Glucocorticoid sensitivity is highly variable in critically ill patients with septic shock and is associated with disease severity

Cohen, Jeremy, Pretorius, Carel J., Ungerer, Jacobus P. J., Cardinal, John, Blumenthal, Antje, Presneill, Jeff, Gatica-Andrades, Marcela, Jarrett, Paul, Lassig-Smith, Melissa, Stuart, Janine, Dunlop, Rachel, Starr, Therese and Venkatesh, Bala (2016) Glucocorticoid sensitivity is highly variable in critically ill patients with septic shock and is associated with disease severity. Critical Care Medicine, 44 6: 1034-1041. doi:10.1097/CCM.0000000000001633


Author Cohen, Jeremy
Pretorius, Carel J.
Ungerer, Jacobus P. J.
Cardinal, John
Blumenthal, Antje
Presneill, Jeff
Gatica-Andrades, Marcela
Jarrett, Paul
Lassig-Smith, Melissa
Stuart, Janine
Dunlop, Rachel
Starr, Therese
Venkatesh, Bala
Title Glucocorticoid sensitivity is highly variable in critically ill patients with septic shock and is associated with disease severity
Journal name Critical Care Medicine   Check publisher's open access policy
ISSN 1530-0293
0090-3493
Publication date 2016-06-01
Year available 2016
Sub-type Article (original research)
DOI 10.1097/CCM.0000000000001633
Open Access Status Not Open Access
Volume 44
Issue 6
Start page 1034
End page 1041
Total pages 8
Place of publication Philadelphia, PA United States
Publisher Lippincott Williams & Wilkins
Collection year 2017
Language eng
Formatted abstract
Objectives: To measure tissue glucocorticoid sensitivity in patients with septic shock and determine its relationship to standard measurements of adrenal function and of outcome.

Design: Prospective observational trial.

Setting: Teaching hospital ICU.

Subjects: Forty-one patients and 20 controls were studied.
Interventions: Glucocorticoid sensitivity was measured by in vitro suppression of cytokine production from lipopolysaccharide-stimulated leukocytes.

Measurements and Main Results: There was no significant difference between the groups in the relative suppression of cytokine production, although there was a greater range and variance in the patient data. Patients in the lowest quartile of glucocorticoid sensitivity had higher Acute Physiology and Chronic Health Evaluation II scores (25 [24–28] vs 20 [14–23]; p = 0.02) and a trend toward higher mortality (30% vs 0%; p = 0.2) compared to those in the highest. The mRNA expression of the [beta] variant of the glucocorticoid receptor and the 11-[beta] hydroxysteroid dehydrogenase 2 isozyme were significantly higher in patients compared to controls (8.6-fold, p = 0.002 and 10.1-fold, p = 0.0002, respectively). Changes in mRNA expression of these genes did not correlate with measurements of glucocorticoid sensitivity.

Conclusions: Patients with septic shock and controls do not differ in their median glucocorticoid sensitivity. However, patients exhibited a greater variability in glucocorticoid responsiveness and had evidence of association between increased sickness sensitivity and reduced glucocorticoid sensitivity. Sensitivity to glucocorticoids did not appear to be mediated by changes in the expression of the [beta] variant of the glucocorticoid receptor or the 11-[beta] hydroxysteroid dehydrogenase 2 isozyme.
Keyword Adrenal insufficiency
Cortisol
Glucocorticoid resistance
Septic shock
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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