title: Biotrauma and Ventilator-Induced Lung Injury: Clinical Implications.
abstract: The pathophysiological mechanisms by which mechanical ventilation can contribute to lung injury, termed "ventilator-induced lung injury" (VILI), is increasingly well understood. "Biotrauma" describes the release of mediators by injurious ventilatory strategies, which can lead to lung and distal organ injury. Insights from preclinical models demonstrating that traditional high tidal volumes drove the inflammatory response helped lead to clinical trials demonstrating lower mortality in patients who underwent ventilation with a lower-tidal-volume strategy. Other approaches that minimize VILI, such as higher positive end-expiratory pressure, prone positioning, and neuromuscular blockade have each been demonstrated to decrease indices of activation of the inflammatory response. This review examines the evolution of our understanding of the mechanisms underlying VILI, particularly regarding biotrauma. We will assess evidence that ventilatory and other "adjunctive" strategies that decrease biotrauma offer great potential to minimize the adverse consequences of VILI and to improve the outcomes of patients with respiratory failure.
authors.affiliation: Department of Anesthesia, St Michael's Hospital, and the Critical Illness and Injury Research Centre, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Curley
authors.affiliation: Department of Anesthesia, St Michael's Hospital, and the Critical Illness and Injury Research Centre, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
authors.affiliation: Department of Anesthesia, St Michael's Hospital, and the Critical Illness and Injury Research Centre, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicine, St Michael's Hospital, and the Critical Illness and Injury Research Centre, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: slutskya@smh.ca.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D016684:Prone Position; D012121:Respiration, Artificial / Q000009:adverse effects*; D012129:Respiratory Function Tests; D013997:Time Factors; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology* / Q000517:prevention & control*
chemical_list: D015415:Biomarkers
keywords: biotrauma; critical care; mechanical ventilation; respiratory failure; ventilator-induced injury