Advancements in Pediatric Intestinal Failure: Innovative Therapies and Improved Outcomes
With Dr. Stephanie Oliveira & Dr. Paul Wales · hosted by Dr. Lizzie Lee
Educational content from recorded physician discussions — not medical advice. Talk to your (or your child's) care team about your situation.
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What the experts said
Intestinal failure is defined as the reduction of functioning intestinal mass below that which can sustain life, resulting in dependence on supplemental parenteral support for a minimum of 60 days within a 74 consecutive day interval.
More than 50% of intestinal failure cases are related to short bowel syndrome, with additional cases from mucosal enteropathies and dysmotility disorders.
Most causes of short bowel syndrome in pediatrics occur during the neonatal period, including gastroschisis, necrotizing enterocolitis, bowel atresia, and intestinal volvulus.
The field is now focusing on neurocognitive outcomes, quality of life, and caregiver burnout as more children survive intestinal failure.
The cause of chronic intestinal inflammation in intestinal failure survivors is not known.
Intestinal rehabilitation treatment strategy lacks clear-cut guidelines because every patient is unique with different gestational age, bowel resection, anatomy, and comorbidities.
The goal of intestinal rehabilitation is to optimize intestinal function and adaptation before the development of irreversible complications.
Intestinal adaptation is an active compensatory process that starts immediately after bowel resection.
Food, bacteria, and hormones in the gut are important factors that enhance intestinal adaptation.
Enteral autonomy is defined as getting off TPN with all nutrition going to the gut, either by mouth or by feeding tube.
From 2010 to 2015, a repeat study with double the number of patients showed approximately 50% still reached enteral autonomy, but the number of transplants and deaths significantly decreased.
The establishment of multidisciplinary teams is one factor that changed outcomes in intestinal failure.
Predictors of reaching enteral autonomy include residual bowel length (more is better), follow-up at an institution with an intestinal rehabilitation program, and no STEP procedure.
Patients should be referred to intestinal rehabilitation programs when not making progress, on prolonged TPN, or have significant comorbidities, preferably sooner rather than later.
Patients should not be referred to intestinal rehabilitation when several irreversible complications have already occurred and transplant is the only remaining option.
Intestinal transplantation is considered when there are irreversible complications, though the number of transplants has significantly decreased over the last several decades.
Liver disease associated with intestinal failure ranges from mild cholestasis to profound steatosis (in older children/adolescents/adults), with progression through inflammation, fibrosis, and ultimately cirrhosis leading to death or transplantation.
Risk factors for intestinal failure-associated liver disease include prematurity, lack of enteral feeding, inability to feed due to anatomy, recurrent infections/sepsis, and components of TPN.
The term 'intestinal rehabilitation program' was coined in the year 2000.
Intestinal rehabilitation teams improve outcomes through integration of care, improved communication, and better continuity.
Intestinal rehabilitation programs rely heavily on speech, language, and occupational therapy specialists.
While patients are on TPN, the goal is to mitigate progression of liver disease, sepsis, and vascular complications.
Families of intestinal failure patients manage significant tasks at home including running TPN pumps, adding vitamins, programming pumps, recording ins and outs, managing G-tubes, and managing stomas.
High-quality families demonstrate evidence of burnout over time despite education and empowerment efforts.
Literature shows intestinal rehabilitation programs improve survival related to liver dysfunction, decrease septic episodes, reduce central line complications, reduce ICU admissions, and enable patients listed for transplant to come off the list due to improved status.
Mortality in intestinal failure has decreased with intestinal rehabilitation programs.
Lipids in parenteral nutrition are a source of essential fatty acids, a non-protein energy source important for growth, and fatty acids have a major role in cellular pathways.
Historically, most lipid emulsions in North America are soybean-based with high phytosterol content, high omega-6 long-chain polyunsaturated fatty acid content, and low antioxidant content.
Prolonged soybean-based lipid exposure is associated with deterioration of liver function, specifically cholestasis.
For every day an infant is exposed to soybean lipid dosed at greater than 2.5 g/kg/day, there is a 3% increase in the odds ratio of developing advanced liver disease.
First-generation lipid emulsions were soybean-based, rich in omega-6 PUFA (such as Intralipid), and have been in use for 40 years.
Third-generation lipid emulsions reduce omega-6 component and change the omega-6 to omega-3 ratio by adding omega-3 lipids.
Omega-6 lipids are metabolized to arachidonic acid, which produces leukotrienes and prostaglandins with a more pro-inflammatory profile.
Omega-3 lipids are metabolized through EPA and DHA, leading to production of cytokines with a less inflammatory profile.
Omega-3 lipids improve bile flow by decreasing lithogenicity of bile, decreasing steatosis, stimulating improved beta-oxidation and clearance, lowering oxidative stress, and supporting immune function.
The two main strategies for improving lipids in parenteral nutrition are lipid minimization and change in composition.
Literature dating back decades shows that restricting exposure to soybean lipid improves cholestasis, particularly when dosed at 1 g/kg/day or less.
In preterm babies, fat is important for growth, especially for neurocognitive development, creating a risk of essential fatty acid deficiency if lipid dosing is restricted too much.
DHA and arachidonic acid are important for retinal and brain development.
None of the current lipid emulsions were designed for premature babies; they were all designed for adults in critical care settings.
Work is currently underway with industry to create a lipid emulsion specifically tailored to preterm babies with higher arachidonic acid content.
Central lines are the lifeline for intestinal failure patients, and without venous access, families cannot be supported.
Central lines are at risk for complications including infections, blockages, thrombosis, and breakage.
In the United States, there are approximately 240,000 central line-associated bloodstream infections (CLABSIs) annually, with each costing about $30,000, totaling approximately $2 billion per year nationwide.
The team pivoted to 4% tetrasodium EDTA (Taurolock/Kitelock) when ethanol became too expensive and difficult to obtain.
4% tetrasodium EDTA (Kitelock) is antithrombotic, anti-fibrinolytic, and antimicrobial, satisfying all three criteria important for a good lock solution.
Kitelock is licensed in Europe and Australia but not available in the United States.
A multi-center randomized trial of Kitelock versus heparin went live 4 weeks ago and is actively recruiting patients, with results expected within the next year.
In short bowel syndrome, there are three anatomical subtypes: Type 1 (high jejunostomy), Type 2 (loss of distal small bowel/ileum and part of colon with small bowel-colonic anastomosis), and Type 3 (loss of mid-small bowel with retained ileum and intact colon).
The most common anatomical subtype of short bowel syndrome in pediatrics is Type 2.
Type 1 and Type 2 short bowel syndrome patients struggle because they lack an ileum.
Native GLP-2 hormone has a half-life of 7 minutes, making it impractical for clinical use.
GLP-2 has been altered by one amino acid to create an analog called teduglutide, which has a half-life of 2 hours and is given once daily by subcutaneous injection.
A multi-center phase 3 study published in 2020 at Cincinnati Children's showed patients receiving teduglutide had a 40% reduction in TPN fluid and calorie requirements over a six-month period.
70% of patients who received teduglutide achieved the study endpoint of a 20% reduction in TPN requirements.
Teduglutide is licensed for children greater than 1 year of age.
Teduglutide has made a big difference in practice, with even children with very extreme anatomy able to get off TPN.
Another GLP-2 analog, apraglutide, has a longer half-life and can be given once weekly.
Apraglutide works even better than teduglutide, producing more bowel lengthening.
These interventions (optimized lipids, central line infection prevention, GLP-2 analogs) have led to a decrease in transplantation since 2008.