Risk Factors for Intolerable Postoperative Pain After Vitreoretinal Surgery Under AoA-Guided General Anesthesia with Intravenous COX-3 Inhibitors: A Post Hoc Analysis

<b>Background/Objectives</b>: Intolerable postoperative pain perception (IPPP) may occur in patients undergoing vitreoretinal surgery (VRS), while general anesthesia (GA) is often preferred over regional techniques due to multiple contraindications. Intraoperative administration of intravenous rescue opioid analgesics (IROA) during GA increases the risk of perioperative adverse events; however, this requirement can be reduced through preventive analgesia. The Adequacy of Anesthesia (AoA) concept, based on entropy EEG and the Surgical Pleth Index (SPI), allows real-time titration of IROA to maintain optimal nociception/anti-nociception balance and create comparable intraoperative conditions across patients. This study aimed to identify risk factors for IPPP after VRS performed under AoA-guided GA combined with intravenous preventive analgesia using COX-3 inhibitors. <b>Methods</b>: A total of 165 patients scheduled for VRS were randomized to receive AoA-guided GA combined with intravenous preventive analgesia using either paracetamol plus metamizole, paracetamol alone, or metamizole alone. <b>Results</b>: Data from 153 patients were analyzed. Neither age, body mass index, smoking status, arterial hypertension, diabetes mellitus, intraoperative noxious maneuvers, demand for IROA, nor length of surgery correlated with the incidence of IPPP under AoA-guided GA. The combination of paracetamol and metamizole resulted in the lowest rate of IPPP among all groups. <b>Conclusions</b>: AoA-guided GA combined with COX-3 inhibitors appears to standardize intraoperative nociception/anti-nociception balance in patients undergoing VRS, effectively mitigating most known risk factors for IPPP, with female sex independently associated with its occurrence. We recommend the optimization of perioperative pharmacotherapy through individualized AoA-guided GA with intravenous COX-3 inhibitors to minimize IPPP incidence.