Medical management of patients with esophageal or supraesophageal gastroesophageal reflux disease

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Abstract

With the common use of proton pump inhibitors (PPIs), the medical treatment of gastroesophageal reflux disease (GERD) and its complications is now successful in relieving symptoms, healing esophagitis, and preventing complications. Physiologic factors that may contribute to a poor response to these drugs include the considerable variation in the bioavailability of PPIs, the need to take PPIs with meals, the influence of Helicobacter pylori–associated gastritis, and genetic variation in enzyme capacity, resulting in rapid and slow metabolizers of PPIs. Subsets of reflux patients, such as the elderly, pregnant women, and those with supraesophageal symptoms or Barrett esophagus, may have special treatment requirements. Medical treatment of GERD with PPIs has been demonstrated to equal the success of antireflux surgery in short- and long-term follow-up with reasonably few side effects. Furthermore, a good response to PPI therapy predicts a successful outcome with antireflux surgery.

Section snippets

Nonresponders to proton pump inhibitor therapy

For the purpose of this article, nonresponders are defined as those patients who have persistent symptoms and abnormal reflux, as demonstrated by 24-hour ambulatory pH monitoring, despite twice-daily treatment with a PPI. Physiologically, several factors may contribute to this phenomenon, including the considerable variation in oral bioavailability of PPIs, the need for the ATPase pumps to be activated by meals, the influence of Helicobacter pylori–associated gastritis, and genetic variation in

Improved pharmacokinetic parameters

The development of newer PPIs has resulted in improved outcomes in some groups of nonresponders. The first available PPI, omeprazole, along with other subsequently developed PPIs, is a racemic mixture of R- and S-isomers. Recent studies suggest that the S-isomer of omeprazole (esomeprazole) is subject to less first-pass metabolism and lower plasma clearance than is omeprazole, thereby offering higher systemic bioavailability, less intersubject variability, and more prolonged acid suppression.

Relation to meals

PPIs bind to H+K+ ATPase molecules that have been recruited to the surface of the parietal cell by the intake of a meal. Because of their short half-lives (0.6 to 3.0 hours) after absorption, the optimal administration of a PPI is 15 to 30 minutes before a meal (usually breakfast) and ideally after a period of fasting. Nevertheless, as shown in Figure 1, from a study of physicians and their prescription patterns, much confusion exists about the optimal time to take a PPI in relation to meals.6

Helicobacter pylori gastritis

The effect of H pylori infection on the prevalence of GERD remains controversial. However, many studies with older PPIs have found that patients who test negative for H pylori have poorer gastric acid control on standard doses of PPIs than their positive counterparts. This phenomenon appears to be due to the acid-suppressive effects of chronic corpus gastritis associated with H pylori infection in positive subjects, whereas H pylori–negative subjects have high volumes of gastric acid. Recent

Nocturnal gastric acid breakthrough

The phenomenon of increasing gastric acidity at night in individuals receiving twice-daily treatment with a PPI was recently described.8 This event has been called nocturnal acid breakthrough and is arbitrarily defined as the appearance of gastric acid, marked by a pH <4 in the fundus, for a period >1 hour overnight during twice-daily PPI therapy. The prevalence of nocturnal acid breakthrough ranges from 69% to 79% in normal volunteers and patients with GERD, and typically appears in the second

Treatment failure in gastroesophageal reflux disease

Table 1 summarizes the most common reasons that patients with GERD symptoms do not improve, or even worsen, on aggressive PPI therapy. In fact, clinical experience suggests that all patients with GERD can now be treated adequately in an acute situation with these highly effective drugs.

The most common reason that patients with heartburn and regurgitation do not improve is an inaccurate diagnosis. Symptoms may be functional in origin, secondary to delayed gastric emptying or even achalasia.

Elderly patients

Older patients with GERD often complain of less severe reflux symptoms than do younger individuals, possibly due to decreased pain sensitivity. However, because of prolonged acid exposure over years, the elderly may have more complicated forms of the disease.14 Treatment of the older GERD patient follows the same principles as treatment of other adults, although it may require more aggressive acid-suppression therapy.15 Pill-induced esophagitis may complicate treatment in this group.

Supraesophageal presentations

A number of supraesophageal complaints have been associated conclusively with GERD, including chest pain; pulmonary diseases such as asthma, bronchitis, microaspiration, and pulmonary fibrosis; and ear, nose, and throat symptoms, including hoarseness, cough, laryngitis, subglottic stenosis, and cancer. The mechanisms by which acid reflux causes or aggravates these diseases is multifactorial, including microaspiration of gastric contents or a vagally mediated reflex triggered by intraesophageal

Barrett esophagus

Symptomatic patients with Barrett esophagus can be easily managed with PPI therapy. Furthermore, their esophagitis, strictures, and ulcers can be healed, and relapse can be prevented, enabling this group to have an enhanced quality of life. As shown in Table 5, 29, 30, 31, 32, 33 however, there is little evidence that PPI therapy promotes predictable regression of Barrett epithelium. Theoretically, the elimination of pulses of acid reflux could reduce proliferation of Barrett epithelium based

The choice of medical or surgical treatment for gastroesophageal reflux disease: personal philosophy

At the Cleveland Clinic Foundation, all patients being considered for antireflux surgery are jointly evaluated by the gastroenterology and surgery teams. When GERD is causing the patient’s symptoms, both groups are convinced that these patients can achieve symptomatic relief and healing of esophagitis, especially with the use of PPI therapy. True “intractable” GERD cases are rare in our collective experience; PPI failure suggests that GERD may be the wrong diagnosis. Noncompliance with drug

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