Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a multispecialty task force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)
Author(s)
Type
Journal Article
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 (SCCM) and the European Society of Intensive Care Medicine (ESICM).
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 the 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.
PARTICIPANTS: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM).
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 the 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.
Date Issued
2017-12-01
Date Acceptance
2017-09-01
Citation
Critical Care Medicine, 2017, 45 (12), pp.2089-2098
ISSN
0090-3493
Publisher
Lippincott, Williams & Wilkins
Start Page
2089
End Page
2098
Journal / Book Title
Critical Care Medicine
Volume
45
Issue
12
Copyright Statement
Copyright © 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/28938251
Subjects
11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1
Corticosteroid insufficiency
Critical Care Medicine
critical illness
GENE-EXPRESSION
General & Internal Medicine
glucocorticoid receptor
GLUCOCORTICOID-RECEPTOR-ALPHA
glucocorticoids
Life Sciences & Biomedicine
NITRIC-OXIDE SYNTHASE
PERSISTENT ELEVATION
PITUITARY-ADRENAL AXIS
RESPIRATORY-DISTRESS-SYNDROME
Science & Technology
sepsis
SEPTIC SHOCK
SYSTEMIC INFLAMMATION
TUMOR-NECROSIS-FACTOR
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2017-09-21