title: Low tidal volume and high positive end-expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs.
abstract: BACKGROUND
  Protective mechanical ventilation with low tidal volume (Vt) and low plateau pressure reduces mortality and decreases the length of mechanical ventilation in patients with acute respiratory distress syndrome. Mechanical ventilation that will protect normal lungs during major surgical procedures of long duration may improve postoperative outcomes. We performed an animal study comparing 3 ventilation strategies used in the operating room in normal lungs. We compared the effects on pulmonary mechanics, inflammatory mediators, and lung tissue injury.
  
  
  METHODS
  Female pigs were randomized into 3 groups. Group H-Vt/3 (n = 6) was ventilated with a Vt of 15 mL/kg predicted body weight (PBW)/positive end-expiratory pressure (PEEP) of 3 cm H(2)O, group L-Vt/3 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 3 cm H(2)O, and group L-Vt/10 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 10 cm H(2)O, for 8 hours. Hemodynamics, airway mechanics, arterial blood gases, and inflammatory markers were monitored. Bronchoalveolar lavage (BAL) was analyzed for inflammatory markers and protein concentration. The right lower lobe was assayed for mRNA of specific cytokines. The right lower lobe and right upper lobe were evaluated histologically.
  
  
  RESULTS
  In contrast to groups H-Vt/3 and L-Vt/3, group L-Vt/10 exhibited a 6-fold increase in inflammatory mediators in BAL (P < 0.001). Cytokines in BAL were similar in groups H-Vt/3 and L-Vt/3. Group H-Vt/3 had a significantly lower lung injury score than groups L-Vt/3 and L-Vt/10.
  
  
  CONCLUSIONS
  Comparing intraoperative strategies, ventilation with high PEEP resulted in increased production of inflammatory markers. Low PEEP resulted in lower levels of inflammatory markers. High Vt/low PEEP resulted in less histologic lung injury.
authors.affiliation: Department of Anesthesiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Caron M
authors.initials: CM
authors.lastname: Hong
authors.forename: Da-Zhong
authors.initials: DZ
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Lu
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Vadim
authors.initials: V
authors.lastname: Pisarenko
authors.forename: Danielle
authors.initials: D
authors.lastname: Doucet
authors.forename: Margaret
authors.initials: M
authors.lastname: Brown
authors.forename: Seena
authors.initials: S
authors.lastname: Aisner
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Ellise
authors.initials: E
authors.lastname: Delphin
mesh_terms: D000758:Anesthesia; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002245:Carbon Dioxide / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006439:Hemodynamics; D008168:Lung / Q000473:pathology; D010100:Oxygen / Q000097:blood; D011014:Pneumonia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D053717:Pneumonia, Ventilator-Associated / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011659:Pulmonary Gas Exchange; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013990:Tidal Volume
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D002245:Carbon Dioxide; D010100:Oxygen