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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1781-1792 |
| Journal | Intensive Care Medicine |
| Volume | 43 |
| Issue number | 12 |
| Early online date | 21 Sept 2017 |
| DOIs | |
| Publication status | Published - Dec 2017 |
Keywords
- Corticosteroid insufficiency
- critical illness
- sepsis
- glucocorticoids
- glucocorticoid receptor