{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:16:14Z","timestamp":1774113374956,"version":"3.50.1"},"reference-count":16,"publisher":"BMJ","issue":"7","funder":[{"name":"Hamilton Health Sciences New Investigator Fund"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2017,6,26]]},"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Observational evidence suggests physiological benefits and lower mortality with lower chloride solutions; however, 0.9% saline remains the most widely used fluid worldwide. Given uncertainty regarding the association of lower chloride on mortality, it is unlikely that practice will change without direct randomised clinical trial (RCT) evidence. This pilot RCT will investigate the feasibility of a large-scale trial directly comparing low chloride with high chloride fluids in patients with septic shock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a randomised, concealed, blinded parallel-group multicentre pilot trial. We will include adult critically ill patients with septic shock, defined as ongoing hypotension despite 1 L of fluid, or a serum lactate &gt;4\u2009mmol\/L, who are within 6\u2009hours of hospital presentation or rapid response team activation. We will exclude patients if they have an aetiology of shock other than sepsis, if they have acute burn injury, elevated intracranial pressure, intent to withdraw life support or previous enrolment in this or a competing trial. Following informed consent, patients will be randomised to a low chloride fluid strategy or a high chloride fluid strategy for the duration of their ICU stay or until 30 days postrandomisation. Clinicians, patients, families and research staff will be blinded. The primary outcome for this trial will be feasibility, assessed by consent rate, recruitment success and protocol adherence. Patient-important clinical outcomes include mortality, receipt of renal replacement therapy, intensive care unit and hospital lengths of stay and surrogate outcomes of incidence of acidosis, hyperkalaemia and acute kidney injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This pilot trial will test the feasibility of conducting the main trial, which will examine the effect of high versus low chloride fluids in patients with septic shock on patient-important outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT02748382, registered 8 April 2016.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Protocol date<\/jats:title>\n                    <jats:p>1 July 2016.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2017-017602","type":"journal-article","created":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T20:40:28Z","timestamp":1500583228000},"page":"e017602","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Fluids in Sepsis and Septic Shock (FISSH): protocol for a pilot randomised controlled trial"],"prefix":"10.1136","volume":"7","clinical-trial-number":[{"clinical-trial-number":"nct02721654","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02875873","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Bram","family":"Rochwerg","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Millen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peggy","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Zeller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9rick","family":"D\u2019Aragon","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke et Facult\u00e9 de M\u00e9decine et des Sciences dela Sant\u00e9, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Jaeschke","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-H\u00e9l\u00e8ne","family":"Masse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangeeta","family":"Mehta","sequence":"additional","affiliation":[{"name":"Mount Sinai Hospital and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francois","family":"Lamontagne","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke et Facult\u00e9 de M\u00e9decine et des Sciences dela Sant\u00e9, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Meade","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon","family":"Guyatt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-7061","authenticated-orcid":false,"given":"Deborah J","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2017,7,20]]},"reference":[{"key":"2025121401041356000_7.7.e017602.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4683-6"},{"key":"2025121401041356000_7.7.e017602.2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.20452\/pamw.1972","article-title":"Fluid resuscitation in severe sepsis and septic shock: systematic description of fluids used in randomized trials","volume":"123","author":"Rochwerg","year":"2013","journal-title":"Pol Arch Med Wewn"},{"key":"2025121401041356000_7.7.e017602.3","unstructured":"Rochwerg BZM , Millen T , Kavsak P , et al . Chloride concentration of IV albumin solutions available at Canadianhospitals. Canadian Critical Care Forum Abstract, 2015."},{"key":"2025121401041356000_7.7.e017602.4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.13356"},{"key":"2025121401041356000_7.7.e017602.5","doi-asserted-by":"publisher","DOI":"10.7326\/M14-0178"},{"key":"2025121401041356000_7.7.e017602.6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.12334"},{"key":"2025121401041356000_7.7.e017602.7","doi-asserted-by":"crossref","first-page":"e311","DOI":"10.1016\/j.jcrc.2011.10.007","article-title":"Fluid resuscitation with 5% albumin versus normal saline in early septic shock: a pilot randomized, controlled trial","volume":"27","author":"McIntyre","year":"2012","journal-title":"J Crit Care"},{"key":"2025121401041356000_7.7.e017602.8","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.iccn.2013.04.006","article-title":"Enhancing the informed consent process for critical care research: strategies from a thromboprophylaxis trial","volume":"29","author":"Smith","year":"2013","journal-title":"Intensive Crit Care Nurs"},{"key":"2025121401041356000_7.7.e017602.9","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-011659","article-title":"CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients","volume":"6","author":"Kho","year":"2016","journal-title":"BMJ Open"},{"key":"2025121401041356000_7.7.e017602.10","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1007\/s00134-016-4237-3","article-title":"Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial","volume":"42","author":"Lamontagne","year":"2016","journal-title":"Intensive Care Med"},{"key":"2025121401041356000_7.7.e017602.11","doi-asserted-by":"publisher","DOI":"10.5492\/wjccm.v1.i2.40"},{"key":"2025121401041356000_7.7.e017602.12","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e3283632e42"},{"key":"2025121401041356000_7.7.e017602.13","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e3283632d46"},{"key":"2025121401041356000_7.7.e017602.14","first-page":"279","article-title":"Advances in fluid resuscitation in critically ill patients: implications for clinical practice","volume":"19","author":"Myburgh","year":"2013","journal-title":"Curr Opin Crit Care"},{"key":"2025121401041356000_7.7.e017602.15","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e3283632d77"},{"key":"2025121401041356000_7.7.e017602.16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280503"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2017-017602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T09:04:19Z","timestamp":1765703059000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2017-017602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":16,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7,20]]},"published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1136\/bmjopen-2017-017602"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2017-017602","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]}}}