Early versus late surfactant treatment in preterm infants of 27 to 32 weeks' gestational age: a multicenter controlled clinical trial. Early versus delayed surfactant administration in extremely premature neonates with respiratory distress syndrome ventilated by high-frequency oscillatory ventilation. Clinical course of premature infants intubated in the delivery room, submitted or not to porcine-derived lung surfactant therapy within the first hour of life. A prospective, randomized trial of early versus late administration of a single dose of surfactant-TA.
To investigate whether early (<1 hour after birth) surfactant administration would be superior to late treatment (2-6 hours after birth) in preterm infants.
                Randomized controlled multicenter clinical trial.
                Prenatal randomization of all infants of 27 to 32 weeks' gestational age stratified by center after parental informed consent. Early treatment: 100 mg/kg body weight bovine surfactant (SF-RI1, Alveofact; Dr K. Thomae, Biberach, Germany) to infants requiring intubation after birth. Late treatment: identical dosage to infants requiring intubation up to 6 hours of age with the fraction of inspired oxygen >0.4 at 2 to 6 hours after birth. Primary endpoint: the time on mechanical ventilation. Main secondary endpoints: mortality, bronchopulmonary dysplasia, intraventricular hemorrhage >/=grade III, and periventricular leukomalacia. Sample size calculation: at least 280 infants to prove superiority of either approach (alpha = 0.05; beta = 0.90).
                Enrollment of 317 infants, 154 randomized to early surfactant treatment, 163 to late surfactant treatment. Study infants (all following data intent-to-treat groups: early versus late surfactant) were similar with respect to: gestational age, 29.5 +/- 1.6 weeks versus 29.7 +/- 1.6 weeks; birth weight, 1227 +/- 367 g versus 1269 +/- 334 g; and the rate of prenatal corticosteroids, 79.9% versus 72.8%. Duration of mechanical ventilation: 3 days (0-8) versus 2 days (0-6) (median, interquartile); further outcome variables: death or bronchopulmonary dysplasia (day 28) 25.9% versus 23.9%, mortality 3.2% versus 1.8%, intraventricular hemorrhage >/=grade III 6.5% versus 3.7%, and periventricular leukomalacia 5.2% versus 5.5% not differing statistically.
                In preterm infants with a high rate of prenatal glucocorticoids, early surfactant administration was not found to be superior to late treatment in terms of relevant outcome variables. To determine whether early surfactant administration is superior to selective delayed treatment in terms of improving survival and/or reducing chronic lung disease in extremely premature neonates with respiratory distress syndrome (RDS) treated by high-frequency oscillatory ventilation (HFOV).
                Prospective randomized clinical trial.
                Tertiary neonatal intensive care unit (NICU) in the Perinatology Center of Prague.
                Forty-three extremely premature infants who needed artificial ventilation within 3 h after delivery.
                Patients were randomly assigned to either early ( n=21) or delayed (n=22) administration of surfactant. All were ventilated by HFOV as the primary mode of ventilation using the high volume strategy aimed at optimizing lung volume. Curosurf at a dose of 100 mg/kg was given as a single bolus via the endotracheal tube within 1 min immediately after intubation in the early group (EARL), or during HFOV only when defined criteria were reached in the delayed (DEL) group.
                No differences were noted in demographic data between the two groups. Fewer infants randomized to the EARL group required oxygen use or died at 36 weeks (combined outcome 29% vs 64%, p=0.021), and there was a lower incidence of any intraventricular hemorrhage in this group (43 vs 82%, p=0.008).
                When compared to delayed dosing, early administration of surfactant followed by HFOV facilitates and accelerates respiratory stabilization during the acute phase of severe RDS, may reduce the incidence of chronic lung disease or death and may positively influence the incidence of severe intracranial pathology in extremely premature infants with primary surfactant insufficiency. The aim of this study was to perform a comparative analysis of the clinical outcome, gasometric course and ventilatory indices of premature infants with a gestational age of < or = 34 weeks who were intubated in the delivery room, owing to respiratory insufficiency, according to whether or not they were submitted to porcine-derived lung surfactant therapy within the first hour of life.
                The study was randomized and controlled. A total of 75 premature infants were classified into two groups: group A, comprising 35 neonates who were submitted to surfactant within the first hour of life; and group B, comprising 40 neonates who were not submitted to surfactant within the first hour of life.
                Exogenous surfactant therapy after establishment of respiratory distress syndrome (RDS) was necessary in eight neonates of group A (22.9%) and 31 neonates of group B (77.5%) (p < 0.001). The neonates in group A presented higher levels in relation to group B for the variables: partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) and PaO2/partial pressure of alveolar oxygen (PAO2), while neonates in group B presented higher levels for FiO2, PAO2 and difference D(A - a)O2 in relation to group A. Weight affected the oxygenation index (OI) parameter, in that neonates with lower weight presented greater values of the OI.
                In premature infants with established RDS, the need for exogenous surfactant was lower in the group that received surfactant within the first hour of life. Furthermore, the gasometric parameters and ventilatory indexes presented a better course in the first 24 h of life among premature infants who received exogenous surfactant within the first hour of life, in relation to those who did not. Thirty-two neonates weighing 500-1500 g with documented surfactant deficiency and without evidence of severe birth asphyxia, infection, prolonged rupture of membranes greater than or equal to 72 h, or oligohydramnios were randomly assigned to receive a single intratracheal dose of surfactant-TA (100 mg/kg) either within 30 min of birth (n = 16, early group) or at 6 h of age (n = 16, late group). By 6 h of age, all neonates of the late group had moderate/severe RDS, while none of the neonates of the early group had either clinical or radiological respiratory distress syndrome. The incidence of bronchopulmonary dysplasia was significantly lower in survivors of the early group than those of the late group (1/15 versus 7/14, a 43% reduction with a 95% confidence interval of 14-72%, P = 0.025). These beneficial effects of early surfactant treatment remained after controlling for the various confounding factors in the logistic models.
Early selective surfactant administration given to infants with RDS requiring assisted ventilation leads to a decreased risk of acute pulmonary injury (decreased risk of pneumothorax and pulmonary interstitial emphysema) and a decreased risk of neonatal mortality and chronic lung disease compared to delaying treatment of such infants until they develop worsening RDS.