title: High PEEP in acute respiratory distress syndrome: quantitative evaluation between improved arterial oxygenation and decreased oxygen delivery.
abstract: BACKGROUND
  Positive end-expiratory pressure (PEEP) is widely used to improve oxygenation and prevent alveolar collapse in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). Although PEEP improves arterial oxygenation predictably, high-PEEP strategies have demonstrated equivocal improvements in ARDS-related mortality. The effect of PEEP on tissue oxygen delivery is poorly understood and is difficult to quantify or investigate in the clinical environment.
  
  
  METHODS
  We investigated the effects of PEEP on tissue oxygen delivery in ARDS using a new, high-fidelity, computational model with highly integrated respiratory and cardiovascular systems. The model was configured to replicate published clinical trial data on the responses of 12 individual ARDS patients to changes in PEEP. These virtual patients were subjected to increasing PEEP levels during a lung-protective ventilation strategy (0-20 cm H2O). Measured variables included arterial oxygenation, cardiac output, peripheral oxygen delivery, and alveolar strain.
  
  
  RESULTS
  As PEEP increased, tissue oxygen delivery decreased in all subjects (mean reduction of 25% at 20 cm H2O PEEP), despite an increase in arterial oxygen tension (mean increase 6.7 kPa at 20 cm H2O PEEP). Changes in arterial oxygenation and tissue oxygen delivery differed between subjects but showed a consistent pattern. Static and dynamic alveolar strain decreased in all patients as PEEP increased.
  
  
  CONCLUSIONS
  Incremental PEEP in ARDS appears to protect alveoli and improve arterial oxygenation, but also appears to impair tissue oxygen delivery significantly because of reduced cardiac output. We propose that this trade-off may explain the poor improvements in mortality associated with high-PEEP ventilation strategies.
authors: Anaesthesia and Critical Care Section, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK marc.chikhani@nottingham.ac.uk.|Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
authors: M
authors: M
authors: Chikhani
authors: School of Engineering, University of Warwick, Coventry CV4 7AL, UK.
authors: A
authors: A
authors: Das
authors: Anaesthesia and Critical Care Section, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK.
authors: M
authors: M
authors: Haque
authors: School of Engineering, University of Warwick, Coventry CV4 7AL, UK.
authors: W
authors: W
authors: Wang
authors: School of Engineering, University of Warwick, Coventry CV4 7AL, UK.
authors: D G
authors: DG
authors: Bates
authors: Anaesthesia and Critical Care Section, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK marc.chikhani@nottingham.ac.uk.|Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
authors: J G
authors: JG
authors: Hardman
mesh_terms: D001784:Blood Gas Analysis; D003198:Computer Simulation; D005069:Evaluation Studies as Topic; D006801:Humans; D010100:Oxygen / Q000097:blood*; D011175:Positive-Pressure Respiration / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000628:therapy*
chemical_list: D010100:Oxygen
keywords: computer simulation; respiration, artificial; respiratory distress syndrome, adult