Role of pharmacological management

The long-term use of antimotility and antisecretory agents is frequently necessary to control stool losses in SBS. Massive enterectomy is associated with a transient gastric hypergastrinemia and hypersecretion [51]. H2 receptor antagonists and proton pump inhibitors may be beneficial, particularly during the first year following resection, in reducing the volume of gastric secretions and, thus, stool losses. The acidity can also lead to peptic complications and/or impairment in the function of digestive enzymes [52]. As gastric acid has a role in suppressing overgrowth of upper intestinal bacteria, acid-suppressing agents should be used sparingly in conditions of bacterial overgrowth [53]. Uncommonly, certain patients, particularly the net secretors such as those with high-output jejunostomies, may benefit from treatment with the somatostatin analogue, octreotide. Octreotide reduces production of a variety of gastrointestinal secretions and slows jejunal transit [54, 55]. Open-label studies suggest clinical benefit of both short-acting (e.g., 100 ^g given subcutaneously three times daily 30min before meals) and long-acting forms [56, 57]. However, this beneficial effect is often short lasting, and, furthermore, the use of octreotide has not been shown to improve absorption or lead to the elimination of the need for PN. Due to an increased risk for cholelithiasis, expense and studies in animal models suggesting that octreotide may inhibit bowel adaptation, the use of this agent should be reserved for patients with large volume stool losses in whom fluid and electrolyte management is problematic and should be avoided in the immediate period soon after intestinal resection [58, 59].

Antidiarrheals work mainly to reduce intestinal motility, but also cause a slight reduction in intestinal secretion. Commonly used agents include loperamide, diphenoxylate, codeine and tincture of opium (Table 8.5). The use of codeine and tincture of opium tends to be

Table 8.5

Antidiarrheal use in Short Bowel Syndrome

Agent

Dosage

Loperamide

Diphenoxylate

Codeine

Tincture of opium

2-8 mg before meals and at bedtime as needed 2.5-10 mg before meals and at bedtime as needed 15-60 mg before meals and at bedtime as needed 0.25-2 ml three times daily (note: 0.25 ml = 2.5 mg morphine)

limited by their sedating effect, potential for addiction when used long term and cost. In adults, loperamide, 4mg four times daily, has been shown to be more effective than codeine, 60 mg four times daily; however, there may be a synergistic effect when these agents are used together [60]. The use of diphenoxylate has been largely replaced by loperamide due to a decreased incidence of central nervous system side effects with the latter agent. It should be remembered that loperamide enters the enterohepatic circulation, which is disrupted in SBS patients without an ileum; therefore, high doses are frequently needed. In the setting of SBS, these agents seem to be most effective when administered before meals and at bedtime. Clonidine, which can be administered transdermally, may also be useful to treat high output stool losses via its effects on intestinal motility and secretion [61, 62]. Finally, it should be noted that while antimotility agents may be effective in reducing intestinal transit, in cases where bowel dilatation has occurred, antimotility agents might actually worsen diarrhea by allowing bacterial proliferation.

With the loss of significant portions of the ileum (i.e., >100cm in adults), bile acid malabsorption may exceed maximal hepatic synthesis, leading to a decrease in the bile acid pool and resulting in impairment of luminal fat digestion. In an attempt to improve the bile salt pool without aggravating stool losses, several uncontrolled case studies using ox bile supplements and the synthetic conjugated bile acid, cholylsarcosine, have demonstrated improvements in fat absorption [63, 64]. While the initial reports are encouraging, these agents are not readily available at present. The use of bile acid sequestrants, such as cholestyramine, may worsen steatorrhea and fat-soluble vitamin losses in those with >100 cm of distal ileum resected and should generally be avoided in the SBS patient [65].

Pancreatic function is reduced in patients on PN when no concomitant enteral diet is given [66]. Nevertheless, there has been no consistent evidence demonstrating a reduction in pancreatic secretions in patients with SBS who are given an oral diet. There is currently no evidence supporting the usefulness of pancreatic enzyme supplementation in humans with SBS.

The development of small intestinal bacterial overgrowth (SIBO) appears to be common in SBS patients and may affect their ability to successfully wean PN because of symptoms that impede oral intake and an exacerbation of malabsorption [67]. The anatomical and physiological changes that occur in SBS together with medications commonly used in these patients facilitate the development of SIBO. Excess bacteria in the small bowel can induce inflammatory changes in the gut impairing nutrient absorption, causing a number of gas-related symptoms and aggravating stool losses [68, 69]. While the identification of an excessive number of bacteria in small bowel fluid is considered the gold standard in the diagnosis of SIBO, it has several limitations that have led some to questions its utility [70]. Nevertheless, the use of the primary noninvasive test to diagnose SIBO, the hydrogen breath test, has greater limitations due to rapid transit in the shortened bowel making it difficult to differentiate small bowel versus colonic hydrogen production. Therefore, collection of small bowel fluid for quantitative culture is recommended to diagnose SIBO in the setting of SBS [67]. Once pathologic SIBO has been identified, oral antimicrobial treatment incorporating a broad spectrum of coverage is generally prescribed. A variety of antibiotics can be used with success being judged by an improvement in symptoms, reduction in stool output and/or weight gain. The continuous use of low-dose antibiotics in SBS may be necessary. To reduce the risk of antibiotic resistance, periodic rotation of the antibiotic used is advised. Although without evidence from controlled studies to support their utility, other strategies for controlling SIBO in SBS include limiting the use of antisecretory and antimotility agents, use of nonabsorbable antibiotics, intermittent bowel flushing with polyethylene glycol, use of probiotic agents and bowel tapering operations [67].

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