Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia.

RATIONALE: Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. OBJECTIVES: To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. METHODS: A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated. MEASUREMENTS AND MAIN RESULTS: The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days. CONCLUSIONS: In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).

A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants.

OBJECTIVE: Our study of early intratracheal instillation of budesonide using surfactant as vehicle showed a significant decrease in death or chronic lung disease (CLD) in preterm infants with severe respiratory distress syndrome (RDS). We now report the long-term outcome at about 2 to 3 years of age. STUDY DESIGN: Of the 75 potential survivors, 67 (90%) were studied (35 budesonide-treated, 32 control). All infants had birth weight <1500 g and had severe RDS requiring intermittent mechanical ventilation shortly after birth. The treated group received a mixture of budesonide and surfactant every 8 hours. The control group received only surfactant. RESULTS: The physical growth and the neurological examinations were comparable between the groups at follow-up. Infants in the group treated with budesonide tended to have higher PDI and MDI scores than infants in the control group (79 +/- 20 vs 74 +/- 18 and 80 +/- 19 vs 75 +/- 20), but these differences were not statistically significant. The incidence of neurodevelopmental impairment was 11 (31%) in the treated group and 13 (40%) in the control group (P = .367). CONCLUSIONS: Early intratracheal instillation of budesonide using surfactant as a vehicle significantly improved pulmonary outcome without causing long-term adverse effects.

Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study.

OBJECTIVE: Budesonide is an inhaled steroid with a strong topical effect but with minimal systemic effects; it has been effectively delivered to animal lungs using surfactant as a vehicle. The purposes of this study were to determine whether early intratracheal instillation of budesonide using surfactant as a vehicle would improve pulmonary status, reduce mortality, and reduce chronic lung disease morbidity. PATIENTS AND METHODS: We conducted a prospective, randomized blind trial in 116 very low birth weight infants (< 1500 g) who had severe radiographic respiratory distress syndrome and required mechanical ventilation with fraction of inspired oxygen > or = 0.6 shortly after birth: 60 were in the treated group (intratracheal instillation of a mixture of 0.25 mg/kg of budesonide and 100.00 mg/kg of survanta, every 8 hours) and 56 were in the control group (100 mg/kg of survanta only, every 8 hours). The end point assessment was the number of infants who would die or develop chronic lung disease at 36 weeks' postconceptional age. RESULTS: Infants in the treatment group required significantly lower mean airway pressure on day 1 and day 3 and had significantly lower oxygen index and PCO(2) during the first 3 days than infants in the control group. More infants were extubated in the treatment group than controls at 1 and 2 weeks. The combined outcome of deaths or chronic lung disease was significantly lower in the treatment group than in the control group (19 of 60 vs 34 of 56). No clinically significant adverse effects were observed during the study. CONCLUSIONS: This pilot study indicated that early postnatal intratracheal instillation of budesonide using surfactant as vehicle significantly improved the combined outcome of death or chronic lung disease in small premature infants without causing immediate adverse effects. The results are encouraging, and a large sample multicenter trial is warranted.