James 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, Balasubramanian Venkatesh
{"title":"Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial.","authors":"James 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, Balasubramanian Venkatesh","doi":"10.1007/s00134-024-07616-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":13665,"journal":{"name":"Intensive Care Medicine","volume":" ","pages":"2050-2060"},"PeriodicalIF":27.1000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588801/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Intensive Care Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00134-024-07616-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/5 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍:
Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.