title: Mechanical breath profile of airway pressure release ventilation: the effect on alveolar recruitment and microstrain in acute lung injury.
abstract: OBJECTIVE
  Improper mechanical ventilation settings can exacerbate acute lung injury by causing a secondary ventilator-induced lung injury. It is therefore important to establish the mechanism by which the ventilator induces lung injury to develop protective ventilation strategies. It has been postulated that the mechanism of ventilator-induced lung injury is the result of heterogeneous, elevated strain on the pulmonary parenchyma. Acute lung injury has been associated with increases in whole-lung macrostrain, which is correlated with increased pathology. However, the effect of mechanical ventilation on alveolar microstrain remains unknown.
  
  
  OBJECTIVE
  To examine whether the mechanical breath profile of airway pressure release ventilation (APRV), consisting of a prolonged pressure-time profile and brief expiratory release phase, reduces microstrain.
  
  
  METHODS
  In a randomized, nonblinded laboratory animal study, rats were randomized into a controlled mandatory ventilation group (n = 3) and an APRV group (n = 3). Lung injury was induced by polysorbate lavage. A thoracotomy was performed and an in vivo microscope was placed on the lungs to measure alveolar mechanics.
  
  
  METHODS
  In the controlled mandatory ventilation group, multiple levels of positive end-expiratory pressure (PEEP; 5, 10, 16, 20, and 24 cm H2O) were tested. In the APRV group, decreasing durations of expiratory release (time at low pressure [T(low)]) were tested. The T(low) was set to achieve ratios of termination of peak expiratory flow rate (T-PEFR) to peak expiratory flow rate (PEFR) of 10%, 25%, 50%, and 75% (the smaller this ratio is [ie, 10%], the more time the lung is exposed to low pressure during the release phase, which decreases end-expiratory lung volume and potentiates derecruitment). Alveolar perimeters were measured at peak inspiration and end expiration using digital image analysis, and strain was calculated by normalizing the change in alveolar perimeter length to the original length. Macrostrain was measured by volume displacement.
  
  
  RESULTS
  Higher PEEP (16-24 cm H2O) and a brief T(low) (APRV T-PEFR to PEFR ratio of 75%) reduced microstrain. Microstrain was minimized with an APRV T-PEFR to PEFR ratio of 75% (mean [SEM], 0.05 [0.03]) and PEEP of 16 cm H2O (mean [SEM], 0.09 [0.08]), but an APRV T-PEFR to PEFR ratio of 75% also promoted alveolar recruitment compared with PEEP of 16 cm H2O (mean [SEM] total inspiratory area, 52.0% [2.9%] vs 29.4% [4.3%], respectively; P < .05). Whole-lung strain was correlated with alveolar microstrain in tested settings (P < .05) except PEEP of 16 cm H2O (P > .05).
  
  
  CONCLUSIONS
  Increased positive-end expiratory pressure and reduced time at low pressure (decreased T(low)) reduced alveolar microstrain. Reduced microstrain and improved alveolar recruitment using an APRV T-PEFR to PEFR ratio of 75% may be the mechanism of lung protection seen in previous clinical and animal studies.
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kollisch-Singule
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Bryanna
authors.initials: B
authors.lastname: Emr
authors.affiliation: Department of Medicine, University of Vermont, Burlington.
authors.forename: Bradford
authors.initials: B
authors.lastname: Smith
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Shreyas
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Joshua
authors.initials: J
authors.lastname: Satalin
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Kathy
authors.initials: K
authors.lastname: Snyder
authors.affiliation: Department of Trauma Critical Care Medicine, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore.
authors.forename: Penny
authors.initials: P
authors.lastname: Andrews
authors.affiliation: Department of Trauma Critical Care Medicine, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore.
authors.forename: Nader
authors.initials: N
authors.lastname: Habashi
authors.affiliation: Department of Medicine, University of Vermont, Burlington.
authors.forename: Jason
authors.initials: J
authors.lastname: Bates
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse4Department of General Surgery, Syracuse Veterans Affairs, Syracuse, New York.
authors.forename: William
authors.initials: W
authors.lastname: Marx
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Gary
authors.initials: G
authors.lastname: Nieman
authors.affiliation: Department of General Surgery, State University of New York Upstate Medical University, Syracuse5Department of Biological Sciences, State University of New York Cortland, Cortland.
authors.forename: Louis A
authors.initials: LA
authors.lastname: Gatto
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D000818:Animals; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D008297:Male; D010366:Peak Expiratory Flow Rate; D011175:Positive-Pressure Respiration; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics; D013312:Stress, Physiological