Free cortisol in sepsis and septic shock.
BACKGROUND
Severe sepsis activates the hypothalamopituitary axis, increasing cortisol production. In some studies, hydrocortisone substitution based on an adrenocorticotropic hormone-stimulation test or baseline cortisol measurement has improved outcome. Because only the free fraction of cortisol is active, measurement of free cortisol may be more important than total cortisol in critically ill patients. We measured total and free cortisol in patients with severe sepsis and related the concentrations to outcome.


METHODS
In a prospective study, severe sepsis was defined according the American College of Chest Physicians/Society of Critical Care Medicine criteria. Blood samples were drawn within 24 h of study entry. Serum cortisol was analyzed by electrochemiluminescence immunoassay. The Coolens method was used for calculating serum free cortisol concentrations.


RESULTS
Blood samples were collected from 125 patients, of whom 62 had severe sepsis and 63 septic shock. Hospital mortality was 21%. Calculated free serum cortisol correlated well with serum total cortisol (r = 0.90, P < 0.001). There was no difference in the total cortisol concentrations in patients with sepsis and septic shock (728 +/- 386 nmol/L vs 793 +/- 439 nmol/L, P = 0.44). Nonsurvivors had higher calculated serum free (209 +/- 151 nmol/L) and total (980 +/- 458 nmol/L) cortisol concentrations than survivors (119 +/- 111 nmol/L, P = 0.002, and 704 +/- 383 nmol/L, P = 0.002). Depending on the definition, the incidence of adrenal insufficiency varied from 8% to 54%.


CONCLUSIONS
Clinically, calculation of free cortisol does not provide essential information for identification of patients who would benefit from corticoid treatment in severe sepsis and septic shock.
Bendel
Stepani
S
Department of Intensive Care, Kuopio University Hospital, PL 16222 Kuopio, Finland. Stepani.Bendel@kuh.fi
Karlsson
Sari
S
Pettilä
Ville
V
Loisa
Pekka
P
Varpula
Marjut
M
Ruokonen
Esko
E
D000304:Adrenal Cortex Function Tests; D000309:Adrenal Insufficiency / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005387:Finland / Q000453:epidemiology; D017052:Hospital Mortality; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D016896:Treatment Outcome
D015415:Biomarkers; D006854:Hydrocortisone