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A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin
Abstract
CONTEXT: The hypothalamic-pituitary-adrenal axis is a major determinant of the host response to stress. The relationship between its activation and patient outcome is not known. OBJECTIVE: To evaluate the prognostic value of cortisol levels and a short corticotropin stimulation test in patients with septic shock. DESIGN AND SETTING: Prospective inception cohort study conducted between October 1991 and September 1995 in 2 teaching hospital adult intensive care units in France. PARTICIPANTS: A total of 189 consecutive patients who met clinical criteria for septic shock. INTERVENTION: A short corticotropin stimulation test was performed in all patients by intravenously injecting 0.25 mg of tetracosactrin; blood samples were taken immediately before the test (T0) and 30 (T30) and 60 (T60) minutes afterward. MAIN OUTCOME MEASURES: Twenty-eight-day mortality as a function of variables collected at the onset of septic shock, including cortisol levels before the corticotropin test and the cortisol response to corticotropin (delta max, defined as the difference between T0 and the highest value between T30 and T60). RESULTS: The 28-day mortality was 58% (95% confidence interval [CI], 51%-65%) and median time to death was 17 days (95% CI, 14-27 days). In multivariate analysis, independent predictors of death (P < or = .001 for all) were McCabe score greater than 0, organ system failure score greater than 2, arterial lactate level greater than 2.8 mmol/L, ratio of PaO2 to fraction of inspired oxygen no more than 160 mm Hg, cortisol level at T0 greater than 34 microg/dL and delta max no more than 9 microg/dL. Three groups of patient prognoses were identified: good (cortisol level at T0 < or = 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 26%), intermediate (cortisol level at T0 34 microg/dL and delta max < or = 9 microg/dL or cortisol level at T0 > 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 67%), and poor (cortisol level at T0 > 34 microg/dL and delta max < or = 9 microg/dL; 28-day mortality rate, 82%). CONCLUSION: Our data suggest that a short corticotropin test has a good prognostic value and could be helpful in identifying patients with septic shock at high risk for death.
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“Short-term hormone dysfunction could also be explained by acute phase inflammation and stress49505152.”
From Endocrine dysfunction following traumatic brain injury: a 5-year follow-up nationwide-based study (2016) · cites this paper as [51]
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“Nevertheless, inadequate adrenal responses have been associated with a poor prognosis in the critically ill (52), and replacement of corticosteroids may improve outcome (53).”
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Hydrocortisone Supplementation Enhances Hemodynamic Stability in Brain-dead Patients
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“The value of supplementary dose of hydrocortisone infusion has been demonstrated variously in patients with septic shock.22,23 Annane et al.21 demonstrated that 7-day shock reversal was achieved significantly more often in treated patients versus in controlled patients, implying a decrease in mortality rate of 31%.”
BackgroundMcKenzie, H. C. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-44329-6.00020-6 · Cited by 46
Individualized prediction of depressive disorder in the elderly: A multitask deep learning approach
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Adrenal Insufficiency in Septic Shock
Maxime, V., Lesur, O., & Annane, D. (2009) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2008.10.003 · Cited by 39
“It is proposed that a baseline cortisol of less than 10 mg/dL or a delta cortisol of less than 9 mg/dL (250 nmol/L) after a 250-mg ACTH infusion test should prompt intensive care unit physicians to consider that adrenal insufficiency is likely,(62,63) and that so-called ‘‘nonresponders’’ are less responsive to vasopre…”
BackgroundSelf-citationCritical Illness–Related Corticosteroid Insufficiency in Small Animals
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“The delta cortisol concentration has been advocated as a method to identify critically ill patients with CIRCI in both human and veterinary medicine.(46,72,73) A study in human patients with septic shock(72) found that basal cortisol concentrations of 34 mg/dL (938 nmol/L) or less combined with delta cortisol concentr…”
MethodPlasma cytokine levels predict response to corticosteroids in septic shock
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Etomidate, Adrenal Function, and Mortality in Critically Ill Patients
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Time for a consensus definition of corticosteroid insufficiency in critically ill patients *
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Endocrine dysfunction following traumatic brain injury: a 5-year follow-up nationwide-based study
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Adrenocortical (dys)function in septic shock - A sick euadrenal state
Venkatesh, B., & Cohen, J. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2011.04.007 · Cited by 36
Hypopituitarism in Traumatic Brain Injury—A Critical Note
Klose, M., & Feldt‐Rasmussen, U. (2015) · Journal of Clinical Medicine · doi:10.3390/jcm4071480 · Cited by 39
“Profound and variable changes occur during the first week after admission for critical illness in the hypothalamo-pituitary-adrenal (HPA)-axis, including HPA-activation [11], reduction in cortisol degradation [12], as well as lowering of cortisol binding globulin [9,13], and increased tissue sensitivity to glucocortic…”
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“…present study was the low number of foals in each of the groups, making it difficult to detect significant differences among groups many studies 4,55,56 of adrenal dysfunction and RAI in people patients with severe sepsis (eg, sepsis with multiorgan dysfunction) and septic shock (ie, severe…”
BackgroundCan 1 μg of Cosyntropin Be Used to Evaluate Adrenal Insufficiency in Critically Ill Patients?
Kozyra, E. F., Wax, R., & Burry, L. (2005) · Annals of Pharmacotherapy · doi:10.1345/aph.1e139 · Cited by 38
Corticosteroids and Septic Shock
Abraham, E. H. (2002) · JAMA · doi:10.1001/jama.288.7.886 · Cited by 36
Langouche, L., Téblick, A., Gunst, J., & den Berghe, G. V. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad021 · Cited by 40
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Role of Corticosteroids in Septic Shock
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Severe Sepsis and Septic Shock in the Emergency Department
Talan, D. A., Moran, G. J., & Abrahamian, F. M. (2008) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2007.09.005 · Cited by 37
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“This relative adrenal failure can be verified by stimulation testing with exogenous ACTH; respective cutoff values have been demonstrated to be of prognostic significance (42) and are used to guide low-dose cortisol substitution (1, 41).”
The use of corticosteroids in severe sepsis and acute respiratory distress syndrome
Chadda, K., & Annane, D. (2002) · Annals of Medicine · doi:10.1080/078538902321117805 · Cited by 36
Self-citationKlose, M., & Feldt‐Rasmussen, U. (2008) · Pituitary · doi:10.1007/s11102-008-0102-x · Cited by 34
“All these changes make assessment extremely difficult as common biochemical definitions of hypoadrenalism cannot be used [9, 10, 15].”
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Metadata
- Authors
- Annane, D.
- Affiliations
- Hôpital Raymond-Poincaré (FR)
- Corresponding author
- Annane, Djillali
- ORCID
- Annane, Djillali
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2000-02-23
- Volume
- 283
- Issue
- 8
- Pages
- 1038
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2156618518
- Cited by
- 1,000
- References
- 40
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 15 · 2023: 19 · 2022: 15 · 2021: 13 · 2020: 19 · 2019: 22 · 2018: 27 · 2017: 27 · 2016: 27 · 2015: 26 · 2014: 44 · 2013: 35 · 2012: 38
- FWCI
- 38.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- 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
- Keywords
- septic shock, cortisol, ACTH stimulation test, tetracosactrin, hypothalamic-pituitary-adrenal axis, prognostic stratification, 28-day mortality, stress response, organ failure, lactate, PaO2/FiO2 ratio, intensive care unit patients, corticosteroid therapy, sepsis
- MeSH terms
- Adult, Cosyntropin, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Prognosis, Prospective Studies, Severity of Illness Index, Shock, Septic, Biomarkers, Multivariate Analysis, Proportional Hazards Models, Survival Analysis
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