title: Time to generate ventilator-induced lung injury among mammals with healthy lungs: a unifying hypothesis.
abstract: OBJECTIVE
  To investigate ventilator-induced lung injury (VILI), several experimental models were designed including different mammalian species and ventilator settings, leading to a large variability in the observed time-course and injury severity. We hypothesized that the time-course of VILI may be fully explained from a single perspective when considering the insult actually applied, i.e. lung stress and strain.
  
  
  METHODS
  Studies in which healthy animals were aggressively ventilated until preterminal VILI were selected via a Medline search. Data on morphometry, ventilator settings, respiratory function and duration of ventilation were derived. For each animal group, lung stress (transpulmonary pressure) and strain (end-inspiratory lung inflation/lung resting volume ratio) were estimated.
  
  
  RESULTS
  From the Medline search 20 studies including five mammalian species (sheep, pigs, rabbits, rats, mice) were selected. Time to achieve preterminal VILI varied widely (18-2,784 min), did not correlate with either tidal volume (expressed in relation to body weight) or airway pressure applied, but was weakly associated with lung stress (r                            (2) = 0.25, p = 0.008). In contrast, the duration of mechanical ventilation was closely correlated with both lung strain (r                            (2) = 0.85, p < 0.0001) and lung strain weighted for the actual time of application during each breath (r                            (2) = 0.83, p < 0.0001), according to exponential decay functions. When it was normalized for the lung strain applied, larger species showed a greater resistance to VILI than smaller species (medians, 25th-75th percentiles: 690, 460-2,001 min vs. 16, 4-59 min, respectively; p < 0.001).
  
  
  CONCLUSIONS
  Lung strain may play a critical role as a unifying rule describing the development of VILI among mammals with healthy lungs.
authors: Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors: Pietro
authors: P
authors: Caironi
authors: Thomas
authors: T
authors: Langer
authors: Eleonora
authors: E
authors: Carlesso
authors: Alessandro
authors: A
authors: Protti
authors: Luciano
authors: L
authors: Gattinoni
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008322:Mammals; D012121:Respiration, Artificial / Q000379:methods*; D012720:Severity of Illness Index; D013997:Time Factors; D055397:Ventilator-Induced Lung Injury / Q000209:etiology / Q000503:physiopathology*