Short-term pulmonary and systemic effects of hydrocortisone initiated 7-14 days after birth in ventilated very preterm infants: a secondary analysis of a randomised controlled trial

Abstract

Objective: Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week. Design: Randomised placebo-controlled trial. Setting: Dutch and Belgian neonatal intensive care units. Patients: Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. Intervention: Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). Main outcome measures: Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models. Results: Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH2O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure. Conclusions: Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance.