Tag Archives: short bowel syndrome

Rehabilitation for Short Bowel Syndrome

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As noted in several blog posts, there have been some important advances in the care of short bowel syndrome (SBS)/intestinal failure (IF) patients which have resulted in improved outcomes.  A recent review of 28 children with ≤20 cm of small bowel has been published (J Pediatr 2013; 163: 1361-6, editorial 1243) and provides tangible evidence of these changes.

This retrospective study reviewed the charts of these children managed at Omaha’s intestinal rehabilitation program.  7 patients had NEC, 6 intestinal atresia, 6 had gastroschisis, 3 omphalocele, 5 had malrotation, and 1 patient had vascular disease.

Key results:

  • 27 survived (96%)
  • 14 (50%) had at least one lengthening procedure; in this cohort, bowel lengthening was not associated with a greater rate of adaptation than native bowel.
  • 13/27 (48%) achieved parenteral nutrition independence (“nutritional autonomy”) with their native bowel.
  • Predictors of “successfully rehabilitated” patients: intact colon and ileocecal valve
  • All patients had improvements in lowering PN requirements, total bilirubin, and growth z-scores.
  • Serum transaminase levels did not improve in the nonrehabilitated patients

The main medical treatments at IRP include use of agents for control of bacterial overgrowth, reducing gastric acid production, lipid minimization, promotility and antimotility agents (eg. loperamide), and ethanol locks.  The editorial comments on the “poor results” for surgical intervention, “particularly among those with ultra-short bowel.” This may be due to ‘marginal motility, ischemia, severe wall thickening, or due to adhesions.’

With regard to ethanol locks, the editorial supports them but states, “the main factor in prevention [of line infections] has been maintaining a consistent and strict protocol for catheter care.”

Previous related blog entries:

Drug Shortages and Selenium Deficiency

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If you participate in the care of patients who are dependent on parenteral nutrition, then you are familiar with frequent component drug shortages.  Generally, attempts to manage these shortages involve rationing and targeting those with the greatest need.  In one institution, this was not effective in preventing biochemical deficiency of selenium (JPEN 2013; DOI 10.1177/0148607113486005).  Thanks to Kipp Ellsworth for this reference.

The authors describe five pediatric patients who were completely dependent on parenteral nutrition due to intestinal failure.  During a 9-month shortage of intravenous selenium, all five who were previously selenium replete had deficiency identified (level <20 ng/mL).

After these deficiencies were identified, the patients were placed on Multitrace-5 (MTE-5).  This multivitamin contains 20 mcg/mL of selenium.  While patients prior to the shortage typically received 50-75 mcg/day, after instituting MTE-5, they received 10-26 mcg/day.  Nevertheless, this helped prevent any clinical evidence of deficiency.  In patients with selenium deficiency, there is an increased risk of cardiomyopathy, chronic illness, and death.

The authors note that their preference is to individually dose the specific trace elements and that MTE-5 can contribute to elevated levels of manganese and chromium with long-term usage.

Related blog links:

Related references:

  • -Gastroenterol 2009; 137: S61-S69.
  • -J Pediatr 2011; 159: 39.

Fish Oil, IFALD, and Liver Fibrosis

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While there has been a lot of enthusiasm for the use of fish oil as a potential breakthrough for intestinal failure-associated liver disease, this has been based largely on the use of surrogate markers of liver disease and based on comparisons with the historical use of conventional intravenous lipids.  The latter problem has been discussed before on this blog (see links below).

A recent study begins to address the issue of surrogate markers by reinforcing the viewpoint that improvements in bilirubin and aminotransferases may not translate into improvement in liver fibrosis or other clinically-meaningful outcomes (JPGN 2013; 56: 364-69).  A previous pediatric study (J Pediatr 2010; 156: 327-31) showed failure of regression of hepatic fibrosis in 2 children receiving FOE therapy.

In this study, the authors sequentially examined 6 children on fish-oil lipid emulsions (FOE) who underwent multiple liver biopsies.  In this cohort, 5 of 6 children had gastroschisis and the mean gestational age was 35 weeks.  Median intestinal (small bowel) length beyond the ligament of Treitz was 26 cm and most children retained about 2/3rds of their colon.  Liver biopsies were obtained at the time of other open abdominal operations (eg. serial transverse enteroplasty, stoma takedown).

Key results:

  • Liver fibrosis persisted in 2 cases, progressed in 3 cases, and regressed in 1 case.
  • Histology and biochemistries indicated improvement in cholestasis and inflammation.
  • One patient has weaned off parenteral nutrition, two patients underwent isolated small bowel transplantation due to recurrent line infections, and three patients receive 25-40% of their calories parenterally.

The biggest limitation of this study besides the small number of enrolled patients was the relatively short  time period that was studied.  Only one patient who was studied had data reported for FOE more than 36 weeks.  The oldest age of any patient at the time of their last biopsy was 131 weeks old.

Take-home points:

  • “There is no direct evidence to support any one [proposed theoretical benefit of FOE] as clinically meaningful as yet.”
  • “Lipid minimization strategies are also effective in reducing cholestasis.”
  • “Many of the biopsies taken right at the time of FOE initiation” showed significant fibrosis which “speaks to how quickly fibrosis can develop.” One child had stage 2 fibrosis at 14 weeks of life.
  • “The biochemical resolution of cholestasis is at best a weak surrogate marker ..for…enteral independence and overall survival.”  “These findings make a strong case for early referral of children with short bowel syndrome to specialized intestinal rehabilitation centers.”

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Copper in Cholestasis

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More data indicate that copper levels in infants receiving parenteral nutrition are usually not affected by cholestasis (JPEN 2013; 37: 92-96).

A retrospective study reviewed all patients younger than 1 year who had copper levels measured between 1999-2009 at Riley Hospital for Children.  Inclusion criteria: parenteral nutrition for at least 50% of caloric needs and cholestasis (direct bilirubin >2 mg/dL).

Key findings:

  • 26 of 28 patients had gastrointestinal disorders.  82% were receiving standard parenteral nutrition (PN) dose of copper (20 mcg/kg/day).
  • Only one elevated copper level was found in a child with congenital heart disease.
  • 46% (n=13) of cholestatic infants had low copper levels.  Three of theses infants had no copper in their PN.
  • There was no correlation between bilirubin level and measured copper values.

Bottomline:

Measure copper values periodically in patients requiring parenteral nutrition.  Most patients, even cholestatic patients, will require standard dosing but some will need less and some more.

Additional References:

  • -JPGN 2010; 50: 650-54.  n=28.  (only 2 had elevated Cu). Typical Cu supplementation in HAL did not lead to significant increase in Cu toxicity or worsening of liver disease in cholestatic infants.  Study prompted by single infant who developed Cu deficiency/anemia.
  • -Clin Gastro & Hepatol 2004; 2: 1074. Two patients with Cu deficiency after bariatric surgery
  • -JPGN 2000; 31: 102-111. (review)

Green beans for short gut syndrome

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A recent article indicates that the addition of green beans may improve diarrhea and reduce dependence on parenteral nutrition (Adding Dietary Green Beans to Formula Resolves the Diarrhea …) (ICAN. DOI: 10.1177/1941406412469403). Thanks to Kipp Ellsworth for pointing out this reference on his twitter feed.

This small retrospective study of 18 infants examined the addition of green beans to the diet of infants with short bowel syndrome (SBS) (1 jar of stage 2 baby food green beans to every 8 ounces of 30 cal formula).  The average gestational age of the patients was 32 weeks (range 23-39 weeks) and the average birth weight was 1938 gram.  Nine patients had NEC, four had gastroschisis, two had Christmas tree defect, and three had other reasons for either SBS or intestinal failure.  The IF group (n=10) was defined as being dependent on parenteral nutrition to meet nutritional needs; the SBS group (n=8), who were more severely affected, was defined as the malabsorptive state that follows a massive resection.

Products that were used:

  • Gerber Natural Select: 3 gm of fiber per 4 ounce
  • Beach-Nut Homestyle: 2 gm of fiber per 4 ounce
  • HyVee Mother Choice: 2 gm of fiber per 4 ounce
  • These products average 32% soluble and 68% insoluble fiber

While the authors note that they use only amino-acid based formulas currently, at the time of the study, 61% were receiving Peptamen Junior.

It is not clear in the manuscript exactly at what age green beans are introduced. However, a previous case study suggested addition of green beans at ~4 months or >44 weeks postconception.  This prior case study indicated that adding stage 2 green beans changed the caloric density of 30 cal formula to 22 cal/ounce (Nutrition in Clinical Practice 2005; 20: 674-77).  In addition, this adds 2 gm/kg/day of fiber.

Results from current study:

  • 9 of 10 IF patients were able to discontinue parenteral nutrition
  • 2 of 8 SBS patients were able to discontinue parenteral nutrition
  • All infants had improvements in stool consistency, typically within 24 hours of dietary change.

While the authors acknowledge the limitations of the study, they hypothesize that the reason for improvement is due to the fiber content of green beans.   Fermentation of dietary fiber produces short chain fatty acids (SCFAs) which in turn have a trophic effect on the mucosa and enhance nutrient absorption.

Studies have shown that adults with IF or SBS have improved stool consistency with the addition of fiber.  However, the authors note that there have been no studies documenting the effectiveness of dietary fiber in the pediatric SBS/IF population.

Whether green beans would outperform other sources of fiber like pectin, guar gum, bananas or benefiber is not clear.

Additional references/links:

Are we missing Vitamin B12?

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This is the question that I wonder after reading a recent review (NEJM 2013; 368: 149-60) -especially since effective treatment is readily available.

While vitamin B12 deficiency is most common in individuals 70 to 80 years, it affects all age groups.  A particularly vulnerable group are infants of mothers with vitamin B12 deficiency.  These infants may be born with deficiency or it may develop if exclusively breast-fed, usually between 4 and 6 months of age.  Indications of this deficiency include failure of brain development, poor growth, hypotonia, and feeding difficulties.  Some infants develop tremors, lethargy, and hyperirritability.  Imaging may show atrophy and delayed myelination.

Mothers who are at most risk:

  • unrecognized pernicious anemia
  • history of gastric bypass
  • short gut syndrome
  • long-term vegetarian or vegan diet

Other pediatric conditions that cause B12 deficiency: ileal resections, Imerslund-Grasbeck syndrome (Imerslund–Gräsbeck syndrome (selective vitamin B12 malabsorption ..), inflammatory bowel disease, and pernicious anemia.

Other Key Points from this review:

  • B12 deficiency causes reversible megaloblastic anemia, demyelinating neurologic disease or both
  • B12 deficiency is the major cause of hyperhomocysteinemia in countries with folate-fortified food and contributes to a risk of vascular disease and thrombosis
  • Autoimmune gastritis (pernicious anemia) is the most common cause of severe deficiency (in adults).  Tests to determine underlying reason for B12 deficiency include the following: anti-intrinsic factor antibodies (must be checked off treatment for at least 7 days), anti-parietal cell antibodies -both help detect pernicious anemia, gastrin level (high level) & pepsinogen I (low levels) both suggestive of atrophic gastritis.  The Schilling test of radioactive B12 is no longer available.  Endoscopy is frequently performed in adults with B12 deficiency.
  • Methylmalonic acid (MMA) is the best indicator for untreated B12 deficiency; MMA >400 nmol/L has 98% sensitivity for B12 deficiency.  Other causes of increased MMA include renal failure and volume depletion.
  • Serum B12 has poor sensitivity and specificity -though performs adequately at higher cut-off value (<350pg/mL has 90% sensitivity)
  • Many individuals require lifelong treatment with either parenteral B12 or high-dose oral tablets (see article for dosing recommendations)

Additional references:

  • -J Pediatr 2010; 157: 162.  B12 deficiency in newborns –especially if mother has had bariatric surgery or vegan diet.
  • -J Pediatr 2001; 138: 10 (review) At risk for deficiency: strict veggie, abnl absorption (gastric resection, pernicious anemia), long term PPI, bacterial overgrowth, ileal disruption (Crohn’s), or ileal receptor d/o (Imersund-Grasbeck),  inborn B12 metabolism d/o

Clinical Sx: FTT, weakness, anorexia, neuro/psych sx, macrocytic anemia, pancytopenia, glossitis, vomit/diarrhea

Dx: low vit B12, incr methylmalonic acid & incr homocysteine.  MMA specific for B12; homocysteine incr also if folate deficient.

If Vit B12 deficient, reason for this needs to be determined.

Teduglutide for Short Bowel Syndrome

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More data on teduglutide indicate its potential for short bowel syndrome (SBS) (Gastroenterol 2012; 143: 1473-81, editorial 1416-20).  Treatments for SBS are needed.  One year of parenteral nutrition often costs the health care system in excess of $100,000 per year.  This cost does not account for laboratory studies, health care visits, complications, and hospitalizations.  Treatment of intestinal failure with transplantation “may cost upwards of $1 million.”

In this study of adult patients with an average of 50 years, teduglutide was given in a prospective randomized double-blind study to 42 patients and another 43 patients received placebo. The dose of 0.05 mg/kg/day via subcutaneous injection was chosen based on a previous trial which showed that a higher dose was less effective.  Among these patients, the most common reasons for SBS were vascular disease (34%), Crohn’s disease (21%), volvulus (11%), and injury ((9%).

Bottom line:

  • Teduglutide over a 24-week study was more effective than placebo.  63% of study patients had a drop in parenteral nutrition requirement of more than 20% compared with only 30% of the placebo group.
  • The mean reduction in parenteral nutrition support of teduglutide-treated patients was 4.4 L/week compared with 2.3 L/week for placebo-treated patients.
  • Citrulline, a biomarker of mucosal mass, was increased in the teduglutide group.  In the treatment group, citrulline increased by 20.6 μmol/L compared with 0.7 μmol/L for the placebo group.

How does teduglutide work?  Teduglutide is a much more stable analog of glucagon-like peptide-2 (GLP-2).  The latter is released by the distal small bowel and colon.  GLP-2 promotes intestinal epithelial growth and increases transit time.

What are the adverse effects of teduglutide? First, there is a concern that teduglutide could promote colonic adenomas based on studies in mice.  GLP-2 receptors are present in the lung, and brain (including hypothalamus); its effects in these areas is poorly understood.  In addition, abdominal pain, distention, nausea, peripheral edema, and nasopharyngitis were more common in the treatment group. The long-term consequences of teduglutide therapy are not known.

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