Cited by 1,000Sepsis Diagnosis and TreatmentAdrenal Hormones and DisordersHyperglycemia and glycemic control in critically ill and hospitalized patients

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A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin

Annane, Djillali·2000·JAMA

DOI 10.1001/jama.283.8.1038

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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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Result
Relative Adrenal Insufficiency in Cardiogenic Shock
Briegel, J., Möhnle, P., Vogeser, M., Thiemermann, C., & Radermacher, P. (2017) · Shock · doi:10.1097/shk.0000000000000870 · Cited by 4
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Diagnosing and treating the elderly individual with hypopituitarism
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BackgroundMethodInfluential
Endocrine interventions in the intensive care unit
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Recent developments in the pharmacologic approach to pediatric critical care
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Corticosteroids and Community-Acquired Pneumonia
Violán, J. S., y Ramos, A. M., Marco, J. A., & de Castro, F. R. (2003) · Clinical Pulmonary Medicine · doi:10.1097/01.cpm.0000087611.74932.d2 · Cited by 4
Current Trends and Future Implications in Sepsis Treatment
Yıldız, B., & Yorgancı, K. (2008) · DergiPark (Istanbul University) · Cited by 4
Adrenocorticotropic hormone and cortisol response to corticotropin releasing hormone in the critically ill—a novel assessment of the hypothalamic-pituitary-adrenal axis
Schuster, K. M., MacLeod, J. B. A., Fernandez, J. B., Kumar, M., & Barquist, E. S. (2011) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2010.11.015 · Cited by 4
“The initial studies that examined provocative testing of the adrenal gland were performed in patients with sepsis physiology.(3,14,15) Improved criteria and testing in various patient populations may allow the definition of patient subgroups that will benefit from glucocorticoid replacement.”
Background
Management of septic shock: current concepts, with a particular emphasis on the role of source control, and future perspectives
Tsiotou, A. G., & Sakorafas, G. H. (2004) · European Journal of Anaesthesiology · doi:10.1017/s0265021504005010 · Cited by 4
Pharmacologic Support of the Failing Heart
London, J. A., & Sena, M. J. (2006) · Surgical Clinics of North America · doi:10.1016/j.suc.2006.08.003 · Cited by 4
Fatal Candida Septic Shock During Systemic Chemotherapy in Lung Cancer Patient Receiving Corticosteroid Replacement Therapy for Hypopituitarism: A Case Report
Morichika, D., Hisamoto, A., Hotta, K., Takata, K., Iwaki, N., Uchida, K., Minami, D., Kubo, T., Tanimoto, M., & Kiura, K. (2014) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyu019 · Cited by 4
Cortisol Levels in Children With Diabetic Ketoacidosis Associated With New-Onset Type 1 Diabetes Mellitus
Williams, K. M., Fazzio, P., Oberfield, S. E., GALLAGHER, M. P., & Aranoff, G. S. (2017) · Clinical Pediatrics · doi:10.1177/0009922816684595 · Cited by 4
Chapter 10 – The Preterm Neonate with Relative Adrenal Insufficiency and Vasopressor-resistant Hypotension
Cole, C. (2008) · Elsevier eBooks · doi:10.1016/b978-1-4160-3162-8.10010-7 · Cited by 4
Steroids and Sepsis: Time for Another Reevaluation
Kenyon, N. J., & Albertson, T. E. (2002) · Journal of Intensive Care Medicine · doi:10.1046/j.1525-1489.2002.17202.x · Cited by 4
Catheter-Related Bloodstream Infections, Part II: Specific Pathogens and Prevention
Ferretti, G., Mandalà, M., Cosimo, S. D., Moro, C., Curigliano, G., & Barni, S. (2003) · Cancer Control · doi:10.1177/107327480301000111 · Cited by 4
Adrenal tea leaves: Is the adrenal response to sepsis discernible?
Woolf, P. D. (2001) · Critical Care Medicine · doi:10.1097/00003246-200102000-00049 · Cited by 4
Testing the waters*
Zimmerman, J. J. (2007) · Pediatric Critical Care Medicine · doi:10.1097/01.pcc.0000262882.51753.d3 · Cited by 4
Shock
Terblanche, M., & Assmann, N. (2010) · Wiley eBooks · doi:10.1002/9781444314502.ch1 · Cited by 4
Adrenal insufficiency
Dannhorn, E., & O’Beirne, J. P. (2015) · Wiley eBooks · doi:10.1002/9781118412640.ch21 · Cited by 4
New concepts to further unravel adrenal insufficiency during critical illness
Boonen, E., & den Berghe, G. V. (2016) · Cited by 3
Evaluation of Serum Cortisol Levels and Response to Cosyntropin Test in Methadone-treated Opium Addicts
Zojaji, F., Khalesi, A. R., Bahrami, A., Ebrahimi, S. A., & Ganjifard, M. (2023) · Anesthesiology and Pain Medicine · doi:10.5812/aapm-135206 · Cited by 3
Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19
Wen, T.-Z., Li, T., Chen, X., Chen, H.-Y., Wang, S., Fu, W.-J., Xiao, S., Luo, J., Tang, R., Ji, J.-L., et al. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155980 · Cited by 3
La sepsis como estresor: asociación con los niveles séricos de cortisol, proteína C reactiva e interleuquina1beta
Gaydou, L., Bertuzzi, R., & Moretti, E. R. A. (2009) · Redalyc (Universidad Autónoma del Estado de México) · Cited by 2
Adrenocortical insufficiency in critical illness
Venkatesh, B., & Cohen, J. (2009) · Elsevier eBooks · doi:10.1016/b978-0-7020-3096-3.00053-1 · Cited by 3
Is Inappropriate Response to Cosyntropin Stimulation Test an Indication of Corticosteroid Resistance in Septic Shock?
Hyvernat, H., Doyen, D., Barel, R., Kaidomar, M., Goubaux, B., Pradier, C., Panaïa‐Ferrari, P., Dellamonica, J., & Bernardin, G. (2017) · Shock · doi:10.1097/shk.0000000000001014 · Cited by 3
“In the substitutive rationale, septic shock is accompanied by critical illness-related corticosteroid insufficiency (CIRCI), which is revealed by a standard cosyntropin stimulation test (CST) (5) and corrected by the administration of hydrocortisone.”
Background
Insuficiencia suprarrenal en el enfermo crítico: nuevos conceptos etiopatogénicos e implicaciones terapéuticas
Moreno, L. M., García, N. P., & García, F. J. E. (2017) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2017.09.004 · Cited by 6
Sepsis
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Inflammation-induced adrenal dysfunction
Chortis, V., & Breault, D. T. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00896-3 · Cited by 3
Critical illness-related corticosteroid insufficiency: What we know and what we don’t know
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“The use of the cosyntropin stimulation test for the diagnosis of CIRCI is based on the results of a study by Annane et al in 189 patients with septic shock in which a lower mortality was observed in those with a delta cortisol of >9 μg/dL.(12) In a subsequent study in which hydrocortisone and fludrocortisone were used…”
Method
Perioperative Addison-Krise
Martin, C., Steinke, T., Bucher, M., & Raspé, C. (2012) · Der Anaesthesist · doi:10.1007/s00101-012-2033-1 · Cited by 3
Autonomic dysfunction in SIRS and sepsis
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General anesthetics and therapeutic gases
Flockton, E., & Leuwer, M. (2012) · Side effects of drugs annual · doi:10.1016/b978-0-444-59499-0.00010-6 · Cited by 3
Adrenal insufficiency in intestinal obstruction from carcinomatosis peritonei--a factor of potential importance in symptom palliation.
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Do pediatric patients with septic shock benefit from steroid therapy? A critical appraisal of ???Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock??? by Oppert et al. (Crit Care Med 2005; 33:2457???2464)
van Schaik, S. M. (2007) · Pediatric Critical Care Medicine · doi:10.1097/01.pcc.0000257037.10815.c9 · Cited by 3
“Relative adrenal insufficiency appears to be common in septic children, but a correlation between adrenal insufficiency and mortality, as found in adults (11), has not been demonstrated for the pediatric population (12, 13).”
Background
Controversy of Corticosteroids in Septic Shock
Miyashita, M. (2010) · Journal of Nippon Medical School · doi:10.1272/jnms.77.67 · Cited by 3
The effect of methylprednisolone on treatment in rats with induced sepsis
Çeti̇nkaya, R. A., Görenek, L., Çoşkun, Ö., Eyigün, C. P., Şenses, Z., İde, T., & Kılıç, S. (2008) · Clinical and Experimental Medicine · doi:10.1007/s10238-008-0016-y · Cited by 3
“In this study, adrenal insufficiency was found to increase mortality significantly [17].”
Background

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
DOI: 10.1001/jama.283.8.1038
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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A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin

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