title: Pressure-limited ventilation with permissive hypercapnia and minimum PEEP in saline-lavaged rabbits allows progressive improvement in oxygenation, but does not avoid ventilator-induced lung injury.
abstract: OBJECTIVE
  To determine whether pressure-limited intermittent mandatory ventilation with permissive hypercapnia and positive end-expiratory pressure (PEEP) titrated to arterial oxygen tension (PaO2) prevents or reduces acute lung injury, compared to conventional ventilation, in saline-lavaged rabbits.
  
  
  METHODS
  Prospective randomised trial.
  
  
  METHODS
  University animal laboratory.
  
  
  METHODS
  18 New Zealand White rabbits.
  
  
  METHODS
  Following five sequential saline lung lavages, anaesthetised rabbits were randomly allocated in pairs to receive either of two ventilation protocols using intermittent mandatory ventilation. The study group had peak inspiratory pressure limited to 15 cm H2O and arterial partial pressure of carbon dioxide (PaCO2) was allowed to rise. The control group received 12 ml/kg tidal volume with rate adjusted for normocarbia. PEEP and fractional inspired oxygen (FIO2) were adjusted to maintain, PaO2 between 8 and 13.3 kPa (60 and 100 mm Hg) using a predetermined protocol. At 10 h or following death, lung lavage was repeated and lung histology evaluated.
  
  
  RESULTS
  The mean increase in lavage cell counts and protein concentration and hyaline membrane scores were not significantly different between the groups. Oxygenation progressively improved more in the study group (p = 0.01 vs control for PaO2/FIO2 ratio and alveolar-arterial oxygen tension gradient (AaDO2)). PEEP was similar and the mean airway pressure higher in the control group, suggesting that this probably resulted from less ventilator-induced injury in the study group. Four deaths occurred in the control group (three due to pneumothorax and one to hypoxaemia) and none in the study group (p = 0.08).
  
  
  CONCLUSIONS
  This ventilatory protocol may have failed to prevent lung overdistension or it may have provided insufficient PEEP to prevent injury in this model; PEEP greater than the lower inflection point of the pressure-volume curve has been shown to prevent injury almost entirely.
authors.affiliation: Department of Intensive Care, Christchurch Hospital, New Zealand.
authors.forename: K G
authors.initials: KG
authors.lastname: Hickling
authors.forename: I G
authors.initials: IG
authors.lastname: Town
authors.forename: M
authors.initials: M
authors.lastname: Epton
authors.forename: A
authors.initials: A
authors.lastname: Neill
authors.forename: A
authors.initials: A
authors.lastname: Tie
authors.forename: M
authors.initials: M
authors.lastname: Whitehead
authors.forename: P
authors.initials: P
authors.lastname: Graham
authors.forename: E
authors.initials: E
authors.lastname: Everest
authors.forename: G
authors.initials: G
authors.lastname: A'Court
authors.forename: B
authors.initials: B
authors.lastname: Darlow
authors.forename: K
authors.initials: K
authors.lastname: Laubscher
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000209:etiology*; D011175:Positive-Pressure Respiration / Q000009:adverse effects / Q000379:methods*; D011817:Rabbits; D011897:Random Allocation; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D012720:Severity of Illness Index; D013990:Tidal Volume