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

ObjectiveObservational 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.DesignRandomised placebo-controlled trial.SettingDutch and Belgian neonatal intensive care units.PatientsInfants born <30 weeks’ gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life.InterventionInfants 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 measuresData 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.ResultsInfants 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.ConclusionsSystemic 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.Trial registration numberNetherlands Trial Register (NTR2768; https://www.trialregister.nl/trial/2640) and European Union Clinical Trials Register (EudraCT, 2010-023777-19).

Outcomes of postnatal systemic corticosteroids administration in ventilated preterm newborns: a systematic review of randomized controlled trials

“…After a manual search of the reference list of the systematic reviews and meta-analyses analyzed in the previous stages, we added 28 RCTs, and 39 RCTs were analyzed in the final step of this systematic review ( Figure 1 ). Data extracted are summarized in Tables 1 – 6 ( 16 – 54 ).…”

“…A graphical representation of the percentage of the studies evaluating the outcomes of interest for this study is shown in Figure 2 ( 16 – 54 ).…”

“…We found that 18 studies evaluated the early extubation rate ( 16 – 18 , 20 , 22 , 27 , 32 , 34 , 36 , 39 – 41 , 43 , 46 – 49 , 53 ). Five of 18 RCTs found no differences between intervention and control groups (2 hydrocortisone vs. placebo, 1 dexamethasone vs. placebo, and 2 with different doses of dexamethasone) ( 22 , 27 , 39 , 48 , 49 ), while 13 found an early time of extubation in newborns who received system corticosteroids (4 hydrocortisone vs. placebo, 7 dexamethasone vs. placebo, and 2 with different doses of dexamethasone) ( 16 – 18 , 20 , 32 , 34 , 36 , 40 , 41 , 43 , 46 , 47 , 53 ). A total of 21RCTs did not evaluate this outcome or declare the rate of extubation in relation to the administration of systemic corticosteroids ( 19 , 21 , 23 – 26 , 28 – 31 , 35 , 37 , 38 , 42 , 44 , 45 , 50 – 52 , 54 ).…”

“…No studies found an increased rate of BPD between the groups. Thirty-three of 39 studies evaluated the pulmonary function ( 16 , 17 , 19 , 20 , 22 , 25 – 34 , 36 , 38 – 54 ). In addition, 21 of 33 RCTs found an improved respiratory outcome for intervention groups (5 hydrocortisone vs. placebo, 12 dexamethasone vs. placebo, and 4 with different doses of dexamethasone) ( 16 , 25 – 27 , 30 , 32 , 33 , 36 , 38 – 46 , 50 , 51 , 53 , 54 ).…”

“…Thirty-three of 39 studies evaluated the pulmonary function ( 16 , 17 , 19 , 20 , 22 , 25 – 34 , 36 , 38 – 54 ). In addition, 21 of 33 RCTs found an improved respiratory outcome for intervention groups (5 hydrocortisone vs. placebo, 12 dexamethasone vs. placebo, and 4 with different doses of dexamethasone) ( 16 , 25 – 27 , 30 , 32 , 33 , 36 , 38 – 46 , 50 , 51 , 53 , 54 ). Twelve did not find a difference ( 17 , 19 , 20 , 22 , 28 , 29 , 31 , 34 , 47 – 49 , 52 ), whereas six did not evaluate this outcome ( 18 , 21 , 23 , 24 , 35 , 37 ).…”