+Opioids are often used for intraoperative and postoperative pain management; however, perioperative opioid use has been associated with significant side effects including nausea, gastrointestinal paralysis, delirium, and hypoxemia. Many nonopioid analgesics are currently available; intravenous ketamine has been established as an effective adjunctive analgesic. Esketamine, a dextroisomer of ketamine, has a strong analgesic effect and has been combined with other drugs in previous studies to implement opioid-free analgesia. Female sex has been previously found to be an independent risk factor that significantly increases the risk of postoperative nausea and vomiting (PONV), and this double-blind parallel randomized controlled trial investigated whether opioid-reduced anesthesia based on esketamine reduces complications and accelerates rehabilitation in patients undergoing gynecologic day surgery. Included in the study were adult women scheduled for hysteroscopy and cervical conization. The primary outcome was the incidence of postoperative nausea within 24 hours following surgery, with secondary endpoints of postoperative vomiting incidence, postoperative length of hospital stay, pain scores evaluated by the visual analogue scale (VAS), length of stay in the post anesthesia care unit (PACU), adverse hemodynamic events, and other adverse reactions. Patients were randomized in a 1:1:1 ratio into three separate groups. During induction, groups C and MO received alfentanil, whereas group LO received a lower dose of alfentanil mixed with esektamine. For anesthetic maintenance, group C received alfentanil, while groups LO and MO received esketamine only. Throughout the surgery, mean arterial pressure (MAP) and heart rate (HR) were recorded at 9 separate time points. In addition, tatients were followed at two postoperative time points – in the PACU and on the first day of discharge. 141 patients were available for primary analysis, with no significant difference found between the three groups with respect to their preoperative PONV risk score. With respect to the primary endpoint, the incidence of nausea within 24 hours was 33.3% in group C, 18.4% in group MO, and 43.2% in group LO. The incidence of nausea within 24 hours was significantly lower in group MO than in group LO (P<.05). With respect to secondary endpoints, the incidence of vomiting within 24 hours after operation was lower in group MO than in group LO (P<.05). Otherwise, the length of stay in PACU was increased in group LO compared to group C (median 60 vs. 42.5, P<.05). The VAS scores for postoperative pain did not significantly differ among the three groups. Interestingly, the number of patients in group LO with bradycardia and hypotension was significantly decreased compared with group C. Overall, the findings from this study suggest that opioid-reduced analgesia using esketamine did not significantly reduce PONV and may have contributed to more serious PONV and longer postoperative rehabilitation. However, esketamine did display a positive analgesic effect comparable to opioids and showed more stable hemodynamics as well. A limitation of this study was the lack of other supplemental medications to completely replace opioids in an opioid-free analgesia group. This is an important trial in exploring opioid-reduced analgesia as an effective alternative, and further research is required to explore ideal combinations of analgesics and sedatives.
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