Free serum cortisol during the postoperative acute phase response determined by equilibrium dialysis liquid chromatography-tandem mass spectrometry

In severely ill patients low concentrations of the corticosteroid
binding globulin are typically found; the aim of this study was to
quantify directly free bioactive cortisol concentrations in the
sera of postoperative cardiosurgical patients. Serum samples of 12
consecutive patients undergoing aortocoronary bypass surgery taken
preoperatively and on the postoperative days 1 to 4 were analyzed.
Total serum cortisol was quantified using liquid
chromatographytandem mass spectrometry with an online sample
extraction system and trideuterated cortisol as the internal
standard, and free serum cortisol was measured after overnight
equilibrium dialysis. Whereas on the first postoperative day, the
median total serum cortisol concentration was approximately twofold
increased compared to preoperative samples (preoperatively, 245
nmol/l (interquartile range (IQR) 203293 nmol/l); first
postoperative day, 512 nmol/l (IQR 410611 nmol/l)), median
dialyzable free cortisol concentration was almost sevenfold
increased (preoperatively, 14.2 nmol/l (IQR 10.920.7 nmol/l); first
postoperative day, 98.3 nmol/l (IQR 81.3134 nmol/l)). On the fourth
postoperative day, median free cortisol was still significantly
increased compared to baseline sampling (p < 0.05), whereas
median total cortisol was not. A median of 5.7% (IQR 5.47.0%) of
total cortisol was found as free cortisol on the preoperative day,
21.2% (IQR 18.9 23.5%) on the first postoperative day and 10.5%
(IQR 9.814.0%) on the fourth postoperative day. It is concluded
that during the postoperative period the freeto bound ratio of
cortisol is highly variable and that during the acute phase
response direct quantification of free bioactive cortisol
concentrations seems to be biologically more appropriate than the
measurement of total cortisol concentrations.