DIAGNOSIS AND MANAGEMENT OF GASTROPARESIS

Gastroparesis is a challenging gastrointestinal condition to manage in clinical practice. The recently published American College of Gastroenterology (ACG) Guideline on Gastroparesis highlighted major features regarding risk factors, diagnosis, and management of this disorder.(1) However, given the complexities of patient care, guideline recommendations can seem impractical or difficult to enact. Therefore, we illustrate the recommendations provided in the guideline through discussion of three vignettes below that illustrate different diagnostic and treatment approaches for gastroparesis (Table 1; Figure 1).

Table 1.

How recommendations were used in each clinical report

Guideline recommendations	VIGNETTE 1	VIGNETTE 2	VIGNETTE 3
Risk Factors
Optimal glucose control in DG	Followed by endocrinologist Great glucose and HbA1c control.	Not DG	Not DG
Diagnosis
GE scintigraphy is the standard test (solid meal; duration of ≥3h test)	Delayed at 4h	Delayed at 4h	Delayed at 4h
Radiopaque testing not suggested	Not needed clinically
Wireless motility capsule testing and Stable isotope (13C-spirulina) breath test - alternative tests
Management
Small particle diet	First line treatment
Pharmacologic treatment to improve GE and symptoms – considering benefits and risks in DG and IG	Off label pyridostigmine
Metoclopramide over no treatment	Modest efficacy	Modest efficacy	Extrapyramidal side effects
Domperidone over no treatment	Not tried since not easily prescribed
5-HT4 agonists over no treatment	Not possible since no such drug available for GP in USA
Antiemetic agents	Only for symptom relief as needed
Central neuromodulators not recommended	Not used in accordance with guideline recommendations
Ghrelin agonists not recommended
Haloperidol not recommended
Non-pharmacological management
Gastric electric stimulation	Not performed	Option not selected in post-fundoplication GP	Not performed
Acupuncture not recommended	Not performed in accordance with guideline
Herbal therapies not recommended
EndoFLIP evaluation	Not performed		During G-POEM procedure
Intrapyloric injection of botulinum toxin not recommended	Performed previously No clinical response	Not performed in accordance with guideline	Not performed as recommended
Refractory GP: pyloromyotomy over no treatment	Not needed	1) Laparoscopic pyloroplasty performed elsewhere – no clinical response 2) Plan to undergo a Y-en-Roux gastric bypass	Outcome still being assessed

Abbreviations: DG, diabetic gastroparesis; GE, gastric emptying; GP, gastroparesis; G-POEM, gastric peroral endoscopic myotomy; HbA1c, glycosylated hemoglobin; IG, idiopathic gastroparesis

Figure 1. Algorithm from ACG Guideline on Gastroparesis (ref. 1) adapted with permission to illustrate the diagnose and management of all three vignettes.

Symbols: 1 – Vignette 1; 2 – Vignette 2; 3 – Vignette 3.

Abbreviations: ACG, American College of Gastroenterology; ECG, esophagogastroduodenoscopy; GE, gastric emptying; GI, gastrointestinal; G-POEM, gastric per-oral endoscopic myotomy; WC, wireless motility capsule.

VIGNETTE 1: Diabetic Gastroparesis

A 76-year-old man previously underwent vagotomy and pyloroplasty for peptic ulcer disease 30 years ago. He had no post-surgical gastrointestinal symptoms. Subsequently, he had been diagnosed with type 2 diabetes mellitus for 12 years and, for 2 years, he experienced recurrent nausea, vomiting, postprandial fullness, and abdominal distension. There was no evidence of structural abnormalities or obstruction on abdominal computerized tomography (CT) scan and upper endoscopy (EGD), except for the presence of a gastric bezoar. Prior to being seen at our center, he had failed trials of metoclopramide, domperidone, and botulinum toxin injection to the pylorus.

Scintigraphic 4-hour gastric emptying (GE) study of a solid 300kcal, 30% fat meal showed that 36% of the meal emptied at 2 hours and 69% at 4 hours (Figure 2). Electrocardiogram (ECG) showed absence of sinus arrhythmia (Figure 3), suggestive of cardiovagal denervation. These data are consistent with moderately severe diabetic gastroparesis (DG). We reinforced dietary instructions to use low residue meals, and cooking and homogenizing vegetables and fruits. An endocrinologist enhanced optimization of glycemia. The patient experienced an excellent clinical response with pyridostigmine 60 mg before each meal and remains well during 15 months’ follow-up.

Figure 2.

Anterior images of gastric emptying scintigraphy studies from all three cases reported, showing the percentage (%) emptied from the stomach at 0h,1h,2h and 4 hours after ingestion of the 300kcal, 30% fat solid meal containing Technetium-99 (⁹⁹Tc).

Figure 3.

Absence of sinus arrythmia shown by the consistent R-R intervals that vary by less than 0.12 seconds (three small squares in the EKG) - indicative of cardiovagal neuropathy

Comment

There is a complex relationship between glycemic control and GE. Experimentally, acute hyperglycemia (>250mg/dL) retards GE. In long-term follow up of patients with type 1 diabetes, baseline HbA1c and overall glycemic control shown by HbA1c trends over years were the most accurate predictors of delay in GE (2). Satisfactory glucose control is recommended to better regulate gastric transit and symptoms.(3) Ideally in DG, glucagon-like peptide 1 agonists should be avoided due to their effect on delaying GE.(4) The goal of the initial gastroparesis evaluation is to rule out mechanical obstruction. Although suggestive, the presence of retained gastric food on EGD is not confirmatory of gastroparesis as demonstrated in 2,991 patients without structural abnormalities who underwent EGD and GE by scintigraphy. The positive predictive value of retained food relative to delayed GE in the absence of an underlying risk factor was only 32%.(5) It is essential to exclude confounding medications and to perform a validated assessment of GE.

First-line pharmacological approaches to gastroparesis are metoclopramide and domperidone, where available. Both agents have predominantly dopaminergic antiemetic effects that may not provide sufficient prokinetic action on the stomach. Prokinetic efficacy may vary among patients, possibly related to the underlying physiopathology of DG (e.g., extrinsic versus enteric neuropathy). Evidence of cardiovagal denervation can be used in this case as a surrogate for abdominal vagal dysfunction as previously reported.(6) Pyridostigmine is an orally active acetylcholinesterase inhibitor that enhances the primary excitatory neurotransmitter, acetylcholine, in the enteric neurons to stimulate gastrointestinal smooth muscle (7) and GI transit in patients with diabetes.(8)

Although botulinum toxin injection to the pylorus is not recommended in the guideline, a recent multicenter study from France showed that evidence of decreased pyloric distensibility may impact outcomes in response to pyloric botulinum toxin injection.(9) If prokinetic and antiemetic medications fail, non-pharmacological approaches to gastroparesis to consider are gastric electric stimulation and pyloromyotomy.

VIGNETTE 2: Post-surgical Gastroparesis

A 61-year-old woman had undergone Nissen fundoplication and Collis gastroplasty for gastroesophageal reflux disease 20 and 15 years, respectively, prior to presentation to our clinic. More recently, she underwent laparoscopic pyloroplasty elsewhere for treatment of gastroparesis and chronic abdominal pain, without clinical response. Abdominal CT and EGD were unremarkable. Dietary management and prokinetic therapy failed to ensure adequate nutritional intake; thus, she required enteral nutrition via jejunal feeding tube. After six months, she presented to our clinic with malnutrition and severe epigastric pain. GE scintigraphy confirmed severe gastroparesis with only 26% emptied after 4 hours (Figure 2). On gastroduodenal manometry, antral hypomotility with transient pyloric contraction was observed during meal ingestion (Figure 4), but there was no consistent pylorospasm identified postprandially.

Figure 4.

Gastroduodenal manometry from vignette 2 showing intraprandial antral hypomotility (normal three per minute low amplitude contraction) with transient pylorospasm

Comment

This patient has post-surgical gastroparesis and is now presenting with pain as her main symptom. Despite evidence of partial improvement in upper abdominal pain using central neuromodulators for functional dyspepsia, the improvement is usually restricted to those with normal gastric emptying, not to those with delayed GE.(10) One large, placebo-controlled trial of nortriptyline in patients with idiopathic gastroparesis showed no benefit, but the trial did not include post-surgical gastroparesis.(11) It is important to emphasize that opioids should be avoided for multiple reasons, including delaying GE. The only efficacious prokinetic for post-surgical gastroparesis is erythromycin.(12) Unfortunately, the response may be short lived as a result of down-regulation of the motilin receptor leading to tachyphylaxis.(13) Although overall management of gastroparesis relies predominantly on dietary modifications and pharmacotherapy, a recent systematic review showed that up to 20–30% of gastroparesis patients present with refractory disease despite these interventions.(14)

The patient illustrated represents the typical failure of medications and non-pharmacological intervention to the pylorus, requiring enteral nutrition to maintain her nutritional status. Gastroduodenal manometry confirmed antral dysmotility and, targeting only the pylorus may be insufficient to achieve satisfactory long-term outcomes. Thus, surgical treatment including gastrectomy or Roux-en-Y gastric bypass (RYGB) is often required. Our patient was referred for RYGB as the next step in her treatment. Significant improvements in vomiting and abdominal pain have been documented one year after the procedure.(15)

VIGNETTE 3: Idiopathic Gastroparesis

A 24-year-old man without underlying comorbidities presented with food intolerance, nausea, vomiting, and weight loss over the last two years. After extensive investigation elsewhere, the only abnormal finding was delayed GE on scintigraphy, suggestive of severe idiopathic gastroparesis. He was unable to tolerate metoclopramide and antiemetics due to side effects and became dependent on total parenteral nutrition (TPN) over the past 18 months. Repeat scintigraphic GE with the 300kcal meal showed less than 60% emptied after 4 hours (Figure 2). An autonomic reflex screen showed no signs of vagal, sympathetic adrenergic, or sympathetic cholinergic neuropathy. An unsatisfactory clinical response with prokinetic therapy, including pyridostigmine, led to gastric peroral endoscopic myotomy (G-POEM). The patient continues rehabilitation with the nutrition team and continues using the prokinetic agent to support oral intake.

Comment

Two major concerns in patients with gastroparesis are nutritional status and weight loss. The first step to manage gastroparesis is dietary modification including use of small-particle, low-fat, and low-fiber diet along with adequate hydration.(16) Gastroparesis patients with severe malnutrition (weight loss greater than 10% within 6 months of diagnosis), nutrient deficiencies, or frequent hospitalizations may require enteral or, rarely, parenteral nutrition to maintain their nutritional status.(14, 17, 18) This young patient with severe idiopathic gastroparesis failed pharmacological therapy and required TPN. Management of refractory gastroparesis includes surgical options such as G-POEM. Based on open-label studies, G-POEM decreases the Gastroparesis Cardinal Symptom Index, both in short- and long-term follow-up. The first sham-controlled study showed improved gastric symptoms after 6 months of follow-up, particularly in patients with diabetic gastroparesis.(19) Adding measurements of pyloric diameter and distensibility (with EndoFLIP) prior to the pyloric intervention may predict response to treatment.(20) Long-term follow-up of this patient should include a multidisciplinary team - gastroenterology, endoscopy, and nutrition.

CONCLUSION

Table 1 summarizes the points of agreement or discrepancy between the guideline recommendations and the clinical management of all patients. The key messages with the above vignettes are highlighted in Table 2. Despite challenges, following the evidence-based recommendations provided by the guideline should aid in the management of gastroparesis by improving symptoms and quality of life for this population. Nevertheless, as acknowledged in the new guideline (1), it is necessary to recognize the limitations of guideline recommendations on pharmacotherapies in view of the dearth of FDA-approved therapies for gastroparesis in the United States and the FDA-recommended prescription for only 3 months for the only currently approved medication, metoclopramide.

Table 2.

Key points of guideline recommendations highlighted in these clinical vignettes

Exclude mechanical obstruction prior to diagnosis

Retained gastric food in esophagogastroduodenoscopy should not be diagnostic of gastroparesis.  - When clinically suspected an appropriate diagnostic test must be performed

Small particle, low-fiber and low-fat diet is recommended to all patients; fibers ideally cooked and blenderized.

Nutritional status and weight should be always evaluated.

If oral intake is not available, enteral or rarely parenteral nutrition should be considered.

Pharmacological approach is limited – metoclopramide as first-line prokinetic therapy

Non-pharmacological therapeutic options must be taken into consideration when available  - Gastric electric stimulation and interventions targeting the pylorus

Management of gastroparesis is suggested to be with a multidisciplinary team, especially in refractory patients.  -- Gastroenterology, Endoscopy and Nutrition team

Gastric surgery can be considered a treatment option when all other approved therapies failed.