Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial

OBJECTIVE: To evaluate if nebulised surfactant reduces intubation requirement in preterm infants with respiratory distress treated with nasal continuous positive airway pressure (nCPAP). DESIGN: Double blind, parallel, stratified, randomised control trial. SETTING: Sole tertiary neonatal unit in West Australia. PATIENTS: Preterm infants (29(0)–33(6) weeks’ gestational age, GA) less than 4 hours of age requiring 22%–30% supplemental oxygen, with informed parental written consent. INTERVENTIONS: Infants were randomised within strata (29(0)–31(6) and 32(0)–33(6) weeks’ GA) to bubble nCPAP or bubble nCPAP and nebulised surfactant (200 mg/kg: poractant alfa) using a customised vibrating membrane nebuliser (eFlow neonatal). Surfactant nebulisation (100 mg/kg) was repeated after 12 hours for persistent supplemental oxygen requirement. MAIN OUTCOME MEASURES: The primary outcomes were requirement for intubation and duration of mechanical ventilation at 72 hours. Data analysis followed the intention-to-treat principle. RESULTS: 360 of 606 assessed infants were eligible; 64 of 360 infants were enrolled and randomised (n=32/group). Surfactant nebulisation reduced the requirement for intubation within 72 hours: 11 of 32 infants were intubated after continuous positive airway pressure (CPAP) and nebulised surfactant compared with 22 of 32 infants receiving CPAP alone (relative risk (95% CI)=0.526 (0.292 to 0.950)). The reduced requirement for intubation was limited to the 32(0)–33(6) weeks’ GA stratum. The median (range) duration of ventilation in the first 72 hours was not different between the intervention (0 (0–62) hours) and control (9 (0–64) hours; p=0.220) groups. There were no major adverse events. CONCLUSIONS: Early postnatal nebulised surfactant may reduce the need for intubation in the first 3 days of life compared with nCPAP alone in infants born at 29(0)–33(6) weeks’ GA with mild respiratory distress syndrome. Confirmation requires further adequately powered studies. TRIAL REGISTRATION NUMBER: ACTRN12610000857000.