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Thresholds for surfactant use in preterm neonates: a network meta-analysis
  1. Aoife Branagan1,2,
  2. Ivan Yu1,2,
  3. Kurinchi Gurusamy2,3,
  4. Jan Miletin1,4,5,6
  1. 1 Paediatric and Newborn Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland
  2. 2 Division of Surgery and Interventional Science, UCL, London, UK
  3. 3 Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moskva, Russian Federation
  4. 4 UCD School of Medicine, University College Dublin, Dublin, Ireland
  5. 5 Institute for the Care of Mother and Child, Prague, Czech Republic
  6. 6 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic
  1. Correspondence to Dr Aoife Branagan, Paediatric and Newborn Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland; branagaa{at}tcd.ie

Abstract

Objective To perform a network meta-analysis of randomised controlled trials of different surfactant treatment strategies for respiratory distress syndrome (RDS) to assess if a certain fraction of inspired oxygen (FiO2) is optimal for selective surfactant therapy.

Design Systematic review and network meta-analysis using Bayesian analysis of randomised trials of prophylactic versus selective surfactant for RDS.

Setting Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Science Citation Index Expanded.

Patients Randomised trials including infants under 32 weeks of gestational age.

Interventions Intratracheal surfactant, irrespective of type or dose.

Main outcome measures Our primary outcome was neonatal mortality, compared between groups treated with selective surfactant therapy at different thresholds of FiO2. Secondary outcomes included respiratory morbidity and major complications of prematurity.

Results Of 4643 identified references, 14 studies involving 5298 participants were included. We found no statistically significant differences between 30%, 40% and 50% FiO2 thresholds. A sensitivity analysis of infants treated in the era of high antenatal steroid use and nasal continuous positive airway pressure as initial mode of respiratory support showed no difference in mortality, RDS or intraventricular haemorrhage alone but suggested an increase in the combined outcome of major morbidities in the 60% threshold.

Conclusion Our results do not show a clear benefit of surfactant treatment at any threshold of FiO2. The 60% threshold was suggestive of increased morbidity. There was no advantage seen with prophylactic treatment. Randomised trials of different thresholds for surfactant delivery are urgently needed to guide clinicians and provide robust evidence.

PROSPERO registration number CRD42020166620.

  • Intensive Care Units, Neonatal
  • Neonatology
  • Respiratory Medicine

Data availability statement

Data are available upon reasonable request. Data is available on reasonable request to the authors.

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Data availability statement

Data are available upon reasonable request. Data is available on reasonable request to the authors.

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Footnotes

  • Contributors JM contributed to the conception and design of the study idea and methodology, performed study selection and reviewed the manuscript. AB contributed to the conception and design of the study idea and methodology, performed study selection, data extraction and risk of bias assessment, contributed to the interpretation of the data and drafted the manuscript. KG contributed to the conception and design of the study idea and methodology and the interpretation of the data. IY performed data extraction and risk of bias assessment and contributed to the interpretation of the data. All authors critically revised the manuscript, agreed to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript. JM is responsible for the overall content as the guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.