GASTROENTEROLOGY 2006;130:S5–S15
`
`Etiology and Initial Management of Short Bowel Syndrome
`
`ALAN L. BUCHMAN
`Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
`
`The normal human small intestine ranges between 3
`
`and 8 m in length, depending on whether measure-
`ment is made by radiologic or surgical techniques or at
`autopsy when the intestine may be desicated.1–5 Short
`bowel syndrome is defined in adults as ⬍200 cm of small
`intestine. Although usually acquired because of one or
`more enterectomies, short bowel syndrome may also be
`congenitally acquired. Nutrient, electrolyte, and fluid
`absorption is proportional to the amount of residual
`intestine. The degree of intestinal function is better
`described in terms of energy absorption/loss rather than
`length of residual intestine.6 Intestinal failure may be
`defined as the inability to sustain adequate nutritional,
`electrolyte, or hydrational status in the absence of spe-
`cialized nutritional support. This requires an increase in
`oral intake because absorption is compromised. Clini-
`cally, nutrient assimilation is a function of intake and
`absorption. As such, some patients with short bowel
`syndrome will not have sufficient loss of functional ca-
`pacity as to develop intestinal failure. Significant indi-
`vidual variability in jejunal absorption efficiency may be
`encountered.7
`The patients with the greatest risk for development of
`dehydration, generalized protein-calorie malnutrition,
`and multiple nutrient deficiencies are those with a duo-
`denostomy or jejunoileal anastomosis and ⬍35 cm of
`residual small intestine; jejunocolic or ileocoloic anasto-
`mosis, and ⬍60 cm of residual small intestine; or end
`jejunostomy with ⬍115 cm of residual small intes-
`tine.6,8 –11 Those patients with residual colon in continu-
`ity will have enhanced energy and fluid absorption.
`Hence, such patients can tolerate greater loss of small
`intestine and retain their nutritional autonomy.
`
`Incidence and Prevalence of Short
`Bowel Syndrome
`It is unclear how many individuals in the United
`States suffer from short bowel syndrome, but, based on
`the numbers in Europe, the incidence is probably ap-
`proximately 2 individuals per million.12 More recent
`data from 1993 indicated that the incidence and preva-
`lence of home parenteral nutrition, for which short bowel
`syndrome was the most prevalent indication, had in-
`
`creased slightly to 2 or 3 per year per million inhabitants
`and 4 per year per million, respectively.13,14 The most
`recent European survey, in 1997, indicated that the
`incidence of home total parenteral nutrition (TPN) had
`remained approximately 3 per million and that the prev-
`alence had increased to 4 per million.15 The largest single
`group of patients who received home TPN were those
`with short bowel syndrome (35%). In comparison, the
`most recent data for incidence and prevalence in the
`United States is from 1992. At that time, it was esti-
`mated based on extrapolated data from the Oley Foun-
`dation Home TPN Registry that approximately 40,000
`patients required TPN each year.16 Approximately 26%
`of the patients in the Oley Registry had short bowel
`syndrome, although some patients with a primary TPN
`indication of malignancy or radiation enteritis may have
`had short bowel syndrome as well. Patients with short
`bowel syndrome who did not require home TPN or were
`successfully weaned from home TPN are not reflected in
`these statistics. Approximately half of the short bowel
`patients who initially require TPN can be weaned off of
`TPN successfully in optimal settings.8 Therefore, the
`number of patients with short bowel syndrome may be
`substantially greater than previously estimated. A regis-
`try of short bowel patients, including those who require
`TPN permanently, transiently, and not at all, should be
`implemented.
`
`Etiology of Short Bowel Syndrome
`Short bowel syndrome may be a congenital or
`acquired condition. Infants may be born with congenital
`jejunal or ileal atresia. Otherwise, short bowel syndrome
`results from surgical resection of bowel. This is usually
`related to multiple resections for recurrent Crohn’s dis-
`ease, massive enterectomy made necessary because of a
`catastrophic vascular event such as mesenteric arterial
`embolism, venous thrombosis, volvulus, trauma, or tu-
`mor resection in adults, and, in children, gastroschisis,
`
`Abbreviations used in this paper: GLP, glucagon-like peptide; ORS,
`oral rehydration solution; TPN, total parenteral nutrition.
`© 2006 by the American Gastroenterological Association
`0016-5085/06/$32.00
`doi:10.1053/j.gastro.2005.07.063
`
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`S6 ALAN BUCHMAN
`
`GASTROENTEROLOGY Vol. 130, No. 2
`
`necrotizing enterocolitis (NEC), volvulus, and extensive
`aganglionosis. Functional short bowel syndrome may
`also occur in cases of severe malabsorption in which the
`bowel length is often intact. Such conditions may in-
`clude chronic intestinal pseudo-obstruction syndrome,
`refractory sprue, radiation enteritis, and congenital villus
`atrophy. Severe nutrient and fluid malabsorption occurs
`following extensive small intestinal resection. Patients
`with less than 100 cm of jejunum remaining generally
`have a net secretory response to food.17
`Patients can be grouped into 2 distinct subgroups:
`those with intact colon in continuity and those without
`colon in continuity. The colon becomes an important
`digestive organ in patients with short bowel syndrome.
`Sodium, water, and some amino acids are absorbed in the
`colon9,18 –20 as well as energy from absorbed short-chain
`fatty acids.
`
`Postresectional Adaptation
`The intestine adapts as well to ensure more effi-
`cient absorption per unit length. Following massive en-
`terectomy, the intestine hypertrophies, and nutrient ab-
`sorption becomes more efficient. Although there are
`limited human data, observations in patients with mas-
`sive enterectomy as well as in the functional short bowel
`patient (JI-bypass) indicate that the intestine lengthens
`some, but more importantly, diameter and villus height
`increase with a resultant increase in absorptive sur-
`face.21–24 This process may evolve over 1 or 2 years.6,9,25
`Patients may be taught to adapt to their decreased ab-
`sorption as well by dramatically increasing their food
`intake (hyperphagia).
`The presence or absence of the colon and ileocecal
`valve;
`location (jejunum versus ileum), health, and
`length of residual bowel; mucosal blood flow; patient
`age; and comorbid conditions such as Crohn’s disease,
`radiation enteritis, carcinoma, or pseudo-obstruction are
`important determinants in the functional adaptation pro-
`cess and clinical outcome.6,26,27 Although the length of
`remaining bowel necessary to prevent dependence on
`TPN is approximately 100 cm in the absence of an intact
`and functional colon, or 60 cm in the presence of a
`completely functional colon,6,9,28 the degree of adapta-
`tion and TPN dependence may be highly individualized.
`Adaptation to full enteral nutrition has been reported
`with as little as 10 cm of residual intestine in infants.25
`Patients with a jejunostomy are at increased risk for TPN
`dependence, and those with a jejunal-ileal anastomosis
`are less likely to be TPN dependent.
`Animal models have suggested that enteroglucagon,
`glucagon peptide II, epidermal growth factor, growth
`
`hormone, cholecystokinin, gastrin, insulin, and neuro-
`tensin are involved in postresection intestinal adapta-
`tion.29 There are little data on the role of either increased
`endogenous hormonal release or exogenous hormone sup-
`plementation during the intestinal adaptation phase in
`humans.
`Residual ileum is able to adapt and to assume the role
`of macronutrient absorption when jejunum has been
`resected. However, the specialized cells of the terminal
`ileum in which vitamin B-12/intrinsic factor receptors
`are located and in which bile salts are reabsorbed cannot
`be replaced by jejunal hypertrophy.
`
`Medical Therapy of Short Bowel
`Syndrome
`The goal of medical therapy is for the patient to
`resume work and a normal lifestyle, or as normal of one
`as possible. This is undertaken via the use of specific
`measures to decrease gradually the requirement for TPN
`and, at best, to eliminate its need. The most important
`aspects of the medical management of the patient with
`short bowel syndrome are to provide adequate nutrition,
`including both macro- and micronutrients, to prevent
`energy malnutrition and specific nutrient deficiencies, to
`provide sufficient fluid to prevent dehydration, and to
`correct and prevent acid-base disturbances. Most macro-
`nutrients, including carbohydrate, nitrogen, and fat, are
`absorbed within the first 100 cm and up to 150 cm of
`jejunum.30
`
`Macronutrient Assimilation and Dietary
`Therapy
`
`Typically, patients who have undergone massive
`enterectomy require TPN for the first 7–10 days. The
`immediate goals during this period are survival and
`hemodynamic stability. Nutritional therapy should not
`be introduced until the patient is hemodynamically sta-
`ble and fluid management issues are relatively stable.
`Patients should be provided approximately 25–35 kcal/
`kg/day and 1.0 –1.5 kg/day of protein. It remains con-
`troversial whether intake should be based on actual body
`weight or ideal body weight.31 Enteral nutrition should
`be started as soon as possible once hemodynamic stability
`has been achieved; standard enteral formula is recom-
`mended. Enteral nutrition should be instituted gradually
`as tolerated. Once patients are able to eat, they should be
`encouraged to eat a regular diet but modified as de-
`scribed below. Patients should also be encouraged to
`adapt their diet to eat substantially more than what was
`usual prior to their catastrophic event (hyperphagia).32
`Separation of liquids and solids has no effect on macro-
`
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`February Supplement 2006
`
`CHARACTERISTICS OF SHORT BOWEL SYNDROME S7
`
`nutrient, electrolyte, or mineral absorption or fecal vol-
`ume or fecal weight.19
`
`Proteins/Amino Acids
`
`Dietary protein is first digested by pancreatic,
`gastric, and intestinal proteases and then absorbed as di-
`and tripeptides. Therefore, it was reasoned that if dietary
`protein were provided in a predigested form, it would be
`more readily absorbed. However, absorption of nitroge-
`neous macronutrients (or proteins) is least affected by the
`decreased intestinal absorptive surface in patients with
`short bowel syndrome. Therefore, the utility of peptide-
`based diets in such patients is theoretically without
`merit.
`McIntyre et al fed 7 patients with an end-jejunostomy
`(60 –150 cm residual small bowel) a peptide-based or an
`essentially isocaloric and isonitrogenous polymeric for-
`mula. Energy, carbohydrate, nitrogen, fat, electrolyte,
`fluid, and mineral absorption and stool weight were
`similar regardless of the enteral formula provided.33 Un-
`controlled data from Levy et al support these findings.34
`A small study of 6 patients (90 –150 cm of residual
`jejunum and end-jejunostomy) reported by Cosnes et al,
`however, suggested that nitrogen absorption may be
`modestly improved with the use of a peptide-based diet,
`although similar to previous studies, energy, other ma-
`cronutrient, electrolyte, mineral, and fluid absorption
`were unaffected.35 These studies were all very small, the
`study populations somewhat heterogeneous, and the var-
`ious peptides used in the formulas differed significantly,
`as did the type and amount of fat (long-chain triglycer-
`ides vs medium-chain triglycerides). It is therefore dif-
`ficult to make definitive comparisons among studies.
`The amino acid glutamine, together with glucose, is
`the preferred fuel for the small intestinal enterocyte.36
`Rodent TPN models suggested that either parenteral or
`enteral glutamine supplements could effect more rapid
`and more significant bowel adaptation following massive
`enterectomy.37,38 Therefore, it was thought that glu-
`tamine supplementation in humans would have a similar
`effect. Although an early case series of 10 patients who
`were beyond the usual 1–2 year adaptation period sug-
`gested that glutamine, combined with growth hormone
`supplementation, and a high complex carbohydrate diet
`could result in decreased stool output and increased
`absorption of energy, protein, carbohydrate, sodium, and
`water,39 2 subsequent, double-blinded, randomized pla-
`cebo-controlled trials failed to confirm any of these ef-
`fects.40,41 In addition, Scolapio et al showed that glu-
`tamine and growth hormone supplementation did not
`lead to morphologic changes in the intestine.40 Glu-
`tamine-supplemented oral rehydration solution (see fluid
`
`and electrolyte management) was associated with de-
`creased Na absorption and a trend toward decreased fluid
`absorption in a small controlled trial in 6 patients.41 All
`of the patients studied by Byrne et al39 had colon in
`continuity; it is likely the treatment-associated increase
`in energy absorption was related solely to the increased
`complex carbohydrate diet as discussed above. Treatment
`with growth hormone and glutamine in the setting of
`short bowel syndrome has been associated with significantly
`increased extracellular fluid and peripheral edema.40,42,43
`A recent study reported by Seguy et al showed that
`low-dose growth hormone (0.05 mg/kg/day) was associ-
`ated with a modest increase in carbohydrate and nitrogen
`absorption.44 A recent randomized, placebo (glutamine)-
`controlled study indicated growth hormone administra-
`tion, when used outside the natural adaptation period,
`led to the ability to reduce parenteral fluid and nutrition
`requirements, although absorptive studies were not un-
`dertaken.45 Neither growth hormone nor glutamine have
`been studied in humans when used in the initial 1–2-
`year periadaptative period. Therefore, treatment with
`glutamine and/or growth hormone cannot be recom-
`mended at the present time. However, it may be that use
`of such exogenous growth factors may have their greatest
`utility if used during the normal adaptive period. There
`are no human studies to test this hypothesis.
`
`Lipid
`
`Lipid digestion may be impaired because of im-
`paired solubility because micelle formation will be im-
`paired when ileal bile salt malabsorption occurs in the
`setting of ileal resection (⬎100 cm).46 Treatment with
`ox bile supplements has been attempted in 3 patients in
`an attempt to increase duodenal bile salt concentration to
`stimulate micellar lipid solubilization.47– 49 This therapy
`has been associated with significantly increased fecal
`volume, at least in those patients with intact colon. A
`preliminary, open-labeled study of 4 patients (2 with
`colon in continuity) indicated that treatment with the
`conjugated bile acid cholylsarcosine (6 g/day) was asso-
`ciated with an increase in fat absorption of 17 ⫾ 3 g/day
`without any effect on stool wet weight.50 Cholylsarcosine
`is a conjugated bile acid and is resistant to colonic
`bacterial deconjugation. Another case series of 4 subjects
`had similar findings.51 However, 1 of the 4 patients
`experienced a significant increase in wet stool output,
`and nausea developed in another patient. Cholestyramine
`should not be used in patients with ⬎100 cm of ileal
`resection because it may actually worsen steatorrhea be-
`cause of the binding of dietary lipid.52
`Regardless of whether a high- or low-fat diet is used,
`the percentage of fat absorption remains stable, and stool
`
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`

`
`S8 ALAN BUCHMAN
`
`GASTROENTEROLOGY Vol. 130, No. 2
`
`weight is unaffected by the fat content of meals.53,54
`However, because of the energy density of fat (9.0 kcal/g)
`when compared with carbohydrate (4.0 kcal/g), it is an
`important dietary energy source. In addition, in short
`bowel syndrome patients, up to 65% of dietary carbo-
`hydrate may be malabsorbed and lost in the feces without
`degradation by colonic bacteria.32
`A mixed long-chain triglyceride:medium-chain tri-
`glyceride (LCT:MCT) diet was studied in 19 patients.
`Those patients with intact colon absorbed 96% ⫾ 3% of
`C8 fatty acids and 87% ⫾ 6% of C10 fatty acids, and
`those patients without colon absorbed 63% ⫾ 25% of
`C8 and 57% ⫾ 28% of C10, (P ⫽ .007 for C8 and P ⫽
`.004 for C10).55 MCT contains 8.3 kcal/g. Energy absorp-
`tion (approximately 2.1 MJ/day; 500 kcal/day) was sig-
`nificantly increased in patients with colon, although the
`LCT:MCT diet did not result in increased energy absorp-
`tion when compared with the LCT-based diet in patients
`with an end-jejunostomy or ileostomy. These patient also
`had increased fecal output with a mixed LCT:MCT diet.
`Some, but not all LCT, can be replaced by MCT in the
`diet because the essential fatty acid linoleic acid is a
`constituent of LCT and is not found in MCT. Excessive
`MCT intake may result in nausea, vomiting, and ketosis.
`In a short bowel patient eating 10.5 MJ/day (2500
`kcal/day), approximately 1.5–3 MJ/day (360 –720 kcal/
`day; 40 – 80 g) of LCT can be replaced with MCT.
`
`Carbohydrates
`
`The proximal jejunum rarely requires resection in
`patients that undergo massive enterectomy. Most intes-
`tinal dissacharidases are present in highest concentration
`in the very proximal small intestine, and, hence, patients
`with more distal resection are not likely to benefit from
`a lactose-free diet. In a study of 14 short bowel patients,
`a lactose-free diet was compared with a diet containing
`20 g/day of lactose (still with ⬍4 g milk).56 Lactose
`absorption, breath hydrogen, subjective symptoms of
`flatulence, and diarrhea were similar regardless of the
`diet. These data confirmed the findings of an earlier
`controlled study in 17 short bowel patients, which found
`that lactose absorption was enhanced when provided in
`yogurt rather than via milk.57 Regardless, in the absence
`of significant jejunal resection, patients with short bowel
`syndrome should not be provided lactose-restricted diets.
`Such diets are also generally low in calcium. Even pa-
`tients with an end-jejunostomy will generally tolerate a
`glass of milk (20 –25 g lactose).57
`
`The Role of the Complex Carbohydrate Diet
`
`and some
`Soluble nonstarch polysaccharides
`starches58 are not generally absorbed by the small intes-
`
`tine. Soluble fiber dissolves in water and is found pri-
`marily in oatmeal, oat bran, psyllium (Metamucil, Proc-
`tor & Gamble, Cincinatti, OH; Konsyl, Konsyl
`Pharmaceuticals, Easton, MD), barley, artichokes, straw-
`berries, legumes, prunes, grapefruit, and squash in de-
`scending order of concentration. Soluble fiber and
`starches pass undigested into the colon in which they are
`fermented by enteric bacteria into hydrogen and methane
`(hence patient “gas” complaints) but also into short-
`chain fatty acids (SCFAs), including butyrate, proprion-
`ate, and acetate. SCFAs are the preferred fuel for colono-
`cytes.59 Therefore, the colon becomes a digestive organ in
`patients with short bowel syndrome. Approximately 75
`mmol SCFA are produced from 10 g unabsorbed carbo-
`hydrate.60 Patients with short bowel syndrome but intact
`colon in continuity were able to decrease fecal energy loss
`by 1.3–3.1 MJ/day (310 –740 kcal) when they were fed
`a diet consisting of 60% carbohydrates.61 Colonic me-
`tabolism of unabsorbed carbohydrate was indicated by
`decreased fecal carbohydrate losses in the patients with
`colon in continuity. The intact colon may absorb up to
`2.2– 4.9 MJ (525–1170 kcal) of energy daily from di-
`etary fiber.9,10,61 Colonic energy absorption may also
`increase some during the postresection adaptation phase,
`related to increased colonic bacterial carbohydrate fer-
`mentation.11,62 The increased fermentation may result
`from increased colonic bacteria and/or an increase in the
`concentration or activity of various enzymes including
`␤-galactosidase during the adaptation period.62 Because
`SCFAs stimulate sodium and water absorption,63 pa-
`tients might be expected to have decreased fecal fluid and
`sodium loss as adaptation progresses, although this has
`not been observed clinically.61
`
`Vitamins
`
`Micronutrients often require supplementation. It
`is unusual for water-soluble vitamin deficiencies to de-
`velop in short bowel patients in the absence of TPN
`(except in those who have proximal jejunostomies or
`duodenostomies) because these are absorbed in the prox-
`imal jejunum. Thiamine deficiency has been described,
`especially during a recent parenteral vitamin shortage.64
`Patients may present with Wernicke’s encephalopathy,
`beriberi, and severe metabolic alkalosis.65 Whole blood
`thiamine concentration may not be indicative of defi-
`ciency as it reflects recent nutritional intake. Erythrocyte
`transketolase activity should be measured and empiric
`therapy begun with 100 mg parenteral thiamine daily.
`Biotin deficiency has rarely been reported in patients
`with short bowel syndrome.66 Scaly dermatitis, alopecia,
`lethargy, hypotonia, and lactic acidosis have been de-
`scribed. Therapy consists of parenteral biotin supplemen-
`
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`February Supplement 2006
`
`CHARACTERISTICS OF SHORT BOWEL SYNDROME S9
`
`tation of 0.3–1 mg daily, although this is not commer-
`cially available in the United States. Vitamin B-12
`supplementation is required (300 ␮g/month subcutane-
`ously) in patients who have had a ⬎60-cm terminal
`ileum resected.67 Folic acid is provided as a constituent of
`most oral and parenteral multivitamins. Folate deficiency
`may develop in patients with proximal jejunal resec-
`tions.68 These patients should receive 1 mg folate daily.
`Fat-soluble vitamin deficiency (A, D, and E) is more
`common in patients with short bowel syndrome because
`of fat maldigestion related to decreased bile salt reab-
`sorption and decreased micelle formation.69 Cholestyra-
`mine may cause fat-soluble vitamin deficiency because of
`its binding of bile salts.70 Night blindness and xeroph-
`thalmia have been described in short bowel syndrome.71
`If not recognized, vitamin A deficiency may progress to
`corneal ulceration and later permanent visual loss may
`develop. The serum vitamin A concentration should be
`monitored in patients who do not require parenteral
`vitamin supplementation. If a low serum vitamin A
`concentration is detected, therapy should be started with
`10,000 –50,000 units daily, administered either orally or
`parenterally.
`Vitamin D deficiency manifests in osteomalacia. Usu-
`ally, dietary intake is a relatively unimportant source of
`vitamin D because the majority is endogenously synthe-
`sized from 7-dehydrocholesterol via ultraviolet light.72,73
`However, because enterohepatic circulation is disrupted
`in patients who have undergone significant ileal resec-
`tions, deficiency may result.74
`Vitamin E deficiency may manifest in hemolysis75 and
`various neurologic deficits.76 Because serum vitamin E
`concentration reflects serum total lipid concentration,
`which may be low in short bowel patients who have
`steatorrhea, low serum vitamin E concentration alone
`may not be indicative of a deficient state; the serum
`vitamin E:total lipid ratio should be calculated.77,78
`Most vitamin K is synthesized by colonic bacteria
`(60%),79 although dietary intake accounts for approxi-
`mately 40% of requirements; deficiency is therefore un-
`common in patients with intact colon. However, vitamin
`K deficiency is frequent in patients who have no residual
`colon or who have taken broad-spectrum antibiotics re-
`cently. The requirement is approximately 1 mg daily.79
`Vitamin K was not a constituent in adult multivitamins
`for TPN until recently, although it has in children.
`
`Trace Metals
`
`Significant amounts of zinc and selenium are lost
`with diarrhea. A significant amount of zinc is also lost in
`small bowel effluent (12 mg/L small intestinal fluid and
`16 mg/L stool).80 Zinc deficiency has been associated
`
`with growth abnormalities,81 delayed wound healing,82
`and cellular immunity dysfunction.83 Patients in whom
`zinc deficiency is suspected should be treated empirically
`with oral zinc sulfate (220 – 440 mg daily) or parenteral
`zinc supplements if they require TPN. Serum and leu-
`kocyte measurements of zinc concentration, although
`helpful, may be unreliable.84 Selenium deficiency has
`been associated with cardiomyopathy85; peripheral neu-
`ropathy, proximal muscle weakness, and pain86; whiten-
`ing of the hair; and macrocytosis.87 Serum selenium is a
`reliable indicator of selenium status, and, if low, oral or
`parenteral supplementation should be provided. Al-
`though there are 3 reported possible cases of chromium
`deficiency in patients requiring long-term TPN,88 defi-
`ciency has not been reported in short bowel patients who
`do not require TPN, and, therefore, routine supplemen-
`tation is not recommended. Chromium is a necessary
`cofactor for insulin’s effects in peripheral tissue.89 How-
`ever, available evidence suggests that there is sufficient
`chromium present in the TPN solutions as a contami-
`nant, and supplemental chromium may result in the
`possibility of nephrotoxicity.90 Copper deficiency is very
`rare in the patient with short bowel syndrome. Defi-
`ciency may result in microcytic anemia, neuropathy, and
`decreased fertility.91
`
`Medication Absorption
`
`Medication absorption is often impaired, just as is
`nutrient absorption in patients with short bowel syn-
`drome, although significant interpatient variability may
`be observed. The oral or enteral route for medication
`delivery should be used whenever possible to avoid ad-
`ditional manipulations of the TPN catheter, which are
`associated with increased infection risk. The degree to
`which a medication is malabsorbed is dependent on the
`residual small bowel surface area and its health (for
`example, whether or not active Crohn’s disease is present)
`and morphologic and physiologic factors, including the
`presence or absence of the terminal ileum (especially
`important for vitamin B-12 and bile salt absorption,
`which are necessary for the absorption of lipid-soluble
`medications such as cyclosporin) or the presence of an
`acidic or alkaline environment (which may be caused by
`the use of H2 blockers in TPN or proton pump inhibi-
`tors). Many, but not all, medications are absorbed in the
`jejunum. Therefore, absorption will be minimally im-
`pacted for most medications in the absence of decreased
`intestinal transit time, which will decrease mucosal con-
`tact time. Most of the available data on oral medication
`absorption in patients with short bowel syndrome are in
`the form of isolated case reports.92 The sublingual route
`
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`GASTROENTEROLOGY Vol. 130, No. 2
`
`for medication delivery may be preferable for some med-
`ications.
`
`Fluid and Electrolyte Management
`
`Massive enterectomy is associated with transient
`gastric hypersecretion and hypergastrinemia, generally
`lasting for up to 6 months following resection.93,94 H2-
`antagonists and proton pump inhibitors are useful to
`reduce gastric fluid secretion and, therefore, also reduce
`fluid losses during this period.17,95–97 However, because
`absorption of orally dosed medications may be impaired,
`either large doses or intravenous delivery may be re-
`quired. Although fluid losses are decreased, macronutri-
`ent and electrolyte absorption are not affected by the
`increased gastric secretion. Reduction of gastric acid
`output is also important to help prevent the deconjuga-
`tion of bile acids in the duodenum and decreased pan-
`creatic lipase excretion to enhance fat digestion.
`Fluid losses usually require chronic control with anti-
`motility agents such as loperamide hydrochloride or
`diphenoxylate. Typical doses are 4 –16 mg/day. If these
`are ineffective, especially in patients with no colon in
`continuity or those who have a minimum of residual
`jejunum or duodenum, codeine sulfate or tincture of
`opium may be necessary. The usual dose for codeine is
`15– 60 mg, 2 or 3 times daily. Rarely, patients will
`require treatment with octreotide. Octreotide’s mecha-
`nism of action is unclear, but it may be useful to slow
`intestinal transit time, which will increase water and
`sodium absorption.98,99 Daily jejunostomy volume was
`reduced from 8.1 ⫾ 1.8 to 4.8 ⫾ 0.7 L/day using a dose
`of 100 ␮g, subcutaneous, 3 times daily, of octreotide 30
`minutes before meals in one open-labeled study of 9
`patients with end-jejuonstomies.100 However, octreotide
`use does not result in TPN discontinuation, and it
`reduces splanchnic protein synthesis, thereby reducing
`mucosal protein incorporation and villus growth rate.
`Therefore postresectional intestinal adaptation may be
`impaired.101 A recent small study with the long-acting
`derivative of octreotide showed no measurable benefit.102
`Octreotide also increases the risk for cholelithiasis103 in a
`patient group already predisposed.104 It should therefore
`be reserved for patients with high-output jejunostomies
`in whom fluid and electrolyte management has proven
`difficult otherwise.
`rehydration solutions
`Glucose-polymer-based oral
`should be used to improve hydration and to decrease
`TPN fluid requirements in patients with residual jeju-
`num ending in a jejunostomy. Patients with ⬍100 cm of
`residual jejunum have significant risk for dehydration
`because they secrete more sodium (Na) and fluid than
`they orally consume.95 Because the jejunum is permeable
`
`to Na and chloride (Cl), passively absorbed solutions
`with high NaCl concentration are readily absorbed. Glu-
`cose promotes salt and water absorption by solvent drag
`and via stimulation of sodium-linked transport.105 How-
`ever, although Na and water are absorbed from hypo-
`tonic isotonic solutions delivered into the jejunum, ab-
`sorption is superior with more hypertonic fluids.106
`Therefore, hypotonic oral rehydration solutions may be
`of benefit in patients with an intact gastrointestinal tract
`and acute infectious diarrhea but may not be of use in the
`short bowel patients. Ingestion of hypotonic fluids may
`be associated with increased Na loss.107–109 Several com-
`mercially available oral rehydration solution (ORS) for-
`mulas are available, although probably the best, and
`certainly the least expensive, is that recommended by the
`World Health Organization (WHO).110 This can be
`formulated by dissolving the following in 1 liter of tap
`water: NaCl (2.5 g), KCl (1.5 g), Na2CO2 (2.5 g), and
`glucose (table sugar, 20 g). Only the KCl requires a
`physician prescription. Most, if not all, of the commer-
`cially available ORS have substantially less sodium (in
`the range of 45–50 mmol/l). Less NaCl may be added,
`but the optimal Na concentration should be at least
`90 –100 mmol/L, which is the usual concentration of
`small bowel effluent.20 Solutions with lower sodium
`concentrations result in increased sodium losses. There-
`fore, patients with short bowel syndrome should be
`cautioned against consumption of plain water and should
`be encouraged to drink ORS whenever they are thirsty.
`More recent evidence has shown that hypotonic (160
`mosm/kg) ORS leads to decreased intraluminal duode-
`nojejunal fluid flow rate in normal volunteers, although
`the effect on gastrointestinal fluid losses or fluid status in
`patients with short bowel has not been evaluated.111
`ORS may still be useful even in patients with residual
`colon in continuity, but, provided sufficient sodium is
`present in the diet, the amount of Na in the ORS may
`not be as critical because the colon readily absorbs Na
`and water against a steep electrochemical gradient.112
`The presence of glucose in the ORS is not critical in
`patients with no remaining jejunum, but who have re-
`sidual ileum, because ileal water absorption is not af-
`fected by the presence of glucose.113
`In addition to Na losses, significant quantities of
`magnesium (Mg) are lost in jejunal or ileal effluent.74
`Given that magnesium deficiency may develop despite a
`normal serum magnesium concentration, it is prudent to
`measure 24-hour urine Mg loss.114 The median 24-hour
`urine Mg in normal volunteers in one study was 127 mg
`(vs 19 mg for magnesium deficient short bowel pa-
`tients).74
`
`Page 6
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`

`
`February Supplement 2006
`
`CHARACTERISTICS OF SHORT BOWEL SYNDROME S11
`
`Mg deficiency may cause calcium (Ca) deficiency be-
`cause hypomagnesemia impairs parathyroid hormone re-
`lease.115 In addition, the majority of patients with short
`bowel syndrome who do not require TPN are in negative
`Ca balance.116 Therefore, in the absence of TPN, oral Ca
`supplementation is recommended routinely (800 –1200
`mg/day). Mg replacement is problematic. Attempts with
`oral MgO or oral consumption of injectable Mg are
`generally not successful and have been associated with
`increased fecal loss because of their cathartic effect.117
`Although Mg gluconate is water soluble, Mg has not
`generally been a constituent of ORS. Therefore, some
`patients may require periodic parenteral Mg infusion
`despite the absence of a TPN or intravenous fluid re-
`quirement otherwise. Iron is absorbed in the duodenum
`and, therefore, in the absence of hemorrhage, is not
`routinely required as a supplement. Phosphorous defi-
`ciency is not well described in short bowel syndrome,
`and, therefore, supplementation is rarely, if ever, re-
`quired.
`
`Ph