Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial1
Göpel, W., Kribs, A., Ziegler, A., Laux, R., Hoehn, T., Wieg, C., Siegel, J., Avenarius, S., von der Wense, A., Vochem, M., Groneck, P., Weller, U., Möller, J., Härtel, C., Haller, S., Roth, B., Herting, E., & German Neonatal Network (2011). Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet (London, England), 378(9803), 1627–1634.
Introduction
At the time of the Göpel study, the INtubate-SURfactant-Extubate (INSURE) method was commonly used to deliver surfactant to preterm infants with respiratory distress syndrome (RDS). While effective, INSURE requires brief intubation and mechanical ventilation (MV), which carries risks of lung injury and other complications including bronchopulmonary dysplasia (BPD).2
Recognising the importance of early, non-invasive intervention, this study aimed to test Less Invasive Surfactant Administration (LISA), an approach designed to deliver surfactant via a thin catheter to spontaneously breathing infants on continuous positive airway pressure (CPAP). By allowing infants to continue breathing on their own, LISA was proposed as a gentler, early intervention strategy that could reduce the need for MV and improve respiratory outcomes, offering a potentially safer alternative for managing RDS in vulnerable preterm infants.1
Study design:1
The Avoiding Mechanical Ventilation (AMV) trial was a multicentre, open-label, randomised controlled trial conducted across 12 neonatal intensive care units in Germany from October 2007 to January 2010.
A total of 220 preterm infants (gestational age [GA] 26–28 weeks, birthweight <1.5 kg) were randomised in a 1:1 ratio to receive either standard care (CPAP with rescue intubation and surfactant if needed) or intervention (CPAP with surfactant administration while spontaneously breathing if FiO₂ >0.30). Randomisation was stratified by treatment centre and multiple births, with an intention-to-treat analysis performed.
| n (%) | Intervention group (n=108) | Standard treatment group (n=112) |
|---|---|---|
| Gestational age (weeks) | 27.6 (0.8) | 27.5 (0.8) |
| Birthweight (g) | 975 (244) | 938 (205) |
| Mean cord blood arterial pH | 7.34 (0.07) | 7.34 (0.08) |
| Postnatal CO2 (mm Hg) | 55 (13)* | 53 (12)† |
| First recorded FiO2 | 0.32 (0.14) | 0.33 (0.18) |
| Boys | 53 (49%) | 58 (52%) |
| Multiple births | 37 (34%) | 35 (31%) |
| Use of antenatal steroids | 104 (96%) | 107 (96%) |
| Caesarean section | 101 (94%) | 104 (93%) |
| Outborn | 0 | 1 (1%) |
*7.3 kPa (1.7); †7.1 kPa (1.6)
Results:1
Out of the 220 enrolled infants, 108 received the intervention, and 112 received standard care.
Key findings include:
Primary endpoint:
The primary outcome was the need for MV or, if not ventilated, having a pCO₂ level over 65 mm Hg (8.6 kPa) or an FiO₂ ≥0.60, or both, for more than 2 h within 25–72 h after birth.
30 infants (28%) in the LISA group required MV by day 2 or 3, compared with 51 infants (46%) in the standard care group, with a relative risk (RR) of 0.70 (95% CI: 0.54–0.90; p=0.008). This equates to an absolute risk reduction of 18% (-0.18 [-0.30 to -0.05]), and a number needed to treat (NNT) of 6 (95% CI: 3–20). The overall values, along with those broken down by GA, are displayed in Figure 2.
Overall MV:
LISA significantly reduced the need for MV across all infants and within each GA group.
During the entire hospital stay, only 36 infants (33%) in the LISA group required MV, compared with 82 infants (73%) in the standard care group (RR 0.42, 95% CI: 0.31–0.59; p<0.0001). This equates to an absolute risk reduction of 40% (-0.40 [-0.52 to -0.27]) with a NNT of 3 (95% CI: 2–4) (Figure 3).
Need for intubation and MV in the first 28 days:
Figure 4 illustrates the number of infants in each arm who avoided intubations entirely during the first 28 days after birth. In both the LISA and standard care groups, the majority of intubations occurred between days 1 and 4.
Additional pulmonary outcomes:
Significant differences were observed in additional pulmonary outcomes between the groups. Infants in the LISA group had significantly fewer days on MV (median 0 days, IQR 0–3) compared with the standard care group (median 2 days, IQR 0–5; p<0.0001). Additionally, at 28 days, only 30 infants (30%) in the LISA group required supplemental oxygen, compared with 49 infants (45%) in the standard care group (p=0.032). Additional outcomes which did not reach statistical significance are also shown in Figure 5.
Conclusion:1
The study demonstrated that LISA is an effective approach for administering surfactant to spontaneously breathing preterm infants, offering several benefits over standard care. Infants in the LISA group experienced a significantly reduced need for MV, fewer days on respiratory support, and a lower requirement for supplemental oxygen at 28 days.
At the time, this study made a significant contribution to neonatal care by providing strong evidence that surfactant could be effectively administered without intubation. By offering a less invasive option with clear benefits, the study paved the way for wider adoption of LISA as a standard approach to managing respiratory distress syndrome in preterm infants, potentially improving early respiratory outcomes and reducing the risks associated with MV.
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Abbreviations
AMV, Avoiding Mechanical Ventilation; BPD, bronchopulmonary dysplasia, CI, confidence interval; CPAP, continuous positive airway pressure; FiO₂, fraction of inspired oxygen; GA, gestational age; IQR, interquartile range; INSURE, intubate-surfactant-extubate; LISA, less invasive surfactant administration; MV, mechanical ventilation; NNT, number needed to treat; pCO₂, partial pressure of carbon dioxide; RDS, respiratory distress syndrome; RR, relative risk; SD, standard deviation.
References
- Göpel W, et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet. 2011;378(9803):1627–34.
- Stevens TP, Harrington EW, Blennow M, Soll R. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev 2007; 4:CD003063.
IE-CUR-2400062 | January 2025
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