Objective: In a previous cross-sectional pilot investigation, an increase in the ratio of active cortisol to inactive cortisone in serum has been found as a general phenomenon during the acute-phase response. The aim of the present study was to further characterize this alteration of cortisol metabolism in patients undergoing elective cardiac bypass surgery. Methods: Cortisol and cortisone were quantified by use of liquid-chromatography tandem mass spectrometry in sera that were sampled preoperatively and on the first 4 postoperative days (POD) from 16 patients undergoing aortocoronary bypass grafting (7.00 a.m.). Results: The median serum cortisol concentration peaked on the first POD and then decreased statistically significantly until the end of the observation period: preoperatively, 245 nmol/l (IQR 198–331); 1st POD, 532 nmol/l (IQR 409–678 ); 4th POD, 373 nmol/l (IQR 306–493); p for trend = 0.019. In contrast, the cortisol:cortisone ratio was constantly increased approximately twofold on all POD compared to preoperative sampling: preoperatively, 5.4 (IQR 5.0–7.2); 1st POD, 11.3 (IQR 9.2–13.6); 4th POD, 9.9 (IQR 7.7–11.0), with no significant trend of normalization. Conclusion: Following major surgery, the substantial increase in the serum cortisol:cortisone ratio – reflecting a shift in the overall set-point of 11β-hydroxysteroid dehydrogenase activity – is more sustained than the increase in serum cortisol; the increase in the cortisol:cortisone ratio seems to be a long-term phenomenon of the activation of the hypothalamic-pituitary-adrenocortical system by surgical stress and systemic inflammation.

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 chromatography-tandem mass spectrometry with an on-line sample extraction system and tri-deuterated cortisol as the internal standard, and free serum cortisol was measured after over-night equilibrium dialysis. Whereas on the first postoperative day, the median total serum cortisol concentration was approximately two-fold increased compared to preoperative samples (preoperatively, 245 nmol/l (interquartile range (IQR) 203 -293 nmol/l); first postoperative day, 512 nmol/l (IQR 410 -611 nmol/l)), median dialyzable free cortisol concentration was almost seven-fold increased (preoperatively, 14.2 nmol/l (IQR 10.9 -20.7 nmol/l); first postoperative day, 98.3 nmol/l (IQR 81.3 -134 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 5.4 -7.0%) 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 9.8 -14.0%) 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. Clin Chem Lab Med 2003; 41(2):146 -151