Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma

Objective: To study the time course of corticosteroid binding-globulin (CBG ) level and the free cortisol index (FCI) in comparison with total cortisol and ACTH concentrations during acute and prolonged critical illness. Design: Prospective observational clinical study. Setting: Twenty-bed medical/surgical intensive care unit. Patients and participants: Thirty patients with septic shock, eight patient s with multitrauma, and forty healthy control subjects. Measurements and results: During 14 days or until discharge/death, we seria lly measured serum concentrations of CBG, cortisol, TNF-alpha, IL-6, plasma ACTH immunoreactivity, and the FCI (= cortisol/CBG x 100). We also recorde d haemodynamic parameters, APACHE II, ISS, SOFA scores, shock duration, ino trope use, and ICU mortality. In both groups we found markedly decreased CB G levels in the early phase (septic shock: 17.5 +/- 5.9, and trauma: 16.1 /- 2.3 mg/l) in comparison with controls (37.3 +/- 5.3 mg/l). The FCI was h igh in this early phase (septic shock: 7.2 +/- 2.7; trauma: 6.5 +/- 1.3, co ntrols: 1.25 +/- 0.76). During follow-up, CBG levels significantly increase d, reaching normal levels from day 7 on. The FCI showed an opposite biphasi c pattern, with near-normalising FCI values during the second phase. Regres sion analysis showed a negative correlation between CBG and IL-6 levels (r( s) = -0.63; P < 0.05), but no relation between CBG concentrations and disea se severity, shock duration or death was found. Conclusions: We found extremely low CBG levels in early stage septic shock and multitrauma. These dramatic changes are reflected in a concomitant high er FCI, indicating a higher free cortisol level. A second phase displays in creasing and normalising CBG levels, independent from clinical parameters. We believe that CBG plays an active role in the glucocorticoid response to severe stress and in the regulation of cortisol availability to target tiss ues.