The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 pg twice daily) vs. placebo administered by metered dose inhaler (MDI) and spacer (Aerochamber MVl5) directly into the endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks) who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n = 9) or placebo (n = 11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during the study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDI and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.
1. Only 20 of the 30 newborns who entered the trial completed the study. Reasons for withdrawal were: sepsis (three placebo and two treatment patients), clinical evidence of PDA (two patients in each group), and occurrence of air leak (one in treatment group). Among the infants for whom complete data were available, there were no clinical differences between groups on entry into the trial (Table 1).
2. No infant achieved the primary outcome of extubation during the 7 day trial period. However, significant improvements in peak inspiratory pressure (PIP), frequency of ventilation, FiO,, VEI, and A-a oxygen difference occurred in the budesonide group without change in the placebo group (Table 2, Fig. 1).
3. Serum cortisol levels were not influenced by treatment, and there was no difference between the groups before, during, or after the trial period. Clinical complications potentially attributable to corticosteroids were not different between the groups. The five cases of sepsis recorded during the trial period were successfully treated with antibiotics (see exclusions above). No other side effects were recorded. No differences were found in total or differential BALF cell counts .
We have shown in this pilot study that topical budesonide given to mechanically ventilated preterm infants by MDI and a small volume spacer has beneficial effects on ventilation and gas exchange. Further trials are needed to establish the most appropriate dose and the usefulness of early therapy.