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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.
- infant, premature
- respiratory distress syndrome
- nebulization
- surfactant
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Footnotes
Contributors SM conceptualised and designed the study, designed the data collection instruments, submitted the ethics application, obtained seed funding from the Women and Infants Research Foundation, was the liaison officer with PARI for provision of the nebulisation devices, was the primary recruiting officer at the main study site, reviewed and revised the draft manuscript, and approved the final manuscript as submitted. CAB assisted SM in the design of the data collection instruments, coordinated and supervised the data collection at the two study sites, critically reviewed the manuscript, and approved the final manuscript as submitted. JJPJJ assisted SM in the development of the study design and data collection instruments, assisted SM in obtaining seed funding for the study, obtained the principal funding from the State Health Research Advisory Committee, had primary responsibility for the study, drafted the initial manuscript and approved the final manuscript as submitted.
Funding Grants from the State Health Research Advisory Committee and the Women and Infants Research Foundation, WA, supported all phases of this study. SM was supported by the Swiss National Science Foundation. JJP is supported by an NHMRC Senior Research Fellowship (GRT1077691). Fisher & Paykel Healthcare provided ventilator circuits for the nebulisation but had no role in the study design, conduct, data analysis, writing of the manuscript or decision to submit it for publication. PARI Pharma provided equipment for nebulisation. PARI Pharma approved the technical description of their equipment in the manuscript but had no other role in the study design, conduct, data analysis, writing of the manuscript or decision to submit it for publication. SM (via the University of Bern, Switzerland) holds a patent with PARI Pharma for nebulisation with a vibrating membrane (EP 1818070 A3).
Competing interests JJP receives unrestricted grants of surfactant product from Chiesi Farmaceutici SpA (Parma, Italy) for unrelated neonatal ventilation research in preterm lambs. Surfactant for the current study was purchased from the hospital pharmacy at retail price using grant funding described above. JJP has also received equipment and unrestricted grant funding from Fisher & Paykel for unrelated preterm lamb research in the past. SM has a conflict of interest as disclosed above in relation to his patent with PARI Pharma.
Patient consent Not required.
Ethics approval The Human Ethics Committees of King Edward Memorial Hospital (KEMH) and the University of Western Australia approved the registered study (ACTRN12610000857000).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Individual de-identified participant data that underlie the results reported in this article are available on reasonable request until 5 years after publication to researchers who provide a methodologically sound proposal and whose use of the data has been approved by an independent review panel, where appropriate.
Collaborators Prof Karen Simmer, Dr Ronny Hagan, A/Prof Sunalene Devadason