Options to Address Delayed Gastric Emptying in Gastroesophageal Reflux Disease

Diagnosis of Delayed Gastric Emptying

Gastroparesis is diagnosed based on the presence of typical signs and symptoms combined with objective tests to verify DGE and the absence of mechanical obstruction. Upper gastrointestinal endoscopy can be performed to exclude luminal obstruction and can also be used to note retained food products despite fasting status.

DGE is most often evaluated using scintigraphy, which is performed with a meal labeled with radioactive markers. Liquids and solids can both be marked with tracers and then followed for rate of emptying using gamma cameras. The stomach can be segmented so that emptying of the proximal and distal stomach can be assessed separately. Some recommend that the study should be performed for at least 4 hours, as shorter test times underrepresent patients with gastroparesis. It should be noted that results of gastric emptying scintigraphy can have significant variability; this is partly dependent on how the food and tracer are prepared. A standardized protocol should therefore be followed to decrease variability of results. Of note, the degree of DGE, usually measured as the gastric retention percentage or the half emptying time, does not correlate well with the severity of symptoms of gastroparesis.

Another technique used to measure DGE is the stable isotope breath test. ¹³ C is a stable isotope that is used as a substrate, combined with food, and ingested. The substrate is absorbed in the small bowel and then oxidized to ¹³ CO ₂ and exhaled. The ratio of the substrate to its oxidized counterpart is used to determine gastric emptying.

Several other techniques are being used to investigate gastric emptying. Magnetic resonance imaging (MRI), which is noninvasive, can evaluate motility in addition to emptying. Ultrasonography, another noninvasive technique, has also been used to evaluate patients for DGE but is dependent on the presence of a skilled technician.

Antroduodenal manometry can be used to evaluate gastric, pyloric, and duodenal motor activity and assess motor dysfunction. This includes antral hypomotility, migrating motor complex (MMC) activity, and focal dysfunction. This procedure is performed with a perfusion manometry system or a solid-state catheter to measure intraluminal pressure of gastric and duodenal wall contractions. Antroduodenal manometry findings can be abnormal in multiple disorders including DGE and gastroesophageal reflux disease (GERD).

Delayed Gastric Emptying in Gastroesophageal Reflux Disease

Gastric emptying is a complex process involving multiple mechanisms and incorporates transport, storage, and digestion. The proximal stomach, or fundus, gradually dilates with receptive relaxation and stores food boluses. In the fundus, relaxation is followed by low-amplitude contractions to transport the food bolus to the distal stomach. The gastric antrum then assists in grinding food and maneuvering it toward the pylorus. The pylorus must then relax to allow for transit of the bolus into the duodenum. The gastric pacemaker, located in the body along the greater curvature, produces approximately three cycles per minute and is responsible for this movement from the body and antrum into the duodenum. This rate of emptying is affected by the meal composition, with liquids passing more quickly than solids. All of these elements involved in gastric emptying are potential sites of therapeutic intervention for the treatment of gastroparesis.

GERD is a failure of the antireflux barrier and is contributed to by a defective lower esophageal sphincter (LES) with reduced pressure, transient LES relaxations (TLESRs), impaired esophageal peristalsis, and possibly DGE. Surgical intervention is warranted for GERD when patients with objective reflux fail medical management, prefer surgical treatment to a lifelong medication requirement, suffer from complications of GERD, or have extraesophageal symptoms. Preoperative evaluation in reflux patients can include esophagogastroduodenoscopy (EGD), esophageal pH monitoring, esophageal manometry, and video esophagram or barium swallow.

It is possible that DGE affects the occurrence of gastroesophageal reflux and has an influence on the refluxate composition. In theory it makes sense that DGE may lead to larger quantities of food in the stomach available to be refluxed. This gastric distention may also cause increased episodes of reflux by generating TLESRs. Yet the relationship between the rate of gastric emptying and GERD has been studied in multiple articles without a consensus on the exact nature or significance of their association.

Maddern et al. assessed solid and liquid gastric emptying simultaneously in 72 patients with symptomatic GERD. Of these, 44% were found to have delayed solid emptying and 37% delayed liquid emptying. There was no significant correlation noted between gastric emptying and the resting LES pressure. Symptoms of regurgitation and epigastric fullness also did not correlate with gastric emptying. Cunningham et al. also demonstrated DGE of solids in 46% of patients with GERD. The authors noted that this may indicate that the role of delayed emptying in GERD was related to gastric distention leading to alteration of gastric wall tension in the region of the LES, thereby increasing reflux events.

Whereas the aforementioned studies noted DGE in a significant percentage of patients with GERD, Schwizer et al. found DGE with similar frequency in GERD patients versus controls. In this study, DGE was associated with a decreased incidence of esophagitis, suggesting that retained food had a buffering effect on the acidity of the stomach. This study concluded that DGE was not a major contributing factor to GERD.

The previous studies demonstrate that it is unclear whether there is a significant link between abnormal gastric emptying and increased gastroesophageal reflux. Yet it has been speculated that gastric distention can contribute to reflux episodes by triggering TLESRs. This theory suggests that although total gastric emptying may be similar in patients with GERD and controls, the difference may lie in the time taken to empty different sections of the stomach. The gastric fundus and antrum have different functions in gastric emptying, and dysfunctional motor activity at either of these sites could have a role in the production of reflux episodes. Herculano et al. compared gastric emptying and food retention in the proximal stomach in these two groups using scintigraphy. This study found that total gastric emptying was similar in GERD patients and controls but patients had decreased proximal retention of a liquid meal with an increased number of reflux episodes. This indicated a negative correlation between proximal gastric retention and reflux episodes. These results are in contrast to the results of Stacher et al., who, using scintigraphy, evaluated total and proximal stomach emptying of a semisolid meal in patients with symptoms of DGE and GERD. Their data showed that delayed proximal gastric emptying was associated with increased reflux episodes.

Attention has also been given to the evaluation of the distal stomach and to assessing its role in GERD. Barbieri et al. used dynamic antral scintigraphy to monitor postprandial antral contractions and their relationship to GERD and DGE. They found that the amplitude of the contractions was linked to gastric emptying time but negatively correlated with reflux episodes. These findings of increased amplitude of antral contractions in the setting of DGE contrast with results that show a similar pattern of distal antral contractions in these two groups.

Carmagnola et al. took a different approach in attempting to determine whether DGE plays a role in the number of reflux episodes in GERD. They evaluated gastric emptying with ultrasonography and esophageal pH monitoring after patient use of cisapride, a prokinetic medication, and compared these results with placebo. Forty percent of their GERD patients were noted to have DGE. Cisapride was seen to increase gastric emptying and decrease the number of reflux episodes and esophageal acid exposure. However, no correlation was seen between changes in gastric emptying and the medication-induced changes in reflux variables.

As these previous reports found discordant results, Gourcerol et al. used combined esophageal pH-impedance measurements to evaluate whether the occurrence of gastroesophageal reflux correlated with gastric emptying rate. Esophageal impedance monitoring was used to help identify the type of reflux (less acidic or nonacidic). Gastric emptying was assessed using the C-octanoic acid breath test. This study found that delay in gastric emptying increased daily liquid and mixed reflux events without affecting esophageal acid exposure. This may be attributed to acid buffering due to gastric food retention and the production of nonacidic or weakly acidic refluxate or reflux of larger volume. Compared with normal gastric emptying, DGE patients had symptomatic reflux with higher proximal extension and a longer bolus clearance time. These patients with DGE and higher proximal extension may be more symptomatic despite a similar number of reflux episodes.

All of these studies indicate that gastric function may affect GERD pathogenesis, but an unequivocal connection between DGE and the degree of reflux symptoms has not been confirmed. In fact, as evidenced by a few of the noted articles, some studies have failed to demonstrate an association between GERD and DGE. This may be because many of these studies differ in inclusion criteria, have small sample sizes, and vary in the ingested meal that is studied. Even when studies show a significant association between GERD and DGE, it remains to be considered whether this has an effect on clinical symptoms or esophageal acid exposure. As noted earlier, it has been described that medication-induced acceleration of gastric emptying does not correlate with decreased acid exposure at the esophagus or other reflux variables. At this time it appears that the studies on gastric motility and emptying in regard to GERD have variable and contradictory results. DGE may play a larger role in less acidic or nonacidic reflux events because of buffering effects and may not be a major determinant of the number of reflux episodes.

Treatment Options

There is no universally accepted treatment option for patients with DGE in the setting of GERD. Multiple medical therapies and surgical procedures are available for both of these disorders, but the number of options for treatment is indicative of the complex nature of this combination of disorders. Treatment may oftentimes be geared toward the predominating symptoms.