Gastroesophageal reflux disease (GERD) is defined as an impairment of quality of life caused by gastroesophageal reflux. Heartburn, which is characterized by discomfort or burning behind the sternum arising from the epigastrium and possibly radiating to the neck, is the most common symptom of GERD. Heartburn generally is intermittent, with most episodes occurring within 60 minutes of eating, during exercise, and while lying down. Drinking water or taking an antacid may relieve the symptoms, but heartburn generally occurs frequently. Kahrilas reviewed the management of refractory heartburn.

Proton pump inhibitor (PPI) therapy is useful as a therapeutic trial because it often successfully reduces acid-related disorders, including GERD. However, response to treatment cannot make or rule out a diagnosis.

Inadequate response to treatment can be explained by inadequate treatment, esophagitis of nonreflux etiology, nonacid reflux, or functional heartburn. After a failed PPI therapeutic trial, options include increasing the potency of GERD therapy with medication, endoscopic treatment, or surgery; endoscopy and monitoring pH; and empiric treatment for functional heartburn with low-dosage tricyclic antidepressants. Because increased dosages of PPIs are not likely to work better than the initial dosage and because functional heartburn is generally a diagnosis of exclusion, the best choice is upper endoscopy, with pH monitoring to follow if no clear pathology is found on visualization of the gastro-esophageal region. Patients should discontinue PPI therapy for five to seven days before starting pH monitoring.

Endoscopy and pH monitoring should clarify the relationship between symptoms and actual acid reflux. If they are not significantly associated, functional heartburn can be diagnosed, and the patient can be treated with a tricyclic antidepressant given in a low dosage at nighttime. Patients with functional heartburn have symptoms that are typical of esophageal disease but that have no physical explanation. Heartburn symptoms usually are more frequent during times of stress.

The author concludes that because PPIs are so effective in treating symptoms of esophagitis, refractory, endoscopy-negative heartburn probably has other etiologies. The latter can include esophagitis where disease is present but not detected; absence of abnormality of esophageal epithelium but evidence of reflux etiology; and heartburn not attributable to gastroesophageal reflux but more likely caused by psychosocial factors. Determining the appropriate category for patients with refractory heartburn will lead to appropriate therapeutic intervention with a greater likelihood of success.