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Chronic complications of short bowel syndrome in children

Chronic complications of short bowel syndrome in children
Literature review current through: Jan 2024.
This topic last updated: Aug 18, 2023.

INTRODUCTION — Short bowel syndrome (SBS) is a congenital or acquired malabsorptive state that usually is caused by extensive resection of the small intestine. It is the most common cause of intestinal failure, which is defined as a condition in which an individual's gastrointestinal function is inadequate to maintain nutrient, growth, and hydration status without intravenous (IV) or enteral supplementation [1]. Common causes of SBS include necrotizing enterocolitis (NEC), congenital intestinal atresia, gastroschisis, and volvulus [1]. (See "Management of short bowel syndrome in children".)

The chronic complications of SBS in children are summarized in the table (table 1 and figure 1) and reviewed below. Initial management and other aspects of SBS are discussed in separate topic reviews:

(See "Pathophysiology of short bowel syndrome".)

(See "Management of short bowel syndrome in children".)

(See "Intestinal failure-associated liver disease in infants".)

GASTROINTESTINAL COMPLICATIONS

Chronic diarrhea — Watery diarrhea is a common complication of SBS in children and may result in excessive fluid losses and electrolyte imbalances. During the initial period of intestinal adaptation (typically the first few months after intestinal resection), management focuses on fluid balance, acid suppression, and gradual advancement of enteral feeds while weaning parenteral nutrition. Details of this approach are discussed in a separate topic review. (See "Management of short bowel syndrome in children".)

The discussion below focuses on chronic or recurrent diarrhea that occurs after the period of rapid intestinal adaptation.

Causes — Diarrhea occurs when the osmotic load in the small intestinal lumen exceeds the absorptive capacity as enteral nutrition is advanced. Common contributors to diarrhea in patients with SBS are:

Insufficient mucosal surface area – This typically improves as intestinal adaptation occurs, although complete intestinal adaptation may take months to years. Dietary interventions may be guided by the patient's anatomy and clinical characteristics, but, ultimately, management must be individualized based upon the patient's response, as outlined below.

Lactose intolerance – Common in patients with SBS because of reduced mucosal surface area, rapid transit, and/or mucosal injury due to bacterial overgrowth, among other causes.

Fat malabsorption – May have several causes, including reduced mucosal surface area, exocrine pancreatic insufficiency, and/or malabsorption of bile salts (which enter the colon and cause a secretory diarrhea, ie, bile acid diarrhea).

Other mechanisms that may contribute to diarrhea in some patients include dysmotility, allergic disease, or small intestinal bacterial overgrowth (SIBO), as discussed below. (See 'Dysmotility' below and 'Allergic and eosinophilic disease' below and 'Small intestinal bacterial overgrowth' below.)

Management of watery diarrhea may include fluid replacement, trials of dietary changes, and pharmacotherapy:

Fluid replacement — Regardless of other interventions for diarrhea, care should be taken to maintain hydration status. Replacement of water and electrolyte losses from diarrhea can be provided by enteral oral rehydration solutions (if tolerated) or intravenous (IV) fluids. In children who require IV fluid replacement, additional fluid may be added to the parenteral nutrition or provided as an IV bolus outside of the parenteral nutrition. For patients with severe hypovolemia due to excessive diarrhea, IV fluid resuscitation with isotonic solutions (eg, normal saline or Lactated Ringer) may be needed. Some patients, such as those with chronic lung disease or congenital heart disease, require particularly careful management to avoid fluid overload. (See "Parenteral nutrition in infants and children" and "Oral rehydration therapy".)

Trials of dietary changes — Unless the diarrhea is clearly attributable to a specific mechanism, the first step is to try dietary changes. These are selected based on individual patient characteristics, such as age and history of response to previous dietary changes. The changes are typically made in collaboration with a dietitian skilled in the management of SBS to ensure adequate nutrition and to help monitor the response to dietary changes. (See "Management of short bowel syndrome in children", section on 'Advancement of enteral feeds'.)

Reduce the osmotic load – The osmotic load in the intestinal lumen can be reduced by slowing the enteral infusion rate, transitioning to a low-carbohydrate/higher-fat enteral formula, and/or switching from bolus to continuous enteral feedings [2]. If patients are having bowel movements overnight while on continuous feeds, it may be beneficial to transition to daytime continuous feedings or try bolus feedings. Once developmentally appropriate and deemed safe, by-mouth feeds should be introduced and this, too, may serve as a small addition of bolus feeds.

Avoid lactose – Lactose intolerance is common in patients with SBS and typically presents with nonspecific symptoms of bloating, diarrhea, or intolerance of enteral feeds. If the patient's diet contains lactose, the next step is either an empiric trial of a milk-free diet or lactose breath testing. If the diagnosis remains unclear, disaccharidase enzyme activity in duodenal biopsy samples obtained during endoscopy can be measured to confirm lactase deficiency. If lactose intolerance is diagnosed, this is managed by maintaining a lactose-free or low-lactose diet and/or supplementing feeds with lactase enzyme, guided by the patient's symptomatic response and in collaboration with a dietitian.

Eliminate cow's milk and/or soy from the diet – A subset of patients with SBS have a food protein intolerance, most commonly to cow's milk or soy protein. Such patients usually benefit from switching to an extensively hydrolyzed or amino acid-based formula [3,4]. However, some amino acid-based formulas may also have a high osmotic load, so transitioning may worsen the diarrhea for some patients. (See 'Allergic and eosinophilic disease' below.)

Blenderized formula – For toddlers and older children, it may be helpful to change to a "blenderized" diet (either a commercial blenderized formula or puréed foods), which can be administered by gastrostomy tube [5,6]. It is unclear if blenderized or puréed feeds are associated with improved tolerance or favorable outcomes in some patients with SBS. Possible mechanisms include increased fiber content, delay in gastric emptying due to viscosity, or alterations in enteroendocrine hormones that decrease intestinal motility.

Add fiber – Dietary fiber can be increased by adding solids with fiber, such as green beans (eg, for infants receiving solid foods) [7]. Older children may benefit from fiber supplements, as discussed below. (See 'Pharmacotherapy' below.)

Changes in dietary fat – Patients with SBS have a variety of responses to dietary fat, depending on their anatomy and other individual characteristics. Considerations include:

Increase fat content – For most patients with SBS, the optimal diet has a relatively high proportion of fat. In addition to meeting caloric needs, a high-fat diet tends to reduce diarrhea because fats have a lower osmotic load than carbohydrates. Moreover, in the early stages of intestinal adaptation, supplemental fat in the enteral feeds helps to promote adaptation. Collaboration with a dietitian to help determine the percentage of macronutrient provision is recommended. While higher fat intake may be helpful, it is recommended to keep total fat intake <50 percent of total calories to avoid ketosis. (See "Management of short bowel syndrome in children", section on 'Diet composition and adjustments'.)

Change type of fat – Changing to a formula with a higher medium-chain triglycerides (MCT) oil content (eg, >50 percent of fat from MCT) may be helpful in selected patients because MCTs do not require bile salts for digestion. Candidates for this diet include patients with cholestatic liver disease (who may have insufficient bile salts in the lumen) or those lacking the terminal ileum (who may malabsorb bile salts, causing choleretic diarrhea).

Reduce fat content – Occasionally, patients with SBS who have steatorrhea due to fat malabsorption may require a reduction in dietary fat. However, this approach should be undertaken with caution because fats are usually an important source of calories for patients with SBS and are often better tolerated than carbohydrates because they have a lower osmotic load. In addition, long-term use of a low-fat formula may increase the risk for essential fatty acid deficiency (EFAD). (See 'Common deficiencies' below.)

Pharmacotherapy — For patients who have chronic diarrhea that is not adequately controlled with dietary changes, pharmacotherapy may be considered (table 2).

Acid suppression

During the initial phase following intestinal resection, most patients should be treated with acid-suppressing medications. In this phase, patients tend to hypersecrete gastric acid. Acid suppression reduces the fluid load entering the intestine, improves pancreatic enzyme function and nutrient absorption, and helps to prevent peptic complications. (See "Management of short bowel syndrome in children", section on 'Early management'.)

Later in the disease course, gastric acid secretion declines and patients are less likely to benefit from acid-suppressing medications. For those with chronic diarrhea who fail dietary management, it is reasonable to do a time-limited trial of a proton pump inhibitor (PPI), but patients should be weaned from the drug if there is no clear benefit. Chronic use of PPIs generally should be avoided because these drugs are associated with electrolyte and bone abnormalities as well as increased rates of respiratory and gastrointestinal infections. They may have effects on the gastric microbiome [8] and predispose to bacterial overgrowth and vitamin B12 deficiency [9,10]. (See 'Esophagitis/peptic ulcer disease' below.)

Antimotility agents

For patients with a high stool output or nighttime stools that do not respond to dietary management, we suggest treating with loperamide. Loperamide helps to slow gut transit and enhance absorption and is generally safe for children. By slowing intestinal motility, water and sodium loss from an ileostomy is reduced by approximately 20 to 30 percent [11]. The use of loperamide to treat chronic diarrhea in pediatric SBS is based on clinical experience and extrapolation from studies of acute diarrhea in the general pediatric population. (See "Management of short bowel syndrome in children", section on 'Pharmacologic therapy'.)

Dosing of loperamide for pediatric patients with SBS is between 0.2 and 0.8 mg/kg/day in one to three divided doses (up to a maximum adult dose of 24 mg/day). We use the tablet or capsule form of loperamide rather than the liquid form because the liquid may contain sugar and/or alcohol that may exacerbate diarrhea in this population. Loperamide may exacerbate SIBO. It should be avoided in patients with known or suspected acute gastrointestinal infection, such as with Clostridioides difficile, due to the risk of toxic megacolon. Caution should also be used in patients with significant bowel dilatation, stricture, or pseudo-obstruction because loperamide can exacerbate dysmotility symptoms. Lomotil, a combination of diphenoxylate and atropine, is contraindicated in the pediatric population due to the side effects associated with the atropine component of this medication. (See 'Small intestinal bacterial overgrowth' below.)

Pancreatic enzymes

The role for pancreatic enzyme replacement therapy (PERT) in children is uncertain, and we generally do not recommend their use in children with chronic diarrhea due to SBS. Although PERT has been used in adults with SBS and may help with watery diarrhea in the acute postoperative setting, evidence supporting PERT in children with SBS is lacking. A small trial confirmed limited efficacy [12]. Traditional testing for pancreatic insufficiency is often inaccurate. Fecal elastase can be falsely low in SBS (false-positive test) and, because steatorrhea and carbohydrate malabsorption are expected sequelae of SBS, does not indicate pancreatic insufficiency.

The rationale for PERT is that patients with SBS have gastric acid hypersecretion during the immediate postoperative period and acid secretions can denature pancreatic enzymes. Moreover, rapid transit may affect pancreaticobiliary digestion of feeds and contribute to watery diarrhea [13].

Digestive enzyme cartridges are used in children receiving enteral tube feeds with cystic fibrosis and pancreatic insufficiency to mimic the function of pancreatic lipase [14]. Enzyme cartridges have been used off-label in SBS, and their safety and efficacy in SBS are being evaluated in a clinical trial (NCT03530852) [15]. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency", section on 'Dosing considerations'.)

Cholestyramine

A trial of cholestyramine may be appropriate for patients with diarrhea after extensive resection of the distal ileum. The diarrhea in these patients may be caused by malabsorbed bile acids entering the colon (bile acid diarrhea), and cholestyramine prevents this process by sequestering bile acids. However, cholestyramine must be used judiciously because other patients with SBS may have bile acid deficiency and, in those patients, cholestyramine may bind the remaining bile salts necessary for fat and fat-soluble vitamin absorption, thereby creating additional nutritional complications [16]. Improvement in the diarrhea during a trial of cholestyramine supports the diagnosis of bile acid diarrhea. In this case, the medication should be continued, but the patient should be monitored for nutritional status and fat-soluble vitamin deficiencies.

The recommended dose of cholestyramine is 240 mg/kg/day (up to a maximum of 8 g/day) in two to three divided doses given before meals. Cholestyramine can interfere with absorption of fat-soluble vitamins (vitamins A, E, D, and K). To avoid this interaction, vitamin and mineral supplements should be given separately from the cholestyramine (eg, more than one hour before or four to six hours after the cholestyramine). (See "Management of short bowel syndrome in children", section on 'Pharmacologic therapy'.)

Fiber

Soluble fiber such as pectin (a structural heteropolysaccharide) or guar gum may be helpful in older infants and children with an intact colon to lengthen transit time and potentially increase absorption [17-19]. Undigested fiber can be metabolized to short-chain fatty acids by aerobic colonic bacteria and used as a primary energy source for colonocytes [20]. Fiber may also add bulk to the stool and mitigate perineal skin breakdown that can be caused by watery diarrhea. Potential risks of soluble fiber are that it promotes bacterial overgrowth, acting as a prebiotic. In addition, fiber can reduce the bioavailability of calcium, zinc, and other divalent cations, especially at doses above 3 percent of formula volume. High doses of fiber have also been associated with gastrointestinal obstruction.

Recommended initial dosing for pectin is 1 percent of total formula volume (ie, 1 g of fiber per 100 mL formula), gradually increasing to 2 to 3 percent of formula volume as tolerated. (See "Management of short bowel syndrome in children", section on 'Diet composition and adjustments'.)

Insoluble fiber (wheat bran) can add bulk to the stool, which may enhance enteral tolerance in patients with SBS who have all or part of their colon, but it probably does not enhance adaptation of the colonic mucosa [21]. Potential adverse effects are constipation and bloating.

Growth factors – Patients with SBS who are unable to wean off of parenteral nutrition may benefit from treatment with teduglutide (Gattex), in conjunction with an intestinal rehabilitation program. Teduglutide, an analog of glucagon-like peptide 2 (GLP-2), may enhance intestinal adaptation and lessen diarrheal losses [22-25]. It is administered by subcutaneous injection and is approved by the US Food and Drug Administration for use in adults and children one year or older who are dependent on parenteral nutrition. Clinical evidence regarding teduglutide is discussed separately. (See "Management of short bowel syndrome in children", section on 'Pharmacologic therapy'.)

Dysmotility — Patients with SBS, especially those with a history of gastroschisis or intestinal dilatation, often have underlying intestinal dysmotility. Gastrointestinal dysmotility can present as abdominal distention, feeding intolerance, emesis, small bowel bacterial overgrowth, and decreased stools or ostomy output.

Evaluation – Bowel dilatation on plain radiograph or upper gastrointestinal series supports the possibility of underlying dysmotility. In a patient with suggestive clinical history and symptoms, this may be sufficient to make a provisional diagnosis.

Manometry testing (esophageal, antroduodenal, colonic, and anorectal) has a role in confirming and characterizing intestinal dysmotility in pediatric patients with chronic intestinal pseudo-obstruction or Hirschsprung disease. However, there are few reports in the literature about the diagnostic value of manometry in pediatric patients with SBS from other causes. In our clinical experience, manometry has been useful in defining which SBS patients may benefit from prokinetic drugs or surgical therapies including bowel tapering/lengthening or determining whether the patient will tolerate ostomy takedown, but future studies are needed to further explore and validate these observations.

Treatment – There are limited options for medications to treat dysmotility in the pediatric SBS population:

Erythromycin ethylsuccinate has positive effects on bowel motility and has an established safety profile, so it is appropriate for a trial in children with SBS and dysmotility. It can be associated with prolonged QTc interval, which can be exacerbated by drug-drug interactions, so baseline and follow-up electrocardiograms are recommended.

Cyproheptadine may be helpful for children with feeding intolerance, vomiting, or dyspeptic symptoms, particularly in those with known proximal dysmotility. Cyproheptadine has antihistaminergic, antiserotonergic, and anticholinergic effects and is thought to increase gastric accommodation and gastric sensation [26,27]. It can also act as an appetite stimulant to improve weight gain. (See 'Feeding problems and oral aversion' below.)

As a second-line approach, some institutions trial azithromycin or amoxicillin-clavulanate and continue the medication chronically if it improves symptoms. This is based on evidence that these drugs have prokinetic effects in the upper gastrointestinal system in other populations with dysmotility [28-31]. There is only anecdotal evidence of this approach in children with SBS. Potential adverse effects include prolonged QTc interval (azithromycin) and C. difficile (amoxicillin-clavulanate).

Metoclopramide is not recommended, due to associated extrapyramidal symptoms and proarrhythmic effects in children.

Cisapride has rarely been used as a prokinetic agent in pediatric SBS patients with gastrointestinal dysmotility and sometimes improves enteral tolerance [32]. In 2000, cisapride was removed from the market in the United States due to cardiac arrhythmias (QT prolongation), heart block, and death but is available under a limited-access program for children with refractory gastrointestinal dysmotility, including those with SBS.

Prucalopride is a selective 5-hydroxytryptamine receptor 4 (5-HT4) receptor agonist with colonic prokinetic activity and is approved by the US Food and Drug Administration for adults with chronic idiopathic constipation [33]. Anecdotal reports describe its off-label use in pediatric SBS patients with chronic intestinal pseudoobstruction or constipation due to dysmotility, but its safety and efficacy in this population are unknown.

Anastomotic ulcers — In patients with SBS due to surgical resection, ulcers may develop at the site of previous intestinal resection and anastomosis. They can develop (or come to medical attention) at any time, including years postoperatively. Their etiology is thought to be multifactorial, including poor tissue perfusion, bacterial inflammation, inflammatory bowel disease-like syndrome, and/or hypersecretion of gastric acid. The ulcers can cause occult or frank bleeding and acute or chronic iron deficiency anemia. Pan-endoscopic examination may be necessary to identify and treat the source of bleeding (picture 1). Anastomotic ulcers have also been noted after intestinal lengthening procedures.

Anastomotic ulcers may be difficult to diagnose because the anastomosis may be difficult to visualize with standard endoscopy and the ulcers may not be visible on small or large bowel contrast imaging. Pan-endoscopy (deep enteroscopy and colonoscopy) may be required. Wireless capsule endoscopy has also been used in such cases and may help aid in diagnosis and treatment [34]. However, patients with small bowel anastomoses have an increased risk for retention of the capsule [35]. This is not an absolute contraindication to capsule endoscopy but warrants careful screening and selection of patients. Candidates should undergo an evaluation with contrast imaging and a "patency" capsule to rule out stricture and/or obstruction before proceeding with wireless capsule endoscopy.

In our clinical experience, a trial of antiinflammatory medications (such as 5-aminosalicylic acid or mesalamine), antibiotics, and/or glucocorticoids (such as oral prednisone or budesonide) as mono- or combination therapy may have some clinical benefit for patients with anastomotic ulcers. Oral or IV iron therapy may be needed to prevent or treat anemia. If bleeding and anemia occur despite these therapies, endoscopic therapy such as argon plasma coagulation can be attempted by advanced endoscopists [36], but, ultimately, surgical resection of the affected area may be required as medical therapy is not always successful. Unfortunately, ulcers can recur after surgery.

Inflammatory bowel disease–like syndrome — Pediatric SBS patients occasionally develop an inflammatory bowel disease-like syndrome, which includes laboratory evidence of inflammation (eg, elevated fecal calprotectin and/or fecal lactoferrin, hypoalbuminemia, elevated platelets, microcytic anemia) and chronic enteritis/colitis with or without granuloma formation that is not related to surgical anastomoses. For these patients, we typically start with a trial of antiinflammatory medications, antibiotics, and/or glucocorticoids [37]. If inflammation and anemia persist, we may escalate the medical therapy to include biologic agents (eg, anti-tumor necrosis factor [TNF]-alpha medications or alpha-4-beta-7 integrin antagonists). Standard follow-up with blood work and stool studies as well as repeat endoscopy are needed to monitor response to biologic therapy. (See "Medical therapies for Crohn disease in children and adolescents".)

There is some evidence to suggest a common etiology with both SBS and inflammatory bowel disease (namely, dysbiosis and mucosal immune dysregulation), but more research is needed to establish this possible connection [38].

Allergic and eosinophilic disease — Children with SBS have a high frequency of allergic gastrointestinal disease. In a series of 105 children with intestinal failure who underwent gastrointestinal endoscopy, 37 percent had evidence of eosinophilic inflammation, most commonly in the colon but also in the esophagus and small intestine [39]. A possible mechanism for the association between SBS and allergic disease is increased permeability of the intestine.

Food protein-induced allergic colitis or enteritis can present as rectal bleeding, malabsorption, and diarrhea in the SBS population. This disorder is sometimes known as cow's milk protein intolerance, although it may be induced by soy or other dietary proteins. In SBS patients with these symptoms, endoscopic evaluation may be warranted and often yields useful diagnostic information [40]. Histology may reveal increased eosinophils in a focal distribution throughout the lamina propria of the colon. Grossly, one may see lymphoid nodular hyperplasia. (See "Food protein-induced allergic proctocolitis of infancy".)

Treatment of allergic proctocolitis often responds to elimination of cow's milk and soy proteins from the diet. More severe or refractory cases of eosinophilic gastrointestinal disease may require transitioning to an elemental diet (eg, enteral feeds with an amino acid-based formula) or medical management with 5-aminosalicylic acid or glucocorticoid enemas/suppositories if the disease is limited to the distal colon/rectum. A milk- and dairy-free diet requires careful clinical monitoring to ensure adequate calcium and vitamin D intake [41]. If applicable, infants may trial breast milk if the mother has eliminated dairy and soy products from her diet. These diet changes can often be difficult for the family and patient and are best made in collaboration with a dietician who specializes in SBS. (See "Food protein-induced allergic proctocolitis of infancy".)

Eosinophilic esophagitis or gastroenteritis can present as vomiting and/or poor weight gain. Endoscopic findings include furrowing of the esophagus with histopathology showing >15 eosinophils per high-power field and eosinophils in the intramuscular layers. Management is similar to that for patients without SBS and includes elimination diets and, occasionally, glucocorticoids or biologic therapy. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)" and "Eosinophilic gastrointestinal diseases" and "Treatment of eosinophilic esophagitis (EoE)".)

Esophagitis/peptic ulcer disease — Infants and children with SBS are at increased risk for peptic esophagitis and gastritis. Contributing factors include gastric acid hypersecretion, which is particularly pronounced in the first few months after intestinal resection, and dysmotility, which may be related to intestinal dilatation or to the underlying cause of the SBS (eg, gastroschisis). (See 'Dysmotility' above.)

Acid-suppressing medications (PPIs) are routinely used during the first few months following intestinal resection. Acid suppression reduces the fluid load entering the intestine, improves pancreatic enzyme function and nutrient absorption, and also helps to prevent peptic complications [42-44]. (See "Management of short bowel syndrome in children", section on 'Early management'.)

By contrast, long-term treatment with acid-suppressing medications should be avoided, if possible. The gastric hypersecretion typically resolves during the first few months after surgery, and weaning of the acid-suppressing medications should be attempted after a few months of treatment. Treatment should be continued only if there is clear and ongoing peptic esophagitis or ulcer disease. This is because chronic treatment with acid-suppressing medications may promote SIBO [8-10] and have adverse effects on bone metabolism. Additionally, chronic use of acid blockers may increase the risk of vitamin B12 deficiency, especially in children who have undergone ileal resections. (See "Management of gastroesophageal reflux disease in children and adolescents", section on 'Proton pump inhibitors'.)

Small intestinal bacterial overgrowth — Patients with SBS are prone to SIBO, which is defined as increased numbers and species of bacteria in the small intestine, resulting in intestinal inflammation [45].

Pathogenesis – In the normal small intestine, bacterial growth is controlled by gastric acid, pancreatic enzyme activity, enterocyte turnover, normal antegrade peristaltic activity in the small intestine, and the ileocecal valve. Patients with SBS are prone to SIBO because of one or more of the following problems: (See "Small intestinal bacterial overgrowth: Etiology and pathogenesis".)

Loss of the ileocecal valve

Dysmotility or abnormal intestinal anatomy (dilated small bowel, surgical blind loops)

Acid-suppressing medications (PPIs)

Lack of enteral feeding

Clinical manifestations and complications – Clinical manifestations of SIBO include malabsorption, which exacerbates diarrhea, increases energy requirements, can cause weight loss, and can delay weaning of parenteral nutrition. Related symptoms include bloating, gassiness, abdominal distension, and foul-smelling stool or breath. In severe cases, colitis and ileitis may occur [46]. Other features of SIBO may include endotoxemia, arthritis, and more frequent blood stream infections [45]. There may be associated vitamin B12 deficiency because the bacteria consume this nutrient. In contrast, folate levels in patients with SIBO may be normal or high due to increased synthesis of folate by small bowel bacteria. (See 'Common deficiencies' below and "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Clinical features'.)

The malabsorption associated with SIBO involves two mechanisms. First, deconjugation of bile acids by the bacteria diminishes the intestinal absorption of monoglycerides and fatty acids. Second, the inflammatory response caused by bacterial overgrowth damages the absorptive surface, resulting in malabsorption and protein loss.

Diagnosis – For patients with a history of SIBO or known risk factors such as intestinal dysmotility or a dilated or dysmotile bowel loop, a provisional diagnosis can be made based on symptoms. The diagnosis is confirmed if the patient responds to empirically selected antibiotics. For patients without these risk factors or when a more definitive diagnosis of SIBO is needed, the preferred method is endoscopy with quantitative culture of duodenal aspirates for aerobes and anaerobes, with sensitivities to guide antibiotic choice [47]. Growth of ≥105 colony-forming units per mL of any bacterial or fungal species is diagnostic of SIBO [48]. Care should be taken to avoid endoscopic suction prior to sampling the duodenal fluid to avoid contamination of the sample with oral flora. Alternative diagnostic methods for SIBO include lactulose and glucose breath tests. Interpretation of breath tests in these patients is complicated because of rapid intestinal transit, which can cause false-positive results. The evaluation and diagnosis of SIBO are discussed in greater detail separately. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis".)

Treatment – SIBO is often treated empirically when typical symptoms occur, especially in patients with known risk factors. SIBO usually responds to treatment with antibiotics, but in many cases repeated or cyclical dosing is required. Predisposing factors such as medications that suppress gastric acid production (PPIs) or reduce motility (loperamide) should be avoided. When bacterial overgrowth is related to small bowel dilation, surgical procedures to taper the bowel, with or without bowel lengthening, may be helpful [49]. Management of SIBO is discussed in greater detail separately. (See "Small intestinal bacterial overgrowth: Management" and "Management of short bowel syndrome in children", section on 'Intestinal lengthening procedures'.)

HEPATOBILIARY DISEASE — Patients with SBS who require long-term parenteral nutrition are at risk for the development of liver disease and cholelithiasis (table 1):

Intestinal failure-associated liver disease — Intestinal failure-associated liver disease (IFALD), also known as parenteral nutrition-associated liver disease (PNALD), historically was seen in 40 to 60 percent of children who receive long-term parenteral nutrition. Severe and progressive liver disease is most common in premature neonates and infants with SBS and can lead to cirrhosis, portal hypertension, and liver failure [50]. A key laboratory feature in the presentation of IFALD is elevation of serum conjugated bilirubin, with variable effects on liver aminotransferases. However, even with normalization of hyperbilirubinemia, IFALD can still be present. Prompt and early referral of children with intestinal failure to intestinal rehabilitation centers may be associated with improved outcomes and is strongly advised [51].

With careful management, many of these children can be weaned from parenteral nutrition before their native liver becomes irreversibly damaged. Important steps include maximizing enteral nutrition, limiting the dose of intravenous (IV) soy-based lipid emulsions, avoiding catheter-related bloodstream infections, and using alternative IV lipid formulations such as fish oil-based monotherapy or mixed lipid emulsions when indicated [52]. A detailed discussion of IFALD, including the possible role of the lipid emulsion in its pathogenesis and management and the potential benefit of fish oil-based lipid emulsions, is presented in a separate topic review. (See "Intestinal failure-associated liver disease in infants".)

Despite these efforts, some patients progress to liver failure and require liver transplantation. If the infant or child has end-stage liver disease but is close to when parenteral nutrition can begin to be discontinued, isolated liver transplantation may be possible [53]. If not, a combined liver-small bowel transplant may be required [54]. (See "Management of short bowel syndrome in children", section on 'Small bowel transplantation'.)

Gallstones — Patients with SBS experience an increased incidence of gallstones [55,56]. One study of 84 adult patients with severe SBS found asymptomatic gallstones in 44 percent [56]. In another report, gallstones were found in 4 of 24 children who had ileal resection in the newborn period [57]. Gallstones or gallbladder sludge is often an incidental finding on routine abdominal ultrasound in children with SBS. Rarely, the condition can progress to cholecystitis, which presents as right upper quadrant pain with elevation in bilirubin, gamma-glutamyl transpeptidase (GGT), and/or liver enzymes. It is also possible to develop gallstone pancreatitis, which can be an emergency.

Pathogenesis – The pathogenesis of cholelithiasis in patients with SBS is not completely understood. At least two factors may contribute:

Altered bile composition – Resection of the ileum interrupts the enterohepatic circulation of bile acids, reduces bile acid secretion into the gallbladder, and causes the bile to become supersaturated with cholesterol.

Bile stasis – In the absence of meals or bolus feeds, there is diminished meal-induced gallbladder contraction, which is mediated by cholecystokinin. This leads to biliary stasis and promotes the formation of biliary sludge and pigmented gallstones. Black stones are likely related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates precipitating with calcium [58] and can occur in patients on chronic parenteral nutrition. Bolus feeds reduce bile stasis, while continuous feeds do not.

Risk factors – Risk factors for the development of gallstones in children with SBS include:

Ileal resection

Absence of an ileocecal valve

Lack of enteral feeding

Motility disorder with stoma [59]

Administration of furosemide (especially in low birth weight infants) [60]

Octreotide use (risk better established in adults) [61,62]

A greater number of abdominal operations

Long duration of parenteral nutrition (>3 months)

Young age at the start of parenteral nutrition

Recurrent sepsis (this effect appears to be mediated at least in part by antagonism of critical hepatic bile salt transporters [63])

Prevention – The primary approach to preventing gallstones is to maximize enteral feeding and reduce dependence on parenteral nutrition. Oral administration of ursodeoxycholic acid (UDCA), typically 10 mg/kg twice daily, is sometimes used to improve bile flow and reduce gall bladder stasis. There are few data to suggest that prophylactic use of UDCA prevents gallstones or IFALD.

Management – Treatment with UDCA is recommended for children on parenteral nutrition who have elevated liver enzymes and/or evidence of gallstones or sludge in the gallbladder on abdominal ultrasound. Cholecystectomy is recommended for symptomatic gallstones, gallstones associated with ductal dilation, cholecystitis, or recurrent pancreatitis related to gallstones.

CATHETER-RELATED COMPLICATIONS — Patients who require long-term parenteral nutrition are at risk for complications related to the indwelling central venous catheter (CVC), including CVC-related blood stream infections and mechanical issues such as CVC breakage and occlusion [45,64,65]. Patients with recurrent CVC complications are at risk for losing central venous access, which, in some cases, is an indication for intestinal transplantation.

Infection — CVC-related bloodstream infections may be caused by contamination and improper care of the catheter. In addition, bacterial translocation from disordered gut epithelium in a patient with SBS can contribute to the risk for recurrent CVC infection [45,66,67].

The immediate risks of CVC-related infections are sepsis as well as dysfunction or loss of the CVC itself. Chronic consequences of recurrent CVC-related bloodstream infections are progressive cholestasis and intestinal failure-associated liver disease (IFALD) [68-70]. Furthermore, in infants with SBS, suboptimal somatic growth (as measured by weight-for-age Z-scores and length-for-age Z-scores) is independently associated with ≥2 CVC-related bloodstream infections [71]. (See "Intestinal failure-associated liver disease in infants", section on 'Pathogenesis'.)

Prevention – The risk of CVC-related infection is particularly high during the first month of home parenteral nutrition use and in children younger than one year of age [72]. Instruction of the parents or caregivers in CVC care should be initiated as soon as the patient has been identified as a candidate for home parenteral nutrition, and their proficiency should be confirmed before discharge [73,74]. It is advised that two caregivers be fully trained in home CVC care.

The CVC should not be submerged in water, due to the risk of infection. Patients with CVCs are encouraged to bathe as long as the area of the body with the CVC is not submerged and is appropriately protected from contamination (eg, by using a protective cover over the CVC dressing such as commercial plastic wrap with tape, AquaGuard, VALguard, or Parafilm). The patient can use a shower if they are able to stand and a bathtub if they cannot. A handheld showerhead is helpful to avoid water contamination. We generally advise patients not to swim, even in chlorinated pools, due to the risk of infection when the catheter is submersed [75]. This is a difficult decision, balancing quality of life against risks for CVC infection and its complications. Decisions about activities that present risks for the CVC are best made in collaboration with the family after detailed discussion of the potential risks and benefits.

A common cause of CVC-related infection is contamination of the central line cap/tubing with fluid (eg, stool, urine, vomitus, water). The use of protective barrier products may reduce contamination in these cases and prevent CVC-related infections. (See "Routine care and maintenance of intravenous devices", section on 'Universal care strategies'.)

Diagnosis – Because children with SBS and fever have a high rate of CVC-related blood stream infection [76], we advise families and caregivers to seek prompt evaluation for any child with a CVC and fever of ≥100.4°F (≥38°C). Management includes obtaining blood cultures, initiation of empiric intravenous (IV) antibiotics, and hospitalization for inpatient monitoring [76]. (See "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis".)

Treatment – Patients with a suspected CVC-related bloodstream infection should be treated promptly with IV antibiotics, which are selected empirically rather than waiting for culture results. Typical empiric antibiotics include vancomycin and cefepime for gram-positive and gram-negative coverage. If intraabdominal infection or process is suspected, metronidazole can be added for anaerobic coverage [77]. Prompt initiation of IV antibiotics may improve morbidity and mortality [78]. Provided that the child is clinically well, an attempt to salvage the catheter is appropriate for children with SBS who require long-term parenteral nutrition because these patients have limited options for venous access. In this case, the CVC is left in place and the infection is treated with the appropriate systemic IV antibiotics administered through the CVC. Treatment is discussed in detail separately. (See "Intravascular non-hemodialysis catheter-related infection: Treatment".)

For patients who are receiving ethanol lock therapy to prevent CVC-related bloodstream infections, the daily ethanol lock therapy can continue while systemic IV antibiotics are used. If a patient is not already on daily ethanol lock therapy, initiation of this therapy should be considered, as discussed below. There is no advantage to adding antibiotic lock therapy concurrently with systemic antibiotics, because we routinely administer the systemic antibiotics through the CVC.

Fungal CVC-associated blood stream infections often require removal of the central line and prolonged IV antifungal therapy. CVC exit site infections can usually be treated with sterile dressing changes and systemic antibiotics if treatment is initiated early in the course. (See "Intravascular non-hemodialysis catheter-related infection: Treatment".)

Prevention of recurrence – Chronic ethanol lock therapy may be helpful in preventing CVC-related sepsis in children on chronic parenteral nutrition [79-83]. The technique involves instilling 70% ethanol to dwell in the CVC when it is not being used for parenteral nutrition. This technique is increasingly utilized in intestinal rehabilitation programs in the United States and is typically initiated after the first CVC-related blood stream infection. Daily administration of the ethanol lock may be more effective than intermittent therapy [70], especially if the patient is deemed high risk. However, a few studies also suggest that ethanol lock therapy may increase risks for CVC occlusion and thrombosis [84-89]. Caution should be used when combining ethanol lock therapy with metronidazole because there is a theoretical risk for disulfiram reaction (characterized by flushing, headache, tachypnea, tachycardia, palpitations, nausea, and vomiting), although the overall risk of a disulfiram reaction is low [90]. (See "Parenteral nutrition in infants and children", section on 'Lock therapy'.)

Chronic antibiotic lock therapy is not recommended for prevention of recurrent CVC infections, due to concerns about development of antibiotic resistance and lack of data supporting its efficacy. However, alternative lock solutions may be considered if ethanol lock therapy is not available, as may occur during a national shortage of ethanol lock therapy. (See "Lock therapy for treatment and prevention of intravascular non-hemodialysis catheter-related infection".)

Mechanical failure — Noninfective complications of CVCs include occlusion (usually due to thrombosis) or damage to the tubing. These problems can be reduced by using standardized protocols for insertion and long-term care, including flushing protocols to maintain patency of the CVC [91]. Efforts to prevent and treat mechanical failures are important to preserve central venous access for children requiring long-term parenteral nutrition.

Occlusion or thrombosis – If the line becomes occluded, thrombolytic agents can be used to restore patency. This procedure is usually performed by nurses in the emergency department or from nutrition support or vascular access teams. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Blocked central venous catheter'.)

Superior vena cava syndrome is caused by obstruction of the superior vena cava and may be a consequence of CVC-related thrombosis. Signs and symptoms include shortness of breath; edema of the face, neck, or arm; and/or headache. The primary treatment is with anticoagulation and thrombolytic agents; CVC removal is sometimes required. In some cases, diuretics can be used to decrease venous return to the heart. Stenting by an interventional radiologist may be required acutely. Special care should be taken with patients on mechanical ventilation because increased airway pressure can further compress the superior vena cava. (See "Venous thrombosis and thromboembolism (VTE) in children: Risk factors, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

Damage – Damage to CVCs (such as from punctures) can be minimized by educating the parents or caregivers about care of the CVC site and device. Over-clamping and using scissors near the line should be avoided. Protective gear to stabilize the line and occlusive dressing may be helpful and are encouraged. If the CVC is damaged, the defective line can often be repaired and/or changed over guide wires to preserve the site of access. Repair of CVCs in children with intestinal failure has not been shown to increase the rate of CVC infection and should be performed if possible [92,93].

NUTRITIONAL COMPLICATIONS — Children with SBS are at greatest risk for nutrient deficiencies while parenteral nutrition support is being weaned and after it is discontinued because the degree of intestinal adaptation and absorption of nutrients are unpredictable. In two series of children undergoing transition from parenteral to enteral nutrition, at least three-quarters had a vitamin or mineral deficiency prior to the transition and the prevalence increased after transition to full enteral feeds [94,95]. The most common deficiencies were of vitamins A, E, and D as well as zinc and iron.

Common deficiencies — Patients should be monitored carefully for nutrient deficiencies after the transition to enteral nutrition. We suggest measuring vitamin and mineral/trace element levels four to eight weeks after parenteral nutrition is discontinued and then serially, as outlined in the table (table 3). (See "Management of short bowel syndrome in children", section on 'Laboratory monitoring'.)

The following nutrient deficiencies are particularly common in children with SBS and should be monitored; the risk in an individual patient is often related to the anatomy and function of the residual intestine (figure 2 and figure 1):

Fat-soluble vitamins – Patients with SBS are at risk for deficiencies of vitamins A, D, E, or K because of fat malabsorption. Patients with cholestasis or pancreatic insufficiency are particularly at risk and warrant special attention to the monitoring of fat-soluble vitamin levels (table 3). For vitamin K deficiency, additional risk factors are lack of a colon and antibiotic usage because vitamin K is synthesized by colonic bacteria. Clinical manifestations, diagnosis, and treatment of these fat-soluble vitamin deficiencies are discussed separately. (See "Overview of vitamin A" and "Vitamin D insufficiency and deficiency in children and adolescents" and "Overview of vitamin E" and "Overview of vitamin K".)

Iron and trace element deficiencies – Deficiencies of iron, zinc, copper, and selenium occur in SBS because of increased fecal losses and, in some cases, decreased intake [96]. Routine screening during and after the transition off of parenteral nutrition can identify these deficiencies before symptoms develop (table 3). Of note, concurrent measurement of C-reactive protein (CRP) is recommended at the time of testing for micronutrient deficiency to determine if an inflammatory state is present and permit accurate interpretation of the results. In the presence of inflammation, serum ferritin and copper levels are increased, whereas zinc, selenium, and iron are decreased.

Iron deficiency may be caused by inadequate absorption of iron and/or gastrointestinal bleeding (eg, from anastomotic ulcers). Routine screening should include measurement of complete blood count with red blood cell indices, serum ferritin, CRP, total iron-binding capacity (TIBC), serum iron, reticulocyte count, and intermittent testing of stools or ostomy output for blood. The anemia associated with iron deficiency is typically microcytic, but this finding may be obscured if there is concurrent vitamin B12 deficiency (which causes macrocytosis). Oral or intravenous (IV) iron therapy may be needed to replete iron stores, with close monitoring of iron studies to mitigate the risk of iron overload with chronic IV iron use. (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis" and "Iron requirements and iron deficiency in adolescents".)

Zinc deficiency may impair intestinal absorption and growth; clinically significant deficiency is suggested by the combination of decreased serum zinc concentration in association with low serum alkaline phosphatase concentrations. Oral supplementation should be initiated as indicated. (See "Zinc deficiency and supplementation in children".)

Copper deficiency can lead to significant metabolic bone disease (MBD) such as osteoporosis, metaphyseal changes, physeal disruptions, and myeloneuropathy [97]. Skeletal surveys should be obtained if chronic copper deficiency is suspected. Copper deficiency can also be associated with cytopenias. (See "Overview of dietary trace elements", section on 'Copper'.)

Selenium deficiency has been associated with fatal cardiomyopathy [98]. An echocardiogram should be performed if cardiac dysfunction is suspected in a patient with selenium deficiency. (See "Overview of dietary trace elements", section on 'Selenium'.)

Vitamin B12 deficiency – Vitamin B12 (cobalamin) deficiency is common in patients who have undergone ileal resection because dietary vitamin B12 is absorbed in the terminal ileum via specific receptors. In addition, if small intestinal bacterial overgrowth (SIBO) is present, the bacteria compete for vitamin B12 and contribute to the deficiency. (See 'Small intestinal bacterial overgrowth' above.)

Vitamin B12 deficiency is characterized by a macrocytic anemia and can lead to neurologic dysfunction (dementia or weakness, sensory ataxia, and paresthesias). Measurement of serum vitamin B12 concentration can be used to screen for vitamin B12 deficiency. If the results are borderline or discordant with other clinical features, some clinicians evaluate further by measuring methylmalonic acid (MMA) and homocysteine in serum or urine. MMA and homocysteine are generally elevated in vitamin B12 deficiency because vitamin B12 is required as a cofactor for the conversions of MMA to succinyl-CoA and of homocysteine to methionine. However, patients with SIBO may have elevated levels of MMA in the absence of B12 deficiency due to bacterial generation of these and other organic acids [99,100], so MMA may not be a reliable marker of vitamin B12 status in children with SBS.(See "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency".)

For patients with vitamin B12 deficiency due to SBS, the first-line treatment is monthly intramuscular cyanocobalamin (vitamin B12) injections. In our experience, effective doses are 500 micrograms monthly for children ≤10 years of age and 1000 micrograms monthly for children >10 years. Patients with terminal ileum resection will likely require lifelong supplementation since they are usually unable to absorb vitamin B12 through their diet. Supplementation using a sublingual vitamin B12 tablet has been described in a case report [101]. This is a novel approach and could be trialed with careful monitoring of serum B12 levels. (See "Treatment of vitamin B12 and folate deficiencies", section on 'Treatment of vitamin B12 deficiency'.)

Vitamin B1 deficiency – Vitamin B1 (thiamine) is a water-soluble vitamin absorbed by the small intestine. Children with SBS may be at risk for deficiency if receiving parenteral nutrition without thiamine, prolonged IV fluids, or breast milk from thiamine-deficient mothers [102]. Symptoms include altered mental status, unsteady gait, and oculomotor abnormalities. Deficiency can lead to beriberi (high-output cardiomyopathy, polyneuritis) and Wernicke encephalopathy (acute, life-threatening neurologic decompensation). (See "Overview of water-soluble vitamins", section on 'Vitamin B1 (thiamine)'.)

If thiamine deficiency is suspected clinically due to risk factors or symptoms, the evaluation may include measurements of thiamine or thiamine pyrophosphate concentrations in whole blood, noting that concentrations may be falsely elevated in the setting of acute inflammation. However, diagnosis is usually clinical because laboratory testing may not be reliable or available. Treatment of symptomatic patients is discussed separately. (See "Overview of water-soluble vitamins", section on 'Deficiency'.)

Calcium and magnesium deficiency – Patients with fat malabsorption tend to malabsorb calcium and magnesium because these divalent cations bind to fatty acids in the intestinal lumen. The primary manifestation of calcium deficiency is MBD (osteopenia or rickets), with elevated alkaline phosphatase activity. (See 'Metabolic bone disease and rickets' below.)

Magnesium deficiency may also contribute to MBD. Severe magnesium deficiency is characterized by symptoms of fatigue, depression, muscle weakness, and neuromuscular excitability. Magnesium deficiency may be difficult to treat because oral magnesium is poorly absorbed and causes osmotic diarrhea. As a result, some patients may require parenteral supplementation [96]. (See "Hypomagnesemia: Clinical manifestations of magnesium depletion" and "Overview of the treatment of malabsorption in adults", section on 'Nutrient repletion and supplementation'.)

Essential fatty acid deficiency (EFAD) – Patients with SBS are at risk for EFAD if adequate essential fatty acids are not provided in parenteral nutrition or when transitioning from parenteral nutrition to enteral feedings because of malabsorption of fats. The essential fatty acids are linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid), which cannot be synthesized by the body and are an integral component of cell membranes, with structural and functional significance in the retina and central nervous system.

EFAD is characterized by hair loss, fatty infiltration of the liver, poor growth, developmental delay, poor wound healing, increased susceptibility to infection, and dermatitis, with hyperproliferation of the epidermis and increased transepidermal water loss. In humans, biochemical evidence of EFAD may develop within days to weeks of inadequate essential fatty acid intake; the dermatitis may not present for weeks to months thereafter [103]. In addition, EFAD may cause thrombocytopenia. In patients with SBS, it is therefore important to consider EFAD as the cause of a low platelet count in addition to a more typical cause such as intestinal failure-associated liver disease (IFALD) with portal hypertension.

Laboratory testing for EFAD should be performed in SBS patients who develop suggestive symptoms or who are receiving chronic parenteral nutrition with restricted IV lipid emulsion and with minimal to no enteral intake [104,105]. EFAD is diagnosed when there is a shift to the omega-9 fatty acid pathway, which increases the ratio of eicosatrienoic acid (mead acid) to arachidonic acid, also known as the triene:tetraene ratio or Holman Index [106]:

Triene:tetraene ≥0.05 – Mild EFAD

Triene:tetraene ≥0.2 – Moderate EFAD

Triene:tetraene ≥0.4 – Severe EFAD

Elevated eicosatrienoic acid (mead acid) has been shown to be an early indicator of EFAD [107].

Metabolic bone disease and rickets — Patients with SBS are at risk for MBD primarily because of malabsorption of vitamin D and calcium [108,109]. Other risk factors include metabolic acidosis, magnesium deficiency, and vitamin D deficiency (which occurs more frequently in preterm infants and with the administration of cholestyramine) [110,111]. The risk of MBD increases with the duration of parenteral nutrition dependence [108,109,112]. In a study of children with intestinal failure (40 percent of whom were on parenteral nutrition), 34 percent had MBD, defined as bone mineral density less than -2.0 standard deviations, measured during mid-childhood [113].

To monitor for MBD in patients with SBS, serum concentrations of 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium, and inorganic phosphorus (Pi) should be measured every three months during the first year after parenteral nutrition has been discontinued. MBD also should be suspected in patients with inappropriately elevated alkaline phosphatase activity.

Most patients with MBD have low or normal Pi with elevated PTH, indicating deficiencies in vitamin D and/or calcium (calcipenic rickets).

Rarely, patients may have low Pi but normal PTH (phosphopenic rickets). This is usually caused by renal phosphate wasting; clinically significant phosphorus malabsorption is rare in SBS.

Magnesium deficiency is characterized by low concentrations of magnesium and calcium as well as normal or low PTH. By contrast, pure hypocalcemia is characterized by elevated PTH.

(See "Overview of rickets in children", section on 'Initial classification'.)

To prevent MBD, supplementation of calcium and/or vitamin D may be required to ensure that the recommended daily intake for each of these nutrients is met. Patients with vitamin D deficiency may require high doses to replace and maintain adequate vitamin D stores. In our SBS patients, we strive to maintain a 25-hydroxyvitamin D concentration >30 ng/mL (75 nmol/L). Concentrated enteral supplements of vitamin D are often tolerated even by patients on minimal oral or enteral feeds. (See "Etiology and treatment of calcipenic rickets in children", section on 'Nutritional rickets'.)

We suggest baseline evaluation of bone density with dual-energy x-ray absorptiometry (DXA) for all children with SBS; screening should begin when the child is old enough to cooperate with the scan (generally around five years of age) [114,115]. DXA should then be followed serially at an interval depending on risk factors and Z-score (eg, every year for patients with reduced bone mineral density and every one to two years for those with a normal bone mineral density and presence of risk factors). Research in this area is ongoing; a study in adults with SBS demonstrated that administration of human growth hormone might improve bone health since it increased markers of bone turnover and stabilized femoral bone neck mass [116]. Marked vitamin D deficiency in children and/or physical findings of frontal bossing or bowed legs warrants plain films of the wrist and hand or knees to evaluate for evidence of rickets. (See "Overview of rickets in children", section on 'Clinical manifestations'.)

SKIN COMPLICATIONS — Patients with SBS may experience complications with gastrostomy tube site, ostomies, or perianal skin breakdown from excessive stool output. Collaboration with specialists in wound care or ostomy care can dramatically reduce ostomy complications.

In particular, patients with a gastrostomy tube and ostomies for stool collection are at risk for the following skin complications:

Granulation tissue – Granulation tissue at a gastrostomy site can develop due to moisture or leakage; friction from mobility of the tube; or ill-fitting, low-profile ("skin-level") gastrostomy devices. Evaluation and placement of a proper-size tube and barrier devices can improve these complications. The granulation tissue also may be ablated by chemical cautery of the granulation tissue with topical silver nitrate (picture 2) or treated with 0.1 to 0.5% triamcinolone cream.

Skin breakdown – Monitoring peristomal skin integrity is a key component of ostomy care. Skin breakdown around ostomy sites occurs due to mechanical trauma from manipulation of an ostomy pouch, chemical damage from gastrointestinal fluids, infectious dermatitis (fungal or bacterial), or contact dermatitis from topical products (picture 3). Barrier cream (which protects the skin from moisture) should be applied around the ostomy to prevent skin breakdown from leaking stool. In patients with ileal disease or resection, bile acid diarrhea may lead to significant skin breakdown. The bile acid sequestrant cholestyramine may be used as a topical ointment and applied to the skin for perianal irritation [117].

Parastomal hernia – A parastomal hernia is a protrusion of bowel through the fascial opening, which may need to be surgically corrected if symptomatic.

Stoma prolapse – Stoma prolapse is the telescoping of the intestine out from the stoma and should be evaluated immediately to rule out ischemia. It can be managed conservatively if there is no abnormal perfusion or obstruction.

(See "Ileostomy or colostomy care and complications".)

RENAL COMPLICATIONS

Hyperoxaluria and kidney stones — Individuals with SBS are prone to hyperoxaluria, which can lead to the formation of calcium oxalate kidney stones [118]. Hyperoxaluria in patients with SBS is caused by fat malabsorption, which leads to binding of calcium to free fatty acids in the intestinal lumen, which, in turn, reduces calcium binding to oxalate. The resulting free oxalate is absorbed through the colon [119,120]. The excess absorbed oxalate is then excreted into the urine where it predisposes to the formation of kidney stones. In addition to increased oxalate excretion, patients with malabsorption may have other factors that predispose to stone formation. The diarrheal fluid losses can lead to a reduction in urine volume and, if the patient has a metabolic acidosis, a low urine pH and a marked decrease in citrate excretion. These changes can promote formation of uric acid or calcium oxalate kidney stones. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Hyperoxaluria'.)

Treatment of hyperoxaluria in the setting of SBS is directed toward diminishing intestinal oxalate absorption [119]. Therapies, which have not been studied in controlled trials, include:

A low-fat, low-oxalate diet may be helpful in reducing the quantity of fatty acids and free oxalate in the colon. However, this diet often is nutritionally inadequate in patients who have SBS.

Increased fluid intake (to ensure dilute urine).

Magnesium and pyrophosphate supplementation. These solutes, when excreted in the urine, inhibit calcium oxalate precipitation.

If metabolic acidosis is present, correct this with potassium citrate.

Cholestyramine can be used to bind both bile acids and oxalate, but this may exacerbate malabsorption of fat and fat-soluble vitamins.

(See "Kidney stones in children: Prevention of recurrent stones", section on 'Hyperoxaluria and oxalosis'.)

Other kidney findings — Renal impairment and the development of chronic kidney disease have been reported in adults who were on long-term parenteral nutrition for intestinal failure [121]. The incidence of kidney dysfunction in pediatric SBS is not well known but appears to be increased compared with a healthy population [122]. Contributing mechanisms include chronic dehydration due to watery diarrhea and malabsorption as well as exposure to many courses of nephrotoxic medications, particularly nephrotoxic antibiotics, during episodes of fever or illness.

Proteinuria may be a sign of chronic renal disease in children with SBS [123]. At our institution, we obtain yearly abdominal ultrasounds in children with SBS on parenteral nutrition to screen for renal disease. We look for evidence of clinically significant renal disease, which can include nephrolithiasis, disproportionate renal growth, renal scarring, hydronephrosis, or echogenicity. Referral to a nephrologist should be considered if there is concern for renal impairment.

To screen for chronic kidney dysfunction, we monitor laboratory indices at regular intervals, which include blood urea nitrogen, cystatin C, creatinine, and bicarbonate trends. If we have concerns for chronic dehydration or progressive kidney dysfunction, we monitor urinalyses for specific gravity abnormalities, proteinuria, casts, crystals, and/or other abnormalities. We work closely with a dietician at each visit to calculate total fluid intake from all sources (oral, enteral, intravenous [IV]) to ensure that the patient is meeting fluid requirements in an attempt to avoid chronic dehydration.

NEUROLOGIC COMPLICATIONS

Neurocognitive development — Intestinal failure during infancy is associated with neurodevelopmental disabilities during early childhood, an effect that is only partly explained by prematurity [124-127]. As an example, among 18- to 24-month-old children with SBS seen in long-term follow-up for prematurity, the prevalence of moderate to severe neurodevelopment impairment was 77 percent, which was significantly higher than in preterm infants with necrotizing enterocolitis (NEC) but without SBS (62 percent) or those without NEC or SBS (44 percent) [127]. Similarly, in a cohort of school-aged children in an intestinal failure rehabilitation program, nearly one-half had a cognitive delay or learning disability [125]. These observations call for systematic screening of this population for neurodevelopmental disabilities and early intervention as needed.

D-lactate encephalopathy — D-lactate encephalopathy, a complication of D-lactic acidosis, is a metabolic complication of SBS that can cause intermittent neurologic dysfunction including confusion, cerebellar ataxia, and slurred speech [128]. It primarily occurs in patients with an intact colon and often in the setting of underlying small intestinal bacterial overgrowth (SIBO) (see 'Small intestinal bacterial overgrowth' above). In such patients, delivery of unabsorbed carbohydrate to the colon causes gram-positive anaerobic bacteria to produce D-lactate (rather than the L-lactate produced by normal metabolic processes) [129,130]. Other risk factors include low intestinal pH, use of certain antibiotics or probiotics that promote D-lactate-producing intestinal flora, continuous enteral feedings, exogenous sources of D-lactate (eg, yogurt, sauerkraut, pickled vegetables, Lactated Ringer), or dietary oxalate (which reduces metabolism of D-lactate by inhibiting of D-2-hydroxy-acid dehydrogenase) [128,131,132]. Laboratory evaluation may show metabolic acidosis with a high anion gap. Patients with SBS frequently have chronically elevated serum concentrations of D-lactate even in the absence of neurologic symptoms [130,133,134].

The clinical manifestations, diagnosis, and treatment of D-lactic acidosis are discussed separately. (See "D-lactic acidosis".)

OTHER ISSUES

Feeding problems and oral aversion — Children with SBS are at risk for feeding problems and oral aversion (a form of pediatric feeding disorder) [135,136]. Risk factors include delayed introduction of oral feeding, airway intubation, prolonged neonatal intensive care, gastroesophageal reflux, painful procedures (nasogastric tube insertion, endoscopy), fundoplication, chronic aspiration, and motility disorders that lead to retching and gagging (eg, children with SBS caused by gastroschisis or intestinal atresia rather than necrotizing enterocolitis [NEC]) [135]. Many SBS patients have a history of prematurity and complicated neonatal courses during which oral feedings were delayed or interrupted [137]. Chronic parenteral nutrition and enteral tube feedings may suppress hunger and appetite, further contributing to oral aversion.

Prevention of oral aversion involves instituting nonnutritive sucking and feeding therapy early in the course of SBS. Consultation with a feeding therapist and/or psychologist as part of an interdisciplinary intestinal rehabilitation program is valuable. (See "Neonatal oral feeding difficulties due to sucking and swallowing disorders".)

For patients with poor appetite who can tolerate oral feedings, adjunctive therapy can include cyproheptadine, which acts as an appetite stimulant and can also improve dyspeptic symptoms and feeding tolerance [26,27,138]. It is an antihistamine and serotonin antagonist with anticholinergic effects that competes with histamine for H1 receptor sites on cells in the gastrointestinal tract [139]. Peptic esophagitis and gastritis should be treated aggressively since this can contribute to aversive behaviors. Parenteral and enteral nutrition should be cycled when possible to help stimulate appetite and allow for time off of pumps and tubing connections. (See "Parenteral nutrition in infants and children", section on 'Cycling'.)

Dental disorders — Dental disorders such as dental caries are common in individuals with SBS. A study of adults with SBS in the United Kingdom identified high rates of oral caries and xerostomia (dry mouth); xerostomia is a risk factor for oral infections [140]. Risk factors for these problems included hyperphagia, sugar-containing "sip" feeds or oral rehydration fluids, dehydration, and use of medications that cause dry mouth. In addition, oral aversion may present an obstacle to routine tooth care because children may have difficulty tolerating the insertion of a toothbrush in the mouth. Early referral to and ongoing monitoring by a pediatric dentist is recommended and should be discussed at every visit.

Eruption of green or discolored teeth also has been described. The tooth discoloration is likely due to prolonged conjugated hyperbilirubinemia during dental development, combined with other risk factors such as extreme low birth weight and antibiotic use (picture 4) [141].

Psychosocial and financial burden — Families of children with SBS encounter substantial social stressors and financial strains that adversely affect family functioning and wellbeing, which are reflected in lower scores on measures of psychosocial health and disease-specific quality of life compared with healthy controls [142,143]. The children require large investments of time from caregivers for routine feeding and care, and many require prolonged hospitalizations for medical and surgical indications. The estimated health care costs for infants with intestinal failure living in the United States average $505,000 in the first year of life and approximately $300,000 in subsequent years, based on an analysis in 2008 [144]. Interdisciplinary teams caring for SBS patients typically include social workers, who can help alleviate some of these strains by providing consultation and resources for financial, behavioral, and social support.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Short bowel syndrome".)

SUMMARY AND RECOMMENDATIONS

Overview – Children with short bowel syndrome (SBS) have a wide range of complications affecting the gastrointestinal tract, hepatobiliary tree, and other organs due to chronic malabsorption and need for prolonged parenteral nutrition (table 1 and figure 1).

Diarrhea – Watery diarrhea is the most common early complication of SBS in children and may also be a chronic or recurrent problem in later stages. It is usually caused by excessive osmotic load that overwhelms the limited absorptive capacity of the small intestine. Contributing factors in some patients include ultrashort length of resident small bowel, lactose intolerance, gastric acid hypersecretion, malabsorbed bile salts in the colon (bile acid diarrhea), dysmotility, allergic disease, or small intestinal bacterial overgrowth (SIBO). (See 'Causes' above.)

Management of diarrhea includes:

Dietary management – For most children with chronic watery diarrhea, a trial of dietary changes is the appropriate first step in management. (See 'Trials of dietary changes' above.)

Pharmacotherapy – Additional treatments depend on the setting (see 'Pharmacotherapy' above):

-Acid-suppressive medications are routinely used during the first few months after intestinal resection, but chronic use should be avoided if possible (table 2). If the diarrhea is not adequately controlled with dietary changes, we suggest a time-limited trial of acid suppression using a proton pump inhibitor (PPI) (Grade 2C). The child should be weaned from the drug if there is no clear benefit. (See 'Chronic diarrhea' above.)

-For patients with SBS who are unable to wean off of parenteral nutrition, treatment with teduglutide in conjunction with an intestinal rehabilitation program may be an option. This issue is discussed separately. (See "Management of short bowel syndrome in children", section on 'Pharmacologic therapy'.)

-For patients with a high stool output or nighttime stools despite dietary management, we suggest adding loperamide to the regimen (Grade 2C).

-For patients who have undergone extensive resection of the distal ileum, we suggest a trial of adding cholestyramine to the regimen (Grade 2C). In this case, the medication should be continued, but the patient should be monitored for nutritional status and fat-soluble vitamin deficiencies.

Dysmotility – This is common in patients with SBS, particularly in those with intestinal dilation or those with a history of gastroschisis. There are limited options for medications to treat dysmotility in the pediatric SBS population. For most children who require prokinetic medication, we suggest cyproheptadine or erythromycin as the first-line agents (Grade 2C). Alternative options include amoxicillin-clavulanate or prucalopride. Surgical tapering of the intestine may be beneficial in carefully selected patients. (See 'Dysmotility' above.)

Intestinal failure-associated liver disease (IFALD) – Discussed in a separate topic review. (See "Intestinal failure-associated liver disease in infants".)

Other complications – Other complications include:

Anastomotic ulcers (see 'Anastomotic ulcers' above)

Chronic inflammation and inflammatory bowel disease–like syndrome (see 'Inflammatory bowel disease–like syndrome' above)

Allergic and eosinophilic disorders (see 'Allergic and eosinophilic disease' above)

SIBO (see 'Small intestinal bacterial overgrowth' above)

Gallstones (see 'Gallstones' above)

Catheter-related complications (bloodstream infections, mechanical failure, and thrombosis) (see 'Catheter-related complications' above)

Nutritional deficiencies, which require monitoring and replacement (table 3) (see 'Nutritional complications' above)

Feeding disorder (oral aversion) (see 'Feeding problems and oral aversion' above)

ACKNOWLEDGMENT — The authors and UpToDate editorial staff acknowledges Jon A Vanderhoof, MD, and Rosemary J Pauley-Hunter, NP-C, MS, RN, who contributed to earlier versions of this topic review.

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Topic 5886 Version 41.0

References

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