{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:53:42Z","timestamp":1790754822264,"version":"4.1.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009702","name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico","doi-asserted-by":"publisher","award":["Ricerca Corrente 2020"],"award-info":[{"award-number":["Ricerca Corrente 2020"]}],"id":[{"id":"10.13039\/501100009702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Crit Care"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Nasal high flow delivered at flow rates higher than 60\u00a0L\/min in patients with acute hypoxemic respiratory failure might be associated with improved physiological effects. However, poor comfort might limit feasibility of its clinical use.\n<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We performed a prospective randomized cross-over physiological study on 12 ICU patients with acute hypoxemic respiratory failure. Patients underwent three steps at the following gas flow: 0.5\u00a0L\/kg PBW\/min, 1\u00a0L\/kg PBW\/min, and 1.5\u00a0L\/kg PBW\/min in random order for 20\u00a0min. Temperature and FiO<jats:sub>2<\/jats:sub> remained unchanged. Toward the end of each phase, we collected arterial blood gases, lung volumes, and regional distribution of ventilation assessed by electrical impedance tomography (EIT), and comfort.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In five patients, the etiology was pulmonary; infective disease characterized seven patients; median PaO<jats:sub>2<\/jats:sub>\/FiO<jats:sub>2<\/jats:sub> at enrollment was 213 [IQR 136\u2013232]. The range of flow rate during NHF 1.5 was 75\u2013120\u00a0L\/min. PaO<jats:sub>2<\/jats:sub>\/FiO<jats:sub>2<\/jats:sub> increased with flow, albeit non significantly (<jats:italic>p<\/jats:italic>\u2009=\u20090.064), PaCO<jats:sub>2<\/jats:sub> and arterial pH remained stable (<jats:italic>p<\/jats:italic>\u2009=\u20090.108 and <jats:italic>p<\/jats:italic>\u2009=\u20090.105). Respiratory rate decreased at higher flow rates (<jats:italic>p<\/jats:italic>\u2009=\u20090.014). Inhomogeneity of ventilation decreased significantly at higher flows (<jats:italic>p<\/jats:italic>\u2009=\u20090.004) and lung volume at end-expiration significantly increased (<jats:italic>p<\/jats:italic>\u2009=\u20090.007), but mostly in the non-dependent regions. Comfort was significantly poorer during the step performed at the highest flow (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>NHF delivered at rates higher than 60\u00a0L\/min in critically ill patients with acute hypoxemic respiratory failure is associated with reduced respiratory rate, increased lung homogeneity, and additional positive pressure effect, but also with worse comfort.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13054-020-03344-0","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T10:03:55Z","timestamp":1606125835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Nasal high flow higher than 60\u00a0L\/min in patients with acute hypoxemic respiratory failure: a physiological study"],"prefix":"10.1186","volume":"24","author":[{"given":"Maria Cristina","family":"Basile","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2709-8162","authenticated-orcid":false,"given":"Tommaso","family":"Mauri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Spinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Dalla Corte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Montanari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Marongiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savino","family":"Spadaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Galazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Grasselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pesenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"issue":"4","key":"3344_CR1","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1007\/s00134-020-05942-6","volume":"46","author":"E Spinelli","year":"2020","unstructured":"Spinelli E, Mauri T, Beitler JR, Pesenti A, Brodie D. Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring, and therapeutic interventions. Intensive Care Med. 2020;46(4):606\u201318.","journal-title":"Intensive Care Med"},{"issue":"6","key":"3344_CR2","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1152\/japplphysiol.00100.2006","volume":"101","author":"FJ Jacono","year":"2006","unstructured":"Jacono FJ, Peng YJ, Nethery D, Faress JA, Lee Z, Kern JA, et al. Acute lung injury augments hypoxic ventilatory response in the absence of systemic hypoxemia. J Appl Physiol. 2006;101(6):1795\u2013802.","journal-title":"J Appl Physiol"},{"issue":"9","key":"3344_CR3","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.23736\/S0375-9393.19.13418-9","volume":"85","author":"DL Grieco","year":"2019","unstructured":"Grieco DL, Menga LS, Eleuteri D, Antonelli M. Patient self-inflicted lung injury: implications for acute hypoxemic respiratory failure and ARDS patients on non-invasive support. Minerva Anestesiol. 2019;85(9):1014\u201323.","journal-title":"Minerva Anestesiol"},{"issue":"9","key":"3344_CR4","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1164\/rccm.201605-0916OC","volume":"195","author":"T Mauri","year":"2017","unstructured":"Mauri T, Turrini C, Eronia N, Grasselli G, Volta CA, Bellani G, et al. Physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure. Am J Respir Crit Care Med. 2017;195(9):1207\u201315.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"3344_CR5","doi-asserted-by":"publisher","first-page":"70","DOI":"10.4187\/respcare.02480","volume":"59","author":"T Itagaki","year":"2014","unstructured":"Itagaki T, Okuda N, Tsunano Y, Kohata H, Nakataki E, Onodera M, et al. Effect of high-flow nasal cannula on thoraco-abdominal synchrony in adult critically ill patients. Respir Care. 2014;59(1):70\u20134.","journal-title":"Respir Care"},{"issue":"11","key":"3344_CR6","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1007\/s00134-011-2354-6","volume":"37","author":"B Sztrymf","year":"2011","unstructured":"Sztrymf B, Messika J, Bertrand F, Hurel D, Leon R, Dreyfuss D, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37(11):1780\u20136.","journal-title":"Intensive Care Med"},{"issue":"5","key":"3344_CR7","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.jcrc.2010.12.015","volume":"26","author":"F Frutos-Vivar","year":"2011","unstructured":"Frutos-Vivar F, Esteban A, Apezteguia C, Gonzalez M, Arabi Y, Restrepo MI, et al. Outcome of reintubated patients after scheduled extubation. J Crit Care. 2011;26(5):502\u20139.","journal-title":"J Crit Care"},{"issue":"4","key":"3344_CR8","doi-asserted-by":"publisher","first-page":"529","DOI":"10.4187\/respcare.04577","volume":"61","author":"M Nishimura","year":"2016","unstructured":"Nishimura M. High-flow nasal cannula oxygen therapy in adults: physiological benefits, indication, clinical benefits, and adverse effects. Respir Care. 2016;61(4):529\u201341.","journal-title":"Respir Care"},{"issue":"10","key":"3344_CR9","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.4187\/respcare.03837","volume":"60","author":"N Rittayamai","year":"2015","unstructured":"Rittayamai N, Tscheikuna J, Praphruetkit N, Kijpinyochai S. Use of high-flow nasal cannula for acute dyspnea and hypoxemia in the emergency department. Respir Care. 2015;60(10):1377\u201382.","journal-title":"Respir Care"},{"issue":"15","key":"3344_CR10","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1001\/jama.2016.14194","volume":"316","author":"G Hernandez","year":"2016","unstructured":"Hernandez G, Vaquero C, Colinas L, Cuena R, Gonzalez P, Canabal A, et al. Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial. JAMA. 2016;316(15):1565\u201374.","journal-title":"JAMA"},{"key":"3344_CR11","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2147\/OAEM.S180197","volume":"11","author":"T Mauri","year":"2019","unstructured":"Mauri T, Wang YM, Dalla Corte F, Corcione N, Spinelli E, Pesenti A. Nasal high flow: physiology, efficacy and safety in the acute care setting, a narrative review. Open Access Emerg Med. 2019;11:109\u201320.","journal-title":"Open Access Emerg Med"},{"issue":"4","key":"3344_CR12","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.chest.2017.01.004","volume":"151","author":"YN Ni","year":"2017","unstructured":"Ni YN, Luo J, Yu H, Liu D, Ni Z, Cheng J, et al. Can high-flow nasal cannula reduce the rate of endotracheal intubation in adult patients with acute respiratory failure compared with conventional oxygen therapy and noninvasive positive pressure ventilation? A systematic review and meta-analysis. Chest. 2017;151(4):764\u201375.","journal-title":"Chest"},{"issue":"2","key":"3344_CR13","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.ajem.2017.07.083","volume":"36","author":"YN Ni","year":"2018","unstructured":"Ni YN, Luo J, Yu H, Liu D, Liang BM, Liang ZA. The effect of high-flow nasal cannula in reducing the mortality and the rate of endotracheal intubation when used before mechanical ventilation compared with conventional oxygen therapy and noninvasive positive pressure ventilation: a systematic review and meta-analysis. Am J Emerg Med. 2018;36(2):226\u201333.","journal-title":"Am J Emerg Med"},{"issue":"Suppl 8","key":"3344_CR14","doi-asserted-by":"publisher","first-page":"S380","DOI":"10.21037\/atm.2019.12.106","volume":"7","author":"JD Ricard","year":"2019","unstructured":"Ricard JD, Gaborieau B, Bernier J, Le Breton C, Messika J. Use of high flow nasal cannula for preoxygenation and apneic oxygenation during intubation. Ann Transl Med. 2019;7(Suppl 8):S380.","journal-title":"Ann Transl Med"},{"key":"3344_CR15","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.jcrc.2019.06.020","volume":"53","author":"T Mauri","year":"2019","unstructured":"Mauri T, Carlesso E, Spinelli E, Turrini C, Corte FD, Russo R, et al. Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: a physiologic study. J Crit Care. 2019;53:183\u20135.","journal-title":"J Crit Care"},{"issue":"10","key":"3344_CR16","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.4187\/respcare.04028","volume":"60","author":"RL Parke","year":"2015","unstructured":"Parke RL, Bloch A, McGuinness SP. Effect of very-high-flow nasal therapy on airway pressure and end-expiratory lung impedance in healthy volunteers. Respir Care. 2015;60(10):1397\u2013403.","journal-title":"Respir Care"},{"issue":"10","key":"3344_CR17","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1007\/s00134-017-4890-1","volume":"43","author":"T Mauri","year":"2017","unstructured":"Mauri T, Alban L, Turrini C, Cambiaghi B, Carlesso E, Taccone P, et al. Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates. Intensive Care Med. 2017;43(10):1453\u201363.","journal-title":"Intensive Care Med"},{"issue":"23","key":"3344_CR18","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1056\/NEJMoa1503326","volume":"372","author":"JP Frat","year":"2015","unstructured":"Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185\u201396.","journal-title":"N Engl J Med"},{"issue":"6","key":"3344_CR19","doi-asserted-by":"publisher","first-page":"638","DOI":"10.4187\/respcare.06735","volume":"64","author":"T Piraino","year":"2019","unstructured":"Piraino T. Noninvasive respiratory support in acute hypoxemic respiratory failure. Respir Care. 2019;64(6):638\u201346.","journal-title":"Respir Care"},{"issue":"1","key":"3344_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/PCC.0000000000000011","volume":"15","author":"S Rubin","year":"2014","unstructured":"Rubin S, Ghuman A, Deakers T, Khemani R, Ross P, Newth CJ. Effort of breathing in children receiving high-flow nasal cannula. Pediatr Crit Care Med. 2014;15(1):1\u20136.","journal-title":"Pediatr Crit Care Med"},{"issue":"12","key":"3344_CR21","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1056\/NEJMoa1714855","volume":"378","author":"D Franklin","year":"2018","unstructured":"Franklin D, Babl FE, Schlapbach LJ, Oakley E, Craig S, Neutze J, et al. A randomized trial of high-flow oxygen therapy in infants with bronchiolitis. N Engl J Med. 2018;378(12):1121\u201331.","journal-title":"N Engl J Med"},{"issue":"8","key":"3344_CR22","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1007\/s00431-018-3191-1","volume":"177","author":"AB Ergul","year":"2018","unstructured":"Ergul AB, Caliskan E, Samsa H, Gokcek I, Kaya A, Zararsiz GE, et al. Using a high-flow nasal cannula provides superior results to OxyMask delivery in moderate to severe bronchiolitis: a randomized controlled study. Eur J Pediatr. 2018;177(8):1299\u2013307.","journal-title":"Eur J Pediatr"},{"issue":"11","key":"3344_CR23","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1097\/PEC.0b013e31827122a9","volume":"28","author":"R Wing","year":"2012","unstructured":"Wing R, James C, Maranda LS, Armsby CC. Use of high-flow nasal cannula support in the emergency department reduces the need for intubation in pediatric acute respiratory insufficiency. Pediatr Emerg Care. 2012;28(11):1117\u201323.","journal-title":"Pediatr Emerg Care"},{"issue":"1","key":"3344_CR24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13613-016-0151-7","volume":"6","author":"R Coudroy","year":"2016","unstructured":"Coudroy R, Jamet A, Petua P, Robert R, Frat JP, Thille AW. High-flow nasal cannula oxygen therapy versus noninvasive ventilation in immunocompromised patients with acute respiratory failure: an observational cohort study. Ann Intensive Care. 2016;6(1):45.","journal-title":"Ann Intensive Care"},{"issue":"13","key":"3344_CR25","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1001\/jama.2016.2711","volume":"315","author":"G Hernandez","year":"2016","unstructured":"Hernandez G, Vaquero C, Gonzalez P, Subira C, Frutos-Vivar F, Rialp G, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: a randomized clinical trial. JAMA. 2016;315(13):1354\u201361.","journal-title":"JAMA"},{"issue":"11","key":"3344_CR26","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1007\/s00134-018-5343-1","volume":"44","author":"C Milesi","year":"2018","unstructured":"Milesi C, Pierre AF, Deho A, Pouyau R, Liet JM, Guillot C, et al. A multicenter randomized controlled trial of a 3-L\/kg\/min versus 2-L\/kg\/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2). Intensive Care Med. 2018;44(11):1870\u20138.","journal-title":"Intensive Care Med"},{"issue":"9","key":"3344_CR27","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1164\/rccm.201701-0006ED","volume":"195","author":"EC Goligher","year":"2017","unstructured":"Goligher EC, Slutsky AS. Not just oxygen? Mechanisms of benefit from high-flow nasal cannula in hypoxemic respiratory failure. Am J Respir Crit Care Med. 2017;195(9):1128\u201331.","journal-title":"Am J Respir Crit Care Med"},{"issue":"10","key":"3344_CR28","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.4187\/respcare.03814","volume":"60","author":"F Vargas","year":"2015","unstructured":"Vargas F, Saint-Leger M, Boyer A, Bui NH, Hilbert G. Physiologic effects of high-flow nasal cannula oxygen in critical care subjects. Respir Care. 2015;60(10):1369\u201376.","journal-title":"Respir Care"},{"issue":"12","key":"3344_CR29","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1097\/CCM.0000000000002693","volume":"45","author":"M Delorme","year":"2017","unstructured":"Delorme M, Bouchard PA, Simon M, Simard S, Lellouche F. Effects of high-flow nasal cannula on the work of breathing in patients recovering from acute respiratory failure. Crit Care Med. 2017;45(12):1981\u20138.","journal-title":"Crit Care Med"},{"issue":"14","key":"3344_CR30","doi-asserted-by":"publisher","first-page":"297","DOI":"10.21037\/atm.2017.06.52","volume":"5","author":"JP Frat","year":"2017","unstructured":"Frat JP, Coudroy R, Marjanovic N, Thille AW. High-flow nasal oxygen therapy and noninvasive ventilation in the management of acute hypoxemic respiratory failure. Ann Transl Med. 2017;5(14):297.","journal-title":"Ann Transl Med"},{"issue":"3","key":"3344_CR31","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1164\/rccm.201402-0364OC","volume":"190","author":"SM Maggiore","year":"2014","unstructured":"Maggiore SM, Idone FA, Vaschetto R, Festa R, Cataldo A, Antonicelli F, et al. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282\u20138.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"3344_CR32","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1097\/CCM.0000000000002818","volume":"46","author":"JP Frat","year":"2018","unstructured":"Frat JP, Ragot S, Coudroy R, Constantin JM, Girault C, Prat G, et al. Predictors of intubation in patients with acute hypoxemic respiratory failure treated with a noninvasive oxygenation strategy. Crit Care Med. 2018;46(2):208\u201315.","journal-title":"Crit Care Med"},{"issue":"1","key":"3344_CR33","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13054-018-2039-4","volume":"22","author":"T Mauri","year":"2018","unstructured":"Mauri T, Galazzi A, Binda F, Masciopinto L, Corcione N, Carlesso E, et al. Impact of flow and temperature on patient comfort during respiratory support by high-flow nasal cannula. Crit Care. 2018;22(1):120.","journal-title":"Crit Care"}],"container-title":["Critical Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13054-020-03344-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13054-020-03344-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13054-020-03344-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T10:27:05Z","timestamp":1606127225000},"score":1,"resource":{"primary":{"URL":"https:\/\/ccforum.biomedcentral.com\/articles\/10.1186\/s13054-020-03344-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["3344"],"URL":"https:\/\/doi.org\/10.1186\/s13054-020-03344-0","relation":{},"ISSN":["1364-8535"],"issn-type":[{"value":"1364-8535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]},"assertion":[{"value":"20 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The Ethical Committee of the Fondazione IRCCS Ca\u2019 GrandaOspedale Maggiore Policlinico, Milan, Italy approved the study (reference number: 665_2018), and informed consent was obtained from each patient.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"TM received personal fees from Drager, Fisher and Paykel, BBraun, Mindray, outside the submitted work. GG received personal fees from Drager, Fisher and Paykel, Getinge, Pfizer, MSD, Biotest, outside the submitted work. The other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"654"}}