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Several limiting assumptions are needed to infer lung parenchymal stress and strain from airway pressure, volume, and flow data from mechanically ventilated patients with injured lungs. These assumptions include the effects of the chest wall on lung-surface pressure, its topographical distribution, and the effects of non-uniform tissue properties on local parenchymal stresses. In addition, there is a spectrum of biophysical lung injury mechanisms that involves normal as well as tangential alveolar wall stresses. To these are added important secondary effects on pulmonary vascular resistance and right heart function. Understanding both the assumptions of lung mechanics and the scope of injury mechanisms operating during ARDS is necessary to interpret the results of clinical trials that inform prevailing ventilator-management guidelines. The implications issuing from these 3 topics inform a safer approach to setting and adjusting the ventilator to minimize the risk of ventilator-induced lung injury. This is enumerated in a 5-step approach that can be used to guide ventilator management of unstable patients with severe lung injury.<\/jats:p>","DOI":"10.4187\/respcare.05900","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T13:30:30Z","timestamp":1516800630000},"page":"219-226","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":37,"title":["Understanding Pulmonary Stress-Strain Relationships in Severe ARDS and Its Implications for Designing a Safer Approach to Setting the Ventilator"],"prefix":"10.1177","volume":"63","author":[{"given":"Rolf D","family":"Hubmayr","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H","family":"Kallet","sequence":"additional","affiliation":[{"name":"Respiratory Care Services, Department of Anesthesia and Perioperative Care, University of California, San Francisco at Zuckerberg San Francisco General Hospital, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,1,26]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201512-2448CP"},{"issue":"6","key":"e_1_3_2_3_2","first-page":"1443","article-title":"Nonuniform lung deformations","volume":"54","author":"Wilson TA","year":"1983","unstructured":"Wilson TA. 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