{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:27:38Z","timestamp":1792009658330,"version":"4.4.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1162182"],"award-info":[{"award-number":["1162182"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001773","name":"University of New South Wales","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001773","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Intensive Care Med"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The combination of intravenous hydrocortisone and enteral fludrocortisone may reduce mortality in patients with septic shock. The optimal dose and reliability of absorption of fludrocortisone in critically ill patients are unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In a multi-centre, open label, phase II randomized clinical trial, intravenous hydrocortisone alone or in combination with one of three doses of enteral fludrocortisone (50\u00a0\u00b5g, 100\u00a0\u00b5g or 200\u00a0\u00b5g daily) for 7\u00a0days was compared in patients with septic shock. The primary outcome was time to shock resolution. We conducted pharmacokinetic studies to assess absorption.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Out of 153 enrolled patients, 38 (25%) received hydrocortisone alone, 42 (27%) received additional 50\u00a0\u00b5g, 36 (24%) received 100\u00a0\u00b5g and 37 (24%) received 200\u00a0\u00b5g fludrocortisone. Plasma concentrations of fludrocortisone were detected in 97% of patients at 3\u00a0h-median (interquartile range [IQR]) 261 (156\u2013334) ng\/L. There was no significant difference in the time to shock resolution between groups with median (IQR) of 3 (2.5\u20134.5), 3 (2\u20134), 3 (2\u20136) and 3 (2\u20135.5) days in the hydrocortisone alone, 50\u00a0\u00b5g, 100\u00a0\u00b5g and 200\u00a0\u00b5g fludrocortisone groups, respectively. The corresponding 28-day mortality rates were 9\/38 (24%), 7\/42 (17%), 4\/36 (11%) and 4\/37 (11%), respectively. There were no significant differences between groups with respect to, recurrence of shock, indices of organ failure or other secondary outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Enteral fludrocortisone resulted in detectable plasma fludrocortisone concentrations in the majority of critically ill patients with septic shock, although they varied widely indicating differing absorption and bioavailability. Its addition to hydrocortisone was not associated with shorter time to shock resolution.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00134-024-07616-z","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T09:05:12Z","timestamp":1725527112000},"page":"2050-2060","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Fludrocortisone dose\u2013response relationship in septic shock: a randomised phase II 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BV and NH receive institutional research support from Baxter for the conduct of a clinical trial in patients with diabetic ketoacidosis. AB is supported by an Australian Research Council Future Fellowship and grants from the Translational Research Institute, Australian Infectious diseases Research Centre and Metro South health. JD, MR and LM are supported by a grant from the Hospital Research Foundation. MY is supported by a grant from the Baker Foundation and the Australian Research Council. SF has received consulting fees from RevImmune Inc and is Director of Sepsis Australia (honorary) and Asia Pacific Sepsis Alliance (honorary). All other others do not report any conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}