Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine
Abstract
OBJECTIVE: To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients. PARTICIPANTS: A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. In addition, international experts in endocrinology were invited to participate. DESIGN/METHODS: The task force members reviewed published literature and provided expert opinion from which the consensus was derived. The consensus statements were developed using a modified Delphi methodology. The strength of each recommendation was quantified using the Modified GRADE system, which classifies recommendations as strong (grade 1) or weak (grade 2) and the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on factors that include the study design, the consistency of the results, and the directness of the evidence. RESULTS: The task force coined the term critical illness-related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness. Critical illness-related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response. Critical illness-related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents, particularly in the setting of sepsis. At this time, the diagnosis of tissue corticosteroid resistance remains problematic. Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 microg/dL after adrenocorticotrophic hormone (250 microg) administration or a random total cortisol of < 10 microg/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome (PaO2/FiO2 of < 200 and within 14 days of onset). The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids. Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day (10 mg/hr) for > or = 7 days is recommended for septic shock. Methylprednisolone in a dose of 1 mg x kg(-1) x day(-1) for > or = 14 days is recommended in patients with severe early acute respiratory distress syndrome. Glucocorticoids should be weaned and not stopped abruptly. Reinstitution of treatment should be considered with recurrence of signs of sepsis, hypotension, or worsening oxygenation. Dexamethasone is not recommended to treat critical illness-related corticosteroid insufficiency. The role of glucocorticoids in the management of patients with community-acquired pneumonia, liver failure, pancreatitis, those undergoing cardiac surgery, and other groups of critically ill patients requires further investigation. CONCLUSION: Evidence-linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary, multispecialty task force.
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Since some of these patients were hospitalized, it is possible that low levels of cortisol binding proteins may have accounted for some of the impaired cortisol responses.
“Since some of these patients were hospitalized, it is possible that low levels of cortisol binding proteins may have accounted for some of the impaired cortisol responses [40].”
From New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol Assays (2021) · cites this paper as [40]
HPA axis dysfunction occurs in 10-20% of critically ill medical patients and up to 60% of septic shock patients, depending on population and diagnostic criteria.
“Depending on the population of patients studied and the diagnostic criteria, dysfunction of the HPA axis has been estimated to occur at rates from 10 to 20% in critically ill medical patients to as high as 60% in patients with septic shock [1].”
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Bornstein, S. R., Allolio, B., Arlt, W., Barthel, A., Don-Wauchope, A., Hammer, G. D., Husebye, E. S., Merke, D. P., Murad, M. H., Stratakis, C. A., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1710 · Cited by 1,769 · see citing works
“Although similar arguments for the utility of the low-dose test have been proposed for other special diagnostic challenges such as the detection of adrenal insufficiency in critically ill patients (critical illness-related corticosteroid insufficiency), more evidence is needed to support such a formal recommendation (…”
BackgroundSelf-citationBacterial infections in cirrhosis: A position statement based on the EASL Special Conference 2013
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- Authors
- Marik, P. E., Pastores, S. M., Annane, D., Meduri, G. U., Sprung, C. L., Arlt, W., Keh, D., Briegel, J., Beishuizen, A., Dimopoulou, I., Tsagarakis, S., Singer, M., Chrousos, G. P., Zaloga, G., Bokhari, F., & Vogeser, M.
- Affiliations
- Thomas Jefferson University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Hôpital Raymond-Poincaré (FR)
- Hadassah Medical Center (IL)
- University of Birmingham (GB)
- Humboldt-Universität zu Berlin (DE)
- Ludwig-Maximilians-Universität München (DE)
- National and Kapodistrian University of Athens (GR)
- Polyclinic General Hospital (GR)
- University College London (GB)
- John H. Stroger, Jr. Hospital of Cook County (US)
- ORCID
- Venue
- Critical Care Medicine
- Published
- 2008-06
- Volume
- 36
- Issue
- 6
- Pages
- 1937-1949
- ISSN
- 0090-3493 (ISSN-L)
- OpenAlex
- W2142927411
- Cited by
- 912
- References
- 127
- Citations by year
- 2026: 13 · 2025: 34 · 2024: 28 · 2023: 28 · 2022: 23 · 2021: 34 · 2020: 30 · 2019: 44 · 2018: 36 · 2017: 52 · 2016: 39 · 2015: 66 · 2014: 74 · 2013: 69 · 2012: 64
- FWCI
- 66.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- critical illness-related corticosteroid insufficiency, adrenal insufficiency, hypothalamic-pituitary-adrenal axis, glucocorticoid therapy, cortisol, septic shock, acute respiratory distress syndrome, adrenocorticotropic hormone stimulation test, pro-inflammatory response
- MeSH terms
- Adrenal Cortex Hormones, Adrenal Insufficiency, Adrenocorticotropic Hormone, Adult, Anti-Inflammatory Agents, Critical Care, Delphi Technique, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Infusions, Intravenous, Methylprednisolone, Pituitary-Adrenal System, Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, Evidence-Based Medicine
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