Djillali Annane1, Stephen M Pastores2, Wiebke Arlt3, Robert A Balk4, Albertus Beishuizen5, Josef Briegel6, Joseph Carcillo7, Mirjam Christ-Crain8, Mark S Cooper9, Paul E Marik10, Gianfranco Umberto Meduri11, Keith M Olsen12, Bram Rochwerg13, Sophia C Rodgers14, James A Russell15, Greet Van den Berghe16. 1. General ICU Department, Raymond Poincaré hospital (APHP), Health Science Centre Simone Veil, Université Versailles SQY-Paris Saclay. 2. Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America. 3. Institute of Metabolism and Systems Research (IMSR), University of Birmingham & Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham, United Kingdom. 4. Division of Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago, IL, United States of America. 5. Department of Intensive Care Medicine, Medisch Spectrum Twente, Enschede, Netherlands. 6. Anesthesiology and Critical Care Medicine, Klinik für Anästhesiologie, Klinikum der Universität, Munich, Germany. 7. Department of Critical Care Medicine and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America. 8. Department of Endocrinology, Diabetology and Metabolism, Department of Clinical Research, University Hospital Basel, Basel, Switzerland. 9. Department of Endocrinology, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia. 10. Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, United States of America. 11. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Memphis Veterans Affairs Medical Center, Memphis, TN, United States of America. 12. Dean, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America. 13. Division of Critical Care, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 14. Clinical Adjunct Faculty, University of New Mexico and Sandoval Regional Medical Center, Albuquerque, NM, United States of America. 15. Division of Critical Care Medicine, Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada. 16. Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University and Hospitals, B-3000 Leuven, Belgium.
Abstract
OBJECTIVE: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI). PARTICIPANTS: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews. RESULTS: Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity. CONCLUSIONS: Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.
OBJECTIVE: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI). PARTICIPANTS: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews. RESULTS: Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity. CONCLUSIONS: Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.
Authors: Ben Gibbison; Daniel M Keenan; Ferdinand Roelfsema; Jon Evans; Kirsty Phillips; Chris A Rogers; Gianni D Angelini; Stafford L Lightman Journal: J Clin Endocrinol Metab Date: 2020-05-01 Impact factor: 5.958
Authors: Gianfranco Umberto Meduri; Djillali Annane; Marco Confalonieri; George P Chrousos; Bram Rochwerg; Amanda Busby; Barbara Ruaro; Bernd Meibohm Journal: Intensive Care Med Date: 2020-11-04 Impact factor: 41.787