Short bowel syndrome in infancy: recent advances and practical management

Abstract

Short bowel syndrome (SBS) is a rare condition characterised by extensive loss of intestinal mass secondary to congenital or acquired disease. The outcomes are determined by dependency on parenteral nutrition (PN), its possible complications and factors that influence intestinal adaptation. In order to achieve the best results, patients should be managed by a specialised multidisciplinary team with the aims of promoting growth and development, stimulating intestinal adaptation and preventing possible complications. This involves timely surgical management aimed at rescuing maximum bowel length and eventually re-establishing intestinal continuity where appropriate. A combination of enteral and parenteral nutrition needs to be targeted towards maintaining a balance between fulfilling the nutritional and metabolic needs of the child while preventing or at least minimising potential complications. Enteral nutrition and establishment of oral feeding play a fundamental role in stimulating bowel adaptation and promoting enteral autonomy. Other measures to promote enteral autonomy include the chyme recycling in patients where bowel is not in continuity, autologous gastrointestinal reconstruction and pharmacological treatments, including promising new therapies like teduglutide. Strategies such as lipid reduction, changing the type of lipid emulsion and cycling PN are associated with a reduction in the rates of intestinal failure–associated liver disease. Even though vast improvements have been made in the surgical and medical management of SBS, there is still lack of consensus in many aspects and collaboration is essential.

Key points.

• Management of short bowel syndrome (SBS) involves using enteral and parenteral nutrition to meet metabolic requirements while preventing complications, with interventions to promote enteral autonomy.

• Blenderised diet is increasingly being used as an alternative to commercially available formulas in children dependent on enteral tube feeding and may have a role in improving enteral tolerance in SBS.

• Teduglutide has shown promising results in decreasing parenteral nutrition dependency, but its effects are not sustained on discontinuation of treatment.

• Chyme recycling can be beneficial in promoting bowel adaptation and subsequent enteral autonomy, but adequate training is needed to avoid complications associated with this technique.

• Phytosterols contained in soybean oil lipid emulsion (SOLE) are implicated in development of intestinal failure–associated liver disease and mixed lipid emulsions with doses of SOLE <1 g/kg/day associated with reduced risk.

• Oral aversion is associated with poorer quality of life and increased parental anxiety, and can be avoided with early intervention from the multidisciplinary team.

• SBS has a huge impact on the mental health of the patients and their families and early support is necessary to improve outcomes.

Introduction

Short bowel syndrome (SBS) is a reduction in functioning bowel length, secondary to surgical resection or congenital absence of bowel. The severity of malabsorption is determined by length and quality of remaining bowel, necessitating a varying degree of support with enteral and parenteral nutrition (PN). The most common cause is surgical resection secondary to necrotising enterocolitis (26%), followed by gastroschisis (16%), congenital atresias (10%), volvulus (9%), intestinal aganglionosis (4%) and others (18%).¹ Eighty per cent of cases develop in the neonatal period, with estimated incidence around 0.02%–0.1% among all live births and 0.5%–2% of all neonatal intensive care admissions.²

The key aspects of management focus on maintaining fluid and nutrient balance to ensure adequate growth and promoting intestinal adaptation, while minimising risk from complications related to aetiology or long-term PN.

Outcomes

Paediatric SBS is a complex condition with variable outcomes based on aetiology, residual bowel length, dependence on PN and associated comorbidities such as presence of intestinal failure–associated liver disease (IFALD) or episodes of catheter-related blood stream infections (CRBSIs). The survival on long-term PN has improved and nearly three quarters of children on long-term PN are expected to be alive at 15 years.³ Causes of death include hepatic failure (62%), lack of venous access (19%), sepsis (10%) and others (10%).⁴ Several studies have tried to define factors that influence survival and ability to wean off PN. The task is difficult due to the rarity and heterogeneity of the condition in terms of aetiology, severity and life expectancy of the patients.⁵ Risk factors thought to contribute to the high morbidity and mortality of SBS include the length of remaining small bowel, sepsis, loss of the ileocaecal valve (ICV) and development of IFALD.⁶ Residual bowel length can predict the probability and timing of weaning.⁷ In term neonates, ≥15 cm of remaining small intestine with an ICV or 40 cm without an ICV is associated with a favourable outcome.⁸ As there is rapid elongation of the small bowel in the third trimester, in preterm infants small bowel length ≥10% can predict eventual weaning off PN.⁹ The type of residual bowel is another important factor with ileum having a better ability to adapt, and so the length of bowel needed for PN weaning is less when compared with jejunum.¹⁰ The presence of ICV was another factor considered over the years to improve outcomes in SBS by preventing the retrograde migration of colonic bacteria into the small bowel and additionally by slowing the transit time.¹¹ Nevertheless, recent studies have challenged the idea that ICV itself is a predictor of outcome and more likely is associated with the presence of a remaining terminal ileum and colon.⁹

Management of SBS

In order to achieve the best outcomes, patients with SBS have to be managed by a specialised multidisciplinary team.¹²

The initial surgical management is aimed at rescuing the maximum length of bowel by excising only the damaged intestine and keeping any viable part in situ. This can also involve a ‘second-look’ procedure within 24 hours for reassessment if the viability is in doubt.¹³ In some cases, the use of a temporary mesh and delayed abdominal closure can reduce the risk of abdominal compartment syndrome and subsequent bowel loss.¹⁴ Following the acute phase, re-establishing the intestinal continuity through stoma closure should be the surgical goal wherever possible. This allows better absorption of fluids and electrolytes, reduces risk of PN-associated cholestasis¹⁵ and decreases PN dependence by generating additional energy.¹⁶

The clinical presentation and subsequently the nutritional management of SBS can be divided into three stages¹⁷ (figure 1). The intestinal adaptation can start 48 hours after resection and can continue for up to 18 months and will depend on the prognostic factors already discussed.¹⁸

Figure 1.

Stages in the management of intestinal failure. PN, parenteral nutrition.

Parenteral nutrition

PN is usually started in the immediate postoperative period to provide adequate calorific and nutrient intake to optimise growth and development. European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines provide recommendations on how to start and monitor PN.^19–22 A central venous access is required and all attempts should be made to use peripherally inserted central venous catheters for as long as possible, as adopting a central vein preservation approach will increase the likelihood of successful long-term PN if needed.²³ When peripheral access is exhausted or home PN is required, the best choice will be a cuffed tunnelled central venous catheter (CVC).²³ Long-term PN needs to be targeted towards maintaining a balance between metabolic needs and potential complications. A well-balanced energy supply of proteins, carbohydrates and fats is essential to sustain growth. Nutritional requirements can be estimated in most cases based on the corrected age, degree of undernutrition and underlying disease. Approximately 75% of non-protein calories should be provided as carbohydrate and 25% as fat. Glucose infusion rates should not exceed oxidation rates, which vary with age, weight and phase of illness.²² Amino acids are essential for protein accretion and their requirements can vary depending on age—in preterm infants can be as high as 4 g/kg/day coming down to around 1 g/kg/day after 1 year of age.²⁰ Patients with SBS are at risk of vitamin, mineral and electrolyte deficiencies and require frequent monitoring.

Enteral nutrition

Enteral feeding has a fundamental role in stimulating bowel adaptation, leading to enteral autonomy. With practices based on experience rather than evidence,¹⁷ it is thought that composition, timing and advancement of enteral feeds all play a part.²⁴ It is important to maximise the amount of enteral nutrition by choosing a feed that is well tolerated and promotes adaptation. The literature unanimously supports human milk as the preferred feed choice due to the glutamine and growth factors that promote gut adaptation.²⁵ There is no evidence supporting the use of hydrolysed feed over whole protein feed to improve enteral tolerance.²⁶ There is the potential for significant malabsorption of carbohydrates especially lactose, so feeds with a glucose polymer as main carbohydrate source are likely to be better tolerated. Formulae containing a combination of medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) are helpful as MCT is absorbed directly across the enterocyte membrane and LCT is required to promote adaptation and deliver essential fatty acids.²⁷ In the absence of breast milk, limited lactose, whole protein/partially hydrolysed formulas with a combination of MCT and LCT and low osmolality provide the best of both worlds.²⁸

There is consensus in the literature that early introduction of enteral feeds is associated with reduced duration on PN and hospital stay.²⁹ How enteral feeds should be administered in terms of oral versus tube feeding and continuous or bolus feeds continues to be debated,¹⁷ although wherever possible the most physiological mode of feeding should be chosen. Feeds administered in a continuous manner are thought to maximise enteral adaptation and absorption due to maximising the contact time the gut has with luminal nutrients.³⁰ However, lack of fasting periods can be detrimental to intestinal bacterial clearance and hinder the development of oral feeding.¹⁷ In addition, oral feeding also stimulates epidermal growth factor from saliva which is important for bowel adaptation.²⁵ In order to benefit from each method, common practice uses a combination of feeding methods, that is, overnight continuous feeding with oral feeding/bolus in the day.²⁴

Infants with SBS are often dependent on artificial nutrition in early life putting them at risk of developing oral aversion and disordered eating due to lack of a hunger–satiety pattern. Other contributing factors include adverse early oral experiences, prolonged periods of nil by mouth, lack of structured mealtimes, delayed weaning and social factors like quality of parent–child relationship. This is associated with poorer quality of life³¹ and increased parental anxiety.³² Early intervention of the multidisciplinary team with strategies such as early introduction of oral feeds, non-nutritive oral motor exercises, increased participation in family mealtimes, messy play therapy and assessment and management of parental anxiety helps in prevention.³³

For those who cannot feed orally, there has been growing interest in the use of family blended diet administered via a gastrostomy feeding tube as it is deemed more natural than commercial feeds. A study by Samela et al successfully converted 10 patients with intestinal failure, over 1 year of age, to full blended diet. This resulted in more formed and less frequent stooling with 90% of the sample tolerating blended diet exclusively and growing adequately after 1 year. The success of this study may have been aided by the fact 80% of the sample had their colon intact.³⁴ The BLEND study successfully transitioned 17 out of 20 chronically ill tube-dependent children onto blended diet and found improved bacterial diversity.³⁵ This could be of value as children with SBS often have altered gut microbiome.³⁰ Sample sizes remain small and more studies are needed to fully establish whether this is a safe feeding approach for children with intestinal failure as there are concerns around hygiene and tube blockage.²⁵

Measures to promote enteral autonomy

The end goal for all children with SBS is enteral autonomy; that is, to be free from PN while maintaining adequate growth and development. Children with SBS often reach a point of saturation with their enteral tolerance or a resting state where continuing to advance feeds becomes counterintuitive due to excessive stool output or electrolyte imbalances. The aim is to provide minimal PN while sustaining adequate growth. The following measures help improve bowel function and promote enteral autonomy:

• Chyme recycling (mucous fistula refeeding) involves instillation of proximal ostomy contents into a mucous fistula/distal enterostomy. Unfortunately, there is a lack of standardised and high-level evidence regarding this intervention in literature.³⁶ Described benefits included weight gain and normalisation of fluid balance with PN reduction and even cessation by improving the distal gut absorption and maturation,³⁷ and subsequently a reduction in PN complications like cholestasis.³⁸ Other advantages of refeeding are the resolution of discrepancy between proximal and distal bowel, prevention of disuse atrophy, and a reduction in anastomotic complications such as leakage or strictures.³⁹ Other studies have questioned the safety of the technique due to possible complications like leakage, effluent reflux and tube dislodgement,³⁶ but even more severe ones—bleeding, bowel perforation and death—have been described.⁴⁰ In addition, from a microbiology point of view, pathogenic bacteria can proliferate in the chyme from the proximal stoma and potentially increase the risk of sepsis⁴¹ if the bag content is recycled after more than 90 min. The decision about refeeding has to be discussed thoroughly by the medical staff and caregivers and adequate training has to be implemented in order to reduce complications.

• Treatment of small intestinal bacterial overgrowth (SIBO)—shortened bowel length increases the risk of SIBO by presenting a higher load of unabsorbed carbohydrates. The risk is further increased by factors such as intestinal dysmotility or absence of the ICV. The presentation is usually in the form of increased stool frequency, abdominal distension or reduced feed tolerance and in severe forms with D-lactic acidosis. The diagnosis can be confirmed by hydrogen/methane breath testing, measurement of serum D-lactate levels, urine 4-hydroxyphenylacetic acid levels and culture of duodenal juice. The management of SIBO should be centred on identifying and correcting underlying causes, treating the overgrowth and addressing the nutrition deficiencies where detected.⁴² Interventions with limited evidence include lowFODMAP diet, antibiotics and probiotics.⁴³ Antibiotic therapy is the cornerstone in SIBO treatment. Rifaximin, a semi-synthetic, rifamycin-based non-systemic antibiotic, is increasingly being used as the first line in children because of low gastrointestinal absorption and a good antibacterial activity. It is used in doses of 10–30 mg/kg/day in children under 8 years and 600 mg/day >8 years for 5 to 28 days.^44–46 Improvement in symptoms and normalisation of hydrogen breath test was seen in >60% of patients treated.⁴⁴ Other possible options are gentamicin, metronidazole, ciprofloxacin and others alone or in combination.⁴⁷

• Gastric acid hypersecretion is common in patients with SBS and proton pump inhibitors or histamine type 2 receptor antagonists are commonly used for treatment.

• Children with SBS have diarrhoea due to abnormal anatomy resulting in rapid small bowel transit which can slow enteral progression. Treatment is often via opioid receptor agonists such as loperamide which slows intestinal motility, increasing transit time.⁴⁸

• Bile acid–binding resins (eg, colestyramine) can be of benefit in patients with SBS to treat diarrhoea caused by bile salt malabsorption.⁴⁸

• A few studies of recombinant human growth hormone alone or in combination with glutamine have been published in PN-dependent children with SBS. Despite some decrease in PN requirements during treatment, these trials showed little benefit on mucosal absorption long term.⁴⁹ Teduglutide, a glucagon-like peptide 2 (GLP-2) analogue, has given promising results, as it has been shown to promote villous growth and thus decrease the need for PN. A 12-week, open-label study concluded that teduglutide was well tolerated and was associated with trends towards reductions in PN requirements and advancements in enteral feeding.⁵⁰ However, the effects of teduglutide are reversible therefore lost when the drug is stopped. Finally, other trophic factors such as EGF and insulin-like growth factor-1 in children with IF and SBS are in early stages of trial to asses efficacy.

• Surgical options in patients with long-term IF, also named autologous gastrointestinal reconstruction, include the longitudinal intestinal lengthening and tailoring (LILT or Bianchi) procedure and serial transverse enteroplasty procedure (STEP). These should only be performed after maximisation of medical management in an attempt to achieve intestinal autonomy. Many publications have compared the procedures and overall the weaning rate is better for LILT although STEP seems easier to be performed and can be used in very short segments, including duodenum.⁵¹ The early complications are fewer for STEP, but long-term complications are similar for both.⁵² Other procedures in this group include simple tapering enteroplasty that can easily manage excessive bowel dilatation in the presence of an adequate bowel length and spiral intestinal lengthening and tailoring, a very recent technique that could be an easy and more physiological alternative to the existing procedures.

Complications of SBS

Children with SBS have a higher morbidity and are at risk of complications either because of their primary aetiology or as a result of therapeutic interventions.

Nutritional complications

Shortened bowel length increases the risk of generalised pervasive nutritional inadequacy or deficiency of specific nutrients. Factors such as poor intake, malabsorption and small intestinal bacterial overgrowth play a role. Body composition is altered and malnutrition with chronic catabolic state leads to sarcopenic obesity associated with poorer long-term outcome.⁵³ Routine monitoring of body composition is therefore recommended.⁵⁴

A proportion of children develop low bone mineral density as a consequence of reduced calcium intake, low vitamin D levels and physiological adaptation to chronic disease state. Regular assessment of bone mineral content is advised with DEXA scans and early treatment should be offered where indicated.⁵⁵

Surgical complications

As a result of surgery and bowel resection in early life, there is an increased risk of long-term surgical complications:

1. Bowel obstruction can be a consequence of surgery and is secondary to luminal narrowing or adhesions, presenting with reduced feed tolerance, abdominal distension or loose stools. These symptoms can sometimes be difficult to differentiate from general worsening of the bowel function delaying the diagnosis.²

2. Anastomotic ulcer can present as chronic iron deficiency anaemia or overt gastrointestinal bleeding. Aetiology is likely multifactorial as a consequence of bowel ischaemia, gastric hypersecretion and small intestinal bacterial overgrowth. Diagnosis is made on ileocolonoscopy or small bowel capsule endoscopy. Treatment is empirically with antibiotics to treat overgrowth, proton pump inhibitors and bile acid sequestrants (colestyramine). A significant proportion do not respond to medical therapies and need endoscopic interventions, for example, argon plasma coagulation or dilation of strictured bowel and if that fails, surgical revision of anastomosis.⁵⁶

3. Stomal complications include prolapse or retraction, prestomal obstruction, excoriation of peristomal skin and ischemia.

CVC-related problems

The problems associated with central lines include infections, mechanical damage, blockages and thrombosis. Infections are the the most common complication with incidence <1 per 1000 PN days.⁵⁷ Prevention is based on optimal catheter placement and catheter care with strategies like use of bactericidal line locks, barrier caps and minimising access to line. Taurolodine has shown a significant reduction in the number of CRBSI when compared with heparin or saline locks without a difference in occurrence of mechanical complications,⁵⁸ but does not seem to be effective in reducing the biofilm or catheter colonisation.⁵⁹ Ethanol too has a positive effect in preventing CRBSI when compared with heparin,⁶⁰ but seems to be associated with increased rates of mechanical complications and subsequently of catheter replacement.⁶¹

Intestinal failure–associated liver disease

The prevalence of IFALD is reducing in all patients on long-term PN including those with SBS. Aetiology is multifactorial and risk factors include prematurity and low birth weight, duration of PN, lack of enteral feeding, recurrent sepsis, inadequate calorie or nutrient intake, and deficiencies of essential fatty acids. In a recent retrospective study on 279 hospitalised children receiving long-term PN, 22% developed IFALD and 4% progressed to end-stage liver disease.⁶² Phytosterols contained in soybean oil lipid emulsion (SOLE) have been found to have a major contribution to IFALD and doses of SOLE >1 g/kg/day have been associated with increased risk of IFALD.⁵⁹ SMOFlipid (mixture of soya bean oil, medium-chain triglycerides, olive oil and fish oil) has shown to cause less liver damage when used long term. Omegaven (pure fish oil lipid emulsion) has been used as rescue therapy in established severe liver disease, but long-term use is debated as it does not contain recommended amounts of essential fatty acids (table 1). Cycling of PN has also shown to be a protective factor for IFALD compared with continuous infusion. In patients with established IFALD, mortality continues to be high and is the main indication for intestinal transplantation.

Table 1.

Comparison of different types of lipids in prevention of IFALD

Author	Lipid formulation used	Population setting	Results
Rayyan et al 63	SMOF vs SOLE	53, neonates	SMOF more hepatoprotective than SOLE
Lam et al 64	SMOF vs SOLE	40, children	SMOF causes less liver damage with long-term use
Diamond et al 65	SMOF vs SOLE	24, infants	Following 8 weeks of use, lower conjugated bilirubin levels seen with SMOF
Gura et al 66	FOLE vs SOLE	18, children	Reversal of cholestasis was nearly 5 times faster with FOLE
Premkumar et al 67	FOLE vs SOLE	97, children	Resolution of cholestasis in a median duration of 40 days with FOLE
Nandivada et al 68	FOLE vs SOLE	30, children	Biochemical improvement of liver disease seen within first year of therapy with FOLE, with improved growth and reduction in PN dependence
Calkins et al 69	FOLE vs SOLE	10, children	Reduced cholestasis in FOLE group compared with SOLE with resolution in 75% by 17 weeks
Wang et al 70	FOLE vs SOLE	48, children	FOLE is effective as rescue strategy in IFALD as it reduces cholestasis, but this is reversed after changing back to SOLE
Matsumoto et al 71	FOLE	7, liver explants	Despite reduction in cholestasis, portal fibrosis persisted
Belza et al 72	FOLE	6, children	Despite reduction in cholestasis, fibrosis persisted with FOLE

FOLE, fish oil lipid emulsion; IFALD, intestinal failure–associated liver disease; PN, parenteral nutrition; SMOF, mixture of soya bean oil, medium-chain triglycerides, olive oil and fish oil; SOLE, soybean oil lipid emulsion.

Nephrolithiasis

Colonic absorption of oxalate in children with SBS results in hyperoxaluria and risk of renal oxalate stones. Ingested oxalate is normally bound to intraluminal calcium, but in patients with SBS, as calcium is bound to unabsorbed fatty acids, it is not available for excretion of oxalate which then gets absorbed in the colon and excreted by the kidneys.

Emotional well-being

Living with SBS has a significant impact on mental health and quality of life of children and their families. Anxiety and depression are more prevalent in carers of children on home PN, with 65% of parents having elevated levels of anxiety and 30% raised depression levels. They are especially high in children on PN due to SBS and those having concomitant enteral tube feeds. Stress levels in this group are also higher than other similar populations reported in the literature including parents of children with inflammatory bowel disease, cancer, diabetes, obesity, sickle cell disease and bladder exostrophy.³² Early assessment and support is required to improve long-term outcome.

Conclusion

The management of SBS is multifaceted and presents considerable challenges. Even though outcomes have improved with improvement in management strategies and development of novel treatments, there still is lack of evidence and consensus in many aspects of the medical and surgical management. There is a need for increased national and international collaboration to help improve outcomes.

Ethics statements

Patient consent for publication

Not required.