title: Open lung ventilation preserves the response to delayed surfactant treatment in surfactant-deficient newborn piglets.
abstract: OBJECTIVE
  Delayed surfactant treatment (>2 hrs after birth) is less effective than early treatment in conventionally ventilated preterm infants with respiratory distress syndrome. The objective of this study was to evaluate if this time-dependent efficacy of surfactant treatment is also present during open lung ventilation.
  
  
  METHODS
  Prospective, randomized controlled animal study.
  
  
  METHODS
  University-affiliated research laboratory.
  
  
  METHODS
  Thirty-eight newborn piglets.
  
  
  METHODS
  Following repeated whole-lung lavage, animals were randomly allocated to conventional positive pressure ventilation (PPVCON) using a positive end-expiratory pressure (PEEP) of 5 cm H2O and a tidal volume of 7 mL/kg or open lung positive pressure ventilation (PPVOLV). During PPVOLV, collapsed alveoli were actively recruited and thereafter stabilized with sufficient PEEP. Within each ventilation group, animals received surfactant (25 mg/kg) either after 2 hrs (PPVCON-2 and PPVOLV-2) or after 4 hrs (PPVCON-4 and PPVOLV-4) of ventilation. A control group received surfactant immediately after lung lavage. Following surfactant administration, all animals were conventionally ventilated for an additional 2 hrs.
  
  
  RESULTS
  Two hours after surfactant treatment, both oxygenation and lung mechanics showed a clear deterioration in the PPVCON-4 group compared with PPVCON-2 and the control group. However, this deterioration of the surfactant response over time was not observed during PPVOLV. Analysis of the bronchoalveolar lavage fluid obtained at the end of the experiment showed that the protein concentration and the conversion of large to small aggregate surfactant was significantly higher in the PPVCON-4 group compared with the PPVCON-2 group while comparable in both PPVOLV groups. In addition, interleukin-8 and myeloperoxidase levels tended to be higher in the PPVCON-4 group compared with the PPVOLV-4 group.
  
  
  CONCLUSIONS
  In contrast to conventional ventilation, open lung ventilation preserves the response to delayed surfactant treatment in surfactant-deficient newborn piglets. This sustained response is accompanied by an attenuation of secondary lung injury.
authors.affiliation: Department of Neonatology, Emma Children's Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mariëtte B
authors.initials: MB
authors.lastname: van Veenendaal
authors.forename: Anton H
authors.initials: AH
authors.lastname: van Kaam
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.forename: Burkhard
authors.initials: B
authors.lastname: Lachmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007385:Intermittent Positive-Pressure Ventilation; D008170:Lung Compliance; D010100:Oxygen / Q000378:metabolism; D011659:Pulmonary Gas Exchange; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy*; D015656:Respiratory Mechanics; D013552:Swine; D013997:Time Factors
chemical_list: D016207:Cytokines; D011663:Pulmonary Surfactants; D010100:Oxygen