title: Positive end-expiratory pressure delays the progression of lung injury during ventilator strategies involving high airway pressure and lung overdistention.
abstract: OBJECTIVE
  Many studies have investigated the protective role of positive end-expiratory pressure (PEEP) on ventilator-induced lung injury. Most assessed lung injury in protocols involving different ventilation strategies applied for the same length of time. This study, however, set out to investigate the protective role of PEEP with respect to the time needed to reach similar levels of lung injury.
  
  
  METHODS
  Prospective, randomized laboratory animal investigation.
  
  
  METHODS
  The University Laboratory of Ospedale Maggiore, Milano, IRCCS.
  
  
  METHODS
  Anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats.
  
  
  METHODS
  Three groups of five Sprague-Dawley rats were ventilated using zero end-expiratory pressure ZEEP (PEEP of 0 cm H(2)O) and PEEP of 3 and 6 cm H(2)O and a similar index of lung overdistension (Paw(p)/P(100) congruent with 1.1; where Paw(p) is peak airway pressure and P(100) is the pressure corresponding to total lung capacity). To obtain this, tidal volume was reduced depending on the PEEP. To reach similar levels of lung injury, we measured respiratory system elastance while ventilating the animals and killed them when respiratory system elastance was 150% of baseline. Once target respiratory system elastance was reached, the lung wet-to-dry ratio was obtained.
  
  
  RESULTS
  Rats were ventilated with comparable high airway pressure (Paw(p) of 42.8 +/- 3.1, 43.5 +/- 2.6, and 46.2 +/- 4.4, respectively, for PEEP 0, 3, and 6) obtaining similar overdistension (Paw(p)/P(100) - index of overdistension: 1.17 +/- 0.2, 1.06 +/- 0.1, and 1.19 +/- 0.2). The respiratory system elastance target was reached and wet-to-dry ratio was not different in the three groups, suggesting a similar degree of lung damage. The time taken to achieve the target respiratory system elastance was three times longer with PEEP 3 and 6 (55 +/- 14 mins and 60 +/- 17) as compared with zero end-expiratory pressure (18 +/- 3 mins, p <.001).
  
  
  CONCLUSIONS
  These findings confirm that PEEP is protective against ventilator-induced lung injury and may enable the clinician to "buy time" in the progression of lung injury.
authors.affiliation: Istituto di Anestesia e Rianimazione, Ospedale Maggiore di Milano, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Valenza
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Guglielmi
authors.forename: Manuela
authors.initials: M
authors.lastname: Irace
authors.forename: Giuliana Anna
authors.initials: GA
authors.lastname: Porro
authors.forename: Silvio
authors.initials: S
authors.lastname: Sibilla
authors.forename: Luciano
authors.initials: L
authors.lastname: Gattinoni
mesh_terms: D000399:Air Pressure; D000818:Animals; D001469:Barotrauma / Q000503:physiopathology* / Q000517:prevention & control; D018450:Disease Progression; D008168:Lung / Q000503:physiopathology; D008170:Lung Compliance / Q000502:physiology*; D055370:Lung Injury; D009929:Organ Size / Q000502:physiology; D011175:Positive-Pressure Respiration; D011654:Pulmonary Edema / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology / Q000517:prevention & control; D013990:Tidal Volume / Q000502:physiology