Correspondence  |   March 2016
In Reply
Author Notes
  • Università degli Studi di Milano, Milan, Italy (L.G.).
  • (Accepted for publication December 2, 2015.)
    (Accepted for publication December 2, 2015.)×
Article Information
Correspondence   |   March 2016
In Reply
Anesthesiology 3 2016, Vol.124, 736-737. doi:10.1097/ALN.0000000000000999
Anesthesiology 3 2016, Vol.124, 736-737. doi:10.1097/ALN.0000000000000999
We thank Dr. Formenti for his careful reading of our work and for his comments. Dr. Formenti is right when he questions the translatability of these healthy animal data in the clinical scenario of acute respiratory distress syndrome. Our study was designed to corroborate the hypothesis that “stress raisers”1,2  are possible facilitators of ventilation-induced lung injury. Our results3  did not contradict the hypothesis. In fact, we found that the lesions first appeared where the stress raisers are physiologically present, primarily at the interface between visceral pleura and subpleural alveoli and, in piglets with consolidation, at the interface between consolidations and the healthy parenchyma. Dr. Formenti suggests that the stress raisers may be less important than overdistension. We believe that stress raisers and overdistension are two aspects of the same reality: in fact, the stress raisers, being pressure multipliers, first induce local overdistension with overstretching and microfractures of the extracellular matrix, which appear as higher density regions due to edema and hemorrhage in the extracellular matrix. Dr. Formenti correctly states that the tidal volume we used (40 ml/kg) is far from what has been shown as harmful in clinical practice (12 ml/kg). However, we believe that it is nearly impossible to produce in a reasonable time (3 days) macroscopic lesions in the healthy parenchyma using 12 ml/kg. In these piglets, it would correspond to a strain of 0.8, which is at least three times lower than the one we found lethal.4  Inferring from our data,3  we could speculate that to obtain lethal stress/strain with 12 ml/kg in these experimental animals, the functional residual capacity should be reduced to two-thirds or the stress raisers should be highly diffused in the parenchyma and be able to multiply three times the applied transpulmonary pressure. These conditions (or their combination) may occur only if the lung is diseased. Unfortunately, we still lack an animal model that could realistically mimic the human acute respiratory distress syndrome as a whole and not only some of its aspects. Finally, with the high tidal volumes we used, we believe unrealistically that 0.5 Fio2 may induce reabsorption atelectasis.5 
This study received institutional funds.
Competing Interests
Drs. Cressoni and Gattinoni have an Italian patent for lung inhomogeneities determination (0001409041) and applied for European and U.S. patents. The other author declares no competing interests.
Massimo Cressoni, M.D., Chiara Chiurazzi, M.D., Luciano Gattinoni, M.D., F.R.C.P. Università degli Studi di Milano, Milan, Italy (L.G.).
Mead, J, Takishima, T, Leith, D Stress distribution in lungs: A model of pulmonary elasticity.. J Appl Physiol. (1970). 28 596–608 [PubMed]
Cressoni, M, Cadringher, P, Chiurazzi, C, Amini, M, Gallazzi, E, Marino, A, Brioni, M, Carlesso, E, Chiumello, D, Quintel, M, Bugedo, G, Gattinoni, L Lung inhomogeneity in patients with acute respiratory distress syndrome.. Am J Respir Crit Care Med. (2014). 189 149–58 [PubMed]
Cressoni, M, Chiurazzi, C, Gotti, M, Amini, M, Brioni, M, Algieri, I, Cammaroto, A, Rovati, C, Massari, D, di Castiglione, CB, Nikolla, K, Montaruli, C, Lazzerini, M, Dondossola, D, Colombo, A, Gatti, S, Valerio, V, Gagliano, N, Carlesso, E, Gattinoni, L Lung inhomogeneities and time course of ventilator-induced mechanical injuries.. Anesthesiology. (2015). 123 618–27 [Article] [PubMed]
Protti, A, Cressoni, M, Santini, A, Langer, T, Mietto, C, Febres, D, Chierichetti, M, Coppola, S, Conte, G, Gatti, S, Leopardi, O, Masson, S, Lombardi, L, Lazzerini, M, Rampoldi, E, Cadringher, P, Gattinoni, L Lung stress and strain during mechanical ventilation: Any safe threshold?. Am J Respir Crit Care Med. (2011). 183 1354–62 [Article] [PubMed]
Borges, JB, Carvalho, CR, Amato, MB Lung recruitment in patients with ARDS.. N Engl J Med. (2006). 355 319–20; author reply 321–2 [Article] [PubMed]