Esophageal high-resolution manometry (HRM) assesses esophageal motor function and is indicated both for evaluation of esophageal symptoms and before antireflux interventions. HRM studies are interpreted and esophageal motor diagnoses made according to the Chicago Classification, version 3.0 algorithm, which is based on ten 5 mL supine water swallows. However, this practice of single liquid swallows performed in the supine position does not reflect typical "real-life" swallowing, and may not reproduce the patient's presenting symptoms. Therefore, provocative maneuvers at HRM-beyond these 10 standard swallows-can afford additional insights into esophageal motor function with clinically significant implications, and represent areas of exciting investigation and innovation. Accordingly, the 2020 American College of Gastroenterology Guidelines on Esophageal Physiologic Testing conditionally recommend their inclusion in the HRM protocol. In this clinical review, we discuss the supporting data for and clinical utility of provocative maneuvers at HRM that include changes in body position or accessories (upright swallows, "bridge" position, straight leg raise, abdominal compression), bolus consistency (solid swallows, test meals, postprandial high-resolution impedance manometry), bolus frequency (multiple rapid swallows), the volume of bolus (rapid drink challenge/multiple water swallows), and the use of pharmacological agents.
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