Diurnal Variation in Intraoperative Opioid Requirements: A Prospective Cohort Study

Purpose: Circadian rhythms regulate pain perception and drug metabolism, but their influence on intraoperative opioid requirements remains unclear. This study investigates how surgery timing is associated with intraoperative opioid use. Patients and Methods: This cohort study enrolled patients undergoing laparoscopic cholecystectomy under general anesthesia at China-Japan Friendship Hospital. Patients were grouped into morning (08:00-12:00) or afternoon (14:00-18:00) groups according to surgery start time. Anesthesia was maintained with sevoflurane and sedation depth was monitored by bispectral index (BIS). Sufentanil was titrated by surgical pleth index (SPI) for analgesia. The primary outcome was sufentanil consumption. Secondary outcomes included plasma sufentanil, cortisol, ACTH and IL-6 concentrations, post-operative pain scores, extubation time, Aldrete scores, post-operative nausea and vomiting (PONV), length of PACU stay and rescue analgesia. Results: 45 patients were enrolled with 24 assigned to the morning group and 21 to the afternoon group. Both groups achieved effective intraoperative sedation and analgesia with no significant differences in vital signs, BIS or SPI. However, the morning group required higher total sufentanil doses (47.50 ± 12.31 vs 36.12 ± 9.98 μg, p = 0.002), and normalized unit doses (0.52 ± 0.12 vs 0.39 ± 0.10 μg/kg/h, p < 0.001), compared to the afternoon group. Cortisol and ACTH levels in the morning group were elevated at all time points (all p < 0.001), whereas postoperative IL-6 levels only increased mildly (p = 0.008). Plasma sufentanil concentrations were higher in the morning group both 5 minutes after incision (2.75 [0.76-4.67] vs 0.83 [0.59-1.58] ng/mL, p = 0.027) and at the end of surgery (0.90 [0.38-1.57] vs 0.31 [0.22-0.54] ng/mL, p = 0.005). Conclusion: In this selected cohort, morning surgery was associated with higher intraoperative sufentanil requirements. These findings are consistent with a possible time-of-day influence on intraoperative opioid needs and may reflect circadian neuroendocrine variation.