Sex-Related Analgesic Effects of Opioid-Based Anesthesia and Low-Opioid Anesthesia with Non-Opioid Postoperative Analgesia—A Clinical Observational Study

Background/Objectives: Sex is a crucial factor in modulating the perioperative aspects of anesthesia. A growing number of studies demonstrate that women and men experience pain differently and respond differentially to analgesics. Methods: This study evaluated the analgesic trajectory of low-opioid anesthesia (LOA) and opioid-based anesthesia (OBA) in women and men after laparoscopic cholecystectomy. The primary objective was to assess pain intensity at various time intervals after surgery (0–2, 2–6, 6–12, and 12–24 h) using the Numerical Rating Scale (NRS). The secondary objective was to assess the difference in mean pain intensity on the first postoperative day between the women and men. Results: The mean pain intensity did not differ significantly for men using LOA and OBA, but the value was significantly lower in the LOA group for women (p = 0.0002). The analgesic trajectory in women and men undergoing LOA presented a negative trend, but the pain intensity at 0–2, 2–6, 6–12, and 12–24 h in women was statistically lower than that of the OBA group (p = 0.01, p = 0.008, p = 0.002, and p = 0.001). Total fentanyl doses of 0.3 mg (sensitivity 44%, specificity 76%, AUC 0.55) and 0.35 mg achieved a mean NRS of <2 for pain intensity in the female and male OBA groups (sensitivity 33%, specificity 100%, AUC 0.53). Conclusions: A model combining low-opioid anesthesia and non-opioid postoperative analgesia presents a favorable therapeutic effect for women. OBA does not provide proper analgesic effects after laparoscopic cholecystectomy.