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STUDY OBJECTIVE: To examine the effect of esomeprazole in a fixed time setting on gastric content volume, gastric acidity, gastric barrier pressure, and reflux propensity. DESIGN: Randomized, controlled, double-blind trial. SUBJECTS: 21 healthy, ASA I physical status volunteers. INTERVENTION: Esomeprazole was given 12 hours and one hour before investigation. Before the study, a multichannel intraluminal impedance catheter, pH monitoring data logger (PHmetry) catheter, and an intragastric-esophageal manometry catheter were placed nasally after topical anesthesia. MEASUREMENTS: Gastric acidity and gastric content volume were determined by PHmetry after aspiration of gastric contents over a nasogastric tube. Gastroesophageal reflux and intragastric-esophageal barrier pressure were investigated by multichannel intraluminal impedance measurement, PHmetry, and intragastric-esophageal manometry. MAIN RESULTS: The pH of gastric contents was significantly (P < 0.001) higher after esomeprazole (mean [25th-75th percentile], 4.2 [3.9-4.8] vs 2.0 [1.9-2.7]), and gastric content volume was significantly (P < 0.001) lower (5.0 mL [3.0-12.0] vs 15 mL [10.0-25.0]) in comparison to placebo. No significant difference between esomeprazole and placebo was found with respect to number of refluxes per person, duration of reflux, or barrier pressure. CONCLUSION: Esomeprazole in a fixed time setting can markedly increase the pH of gastric contents and decrease gastric content volume, but has no influence on the frequency, duration of refluxes, or gastroesophageal barrier pressure.