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Passive regurgitation may occur throughout the perioperative period, increasing the risk for pulmonary aspiration and postoperative pulmonary complications. Hypnotics and opioids, especially remifentanil, that are used during anesthesia have been shown to decrease the pressure in the esophagogastric junction (EGJ), that otherwise acts as a barrier against passive regurgitation of gastric contents. Esmolol, usually used to counteract tachycardia and hypertension, has been shown to possess properties useful during general anesthesia. Like remifentanil, the β-1-adrenoreceptor antagonist may be used to attenuate the stress reaction to tracheal intubation and to modify perioperative anesthetic requirements. It may also reduce the need for opioids in the postoperative period. Its action on the EGJ is however unknown.The aim of this trial was to compare the effects of esmolol and remifentanil on EGJ pressures in healthy volunteers, when administrated as single drugs.Measurements of EGJ pressures were made in 14 healthy volunteers using high-resolution solid-state manometry. Interventions were administered in a randomized sequence and consisted of esmolol that was given IV as a bolus dose of 1 mg/kg followed by an infusion of 10 μg·kg−1·minute−1 over 15 minutes, and remifentanil with target-controlled infusion of 4 ng/mL over 15 minutes. Interventions were separated by a 20-minute washout period. Analyses of EGJ pressures were performed at baseline, and during drug administration at 2 (T2) and 15 minutes (T15). The primary outcome was the inspiratory EGJ augmentation, while the inspiratory and expiratory EGJ pressures were secondary outcomes.There was no effect on inspiratory EGJ augmentation when comparing remifentanil and esmolol (mean difference −4.0 mm Hg [−9.7 to 1.7]; P= .15). In contrast, remifentanil significantly decreased both inspiratory and expiratory pressures compared to esmolol (−12.2 [−18.6 to −5.7]; P= .003 and −8.0 [−13.3 to −2.8]; P= .006).Esmolol, compared with remifentanil, does not affect EGJ function. This may be an advantage regarding passive regurgitation and esmolol may thus have a role to play in anesthesia where maintenance of EGJ barrier function is of outmost importance.