Diagnosis and Management of Gastroparesis : Official journal of the American College of Gastroenterology | ACG

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THE RED SECTION: GUIDE TO THE GUIDELINES

Diagnosis and Management of Gastroparesis

Ramos, Gabriela Piovezani MD1; Law, Ryan J. DO1; Camilleri, Michael MD, DSc1

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The American Journal of Gastroenterology 117(12):p 1894-1898, December 2022. | DOI: 10.14309/ajg.0000000000002003
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Gastroparesis is a challenging gastrointestinal condition to manage in clinical practice. The recently published American College of Gastroenterology 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 3 vignettes below that illustrate different diagnostic and treatment approaches for gastroparesis (Figure 1; Table 1).

F1
Figure 1.:
Algorithm from the ACG Guideline on Gastroparesis, adapted with permission (ref. 1) to illustrate the diagnose and management of all 3 vignettes. Symbols: 1, vignette 1; 2, vignette 2; 3, vignette 3. ACG, American College of Gastroenterology; ECG, esophagogastroduodenoscopy; GE, gastric emptying; GI, gastrointestinal; G-POEM, gastric peroral endoscopic myotomy; WC, wireless motility capsule.
T1
Table 1.:
How recommendations were used in each clinical report

VIGNETTE 1: DIABETIC GASTROPARESIS

A 76-year-old man previously underwent vagotomy and pyloroplasty for peptic ulcer disease 30 years ago. He had no postsurgical 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 computed tomography scan and upper endoscopy (EGD), except for the presence of a gastric bezoar. Before being seen at our center, he had failed trials of metoclopramide, domperidone, and botulinum toxin injection to the pylorus.

A scintigraphic 4-hour gastric emptying (GE) study of a solid 300 kcal, 30% fat meal showed that 36% of the meal emptied at 2 hours and 69% at 4 hours (Figure 2). Electrocardiogram 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-month follow-up.

F2
Figure 2.:
Anterior images of gastric emptying scintigraphy studies from all 3 cases reported, showing the percentage (%) emptied from the stomach at 0, 1, 2, and 4 hours after ingestion of the 300 kcal, 30% fat solid meal containing technetium-99 (99Tc).
F3
Figure 3.:
Absence of sinus arrythmia shown by the consistent R-R intervals that vary by less than 0.12 seconds (3 small squares in the EKG)—indicative of cardiovagal neuropathy.

Comment

There is a complex relationship between glycemic control and GE. Experimentally, acute hyperglycemia (>250 mg/dL) retards GE. In long-term follow-up of patients with type 1 diabetes, baseline glycosylated hemoglobin and overall glycemic control shown by glycosylated hemoglobin 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 because of 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 a 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 gastrointestinal 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 affect outcomes in response to pyloric botulinum toxin injection (9). If prokinetic and antiemetic medications fail, nonpharmacological approaches to gastroparesis to consider are gastric electric stimulation and pyloromyotomy.

VIGNETTE 2: POSTSURGICAL GASTROPARESIS

A 61-year-old woman had undergone Nissen fundoplication and Collis gastroplasty for gastroesophageal reflux disease 20 and 15 years, respectively, before presentation to our clinic. More recently, she underwent laparoscopic pyloroplasty elsewhere for treatment of gastroparesis and chronic abdominal pain, without clinical response. Abdominal computed tomography and EGD were unremarkable. Dietary management and prokinetic therapy failed to ensure adequate nutritional intake; thus, she required enteral nutrition through a jejunal feeding tube. After 6 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.

F4
Figure 4.:
Gastroduodenal manometry from vignette 2 showing intraprandial antral hypomotility (normal 3 per minute low-amplitude contraction) with transient pylorospasm.

Comment

This patient has postsurgical 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 postsurgical gastroparesis (11). It is important to emphasize that opioids should be avoided for multiple reasons, including delaying GE. The only efficacious prokinetic for postsurgical gastroparesis is erythromycin (12). Unfortunately, the response may be short lived as a result of downregulation 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 patients with gastroparesis present with refractory disease despite these interventions (14).

The patient illustrated represents the typical failure of medications and nonpharmacological 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 is often required. Our patient was referred for Roux-en-Y gastric bypass as the next step in her treatment. Significant improvements in vomiting and abdominal pain have been documented 1 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 past 2 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 over the past 18 months. Repeat scintigraphic GE with a 300 kcal 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). Patients with gastroparesis 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). Pharmacological therapy failed for this young patient with severe idiopathic gastroparesis and required total parenteral nutrition. 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-term 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) before 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 the US Food and Drug Administration (FDA)-approved therapies for gastroparesis in the United States and the US FDA-recommended prescription for only 3 months for the only currently approved medication, metoclopramide.

T2
Table 2.:
Key points of guideline recommendations highlighted in these clinical vignettes

CONFLICTS OF INTEREST

Guarantor of the article: Michael Camilleri, MD.

Specific author contributions: The authors designed the article structure, conducted literature review, and wrote and revised the manuscript. All authors approved the final version of the article, including the authorship list.

Financial support: M.C. receives funding for research on gastroparesis from the National Institutes of Health (R01-DK122280 and R01-DK125680)

Potential competing interests: M.C. has consulted for AEON Pharma, Zealand Biopharma, Aditum Bio, Takeda, and Aclipse Therapeutics regarding the topic of gastroparesis. The other authors have no conflicts of interest.

ACKNOWLEDGMENT

We thank Cindy Stanislav for secretarial assistance.

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