The Medical and Surgical Management of Short Bowel Syndrome

What Is Short Bowel Syndrome?

The definition of short bowel syndrome is controversial; however, patients who are at the greatest nutritional and dehydration risk generally have < 115 cm of residual small intestine in the absence of colon in continuity or < 60 cm of residual small intestine with colon in continuity. Patients with < 100 cm of residual jejunum often have a net secretory response to food and may actually secrete more fluid than they ingest.[1] “Functional” short bowel syndrome may develop in patients with chronic intestinal obstructions, radiation enteritis, refractory sprue, chronic intestinal pseudoobstruction, or congenital villus atrophy (infants) because of poor absorption. Therefore, “intestinal failure” may be better defined by fecal energy loss than by residual bowel length.[2] However, fecal energy loss should be evaluated in the context of energy intake.

The Occurrence of Short Bowel Syndrome

In the absence of registry data, it is impossible to know the precise incidence and prevalence of short bowel syndrome in the United States. On the basis of European data, the incidence of total parenteral nutrition (TPN)-dependent short-bowel patients is estimated between 2 and 3 per million per year, with the prevalence at approximately 4 per year per million.[3] These figures reflect the fact that with appropriate management, many patients with short bowel syndrome can be successfully weaned from TPN with conventional techniques, as described below.

Several different processes — congenital and acquired — may result in the development of short bowel syndrome. These include congenital intestinal atresia or conditions for which massive enterectomy may be required, such as gastroschisis, necrotizing enterocolitis, and extensive aganglionosis in infants as well as catastrophic vascular events (mesenteric vein or arterial thrombosis or arterial embolism), midgut volvulus, trauma, or tumor resection in adults. Although less common in the last several years with the use of medications, such as infliximab and surgical strictuloplasties, patients with Crohn's disease who undergo repeated intestinal resections may eventually develop short bowel syndrome as well.

From a medical-management standpoint, patients can be divided into 2 distinct subgroups: those with colon in continuity with their small intestine and those without colon. The colon becomes an important digestive organ in patients with short bowel syndrome — it absorbs fluid, medium-chain triglycerides, short-chain fatty acids (from carbohydrate salvage, as discussed below), a small amount of amino acids, sodium, and calcium.

Intestinal Adaptation Following Massive Enterectomy

Although there are few human data, observations in animal models of short bowel syndrome have indicated that following massive enterectomy, the bowel lengthens some, but more importantly, it increases in diameter. The number and size of intestinal villi increase, and therefore the absorptive surface area increases.[3] This process is generally thought to occur over 1–2 years in humans, although there are isolated reports of patients gaining weight and eventually being weaned from TPN after 5–7 years. Oral food intake and, to a lesser extent, intragastric and intrajejunal feeding are important stimulants to intestinal hypertrophy. This adaptive response is mediated by enteroglucagon, glucagon-like peptide (GLP)-II, epidermal growth factor, growth hormone, cholecystokinin, gastrin, insulin, and neurotensin. Peptide YY, released from L cells in the distal ileum and colon, slows gastric emptying and intestinal transit. In the event of distal ileal and colonic resection, this feedback inhibition is lost. Patients with < 100 cm of residual jejunum have rapid gastric emptying.[4] Several factors positively influence the prognosis for bowel adaptation — these include younger age, health of the residual bowel, adequate mesenteric blood flow to the residual bowel, and comorbid conditions. The intestine has significant redundancy. Although each individual normally has some 400–700 cm of small intestine, most nutrient absorption occurs within the proximal 100–150 cm. In the event of significant jejunal resection, nutrients will be absorbed in the ileum and vice versa. However, the jejunum is unable to compensate for the loss of vitamin B12 and bile salt absorption in the case of ileal resection. Because intestinal transit time is significantly decreased in short bowel syndrome, thus reducing the time nutrients have in contact with the absorptive surface, the presence of an intact ileocecal valve improves nutritional outcome. In addition to acting as a “brake,” the ileocecal valve also inhibits bacteria from reaching the small bowel from the colon. In the absence of an ileocecal valve, bacterial contamination of the small bowel occurs, and the potential exists for the development of bacterial overgrowth.[5] Such bacteria would compete with the enterocytes for nutrients. In these cases, small bowel-colonic anastomosis should be attempted as soon as the patient is stable.

Medical Management of Short Bowel Syndrome

Fluid and Electrolyte Management

Fluid and electrolyte management is the most critical part of medical management for the patient with short bowel syndrome. Virtually no patient with this disorder requires macronutrient supplementation alone, but patients may often be weaned successfully from TPN, yet still require fluid and electrolyte support.

During the initial 6 months after massive enterectomy, gastric hypersecretion develops.[6] Basal acid secretion as well as gastrin secretion significantly increase. These increases are associated with an increased risk for peptic ulcer disease as well as with increased fluid losses. In addition, at an acidic pH, pancreatic lipase is deactivated and fat maldigestion worsens. Therefore, high-dose intravenous H₂ receptor antagonists or oral proton-pump inhibitors should be prescribed during this period. Just as nutrient malabsorption occurs, so does medication malabsorption, and therefore, increased doses of orally administered medication may be required.

Fluid losses can be controlled with antimotility agents, such as loperamide hydrochloride or diphenoxylate (4–16 mg/day). Patients whose fluid losses are not controlled and who develop dehydration may require codeine (15–60 mg, 2–4 times daily) or a tincture of opium. Rarely, patients with proximal jejunostomy and several liters of daily stomal output will require octreotide (50–100 mcg subcutaneous, 2–4 times daily).[3] Its use should be discouraged because animal studies have suggested that octreotide inhibits intestinal adaptation and increases the risk for cholelithiasis.

Oral rehydration solutions (ORS) are important in the maintenance of adequate fluid balance and help decrease the need for parenteral fluids — this is especially critical in patients with proximal jejunostomies who are net fluid and sodium excretors. The jejunum is permeable to sodium and chloride; therefore, solutions with a high NaCl content are readily and passively absorbed. Neither sodium nor water is absorbed from hypo- or isotonic solutions in the jejunum. In addition, glucose promotes both salt and water absorption via “solvent drag.” Sodium and glucose absorption are mediated by a cotransporter. Although ORS do not decrease fluid losses, their use increases intracellular hydration. Several commercial formulas are available, although the least costly option is for the patient to formulate the solution recommended by the World Health Organization at home. The patient is instructed to mix 2.5 g of NaCl (table salt), 20 g of glucose (table sugar), 1.5 g of KCl (requires prescription), and 2.5 g of Na₂CO₂ in 1 L of tap water.[7] The critical aspect of ORS is that the optimal sodium concentration should be in the range of 90–120 mEq/L.[8] Most commercially available solutions have substantially less sodium. The use of solutions with less sodium may result in increased sodium loss. Therefore, patients should be strongly encouraged to avoid “plain” water consumption when they are thirsty and to substitute ORS. The need for ORS is not as critical for patients with colon in continuity as long as there is sufficient sodium in the diet because the colon readily absorbs the ion, even against a strong electrochemical gradient.[9] In addition, because ileal water absorption is unaffected by glucose, the glucose concentration of the ORS in patients whose jejunum has been resected has less importance.[10]

Significant quantities of magnesium are lost in jejunal and ileal effluent — thus, magnesium deficiency may occur. This deficiency often develops despite a normal serum concentration; therefore, a 24-hour urine magnesium measurement is often required.[11] Supplementation may be problematic because magnesium is a cathartic; parenteral supplementation may be required. Magnesium deficiency may also result in calcium deficiency because of impaired parathyroid hormone release. Patients with short bowel syndrome who do not receive TPN are generally in negative calcium balance,[12] and a supplement (800–1500 mg/day) should be prescribed.

Macronutrients and Dietary Therapy

Most patients will require TPN for the first 7–10 days following massive enterectomy. However, this therapy should not be introduced until the patient is hemodynamically stable and in appropriate fluid and electrolyte balance. Energy requirements are generally 25–35 kcal/kg/day, and protein (amino acid) requirements are 1.0–1.5 g/kg/day.[3] Neonates and young children have increased energy and protein requirements. Enteral nutrition therapy with polymeric formulas should be introduced gradually. There is limited, if any benefit, from the use of elemental or free amino acid-based formulas,[13–15] and animal investigations have suggested that use of such formulas may be associated with ileal atrophy.[16] Once the patient is able to eat, a regular diet should be prescribed, although patients with colon in continuity should be provided an oxalate-restricted diet to decrease the risk for development of calcium-oxalate nephrolithiasis.[17] Lactose should not be restricted except in the case of proximal jejunal resection.[18,19] Lactose-containing foods are a significant source for dietary calcium. There is no benefit derived from the separation of solid and liquid dietary contents.[20]

Double-blind, randomized, placebo-controlled studies have shown no role for glutamine supplementation in the enhancement of intestinal adaptation and improvement of fluid and/or nutrient absorption.[21–23] Glutamine, either with or without growth hormone, has not been shown to increase intestinal villus height or to improve energy, nitrogen, carbohydrate, fat, fluid, or electrolyte absorption.

Soluble, nonstarch polysaccharides and some starches are not normally digested in the intestine. As much as 65% of dietary carbohydrate will be malabsorbed in the patient with short bowel syndrome.[24] This unabsorbed carbohydrate and soluble fiber are fermented by colonic bacteria. Energy can be absorbed in the form of short-chain fatty acids (butyrate, acetate, and propionate), which are the preferred fuel of the colonocyte.[25] As such, the colon becomes an important organ for energy assimilation in patients with short bowel syndrome. An intact colon may absorb up to nearly 1200 kcal/day.[2,17,26] Patients should be encouraged to ingest diets rich in complex carbohydrate and soluble fiber if they have colon in continuity. However, it must be recognized that these diets may also provoke some degree of early satiety and may ultimately reduce overall food intake. It is important for patients to adjust to eating 2–3 times their caloric intake preenterectomy and to eat throughout the day rather than primarily in 3 distinct meals.

Patients with short bowel syndrome will have significant fat malabsorption because of decreased surface area as well as bile salt malabsorption. The latter is associated with decreased micelle formation and deficient fat digestion. However, cholestyramine should not be used in patients who have had > 100 cm of ileum resected because steatorrhea will worsen because of the binding of dietary lipid (as well as binding of fat-soluble vitamins).[27] Dietary fat restriction will decrease steatorrhea, but this must be weighed against the fact that lipid is an energy-dense substrate (9 kcal/g), and dietary fat restriction would thereby significantly reduce energy intake. Medium-chain triglycerides (MCTs) may be added to the diet for additional energy. Their use, however, is limited by their poor taste, induced nausea, and ketosis with excessive intake as well as by a low smoking point (ie, they cannot be used in cooking). Recipes are available from MCT manufacturers. MCTs do not require micelles for absorption and are absorbed directly into the portal circulation. In addition, there is some colonic absorption.[28] MCTs, however, do not provide the essential fatty acid, linoleic acid.

Micronutrient and Trace Metal Supplementation

Patients with short bowel syndrome will have decreased fat-soluble vitamin absorption and will often require relatively large doses of replacement therapy.[3,29] Vitamin A, D, and E status should be determined at regular intervals. In addition, vitamin K deficiency may occur in patients who do not have a colon because colonic bacteria synthesize 60% of daily vitamin K requirements.[30] Water-soluble vitamin deficiency is uncommon. Trace metals, such as zinc and selenium, are lost in fecal effluent; thus, deficiencies may develop.[31] Vitamin and trace metal status should be monitored at regular intervals, especially in patients who do not require TPN.

Pharmacologic Enhancement of Bowel Adaptation

GLP-II was administered in a small study[32] involving non-TPN-dependent patients and resulted in slightly increased jejunal villus height, energy, and fluid absorption. More recently, a synthetic analogue of GLP-II — teduglutide — was found to be associated with increased villus height and fluid absorption, both of which regressed once the medication was discontinued.[33]

Initial small studies with growth hormone in patients outside the adaptive period showed marginal, if any benefit, on fluid, electrolyte, or nutrient absorption.[21,22,34,35] However, a recent double-blind, randomized, controlled trial involving 41 patients with short bowel syndrome showed that the use of growth hormone could reduce TPN by approximately 2 L/week, in addition to the reduction achieved with standard therapy — this translated into a reduction of 1 night of infusion in patients who received growth hormone at 0.1 mg/kg/day for 4 weeks.[36] It is unclear whether these effects were related to improved absorption or to appetite stimulation. This study led to the US Food and Drug Administration (FDA) approval of growth-hormone injections for the treatment of TPN-dependent short bowel syndrome. The benefit associated with this therapy lasted nearly 4 months following completion of the 3 weeks of daily growth-hormone injections. It is also unclear whether “booster” injections will be required. The benefits of this therapy must be weighed against the potential side effects, which include fluid retention and edema, arthralgias, and carpal tunnel syndrome.

It is not known whether these therapies would be more effective if administered during the adaptive phase following enterectomy.

Home TPN

Patients who will require TPN at home should have their TPN cycled to infuse over 10–12 hours during the overnight period, with an additional 30–60 minutes for tapering off. This strategy permits the patient to be ambulatory, allows the patient to work, and improves overall quality of life. Cycling should be a gradual process (compress infusion time by 2–4 hours per day) to allow for an adaptive pancreatic response to the rapid rate of dextrose administration. Small ambulatory pumps that easily fit into a backpack along with the TPN solution are available for ambulatory infusion and travel. TPN and supplies can be shipped to hotels and cruise ships for vacation travels. Some individuals with high-output proximal ileostomies may require additional hydration fluid delivered, just before or after the TPN infusion and occasionally, during the day.

TPN should be infused via a single lumen catheter that is used only for TPN to reduce the risk of catheter-related infection.[3] Patients need to be instructed regarding proper catheter care/dressing changes and how to recognize signs of infection and other catheter-related complications. Patients should not be discharged home until their TPN formula and fluid requirements are stabilized and the home environment has been set up for home TPN.[3]

Short bowel syndrome and long-term TPN are associated with several potentially life-threatening complications. These include catheter-related infections (risk of 1 in every 2.7 years of catheter use with appropriate catheter care),[37] catheter and large vessel thrombosis,[38] gallstones,[39] liver disease,[40] metabolic bone disease,[41] nephropathy,[42] and memory deficits.[43]

Patients with short bowel syndrome, as well as other individuals who require long-term TPN, are complicated cases and are probably best managed by experienced centers specialized in the care of such patients.[44]

Surgical Management of Short Bowel Syndrome

Nontransplant Surgery

Residual colon should be reanastomosed to the residual small bowel to restore intestinal continuity as soon as the patient is stable for surgery. Surgical procedures to slow intestinal transit, including the creation of recirculating loops, reversed segments, longitudinal intestinal lengthening and tailoring (Bianchi procedure), colonic interposition between small-bowel segments, and insertion of intestinal valves, have been described in case reports or small-case series only.[3] Outcome has been less than desirable, and little long-term follow-up has been reported. However, patients with dilated segments of intestine may be candidates for intestinal-lengthening procedures designed to taper and lengthen the relatively nonfunctional segment.

Intestinal Transplantation

Combined intestine-liver transplantation is the only alternative for patients who have developed end-stage liver disease related to short bowel syndrome or long-term TPN therapy. Isolated intestinal transplantation may be considered for patients with significant liver disease that has not yet progressed to cirrhosis.[45] In rare cases, patients who have significant fluid losses and who have episodes of frequent, severe dehydration despite appropriate medical management may also be candidates for isolated intestinal transplantation. Medicare has now approved payment for intestinal transplantation for other indications, including 2 major vessel thromboses, a single episode of fungemia, a single episode of bacteria-related sepsis with shock, or 2 lifetime episodes of catheter-related sepsis. However, this author believes that the available evidence suggests that the decision to approve these indications was poorly conceived and was not evaluated on the basis of the evidence available or expert, nontransplant opinion.

Survival has improved considerably since intestinal transplantation was first initiated. As of 2001 (the most recent data available), 696 transplants had been performed worldwide in 651 patients; 335 are still alive — this included 291 isolated intestines, 310 intestine-liver transplants, and 95 multivisceral transplants. More-recent transplantations have superior survival as experience improves, and immunosuppressive regimens continue to be perfected. Mean hospitalization stay was 59.5 ± 56 days (range, 8–431 days) for isolated intestine, 81.8 ± 79 days (range, 17–827 days) for intestine-liver transplants, and 83.5 ± 56 days (range, 13–260 days) for multivisceral transplant recipients.

Current (2003) patient and graft survival data for the United States is shown in the Table 1.

Table 1.

Patient and Graft Survival for Isolated Intestine and Combined Liver-Intestine Transplantation in the United States (August 1, 2003; The Organ Procurement and Transplantation Network Scientific Registry of Transplant Recipients)

	1-Year Patient	1-Year Graft	3-Year Patient	3-Year Graft	5-Year Patient	5-Year Graft
Isolated intestine	79.1	71.8	73.1	43.6	47.4	33.3
Liver-intestine	60.0	56.1	39.1	39.2	38.6	37.3

It warrants mention that the mortality rate for patients waiting for an intestinal-liver transplant is significantly higher than for those waiting for an isolated liver transplant.[3] Therefore, early referral to an intestinal transplantation center at the first sign of liver disease is recommended, even if transplantation does not ultimately become necessary.

Financial issues must also be considered in managing patients with intestinal failure. Intestinal and multiorgan transplantation are expensive procedures, ranging between $250,000 and $3 million per case. Posttransplant complications include acute rejection, chronic rejection, cytomegalovirus infection, and posttransplant lymphoproliferative disease.[46] The cost of antirejection medications adds an additional $10,000 annually, in addition to rehospitalization for infection and rejection. However, for those patients who do well, nearly all are successfully weaned from TPN — although a few patients may require some maintenance intravenous fluids. This compares with a charge of $100,000–$150,000 per year for home TPN therapy in addition to the costs associated with yearly hospitalization for complications. However, the actual costs associated with TPN (including pharmacists' time) are closer to $18–$25/day.

Concluding Remarks

Patients with short bowel syndrome are the most complex of patients in gastroenterology. Proper management of these patients — to treat and to avoid disease and therapy-related complications in a cost-effective manner — requires knowledge of nutrient digestion, assimilation and metabolism, hepatology, nephrology, endocrinology, infectious diseases, psychiatric issues, social services, radiology, and surgery. Isolated intestine and multivisceral transplantation are the most rigorous surgeries performed today. Therefore, the care of such patients is best served in established tertiary care facilities with significant experience in the management of these individuals.