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Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis

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Abstract

Less invasive surfactant therapies (LIST) use surfactant instillation through a thin tracheal catheter in spontaneously breathing infants. This review and meta-analysis investigates respiratory outcomes for preterm infants with respiratory distress syndrome treated with LIST rather than administration of surfactant through an endotracheal tube. Randomised controlled trial (RCT) full texts provided outcome data for bronchopulmonary dysplasia (BPD), death or BPD, early CPAP failure, invasive ventilation requirements and usual neonatal morbidities. Relative risks (RR) from pooled data, with subgroup analyses, were obtained from a Mantel-Haenszel analysis using a random effect model. Six RCTs evaluated LIST: 4 vs InSurE and 1 each vs delayed or immediate intubation for surfactant. LIST resulted in decreased risks of BPD (RR = 0.71 [0.52–0.99]; NNT = 21), death or BPD (RR = 0.74 [0.58–0.94]; NNT = 15) and early CPAP failure or invasive ventilation requirements (RR = 0.67 [0.53–0.84]; NNT = 8 and RR = 0.69 [0.53–0.88]; NNT = 6). Compared to InSurE, LIST decreased the risks of BPD or death (RR = 0.63 [0.44–0.92]; NNT = 11) and of early CPAP failure (RR = 0.71 [0.53–0.96]; NNT = 11). Common neonatal morbidities were not different.

Conclusions: Respiratory management with LIST decreases the risks of BPD and BPD or death, and the need for invasive ventilation. This strategy appears safe, but long-term follow-up is lacking.

What is Known:

• Initial management of preterm infants with CPAP decreases the risk of death or BPD, but many still require surfactant or invasive ventilation.

• Surfactant can be instilled through a tracheal thin catheter while the infant breathes on CPAP, but improvement in BPD is inconsistent between studies.

What is New:

• Less invasive surfactant therapy (LIST) strategies decrease the risks of BPD, of death or BPD, and of CPAP failure compared to strategies where surfactant is administered through an endotracheal tube.

• LIST strategies decrease the risks of the composite outcome of BPD or death and of early CPAP failure when compared to “intubation-surfactant-extubation” approaches.

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Abbreviations

AMV:

Avoidance of Mechanical Ventilation Study

BPD:

Bronchopulmonary dysplasia (here: moderate to severe)

cPVL:

Cystic periventricular leucomalacia

InSurE:

Intubation-surfactant-extubation

IVH:

Intraventricular haemorrhage

LISA:

Less invasive surfactant administration

LIST:

Less invasive surfactant therapy

MV:

Mechanical ventilation

MIST:

Minimally invasive surfactant therapy

nCPAP:

Nasal continuous positive airway pressure

NEC:

Necrotising enterocolitis

NNT/H:

Numbers needed to treat/to harm

NINSAP:

Nonintubated Surfactant Application Study

PDA:

Patent ductus arteriosus

RCT:

Randomised controlled trial

ROP:

Retinopathy of prematurity

RR:

Relative risk

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Acknowledgments

We thank Professor Filip Cools (AZ-VUB, Brussels) for his helpful comments on a previous version of this manuscript. We thank Mr. Luc Hourlay (KCE, Centre fédéral d’expertise des soins de santé, Brussels) for his assistance in the EMBASE search.

Authors’ Contributions

VR designed the study, analysed the data and wrote the initial draft of the manuscript. VR and CL performed the literature search. VR and IB evaluated the RCTs and extracted the data. All the authors interpreted the results and revised and approved the manuscript.

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Authors and Affiliations

  1. Neonatology division, CHU de Liège, University of Liège, and CHR Citadelle, Boulevard du 12ème de Ligne 1, 4000, Liège, Belgium

    Vincent Rigo, Caroline Lefebvre & Isabelle Broux

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  1. Vincent Rigo
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  2. Caroline Lefebvre
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  3. Isabelle Broux
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Corresponding author

Correspondence to Vincent Rigo.

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Conflict of interest

VR has received speaker honoraria and sponsoring to attend a scientific meeting from Chiesi Belgium, a surfactant-producing company. The company was not involved in this study. CL and IB declare having no conflict of interest.

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Ethical approval

This article does not contain any study with human participants performed by any of the authors. All studies included in the meta-analysis were approved by ethical review boards and requested parental consent.

Additional information

Communicated by Patrick Van Reempts

Electronic supplementary material

Online Resource 1

Figure: Flow diagram for selection of eligible studies. (PDF 224 kb)

Online Resource 2

Table: Risk of bias assessment. (PDF 41 kb)

Online Resource 3

Figure: Forest plots for each dichotomous outcomes. (PDF 318 kb)

Online Resource 4

Figure: Forest plots for infants born below 29 weeks. (PDF 124 kb)

Online Resource 5

Table: Data for continuous outcomes. (PDF 55 kb)

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Rigo, V., Lefebvre, C. & Broux, I. Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis. Eur J Pediatr 175, 1933–1942 (2016). https://doi.org/10.1007/s00431-016-2789-4

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