Elevated plasma-free cortisol concentrations and ratios are associated with increased mortality even in the presence of statin therapy in patients with severe sepsis

Balasubramanian Venkatesh, Lee Imeson, Peter Kruger, Jeremy Cohen, Mark Jones, Rinaldo Bellomo

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Background: Dissociation between plasma free cortisol and total cortisol profiles exists in critical illness. Data on plasma free cortisol are based on either calculated values or immunoassay-based measurements. Both have significant limitations. Statins have been advocated as a therapy in sepsis. Whether they impact on plasma cortisol through inhibition of cholesterol synthesis is unclear. Objectives: In patients enrolled into a randomized trial of statins in sepsis (n = 250), we examined the association of mass spectrometry measured plasma free cortisol, plasma free cortisol/plasma total cortisol ratios, and outcome and the impact of concomitant statin therapy on cortisol profiles in 80 steroid naive patients. Patients: Two hundred twenty serial measurements of plasma free cortisol, plasma total cortisol, and interleukin-6 were collected from 80 patients (43 placebo and 37 statins). Data from 10 volunteers were used as controls. Measurements and Main Results: Data are presented as median and interquartile range. Compared with controls, in severe sepsis, baseline plasma total cortisol was elevated two-fold (463 nmol/L [284-742 nmol/L] vs 245 nmol/L [200-299 nmol/L], p <0.001), plasma free cortisol 20-fold (75 nmol/L [20-151 nmol/L] vs 5 nmol/L [5-7 nmol/L], p <0.001), and plasma free cortisol/plasma total cortisol ratio six-fold (0.15 vs 0.02, p = 0.058). Baseline interleukin-6 was elevated at 121 pg/mL (65-611 pg/mL). In severe sepsis, there were no differences in plasma total cortisol (p = 0.66), plasma free cortisol (p = 0.77), and interleukin-6 (p = 0.29) between statins and placebo groups. Plasma free cortisol, plasma total cortisol, and plasma free cortisol/plasma total cortisol were positively correlated with interleukin-6 (p = 0.0001, p <0.0004, and p <0.001, respectively) and day 90 mortality (p = 0.03, p = 0.03, and p = 0.058, respectively). Elevated plasma free cortisol/plasma total cortisol ratios were associated with increased length of st
Original languageEnglish
Pages (from-to)630 - 635
Number of pages6
JournalCritical Care Medicine
Volume43
Issue number3
DOIs
Publication statusPublished - 2015

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