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Purpose: Controversy surrounds the optimal technique to moderate pain after laparoscopic cholecystectomy (LC). Opioid analgesics, sympatholytic drugs, and adjuvants, such as ketamine, have all been used. We compared esmolol with a combination of remifentanil plus ketamine in patients undergoing LC to determine the impact of these drugs on morphine requirements and pain control., Methods: Sixty American Society of Anesthesiologists physical status I-II patients undergoing LC and anesthetized with sevoflurane were randomized to one of two groups. Group E patients received a bolus of esmolol 0.5 mg·kg(-1) iv at induction followed by an infusion of 5-15 μg·kg(-1)·min(-1), and Group R-K patients received a bolus of ketamine 0.5 mg·kg(-1) iv and remifentanil 0.5 μg·kg(-1) iv at induction followed by a remifentanil infusion titrated over a range of 0.1-0.5 μg·kg(-1)·min(-1). All patients received paracetamol, dexketoprofen, and levobupivacaine via infiltration of laparoscopic port sites. After surgery, a predetermined bolus of morphine was administered according to a verbal numerical rating scale (VNRS) for pain intensity. The primary outcome of interest was postoperative morphine requirement., Results: Median consumption of morphine was higher in Group R-K than in Group E (5 mg [4-6] vs 0 mg [0-2], respectively; P < 0.001). In the postanesthesia care unit, patients in Group R-K had higher pain scores than patients in Group E (difference in maximum VNRS, -11; 95% confidence interval (CI), -19 to -3). The concentration of sevoflurane to maintain a bispectral index~40 was higher in Group E than in Group R-K (between-group difference 0.3%; 95% CI, 0.15 to 0.40). The incidence of postoperative nausea and vomiting was similar between the two groups., Conclusion: Intraoperative esmolol infusion reduces morphine requirements and provides more effective analgesia compared with a combination of remifentanil-ketamine given by infusion in patients undergoing LC.