KEY POINTS
- 1.
Intestinal failure (IF) is defined as the loss of functional gut mass to levels below those needed for digestion and absorption of fluid and nutrients required to support adequate nutrition and growth.
- 2.
Short bowel syndrome (SBS) is a subtype of IF that occurs due to the anatomic loss of a part of the intestines.
- 3.
Gastroschisis and necrotizing enterocolitis (NEC) are the most frequently seen congenital and acquired causes of IF in neonates and young infants.
- 4.
Loss of specific parts of the intestine may predispose an infant to various nutritional deficiencies.
- 5.
SBS from surgical resection of the intestine may show phasic adaptive recovery: an initial acute period of intestinal dysfunction, subacute recovery over several weeks, and then a chronic phase of consolidation over months to years depending on the extent of the loss.
- 6.
Many infants with IF require parenteral nutrition for long periods and are consequently at risk of cholestasis and liver failure.
- 7.
In many patients, specific nutritional supplements such as dietary fiber, lipid preparations such as fish oil, probiotics; and motility-altering agents may be helpful.
Introduction
Intestinal failure (IF) is defined as the reduction of functional gut mass to levels below those needed for digestion and absorption of fluid and nutrients at levels adequate for nutrition and growth, resulting in prolonged dependence on parenteral nutrition. , It can result from either anatomic or functional loss of the intestines ( Table 21.1 ). The term “short bowel syndrome” (SBS) refers to a specific subtype of IF that results from the anatomic loss of absorptive and digestive surface of the intestines. IF can also result from mucosal dysfunction due to various congenital and acquired enteropathies and from gastrointestinal dysmotility states.
Anatomic Loss of Function: Reduced Absorptive Area (Short Bowel Syndrome)
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Mucosal Dysfunction: Inefficient Mucosal Surface
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Neuromuscular Dysfunction: Motility Disorders
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Congenital IF is associated most frequently with gastroschisis, which accounts for about 15% of all cases of IF and SBS in infants (Pediatric Intestinal Failure Consortium study). In the same study, necrotizing enterocolitis (NEC) was noted to be the most frequent postnatal cause, accounting for 26% of IF in infants ( Fig. 21.1 ). These data are not surprising, because NEC still has a fairly high incidence; in a study from 820 centers in the United States, NEC occurred in 7.6% of all very low birth weight (VLBW) infants. In another study conducted by the Neonatal Research Network of the National Institute for Child Health and Human Development (NICHD), NEC caused 96% of all IF and SBS in VLBW infants. The increasing prevalence of SBS is likely related to improved survival of extremely premature infants with severe NEC and other gastrointestinal conditions. , The NICHD network has reported the incidence of SBS to be 7 per 1000 VLBW infants and 11 per 1000 extremely low birth weight infants. SBS is also an important cause of infant morbidity and mortality in other countries; the Canadian Collaborative Study Group reported an overall incidence of 0.25 cases of SBS per all 1000 live births, increasing to 3.5 per 1000 in preterm infants.
Development of the Gastrointestinal System and Relevance to Short Bowel Syndrome
The human gut develops from an infolding of the endodermal layer of the embryo, beginning at about 2 to 3 weeks after conception. All three germ layers are involved: the endoderm, the mesoderm, and the ectoderm. Many endodermal cells differentiate into gut epithelium and associated glands; mesoderm contributes to the lamina propria, muscularis mucosa, muscularis externa, and the blood vessels; and the ectoderm gives rise to the gut neuronal network in the submucosal and myenteric plexuses. The longitudinal growth of the small intestines can be described in three phases: an initial linear phase, a second and more accelerated phase between 20 and 40 weeks of gestation, and then a second phase of linear growth during infancy. The small intestines grow from about 2 to 20 cm between the 7th and 14th weeks of gestation and then double in length from 20 to 40 weeks. The mean length of the small intestines at 20 weeks is 125 cm, and this increases to 275 cm at full term. The cylindrical growth, both linear and circumferential, occurs secondary to binary fission or duplication of intestinal crypts and is most prominent in the submucosa. The surface area of the intestinal mucosa increases with the formation of mucosal folds of Kerckring, deepening of the crypts, and the development of microvilli in the brush border. This mucosal and submucosal growth increases the absorptive area of the intestines by more than 600 times. Finger-shaped villi with apical microvilli can be seen as early as the 14 weeks’ gestation, and this development continues during early infancy. , This “reserve” ability of the small intestines to grow in structure and function in the second half of gestation provides some adaptability to the loss of some length secondary to disease and/or surgical resection.
Nutritional Challenges in Short Bowel Syndrome
The signs and symptoms of SBS are defined by the loss of function of specific parts of the gastrointestinal tract. The direct impact of SBS is attributed to the loss of the digestive and absorptive surface of the mucosal ultrastructure and/or shortened length of the intestine. The transit of the food may also be reduced, and the resulting feeding intolerance (emesis) may reduce its contact period with the mucosa, thus impairing digestion and absorption. The loss of specific parts of the gastrointestinal tract, which have evolved to absorb different nutrients, may also predispose the infant to various nutritional deficiencies. Fig. 21.2 summarizes these data.
The stomach is resected less frequently, but the disturbances to gastric physiology can lead to several signs and symptoms seen in SBS. The stomach primarily receives the ingested food, initiates digestion, and transfers the food in a series of well-coordinated movements between the fundus-body and the pylorus-antrum. Gastric hypersecretion is a state of increased gastric secretions often noted with resection of the terminal ileum. The terminal ileum secretes a hormone called peptide YY, which slows down the motility and secretion of the stomach and the duodenum. , After resection of the ileum, this negative feedback look is lost, leading to states of hypergastrinemia and hypermotility. Incoordination between different parts of the stomach can lead to gastroparesis, impairing the ability to transfer gastric content to the duodenum, leading to increased gastrointestinal output.
Pancreatic enzymes are detected as early as 15 weeks’ gestation, but the ontogeny of pancreatic exocrine function is slower compared with the anatomic development of the gut. The pancreatic exocrine function is fairly mature beyond 20 to 25 weeks but then plateaus to continue to develop through early infancy. In SBS, the loss of pancreatic function leads to exocrine pancreas insufficiency and subsequent malabsorption of nutrients. Pancreatic amylase in the duodenum resumes the digestion of complex carbohydrates initiated by salivary amylase in the mouth. Thereafter, brush border hydrolases found on the enterocytes, such as lactase, maltase, and sucrase, continue the disintegration of disaccharides into monosaccharides and facilitate their absorption into the bloodstream via hexose transporters such as SGLUT-1 and GLUT5. Intestinal lactase activity is low between 14 and 20 weeks’ gestation before reaching a high level at term. Although human milk is high in lactose concentration, VLBW infants tolerate human milk very well. This is probably aided by the colonic salvage pathways that convert unabsorbed lactose into short-chain fatty acids, which are then absorbed and used for energy production. In fact, early feeding promotes increased intestinal lactase in preterm infants. Many other effects of SBS may not be directly related to the loss of digestion and absorption of nutrients. Examples include intestinal failure–associated liver disease (IFALD), cholelithiasis, bloodstream infections, metabolic bone disease, oral aversion, and long-term growth failure with neurodevelopmental delays.
Intestinal Adaptation/Rehabilitation
The events and recovery of intestinal functions after the sentinel event resulting in IF can be broadly categorized into three stages ( Fig. 21.3 ):
- 1.
Acute phase, seen immediately after a surgical event, lasting between a few days to weeks. The acute phase is characterized by postoperative ileus and consequent high outputs either through the gastric tube or the gastrostomy. Consequent to high gastrointestinal outputs, this is accompanied by fluid and electrolyte losses and acid–base imbalance.
- 2.
Subacute phase, spanning several weeks. The intestinal function gradually returns; the previously high gastrointestinal output decreases with less severe fluid and electrolyte disturbances. During this period, enteral nutrition is initiated and advanced on a foundation of a stable parenteral nutritional regimen. This phase is significant for linear and circumferential growth and the adaptation of previously retained sections of the intestines. This process facilitates feed tolerance, enabling the advancement of enteral nutrition and weaning of parenteral nutrition.
- 3.
Chronic consolidation phase, spanning several months to years depending on the extent of the loss.
All stages show progressive intestinal adaptation, marked by a series of anatomic and physiologic changes that begin as early as 48 hours after surgery and continue throughout rehabilitation. , During this process, compensatory changes are observed in the mucosa and muscular layers of the intestines. Changes in the mucosal cytoarchitecture involve lengthening of villi, deepening of crypts, and enterocyte proliferation resulting in expansion of the subluminal mucosal surface, increasing the surface area by many times. This process results in increased enterocyte per villus and is achieved by increasing mucosal DNA and RNA content. This process of intestinal adaptation is mediated by gastrointestinal hormones such as growth hormone, insulin-like growth factor, glucagon-like peptides, peptide YY, and neurotensin. This process of intestinal adaptation is further enhanced by exposure of the intestinal mucosa to enteral feeds, which prompts the release of hormonal mediators mentioned above, facilitating a trophic effect. The extent of intestinal adaptation varies with the anatomic site of the gastrointestinal tract; studies suggest that the capacity for anatomic and function adaptation is highest in the ileum and limited in the jejunum. The process of intestinal adaptation provides the host with the anatomic and physiologic machinery required to improve the function of the residual bowel. As the intestinal adaptation progresses, it results in the gradual return of the function of the residual bowel, restoring the capacity to digest and absorb fluids, electrolytes, and nutrients.
Goals of Intestinal Rehabilitation
The goals of intestinal rehabilitation are listed sequentially in the order of appearance in Table 21.2 . Enteral autonomy is often mentioned as the final goal in the process of intestinal rehabilitation. Enteral autonomy is defined as a clinical state in which the demands for adequate nutrition are met entirely by enteral feeds with complete independence from parenteral nutrition. However, the ultimate goal should be to promote and achieve appropriate developmental milestones with the best-tolerated combination of enteral and parenteral nutrition while striving toward enteral autonomy. There is wide variability in the definition of enteral autonomy, with different durations of independence from parenteral nutrition used as criteria. Short-term definitions have included achievement of feeds of 130 mL/kg/day with freedom from parenteral nutrition for a period as short as 48 hours. , However, long-term definitions in which independence from parenteral nutrition for over 3 to 12 months with appropriate growth parameters offer a more meaningful definition of enteral autonomy. The latter is a better definition because it stands the test of a more significant duration of time and incorporates goals of growth and development. Although the parenteral nutrition–free period of 12 months is more stringent, it is reported that a period of 3 months free from parenteral nutrition captures most instances of enteral autonomy without any relapses.
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Nutritional Strategies in Short Bowel Syndrome
Replacement of Fluid and Electrolyte Losses
Fluid and electrolyte losses are a significant concern in the acute phase after intestinal surgery. The most common cause of gastric losses is postoperative ileus. As the ileus resolves over days to weeks, the gastric secretions decrease. As the acute phase transitions to the subacute phase, gastric secretions through the gastric tube or gastrostomy can still be a concern even after the ileus has resolved. In these situations, the cause for increased gastric output is either due to gastroparesis or gastric hypersecretion. Gastroparesis is treated symptomatically with promotility medications. The most commonly used promotility medication is erythromycin. Erythromycin acts on the motilin receptors by promoting the type 3 migrating motor complexes, propagating the luminal content down the intestines. Gastric hypersecretion is often due to the loss of the inhibitory loop from the terminal ileum transmitted through peptide YY. , H2 blockers and proton pump inhibitors are of some benefit in treating gastric hypersecretion.
The fluid losses from the gastrointestinal tract should be closely monitored because they are a source of dehydration and electrolyte derangements. Small-volume fluid losses equal to or slightly greater than physiologic secretions do not require any intervention. The volume of output greater than accounted by the normal physiologic secretions are replaced either half or full volume (0.5 or 1 mL 0.9% normal saline replacement for every 1 mL of gastrointestinal output). Volumes greater than 20 to 30 mL/kg/day are replaced with 0.9% normal saline either in half or full volume. Volumes greater than 40 mL/kg/day can cause fluid and electrolyte imbalance; hence such volumes are repleted at frequent intervals and full volume with close monitoring of fluid and electrolyte status.
Parenteral Nutrition
Parenteral nutrition forms an essential mode of nutrition delivery from the time of diagnosis of SBS until enteral autonomy is achieved. During the acute and subacute phases, parenteral nutrition is the mainstay of nutrient delivery. For the recommended goals for energy and protein delivered through parenteral nutrition, please refer to Chapter 25 on Parenteral Nutrition. The goal for calories ranges from 90 to 110 calories/kg/day depending on the age and maturity of the infant, the nutritional state, and the metabolic demands. This goal can be achieved with a combination of glucose, proteins, and lipids delivery. A glucose infusion rate of 11 to 12 mg/kg/min is regularly reached; In situations where calories originating from lipids are restricted, the glucose infusion rate is increased to a rate as high as 14 mg/kg/min. Proteins are delivered at 3.2 to 4 g/kg/day in preterm infants and at a lower delivery rate of 2 to 3 g/kg/day in term infants, based on the nutritional demands.
Deficiencies of micronutrients in infants with SBS are common but underreported. , In a retrospective study of 178 children with IF, deficiencies of multiple micronutrients were noted during the transition from parenteral nutrition to enteral nutrition and after enteral autonomy. Iron was the most common micronutrient deficiency, with 84% and 37% of children with IF having iron deficiency and iron deficiency anemia, respectively. In the United States, parenteral nutrition solutions are usually devoid of iron due to issues with compatibility and anaphylaxis. For this reason, iron is often supplemented as 25 to 50 mg/month as a separate intravenous infusion. Infants with an ostomy are at an increased risk for deficiencies of zinc and copper due to losses from the ostomy. Extra supplementation with zinc and copper is made to offset the losses from the ostomy (100–150 μg/kg/day of zinc; 10–15 μg/kg/day of copper). However, because copper and manganese are excreted through bile, these micronutrients are retained in cholestatic states. In presence of cholestasis, the delivery of copper and manganese should be restricted to prevent the toxicities. Periodic biochemical measurements of these micronutrients in infants with SBS will help deliver appropriate amounts.
Intravenous Lipid Emulsions
Lipids are integral building blocks of the cell wall and play a crucial role in retinal and brain development. As a nutrient source, lipids are a calorie-rich source and act as a vehicle for fat-soluble vitamins and essential fatty acids. IFALD is a multifactorial complication noted in SBS. It is diagnosed by increased blood levels of conjugated bilirubin (≥2 mg/dL) and transaminases and may affect 22% to 30% of all infants on long-term parenteral nutrition. There is a strong association between the use of 100% soybean oil–based lipid emulsion and IFALD, , possibly due to the high content of n-6 fatty acids that have a proinflammatory profile. Stigmasterol, a phytosterol present in soybean oil–based lipid emulsion, antagonizes the hepatoprotective farnesoid X receptor and causes hepatocyte damage. Based on these concerns, efforts have focused on reducing the administration of soybean oil–based lipids to prevent IFALD. , , This lipid-limiting technique has involved the use of lower doses (1–1.5 g/kg daily or just twice a week) of 100% soybean oil–based lipid emulsions. However, randomized controlled trials showed only a modest clinical impact and actually increased the frequency of essential fatty acid deficiency with this strategy. , Newer-generation lipid emulsions have been formulated to mitigate the proinflammatory profile of n-6 fatty acids and to augment the antiinflammatory profile of n-3 fatty acids. This led to the emergence of fourth-generation lipid emulsions, namely multi-oil-based and 100% fish oil–based lipid emulsions. The multi-oil-based lipid emulsions contain soybean oil, medium-chain triglyceride oil (coconut oil), olive oil, and fish oil in proportions of 30:30:25:15, respectively. The newer-generation lipid emulsions, compared with 100% soybean oil–based lipid emulsion, have a higher antiinflammatory profile due to n-3 content, higher antioxidant activity due to greater content of vitamin E, and lower levels of the hepatotoxic phytosterol. Because of the improved antiinflammatory profile, the fourth-generation lipid emulsions have become a major strategy in both prevention and treatment of IFALD. The use of 100% fish oil–based lipid emulsions has been shown to be effective in treating IFALD in several retrospective and prospective cohort studies. In a pair-matched analysis, infants with cholestasis who received 100% fish oil–based emulsion, in comparison with 100% soybean oil–based emulsion, showed higher rates of resolution of cholestasis (65% versus 16%) and lower rates of liver transplantation (4% versus 12%). The sole randomized controlled trial comparing 100% soybean oil–based lipid emulsion versus 100% fish oil–based lipid emulsion was inconclusive due to early termination after parental refusal to participate in the study. A recent meta-analysis showed multi-oil-based lipid emulsions to have only a modest effect on prevention and treatment of IFALD. , A meta-analysis conducted by the European Society for Paediatric Gastroenterology Hepatology and Nutrition suggested that multi-oil-based lipid emulsions may be beneficial to infants with prolonged exposure to lipid emulsion. Infants who received multi-oil-based lipid emulsions for >4 weeks had decreased levels of conjugated bilirubin. Although the quality of evidence to support the use of newer-generation lipid emulsions is of very low quality, the use of 100% fish oil–based lipid emulsion in the treatment of and the use of multi-oil-based lipid emulsion in the prevention of IFALD should be considered.
Enteral Nutrition
Because intestinal adaptation begins within 48 hours, enteral feeding should be commenced as soon as the postoperative ileus resolves. Enteral feeding promotes intestinal adaptation and improves feed tolerance, facilitating earlier achievement of enteral autonomy. Early introduction of enteral feeding reduces the number of days with central venous catheters, decreases the risk of catheter-related bloodstream infections, and reduces the risk of IFALD. Apart from the early introduction of feeds, there is little consensus on the choice of initial feeds (breast milk versus formula feeds), route of feeds (oral versus enteric drip), or continuous versus bolus feeds. There is a serious limitation in data to make confident recommendations; most of our current information is from observational studies.
If available, the first choice of initial feeds in infants with SBS is breast milk. Human breast milk contains many protective and trophic factors, which offer numerous benefits, including effects on digestion, immunity, and the development of a healthy gut microbiome. Factors such as α 1 -antitrypsin and β-casein in the breast milk aid in the process of nutrient digestion and absorption and facilitate enterocyte proliferation and growth. Despite its content of lactose, relatively low content of medium-chain triglycerides, and complex proteins, breast milk is well tolerated in infants with SBS.
There are no randomized controlled trials comparing the outcomes between breast milk and formula in infants with SBS. If there are concerns for persistent feeding intolerance, protein allergy, or increased risk of NEC, hydrolyzed protein or amino acid–based formula can be used. In a retrospective study involving 32 patients with SBS, those who received either breast milk or amino acid–based formula had shorter durations of parenteral nutrition. Medium-chain triglycerides do not require emulsification and esterification; these are converted to free fatty acids and can be directly transported to the liver by portal circulation, even in states of pancreatic deficiency. For this reason, formulas high in medium-chain triglycerides are often preferred. However, long-chain triglycerides in the diet are also important as sources of the essential fatty acids linoleic and α-linolenic acid. In animal studies, long-chain triglycerides demonstrate more trophic effects with better mucosal hyperplasia compared with medium-chain triglycerides.
Continuous enteral feeds are achieved by either nasogastric or orogastric tube feeding, feeding gastrostomy, or jejunal tube feeding. Continuous feeds thoroughly saturate the luminal receptors and optimize the transporters, thereby promoting better digestion and absorption. Small-volume feeds provided continuously is often the strategy when feeds are introduced after recovery from postoperative ileus. However, the downsides include loss of calories to adherence of fats to the tubing, , loss of appetite, and alterations in gastrointestinal motility due to the absence of type 3 migrating motor complexes seen during fasting states. The advantages of bolus feeds include better gut motility and adaptation and better amino acid and insulin levels after the feed. Transpyloric feeds are tried in the presence of concerns for emesis and gastric distension due to gastric hypomotility.
In general, in the initial states of SBS, feedings are initiated as continuous enteral feeds at a rate of 0.5 to 1 mL/hour or 5 to 10 mL/kg/day. As tolerance to feeds is demonstrated, feeds are advanced once in 2 to 4 days by increasing the infusion rate while closely monitoring the stoma or stool output. Feed advancement is continued even if stoma or stool output of 20 to 30 mL/kg/day is noted as long as adequate weight gain and electrolyte balance are maintained. If the stool output is more than 30 mL/kg/day, feed advancement should be held, or feeds should be decreased until an improvement in stool output is noted. As one approaches the volumes of full feeds, fortification of milk should be considered to meet the growth demands.
Oral feeds should be attempted in smaller quantities when the infant shows appropriate behavioral cues. Early introduction of oral feeding facilitates the development of safe suck-swallow cycle skills and decreases the likelihood of oral aversion. Oral feeding may stimulate gall bladder contractions and release of luminal and pancreatic hormones, which promote digestion and gastrointestinal motility. Provision of parenteral nutrition during the night and bolus tube feeds during the daytime facilitates the development of oral feeding skills. For recommended energy and protein goals for complete enteral nutrition, please refer to Chapter 26 on Enteral Nutrition.
Although enteral autonomy is the ultimate goal, this should not be achieved at the expense of appropriate growth. Parenteral nutrition should be increased, resumed, or extended to augment growth when the expected growth requirements are not satisfied, even if enteral feeds are well tolerated. The goals of nutritional support in infants with SBS should meet the appropriate growth parameters as measured by weight, head circumference, and height.
Nonnutritional Strategies in the Management of Short Bowel Syndrome
Mucous Fistula Refeeding
In infants with SBS after resection of the intestines, two conduits or ostomies are often created, namely a proximal stoma and a distal mucus fistula. Mucus fistula refeeding is the practice of collecting proximal ostomy effluent and reinfusing it into the distal mucous fistula to mimic the normal physiologic intestinal flow, digestion, and absorption. In infants with ostomies, the likelihood of achieving sustained enteral autonomy without mucous fistula refeeding is very challenging and hence low. The process of mucous fistula refeeding exposes the otherwise unused portion of the intestines and colon distal to the mucous fistula to enteral feeds. This exposure of the distal intestine to stoma effluent stimulates and sustains the process of intestinal adaptation. There is emerging evidence suggesting that mucous fistula refeeding provides several advantages to the patient with IF. Mucous fistula refeeding improves the absorptive capacity of the distal bowel for nutrition, with related notable effects including an increase in weight gain, decreased electrolyte imbalance, decreased dependence on parenteral nutrition, and lower peak conjugated bilirubin levels. Although mucous fistula refeeding has emerged as the standard of care in infants with IF and ostomy, more research is required to better define the short and long-term outcomes associated with mucous fistula refeeding.
Cycling of Parenteral Nutrition
Once a steady metabolic state has been stabilized with a combination of parenteral and enteral nutrition in infants with SBS, cycling of parenteral nutrition should be initiated. Cycling parenteral nutrition has several benefits. It has been shown to decrease the risk of hyperglycemia, hyperinsulinemia, hepatic steatosis, and IFALD. In a retrospective study involving 107 infants with gastroschisis, cycling of parenteral nutrition was associated with reduced incidence of cholestasis at 25 and 50 days. However, the evidence to support the cycling of parenteral nutrition in the prevention of IFALD is weak. In a randomized clinical trial, VLBW infants who received cycling of parenteral nutrition did not demonstrate a reduction in IFALD. Importantly, cycling of parenteral nutrition during the day releases the infant from being tethered to the parenteral nutrition pole, improving mobility and physical activity, thus promoting neurodevelopment. Cycling of parenteral nutrition should be instituted before discharge from the hospital and continued at home.
Multidisciplinary Care
Multidisciplinary care of infants with SBS in a tertiary center has been shown to improve the chances of achieving enteral autonomy. , , Multidisciplinary care brings together expertise from various specialties such as neonatology, surgery, gastroenterology, nursing, nutrition, pharmacy, and family support. Standardization of feeding regimens, medical therapies, surgical techniques, and nursing has improved survival and decreased morbidity. In a study conducted in Canada, the outcomes from two different eras, before and after instituting multidisciplinary care, were compared. In the latter epoch, feeding protocols were standardized, prophylactic antibiotics were used, lipid was minimized, and the use of newer lipid emulsions were introduced. The era of multidisciplinary care was associated with improved outcomes, including decreased mortality, higher rates of achievement of enteral autonomy, and shorter durations of parenteral nutrition.
Medications
Advancement and tolerance of enteral feeds are often hampered by complications of SBS such as slow motility, hypermotility, hypergastrinemia, and small intestinal bacterial overgrowth. Treatment of these conditions with medications can alleviate the symptoms associated with these complications and improve the tolerance to enteral feeds. Gastroparesis and hypomotility of the small intestines have been treated with promotility agents. Erythromycin and amoxicillin-clavulanate are motilin agonists, which act on the motilin receptors in the upper gastrointestinal tract and stimulate gastric and intestinal motility. , Studies of erythromycin in infants with SBS are limited. Erythromycin failed to show significant benefits in patients with gastroschisis compared with placebo in the only randomized controlled trial. Amoxicillin-clavulanate acts on the duodenum and jejunum and is a better prokinetic medication than erythromycin. Although there are very few studies of amoxicillin-clavulanate in infants with an intact gastrointestinal system, there are no studies in infants with SBS. Antidopaminergic medications such as domperidone and metoclopramide and serotoninergic agents such as cisapride are avoided in infants due to their unfavorable side effects, including tardive dyskinesia and cardiac arrhythmia, respectively. , Opioid medications used as antidiarrheal agents include loperamide and diphenoxylate, to treat hypermotility in infants with SBS. Small intestinal bacterial overgrowth is a common complication of short bowel syndrome associated with decreased transit times, seen in hypomotility and blind intestinal loops. Antibacterial agents such as metronidazole, amoxicillin-clavulanate, and trimethoprim-sulfamethoxazole are often used to treat small intestinal bacterial overgrowth. The GLP-2 analog teduglutide is a modulator that increases the enterocyte mass by the expansion of mucosa by crypt cell growth and reduction in enterocyte apoptosis. In a 12-week-long open-label study, infants and children who received teduglutide showed a reduction in parenteral nutrition volume and an increase in tolerated enteral feed volume with no serious adverse effects. The use of teduglutide in children less than a year old with SBS has not been studied.
Dietary Fibers
Dietary fibers act as absorbents and are of two varieties: insoluble and soluble. Both these forms work by osmotically absorbing water, slowing transit, and improving stool consistency. Examples of dietary fiber include substances such as guar gum and pectin. When dietary fiber reaches the colon in an undigested form, it is acted on by the intestinal bacteria–liberating short-chain fatty acids, which serve as metabolic fuel to the enterocytes in the colon, supporting their proliferation and growth. The use of dietary fibers in children with SBS has demonstrated a reduction in stool output, increased gastrointestinal transit time, and increased positive nitrogen balance.
Enteral Fish Oil and Lipid Supplements
Enteral lipid preparations are obtained from various sources, including plant oil, fish oil, or synthetic preparations. The benefits of enteral lipid supplementation include enhancing nutrient absorption, improving intestinal motility, promoting mucosal growth, and reducing IFALD. In experimental models of SBS, enteral fish oil supplementation improved absorption of total fat and individual fatty acids and increased the DNA content of enterocyte. , Enteral lipid also enhances the level of the hormone peptide YY that slows motility, lengthening the transit time and resulting in increased mucosal contact with the nutrients. The use of enteral lipid in infants with SBS is promising and deserves more research.
Probiotics
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The data on probiotics in children with SBS dependent on parenteral nutrition are limited. The altered gut permeability and dysmotility in SBS increase the risks for bacterial translocation and subsequent bacteremia with the use of probiotics. The use of probiotics in animal models of SBS has demonstrated an increase in villus length, crypt depth, and increase in enterocyte count in the jejunum but not the ileum. Saccharomyces boulardii in rat models of SBS has been demonstrated to reduce bacterial translocation along with having trophic effects on the mucosa. The data regarding the use of probiotics in infants with SBS are restricted to observation studies and case reports. Although laboratory studies suggest potential benefits, observations of bacteremia in infants with SBS treated with probiotics raise serious concerns. In one account, two patients with SBS and cholestasis developed Lactobacillus bacteremia during supplementation with Lactobacillus rhamnosus GG . In another case series, four patients with SBS and a central venous catheter developed S. boulardii fungemia. These patients were receiving S. boulardii as a nutritional supplement to treat diarrhea. In a systematic review on the use of probiotics in infants with SBS, the authors highlighted the absence of randomized controlled trials of the use of probiotics in infants with SBS. The authors further reported that the benefits of probiotics in infants and children with SBS were inconsistent. Apart from the aforementioned adverse effects of Lactobacillus bacteremia, the authors also reported concerns for lactic acidosis. In light of the yet unproven benefits and reported concerns of bacteremia, they concluded that the current data were insufficient to support the use of probiotics in infants and children with SBS. Until evidence for safety and efficacy emerges, the use of probiotics in infants with SBS should perhaps be restricted to closely monitored research protocols.
Predictors of Successful Outcomes
Although the survival of infants with SBS has improved dramatically, the morbidity continues to be high. In a study of infants with neonatal-onset SBS, the overall survival at last follow-up exceeded 95%, and nearly 85% of infants achieved enteral autonomy. However, in infants with ultra-SBS, the achievement of enteral autonomy can be challenging and delayed. In infants with a residual bowel length <31 cm, only 50% achieved enteral autonomy at the last follow-up of 44 months. Also, in those infants with <31 cm residual bowel length, it took a median of 585 days to achieve enteral autonomy. Patient variables associated with improved outcomes include a longer length of the residual bowel, presence of ileocecal valve and colon, fewer infections, and use of breast milk or elemental formula. , , ,
Future Directions
The advances in the past two decades in the nutritional management of SBS have improved the outcomes tremendously. The survival is high, and the rates of intestinal and liver transplants are low. This vast improvement in outcomes is widely attributed to the multidisciplinary care in highly specialized centers, wide use of newer-generation lipid emulsions, and better infection-control bundles. Although the mortality is low, morbidity is still high, stressing the need for improvements in the care of infants with SBS. Because residual bowel length is a crucial variable on the outcomes of infants with SBS, advances in surgical techniques resulting in retaining longer bowel lengths are needed. Although newer-generation lipid emulsions have vastly improved the outcomes of infants with SBS, the search for the ideal intravenous lipid emulsions is not over. Current development of the newer generation of lipid emulsions includes further depletion of phytosterols, enhancing antioxidant properties, and optimizing the n-3:n-6 ratio. The hope is to generate a lipid emulsion with the optimal balance of fatty acids, readily metabolized, with a reduced oxidative stress and antiinflammatory profile promoting a better long-term neurodevelopmental outcome. The use of intestinal growth modulators such as GLP-2 has not been adequately studied, particularly in infancy, and can improve outcomes significantly. The use of probiotics in animal models with SBS is promising and deserves further study in closely monitored trials in infants with SBS. The beneficial effect of probiotics observed in preventing NEC and the benefits noted in animal models of SBS raises the possibility of similarly improved infant outcomes. Finally, there is an urgent need to address the lack of an evidence base for the current practices of intestinal rehabilitation. The current treatment strategies are mainly experience-based rather than evidence-based. In particular, with the increasing availability of donor breast milk and evolving technologies with lacto-engineering, there is an urgent need to determine the best choice of enteral feeding in infants with SBS. Studies that promote the development of evidence-based therapeutic approaches are needed.
REFERENCES
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