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Intraoperative systemic esmolol has been shown to reduce postsurgical pain. Nonetheless, it is unknown whether the use of intraoperative systemic esmolol can improve patient-reported postsurgical quality of recovery. The main objective of the current investigation was to evaluate the effect of intraoperative esmolol on postsurgical quality of recovery. We hypothesized that patients receiving intraoperative esmolol would report better quality of postsurgical recovery than the ones receiving saline.The study was a prospective randomized double-blinded, placebo-controlled, clinical trial. Healthy female subjects undergoing outpatient hysteroscopic surgery under general anesthesia were randomized to receive intravenous esmolol administered at a rate of 0.5 mg/kg bolus followed by an infusion of 5 to 15 μg/kg/min or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included postoperative opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test.Seventy subjects were randomized and 58 completed the study. There was not a clinically significant difference in the global QoR-40 scores between the esmolol and saline groups at 24 hours, median (interquartile range) of 179 (171–190) and 182 (173–189), respectively, P = .82. In addition, immediate post-surgical data in the post-anesthesia care unit did not show a benefit of using esmolol compared to saline in regard to pain scores, morphine consumption, and postoperative nausea and vomiting.Despite current evidence in the literature that intraoperative esmolol improves postsurgical pain, we did not detect a beneficial effect of intraoperative esmolol on patient-reported quality of recovery after ambulatory surgery. Our results confirm the concept that the use of patient-centered outcomes rather than commonly used outcomes (e.g., pain scores and opioid consumption) can change the practice of perioperative medicine.