The Serum Cortisol:Cortisone Ratio in the Postoperative Acute-Phase Response

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.