Author:

Keywords:

0601 Biochemistry and Cell Biology, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine, Endocrinology & Metabolism, 3202 Clinical sciences, 3215 Reproductive medicine

Abstract:

Objective: Critical illness is hallmarked by low plasma ACTH in the face of high plasma cortisol.1,2 We hypothesized that frequently used drugs could play a role by affecting the hypothalamic-pituitary-adrenal axis. Methods: For 156 medical-surgical critically ill patients, plasma concentrations of ACTH and total and free cortisol were quantified upon ICU admission and throughout the first 3 ICU days. The independent associations between drugs administered 24h prior to ICU-admission and plasma ACTH and cortisol concentrations upon ICU-admission were quantified with use of multivariable linear regression analyses. Results: Upon ICU-admission, compared with healthy subjects, patients revealed low mean±SEM plasma ACTH concentrations (11.8±2.7 pg ml-1 vs. 41.0±7.2 pg ml-1, P<0.0001) in the face of unaltered total plasma cortisol (12.2±1.1 µg dl-1 vs. 10.9±0.6 µg dl-1, P=0.3) and elevated free plasma cortisol concentrations (1.5±0.2 µg dl-1 vs. 0.2±0.03 µg dl-1, P=0.04). Plasma ACTH concentrations remained low (P<0.001) until day 3 whereas plasma (free)cortisol concentrations steeply increased and remained high (P<0.001). No independent correlations with plasma ACTH were found. In contrast, the total admission plasma cortisol concentration was independently and negatively associated with the cumulative opioid (P=0.001) and propofol (P=0.02) dose, the use of etomidate (P=0.03), and positively with the cumulative dobutamine dose (P=0.0007). Conclusions: Besides the known suppressive effect of etomidate, also opioids and propofol may suppress and dobutamine increase plasma cortisol in a dose-dependent manner. The observed independent associations suggest drug effects not mediated centrally via ACTH, but rather peripherally by a direct or indirect action on the adrenal cortex.