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`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease
`Management. Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005)
` Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
` Nutritional Issues in the Short Bowel
`Syndrome – Total Parenteral Nutrition,
`Enteral Nutrition and the Role of
`Transplantation
`
` Stephen J.D. O’Keefe
` Division of Gastroenterology, University of Pittsburgh, Pittsburgh, PA , USA
`
`
` Abstract
` In this review, I focus on the extreme of the short bowel syndrome where the loss of in-
`testine is so great that patients cannot survive without intravenous feeding. This condi-
`tion is termed short bowel intestinal failure. The review outlines the principles behind
`diagnosis, assessing prognosis and management. The advent of intravenous feeding (par-
`enteral nutrition) in the 1970s enabled patients with massive (>90%) bowel resection to
`survive for the first time and to be rehabilitated back into normal life. To achieve this,
`central venous catheters were inserted preferably into the superior vena cava and intra-
`venous infusions were given overnight so that the catheter could be sealed by day in
`order to maximize ambulation and social integration. However, quality of life has suffered
`by the association of serious complications related to permanent catheterization – most-
`ly in the form of septicemias, thrombosis, metabolic intolerance and liver failure – from
`the unphysiological route of nutrient delivery. This has led to intense research into restor-
`ing gut function. In addition to dietary modifications and therapeutic suppression of mo-
`tility, novel approaches have been aimed at enhancing the natural adaptation process,
`first with recombinant growth hormone and more recently with gut-specific glucagon-
`like peptide-2 analogues, e.g. teduglutide. These approaches have met with some suc-
`cess, reducing the intravenous caloric needs by approximately 500 kcal/day. In controlled
`clinical trials, teduglutide has been shown to permit >20% reductions in intravenous re-
`quirements in over 60% of patients after 6 months of treatment. Some patients have been
`weaned, but more have been able to drop infusion days. The only approach that
`
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` predictably can get patients with massive intestinal loss completely off parenteral nutri-
`tion is small bowel transplantation, which, if successful (1-year survival for graft and host
`>90%) is accompanied by dramatic improvements in quality of life.
` © 2015 Nestec Ltd., Vevey/S. Karger AG, Basel
`
` Introduction
`
` It should be noted that the severity of the short bowel syndrome (SBS) varies
`from mild to severe, and that the degree of severity is directly related to the loss
`of absorption capacity. For example, the management of mild disease is easy and
`based on increased oral supplementation to overcome the reduced efficiency of
`absorption, for example oral B 12 supplementation in patients with ileal resec-
`tion, whilst the management of severe disease includes intravenous supplemen-
`tation of water, electrolytes and nutrients.
`
` Definition of Severe Short Bowel Syndrome or Short Bowel Syndrome and
`Intestinal Failure
`
` SBS and intestinal failure (SB-IF) is the most severe form of the syndrome and
`can only be managed with long-term use of intravenous nutrition, i.e. home
`(HPN) or total parenteral nutrition (TPN). It is this condition that we will focus
`on in this article. It has been defined as a condition that results from surgical
`resection, congenital defects or disease-associated loss of absorption, and is
`characterized by the inability to maintain protein energy when on a convention-
`ally accepted normal diet [1] .
`
` Prediction of Short Bowel Syndrome and Intestinal Failure
`
` Studies performed by Messing et al. [2] in France have indicated that patients
`with massive intestinal resection or loss can be categorized into those who are
`likely to become permanently dependent on parenteral nutrition (PN) and those
`who are not. Measurements suggest that patients with <80 cm of small intestine
`plus colon are likely to become independent of parenteral support (PS). How-
`ever, those who have lost their colons as well, i.e. those with end-jejunostomies,
`will likely need >200 cm of small intestine to remain independent of PS. Of
`course, this assumes that the remaining small intestine is functionally normal. If
`it is diseased, as in Crohn’s disease, then greater lengths of small intestine will be
`required.
`
`76
`
` O’Keefe
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
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` Clinical Determination of Short Bowel and Intestinal Failure
`
` The best practical way of assessing whether a patient has SB-IF is to measure
` 24-hour urine output volumes plus sodium content when they are off all intra-
`venous infusions and eating normally. If the 24-hour urine volume is greater
`than 1 liter and if urinary sodium is greater than 20 mEq/day, then it is not pres-
`ent. These measurements are also very useful in gauging intravenous fluid and
`electrolyte requirements in patients requiring TPN or HPN.
`
` Adaptation
`
` The remarkable thing about the intestine is its ability to adapt to the loss of
`length. Consequently, it is important to reassess absorption in the months fol-
`lowing intestinal loss to reassess PS requirements. Some patients might well be-
`come independent of intravenous infusions in the 2 years following resection.
`The process of adaptation begins almost immediately following resection or loss,
`and can continue for over 2 years [3, 4] . Adaptation is characterized by villous
`hyperplasia, which increases the absorptive surface 200-fold. In the days before
`the advent of intravenous feeding, this process allowed some patients to survive
`with only 15 cm of small intestine [5] . Villous hyperplasia is far more evident in
`studies in experimental animals than in humans. The hyperplasia is associated
`with increased digestive enzyme secretion, muscular hypertrophy, delayed food
`transit through changes in motility and increased blood flow. The net result is
`increased absorption. These features are illustrated in figure 1 . Probably the
`driving force for adaptation is the increased contact between food and the re-
`maining mucosa resulting from the associated hyperphagia. Studies have shown
`that adapted patients usually consume 1.5–2.0 times the recommended dietary
`allowance for protein and calories [6] . Studies of ours have revealed that food-
`induced pancreatic secretion is also twice normal ( fig. 2 ) [6, 7] .
`
` General Principles of Management
`
` (1) It must be remembered that most food digestion occurs in the jejunum
`and proximal jejunum. Consequently, digestion is rarely a problem and there is
`no indication for pancreatic enzyme supplementation to improve absorption in
`SB-IF patients.
` (2) The reason why we have an extraordinary long small intestine is to allow
`for the reabsorption of the massive quantities of fluid (>7 liters/day) and elec-
`
` Nutritional Issues in the Short Bowel Syndrome
`
`77
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
`Page 3
`
`

`
`Normal
`
`Adapted
`
`Nutrient layer
`Motility
`
`Villi
`
`Blood flow
`
`Nutrient layer
`Motility
`
`Villi
`
`Blood flow
`
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` Fig. 1. Key factors in
`intestinal adaptation.
`
`trolytes that are secreted by the upper gastrointestinal tract to ensure optimal
`enzymatic digestion. Consequently, fluid and electrolyte depletion is the earliest
`event in SBS.
` (3) As mentioned above, digestive function and absorption improves with
`time because of adaptation, but absorptive capacity must be rechecked over the
`course of time to reassess basic needs.
` (4) As mentioned above, digestion is not the problem, transit is. Consequent-
`ly, it is important to tailor management to keep food in contact with the remain-
`ing intestinal surface for as long as possible.
`
` Practical Management
`
` (1) Avoid dietary restriction [8] . Remember hyperphagia is part of the adap-
`tation response.
` (2) Prolong nutrient-mucosa contact time. Break down normal meals into
`small frequent meals, supplement with nutrient-dense liquids and use drugs to
`reduce motility. Patients need to understand that they have to change the way
`they eat; they must train themselves to ‘nibble like rabbits’. This reduces the load
`on the remaining intestine and ensures a longer contact time between food and
`the absorptive mucosa. The most effective way is to provide continuous slow
`enteral feeding. This was beautifully illustrated by Joly et al. [9] in their random-
`
`78
`
` O’Keefe
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
`Page 4
`
`

`
`Net absorbtion for total calories, lipids,
`and proteins during the 3 study periods
`*
`
`**
`
`**
`
`ETF
`
`OF
`
`OCEF
`
`*
`
`**
`
`**
`
`ETF
`
`OF
`
`OCEF
`
`*
`
`**
`
`**
`
`ETF
`
`OF
`
`OCEF
`
`4,000
`
`3,000
`
`2,000
`
`1,000
`
`0
`
`–1,000
`
`Energy (kcal/day)
`
`a
`
`150
`
`100
`
`50
`
`0
`
`–50
`
`–100
`
`Lipids (g/day)
`
`b
`
`150
`
`100
`
`50
`
`0
`
`–50
`
`Proteins (g/day)
`
`c
`
` Fig. 2. A randomized
`crossover study compared
`absorption between
`isocaloric tube feeding
`and OF in 15 SBS patients
`>3 months after short
`bowel constitution. An OF
`period combined with
`enriched (1,000 kcal/day)
`tube feeding was also
`tested. Means ± SD. Net
`absorption for total
`calories ( a ), lipids ( b ) and
`proteins ( c ) during the 3
`study periods. In the
` histograms , intakes (light
`grey) and losses (in black)
`are above and below the
`zero line, respectively, the
`dark grey being the net
`absorption (intake losses).
`Total caloric, lipid and
`protein intakes (light grey
`bars) were significantly
`higher with OF combined
`with tube feeding (OCEF)
`than with OF and enteral
`
`tube feeding (ETF; *  p =
`with OF ( * *  p 0.001) with
`
`0 . 001). Net absorption for
`total calories, lipids and
`proteins (dark grey bars)
`was significantly higher
`with ETF and OCEF than
`
`permission [9].
`
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`ized crossover study of 15 SBS patients; they compared absorption between iso-
`caloric tube feeding and oral feeding (OF), and then a combination of OF and
`1,000 kcal/day tube feeding. Figure 2 shows that absorption of calories, lipids
`and protein was significantly higher with exclusive enteral tube feeding than OF.
`The combination enhanced absorption further, illustrating the importance of
`hyperphagia in maximizing absorption in SB-IF patients.
`
` Nutritional Issues in the Short Bowel Syndrome
`
`79
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
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` (3) Opiates are the most effective antimotility agents to use in this situation
`to increase nutrient-mucosa contact time. However, it is best to avoid opiates in
`the long term and use their derivatives such as Imodium, which have little cen-
`tral side effects. Imodium should be given in much higher quantities, i.e. up to
`16 mg 6 hourly, than recommended for people with normal intestines because
`of the reduced absorption of medications and high therapeutic index.
` (4) Studies have shown that with adaptation, colonic bacterial fermentation
`increases dramatically and can result in a net salvage of up to 1,000 kcal/day in
`the form of short-chain fatty acids [10] . Consequently, in order to maximize ab-
`sorption, patients with SB-IF with colons should be given diets enriched with
`complex carbohydrates.
` (5) Previously, patients with SB-IF were encouraged to limit the amount of
`fat they consumed in order to reduce steatorrhea. However, when formally test-
`ed, it was shown that the amounts of calories absorbed were higher when pa-
`tients consumed a high-fat diet despite the fact that stool fat also increased [11,
`12] .
` (6) One of the key principles of SB-IF management is to restrict water con-
`sumption. The reason for this is that the mucosa of the duodenum and jejunum
`is freely permeable to fluid and electrolytes and cannot maintain a concentration
`gradient. Thus, in patients with end jejunostomies, the consumption of water
`will draw electrolytes accompanied by water from the body and exacerbate de-
`hydration and electrolyte deficiencies. In order to prevent this, the use of WHO-
`type solutions is encouraged. With these solutions, salt and glucose are actively
`taken up across the mucosa by specific transport mechanisms into the body ac-
`companied by water. Thus, it is always important to encourage patients to take
`fluids containing sugar and salt in the ratios suggested by the study by Lennard-
`Jones [13] shown in figure 3 . The problem is that patients are tired of drinking
`these solutions. A pragmatic alternative is to use flavored sport drinks, such as
`Gatorade. Blenderized soups are also very useful if they contain salt and a car-
`bohydrate source such as pasta, rice or potato.
` (7) Another approach is the suppression of secretion. The use of acid sup-
`pressants such as H 2 antagonists or proton pump inhibitors is encouraged early
`following intestinal loss when gastric secretion is increased. Long-term use is,
`however, contraindicated as acid secretion decreases with time and complete
`suppression will lead to bacterial overgrowth in the remnant intestine and exac-
`erbation of fluid and electrolyte losses [6, 7] . The most dramatic therapeutic ap-
`proach to the suppression of secretion is to use octreotide. In a study of 8 well-
`adapted patients with severe SB-IF, we were able to show that injections of oc-
`treotide 50 μg t.i.d. resulted in 50% reductions in stomal fluid and electrolyte
`losses [6, 7] ( fig. 4 ). Interestingly, while fat absorption was not affected, there was
`
`80
`
` O’Keefe
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
`Page 6
`
`

`
`Oral rehydration solutions
`
`20
`
`10
`
`0
`
`Sodium balance (mmol)
`
`–10
`Sodium (mmol/l)
`Glucose (mmol/l)
`
`60
`165
`
`90
`110
`
`120
`55
`
`150
`0
`
` Fig. 3. The physiological basis for WHO rehydration fluids. Sodium balance is only
`achieved when luminal concentrations exceed 70 mmol/l with glucose concentrations of
`140 mmol/l (Lennard-Jones [13] ).
`
`Daily stomal output rates
`Effect of octreotide
`
`Volume, l
`Fat, g
`Nitrogen, g
`Sodium, mEq
`Potassium, mEq
`Chloride, mEq
`
`Before
`12.3±8.7
`67±39
`23±8
`605±301
`148±92
`614±273
`
`After
`5.8±2.1*
`64±48
`15±7*
`316±109*
`92±28*
`363±109*
`
` Fig. 4. The effect of
`octreotide, a long-acting
`somatostatin analogue, on
`end-jejunostomy losses in
`hyperphagic SB-IF patients
`[7].
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`a significant increase in nitrogen reabsorption, presumably because of the abil-
`ity of the drug to reduce motility thereby increasing food-mucosa contact time.
` We performed studies in this group of patients to examine the effects of oc-
`treotide on mucosal growth ( fig. 5 ), using primed continuous 8-hour intrave-
`nous infusions of isotope-labeled leucine [7] . The results showed that despite the
`beneficial effects of the drug, i.e. decreased fluid and electrolyte secretory losses,
`it had negative effects on mucosal protein synthesis and villous growth, thus
`countering the physiological adaptation process. Consequently, we only recom-
`mend short courses of octreotide to control extremely high secretory stomal
`losses before adaptation has had time to establish itself.
`
` Nutritional Issues in the Short Bowel Syndrome
`
`81
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
`Page 7
`
`

`
`200
`
`100
`
`Villous growth (μm/day)
`
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`0
`
`Baseline
`
`After octreotide
`
` Fig. 5. Octreotide inhibits mucosal protein synthesis and may have anti-adaptational
`properties [7] .
`
` (8) Another approach is to increase adaptation. Much attention has recently
`been devoted to developing gut hormonal approaches enhancing the natural ad-
`aptation process. The first hormone to be used was recombinant growth hormone.
`Several studies (initially uncontrolled, later controlled) showed that injections of
`recombinant growth hormone increased electrolyte and energy absorption in SB-
`IF patients. Perhaps the best of these is the one reported by Seguy et al. [14] ( fig. 6 ).
`Despite using lower and more physiological doses, their results were very positive,
`with significant increases in energy, nitrogen, carbohydrate and D -xylose absorp-
`tion. However, in its marketed form, Zorptive, the drug has been little used in
`clinical practice primarily because it can only be used during a short time frame
`and because of its high side effect profile. A Cochrane review [15] of all the con-
`trolled trials came up with the following conclusion: ‘The results suggest a positive
`effect of human growth hormone on weight gain and energy absorption. However,
`in the majority of trials, the effects are short-lived returning to baseline shortly after
`cessation of therapy. The temporary benefit calls into question the clinical utility
`of this treatment. To date, the evidence is inconclusive to recommend this therapy’.
` Perhaps the most exciting recent developments in the therapeutic manage-
`ment of SB-IF is the protease-resistant form of glucagon-like peptide GLP-2.
`GLP-2 is secreted by L-cells in the distal bowel. Many of their properties are
`those seen in natural adaptation. For example, the peptide slows gastric empty-
`ing, reduces gastric secretion, increases mucosal blood flow, stimulates the
`growth of small and large intestine, increases epithelial proliferation and reduc-
`
`82
`
` O’Keefe
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
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`after ingestion (mmol(cid:135)l–1)
`D-Xylose serum level 2 h
`
`2.0
`
`1.5
`
`1.0
`
`0.5
`
`0
`
`***
`
`X
`
`X
`
`Placebo
`
`HGH
`
`**
`
`X
`
`X
`
`*
`
`X
`
`X
`
`**
`
`X
`
`X
`
`X
`
`X
`
`Energy
`
`Nitrogen Carbohydrates
`
`Fat
`
`D-Xylose
`
`160
`
`80
`
`60
`
`40
`
`20
`
`0
`
`–20
`
`–40
`
`Net intestinal absorption (%)
`
` Fig. 6. Three weeks of human growth hormone (HGH) increases intestinal absorption of
`macronutrients with permission [14] . Lower dose (physiological) recombinant HGH sig-
`nificantly affected energy (440 kcal/day), nitrogen and carbohydrate absorption in 12 SB-
`IF patients (Crohn’s disease 3/12, residual small intestine mean 43 cm range 0–120 cm,
`9/12 had colons, 9/12 colon: study design: randomized double-blind, placebo controlled,
`cross-over trial GH 0.05 mg/kg/day for 3 weeks placebo controlled, cross-over trial GH
`
`0.05 mg/kg/day for 3 weeks). *  p < 0.002, * *  p < 0.04, * * *  p < 0.02, vs. placebo.
`
`es apoptosis [16] . Thus, unlike growth hormone, its effects are specific to the
`small intestine. With chemical engineering, the substitution of a glycine mole-
`cule for alanine in natural GLP-2 made the product, teduglutide, protease resis-
`tant, thus increasing its half-life from minutes to several hours [17] . This is im-
`portant as it can now be given as a single daily injection.
` Two multicenter, multinational randomized controlled trials which verify
`the potency and efficacy of the drug in reducing intravenous fluid requirements
`have now been completed. Because the condition is relatively rare, sufficient
`numbers could only be achieved with international collaborations through 29
`sites in 10 countries (USA and Europe). In the first study [18] , two dose levels
`were compared to placebo in 84 patients. Surprisingly, the lower dose (0.05 mg/
`kg per day) proved more effective in achieving the primary end point of ‘clini-
`cally significant’ (>20%) reductions in intravenous fluid requirements to main-
`tain normal renal function as defined by a stable plasma creatinine and urine
`volume of 1–2 l/day (46 vs. 6%, p = 0.01). Secondary benefits included increased
`fasting plasma citrulline, a marker of enterocyte function, and increased lean
`body mass. In the second confirmatory study, a more simple randomized con-
`trolled trial was conducted between placebo and the teduglutide dose of 0.05 mg/
`kg per day ( fig. 7 ) in 86 patients [19] . Here, 63% achieved >20% reduction in PS
`
` Nutritional Issues in the Short Bowel Syndrome
`
`83
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
`Page 9
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`

`
`Results:
`Primary efficacy endpoint–responder rate
`
`63%
`
`*
`(n = 27)
`
`30%
`
`Teduglutide
`(n = 43)
`
`Placebo
`(n = 43)
`
`100
`
`80
`
`60
`
`40
`
`20
`
`0
`
`Subjects (%)
`
` Fig. 7. The long-acting
`protease-resistant
`modification of the gut
`peptide GLP-2,
`teduglutide, reduced
`intravenous fluid
`requirements by >20% in
`63% of SB-IF patients
`within 6 months, which
`translated into a shorter
`duration of intravenous
`infusion and total weaning
`back to normal food in 4
`patients (Jeppesen et al.
`
` [19] ). *  p < 0.002, vs.
`
`placebo (Cochran-Mantel-
`Haenszel test).
`
` Fig. 8. A common side
`effect of teduglutide is
`swelling of the stoma,
`which indicates the
`powerful effects the drug
`has on the residual bowel.
`
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`compared to 43% on placebo (p = 0.002). Importantly, this translated into more
`patients being able to drop the frequency of intravenous infusions, and 11 pa-
`tients were successfully and completely weaned from intravenous therapy dur-
`ing the two studies [20] . Interestingly, the time of weaning varied from 12 to 110
`weeks on the drug. There is no doubt about the potent hypertrophic effects of
`this drug, which can readily be seen with endoscopy and examination of the
`stoma, which commonly enlarges considerably, as shown in figure 8 .
`
`84
`
` O’Keefe
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
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`Table 1. Three-year analysis of the Mayo Clinic HPN Program [21]
`
`Patients: 63
`Short bowel: 40
`Chronic obstruction: 23
`
`Hospitalizations: 73% (average stay: 11 days)
`71% were due to catheter infections (Staphylococcus epidermidis: 12, fungi: 8)
`• 70% of them required catheter replacement
`• 2 weeks of intravenous antibiotics
`25% for catheter replacement for thrombosis or damage
`All had intermittent abnormalities in complete blood cell count, urinary excretion, and
`renal and liver tests
`
` Another interesting fact was the high placebo response. There is no clear ex-
`planation, but it is possible that adaptation continues longer than previously
`thought, or it could be that tighter management in the clinical trial setting al-
`lowed further intravenous fluid reductions. The drug has now been marketed.
`Postmarketing surveillance will be essential to rule out unanticipated long-term
`side effects, e.g. neoplastic changes bearing in mind its proliferative properties,
`but to date the safety profile looks good.
`
` Problems with Home Parenteral Nutrition
`
` PS is the only life-sustaining form of medical treatment for SB-IF. However, PS
`is expensive, impairs quality of life (QoL) and is associated with serious compli-
`cations, such as catheter sepsis, central venous thrombosis and liver failure
` ( table 1 ) [21, 22] .
`
` Quality of Life
` Many studies have examined this and found that QoL is severely impaired. This
`is not surprising, as patients lose their freedom as they are tethered to intrave-
`nous catheters for the rest of their days. This severely limits social intercourse
`and the ability to return to a normal occupation and lifestyle. They also have to
`be vigilant in preserving catheter sterility, as breaks in the line will result in bac-
`teremia, septicemia and repeated hospitalizations.
`
` Complications of Total Parenteral Nutrition
` It must be appreciated that although TPN has allowed patients to survive
`without significant gut function and food absorption, feeding into the right
`side of the heart can never substitute for feeding through the gut and portal
`
` Nutritional Issues in the Short Bowel Syndrome
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`85
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`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
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` Fig. 9. Illustration of the complexity of the management of patients with massive intes-
`tinal resection. This elderly patient had suffered thrombosis of his superior mesenteric
`artery resulting in gangrene of all of the small intestine from the ligament of Treitz. He
`was managed with gastrostomy with jejunal extension and central feeding via a periph-
`erally inserted central catheter. Massive stomal losses were associated with recurrent
`bouts of catheter sepsis and progressive liver dysfunction. A small bowel transplant was
`performed with successful removal of all these tubes and reestablishment of normal
`eating.
`
`vein. Even the freshest of foods is heavily colonized by microbes, which are
`safe if they stay intraluminal but could be fatal if they enter the systemic cir-
`culation. Consequently, the prime function of the gut, other than absorption,
`is to break down food into a sterile solution that can be absorbed into the por-
`tal vein, sensed by the pancreas and assimilated by the liver. To achieve this,
`microbe quantities are progressively diminished by the action of gastric acid,
`pancreatic enzymes and bile, and finally sterilized by the action of the gut im-
`mune system, which surrounds the lumen and engulfs any remaining bacteria.
`If you contrast this to TPN, it is easy to understand that the chief complica-
`tions are septicemia, metabolic instability, liver dysfunction and progressive
`occlusion of the central veins through trauma of the intima by repeated cath-
`eterization. A further problem is that systemically administered nutrients are
`not as well assimilated and utilized by the liver. Consequently, it is always
`important to maintain oral intake for hepatic nutrition, even if most is mal-
`absorbed.
` Complications are directly related to the quality of catheter care at home
`( fig. 9 ). Our analysis showed that some patients never experienced catheter in-
`fections, whilst others had to be rehospitalized every few weeks [22] . Other
`risk  factors for catheter infections included the presence of a high-output
`
`86
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` O’Keefe
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
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`Table 2. Indications for TPN failure
`
`Medicare indications
`(1) Life-threatening sepsis
`(2) Venous thrombosis – loss of access
`(3) Liver disease – progressive fibrosis, cholestasis, cirrhosis
`
` jejunostomy, chronic obstruction and gut stasis leading to bacterial overgrowth
`and Crohn’s disease.
` Perhaps the most life-threatening complication is liver failure. While minor
`liver function test abnormalities are common and not serious, progressive cho-
`lestasis, liver fibrosis and cirrhosis, and eventual liver failure is devastating and
`uniformly fatal unless a successful liver-small bowel transplant is performed.
`Luckily, the complication only occurs in ∼ 5% of patients. The etiology is com-
`plex and involves repeated infections, absence of oral intake, an extremely short
`bowel and too many PN calories in the form of fat or dextrose.
`
` Small Bowel Transplantation
`
` The efficacy of small bowel transplantation (SBTx) lagged behind that for renal
`and liver transplantation until recently, when the Intestine Transplant Registry
`participants announced that ‘a new era has dawned’ as outcome now is very
`similar to that of liver transplantation, i.e. 1-year survival of graft and host >90%
`due to improved surgery and immunosuppression [23] .
` In the USA, Medicare has accepted ‘TPN failure’ as the chief indication for
`SBTx. The chief criteria are summarized in table 2 . It is important to stress that
`although the novel pharmaceutical approaches to reduce PN requirements cer-
`tainly contribute to an improved outcome and QoL, only SBTx can predictably
`get patients off intravenous infusions and make them nutritionally autonomous.
`We have argued that consideration for SBTx should be made early in patients
`with risk factors for developing liver failure (e.g. ultrashort bowel <50 cm with-
`out colon), as this will preserve the liver and obviate the need for a combined
`liver-small intestine transplant [24] .
` To illustrate theses points, we conducted a prospective 2-year study of 46
`consecutive patients transplanted between June 2003 and July 2004 [25] . PN was
`stopped completely by day 17 after transplantation. After a mean follow-up time
`of 21 months, 40/46 (87%) were well with good graft function. Perhaps, most
`importantly, average QoL, measured with a QoL tool based on a validated self-
`administered questionnaire containing 26 domains and 130 questions, was
`
` Nutritional Issues in the Short Bowel Syndrome
`
`87
`
`Meier RF, Reddy BR, Soeters PB (eds): The Importance of Nutrition as an Integral Part of Disease Management.
`Nestlé Nutr Inst Workshop Ser, vol 82, pp 75–90, (DOI: 10.1159/000382005) Nestec Ltd., Vevey/S. Karger AG., Basel, © 2015
`
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`
`Before SBTx
`After SBTx
`HPN
`
`Vocational
` effects
`
`Medical
`compliance
`
`Optimism
`
`Energy
`
`35
`30
`25
`20
`15
`10
`5
`0
`
`Digestive and
`urinary effects
`
`Cell
`
` Fig. 10. QoL was
`significantly improved
`when patients with
`intestinal failure
`dependent on HPN were
`successfully transplanted.
`Results were evaluated by
`comparison to
`nontransplanted HPN
`patients. Key
`improvements following
`SBTx in some of the 26
`domains that improved
`specifically (split by
`period) are shown.
`Means ± SE [25].
`
` dramatically improved. A summary of some of the key improvements is shown
`in figure 10 . It should also be noted that we evaluated baseline QoL compared to
`HPN in patients who declined transplantation and showed that the indices of
`QoL in transplanted patients prior to transplantation were significantly lower,
`indicating the gravity of their illness.
` Despite these exciting observations, there remains a reluctance to refer pa-
`tients with Medicare indications for SBTx, as evidenced by the review by Pironi
`et al. [26] in Europe.