A Randomized Clinical Trial of Intratracheal Administration of Surfactant and Budesonide Combination in Comparison to Surfactant for Prevention of Bronchopulmonary Dysplasia

OBJECTIVES: Bronchopulmonary dysplasia (BPD) remains a major problem in preterm infants occurring in up to 50% of infants born at < 28 weeks gestational age. Inflammation plays an important role in the pathogenesis of BPD. This study was conducted to evaluate the efficacy of intratracheal budesonide administration in combination with a surfactant in preventing BPD in preterm infants. METHODS: In a randomized clinical trial, 128 preterm infants at < 30 weeks gestational age and weighing < 1500 g at birth were studied. All had respiratory distress syndrome (RDS) and needed surfactant replacement therapy. They were randomly allocated into two groups; surfactant group (n = 64) and surfactant + budesonide group (n = 64). Neonates in the surfactant group received intratracheal Curosurf 200 mg/kg/dose. Patients in the surfactant + budesonide group were treated with intratracheal instillation of a mixed suspension of budesonide 0.25 mg/kg and Curosurf 200 mg/kg/dose. Neonates were followed untill discharge for the primary outcome which was BPD and secondary outcomes including sepsis, patent ductus arteriosus (PDA), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC). RESULTS: The mean gestational age and birth weight of the studied neonates were 28.3±1.6 weeks and 1072.0±180.0 g, respectively. The demographic characteristics and RDS score were similar in the two groups. BPD occurred in 24 (37.5%) neonates in the surfactant + budesonide group and 38 (59.4%) neonates in surfactant group, p = 0.040. Hospital stay was 29.7±19.2 days (median = 30 days) in the surfactant group and 23.3±18.1 days (median = 20 days) in the surfactant + budesonide group, p = 0.050. The rates of sepsis, PDA, ROP, and NEC were not significantly different in the two groups. CONCLUSIONS: The use of budesonide in addition to surfactant for rescue therapy of RDS in preterm infants decreases the incidence of BPD and duration of respiratory support significantly. Large adequately powered clinical trials with long-term safety assessments are needed to confirm our findings before its routine use can be recommended.