{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:18:24Z","timestamp":1788787104758,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Adv. Respir. Med.","ARM"],"abstract":"<jats:p>Despite decades of clinical experience, the physiological rationale for extracorporeal life support (ECLS) in acute respiratory distress syndrome (ARDS) remains incompletely defined. Existing trials have primarily evaluated ECLS as a rescue intervention, with limited attention to the physiological adaptations required to sustain extracorporeal gas exchange. We propose that the maternal\u2013fetal circulation, the only naturally occurring example of prolonged extracorporeal gas exchange, provides a hypothesis-generating physiological analogy. In this paradigm, gas exchange is externalized through a low-resistance, high-flow circuit while systemic physiology reorganizes to unload the native lung. Translating this concept to severe ARDS suggests that ECLS should be viewed not simply as an adjunct to conventional support, but as a transition to an alternative physiological state centered on extracorporeal gas exchange. This perspective may inform physiology-based patient selection, management strategies, and the design of future clinical trials.<\/jats:p>","DOI":"10.3390\/arm94050065","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracorporeal Life Support in ARDS: Lessons from Maternal\u2013Fetal Physiology"],"prefix":"10.3390","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0159-1426","authenticated-orcid":false,"given":"Raffaele","family":"Merola","sequence":"first","affiliation":[{"name":"Anesthesia and Intensive Care Medicine, Department of Critical Care, AORN Ospedali Dei Colli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-6442","authenticated-orcid":false,"given":"Denise","family":"Battaglini","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care, IRCCS AOM, Ospedale Policlinico San Martino, 16132 Genoa, Italy"},{"name":"Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-0958","authenticated-orcid":false,"given":"Sung-Min","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Neuroscience Critical Care, Departments of Neurology, Surgery, and Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1007\/s00134-020-06290-1","article-title":"Extracorporeal life support for adults with acute respiratory distress syndrome","volume":"46","author":"Combes","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s40635-023-00563-x","article-title":"Current knowledge gaps in extracorporeal respiratory support","volume":"11","author":"Tonetti","year":"2023","journal-title":"Intensive Care Med. Exp."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/S0140-6736(09)61069-2","article-title":"Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): A multicentre randomised controlled trial","volume":"374","author":"Peek","year":"2009","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1056\/NEJMoa1800385","article-title":"Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome","volume":"378","author":"Combes","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1007\/s00134-019-05567-4","article-title":"Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: The SUPERNOVA study","volume":"45","author":"Combes","year":"2019","journal-title":"Intensive Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1186\/s13054-022-04272-x","article-title":"Ultra-lung-protective ventilation and biotrauma in severe ARDS patients on veno-venous extracorporeal membrane oxygenation: A randomized controlled study","volume":"26","author":"Guervilly","year":"2022","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jointm.2025.08.002","article-title":"Redefining ARDS phenotypes: Challenges in the precision medicine era","volume":"5","author":"Merola","year":"2025","journal-title":"J. Intensive Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Merola, R., Vargas, M., and Battaglini, D. (2025). Ventilator-Induced Lung Injury: The Unseen Challenge in Acute Respiratory Distress Syndrome Management. J. Clin. Med., 14.","DOI":"10.3390\/jcm14113910"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1001\/jama.2021.13374","article-title":"Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients with Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial","volume":"326","author":"McNamee","year":"2021","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00134-023-07050-7","article-title":"ESICM guidelines on acute respiratory distress syndrome: Definition, phenotyping and respiratory support strategies","volume":"49","author":"Grasselli","year":"2023","journal-title":"Intensive Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1097\/MAT.0000000000001432","article-title":"Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO)","volume":"67","author":"Tonna","year":"2021","journal-title":"ASAIO J."},{"key":"ref_12","first-page":"270","article-title":"Physiology of the placenta\u2014Gas exchange","volume":"15","author":"Goplerud","year":"1985","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/S0002-9440(10)64849-3","article-title":"Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure","volume":"157","author":"Jauniaux","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/S0002-9440(10)64813-4","article-title":"Uteroplacental blood flow. The story of decidualization, menstruation, and trophoblast invasion","volume":"157","author":"Kliman","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vali, P., and Lakshminrusimha, S. (2017). The Fetus Can Teach Us: Oxygen and the Pulmonary Vasculature. Children, 4.","DOI":"10.3390\/children4080067"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1183\/20734735.008615","article-title":"Respiratory physiology of pregnancy: Physiology masterclass","volume":"11","author":"LoMauro","year":"2015","journal-title":"Breathe"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Merola, R., Battaglini, D., Schultz, M.J., and Rocco, P.R.M. (2026). Physiology-guided personalized mechanical ventilation to prevent ventilator-induced lung injury. Front. Med., 13.","DOI":"10.3389\/fmed.2026.1764151"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1136\/thorax-2025-224250","article-title":"Global ARDS subphenotyping: Separating apples from oranges","volume":"81","author":"Battaglini","year":"2025","journal-title":"Thorax"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Merola, R., Lomonaco, V., Gaetano, D., Corcione, A., Malbrain, M.L., Rocco, P.R., and Battaglini, D. (2026). Right ventricular dysfunction in acute respiratory distress syndrome: From cardiopulmonary mechanisms to precision management-a narrative review. Br. J. Anaesth., online ahead of print.","DOI":"10.1016\/j.bja.2026.07.002"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13054-025-05679-y","article-title":"Mechanical power of ventilation: Tracking the damaging component","volume":"30","author":"Marini","year":"2026","journal-title":"Crit. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13054-025-05827-4","article-title":"A prospective clinical evaluation of new ECCO2R technology in mild to moderate ARDS patients: Assessing ultra-lung-protective ventilation with PRISMALUNG","volume":"30","author":"Combes","year":"2026","journal-title":"Crit. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e20260266","DOI":"10.62675\/2965-2774.20260266","article-title":"Why have extracorporeal carbon dioxide removal clinical trials failed?","volume":"38","author":"Santos","year":"2026","journal-title":"Crit. Care Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"305","DOI":"10.4103\/mgr.MEDGASRES-D-25-00113","article-title":"Permissive hypercapnia in acute respiratory distress syndrome: Physiological mechanisms and clinical implications","volume":"16","author":"Teri","year":"2026","journal-title":"Med. Gas Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"288","DOI":"10.4103\/mgr.MEDGASRES-D-24-00051","article-title":"Advancing extracorporeal carbon dioxide removal technology: Bridging basic science and clinical practice","volume":"15","author":"Lassola","year":"2025","journal-title":"Med. Gas Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Merola, R., Battaglini, D., and De Rosa, S. (2026). Extracorporeal Carbon Dioxide Removal in Acute Respiratory Distress Syndrome: Physiologic Rationale and Phenotype-Based Perspectives. Medicina, 62.","DOI":"10.3390\/medicina62020236"}],"container-title":["Advances in Respiratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2543-6031\/94\/5\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:04:20Z","timestamp":1788786260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2543-6031\/94\/5\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["arm94050065"],"URL":"https:\/\/doi.org\/10.3390\/arm94050065","relation":{},"ISSN":["2543-6031"],"issn-type":[{"value":"2543-6031","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}