants was 19 (6) days (range 9–29). Mean Fio2 decreased from baseline (0.75) to 0.58 at 72 hours. Duration of therapy was seven days. Tracheal aspirate concentrations of IL-1β, IL-8, 8-epi-PGF, ET-1, and laminin were unchanged between baseline and 48 hours of INO, and 48 hours after discontinuation of INO. No new cases of, nor extension of, intraventricular haemorrhage occurred. Four infants died.

Conclusion: INO (≤20 ppm) improved oxygenation in most infants with early CLD, without inducing changes in markers of inflammatory or oxidative injury.

  • chronic lung disease
  • inhaled nitric oxide
  • lung inflammation
  • endothelin 1
  • CLD, chronic lung disease
  • CMV, conventional mechanical ventilation
  • ELISA, enzyme linked immunoassay
  • HFOV, high frequency oscillatory ventilation
  • INO, inhaled nitric oxide
  • IVH, intraventricular haemorrhages
  • PCA, postconceptional age
  • PVR, pulmonary vascular resistance
  • sSC-IgA, soluble secretory component of IgA
  • VLBW, very low birthweight
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