Examining the Variability in Adrenal Cortical Suppression Among Patients Receiving Etomidate for General Anesthesia in Morning vs. Evening Sessions: A Randomized Clinical Trial

Etomidate provides significant clinical benefits; however, its potential to suppress adrenal cortical function raises concerns. Adrenocorticosteroid secretion follows a distinct circadian rhythm, peaking in the morning and declining significantly in the evening. Nevertheless, the impact of these fluctuations on etomidate-induced adrenal suppression and postoperative outcomes remains unclear. In this study, we aim to investigate the differences in the inhibitory effects of etomidate on adrenal cortical function when administered in the morning versus the evening. 156 participants were randomized into the Morning Group (M group, receiving anesthesia between 8:00 and 9:00 AM) or the Evening Group (E group, receiving anesthesia between 4:00 and 5:00 PM). Anesthesia induction involved 0.3 mg kg ^-1 of etomidate, followed by maintenance with a 2:1 mixture of etomidate and propofol. Primary endpoints included serum cortisol, aldosterone, and adrenocorticotropic hormone concentrations preoperatively, immediately postoperatively, and at 8:00 AM on the first and third postoperative days. Secondary endpoints assessed postoperative recovery quality and related complications. Compared to the M group, the E group experienced a greater decrease in cortisol concentrations (34.0% [26.6% to 45.0%] vs. 27.2% [19.9% to 42.7%]; P = 0.0228) and aldosterone concentrations (44.8% [29.9% to 58.6%] vs. 26.2% [7.1% to 75.8%]; P < 0.0001) and a more pronounced increase in adrenocorticotropic hormone concentrations (39.0% [-3.8% to 121.1%] vs. 5.7% [-20.0% to 38.5%]; P = 0.0009). The correlation between the degree of etomidate inhibition and its total dose was higher in the E group (r = 0.4839 vs. r = 0.3666). Moreover, the proportions of patients maintaining normal aldosterone and adrenocorticotropic hormone levels immediately postoperatively were significantly lower in the E group ( P < 0.0001). However, there were no significant differences in postoperative recovery or complication rates between the two groups ( P > 0.05). Etomidate exerted stronger adrenal cortical suppression in the evening than in the morning, but postoperative recovery and complication rates were comparable in non-critically ill patients, supporting its safe clinical use. Trial registration Chinese Clinical Trial Registry identifier: ChiCTR2400082034, Date: 19/03/2024