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Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome (review)1

 

Abdel-Latif, M. E., Davis, P. G., Wheeler, K. I., De Paoli, A. G., & Dargaville, P. A. (2021). Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome. The Cochrane database of systematic reviews, 5(5)

 

Introduction

 
 

Preterm infants with respiratory distress syndrome (RDS) require surfactant therapy to address surfactant deficiency. Traditional surfactant administration via an endotracheal tube (ETT) often necessitates intubation and mechanical ventilation (MV), increasing the risk of lung injury and complications like bronchopulmonary dysplasia (BPD).

 

 

 

Non-invasive respiratory support is increasingly used for the management of RDS in preterm infants, but this approach can risk undertreating infants with RDS who require surfactant. Several methods of minimally invasive surfactant therapy (MIST) have been described. This Cochrane review by Abdel-Latif et al. evaluated the efficacy and safety of surfactant administration via a thin catheter briefly inserted into the trachea to spontaneously breathing infants.

 

Study design:

  • Study Design Type: Cochrane systematic review and meta-analysis
  • Participants: Preterm infants (<37 weeks’ gestation) with established or at-risk RDS
  • Included Studies: 16 randomised controlled trials (RCTs) with 2,164 infants (Figure 1)  
  • Primary objectives:

    In non-intubated preterm infants with established RDS or at risk of developing RDS to compare surfactant administration via thin catheter with:
    • Intubation and surfactant administration through an ETT
    • Continuation of non-invasive respiratory support without surfactant administration or intubation
  •  Secondary objective:
    • To compare different methods of surfactant administration via thin catheter
 

Planned subgroup analyses included gestational age, timing of intervention, and use of sedating pre-medication during the intervention.

 

Adapted from Abdel-Latif, et al. 2021. 

 

Results:1

 
 

Death or BPD (Figure 1):

  • LISA vs. InSurE:
    • Meta-analysis of nine studies (1,113 infants) demonstrated a significant reduction in risk with LISA (RR 0.52 [95% CI: 0.40 to 0.68]; RD -0.11 [95% CI: -0.16 to -0.07]; NNTB 9 [95% CI: 6 to 15]; heterogeneity among the studies was low [I2 = 2 %]).
  • LISA vs. surfactant via ETT with delayed extubation:
    • One study (211 infants) found no significant difference in risk (RR 0.79 [95% CI: 0.55 to 1.13]; RD -0.09 [95% CI: -0.22 to -0.04]).
    • Meta-analysis of 10 studies (1,324 infants) demonstrated a significant reduction in risk with LISA (RR 0.59 [95% CI: 0.48 to 0.73]; RD -0.11 [95% CI: -0.15 to -0.07]; NNTB 9 [95% CI: 7 to 16]; heterogeneity among the studies was low [I2 = 19%]).
 
 
 

Need for MV within the first 72 hours (Figure 2): 

  • LISA vs. InSurE:
    • Meta-analysis of 10 studies (1,166 infants) demonstrated a significant reduction in risk with LISA (RR 0.61 [95% CI: 0.50 to 0.75]; RD -0.12 [95% CI: -0.17 to -0.07]; NNTB 8 [95% CI: 6 to 14]). There was no heterogeneity (I² = 0%)
  • LISA vs. surfactant via ETT with delayed extubation:
    • Meta-analysis of two studies (256 infants) showed a significant reduction in risk with LISA (RR 0.68 [95% CI: 0.53 to 0.86]; RD -0.21 [95% CI: -0.32 to -0.09]; NNTB 5 [95% CI: 3 to 12]). Heterogeneity was high (I² = 85%)
    • Meta-analysis of 12 studies (1,422 infants) revealed a significant risk reduction with LISA (RR 0.63 [95% CI: 0.54 to 0.74]; RD -0.14 [95% CI: -0.18 to -0.09]; NNTB 8 [95% CI: 6 to 12]). Heterogeneity was low
      z(I² = 31%). Funnel plot analysis indicated no evidence of publication bias (Egger test, p=0.322)
 
 
 

Air leak requiring drainage (during first hospitalisation) (Figure 3): 

  • LISA vs. InSurE:
    • Meta-analysis of four studies (783 infants) showed no significant difference in risk between LISA and InSurE (RR 0.72 [95% CI: 0.35 to 1.48]; RD -0.01 [95% CI: -0.04 to -0.01]). There was no heterogeneity (I² = 0%)
  • LISA vs. surfactant via ETT with delayed extubation:  
    • Meta-analysis of two studies (253 infants) showed no significant difference in risk between LISA and surfactant via ETT with delayed extubation (RR 0.41 [95% CI: 0.16 to 1.05]; RD -0.07 [95% CI: -0.13 to -0.00]). Heterogeneity was absent (I² = 0%)
    • Meta-analysis of six studies (1,036 infants) revealed no significant difference in risk between LISA and surfactant via ETT (RR 0.58 [95% CI: 0.33 to 1.02]; RD -0.03 [95% CI: -0.05 to -0.00]). There was no heterogeneity (I² = 0%) 
 
 
 

Severe IVH, including Grade 3 and 4 (Figure 4): 

  • LISA vs. InSurE:
    • Meta-analysis of four studies (646 infants) showed no significant difference in risk between LISA and InSurE (RR 0.77 [95% CI: 0.45 to 1.32]; RD -0.02 [95% CI: -0.06 to -0.02]). There was no heterogeneity (I² = 0%)
  • LISA vs. surfactant via ETT with delayed extubation:  
    • One study (211 infants) demonstrated a significant reduction in risk with LISA compared with surfactant via ETT with delayed extubation (RR 0.46 [95% CI: 0.24 to 0.90]; RD -0.12 [95% CI: -0.22 to -0.02]; NNTB 8 [95% CI: 5 to 49])
    • Meta-analysis of five studies (857 infants) revealed a significant reduction in risk with LISA compared with surfactant via ETT (RR 0.63 [95% CI: 0.42 to 0.96]; RD -0.04 [95% CI: -0.08 to -0.00]; NNTB 22 [95% CI: 2 to 193]). There was no heterogeneity (I² = 0%)  
 
 
 

Death during first hospitalisation (Figure 5): 

  • LISA vs. InSurE:
    • Meta-analysis of nine studies (1,213 infants) demonstrated a significant reduction in risk with LISA compared with InSurE (RR 0.60 [95% CI: 0.44 to 0.82]; RD -0.05 [95% CI: -0.09 to -0.02]; NNTB 19 [95% CI: 11 to 52]) Heterogeneity was low (I² = 0%) 
  • LISA vs. surfactant via ETT with delayed extubation:  
    • One study (211 infants) showed no significant difference in risk between LISA and surfactant via ETT with delayed extubation (RR 0.81 [95% CI: 0.37 to 1.79]; RD -0.02 [95% CI: -0.10 to -0.06]) 
    • Meta-analysis of 10 studies (1,424 infants) revealed a significant reduction in risk with LISA compared with surfactant via ETT (RR 0.63 [95% CI: 0.47 to 0.84]; RD -0.02 [95% CI: -0.10 to -0.06]; NNTB 20 [95% CI: 12 to 58]). Heterogeneity among the studies was low (I² = 0%). Funnel plot analysis showed no evidence of publication bias (Egger test, p=0.217; data not shown) 
 
 
 

BPD among survivors at 36 weeks PMA (Figure 6): 

  • LISA vs. InSurE:
    • Meta-analysis of 10 studies (1,378 infants) showed a significant reduction in risk with LISA compared with InSurE (RR 0.57 [95% CI: 0.44 to 0.75]; RD -0.07 [95% CI: -0.11 to -0.04]; NNTB 14 [95% CI: 9 to 28]). Heterogeneity was low (I² = 15%)
  • LISA vs. surfactant via ETT with delayed extubation:  
    • One study (189 infants) showed no significant difference in risk between LISA and surfactant via ETT with delayed extubation
      (RR 0.58 [95% CI: 0.32 to 1.05]; RD -0.11 [95% CI: -0.22 to -0.01])
  •   
    • Meta-analysis of 11 studies (1,567 infants) demonstrated a significant reduction in risk with LISA compared with surfactant via ETT (RR 0.57 [95% CI: 0.45 to 0.74]; RD -0.08 [95% CI: -0.11 to -0.04]; NNTB 13 [95% CI: 9 to 24]). There was no heterogeneity (I² = 0%). Funnel plot analysis showed no evidence of publication bias (Egger test, p=0.373; data not shown) 
 
 

Safety:

 

The meta-analysis found that LISA was ‘generally safe and well-tolerated’, with similar rates of bradycardia, hypoxaemia, and procedural complications compared with surfactant administration via ETT.

 

There was no significant difference in the number of attempts needed to instrument the trachea with a thin catheter versus an ETT. However, surfactant reflux occurred more frequently with the thin catheter technique. Other hospital outcomes, including PDA, IVH, and ROP, were comparable between the two methods (data not shown).

 

Conclusion:

 

LISA significantly reduces the risk of death or BPD, need for MV, severe IVH, and in-hospital death during first hospitalisation compared to traditional ETT administration. The technique demonstrated similar safety profiles and reduced the invasiveness of treatment. 

 
 
 

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Abbreviations

 

Apgar, appearance, pulse, grimace, activity, and respiration; BPD, bronchopulmonary dysplasia; CI, confidence interval; ETT, endotracheal tube; I², measure of heterogeneity in meta-analyses; IVH, intraventricular haemorrhage; LISA, less invasive surfactant administration; MV, mechanical ventilation; NNTB, number needed to treat for benefit; PDA, patent ductus arteriosus; PMA, postmenstrual age; RD, risk difference; RDS, respiratory distress syndrome; ROP, retinopathy of prematurity; RR, relative risk; S-TC, surfactant administration via thin catheter. 

 
 

References

  1. Abdel-Latif M, et al. Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2021;5(5):CD011672. doi: 10.1002/14651858.CD011672.pub2.
 
 

IE-CUR-2500003 | April 2025

 

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