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.


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.
Yeh
Tsu F
TF
Department of Pediatrics, College of Medicine, China Medical University, 91 Hsieh Shih St, Taichung, Taiwan. tsufuhy@yahoo.com
Lin
Hong C
HC
Chang
Chien H
CH
Wu
Tien S
TS
Su
Bai H
BH
Li
Tsai C
TC
Pyati
Suma
S
Tsai
Chang H
CH
D001688:Biological Products / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D007322:Instillation, Drug; D008171:Lung Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D014677:Pharmaceutical Vehicles; D011239:Prednisolone / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate
C093190:16-hydroxyprednisolone; D001688:Biological Products; D005938:Glucocorticoids; D014677:Pharmaceutical Vehicles; D011663:Pulmonary Surfactants; D019819:Budesonide; D011239:Prednisolone; C072197:beractant