title: Lung-protective ventilation strategies in neonatology: what do we know--what do we need to know?
abstract: OBJECTIVE
  Randomized controlled trials (RCTs) investigating various lung-protective ventilation modes or strategies in newborn infants have failed to show clear differences in mortality or bronchopulmonary dysplasia. This review tries to identify possible reasons for this observation, applying modern concepts on ventilator-induced lung injury and lung-protective ventilation.
  
  
  METHODS
  Published RCTs and systematic reviews on mechanical ventilation in newborn infants were identified by searching PubMed and the Cochrane Library.
  
  
  RESULTS
  A total of 16 RCTs and four systematic reviews comparing high-frequency ventilation with conventional mechanical ventilation (CMV) failed to show consistent differences in mortality and bronchopulmonary dysplasia. Unfortunately, clear information or data on ventilation and oxygenation targets in the search for optimal lung volumes during high-frequency ventilation or CMV is lacking in many RCTs, questioning the validity of the results and the meta-analytic subgroup analysis. Based on improvement in oxygenation, only three RCTs successfully applied the optimal lung volume strategy during high-frequency ventilation. A total of 24 RCTs and three systematic reviews comparing various CMV modes and settings and two RCTs investigating permissive hypercapnia reported no differences in mortality or bronchopulmonary dysplasia. However, the intervention arms in these RCTs did not differ in tidal volume or positive end-expiratory pressures, variables that are considered important determinants in ventilator-induced lung injury. In fact, no RCT in newborn infants has substantiated so far the experimental finding that avoiding large tidal volumes and low positive end-expiratory pressure during CMV is lung protective in newborn infants.
  
  
  CONCLUSIONS
  RCTs investigating lung-protective ventilation in neonates have mainly focused on comparing high-frequency ventilation with CMV. Most of these RCTs show weaknesses in the design, which may explain the inconsistent effect of high-frequency ventilation on bronchopulmonary dysplasia. RCTs on CMV only focused on comparing various modes and settings, leaving the important question whether reducing tidal volume or increasing positive end-expiratory pressure is also lung protective in newborn infants unanswered.
authors.affiliation: Department of Neonatology, Emma Children's Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anton H
authors.initials: AH
authors.lastname: van Kaam
authors.forename: Peter C
authors.initials: PC
authors.lastname: Rimensberger
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000401:mortality / Q000517:prevention & control*; D002245:Carbon Dioxide / Q000097:blood; D006612:High-Frequency Ventilation / Q000379:methods; D017052:Hospital Mortality; D006801:Humans; D007231:Infant, Newborn; D008176:Lung Volume Measurements; D015201:Meta-Analysis as Topic; D010100:Oxygen / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012121:Respiration, Artificial / Q000379:methods*; D012127:Respiratory Distress Syndrome, Newborn / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen