Chapter 18. Disorders of Gastric & Small Bowel Motility

• The three most common causes of gastroparesis are idiopathic, diabetic, and postsurgical.
• Chronic intestinal pseudo-obstruction (CIPO) involves intermittent failure of intestinal peristalsis in the small or large intestine, or both.
• Noninvasive imaging or endoscopy, or both, should be used to rule out mechanical obstruction in patients being worked up for gastroparesis or CIPO.
• The 4-hour gastric emptying scintigraphy scan using a low-fat, egg-white meal is the best test for gastroparesis.
• Accelerated gastric emptying and dumping syndrome are often related to postgastric surgery.

Altered gastric and small bowel motility result in either delayed gastric emptying or rapid transit. Among the disorders of gastric and small bowel motility discussed in this chapter are gastroparesis, chronic intestinal pseudo-obstruction (CIPO), dumping syndrome, and rapid transit dysmotility of the small bowel.

Gastroparesis and CIPO are chronic long-term problems that have a variety of causes and can be neuropathic or myopathic. Treatment of these conditions includes dietary, medical, and, rarely, surgical therapies. Research in gastroparesis is ongoing with a focus on improving diagnostics and newer therapeutic agents. Dumping syndrome is a postsurgical iatrogenic problem that is occurring less often in relation to gastric ulcer surgery, but may be increasing among bariatric surgery patients in tandem with the increase in surgical treatment of obesity. Patient education, dietary change, and management of underlying medical problems are important factors in the overall management of these motility disorders.

Normal gastric emptying requires coordinated efforts by the muscles that control the four regions of the stomach, nerves that modulate the actions of these muscles, and chemical mediators. Important events that occur during gastric filling and emptying include fundic relaxation (accommodation) in response to food ingestion, antral contractions and churning (trituration) of large food particles, and finally pyloric relaxation.

The neurogenic network of the stomach includes elements of both the central nervous system (CNS) and the enteric nervous system (ENS). The CNS elements involve both sympathetic fibers and parasympathetic fibers. Sympathetic fibers arise from the thoracic spinal nerves, extending to postganglionic nerves that run along the celiac plexus and the vascular supply to the stomach. The sympathetic innervation includes afferent pain fibers that arise from the stomach, as well as motor fibers that innervate the pyloric sphincter. The parasympathetic innervation stems from the right and left vagal trunks, which eventually divide into multiple branches that course throughout the stomach wall and synapse with the ENS.

The ENS is an independent branch of the peripheral nervous system that is divided into two plexuses: the submucosal (Meissner) and the myenteric (Auerbach) plexuses. The submucosal plexus receives only parasympathetic input and innervates the cells of epithelial layer and muscular externa. The myenteric plexus, on the other hand, is situated between the middle circular and the outer longitudinal muscle layers, receiving both sympathetic and parasympathetic input. It mediates the motor function of both muscle layers and the secretory functions of the mucosa.

The interstitial cells of Cajal (ICCs) are the "pacemaker cells" of the stomach. They are located in the myenteric plexus and are responsible for basal slow-wave activity, which occurs at 3 cycles per minute. This slow-wave activity is also called the electronic control activity or the pacesetter potential. The ICCs are also responsible for bridging the myogenic and neurogenic control mechanisms.

The migrating motor complex (MMC) is the pattern of motility activity that occurs in the fasted state. It is a 1–2 hour cycle beginning in the stomach or small intestine and divided into three phases. Phase I (45–60 minutes) is a quiescent period. Phase II (30 minutes) is a period of random intermittent contractions. Lastly, phase III (5–15 minutes), also called the activity front, is a period in which bursts of rapid, even-paced uninterrupted peristaltic contractions occur.

Upon ingesting a meal, the MMC is abolished. Gastric accommodation occurs with distention of the fundus to make room for the incoming ingested contents. This response is mediated by the parasympathetic activity from the vagal nerve through cholinergic neurotransmitters, and inhibitory input by neurotransmitters such as nitric oxide, vasointestinal peptide, and serotonin.

The ingested contents upon entering the stomach are distributed, triturated, and then emptied into the duodenum. Liquids are usually dispersed and emptied immediately. The rate of liquid emptying is slowed by high osmolarity, high nutrient content, and carbonation. Solids, on the other hand, are stored in the fundus, churned in the antrum, and emptied in two phases: a lag period and a linear emptying period. The two periods occur over 3–4 hours, with the lag period lasting 1–3 hours. During the lag period, food particles move proximally to distally and undergo trituration and redistribution. Trituration occurs in the antrum with high-amplitude contraction waves that propagate proximally to distally. The food particles are reduced to a size of approximately 1–2 mm in diameter prior to emptying. The pylorus ultimately regulates how much content is emptied into the duodenal bulb by coordinated contractions and maintenance of the lumen with fixed tone.

Besides mechanical factors, neurohormonal factors also control the rate of emptying. Glucagon and incretins (eg, amylin and glucagon-like peptide 1) slow gastric emptying. The vagus provides both excitatory and inhibitory innervation. The presence of chyme in the duodenum provides negative feedback on the rate of emptying as mediated by duodenal distention, acidification, or perfusion with fats and protein. The regulation of duodenal intake controls the level of postprandial hyperglycemia from nutrient absorption.

General Considerations

Gastroparesis is characterized by delayed gastric emptying that is not associated with the presence of an obstructing structural lesion in the stomach or distally in the gastrointestinal tract. Many disorders that interfere with the normal neuromuscular coordination of the stomach can lead to gastroparesis (Table 18–1). The three most common causes are idiopathic, diabetic, and postsurgical. A tertiary referral series of 146 patients showed the causes of gastroparesis to be 36% idiopathic, 29% diabetic, 14% postgastric surgery, 7.5% Parkinson disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudo-obstruction, and 6% miscellaneous causes (eg, paraneoplastic syndrome, superior mesenteric artery syndrome, and median arcuate ligament syndrome). The idiopathic causes included acute viral-like gastroenteritis (23%), gastroesophageal reflux disease (GERD) and nonulcer dyspepsia (19%), and cholecystectomy.

CIPO is characterized by obstructive symptoms generated from the small or large bowel occurring in the absence of anatomic obstruction. It is a severe form of dysmotility that is considered a failure or insufficiency of the "intestinal pump." Like gastroparesis, CIPO has a wide variety of causes (Table 18–2). These can generally be separated into congenital versus acquired causes, and myopathic versus neuropathic processes. Because gastroparesis and CIPO have very similar clinical approaches, this section discusses the assessment and treatment of these conditions together.

The true prevalence of gastroparesis has been difficult to study due to underdiagnosis and the lack of inexpensive diagnostic testing that is also widely available. A large population-based study in Olmsted County, Minnesota, estimated the age-adjusted prevalence of definite gastroparesis, defined as delayed gastric emptying on scintigraphy and typical symptoms for more than 3 months, to be 24.4 per 100,000 persons (95% confidence interval [CI], 15.7–32.6). Other population studies have shown upper gastrointestinal symptoms to be present in 11–18% of diabetic patients, with 50–65% of them having delayed gastric emptying. The mean age of gastroparetic patients in one study was 45 years old, with a mean age of onset of 33.7 years. The prevalence of gastroparesis per 100,000 persons was 9.6 among men versus 37.8 among women. It is unclear whether gender influences the pathophysiology of gastroparesis or if this represents a difference in health care–seeking behavior between men and women. An overlap syndrome of gastroparesis and functional dyspepsia has been noted, and 25–42% of patients with functional dyspepsia have concomitant gastroparesis.

Clinical Findings

Symptoms and Signs

Typical complaints of gastroparesis include postprandial nausea, vomiting, belching, early satiety, bloating, discomfort, or pain. Reflux symptoms are also common. Chronic symptoms include weight loss or electrolyte disturbances, or both. Signs and symptoms of nutritional and vitamin deficiencies that may be noted include temporal wasting and loss of subcutaneous fat (malnutrition), gum bleeding (vitamin C), visual changes with night blindness (vitamin A), neuropathy, or impaired memory and confusion (folate, vitamin B12). Dysphagia or odynophagia may occur as a result of reflux esophagitis. Diarrhea and malabsorption may be a consequence of bacterial overgrowth caused by altered peristalsis. Symptoms to look for include dry mouth, eyes, or vagina; difficulties with visual accommodation in bright light; anhidrosis (absence of sweating); impotence; dizziness on standing; scleroderma symptoms such as Raynaud phenomenon, skin tightening, and peripheral paresthesia; and numbness or focal weaknesses. A medication history can elicit drugs that may contribute to altered gastric motility (Table 18–3).

The examination should include assessment of volume status for dehydration (eg, orthostasis, pallor, and poor skin turgor) and signs of metabolic alkalosis, such as decreased respirations. Abdominal examination may reveal distention or surgical scars. The examiner should auscultate for obstructive high-pitched or absent bowel sounds, and palpate for focal tenderness or mass. A succussion splash may be heard when auscultating over the stomach while shaking the abdomen from side to side 1 hour or more postprandially. The examiner should also test for abdominal wall–related pain by observing for Carnett sign (positive when tenderness is increased upon tensing of the abdominal muscles). Findings suggesting diabetic microvascular complications should be noted (eg, retinopathy and sensory or autonomic neuropathy). Signs of recurrent vomiting may include worn tooth enamel. Nutritional deficiencies may manifest as brittle hair and nails, cheilosis, glossitis, and tetany.

Symptoms can also be assessed by a validated instrument, the Gastroparesis Cardinal Symptom Index (GCSI), which was developed for measurement of three subsets of symptoms, including postprandial fullness/early satiety, nausea/vomiting, and bloating. The GCSI has been validated for measuring symptom severity.

Imaging and Endoscopic Studies

Radiologic studies include plain film abdominal radiographs, computed tomography of the abdomen, small bowel follow-through examination, and magnetic resonance imaging (MRI). Oral contrast should be water soluble to prevent formation of barium concretions in the gastrointestinal tract with dysmotility. Gastroparesis may be demonstrated by retained contrast in the stomach or its slow gastric transit into the small bowel. In CIPO, abdominal films may show dilated loops of small bowel and air-fluid levels (Figure 18–1), and small bowel follow-through studies may help rule out obstructive lesions. MRI can measure gastric emptying and may provide additional information including gastroduodenal motility. However, its use in the evaluation for gastroparesis is still limited to the research setting.

Upper endoscopy is useful for ruling out a mechanical obstruction of the upper gastrointestinal tract (eg, masses, peptic ulcer disease [PUD], complications of pyloric stenosis, or acute PUD with antral edema). Retained food despite overnight fast may also be seen in the stomach during upper endoscopy in patients with gastroparesis.

Scintigraphy

The best current clinical test for delayed gastric emptying is gastric emptying scintigraphy using radionuclide technetium 99–labeled food. The test involves ingestion of a radiolabeled meal prepared by cooking radioisotope into the solid portion, which is usually a soft-textured food such as eggs. Scintigraphy is then performed 1–4 hours after ingestion (Figures 18–2A and 18–2B). Retention is abnormal when more than 90% of the tracer remains in the stomach at 1 hour, more than 60% at 2 hours, or more than 10% at 4 hours.

Tests shorter than 4 hours are less accurate for several reasons, including reduced sensitivity. Furthermore, the lag period is variable; some patients with prolonged lag phases have apparently normal 4-hour tests due to a "catch-up" in gastric emptying. Gastric residual measured at 4 hours after ingestion has a 100% sensitivity and 70% specificity for gastroparesis.

There had been some concerns about the lack of standardization of the procedure, and several proposed protocols have been suggested. Most recently, a consensus statement from experts of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine recommends a standardized protocol with a 4-hour test using low-fat, egg-white meal. Scintigraphy measurements are then taken at 0, 1, 2, and 4 hours after ingestion.

Another use of scintigraphy is the assessment of gastric accommodation. By dividing the area of interest into a distal and proximal segment and radiographically measuring the gastric volume in each segment, the regional changes over time can be assessed. A normal stomach with appropriate accommodation usually shows redistribution of the meal to the distal segment after accumulation in the proximal segment. Impaired gastric accommodation can be seen in diabetic vagal neuropathy, postvagotomy surgery, post-fundoplication dyspepsia, and functional dyspepsia.

Breath Testing

Another tool to measure gastric emptying is breath testing using a solid meal with nonradioactive isotope 13C-labeled medium-chain triglycerides, octanoate, or spirulina. When ingested, the 13C-labeled octanoate or spirulina is rapidly absorbed in the small intestine and metabolized into 13CO2, which can then be measured in breath samples to indirectly estimate the rate of gastric emptying. This test has been shown to correlate strongly with scintigraphy by some clinical studies, and its execution has been simplified with recent development of a standardized test meal for octanoate. Further research in this method of measuring gastric emptying is ongoing with the goal of using breath testing possibly as an office-based test in the future.

Special Tests of Motility

Ingestion and counting of radiopaque markers at 6 hours has been used to help identify the location of functional dysmotility. However, the clinical utility of this test is limited due to lack of standardization and possible uncertainty about whether markers are located in the stomach or within a segment of small bowel that overlaps the stomach.

For evaluation of small bowel motility, upper gastrointestinal and small bowel film series provide rough assessments at best. Quantification can be done by scintigraphy.

Antroduodenal manometry, which is not widely available, can provide information about the coordination of gastric and duodenal motility and can help differentiate between a neuropathic and a myopathic motility problem in CIPO. It involves inserting a large catheter with multiple manometric sensors down to the antrum and the proximal small bowel, usually with the aid of fluoroscopy. The test is then performed over several hours in the fasting state, with a test meal, and sometimes with motility agents such as erythromycin. A neuropathic process that is intrinsic or visceral is usually characterized by uncoordinated contractions of normal amplitude, and abnormal or even absent phase III contractions of the MMC. The presence of phase III of the MMC is associated with a favorable prognosis, with better tolerance of enteral feedings and response to prokinetic drugs. In contrast, contraction amplitudes are reduced with myopathic processes, while spatial and temporal organization is preserved. Other antroduodenal manometric findings in CIPO may include simultaneous waveforms, retrograde propagation of phase III of the MMC, high-amplitude and high-frequency bursts during both fasting and fed periods, and sustained high-pressure zones in limited small bowel segments, or inability of a meal to initiate the fed period activity pattern.

Electrogastrography

Electrogastrography can record gastric muscular activity waveforms via cutaneously placed pads, similar to an electrocardiogram for the myocardium. Abnormal electrogastrograms are defined as observed dysrhythmia for more than 30% of the recording time or failure of an ingested meal to elicit increased amplitude in gastric signals. However, the electrogastrogram has not been widely used clinically. Furthermore, there has been little evidence that electrogastrography aids in the management of patients with gastroparesis.

SmartPill Capsule Monitoring

The SmartPill GI Monitoring System is an ingested capsule that can deliver information on pressure, pH, and temperature wirelessly to a data recorder worn by the patient. The pill is swallowed after ingesting a standard 220-kcal meal. The data permit estimates of gastric emptying time, combined small and large bowel transit time, and total transit time, as well as study of pressure patterns from the gastrointestinal tract in the stomach, small bowel, and colon. The capsule has been approved by the U.S. Food and Drug Administration (FDA) for use in studying gastroparesis. The device has been compared with gastric scintigraphy at a 2-hour emptying time (r = 0.63) and at a 4-hour emptying time (r = 0.73). The better correlation with 4-hour emptying time is likely due to the capsule, a nondigestible solid, being emptied from the stomach after the emptying of most of the test meal in the subject. The device is a reasonable alternative to conventional scintigraphy for gastroparesis. The utility of SmartPill in the study of small and large intestinal dysmotility in the clinical setting remains unclear, given the current lack of standard parameters.

Differential Diagnosis

Once mechanical obstruction is ruled out, vomiting related to gastroparesis must be distinguished from regurgitation, rumination syndrome, and the eating disorders of anorexia nervosa and bulimia. Rumination syndrome is characterized by daily, early postprandial regurgitation of food that occurs effortlessly without nausea, likely as a learned behavior. Daily vomiting is seen only in severe gastroparesis. In addition, associated symptoms of abdominal pain, discomfort, and bloating are more suggestive of gastroparesis. Other non-obstructive disorders with symptoms that may mimic gastroparesis include functional dyspepsia (postprandial distress syndrome subtype), accelerated gastric emptying, and esophageal dysmotility.

Treatment

Treatment should be tailored for each individual. The general approach to management involves correction of dehydration, malnutrition, and nutritional deficiencies; dietary modifications; use of pharmacologic motility agents, including prokinetics and antiemetics; and normalization of hyperglycemia in diabetic gastroparesis. For patients with refractory gastroparesis, more aggressive therapies include decompression by gastrostomy tubes, consideration of gastric pacing, pyloric injection with botulinum toxin, and surgical treatment.

Correction of Dehydration and Nutritional Deficiencies

During acute exacerbation of gastroparesis, dehydration and electrolyte imbalances should be corrected promptly. Hypokalemia and metabolic alkalosis are common in patients with persistent vomiting. Repletion can be instituted orally, enterally through feeding tubes, or parenterally. If the gastrointestinal tract is severely impaired, parenteral nutrition should be considered. Prolonged enteral feeding may require a jejunostomy tube to bypass the pylorus.

Dietary Modifications

Dietary recommendations include eating frequent, smaller sized meals. Solid foods can also be substituted for those that are pureed or liquid, such as soups. High-fat foods delay gastric emptying, as do high-fiber foods.

Pharmacotherapy

Prokinetics

Prokinetics available in the United States include metoclopramide and erythromycin, both of which can be administered orally and intravenously. Erythromycin (40–250 mg three times daily) is a macrolide antibiotic that has activity on motilin receptors on both neurons and smooth muscles. Metoclopramide (starting with 5 mg twice daily to 10–20 mg two to three times daily) is a 5-HT4 agonist and dopamine antagonist, and, therefore, contains both antiemetic and prokinetic activity. Both of these drugs have been shown in randomized controlled trials to improve symptoms by 25–68% and to increase gastric emptying in objective tests by 25–72%. Elixir forms of both drugs may have better absorption and subsequent bioavailability than pill forms. Intravenous erythromycin at 3 mg/kg (given at 125–250 mg three to four times daily) is more effective than placebo in hospitalized patients with gastroparesis and has been demonstrated to decrease symptoms, with positive objective measures of improved emptying. Unfortunately, the beneficial effect of erythromycin is often short-lived due to tachyphylaxis, or tolerance to the medication. Rapid development of tolerance to the medication may be due to saturation of motilin receptors and their subsequent down regulation. The treatment effect of erythromycin significantly drops after 4 weeks, although some patients may continue to experience benefit. Therefore, erythromycin may be best used during exacerbations of symptoms or on an intermittent basis in those unable to tolerate, those who need a holiday from, or those unresponsive to metoclopramide.

Several other prokinetics have been used clinically for gastroparesis but are not widely available in the United States. Other agents include cisapride, a parasympathomimetic that acts as a serotonin 5-HT4 agonist, and domperidone, a dopamine (D2) receptor antagonist. Both drugs are available in Canada, Mexico, and Europe. Domperidone is available in the United States through an FDA investigational new drug (IND) program. Cisapride has been associated with long QT syndrome, which can predispose to torsades de pointes, causing the drug to be taken off the U.S. market in March 2000. Likewise, domperidone has not been approved by the FDA due to risk of cardiac arrhythmia and its bioavailability in breast milk. However, both drugs have been found to be efficacious in treating gastroparesis. Additional concerns with metoclopramide and domperidone relate to CNS side effects, which include somnolence, mental function, anxiety, and depression. There are also medicolegal concerns about the chronic use of metoclopramide owing to adverse reactions (ie, neurologic effects and movement disorders). Early effects include akathisia (a sensation of "inner restlessness") and dystonia, and later effects may include tardive dyskinesia and parkinsonism. Because domperidone does not cross the blood-brain barrier, its CNS effects are notably less compared to metoclopramide. On the other hand, both domperidone and metoclopramide are equally effective in controlling symptoms of diabetic gastroparesis in comparative trials.

Antiemetics

Antiemetics such as diphenhydramine, phenothiazine compounds, and even metoclopramide can help control symptoms of nausea. The more commonly used agents include prochlorperazine, trimethobenzamide, and promethazine. Serotonin (5-HT3) antagonists, such as granisetron and ondansetron, are frequently used in chemotherapy patients but are also useful in gastroparesis. They act on the area postrema and peripheral afferent nerves. Other agents used in clinical practice, albeit without strong supportive data, include benzodiazepines, synthetic cannabinoids, and transdermal scopolamine.

Alternative Agents

Multiple other agents with different mechanisms have also been tried. Tegaserod (Zelnorm; 2–6 mg twice daily) is a partial 5-HT4 receptor agonist that enhances gastric emptying, but no clinical trials have been undertaken specifically in patients with gastroparesis. It has been used with anecdotal success, but was removed from the market in early 2007 due to concerns about increased risk of myocardial infarction and stroke. Agents with limited success and also with notable adverse cholinergic side effects include bethanechol (10–20 mg two to three times daily), a muscarinic cholinergic agent, and pyridostigmine (30 mg four times daily), an anticholinesterase.

Pain Management

The management of pain in gastroparesis has not been specifically addressed in clinical studies. Currently, the most commonly used agents are tricyclic antidepressants (nortriptyline, amitriptyline), which have been shown to be effective in treating functional bowel disorders. Other approaches to pain management in gastroparesis include the use of tramadol, a weak μ-opioid receptor agonist, and gabapentin, a γ-aminobutyric acid analog. Opioids commonly prescribed for chronic pain syndromes should be avoided given their effects on gastrointestinal motility.

Other Drugs

Pharmacologic treatment for disorders associated with CIPO include antibiotic regimens for bacterial overgrowth, which is usually treated with common antibiotics such as doxycycline, ciprofloxacin, metronidazole, or double-strength trimethoprim–sulfamethoxazole for 7–10 days. More recently, rifaximin (400–1200 mg/day), a nonabsorbable antibiotic approved for use in traveler's diarrhea, has been effective for small bowel bacterial overgrowth and normalizing hydrogen breath tests.

Short-acting subcutaneous octreotide (50 mcg subcutaneously at night) has been tried in patients with CIPO, and studies have shown that it increases MMCs in the small bowel. This therapy should be avoided in patients with concomitant bacterial overgrowth.

Investigational Drugs

Some of the drugs currently under investigation include other prokinetics such as itopride, a dopamine receptor antagonist, and mosapride, a 5-HT4 receptor agonist. Ghrelin agonists are also under investigation. Several motilitides, which are motilin receptor agonists without some of the undesirable features of erythromycin, are also being studied. Azithromycin given intravenously has been compared with erythromycin and was found to result in higher antral contraction amplitude and motility index. Further study of its effects on symptom improvement is needed.

Normalization of Hyperglycemia

There is little evidence that controlling hyperglycemia has a direct relationship to symptom improvement. However, there is a well-established inverse relationship between blood glucose levels and rate of gastric emptying. Hyperglycemia is associated with delayed gastric emptying, as are euglycemia with normal gastric emptying and hypoglycemia with accelerated gastric emptying. Moreover, acute changes in blood glucose concentration have an effect on both gastric motor function and upper gastrointestinal symptoms. Evidence also suggests that response to prokinetics is partially determined by hyperglycemia. With regard to practical care of diabetic patients with gastroparesis, short-acting insulin should be dosed after, rather than prior, to eating to ensure that the patient tolerates the entire meal and to avoid hypoglycemia.

Decompression Gastrostomy Tubes and Jejunal Feeding Tubes

Advanced gastroparesis or CIPO may require decompression. Venting can be accomplished by a nasogastric tube or by a percutaneous endoscopic gastrostomy (PEG) or jejunostomy tube. Several feeding tubes have both a venting port upstream and a feeding port downstream. However, before placing the tube in a patient with severe symptoms, it is prudent to try nasal jejunal tube feeding first to test whether the patient can tolerate enteral feeding. Criteria for tube feeding include severe weight loss, multiple hospitalizations, and malnutrition.

Gastric Electrical Stimulation (GES)

Electrical stimulation of the stomach for treatment of gastroparesis is done laparoscopically by implanting a device into the antral muscular wall, with electrodes that connect to a pacemaker pocketed into the abdominal wall. The stimulation is classified based on the frequency of the electrical stimulus (high or low frequency). A high-frequency electrical stimulation device (Enterra, Medtronic) has been approved by the FDA through a humanitarian device exemption. A crossover controlled trial of 33 patients with idiopathic or diabetic gastroparesis showed that the frequency of vomiting was decreased significantly, but overall effect on symptoms was not significant. Open-label long-term studies with follow-up of 3.4–3.7 years have shown relief of symptoms and decreased need for nutritional supplementation. Predictors of treatment success in patients receiving GES include diabetic gastroparesis, symptoms that are predominantly nausea and vomiting, and symptoms that do not require narcotic therapy. Although GES is a promising therapy, further studies are needed in this area.

Pyloric Injection with Botulinum Toxin

Gastric emptying may be facilitated by keeping the pylorus relaxed. Injection of botulinum A toxin into the pyloric sphincter has been thought to paralyze the smooth muscle of the pylorus and antrum by inhibiting acetylcholine release. Several uncontrolled open-label trials have previously reported its efficacy in gastroparesis. However, two randomized, controlled trials have shown no treatment benefit in both subjective (symptoms) and objective (gastric emptying) endpoints. These results suggest no role for pyloric sphincter botulinum toxin injection in the treatment of gastroparesis.

Surgical Treatment

Surgical treatment is the last resort for both gastroparesis and CIPO and is rarely indicated. For gastroparesis, surgical placement of gastrostomy and jejunostomy tubes may be done for feeding and decompression. Definitive surgical treatment for gastroparesis includes a subtotal or complete gastrectomy. A systematic review of surgical therapy for gastroparesis found that gastrectomy may help postsurgical gastroparesis, but issued caution on surgical therapy for diabetic or idiopathic gastroparesis.

For CIPO, the surgical therapy aims to bypass areas of localized disease in the small intestine, or resect the colon for severe constipation. Again, caution is warranted when considering surgery in this condition as the original problem may manifest itself in unresected portions of the gut. If the disease is within the upper and lower intestinal tract, colectomy is less likely to be beneficial. Gastrostomy, jejunostomy, or loop enterostomy may be done to shorten the gut, facilitate transit, and vent the bowel. Percutaneous colonoscopy in adult CIPO patients has shown success in reducing distention.

Small bowel transplantation is indicated for patients with end-stage parenteral nutrition–dependant pseudo-obstruction and complications of prolonged parenteral nutrition or line access.

Prognosis

Little is known about either the overall prognosis or the quality of life of patients with gastroparesis and CIPO. The disease can be long-standing and have a substantial impact on well-being. Symptom severity scales have been developed and validated and may be useful in clinical and research settings. The overall long-term prognosis is determined by the underlying disease process, if known.

General Considerations

Dumping syndrome and accelerated gastric emptying are diseases that can occur after gastric surgery when a truncal vagotomy or gastrectomy has been performed. With the onset of medical treatment for PUD and Helicobacter pylori eradication, gastric ulcer surgery has significantly decreased, and expectedly, these postoperative accelerated gastric states have also decreased. Presently, bariatric surgery with Roux-en-Y gastric bypasses causes dumping syndrome in as many as 50% of patients. Aside from the iatrogenic causes, diabetes with vagal dysfunction and Zollinger-Ellison syndrome can also be associated with rapid gastric emptying. Rapid gastric emptying is caused by high gastric pressures, impaired gastric accommodation, and the lack of a regulating pyloric sphincter.

Clinical Findings

Symptoms and Signs

Dumping syndrome can be characterized as early or late, each with different symptoms. Both types of dumping syndrome can occur in the same patient. Early dumping syndrome occurs during or immediately after a meal and is characterized by nausea, vomiting, bloating, cramping, diarrhea, dizziness, and fatigue. These early symptoms are hypothesized to be due to a hyperosmolar load in the small bowel. Some of the postprandial upper abdominal symptoms associated with early dumping syndrome can be indistinguishable from those of delayed gastric emptying. Late dumping happens 1–3 hours after a meal and is characterized by hypoglycemia, weakness, sweating, and dizziness. Hypoglycemia occurs because a high carbohydrate content absorption into the small bowel evokes a strong insulin response with secondary hypoglycemia.

Diagnostic Tests

Dual-phase gastric scintigraphy using radiolabeled solids and liquids is the best diagnostic test. Hydrogen breath tests can be diagnostic in the appropriate clinical scenario. If early dumping is suspected, an early peak will be noted, usually within 1 hour of ingestion.

Treatment

The treatment of dumping syndrome involves mainly dietary modifications. These include switching to smaller, more frequent meals; minimizing ingestion of simple carbohydrates; avoiding simultaneous fluid intake with solids; and adding supplemental fiber (pectin, guar gum) to increase the viscosity of the ingested food and delay gastric emptying. Medical therapy includes acarbose (50–100 mg three times daily), an α-glucosidase inhibitor that blunts the rapid absorption of glucose. Short-acting (50 mcg subcutaneously three times daily) or long-acting (10 mg intramuscularly every 4 weeks) octreotide acts by inhibiting effects on insulin and gut hormone release, as well as decreasing intestinal transit time. Short-term use is initially effective, but response is less optimal with longer use.

Rapid transit of small bowel contents occurs in postvagotomy diarrhea, short bowel syndrome, irritable bowel, diabetic enteropathy, or carcinoid syndrome. These syndromes, except for irritable bowel syndrome, can cause severe dehydration and electrolyte disturbances.

Scintigraphy or the lactulose hydrogen breath test can be diagnostic. Small bowel manometry is not widely available but may show high-amplitude contractions, rapid peristalsis, and prolonged duration.

Treatment

The initial focus of treatment is on correction of dehydration and electrolyte imbalance. Patients, once stabilized, should avoid hyperosmolar drinks and receive rehydration with iso-osmolar fluids. Parenteral support with intravenous fluids or even parenteral nutrition may be necessary for patients with less than 1 meter of small bowel.

Loperamide (4 mg, 30 minutes prior to meals and bedtime) can decrease the gastrocolic reflex and slow motility. Verapamil (40 mg twice daily) or clonidine (0.1 mg twice daily), or both, may be used in conjunction with loperamide. Subcutaneous octreotide (50 mcg twice daily) can be considered if other drugs fail.

This chapter is a revised version of the chapter by Dr. Victor S. Wang and Dr. Robert Burakoff that was in the previous edition of Current Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy.