CINXE.COM
Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial | Critical Care Medicine | JAMA | JAMA Network
<!DOCTYPE html> <html id="doc" lang="en" class="page-article"> <head id="Head1"> <!-- charset must appear in the first 1024 bytes of the document --> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <script> var SCM = SCM || {}; if (SCM.AMA && SCM.AMA.DataLayerAsync) { SCM.AMA.DataLayerAsync.push("arrSisAffinity", "", "array"); SCM.AMA.DataLayerAsync.push("SubStatus", "no", "string"); } var googletag = window.googletag || {}; googletag.cmd = googletag.cmd || []; if (typeof Storage !== "undefined") { var targetingParamStr = localStorage.getItem("bcDFPTargetingParams"); if (targetingParamStr) { var targetingParameters = JSON.parse(targetingParamStr); // set page-level targeting parameters jQuery.each(targetingParameters, function (index, param) { googletag.cmd.push(function () { window.googletag.pubads().setTargeting(param.key, param.value); }); }); } } if (!googletag.pubads) { (function () { var gads = document.createElement('script'); var useSSL = 'https:' == document.location.protocol; gads.src = (useSSL ? 'https:' : 'http:') + '//securepubads.g.doubleclick.net/tag/js/gpt.js'; gads.setAttribute("async", ""); gads.setAttribute("defer", ""); var node = document.getElementsByTagName('script')[0]; node.parentNode.insertBefore(gads, node); })(); var App = App || {}; App.Ads = App.Ads || {}; App.Ads.adPath = App.Ads.adPath || '/6479/' + 'ama.jama'; App.Ads.Mappings = App.Ads.Mappings || {}; App.Ads.slots = App.Ads.slots || []; App.Ads.fromGoogle = !('yes' === 'yes'); App.isCollection = App.isCollection || !!document.getElementsByClassName('pg_collection').length; googletag.cmd.push(function () { googletag.pubads() .setTargeting('environment', ['newjama']) .setTargeting('site', ['ama.jama']) .setTargeting('sect', ['scholarly']) .setTargeting('sub', ['no']) .setTargeting('device', ['Mozilla%2F4.0%20%28compatible%3B%20MSIE%207.0%3B%20Windows%20NT%206.0%3B%20SLCC1%3B%20.NET%20CLR%202.0.50727%3B%20.NET%20CLR%203.0.04506%3B%20.NET%20CLR%203.5.21022%3B%20.NET%20CLR%201.0.3705%3B%20.NET%20CLR%201.1.4322%29']) .setTargeting('usaphys', ['no']) .setTargeting('memberstat', ['no']) .setTargeting('pracset', ['']) .setTargeting('specialty', ['other']) .setTargeting('occupation', ['']) .setTargeting('useraffinity', ['']) .setTargeting('direct', ['yes']) .setTargeting('bot', ['']) .setTargeting('datacenter', ['no']) .setTargeting('selfMPA', ['']) .setTargeting('selfSpecialty', ['']); if (App.isCollection) { googletag.pubads().setTargeting('collection', ['']); } var testParam = getQueryVariable('test'); if (testParam) { googletag.pubads().setTargeting('test', [testParam]); } function getQueryVariable(variable) { var query = window.location.search.substring(1); var vars = query.split('&'); for (var i = 0; i < vars.length; i++) { var pair = vars[i].split('='); if (decodeURIComponent(pair[0]) == variable) { return decodeURIComponent(pair[1]); } } } googletag.pubads().disableInitialLoad(); googletag.enableServices(); }); } </script> <meta name="viewport" content="width=device-width, initial-scale=1" /><meta name="format-detection" content="telephone=no" /><link rel="shortcut icon" href="//cdn.jamanetwork.com/UI/app/img/favicons/jama/favicon.ico"> <link rel="icon" type="image/png" href="//cdn.jamanetwork.com/UI/app/img/favicons/jama/favicon-192x192.png" sizes="192x192"> <link rel="apple-touch-icon" sizes="180x180" href="//cdn.jamanetwork.com/UI/app/img/favicons/jama/apple-touch-icon-180x180.png"> <meta http-equiv="X-UA-Compatible" content="IE=Edge" /> <link rel="stylesheet" href="//cdn.jamanetwork.com/UI/app/dist/app.min.css?v=638677764476993385"> <link href="//cdn.jsdelivr.net/chartist.js/latest/chartist.min.css" type="text/css" rel="stylesheet" /> <meta property="og:title" content="Effect of Titrated vs Low Positive End-Expiratory Pressure (PEEP) on Mortality in ARDS" /> <meta property="og:type" content="Article" /> <meta property="og:url" content="https://jamanetwork.com/journals/jama/fullarticle/2654894" /> <meta property="og:image" content="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f1.png?Expires=2147483647&Signature=pU0pHyb7NPksZlo-Jx-Dp9COiSuWvBUUjZbmrk5QJ7ZWwm5g2GfNu2M~4G9EcejS2wbobv2ImZr4rD2qmQquQ-JmoE6suIdPFEv9OFVuooDlP2Vu8lxCvEIFJbdBhKD4DoxzylShgShvuGoYz50PeNeu0w705QynAY7mrjaLV8zaMB8qxQhPNEjQLl1nkt7qPW6OIsmeI21XjQ-O6yEeh9uD7NO-naFdqjIPYHvIUCfud6dgaP5ETYAD5VyjDqIm2-hYepMJqZwLfs7IcYvjmH7R~KnA-gvMGN1W62GJ45Ow~HTK37uF4osjBhu1NW2ohuOLpnVtE6BhTqzWHTwNGA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:image" content="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t1.png?Expires=2147483647&Signature=EwiJc6ITNTqnpD~W0z55ZbTvv5lDQrZLlHqFtrxhxmFYgQ3H9n6GWZ4~k7hwqXtBpUmnTvybk1ls-IFv4eK-doaWL8ELiYvAU7dLwVEAbUilNaPkYTeOPQ0c5~GZamwgF581qoCa1cv-oO5OJ79adihuvFdzyckhIQBY-9uDEHVEqJFc-rSxnQ65cVZEhGYDqv49UMxXDYuSZR1N2vGtsh~tHNFBGGCgsSAjf6zmyNhFl1HlKzohv-YfGgbYEAE4aBWueJedxt06JBURXhAV~ZIKKisReNJ5dOspy0xwvEQoNG~zs071NiAjoHuSHwmdTLKoSiznf3qfBXDeQmXcWA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:image" content="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f2.png?Expires=2147483647&Signature=lwWxPJFGiJ6nKCHKP18~B8aUCxJIPmoVprMIrOENzQVi7ck5ms3HCibByA8ORZionraCuFPNNJiKiph7BKLPLp0MrGa1yKGlCO9JiIQ4TdFlV7E9c8q6Fm0-4HJRFkc9-jDoz7F3Ma1Z4NsJZAUPWDOGxPop8PZA9DdtEJB4zJOEIbiNEYp7pRBZk8oRiIkzNpGXLCHHk1ixEtgmfUQUpKrBZ6GWY27eyB1c9EJEu5LucMTQuNDBuR6jTmtR~5e5oTfM7frtUELw6oMHUZd0KPGLe3bcSsm6k4pt94-VPI3laaxGuMC6TErqLhEDnEm8AK~JdrrgPVGnZiLmnBg42Q__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:image" content="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t2.png?Expires=2147483647&Signature=G1IMyGHrvOPNVhTJPeDGOTxkfw8n8sXOh-uiTGHry7lH5Q1toZf1HHijT1yAOccfXwERssGkaIZdKpw4L1lBLZJcgV5qZYLsIauvl9Uws8wgGVevk5HeP8PogwfkvpWcaqZh26zd1F~3IXHnymP3mm2CUfkc96hPVKncBCzM~EZccs4n2LPrLfVkOqs10eo2YTa6jqmDMIj0ncI4FDd~NWzw~JNmy9iCb9sWZNohed1SrCV72tAoQ1clc-4FQOUbbW5E-r-GGltLpZuCJoCFxsEh7kQkHj80FG9LM-NiDY-vFMdVINhNnva61wba07RCNO9X~-TF~AaYxztkaD4zUQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:image" content="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f3.png?Expires=2147483647&Signature=tmWLY7xYm19nQoNNtFSiyf9ygYTE4TMPzLvoprdJm7ZDtsVr6P~pcw9kMZ6se4~ahNFzDbVeMLSj2ZfSKQsvNNrriPY0c8QJLagjyV3G2-7YjahK4zE8iGfHMuztG7VIWqab-ma8-NtYP--d6X3Z7Q7y19ojqW3IdtLldd27bU5sfkwhkAfZ7oRolRe8QGSFRUtd3mZNglgA5TQhlFUyJWX8Gzp6CVxB7mPQg6Tg50YmtRmceQx~royeRT~fbuBKx3uMQjWaUa2RQ5wl2qyyu6zGcTLkL9LV3Mt-S4R0~kw79PNoC7MOd1V15m4Jiw3T4~8mlGCcvqFi-qTI84RiAg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:description" content="This randomized trial compares the effects of ventilator lung recruitment using PEEP titration vs a conventional low-PEEP strategy on 28-day mortality in patients with moderate to severe acute respiratory distress syndrome (ARDS)." /> <meta property="fb:pages" content="87087958340" /> <meta property="fb:pages" content="122228711814384" /> <meta property="fb:pages" content="1648414928738217" /> <meta property="fb:pages" content="117506346528" /> <meta property="fb:pages" content="97538728726" /> <meta property="fb:pages" content="114116793520" /> <meta property="fb:pages" content="100679858757" /> <meta property="fb:pages" content="759822190741773" /> <meta property="fb:pages" content="100265333750" /> <meta property="fb:pages" content="234770525256" /> <meta property="fb:pages" content="98784919862" /> <meta property="fb:pages" content="120829458202" /> <meta property="fb:pages" content="124842870398" /> <meta property="fb:pages" content="110245330325636" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:site" content="@JAMA_current" /> <meta name="twitter:image" content="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f1.png?Expires=2147483647&Signature=pU0pHyb7NPksZlo-Jx-Dp9COiSuWvBUUjZbmrk5QJ7ZWwm5g2GfNu2M~4G9EcejS2wbobv2ImZr4rD2qmQquQ-JmoE6suIdPFEv9OFVuooDlP2Vu8lxCvEIFJbdBhKD4DoxzylShgShvuGoYz50PeNeu0w705QynAY7mrjaLV8zaMB8qxQhPNEjQLl1nkt7qPW6OIsmeI21XjQ-O6yEeh9uD7NO-naFdqjIPYHvIUCfud6dgaP5ETYAD5VyjDqIm2-hYepMJqZwLfs7IcYvjmH7R~KnA-gvMGN1W62GJ45Ow~HTK37uF4osjBhu1NW2ohuOLpnVtE6BhTqzWHTwNGA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <script type="application/ld+json"> { "@context": "https://schema.org/", "@type": "Article", "headline": "Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in", "author": "Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators", "url": "https://jamanetwork.com/journals/jama/fullarticle/2654894", "datePublished": "2017-10-10", "description": "This randomized trial compares the effects of ventilator lung recruitment using PEEP titration vs a conventional low-PEEP strategy on 28-day mortality in patients with moderate to severe acute respiratory distress syndrome (ARDS).", "publisher": { "@type": "Organization", "name": "JAMA Network", "logo": { "@type": "ImageObject", "url": "//cdn.jamanetwork.com/UI/app/img/favicons/jama/favicon.ico" } }, "image": [ "https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f1.png?Expires=2147483647&Signature=pU0pHyb7NPksZlo-Jx-Dp9COiSuWvBUUjZbmrk5QJ7ZWwm5g2GfNu2M~4G9EcejS2wbobv2ImZr4rD2qmQquQ-JmoE6suIdPFEv9OFVuooDlP2Vu8lxCvEIFJbdBhKD4DoxzylShgShvuGoYz50PeNeu0w705QynAY7mrjaLV8zaMB8qxQhPNEjQLl1nkt7qPW6OIsmeI21XjQ-O6yEeh9uD7NO-naFdqjIPYHvIUCfud6dgaP5ETYAD5VyjDqIm2-hYepMJqZwLfs7IcYvjmH7R~KnA-gvMGN1W62GJ45Ow~HTK37uF4osjBhu1NW2ohuOLpnVtE6BhTqzWHTwNGA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA", "https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t1.png?Expires=2147483647&Signature=EwiJc6ITNTqnpD~W0z55ZbTvv5lDQrZLlHqFtrxhxmFYgQ3H9n6GWZ4~k7hwqXtBpUmnTvybk1ls-IFv4eK-doaWL8ELiYvAU7dLwVEAbUilNaPkYTeOPQ0c5~GZamwgF581qoCa1cv-oO5OJ79adihuvFdzyckhIQBY-9uDEHVEqJFc-rSxnQ65cVZEhGYDqv49UMxXDYuSZR1N2vGtsh~tHNFBGGCgsSAjf6zmyNhFl1HlKzohv-YfGgbYEAE4aBWueJedxt06JBURXhAV~ZIKKisReNJ5dOspy0xwvEQoNG~zs071NiAjoHuSHwmdTLKoSiznf3qfBXDeQmXcWA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA", "https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f2.png?Expires=2147483647&Signature=lwWxPJFGiJ6nKCHKP18~B8aUCxJIPmoVprMIrOENzQVi7ck5ms3HCibByA8ORZionraCuFPNNJiKiph7BKLPLp0MrGa1yKGlCO9JiIQ4TdFlV7E9c8q6Fm0-4HJRFkc9-jDoz7F3Ma1Z4NsJZAUPWDOGxPop8PZA9DdtEJB4zJOEIbiNEYp7pRBZk8oRiIkzNpGXLCHHk1ixEtgmfUQUpKrBZ6GWY27eyB1c9EJEu5LucMTQuNDBuR6jTmtR~5e5oTfM7frtUELw6oMHUZd0KPGLe3bcSsm6k4pt94-VPI3laaxGuMC6TErqLhEDnEm8AK~JdrrgPVGnZiLmnBg42Q__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA", "https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t2.png?Expires=2147483647&Signature=G1IMyGHrvOPNVhTJPeDGOTxkfw8n8sXOh-uiTGHry7lH5Q1toZf1HHijT1yAOccfXwERssGkaIZdKpw4L1lBLZJcgV5qZYLsIauvl9Uws8wgGVevk5HeP8PogwfkvpWcaqZh26zd1F~3IXHnymP3mm2CUfkc96hPVKncBCzM~EZccs4n2LPrLfVkOqs10eo2YTa6jqmDMIj0ncI4FDd~NWzw~JNmy9iCb9sWZNohed1SrCV72tAoQ1clc-4FQOUbbW5E-r-GGltLpZuCJoCFxsEh7kQkHj80FG9LM-NiDY-vFMdVINhNnva61wba07RCNO9X~-TF~AaYxztkaD4zUQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA", "https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f3.png?Expires=2147483647&Signature=tmWLY7xYm19nQoNNtFSiyf9ygYTE4TMPzLvoprdJm7ZDtsVr6P~pcw9kMZ6se4~ahNFzDbVeMLSj2ZfSKQsvNNrriPY0c8QJLagjyV3G2-7YjahK4zE8iGfHMuztG7VIWqab-ma8-NtYP--d6X3Z7Q7y19ojqW3IdtLldd27bU5sfkwhkAfZ7oRolRe8QGSFRUtd3mZNglgA5TQhlFUyJWX8Gzp6CVxB7mPQg6Tg50YmtRmceQx~royeRT~fbuBKx3uMQjWaUa2RQ5wl2qyyu6zGcTLkL9LV3Mt-S4R0~kw79PNoC7MOd1V15m4Jiw3T4~8mlGCcvqFi-qTI84RiAg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" ], "articleSection": [ "Introduction", "Methods", "Study Design and Oversight", "Patients", "Randomization and Masking", "Interventions", "Outcomes", "Statistical Analysis", "Results", "Patients", "Lung Recruitment", "Ventilator Settings and Respiratory Variables", "Cointerventions", "Outcomes", "Subgroup and Exploratory Analyses", "Discussion", "Limitations", "Conclusions", "Article Information" ], "keyWords": "positive end-expiratory pressure, respiratory distress syndrome, adult, titration method, alveolar recruitment ventilation strategy, respiratory system" } </script> <meta name="citation_author" content="Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators" /><meta name="citation_author" content="Alexandre Biasi Cavalcanti" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Érica Aranha Suzumura" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Ligia Nasi Laranjeira" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Denise de Moraes Paisani" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Lucas Petri Damiani" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Helio Penna Guimarães" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Edson Renato Romano" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Marisa de Moraes Regenga" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Luzia Noriko Takahashi Taniguchi" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Cassiano Teixeira" /><meta name="citation_author_institution" content="Hospital Moinhos de Vento, Porto Alegre, Brazil" /><meta name="citation_author" content="Roselaine Pinheiro de Oliveira" /><meta name="citation_author_institution" content="Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil " /><meta name="citation_author" content="Flavia Ribeiro Machado" /><meta name="citation_author_institution" content="Anesthesiology, Pain, and Intensive Care Department, Federal University of São Paulo–UNIFESP, São Paulo, Brazil" /><meta name="citation_author" content="Fredi Alexander Diaz-Quijano" /><meta name="citation_author_institution" content="Epidemiology Department, School of Public Health, University of São Paulo, São Paulo, Brazil" /><meta name="citation_author" content="Meton Soares de Alencar Filho" /><meta name="citation_author_institution" content="Hospital Maternidade São Vicente de Paulo, Barbalha, Brazil" /><meta name="citation_author" content="Israel Silva Maia" /><meta name="citation_author_institution" content="Hospital Nereu Ramos, Florianópolis, Brazil" /><meta name="citation_author" content="Eliana Bernardete Caser" /><meta name="citation_author_institution" content="Hospital Unimed Vitória, Vitória, Brazil " /><meta name="citation_author" content="Wilson de Oliveira Filho" /><meta name="citation_author_institution" content="Hospital e Pronto-Socorro 28 de Agosto, Manaus, Brazil " /><meta name="citation_author" content="Marcos de Carvalho Borges" /><meta name="citation_author_institution" content="Unidade de Emergência do Hospital das Clínicas da FMRP-USP, Ribeirão Preto, Brazil" /><meta name="citation_author" content="Priscilla de Aquino Martins" /><meta name="citation_author_institution" content="Hospital Estadual Dr Jayme dos Santos Neves, Serra, Brazil" /><meta name="citation_author" content="Mirna Matsui" /><meta name="citation_author_institution" content="Hospital Universitário da Universidade Federal da Grande Dourados, Dourados, Brazil" /><meta name="citation_author" content="Gustavo Adolfo Ospina-Tascón" /><meta name="citation_author_institution" content="Department of Intensive Care Medicine, Fundación Valle del Lili - Universidad ICESI, Cali, Colombia" /><meta name="citation_author" content="Thiago Simões Giancursi" /><meta name="citation_author_institution" content="Hospital Universitário do Oeste do Paraná, Cascavel, Brazil" /><meta name="citation_author" content="Nelson Dario Giraldo-Ramirez" /><meta name="citation_author_institution" content="Hospital Pablo Tóbon Uribe, Medellín, Colombia" /><meta name="citation_author" content="Silvia Regina Rios Vieira" /><meta name="citation_author_institution" content="Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil" /><meta name="citation_author" content="Maria da Graça Pasquotto de Lima Assef" /><meta name="citation_author_institution" content="Hospital Regional Hans Dieter Schmidt, Joinville, Brazil" /><meta name="citation_author" content="Mohd Shahnaz Hasan" /><meta name="citation_author_institution" content="University Malaya Medical Centre, Kuala Lumpur, Malaysia" /><meta name="citation_author" content="Wojciech Szczeklik" /><meta name="citation_author_institution" content="Jagiellonian University Medical College; Department of Intensive Care and Perioperative Medicine, Krakow, Poland" /><meta name="citation_author" content="Fernando Rios" /><meta name="citation_author_institution" content="Hospital Nacional Alejandro Posadas, Moron, Argentina" /><meta name="citation_author" content="Marcelo Britto Passos Amato" /><meta name="citation_author_institution" content="Cardio-Pulmonary Department, Pulmonary Division, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil" /><meta name="citation_author" content="Otávio Berwanger" /><meta name="citation_author_institution" content="HCor Research Institute, São Paulo, Brazil" /><meta name="citation_author" content="Carlos Roberto Ribeiro de Carvalho" /><meta name="citation_author_institution" content="Cardio-Pulmonary Department, Pulmonary Division, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil" /><meta name="citation_title" content="Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial" /><meta name="citation_firstpage" content="1335" /><meta name="citation_lastpage" content="1345" /><meta name="citation_doi" content="10.1001/jama.2017.14171" /><meta name="citation_keyword" content="positive end-expiratory pressure" /><meta name="citation_keyword" content="respiratory distress syndrome, adult" /><meta name="citation_keyword" content="titration method" /><meta name="citation_keyword" content="alveolar recruitment ventilation strategy" /><meta name="citation_keyword" content="respiratory system" /><meta name="citation_abstract" content="<h3>Importance</h3><p>The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain.</p><h3>Objective</h3><p>To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy.</p><h3>Design, Setting, and Participants</h3><p>Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS.</p><h3>Interventions</h3><p>An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory–system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning.</p><h3>Main Outcomes and Measures</h3><p>The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality.</p><h3>Results</h3><p>A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42;<i>P</i> = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38;<i>P</i> = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1;<i>P</i> = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%;<i>P</i> = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%;<i>P</i> = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.</p><h3>Conclusions and Relevance</h3><p>In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.</p><h3>Trial Registration</h3><p>clinicaltrials.gov Identifier:NCT01374022</p>" /><meta name="citation_journal_title" content="JAMA" /><meta name="citation_journal_abbrev" content="JAMA" /><meta name="citation_volume" content="318" /><meta name="citation_issue" content="14" /><meta name="citation_publication_date" content="2017/10/10" /><meta name="citation_issn" content="0098-7484" /><meta name="citation_publisher" content="American Medical Association" /><meta name="citation_reference" content="citation_title=Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries.; citation_author=LUNG SAFE Investigators; citation_author=Bellani G; citation_author=Laffey JG; citation_author=Pham T; citation_journal_title=JAMA; citation_year=2016; citation_volume=315; citation_issue=8; citation_pages=788-800; " /><meta name="citation_reference" content="citation_title=Functional disability 5 years after acute respiratory distress syndrome.; citation_author=Canadian Critical Care Trials Group; citation_author=Herridge MS; citation_author=Tansey CM; citation_author=Matté A; citation_journal_title=N Engl J Med; citation_year=2011; citation_volume=364; citation_issue=14; citation_pages=1293-1304; " /><meta name="citation_reference" content="citation_title=The “baby lung” became an adult.; citation_author=Gattinoni L; citation_author=Marini JJ; citation_author=Pesenti A; citation_author=Quintel M; citation_author=Mancebo J; citation_author=Brochard L; citation_journal_title=Intensive Care Med; citation_year=2016; citation_volume=42; citation_issue=5; citation_pages=663-673; " /><meta name="citation_reference" content="citation_title=Ventilator-induced lung injury: the anatomical and physiological framework.; citation_author=Gattinoni L; citation_author=Protti A; citation_author=Caironi P; citation_author=Carlesso E; citation_journal_title=Crit Care Med; citation_year=2010; citation_volume=38; citation_issue=10; citation_pages=S539-S548; " /><meta name="citation_reference" content="citation_title=Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.; citation_author=Amato MB; citation_author=Barbas CS; citation_author=Medeiros DM; citation_journal_title=N Engl J Med; citation_year=1998; citation_volume=338; citation_issue=6; citation_pages=347-354; " /><meta name="citation_reference" content="citation_title=Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.; citation_author=Acute Respiratory Distress Syndrome Network; citation_author=Brower RG; citation_author=Matthay MA; citation_author=Morris A; citation_author=Schoenfeld D; citation_author=Thompson BT; citation_author=Wheeler A; citation_journal_title=N Engl J Med; citation_year=2000; citation_volume=342; citation_issue=18; citation_pages=1301-1308; " /><meta name="citation_reference" content="citation_title=Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome.; citation_author=Borges JB; citation_author=Okamoto VN; citation_author=Matos GF; citation_journal_title=Am J Respir Crit Care Med; citation_year=2006; citation_volume=174; citation_issue=3; citation_pages=268-278; " /><meta name="citation_reference" content="citation_title=How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography.; citation_author=de Matos GF; citation_author=Stanzani F; citation_author=Passos RH; citation_journal_title=Crit Care; citation_year=2012; citation_volume=16; citation_issue=1; citation_pages=R4" /><meta name="citation_reference" content="citation_title=A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome.; citation_author=Hodgson CL; citation_author=Tuxen DV; citation_author=Davies AR; citation_journal_title=Crit Care; citation_year=2011; citation_volume=15; citation_issue=3; citation_pages=R133" /><meta name="citation_reference" content="citation_title=Open lung approach for the acute respiratory distress syndrome: a pilot, randomized controlled trial.; citation_author=Open Lung Approach Network; citation_author=Kacmarek RM; citation_author=Villar J; citation_author=Sulemanji D; citation_journal_title=Crit Care Med; citation_year=2016; citation_volume=44; citation_issue=1; citation_pages=32-42; " /><meta name="citation_reference" content="citation_title=Effects of alveolar recruitment maneuvers on clinical outcomes in patients with acute respiratory distress syndrome: a systematic review and meta-analysis.; citation_author=Suzumura EA; citation_author=Figueiró M; citation_author=Normilio-Silva K; citation_journal_title=Intensive Care Med; citation_year=2014; citation_volume=40; citation_issue=9; citation_pages=1227-1240; " /><meta name="citation_reference" content="citation_title=Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation.; citation_author=Hodgson C; citation_author=Goligher EC; citation_author=Young ME; citation_journal_title=Cochrane Database Syst Rev; citation_year=2016; citation_volume=11; citation_pages=CD006667" /><meta name="citation_reference" content="citation_title=Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial.; citation_author=ART Investigators; citation_journal_title=Trials; citation_year=2012; citation_volume=13; citation_issue=1; citation_pages=153" /><meta name="citation_reference" content="citation_title=Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART): a randomized controlled trial.; citation_author=Damiani L; citation_author=Berwanger O; citation_author=Paisani D; citation_journal_title=Rev Bras Ter Intensiva; citation_year=2017; citation_volume=29; citation_issue=2; citation_pages=142-153; " /><meta name="citation_reference" content="citation_title=The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.; citation_author=Bernard GR; citation_author=Artigas A; citation_author=Brigham KL; citation_journal_title=Am J Respir Crit Care Med; citation_year=1994; citation_volume=149; citation_issue=3 pt 1; citation_pages=818-824; " /><meta name="citation_reference" content="citation_title=Prone positioning in severe acute respiratory distress syndrome.; citation_author=PROSEVA Study Group; citation_author=Guérin C; citation_author=Reignier J; citation_author=Richard JC; citation_journal_title=N Engl J Med; citation_year=2013; citation_volume=368; citation_issue=23; citation_pages=2159-2168; " /><meta name="citation_reference" content="citation_title=Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.; citation_author=Expiratory Pressure (Express) Study Group; citation_author=Mercat A; citation_author=Richard JC; citation_author=Vielle B; citation_journal_title=JAMA; citation_year=2008; citation_volume=299; citation_issue=6; citation_pages=646-655; " /><meta name="citation_reference" content="citation_title=High PEEP levels are associated with overdistension and tidal recruitment/derecruitment in ARDS patients.; citation_author=Retamal J; citation_author=Bugedo G; citation_author=Larsson A; citation_author=Bruhn A; citation_journal_title=Acta Anaesthesiol Scand; citation_year=2015; citation_volume=59; citation_issue=9; citation_pages=1161-1169; " /><meta name="citation_reference" content="citation_title=Efficacy and safety of recruitment maneuvers in acute respiratory distress syndrome.; citation_author=Guerin C; citation_author=Debord S; citation_author=Leray V; citation_journal_title=Ann Intensive Care; citation_year=2011; citation_volume=1; citation_issue=1; citation_pages=9" /><meta name="citation_reference" content="citation_title=Driving pressure and survival in the acute respiratory distress syndrome.; citation_author=Amato MB; citation_author=Meade MO; citation_author=Slutsky AS; citation_journal_title=N Engl J Med; citation_year=2015; citation_volume=372; citation_issue=8; citation_pages=747-755; " /><meta name="citation_reference" content="citation_title=Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials.; citation_author=investigators of the Acurasys and Proseva trials; citation_author=Guérin C; citation_author=Papazian L; citation_author=Reignier J; citation_author=Ayzac L; citation_author=Loundou A; citation_author=Forel JM; citation_journal_title=Crit Care; citation_year=2016; citation_volume=20; citation_issue=1; citation_pages=384" /><meta name="citation_reference" content="citation_title=Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis.; citation_author=Briel M; citation_author=Meade M; citation_author=Mercat A; citation_journal_title=JAMA; citation_year=2010; citation_volume=303; citation_issue=9; citation_pages=865-873; " /><meta name="citation_reference" content="citation_title=Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.; citation_author=National Heart, Lung, and Blood Institute ARDS Clinical Trials Network; citation_author=Brower RG; citation_author=Lanken PN; citation_author=MacIntyre N; citation_journal_title=N Engl J Med; citation_year=2004; citation_volume=351; citation_issue=4; citation_pages=327-336; " /><meta name="citation_reference" content="citation_title=Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria.; citation_author=Beitler JR; citation_author=Sands SA; citation_author=Loring SH; citation_journal_title=Intensive Care Med; citation_year=2016; citation_volume=42; citation_issue=9; citation_pages=1427-1436; " /><meta name="citation_reference" content="citation_title=Impact of ventilator adjustment and sedation-analgesia practices on severe asynchrony in patients ventilated in assist-control mode.; citation_author=Chanques G; citation_author=Kress JP; citation_author=Pohlman A; citation_journal_title=Crit Care Med; citation_year=2013; citation_volume=41; citation_issue=9; citation_pages=2177-2187; " /><meta name="citation_reference" content="citation_title=Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.; citation_author=Lung Open Ventilation Study Investigators; citation_author=Meade MO; citation_author=Cook DJ; citation_author=Guyatt GH; citation_journal_title=JAMA; citation_year=2008; citation_volume=299; citation_issue=6; citation_pages=637-645; " /><meta name="citation_reference" content="citation_title=Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials.; citation_author=NHLBI ARDS Network; citation_author=Calfee CS; citation_author=Delucchi K; citation_author=Parsons PE; citation_author=Thompson BT; citation_author=Ware LB; citation_author=Matthay MA; citation_journal_title=Lancet Respir Med; citation_year=2014; citation_volume=2; citation_issue=8; citation_pages=611-620; " /><meta name="citation_reference" content="citation_title=Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy.; citation_author=ARDS Network; citation_author=Famous KR; citation_author=Delucchi K; citation_author=Ware LB; citation_journal_title=Am J Respir Crit Care Med; citation_year=2017; citation_volume=195; citation_issue=3; citation_pages=331-338; " /><meta name="citation_reference" content="citation_title=Lung recruitment in patients with the acute respiratory distress syndrome.; citation_author=Gattinoni L; citation_author=Caironi P; citation_author=Cressoni M; citation_journal_title=N Engl J Med; citation_year=2006; citation_volume=354; citation_issue=17; citation_pages=1775-1786; " /><meta name="citation_reference" content="citation_title=Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials.; citation_author=Goligher EC; citation_author=Kavanagh BP; citation_author=Rubenfeld GD; citation_author=Ferguson ND; citation_journal_title=Am J Respir Crit Care Med; citation_year=2015; citation_volume=192; citation_issue=12; citation_pages=1416-1419; " /><meta name="citation_pdf_url" content="https://jamanetwork.com/journals/jama/articlepdf/2654894/jama_cavalcanti_2017_oi_170110.pdf" /> <meta name="citation_xml_url" content="https://datafeed.jamanetwork.com/journals/jama/xml/2654894" /> <title>Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial | Critical Care Medicine | JAMA | JAMA Network</title> <meta name="description" content="This randomized trial compares the effects of ventilator lung recruitment using PEEP titration vs a conventional low-PEEP strategy on 28-day mortality in"> <link rel="canonical" href="https://jamanetwork.com/journals/jama/fullarticle/2654894" /> <script src="//cdn.jamanetwork.com/UI/app/dist/head.min.js?v=638677764511843155"></script> <script src="https://r451.jamanetwork.com/script.js" defer></script> <div class="widget-WidgetLoader widget-instance-AMA_AdTag_HeaderScript"> <meta class="SCM-SharedWidgets-AsyncHeaderAdLoader" data-url="/AMA/AdTag/AMA_AdTag_HeaderScript" data-params="{"parameters":{"siteName":"jama","siteId":3,"journalId":67,"adDisplay":0,"adSection":"scholarly","adPosition":"","fromGoogle":false},"dynamicParameters":{"localParams":"[REPLACE_WITH_LOCAL]"}}"> </div> </head> <body data-sitename="jama" class="pg_article " data-thm="jama"> <script> var App = App || {}; App.suppressAds = App.suppressAds || !!document.getElementsByClassName('suppress-ads').length; App.suppressGtm = App.suppressGtm || !!document.getElementsByClassName('suppress-gtm').length; </script> <div id="ad-interstitial" class="ad-interstitial"> <script defer> googletag.cmd.push(function() { if (App.suppressAds) { return; } // Define a web interstitial ad slot. let interstitialSlot = googletag.defineOutOfPageSlot( App.Ads.adPath + '/scholarly', googletag.enums.OutOfPageFormat.INTERSTITIAL, ); if (interstitialSlot) { App.Ads.slots[13] = interstitialSlot; // Enable optional interstitial triggers and register the slot. interstitialSlot .setTargeting('pos', ['interstitial']) .addService(googletag.pubads()) .setConfig({ interstitial: { triggers: { navBar: true, unhideWindow: true, }, }, }); googletag.display(interstitialSlot); googletag.pubads().refresh([interstitialSlot], { changeCorrelator: false }); googletag.enableServices(); } }); </script> </div> <a class="accessible js-skip-to-navigation" href="#skip-to-navigation">[Skip to Navigation]</a> <!-- Google Tag Manager --><noscript><iframe src="//www.googletagmanager.com/ns.html?id=GTM-WNKSNP" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript><script>(function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-WNKSNP');</script><!-- End Google Tag Manager --> <span class="hide tagmanagervalue" data-attribute="productName" data-value="JAMA" data-type="string"></span> <form method="post" action="./2654894" id="webform" class="m0"> <div class="aspNetHidden"> <input type="hidden" name="__VIEWSTATE" id="__VIEWSTATE" value="f76gCeISXrxCWPpJe0aYhljqKKUwpi1l93kWZXIxSOfSmSpkOrfyOxOKSQsd/kSfDYB3k1h6Poy4VFSZ5aLa22vTNnk=" /> </div> <div class="aspNetHidden"> <input type="hidden" name="__VIEWSTATEGENERATOR" id="__VIEWSTATEGENERATOR" value="2173C2F0" /> <input type="hidden" name="__EVENTVALIDATION" id="__EVENTVALIDATION" value="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" /> </div> <input id="hdnSiteID" type="hidden" value="3" /> <input id="hdnDomain" type="hidden" value=".jamanetwork.com" /> <section class="master-header"> <script type='text/javascript'> var App = App || {}; App.LoginUserInfo = { isInstLoggedIn: [0], currentSessionId: 'cig1wbp4druq4sioybzd2lrt' }; </script> <input name="ctl00$ctl00$BodyContent$Header$hfGlobalSearchSiteURL" type="hidden" id="hfGlobalSearchSiteURL" value="https://jamanetwork.com/" /> <input name="ctl00$ctl00$BodyContent$Header$hfAppIsPaidUser" type="hidden" id="hfAppIsPaidUser" value="false" /> <input name="ctl00$ctl00$BodyContent$Header$hfAppIsMember" type="hidden" id="hfAppIsMember" value="false" /> <input name="ctl00$ctl00$BodyContent$Header$hfAppSubscribedTo" type="hidden" id="hfAppSubscribedTo" /> <input name="ctl00$ctl00$BodyContent$Header$hfAppIsIndividual" type="hidden" id="hfAppIsIndividual" value="false" /> <input name="ctl00$ctl00$BodyContent$Header$hfAppHasAccess" type="hidden" id="hfAppHasAccess" value="false" /> <input name="ctl00$ctl00$BodyContent$Header$hfAppIsReferredFromGoogle" type="hidden" id="hfAppIsReferredFromGoogle" value="False" /> <input name="ctl00$ctl00$BodyContent$Header$hfSolrAutoSuggestMinimumCharactersLength" type="hidden" id="hfSolrAutoSuggestMinimumCharactersLength" value="2" /> <input name="ctl00$ctl00$BodyContent$Header$hfSolrJournalName" type="hidden" id="hfSolrJournalName" value="JAMA" /> <input name="ctl00$ctl00$BodyContent$Header$hfSolrJournalID" type="hidden" id="hfSolrJournalID" value="J67" /> <input name="ctl00$ctl00$BodyContent$Header$hfAppIsLucy" type="hidden" id="hfAppIsLucy" value="false" /> <div class="header-wrap"> <header class="header"> <div class="widget-GdprCookieBanner widget-instance-GdprCookieBanner"> <div class="gdpr-cookie-wrapper js-gdpr-banner"> <div class="gdpr-cookie-body"> Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our <a href="https://jamanetwork.com/pages/privacy-policy#cookies">Cookie Policy</a> <span class="pipe">|</span> <a href="javascript:;" class="js-gdpr-cookie-acceptLink at-acceptgdpr">Continue</a> </div> <input id="hdnDomain" type="hidden" value=".jamanetwork.com" /> <input id="hdnDomainGdpr" type="hidden" value=".jamanetwork.com" /> <input id="hdnClientIdGdpr" type="hidden" value="3" /> </div> </div> <div class="network-bar"> <a class="jama-network" href="/" title="JAMA Network Home"> <img alt="JAMA Network Home" class="title-image" width="443" height="52" src="//cdn.jamanetwork.com/UI/app/svg/Jama_Network_Logo.svg"> </a> </div> <a class="nav-toggler" href="#nav"> <div class="nav-toggler-indicator"> <span class="indicator-stroke"></span> <span class="indicator-stroke"></span> <span class="indicator-stroke"></span> <span class="indicator-stroke"></span> </div> <div class="nav-toggler-site"> <span id="BodyContent_Header_siteFullNamenav" class="nav-toggler-microsite"><span class='network'>JAMA</span></span> </div> </a> <nav id="nav" class="nav hide" > <div class="nav-journal-level sb-nav-journal-level"> <a href="https://jamanetwork.com/journals/jama" id="BodyContent_Header_rptMicrositeHeaders_aItemResourceList_0" class="home">Home</a><a href="https://jamanetwork.com/journals/jama/newonline" id="BodyContent_Header_rptMicrositeHeaders_aItemResourceList_1" class="new-online">New Online</a><a href="https://jamanetwork.com/journals/jama/currentissue" id="BodyContent_Header_rptMicrositeHeaders_aItemResourceList_2" class="current-issue">Current Issue</a><a href="https://jamanetwork.com/journals/jama/pages/for-authors" id="BodyContent_Header_rptMicrositeHeaders_aItemResourceList_3" class="for-authors">For Authors</a> </div> <div class="nav-journals"> <div class="widget-SelfServeContent widget-instance-HamburgerPublicationMenu"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="HamburgerPublicationMenu" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <style type="text/css"> .nav-journals {margin-bottom: 1em;} .nav-heading {color: #B9B9B9;border-bottom: 0;border-top: 1px solid #242424;font-size: 1.15em;font-weight: 400;margin: 0;padding: .7em .75em .25em;text-transform: uppercase;} a.no-bullet:before {content:none !important;} .nav-heading {font-size: 1.15em;margin-bottom:0;padding-left: 38px;} /* .nav-journals a.theme-jama {background-color: #242424;border-bottom: 1px solid #fff;border-top: 1px solid #fff;color: #fff;font-size: 1.15em;margin-bottom: 8px;padding: 11px 0 9px 37px;} .nav-journals a.theme-jama::before {background: unset;content: "\e91b";display: none;font-family: ama_icons !important;font-size: 1.25em;line-height: 1;} .nav-journals a.theme-jama-network-open {border-bottom:0;} */ .nav .widget-instance-HamburgerPublicationMenu a {padding-left: 36px;} .fake-ribbon {border-left: 8px solid #BE1E32;} .fake-ribbon a:before {content:none;} .nav .widget-instance-HamburgerPublicationMenu .fake-ribbon a {padding-left:30px;} .nav-journals a.theme-plus:before {background:#d71635;} .nav-journals a.theme-jama-network-open {border-bottom:0;} </style> <h2 class="nav-heading">JAMA+</h2> <a href="/channels/ai" class="theme-plus">AI</a> <h2 class="nav-heading">Journals</h2> <a href="/journals/jama" class="theme-jama">JAMA</a> <a href="/journals/jamanetworkopen" class="theme-jama-network-open">JAMA Network Open</a> <a href="/journals/jamacardiology" class="theme-jama-cardiology">JAMA Cardiology</a> <a href="/journals/jamadermatology" class="theme-jama-dermatology">JAMA Dermatology</a> <a href="/journals/jama-health-forum" class="theme-jama-health-forum">JAMA Health Forum</a> <a href="/journals/jamainternalmedicine" class="theme-jama-internal-medicine">JAMA Internal Medicine</a> <a href="/journals/jamaneurology" class="theme-jama-neurology">JAMA Neurology</a> <a href="/journals/jamaoncology" class="theme-jama-oncology">JAMA Oncology</a> <a href="/journals/jamaophthalmology" class="theme-jama-ophthalmology">JAMA Ophthalmology </a> <a href="/journals/jamaotolaryngology" class="theme-jama-otolaryngology-head-neck-surgery">JAMA Otolaryngology–Head & Neck Surgery</a> <a href="/journals/jamapediatrics" class="theme-jama-pediatrics">JAMA Pediatrics</a> <a href="/journals/jamapsychiatry" class="theme-jama-psychiatry">JAMA Psychiatry</a> <a href="/journals/jamasurgery" class="theme-jama-surgery">JAMA Surgery</a> <a href="/journals/archneurpsyc" class="theme-archives-of-neurology-psychiatry-1919-1959-">Archives of Neurology & Psychiatry (1919-1959)</a> <h2 class="nav-heading">Podcasts</h2> <a href="/journals/jama/pages/jama-clinical-reviews">Clinical Reviews</a> <a href="/journals/jama/pages/jama-editors-summary">Editors' Summary</a> <a href="/journals/jama/pages/jama-medical-news">Medical News</a> <a href="/journals/jama/pages/jama-author-interviews">Author Interviews</a> <a href="/pages/audio" class="no-bullet">More</a> </div> </div> </div> <div class="nav-network-other"> <a href="https://edhub.ama-assn.org/jn-learning" id="BodyContent_Header_rptOtherResources_aItemResourceList_0" class="is-b link-jn-learning-cme" target="_blank">JN Learning / CME</a><a href="https://store.jamanetwork.com/index.aspx?productcode=64" id="BodyContent_Header_rptOtherResources_aItemResourceList_1" class="is-b link-subscribe" target="_blank">Subscribe</a><a href="https://careers.jamanetwork.com/" id="BodyContent_Header_rptOtherResources_aItemResourceList_2" class="is-b link-jobs" target="_blank">Jobs</a><a href="https://jamanetwork.com/pages/resources-for-librarians" id="BodyContent_Header_rptOtherResources_aItemResourceList_3" class="is-b link-institutions-librarians">Institutions / Librarians</a><a href="https://jamanetwork.com/pages/reprints-and-permissions" id="BodyContent_Header_rptOtherResources_aItemResourceList_4" class="is-b link-reprints-permissions" rel="nofollow">Reprints & Permissions</a> </div> <div class="white text-xxs"> <div class="p05 ml4 mr3 mb1 mt10 flex hamburger-menu-legal"> <a href="/pages/conditions-of-use" class="p0" rel="nofollow">Terms of Use</a> <span class="pl1 pr1">| </span> <a href="/pages/privacy-policy" class="p0" rel="nofollow">Privacy Policy</a> <span class="pl1 pr1">| </span> <a href="/pages/accessibility-statement" class="p0" rel="nofollow">Accessibility Statement</a> </div> <div class="ta-c"> <span class="pb1">2024 American Medical Association. All Rights Reserved</span> </div> </div> </nav> <a class="toolbar-search-trigger is-b" data-mobile-tog-target=".site-search"></a> <div id="site-search" role="search" class="site-search"> <div class="site-search-bar"> <div role="search"> <select name="ctl00$ctl00$BodyContent$Header$ddlForSearch" id="BodyContent_Header_ddlForSearch" Name="dropDownList" class="cs-select cs-skin-border" title="Search Site Selector" role="options" aria-labelledby="searchLabel"> <option value="J*">Search All</option> <option value="3">JAMA</option> <option value="214">JAMA Network Open</option> <option value="192">JAMA Cardiology</option> <option value="12">JAMA Dermatology</option> <option value="261">JAMA Forum Archive</option> <option value="193">JAMA Health Forum</option> <option value="15">JAMA Internal Medicine</option> <option value="16">JAMA Neurology</option> <option value="159">JAMA Oncology</option> <option value="17">JAMA Ophthalmology</option> <option value="18">JAMA Otolaryngology–Head & Neck Surgery</option> <option value="19">JAMA Pediatrics</option> <option value="14">JAMA Psychiatry</option> <option value="20">JAMA Surgery</option> <option value="23">Archives of Neurology & Psychiatry</option> </select> </div> <div class="search-input-container"> <input type="search" name="textbox" autocomplete="off" role="textbox" id="search-term" aria-labelledby="searchLabel" class="search-term at-microsite-search-term" placeholder="Enter Search Term" maxlength="255" title="Enter Search Term"> <ul id="umbrellaSiteAutoCompleteResults" class="term-list hidden"></ul> <label style="display:none" for="umbrellaSiteSearchInputHint" id="searchLabel">Input Search Term</label> <input class="searchTerm search-input" name="textbox" role="textbox" type="text" id="umbrellaSiteSearchInputHint" aria-labelledby="searchLabel" title="Input Search Term" autocomplete="off"> </div> <!-- /.search-input-container --> <a name="button" role="button" class="search-button is-b js-search-button" alt="search button" href="/searchresults"></a> </div> </div> <div id="BodyContent_Header_GlobalSignIn_auth" class="auth"> <a class="auth--trigger is-b is-a" href="javascript:;"> <span id="BodyContent_Header_GlobalSignIn_spnUserFullName" class="user-full-name">Sign In</span> </a> <div class="auth--dropdown js-signIn-dropdown"> <div class="auth--option auth--ind"> <div id="BodyContent_Header_GlobalSignIn_divUserFullName" class="auth--ind-user"></div> <div id="BodyContent_Header_GlobalSignIn_divIndSignIn" class="auth--ind-auth"> <div class="auth--title">Individual Sign In</div> <a href="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894" id="BodyContent_Header_GlobalSignIn_oauthSignInLink" rel="nofollow" class="auth--ind-sign-in">Sign in</a><a href="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894" id="BodyContent_Header_GlobalSignIn_oauthSignUpLink" rel="nofollow" class="auth--ind-create">Create an Account</a> </div> </div> <div id="BodyContent_Header_GlobalSignIn_divInstSignIn" class="auth--option auth--inst"> <div class="auth--inst-auth"> <div class="auth--title">Access through your institution</div> <a href="/signinshibboleth?returnUrl=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894" id="BodyContent_Header_GlobalSignIn_institutionSignIn" rel="nofollow" class="auth--shib">Sign In</a> </div> </div> <div id="BodyContent_Header_GlobalSignIn_divPurchaseOptions" class="auth--option auth--purchase"> <div class="auth--title">Purchase Options:</div> <a id="BodyContent_Header_GlobalSignIn_lnkSubscribeJournal" class="auth--subscribe" rel="nofollow" href="https://store.jamanetwork.com/index.aspx?productcode=64">Subscribe to the JAMA journal</a> </div> </div> </div> </header> </div> <div class="editors-choice-header"> </div> <div id="BodyContent_Header_divAds" class="header-ad-wrap sb-background-primary-dark"> <div class="leader-ad desktop-only"> <div class="widget-WidgetLoader widget-instance-AMA_AdTag_LeaderboardAd"> <div class="SCM-SharedWidgets-AsyncAdLoader" data-url="/AMA/AdTag/AMA_AdTag_LeaderboardAd" data-params="{"parameters":{"siteName":"jama","siteId":3,"journalId":67,"adDisplay":1,"adSection":"scholarly","adPosition":"atf","fromGoogle":false},"dynamicParameters":{"localParams":"[REPLACE_WITH_LOCAL]"}}"></div> </div> </div> </div> <!-- /.header-ad-wrap --> </section> <section class="master-main"> <div class="social-share hide" data-share-journal="JAMA_current" data-share-title="Effect of Titrated vs Low Positive End-Expiratory Pressure (PEEP) on Mortality in ARDS"></div> <div class="widget-UserContentAccessWrite widget-instance-AMA_LocalStorage_Article"> <div class="SCM-SharedWidgets-LocalStorage-UserContentAccessWrite" data-values='{"id":"2654894","type":"Article","date":"11/23/2024 6:40:47 PM"}'></div> </div> <div class="widget-ArticleToggleView widget-instance-AMA_ArticleToggleView"> <div class="widget-ArticleFullView widget-instance-AMA_ArticleFullView"> <script> (function () { var bodyElem = document.querySelector('body'); var className = 'split-screen'; if (bodyElem.classList) { bodyElem.classList.add(className); } else { el.className += ' ' + className; } })(); </script> <div id="resources-panel" class="resources-panel"> <span class="hide tagmanagervalue" data-attribute="template" data-value="splitscreen" data-type="string"></span> <div class="tab-nav"> <a class="tab-nav-trigger tab-nav-full-text tablet-down" href="#full-text-tab"> <i class="icon-full_text"><span class="sr-t">full text icon</span></i> <div class="tab-nav-tab-name">Full Text</div> </a> <a class="tab-nav-trigger tab-nav-contents target-tab-active" href="#contents-tab"> <i class="icon-contents"><span class="sr-t">contents icon</span></i> <div class="tab-nav-tab-name">Contents</div> </a> <a class="tab-nav-trigger tab-nav-figure-table" href="#figure-table-tab"> <i class="icon-figures"><span class="sr-t">figure icon</span></i> <div class="tab-nav-tab-name">Figures / <br> Tables</div> </a> <a class="tab-nav-trigger tab-nav-multimedia" href="#multimedia-tab"> <i class="icon-multimedia"><span class="sr-t">multimedia icon</span></i> <div class="tab-nav-tab-name">Multimedia</div> </a> <a class="tab-nav-trigger tab-nav-supplemental" href="#supplemental-tab"> <i class="icon-attach"><span class="sr-t">attach icon</span></i> <div class="tab-nav-tab-name">Supplemental <br> Content</div> </a> <a class="tab-nav-trigger tab-nav-references" href="#references-tab"> <i class="icon-references"><span class="sr-t">references icon</span></i> <div class="tab-nav-tab-name">References</div> </a> <a class="tab-nav-trigger tab-nav-related" href="#related-tab"> <i class="icon-related"><span class="sr-t">related icon</span></i> <div class="tab-nav-tab-name">Related</div> </a> <a class="tab-nav-trigger tab-nav-comments" href="#comments-tab"> <i class="icon-user-comments"><span class="sr-t">comments icon</span></i> <div class="tab-nav-tab-name">Comments</div> </a> </div> <div class="resource-tabs"> <div id="contents-tab" class="resource-tab js-resource-tab contents-tab tab-active"> <div class="contents-tab-contents"> <a id="pdf-link" href="/journals/jama/articlepdf/2654894/jama_cavalcanti_2017_oi_170110.pdf" class="toolbar-tool toolbar-pdf al-link pdfaccess js-pdfaccess" data-article-id="2654894" data-article-url="/journals/jama/articlepdf/2654894/jama_cavalcanti_2017_oi_170110.pdf" data-ajax-url="/Content/CheckPdfAccess"><span class="toolbar-pdf-text"><span class="toolbar-link-text-extra">Download </span><span class="toolbar-link-text">PDF</span></span> </a> <div class="widget-ArticleJumpLinks widget-instance-AMA_ArticleJumpLinks_Widget"> <a href="#top" class="section-jump-link contents-tab-jump-link top-of-article" data-tab-toggle=".tab-nav-full-text">Top of Article</a> <ul class="section-jump-links bullet ml2 pl1"> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419536" data-tab-toggle=".tab-nav-full-text">Key Points</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419537" data-tab-toggle=".tab-nav-full-text">Abstract</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419543" data-tab-toggle=".tab-nav-full-text">Introduction</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419546" data-tab-toggle=".tab-nav-full-text">Methods</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419569" data-tab-toggle=".tab-nav-full-text">Results</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419589" data-tab-toggle=".tab-nav-full-text">Discussion</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419598" data-tab-toggle=".tab-nav-full-text">Conclusions</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419600" data-tab-toggle=".tab-nav-full-text">Article Information</a></li> <li><a class="section-jump-link contents-tab-jump-link scroll-to head-1" href="#172419602" data-tab-toggle=".tab-nav-full-text">References</a></li> </ul> </div> <div class="widget-SelfServeContent widget-instance-AMA_Contents_Tab_SelfServe"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="v2_article_content_tab" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="bc_rr_theme_promo"><!-- Content Goes Here --></div> <div class="bc_right_rail_article_promo"><!-- Content Goes Here --></div> </div> </div> </div> <div class="contents-tab-ad"> <div id="split-screen-contab"></div> </div> </div> <div id="figure-table-tab" class="resource-tab js-resource-tab figure-table-tab need-jobs-ad"> <div class="widget-ArticleFiguresAndTables widget-instance-AMA_Article_Figures_Tab"> <div class="figure-table-wrapper thm-bd-top"><div class="figure-label">Figure 1. Flow of Patients in the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial</div><a id="joi170110f1" class="figure-table-anchor"> </a><div class="figure-table-links right"><a class="view-large figure-table-link is-b desktop-only" path-from-xml="joi170110f1" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f1.png?Expires=1735327992&Signature=uP4SrB7d93KavzBZtUczB3VU9aeoS4K1p5corg-QjF7r~Zn4ulRnpI1LybJgqvuRucVXu~ucMBV3~NGenlWz0ukLITm94Bvx5xydOmacV1wXcX7NjNJNyKVDiDM9a8oFpO5BroYjIvVCI5EzQrMJAvS6jZTfv~BH2TX~T~7y0ntMBdxQPcBn6jXY5-UUoWRLQ1EOFVY2nVOm-CVOSWKhc9oZFmoRE8UrDMduxXBOWp18r17fjlmP-CNOpC4CQ96wAOKkfv92UxArdnqAP3BJnWumn58f6whuO5liClk2hG7hqjROWsxJ4Mvt9yJNJ7ugqKKwpU-yQyBOwd~w5OJzVA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" rel="nofollow"><span class="view-large-text">View Large</span></a><a class="download-ppt figure-table-link is-b stats-download-figure-table" path-from-xml="joi170110f1" href="/downloadimage.aspx?image=https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f1.png?Expires=1735327992&Signature=uP4SrB7d93KavzBZtUczB3VU9aeoS4K1p5corg-QjF7r~Zn4ulRnpI1LybJgqvuRucVXu~ucMBV3~NGenlWz0ukLITm94Bvx5xydOmacV1wXcX7NjNJNyKVDiDM9a8oFpO5BroYjIvVCI5EzQrMJAvS6jZTfv~BH2TX~T~7y0ntMBdxQPcBn6jXY5-UUoWRLQ1EOFVY2nVOm-CVOSWKhc9oZFmoRE8UrDMduxXBOWp18r17fjlmP-CNOpC4CQ96wAOKkfv92UxArdnqAP3BJnWumn58f6whuO5liClk2hG7hqjROWsxJ4Mvt9yJNJ7ugqKKwpU-yQyBOwd~w5OJzVA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=172419572&ar=2654894&imagename=&siteId=3" rel="nofollow"><span class="download-ppt-text">Download</span></a><a class="figure-table-twitter figure-table-link figure-table-social addthis_button_twitter is-b" rel="nofollow"><span class="share-text"> </span></a><a class="figure-table-facebook figure-table-link figure-table-social addthis_button_facebook is-b" rel="nofollow"><span class="share-text"> </span></a></div><div class="figure-table cf cb"><div class="figure-table-image"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f1.png?Expires=1735327992&Signature=uP4SrB7d93KavzBZtUczB3VU9aeoS4K1p5corg-QjF7r~Zn4ulRnpI1LybJgqvuRucVXu~ucMBV3~NGenlWz0ukLITm94Bvx5xydOmacV1wXcX7NjNJNyKVDiDM9a8oFpO5BroYjIvVCI5EzQrMJAvS6jZTfv~BH2TX~T~7y0ntMBdxQPcBn6jXY5-UUoWRLQ1EOFVY2nVOm-CVOSWKhc9oZFmoRE8UrDMduxXBOWp18r17fjlmP-CNOpC4CQ96wAOKkfv92UxArdnqAP3BJnWumn58f6whuO5liClk2hG7hqjROWsxJ4Mvt9yJNJ7ugqKKwpU-yQyBOwd~w5OJzVA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" path-from-xml="joi170110f1" rel="nofollow"><img data-original="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/m_joi170110f1.png?Expires=1735327992&Signature=fX3OyFRDwWPM3KRev6tZ8NTfA32gbXJf5pV0Nv4TmKnRVTPhk3Y7IqEbg6HirM2PQaGY7w3DSjudk2-jvoCFn0wF~U3t3v93QFGlmBpiybKdPYh8qgDJSlZK-rGRVniiUi9v5ix4mjc~gaa7S95WLhYyRPCD~dT7Mp9gzJTGRPS7Fs8cNHswU6ni7wI2NBXK~Xrrr3Foori5et2j4JGter7JyNVYHWwsr99W5GZMHdXf9aPDmYDrZRJ3FAIY8wnsbxJCFpUvN7APgWuf4nGucVDlz1-Gt8uPOcc8jyTUuHiEKOGeeQpPUdQ-aPPIJ9nkLpMRt4Xne4mddF-X92no9Q__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="Flow of Patients in the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial" class="content-img lazy" path-from-xml="joi170110f1" /></a></div></div><div class="figure-caption clip-last-child"><p class="para">ARDS indicates acute respiratory distress syndrome; F<span style="font-variant:small-caps;">io</span><sub>2</sub>, fraction of inspired oxygen; MAP, mean arterial pressure; Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>, partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure.</p><p class="para"><sup>a</sup>Patients could have more than 1 reason for exclusion.</p></div></div><div class="figure-table-wrapper thm-bd-top"><div class="figure-label">Figure 2. 28-Day Mortality in the Lung Recruitment Maneuver With Titrated PEEP Group vs the Low-PEEP Group</div><a id="joi170110f2" class="figure-table-anchor"> </a><div class="figure-table-links right"><a class="view-large figure-table-link is-b desktop-only" path-from-xml="joi170110f2" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f2.png?Expires=1735327992&Signature=y-Ort-L70EWHJWar-gIDLHeMxsqwrvYnXeDRlu3pe3UbSNtYYh-VQrqFXJIfDkJ1WKHBo6lJ47Vty255bDTK7Mk-UqAY~A9lYlC2ZcDYjd-Xocm~s8x3sIVKk1R5CT9k~9jhjVBoiLvp2C3hcN~Ilv1KVAVhHSk5e-FtYzut~S0zOksO9s5xBRGeyb94sc-HnSpBRiS8V7uN269ku3EECcvbBvsloMtk5SMfobwj0EBg6y-eotimZ3cErdVoI4Tx0kVF51EKGDWcUa1gsRC73rIbe~F~iygWLC6HvMj4KCd4N510UfGfoh1FYYwlTvsUuDyuDI0XADa8xhUzHngSqQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" rel="nofollow"><span class="view-large-text">View Large</span></a><a class="download-ppt figure-table-link is-b stats-download-figure-table" path-from-xml="joi170110f2" href="/downloadimage.aspx?image=https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f2.png?Expires=1735327992&Signature=y-Ort-L70EWHJWar-gIDLHeMxsqwrvYnXeDRlu3pe3UbSNtYYh-VQrqFXJIfDkJ1WKHBo6lJ47Vty255bDTK7Mk-UqAY~A9lYlC2ZcDYjd-Xocm~s8x3sIVKk1R5CT9k~9jhjVBoiLvp2C3hcN~Ilv1KVAVhHSk5e-FtYzut~S0zOksO9s5xBRGeyb94sc-HnSpBRiS8V7uN269ku3EECcvbBvsloMtk5SMfobwj0EBg6y-eotimZ3cErdVoI4Tx0kVF51EKGDWcUa1gsRC73rIbe~F~iygWLC6HvMj4KCd4N510UfGfoh1FYYwlTvsUuDyuDI0XADa8xhUzHngSqQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=172419583&ar=2654894&imagename=&siteId=3" rel="nofollow"><span class="download-ppt-text">Download</span></a><a class="figure-table-twitter figure-table-link figure-table-social addthis_button_twitter is-b" rel="nofollow"><span class="share-text"> </span></a><a class="figure-table-facebook figure-table-link figure-table-social addthis_button_facebook is-b" rel="nofollow"><span class="share-text"> </span></a></div><div class="figure-table cf cb"><div class="figure-table-image"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f2.png?Expires=1735327992&Signature=y-Ort-L70EWHJWar-gIDLHeMxsqwrvYnXeDRlu3pe3UbSNtYYh-VQrqFXJIfDkJ1WKHBo6lJ47Vty255bDTK7Mk-UqAY~A9lYlC2ZcDYjd-Xocm~s8x3sIVKk1R5CT9k~9jhjVBoiLvp2C3hcN~Ilv1KVAVhHSk5e-FtYzut~S0zOksO9s5xBRGeyb94sc-HnSpBRiS8V7uN269ku3EECcvbBvsloMtk5SMfobwj0EBg6y-eotimZ3cErdVoI4Tx0kVF51EKGDWcUa1gsRC73rIbe~F~iygWLC6HvMj4KCd4N510UfGfoh1FYYwlTvsUuDyuDI0XADa8xhUzHngSqQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" path-from-xml="joi170110f2" rel="nofollow"><img data-original="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/m_joi170110f2.png?Expires=1735327992&Signature=R~PUuMNSFFQxSdP-zMBKm0j-GAvUr9RPlq~AxfZbNqSCtkyTCk-G5DY1NzHWVrjDhrep0laLz3hstd6p~JI7qce6vTxemYAWgRllE4uTFwt~j3WALEo2vBO63yYZrxW7qiqv4xQVTAGiUVXpTiPoxmrB7pT2cbAypo1ILNwwxgSi99XhbxAAoqSADoPT6KlFGecD3~M6OSH~4I-HRPn~h5H59HHpUWfhQ-SQd5Nnyu5c8HsbAWRHobed7FQ3JrEYW1FA0akSrIBPCFsfEku2xM5TdNreVt07Iwm4rv8PGVMhZ6MyRMHjw3JdZx1NYVWLAplXU~O2hRe5E~eCr~M9uA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="28-Day Mortality in the Lung Recruitment Maneuver With Titrated PEEP Group vs the Low-PEEP Group" class="content-img lazy" path-from-xml="joi170110f2" /></a></div></div><div class="figure-caption clip-last-child"><p class="para">PEEP indicates positive end-expiratory pressure.</p></div></div><div class="figure-table-wrapper thm-bd-top"><div class="figure-label">Figure 3. Effects of the Lung Recruitment Maneuver With Titrated PEEP vs the Low-PEEP Group on Mortality According to Subgroups</div><a id="joi170110f3" class="figure-table-anchor"> </a><div class="figure-table-links right"><a class="view-large figure-table-link is-b desktop-only" path-from-xml="joi170110f3" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f3.png?Expires=1735327992&Signature=1PkHEnBt4tlB3~fYNp5KL37TEOLJ25p1LaAxQv6gok~Sf1I9Zw4Cu01tc9vw6n9O4uFUP50CbkNlzkL3QRsL3zKvPh2A-HhA7AJ95FSneeTtwB3YU2cqHbpDmwVd6eE5ySQtMlZ4R5lcyesaBM2NZLkcn8wFt9q5WUM2PhINp9kouvo~JSYYIWebHvwNrPfkvV2~OGJZiYYqTQ7Dcv6ng~0ZUIKsYgyWcd37WfaWWGq2A~JYDSRd~tqs~rQZoF5-Maie0zY7YwZer1xOUCBYhFo~X6TvwO5E5J9O0RMioDvAwVgbLL-24endewDLbZWXUobEnCT1aMd3QmPBknEIaA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" rel="nofollow"><span class="view-large-text">View Large</span></a><a class="download-ppt figure-table-link is-b stats-download-figure-table" path-from-xml="joi170110f3" href="/downloadimage.aspx?image=https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f3.png?Expires=1735327992&Signature=1PkHEnBt4tlB3~fYNp5KL37TEOLJ25p1LaAxQv6gok~Sf1I9Zw4Cu01tc9vw6n9O4uFUP50CbkNlzkL3QRsL3zKvPh2A-HhA7AJ95FSneeTtwB3YU2cqHbpDmwVd6eE5ySQtMlZ4R5lcyesaBM2NZLkcn8wFt9q5WUM2PhINp9kouvo~JSYYIWebHvwNrPfkvV2~OGJZiYYqTQ7Dcv6ng~0ZUIKsYgyWcd37WfaWWGq2A~JYDSRd~tqs~rQZoF5-Maie0zY7YwZer1xOUCBYhFo~X6TvwO5E5J9O0RMioDvAwVgbLL-24endewDLbZWXUobEnCT1aMd3QmPBknEIaA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=172419588&ar=2654894&imagename=&siteId=3" rel="nofollow"><span class="download-ppt-text">Download</span></a><a class="figure-table-twitter figure-table-link figure-table-social addthis_button_twitter is-b" rel="nofollow"><span class="share-text"> </span></a><a class="figure-table-facebook figure-table-link figure-table-social addthis_button_facebook is-b" rel="nofollow"><span class="share-text"> </span></a></div><div class="figure-table cf cb"><div class="figure-table-image"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110f3.png?Expires=1735327992&Signature=1PkHEnBt4tlB3~fYNp5KL37TEOLJ25p1LaAxQv6gok~Sf1I9Zw4Cu01tc9vw6n9O4uFUP50CbkNlzkL3QRsL3zKvPh2A-HhA7AJ95FSneeTtwB3YU2cqHbpDmwVd6eE5ySQtMlZ4R5lcyesaBM2NZLkcn8wFt9q5WUM2PhINp9kouvo~JSYYIWebHvwNrPfkvV2~OGJZiYYqTQ7Dcv6ng~0ZUIKsYgyWcd37WfaWWGq2A~JYDSRd~tqs~rQZoF5-Maie0zY7YwZer1xOUCBYhFo~X6TvwO5E5J9O0RMioDvAwVgbLL-24endewDLbZWXUobEnCT1aMd3QmPBknEIaA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" path-from-xml="joi170110f3" rel="nofollow"><img data-original="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/m_joi170110f3.png?Expires=1735327992&Signature=yGsAzv6qK6oDTL7GrHWkMAn2VOZYBzOJskqiK9vwvbfScbDfTTenXymyHzYgHCIQbDLsl4QWHHtI0z-aLUyyt7Thqs6tJJtIEnkt3Kd08BkmwE62lcM-za1C4qlja8oVnIfQfxGqd691~SM9oMYw2yJ7AZHVUV8aKEUvPGA-SKoZPQcq-p5OdiupRBVDrmh8FkdIgsvJiYPlQwpHqaLcx2nY5mL7tfP5snIosJsi3m0kQmiMIs4T27aKXjcjAIL7swJRzgbRIqtu4ovJbyE-JgAxADFMd6FBLb~rP1Sei2oL4q4olzulcGVPzHLrRpt-ajHnXelR0gNk7epXS03ciQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="Effects of the Lung Recruitment Maneuver With Titrated PEEP vs the Low-PEEP Group on Mortality According to Subgroups" class="content-img lazy" path-from-xml="joi170110f3" /></a></div></div><div class="figure-caption clip-last-child"><p class="para">The size of data markers is proportional to the inverse of variance. Protocol modification indicates the modification in the experimental group strategy after the 556th patient, with decreases in the pressures and duration of the recruitment maneuver.</p><p class="para">ARDS indicates acute respiratory distress syndrome; F<span style="font-variant:small-caps;">io</span><sub>2</sub>,fraction of inspired oxygen; Pa<span style="font-variant:small-caps;">o</span><sub>2,</sub> partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure. </p></div></div> </div> <div class="widget-ArticleFiguresAndTables widget-instance-AMA_Article_Tables_Tab"> <div class="figure-table-wrapper thm-bd-top"><div class="table-label">Table 1. Baseline Characteristics of the Patients</div><a class="figure-table-anchor" id="joi170110t1"> </a><div class="figure-table-links right"><a class="view-large figure-table-link is-b desktop-only" path-from-xml="joi170110t1" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t1.png?Expires=1735327992&Signature=pkosUGuWSHH2n236Cw9dXZn4f2VbsRUBgdeFT0MrT86VeEzzkUFft7svhRBl4t9mY3cjZ8cLPb6lWNqxwkclq~CR8Ou0MObLRGyIuYCz7DjA3pR9X04fxFuLQaIOdost7BYTOBVBF8uv~c4RU4wukqQrPcZJx44tcaCNZjK~uLzQI3HIdm254T0kKi983EpG5eEGJc-i9Qq-~QS~60W522Pynqkesfcvsmzkb1YLaJ68Szi1ohhfyJmHmUzWam~S3LrVqGLt9hxdveooTWm5r2cGx1rLDxpPc6lYY9bjZdOCqcu6-OukOPGB5LnBIVsza~R7Mm1QTjyt7TnRYt1Pzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" rel="nofollow"><span class="view-large-text">View Large</span></a><a class="download-ppt figure-table-link is-b stats-download-figure-table" path-from-xml="joi170110t1" href="/downloadimage.aspx?image=https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t1.png?Expires=1735327992&Signature=pkosUGuWSHH2n236Cw9dXZn4f2VbsRUBgdeFT0MrT86VeEzzkUFft7svhRBl4t9mY3cjZ8cLPb6lWNqxwkclq~CR8Ou0MObLRGyIuYCz7DjA3pR9X04fxFuLQaIOdost7BYTOBVBF8uv~c4RU4wukqQrPcZJx44tcaCNZjK~uLzQI3HIdm254T0kKi983EpG5eEGJc-i9Qq-~QS~60W522Pynqkesfcvsmzkb1YLaJ68Szi1ohhfyJmHmUzWam~S3LrVqGLt9hxdveooTWm5r2cGx1rLDxpPc6lYY9bjZdOCqcu6-OukOPGB5LnBIVsza~R7Mm1QTjyt7TnRYt1Pzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=172419574&ar=2654894&imagename=&siteId=3" rel="nofollow"><span class="download-ppt-text">Download</span></a><a class="figure-table-twitter figure-table-link figure-table-social addthis_button_twitter is-b" rel="nofollow"><span class="share-text"> </span></a><a class="figure-table-facebook figure-table-link figure-table-social addthis_button_facebook is-b" rel="nofollow"><span class="share-text"> </span></a></div><div class="figure-table cf cb"><div class="figure-table-image"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t1.png?Expires=1735327992&Signature=pkosUGuWSHH2n236Cw9dXZn4f2VbsRUBgdeFT0MrT86VeEzzkUFft7svhRBl4t9mY3cjZ8cLPb6lWNqxwkclq~CR8Ou0MObLRGyIuYCz7DjA3pR9X04fxFuLQaIOdost7BYTOBVBF8uv~c4RU4wukqQrPcZJx44tcaCNZjK~uLzQI3HIdm254T0kKi983EpG5eEGJc-i9Qq-~QS~60W522Pynqkesfcvsmzkb1YLaJ68Szi1ohhfyJmHmUzWam~S3LrVqGLt9hxdveooTWm5r2cGx1rLDxpPc6lYY9bjZdOCqcu6-OukOPGB5LnBIVsza~R7Mm1QTjyt7TnRYt1Pzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" path-from-xml="joi170110t1" rel="nofollow"><img data-original="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/m_joi170110t1.png?Expires=1735327992&Signature=YhuTvSmM6CzLzw-7ixqdS-p3ZjeygBBWP3sQ~0OtgZv~iJK2q0YbGc~nbuJDnI-ng7MeAq3nDpBYmXai-3UCVcdY-6fUeudThNRuywefiGO8dlQYlC-F0l~~g524F94Dxg66d~ogsH3NWmyittc6Y58opN~ZzxlISfFIYg~QPUMyoElFtpxf464Dq6g3XJ2nTlZrD1UgoREvsxrVQC1RXZwbvjMlW-TUM4hFaJXGwciECoQ73Y7McEVUez2DOuJJ7CN7LnrrsYKYFOfqiprGOyxzNjvx19VXJpFn6bwUDbUAShIgNT9jvOtT1XQX8mtl8T5Klhl7IPIaYsKDFqTH0Q__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="Baseline Characteristics of the Patients" class="content-img lazy" path-from-xml="joi170110t1" /></a></div></div><div class="table-caption"></div></div><div class="figure-table-wrapper thm-bd-top"><div class="table-label">Table 2. Outcomes Among Patients Treated With Lung Recruitment Maneuver With Positive End-Expiratory Pressure (PEEP) vs Low-PEEP Strategy </div><a class="figure-table-anchor" id="joi170110t2"> </a><div class="figure-table-links right"><a class="view-large figure-table-link is-b desktop-only" path-from-xml="joi170110t2" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t2.png?Expires=1735327992&Signature=sju~i9zFP~Q~FUwK5ZSdBXNH7tzIWLoQKXCQJPrWffMEsqe0HVHQS0LOrN0G3S9vDn7m9ySul04BW4kD17SNeZw~m5nnORp0btpG9JU3LkQHC9ugG19iq74iySfPfR6tEOZv~9amxs6hrA94vXgSs1prZFpVdZ1Ac2i1NVhFv8U~IbcKeH~QGne5AycrwQNspP6oBvxPF-nUfk22FdOlRwvi1GRtkVHgKrDYorsIXIzYDdGHHJocf8qL9Kfk8rCu-3zHAB5xqj97nSotlH68~80GVw5E79XwcdvPMd4xhQemrcce6vqCuSsi3g0~~M5h5-IoCMNcOxICLNoit8oXig__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" rel="nofollow"><span class="view-large-text">View Large</span></a><a class="download-ppt figure-table-link is-b stats-download-figure-table" path-from-xml="joi170110t2" href="/downloadimage.aspx?image=https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t2.png?Expires=1735327992&Signature=sju~i9zFP~Q~FUwK5ZSdBXNH7tzIWLoQKXCQJPrWffMEsqe0HVHQS0LOrN0G3S9vDn7m9ySul04BW4kD17SNeZw~m5nnORp0btpG9JU3LkQHC9ugG19iq74iySfPfR6tEOZv~9amxs6hrA94vXgSs1prZFpVdZ1Ac2i1NVhFv8U~IbcKeH~QGne5AycrwQNspP6oBvxPF-nUfk22FdOlRwvi1GRtkVHgKrDYorsIXIzYDdGHHJocf8qL9Kfk8rCu-3zHAB5xqj97nSotlH68~80GVw5E79XwcdvPMd4xhQemrcce6vqCuSsi3g0~~M5h5-IoCMNcOxICLNoit8oXig__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=172419585&ar=2654894&imagename=&siteId=3" rel="nofollow"><span class="download-ppt-text">Download</span></a><a class="figure-table-twitter figure-table-link figure-table-social addthis_button_twitter is-b" rel="nofollow"><span class="share-text"> </span></a><a class="figure-table-facebook figure-table-link figure-table-social addthis_button_facebook is-b" rel="nofollow"><span class="share-text"> </span></a></div><div class="figure-table cf cb"><div class="figure-table-image"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110t2.png?Expires=1735327992&Signature=sju~i9zFP~Q~FUwK5ZSdBXNH7tzIWLoQKXCQJPrWffMEsqe0HVHQS0LOrN0G3S9vDn7m9ySul04BW4kD17SNeZw~m5nnORp0btpG9JU3LkQHC9ugG19iq74iySfPfR6tEOZv~9amxs6hrA94vXgSs1prZFpVdZ1Ac2i1NVhFv8U~IbcKeH~QGne5AycrwQNspP6oBvxPF-nUfk22FdOlRwvi1GRtkVHgKrDYorsIXIzYDdGHHJocf8qL9Kfk8rCu-3zHAB5xqj97nSotlH68~80GVw5E79XwcdvPMd4xhQemrcce6vqCuSsi3g0~~M5h5-IoCMNcOxICLNoit8oXig__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" path-from-xml="joi170110t2" rel="nofollow"><img data-original="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/m_joi170110t2.png?Expires=1735327992&Signature=bVJA140FncMBiZdwwkSADi2RO1tWEQ5-iW7NO5y6h0WsG0S1ETiNHjhQ7PZ5Xd4xpMLoKvXqwW7wf52p-K6zW7GhePeN0AvPN~qka-jEFRGwYodXu6i~teZe2BtBBznykJCAGws0wHIwQW8NfRlLjTEDOYsSI-el7Pe7kHqWcNHXuhMFTNTDnRZxVoCZO-nL5kr6kislamEfqWb-Gd1h07o0Mc~SYhjLwss9wt2pq9qV5e5BNjI1-IohFJ3X6IIyF68XuutNSTWz-HChqmxSkXD9UQWY22taHMeYxkLpGDDhx70Hjd6J5654uE6xX-ptMglWHKy7Uyl4a3k3MrhmQQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="Outcomes Among Patients Treated With Lung Recruitment Maneuver With Positive End-Expiratory Pressure (PEEP) vs Low-PEEP Strategy " class="content-img lazy" path-from-xml="joi170110t2" /></a></div></div><div class="table-caption"></div></div> </div> </div> <div id="multimedia-tab" class="resource-tab js-resource-tab multimedia-tab need-jobs-ad"> <div class="widget-MultimediaInfo widget-instance-AMAv2MultimediaContent"> <div class="video-border-top thm-bg-col sb-background-pc"></div> <div class="multimedia-item brightcove extrinsic-video"> <div class="multimedia-content-wrap"> <a class="learning-link td-n" href="https://jamanetwork.com/learning/video-player/14821584" target="_blank"> <div class="multimedia-content"> <div class="multimedia-title"><div class='video-group'>Video</div> Effects on Mortality of a Lung Recruitment Ventilation Strategy Using Titrated vs Low PEEP in Patients With ARDS</div> </div> </a> </div> <a class="video-anchor"></a> <div class="brightcove-video relative" style="height: 0; padding-bottom: 56.25%;"> <video data-video-id="5602989976001" data-account="864352215001" data-player="ByudjMUZ" data-embed="default" class="video-js" controls style="width: 100%; height: 100%; position: absolute; top: 0px; bottom: 0px; right: 0px; left: 0px;"></video> </div> <div class="multimedia-caption-wrap"> <div class="multimedia-caption-container"> <div class="video-caption"><Content><p specific-use="short-description">Alexandre Biasi Cavalcanti, MD, PhD, of the Hospital do Coração in São Paulo, Brazil, presents findings from the ART trial at the European Society of Intensive Care Medicine, Vienna, Austria, on September 27, 2017. Used with permission.</p></Content></div> </div> </div> </div> <div class="video-border-top thm-bg-col sb-background-pc"></div> <div class="multimedia-item brightcove extrinsic-video"> <div class="multimedia-content-wrap"> <a class="learning-link td-n" href="https://jamanetwork.com/learning/video-player/14821586" target="_blank"> <div class="multimedia-content"> <div class="multimedia-title"><div class='video-group'>Video Interview</div> Effects on Mortality of a Lung Recruitment Ventilation Strategy Using Titrated vs Low PEEP in Patients With ARDS</div> </div> </a> </div> <a class="video-anchor"></a> <div class="brightcove-video relative" style="height: 0; padding-bottom: 56.25%;"> <video data-video-id="5602995014001" data-account="864352215001" data-player="ByudjMUZ" data-embed="default" class="video-js" controls style="width: 100%; height: 100%; position: absolute; top: 0px; bottom: 0px; right: 0px; left: 0px;"></video> </div> <div class="multimedia-caption-wrap"> <div class="multimedia-caption-container"> <div class="video-caption"><Content><p specific-use="short-description">Alexandre Biasi Cavalcanti, MD, PhD, discusses the design, settings, interventions, and hypotheses of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART), which demonstrated an increase in mortality among patients with ARDS with use of a lung recruitment ventilation strategy using titrated PEEP. Recorded September 27, 2017. Used with permission.</p></Content></div> </div> </div> </div> <div class="video-border-top thm-bg-col sb-background-pc"></div> <div class="multimedia-item brightcove extrinsic-video"> <div class="multimedia-content-wrap"> <a class="learning-link td-n" href="https://jamanetwork.com/learning/video-player/14821588" target="_blank"> <div class="multimedia-content"> <div class="multimedia-title"><div class='video-group'>Video Interview</div> Effects on Mortality of a Lung Recruitment Ventilation Strategy Using Titrated vs Low PEEP in Patients With ARDS</div> </div> </a> </div> <a class="video-anchor"></a> <div class="brightcove-video relative" style="height: 0; padding-bottom: 56.25%;"> <video data-video-id="5602986337001" data-account="864352215001" data-player="ByudjMUZ" data-embed="default" class="video-js" controls style="width: 100%; height: 100%; position: absolute; top: 0px; bottom: 0px; right: 0px; left: 0px;"></video> </div> <div class="multimedia-caption-wrap"> <div class="multimedia-caption-container"> <div class="video-caption"><Content><p specific-use="short-description">Alexandre Biasi Cavalcanti, MD, PhD, reviews findings and implications of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART), which demonstrated an increase in mortality among patients with ARDS with use of a lung recruitment ventilation strategy using titrated PEEP. Recorded September 27, 2017. Used with permission.</p></Content></div> </div> </div> </div> <script src="//players.brightcove.net/864352215001/ByudjMUZ_default/index.min.js"></script> <span class="hide tagmanagervalue" data-attribute="arrRelatedVideo" data-value="10.1001/jama.2017.16551,10.1001/jama.2017.16552,10.1001/jama.2017.16553" data-type="array"></span> </div> </div> <div id="supplemental-tab" class="resource-tab js-resource-tab supplemental-tab need-jobs-ad"> <div class="widget-ArticleDataSupplements widget-instance-AMA_Data_Supplements_Tab"> <div class="supplement"> <a id="note-JOI170110-1" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110supp1_prod.pdf?Expires=1735359761&Signature=oYtgT7O8ZsUe9f2EbPThYSItPPUgO7TmdvC9x17pjqr7HYWffddf6BYx7pq8dEdyWmQoKb5gE4s0Bo3Lp-eicWioe1vWZphbYfvTpN37Ss2fbYbe-zTFC9mLpGwGLqGdBCoETkyCaerq89XwyGbdvmpbD3BfXePY7iUnFR8mcarE31rIwJdZpdGXauMvMXFWzOIulqlziY1uflhXPeicgqrX3doRXTGAKzOikc1EBROFnfdUmpbB1Oip9w000Srou1pLtMDnufNiGkaO~Tt1BeKxU9k2pNZFpnSacfYacld3BexsA23SX1xUaS4p9ILH5l5w4DztBcv5hV~-DCufmQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" class="supplement-link supplement-download stats-supplement-download" rel="nofollow"> <div class="pdf supplement-type"></div> <div class="supplement-title"><span class="title-label">Supplement 1.</span><p class="para">Trial Protocol and Statistical Analysis Plan</p></div> </a> </div> <div class="supplement"> <a id="note-JOI170110-1" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110supp2_prod.pdf?Expires=1735359761&Signature=d8lkQBnK~YJzz21ULJGbSKhPo0FZogAuh2WafS7rRuZQvc-GN1Ub2pXMSchB9VHftSGMHijiyKYPMTWDx2~HHYOaFZFsxugY1dFnHRtPxaFuMMchOp5uTqvcdGkmJa9Bh2NWe5kkGcdVFhW2LAzbaTlWxduDpJQ~aHtdpnNkjjXxkyzP6cCTl7Hls6wiUstx5Xg2ySukvqB3FpeVazziRCm8PaFfheL92fMpaIXScvzjlLAYCuotgwrAn1AWLcrJcs8wiNxsFxuAFSiUamfcTqwPVkB5sTZRwa06WWKXISyKwyZM6VYl8yJ1HhmrLMC1K1cLflSQW1MguT~hPM~Wzg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" class="supplement-link supplement-download stats-supplement-download" rel="nofollow"> <div class="pdf supplement-type"></div> <div class="supplement-title"><span class="title-label">Supplement 2.</span><p class="para">eAppendix</p><p class="para"><strong>eTable 1.</strong> Lung recruitment maneuver and titrated positive end-expiratory pressure levels</p><p class="para"><strong>eTable 2.</strong> Respiratory variables during the first seven days of treatment</p><p class="para"><strong>eTable 3.</strong> Fluid balance, weight gain and co-interventions during the first seven days of treatment</p><p class="para"><strong>eFigure.</strong> Breath stacking in patients ventilating with low tidal volume</p></div> </a> </div> <div class="supplement"> <a id="note-JOI170110-1" href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/936523/joi170110supp3_prod.pdf?Expires=1735359761&Signature=j30DGJh1OX7MIkhB-RUM3DzIyytyG1fq4Ht3koXOLBOiYEvL4WxEUBGH3u5yMIivFr6-GRy3doWkUnxVyAvFchvuPE27vxTdd9SCm8~nNrog0zDsOTwY6njU2TvNuaqVU8MwC1~EV-I~gfLyiqpwuSE8XyrBKi2pWfOr0autr3kOMtxNyOPElbHX2~h60hXPoAc-PE2ws2O7Jmg1htoWGu9MniDi3IZJjgBW~MpdDKSJFYgSNG15UphQEg3ND5BDi6JJ6CgtAXkvxtoYxHhBtFgOIyxiqpwMjfKzQlyOK5dXCwJHbOHCyuTt~7D3nxqO0m2ql57Pv4chcNRLXm4vzg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" class="supplement-link supplement-download stats-supplement-download" rel="nofollow"> <div class="pdf supplement-type"></div> <div class="supplement-title"><span class="title-label">Supplement 3.</span><p class="para">Manual of Operations</p></div> </a> </div> </div> </div> <div id="references-tab" class="resource-tab js-resource-tab references-tab need-jobs-ad"> <div class="references-wrap"> <div class="widget-SectionDisplay widget-instance-AMA_References_Tab"> <div class="references"><div class="reference"><a class="reference-number" id="joi170110r1">1.</a><div class="reference-content">Bellani G, Laffey JG, Pham T, et al; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2016;315(8):788-800.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26903337" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Epidemiology%2C%20patterns%20of%20care%2C%20and%20mortality%20for%20patients%20with%20acute%20respiratory%20distress%20syndrome%20in%20intensive%20care%20units%20in%2050%20countries.&author=G%20Bellani&author=JG%20Laffey&author=T%20Pham&publication_year=2016&journal=JAMA&volume=315&pages=788-800" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.2016.0291" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.2016.0291" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r2">2.</a><div class="reference-content">Herridge MS, Tansey CM, Matté A, et al; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2011;364(14):1293-1304.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21470008" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Functional%20disability%205%20years%20after%20acute%20respiratory%20distress%20syndrome.&author=MS%20Herridge&author=CM%20Tansey&author=A%20Matté&publication_year=2011&journal=N%20Engl%20J%20Med&volume=364&pages=1293-1304" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa1011802" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa1011802" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r3">3.</a><div class="reference-content">Gattinoni L, Marini JJ, Pesenti A, Quintel M, Mancebo J, Brochard L. The “baby lung” became an adult. <i xmlns:helper="urn:XsltStringHelper"> Intensive Care Med</i>. 2016;42(5):663-673.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26781952" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=The%20%E2%80%9Cbaby%20lung%E2%80%9D%20became%20an%20adult.&author=L%20Gattinoni&author=JJ%20Marini&author=A%20Pesenti&author=M%20Quintel&author=J%20Mancebo&author=L%20Brochard&publication_year=2016&journal=Intensive%20Care%20Med&volume=42&pages=663-673" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1007/s00134-015-4200-8" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1007/s00134-015-4200-8" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r4">4.</a><div class="reference-content">Gattinoni L, Protti A, Caironi P, Carlesso E. Ventilator-induced lung injury: the anatomical and physiological framework. <i xmlns:helper="urn:XsltStringHelper"> Crit Care Med</i>. 2010;38(10)(suppl):S539-S548.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21164395" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Ventilator-induced%20lung%20injury%3A%20the%20anatomical%20and%20physiological%20framework.&author=L%20Gattinoni&author=A%20Protti&author=P%20Caironi&author=E%20Carlesso&publication_year=2010&journal=Crit%20Care%20Med&volume=38&pages=S539-S548" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1097/CCM.0b013e3181f1fcf7" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1097/CCM.0b013e3181f1fcf7" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r5">5.</a><div class="reference-content">Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 1998;338(6):347-354.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/9449727" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Effect%20of%20a%20protective-ventilation%20strategy%20on%20mortality%20in%20the%20acute%20respiratory%20distress%20syndrome.&author=MB%20Amato&author=CS%20Barbas&author=DM%20Medeiros&publication_year=1998&journal=N%20Engl%20J%20Med&volume=338&pages=347-354" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJM199802053380602" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJM199802053380602" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r6">6.</a><div class="reference-content">Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A; Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2000;342(18):1301-1308.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/10793162" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Ventilation%20with%20lower%20tidal%20volumes%20as%20compared%20with%20traditional%20tidal%20volumes%20for%20acute%20lung%20injury%20and%20the%20acute%20respiratory%20distress%20syndrome.&author=RG%20Brower&author=MA%20Matthay&author=A%20Morris&author=D%20Schoenfeld&author=BT%20Thompson&author=A%20Wheeler&publication_year=2000&journal=N%20Engl%20J%20Med&volume=342&pages=1301-1308" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJM200005043421801" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJM200005043421801" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r7">7.</a><div class="reference-content">Borges JB, Okamoto VN, Matos GF, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 2006;174(3):268-278.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/16690982" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Reversibility%20of%20lung%20collapse%20and%20hypoxemia%20in%20early%20acute%20respiratory%20distress%20syndrome.&author=JB%20Borges&author=VN%20Okamoto&author=GF%20Matos&publication_year=2006&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=174&pages=268-278" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1164/rccm.200506-976OC" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1164/rccm.200506-976OC" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r8">8.</a><div class="reference-content">de Matos GF, Stanzani F, Passos RH, et al. How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography. <i xmlns:helper="urn:XsltStringHelper"> Crit Care</i>. 2012;16(1):R4.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/22226331" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=How%20large%20is%20the%20lung%20recruitability%20in%20early%20acute%20respiratory%20distress%20syndrome%3A%20a%20prospective%20case%20series%20of%20patients%20monitored%20by%20computed%20tomography.&author=GF%20de Matos&author=F%20Stanzani&author=RH%20Passos&publication_year=2012&journal=Crit%20Care&volume=16&pages=R4" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/cc10602" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/cc10602" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r9">9.</a><div class="reference-content">Hodgson CL, Tuxen DV, Davies AR, et al. A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> Crit Care</i>. 2011;15(3):R133.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21635753" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=A%20randomised%20controlled%20trial%20of%20an%20open%20lung%20strategy%20with%20staircase%20recruitment%2C%20titrated%20PEEP%20and%20targeted%20low%20airway%20pressures%20in%20patients%20with%20acute%20respiratory%20distress%20syndrome.&author=CL%20Hodgson&author=DV%20Tuxen&author=AR%20Davies&publication_year=2011&journal=Crit%20Care&volume=15&pages=R133" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/cc10249" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/cc10249" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r10">10.</a><div class="reference-content">Kacmarek RM, Villar J, Sulemanji D, et al; Open Lung Approach Network. Open lung approach for the acute respiratory distress syndrome: a pilot, randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> Crit Care Med</i>. 2016;44(1):32-42.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26672923" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Open%20lung%20approach%20for%20the%20acute%20respiratory%20distress%20syndrome%3A%20a%20pilot%2C%20randomized%20controlled%20trial.&author=RM%20Kacmarek&author=J%20Villar&author=D%20Sulemanji&publication_year=2016&journal=Crit%20Care%20Med&volume=44&pages=32-42" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1097/CCM.0000000000001383" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1097/CCM.0000000000001383" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r11">11.</a><div class="reference-content">Suzumura EA, Figueiró M, Normilio-Silva K, et al. Effects of alveolar recruitment maneuvers on clinical outcomes in patients with acute respiratory distress syndrome: a systematic review and meta-analysis. <i xmlns:helper="urn:XsltStringHelper"> Intensive Care Med</i>. 2014;40(9):1227-1240.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/25097070" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Effects%20of%20alveolar%20recruitment%20maneuvers%20on%20clinical%20outcomes%20in%20patients%20with%20acute%20respiratory%20distress%20syndrome%3A%20a%20systematic%20review%20and%20meta-analysis.&author=EA%20Suzumura&author=M%20Figueiró&author=K%20Normilio-Silva&publication_year=2014&journal=Intensive%20Care%20Med&volume=40&pages=1227-1240" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1007/s00134-014-3413-6" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1007/s00134-014-3413-6" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r12">12.</a><div class="reference-content">Hodgson C, Goligher EC, Young ME, et al. Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation. <i xmlns:helper="urn:XsltStringHelper"> Cochrane Database Syst Rev</i>. 2016;11:CD006667.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27855477" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Recruitment%20manoeuvres%20for%20adults%20with%20acute%20respiratory%20distress%20syndrome%20receiving%20mechanical%20ventilation.&author=C%20Hodgson&author=EC%20Goligher&author=ME%20Young&publication_year=2016&journal=Cochrane%20Database%20Syst%20Rev&volume=11&pages=CD006667" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a></div></div><div class="reference"><a class="reference-number" id="joi170110r13">13.</a><div class="reference-content">ART Investigators. Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> Trials</i>. 2012;13(1):153.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/22929542" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Rationale%2C%20study%20design%2C%20and%20analysis%20plan%20of%20the%20Alveolar%20Recruitment%20for%20ARDS%20Trial%20%28ART%29%3A%20study%20protocol%20for%20a%20randomized%20controlled%20trial.&publication_year=2012&journal=Trials&volume=13&pages=153" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/1745-6215-13-153" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/1745-6215-13-153" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r14">14.</a><div class="reference-content">Damiani L, Berwanger O, Paisani D, et al. Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART): a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> Rev Bras Ter Intensiva</i>. 2017;29(2):142-153.<a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Statistical%20analysis%20plan%20for%20the%20Alveolar%20Recruitment%20for%20Acute%20Respiratory%20Distress%20Syndrome%20Trial%20%28ART%29%3A%20a%20randomized%20controlled%20trial.&author=L%20Damiani&author=O%20Berwanger&author=D%20Paisani&publication_year=2017&journal=Rev%20Bras%20Ter%20Intensiva&volume=29&pages=142-153" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.5935/0103-507X.20170024" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.5935/0103-507X.20170024" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r15">15.</a><div class="reference-content">Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 1994;149(3 pt 1):818-824.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/7509706" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=The%20American-European%20Consensus%20Conference%20on%20ARDS%3A%20definitions%2C%20mechanisms%2C%20relevant%20outcomes%2C%20and%20clinical%20trial%20coordination.&author=GR%20Bernard&author=A%20Artigas&author=KL%20Brigham&publication_year=1994&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=149&pages=818-824" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1164/ajrccm.149.3.7509706" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1164/ajrccm.149.3.7509706" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r16">16.</a><div class="reference-content">Guérin C, Reignier J, Richard JC, et al; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2013;368(23):2159-2168.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/23688302" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Prone%20positioning%20in%20severe%20acute%20respiratory%20distress%20syndrome.&author=C%20Guérin&author=J%20Reignier&author=JC%20Richard&publication_year=2013&journal=N%20Engl%20J%20Med&volume=368&pages=2159-2168" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa1214103" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa1214103" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r17">17.</a><div class="reference-content">Mercat A, Richard JC, Vielle B, et al; Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2008;299(6):646-655.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/18270353" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Positive%20end-expiratory%20pressure%20setting%20in%20adults%20with%20acute%20lung%20injury%20and%20acute%20respiratory%20distress%20syndrome%3A%20a%20randomized%20controlled%20trial.&author=A%20Mercat&author=JC%20Richard&author=B%20Vielle&publication_year=2008&journal=JAMA&volume=299&pages=646-655" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.299.6.646" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.299.6.646" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r18">18.</a><div class="reference-content">Retamal J, Bugedo G, Larsson A, Bruhn A. High PEEP levels are associated with overdistension and tidal recruitment/derecruitment in ARDS patients. <i xmlns:helper="urn:XsltStringHelper"> Acta Anaesthesiol Scand</i>. 2015;59(9):1161-1169.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26061818" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=High%20PEEP%20levels%20are%20associated%20with%20overdistension%20and%20tidal%20recruitment%2Fderecruitment%20in%20ARDS%20patients.&author=J%20Retamal&author=G%20Bugedo&author=A%20Larsson&author=A%20Bruhn&publication_year=2015&journal=Acta%20Anaesthesiol%20Scand&volume=59&pages=1161-1169" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1111/aas.2015.59.issue-9" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1111/aas.2015.59.issue-9" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r19">19.</a><div class="reference-content">Guerin C, Debord S, Leray V, et al. Efficacy and safety of recruitment maneuvers in acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> Ann Intensive Care</i>. 2011;1(1):9.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21906333" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Efficacy%20and%20safety%20of%20recruitment%20maneuvers%20in%20acute%20respiratory%20distress%20syndrome.&author=C%20Guerin&author=S%20Debord&author=V%20Leray&publication_year=2011&journal=Ann%20Intensive%20Care&volume=1&pages=9" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/2110-5820-1-9" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/2110-5820-1-9" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r20">20.</a><div class="reference-content">Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2015;372(8):747-755.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/25693014" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Driving%20pressure%20and%20survival%20in%20the%20acute%20respiratory%20distress%20syndrome.&author=MB%20Amato&author=MO%20Meade&author=AS%20Slutsky&publication_year=2015&journal=N%20Engl%20J%20Med&volume=372&pages=747-755" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMsa1410639" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMsa1410639" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r21">21.</a><div class="reference-content">Guérin C, Papazian L, Reignier J, Ayzac L, Loundou A, Forel JM; investigators of the Acurasys and Proseva trials. Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials. <i xmlns:helper="urn:XsltStringHelper"> Crit Care</i>. 2016;20(1):384.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27894328" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Effect%20of%20driving%20pressure%20on%20mortality%20in%20ARDS%20patients%20during%20lung%20protective%20mechanical%20ventilation%20in%20two%20randomized%20controlled%20trials.&author=C%20Guérin&author=L%20Papazian&author=J%20Reignier&author=L%20Ayzac&author=A%20Loundou&author=JM%20Forel&publication_year=2016&journal=Crit%20Care&volume=20&pages=384" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/s13054-016-1556-2" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/s13054-016-1556-2" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r22">22.</a><div class="reference-content">Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2010;303(9):865-873.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/20197533" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Higher%20vs%20lower%20positive%20end-expiratory%20pressure%20in%20patients%20with%20acute%20lung%20injury%20and%20acute%20respiratory%20distress%20syndrome%3A%20systematic%20review%20and%20meta-analysis.&author=M%20Briel&author=M%20Meade&author=A%20Mercat&publication_year=2010&journal=JAMA&volume=303&pages=865-873" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.2010.218" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.2010.218" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r23">23.</a><div class="reference-content">Brower RG, Lanken PN, MacIntyre N, et al; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2004;351(4):327-336.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/15269312" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Higher%20versus%20lower%20positive%20end-expiratory%20pressures%20in%20patients%20with%20the%20acute%20respiratory%20distress%20syndrome.&author=RG%20Brower&author=PN%20Lanken&author=N%20MacIntyre&publication_year=2004&journal=N%20Engl%20J%20Med&volume=351&pages=327-336" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa032193" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa032193" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r24">24.</a><div class="reference-content">Beitler JR, Sands SA, Loring SH, et al. Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria. <i xmlns:helper="urn:XsltStringHelper"> Intensive Care Med</i>. 2016;42(9):1427-1436.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27342819" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Quantifying%20unintended%20exposure%20to%20high%20tidal%20volumes%20from%20breath%20stacking%20dyssynchrony%20in%20ARDS%3A%20the%20BREATHE%20criteria.&author=JR%20Beitler&author=SA%20Sands&author=SH%20Loring&publication_year=2016&journal=Intensive%20Care%20Med&volume=42&pages=1427-1436" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1007/s00134-016-4423-3" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1007/s00134-016-4423-3" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r25">25.</a><div class="reference-content">Chanques G, Kress JP, Pohlman A, et al. Impact of ventilator adjustment and sedation-analgesia practices on severe asynchrony in patients ventilated in assist-control mode. <i xmlns:helper="urn:XsltStringHelper"> Crit Care Med</i>. 2013;41(9):2177-2187.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/23782972" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Impact%20of%20ventilator%20adjustment%20and%20sedation-analgesia%20practices%20on%20severe%20asynchrony%20in%20patients%20ventilated%20in%20assist-control%20mode.&author=G%20Chanques&author=JP%20Kress&author=A%20Pohlman&publication_year=2013&journal=Crit%20Care%20Med&volume=41&pages=2177-2187" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1097/CCM.0b013e31828c2d7a" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1097/CCM.0b013e31828c2d7a" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r26">26.</a><div class="reference-content">Meade MO, Cook DJ, Guyatt GH, et al; Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2008;299(6):637-645.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/18270352" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Ventilation%20strategy%20using%20low%20tidal%20volumes%2C%20recruitment%20maneuvers%2C%20and%20high%20positive%20end-expiratory%20pressure%20for%20acute%20lung%20injury%20and%20acute%20respiratory%20distress%20syndrome%3A%20a%20randomized%20controlled%20trial.&author=MO%20Meade&author=DJ%20Cook&author=GH%20Guyatt&publication_year=2008&journal=JAMA&volume=299&pages=637-645" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.299.6.637" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.299.6.637" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r27">27.</a><div class="reference-content">Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. <i xmlns:helper="urn:XsltStringHelper"> Lancet Respir Med</i>. 2014;2(8):611-620.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/24853585" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Subphenotypes%20in%20acute%20respiratory%20distress%20syndrome%3A%20latent%20class%20analysis%20of%20data%20from%20two%20randomised%20controlled%20trials.&author=CS%20Calfee&author=K%20Delucchi&author=PE%20Parsons&author=BT%20Thompson&author=LB%20Ware&author=MA%20Matthay&publication_year=2014&journal=Lancet%20Respir%20Med&volume=2&pages=611-620" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1016/S2213-2600(14)70097-9" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1016/S2213-2600(14)70097-9" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r28">28.</a><div class="reference-content">Famous KR, Delucchi K, Ware LB, et al; ARDS Network. Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 2017;195(3):331-338.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27513822" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Acute%20respiratory%20distress%20syndrome%20subphenotypes%20respond%20differently%20to%20randomized%20fluid%20management%20strategy.&author=KR%20Famous&author=K%20Delucchi&author=LB%20Ware&publication_year=2017&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=195&pages=331-338" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a></div></div><div class="reference"><a class="reference-number" id="joi170110r29">29.</a><div class="reference-content">Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2006;354(17):1775-1786.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/16641394" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Lung%20recruitment%20in%20patients%20with%20the%20acute%20respiratory%20distress%20syndrome.&author=L%20Gattinoni&author=P%20Caironi&author=M%20Cressoni&publication_year=2006&journal=N%20Engl%20J%20Med&volume=354&pages=1775-1786" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa052052" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa052052" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r30">30.</a><div class="reference-content">Goligher EC, Kavanagh BP, Rubenfeld GD, Ferguson ND. Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 2015;192(12):1416-1419.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/25580530" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Physiologic%20Responsiveness%20Should%20Guide%20Entry%20into%20Randomized%20Controlled%20Trials.&author=EC%20Goligher&author=BP%20Kavanagh&author=GD%20Rubenfeld&author=ND%20Ferguson&publication_year=2015&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=192&pages=1416-1419" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1164/rccm.201410-1832CP" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1164/rccm.201410-1832CP" xmlns:helper="urn:XsltStringHelper"> </span></div></div></div> </div> </div> </div> <div id="related-tab" class="resource-tab js-resource-tab related-tab need-jobs-ad"> <div class="widget-ArticleLinks widget-instance-AMA_See_Also_Related_Content"> <ul class="article-links related-content"> <li class="article-link related-article odd"> <a href="https://jamanetwork.com/journals/jama/fullarticle/2654890" class="td-n"> <div class="related-article-title">Lung Recruitment and Titrated PEEP in Moderate to Severe ARDS</div> <div class="related-journal-name">JAMA</div> <div class="related-article-type">Editorial</div> <div class="related-article-date">October 10, 2017</div> <div class="related-article-excerpt"></div> <div class="related-article-authors">Sarina K. Sahetya, MD; Roy G. Brower, MD</div> </a> </li> <li class="article-link related-article even"> <a href="https://jamanetwork.com/journals/jama/fullarticle/2673961" class="td-n"> <div class="related-article-title">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS</div> <div class="related-journal-name">JAMA</div> <div class="related-article-type">Comment & Response</div> <div class="related-article-date">March 6, 2018</div> <div class="related-article-excerpt"></div> <div class="related-article-authors">Carmen Silvia Valente Barbas, MD, PhD; Sérgio Nogueira Nemer, RRT, PhD</div> </a> </li> <li class="article-link related-article odd"> <a href="https://jamanetwork.com/journals/jama/fullarticle/2673962" class="td-n"> <div class="related-article-title">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS</div> <div class="related-journal-name">JAMA</div> <div class="related-article-type">Comment & Response</div> <div class="related-article-date">March 6, 2018</div> <div class="related-article-excerpt"></div> <div class="related-article-authors">Idunn S. Morris, MBChB, FRCA; Andrew S. Lane, MBBS, PhD, FCICM; Ian Seppelt, MBBS, BSc(Med) FANZCA</div> </a> </li> <li class="article-link related-article even"> <a href="https://jamanetwork.com/journals/jama/fullarticle/2673963" class="td-n"> <div class="related-article-title">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS</div> <div class="related-journal-name">JAMA</div> <div class="related-article-type">Comment & Response</div> <div class="related-article-date">March 6, 2018</div> <div class="related-article-excerpt"></div> <div class="related-article-authors">Andrew C. McKown, MD; Matthew W. Semler, MD, MSc; Todd W. Rice, MD, MSc</div> </a> </li> <li class="article-link related-article odd"> <a href="https://jamanetwork.com/journals/jama/fullarticle/2673965" class="td-n"> <div class="related-article-title">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS—Reply</div> <div class="related-journal-name">JAMA</div> <div class="related-article-type">Comment & Response</div> <div class="related-article-date">March 6, 2018</div> <div class="related-article-excerpt"></div> <div class="related-article-authors">Alexandre Biasi Cavalcanti, MD, PhD; Marcelo Britto Passos Amato, MD, PhD; Carlos Roberto Ribeiro de Carvalho, MD, PhD</div> </a> </li> <li class="article-link related-article even"> <a href="https://jamanetwork.com/journals/jama/fullarticle/2725206" class="td-n"> <div class="related-article-title">Effect of an Esophageal Pressure–Guided PEEP Titration Strategy vs an Empirical High PEEP-F<span style="font-variant:small-caps;">io</span><sub>2</sub> Strategy in ARDS</div> <div class="related-journal-name">JAMA</div> <div class="related-article-type">Original Investigation</div> <div class="related-article-date">March 5, 2019</div> <div class="related-article-excerpt">This randomized trial compares the effect of guiding PEEP titration using esophageal pressure vs empirical high PEEP–fraction of inspired oxygen (Fio2) on a composite of death and days free from mechanical ventilation at 28 days in patients with moderate to severe acute respiratory distress syndrome (ARDS).</div> <div class="related-article-authors">Jeremy R. Beitler, MD, MPH; Todd Sarge, MD; Valerie M. Banner-Goodspeed, MPH; Michelle N. Gong, MD, MSc; Deborah Cook, MD; Victor Novack, MD, PhD; Stephen H. Loring, MD; Daniel Talmor, MD, MPH; for the EPVent-2 Study Group</div> </a> </li> </ul> </div> <div class="widget-EditorsChoice widget-instance-AMA_EditorsChoice_Links"> </div> <div class="widget-RelatedTopics widget-instance-AMA_Related_Topics"> <div class="related-topics-block"> <h4 class="related-topics-heading topic-suggestions-heading sb-sc"> See More About </h4> <div class="related-topics topic-suggestions"> <a href="https://jamanetwork.com/collections/5584/critical-care-medicine" id="item_Link" class="related-topic topic-suggestion no-wrap sb-anchor-light">Critical Care Medicine</a> <a href="https://jamanetwork.com/collections/42131/respiratory-failure-and-ventilation" id="item_Link_1" class="related-topic topic-suggestion no-wrap sb-anchor-light">Respiratory Failure and Ventilation</a> </div> </div> </div> <div class="ymal--footer"> <div class="widget-WidgetLoader widget-instance-AMA_PersonalizedContent_SplitScreenView_Footer"> <div class="SCM-SharedWidgets-AsyncWidgetLoader" data-url="/Personalization/PersonalizedContent/AMA_PersonalizedContent_SplitScreenView_Footer" data-params="{"parameters":{"resourceIdToExclude":2654894,"resourceTypeToExclude":3},"dynamicParameters":{"localParams":"[REPLACE_WITH_LOCAL]"}}"></div> </div> </div> <hr /> <div class="manage-interest"> <h4><a href="#" class="manage-interests-link-no-access thm-col-sec">Select Your Interests</a></h4> <div class="widget-ManageCollectionInterests widget-instance-ManageCollectionInterests_SplitScreen"> <div class="manage-interests-modal reveal-modal small modal" data-reveal> <div class="manage-interests--header"> <div class="widget-SelfServeContent widget-instance-AMA_ManageInterests_Header"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="AllSitesManageInterestsHeader" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <style> h4 { font-size: 20px !important; } </style> <h4>Select Your Interests</h4> <p>Customize your JAMA Network experience by selecting one or more topics from the list below.</p> </div> </div> </div><div class="manage-interests--categories"> <ul class="category-list"> <li><span class="category-list-item " data-categoryid="46425">Academic Medicine</span></li> <li><span class="category-list-item " data-categoryid="5489">Acid Base, Electrolytes, Fluids</span></li> <li><span class="category-list-item " data-categoryid="5504">Allergy and Clinical Immunology</span></li> <li><span class="category-list-item " data-categoryid="46447">American Indian or Alaska Natives</span></li> <li><span class="category-list-item " data-categoryid="5510">Anesthesiology</span></li> <li><span class="category-list-item " data-categoryid="42143">Anticoagulation</span></li> <li><span class="category-list-item " data-categoryid="6261">Art and Images in Psychiatry</span></li> <li><span class="category-list-item " data-categoryid="42097">Assisted Reproduction</span></li> <li><span class="category-list-item " data-categoryid="42099">Bleeding and Transfusion</span></li> <li><span class="category-list-item " data-categoryid="5548">Cardiology</span></li> <li><span class="category-list-item " data-categoryid="44036">Caring for the Critically Ill Patient</span></li> <li><span class="category-list-item " data-categoryid="6255">Challenges in Clinical Electrocardiography</span></li> <li><span class="category-list-item " data-categoryid="46435">Climate and Health</span></li> <li><span class="category-list-item " data-categoryid="46448">Climate Change</span></li> <li><span class="category-list-item " data-categoryid="44038">Clinical Challenge</span></li> <li><span class="category-list-item " data-categoryid="44039">Clinical Implications of Basic Neuroscience</span></li> <li><span class="category-list-item " data-categoryid="5614">Clinical Pharmacy and Pharmacology</span></li> <li><span class="category-list-item " data-categoryid="46499">Coaching</span></li> <li><span class="category-list-item " data-categoryid="5575">Complementary and Alternative Medicine</span></li> <li><span class="category-list-item " data-categoryid="44040">Consensus Statements</span></li> <li><span class="category-list-item " data-categoryid="46099">Coronavirus (COVID-19)</span></li> <li><span class="category-list-item " data-categoryid="5584">Critical Care Medicine</span></li> <li><span class="category-list-item " data-categoryid="46325">Cultural Competency</span></li> <li><span class="category-list-item " data-categoryid="44019">Dental Medicine</span></li> <li><span class="category-list-item " data-categoryid="5598">Dermatology</span></li> <li><span class="category-list-item " data-categoryid="44011">Diabetes and Endocrinology</span></li> <li><span class="category-list-item " data-categoryid="46320">Diagnostic Test Interpretation</span></li> <li><span class="category-list-item " data-categoryid="46498">Digital Health</span></li> <li><span class="category-list-item " data-categoryid="42054">Drug Development</span></li> <li><span class="category-list-item " data-categoryid="5621">Emergency Medicine</span></li> <li><span class="category-list-item " data-categoryid="5819">End of Life, Hospice, Palliative Care</span></li> <li><span class="category-list-item " data-categoryid="42107">Environmental Health</span></li> <li><span class="category-list-item " data-categoryid="46387">Equity, Diversity, and Inclusion</span></li> <li><span class="category-list-item " data-categoryid="42108">Ethics</span></li> <li><span class="category-list-item " data-categoryid="5644">Facial Plastic Surgery</span></li> <li><span class="category-list-item " data-categoryid="44012">Gastroenterology and Hepatology</span></li> <li><span class="category-list-item " data-categoryid="5664">Genetics and Genomics</span></li> <li><span class="category-list-item " data-categoryid="44041">Genomics and Precision Health</span></li> <li><span class="category-list-item " data-categoryid="5668">Geriatrics</span></li> <li><span class="category-list-item " data-categoryid="5670">Global Health</span></li> <li><span class="category-list-item " data-categoryid="46427">Guide to Statistics and Methods</span></li> <li><span class="category-list-item " data-categoryid="5672">Guidelines</span></li> <li><span class="category-list-item " data-categoryid="5674">Hair Disorders</span></li> <li><span class="category-list-item " data-categoryid="42113">Health Care Delivery Models</span></li> <li><span class="category-list-item " data-categoryid="42114">Health Care Economics, Insurance, Payment</span></li> <li><span class="category-list-item " data-categoryid="42116">Health Care Quality</span></li> <li><span class="category-list-item " data-categoryid="5680">Health Care Reform</span></li> <li><span class="category-list-item " data-categoryid="5830">Health Care Safety</span></li> <li><span class="category-list-item " data-categoryid="5682">Health Care Workforce</span></li> <li><span class="category-list-item " data-categoryid="5679">Health Disparities</span></li> <li><span class="category-list-item " data-categoryid="46328">Health Inequities</span></li> <li><span class="category-list-item " data-categoryid="44020">Health Policy</span></li> <li><span class="category-list-item " data-categoryid="46451">Health Systems Science</span></li> <li><span class="category-list-item " data-categoryid="5688">Hematology</span></li> <li><span class="category-list-item " data-categoryid="5692">History of Medicine</span></li> <li><span class="category-list-item " data-categoryid="5514">Humanities</span></li> <li><span class="category-list-item " data-categoryid="5697">Hypertension</span></li> <li><span class="category-list-item " data-categoryid="44043">Images in Neurology</span></li> <li><span class="category-list-item " data-categoryid="45887">Implementation Science</span></li> <li><span class="category-list-item " data-categoryid="5702">Infectious Diseases</span></li> <li><span class="category-list-item " data-categoryid="44044">Innovations in Health Care Delivery</span></li> <li><span class="category-list-item " data-categoryid="46477">JAMA Forum</span></li> <li><span class="category-list-item " data-categoryid="44070">JAMA Infographic</span></li> <li><span class="category-list-item " data-categoryid="5716">Law and Medicine</span></li> <li><span class="category-list-item " data-categoryid="45308">Leading Change</span></li> <li><span class="category-list-item " data-categoryid="44045">Less is More</span></li> <li><span class="category-list-item " data-categoryid="46327">LGBTQIA Medicine</span></li> <li><span class="category-list-item " data-categoryid="5720">Lifestyle Behaviors</span></li> <li><span class="category-list-item " data-categoryid="45311">Medical Coding</span></li> <li><span class="category-list-item " data-categoryid="5738">Medical Devices and Equipment</span></li> <li><span class="category-list-item " data-categoryid="44023">Medical Education</span></li> <li><span class="category-list-item " data-categoryid="5739">Medical Education and Training</span></li> <li><span class="category-list-item " data-categoryid="5713">Medical Journals and Publishing</span></li> <li><span class="category-list-item " data-categoryid="5746">Melanoma</span></li> <li><span class="category-list-item " data-categoryid="5766">Narrative Medicine</span></li> <li><span class="category-list-item " data-categoryid="5769">Nephrology</span></li> <li><span class="category-list-item " data-categoryid="5777">Neurology</span></li> <li><span class="category-list-item " data-categoryid="44052">Neuroscience and Psychiatry</span></li> <li><span class="category-list-item " data-categoryid="44053">Notable Notes</span></li> <li><span class="category-list-item " data-categoryid="5787">Nursing</span></li> <li><span class="category-list-item " data-categoryid="5788">Nutrition</span></li> <li><span class="category-list-item " data-categoryid="44027">Nutrition, Obesity, Exercise</span></li> <li><span class="category-list-item " data-categoryid="5791">Obesity</span></li> <li><span class="category-list-item " data-categoryid="44013">Obstetrics and Gynecology</span></li> <li><span class="category-list-item " data-categoryid="5796">Occupational Health</span></li> <li><span class="category-list-item " data-categoryid="5801">Oncology</span></li> <li><span class="category-list-item " data-categoryid="5804">Ophthalmology</span></li> <li><span class="category-list-item " data-categoryid="5808">Orthopedics</span></li> <li><span class="category-list-item " data-categoryid="5811">Otolaryngology</span></li> <li><span class="category-list-item " data-categoryid="44028">Pain Medicine</span></li> <li><span class="category-list-item " data-categoryid="46446">Palliative Care</span></li> <li><span class="category-list-item " data-categoryid="44029">Pathology and Laboratory Medicine</span></li> <li><span class="category-list-item " data-categoryid="45306">Patient Care</span></li> <li><span class="category-list-item " data-categoryid="6258">Patient Information</span></li> <li><span class="category-list-item " data-categoryid="5843">Pediatrics</span></li> <li><span class="category-list-item " data-categoryid="44060">Performance Improvement</span></li> <li><span class="category-list-item " data-categoryid="45315">Performance Measures</span></li> <li><span class="category-list-item " data-categoryid="42050">Perioperative Care and Consultation</span></li> <li><span class="category-list-item " data-categoryid="42125">Pharmacoeconomics</span></li> <li><span class="category-list-item " data-categoryid="42126">Pharmacoepidemiology</span></li> <li><span class="category-list-item " data-categoryid="5851">Pharmacogenetics</span></li> <li><span class="category-list-item " data-categoryid="44030">Pharmacy and Clinical Pharmacology</span></li> <li><span class="category-list-item " data-categoryid="5856">Physical Medicine and Rehabilitation</span></li> <li><span class="category-list-item " data-categoryid="42059">Physical Therapy</span></li> <li><span class="category-list-item " data-categoryid="45313">Physician Leadership</span></li> <li><span class="category-list-item " data-categoryid="44061">Poetry</span></li> <li><span class="category-list-item " data-categoryid="45316">Population Health</span></li> <li><span class="category-list-item " data-categoryid="46445">Primary Care</span></li> <li><span class="category-list-item " data-categoryid="45309">Professional Well-being</span></li> <li><span class="category-list-item " data-categoryid="44064">Professionalism</span></li> <li><span class="category-list-item " data-categoryid="5871">Psychiatry and Behavioral Health</span></li> <li><span class="category-list-item " data-categoryid="42128">Public Health</span></li> <li><span class="category-list-item " data-categoryid="5877">Pulmonary Medicine</span></li> <li><span class="category-list-item " data-categoryid="42129">Radiology</span></li> <li><span class="category-list-item " data-categoryid="42058">Regulatory Agencies</span></li> <li><span class="category-list-item " data-categoryid="46443">Reproductive Health</span></li> <li><span class="category-list-item " data-categoryid="5916">Research, Methods, Statistics</span></li> <li><span class="category-list-item " data-categoryid="42142">Resuscitation</span></li> <li><span class="category-list-item " data-categoryid="5896">Rheumatology</span></li> <li><span class="category-list-item " data-categoryid="46326">Risk Management</span></li> <li><span class="category-list-item " data-categoryid="38802">Scientific Discovery and the Future of Medicine</span></li> <li><span class="category-list-item " data-categoryid="46495">Sexual Health</span></li> <li><span class="category-list-item " data-categoryid="5833">Shared Decision Making and Communication</span></li> <li><span class="category-list-item " data-categoryid="5912">Sleep Medicine</span></li> <li><span class="category-list-item " data-categoryid="5915">Sports Medicine</span></li> <li><span class="category-list-item " data-categoryid="5533">Stem Cell Transplantation</span></li> <li><span class="category-list-item " data-categoryid="5921">Substance Use and Addiction Medicine</span></li> <li><span class="category-list-item " data-categoryid="5923">Surgery</span></li> <li><span class="category-list-item " data-categoryid="44065">Surgical Innovation</span></li> <li><span class="category-list-item " data-categoryid="44066">Surgical Pearls</span></li> <li><span class="category-list-item " data-categoryid="44067">Teachable Moment</span></li> <li><span class="category-list-item " data-categoryid="44034">The Art of JAMA</span></li> <li><span class="category-list-item " data-categoryid="44037">The Arts and Medicine</span></li> <li><span class="category-list-item " data-categoryid="6257">The Rational Clinical Examination</span></li> <li><span class="category-list-item " data-categoryid="5936">Tobacco and e-Cigarettes</span></li> <li><span class="category-list-item " data-categoryid="5938">Toxicology</span></li> <li><span class="category-list-item " data-categoryid="46433">Translational Medicine</span></li> <li><span class="category-list-item " data-categoryid="42136">Trauma and Injury</span></li> <li><span class="category-list-item " data-categoryid="5942">Treatment Adherence</span></li> <li><span class="category-list-item " data-categoryid="46323">Ultrasonography</span></li> <li><span class="category-list-item " data-categoryid="5947">Urology</span></li> <li><span class="category-list-item " data-categoryid="44069">Users' Guide to the Medical Literature</span></li> <li><span class="category-list-item " data-categoryid="5950">Vaccination</span></li> <li><span class="category-list-item " data-categoryid="5955">Venous Thromboembolism</span></li> <li><span class="category-list-item " data-categoryid="45312">Veterans Health</span></li> <li><span class="category-list-item " data-categoryid="5957">Violence</span></li> <li><span class="category-list-item " data-categoryid="42139">Women's Health</span></li> <li><span class="category-list-item " data-categoryid="45307">Workflow and Process</span></li> <li><span class="category-list-item " data-categoryid="42140">Wound Care, Infection, Healing</span></li> </ul> </div> <div class="manage-interests--save-preferences"> <div class="save-preferences-btn thm-bg "> <span class="save-preferences-btn-text fw-b">Save Preferences</span> </div> </div> <div class="manage-interests--privacy-terms"> <a class="manage-interests--privacy-terms-color" href="/pages/privacy-policy">Privacy Policy</a> | <a class="manage-interests--privacy-terms-color" href="/pages/terms-of-use">Terms of Use</a></div> <a class="close-reveal-modal icon-close"></a> </div> </div> </div> <h4 class="thm-col-sec" align="center"> Others Also Liked </h4> <div id="trendmd-suggestions"></div> </div> <div id="comments-tab" class="resource-tab js-resource-tab comments-tab js-comments-tab single-comment-view"> </div> </div> </div> <a id="skip-to-navigation" href="#" tabindex="-1"></a> <div id="content-panel" class="content-panel"> <a id="top"></a> <div id="full-text-tab" class="resource-tab js-resource-tab full-text-tab"> <div class="widget-ArticleLinks widget-instance-AMA_ErrataArticleLinks_FullText"> </div> <div class="widget-ArticleLinks widget-instance-AMA_ArticleLinks_ToErrata_FullText"> </div> <div class="widget-ArticleNavLinks widget-instance-AMA_ArticleNavLinks"> <a class="toc-link btn" href="https://jamanetwork.com/journals/jama/issue/318/14">This Issue</a> </div> <div class="article-metrics-wrapper" id="divArticleLevelMetrics"> <div class="widget-ArticleLevelMetrics widget-instance-AMA_ArticleMetrics"> <div class="artmet-condensed-wrap clearfix"> <div class="artmet-condensed-stats clearfix"> <div class="artmet-item artmet-views"> <span class="artmet-text sb-sc">Views</span> <span class="artmet-number sb-sc">199,133</span> </div> <div class="artmet-item artmet-citations"> <a class="artmet-citations-link" href="https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=silverchair&SrcAuth=WosAPI&KeyUT=WOS:000412838900017&DestLinkType=FullRecord&DestApp=WOS_CPL" target="_blank"> <span class="artmet-text">Citations</span> <span class="artmet-number">633</span> </a> </div> <div class="artmet-item artmet-altmetric"> <div class="widget-AltmetricLink widget-instance-AMAv2_ArticleLevelMetrics_AltmetricLinkSummary"> <!-- Altmetrics --> <div id="altmetricEmbedId" class='altmetric-embed' data-link-target="_blank" data-badge-type="text" data-hide-no-mentions="false" data-doi="10.1001/jama.2017.14171" ></div> </div> </div> </div> <div class="artmet-modal-trigger-wrap"> <a rel="nofollow" class="artmet-modal-trigger" data-article-id="2654894"><i class="icon-metrics"></i><span>View Metrics</span></a> </div> </div> </div> </div> <ul class="toolbar"> <li class="toolbar-pdf-wrap toolbar-tool-wrap"> <a id="pdf-link" href="/journals/jama/articlepdf/2654894/jama_cavalcanti_2017_oi_170110.pdf" class="toolbar-tool toolbar-pdf al-link pdfaccess js-pdfaccess" data-article-id="2654894" data-article-url="/journals/jama/articlepdf/2654894/jama_cavalcanti_2017_oi_170110.pdf" data-ajax-url="/Content/CheckPdfAccess"><span class="toolbar-pdf-text"><span class="toolbar-link-text-extra">Download </span><span class="toolbar-link-text">PDF</span></span> </a> </li> <li class="toolbar-share-wrap toolbar-tool-wrap"> <div class="toolbar-tool"> <a class="st-custom-button addthis_button_twitter is-b toolbar-twitter toolbar-share" data-network="twitter" data-title="" data-url="" data-email-subject="" rel="nofollow" href="javascript:;"> <span class="share-text">X</span> </a> <a class="st-custom-button addthis_button_facebook is-b toolbar-facebook toolbar-share" data-network="facebook" data-title="" data-url="" data-email-subject="" rel="nofollow" href="javascript:;"> <span class="share-text">Facebook</span> </a> <a class="toolbar-share-more-link is-a" rel="nofollow"><span class="icon icon-carrot_down social-arrow"></span><span class="more-text-wrap">More</span></a> <div class="toolbar-share-more"> <a class="st-custom-button addthis_button_linkedin is-b toolbar-linkedin toolbar-share" data-network="linkedin" data-title="" data-url="" data-email-subject="" rel="nofollow" href="javascript:;"> <span class="share-text">LinkedIn</span> </a> </div> </div> </li> <li class="toolbar-citation-wrap toolbar-tool-wrap"> <div class="widget-ToolboxGetCitation widget-instance-AMA_Get_Citation"> <a class="toolbar-tool toolbar-citation is-b stats-citation" rel="nofollow" data-reveal-id="get-citation" data-reveal> <span class="toolbar-link-text">Cite</span> <span class="toolbar-link-text-extra">This</span> </a> <div id="get-citation" class="reveal-modal get-citation" data-reveal> <h3 class="get-citation-title">Citation</h3> <p class="get-citation-citation">Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome<span class="subtitle"><span class="colon-for-citation-subtitle">: </span>A Randomized Clinical Trial</span>. <em>JAMA.</em> 2017;318(14):1335–1345. doi:10.1001/jama.2017.14171</p> <h4 class="get-citation-download-heading">Manage citations:</h4> <div class="get-citation-types"> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=0">Ris (Zotero)</a> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=1">EndNote</a> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=2">BibTex</a> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=3">Medlars</a> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=0">ProCite</a> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=3">RefWorks</a> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=0">Reference Manager</a> <a class="get-citation-format" rel="nofollow" href="/Citation/Download?resourceId=2654894&resourceType=3&citationFormat=0">Mendeley</a> </div> <p class="get-citation-copyright">© 2024 </p> <a class="close-reveal-modal icon-close" rel="nofollow"></a> </div> </div> </li> <li class="toolbar-permissions-wrap toolbar-tool-wrap"> <div class="widget-ToolboxPermissions widget-instance-AMA_Get_Permissions"> <a href="http://s100.copyright.com/AppDispatchServlet?publisherName=AMA&publication=0098-7484&title=Effect+of+Lung+Recruitment+and+Titrated+Positive+End-Expiratory+Pressure+(PEEP)+vs+Low+PEEP+on+Mortality+in+Patients+With+Acute+Respiratory+Distress+Syndrome%3a+A+Randomized+Clinical+Trial&publicationDate=2017-10-10&volumeNum=318&issueNum=14&author=Writing+Group+for+the+Alveolar+Recruitment+for+Acute+Respiratory+Distress+Syndrome+Trial+(ART)+Investigators%3b+Cavalcanti%2c+Alexandre+Biasi&startPage=1335&endPage=1345&contentId=10.1001%2fjama.2017.14171&oa=&orderBeanReset=True" rel="nofollow" id="PermissionsLink" class="toolbar-tool toolbar-permissions is-b" target="_blank"><span class="toolbar-link-text">Permissions</span></a> </div> </li> </ul> <div class="widget-ArticleTopInfo widget-instance-AMA_ArticleTop_Info_Widget"> <div class="meta-access-type free-access is-b"></div> <span class="hide tagmanagervalue" data-attribute="articleId" data-value="2654894" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="arrArticleAuthor" data-value="Writing%20Group%20for%20the%20Alveolar%20Recruitment%20for%20Acute%20Respiratory%20Distress%20Syndrome%20Trial%20%28ART%29%20Investigators" data-type="array"></span> <span class="hide tagmanagervalue" data-attribute="articleDOI" data-value="10.1001/jama.2017.14171" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="articleTitle" data-value="Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome<span class="subtitle"><span class="colon-for-citation-subtitle">: </span>A Randomized Clinical Trial</span>" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="type" data-value="Original Investigation" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="thematicLabel" data-value="Caring for the Critically Ill Patient" data-type="array"></span> <span class="hide tagmanagervalue" data-attribute="issueVolume" data-value="318" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="issueNo" data-value="14" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="publishDate" data-value="October 10, 2017" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="topics" data-value="Critical Care Medicine, Respiratory Failure and Ventilation" data-type="array"></span> <span class="hide tagmanagervalue" data-attribute="topicCode" data-value="5584, 42131" data-type="array"></span> <span class="hide tagmanagervalue" data-attribute="category" data-value="Research" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="journalClub" data-value="No" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="contentStatus" data-value="Free" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="articlePubState" data-value="Final" data-type="string"></span> <span class="hide tagmanagervalue" data-attribute="contentMedium" data-value="Article" data-type="string"></span> <div class="meta-article-type-wrap"> <div class="meta-article-type thm-col">Original Investigation </div> <div class="meta-super-class">Caring for the Critically Ill Patient</div> </div> <div class="meta-date"><span class="ppub"><span class="month">October </span><span class="day">10, </span><span class="year">2017</span></span></div> <div class="meta-article-title-wrap"> <h1 class="meta-article-title ">Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome<span class="subtitle"><span class="colon-for-citation-subtitle">: </span>A Randomized Clinical Trial</span></h1> </div> <div class="meta-authors"> Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators<sup></sup> </div> <div class="meta-author"> <a class="meta-articleinfo-jumplink no-affiliations section-jump-link scroll-to" data-tab-toggle=".tab-nav-full-text" href="#172419600">Article Information</a> </div> <div class="meta-citation-wrap"> <span class="meta-citation-journal-name">JAMA. </span><span class="meta-citation"> 2017;318(14):1335-1345. doi:10.1001/jama.2017.14171</span> </div> </div> <div class="widget-EditorsChoice widget-instance-AMA_EditorsChoice_Links"> </div> <div class="widget-LinkedContentToolbar widget-instance-AMA_LinkedContentToolbar"> <div class="linked-content-toolbar"> <div class="hidden js-search-open-multimedia-by-default" showContentByDefault="False"></div> <div class="linked-content-controls"> <a class="linked-content-trigger td-n stats-graphical-abstract" href="#graphical-abstract-tab"> <i class="icon-visual-abstract"><span class="sr-t">visual abstract icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Visual <div>Abstract</div></div> </a> <a class="linked-content-trigger td-n stats-editorial-comment" href="#editorial-comment-tab"> <i class="icon-document"><span class="sr-t">editorial comment icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Editorial <div>Comment</div></div> </a> <a class="linked-content-trigger td-n stats-related-articles" href="#related-articles-tab"> <i class="icon-related"><span class="sr-t">related articles icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Related <div>Articles</div></div> </a> <a class="linked-content-trigger td-n stats-author-interviews" href="#author-interviews-tab"> <i class="icon-author_interview"><span class="sr-t">author interview icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Interviews</div> </a> <a class="linked-content-trigger td-n stats-more-multimedia" href="#more-multimedia-tab"> <i class="icon-multimedia"><span class="sr-t">multimedia icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Multimedia</div> </a> <a class="linked-content-trigger td-n stats-listen-to-this-article" href="#listen-to-this-article-tab"> <i class="icon-audio"><span class="sr-t">audio icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Listen to <div>this article</div></div> </a> </div> <div class="linked-content-tabs"> <div id="graphical-abstract-tab" class="linked-content-tab graphical-abstract-tab"> <div class="widget-SectionDisplay widget-instance-AMA_GraphicalAbstract_Tab"> </div> </div> <div id="editorial-comment-tab" class="linked-content-tab editorial-comment-tab"> <div class="widget-ArticleLinks widget-instance-AMA_LinkedContentToolbar_EditorialComments"> <ul class="article-abstract-links related-abstract-content"> <li class="article-link related-abstract-article"> <a class="related-article-title" href="https://jamanetwork.com/journals/jama/fullarticle/2654890"> <div class="related-article-type">Editorial</div> <div class="related-article-title sb-tc">Lung Recruitment and Titrated PEEP in Moderate to Severe ARDS</div> </a> <div class="related-article-authors">Sarina K. Sahetya, MD; Roy G. Brower, MD</div> <div class="related-article-journal-name">JAMA</div> </li> </ul> </div> </div> <div id="related-articles-tab" class="linked-content-tab related-article-tab"> <div class="widget-ArticleLinks widget-instance-AMA_LinkedContentToolbar_RelatedArticle"> <ul class="article-abstract-links related-abstract-content"> <li class="article-link related-abstract-article"> <a class="related-article-title" href="https://jamanetwork.com/journals/jama/fullarticle/2673961"> <div class="related-article-type">Comment & Response</div> <div class="related-article-title sb-tc">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS</div> </a> <div class="related-article-authors">Carmen Silvia Valente Barbas, MD, PhD; Sérgio Nogueira Nemer, RRT, PhD</div> <div class="related-article-journal-name">JAMA</div> </li> <li class="article-link related-abstract-article"> <a class="related-article-title" href="https://jamanetwork.com/journals/jama/fullarticle/2673962"> <div class="related-article-type">Comment & Response</div> <div class="related-article-title sb-tc">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS</div> </a> <div class="related-article-authors">Idunn S. Morris, MBChB, FRCA; Andrew S. Lane, MBBS, PhD, FCICM; Ian Seppelt, MBBS, BSc(Med) FANZCA</div> <div class="related-article-journal-name">JAMA</div> </li> <li class="article-link related-abstract-article"> <a class="related-article-title" href="https://jamanetwork.com/journals/jama/fullarticle/2673963"> <div class="related-article-type">Comment & Response</div> <div class="related-article-title sb-tc">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS</div> </a> <div class="related-article-authors">Andrew C. McKown, MD; Matthew W. Semler, MD, MSc; Todd W. Rice, MD, MSc</div> <div class="related-article-journal-name">JAMA</div> </li> <li class="article-link related-abstract-article"> <a class="related-article-title" href="https://jamanetwork.com/journals/jama/fullarticle/2673965"> <div class="related-article-type">Comment & Response</div> <div class="related-article-title sb-tc">Effect of Titrated vs Low Positive End-Expiratory Pressure on Mortality in ARDS—Reply</div> </a> <div class="related-article-authors">Alexandre Biasi Cavalcanti, MD, PhD; Marcelo Britto Passos Amato, MD, PhD; Carlos Roberto Ribeiro de Carvalho, MD, PhD</div> <div class="related-article-journal-name">JAMA</div> </li> <li class="article-link related-abstract-article"> <a class="related-article-title" href="https://jamanetwork.com/journals/jama/fullarticle/2725206"> <div class="related-article-type">Original Investigation</div> <div class="related-article-title sb-tc">Effect of an Esophageal Pressure–Guided PEEP Titration Strategy vs an Empirical High PEEP-F<span style="font-variant:small-caps;">io</span><sub>2</sub> Strategy in ARDS</div> </a> <div class="related-article-authors">Jeremy R. Beitler, MD, MPH; Todd Sarge, MD; Valerie M. Banner-Goodspeed, MPH; Michelle N. Gong, MD, MSc; Deborah Cook, MD; Victor Novack, MD, PhD; Stephen H. Loring, MD; Daniel Talmor, MD, MPH; for the EPVent-2 Study Group</div> <div class="related-article-journal-name">JAMA</div> </li> </ul> </div> <div class="widget-ArticleLinks widget-instance-AMA_LinkedContentToolbar_RelatedEditorsChoices"> </div> </div> <div id="author-interviews-tab" class="linked-content-tab linked-author-interviews-tab"> <div class="widget-AudioPlayer widget-instance-AMA_LinkedContentToolbar_PlatformAudioPlayer_AuthorInterviews"> </div> <div class="widget-MultimediaInfo widget-instance-AMA_LinkedContentToolbar_AuthorInterviews"> <div class="multimedia-item brightcove extrinsic-video"> <a class="multimedia-link sb-anchor-light" target="_blank" href="https://jamanetwork.com/learning/video-player/14821586"> <span class="multimedia-group-type">Video Interview</span> <span class="multimedia-duration">(3:58)</span> <div class="multimedia-title sb-tc"> <div class="multimedia-title">Effects on Mortality of a Lung Recruitment Ventilation Strategy Using Titrated vs Low PEEP in Patients With ARDS</div> </div> </a> </div> <div class="multimedia-item brightcove extrinsic-video"> <a class="multimedia-link sb-anchor-light" target="_blank" href="https://jamanetwork.com/learning/video-player/14821588"> <span class="multimedia-group-type">Video Interview</span> <span class="multimedia-duration">(4:07)</span> <div class="multimedia-title sb-tc"> <div class="multimedia-title">Effects on Mortality of a Lung Recruitment Ventilation Strategy Using Titrated vs Low PEEP in Patients With ARDS</div> </div> </a> </div> <span class="hide tagmanagervalue" data-attribute="arrRelatedVideo" data-value="10.1001/jama.2017.16552,10.1001/jama.2017.16553" data-type="array"></span> </div> </div> <div id="listen-to-this-article-tab" class="linked-content-tab linked-listen-to-this-article-tab"> <div class="widget-AudioPlayer widget-instance-AMA_LinkedContentToolbar_PlatformAudioPlayer_ListenToThisArticle"> </div> </div> <div id="more-multimedia-tab" class="linked-content-tab more-multimedia-tab"> <div class="widget-MultimediaInfo widget-instance-AMA_LinkedContentToolbar_MoreMultimedia"> <div class="multimedia-item brightcove extrinsic-video"> <a class="multimedia-link sb-anchor-light" target="_blank" href="https://jamanetwork.com/learning/video-player/14821584"> <span class="multimedia-group-type">Video</span> <span class="multimedia-duration">(14:58)</span> <div class="multimedia-title sb-tc"> <div class="multimedia-title">Effects on Mortality of a Lung Recruitment Ventilation Strategy Using Titrated vs Low PEEP in Patients With ARDS</div> </div> </a> </div> <span class="hide tagmanagervalue" data-attribute="arrRelatedVideo" data-value="10.1001/jama.2017.16551" data-type="array"></span> </div> </div> </div> </div> </div> <div class="widget-ArticleFulltext widget-instance-AMA_Article_FullText_Widget"> <div class="article-full-text" data-userHasAccess="True"> <a class="article-section-id-anchor" id="172419536"></a> <span class="heading-text thm-col h3 cb section-type-keyPoints decorated-hed sb-sc ">Key Points</span><p><strong>Question</strong> <span>Does use of a lung recruitment maneuver associated with positive end-expiratory pressure (PEEP) titration according to the best respiratory-system compliance reduce 28-day mortality of patients with moderate to severe acute respiratory distress syndrome (ARDS) compared with a conventional low-PEEP strategy?</span></p><p><strong>Findings</strong> <span>In this randomized trial of 1010 patients, 28-day mortality was significantly higher among patients treated with a strategy of lung recruitment and PEEP titration (55.3%) than those treated with a conventional low-PEEP strategy (49.3%).</span></p><p><strong>Meaning</strong> <span>A strategy using a lung recruitment maneuver and titrated PEEP, in association with volume-assist control ventilation, increased mortality of patients with moderate to severe ARDS.</span></p> <a class="article-section-id-anchor" id="172419537"></a> <div class="h3 cb section-type-abstract decorated-hed "> <div class="heading-text thm-col sb-sc"> Abstract </div> </div> <p><strong>Importance</strong> <span>The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain.</span></p><p><strong>Objective</strong> <span>To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy.</span></p><p><strong>Design, Setting, and Participants</strong> <span>Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS.</span></p><p><strong>Interventions</strong> <span>An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory–system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning.</span></p><p><strong>Main Outcomes and Measures</strong> <span>The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality.</span></p><p><strong>Results</strong> <span>A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; <i>P</i> = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; <i>P</i> = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; <i>P</i> = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; <i>P</i> = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; <i>P</i> = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.</span></p><p><strong>Conclusions and Relevance</strong> <span>In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.</span></p><p><strong>Trial Registration</strong> <span>clinicaltrials.gov Identifier: <a href="http://clinicaltrials.gov/show/NCT01374022">NCT01374022</a></span></p> <div class="movable-ad-target bta"> </div> <a class="article-section-id-anchor" id="172419543"></a> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Introduction </div> </div> <a class="article-section-id-anchor" id="172419544"></a> <p class="para"><a name="q1"><span style="display:none;">Quiz Ref ID</span></a><span class="quizSection">Acute respiratory distress syndrome (ARDS) is a common clinical problem among critically ill patients and is associated with high mortality and limited long-term quality of life.<sup><a href="#joi170110r1" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">1</a></sup><sup>,<a href="#joi170110r2" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">2</a></sup> The functional lung size is decreased in ARDS, since many lung units become poorly or nonaerated due to collapse, flooding, or consolidation.<sup><a href="#joi170110r3" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">3</a></sup> This places patients at increased risk of ventilator-induced lung injury due both to overdistention of aerated lung units and cyclic opening and closing of small airways and alveoli (atelectrauma).</span><sup><a href="#joi170110r4" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">4</a></sup><sup>-<a href="#joi170110r4" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup></p> <a class="article-section-id-anchor" id="172419545"></a> <p class="para"><a name="q2"><span style="display:none;">Quiz Ref ID</span></a><span class="quizSection">The aim of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration is to open collapsed lung units and keep them opened, potentially decreasing the risk of atelectrauma.</span> Prospective noncontrolled trials have shown that a lung recruitment maneuver with stepwise increases in PEEP, achieving inspiratory pressures up to 60 cm H<sub>2</sub>O, is able to open most of the collapsed lung tissue in patients with ARDS.<sup><a href="#joi170110r7" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">7</a></sup><sup>,<a href="#joi170110r8" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">8</a></sup> Two randomized trials<sup><a href="#joi170110r9" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">9</a></sup><sup>,<a href="#joi170110r10" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">10</a></sup> comparing similar recruitment maneuvers followed by decremental PEEP titration vs a well-established low-PEEP strategy<sup><a href="#joi170110r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup> suggested beneficial effects on oxygenation, respiratory-system compliance, and biomarkers of systemic inflammation, without increasing barotrauma or other adverse events. Additionally, systematic reviews evaluating recruitment maneuvers suggested a reduction in mortality, also without increase in barotrauma.<sup><a href="#joi170110r11" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">11</a></sup><sup>,<a href="#joi170110r12" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">12</a></sup> However, quality of evidence is limited by high risk of bias in most trials and variable use of cointerventions. Thus, the Alveolar Recruitment for ARDS Trial (ART) was conducted to assess whether a strategy of lung recruitment maneuver associated with PEEP titrated according to the best respiratory-system compliance vs a well-established low-PEEP strategy<sup><a href="#joi170110r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup> improves clinical outcomes of patients with moderate to severe ARDS.</p> <a class="article-section-id-anchor" id="172419546"></a> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Methods </div> </div> <a class="article-section-id-anchor" id="172419547"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Study Design and Oversight </div> </div> <a class="article-section-id-anchor" id="172419548"></a> <p class="para">We conducted a randomized clinical trial in 120 intensive care units (ICUs) from 9 countries (Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay). The protocol and statistical analysis plan (in <a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplement 1</a>) were published previously.<sup><a href="#joi170110r13" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">13</a></sup><sup>,<a href="#joi170110r14" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">14</a></sup> Data analysis started after the statistical analysis plan was accepted for publication (see eAppendix in <a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplement 2</a> for details). Ethics committees of all institutions approved the study. Informed consent was obtained from all patients’ representatives. An independent data monitoring committee oversaw efficacy and safety data.</p> <a class="article-section-id-anchor" id="172419549"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Patients </div> </div> <a class="article-section-id-anchor" id="172419550"></a> <p class="para">We enrolled patients receiving invasive mechanical ventilation with moderate to severe ARDS of less than 72 hours of duration. Eligibility was evaluated in 2 phases, a screening and a confirmatory phase. In the screening phase, patients were considered for inclusion in the study if they met the American-European Consensus Conference criteria<sup><a href="#joi170110r15" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">15</a></sup> for ARDS. The exclusion criteria were age younger than 18 years; use of vasoconstrictor drugs in increasing doses over the past 2 hours or mean arterial pressure (MAP) less than 65 mm Hg; contraindications to hypercapnia, such as intracranial hypertension or acute coronary syndrome; pneumothorax, subcutaneous emphysema, pneumomediastinum or pneumatocele; patients in palliative care only; or previously enrolled patients.</p> <a class="article-section-id-anchor" id="172419551"></a> <p class="para">Before confirming eligibility, patients received at least 3 hours of mechanical ventilation using a low-PEEP and low-tidal volume strategy proposed by the Acute Respiratory Distress Syndrome Network (ARDSNet).<sup><a href="#joi170110r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup> After that, the fraction of inspired oxygen (F<span style="font-variant:small-caps;">io</span><sub>2</sub>) was set at 100% and the PEEP at 10 cm H<sub>2</sub>O or more for 30 minutes and arterial blood gases were collected. Eligibility was confirmed if the ratio of the partial pressure (Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>) of oxygen to the F<span style="font-variant:small-caps;">io</span><sub>2</sub> (Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub>) was 200 or lower and less than 72 hours had passed since the first time a Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub> ratio of 200 or less was determined.</p> <a class="article-section-id-anchor" id="172419552"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Randomization and Masking </div> </div> <a class="article-section-id-anchor" id="172419553"></a> <p class="para">Patients were randomized in a 1:1 ratio to a strategy of lung recruitment associated with PEEP adjusted according to the respiratory-system compliance or to a low-PEEP strategy. The random allocation list was generated by a statistician with no clinical involvement in the trial using a computer-generated random number list. Randomization was conducted with blocks of 4 and stratification by site, age (≤55 years or >55 years) and Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub> ratio (≤100 or >100). Allocation concealment was ensured via a central web-based system. The treatment to which a patient was allocated was disclosed only after the patient was enrolled in the study.</p> <a class="article-section-id-anchor" id="172419554"></a> <p class="para">Participant, clinicians, and outcome assessors were aware of the assigned treatment.</p> <a class="article-section-id-anchor" id="172419555"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Interventions </div> </div> <a class="article-section-id-anchor" id="172419556"></a> <p class="para">Patients assigned to the control group continued to receive the low-PEEP strategy.<sup><a href="#joi170110r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup> Immediately after randomization, patients assigned to the experimental strategy received a bolus of neuromuscular blocker and hemodynamic status was maintained by administering intravenous fluids when there were signs of fluid responsiveness. Then, we conducted a lung recruitment maneuver with incremental PEEP levels, followed by a decremental PEEP titration according to the best respiratory-system static compliance and by a second recruitment maneuver. The lung recruitment maneuver and PEEP titration technique were based on those used in previous noncontrolled studies.<sup><a href="#joi170110r7" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">7</a></sup><sup>,<a href="#joi170110r8" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">8</a></sup> After recruitment and PEEP titration, patients were ventilated under volume-assist control mode with PEEP set at the titrated value (the PEEP associated with highest respiratory-system compliance plus 2 cm H<sub>2</sub>O). If Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub> levels were stable or increasing for 24 hours or more after recruitment, weaning of PEEP was started with decreases of 2 cm H<sub>2</sub>O every 8 hours. Apart from the lung recruitment maneuver and PEEP titration scheme, other aspects of care were similar for both groups. The experimental and control group procedures are detailed in the protocol and the manual of operations (<a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplements</a> 1 and 3).</p> <a class="article-section-id-anchor" id="172419557"></a> <p class="para"><a name="q3"><span style="display:none;">Quiz Ref ID</span></a><span class="quizSection">Initially, we applied a recruitment maneuver using pressure-controlled ventilation and driving pressure of 15 cm H<sub>2</sub>O. We started with a PEEP of 25 cm H<sub>2</sub>O for 1 minute, then a PEEP of 35 cm H<sub>2</sub>O for 1 minute, and then 45 cm H<sub>2</sub>O for 2 minutes. After recruitment, decremental PEEP titration was started with a PEEP of 23 cm H<sub>2</sub>O in volume-controlled mode. PEEP levels were decreased in steps of 3 cm H<sub>2</sub>O down to a minimum of 11 cm H<sub>2</sub>O. After 4 minutes in each step, we measured respiratory-system static compliance. The PEEP associated with the best compliance plus 2 cm H<sub>2</sub>O was considered the optimal PEEP. After PEEP titration, a new recruitment in pressure-controlled ventilation was conducted in 1 step using PEEP of 45 cm H<sub>2</sub>O for 2 minutes.</span></p> <a class="article-section-id-anchor" id="172419558"></a> <p class="para">In June 2015, starting with the 556th patient, the steering committee, in consultation with the data monitoring committee, decided to modify the recruitment maneuver and PEEP titration strategy after 3 cases of resuscitated cardiac arrest possibly associated with the experimental group treatment were observed. During the recruitment maneuver, PEEP was increased to 25 cm H<sub>2</sub>O, 30 cm H<sub>2</sub>O, and then 35 cm H<sub>2</sub>O, in steps of 1 minute. Maximum plateau pressure was 50 cm H<sub>2</sub>O. Decremental PEEP trial was shorter, with each PEEP step lasting 3 minutes, followed by a new recruitment maneuver with PEEP of 35 cm H<sub>2</sub>O.</p> <a class="article-section-id-anchor" id="172419559"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Outcomes </div> </div> <a class="article-section-id-anchor" id="172419560"></a> <p class="para">Our primary outcome was mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days from day 1 until day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. We defined as pneumothorax requiring drainage for any case that was possibly due to barotrauma; that is, we did not consider cases judged to be clearly caused by invasive procedures such as central venous punction or thoracocentesis. We defined as barotrauma within 7 days any pneumothorax, pneumomediastinum, subcutaneous emphysema, or pneumatocele of more than 2 cm detected on image examinations between randomization and 7 days, except those judged to be clearly caused by invasive procedures.</p> <a class="article-section-id-anchor" id="172419561"></a> <p class="para">Other exploratory outcomes were death with refractory hypoxemia within 7 days; death with refractory acidosis within 7 days; death with barotrauma within 7 days; cardiorespiratory arrest on day 1; need of commencement or increase of vasopressors or hypotension (MAP<65 mm Hg) within 1 hour after randomization; refractory hypoxemia (Pa<span style="font-variant:small-caps;">o</span><sub>2</sub><55 mm Hg) within 1 hour after randomization; and severe acidosis (pH<7.10) within 1 hour after randomization.</p> <a class="article-section-id-anchor" id="172419562"></a> <p class="para">Length of ICU stay (secondary outcome) and all other exploratory outcomes were included in our statistical analysis plan<sup><a href="#joi170110r14" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">14</a></sup> and ClinicalTrials.gov, although they were not originally in our study protocol (see eAppendix in <a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplement 2</a> for details).</p> <a class="article-section-id-anchor" id="172419563"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Statistical Analysis </div> </div> <a class="article-section-id-anchor" id="172419564"></a> <p class="para">ART was an event-driven study designed to continue until 520 events (28-day deaths) had accrued. This number of events was estimated to provide 90% power, assuming a hazard ratio of 0.75 and type I error of 5%. This hazard ratio is similar to the size of effect used to estimate sample size in other trials in the field.<sup><a href="#joi170110r16" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">16</a></sup><sup>,<a href="#joi170110r17" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">17</a></sup></p> <a class="article-section-id-anchor" id="172419565"></a> <p class="para">All analyses followed the intention-to-treat principle, considering all patients in the treatment groups to which they were randomly assigned, except for cases lost to follow-up. We carried out complete-case analysis for all outcomes. We planned to conduct sensitivity analysis for the primary outcome using multiple imputation techniques only if follow-up data of 1% or more of the patients was lost. Baseline characteristics were reported as counts and percentages, mean and standard deviation (SD), or median and interquartile range (IQR), whenever appropriate. Hypothesis tests were 2-sided. Two interim analyses were performed after recruitment of one-third and two-thirds of the planned sample size to assess effects on clinical outcomes. The data monitoring committee would consider stopping the trial early if there was evidence of harm with 1-sided <i>P</i> value <.01. The significance level for the primary outcome final analysis was .042, to maintain overall α at .05. For all other outcomes, the significance level was .05, without adjustment for multiple comparisons. Because of this, all secondary outcomes and analyses should be interpreted as exploratory.</p> <a class="article-section-id-anchor" id="172419566"></a> <p class="para">We assessed the effect of the trial treatments on the primary outcome using Kaplan-Meier curves and calculated the hazard ratio with 95% CI using the Cox proportional hazard model. We conducted 2 sensitivity analyses. The first was a prespecified Cox proportional hazards model adjusted for age, Simplified Acute Physiology Score 3 (SAPS 3) score, and Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub> ratio. The second was a post hoc frailty Cox model with stratification variables (site, age, and Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub>) as random effects.</p> <a class="article-section-id-anchor" id="172419567"></a> <p class="para">We used Kaplan-Meier curves and the Cox proportional hazard model to assess the effect of treatment on 6-month survival. We assessed the effects of the intervention on categorical variables with risk ratios and 95% CIs, and we used the χ<sup>2</sup> test to compare between-group differences. For continuous outcomes, we estimated the effects of the intervention with generalized linear models using gamma distributions (for lengths of ICU and hospital stay) or a truncated Poisson distribution (for ventilator-free days).</p> <a class="article-section-id-anchor" id="172419568"></a> <p class="para">We used Cox proportional hazards to assess interactions between treatment effect and the following prespecified subgroups: Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub> (≤100 vs >100 mm Hg); SAPS 3 score (<50 vs ≥50); pulmonary vs extrapulmonary ARDS; duration of ARDS (≤36 hours vs >36 to <72 hours); mechanical ventilation (≤2 days, 3-4 days, ≥5 days); and prone position. As an exploratory analysis, we tested whether treatment effects were similar before and after the protocol amendment of June 2015. We also tested in a post hoc analysis whether treatment effects per quartiles according to order of enrollment in the trial (earlier vs later) were homogeneous. All analyses were performed using the R (R Core Team, 2016) software.</p> <a class="article-section-id-anchor" id="172419569"></a> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Results </div> </div> <a class="article-section-id-anchor" id="172419570"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Patients </div> </div> <a class="article-section-id-anchor" id="172419571"></a> <p class="para"><a name="q4"><span style="display:none;">Quiz Ref ID</span></a><span class="quizSection">From November 17, 2011, through April 25, 2017, we screened 2077 patients with moderate to severe ARDS. A total of 1064 were not enrolled, of whom 863 (81.1%) met exclusion criteria and 201 (18.9%) were eligible but were not enrolled for other reasons. We randomized 1013 patients, 501 to the lung recruitment strategy and 512 to the low-PEEP strategy. Representatives of 3 patients assigned to the control group withdrew consent to use study data. We obtained 28-day and 6-month follow-up data of all remaining patients, except for 23 who were followed up and censored between 2 and 6 months. Thus, data of 1010 patients (501 in the experimental group and 509 in the control groups) were considered for the final analysis. The data monitoring committee evaluated 2 interim analyses and recommended the trial to be continued.</span> (<a href="#joi170110f1" class="figure-link section-jump-link" data-tab-toggle=".tab-nav-figure-table">Figure 1</a>)</p> <a class="article-section-id-anchor" id="172419573"></a> <p class="para">Baseline characteristics were well balanced between the study groups (<a href="#joi170110t1" class="table-link section-jump-link" data-tab-toggle=".tab-nav-figure-table">Table 1</a>). Two-thirds of the patients had septic shock. The mean number of nonpulmonary organ failures was more than 2. Most ARDS cases were of pulmonary (62.0%) rather than extrapulmonary origin (38.0%). In the experimental and control groups, baseline mean (SD) tidal volume and plateau pressures were 5.8 (1.1) and 5.8 (1.0) mL/Kg of predicted body weight, and 25.8 (4.7) and 26.2 (5.2) cm H<sub>2</sub>O, respectively.</p> <a class="article-section-id-anchor" id="172419575"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Lung Recruitment </div> </div> <a class="article-section-id-anchor" id="172419576"></a> <p class="para">A total of 480 patients (95.8%) in the experimental group received a lung recruitment maneuver after randomization (eTable 1 in <a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplement 2</a>). In 78 cases (15.6%) the maneuver had to be interrupted, most often due to hypotension or a decrease in oxygen saturation. In 21 cases, a recruitment maneuver was not attempted due to uncontrolled hypotension (14 cases), detection of pneumothorax (3 cases) after randomization, or other reasons (4 cases). The mean (SD) titrated PEEP was 16.8 (3.8) cm H<sub>2</sub>O. Lung recruitment was repeated after PEEP titration in 393 patients (78.4%). After the initial recruitment and PEEP titration, alveolar recruitment was not repeated from day 1 to 7 in most patients (62.7%). Conversely, 28 patients in the control group also received a recruitment maneuver within the first 7 days.</p> <a class="article-section-id-anchor" id="172419577"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Ventilator Settings and Respiratory Variables </div> </div> <a class="article-section-id-anchor" id="172419578"></a> <p class="para">Mean PEEP values from hour 1 through day 7 were higher in the experimental than in the control group (eTable 2 in <a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplement 2</a>). Mean values of plateau pressure were also higher in the experimental group, although always below 30 cm H<sub>2</sub>O in both groups. Mean tidal volumes were below 6 mL/kg of predicted body weight in both groups from hour 1 through day 3. The mean Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub> ratios were higher in the experimental group. Yet decreases in driving pressure from control to experimental group were limited to less than 2 cm H<sub>2</sub>O from day 1 through day 7. Partial pressure of carbon dioxide was higher and arterial pH was lower in experimental group only at the first hour, with values that were not significantly different after day 1.</p> <a class="article-section-id-anchor" id="172419579"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Cointerventions </div> </div> <a class="article-section-id-anchor" id="172419580"></a> <p class="para">Use of neuromuscular blockers was higher in the experimental than the control group (96.8% vs 73.3%; difference, 23.5%; 95% CI, 19.2%-27.9%; <i>P</i> < .001), reflecting the protocol requirement for their use before the recruitment maneuver (eTable 3 in <a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplement 2</a>). The proportion of patients who received sedatives on any day was higher in the experimental group (99.0% vs 97.1%; difference, 1.9%; 95% CI, 0.0%-3.9%; <i>P</i> = .05), although there was no difference between groups in the median number of days receiving sedatives. There were no differences among groups in other cointerventions or on the need of rescue therapies for hypoxemia.</p> <a class="article-section-id-anchor" id="172419581"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Outcomes </div> </div> <a class="article-section-id-anchor" id="172419582"></a> <p class="para">At 28 days, there were 277 deaths (55.3%) among 501 patients in the experimental group and 251 deaths (49.3%) among 509 patients in the control group, with a hazard ratio of 1.20 (95% CI, 1.01-1.42; <i>P</i> = .041) (<a href="#joi170110f2" class="figure-link section-jump-link" data-tab-toggle=".tab-nav-figure-table">Figure 2</a>). After adjustment for baseline covariates, age, SAPS 3, and Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>:F<span style="font-variant:small-caps;">io</span><sub>2</sub>, the hazard ratio for 28-day mortality was 1.22 (95% CI, 1.03-1.45; <i>P</i> = .02). In the post hoc frailty Cox model, the hazard ratio was 1.21 (95% CI, 1.02-1.44; <i>P</i> = .03).</p> <a class="article-section-id-anchor" id="172419584"></a> <p class="para">All-cause mortality was also higher within 6 months in the experimental than in the control group (65.3% vs 59.9%; hazard ratio, 1.18; 95% CI, 1.01-1.38; <i>P</i> = .04) (<a href="#joi170110t2" class="table-link section-jump-link" data-tab-toggle=".tab-nav-figure-table">Table 2</a>). Differences in the ICU or in-hospital mortality between groups were not statistically significant. Compared with the control group, mortality in the experimental group was higher during the first 7 days, with increased rates of death with barotrauma (<a href="#joi170110t2" class="table-link section-jump-link" data-tab-toggle=".tab-nav-figure-table">Table 2</a>). There were no significant differences in the rates of death with refractory hypoxemia, death with acidosis, and cardiorespiratory arrest between groups. Lengths of stay in the ICU or hospital were also not significantly different. The experimental group had fewer ventilator-free days during the first 28 days. The rates of pneumothorax requiring drainage and rates of any barotrauma increased in the experimental group. Within 1 hour, commencement or increase in vasopressors or hypotension were more common in the experimental group, but there were no differences in refractory hypoxemia or severe acidosis.</p> <a class="article-section-id-anchor" id="172419586"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Subgroup and Exploratory Analyses </div> </div> <a class="article-section-id-anchor" id="172419587"></a> <p class="para">Effects of experimental vs control strategy on 28-day mortality were not significantly different across subgroups (<a href="#joi170110f3" class="figure-link section-jump-link" data-tab-toggle=".tab-nav-figure-table">Figure 3</a>). Treatment effects were also not significantly different in the periods of study before and after the protocol was modified with reduction in the length and in the maximum PEEP and pressure levels of the recruitment maneuver (<i>P</i> = .89). Treatment effects were also not significantly different per quartiles according to order of enrollment in the trial (<i>P</i> = .76).</p> <a class="article-section-id-anchor" id="172419589"></a> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Discussion </div> </div> <a class="article-section-id-anchor" id="172419590"></a> <p class="para">In this trial enrolling adults with moderate to severe ARDS, a strategy of lung recruitment and PEEP titration according to the respiratory-system compliance increased 28-day mortality compared with an established low-PEEP strategy. In addition, the lung recruitment strategy increased 6-month mortality, the risk of any barotrauma and death with barotrauma, and the need for vasopressors or hypotension in the first hour. Conversely, the lung recruitment strategy decreased the number of days free of mechanical ventilation during 28 days.</p> <a class="article-section-id-anchor" id="172419591"></a> <p class="para">One potential explanation for the findings of this trial relates to an unfavorable balance between potential positive (reduction in driving pressure)<sup><a href="#joi170110r10" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">10</a></sup> and negative (increase in overdistention, hemodynamic impairment)<sup><a href="#joi170110r18" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">18</a></sup><sup>,<a href="#joi170110r19" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">19</a></sup> physiological consequences of lung recruitment and PEEP. Although some studies showed almost full opening of collapsed alveoli after recruitment maneuvers achieving high inspiratory pressures,<sup><a href="#joi170110r7" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">7</a></sup><sup>,<a href="#joi170110r8" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">8</a></sup> only mild responses were observed in this trial as suggested by the small increments in the respiratory-system compliance and reductions in driving pressure. Furthermore, the driving pressure, a strong predictor of survival in ARDS,<sup><a href="#joi170110r20" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">20</a></sup><sup>,<a href="#joi170110r21" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">21</a></sup> decreased by a mean of only less than 2 cm of water. On the contrary, the risk of barotrauma within 7 days and signs of hemodynamic impairment within 1 hour increased in the experimental group, suggesting lung injury and hemodynamic impairment as mechanisms that may have driven increased mortality. Nevertheless, the incidence of barotrauma, even in the experimental group, was lower than in any previous studies using high PEEP levels.<sup><a href="#joi170110r22" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">22</a></sup></p> <a class="article-section-id-anchor" id="172419592"></a> <p class="para">Another potential explanation for the results observed in this trial lies in the lung protective characteristics of the control group, which may have offset any potential physiological advantages of the lung recruitment and PEEP titration strategy. The control group strategy called for a tidal volume of 6 mL/kg (or less if plateau pressure was >30 cm H<sub>2</sub>O) and use of lower PEEP levels.<sup><a href="#joi170110r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup> Adherence to low tidal volume was very strict, with lower mean tidal volumes than the ARDSNet trials.<sup><a href="#joi170110r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup><sup>,<a href="#joi170110r23" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">23</a></sup> Conversely, PEEP values were approximately 3 cm H<sub>2</sub>O higher than that observed in control groups from previous studies.<sup><a href="#joi170110r22" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">22</a></sup> The use of strictly low tidal volumes and resulting low driving pressures may have reduced lung injury due to tidal overdistention. Furthermore, intermediate levels of PEEP may have contributed to maximizing homogeneity and preventing atelectrauma.</p> <a class="article-section-id-anchor" id="172419593"></a> <p class="para">A third possible explanation for the findings of this trial is the breath stacking phenomenon, which may occur inadvertently in patients receiving protective ventilation, especially in the volume-assist control mode and with low tidal volumes.<sup><a href="#joi170110r24" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">24</a></sup><sup>,<a href="#joi170110r25" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">25</a></sup> It was documented in 1 patient enrolled in the experimental group and routinely monitored with electrical impedance tomography (eFigure 1 in <a class="supplement-link section-jump-link" data-tab-toggle=".tab-nav-supplemental" href="#note-JOI170110-1">Supplement 2</a>). The patient received 12 mL/kg of effective tidal volume in more than 40% of the breaths, whereas the ventilator displayed 6 mL/kg. Although the incidence of this phenomenon was likely similar in both groups, it may have caused more lung overstretch with disproportionally higher driving pressures in patients submitted to higher PEEP levels.</p> <a class="article-section-id-anchor" id="172419594"></a> <p class="para">The choice of the ARDSNet table of lower instead of higher PEEP values for the control group in this trial might be questioned, since an individual patient data meta-analysis suggested a survival benefit for higher PEEP levels in the subgroup of patients with moderate to severe ARDS.<sup><a href="#joi170110r22" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">22</a></sup> Three main reasons supported the option for lower PEEP values. First, the meta-analysis did not show benefit of high PEEP for the overall group of patients with ARDS.<sup><a href="#joi170110r22" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">22</a></sup> Second, none of the individual trials showed a significant effect on mortality.<sup><a href="#joi170110r17" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">17</a></sup><sup>,<a href="#joi170110r23" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">23</a></sup><sup>,<a href="#joi170110r26" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">26</a></sup> Third, the trials included in the meta-analysis used substantially different strategies both in the experimental and control groups, with variable use of recruitment maneuvers. Therefore, it is uncertain whether the potential benefit was due to higher PEEP or to the lung recruitment maneuver itself.</p> <a class="article-section-id-anchor" id="172419595"></a> <p class="para">This trial has strengths. Bias was controlled by using concealed allocation, intention-to-treat analysis, and by avoiding losses to follow-up. Analyses were based on a large number of events, which allowed for adequate random error control. Patient eligibility was confirmed only after ventilation with a lung protective low-tidal volume strategy and standardized F<span style="font-variant:small-caps;">io</span><sub>2</sub> and PEEP settings before collecting arterial blood gases. Except for the lung recruitment maneuvers and PEEP titration scheme, identical mechanical ventilation protocol with low-tidal volume was applied for both groups. In addition, the study involved centers from 9 countries, which contributes to generalizability of its results.</p> <a class="article-section-id-anchor" id="172419596"></a> <div class="h4 cb section-type-section "> <div class="heading-text "> Limitations </div> </div> <a class="article-section-id-anchor" id="172419597"></a> <p class="para">This study has several limitations. First, it was not feasible to blind participants, clinicians, and outcome assessors. It is possible that processes of care might have been affected by knowledge of treatment allocation. Conversely, blinding would not affect classification of the primary outcome. Second, it was not possible to classify enrolled patients into ARDS subphenotypes, which may respond differently to therapies such as PEEP.<sup><a href="#joi170110r27" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">27</a></sup><sup>,<a href="#joi170110r28" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">28</a></sup> Determination of subphenotype requires collecting plasma samples to perform analysis of biomarkers; however, this was not conducted due to funding restrictions. Third, it has been suggested that baseline responsiveness to a test of PEEP elevation predicts percentage of potentially recruitable lung and the clinical response to a strategy of lung recruitment associated with high PEEP.<sup><a href="#joi170110r29" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">29</a></sup><sup>,<a href="#joi170110r30" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">30</a></sup> However, since responsiveness to PEEP at baseline was not assessed, it is not possible to analyze whether this characteristic modifies treatment effect. Nevertheless, there was no evidence of heterogeneity of treatment effect in any of the subgroups examined. Fourth, patients were enrolled in the trial over 6 years. The care of patients with ARDS may have changed during this period, which might have affected results. However, an analysis of treatment effects on mortality according to order of enrollment provides no evidence that effects changed over time. Fifth, a strategy involving lung recruitment and PEEP titration (primary interventions) is complex in the sense that not only the primary interventions are part of it, but also cointerventions that need to be aggregated. For example, administering neuromuscular blockers and fluids in preparation for the recruitment maneuver. As a consequence, it is not possible to ascribe observed clinical effects exclusively to the direct effects of lung recruitment maneuver and PEEP.</p> <a class="article-section-id-anchor" id="172419598"></a> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Conclusions </div> </div> <a class="article-section-id-anchor" id="172419599"></a> <p class="para"><a name="q5"><span style="display:none;">Quiz Ref ID</span></a><span class="quizSection">In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.</span></p> <a class="article-section-id-anchor" id="172419600"></a> <div class="para back-extra"><strong>Section Editor:</strong> Derek C. Angus, MD, MPH, Associate Editor, <i>JAMA</i> (<a href="mailto:angusdc@upmc.edu" target="_blank">angusdc@upmc.edu</a>).</div> <a class="article-section-id-anchor" id="172419601"></a> <div class="h3 cb section-type-acknowledgements has-back-to-top"> <a href="#top" class="section-jump-link back-to-top" data-tab-toggle=".tab-nav-full-text">Back to top</a> <div class="heading-text thm-col sb-sc"> Article Information </div> </div> <p class="para"><strong>Accepted for Publication:</strong> September 1, 2017.</p><p class="authorInfoSection"><strong>Corresponding Author:</strong> Alexandre Biasi Cavalcanti, MD, PhD, HCor Research Institute—Hospital do Coração, Rua Abílio Soares 250, 12th Floor, CEP: 04005-000, São Paulo, SP, Brazil (<a href="mailto:abiasi@hcor.com.br" target="_blank">abiasi@hcor.com.br</a>).</p><p class="parapublished-online"><strong>Published Online:</strong> September 27, 2017. doi:10.1001/jama.2017.14171</p><p class="paranonbyline-authors-end"><strong>Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators:</strong> Alexandre Biasi Cavalcanti, MD, PhD; Érica Aranha Suzumura, MSc; Ligia Nasi Laranjeira, RT; Denise de Moraes Paisani, PhD; Lucas Petri Damiani, MSc; Helio Penna Guimarães, MD, PhD; Edson Renato Romano, MD, PhD; Marisa de Moraes Regenga, RT; Luzia Noriko Takahashi Taniguchi, RT; Cassiano Teixeira, MD, PhD; Roselaine Pinheiro de Oliveira, MD, PhD; Flavia Ribeiro Machado, MD, PhD; Fredi Alexander Diaz-Quijano, MD, PhD; Meton Soares de Alencar Filho, MD; Israel Silva Maia, MD; Eliana Bernardete Caser, MD, PhD; Wilson de Oliveira Filho, MD; Marcos de Carvalho Borges, MD, PhD; Priscilla de Aquino Martins, MD; Mirna Matsui, MD, PhD; Gustavo Adolfo Ospina-Tascón, MD, PhD; Thiago Simões Giancursi, MD; Nelson Dario Giraldo-Ramirez, MD, MSc; Silvia Regina Rios Vieira, MD, PhD; Maria da Graça Pasquotto de Lima Assef, MD, PhD; Mohd Shahnaz Hasan, MD, PhD; Wojciech Szczeklik, MD, PhD; Fernando Rios, MD, PhD; Marcelo Britto Passos Amato, MD, PhD; Otávio Berwanger, MD, PhD; Carlos Roberto Ribeiro de Carvalho, MD, PhD.</p><p class="paranonbyline-affils-end"><strong>Affiliations of Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators: </strong>HCor Research Institute, São Paulo, Brazil (Cavalcanti, Suzumura, Laranjeira, Paisani, Damiani, Guimarães, Romano, Regenga, Taniguchi, Berwanger); Cardio-Pulmonary Department, Pulmonary Division, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil (Amato, Ribeiro de Carvalho); Hospital Moinhos de Vento, Porto Alegre, Brazil (Teixeira); Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil (Pinheiro de Oliveira); Anesthesiology, Pain, and Intensive Care Department, Federal University of São Paulo–UNIFESP, São Paulo, Brazil (Machado); Epidemiology Department, School of Public Health, University of São Paulo, São Paulo, Brazil (Diaz-Quijano); Hospital Maternidade São Vicente de Paulo, Barbalha, Brazil (M. S. d. Filho); Hospital Nereu Ramos, Florianópolis, Brazil (Maia); Hospital Unimed Vitória, Vitória, Brazil (Caser); Hospital e Pronto-Socorro 28 de Agosto, Manaus, Brazil (W. d. O. Filho); Unidade de Emergência do Hospital das Clínicas da FMRP-USP, Ribeirão Preto, Brazil (Borges); Hospital Estadual Dr Jayme dos Santos Neves, Serra, Brazil (Martins); Hospital Universitário da Universidade Federal da Grande Dourados, Dourados, Brazil (Matsui); Department of Intensive Care Medicine, Fundación Valle del Lili - Universidad ICESI, Cali, Colombia (Ospina-Tascón); Hospital Universitário do Oeste do Paraná, Cascavel, Brazil (Giancursi); Hospital Pablo Tóbon Uribe, Medellín, Colombia (Giraldo-Ramirez); Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (Vieira); Hospital Regional Hans Dieter Schmidt, Joinville, Brazil (Assef); University Malaya Medical Centre, Kuala Lumpur, Malaysia (Hasan); Jagiellonian University Medical College; Department of Intensive Care and Perioperative Medicine, Krakow, Poland (Szczeklik); Hospital Nacional Alejandro Posadas, Moron, Argentina (Rios).</p><p class="paraauthor-contributions"><strong>Author Contributions:</strong> Dr Cavalcanti had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The writing group vouches for the accuracy and completeness of the data and for the fidelity of the study to the protocol.</p><p class="para"><i>Concept and design:</i> Cavalcanti, Suzumura, Amato, Berwanger, Carvalho.</p><p class="para"><i>Acquisition, analysis, or interpretation of data:</i> Cavalcanti, Suzumura, Laranjeira, Paisani, Damiani, Guimarães, Romano, Regenga, Taniguchi, Teixeira, Oliveira, Machado, Diaz-Quijano, Alencar Filho, Maia, Caser, Oliveira Filho, Borges, Martins, Matsui, Ospina-Tascón, Giancursi, Giraldo-Ramirez, Vieira, Assef, Hasan, Szczeklik, Rios, Amato, Berwanger, Carvalho.</p><p class="para"><i>Drafting of the manuscript:</i> Cavalcanti, Laranjeira, Paisani, Damiani, Amato, Berwanger.</p><p class="para"><i>Critical revision of the manuscript for important intellectual content:</i> Suzumura, Guimarães, Romano, Regenga, Taniguchi, Teixeira, Oliveira, Machado, Diaz-Quijano, Alencar Filho, Maia, Caser, Oliveira Filho, Borges, Martins, Matsui, Ospina-Tascón, Giancursi, Giraldo-Ramirez, Vieira, Assef, Hasan, Szczeklik, Rios, Carvalho.</p><p class="para"><i>Statistical analysis:</i> Cavalcanti, Paisani, Damiani, Amato, Berwanger.</p><p class="para"><i>Obtained funding:</i> Cavalcanti, Berwanger.</p><p class="para"><i>Administrative, technical, or material support:</i> Cavalcanti, Suzumura, Laranjeira, Paisani, Diaz-Quijano, Szczeklik, Rios, Amato, Berwanger, Carvalho.</p><p class="para"><i>Supervision:</i> Cavalcanti, Laranjeira, Suzumura, Paisani, Machado, Diaz-Quijano, Amato, Berwanger, Carvalho.</p><p class="parafinancial-disclosure"><strong>Conflict of Interest Disclosures:</strong> All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. All authors received grant support from Program to Support Institutional Development of Universal System (PROADI) from the Brazilian Ministry of Health to conduct the study. Dr Amato also received grants from Timpel S. A. and Medtronic. No other disclosures are reported.</p><p class="parastudy-group-members-end"><strong>Site Investigators: Argentina:</strong><i>Hospital Nacional Alejandro Posadas:</i> Fernando Rios, Judith Sagardia, Roger Rodrigues Lamoglie, Juan Manuel Vincenti; <i>Sanatorio Juncal:</i> Marcelo Lareu, Maria Soledad Esteban, Valeria Cerrato, and Rodrigo Fodor; and <i>Sanatorio Las Lomas:</i> Fernando Rios, Pablo E Gomez, and Alejandro Riso Vasquez.</p><p class="parastudy-group-members-end"><strong>Brazil:</strong><i>AC Camargo Cancer Center:</i> Mauro Roberto Tucci, Lucio Souza dos Santos, Maria Cristina França de Oliveira, Ivan Peres, and Isabel Freitas; <i>Fundação Hospital de Clínicas Gaspar Vianna:</i> Helder Reis, Adriana Veríssimo, Daniel Torres, and Amanda Barroso; <i>Fundação Hospitalar São Sebastião:</i> Wesley Semboloni Bitencourt, Mônica Ribeiro Franco, and Jarbas Oliveira Lage; <i>Hospital Municipal Dr José Soares Hungria:</i> Katia Aparecida Pessoa Conde, Fernando Antonio Charro, and Andrea Naia; <i>Hospital Adventista de Belém:</i> Edgar de Brito Sobrinho, Adriana Lameira Veríssimo, and Milce Ellen Barros de Oliveira; <i>Hospital Alemão Oswaldo Cruz:</i> Fernando Zampieri, José Paulo Ladeira, Ricardo Cordioli, Andrea Diogo Sala, and Dimas Tadahiro Ikeoka; <i>Hospital Bandeirantes:</i> Mario Lucio A. Baptista Filho, Alexandre Ray, Andre Guerra de Almeida, and Claudio Nazareno Conceição; <i>Hospital Barra D'Or:</i> Diamantino Ribeiro Salgado, Juan Carlos Rosso Verdeal, and Glória Adriana Martins; <i>Hospital Cônego Monte Raso:</i> Wesley Semboloni Bitencourt, Lauriane Junqueira Ribeiro, and Helder Vilela Siqueira; <i>Hospital da Luz:</i> Francisco Flávio Costa Filho, Bruno Adler Maccagnan Pinheiro Besen, Eliana Vieira do Nascimento Martins, and Joyce Aparecida Pereira; <i>Hospital das Clinicas da Universidade Federal de Goiás (UFG):</i> Denise Milioli Ferreira, Fernanda Alves Ferreira Gonçalves, Marciano de Souza Nobrega, and Italo Julierme Barros Duarte; <i>Hospital das Clinicas da Universidade Federal de Minas Gerais:</i> Vandack Nobre, Lídia Miranda Barreto Mourão, Cecília Gómez Ravetti, and Anna Carolina Scalzo; <i>Hospital das Clinicas de Botucatu:</i> Laercio Martins De Stefano and Ana Lucia Gut; <i>Hospital das Clínicas Luzia de Pinho Melo:</i> Wilson Nogueira Filho, Ciro Gatti Cirillo, and Shizuo Ishiwaki Jr; <i>Hospital de Base de São José do Rio Preto:</i> Suzana Lobo, Neymar Elias de Oliveira, Luana Fernandes Machado, and Lais Sisconetto; <i>Hospital de Clínicas de Porto Alegre (HCPA):</i> Silvia Regina Rios Vieira, Lea Fialkow, Karen Fontoura Prado, Cristiano Franke, Rafael Barberena Moraes, Iuri Christmann Wawrzeniak, Tatiana Helena Rech, Edino Parolo, and Josué Almeida Victorino; <i>Hospital de Urgências e Emergências de Rio Branco:</i> Claudineia Marques Barroso, Márcia Odilia Marçal de Vasconcelos, Rosicley Souza da Silva, and André Rafael Lesti Esteves; <i>Hospital do Círculo:</i> Ana Paula Camassola, Rodrigo Antoniazzi, Morgana Griebler, and Jean Favretto; <i>Hospital do Coração-HCor:</i> Marcelo Romano, André Franz da Costa, Vinicius Werneck, Mieko Cláudia Miura, Jorge Farran, and Rosianne de Vasconcelos; <i>Hospital do Servidor Público Estadual de São Paulo (IAMSPE-HSPE):</i> Alexandre Isola, Ederlon Resende, Ricardo Goulart, and Sérgio Luzzi; <i>Hospital do Trabalhador:</i> Alvaro Réa-Neto, Mirella Cristine de Oliveira, Mariana Bruinje Cosentino, Bruna Martins Dzivielevski, Fernanda B. Reese, Sabrina Donatti Ferreira da Silva, Esperidião Elias Aquim, and Fabiane Girotto; <i>Hospital e Pronto Socorro Dr Aristóteles Platão Bezerra de Araújo:</i> Riani Helenditi Fernandes Camurça Martins and Altamira Lima de Andrade; <i>Hospital e Pronto-Socorro 28 de Agosto:</i> Wilson de Oliveira Filho, Débora Cristine Breckenfeld Heirel, Rodrigo Ryoji Takatani, Samara Dias de Almeida, Adriano Medina Matos, Tomomi Iwamoto, and Paulo Eugênio do Val Tavares; <i>Hospital Escola Padre Albin-Faculdades Integradas Padre Albino-Medicina:</i> Jorge Luis Valiatti, Francisco Carllos de Lucca, Júlio Cezar Fornazari, and Izabela Dias Brugugnolli; <i>Hospital Especializado Octávio Mangabeira:</i> Marcelo de Araújo Nazaré, Nathan Nascimento Loureiro, Gilmara Vasconcelos de Sousa, and Lucas Staffa Gonzaga da Silva; <i>Hospital Estadual Dr Jayme dos Santos Neves:</i> Priscilla de Aquino Martins, Fernando Cesar dos Anjos Sad, Enrico Miguel Stucchi, Rafael Melo Silva, and Thais Fonseca Silva; <i>Hospital Estadual e Pronto Socorro João Paulo II:</i> Sérgio Paulo Mendes Filho, Thattyane Borba Pereira, and Patrícia Nicoleit da Silva; <i>Hospital Estatual Getúlio Vargas:</i> Giulliana Martines Moralez, Simone Abrantes Saraiva, Alexandre Abrunhosa, and Claudio Eduardo Ranger C. Chagas; <i>Hospital Evangélico de Cachoeiro de Itapemirim:</i> Marlus Muri Thompson, Claudio Henrique Pinto Gonçalves, Renata de Oliveira Dias, and Fernando Schwan Filho; <i>Hospital Evangélico de Londrina:</i> Cintia Magalhães Carvalho Grion, Ana Luzia Mezzaroba, and Josiane Festti; <i>Hospital Evangélico de Vila Velha:</i> Priscilla de Aquino Martins, Thiago Carlos Massariol, and Gedealvares Francisco de Souza Jr; <i>Hospital Geral da Vitória da Conquista:</i> Miquéias Martins Lima Silva, José de Souza Andrade Neto, Graziele Costa, and Mário Souza Ribeiro II; <i>Hospital Geral de Roraima:</i> Marcus Coelho, Roberto Carlos Cruz Carbonell, and Renata de Souza Trindade; <i>Hospital Israelita Albert Einstein:</i> Carmen Silvia Valente Barbas, Thiago Domingos Correa, Ary Serpa Neto, and Murillo Santucci Cesar de Assunção; <i>Hospital Lifecenter:</i> Bruno Vilela Costa Pinto and Priscila Gonçalves Libânio; <i>Hospital Marcelino Champagnat:</i> Alvaro Réa-Neto, Jarbas da Silva Motta Jr, Esperdião Elias Aquim, Gabriela Santa Maria Lucin, and Lorena Macedo Araujo; <i>Hospital Maternidade São Vicente de Paulo:</i> Meton Soares de Alencar Filho, Thales Anibal Leite Barros Agostinho, Kiara Monteiro de Andrade, Moisés Sampaio da Silva, Emerson Pereira da Silva, Rodrigo Luis Mousinho Gomes, Nilma Maria P. Campos, and Jairo Fonseca de Sousa; <i>Hospital Metropolitano de Urgência e Emergência:</i> Leonardo Ramos Nicolau da Costa, Norma Suely de Carvalho Fonseca Assunção, and Gabriela Martins de Lima; <i>Hospital Moinhos de Vento:</i> Cassiano Teixeira, Roselaine Pinheiro de Oliveira, Juçara Gasparetto Maccari, Patrícia de Campos Balzano, and Luciana Tagliari; <i>Hospital Municipal da Vila Santa Catarina:</i> Ana Paula Metran Nascente, Mônica Andrade de Carvalho, Monique Buttignol, and Renata Henn Moura; <i>Hospital Municipal Dr Mario Gatti:</i> Marcus Vinicius Pereira, Gabriel Alberti da Silva, Marina Akemi Higo, and Mariana Morales: <i>Hospital Municipal Dr Moysés Deutsch (M'Boi Mirim):</i> Ana Helena Vicente Andrade, Ana Paula de Paiva, Karina Suzane da Silva Pereira, Priscila Andrioli de Araujo, and Carlos Alberto Cordeiro de Abreu Filho; <i>Hospital Municipal São Francisco de Assis:</i> Guilherme Abdalla, Marcia Loureiro Sebold, and Rene Moreira; <i>Hospital Municipal São José de Joinville:</i> Milton Caldeira Filho, Rodrigo de Brito Cordeiro, and Felipe Pfuetzenreiter; <i>Hospital Naval Marcílio Dias:</i> Luiz Fernando Costa Carvalho, Bruno Leonardo da Silva Guimarães, Hebe de Faria Cordeiro, Sergio Hernando Pimentel Alvim, and José Amalth do Espirito Santo; <i>Hospital Nereu Ramos:</i> Israel Silva Maia, Mariangela Pincelli, Cassio Luis Zandonai, Ana Cristina Burigo Grumann, and Lara Patrícia Kretzer; <i>Hospital Nossa Senhora da Conceição:</i> Wagner Nedel, Márcio Manozzo Boniatti, and José Augusto Santos Pellegrini, and Leonardo da Silva Marques; <i>Hospital Novo Atibaia:</i> Walter Carlos Girardelli Baptista, Rubens Sérgio da Silva Franco, Manoela Moreira de Sousa, and Amauri Francisco de Marchi Benfica; <i>Hospital Primavera:</i> André Luis Veiga de Oliveira, Diego L. Reis, Mirene de O. Morais, and Hericalizandra Santa Rosa Santana; <i>Hospital Regional da Asa Norte (HRAN):</i> Sergio Murilo Domingues Jr, Cassia de Menezes Ferreira, and Livia Amado Rabelo; <i>Hospital Regional de Mato Grosso do Sul Rosa Pedrossian:</i> Claudnei Menezes de Rezende, Paula Riccio, Patrícia Silva de Almeida, and Patrícia Rubini; <i>Hospital Regional Hans Dieter Schmidt:</i> Maria da Graça Pasquotto de Lima Assef, Rafael Nardela, Laise Locks Stahlhöfer, and Carolina Gatelli Noronha; <i>Hospital Samaritano de Governador Valadares:</i> Sérgio de Azevedo Naves and Fabiano Dias da Silva; <i>Hospital Samaritano de São Paulo:</i> Bruno Franco Mazza, Samantha Longhi Simões de Almeida, Rosana Mayumi Higa, and Cristiane Helena Papacídero; <i>Hospital Samur:</i> Miquéias Martins Lima Silva, Livia de Assunção Melo, Manuele Miranda Mafra Oliveira, and Cynthia Matos Brito Coelho; <i>Hospital Santa Casa de Bragança Paulista:</i> Jocimar António Machado, Yara Lucia de Souza Machado, João Vitor Fera, and Nadia Cristina dos Santos Ramos; <i>Hospital Santa Cruz, Santa Cruz do Sul:</i> Rafael Botelho Foernges, Roberto Ritter de Souza, and William Rutzen; <i>Hospital Santa Juliana:</i> Edgar Miguel Villasante Troncoso, Thaiane K. B. Paiva, and Normando Melo Vieira de Lacerda; <i>Hospital Santa Luzia:</i> José Aires de Araújo Neto, Marcelo de Oliveira Maia, Edmilson Bastos de Moura, and Gisele Brocco Magnan; <i>Hospital Santa Rosa:</i> Mara Lílian Soares Nasrala, Rogéria Lobato Campos Tonussi, Eloisa Kohl Pinheiro, and Fabio Simões da Silva; <i>Hospital São José–Criciúma:</i> Felipe Dal-Pizzol, Fernando Schmitz de Figueiredo, and Cristiane Ritter; <i>Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS):</i> Sérgio de Vasconcellos Baldisserotto, Clarissa Blattner, Rafael Saldanha dos Santos, and Fernanda da Silva Bettega; <i>Hospital São Lucas de Governador Valadares:</i> Sérgio de Azevedo Naves and Fabiano Dias da Silva; <i>Hospital São Lucas-FAG:</i> Péricles Almeida Delfino Duarte, Tatiane Cristina Tozo, and Priscila Peliser; <i>Hospital São Luiz—Unidade Anália Franco:</i> Rafaela Deczka Morsch, Érika Guimarães Leal Guadalupe, and Denise Souza Amorim; <i>Hospital Saúde da Mulher:</i> Leila Rezegue de Moraes Rego; <i>Hospital Sirio-Libanês:</i> Luciano Azevedo, Fernando Ramos, Laerte Pastore, and Patricia Nery; <i>Hospital Unimed Araçatuba:</i> Marcelo Spegiorin Moreno, Vinicius Nakad Orsatti, Fabio Yudi Horikawa, and Gabriela Samartino Zavanelli; <i>Hospital Unimed Joinville:</i> Glauco Adrieno Westphal, Geonice Sperotto, and Micheli Dadam; <i>Hospital Unimed Santa Helena:</i> Marcelo Nunes, Sílvio Luis Pantaleão, and Roberto Camargo Narciso; <i>Hospital Unimed Vitória:</i> Eliana Bernadete Caser, Jansen G. Falcão, Gustavo Genelhu, Felipe Lessa Soares, Betania Silva Sales, Karinne Rebello de Jesus, Daniela Correia Santos Bonomo, and Juliano Martins Arruda; <i>Hospital Unimed-Rio:</i> João Carlos de Pinho, Janine Belacho Azeredo Coutinho, Rafaela Braga Hagreaves Ribeiro de Freitas, and Tiego de Souza Oliveira Garcia; <i>Hospital Universitário Cassiano Antonio de Moraes da Universidade Federal do Espirito Santo (UFES):</i> Paula Frizera Vassallo and Maria Helena Buarque Souza de Lima; <i>Hospital Universitário da Universidade Federal da Grande Dourados:</i> Mirna Matsui, Ervin, Eberhart Neto, Alexandre Satoshi Inagaki, Aline Evangelista Oliveira de Paula, Tiago Amador Correia, Silmara Nomoto, Fernando Seiji Ueno Gil, Mario Florizel Almeida de Araújo, and Zildamara Bezerra Lima; <i>Hospital Universitário do Oeste do Paraná:</i> Thiago Simões Giancursi, Cláudia Rejane de Lima, Macedo Costa, Erica Fernanda Osaku, and Amaury Cezar Jorge; <i>Hospital Universitário Pedro Ernesto:</i> Mônica Rodrigues da Cruz, Sergio da Cunha, Katia Silva Cavallaro Torres, and Fernanda Rocha Rodrigues da Silva; <i>Hospital Universitário Polydoro Ernani de São Thiago:</i> Rafael Lisboa de Souza, Fernando Osni Machado, Elizabeth Kristiane Buss, and Kelly Cattelan Bonorino; <i>Hospital Universitário Regional de Maringá:</i> Almir Germano, Sandra Regina Bin da Silva, Andrea Herek, and Sanderland José Tavares Gurgel; <i>Hospital Universitário Regional do Norte do Paraná:</i> Cintia Magalhães Carvalho Grion, Alexandre Sanches Laranjeira, Marcos Toshiyuki Tanita, and Lucienne Tibery Queiroz Cardoso; <i>Hospital Universitário São Francisco de Paula:</i> Márcio Osorio Guerreiro, Marina Peres Bainy, and Luciano de Oliveira Teixeira; <i>Hospital Universitário São Francisco:</i> Giovana Colozza Mecatti, Maria Carolina Salomão, Aline Ribeiro Moreira, and Camila Vantini Capasso Palamim; <i>Hospital Vita Batel:</i> Alvaro Réa-Neto, Esperdião Elias Aquim, Rafael Alexandre O. Deucher, and Francine Castro Escobar Furlan; <i>Instituto de Infectologia—Emílio Ribas:</i> Fabrício Rodrigues Torres de Carvalho, Roberto Muniz Jr, Hélio Penna Guimarães, and Lucia Conceição Andrade; <i>Instituto do Câncer do Estado de São Paulo—ICESP:</i> Ludhmila Abrahão Hajjar, Filomena Regina Barbosa Gomes Galas, and Juliano Pinheiro de Almeida; <i>Irmandade da Santa Casa de Misericórdia de São Paulo:</i> Roberto Marco, Elzo Peixoto, Fabiano Hirata, and Chen Yen Ju; <i>MEDIMIG:</i> Bruno Bonaccorsi Fernandino, Daniel Lage de Assis Rocha, and Nathalia Azzi Barbosa; <i>Santa Casa da Misericórdia de Ouro Preto:</i> Janine Dias Alves, Ludmila Furtado Lamego, and Juliana Maria de Linhares; <i>Santa Casa de Caridade de Diamantina:</i> Marcelo Ferreira Sousa, Marcia Maria Ferreira de Souza, Fernanda Luiza Guimarães de Carvalho, and Monica Aparecida Leite; <i>Santa Casa de Maringá:</i> Paulo Torres, Daniel Bolognese, and Valintin Lacerda; <i>Sociedade Brasileira de Amparo a Saúde (SOBRASA):</i> Giovanni Cisari, Alexandre Souza Marques, Alex Amarante Costa, and Leonardo Bonin Campos; <i>Unidade de Emergência do Hospital das Clínicas da FMRP-USP:</i> Marcos de Carvalho Borges, Wilson José Lovato, Bruno Guimarães Dantas, Débora Ribeiro Campos, Larissa Christina Pires Barrientto, Vivian Rossi Peras Américo, Thatiana Barboza Carnevalli Bueno, Daniela Morales, Tania Mara Gomes, and Rodrigo Barbosa Cerantola; <i>UTI Central da Irmandade Santa Casa de Misericórdia de Porto Alegre:</i> Roselaine Pinheiro de Oliveira, Cassiano Teixeira, and Jorge Höher; <i>UTIs da Anestesiologia, da Emergência Cirúrgica e Gastroenterologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP):</i> Luiz Marcelo Sá Malbouisson, Filipe Matheus Cadamuro, Estevão Bassi, Rafaella Maia, João Alexandre Dias e Santos, Catherine Oliveira, Ana Paula Balzi, Paulo Tierno, and Guilherme Marques Andrade; <i>UTI Clínica do Hospital São Paulo da Universidade Federal de São Paulo (UNIFESP):</i> Renato Delascio Lopes, Marcos Cesar Ramos Mello, Hélio Penna Guimarães, and Leticia Sandre Vendrame; <i>UTI da Disciplina de Anestesiologia, Dor e Terapia Intensiva do Hospital São Paulo da Universidade Federal de São Paulo (UNIFESP):</i> Flávia Ribeiro Machado, Heloisa Baccaro Rossetti Santana, Alessandre de Carvalho Jr, Vanessa Marques Ferreira Mendez, Walkyria de Araujo Macedo Pinto, Renata dos Santos Francisco, Flavio Steponovicius Piedade Cruz, Abigail Silva de Araujo, Alda Paiva de Souza, and Tuanny Teixeira Pinheiro; <i>UTI de Emergências Clínicas do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP):</i> Thiago Martins Santos, Carolina Matida Gontijo-Coutinho, Daniel Franci, and Marco Antonio de Carvalho-Filho; <i>UTI de Queimados do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP):</i> Amanda Maria Ribas Rosa de Oliveira and João Manoel Silva Jr; <i>UTI do Hospital Santa Rita—Irmandade Santa Casa de Misericórdia de Porto Alegre:</i> Thiago Costa Lisboa, André Peretti Torelly, Alldren Silva de Souza, and Martha Hadrich; <i>UTI do Pavilhão Pereira Filho da Irmandade Santa Casa de Misericórdia de Porto Alegre:</i> Patricia Schwarz, Paula Berto and José Augusto Santos Pellegrini; <i>UTI do Pronto Socorro do Hospital São Paulo da Universidade Federal de São Paulo (UNIFESP):</i> Aécio Flavio Teixeira de Gois, Moacyr Silva Jr, Paulo Gessolo Lins, and Eulália Priscila Cavalcante Lola Biazzoto; <i>UTI Geral dos Adultos do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP):</i> Desanka Dragosavac; <i>UTI Respiratória do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP):</i> Carlos Roberto Ribeiro de Carvalho, Marcelo Britto Passos Amato, Carlos Toufen Jr, Roberta Ribeiro de Santis Santiago, and Adriana S. Hirota; <i>UTI Respiratória do Hospital São Paulo da Universidade Federal de São Paulo (UNIFESP):</i> Milton Rodrigues Jr, Luciana Dias Chiavegato, Paulo César Bastos Vieira, Marcella Marson M. F. de Almeida, and Pedro Gabriel Barbosa; <i>Vila Velha Hospital:</i> José Roberto Pereira Santos and Ludmila Nogueira de Paula; and <i>Vitória Apart Hospital:</i> Claudio Piras, Jonas Giuberti Jr, Albano Siqueira da Silva, and Rodrigo Conti Ramos.</p><p class="parastudy-group-members-end"><strong>Colombia:</strong><i>Organización Latinoamericana para el Fomento de la Investigación en Salud (OLFIS), Bucaramanga, Colombia. National Coordination of Sites in Colombia:</i> Fredi Alexander Diaz-Quijano; <i>Clinica Chicamocha:</i> Reinaldo Plata Valdivieso, Hugo Hernan Gonzalez, and Myriam Ortiz; <i>Department of Intensive Care Medicine, Fundación Valle del Lili—Universidad ICESI:</i> Gustavo A. Ospina-Tascón, Diego F. Bautista-Rincón, Edgardo Quiñones, Luis Eduardo Calderon, and Monica Vargas; <i>Fundación Cardiovascular de Colombia:</i> Camilo Pizarro, Mauricio Orozco Levi and Angela Maria Espitia Hernández; <i>Hospital Pablo Tóbon Uribe:</i> Carlos Cadavid Gutierrez, Nelson Giraldo Ramirez, Diego Alejandro Gallego, and Santiago Naranjo Sierra; <i>Hospital Santa Clara:</i> Guillermo Ortiz, Maria Esneda Rocha Gaona, and Manuel Garay; and <i>Hospital Universitario del Valle:</i> Elías Vieda, William F. Bermúdez, and Julieth A. Castañeda.</p><p class="parastudy-group-members-end"><strong>Italy:</strong><i>Policlinico Paolo Giaccone. University of Palermo:</i> Andrea Cortegiani, Vincenzo Russotto, Santi Maurizio Raineri, and Antonino Giarratano.</p><p class="parastudy-group-members-end"><strong>Malaysia:</strong><i>University Malaya Medical Centre:</i> Mohd Shahnaz Hasan, Vineya Rai Hakumat Rai, Mohamad Fadhil Hadi bin Jamaluddin, and Mohamad Afiq Syahmi Ramli.</p><p class="parastudy-group-members-end"><strong>Poland:</strong><i>Jagiellonian University Medical College; Department of Intensive Care and Perioperative Medicine:</i> Wojciech Szczeklik, Jacek Gorka, Ilona Nowak, Bozena Seczynska, and Aurelia Sega.</p><p class="parastudy-group-members-end"><strong>Portugal:</strong><i>Hospital de São Francisco Xavier, Centro Hospitalar de Lisboa Ocidental:</i> Carolina Paulino and Pedro Póvoa.</p><p class="parastudy-group-members-end"><strong>Spain:</strong><i>Hospital Clinico Universitario. University of Valencia:</i> F. Javier Belda, Carlos Ferrando, Jose A. Carbonell, Jaume Puig, and Marina Soro.</p><p class="parastudy-group-members-end"><strong>Uruguay:</strong><i>Hospital Español, JJ Crottogini:</i> Nicolas Nin, Javier Hurtado, Ariel Gacel, Agustin Gaudin, and Leonardo Sande.</p><p class="para"><strong>Data Monitoring Committee:</strong> Gordon Guyatt, MD, PhD; Niall Ferguson, MD, PhD; and Stephen Walter, PhD.</p><p class="para"><strong>Study Coordinating Office:</strong><i>HCor Research Institute, São Paulo, Brazil:</i> Alexandre Biasi Cavalcanti, MD, PhD; Ligia Nasi Laranjeira, RT; Denise de Moraes Paisani, PhD; Lucas Petri Damiani, MSc; Érica Aranha Suzumura, MSc; Samara Pinheiro do Carmo Gomes, BSc; Alessandra Akiko Kodama, MSc; Bruna dos Santos Sampaio, BSc; and Otávio Berwanger, MD, PhD.</p><p class="parafunding-statement"><strong>Funding/Support:</strong> This study was funded by and conducted as part of the Program to Support Institutional Development of Universal System (PROADI) from the Brazilian Ministry of Health. The trial was coordinated by the HCor Research Institute and endorsed by the Brazilian Research in Intensive Care Network (BRICNet). </p><p class="para"><strong>Role of the Funder/Sponsor:</strong> The funding sources had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. </p><p class="para"><strong>Reproducible Research Statement:</strong> We will share the database containing deidentified individual participant data, data dictionary documentation, statistical analysis plan, and analysis code. Beginning 6 months and ending 24 months following article publication, the trial steering committee will evaluate proposals of studies accompanied by a statistical analysis plan and may grant access to the data for approved proposals. After 24 months, the database and accompanying documents will be publicly available in an institutional data repository (<a href="http://www.hcor.com.br">http://www.hcor.com.br</a>).</p><p class="para"><strong>Additional Contributions:</strong> We thank the Brazilian Association of Intensive Care Medicine for assisting with facilitating invitation to Brazilian intensivists. We thank all multidisciplinary teams in participant centers for their enthusiastic support and following the study interventions.</p> <a class="article-section-id-anchor" id="172419602"></a> <div class="h3 cb section-type-references "> <div class="heading-text thm-col sb-sc"> References </div> </div> <div class="references"><div class="reference"><a class="reference-number" id="joi170110r1">1.</a><div class="reference-content">Bellani G, Laffey JG, Pham T, et al; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2016;315(8):788-800.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26903337" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Epidemiology%2C%20patterns%20of%20care%2C%20and%20mortality%20for%20patients%20with%20acute%20respiratory%20distress%20syndrome%20in%20intensive%20care%20units%20in%2050%20countries.&author=G%20Bellani&author=JG%20Laffey&author=T%20Pham&publication_year=2016&journal=JAMA&volume=315&pages=788-800" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.2016.0291" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.2016.0291" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r2">2.</a><div class="reference-content">Herridge MS, Tansey CM, Matté A, et al; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2011;364(14):1293-1304.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21470008" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Functional%20disability%205%20years%20after%20acute%20respiratory%20distress%20syndrome.&author=MS%20Herridge&author=CM%20Tansey&author=A%20Matté&publication_year=2011&journal=N%20Engl%20J%20Med&volume=364&pages=1293-1304" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa1011802" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa1011802" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r3">3.</a><div class="reference-content">Gattinoni L, Marini JJ, Pesenti A, Quintel M, Mancebo J, Brochard L. The “baby lung” became an adult. <i xmlns:helper="urn:XsltStringHelper"> Intensive Care Med</i>. 2016;42(5):663-673.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26781952" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=The%20%E2%80%9Cbaby%20lung%E2%80%9D%20became%20an%20adult.&author=L%20Gattinoni&author=JJ%20Marini&author=A%20Pesenti&author=M%20Quintel&author=J%20Mancebo&author=L%20Brochard&publication_year=2016&journal=Intensive%20Care%20Med&volume=42&pages=663-673" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1007/s00134-015-4200-8" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1007/s00134-015-4200-8" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r4">4.</a><div class="reference-content">Gattinoni L, Protti A, Caironi P, Carlesso E. Ventilator-induced lung injury: the anatomical and physiological framework. <i xmlns:helper="urn:XsltStringHelper"> Crit Care Med</i>. 2010;38(10)(suppl):S539-S548.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21164395" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Ventilator-induced%20lung%20injury%3A%20the%20anatomical%20and%20physiological%20framework.&author=L%20Gattinoni&author=A%20Protti&author=P%20Caironi&author=E%20Carlesso&publication_year=2010&journal=Crit%20Care%20Med&volume=38&pages=S539-S548" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1097/CCM.0b013e3181f1fcf7" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1097/CCM.0b013e3181f1fcf7" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r5">5.</a><div class="reference-content">Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 1998;338(6):347-354.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/9449727" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Effect%20of%20a%20protective-ventilation%20strategy%20on%20mortality%20in%20the%20acute%20respiratory%20distress%20syndrome.&author=MB%20Amato&author=CS%20Barbas&author=DM%20Medeiros&publication_year=1998&journal=N%20Engl%20J%20Med&volume=338&pages=347-354" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJM199802053380602" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJM199802053380602" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r6">6.</a><div class="reference-content">Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A; Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2000;342(18):1301-1308.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/10793162" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Ventilation%20with%20lower%20tidal%20volumes%20as%20compared%20with%20traditional%20tidal%20volumes%20for%20acute%20lung%20injury%20and%20the%20acute%20respiratory%20distress%20syndrome.&author=RG%20Brower&author=MA%20Matthay&author=A%20Morris&author=D%20Schoenfeld&author=BT%20Thompson&author=A%20Wheeler&publication_year=2000&journal=N%20Engl%20J%20Med&volume=342&pages=1301-1308" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJM200005043421801" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJM200005043421801" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r7">7.</a><div class="reference-content">Borges JB, Okamoto VN, Matos GF, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 2006;174(3):268-278.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/16690982" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Reversibility%20of%20lung%20collapse%20and%20hypoxemia%20in%20early%20acute%20respiratory%20distress%20syndrome.&author=JB%20Borges&author=VN%20Okamoto&author=GF%20Matos&publication_year=2006&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=174&pages=268-278" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1164/rccm.200506-976OC" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1164/rccm.200506-976OC" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r8">8.</a><div class="reference-content">de Matos GF, Stanzani F, Passos RH, et al. How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography. <i xmlns:helper="urn:XsltStringHelper"> Crit Care</i>. 2012;16(1):R4.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/22226331" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=How%20large%20is%20the%20lung%20recruitability%20in%20early%20acute%20respiratory%20distress%20syndrome%3A%20a%20prospective%20case%20series%20of%20patients%20monitored%20by%20computed%20tomography.&author=GF%20de Matos&author=F%20Stanzani&author=RH%20Passos&publication_year=2012&journal=Crit%20Care&volume=16&pages=R4" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/cc10602" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/cc10602" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r9">9.</a><div class="reference-content">Hodgson CL, Tuxen DV, Davies AR, et al. A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> Crit Care</i>. 2011;15(3):R133.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21635753" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=A%20randomised%20controlled%20trial%20of%20an%20open%20lung%20strategy%20with%20staircase%20recruitment%2C%20titrated%20PEEP%20and%20targeted%20low%20airway%20pressures%20in%20patients%20with%20acute%20respiratory%20distress%20syndrome.&author=CL%20Hodgson&author=DV%20Tuxen&author=AR%20Davies&publication_year=2011&journal=Crit%20Care&volume=15&pages=R133" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/cc10249" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/cc10249" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r10">10.</a><div class="reference-content">Kacmarek RM, Villar J, Sulemanji D, et al; Open Lung Approach Network. Open lung approach for the acute respiratory distress syndrome: a pilot, randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> Crit Care Med</i>. 2016;44(1):32-42.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26672923" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Open%20lung%20approach%20for%20the%20acute%20respiratory%20distress%20syndrome%3A%20a%20pilot%2C%20randomized%20controlled%20trial.&author=RM%20Kacmarek&author=J%20Villar&author=D%20Sulemanji&publication_year=2016&journal=Crit%20Care%20Med&volume=44&pages=32-42" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1097/CCM.0000000000001383" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1097/CCM.0000000000001383" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r11">11.</a><div class="reference-content">Suzumura EA, Figueiró M, Normilio-Silva K, et al. Effects of alveolar recruitment maneuvers on clinical outcomes in patients with acute respiratory distress syndrome: a systematic review and meta-analysis. <i xmlns:helper="urn:XsltStringHelper"> Intensive Care Med</i>. 2014;40(9):1227-1240.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/25097070" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Effects%20of%20alveolar%20recruitment%20maneuvers%20on%20clinical%20outcomes%20in%20patients%20with%20acute%20respiratory%20distress%20syndrome%3A%20a%20systematic%20review%20and%20meta-analysis.&author=EA%20Suzumura&author=M%20Figueiró&author=K%20Normilio-Silva&publication_year=2014&journal=Intensive%20Care%20Med&volume=40&pages=1227-1240" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1007/s00134-014-3413-6" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1007/s00134-014-3413-6" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r12">12.</a><div class="reference-content">Hodgson C, Goligher EC, Young ME, et al. Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation. <i xmlns:helper="urn:XsltStringHelper"> Cochrane Database Syst Rev</i>. 2016;11:CD006667.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27855477" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Recruitment%20manoeuvres%20for%20adults%20with%20acute%20respiratory%20distress%20syndrome%20receiving%20mechanical%20ventilation.&author=C%20Hodgson&author=EC%20Goligher&author=ME%20Young&publication_year=2016&journal=Cochrane%20Database%20Syst%20Rev&volume=11&pages=CD006667" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a></div></div><div class="reference"><a class="reference-number" id="joi170110r13">13.</a><div class="reference-content">ART Investigators. Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> Trials</i>. 2012;13(1):153.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/22929542" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Rationale%2C%20study%20design%2C%20and%20analysis%20plan%20of%20the%20Alveolar%20Recruitment%20for%20ARDS%20Trial%20%28ART%29%3A%20study%20protocol%20for%20a%20randomized%20controlled%20trial.&publication_year=2012&journal=Trials&volume=13&pages=153" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/1745-6215-13-153" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/1745-6215-13-153" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r14">14.</a><div class="reference-content">Damiani L, Berwanger O, Paisani D, et al. Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART): a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> Rev Bras Ter Intensiva</i>. 2017;29(2):142-153.<a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Statistical%20analysis%20plan%20for%20the%20Alveolar%20Recruitment%20for%20Acute%20Respiratory%20Distress%20Syndrome%20Trial%20%28ART%29%3A%20a%20randomized%20controlled%20trial.&author=L%20Damiani&author=O%20Berwanger&author=D%20Paisani&publication_year=2017&journal=Rev%20Bras%20Ter%20Intensiva&volume=29&pages=142-153" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.5935/0103-507X.20170024" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.5935/0103-507X.20170024" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r15">15.</a><div class="reference-content">Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 1994;149(3 pt 1):818-824.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/7509706" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=The%20American-European%20Consensus%20Conference%20on%20ARDS%3A%20definitions%2C%20mechanisms%2C%20relevant%20outcomes%2C%20and%20clinical%20trial%20coordination.&author=GR%20Bernard&author=A%20Artigas&author=KL%20Brigham&publication_year=1994&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=149&pages=818-824" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1164/ajrccm.149.3.7509706" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1164/ajrccm.149.3.7509706" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r16">16.</a><div class="reference-content">Guérin C, Reignier J, Richard JC, et al; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2013;368(23):2159-2168.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/23688302" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Prone%20positioning%20in%20severe%20acute%20respiratory%20distress%20syndrome.&author=C%20Guérin&author=J%20Reignier&author=JC%20Richard&publication_year=2013&journal=N%20Engl%20J%20Med&volume=368&pages=2159-2168" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa1214103" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa1214103" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r17">17.</a><div class="reference-content">Mercat A, Richard JC, Vielle B, et al; Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2008;299(6):646-655.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/18270353" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Positive%20end-expiratory%20pressure%20setting%20in%20adults%20with%20acute%20lung%20injury%20and%20acute%20respiratory%20distress%20syndrome%3A%20a%20randomized%20controlled%20trial.&author=A%20Mercat&author=JC%20Richard&author=B%20Vielle&publication_year=2008&journal=JAMA&volume=299&pages=646-655" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.299.6.646" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.299.6.646" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r18">18.</a><div class="reference-content">Retamal J, Bugedo G, Larsson A, Bruhn A. High PEEP levels are associated with overdistension and tidal recruitment/derecruitment in ARDS patients. <i xmlns:helper="urn:XsltStringHelper"> Acta Anaesthesiol Scand</i>. 2015;59(9):1161-1169.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/26061818" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=High%20PEEP%20levels%20are%20associated%20with%20overdistension%20and%20tidal%20recruitment%2Fderecruitment%20in%20ARDS%20patients.&author=J%20Retamal&author=G%20Bugedo&author=A%20Larsson&author=A%20Bruhn&publication_year=2015&journal=Acta%20Anaesthesiol%20Scand&volume=59&pages=1161-1169" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1111/aas.2015.59.issue-9" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1111/aas.2015.59.issue-9" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r19">19.</a><div class="reference-content">Guerin C, Debord S, Leray V, et al. Efficacy and safety of recruitment maneuvers in acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> Ann Intensive Care</i>. 2011;1(1):9.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/21906333" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Efficacy%20and%20safety%20of%20recruitment%20maneuvers%20in%20acute%20respiratory%20distress%20syndrome.&author=C%20Guerin&author=S%20Debord&author=V%20Leray&publication_year=2011&journal=Ann%20Intensive%20Care&volume=1&pages=9" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/2110-5820-1-9" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/2110-5820-1-9" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r20">20.</a><div class="reference-content">Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2015;372(8):747-755.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/25693014" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Driving%20pressure%20and%20survival%20in%20the%20acute%20respiratory%20distress%20syndrome.&author=MB%20Amato&author=MO%20Meade&author=AS%20Slutsky&publication_year=2015&journal=N%20Engl%20J%20Med&volume=372&pages=747-755" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMsa1410639" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMsa1410639" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r21">21.</a><div class="reference-content">Guérin C, Papazian L, Reignier J, Ayzac L, Loundou A, Forel JM; investigators of the Acurasys and Proseva trials. Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials. <i xmlns:helper="urn:XsltStringHelper"> Crit Care</i>. 2016;20(1):384.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27894328" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Effect%20of%20driving%20pressure%20on%20mortality%20in%20ARDS%20patients%20during%20lung%20protective%20mechanical%20ventilation%20in%20two%20randomized%20controlled%20trials.&author=C%20Guérin&author=L%20Papazian&author=J%20Reignier&author=L%20Ayzac&author=A%20Loundou&author=JM%20Forel&publication_year=2016&journal=Crit%20Care&volume=20&pages=384" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1186/s13054-016-1556-2" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1186/s13054-016-1556-2" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r22">22.</a><div class="reference-content">Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2010;303(9):865-873.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/20197533" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Higher%20vs%20lower%20positive%20end-expiratory%20pressure%20in%20patients%20with%20acute%20lung%20injury%20and%20acute%20respiratory%20distress%20syndrome%3A%20systematic%20review%20and%20meta-analysis.&author=M%20Briel&author=M%20Meade&author=A%20Mercat&publication_year=2010&journal=JAMA&volume=303&pages=865-873" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.2010.218" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.2010.218" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r23">23.</a><div class="reference-content">Brower RG, Lanken PN, MacIntyre N, et al; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2004;351(4):327-336.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/15269312" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Higher%20versus%20lower%20positive%20end-expiratory%20pressures%20in%20patients%20with%20the%20acute%20respiratory%20distress%20syndrome.&author=RG%20Brower&author=PN%20Lanken&author=N%20MacIntyre&publication_year=2004&journal=N%20Engl%20J%20Med&volume=351&pages=327-336" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa032193" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa032193" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r24">24.</a><div class="reference-content">Beitler JR, Sands SA, Loring SH, et al. Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria. <i xmlns:helper="urn:XsltStringHelper"> Intensive Care Med</i>. 2016;42(9):1427-1436.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27342819" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Quantifying%20unintended%20exposure%20to%20high%20tidal%20volumes%20from%20breath%20stacking%20dyssynchrony%20in%20ARDS%3A%20the%20BREATHE%20criteria.&author=JR%20Beitler&author=SA%20Sands&author=SH%20Loring&publication_year=2016&journal=Intensive%20Care%20Med&volume=42&pages=1427-1436" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1007/s00134-016-4423-3" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1007/s00134-016-4423-3" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r25">25.</a><div class="reference-content">Chanques G, Kress JP, Pohlman A, et al. Impact of ventilator adjustment and sedation-analgesia practices on severe asynchrony in patients ventilated in assist-control mode. <i xmlns:helper="urn:XsltStringHelper"> Crit Care Med</i>. 2013;41(9):2177-2187.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/23782972" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Impact%20of%20ventilator%20adjustment%20and%20sedation-analgesia%20practices%20on%20severe%20asynchrony%20in%20patients%20ventilated%20in%20assist-control%20mode.&author=G%20Chanques&author=JP%20Kress&author=A%20Pohlman&publication_year=2013&journal=Crit%20Care%20Med&volume=41&pages=2177-2187" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1097/CCM.0b013e31828c2d7a" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1097/CCM.0b013e31828c2d7a" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r26">26.</a><div class="reference-content">Meade MO, Cook DJ, Guyatt GH, et al; Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. <i xmlns:helper="urn:XsltStringHelper"> JAMA</i>. 2008;299(6):637-645.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/18270352" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Ventilation%20strategy%20using%20low%20tidal%20volumes%2C%20recruitment%20maneuvers%2C%20and%20high%20positive%20end-expiratory%20pressure%20for%20acute%20lung%20injury%20and%20acute%20respiratory%20distress%20syndrome%3A%20a%20randomized%20controlled%20trial.&author=MO%20Meade&author=DJ%20Cook&author=GH%20Guyatt&publication_year=2008&journal=JAMA&volume=299&pages=637-645" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1001/jama.299.6.637" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1001/jama.299.6.637" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r27">27.</a><div class="reference-content">Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. <i xmlns:helper="urn:XsltStringHelper"> Lancet Respir Med</i>. 2014;2(8):611-620.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/24853585" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Subphenotypes%20in%20acute%20respiratory%20distress%20syndrome%3A%20latent%20class%20analysis%20of%20data%20from%20two%20randomised%20controlled%20trials.&author=CS%20Calfee&author=K%20Delucchi&author=PE%20Parsons&author=BT%20Thompson&author=LB%20Ware&author=MA%20Matthay&publication_year=2014&journal=Lancet%20Respir%20Med&volume=2&pages=611-620" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1016/S2213-2600(14)70097-9" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1016/S2213-2600(14)70097-9" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r28">28.</a><div class="reference-content">Famous KR, Delucchi K, Ware LB, et al; ARDS Network. Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 2017;195(3):331-338.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/27513822" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Acute%20respiratory%20distress%20syndrome%20subphenotypes%20respond%20differently%20to%20randomized%20fluid%20management%20strategy.&author=KR%20Famous&author=K%20Delucchi&author=LB%20Ware&publication_year=2017&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=195&pages=331-338" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a></div></div><div class="reference"><a class="reference-number" id="joi170110r29">29.</a><div class="reference-content">Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. <i xmlns:helper="urn:XsltStringHelper"> N Engl J Med</i>. 2006;354(17):1775-1786.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/16641394" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Lung%20recruitment%20in%20patients%20with%20the%20acute%20respiratory%20distress%20syndrome.&author=L%20Gattinoni&author=P%20Caironi&author=M%20Cressoni&publication_year=2006&journal=N%20Engl%20J%20Med&volume=354&pages=1775-1786" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1056/NEJMoa052052" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1056/NEJMoa052052" xmlns:helper="urn:XsltStringHelper"> </span></div></div><div class="reference"><a class="reference-number" id="joi170110r30">30.</a><div class="reference-content">Goligher EC, Kavanagh BP, Rubenfeld GD, Ferguson ND. Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials. <i xmlns:helper="urn:XsltStringHelper"> Am J Respir Crit Care Med</i>. 2015;192(12):1416-1419.<a class="pubmed-link" href="https://www.ncbi.nlm.nih.gov/pubmed/25580530" target="_blank" xmlns:helper="urn:XsltStringHelper">PubMed</a><a class="google-scholar-ref-link" href="https://scholar.google.com/scholar_lookup?title=Physiologic%20Responsiveness%20Should%20Guide%20Entry%20into%20Randomized%20Controlled%20Trials.&author=EC%20Goligher&author=BP%20Kavanagh&author=GD%20Rubenfeld&author=ND%20Ferguson&publication_year=2015&journal=Am%20J%20Respir%20Crit%20Care%20Med&volume=192&pages=1416-1419" target="_blank" xmlns:helper="urn:XsltStringHelper">Google Scholar</a><a href="https://doi.org/10.1164/rccm.201410-1832CP" class="crossref-doi" target="_blank" xmlns:helper="urn:XsltStringHelper">Crossref</a><span class="inst-open-url-holders" data-targetId="10.1164/rccm.201410-1832CP" xmlns:helper="urn:XsltStringHelper"> </span></div></div></div> </div> </div> <div class="movable-ad bta"> <div class="widget-WidgetLoader widget-instance-AMA_AdTag_textbreak_bta_dual"> <div class="SCM-SharedWidgets-AsyncAdLoader" data-url="/AMA/AdTag/AMA_AdTag_textbreak_bta_dual" data-params="{"parameters":{"siteName":"jama","siteId":3,"journalId":67,"adDisplay":8,"adSection":"textbreak","adPosition":"bta","fromGoogle":false},"dynamicParameters":{}}"></div> </div> </div> </div> </div> <div class="hidden-jobs-ad hide"> <div class="widget-WidgetLoader widget-instance-AMA_JobsAd"> <div class="SCM-SharedWidgets-AsyncJobsAdLoader" data-url="/AMA/JobsAd/AMA_JobsAd" data-params="{"parameters":{"SiteId":3},"dynamicParameters":{"localParams":"[REPLACE_WITH_LOCAL]"}}"></div> </div> </div> <script> var App = App || {}; App.ArticleSplitScreen = App.ArticleSplitScreen || {}; App.ArticleSplitScreen.siteName = 'jama'; App.ArticleSplitScreen.siteId = 3; App.ArticleSplitScreen.journalId = 67; App.ArticleSplitScreen.adDisplay = 'ArticleContentsSkyBox'; App.ArticleSplitScreen.adSection = "scholarly"; App.ArticleSplitScreen.adPosition = "contab"; App.ArticleSplitScreen.controlId = "AMA_AdTag_Contents_Skybox"; App.ArticleSplitScreen.fromGoogle = "False"; App.ArticleSplitScreen.slotLocationOverride = "50"; </script> </div> </div> </section> <section id="secFooterControl" class="master-footer"> <script> var App = App || {}; function scmByClass(className) { return document.getElementsByClassName(className); } function scmById(id) { return document.getElementById(id); } function scmquery(selector) { return document.querySelector(selector); } function queryAll(selector) { return document.querySelectorAll(selector); } function isTrueString(string) { if (typeof string === 'string') { return string.toLowerCase() === 'true'; } return undefined; } function updateViewportDimensions() { var w = window, d = document, e = d.documentElement, g = d.getElementsByTagName('body')[0], x = w.innerWidth || e.clientWidth || g.clientWidth, y = w.innerHeight || e.clientHeight || g.clientHeight; return { width: x, height: y }; } var viewport = updateViewportDimensions(); var debounce = function (func, wait, immediate) { var timeout; return function () { var context = this, args = arguments; var later = function () { timeout = null; if (!immediate) func.apply(context, args); }; var callNow = immediate && !timeout; clearTimeout(timeout); timeout = setTimeout(later, wait); if (callNow) func.apply(context, args); }; }; (function (App) { App.mobileUpperBreakpoint = 767; App.mobileAltBreakpoint = 640; App.mobileMinBreakpoint = 547; App.tabletUpperBreakpoint = 1023; function setVariables() { viewport = updateViewportDimensions(); App.isMobile = (viewport.width <= App.mobileUpperBreakpoint); App.isMobileAlt = (viewport.width <= App.mobileAltBreakpoint); App.isTablet = (viewport.width > App.mobileUpperBreakpoint && viewport.width <= App.tabletUpperBreakpoint); App.isTabletDown = (viewport.width <= App.tabletUpperBreakpoint); App.isDesktop = (viewport.width > App.tabletUpperBreakpoint); App.activeViewport = App.isMobile ? 'small' : App.isTablet ? 'med' : 'large'; } setVariables(); App.cachedViewport = App.isMobile ? 'small' : App.isTablet ? 'med' : 'large'; App.isAnyArticle = !!(scmByClass('widget-ArticleFullView').length || scmByClass('pg_abstract').length || scmByClass('widget-MagazineView').length || scmByClass('widget-ChannelsMagazineView').length); App.isSplitScreen = !!scmByClass('widget-ArticleFullView').length; App.isArticleRedesign = !!scmByClass('widget-ArticleWrapper').length; App.isAbstract = !!scmByClass('pg_abstract').length; App.isMag = !!(scmByClass('widget-MagazineView').length); App.isChannel = !!(scmByClass('channel-site').length); App.isChannelMag = !!(scmByClass('widget-ChannelsMagazineView').length); App.isFreeArticle = !!(scmquery('.widget-ArticleTopInfo .free-access') || scmquery('.widget-ArticleTopInfo .open-access') || scmquery('.widget-ArticleTopInfo .icon-free') || scmquery('.widget-ChannelsMagazineView .free-access')); App.isTollFreeAccess = false; App.isIssue = !!scmByClass('pg_issue').length || !!scmByClass('pg_newonline').length || !!scmByClass('pg_currentissue').length || !!scmByClass('pg_pastissues').length; App.isNewOnline = !!scmByClass('pg_newonline').length; App.isCurrentIssue = !!scmByClass('pg_currentissue').length; App.isPastIssues = !!scmByClass('pg_pastissues').length; App.isJournal = !!scmByClass('pg_journal').length; App.isNetworkHome = !!scmByClass('pg_index').length; App.isSearch = !!scmByClass('pg_searchresults').length; App.isAdvancedSearch = !!scmByClass('pg_advancedsearch').length; App.isPlayer= !!scmByClass('pg_multimediaplayer').length; App.isSelfServe = !!scmByClass('pg_sspage').length; App.isCmsPage = !!scmByClass('pg_cmspage').length; App.isMyAccount = !!scmByClass('pg_myaccount').length; App.supportsFlexbox = !!scmByClass('flexbox').length; App.isCollection = !!scmByClass('pg_collection').length; App.isPaidUser = isTrueString(scmById('hfAppIsPaidUser').getAttribute('value')); App.isMember = isTrueString(scmById('hfAppIsMember').getAttribute('value')); App.isIndividual = isTrueString(scmById('hfAppIsIndividual').getAttribute('value')); App.hasAccess = isTrueString(scmById('hfAppHasAccess').getAttribute('value')); App.isReferredFromGoogle = isTrueString(scmById('hfAppIsReferredFromGoogle').getAttribute('value')); var subscribedTo = scmById('hfAppSubscribedTo').getAttribute('value'); App.userSubscribedTo = subscribedTo ? subscribedTo.split(',') : undefined; App.isLucy = isTrueString(scmById('hfAppIsLucy').getAttribute('value')); App.currentJournalCount = 27; App.isChannelPage = !!(scmByClass('channels-page')); App.updateAppVariables = debounce(function () { setVariables(); }, 50, false); })(App); </script> <div class="footer-ad-wrapper"> <div id="BodyContent_Footer_divAds" class="footer-ad desktop-only"> <div class="widget-WidgetLoader widget-instance-AMA_AdTag_AnchorboardAd_btf"> <div class="SCM-SharedWidgets-AsyncAdLoader" data-url="/AMA/AdTag/AMA_AdTag_AnchorboardAd_btf" data-params="{"parameters":{"siteName":"jama","siteId":3,"journalId":67,"adDisplay":11,"adSection":"scholarly","adPosition":"btf","fromGoogle":false},"dynamicParameters":{"localParams":"[REPLACE_WITH_LOCAL]"}}"></div> </div> </div> </div> <div class="ad-riser-wrap desktop-only"> <div class="ad-riser--dismiss t-c">X</div> <div class="widget-WidgetLoader widget-instance-AMA_AdTag_Riser"> <div class="SCM-SharedWidgets-AsyncAdLoader" data-url="/AMA/AdTag/AMA_AdTag_Riser" data-params="{"parameters":{"siteName":"jama","siteId":3,"journalId":67,"adDisplay":12,"adSection":"scholarly","adPosition":"Riser","fromGoogle":false},"dynamicParameters":{"localParams":"[REPLACE_WITH_LOCAL]"}}"></div> </div> </div> <div class="footer-wrap"> <footer class="footer" id="footer"> <div id="footer-microsite" class="footer-microsite"> <input type="hidden" class="SelfServeContentId" value="v2_Footer_Left" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <style type="text/css"> @media (min-width: 1024px) {.split-screen .footer-microsite-contents {border-bottom:0 !important;}} .footer-microsite-contents {margin-bottom:1em;width:100%;} .footer-network-other .link-apps:before {width: 23px;} .footer-network-other .link-institutions-librarians:before {width: 23px;} .jn-ss-footer-border-top {border-top:1px solid #555;padding-top:15px;} .jn-ss-footer-border-bottom {border-bottom:1px solid #555;padding-bottom:10px;padding-right:3px;} </style> <div class="footer-heading-wrap"> <h3 id="BodyContent_Footer_h3SiteName" class="footer-heading is-b footer-microsite-heading" data-mobile-tog-target=".footer-microsite-links-wrap">JAMA</h3> </div> <div class="footer-microsite-links-wrap"> <div class="footer-microsite-contents jn-ss-footer-border-bottom"> <h4 id="BodyContent_Footer_ContentHeader" class="footer-subheading">Content</h4> <a href="/journals/jama">Home</a> <a href="/journals/jama/newonline">New Online</a> <a href="/journals/jama/currentissue">Current Issue</a> </div> <div class="footer-microsite-contents jn-ss-footer-border-bottom"> <h4 class="footer-subheading">Podcasts</h4> <a href="/journals/jama/pages/covid-19-interviews#audio">Coronavirus (COVID-19) Q&A</a> <a href="/journals/jama/pages/jama-clinical-reviews">Clinical Reviews</a> <a href="/journals/jama/pages/jama-editors-summary">Editors' Summary</a> <a href="/journals/jama/pages/jama-medical-news">Medical News</a> <a href="/journals/jama/pages/jama-author-interviews">Author Interviews</a> <a href="/journals/jama/pages/jamaevidence-jama-guide-to-statistics-and-methods">JAMAevidence: <em>JAMA Guide to Statistics and Methods</em></a> <a href="/journals/jama/pages/jamaevidence-the-rational-clinical-examination">JAMAevidence: The Rational Clinical Examination</a> <a href="/journals/jama/pages/jamaevidence-users-guides-to-the-medical-literature">JAMAevidence: Users' Guides to the Medical Literature</a> </div> <div class="footer-microsite-services cf"> <h4 id="BodyContent_Footer_ServiceHeader" class="footer-subheading">Journal Information</h4> <a href="/journals/jama/pages/for-authors">For Authors</a> <a href="/journals/jama/pages/jama-editors">JAMA Editors</a> <a href="/journals/jama/editors-and-publishers">Editors & Publishers</a> <a href="/pages/rss">RSS</a> <a href="/journals/jama/pages/contact-us">Contact Us</a> </div> <div class="footer-network-other jn-ss-footer-border-bottom"> <a href="https://edhub.ama-assn.org/jn-learning" class="link-network-other is-b link-learning">JN Learning / CME</a> <a href="https://store.jamanetwork.com" class="link-network-other is-b link-store" target="_blank">Store</a> <a href="/pages/apps" class="link-network-other is-b link-mobile" target="_blank">Apps</a> <a href="https://careers.jamanetwork.com/" class="link-network-other is-b link-jobs" target="_blank">Jobs</a> <a href="/pages/resources-for-librarians" class="link-network-other is-b link-institutions-librarians" target="_blank">Institutions</a> <a href="/pages/reprints-and-permissions" class="link-network-other is-b link-reprints-permissions">Reprints & Permissions</a> </div> <div id="BodyContent_Footer_divSubscribe" class="footer-microsite-subscribe"> <img src="//cdn.jamanetwork.com/UI/app/img/covers/jama.jpg" class="subscribe-image" alt="Journal Cover"> <div class="subscribe-meta"> <h4 class="subscribe-heading footer-subheading">Subscribe</h4> <a href="https://store.jamanetwork.com/productDetails.aspx?productcodeID=64" class="subscribe-submit btn">Go</a> </div> </div> </div> </div> <div id="footer-network" class="footer-network"> <input type="hidden" class="SelfServeContentId" value="v2_Footer_Middle" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <style type="text/css"> .footer-network-sites {width: 62.85542%;} .footer-network-info {width: 35.93976%} .jn-ss-subheading-mt {margin-top: 1.5em;} .jn-registered:after {content: "\00AE";font-size: 50%;vertical-align: top;} .jn-trademark:after {content: "\2122";font-size: 50%;vertical-align: top;} .nav-logo-cme-signin-container .nav-logo .site-logo img { min-width:50px;} </style> <div class="footer-heading-wrap"> <h3 class="footer-heading is-b jn-registered" data-mobile-tog-target=".footer-network-links-wrap"><strong>JAMA</strong> Network</h3> </div> <div class="footer-network-links-wrap"> <div class="footer-network-sites"> <div class="internal"> <h4 id="BodyContent_Footer_JournalHeader" class="footer-subheading">Publications</h4> <a href="/journals/jama">JAMA</a> <a href="/journals/jamanetworkopen" target="_blank">JAMA Network Open</a> <a href="/journals/jamacardiology">JAMA Cardiology</a> <a href="/journals/jamadermatology">JAMA Dermatology</a> <a href="/journals/jama-health-forum">JAMA Health Forum</a> <a href="/journals/jamainternalmedicine">JAMA Internal Medicine</a> <a href="/journals/jamaneurology">JAMA Neurology</a> <a href="/journals/jamaoncology">JAMA Oncology</a> <a href="/journals/jamaophthalmology">JAMA Ophthalmology</a> <a href="/journals/jamaotolaryngology">JAMA Otolaryngology–Head & Neck Surgery</a> <a href="/journals/jamapediatrics">JAMA Pediatrics</a> <a href="/journals/jamapsychiatry">JAMA Psychiatry</a> <a href="/journals/jamasurgery">JAMA Surgery</a> <a href="/journals/archneurpsyc">Archives of Neurology & Psychiatry (1919-1959)</a> </div> <div class="external"> <h4 class="footer-subheading">Sites</h4> <div id="BodyContent_Footer_ssFooterSiteMenu"> <div class="selfServe"> <a target="_blank" href="https://sites.jamanetwork.com/art-and-images-in-psychiatry/">Art and Images in Psychiatry</a> <a target="_blank" href="/journals/jama/pages/2023-most-viewed-jama">Best of the JAMA Network</a> <a target="_blank" href="/channels/caring-for-the-critically-ill-patient">Caring for the Critically Ill Patient</a> <a target="_blank" href="/journals/jama/pages/crosswords">Clinical Crosswords from JAMA</a> <a target="_blank" href="/journals/jama/pages/coronavirus-alert">Coronavirus Resource Center</a> <a target="_blank" href="https://ebm.jamanetwork.com/index.html">Evidence-Based Medicine: An Oral History</a> <a target="_blank" href="/pages/fishbein-fellowship">Fishbein Fellowship</a> <a target="_blank" href="/channels/genomics/">Genomics and Precision Health</a> <a target="_blank" href="/pages/health-and-the-2024-us-election">Health and the 2024 US Election</a> <a target="_blank" href="/channels/hypertension">Hypertension</a> <a target="_blank" href="/channels/health-forum/archive">JAMA Forum Archive</a> <a target="_blank" href="https://sites.jamanetwork.com/audio">JAMA Network Audio</a> <a target="_blank" href="/pages/video">JAMA Network Video</a> <a target="_blank" href="/pages/conferences">JAMA Network Conferences </a> <a target="_blank" href="/channels/ai">JAMA+ AI</a> <a target="_blank" href="/pages/jama-summit">JAMA Summit </a> <a target="_blank" href="/journals/jamasurgery/pages/statistics-and-methods">JAMA Surgery Guide to Statistics and Methods</a> <a target="_blank" href="/channels/medical-news">Medical News</a> <a target="_blank" href="/channels/monkeypox">Mpox (Monkeypox)</a> <a target="_blank" href="https://sites.jamanetwork.com/research-ethics/">Research Ethics</a> <a target="_blank" href="/pages/collections">Topics and Collections</a> <a target="_blank" href="/pages/visual-abstracts">Visual Abstracts</a> <a target="_blank" href="/channels/war">War and Health</a> <a target="_blank" href="/channels/womens-health">Women's Health</a> <h4 class="footer-subheading jn-ss-subheading-mt">Featured Articles</h4> <a href="/journals/jama/fullarticle/2781397">CONSERVE 2021 Guidelines for Reporting Trials Modified for the COVID-19 Pandemic</a> <a href="/journals/jama/fullarticle/2808296">Creation and Adoption of Large Language Models in Medicine</a> <a href="/journals/jamaoncology/fullarticle/2787350">Global Burden of Cancer, 2010-2019</a> <a href="/journals/jama/fullarticle/2797443">Global Burden of Long COVID</a> <a href="/journals/jamadermatology/fullarticle/2790344">Global Burden of Melanoma</a> <a href="/journals/jamadermatology/fullarticle/2787350">Global Burden of Skin Diseases, 1990-2017</a> <a href="/journals/jamaneurology/fullarticle/2793874">Global Disparities in Parkinson Disease</a> <a href="/journals/jama/fullarticle/2799547">Guidelines for Reporting Outcomes in Trial Protocols: The SPIRIT-Outcomes 2022 Extension</a> <a href="/journals/jamapsychiatry/fullarticle/2799486">Mass Violence and the Complex Spectrum of Mental Illness and Mental Functioning</a> <a href="/journals/jamapsychiatry/fullarticle/2793903">Neuropsychiatry Sequelae of COVID-19</a> <a href="/journals/jamaneurology/fullarticle/2810313">A New Framework for Dementia Nomenclature</a> <a href="/journals/jama/fullarticle/2800656">Organization and Performance of US Health Systems</a> <a href="/journals/jama-health-forum/fullarticle/2791195">Pharmacy Benefit Managers: History, Business Practices, Economics, and Policy</a> <a href="/journals/jama-health-forum/fullarticle/2791195">Promoting EDI in Genetics Research</a> <a href="/journals/jamacardiology/fullarticle/2781972">PTSD and Cardiovascular Disease</a> <a href="/journals/jama/fullarticle/2810754">Red Blood Cell Transfusion: 2023 AABB International Guidelines</a> <a href="/journals/jamapediatrics/fullarticle/2797600">Reimagining Children’s Rights in the US</a> <a href="/journals/jama/fullarticle/2794049">Spirituality in Serious Illness and Health</a> <a href="/journals/jama/fullarticle/2796374">The US Medicaid Program: Coverage, Financing, Reforms, and Implications for Health Equity</a> <h4 class="footer-subheading jn-ss-subheading-mt">USPSTF Recommendation Statements</h4> <a href="/journals/jama/fullarticle/2779985">Screening for Colorectal Cancer</a> <a href="/journals/jama/fullarticle/2779190">Screening for Hypertension</a> <a href="/journals/jama/fullarticle/2777244">Screening for Lung Cancer</a> <a href="/journals/jama/fullarticle/2796244">Screening for Prediabetes and Type 2 Diabetes In Children</a> <a href="/journals/jama/fullarticle/2783414">Screening for Prediabetes and Type 2 Diabetes In Adults</a> <a href="/journals/jama/fullarticle/2795521">Statins for Primary Prevention of Cardiovascular Disease</a> <a href="/journals/jama/fullarticle/2793446">Vitamin and Mineral Supplements for Primary Prevention of of Cardiovascular Disease and Cancer</a> <h4 class="footer-subheading jn-ss-subheading-mt">Blogs</h4> <a target="_blank" href="https://amastyleinsider.com/">AMA Style Insider</a> </div> </div> </div> </div> <div id="footer-network-info" class="footer-network-info"> <div class="information-for-links"> <h4 id="BodyContent_Footer_InfoHeader" class="footer-subheading">Information</h4> <a href="/pages/for-authors">For Authors</a> <a href="/pages/resources-for-librarians">For Institutions & Librarians</a> <a href="/pages/advertisers">For Advertisers</a> <a href="/pages/subscription-agents">For Subscription Agents</a> <a href="https://careers.jamanetwork.com/" target="_blank">For Employers & Job Seekers</a> <a href="https://media.jamanetwork.com" rel="nofollow" target="_blank">For the Media</a> <a href="/pages/equity-diversity-inclusion">Equity, Diversity, Inclusion</a> <a href="/pages/commenting-policy">Online Commenting Policy</a> <a href="/pages/access-at-jama-network">Public Access and Open Access Policy</a> <a href="/pages/offensive-content-statement">Statement on Potentially Offensive Content</a> </div> <div class="services-links"> <h4 id="BodyContent_Footer_JAMANetworkProductsHeader" class="footer-subheading">JAMA Network Products</h4> <a href="http://www.amamanualofstyle.com/" class="footer-service-link" target="_blank">AMA Manual of Style</a> <a href="https://jamaevidence.mhmedical.com/" class="footer-service-link" target="_blank"><span class="jn-registered">JAMAevidence</span></a> <a href="http://www.peerreviewcongress.org/" class="footer-service-link" target="_blank">Peer Review Congress</a> </div> <div class="learning-links"> <h4 id="BodyContent_Footer_LearningHeader" class="footer-subheading">JN Learning</h4> <a href="https://edhub.ama-assn.org/jn-learning">Home</a> <a href="https://edhub.ama-assn.org/jn-learning/state-cme">State CME</a> <a href="https://edhub.ama-assn.org/jn-learning/pages/clinical-challenge-courses">Clinical Challenge CME</a> <a href="https://edhub.ama-assn.org/jn-learning/course/288 ">Atrial Fibrillation Course</a> <a href="https://edhub.ama-assn.org/jn-learning/course/294 ">Women's Health Course</a> <a target="_blank" href="https://edhub.ama-assn.org/pages/auto-credit-reporting">CME / MOC Reporting Preferences</a> <a href="https://edhub.ama-assn.org/jn-learning/pages/about-cme">About CME & MOC</a> </div> </div> </div> </div> <div id="footer-resources-wrap" class="footer-resources-wrap"> <input type="hidden" class="SelfServeContentId" value="v2_Footer_Right" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <style type="text/css"> .footer-resources-wrap .footer-subheading {color: grey;display:block !important;font-size: 1.17647em;font-weight: 400;text-transform: uppercase;} </style> <div class="footer-heading-wrap"> <h3 class="footer-heading is-b footer-resources-heading" data-mobile-tog-target=".footer-resources">Help</h3> </div> <div class="footer-resources"> <a href="https://store.jamanetwork.com" class="footer-service-link" target="_blank">Subscriptions & Renewals</a> <a href="https://jamanetwork.com/oauthsignin?return_url=http%3A%2F%2Fjamanetwork.com%2Fmyaccount%23my-alerts" class="footer-service-link" rel="nofollow">Manage Emails</a> <a href="https://jamanetwork.com/oauthsignin?return_url=http%3A%2F%2Fjamanetwork.com%2Fmyaccount%23my-profile" class="footer-service-link" rel="nofollow">Update My Address</a> <a href="https://support.jamanetwork.com/hc/en-us" class="footer-service-link">Support Center</a> <a href="/myaccount " class="footer-service-link">My Account</a> <h4 class="footer-subheading jn-ss-subheading-mt">JAMA Career Center</h4> <a href="https://careers.jamanetwork.com/" class="footer-service-link" target="_blank">Physician Job Listings</a> </div> <input type="hidden" class="SelfServeContentId" value="v2_Footer_Socials" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <style type="text/css"> .widget-instance-AMA_Journal_Home_Socials .iconsocial {display: inline-block !important;width: 34px;height: 34px;min-width: unset !important;margin: 0 2px !important;background-color: #fff;border-radius: 20px;border: 1px solid #191919;vertical-align: middle;} .widget-instance-AMA_Journal_Home_Socials .iconsocial.instagram {background-image: url(https://cdn.jamanetwork.com/ImageLibrary/JamaNetwork/social/instagram-icon-black.svg);background-position: 7px 7px;background-repeat: no-repeat;background-size: 18px;} .widget-instance-AMA_Journal_Home_Socials .iconsocial.instagram:hover, .widget-instance-AMA_Journal_Home_Socials .iconsocial.instagram:focus {background-image: url(https://cdn.jamanetwork.com/ImageLibrary/JamaNetwork/social/instagram-icon-fill.png);border-color: #C13584;} .footer-resources-wrap .iconsocial {display: inline-block !important;width: 32px;height: 32px;min-width: unset !important;margin: 0 2px 0 3px !important;background-color: #fff;border-radius: 20px;border: 1px solid #191919;vertical-align: middle;} .footer-resources-wrap .iconsocial.instagram {background-image: url(https://cdn.jamanetwork.com/ImageLibrary/JamaNetwork/social/instagram-icon-black.svg);background-position: 6px 6px;background-repeat: no-repeat;background-size: 18px;} .footer-resources-wrap .iconsocial.instagram:hover, .footer-resources-wrap .iconsocial.instagram:focus {background-color: #C13584;border-color: #191919;} #load-instagram-image { background: url(https://cdn.jamanetwork.com/ImageLibrary/JamaNetwork/social/instagram-icon-fill.png) no-repeat -9999px -9999px; } </style> <div id="BodyContent_Footer_divSocial" class="social-links footer-social-links"> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="https://www.facebook.com/JAMAJournal/" class="social-link is-b facebook"></a> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="https://twitter.com/JAMA_current" class="social-link is-b twitter"></a> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="https://www.instagram.com/jamanetwork/?hl=en" class="iconsocial instagram"></a> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="https://www.linkedin.com/company/jamanetwork/" class="social-link is-b linked-in"></a> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="https://www.youtube.com/jamanetwork" class="social-link is-b you-tube"></a> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="https://www.pinterest.com/jamanetwork/" class="social-link is-b pinterest"></a> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="/rss/site_3/67.xml" class="social-link is-b rss"></a> <a target="_blank" rel="nofollow" data-emailid="6d35777a-fc12-4d2d-9b49-81d031835d91" href="https://jamanetwork.com/journals/jama/pages/jama-editors-summary" class="social-link is-b podcast"></a> <div id="load-instagram-image"> </div> </div> <div id="BodyContent_Footer_divEmailUpdate" class="footer-email-updates"> <div class="widget-EmailListSignUp widget-instance-AMAv2_EmailListSignUp_Footer"> <div class="email-signup"> <div class="email-signup--text sb-pc">Get the latest from JAMA</div> <div class="email-signup--input-wrap is-b"> <input type="text" name="email" class="email-signup--input" placeholder="Email address" title="Email address" /> <a rel="nofollow" href="javascript:;" class="email-signup--submit sb-sc btn">Sign Up</a> </div> <div class="email-signup--link"> <a class="email-signup--privacy" href="/pages/privacy-policy">Privacy Policy</a> | <a class="email-signup--terms" href="/pages/terms-of-use">Terms of Use</a></div> <div class="email-signup--user-message"></div> </div> </div> </div> </div> <div class="footer-bar" itemscope itemtype="https://schema.org/Organization"> <input type="hidden" class="SelfServeContentId" value="v2_Footer_Bottom_Bar" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <style type="text/css"> .network-bar .auth--inst {color:#B8B8B8;} .multimedia-caption-container div.video-caption {color: #262626;font-size: 15px;font-weight: 700;line-height: 1.5;} .nav-journals a.theme-jama-health-forum:before {background: #133763;} .jn-bottom-bar {color: #fff; float: left;font-size: 10px;padding: 13px 20px;width: 33.33%;} .jn-bottom-bar p {line-height: 2;} @media (max-width: 900px) {.jn-bottom-bar {float: none;width: 100%;}} .jn-footer-copyright {font-size:12px;line-height:1.5;margin-bottom:10px;} .jn-footer-pipe {margin:0 10px;} .footer-bar-jn-logo img {width: 230px;} @media (max-width: 900px) {.footer-bar-jn-logo img {width: 200px;}} [data-thm=umb] .jobs-ad--text h6 {color: #d71635 !important;} [data-thm=jama] .jobs-ad--text h6 {color: #d71635 !important;} [data-thm=jaman] .jobs-ad--text h6 {color: #ed0973 !important;} [data-thm=cardi] .jobs-ad--text h6 {color: #be1e32 !important;} [data-thm=derm] .jobs-ad--text h6 {color: #006f3b !important;} [data-thm=faci] .jobs-ad--text h6 {color: #ed1c24 !important;} [data-thm=jama-] .jobs-ad--text h6 {color: #fb5252 !important;} [data-thm=intem] .jobs-ad--text h6 {color: #006e96 !important;} [data-thm=neur] .jobs-ad--text h6 {color: #981b1e !important;} [data-thm=oncol] .jobs-ad--text h6 {color: #3b923f !important;} [data-thm=ophth] .jobs-ad--text h6 {color: #66bc29 !important;} [data-thm=otol] .jobs-ad--text h6 {color: #34b6e4 !important;} [data-thm=peds] .jobs-ad--text h6 {color: #0084c0 !important;} [data-thm=psych] .jobs-ad--text h6 {color: #005276 !important;} [data-thm=surg] .jobs-ad--text h6 {color: #f47920 !important;} .blockquote .para {margin: 0 0 1em 1em;} .jn-footer-copyright {display: block;} .inline-block {display: inline-block;} </style> <a class="footer-bar-jn-logo d-b no-mw mb1" href="/" title="JAMA Network Home"><img class="mw-100" src="https://cdn.jamanetwork.com/ImageLibrary/global/jn-signature-reversed-r.svg?versionId=82308" alt="Jama Network Logo"></a> <div class="jn-bottom-bar"> <p> <span class="jn-footer-copyright">© 2024 American Medical Association. <span class="inline-block">All rights reserved,</span> including those for text and data mining, AI training, <span class="inline-block">and similar technologies.</span></span> <span class="inline-block"><a href="https://www.ama-assn.org/about/terms-use" rel="nofollow" class="p0">Terms of Use</a><span class="jn-footer-pipe">|</span></span> <span class="inline-block"><a href="https://www.ama-assn.org/about/privacy-policy" rel="nofollow" class="p0">Privacy Policy</a><span class="jn-footer-pipe">|</span></span> <span class="inline-block"><a href="https://www.ama-assn.org/about/accessibility-statement" rel="nofollow" class="p0">Accessibility Statement</a><span class="jn-footer-pipe">|</span></span> <span class="inline-block"><a onclick="OneTrust.ToggleInfoDisplay()" rel="nofollow" class="p0" id="CookieFooter">Cookie Settings</a></span> </p> </div> <!-- #selfserve-maintenance {display:block;margin:20px 0;max-height:none !important;min-height:200px;visibility:visible;} #selfserve-maintenance {display:block;margin:20px 0;max-height:none !important;min-height:200px;visibility:visible;} --> <a class="footer-bar-sis no-mw relative nudge-down" href="https://www.silverchair.com" target="_blank"><img class="footer-bar-sis-img mt05 mw-100" width="600" height="70" src="//cdn.jamanetwork.com/UI/app/img/powered.png" alt="Silverchair Logo" /></a> </div> </footer> </div> <div class="ss-ui-only"> <div class="widget-SelfServeContent widget-instance-AMA_SS_UI_Only"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SsUiOnly" /> <input type="hidden" class="SelfServeVersionId" value="0" /> . </div> </div> </div> </section> <div id="revealModal" class="reveal-modal" data-reveal> <div id="revealContent"></div> <a class="close-reveal-modal icon-close"></a> </div> <div class="artmet-modal" id="MetricsModal"> <div class="artmet-modal-contents"> <a class="artmet-close-modal">×</a> </div> </div> <div class="widget-SigninModals widget-instance-AMA_SigninModals"> <div class="js-modal-no-access-reveal no-access reveal-modal modal tiny" data-reveal> <div class="modal--box"> <div class="modal--title">Access your subscriptions</div> <hr /> <button type="button" role="button" class="modal--btn js-btn-signin-personal" data-oauth-signin-url="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894"> Sign in<span class="fw-normal"> | personal account</span> </button> <div class="widget-AmaAdvancedSeamlessAccess widget-instance-AMA_NoAccess_AdvancedSeamlessAccessButton"> <div class="seamless-access-button--wrap"> <button class="d-flex sa-button align-items-center" role="button" type="button"> <div class="sa-button-logo-wrap"> <img src="//cdn.jamanetwork.com/UI/app/svg/seamless-access.svg" class="sa-button-logo" alt="Seamless Access Logo" /> </div> <div class="d-flex justify-content-center align-items-center sa-button-text text-truncate"> <div class="sa-button-text-primary text-truncate">Access through your institution</div> </div> </button> <div class="sa-access-text text-truncate hide"> <div class="sa-cta-access"><span>Add or change institution</span></div> </div> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_NoAccess_SigninModal_CreateAccount"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_CreateAccount" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Free access to newly published articles</div> <hr> <button class="modal--btn js-btn-create-personal-account" type="button" role="button"> <div class="text-truncate">Create a free personal account</div> </button> <div class="modal--btn-desc">To register for email alerts, access free PDF, and more</div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_CreateAccount</div>--> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_NoAccess_SigninModal_PurchaseOptions_NoAccessAndPaidPDF"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_PurchaseOptions_NoAccessAndPaidPDF" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Purchase access</div> <hr> <button class="modal--btn js-btn-subscribe-journal" type="button" role="button"> <div class="text-truncate">Subscribe to journal</div> </button> <div class="modal--btn-desc">Get full journal access for 1 year</div> <button class="modal--btn js-btn-purchase-article" type="button" role="button"> <div class="text-truncate">Buy article</div> </button> <div class="modal--btn-desc">Get unlimited access and a printable PDF ($40.00)—<br> <em>Sign in or create a free account</em></div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_PurchaseOptions_NoAccessAndPaidPDF</div>--> </div> </div> <div class="widget-DeepDyve widget-instance-AMA_NoAccess_DeepDyve"> <button type="button" role="button" class="modal--btn js-deepdyve-link hiddenRentalLink" data-deepdyveurl="https://www.deepdyve.com/doc-view?docId=10.1001/jama.2017.14171&fieldName=journal_doi&affiliateId=JAMA" data-doi="10.1001/jama.2017.14171" data-fieldname="journal_doi" data-issneissn="0098-7484" data-affiliate="JAMA">Rent article</button> <div class="modal--btn-desc js-deepdyve-desc hiddenRentalLink">Rent this article from DeepDyve</div> </div> </div> <a class="close-reveal-modal icon-close"></a> </div> <div class="js-modal-paid-pdf-reveal no-access reveal-modal modal tiny" data-reveal> <div class="modal--box"> <div class="modal--title">Access your subscriptions</div> <hr /> <button type="button" role="button" class="modal--btn js-btn-signin-personal" data-oauth-signin-url="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894"> Sign in<span class="fw-normal"> | personal account</span> </button> <div class="widget-AmaAdvancedSeamlessAccess widget-instance-AMA_PaidPdf_AdvancedSeamlessAccessButton"> <div class="seamless-access-button--wrap"> <button class="d-flex sa-button align-items-center" role="button" type="button"> <div class="sa-button-logo-wrap"> <img src="//cdn.jamanetwork.com/UI/app/svg/seamless-access.svg" class="sa-button-logo" alt="Seamless Access Logo" /> </div> <div class="d-flex justify-content-center align-items-center sa-button-text text-truncate"> <div class="sa-button-text-primary text-truncate">Access through your institution</div> </div> </button> <div class="sa-access-text text-truncate hide"> <div class="sa-cta-access"><span>Add or change institution</span></div> </div> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_PaidPdf_SigninModal_CreateAccount"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_CreateAccount" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Free access to newly published articles</div> <hr> <button class="modal--btn js-btn-create-personal-account" type="button" role="button"> <div class="text-truncate">Create a free personal account</div> </button> <div class="modal--btn-desc">To register for email alerts, access free PDF, and more</div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_CreateAccount</div>--> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_PaidPdf_SigninModal_PurchaseOptions_NoAccessAndPaidPDF"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_PurchaseOptions_NoAccessAndPaidPDF" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Purchase access</div> <hr> <button class="modal--btn js-btn-subscribe-journal" type="button" role="button"> <div class="text-truncate">Subscribe to journal</div> </button> <div class="modal--btn-desc">Get full journal access for 1 year</div> <button class="modal--btn js-btn-purchase-article" type="button" role="button"> <div class="text-truncate">Buy article</div> </button> <div class="modal--btn-desc">Get unlimited access and a printable PDF ($40.00)—<br> <em>Sign in or create a free account</em></div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_PurchaseOptions_NoAccessAndPaidPDF</div>--> </div> </div> <div class="widget-DeepDyve widget-instance-AMA_PaidPDF_DeepDyve"> <button type="button" role="button" class="modal--btn js-deepdyve-link hiddenRentalLink" data-deepdyveurl="https://www.deepdyve.com/doc-view?docId=10.1001/jama.2017.14171&fieldName=journal_doi&affiliateId=JAMA" data-doi="10.1001/jama.2017.14171" data-fieldname="journal_doi" data-issneissn="0098-7484" data-affiliate="JAMA">Rent article</button> <div class="modal--btn-desc js-deepdyve-desc hiddenRentalLink">Rent this article from DeepDyve</div> </div> </div> <a class="close-reveal-modal icon-close"></a> </div> <div class="js-modal-free-pdf-reveal no-access reveal-modal modal tiny" data-reveal> <div class="modal--box"> <div class="modal--title">Sign in to access free PDF</div> <hr /> <button type="button" role="button" class="modal--btn js-btn-signin-personal" data-oauth-signin-url="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894"> Sign in<span class="fw-normal"> | personal account</span> </button> <div class="widget-AmaAdvancedSeamlessAccess widget-instance-AMA_FreePdf_AdvancedSeamlessAccessButton"> <div class="seamless-access-button--wrap"> <button class="d-flex sa-button align-items-center" role="button" type="button"> <div class="sa-button-logo-wrap"> <img src="//cdn.jamanetwork.com/UI/app/svg/seamless-access.svg" class="sa-button-logo" alt="Seamless Access Logo" /> </div> <div class="d-flex justify-content-center align-items-center sa-button-text text-truncate"> <div class="sa-button-text-primary text-truncate">Access through your institution</div> </div> </button> <div class="sa-access-text text-truncate hide"> <div class="sa-cta-access"><span>Add or change institution</span></div> </div> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_FreePdf_SigninModal_CreateAccount"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_CreateAccount" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Free access to newly published articles</div> <hr> <button class="modal--btn js-btn-create-personal-account" type="button" role="button"> <div class="text-truncate">Create a free personal account</div> </button> <div class="modal--btn-desc">To register for email alerts, access free PDF, and more</div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_CreateAccount</div>--> </div> </div> </div> <a class="close-reveal-modal icon-close"></a> </div> <div class="js-modal-save-search-reveal no-access reveal-modal modal tiny" data-reveal> <div class="modal--box"> <div class="modal--title">Save your search</div> <hr /> <button type="button" role="button" class="modal--btn js-btn-signin-personal" data-oauth-signin-url="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894"> Sign in<span class="fw-normal"> | personal account</span> </button> <div class="widget-SelfServeContent widget-instance-AMA_SaveSearch_SigninModal_CreateAccount"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_CreateAccount" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Free access to newly published articles</div> <hr> <button class="modal--btn js-btn-create-personal-account" type="button" role="button"> <div class="text-truncate">Create a free personal account</div> </button> <div class="modal--btn-desc">To register for email alerts, access free PDF, and more</div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_CreateAccount</div>--> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_SigninModal_PurchaseOptions_SaveSearch"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_PurchaseOptions_SaveSearch" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Purchase access</div> <hr /> <button class="modal--btn js-btn-subscribe-now">Subscribe now</button> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_PurchaseOptions_SaveSearch</div>--> </div> </div> </div> <a class="close-reveal-modal icon-close"></a> </div> <div class="js-modal-follow-collection-reveal no-access reveal-modal modal tiny" data-reveal> <div class="modal--box"> <div class="modal--title">Customize your interests</div> <hr /> <button type="button" role="button" class="modal--btn js-btn-signin-personal" data-oauth-signin-url="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894"> Sign in<span class="fw-normal"> | personal account</span> </button> <div class="widget-SelfServeContent widget-instance-AMA_FollowCollection_SigninModal_CreateAccount"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_CreateAccount" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Free access to newly published articles</div> <hr> <button class="modal--btn js-btn-create-personal-account" type="button" role="button"> <div class="text-truncate">Create a free personal account</div> </button> <div class="modal--btn-desc">To register for email alerts, access free PDF, and more</div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_CreateAccount</div>--> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_SigninModal_PurchaseOptions_FollowCollection"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_PurchaseOptions_FollowCollection" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--sub-title">Create a personal account or sign in to:</div> <ul> <li>Register for email alerts with links to free full-text articles</li> <li>Access PDFs of free articles</li> <li>Manage your interests</li> <li>Save searches and receive search alerts</li> <ul> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_PurchaseOptions_FollowCollection</div>--> </div> </div> <div class="modal--link-wrap"> <a class="modal--link" href="/pages/privacy-policy" rel="nofollow">Privacy Policy</a> </div> </div> <a class="close-reveal-modal icon-close"></a> </div> <div class="js-modal-user-comment-reveal no-access reveal-modal modal tiny" data-reveal> <div class="modal--box"> <div class="modal--title">Make a comment</div> <hr /> <button type="button" role="button" class="modal--btn js-btn-signin-personal" data-oauth-signin-url="https://jamanetwork.com/oauthsignin?return_url=https%3a%2f%2fjamanetwork.com%2fjournals%2fjama%2ffullarticle%2f2654894"> Sign in<span class="fw-normal"> | personal account</span> </button> <div class="widget-SelfServeContent widget-instance-AMA_UserComment_SigninModal_CreateAccount"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_CreateAccount" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--title">Free access to newly published articles</div> <hr> <button class="modal--btn js-btn-create-personal-account" type="button" role="button"> <div class="text-truncate">Create a free personal account</div> </button> <div class="modal--btn-desc">To register for email alerts, access free PDF, and more</div> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_CreateAccount</div>--> </div> </div> <div class="widget-SelfServeContent widget-instance-AMA_SigninModal_PurchaseOptions_UserComment"> <div class="self-serve"> <input type="hidden" class="SelfServeContentId" value="SigninModal_PurchaseOptions_UserComment" /> <input type="hidden" class="SelfServeVersionId" value="0" /> <div class="modal--sub-title">Create a personal account or sign in to:</div> <ul> <li>Register for email alerts with links to free full-text articles</li> <li>Access PDFs of free articles</li> <li>Manage your interests</li> <li>Save searches and receive search alerts</li> <ul> <!--<div class="jn-selfServe-modal-label">JAMA|SigninModal_PurchaseOptions_UserComment</div>--> </div> </div> <div class="modal--link-wrap"> <a class="modal--link" href="/pages/privacy-policy" rel="nofollow">Privacy Policy</a> </div> </div> <a class="close-reveal-modal icon-close"></a> </div> <div class="hidden-true js-modal-page-data" data-store-url="https://store.jamanetwork.com" data-store-purchase-url="https://jamanetwork.com/oauthsignin?return_url=https://store.jamanetwork.com" data-store-subscribe-url="https://store.jamanetwork.com/index.aspx?productcode=64"> </div> </div> <script src="//cdn.jamanetwork.com/UI/app/vendor/jquery-2.2.4.min.js?v=638654734634555810"></script> <script>window.jQuery || document.write('<script src="/UI/app/vendor/jquery-2.2.4.min.js">\x3C/script>')</script> <script src="//cdn.jamanetwork.com/UI/app/dist/app.min.js?v=638677764559592887" defer></script> <script src="//cdn.jsdelivr.net/chartist.js/latest/chartist.min.js" type="text/javascript"></script> <script src="//d1bxh8uas1mnw7.cloudfront.net/assets/embed.js" type="text/javascript"></script> <script defer src='//js.trendmd.com/trendmd.min.js' data-trendmdconfig='{"element":"#trendmd-suggestions"}'></script> <script type='text/javascript' src='https://platform-api.sharethis.com/js/sharethis.js#property=643701de45aa460012e1032e&product=sop' async='async'></script> <script> var App = App || {}; App.showCmePromo = false; </script> </form> <link rel="stylesheet" href="//cdn.jamanetwork.com/UI/app/scss/modules/_trendMD.css"> <div class="widget-CustomJSScript widget-instance-"> <script src="//cdn.jamanetwork.com/ama/ama.proxylogging.js" async></script> </div> </body> </html>