Gastroparesis

Definition, Etiology, PathogenesisTop

Gastroparesis is chronic delayed gastric emptying with no evidence of mechanical obstruction, resulting in food stasis in the stomach and gastric wall distention. The prevalence is ~10/100,000 in men and 40/100,000 in women in the age-adjusted general population.

Causes:

1) Frequent: Idiopathic gastroparesis (in ~20% of cases gastroparesis may be caused by infections with cytomegalovirus [CMV]; Epstein-Barr virus [EBV]; or human herpesvirus 3 [HHV–3], also referred to as varicella-zoster virus (VZV)]) and diabetes (gastroparesis as a clinical manifestation of diabetic autonomic neuropathy).

2) Less frequent: Surgical complications after gastric or vagal surgery, drugs (eg, opioids, anticholinergic agents, glucagon-like peptide-1 [GLP-1] analogues), Parkinson disease, systemic sclerosis, systemic lupus erythematosus, paraneoplastic syndromes, amyloidosis, systemic mastocytosis, intestinal ischemia.

Clinical FeaturesTop

Signs and symptoms: Nausea and vomiting (most frequently; vomiting >1 h following a meal, usually after 2-6 h), postprandial fullness, early satiety, epigastric pain or discomfort, flatulence. Severe gastroparesis may cause weight loss, malnutrition, dehydration, and electrolyte disturbances. The clinical manifestations are independent of etiology and often do not correlate with the severity of delay in gastric emptying seen in diagnostic studies.

DiagnosisTop

Diagnostic Tests

1. Gastric emptying studies:

1) Scintigraphy using a standardized meal labeled with radioactive technetium (first-line test).

2) Wireless motility capsule (WMC) measuring pH in its immediate surroundings.

3) Breath testing: Analysis of 13CO2 concentration in exhaled air after a test meal labeled with 13CO2.

2. Upper gastrointestinal tract endoscopy: Needed to exclude mechanical obstruction.

3. Imaging: Computed tomography enterography (CTE) or magnetic resonance enterography (MRE) help exclude mechanical obstruction.

4. Laboratory tests: Serum thyroid-stimulating hormone (TSH) excludes hypothyroidism. Preprandial glucose levels and antinuclear antibodies (ANAs) are measured in the diagnostic workup of conditions that may cause delayed gastric emptying.

Diagnostic Criteria

Diagnosis is based on the presence of typical symptoms and objectively confirmed by delayed gastric emptying in the absence of mechanical obstruction.

Differential Diagnosis

1. Peptic ulcer disease and gastroduodenitis.

2. Regurgitation in the course of other conditions, including rumination syndrome and gastroesophageal reflux disease.

3. Functional dyspepsia.

4. Anorexia nervosa and bulimia.

5. Cyclic vomiting syndrome.

6. Hypothyroidism.

7. Long-term use of cannabinoids.

TreatmentTop

1. Nutrition therapy: The aim of the treatment is to alleviate symptoms and prevent nutritional deficiency. Patients are advised to reduce the volume of meals and intake of fat and fiber and to avoid alcohol. Those who poorly tolerate solid meals may switch to crushed or mixed foods. Patients with severe gastroparesis may require enteral or parenteral nutrition.

2. Pharmacologic treatment:

1) Prokinetic agents: Domperidone (10 mg tid before meals for ≤7 days) or, if not effective, oral erythromycin (100-200 mg bid to tid before meals for up to 4 weeks). In the United States metoclopramide is the most commonly used prokinetic agent (5-10 mg tid before meals, for up to 12 weeks). Both domperidone and metoclopramide, drugs belonging to dopamine-2 receptor antagonists, may prolong QT interval, with metoclopramide carrying the risk of extrapyramidal adverse effects. Another dopamine antagonist, itopride (50 mg tid), is not available in North America. Previously widely used cisapride (one of the 5-hydroxytryptamine 4 [5-HT4] receptor agonists) has been withdrawn from Canada, and its use is very restricted in the United States. A drug from the same class, approved in Canada for the treatment of irritable bowel syndrome (IBS) with constipation—tegaserod (6 mg tid)—has been tried in those who do not respond to other prokinetic agents and showed some symptomatic improvement. Preliminary study results suggest that prucalopride, another 5-HT4 agonist, may be effective in the treatment of idiopathic gastroparesis, but it is not available for this indication in Canada.

2) Symptomatic treatment of nausea and vomiting: 5-hydroxytryptamine 3 (5–HT3) receptor antagonists (ondansetron, granisetron), phenothiazines (prochlorperazine, thiethylperazine), antihistamine agents (eg, dimenhydrinate). If possible, use liquid formulations of oral agents, or parenteral drugs when necessary. Improvement in gastric emptying may not result in clinical improvement (and vice versa).

3) Other: Gastric electrical stimulation, injection of botulinum toxin into the pylorus, pyloric balloon dilation, endoscopic pyloromyotomy, surgical pyloroplasty, acupuncture.