Digestive Diseases and Sciences, Vol. 50, No. 11 (November 2005), pp. 2019–2024 ( C  2005) DOI: 10.1007/s10620-005-3001-2 A Prospective Study of Gastric Acid Analysis and Esophageal Acid Exposure in Patients with Gastroesophageal Reflux Refractory to Medical Therapy SUSHIL K. AHLAWAT, MD, RAJA MOHI-UD-DIN, MD, DIONNE C. WILLIAMS, RN, KATHLEEN A. MAHER, RN, and STANLEY B. BENJAMIN, MD, FACP A number of factors have been proposed to account for the lack of response to medical therapy in patients with gastroesophageal reflux; however, no controlled studies are available in the literature. The goal of this study was to determine possible causes of medical refractoriness in patients with gastroesophageal reflux. Gastric acid output and esophageal acid exposure were measured in patients who continue to have reflux symptoms despite aggressive antisecretory therapy. In addition, an upper endoscopy was also performed in each patient. Patients with a drug-controlled acid output <1 mEq/hr and a supine total esophageal pH < 4 for less than 1.7% of the time measured were considered responsive to therapy; on the other hand, those with a drug-controlled gastric acid output >1 mEq/hr and a supine esophageal pH < 4 for more than 1.7% of the time measured were considered resistant to therapy. Twenty -four patients met the inclusion criteria (13 male and 11 female; mean age, 52). Drug- controlled gastric acid output was more than 1 mEq/hr in 25% of patients and less than 1 mEq/hr in the remainder. Of those patients with a gastric acid output of less than 1 mEq/hr (18 patients), 8(44%) had a supine esophageal pH < 4 for more than 1.7% of the time, suggesting that factors other than gastroesophageal reflux likely contributed to their reflux-like symptoms. Acid suppression appears adequate in the majority of patients with gastroesophageal reflux refractory to medical therapy. The exact cause of persistent reflux-like symptoms in patients who fail medical treatment is uncertain but may be related to non-acid-related factors such as esophageal hypersensitivity to physiologic reflux, increased intake of air resulting in aerophagia, or other factors such as bile reflux. KEY WORDS: gastoesophageal reflux; gastric acid analysis; esophageal acid exposure; refractory gastroesophageal reflux. Gastroesophageal reflux (GER) is best defined as symp- toms due to abnormal reflux of gastric contents into the esophagus. This movement of gastric contents may re- sult in mucosal injury, and the symptoms must be to a Manuscript received November 28, 2004; accepted February 8, 2005. From the Division of Gastroenterology, Department of Medicine, Georgetown University Hospital, Washington, DC, USA. Address for reprint requests: Stanley B. Benjamin, MD, FACP, Divi- sion of Gastroenterology, Department of Medicine, Georgetown Univer- sity Hospital, 3800 Reservoir Road, NW, Washington, DC 20007-2197, USA; sushilka@aol.com. degree that impairs quality of life to constitute gastroe- sophageal reflux disease (GERD) (1). The most common symptoms of GER are heartburn, regurgitation, and dys- phagia. In addition, a variety of extra esophageal mani- festations have been described including asthma, chronic cough, and laryngitis. Approximately one-third of the U.S. population suffers from GER at least once a month and 4 to 7% experience symptoms on a daily basis. The primary aim of treating reflux disease is to relieve symptoms. Usually with adequate therapy, symptom re- lief is achieved; however, some patients fail to respond to Digestive Diseases and Sciences, Vol. 50, No. 11 (November 2005) 2019 0163-2116/05/1100-2019/0 C  2005 Springer Science+Business Media, Inc.