Background: Sepsis and septic shock produce marked hypercortisolaemia . Cortisol maintains vascular tone and cardiac contractility and has potent anti-inflammatory effects crucial to survival. Circulating CBG transports 80% of cortisol. Cleavage of high cortisol-binding affinity CBG (haCBG) reduces CBG:cortisol binding affinity 10-fold, producing high and low cortisol-binding affinity CBG (laCBG) and elevating free cortisol levels. We propose that prolonged inflammation may lead to depletion of haCBG, limiting cortisol distribution to inflammatory sites and perpetuating chronic inflammation. We measured haCBG and laCBG in sepsis and septic shock.
Hypothesis: That sepsis causes marked depletion in haCBG in accordance with illness severity, comparing septic shock to sepsis.
Methods: A prospective, observational cohort study was performed in an adult tertiary level intensive care unit in Adelaide, Australia, between May and October 2013.Twice-daily blood samples were collected for up to five days from patients with initial diagnoses of sepsis (S) or septic shock (SS).Total and haCBG were assayed in parallel with specific monoclonal antibodies using our novel in-house method . Free and total cortisol were also measured.
Results: 103 samples from 29 patients were analysed. These were categorised into S, SS or SS with death (SS-D). haCBG decreased in accordance with illness severity category (p = 0.0003). haCBG levels fell significantly from (mean±SEM) 411.7±13.0 to 318.3±22.4 to 201.7±30.9 and 151.2±22.2nmol/L, in control, S, SS and SS-D groups respectively. Patients dying with septic shock had the lowest proportion of haCBG to total CBG of all groups at 54.3 (6.1) %.
Conclusion: haCBG, which may have a crucial role in cortisol transport to inflammatory sites, bore a close relationship to illness severity. We suggest that depletion of available haCBG may impair optimal tissue delivery of cortisol in critical illness.
This project was undertaken whilst holding a Royal Adelaide Hospital AR Clarkson Scholarship and 2014 Clinical Project Grant