Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Abstract Rationale Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients. Objectives We investigated whether steroid profiles before and after corticotropin stimulation can predict the ri...

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Main Authors: Josef Briegel, Patrick Möhnle, Didier Keh, Johanna M. Lindner, Anna C. Vetter, Holger Bogatsch, Dorothea Lange, Sandra Frank, Ludwig C. Hinske, Djillali Annane, Michael Vogeser, SepNet Critical Care Trials Group
Format: Article
Language:English
Published: BMC 2022-11-01
Series:Critical Care
Subjects:
Online Access:https://doi.org/10.1186/s13054-022-04224-5
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author Josef Briegel
Patrick Möhnle
Didier Keh
Johanna M. Lindner
Anna C. Vetter
Holger Bogatsch
Dorothea Lange
Sandra Frank
Ludwig C. Hinske
Djillali Annane
Michael Vogeser
SepNet Critical Care Trials Group
author_facet Josef Briegel
Patrick Möhnle
Didier Keh
Johanna M. Lindner
Anna C. Vetter
Holger Bogatsch
Dorothea Lange
Sandra Frank
Ludwig C. Hinske
Djillali Annane
Michael Vogeser
SepNet Critical Care Trials Group
author_sort Josef Briegel
collection DOAJ
description Abstract Rationale Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients. Objectives We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis. Methods An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC–MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality. Measurements and main results Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70–0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality. Conclusions In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death. Trial registration Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254 .
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spelling doaj.art-ec704e575f7f401088f955b755c3edee2022-12-22T04:14:14ZengBMCCritical Care1364-85352022-11-0126111010.1186/s13054-022-04224-5Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS studyJosef Briegel0Patrick Möhnle1Didier Keh2Johanna M. Lindner3Anna C. Vetter4Holger Bogatsch5Dorothea Lange6Sandra Frank7Ludwig C. Hinske8Djillali Annane9Michael Vogeser10SepNet Critical Care Trials GroupDepartment of Anesthesiology, University Hospital, LMU MunichDepartment of Transfusion Medicine, Cellular Therapeutics and Hemostaseology, Department of Anesthesiology, LMU MunichDepartment of Anesthesiology and Intensive Care Medicine, Charité University HospitalInstitute of Laboratory Medicine, University Hospital, LMU MunichInstitute of Laboratory Medicine, University Hospital, LMU MunichClinical Trial Centre, Leipzig UniversityDepartment of Anesthesiology, University Hospital, LMU MunichDepartment of Anesthesiology, University Hospital, LMU MunichDepartment of Anesthesiology, University Hospital, LMU MunichGeneral ICU - Raymond Poincaré Hospital, Assistance Publique - Hôpitaux de Paris (APHP)Institute of Laboratory Medicine, University Hospital, LMU MunichAbstract Rationale Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients. Objectives We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis. Methods An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC–MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality. Measurements and main results Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70–0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality. Conclusions In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death. Trial registration Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254 .https://doi.org/10.1186/s13054-022-04224-5SepsisShockSepticSteroidsMass spectrometryCorticosterone
spellingShingle Josef Briegel
Patrick Möhnle
Didier Keh
Johanna M. Lindner
Anna C. Vetter
Holger Bogatsch
Dorothea Lange
Sandra Frank
Ludwig C. Hinske
Djillali Annane
Michael Vogeser
SepNet Critical Care Trials Group
Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
Critical Care
Sepsis
Shock
Septic
Steroids
Mass spectrometry
Corticosterone
title Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
title_full Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
title_fullStr Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
title_full_unstemmed Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
title_short Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
title_sort corticotropin stimulated steroid profiles to predict shock development and mortality in sepsis from the hypress study
topic Sepsis
Shock
Septic
Steroids
Mass spectrometry
Corticosterone
url https://doi.org/10.1186/s13054-022-04224-5
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