Serum cortisol level and depth of propofol-induced sedationSir, Recently, it was demonstrated that preoperative anxiety modified the amount of propofol required for induction and maintenance of anesthesia (1). Another study similarly suggested that increased anxiety before surgery was associated with increased intraoperative anesthetic requirements (2). Anxiety is known to elicit physiological stress responses, including an elevation of the serum cortisol level. Cortisol has been found to modulate the central nerve system (3), and an increase in neuronal activity by the iontophoretic application of cortisol was demonstrated in rat brain (4). It can be hypothesized that cortisol response modulates an anesthetic effect and depth of sedation with intravenous anesthetic. Thus, we investigated the relationship between the serum cortisol level and the depth of propofolinduced sedation.After local Ethics Committee approval, we studied 11 healthy male volunteers aged 26-39 years taking no chronic medications, for whom written informed consent was obtained. To avoid possible diurnal variations in the serum cortisol level, all studies started at 09.30 hours. Following a rest of 20 min, propofol was administered at a rate of 6 mg.kg À1 .h À1 for the initial 5 min, then maintained at a rate of 3 mg.kg À1 .h À1 . Venous blood samples for the measurement of serum cortisol and propofol were obtained before propofol infusion (baseline) and at 30, 60, and 90 min after the start of infusion. Depth of sedation was assessed using the Ramsay scale and the bispectral index (BIS) value obtained with a BIS monitor (model A-1050, Aspect Medical Systems, Inc., Newton, MA) immediately before blood collection. Serum cortisol and propofol were measured using an enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Statistical analyses of changes in each variable over time were performed by repeated-measures ANOVA, followed by the Bonferroni t-test, and the relationship between the variables by analysis of linear regression or Kendall's rank correlation coefficients. Significant difference was defined as P < 0.05.Bispectral index values and serum cortisol levels significantly decreased at 30, 60, and 90 min after the start of propofol infusion in a similar pattern. Ramsay scales during sedation varied among the subjects and ranged between 2 and 5, increasing significantly after the propofol administration. The depth of sedation indicated by the Ramsay scale and the BIS value was significantly related to the serum cortisol level and blood propofol concentration. However, there was no relationship between the serum cortisol level and the blood propofol concentration. Furthermore, the serum cortisol level at baseline was significantly related to the Ramsay scales and the BIS values at 30 and 60 min after the start of propofol infusion. A subject with a low baseline serum cortisol level had a tendency to experience deeper sedation than a subject with a higher level. In particular, a strong relationship betwee...
