Glucocorticoids with or without fludrocortisone in septic shock : a narrative review from a biochemical and molecular perspective
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved..
Two randomised controlled trials have reported a reduction in mortality when adjunctive hydrocortisone is administered in combination with fludrocortisone compared with placebo in septic shock. A third trial did not support this finding when hydrocortisone administered in combination with fludrocortisone was compared with hydrocortisone alone. The underlying mechanisms for this mortality benefit remain poorly understood. We review the clinical implications and potential mechanisms derived from laboratory and clinical data underlying the beneficial role of adjunctive fludrocortisone with hydrocortisone supplementation in septic shock. Factors including distinct biological effects of glucocorticoids and mineralocorticoids, tissue-specific and mineralocorticoid receptor-independent effects of mineralocorticoids, and differences in downstream signalling pathways between mineralocorticoid and glucocorticoid binding at the mineralocorticoid receptor could contribute to this interaction. Furthermore, pharmacokinetic and pharmacodynamic disparities exist between aldosterone and its synthetic counterpart fludrocortisone, potentially influencing their effects. Pending publication of well-designed, randomised controlled trials, a molecular perspective offers valuable insights and guidance to help inform clinical strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:132 |
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| Enthalten in: |
British journal of anaesthesia - 132(2024), 1 vom: 01. Jan., Seite 53-65 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nethathe, Gladness D [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 21.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bja.2023.10.034 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Two randomised controlled trials have reported a reduction in mortality when adjunctive hydrocortisone is administered in combination with fludrocortisone compared with placebo in septic shock. A third trial did not support this finding when hydrocortisone administered in combination with fludrocortisone was compared with hydrocortisone alone. The underlying mechanisms for this mortality benefit remain poorly understood. We review the clinical implications and potential mechanisms derived from laboratory and clinical data underlying the beneficial role of adjunctive fludrocortisone with hydrocortisone supplementation in septic shock. Factors including distinct biological effects of glucocorticoids and mineralocorticoids, tissue-specific and mineralocorticoid receptor-independent effects of mineralocorticoids, and differences in downstream signalling pathways between mineralocorticoid and glucocorticoid binding at the mineralocorticoid receptor could contribute to this interaction. Furthermore, pharmacokinetic and pharmacodynamic disparities exist between aldosterone and its synthetic counterpart fludrocortisone, potentially influencing their effects. Pending publication of well-designed, randomised controlled trials, a molecular perspective offers valuable insights and guidance to help inform clinical strategies | ||
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