#NASPGHAN19 Intestinal Failure Session Part 1

Here are some notes and a few slides from NASPGHAN’s plenary session.  There could be errors of transcription in my notes.

Benjamin Gold, NASPGHAN president and part of our GI group, GI Care For Kids, welcomed everyone to the meeting.

Link to NASPGHAN_Annual_Meeting_Program 2019

John Kerner  Potential Role of New Fat Emulsions

Key points:

  • Both SMOFlipid and Omegaven help prevent and/or treat parenteral nutrition associated cholestasis.
  • SMOFlipid is much less expensive (see slide below) -50 gm of SMOFlipid ~$5 compared to 10 gm of Omegaven at $35, thus omegaven costs more than 30 times SMOFlipid.
  • Though SMOFlipid is not FDA approved in children, it is being used widely and allows for increased calories compared to lipid minimization with intralipid and could improve neurocognitive outcomes.
  • SMOF dosing (listed below) with goal of 3 g/kg in preterm infants.
  • Resolution of cholestasis does not mean reversal of cirrhosis.  Thus, lipid emulsion intervention at earlier stage may be important.

Bram Raphael  Getting In Line: Towards a Clinical Practice Guideline For CVC Salvage

Key points:

  • Several infections are very difficult to clear, especially yeast, enterococcus, and pseudomonas
  • Salvaging central lines may obviate the need for multi-visceral transplant which carries a 5-year ~50% mortality rate
  • Cefepime provides good gram-negative coverage; consider meropenem in those with septic shock

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SMOFlipid vs. Intralipid for Intestinal Failure Patients

A recent study (C Belza et al. JPEN 2019; https://doi.org/10.1002/jpen.1692) showed that SMOFlipid reduced the frequency of cholestasis in intestinal failure patients. Thanks to Kipp Ellsworth for reference.

An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure–Associated Liver Disease in Infants With Intestinal Failure. From Abstract:

Methods

This was a retrospective cohort study of infants with IF with a minimum follow‐up of 12 months in 2008–2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels…

Results

Thirty‐seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z‐scores were improved for patients receiving SMOFlipid at 3 months (−0.932 vs −2.092; P = 0.028) and 6 months (−0.633 vs −1.614; P = 0.018).

Related blog posts:

Crater Lake, OR

SMOF Neurodevelopmental Data Looks Good –In Five Years We’ll Know More

A recent study (C Binder et al. J Pediatr 2019; 211: 46-53) examined electrophysiological brain maturation in a randomized double-blinded controlled trial of SMOF lipid compared to soybean lipid emulsion for extremely low birth weight (ELBW) premature infants. This was a prespecified secondary outcome analysis of a randomized trial of 230 infants (2012-2015).

It is recognized that the ELBW infants have very little nutritional reserve.  In addition, DHA which is transferred to the fetus in high amounts in the last trimester is absent from parenteral soybean lipid emulsions.  Thus, the authors explored whether SMOF lipid which is a mixture of lipids (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and  15% fish oil) and contains DHA would have a favorable effect on neurocognitive outcomes.

In this study, the authors examined amplitude-integrated electroencephalography measurements (aEEG)  to assess neurodevelopment. Both groups received similar lipid dosing, SMOF 2.2 g/day and Soybean 2.1 g/day.

Key findings:

  • Among the available 121 infants in the subgroup with aEEG (n=63 SMOF, n=58 soybean), maximum maturational scores on aEEG were achieved 2 weeks earlier in the SMOF group (36.4 weeks vs 38.4 weeks, P<.001).

Limitation:

  • aEEG is a marker of neurocognitive development; however, more adequate outcomes of  neurodevelopmental progress are needed. The authors plan to follow these infants up to 5 years of age.

My take: This study is very favorable for the use of SMOF lipids in premature infants.  — SMOF lipid emulsion by itself may improve neurocognitive outcomes. In addition, clinicians are more likely to provide adequate amounts of lipid calories with SMOF as compared to soybean emulsion which is often restricted to minimize liver injury.  Giving adequate lipid calories is also likely to enhance neurological outcomes.

Related blog posts:

Incredibly blue waters of Crater Lake, Oregon -from Wizard Island

 

Double-Blind Randomized SMOFLipid Study

A recent double-blind randomized study (A Repa et al. J Pediatr 2018; 194: 87-93) compared a mixed lipid emulsion (SMOFlipid) to a soybean-oil lipid in 223 extremely low birth weight infants. Median time on parenteral nutrition was ~23 days.

Key findings:

  • The primary outcome of parenteral nutrition associated cholestasis (PNAC) was NOT significantly different in the two groups: 10.1% for SMOF and 15.9% for control group (P=.20).
  • No other outcome measures were affected, including ROP, BPD and growth.

The authors note that even the control group had less cholestasis than previous cohorts and indicated that the use of probiotics and possibly more aggressive enteral feeds were at work.

My take (borrowed in part from authors): These results “cannot be generalized to infants with substantially longer time on PN.” However, this study shows that SMOFlipid alone will not prevent cholestasis, which is well-known to be multifactorial.

Sandy Springs

#NASPGHAN17 Presentations at Annual Meeting: GGT in PSC, Nutrition for Intestinal Failure

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Improvement in GGT Predicts Event-free Survival in Primary Sclerosing Cholangitis Regardless of Ursodeoxycholic Acic Treatment. 

Mark Deneau et al. (Grand Watkins Prize).

Key points:

  • PSC is difficult to study due to its rarity and due to its slow progression; thus surrogate biomarkers are needed.
  • Alkaline phosphatase is not a good biomarker in children
  • GGT level at one year after diagnosis was predictive of prognosis
  • Ursodeoxycholic acid does not appear to be effective

Optimizing Nutrition in Intestinal Failure

Justine Turner, University of Alberta

Key points:

  • Human milk is an ideal “formula” for infants, including those with intestinal failure
  • Oral feedings are important
  • Combination of bolus feeds and continuous feeds is reasonable
  • SMOFlipid allows higher lipid dose administration without hepatoxicity; this may improve cognitive outcomes
  • Amino acid based formulas have higher osmolality which can contribute to diarrhea

Patients with >50% of small bowel and >50% of colon were most likely to achieve enteral autonomy (GIFT registry)

 

 

NASPGHAN Postgraduate Course 2017 (Part 3): Biliary Atresia, NAFLD, SMOFlipid, Pancreatic Pain

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017

Biliary Atresia: Update on diagnostic and prognostic biomarkers and therapeutic interventions

Cara Mack    Children’s Hospital of Colorado

Key points:

  • 84% of biliary atresia is isolated; 16% are syndromic with other defects
  • Direct bilirubin is (mildly) elevated at birth in patients with biliary atresia
  • Total bilirubin 3 months after Kasai predicts outcome. If <2 mg/dL, then unlikely to need a transplant in the first 2 years of life.
  • Reviewed biomarkers including Th1, Autotaxin, IL-8

Therapeutic interventions:

  • Nutritional support. Better nutrition improves outcomes after liver transplantation.
  • Fat soluble vitamin supplementation
  • Cholangitis prevention. Some studies have shown that prophylactic antibiotics may reduce incidence of cholangitis.
  • No therapeutic interventions that delay progression of this disease

 

 

CHILDREN Cohort Mgt of Vitamin Supplementation

Steroids are not helpful after Kasai procedure

Diagnosis and Management of Pediatric NAFLD 2017

Stavra Xanthokos   Cincinnati Children’s Hospital Medical Center

Key points:

  • NAFLD is #2 cause of liver transplantation in adults and on its way to becoming #1
  • ALT is still the best screening tool; NASPGHAN guidelines recommends screening overweight/obese children 9-11 years of age
  • Ultrasound has poor sensitivity and specificity for NAFLD; it is helpful for detecting gallbladder disease
  • Bariatric surgery has been effective for NAFLD

 

SMOFlipid and the Pediatric Patient

Peter Wales  Hospital for Sick Children (Toronto)

Slides are not available in syllabus

Key points:

  • Improving outcomes noted in the intestinal failure population
  • Dr. Wales reviewed proposed improvements with Omega-3 lipids -less cholestasis, less hepatitis, and less fibrosis
  • Compared improvements with lipid minimization (1 g/kg/day) compared to newer agents: omegaven and SMOFlipid. Additional studies are needed due to limitations of previous studies
  • Discussed SMOFlipid vs. Intralipid trial at 5 centers in Canada. N=24.
  • At SickKids: SMOFlipid for all preterms at admission & for term infants after 2 weeks of PN. Dosing 2-2.5 g/kg & now accounts for 85% of lipid usage at institution
  • None of the lipid products were designed for preterm infants. Intralipid has a pediatric indication and other products are used off label
  • Lipid restriction probably affects brain size/development; thus, a lipid agent that allows for higher doses likely will be beneficial for developmental outcomes.  The retina can be used as a biomarker of the brain affects of lipids.

Painful Chronic Pancreatitis: Management/therapeutic interventions

Vikesh Singh  Johns Hopkins University School of Medicine

Slides are not available in syllabus