Comparative efficacy of methods for surfactant administration: a network meta-analysis

Arch Dis Child Fetal Neonatal Ed. 2021 Sep;106(5):474-487. doi: 10.1136/archdischild-2020-319763. Epub 2021 Jan 15.


Objectives: To compare surfactant administration via thin catheters, laryngeal mask, nebulisation, pharyngeal instillation, intubation and surfactant administration followed by immediate extubation (InSurE) and no surfactant administration.

Design: Network meta-analysis.

Setting: Medline, Scopus, CENTRAL, Web of Science, Google-scholar and databases were systematically searched from inception to 15 February 2020.

Patients: Preterm neonates with respiratory distress syndrome.

Interventions: Less invasive surfactant administration.

Main outcome measures: The primary outcomes were mortality, mechanical ventilation and bronchopulmonary dysplasia.

Results: Overall, 16 randomised controlled trials (RCTs) and 20 observational studies were included (N=13 234). For the InSurE group, the median risk of mortality, mechanical ventilation and bronchopulmonary dysplasia were 7.8%, 42.1% and 10%, respectively. Compared with InSurE, administration via thin catheter was associated with significantly lower rates of mortality (OR: 0.64, 95% CI: 0.54 to 0.76), mechanical ventilation (OR: 0.43, 95% CI: 0.29 to 0.63), bronchopulmonary dysplasia (OR: 0.57, 95% CI: 0.44 to 0.73), periventricular leukomalacia (OR: 0.66, 95% CI: 0.53 to 0.82) with moderate quality of evidence and necrotising enterocolitis (OR: 0.67, 95% CI: 0.41 to 0.9, low quality of evidence). No significant differences were observed by comparing InSurE with administration via laryngeal mask, nebulisation or pharyngeal instillation. In RCTs, thin catheter administration lowered the rates of mechanical ventilation (OR: 0.39, 95% CI: 0.26 to 0.60) but not the incidence of the remaining outcomes.

Conclusion: Among preterm infants, surfactant administration via thin catheters was associated with lower likelihood of mortality, need for mechanical ventilation and bronchopulmonary dysplasia compared with InSurE. Further research is needed to reach firm conclusions about the efficacy of alternative minimally invasive techniques of surfactant administration.

Keywords: mortality; neonatology; resuscitation.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Administration, Inhalation
  • Bronchopulmonary Dysplasia / etiology
  • Catheterization
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Laryngeal Masks
  • Leukomalacia, Periventricular / etiology
  • Nebulizers and Vaporizers
  • Network Meta-Analysis
  • Pulmonary Surfactants / administration & dosage*
  • Respiration, Artificial
  • Respiratory Distress Syndrome, Newborn / complications
  • Respiratory Distress Syndrome, Newborn / drug therapy*


  • Pulmonary Surfactants

Supplementary concepts

  • Respiratory Distress Syndrome In Premature Infants