title: Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial.
abstract: BACKGROUND
  Surfactant is usually given to mechanically ventilated preterm infants via an endotracheal tube to treat respiratory distress syndrome. We tested a new method of surfactant application to spontaneously breathing preterm infants to avoid mechanical ventilation.
  
  
  METHODS
  In a parallel-group, randomised controlled trial, 220 preterm infants with a gestational age between 26 and 28 weeks and a birthweight less than 1·5 kg were enrolled in 12 German neonatal intensive care units. Infants were independently randomised in a 1:1 ratio with variable block sizes, to standard treatment or intervention, and randomisation was stratified according to centre and multiple birth status. Masking was not possible. Infants were stabilised with continuous positive airway pressure and received rescue intubation if necessary. In the intervention group, infants received surfactant treatment during spontaneous breathing via a thin catheter inserted into the trachea by laryngoscopy if they needed a fraction of inspired oxygen more than 0·30. The primary endpoint was need for any mechanical ventilation, or being not ventilated but having a partial pressure of carbon dioxide more than 65 mm Hg (8·6 kPa) or a fraction of inspired oxygen more than 0·60, or both, for more than 2 h between 25 h and 72 h of age. Analysis was by intention to treat. This study is registered, number ISRCTN05025922.
  
  
  RESULTS
  108 infants were assigned to the intervention group and 112 infants to the standard treatment group. All infants were analysed. On day 2 or 3 after birth, 30 (28%) infants in the intervention group were mechanically ventilated versus 51 (46%) in the standard treatment group (number needed to treat 6, 95% CI 3-20, absolute risk reduction 0·18, 95% CI 0·30-0·05, p=0·008). 36 (33%) infants in the intervention group were mechanically ventilated during their stay in the hospital compared with 82 (73%) in the standard treatment group (number needed to treat: 3, 95% CI 2-4, p<0·0001). The intervention group had significantly fewer median days on mechanical ventilation, (0 days. IQR 0-3 vs 2 days, 0-5) and a lower need for oxygen therapy at 28 days (30 infants [30%] vs 49 infants [45%], p=0·032) compared with the standard treatment group. We recorded no differences between groups for mortality (seven deaths in the intervention group vs five in the standard treatment group) and serious adverse events (21 vs 28).
  
  
  CONCLUSIONS
  The application of surfactant via a thin catheter to spontaneously breathing preterm infants receiving continuous positive airway pressure reduces the need for mechanical ventilation.
  
  
  BACKGROUND
  German Ministry of Research and Technology, University of Lübeck, and Chiesi Pharmaceuticals.
authors.affiliation: University of Lübeck, Lübeck, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Laux
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoehn
authors.forename: Christian
authors.initials: C
authors.lastname: Wieg
authors.forename: Jens
authors.initials: J
authors.lastname: Siegel
authors.forename: Stefan
authors.initials: S
authors.lastname: Avenarius
authors.forename: Axel
authors.initials: A
authors.lastname: von der Wense
authors.forename: Matthias
authors.initials: M
authors.lastname: Vochem
authors.forename: Peter
authors.initials: P
authors.lastname: Groneck
authors.forename: Ursula
authors.initials: U
authors.lastname: Weller
authors.forename: Jens
authors.initials: J
authors.lastname: Möller
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Haller
authors.forename: Bernhard
authors.initials: B
authors.lastname: Roth
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
mesh_terms: D000280:Administration, Inhalation; D002245:Carbon Dioxide / Q000378:metabolism; D057785:Catheters; D045422:Continuous Positive Airway Pressure; D005260:Female; D006339:Heart Rate; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D008297:Male; D010100:Oxygen / Q000097:blood; D010102:Oxygen Inhalation Therapy / Q000706:statistics & numerical data; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D012121:Respiration, Artificial / Q000706:statistics & numerical data*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy*
chemical_list: D011663:Pulmonary Surfactants; D002245:Carbon Dioxide; D010100:Oxygen