{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:27:52Z","timestamp":1792787272173,"version":"4.5.0"},"reference-count":20,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Ministry of Health, France","award":["PHRC-N 2018-000671-16"],"award-info":[{"award-number":["PHRC-N 2018-000671-16"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,7,21]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>When both severe metabolic acidemia (pH equal or less than 7.20; PaCO2 equal or less than 45\u2009mm Hg and bicarbonate concentration equal or less than of 20\u2009mmol\/L) and moderate-to-severe acute kidney injury are observed, day 28 mortality is approximately 55%\u201360%. A multiple centre randomised clinical trial (BICARICU-1) has suggested that sodium bicarbonate infusion titrated to maintain the pH equal or more than 7.30 is associated with a higher survival rate (secondary endpoint) in a prespecified stratum of patients with both severe metabolic acidemia and acute kidney injury patients. Whether sodium bicarbonate infusion may improve survival at day 90 (primary outcome) in these severe acute kidney injury patients is currently unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: a randomised clinical trial (BICARICU-2) trial is an investigator-initiated, multiple centre, stratified, parallel-group, unblinded trial with a computer-generated allocation sequence and an electronic system-based randomisation. After randomisation, the intervention group will receive 4.2% sodium bicarbonate infusion to target a plasma pH equal or more than 7.30 while the control group will not receive sodium bicarbonate. The primary outcome is the day 90 mortality. Main secondary outcomes are organ support dependences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The trial has been approved by the appropriate ethics committee (CPP Nord Ouest, Rouen, France, 25 April 2019, number: 19.03.15.72446). Informed consent is required. If sodium bicarbonate improves day 90 mortality, it will become part of the routine care.<\/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=\"NCT04010630\">NCT04010630<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-073487","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T11:16:32Z","timestamp":1692270992000},"page":"e073487","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: protocol for a randomised clinical trial (BICARICU-2)"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct04010630","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04010630","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2522-1531","authenticated-orcid":false,"given":"Boris","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Medical Intensive Care, Montpellier University Hospital, Montpellier, France"},{"name":"PhyMedExp Laboratory, University of Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Huguet","sequence":"additional","affiliation":[{"name":"Department of Statistics, Montpellier Universit\u00e9 d\u2019Excellence, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Molinari","sequence":"additional","affiliation":[{"name":"Department of Statistics, Montpellier Universit\u00e9 d\u2019Excellence, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7257-8069","authenticated-orcid":false,"given":"Samir","family":"Jaber","sequence":"additional","affiliation":[{"name":"PhyMedExp Laboratory, University of Montpellier, Montpellier, France"},{"name":"Saint Eloi Department of Anesthesiology and Critical Care Medicine, Montpellier University Hospital, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"2025121605513138000_13.8.e073487.1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.e7586","article-title":"SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"Chan","year":"2013","journal-title":"BMJ"},{"key":"2025121605513138000_13.8.e073487.2","doi-asserted-by":"crossref","DOI":"10.1186\/cc10487","article-title":"Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study","volume":"15","author":"Jung","year":"2011","journal-title":"Crit Care"},{"key":"2025121605513138000_13.8.e073487.3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(18)31080-8","article-title":"Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial","volume":"392","author":"Jaber","year":"2018","journal-title":"Lancet"},{"key":"2025121605513138000_13.8.e073487.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2012.186"},{"key":"2025121605513138000_13.8.e073487.5","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-112-7-492"},{"key":"2025121605513138000_13.8.e073487.6","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199111000-00008"},{"key":"2025121605513138000_13.8.e073487.7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007121329"},{"key":"2025121605513138000_13.8.e073487.8","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-006-0408-9"},{"key":"2025121605513138000_13.8.e073487.9","doi-asserted-by":"crossref","unstructured":"Serpa Neto A , Fujii T , McNamara M , et al . Sodium bicarbonate for metabolic acidosis in the ICU: results of a pilot randomized double-blind clinical trial. Critical Care Medicine 2023;Publish Ahead of Print. doi:10.1097\/CCM.0000000000005955","DOI":"10.1097\/CCM.0000000000005955"},{"key":"2025121605513138000_13.8.e073487.10","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1053\/j.jvca.2021.10.023","article-title":"Pro: metabolic acidosis should be corrected with sodium bicarbonate in cardiac surgical patients","volume":"36","author":"Smeltz","year":"2022","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2025121605513138000_13.8.e073487.11","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1053\/j.jvca.2021.10.021","article-title":"Con: metabolic acidosis should not be corrected with sodium bicarbonate in cardiac surgical patients","volume":"36","author":"Jia","year":"2022","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2025121605513138000_13.8.e073487.12","doi-asserted-by":"crossref","first-page":"974271","DOI":"10.3389\/fphar.2022.974271","article-title":"Effectiveness of sodium bicarbonate infusion on mortality for elderly septic patients with acute metabolic acidosis","volume":"13","author":"Huang","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025121605513138000_13.8.e073487.13","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.2"},{"key":"2025121605513138000_13.8.e073487.14","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1056\/NEJMoa1603017","article-title":"Initiation strategies for renal-replacement therapy in the intensive care unit","volume":"375","author":"Gaudry","year":"2016","journal-title":"N Engl J Med"},{"key":"2025121605513138000_13.8.e073487.15","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.5828"},{"key":"2025121605513138000_13.8.e073487.16","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-012-2706-x"},{"key":"2025121605513138000_13.8.e073487.17","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1097\/CCM.0000000000005706","article-title":"Long-term outcome of severe metabolic acidemia in ICU patients, a BICAR-ICU trial post hoc analysis","volume":"51","author":"Bendiab","year":"2023","journal-title":"Crit Care Med"},{"key":"2025121605513138000_13.8.e073487.18","doi-asserted-by":"publisher","DOI":"10.1007\/BF01709751"},{"key":"2025121605513138000_13.8.e073487.19","doi-asserted-by":"crossref","DOI":"10.1186\/s13054-020-03431-2","article-title":"Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: an international observational study","volume":"25","author":"Fujii","year":"2021","journal-title":"Crit Care"},{"key":"2025121605513138000_13.8.e073487.20","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.665907","article-title":"Risk potential for organ dysfunction associated with sodium bicarbonate therapy in critically ill patients with hemodynamic worsening","volume":"8","author":"Wang","year":"2021","journal-title":"Front Med (Lausanne)"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-073487","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T13:51:37Z","timestamp":1765893097000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-073487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":20,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,17]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/bmjopen-2023-073487"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-073487","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}