Hydrocortisone and bronchopulmonary dysplasia: variables associated with response in premature infants

Abstract

Objective: The primary objective was to evaluate hydrocortisone's efficacy for decreasing respiratory support in premature infants with developing bronchopulmonary dysplasia (BPD). Secondary objectives included assessment of the impact of intrauterine growth restriction (IUGR), maternal history of chorioamnionitis, side effects and route of administration associated with hydrocortisone's efficacy. Dexamethasone as second-line treatment to decrease respiratory support was reviewed.

Methods: Retrospective chart review of preterm infants requiring respiratory support receiving hydrocortisone.

Results: A total of 48 patients were included. Successful extubation was achieved in 50% of intubated patients after hydrocortisone treatment with no major complications. In our small study, history of maternal chorioamnionitis, IUGR or route of administration did not affect the response. Rescue dexamethasone after hydrocortisone therapy was ineffective in the ten patients who failed extubation following hydrocortisone.

Conclusion: Hydrocortisone is effective in decreasing respiratory support in patients with developing BPD without major complications. Randomized studies are warranted to confirm our findings.

Fig. 1. Patient flow and patients’ characteristics.

a Diagram of patient flow. b Patient characteristics of the studied population (n = 48). DOL: days of life, PMA: postmenstrual age, PDA: patent ductus arteriosus, IUGR: intrauterine growth restriction, IV: intravenous, PO: oral/enteral.

Fig. 2. Hydrocortisone efficacy.

a Respiratory outcomes in patients who received hydrocortisone. Extubation was observed in 50% of patients (20/40) who were intubated at initiation. FiO₂ decrease of ≥10% at 10 days post hydrocortisone completion was seen in 52.1% (25/48) of patients. The combined outcome of extubation or decreased FiO₂ by 10% was achieved in 66.7% patients (32/48). Extubation rate was based only on the n = 40 subjects who were intubated. b Respiratory severity score (RSS = MAP × FiO₂) was calculated at day 0 and day 10 of hydrocortisone treatment. A statistically significant decrease was detected using the Wilcoxon signed rank test in RSS between day 0 of the hydrocortisone treatment and day 10 after the initiation (p < 0.0399). Std dev: Standard Deviation. Pctl: Percentile. c Efficacy was not affected by intrauterine growth restriction (IUGR) status, maternal history of chorioamnionitis (CAM), route of administration of hydrocortisone, gender, tapering of the dose, gestational age, days of life (DOL) at hydrocortisone initiation, birth weight, postmenstrual age (PMA) at the time of treatment initiation. The primary efficacy outcome was defined as extubation in the 40 patients who were intubated at hydrocortisone initiation or effective weaning to room air in the patients on noninvasive ventilation (n = 8) at hydrocortisone initiation. The univariate logistic regression with efficacy for decreased ventilator support as the outcome was used for these analyses.

Fig. 3. Hydrocortisone and safety outcomes.

a Complication rate in the studied population (n = 48). b Younger patients, based on both gestational age and PMA, had a trend of an increased risk of infection compared with older infants. Infection was identified based on positive cultures during and up to 1 week after the end of hydrocortisone treatment. The Mann–Whitney test, the non-parametric counterpart to the two-sample t-test, was used to compare those subjects with and without infection for gestational age and PMA at initiation of hydrocortisone. IQR: Interquartile range. c Head circumference is depicted as the mean growth from initiation of hydrocortisone to 2 months after therapy.

Fig. 4. Dexamethasone (DART) efficacy and patient characteristics.

a Extubation was observed in 2 out of 10 patients who received DART after hydrocortisone treatment. However, both of the infants were reintubated within 10 days. b Respiratory severity score (RSS = MAP × FiO₂) was calculated at day 0 and day 10 of dexamethasone treatment. There was not a significant decrease in the median RSS from day 0 to day 10 in the DART group. Wilcoxon signed rank test in RSS between day 0 of the DART treatment and day 10 after the initiation (p < 0.2754). Std Dev: standard deviation. Pctl: percentile. c Dexamethasone was administered via the DART protocol to 50% (10/20) after failure to respond to hydrocortisone. Patients who later received DART compared with infants who responded to hydrocortisone and therefore did not receive DART (NO DART) were younger at time of hydrocortisone administration, with a median of 25 days of life and PMA at initiation of hydrocortisone of 29.7 weeks. The Mann–Whitney test, the non-parametric counterpart to the two-sample t-test, was used to compare those who received DART to those who did not receive DART. HC-NR: Hydrocortisone non-responder. IQR: Interquartile range.