Online Laboratory Investigation

Critical Care Medicine www.ccmjournal. org e241 Objectives: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. “Flow-controlled ventilation”, providing a constant expiratory flow, has been suggested as a new lungprotective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome. Design: Preclinical, randomized controlled animal study. Setting: Animal research facility. Subjects: Nineteen German landrace hybrid pigs. Intervention: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid. Measurements and Main Results: Pao2 and Paco2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A concentration in bronchoalveolar lavage fluid. Five pigs were excluded leaving n equals to 7 for each group. Compared with control, flow-controlled ventilation elevated Pao2 (154 ± 21 vs 105 ± 9 torr; 20.5 ± 2.8 vs 14.0 ± 1.2 kPa; p = 0.035) and achieved comparable Paco2 (57 ± 3 vs 54 ± 1 torr; 7.6 ± 0.4 vs 7.1 ± 0.1 kPa; p = 0.37) with a lower minute volume (6.4 ± 0.5 vs 8.7 ± 0.4 L/ min; p < 0.001). Inspiratory plateau pressure was comparable in both groups (31 ± 2 vs 34 ± 2 cm H2O; p = 0.16). Flow-controlled ventilation increased normally aerated (24% ± 4% vs 10% ± 2%; p = 0.004) and decreased nonaerated lung volume (23% ± 6% vs 38% ± 5%; p = 0.033) in the dependent lung region. Alveolar walls were thinner (5.5 ± 0.1 vs 7.8 ± 0.2 μm; p < 0.0001), cell infiltration was lower (20 ± 2 vs 32 ± 2 n/field; p < 0.0001), and normalized surfactant protein A concentration was higher with flow-controlled ventilation (1.1 ± 0.04 vs 1.0 ± 0.03; p = 0.039). Conclusions: Flow-controlled ventilation enhances lung aeration in the dependent lung region and consequently improves gas exchange and attenuates lung injury. Control of the expiratory flow DOI: 10.1097/CCM.0000000000004209 1Department of Anesthesiology and Critical Care, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2Experimental Surgery, Center for Experimental Models and Transgenic Service, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 3Department of Neuroradiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Presented as an abstract at Euroanaesthesia, Copenhagen, Denmark, June 3, 2018. This work was carried out at the Department of Anesthesiology and Critical Care, Medical Center University of Freiburg. Drs. Schmidt’s, Wenzel’s, Spassov’s, Borgmann’s, Lin’s, Wirth’s, and Schumann’s institution received funding for the submitted work from the European Union’s Horizon 2020 research and innovation program, grant agreement No. 691519, in cooperation with Ventinova Medical B.V. (Eindhoven, The Netherlands), Unitron Group B.V. (IJzendijke, The Netherlands), and the Department of Anaesthesia, Rigshospitalet (Copenhagen, Denmark). Dr. Wollborn reports grants from Deutsche Forschungsgemeinschaft, outside the submitted work. Dr. Meckel reports personal fees from Acandis GmbH, Covidien, Medtronic, Microvention, and Stryker; grants from Bracco S.p.A. ; and personal fees from Novartis, outside the submitted work. He received funding from Acandis, Medtronic, Stryker, Microvention, and Novartis Pharma. Dr. Schumann reports personal fees from Gründler medical and grants from Deutsche Forschungsgemeinschaft outside the submitted work. Dr. Schumann’s institution received grant funding from the Deutsche Forschungsgemeinschaft # SCHU 2499/4-1, # SCHU 2499/5-1, # SCHU 2499/7-1, and # SCHU 2499/8-1. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Johannes Schmidt, MD, Department of Anesthesiology and Critical Care, Medical Center University of Freiburg, Hugstetter Str 55, 79106 Freiburg, Germany. E-mail: johannes.schmidt@ uniklinik-freiburg.de Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Flow-Controlled Ventilation Attenuates Lung Injury in a Porcine Model of Acute Respiratory Distress Syndrome: A Preclinical Randomized Controlled Study