History: Gastroparesis is a heterogeneous disorder; its etiology affects symptoms and severity.[4] Patients with gastroparesis can present with various symptoms. The predominant symptom may vary depending on the underlying etiology. Overall, nausea is present in about 93 percent of cases, vomiting in 68 to 84 percent, abdominal pain in 46 to 90 percent, early satiety 60 to 86 percent. Other symptoms include postprandial fullness, bloating, and weight loss in severe and persistent cases. Characteristically vomitus may contain food ingested several hours ago.[20][3] There are similarities and differences in the clinical characteristics of Diabetic gastroparesis and Idiopathic gastroparesis. Patients with idiopathic gastroparesis reported more symptoms of early satiety, postprandial fullness, and abdominal pain as compared with patients with diabetic gastroparesis. Patients with diabetic gastroparesis had more severe retching and vomiting.[4] Even though abdominal pain is a frequent complaint in patients with gastroparesis, it is rarely the predominant symptom (present in about 18 percent). In patients whose principal symptom is abdominal pain, other causes merit consideration.[21] On physical examination, providers may elicit epigastric distention or tenderness, but no guarding or rigidity. Patients may have signs of the underlying disorder causing gastroparesis.

Gastroparesis gets evaluated in clinical practice through the recognition of the clinical symptoms and documentation of delayed gastric emptying. The goal of the evaluation is to exclude a mechanical obstruction and establish the diagnosis of gastroparesis by an assessment of gastric motility. Robust patient history should point to suspicion of a possible diagnosis. Gastroparesis should be a suspicion in patients with chronic nausea, vomiting, early satiety, postprandial fullness, abdominal pain, or bloating. The next step would be ruling out mechanical obstruction, which could be done with a careful upper GI endoscopy to rule out malignancy or strictures due to peptic ulcer disease.

Imaging modalities like computed tomographic (CT) scan or magnetic resonance imaging (MRI) abdomen may be needed to exclude mechanical obstruction. After ruling out mechanical causes, gastric emptying studies (GES) are performed by scintigraphy to confirm the presence of delayed gastric emptying of solids. A solid or liquid radioisotope containing meal may be used to measure gastric emptying.[22] Upon scintigraphy, based on the gastric retention of contents at the end of four hours, gastroparesis could be graded into mild (less than 15 percent), moderate (15 to 35 percent), and severe (over 35 percent). Symptoms of gastroparesis may also be quantifiable via GCSI (gastroparesis cardinal symptom index), a questionnaire based on the severity of symptoms postprandial fullness, early satiety, nausea vomiting, and bloating.[23][24] As compared to the traditional method of GES (testing for 2 hours or less), the sensitivity of the test results could increase by extending the imaging of solid gastric emptying to 4 hours. In patients with normal solid gastric emptying, adding a liquid GES study could further increase its sensitivity to diagnose gastroparesis.[25]

Management of gastroparesis should include a holistic approach to target different aspects of the disease such as assessment of nutritional status, measures to correct fluid, electrolyte, and nutritional deficiencies, relief of symptoms of gastroparesis, improving gastric emptying, recognize and rectify the underlying cause of gastroparesis to prevent progressing of the disease, e.g., tight glycemic control in diabetes, stopping causative medications.[9]

Diet modifications: Small Meal size could limit emptying time and help symptom alleviation. Patients may need to eat 4 or 5 times per day to compensate for the small meal size. Carbonated drinks like soda and beer could release carbon dioxide, which can aggravate gastric distention. Smoking or high doses of alcohol can decrease antral contractility and impair gastric emptying.[9] The nutritional state of the patient should be promptly assessed, utilizing ancillary service consultation. If oral intake is not adequate, then enteral nutrition via jejunostomy tube should be considered. Parenteral nutrition is rarely required.

Medical treatment: As needed antiemetics such as prochlorperazine (5 to 10 mg up to 3 times a day), diphenhydramine (12.5 mg up to 3 or 4 times a day) and ondansetron (4 or 8 mg up to 3 times a day) can provide symptomatic relief in gastroparesis. Metoclopramide, a prokinetic medication, is the only FDA approved drug for gastroparesis. It is usually started with 5 mg three times a day, fifteen minutes before meals. It can be titrated up to 40 mg per day but need very close monitoring for adverse effects. Also, the duration of treatment approved by the FDA is 12 weeks due to the possibility of severe side effects.[26] Common side effects include anxiety, restlessness, hyperprolactinemia, and QT prolongation. Metoclopramide has a black box warning for extrapyramidal symptoms like dystonia and tardive dyskinesia in about 1 percent of patients. Other off-label medications aimed at symptom relief include domperidone, erythromycin (short term), tegaserod (5-HT4 partial agonist), and centrally acting antidepressants.[9] Domperidone is a dopamine 2 antagonist, works more like metoclopramide to improve gastric emptying and decrease nausea and vomiting. The FDA restricts domperidone use in the United States, and it is currently under review as an investigational drug. Domperidone is usually started at 10mg three a day, and dosing could potentially increase to 20mg per dose. Significant adverse effects are cardiac arrhythmias and hyperprolactinemia. It is a recommendation to monitor the QT interval while being on domperidone, avoid use for QT over 450 ms. Drug interactions may occur with cisapride, azole antifungals, and antiretrovirals. Patients resistant to metoclopramide and domperidone could have treatment with erythromycin, a macrolide antibiotic that has shown to stimulate high-amplitude gastric fundal peristaltic contractions, thereby improving symptoms in acute exacerbation. The Route of administration is intravenous (3 g/kg every eight hours) in acute cases and high dose oral administration (250 to 500 mg three times a day) for maintenance. But erythromycin is prone to tachyphylaxis (decrease in response quickly due to desensitization), and so its use is restricted to a maximum of four weeks at a time. Common side effects of erythromycin include GI toxicity, ototoxicity, bacterial resistance, QT prolongation.

Non-medical approaches: Gastric electrical stimulation (GES) has shown to relieve symptoms, mainly vomiting frequency and the need for nutrition supplementation.[1] In patients with refractory symptoms even after trial of the medications mentioned above, GES is considered as compassionate treatment approved for diabetic and idiopathic gastroparesis patients as a humanitarian exemption device. Diabetic patients respond more effectively than other groups of gastroparesis patients. Implantation of GES stimulator needs surgical procedure either via laparotomy or laparoscopic approach. The device consists of a pair of leads, implanted in the muscularis propria about 10 cm proximal to the pylorus, and then connected to a pulse generator. Risks of GES include infection of the device, lead migration, and perforation, necessitating repeat surgical procedures. Also may need battery replacement about every ten years or so. Other available interventions, with no substantial evidence, that are under consideration are venting gastrostomy or feeding jejunostomy, intra-pyloric botulinum toxin injection (not shown to be effective in randomized controlled trials), partial gastrectomy and pyloroplasty (used rarely, only in carefully selected patients). 

Future prospects: Multiple prospective treatments have been considered or being investigated for the management of gastroparesis. Granisetron, a 5-HT3 antagonist, administered as a transdermal patch, has improved gastroparesis symptoms of nausea and vomiting, as evident in a prospective study.[27] Similarly, a randomized control trial involving aprepitant, a neurokinin-1 receptor antagonist, showed positive results of symptom improvement in gastroparesis patients.[28] A scopolamine patch has undergone an evaluation with no significant effects. Also, research is ongoing studying the effects of transcutaneous acupuncture (TEA) in gastroparesis. Cannabinoids (dronabinol) have been considered in the treatment of gastroparesis symptoms, but there are no clinical trials reported. Cannabinoids are likely to be ineffective since they are known to delay gastric emptying. Attention should be given to the development of new effective therapies for symptomatic control. Relamorelin (a pentapeptide ghrelin receptor agonist) prucalopride and velusetrag (both are 5HT-4 receptor agonists) and metoclopramide nasal spray are investigational therapies undergoing evaluation in patients with gastroparesis.[29][30][31][32][31]

Symptoms of nausea and vomiting are so nonspecific that they could have a wide variety of differential diagnoses. But the following conditions mentioned below could pose a very similar presentation to gastroparesis.

1. Gastric Outlet Obstruction: very similar presentation but with underlying mechanical obstruction. 

2. Cyclical vomiting syndrome: Typically has recurrent cyclical episodes of intractable nausea and vomiting lasting few hours to days.

3. Functional dyspepsia: diagnosed by Rome IV criteria for functional dyspepsia.[33]

4. Rumination syndrome: A behavioral disorder consists of daily, effortless regurgitation of undigested food after ingestion of a meal. In contrast, it is not preceded by nausea or wretching.[34][35]

5. Psychiatric diseases – many psychiatric conditions, including anxiety neurosis, eating disorders like anorexia nervosa, bulimia could have persistent upper GI symptoms confusing with gastroparesis. It could get complicated, especially as some psychiatric medications can cause delayed gastric emptying. 

Gastroparesis is a rather uncommon condition in the community but can be associated with poor outcome.[14] The natural history of gastroparesis is unclear and poorly outlined. In one small study of 20 patients with diabetes followed for 12 years, gastric emptying symptoms were reasonably stable.[36] In another study, 86 patients with diabetes were studied; after adjusting for comorbidities, gastroparesis symptoms did not correlate with mortality.[37] In contrast, results from a study done at a tertiary center suggested 7% of gastroparesis patients had died, and 22% of patients needed long-term enteral or parenteral nutrition after six years follow up; this indicates gastroparesis could be associated with significant mortality and morbidity.[3] Controlled community studies for the prognosis of gastroparesis are needed, and data from tertiary care hospitals may not represent the disease in the general population. Postviral gastroparesis often improves over one year.[7][8]

The incidence of complications from gastroparesis could vary according to underlying etiology. Longstanding patients of gastroparesis will most likely suffer from the following complications.

• Severe protein-calorie malnourishment
• Bezoars
• Mallory Weiss tears from retching and vomiting
• Procedure-related complications
• Narcotic dependence and social stigma
• Recurrent hospitalizations
• Significant healthcare burden

Bezoar - a solid mass of indigestible material that accumulates in the stomach, eventually mechanical obstruction. Bezoars can cause loss of appetite, weight loss, and a feeling of fullness. They can also lead to gastric ulcers, GI bleeding, and bowel obstruction. Usually diagnosed by endoscopy and large bezoars often require surgical intervention.

Patients with gastroparesis frequently present challenging clinical, diagnostic, and therapeutic problems.[3] The nature of the disease itself could be a significant deterrence in obtaining appropriate healthcare. Systematic education targeting at different levels should help tackle this issue. Gastroparesis is a common diagnosis among diabetic patients. But it can affect people without diabetes or any attributable underlying disorder. It also can occur after viral gastroenteritis. All people with diabetes and other appropriate patients should receive education about symptoms and the natural history of gastroparesis. Diagnosed patients should have a detail education about diet and lifestyle modifications, including eating multiple small meals, avoiding alcohol, smoking, and fizzy drinks, which could cause bloating. Due to the chronicity of symptoms and the lack of definitive treatment options, plus the social implications it can cause, gastroparesis could drastically affect the quality of life of the patients. This aspect could be the most significant deterrence in the management of gastroparesis patients.

The number of gastroparesis-related hospitalizations has been increasing in the United States, and the economic impact of gastroparesis-related hospitalizations is significant and may be increasing.[14] Due to chronicity and idiopathic etiology in most cases, gastroparesis patients could face social stigma and become medication dependent.

An interprofessional team approach is essential to improve the morbidity of the disorder. The pharmacist should educate the patient on medications that can help improve gastric motility but at the same time, warn them about the adverse effects. The diabetes educator nurse should inform the patient on control of blood glucose, and the dietitian should recommend smaller meals at each setting. Patients should be encouraged to eat a healthy diet and consume ample water. Any food that triggers gastroparesis should be avoided. Healthy body weight and regular exercise are also recommended interventions. These examples demonstrate how an interprofessional team approach to gastroparesis can improve patient outcomes [Level 5]

One of the main aspects overlooked is the quality of life of the patient. Both patient and healthcare provider education plays a critical role in identifying and managing patients of gastroparesis. Most parts of the diagnostic approach to gastroparesis and recommendations regarding its treatment have their basis on the cumulative experience and opinions of physicians who specialize in the care of these patients. A more controlled investigation is needed to validate any therapeutic algorithm in managing this challenging condition.[9]

Interprofessional team dynamics can bring about optimal patient results. [Level 5]