Intensive Care Medicine

, Volume 37, Issue 12, pp 1913–1920 | Cite as

Time to generate ventilator-induced lung injury among mammals with healthy lungs: a unifying hypothesis

  • Pietro Caironi
  • Thomas Langer
  • Eleonora Carlesso
  • Alessandro Protti
  • Luciano Gattinoni



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.


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.


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 (r2 = 0.25, p = 0.008). In contrast, the duration of mechanical ventilation was closely correlated with both lung strain (r2 = 0.85, p < 0.0001) and lung strain weighted for the actual time of application during each breath (r2 = 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).


Lung strain may play a critical role as a unifying rule describing the development of VILI among mammals with healthy lungs.


Ventilator-induced lung injury Mechanical ventilation Lung stress Lung strain Comparative physiology 

Supplementary material

134_2011_2388_MOESM1_ESM.doc (502 kb)
Supplementary material 1 (DOC 502 kb)


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Copyright information

© Copyright jointly held by Springer and ESICM 2011

Authors and Affiliations

  • Pietro Caironi
    • 1
    • 3
  • Thomas Langer
    • 1
  • Eleonora Carlesso
    • 1
  • Alessandro Protti
    • 1
  • Luciano Gattinoni
    • 1
    • 2
    • 3
  1. 1.Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Fondazione IRCCS Ca′ Granda—Ospedale Maggiore PoliclinicoUniversità degli Studi di MilanoMilanItaly
  2. 2.Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Fondazione IRCCS—Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena di MilanoUniversità degli Studi di MilanoMilanItaly
  3. 3.Dipartimento di AnestesiaRianimazione e Terapia del Dolore, Fondazione IRCCS Ca′ Granda—Ospedale Maggiore PoliclinicoMilanItaly

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