title: Nonintubated Surfactant Application vs Conventional Therapy in Extremely Preterm Infants: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Treatment of respiratory distress syndrome in premature infants with continuous positive airway pressure (CPAP) preserves surfactant and keeps the lung open but is insufficient in severe surfactant deficiency. Traditional surfactant administration is related to short periods of positive pressure ventilation and implies the risk of lung injury. CPAP with surfactant but without any positive pressure ventilation may work synergistically. This randomized trial investigated a less invasive surfactant application protocol (LISA).
  
  
  OBJECTIVE
  To test the hypothesis that LISA increases survival without bronchopulmonary dysplasia (BPD) at 36 weeks' gestational age in extremely preterm infants.
  
  
  METHODS
  The Nonintubated Surfactant Application trial was a multicenter, randomized, clinical, parallel-group study conducted between April 15, 2009, and March 25, 2012, in 13 level III neonatal intensive care units in Germany. The final follow-up date was June 21, 2012. Participants included 211 of 558 eligible (37.8%) spontaneously breathing preterm infants born between 23.0 and 26.8 weeks' gestational age with signs of respiratory distress syndrome. In an intention-to-treat design, infants were randomly assigned to receive surfactant either via a thin endotracheal catheter during CPAP-assisted spontaneous breathing (intervention group) or after conventional endotracheal intubation during mechanical ventilation (control group). Analysis was conducted from September 6, 2012, to June 20, 2013.
  
  
  METHODS
  LISA via a thin catheter.
  
  
  METHODS
  Survival without BPD at 36 weeks' gestational age.
  
  
  RESULTS
  Of 211 infants who were randomized, 104 were randomized to the control group and 107 to the LISA group. Of the infants who received LISA, 72 (67.3%) survived without BPD compared with 61 (58.7%) of those in the control group. The reduction in absolute risk was 8.6% (95% CI, -5.0% to 21.9%; P = .20). Intervention group infants were less frequently intubated (80 infants [74.8%] vs 103 [99.0%]; P < .001) and required fewer days of mechanical ventilation. Significant reductions were seen in pneumothorax (5 of 105 intervention group infants [4.8%] vs 13 of 103 12.6%]; P = .04) and severe intraventricular hemorrhage (11 infants [10.3%] vs 23 [22.1%]; P = .02), and the combined survival without severe adverse events was increased in the intervention group (54 infants [50.5%] vs 37 [35.6%]; P = .02; absolute risk reduction, 14.9; 95% CI, 1.4 to 28.2).
  
  
  CONCLUSIONS
  LISA did not increase survival without BPD but was associated with increased survival without major complications. Because major complications are related to lifelong disabilities, LISA may be a promising therapy for extremely preterm infants.
  
  
  BACKGROUND
  isrctn.org Identifier: ISRCTN64011614.
authors.affiliation: Department of Neonatology, Children's Hospital University of Cologne, Cologne, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.affiliation: Department of Neonatology and Pediatric Intensive Care, University Witten-Herdecke, Vest Children's Hospital, North Rhine-Westphalia, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Roll
authors.affiliation: Department of Neonatology, Children's Hospital, University of Lübeck, Lübeck, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
authors.affiliation: Department of Neonatology, Children's Hospital Aschaffenburg, Aschaffenburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wieg
authors.affiliation: Department of Neonatology, Children's Hospital Leverkusen, Leverkusen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Groneck
authors.affiliation: Department of Neonatology, Asklepios Klinik Barmbek, Hamburg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Laux
authors.affiliation: Department of Neonatology, Children's Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Teig
authors.affiliation: Department of General Pediatrics, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoehn
authors.affiliation: Department of Neonatology, Children's Hospital Siegen, Siegen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Böhm
authors.affiliation: Department of Neonatology, University of Bonn, Bonn, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Welzing
authors.affiliation: Department of Neonatology, Olgahospital Stuttgart, Stuttgart, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Vochem
authors.affiliation: Department of Neonatology and Pediatric Intensive Care Medicine, Children's Hospital, Cologne, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Hoppenz
authors.affiliation: Department of Neonatology, Charité University Medical Center, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
authors.affiliation: Department of Neonatology, Children's Hospital University of Cologne, Cologne, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Mehler
authors.affiliation: Institute of Medical Statistics, Informatics, and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Stützer
authors.affiliation: Institute of Medical Statistics, Informatics, and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Franklin
authors.affiliation: Center for Clinical Studies, Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stöhr
authors.affiliation: Department of Neonatology, Children's Hospital, University of Lübeck, Lübeck, Germany.
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
authors.affiliation: Department of Neonatology, Children's Hospital University of Cologne, Cologne, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Roth
mesh_terms: D002404:Catheterization; D045422:Continuous Positive Airway Pressure; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007442:Intubation, Intratracheal; D008297:Male; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D011663:Pulmonary Surfactants