Early Surfactant Replacement Study

To evaluate the effect of intubation and early surfactant administration in spontaneously breathing premature infants with signs and symptoms of respiratory distress syndrome

Study Design
Multicenter randomized clinical trial in 27 neonatal intensive care units of the Vermont Oxford Network.

Infants randomized to either early intubation and surfactant treatment (ER) or standard respiratory management (SM), including possible intubation and surfactant treatment based on clinical indications. Entry criteria for the study included:

  • birth weight 1501 to 2500 grams
  • appropriate for gestational age
  • age 2- 24 hours
  • respiratory distress including tachypnea or retractions
  • requires 30% supplemental oxygen via oxyhood or nasal CPAP in order to maintain oxygen saturation 88-96%
  • no evidence of respiratory failure (PCO2 < 65 mmHg)
  • chest radiogram compatible with RDS
  • written informed consent obtained

Primary Outcome
Need for mechanical ventilation during the first week of life

Secondary Outcomes
Number of infants receiving surfactant treatment, number of surfactant doses, clinical status during first 7 days of life, clinical status at day 7 and day 28 of life, days on assisted ventilation, days on nasal CPAP, days on supplemental oxygen, age at cessation of NCPAP, age at cessation of assisted ventilation, days to full enteral alimentation (no additional IV nutrition), daily weight gain, pneumothorax, duration of hospitalization, mortality, other complications of prematurity.

Two hundred and sixty-seven infants were randomized and enrolled at 33 participating centers. Infants in the ER Group (N=137) were comparable to those in the SM Group (N=130) regarding birth weight, gestational age, race, prenatal care, and need for initial respiratory support. Fewer infants randomized to the ER Group required mechanical ventilation during the first week of life [38% vs. 48%, p=0.07, Relative Risk (RR) 0.78, 95% Confidence Interval (CI) 0.59, 1.03]. There were no differences between the groups in the duration of mechanical ventilation. Infants in the ER Group received more surfactant doses than infants in the SM Group (1.3 vs. 0.8, p < 0.001). In a subgroup analysis, fewer infants in the lower birth weight strata in the ER group required mechanical ventilation than infants in the SM Group (41% vs. 55%, p=0.09, RR 0.73, 95% CI 0.51, 1.05). Pneumothorax occurred in 6% of the ER Group vs. 10% in the SM Group (RR 0.58, 95%CI 0.25, 1.35). There were no differences between the groups in pulmonary hemorrhage, patent ductus arteriosus, bacterial sepsis, intraventricular hemorrhage, and necrotizing enterocolitis.

Spontaneously breathing infants treated with early intubation, surfactant replacement, and rapid extubation appear to require less mechanical ventilation during the first week of life than infants who received standard respiratory care. Additionally, there was a trend towards a decreased rate of pneumothorax in infants in the early treatment group, a finding noted in previous studies of this treatment approach.

Soll RF, Conner JM, Howard D; Early Surfactant Replacement Study Group. Early surfactant replacement therapy in spontaneously breathing premature infants with RDS. Pediatric Academic Societies Annual Meeting, Seattle WA, May 2003. Pediatric Research 2003; 4213C.

Study Sponsors
Ross Laboratories, Abbott Labs Inc.