Diagnosis and Treatment of Dumping Syndrome After Gastric Bypass for Morbid Obesity

Fig. 16.1

Pathophysiology of dumping syndrome and mode of action of different therapeutic agents

The rapid emptying of hyperosmolar contents into the small intestine is followed by a fluid shift from the intravascular compartment into the intestinal lumen, resulting in a fall in blood volume and thus significant sympathetic stimulation from various pressure receptors; in addition it leads to small bowel distention, which initiates the release of various humoral and neural mediators [11–13]. This is associated with increased intestinal contractility believed to be responsible for nausea, bloating, and abdominal cramps and can lead to urgency and diarrhea. It has been also stated that the effect of hyperosmolar fluid on the argentaffin cells in the small intestinal mucosa causes the release of vasoactive serotonin (5-hydroxytryptamine), resulting in vasomotor effects, including an early increase in peripheral and mesenteric blood flow [14, 15].

On the other hand, the rapid delivery of gastric contents to the small bowel also causes rapid absorption of glucose into the circulation and hyperglycemia that consequently stimulates an inadequately high insulin response followed by reactive hypoglycemia and hypokalemia, as potassium accompanies glucose when entering the cells [12, 16] (Fig. 16.1).

In recent times new theories have been proposed; the first includes intestinal hormones that stimulate insulin secretion called incretins, particularly glucagon-like peptide-1 (GLP-1) [13, 17–20]. When food is presented rapidly to the hindgut, the L cells are stimulated and secrete GLP-1, which is stimulatory and trophic for beta cells, resulting in a sudden insulin secretion that may provoke hypoglycemia.

The second theory that has been proposed in the past decade is related to nesidioblastosis or beta-cell hypertrophy. This disorder is associated with elevation of serum insulin and the C-peptide fraction presumably due to an abnormality of differentiation of the islets of Langerhans from pancreatic ductal epithelium. It has been postulated that beta-cell trophic factors increase following gastric bypass [13, 21, 22].

All these theories demonstrate that the pathophysiology of DS is still unclear and controversial, requiring further study.

Symptoms

Symptoms typically occur after ingestion of a meal and are subdivided into early dumping and late dumping [16].

The early DS typically occurs within 20–30 min after ingestion of a meal characteristically while the patient is seated at the table eating or shortly after eating. It includes gastrointestinal (GI) and cardiovascular symptoms. The GI symptoms may include nausea and vomiting, epigastric fullness, eructation, cramping, abdominal pain, bloating, borborygmi, and sometimes explosive diarrhea. The cardiovascular symptoms may include palpitations, tachycardia, diaphoresis, fainting, syncope, dizziness, flushing, pallor, and blurred vision [23] (Table 16.1).

Table 16.1

Symptoms of early and late dumping

Early dumping

Gastrointestinal symptoms

• Abdominal pain

• Diarrhea

• Borborygmi

• Bloating

• Nausea

Vasomotor symptoms

• Flushing

• Palpitations

• Perspiration

• Tachycardia

• Hypotension

• Syncope

Late dumping

Hypoglycemia

• Perspiration

• Palpitations

• Hunger

• Weakness

• Confusion

• Tremor

• Syncope

Late DS appears 2–3 h after a meal that is generally high in carbohydrates. The delivery of this meal in the small intestine and its accelerated absorption result in hyperglycemia and the consequent release of large amounts of insulin. In response to the insulin, hypoglycemia occurs; this activates the adrenal gland to release catecholamines causing diaphoresis, shaking, light-headedness, tachycardia, and confusion [23] (Table 16.1).

The expression of these symptoms fluctuates between individuals. Most patients with early dumping have both GI and vasomotor symptoms; and those with late dumping have mainly vasomotor symptoms.

The majority of patients have early dumping, approximately 25% of them have late dumping, and only a minority have symptoms of both [24]. Both early and late dumping symptoms can be socially and professionally incapacitating.

Diagnosis

A suggestive symptom pattern in a patient who has undergone gastric surgery should provide grounds to explore the possibility of DS. In 1970, Sigstad developed a diagnostic scoring system based on the occurrence of different symptoms of DS, to calculate a diagnostic index, that if reaches seven is suggestive of DS. Sigstad’s scoring system is shown in Table 16.2. The presence of hypoglycemia concurrently with several other symptoms is a strong indicator of DS (although the occurrence of insulinoma needs to be excluded). This system is easy to apply, but its disadvantage is difficulty in separating other postprandial symptoms from dumping. The score index is useful in clinical practice as first evaluation and to assess response to therapy.

Table 16.2

Sigstad’s scoring system for dumping syndrome

A total score >7 is suggestive of dumping syndrome, whereas a score <4 suggests other diagnoses

• Shock +5

• Fainting, syncope, unconsciousness +4

• Desire to lie or sit down +4

• Breathlessness, dyspnea +3

• Weakness, exhaustion +3

• Sleepiness, drowsiness, apathy, falling asleep +3

• Palpitation +3

• Restlessness +2

• Dizziness +2

• Headaches +1

• Feeling of warmth, sweating, pallor, clammy skin +1

• Nausea +1

• Abdominal fullness, meteorism +1

• Borborygmus +1

• Eructation +1

• Vomiting n

A provocative test for assessing DS can be used to confirm clinical suspicion. This test is a modification of the oral glucose tolerance test and involves the ingestion of 50 g or 75 g glucose in solution after an overnight fast. Immediately before and up to 180 min after ingestion of this solution, the blood glucose concentration, hematocrit, pulse rate, and blood pressure are measured at 30 min intervals. The provocative test is considered positive if late (120–180 min) hypoglycemia occurs or if an early (30 min) increase in hematocrit of more than 3% occurs. A rise in the heart rate by 10 beats per minute or more in the first hour after an oral glucose challenge of 50 g after 10-h fasting was found to be 100% sensitive and 92% specific for early dumping. Moreover, a positive hydrogen breath test after glucose ingestion has been reported to be 100% sensitive for early dumping by the same authors [25]. Use of higher amount of glucose for provocation test is controversial because it can induce symptoms of dumping in nondumpers.

In addition, measurement of gastric emptying can be helpful in documenting rapid gastric emptying. In the past, gastric emptying was usually assessed by barium studies, but now, gastric emptying scintigraphy is commonly performed to evaluate patients with symptoms that suggest an alteration of gastric emptying and/or motility. Gastric emptying methodology relies on radionuclide techniques of isotope-labeled meals, with the current “gold standard” being a 4-h gastric emptying test (GET) using a low-fat (2%) scrambled egg meal. There has been intensive interest in defining criteria for slow gastric emptying or gastroparesis (10% retention at 4 h and/or 60% at 2 h), but less attention has been focused on defining gastric emptying guidelines for “rapid” emptying. The radionuclide scrambled egg meal meets all criteria for a standardized GET by providing a physiologic, noninvasive, and quantitative measure of gastric emptying [26]. For this reason, guidelines for dumping could be determined. After radiolabeling the solid or liquid component of a meal, the gastric counts measured by scintigraphy correlate directly with the volume of the meal remaining, without the need for geometric assumptions about the shape of the stomach.

Another gastric emptying measurement method is ultrasound, which is operator dependent, requires geometric assumptions, and generally measures only liquid emptying. Other indirect test for gastric emptying is the breath testing, as gastric emptying is the rate-limiting step in the processing and excretion of 13C-octanoic acid. The test assumes normal small bowel absorption and pulmonary function [26, 27].

Treatment

In most patients, effective control of symptoms can be achieved with dietary modifications and advice in lifestyle. If this approach is unsatisfactory, medical therapy is the following step; however, in some cases surgery might be considered. The management of dumping syndrome should be aimed at resolving clinical symptoms and improving nutrition simultaneously.

Dietary Measures

Nutritional measures are the first approach to manage DS and are probably helpful for the majority of the cases. Daily food intake should be divided into at least six meals, dividing the recommended daily energy intake; thus, the patient consumes smaller amounts of food in each meal. During meals, fluid intake must be restricted, and patients should delay any liquid intake until at least 30 min after a meal.

Many patients modify their diet according to a personal experience with food tolerance, but in general rapidly absorbable carbohydrates like simple sugars, as well as milk and dairy products, should be avoided from the diet to prevent late dumping symptoms. Nonetheless, complex carbohydrates like unsweetened cereals, pasta, potatoes, fresh fruit, and vegetables are preferred. For patients with severe vasomotor symptoms (postprandial hypotension), it is recommended to lie down supine for 30 min after meals because this can prolong gastric emptying, improve venous return helping to reduce the symptoms of hypovolemia, and decrease the chance of syncope. Supplementation of dietary fibers (bran, methylcellulose) with meals also has been proven effective.

Pectin and Guar Gum

In order to delay gastric emptying increasing the viscosity of food, pectin and guar gum are recommended with each meal. Pectin is a structural heteropolysaccharide contained in the primary cell walls of plants, guar gum is a polysaccharide, and both are used as thickening agents and stabilizers in food [9, 11]. These dietary additives form gels with carbohydrates, and they delay glucose absorption and prolong transit time [11]. However, these substances are usually not readily available as pharmaceutical products at sufficiently high doses, and the palatability and tolerability of these supplements is poor.

Acarbose

Acarbose has been found to be useful in the management of late dumping because it is a potent competitive inhibitor of α-glycosidase hydrolase that interferes with carbohydrate absorption in the small intestine. Acarbose inhibits the α-glycosidase-mediated production of monosaccharides from carbohydrates in the epithelial brush border cells of the small intestine, delaying carbohydrate digestion, which decreases the postprandial rise of glucose and insulin. Because of the reversible nature of the inhibitor–enzyme interaction, conversion of complex carbohydrates (starch and sucrose) to monosaccharides is delayed rather than completely blocked.

This treatment affects only the symptoms of late dumping. Furthermore, as the unabsorbed carbohydrates undergo bacterial fermentation in the small intestine, acarbose treatment can result in bloating, flatulence, or diarrhea. Although severity of those adverse effects usually decreases over time, they might affect treatment compliance.

Somatostatin Analogs

Somatostatin and its synthetic analog octreotide (OCT) have been demonstrated to be effective in patients with DS refractory to standard therapy [28]. Somatostatin analogs reduce antral contractility, thus delaying gastric emptying. In the small bowel, OCT induces phase 3 of the migrating motor complex and prolongs orocecal transit time [29, 30]. OCT also inhibits the postprandial secretion of several vasoactive and metabolic hormones such as insulin, gastrin, pancreatic polypeptide, cholecystokinin, glucagon, neurotensin, and secretin [31, 32]. The reduction in peak insulin concentration and prolongation of maximal plasma glucose prevent late hypoglycemia. In a short-term use, OCT has been shown to decrease the symptom index score, pulse rate, minimizes changes in orthostatic blood pressure, packed cell volume, and plasma osmolarity [33]. Short-acting or long-acting repeatable (LAR) formulations of OCT are the agents that have been used. The usual initial dose of OCT is 25–50 mcg administered subcutaneously (SC), two to three times daily, 15–30 min before meals. The dose can be increased to 100 mcg if the smaller dose is ineffective [11].

The major disadvantage is the SC administration before each meal, and this is potentially a major limitation for the long-term application of short-acting somatostatin analogs. The use of a long-acting repeatable (LAR) formulation of OCT, allowing monthly injections, may provide an attractive alternative. Arts et al. in 2008 published a study that compared the efficacy of subcutaneous OCT with that of the LAR OCT formulation, administered monthly. The study included 30 patients with postoperative dumping and insufficient response to dietary measures. They concluded that although OCT subcutaneously provided significantly better control of late dumping symptoms, patient’s preference ratings were higher for LAR, and that it was likely that patients took into account several aspects of the treatment, and that the ease of administration played an important role in patients’ assessment of the overall treatment effect [34, 35]. The development of an oral or nasal formulation should further improve the application of OCT in the treatment for DS.

The use of OCT is limited by the occurrence of side effects such as diarrhea and injection aversion. Steatorrhea or early-morning diarrhea associated with long-term therapy can be managed with pancreatic enzyme replacement or an extra dose of OCT before bedtime. However, diarrhea in patients who already have malabsorption and maldigestion can be a major limiting factor in use of OCT. This therapy has been also associated with a high rate of gallbladder stone formation through inhibition of gallbladder contractility [36]. In summary, OCT should be offered to patients with severe dumping when other options have been exhausted.

Diazoxide

Diazoxide is a potassium channel activator that hyperpolarizes cells, inhibiting voltage-sensitive calcium channels. The drug has been used clinically in the treatment of hypertension and insulinoma, as it inhibits calcium-induced insulin release by β cells. No effect on the early symptoms of DS is expected with diazoxide treatment owing to its mode of action. The use of diazoxide administered three times daily at 100–150 mg for late dumping symptoms has been anecdotally reported, underscoring the importance of further studies in this subject [37].

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