Tehran University of Medical Sciences Archives of Anesthesiology and Critical Care 2423-5849 0 0 2026 08 01 1581 1581 Hamid Saryazdi Department of Anesthesiology, Alzahra Hospital, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Reihanak Talakoub Department of Anesthesiology, Alzahra Hospital, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Maryam Golestan Hashemi Department of Anesthesiology, Alzahra Hospital, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 2026 02 23 2026 05 19 Background: Postoperative pain and nausea/vomiting remain common and clinically significant complications following laparoscopic cholecystectomy. Although both ketamine and dexamethasone have demonstrated preemptive analgesic and antiemetic properties, direct comparative evidence between these agents is limited. The objective is to compare the effectiveness of preemptive ketamine versus dexamethasone in reducing postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy. Methods: In this triple-blind randomized controlled trial, 102 patients undergoing elective laparoscopic cholecystectomy at Alzahra Hospital (Isfahan, Iran) in 2024 were randomly assigned to receive intravenous ketamine (0.75 mg/kg), dexamethasone (0.1 mg/kg), or placebo immediately after surgical incision. The main outcomes focused on patients' recovery experience, including the level of postoperative pain measured on a 0-10 scale, the severity of nausea assessed on a 0-10 visual analog scale, and the frequency of vomiting during the recovery period.Secondary outcomes included rescue analgesic requirements and adverse events. Results: All 102 randomized participants (34 per group) completed the study. At recovery room admission, mean pain scores were significantly lower in the ketamine group (3.4 ± 1.8) compared with the dexamethasone (4.5 ± 1.9) and placebo (6.2 ± 2.1) groups (p < 0.001). In contrast, mean nausea scores were significantly lower in the dexamethasone group (2.3 ± 1.7) compared with the ketamine (4.1 ± 2.2) and placebo (5.8 ± 2.4) groups (p < 0.001). Vomiting incidence was lowest with dexamethasone (23.5%) relative to ketamine (44.1%) and placebo (70.6%) (P < 0.001). Rescue morphine use was required in 55.9% of ketamine, 64.7% of dexamethasone, and 82.4% of placebo recipients (p = 0.029). No serious adverse events were observed. Conclusion: Preemptive ketamine provides superior postoperative analgesia, whereas dexamethasone offers superior antiemetic efficacy compared with placebo in patients undergoing laparoscopic cholecystectomy. Selection between these agents should be individualized based on whether postoperative pain or prevention of nausea/vomiting is the primary clinical priority. https://aacc.tums.ac.ir/index.php/aacc/article/view/1581