ArticlesAvoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial
Introduction
Continuous positive airway pressure (CPAP) and non-invasive ventilation are used in adults and children to avoid endotracheal intubation.1, 2, 3 Preterm infants are frequently treated with surfactant for respiratory distress syndrome.4 Surfactant is usually given via the endotracheal tube during mechanical ventilation. Therefore, preterm infants who are stabilised after birth without intubation are not treated with surfactant, which is a disadvantage of CPAP.
An approach of intubation, surfactant application during brief mechanical ventilation, and extubation before nasal CPAP has previously been used.5, 6, 7, 8, 9, 10 A meta-analysis of the use of this technique reported a reduced need for mechanical ventilation but increased surfactant use.11 The method still requires sedation, intubation, and short mechanical ventilation, and because similar outcomes have been reported for infants treated with CPAP alone,2, 9, 12 the technique of intubation, surfactant, and extubation has not been widely used.
A method of surfactant application without endotracheal intubation and mechanical ventilation has become widespread in German neonatal intensive care units. Surfactant is given to spontaneously breathing preterm infants on CPAP via a thin catheter placed in the trachea only for the time needed to give the surfactant (webvideo 1).13, 14 Observational, multicentre data suggest that this method might reduce the need for mechanical ventilation.15 However, the safety and efficacy of this method have not been tested in a randomised controlled trial.
We postulated that the application of surfactant to spontaneously breathing preterm infants would reduce the percentage of infants who subsequently need mechanical ventilation.
Section snippets
Study design and patients
The Avoiding Mechanical Ventilation (AMV) trial was a multicentre, randomised, controlled parallel-group study done at 12 neonatal intensive care units (level three) in Germany between October, 2007, and January, 2010. The protocol was approved by the ethics committee of each participating centre and done in accordance with good clinical practice guidelines and all applicable regulatory rules. Preterm infants with a gestational age from 26 weeks to 28 weeks plus 6 days, and with a birthweight
Results
Figure 1 shows the trial profile. Between Oct, 8, 2007, and Aug 1, 2009, 403 infants were eligible for the study in 12 centres. 220 infants (55%) were enrolled and analysed (figure 1). No significant differences were reported between included and excluded infant's birthweight, gestational age, bronchopulmonary dysplasia or death (data not shown). The trial was completed as planned; the last patient was discharged in January, 2010. 112 infants were randomly assigned to receive standard treatment
Discussion
Findings from this study have shown that the application of surfactant to spontaneously breathing preterm infants is feasible and reduces the need for subsequent mechanical ventilation. This effect was apparent in our primary analysis, which was designed to account for the variability of each gestational age group, but was even more pronounced in the subgroup of infants who were stabilised with CPAP after birth.
Infants with established respiratory distress syndrome who received animal-derived
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These authors contributed equally to the work