Olivier Goulet
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of cholestasis [2] . The cause of resection and the age of a patient also influence the functional ca- pacity of the remnant gut and its potential for ad- aptation [2, 3] . Management of SBS involves mea- sures aimed at promoting small bowel adaptation and villous hyperplasia by enteral (oral or tube) feeding, by providing normal somatic growth with parenteral nutrition (PN), and by optimiz- ing the bowel’s absorptive surface via nontrans- plant surgical techniques. PN is the cornerstone of management, but as much enteral feeding (EF) as possible should be provided to the patient to improve the physiological processes of small bowel adaptation. Moreover, in infants or chil- dren, oral feeding (OF) skills have to be acquired or maintained. Different concepts exist with re- spect to what the composition of feeds (elemental, semi-elemental or polymeric) and their mode of delivery (OF or gastric tube feeding) should be.
Current studies do not provide evidence-based data for establishing recommendations for SBS patients.
Rationale for EF
The use of the gastrointestinal (GI) tract is vital for preserving or restoring normal intestinal structure and function [3] . Functional intestinal adaptation refers to the gross anatomic and histo- logic changes that occur after extensive intestinal resection. Following bowel enlargement and lengthening of villi, the intestinal absorptive sur- face area increases, and absorptive function grad- ually improves. Changes in intestinal motility, commensal microbiota and barrier function are associated with the anatomic and histologic changes. The use of the intestinal tract has a criti- cal role in the process of intestinal adaptation, based on the effects of direct nutrient contact with the mucosa, pancreatic and hepatobiliary secre- tions, and circulating hormones. OF promotes the release of epidermal growth factor (EGF) from salivary glands, increases GI secretion of
trophic factors and helps prevent feeding disor- ders. Only few clinical trials have been performed on patients with PDI or SBS, but they support that EF maintains and/or promotes intestinal func- tion [4–6] . The choice of diet as well the mode of delivery remain debated ( tables 1 , 2 ).
Which Diet Should Be Used
Breast milk contains lactose and theoretically is considered to be not well tolerated by patients with a reduced intestinal surface area. However, breast milk contains many factors that may pro- mote intestinal adaptation and has been shown to improve immune function as well as the genesis of a fecal microbiota rich in lactobacilli and bifi- dobacteria. With infants with SBS, the percentage of days that they received breast milk was corre- lated with fewer days of PN use [7] . To patients with neonatal SBS, breast milk should be given as often as possible – by breastfeeding or, if neces- sary, by tube feeding.
The choice of enteral formula is controversial.
A limited mucosal absorptive surface area can lead to lactose, long-chain fatty acid and protein malabsorption. In PDI, electrolyte and metabolic balance can be difficult to achieve. In SBS pa- tients, complex nutrients may promote mucosal cell proliferation via direct contact with disac- charides [8] . Additionally, colonic exposure to lu- minal nutrients promotes the release of trophic factors that enhance small bowel mucosal troph- icity.
Oligo- and polysaccharides are poorly tolerat- ed by these patients, being broken down into os- motically active organic acids that can present a major osmotic load to the distal small intestine and colon. For patients with intractable diarrhea of infancy, the carbohydrate content should not exceed 40% of calories, and be lactose free.
Fiber supplementation , by promoting the pro- duction of short-chain fatty acids such as butyrate, has trophic effects on the small intestine. Short-
184 Goulet Table 1. Which type of diet should be used
Breast milk
– Contains lactose, growth factors, nucleotides, long-chain fatty acids, glutamine and other amino acids that promote intestinal adaptation
– Promotes microbiota rich in lactobacilli and bifidobacteria – In infants with SBS, it reduces the duration of PN – Should be used as much as possible in neonatal SBS Enteral formulas
Carbohydrates
Oligo- and polysaccharides
– Poorly tolerated by patients with limited mucosal absorptive surface area
– Broken down in small intestinal lumen into osmotically active organic acids
– Should not exceed 40% of calories, and be lactose free for patients with intractable diarrhea of infancy Fiber supplementation
– Helpful in older children with SBS with intact colon – Promotes colonic bacterial production of short-chain
fatty acids Lipids
Long-chain triglycerides
– Poorly digested in case of small intestinal bacterial overgrowth because of bile acid changes
– Poorly absorbed in patients with severe malabsorption – Have trophic effects on small intestinal mucosa – Supplementation with n–3 or n–6 polyunsaturated
fatty acids may enhance mucosal growth MCT
– Rapidly hydrolyzed by pancreatic lipase – Do not provide essential fatty acids
– Less dependent on an extensive absorptive surface for adequate absorption
– Water soluble, and absorbed intact directly into the portal circulation
– As part of lipid supply appropriate for most infants with SBS
– Excessive intake can cause diarrhea
– Recommended use of formulas containing no more than 60% MCT as fat
Nitrogen HPF
– Have changed the incidence and outcome of PDI – No demonstrated advantages in comparison with
intact protein infant formulas – Lactose free and containing MCT – Recommended for SBS patients Elemental amino acid-based formulas
– Not yet established whether this type of formula can influence the outcome of SBS
– Contain lower amounts of MCT than HPF Glutamine
– Currently no benefit demonstrated
MCT = Medium-chain triglycerides; HPF = hydrolyzed protein formulas.
Table 2. Management and outcome of neonatal SBS ac- cording to anatomic characteristics
SBS is a very variable condition, which can be as mild as that following terminal ileal resection and also very debilitating follo- wing total jejunoileal and colonic resection. Management and outcome vary according to the cause, extent and site of resecti- on and the degree of adaptation of the remaining bowel. Pati- ents with dilated, poorly motile segments of small bowel (gast- roschisis, atresia and necrotizing enterocolitis) should benefit from an approach aiming to reduce bowel dilatation and SIBO, since they may develop progressive liver disease. PN should be delivered, as soon as tolerance permits, by cyclical infusion. Ear- ly OF should be promoted, while the benefits of continuous EF should be balanced in combination with PN, the risk of ‘intesti- nal overload’ with subsequent SIBO, and tube feeding-induced food aversion and eating disorders
SBS with SBL of <40 cm with loss of the ICV and associated partial or large colectomy
Patients need home PN over a very long period of time. Indica- tions for reducing PN are appropriate weight gain and tolerance to other feeds. However, digestive outcome for patients with SBL <40 cm and loss of the colon is poor; they will mostly remain dependent on permanent PN or intestinal transplantation SBS with SBL of <40 cm or only duodenum, with totally or largely intact colon
Patients need long-term home PN. However, many infants and children may have a degree of adaptation and require less PN and benefit from orally and/or enterally administered nutrients.
Some of them may be progressively weaned from PN. Infants with duodeno-right colon anastomosis have little chance of being weaned from PN and should receive OF to promote opti- mal psychological behavior. These patients are at risk of develo- ping D-lactic acidosis
SBS with SBL of 40 – 100 cm with loss of the ICV and associated par- tial or large colectomy
Patients require midterm home PN and can immediately be fed orally. Combination of continuous EF and OF may help in re- ducing PN duration. Bile salt-induced diarrhea may impede ra- pid weaning from PN
SBS with SBL of 40 – 100 cm with terminal ileum and the entire co- lon
Patients require very short-term PN and can immediately be fed orally. EF in combination with OF may help in reducing PN dura- tion. These patients are at risk of developing D-lactic acidosis SBS with terminal ileum resection
Patients have bile salt-induced diarrhea and benefit from the ad- ministration of 1 – 2 g of cholestyramine 3 times a day to bind bile salts left unabsorbed by the resected ileum. Vitamin B12 plas- ma levels should be measured, and if low, supplemental vitamin B12 should be provided by intramuscular injection at a dose of 100 – 150 μg per month or 1,000 μg every 6 months
SIBO = Small intestinal bacterial overgrowth; SBL = small bowel length.
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 182–189 DOI: 10.1159/000360339
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chain fatty acids, especially butyrate, are known to promote glucagon-like peptide-2 release.
Long-chain triglycerides are poorly absorbed by patients with a reduced absorptive surface. In case of small intestinal bacterial overgrowth (SIBO), bacteria metabolize and inactivate bile acids, preventing the solubilization necessary for long-chain triglyceride digestion.
Medium-chain triglycerides (MCT) are rapidly hydrolyzed by pancreatic lipase and are less de- pendent on an extensive absorptive surface for adequate absorption. They are water soluble, and can be absorbed intact directly into the portal circulation [9] . Excessive intake of MCT can cause diarrhea and ketosis, while MCT do not provide essential fatty acids. Current clinical practice is based on formulas containing no more than 60% MCT as fat.
Whether the molecular form of the nitrogen taken up might influence PN duration and/or the occurrence of non-IgE-mediated sensitization and allergic enteritis remains debated. A link be- tween SIBO, abnormal mucosal permeability and protein sensitization is possible, but the use of el- emental diets (amino acid-based formulas) is not clinically established ( table 3 ). Patients with di- lated, poorly motile segments of the small bowel should benefit first from an approach aiming to reduce bowel dilatation and SIBO, with subse- quent bacterial translocation [10] .
Hydrolyzed protein formulas (HPF) have been used for many years and have changed the inci- dence and outcome of PDI during the last decades.
HPF have been evaluated by comparison with in- tact protein infant formulas in a crossover study of 60 days duration on 10 infants with SBS [11] . No effect of formula type was observed on growth, ni- trogen absorption or mucosal permeability. In gen- eral, HPF are lactose free and contain MCT [11, 12] .
Elemental amino acid-based formulas (EAABF) have been introduced more recently for infants suffering from severe allergic diseases.
It is not yet established whether this type of for- mula may influence the outcome of SBS. A ben-
Table 3. Small intestinal bacterial overgrowth General remarks
– Several factors intrinsic to SBS predispose to SIBO and explain its high prevalence in this patient population – Poorly motile segments of the small bowel in close proximity
to the colon are common in patients with SBS and dysmotility, and the intestinal stasis and contamination that results promotes abnormal growth of bacteria in the small intestine – The link between SIBO, translocation, cholestasis, portal
fibrosis and cirrhosis is now clearly established
– SIBO may significantly compromise digestive and absorptive functions and may delay or prevent weaning from PN – Traditional clinical tests for overgrowth may be unreliable – Management may include surgery if advocated; antibiotic
therapy should be carefully selected to avoid resistance – The intestinal microbiota plays an important role in intestinal
adaptation and should be preserved as much as possible – The use of probiotics might offer potential based on
experimental evidence, but there is a lack of sufficient data from human studies. The use of D-lactate producing probiotics should be avoided
– D-Lactic acidosis is secondary to bacterial hypermetabolism, especially in the colon, as a consequence of intestinal malabsorption
Definition
CFU per milliliter of bacteria in the proximal small bowel – Overgrowth of >105 CFU/ml
– Overgrowth of >103 CFU/ml provided that the species of bacteria isolated from the jejunal aspirate are those that normally colonize the large bowel or provided that those same species are absent from the saliva and gastric juice – Breath hydrogen testing
Caused by small intestine stasis from:
– Intestinal obstruction (e.g. stenosis, narrowed anastomosis) – Blind loop from terminolateral anastomosis
– Dilated and poorly motile segments of the small bowel in close proximity to the colon
Consequences
– Small intestinal mucosal injury with villous atrophy and subsequent malabsorption
– Increased small intestinal mucosal permeability – IgE-mediated sensitization and allergic enteritis – Gram-negative sepsis from bacterial translocation
– Portal inflammation, cholestasis, fibrosis and end-stage liver disease (cirrhosis)
Management
Reversal or removal of any predisposing condition(s) – Redo anastomosis
– Enteroplasty
• Small intestinal tapering and lengthening (Bianchi procedure)
• Serial transverse enteroplasty (STEP procedure) Appropriate nutritional support/replacement
Suppression or eradication of the contaminating bacterial flora – Intermittent bowel decontamination with antibiotics – Use of probiotics (Lactobacillus rhamnosus GG,
Saccharomyces boulardii, etc.) CFU = Colony-forming unit.
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eficial effect of EAABF was reported in an open case study involving only 4 SBS patients with per- sistent feeding intolerance [13] . A retrospective study found a shorter duration of PN dependency with the use of EAABF [14] . Current data are in- sufficient to recommend such expensive formu- las with often increased osmolality for infants and children with SBS.
Glutamine (Gln) , a nonessential amino acid, plays an important role in energy metabolism of the intestinal mucosa and other rapid-turnover tissues. A randomized controlled pilot study of Gln-supplemented EF in infants with IF failed to show any advantages [15] . Gln cannot be recom- mended unless larger multicenter trials on infants with IF provide evidence for beneficial effects.
Table 4. Different routes of feeding
Devices Indications Contraindications Advantages Disadvantages or risks
OF
None To be used
systematically
Artificial ventilation Orofacial malformation
Discontinuous physiologic mode of feeding Self-regulation of intake EGF release by salivary glands
Promotes bowel adaptation
Psychological behavior
Insufficient intake
Gastric feeding
Nasogastric Nutritional support
<3 months
Severe GE reflux Slow gastric emptying
Easy to place even at home Frequent dislodgements Nasal symptoms Percutaneous
endoscopic gastrostomy
Nutritional support
>3 months
Repeated abdominal surgery
Abnormal gastric anatomy
Fewer occlusions with larger bore, one-step low- profile devices available
Skin injury at abdominal exit site
Surgical gastrostomy
Nutritional support
>3 months
Poor candidate for surgery
Immediate placement of low-profile device, direct visualization of stomach
Open surgery
Duodenal or jejunal feeding Nasojejunal Short term for
patients with severe GERD, gastric dysmotility
Recent proximal surgical anastomosis
Radiologic or bedside placement techniques Noninvasive
Frequent dislodgements Risk of intussusception Nasal symptoms Intestinal contamination Gastrojejunal Longer-term EF for
patients with severe GERD, gastric dysmotility or need for gastric decompression
Recent proximal surgical anastomosis
Endoscopic or radiologic placement through existing gastrostomy tube
Requires healing of gastrostomy tract prior to placement
Skin injury at abdominal exit site
Frequent occlusions of jejunal port
Intestinal contamination Jejunal Long-term EF for
patients with severe GERD and upper intestinal dysmotility
Dysmotility Direct surgical access to small intestine
Open surgical procedure Mechanical problems Intestinal contamination
GE = Gastroesophageal; GERD = gastroesophageal reflux disease.
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 182–189 DOI: 10.1159/000360339
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Water electrolyte losses from persistent diar- rhea or end jejunostomies should be replaced par- enterally, based on the electrolyte concentration of the lost fluids. Monitoring urine sodium con- centration provides guidance for correcting or preventing Na depletion (<10 mEq/l), even if se- rum sodium is near normal. Magnesium and
trace element losses can occur with high stoma output. Zinc supplements are often used empiri- cally, given that serum values do not reliably re- flect body stores. Ileal resection or diversion leads to fat-soluble vitamin and vitamin B 12 deficiency requiring monitoring and (parenteral) supple- mentation.
Table 5. Modes and management of feeding Modes
OF is the most physiological and most stimulates intestinal adaptation
Continuous EF is beneficial to patients with SBS or intractable diarrhea of infancy by improving saturation of carrier transport proteins, thus taking full advantage of the available absorptive surface area as compared with intermittent feeding
Oropharyngeal shunting suppresses direct stimulation of the salivary glands, resulting in lower release of EGF, an important intestinal mucosal trophic factor
Continuous infusion leads to a loss of self-regulation of intake with vomiting, or to intestinal stasis with an increased risk of SIBO and subsequent mucosal injury, sepsis, liver disease, etc.
In the case of full EF, a small extent of OF should be introduced in infants 2 or 3 times a day, to stimulate sucking and swallowing and to minimize the chances of eating disorders in the future
A nasogastric tube may impair normal acquisition of oral behavior and induces eating disorders Percutaneous gastrostomy is indicated with children who require EF for >3 months
Jejunal feeding
– Whatever the device (nasojejunal, gastrojejunal or jejunal), it should be limited to very special situations
– Exposes to the risk of intestinal contamination with subsequent SIBO and sepsis – Excessive infusion rate may be responsible for severe diarrhea and dehydration Progression and monitoring of feeding program
Intestinal transit must be well established by coloanal transit or ostomy Absence of contraindications
– Patient’s general condition (sepsis, bleeding, respiratory distress syndrome, etc.) – Bloody stools
– High ostomy or stool output of >3 ml/kg/h – Bilious and/or persistent vomiting – Electrolyte imbalance
Quantify feeding tolerance – Stool or ostomy output
– Reducing substances in stools or ostomy output – Recurrent vomiting and abdominal distension Ultimate goals
– Provide 150 – 200 ml/kg/day or 100 – 140 kcal/kg/day
– If ostomy/stool output precludes advancement at 20 cal/oz for 7 days – Increasing caloric density of the formula can be performed
– Isocaloric reductions in PN support simultaneously with feeding advancement Warnings
– EF can induce severe adverse effects related to intestinal overload and/or bacterial contamination with subsequent SIBO
– A meticulous approach, avoidance of excessive enteral formula supply, strict hygiene measures – Concomitant OF prevents psychological disorders and eating aversion
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Advancement of Feeding
Whatever the route of feeding ( table 4 ), EF ad- vancement can occur as long as fluid and electro- lyte balance is maintained and nutritional goals are achieved ( table 5 ). EF may eventually be tran- sitioned to oral/bolus feeding, or oral/bolus and nocturnal feeding, in order to allow more free- dom from the feeding pump. The transition from IF to adequate intestinal function can take weeks, months and sometimes years. The bowel function of infants with SBS improves over time due to the opportunity for further intestinal growth. Provi-
sion of EF plays a major role in the management of any child with IF, even of those for whom com- plete weaning from PN seems unlikely ( fig. 1 ).
Conclusions
• Intestinal adaptation following resection is a physiological process best enhanced by early use of the GI tract, especially by OF, which is more physiological, furthers oral skills and promotes the release of trophic factors such as EGF from the salivary glands
SBS
Promote early oral feeding:
• Human milk
• Previously fed formula Dumping (high stool volume
with reducing substances)
>40% of recommended daily allowance
‘Drip feeds’
Diluted formulas
Good toleranceNo of feeding High PN intake forYes
achieving growth Semi-elemental
ready-to-feed formula
Not tolerated continued
dumping Elemental formula
challenge Adjunctive treatment
PN Pharmacologic management
(loperamide, cholestyramine, ursodeoxycholic acid) Identify risk and setting of SIBO and discuss lengthening surgery feedingTube
Fig. 1. Algorithm for management of feeding.
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 182–189 DOI: 10.1159/000360339