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

Stefan Minocchieri; Clare A Berry; J Jane Pillow; CureNeb Study Team

doi:10.1136/archdischild-2018-315051

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

Arch Dis Child Fetal Neonatal Ed. 2019 May;104(3):F313-F319. doi: 10.1136/archdischild-2018-315051. Epub 2018 Jul 26.

Authors

Stefan Minocchieri^{1

2

3}, Clare A Berry¹, J Jane Pillow^{1

2

4}; CureNeb Study Team

Affiliations

¹ Centre for Neonatal Research and Education, School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
² Neonatal Clinical Care Unit, Women and Newborn Health Service, Perth, Western Australia, Australia.
³ Neonatologie, Kantonsspital Winterthur, Winterthur, Switzerland.
⁴ School of Human Sciences, University of Western Australia, Perth, Western Australia, Australia.

Abstract

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 (29⁰-33⁶ 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 (29⁰-31⁶ and 32⁰-33⁶ 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 32⁰-33⁶ 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 29⁰-33⁶ weeks' GA with mild respiratory distress syndrome. Confirmation requires further adequately powered studies.

Trial registration number: ACTRN12610000857000.

Keywords: infant, premature; nebulization; respiratory distress syndrome; surfactant.

Publication types

Randomized Controlled Trial

MeSH terms

Continuous Positive Airway Pressure / methods
Double-Blind Method
Feasibility Studies
Female
Humans
Infant, Newborn
Infant, Premature
Intubation, Intratracheal / statistics & numerical data
Male
Nebulizers and Vaporizers
Pulmonary Surfactants / administration & dosage
Pulmonary Surfactants / therapeutic use*
Respiratory Distress Syndrome, Newborn / drug therapy*
Treatment Outcome

Substances

Pulmonary Surfactants