Anesthesiology, V 122 • No 1 106 January 2015 G ENERAL anesthesia usually requires mechanical ven- tilation to maintain adequate gas exchange. However, mechanical ventilation may impose stress on the lung paren- chyma, triggering a proinfammatory response that damages the lung, a phenomenon known as ventilator-induced lung injury (VILI). 1 In patients with the acute respiratory distress syndrome, the use of protective mechanical ventilation with tidal volumes (V T ) of 4 to 8 ml/kg and positive end-expira- tory pressure (PEEP) has been shown to reduce lung infam- mation and mortality. 2 Most surgical patients undergoing general anesthesia dif- fer from intensive care patients in terms of the absence of lung injury. However, because infammatory mediators can be released into the circulation during surgery, making lungs vulnerable to VILI, 3 the use of protective mechanical ven- tilation has been recommended during general anesthesia. 4 What We Already Know about This Topic • Mechanical ventilation can lead to lung biotrauma when the mechanical stress caused by the ventilation exceeds safety thresholds What This Article Tells Us That Is New • In a mild acute lung infammation model in rats, using mechanical ventilation with an inspiratory-to-expiratory ratio of 1:1 minimized lung damage, whereas an inspiratory- to-expiratory ratio of 2:1 led to increased gene expression of in- fammatory mediators and markers of alveolar epithelial cell injury Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2015; 122:106-16 ABSTRACT Background: Mechanical ventilation can lead to lung biotrauma when mechanical stress exceeds safety thresholds. Te authors investigated whether the duration of mechanical stress, that is, the impact of a stress versus time product (STP), infuences biotrauma. Te authors hypothesized that higher STP levels are associated with increased infammation and with alveolar epithelial and endothelial cell injury. Methods: In 46 rats, Escherichia coli lipopolysaccharide (acute lung infammation) or saline (control) was administered intra- tracheally. Both groups were protectively ventilated with inspiratory-to-expiratory ratios 1:2, 1:1, or 2:1 (n = 12 each), cor- responding to low, middle, and high STP levels (STP low , STP mid , and STP high , respectively). Te remaining 10 animals were not mechanically ventilated. Results: In animals with mild acute lung infammation, but not in controls: (1) messenger RNA expression of interleukin-6 was higher in STP high (28.1 ± 13.6; mean ± SD) and STP low (28.9 ± 16.0) versus STP mid (7.4 ± 7.5) (P < 0.05); (2) expression of the receptor for advanced glycation end-products was increased in STP high (3.6 ± 1.6) versus STP low (2.3 ± 1.1) (P < 0.05); (3) alveolar edema was decreased in STP mid (0 [0 to 0]; median, Q1 to Q3) compared with STP high (0.8 [0.6 to 1]) (P < 0.05); and (4) expressions of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were higher in STP low (3.0 ± 1.8) versus STP high (1.2 ± 0.5) and STP mid (1.4 ± 0.7) (P < 0.05), respectively. Conclusions: In the mild acute lung infammation model used herein, mechanical ventilation with inspiratory-to-expiratory of 1:1 (STP mid ) minimized lung damage, whereas STP high increased the gene expression of biological markers associated with infammation and alveolar epithelial cell injury and STP low increased markers of endothelial cell damage. (ANESTHESIOLOGY 2015; 122:106-16) Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www. anesthesiology.org). The first two authors contributed equally to this work. Submitted for publication December 18, 2013. Accepted for publication July 8, 2014. From the Pulmonary Engineering Group, Department of Anes- thesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Dresden, Technische Universität Dresden, Dresden, Germany (P.M.S., A.G., R.H., T.K., M.G.d.A.); Laboratory of Pulmonary Investigation (P.L.S., C.S.N.B.G., D.S.O., C.S.S., L.M., M.B., P.R.M.R.), and Laboratory of Cellular and Molecular Biology (M.M.M.), Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Rio de Janeiro Fed- eral Institute of Education, Science and Technology, Rio de Janeiro, Brazil (C.S.N.B.G.); Institute of Anatomy, Technical University Dresden, Dresden, Germany (M.K.); and IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy (P.P.). Modulation of Stress versus Time Product during Mechanical Ventilation Influences Inflammation as Well as Alveolar Epithelial and Endothelial Response in Rats Peter M. Spieth, M.D., Pedro L. Silva, Ph.D., Cristiane S. N. B. Garcia, Ph.D., Debora S. Ornellas, Ph.D., Cynthia S. Samary, Ph.D., Lillian Moraes, M.Sc., Maira Bentes, R.R.T., Marcelo M. Morales, M.D., Ph.D., Michael Kasper, Ph.D., Andreas Güldner, M.D., Robert Huhle, M.Sc., Thea Koch, M.D., Ph.D., Paolo Pelosi, M.D., Marcelo Gama de Abreu, M.D., Ph.D., Patricia R. M. Rocco, M.D., Ph.D. Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/122/1/106/485409/20150100_0-00024.pdf by guest on 27 November 2022