Background/Objectives: Some patients undergoing vitreoretinal surgery (VRS) require general anesthesia (GA), despite the possibility of developing intolerable postoperative pain perception (IPPP). Intraoperative rescue opioid analgesia (IROA) administration during GA poses a risk of perioperative nausea and vomiting (PONV), which may result in suprachoroidal hemorrhage with permanent visual impairment. Adequacy of Anesthesia (AoA) optimizes intraoperative IROA titration. Intravenous preemptive analgesia (IPA) with cyclooxygenase-3 (COX-3) inhibitors is added to GA to reduce the IROA dose. In this additional analysis, we assessed the impact of preemptive analgesia with COX-3 inhibitors, administered alongside GA with AoA-guided IROA, on the incidence of PONV, oculocardiac reflex (OCR), and oculoemetic reflex (OER) in patients undergoing VRS as secondary outcomes. Methods: A total of 165 patients scheduled for VRS were randomly assigned to receive AoA-guided GA combined with IPA at a single dose of 1 g of paracetamol (acetaminophen) or 2.5 g of metamizole or both. A total of nine patients were excluded due to technical problems with the intraoperative surgical pleth index (SPI) measurement, inability to report postoperative pain, and postoperative arousal resulting in a loss of follow-up in Stage 5. Results: Regardless of the group assignment, AoA guidance of GA resulted in PONV in 4%, OCR in 10%, and OER in 0% of the 153 analyzed patients undergoing VRS. No significant differences were observed between the groups regarding the type of IPA. PONV was observed in 2.11% (3/142) of patients with zero, one, or two risk factors of PONV, as compared to 27% (3/11) of patients with at least three PONV risk factors, assessed using the Apfel score. Conclusions: IPA with both paracetamol and metamizole did not demonstrate a benefit in reducing the analyzed adverse events compared with their single use in patients undergoing VRS under AoA guidance during GA. Surprisingly, PONV was hardly observed in patients with zero, one, or two PONV risk factors assessed by the Apfel score who underwent AoA-guided VRS during GA with IPA using one or two COX-3 inhibitors.
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