Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial

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dc.contributor.authorWalsham, J.
dc.contributor.authorHammond, N.
dc.contributor.authorBlumenthal, A.
dc.contributor.authorCohen, J.
dc.contributor.authorMyburgh, J.
dc.contributor.authorFinfer, S.
dc.contributor.authorEvans, D.
dc.contributor.authorPeake, S.
dc.contributor.authorKruger, P.
dc.contributor.authorMcCullough, J.
dc.contributor.authorJohnk, L.
dc.contributor.authorGhelani, D.
dc.contributor.authorBillot, L.
dc.contributor.authorShan, S.
dc.contributor.authorMeyer, J.
dc.contributor.authorRajbhandari, D.
dc.contributor.authorKoch, C.
dc.contributor.authorBellomo, R.
dc.contributor.authorBurrell, L.M.
dc.contributor.authorYoung, M.
dc.contributor.authoret al.
dc.date.issued2024
dc.description.abstractThe 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. 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 µg, 100 µg or 200 µg daily) for 7 days was compared in patients with septic shock. The primary outcome was time to shock resolution. We conducted pharmacokinetic studies to assess absorption. Out of 153 enrolled patients, 38 (25%) received hydrocortisone alone, 42 (27%) received additional 50 µg, 36 (24%) received 100 µg and 37 (24%) received 200 µg fludrocortisone. Plasma concentrations of fludrocortisone were detected in 97% of patients at 3 h-median (interquartile range [IQR]) 261 (156-334) ng/L. There was no significant difference in the time to shock resolution between groups with median (IQR) of 3 (2.5-4.5), 3 (2-4), 3 (2-6) and 3 (2-5.5) days in the hydrocortisone alone, 50 µg, 100 µg and 200 µg 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. 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.
dc.description.statementofresponsibilityJames Walsham, Naomi Hammond, Antje Blumenthal, Jeremy Cohen, John Myburgh, Simon Finfer, David Evans, Sandra Peake, Peter Kruger, James McCullough, Loki Johnk, Dhaval Ghelani, Laurent Billot, Sana Shan, Jason Meyer, Dorrilyn Rajbhandari, Carolyn Koch, Rinaldo Bellomo, Louise M. Burrell, Morag Young, Michael Roberts, Lorraine Mackenzie, Gregory Medley, Joshua Dalton, and Balasubramanian Venkatesh
dc.identifier.citationIntensive Care Medicine, 2024; 50(12):2050-2060
dc.identifier.doi10.1007/s00134-024-07616-z
dc.identifier.issn0342-4642
dc.identifier.issn1432-1238
dc.identifier.orcidPeake, S. [0000-0001-6682-7973]
dc.identifier.urihttps://hdl.handle.net/2440/143687
dc.language.isoen
dc.publisherSpringer
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1162182
dc.rights© 2024 Crown, corrected publication 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.
dc.source.urihttps://doi.org/10.1007/s00134-024-07616-z
dc.subjectFludrocortisone
dc.subjectHydrocortisone
dc.subjectPharmacokinetics
dc.subjectSeptic shock
dc.subject.meshHumans
dc.subject.meshShock, Septic
dc.subject.meshCritical Illness
dc.subject.meshHydrocortisone
dc.subject.meshFludrocortisone
dc.subject.meshAnti-Inflammatory Agents
dc.subject.meshTreatment Outcome
dc.subject.meshDrug Therapy, Combination
dc.subject.meshDose-Response Relationship, Drug
dc.subject.meshAged
dc.subject.meshMiddle Aged
dc.subject.meshFemale
dc.subject.meshMale
dc.titleFludrocortisone dose-response relationship in septic shock: a randomised phase II trial
dc.typeJournal article
pubs.publication-statusPublished

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