Chronic complications of the short bowel syndrome in adults

INTRODUCTION — Short bowel syndrome (SBS) is a malabsorptive state that typically occurs following extensive resection of the small intestine. It is a functional definition, implying a significant amount of malabsorption of both macronutrients and micronutrients and is not necessarily dependent on the loss of bowel or a particular length of bowel. Patients with SBS are at risk for several complications. These complications may result from the underlying disease, altered bowel anatomy and physiology, or its treatment, including the need for parenteral nutrition and the use of a central venous catheter. Acute complications that can occur at any time include watery diarrhea, electrolyte disturbances, and catheter-related complications.

This topic will review the chronic complications of SBS in adults. The pathophysiology and management of SBS, including small bowel transplantation, are discussed separately.

ESOPHAGITIS/PEPTIC ULCER DISEASE — Gastric hypersecretion is common after SBS and may last 6 to 12 months postoperatively [1]. In a minority of cases, gastric hypersecretion may lead to esophagitis and/or peptic ulcer disease and patients may present with symptoms of heartburn, regurgitation, dysphagia, or abdominal pain. (See "Pathophysiology of short bowel syndrome", section on 'Ileal versus jejunal adaptation' and "Clinical manifestations and diagnosis of gastroesophageal reflux in adults" and "Peptic ulcer disease: Clinical manifestations and diagnosis".)

Gastric hypersecretion is thought to occur as a result of the loss of inhibitory hormones produced in the proximal gut (eg, gastric inhibitory peptide and vasoactive intestinal peptide). The volume of secretions entering the small bowel increases and the pH of the secretions in the proximal gut is lowered, aggravating fluid losses and leading to peptic complications and impairment in the function of pancreatic exocrine secretions, further contributing to fat maldigestion. (See "Pathophysiology of short bowel syndrome", section on 'Ileal versus jejunal adaptation'.)

Antisecretory medications (eg, proton pump inhibitors or histamine 2-receptor antagonists) used in the early postoperative period in patients with SBS reduce gastric secretions, improve digestion and absorption, and can prevent peptic complications. In patients with gastroesophageal reflux disease or peptic ulcer disease, acid-suppressing medications are used to treat symptoms. However, acid-suppressing medications should be weaned or used at the lowest possible dose in patients with SBS as long-term use is associated with an increased risk of small intestinal bacterial overgrowth and other side effects [2]. (See "Management of short bowel syndrome in adults" and "Antiulcer medications: Mechanism of action, pharmacology, and side effects" and "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Adverse effects'.)

DIARRHEA — Diarrhea in patients with SBS may be multifactorial in etiology. Diarrhea can result from a reduction of absorptive surface area; decrease in intestinal transit time; humorally mediated gastric, small intestinal, and colonic hypersecretion; impairment in the function of pancreatic exocrine secretions, leading to fat maldigestion; or small intestinal bacterial overgrowth [3]. Additionally, it is important to recognize that diarrhea may occur due to the underlying disease (eg, Crohn disease) or an acute process (eg, Clostridioides difficile infection [formerly known as Clostridium difficile]).

Small intestinal bacterial overgrowth — Patients with small intestinal bacterial overgrowth can present with bloating, flatulence, abdominal discomfort, diarrhea, or steatorrhea. Symptoms of small intestinal bacterial overgrowth can lead to a reduction in oral intake and, in turn, delay weaning of parenteral nutrition. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Clinical features'.)

Bacterial overgrowth in patients with SBS results from progressive dilation of the small intestine as part of the intestinal adaptation response to resection [4]. This limits the efficacy of peristalsis in ridding the small intestine of bacteria. Other contributing factors include the absence of an ileocecal valve to prevent reflux of bacteria into the small intestine, compromised enterocyte turnover due to suboptimal enteral nutrient stimulation, and theoretically, the use of acid-suppressive and antimotility medications. (See "Pathophysiology of short bowel syndrome", section on 'Ileal versus jejunal adaptation'.)

Diagnosis — The diagnosis of small intestinal bacterial overgrowth in patients with SBS requires small bowel aspirate with quantitative bacterial cultures [3]. If small bowel aspirate is not available, a presumptive diagnosis is generally made in patients with SBS and bloating, flatulence, abdominal discomfort, diarrhea, or steatorrhea. Hydrogen breath tests should not be used to diagnose small intestinal bacterial overgrowth in patients with SBS as rapid transit in the shortened bowel makes it difficult to differentiate small bowel versus colonic hydrogen production. The diagnosis of small intestinal bacterial overgrowth is discussed separately. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

Management — Small intestinal bacterial overgrowth is managed with antibiotics and dietary modification with a proportionally higher fat-containing diet to reduce the carbohydrate substrate available for bacterial metabolism [5]. The continuous use of low-dose antibiotics in SBS may be necessary in some patients. While without supporting evidence to reduce the risk of antibiotic resistance, it is often recommended that antibiotics should be periodically rotated. Other strategies that have been suggested to be useful for controlling bacterial overgrowth include limiting the use of antisecretory and antimotility agents and intermittent bowel flushing with polyethylene glycol. Although the use of surgical bowel tapering has been reported, there are insufficient data to recommend it for management of small intestinal bacterial overgrowth in patients with SBS [6]. The management of small intestinal bacterial overgrowth is discussed in detail, separately. (See "Small intestinal bacterial overgrowth: Management".)

HEPATIC STEATOSIS AND CHOLESTASIS — Approximately 15 to 40 percent of adults with SBS develop liver disease due to the use of parenteral nutrition and other factors present in SBS patients with intestinal failure (ie, require parenteral fluid or nutrition support). For this reason, the term intestinal failure-associated liver disease (IFALD) is preferred over parenteral nutrition-associated liver disease (PNALD). Diagnosis includes a combination of biochemical, clinical, and in some cases, histologic findings, and is considered after excluding other causes of liver dysfunction. While steatosis is more commonly seen in adults, cholestasis occurs more commonly in children. In adults, the risk of liver disease is greatest in those with a small bowel segment <50 cm, lack of colon-in-continuity, absence of oral/enteral intake, presence of intra-abdominal inflammation, recurrent central venous catheter-related sepsis, small intestinal bacterial overgrowth, and parenteral nutrition-related factors, particularly lipid or glucose overload and the type of intravenous lipid emulsion [7]. Most patients are asymptomatic but may have elevations in hepatic aminotransferases. Severe steatosis and cholestasis can progress to end-stage liver disease. Cholestatic liver dysfunction may lead to cirrhosis and portal hypertension and is an indication for combined liver/intestine transplantation [8,9]. Life-threatening liver disease caused by parenteral nutrition is rare, particularly in adults. However, when it occurs, it is most often due to sepsis, drug toxicity, and, possibly, bacterial overgrowth [10]. (See "Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults" and "Management of nonalcoholic fatty liver disease in adults" and "Intestinal failure-associated liver disease in infants".)

Prevention and management — Several strategies have been suggested for preventing or slowing the development of liver disease [7,10]. These include the following (see "Intestinal failure-associated liver disease in infants"):

●Adjusting parenteral nutrition to provide the minimum level of total energy and macronutrients required, limiting the lipid dose to 1 g/kg/day, cycling parenteral nutrition, treating deficiencies (choline, essential fatty acids, carnitine, taurine, glutathione), and preventing and promptly treating catheter-related sepsis [11].

●Intestinal rehabilitation programs that involve aggressive use of enteral nutrition, control of small bowel bacterial overgrowth, and prevention of catheter sepsis [12,13]. (See "Small intestinal bacterial overgrowth: Management" and "Routine care and maintenance of intravenous devices".)

●Ursodeoxycholic acid (UDCA) is beneficial in some chronic cholestatic liver diseases, particularly primary biliary cholangitis [14]. Most studies of UDCA in patients with parenteral nutrition-associated cholestasis have been in children. In adults, 10 to 15 mg/kg/day administered in two to three doses seems to improve the biochemical and clinical signs and symptoms of cholestasis [15]. However, studies with long-term follow-up are needed to determine if UDCA improves clinical outcomes.

●Novel intravenous lipid emulsions (eg, fish oil and combination soybean, medium chain triglyceride, olive oil and fish oil) have become available for clinical use in the US as traditional soybean lipid emulsions, which have a high content of omega-6 fatty acids, have been implicated in the pathogenesis of IFALD [16-21]. However, while these are FDA-approved for use, their benefit in adults remains to be clearly demonstrated in clinical trials. The use of fish oil-containing emulsions in parenteral nutrition-associated cholestasis in infants does not contain essential fatty acids and is discussed in detail, separately. (See "Intestinal failure-associated liver disease in infants", section on 'Fish oil-based lipid emulsions'.)

CHOLELITHIASIS — Patients with SBS are at increased risk for cholelithiasis, particularly cholesterol stones [22,23]. In one study that included 84 patients with SBS, asymptomatic cholelithiasis was detected in 44 percent [22]. Risk factors for cholelithiasis include the use of parenteral nutrition, resection of the terminal ileum, and an intestinal remnant <120 cm [22,24]. As the risk of complications of cholelithiasis may be higher in patients with SBS as compared with the general population, prophylactic cholecystectomy may have a role when abdominal surgery is being undertaken for other reasons [25].

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

●Altered bile composition – Interruption of the enterohepatic circulation of bile acids by ileal resection results in a reduction in hepatic bile acid secretion and an altered composition of hepatic bile, which becomes supersaturated with cholesterol.

●Bile stasis – Diminished enteric hormonal stimulation of gallbladder contraction may lead to biliary stasis and the formation of biliary sludge.

ELECTROLYTE AND MICRONUTRIENT DEFICIENCIES — Electrolyte and micronutrient deficiencies are uncommon in short bowel patients who are receiving parenteral nutrition. However, patients with SBS are at greatest risk for nutrient deficiencies during and after the time that parenteral nutrition is being weaned and discontinued [26].

Screening — We measure vitamin and mineral levels semiannually in those receiving parenteral nutrition, at the time of parenteral nutrition discontinuation, followed by every three months for the first year, and then at least annually based on the requirements for supplementation [27].

Management

●Fat-soluble vitamin and essential fatty acids – In the absence of supplementation, deficiencies in fat-soluble vitamins and essential fatty acids frequently occur in patients with SBS and large doses may be required to maintain normal plasma levels. Aqueous preparations of vitamins A, D, and E should be used for supplementation. In contrast, as water-soluble vitamins are absorbed in the proximal small bowel, deficiencies in SBS patients are uncommon.

●Vitamin B12 – Deficiency of vitamin B12 occurs in patients who have undergone resection of more than 50 to 60 cm of the terminal ileum. In patients with small intestinal bacterial overgrowth, the bacteria compete for vitamin B12 and contribute to the deficiency. Vitamin B12 deficiency is characterized by a macrocytic anemia and can lead to neurologic dysfunction (dementia or weakness, sensory ataxia, and paresthesias). Patients with SBS and vitamin B12 deficiency generally require nasal or parenteral administration, although some may respond satisfactorily to high dose oral administration. (See "Treatment of vitamin B12 and folate deficiencies" and "Treatment of vitamin B12 and folate deficiencies", section on 'Vitamin B12'.)

●Trace elements – Supplemental zinc and occasionally copper and selenium may be required in the presence of excessive stool losses. Although iron is absorbed in the proximal small bowel, which remains intact in most patients with SBS, iron deficiency is one of the most common deficiencies, particularly in those patients who have limited oral intake and those who require chronic parenteral nutrition as it does not contain iron due to its incompatibility with lipids and propensity to cause allergic reactions [28]. (See "Overview of dietary trace elements".)

●Electrolytes – Magnesium, potassium, calcium, and occasionally bicarbonate supplementation may be needed in patients with SBS who have large stool losses (eg, end-jejunostomy). Hypomagnesemia occurs as a consequence of loss of magnesium-absorbing gut, the binding of magnesium by unabsorbed fatty acids, and sodium/water depletion that increases urinary magnesium losses. Hypomagnesemia may lead to hypocalcemia as a result of impaired parathyroid hormone release [29]. (See "Hypomagnesemia: Causes of hypomagnesemia", section on 'Gastrointestinal losses'.)

Oral magnesium salts can be administered in doses of 12 to 24 mEq/day and do not appear to increase stomal output, particularly when taken at night when intestinal transit is at its slowest. However, higher doses are frequently needed and may be difficult to use because they worsen diarrhea. Magnesium heptogluconate is especially useful in correcting hypomagnesemia without diarrhea and is available as a liquid that can be added to oral rehydration therapy. The correction of sodium depletion is critical in treating hypomagnesemia. The oral administration of 1-alpha-hydroxycholecalciferol increases both intestinal absorption and renal absorption of magnesium [30]. However, if moderate to severe hypomagnesemia (<1 mg/dL) and/or symptoms persists, parenteral magnesium may be necessary. Of note, patients with impaired kidney function are at risk for developing hypermagnesemia when replacement is provided in large doses as magnesium is renally cleared.

METABOLIC BONE DISEASE — Patients with SBS are at increased risk for osteomalacia, osteoporosis, osteopenia, and secondary hyperparathyroidism. Specific risk factors for metabolic bone disease in patients with SBS include the effects of the parenteral nutrition, malabsorption of macro- and micronutrients (eg, vitamin D), electrolyte alterations (eg, hypocalcemia, hypomagnesemia), and chronic metabolic acidosis [31-33]. (See "Etiology of osteoporosis in men" and "Epidemiology and etiology of premenopausal osteoporosis".)

Screening — An assessment of bone density, preferably with dual-energy X-ray absorptiometry, should be undertaken in all patients with SBS, regardless of the need of parenteral nutrition, and should be repeated biannually. The identification of significant bone disease should lead to an assessment of levels of calcium, phosphorus, magnesium, vitamin D (25-hydroxy vitamin D), and parathyroid hormone, and for the presence of metabolic acidosis.

Management — Management of osteoporosis includes lifestyle measures, calcium, magnesium, and vitamin D replacement and correction of metabolic acidosis. Given the poor bioavailability of bisphosphonates, intravenous agents should be used in the setting of SBS. The diagnosis and management of osteoporosis are discussed in detail, separately. (See "Screening for osteoporosis in postmenopausal women and men" and "Overview of the management of low bone mass and osteoporosis in postmenopausal women".)

NEPHROLITHIASIS — Patients with SBS are at increased risk for calcium oxalate nephrolithiasis [34,35]. In patients with SBS with fat malabsorption and a colon-in-continuity, calcium binds to unabsorbed fatty acids, leaving oxalate free to pass into the colon to be absorbed and then filtered by the kidney. In the kidney, oxalate binds to calcium, resulting in oxalate nephrolithiasis and progressive obstructive nephropathy. Increased colonic permeability to small molecules such as oxalate induced by nonabsorbed bile acids facilitates oxalate entry into the bloodstream. A reduction in bacterial breakdown of oxalate due to decreased Oxalobacter formigenes also leads to increased absorption of oxalate in patients with SBS. The diarrheal fluid losses can lead to a reduction in urine volume and, in patients with metabolic acidosis, a low urine pH and a marked decrease in citrate excretion can promote uric acid as well as calcium oxalate stone formation. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine oxalate'.)

Prevention and management — Similar to the management of nephrolithiasis in the general population, the maintenance of adequate urine output by increasing fluid intake (>1.5 L/d if prior stones) is of paramount importance. Treatment of enteric hyperoxaluria is directed at diminishing intestinal oxalate absorption [36,37] and consists of a low-oxalate diet, high fluid intake, potassium citrate to correct metabolic acidosis if present, and oral calcium carbonate (1 to 4 g/day) to bind oxalate in the intestinal lumen. A low-fat, low-oxalate diet can reduce the quantity of fatty acids and free oxalate in the colon; however, is often nutritionally inadequate in patients who have SBS. The oxalate content of foods is available at the following website: http://regepi.bwh.harvard.edu/health/nutrition.html. Cholestyramine should be avoided as it can worsen fat malabsorption in patients with SBS. (See "Kidney stones in adults: Prevention of recurrent kidney stones".)

D-LACTIC ACIDOSIS — D-lactic acidosis is a rare neurologic syndrome characterized by altered mental status ranging from confusion to coma, slurred speech, seizures, and ataxia resulting from bacterial fermentation of unabsorbed carbohydrates. It primarily occurs in patients with an intact colon and often in the setting of underlying bacterial overgrowth. It appears to be more common in children with SBS than adults. In such patients, delivery of unabsorbed carbohydrate to the colon causes Gram-positive anaerobic bacteria to produce D-lactate (rather than the L-lactate that is produced by normal metabolic processes) [38]. The pathogenesis, clinical manifestations, diagnosis, and management of D-lactic acidosis are discussed separately. (See "D-lactic acidosis".)

CATHETER-RELATED COMPLICATIONS — Most patients who require long-term parenteral nutrition experience complications related to the indwelling central venous catheter, which may include blood stream infections and mechanical issues such as catheter breakage and occlusion. The prevention, diagnosis, and management of catheter-related complications are discussed in detail, separately. (See "Nutrition support in intubated critically ill adult patients: Parenteral nutrition", section on 'Complications' and "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis" and "Intravascular non-hemodialysis catheter-related infection: Treatment" and "Lock therapy for treatment and prevention of intravascular non-hemodialysis catheter-related infection" and "Routine care and maintenance of intravenous devices".)

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

●Chronic complications of short bowel syndrome (SBS) may result from the underlying disease, altered bowel anatomy and physiology, or its treatment, including the need for parenteral nutrition and the use of a central venous catheter. (See 'Introduction' above.)

●Gastric hypersecretion is common after SBS and may last 6 to 12 months postoperatively. In a minority of cases, gastric hypersecretion may lead to esophagitis and/or peptic ulcer disease and patients may present with symptoms of heartburn, regurgitation, and dysphagia or abdominal pain. Acid-suppressing medications should be used at the lowest possible dose in patients with SBS as long-term use is associated with an increased risk of small intestinal bacterial overgrowth and other side effects. (See 'Esophagitis/peptic ulcer disease' above and 'Small intestinal bacterial overgrowth' above.)

●Patients with SBS who require long-term parenteral nutrition are at risk for the development of liver disease and cholelithiasis. Strategies for prevention of liver disease include adjusting parenteral nutrition to provide the minimum level of total energy and macronutrients required, (possibly) using novel intravenous lipid emulsions instead of soybean-based, cycling parenteral nutrition, aggressive use of enteral nutrition, treating small intestinal bacterial overgrowth, and preventing and promptly treating catheter-related sepsis. (See 'Hepatic steatosis and cholestasis' above.)

●Diarrhea can result from a reduction of absorptive surface area; decrease in intestinal transit time; humorally mediated gastric, small intestinal, and colonic hypersecretion; impairment in the function of pancreatic exocrine secretions, leading to fat maldigestion; or small intestinal bacterial overgrowth. The diagnosis of small intestinal bacterial overgrowth in patients with SBS is made with small bowel aspirate with quantitative bacterial cultures. Small intestinal bacterial overgrowth is managed with antibiotics and dietary manipulation to reduce the carbohydrate substrate available for bacterial metabolism. (See 'Diarrhea' above.)

●Electrolyte and micronutrient deficiencies are uncommon in short bowel patients who are receiving parenteral nutrition. However, patients with SBS are at greatest risk for nutrient deficiencies during and after the time that parenteral nutrition is being weaned and discontinued. We measure vitamin and mineral levels semiannually in those receiving parenteral nutrition, at the time of parenteral nutrition discontinuation, followed by every three months for the first year, and then at least annually based on the requirements for supplementation. (See 'Electrolyte and micronutrient deficiencies' above.)

●Patients with SBS are at risk for metabolic bone disease and can develop osteomalacia, osteoporosis, osteopenia, and secondary hyperparathyroidism. Specific risk factors for metabolic bone disease in patients with SBS include the effects of the parenteral nutrition, malabsorption of macro- and micronutrients (eg, vitamin D), electrolyte alterations (eg, hypocalcemia, hypomagnesemia), and chronic metabolic acidosis. We therefore screen for bone disease in patients with SBS with dual-energy X-ray absorptiometry at baseline and then every two years. (See 'Metabolic bone disease' above.)

●Patients with SBS and a colon–in-continuity with intestinal contents are at increased risk for oxaluria and nephrolithiasis. The management of patients with enteric hyperoxaluria includes a low-oxalate diet, high fluid intake, potassium citrate to correct metabolic acidosis if present, and oral calcium carbonate to bind oxalate in the intestinal lumen. (See 'Nephrolithiasis' above.)

●D-lactic acidosis is a rare neurologic syndrome characterized by altered mental status ranging from confusion to coma, slurred speech, seizures, and ataxia resulting from bacterial fermentation of unabsorbed carbohydrates. It primarily occurs in patients with an intact colon and often in the setting of underlying bacterial overgrowth. (See 'D-lactic acidosis' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Jon Vanderhoof, MD, and Rosemary Pauley-Hunter, NP-C, who contributed to an earlier version of this topic review.