{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:03:02Z","timestamp":1789646582117,"version":"4.0.0"},"reference-count":37,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"unspecified","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Resp Res"],"accepted":{"date-parts":[[2026,8,31]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Mechanical power (MP) of ventilation is a summary variable of determinants of ventilator-induced lung injury and is consistently associated with worse outcomes. Lung-protective ventilation (LPV) using a lower respiratory rate (RR) is an appealing strategy to reduce MP, but it is unclear whether reducing RR is feasible and safe in critically ill patients under invasive mechanical ventilation. Therefore, we test the hypothesis that a ventilation strategy that targets the lowest acceptable RR is feasible and safe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      The \u2018Effects of PERMISSive Lung-protective Ventilation on Outcome in Critically Ill, Invasively Ventilated Patients (PERMISS)\u2019 pilot study is an international, multicentre randomised clinical feasibility and safety trial in critically ill, invasively ventilated adult patients with an expected duration of ventilation &gt;24\u2009hours. Patients will be randomly assigned to \u2018permissive\u2019 LPV with a lower RR, within safety limits of arterial partial pressure of carbon dioxide (PaCO\n                      <jats:sub>2<\/jats:sub>\n                      ) and pH, compared with conventional LPV with RR to target normal PaCO\n                      <jats:sub>2<\/jats:sub>\n                      and pH. The primary endpoint is the difference in RR between the two groups from the start of ventilation until the first extubation. Secondary endpoints include safety, assessed by the incidence of unacceptable hypercapnia (PaCO\n                      <jats:sub>2<\/jats:sub>\n                      &gt;70\u2009mm Hg and pH&lt;7.20), severe hypoxaemia (arterial partial pressure of oxygen (PaO\n                      <jats:sub>2<\/jats:sub>\n                      )&lt;60\u2009mm Hg), ventilator-associated complications and compliance with the protocol and quality of data collection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>\n                      The current version of the protocol is V.3 (issued on 11 December 2025). The trial was approved by the medical research ethics committee of Leiden Den Haag Delft (approval number NL-009624.P25.028) on 2 June 2025, including all amendments, and was registered on\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"www.ClinicalTrials.gov\">www.ClinicalTrials.gov<\/jats:ext-link>\n                      (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT07077174\">NCT07077174<\/jats:ext-link>\n                      ). The PERMISS pilot is currently recruiting patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT07077174\">NCT07077174<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjresp-2026-004532","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:25:22Z","timestamp":1789644322000},"page":"e004532","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of PERMISSive lung-protective ventilation on outcome in critically ill, invasively ventilated patients (PERMISS): protocol for a feasibility and safety randomised clinical trial"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct07077174","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct07077174","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct07077174","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2140-0808","authenticated-orcid":false,"given":"Alessandro","family":"Caroli","sequence":"first","affiliation":[{"name":"Intensive Care, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands"},{"name":"Department of Intensive Care, Austin Hospital, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarens","family":"Hoogenboom","sequence":"additional","affiliation":[{"name":"Intensive Care, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Bugedo","sequence":"additional","affiliation":[{"name":"Department of Physical Care, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe L","family":"Damiani","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Respiratory ICU, University of Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Gama de","family":"Abreu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Anesthesia, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Willem","family":"Geerts","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Reinier de Graaf Hospital, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P","family":"Grady","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Hospital Group Twente, Almelo, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie S","family":"List","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Dijklander Hospital, Hoorn, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M P","family":"van Meenen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Amsterdam University Medical Centres, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Morales-Quinteros","sequence":"additional","affiliation":[{"name":"Intensive Care Department, Vall d\u2019Hebron University Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederique","family":"Paulus","sequence":"additional","affiliation":[{"name":"Intensive Care, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ary","family":"Serpa Neto","sequence":"additional","affiliation":[{"name":"Department of Critical Care, Austin Hospital, Heidelberg, Victoria, Australia"},{"name":"Monash University Australian and New Zealand Intensive Care Research Centre, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus J","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Medical University of Vienna, Vienna, Austria"},{"name":"Department of Anaesthesiology, Rescue- and Pain Medicine, Cantonal Hospital St. Gallen, St Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur S","family":"Slutsky","sequence":"additional","affiliation":[{"name":"Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwalpreet","family":"Sodhi","sequence":"additional","affiliation":[{"name":"Department of Critical Care, Deep Hospital, Ludhiana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Urlings-Strop","sequence":"additional","affiliation":[{"name":"Intensive care, Reinier de Graaf Gasthuis, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A","family":"Buiteman-Kruizinga","sequence":"additional","affiliation":[{"name":"Intensive Care, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands"},{"name":"Department of Intensive Care, Reinier de Graaf Hospital, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PERMISS collaborative group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"2026091704251276000_13.1.e004532.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421801"},{"key":"2026091704251276000_13.1.e004532.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208707"},{"key":"2026091704251276000_13.1.e004532.3","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S2213-2600(23)00225-4","article-title":"Ultra-low tidal volume ventilation for lung protection: not so fast","volume":"11","author":"Buiteman-Kruizinga","year":"2023","journal-title":"Lancet Respir Med"},{"key":"2026091704251276000_13.1.e004532.4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/anae.16537","article-title":"Association of ventilation volumes, pressures and rates with the mechanical power of ventilation in patients without acute respiratory distress syndrome: exploring the impact of rate reduction","volume":"80","author":"Buiteman-Kruizinga","year":"2025","journal-title":"Anaesthesia"},{"key":"2026091704251276000_13.1.e004532.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-016-4505-2"},{"key":"2026091704251276000_13.1.e004532.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-018-5375-6"},{"key":"2026091704251276000_13.1.e004532.7","doi-asserted-by":"crossref","DOI":"10.1186\/s13054-020-02963-x","article-title":"Effect of mechanical power on intensive care mortality in ARDS patients","volume":"24","author":"Coppola","year":"2020","journal-title":"Crit Care"},{"key":"2026091704251276000_13.1.e004532.8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/EJA.0000000000001778","article-title":"Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome: An analysis of three randomised clinical trials","volume":"40","author":"van Meenen","year":"2023","journal-title":"Eur J Anaesthesiol"},{"key":"2026091704251276000_13.1.e004532.9","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S2213-2600(20)30325-8","article-title":"Time-varying intensity of mechanical ventilation and mortality in patients with acute respiratory failure: a registry-based, prospective cohort study","volume":"8","author":"Urner","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2026091704251276000_13.1.e004532.10","doi-asserted-by":"crossref","DOI":"10.1186\/s40560-023-00662-7","article-title":"Mechanical power and 30-day mortality in mechanically ventilated, critically ill patients with and without Coronavirus Disease-2019: a hospital registry study","volume":"11","author":"Azizi","year":"2023","journal-title":"J Intensive Care"},{"key":"2026091704251276000_13.1.e004532.11","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1097\/ALN.0000000000001056","article-title":"Mechanical Power and Development of Ventilator-induced Lung Injury","volume":"124","author":"Cressoni","year":"2016","journal-title":"Anesthesiology"},{"key":"2026091704251276000_13.1.e004532.12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1164\/rccm.202009-3467OC","article-title":"Ventilatory Variables and Mechanical Power in Patients with Acute Respiratory Distress Syndrome","volume":"204","author":"Costa","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026091704251276000_13.1.e004532.13","doi-asserted-by":"publisher","DOI":"10.1111\/aas.13830"},{"key":"2026091704251276000_13.1.e004532.14","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s00134-016-4571-5","article-title":"Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study","volume":"42","author":"Laffey","year":"2016","journal-title":"Intensive Care Med"},{"key":"2026091704251276000_13.1.e004532.15","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1164\/rccm.201804-0726CI","article-title":"The Injurious Effects of Elevated or Nonelevated Respiratory Rate during Mechanical Ventilation","volume":"199","author":"Akoumianaki","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026091704251276000_13.1.e004532.16","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1001\/jama.2018.14280","article-title":"Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS","volume":"320","author":"Simonis","year":"2018","journal-title":"JAMA"},{"key":"2026091704251276000_13.1.e004532.17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.23517"},{"key":"2026091704251276000_13.1.e004532.18","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1001\/jama.2025.24384","article-title":"Effect of Automated Closed-Loop Ventilation vs Protocolized Conventional Ventilation on Ventilator-Free Days in Critically Ill Adults","volume":"335","author":"Sinnige","year":"2026","journal-title":"JAMA"},{"key":"2026091704251276000_13.1.e004532.19","doi-asserted-by":"crossref","DOI":"10.1186\/s40635-025-00782-4","article-title":"Effect of decreasing respiratory rate on the mechanical power of ventilation and lung injury biomarkers: a randomized cross-over clinical study in COVID-19 ARDS patients","volume":"13","author":"Damiani","year":"2025","journal-title":"Intensive Care Med Exp"},{"key":"2026091704251276000_13.1.e004532.20","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.09938"},{"key":"2026091704251276000_13.1.e004532.21","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.2.9811008"},{"key":"2026091704251276000_13.1.e004532.22","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200207000-00001"},{"key":"2026091704251276000_13.1.e004532.23","first-page":"1022","article-title":"Epidemiological Characteristics, Ventilator Management, and Clinical Outcome in Patients Receiving Invasive Ventilation in Intensive Care Units from 10 Asian Middle-Income Countries (PRoVENT-iMiC): An International, Multicenter, Prospective Study","volume":"104","author":"Pisani","year":"2021","journal-title":"Am J Trop Med Hyg"},{"key":"2026091704251276000_13.1.e004532.24","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S2213-2600(16)30305-8","article-title":"Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study","volume":"4","author":"Neto","year":"2016","journal-title":"Lancet Respir Med"},{"key":"2026091704251276000_13.1.e004532.25","doi-asserted-by":"crossref","first-page":"e130","DOI":"10.1016\/j.bja.2020.02.018","article-title":"Ventilatory frequency during intraoperative mechanical ventilation and postoperative pulmonary complications: a hospital registry study","volume":"125","author":"Santer","year":"2020","journal-title":"Br J Anaesth"},{"key":"2026091704251276000_13.1.e004532.26","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000159532.56865.8A"},{"key":"2026091704251276000_13.1.e004532.27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.chest.2020.02.033","article-title":"Impact of Respiratory Rate and Dead Space in the Current Era of Lung Protective Mechanical Ventilation","volume":"158","author":"Lellouche","year":"2020","journal-title":"Chest"},{"key":"2026091704251276000_13.1.e004532.28","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000194533.75481.03"},{"key":"2026091704251276000_13.1.e004532.29","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1513\/AnnalsATS.202102-104OC","article-title":"An Exploratory Analysis of the Association between Hypercapnia and Hospital Mortality in Critically Ill Patients with Sepsis","volume":"19","author":"Tiruvoipati","year":"2022","journal-title":"Ann Am Thorac Soc"},{"key":"2026091704251276000_13.1.e004532.30","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1016\/j.chest.2020.05.605","article-title":"Patterns and Impact of Arterial CO2 Management in Patients With Acute Respiratory Distress Syndrome: Insights From the LUNG SAFE Study","volume":"158","author":"Madotto","year":"2020","journal-title":"Chest"},{"key":"2026091704251276000_13.1.e004532.31","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00134-022-06640-1","article-title":"The role of acute hypercapnia on mortality and short-term physiology in patients mechanically ventilated for ARDS: a systematic review and meta-analysis","volume":"48","author":"Gendreau","year":"2022","journal-title":"Intensive Care Med"},{"key":"2026091704251276000_13.1.e004532.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.10.014"},{"key":"2026091704251276000_13.1.e004532.33","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s00134-016-4611-1","article-title":"Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome","volume":"43","author":"Nin","year":"2017","journal-title":"Intensive Care Med"},{"key":"2026091704251276000_13.1.e004532.34","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1001\/jamaneurol.2018.0123","article-title":"Association of Hypercapnia and Hypercapnic Acidosis With Clinical Outcomes in Mechanically Ventilated Patients With Cerebral Injury","volume":"75","author":"Tiruvoipati","year":"2018","journal-title":"JAMA Neurol"},{"key":"2026091704251276000_13.1.e004532.35","doi-asserted-by":"crossref","first-page":"e649","DOI":"10.1097\/CCM.0000000000002332","article-title":"Effects of Hypercapnia and Hypercapnic Acidosis on Hospital Mortality in Mechanically Ventilated Patients","volume":"45","author":"Tiruvoipati","year":"2017","journal-title":"Crit Care Med"},{"key":"2026091704251276000_13.1.e004532.36","doi-asserted-by":"crossref","unstructured":"World Medical Association . World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA 2013;310. doi:10.1001\/jama.2013.281053","DOI":"10.1001\/jama.2013.281053"},{"key":"2026091704251276000_13.1.e004532.37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/105294199277860","article-title":"The international conference on harmonization good clinical practice guideline","volume":"6","author":"Dixon","year":"1999","journal-title":"Quality Assurance"}],"container-title":["BMJ Open Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjresp-2026-004532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:25:28Z","timestamp":1789644328000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopenrespres.bmj.com\/lookup\/doi\/10.1136\/bmjresp-2026-004532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,9,17]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1136\/bmjresp-2026-004532"],"URL":"https:\/\/doi.org\/10.1136\/bmjresp-2026-004532","relation":{},"ISSN":["2052-4439"],"issn-type":[{"value":"2052-4439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]}}}