Hydrocortisone in BPD: a meta-analysis

The efficacy of corticosteroid administration to treat or prevent bronchopulmonary dysplasia (BPD) requires further evaluation. Recent evidence have suggested hydrocortisone as a safer alternative to dexamethasone in treating or preventing BPD, in accordance to the results of observational long-term studies indicating fewer adverse behavioural, cardiovascular, neurological and immune outcomes. These findings are supported by experimental studies reporting fewer changes in the hypothalamus of adolescent rats exposed as neonates to hydrocortisone, compared with dexamethasone. However, further evidence is required to support the routinely use of hydrocortisone in clinical practice.
In this paper, the authors have performed a meta-analysis of randomized controlled trials (RCTs) conducted in pretem infants where postnatal hydrocortisone therapy for treatment or prevention of BPD was compared to placebo.
A total of 8 RCTs and 880 participants were included in the meta-analysis. In all trials treatment was started in the first week of life, before BPD is established. There were no trials of treatment started in infants who were chronically ventilator-dependent after the first week of life with established or evolving BPD.
Overall, there was little evidence that hydrocortisone reduced mortality, the rate of BPD at 36 weeks' post-menstrual age (PMA), the incidence of death or BPD at 36 weeks' PMA, the proportion of survivors discharged home on oxygen, or the rate of extubation failure.
Hydrocortisone significantly increased the risks of GI perforation (number needed to harm=20), but reduced the risk of patent ductus arteriosus (number needed to treat=14). There was little evidence of any other harmful effect of hydrocortisone, including the rate of cerebral palsy.
The results of this meta-analysis, conducted in a large sample of patients, overall show that there is little evidence to support the use of hydrocortisone as prophylaxis for BPD in the dose regimens employed in the studies reviewed. RCTs with dexamethasone showed the drug to be substantially effective in preventing extubation failure and rate of BDP. This discrepancy might be explained by use of much lower doses of hydrocortisone than dexamethasone, in equivalent terms. In order to provide new evidence on the use of hydrocortisone, RCTs of this drug should report late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in the studies. Future studies are needed to identify those infants most at risk of either dying or surviving with neurological disability, as a consequence of prolonged assisted ventilation and evolving BPD.

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