TY - JOUR
T1 - Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia
AU - Cortés-Puch, Irene
AU - Hicks, Caitlin W.
AU - Sun, Junfeng
AU - Solomon, Steven B.
AU - Eichacker, Peter Q.
AU - Sweeney, Daniel A.
AU - Nieman, Lynnette K.
AU - Whitley, Elizabeth M.
AU - Behrend, Ellen N.
AU - Natanson, Charles
AU - Danner, Robert L.
N1 - Publisher Copyright:
© 2014 American Physiological Society. All Rights reserved.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycor-ticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hypore-sponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsive-ness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.
AB - The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycor-ticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hypore-sponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsive-ness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.
KW - Adrenal insufficiency
KW - Adrenocorticotropic hormone
KW - Aldosterone
KW - Corticosteroids
KW - Cortisol
KW - Sepsis
KW - Septic shock
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U2 - 10.1152/ajpendo.00345.2014
DO - 10.1152/ajpendo.00345.2014
M3 - Article
C2 - 25294215
AN - SCOPUS:84913568831
SN - 0193-1849
VL - 307
SP - E994-E1008
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 11
ER -