Role of Gastric Emptying in Symptoms of Gastroparesis

Abstract

The symptoms of gastroparesis, such as nausea, vomiting, postprandial fullness, early satiety and abdominal pain, frequently impair the quality of life of the affected individuals. The diagnosis of gastroparesis is made after structural etiologies are ruled out and an assessment of gastric function shows delayed gastric emptying. The role of the delay in gastric emptying in the pathogenesis of symptoms of gastroparesis has been debated, with some studies suggesting an association between delayed gastric emptying and the upper gastrointestinal symptoms, while others do not. The recent literature supports the importance of using reliable methods to assess gastric emptying, as delay in gastric emptying measured on a reliable test (4-h scintigraphy or breath test) is associated with the severity of upper gastrointestinal symptoms. In addition to measuring total gastric emptying, evaluation of regional gastric retention in the proximal and distal stomach and whole gut transit to assess small intestinal and colonic transit may provide additional useful information in patients with more generalized symptoms of gastrointestinal dysmotility.

Randomised clinical trial: safety, pharmacokinetics and pharmacodynamics of trazpiroben (TAK‐906), a dopamine D2/D3 receptor antagonist, in patients with gastroparesis

“…It is noteworthy that domperidone, a promotility agent and D 2 receptor antagonist, has also demonstrated inconsistent results with respect to its ability to accelerate gastric emptying, with a recent meta‐analysis noting that, based on available studies, domperidone did not exert a significant effect on gastric t 1/2 31,47,51 . The absence of an effect on gastric emptying in this study is therefore not entirely unexpected, and alternative measures of gastric emptying, such as scintigraphy, may be required to confirm the observations of the gastric emptying breath test, as previous studies have demonstrated there is good correlation between scintigraphy and breath test methods of assessing gastric emptying 1,52,53,54 …”

“…While gastric emptying is the hallmark for the diagnosis of gastroparesis, there may be various other mechanisms which produce and influence gastroparesis symptoms. 52 A significant increase in volume to fullness with the trazpiroben 25 mg dose was observed, which may explain the trend in American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary symptom scores; particularly patient-rated overall severity scores, for which the response appeared to correlate reciprocally with dose. The mechanism for the positive effect of the drug on volume to fullness may be related to the previously documented reduction in upper gastrointestinal symptoms with dopaminergic antagonists, which led to participants' ability to tolerate a greater volume of the nutrient drink.…”

“…31,47,51 The absence of an effect on gastric emptying in this study is therefore not entirely unexpected, and alternative measures of gastric emptying, such as scintigraphy, may be required to confirm the observations of the gastric emptying breath test, as previous studies have demonstrated there is good correlation between scintigraphy and breath test methods of assessing gastric emptying. 1,52,53,54 Participant symptom scores (particularly for postprandial fullness and nausea, and patient-rated overall severity of gastroparesis symptoms) were numerically greater (with the exception of upper abdominal pain) in all trazpiroben treatment groups compared with placebo, albeit without statistical significance. Symptoms of postprandial fullness and nausea, vomiting and early satiety, but not abdominal pain and bloating, have been reported as being associated with delayed gastric emptying, and is broadly in line with the trend observed in this study.…”

“…While gastric emptying is the hallmark for the diagnosis of gastroparesis, there may be various other mechanisms which produce and influence gastroparesis symptoms 52 . A significant increase in volume to fullness with the trazpiroben 25 mg dose was observed, which may explain the trend in American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index‐Daily Diary symptom scores; particularly patient‐rated overall severity scores, for which the response appeared to correlate reciprocally with dose.…”

Measurement of Pyloric Pressures in Gastroparesis: Stiff Competition from EndoFLIP™

“…Importantly, the investigators acknowledge that since some patients did not symptomatically improve after pyloric intervention, this finding reinforces the concept that pyloric dysfunction is not the sole factor in the etiopathogenesis of gastroparesis. Other mechanisms of action that may affect gastroparesis symptoms include "impaired gastric accommodation, hypersensitivity, and extragastric transit abnormalities" [12].…”