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Parenteral Nutrition: “The Scar Remains”

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A recent study (KM Gura et al. J Pediatr 2021; 230: 46-54. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study) provides multicenter data comparing fish oil emulsion (FOLE) (Omegaven) with a historical control of soybean emulsion (SOLE) (Intralipid). The FOLE group was enrolled between 2004-2018; the SOLE group had data from 1999-2012.

Key points:

  • Among FOLE recipients (n=189), 65% experienced cholestasis resolution vs 16% of SOLE recipients (n=73) (P < .0001).
  • The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) 
  • Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245).

My main criticisms of the study:

  1. While the methods explain that FOLE received 1 gm/kg/d, compared with 3 gm/kg/d for SOLE, this was NOT reviewed in the discussion. This is quite important in terms of proving that one product is preferred over the other. With lipid toxicity, it would be expected that delivering 3 times as much would be more damaging on the liver.
  2. The discussion does not discuss the potential neurological consequences of lipid minimization/lower doses of lipids. In the same Journal of Pediatrics issue, Bell et al report that 77% of SBS in their cohort of extremely premature infants with short bowel syndrome had moderate-to-severe neurodevelopmental impairment (related blog post: Neurodevelopmental Impairment in the Majority of Extremely Premature Infants with Short Bowel Syndrome)
  3. The discussion has only a single sentence regarding the change in care between the eras of SOLE and FOLE: “Additional limitations include a relatively small sample size and changes in surgical, medical, and nutritional practice between the 2 eras that could not be controlled for this study.”
  4. Also, the discussion omits the development of other FOLE alternatives (eg. SMOFlipid) which has been a very important advance in the management of patients with SBS.

The commentary by Samuel Kocoshis (J Pediatr 2021; 230: 11-12) provides a good deal of insight. The title and first paragraph provides some interesting historical context: (full text) “Even When the Would Is Healed, the Scar Remains” “The above maxim was coined by the Roman author Publilius Syrus when referring to wounds of most tissues or body parts.1 Because hepatic regeneration was recognized (as evidenced by the story of Prometheus’s liver being eaten daily by an eagle only to regenerate the next day) in Syrus’s time, his dictum was too far too simplistic when applied to the liver. One must delve more deeply into the mechanism of liver injury to ascertain just when hepatic scaring persists or when it disappears.”

My take: This study illustrates harm reduction with the change in lipid administration. The development of new lipid products has made a huge difference in the outcomes of children with short bowel syndrome.

Related blog posts:

“Pediatric Formula Basics”

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CHOA Nutrition Support Core Seminar -Thanks to Kipp Ellsworth for organizing this series and sharing content. This lecture is a really good review and would be a great place to start when discussing formulas with medical students and residents.

Link to Webex (49 min): “Pediatric Formula Basics” by Clancy Bryant, MS, RD (March 2, 2021). Password: FbhSgup5

Also, can reach via: Our first Nutrition Support Core Lecture of 2021: “Pediatric Formula Basics” by Clancy Bryant, MS, RD-20210302 1810-1

Key points:

  • This lecture reviewed selection of formulas for infants, children and adolescents; some of the most common formula choices (but not all) were reviewed
  • This talk reviewed reflux guidelines as reflux symptoms often impact decisions on formula choice in infancy. Thickened formulas like Enfamil AR and Similac Spit Up do not work with acid suppression medications.
  • WIC resources (for children <5 years) -can identify through website: https://dph.georgia.gov/WIC/wic-formula-resources
    • WIC script requires 2 ICD-10 diagnosis which are relevant to chosen formula
    • For standard formula, no prescription is needed; if formula is not on WIC formulary, it will not be covered
    • If child is NPO, write for “patient is NPO, please give maximum formula”
  • For cholestatic liver disease: high MCT formulas include pregestamil (55%), Alimentum (33%) and elemental formulas (33-49%)
  • For chylous effusions, very high MCT formulas (83%, 84%) include enfaport and monogen (needs EFA supplementation)
  • Formulas for children and adolescents come in concentrations of 0.6 kcal/mL to 2.0 kcal/mL
    • Reduced calorie formulas (eg. Pediasure Reduced Calorie or Compleat Pediatric Reduced Calorie) are helpful to provide adequate micronutrients/protein in children with hypocaloric needs
  • Blenderized formulas often helpful for children with retching (when given via gastric route); some of these may increase vitamin A levels and beta-carotene (eg. Nourish, Compleat Pediatric Organic Blends). Real food blends are not nutritionally-complete. Harvest is able to run through enteral tube without dilution.
    • For those older than 10 years of age, Liquid Hope is similar to Nourish and Compleat Organic Blends is similar to Compleat Pediatric Organic Blends
  • Low electrolyte formulas, like Renalcal and Renastart, may be useful for children with kidney dysfunction. Corresponding formulas for >10 years of age include Suplena and Novasource Renal
  • Kate Farms is often a good choice for patients with multiple allergies or eosinophilic esophagitis

Some of the slides:

Formulas for 1-10 years of age.

Adult formulas (>10 years):

Related blog posts:

Paradoxical Chronic Recurrent Multifocal Osteomyelitis (CRMO)

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A recent case series (A Cordesse et al. JPGN Reports; 2020. November 2020 – Volume 1 – Issue 2 – p e007doi: 10.1097/PG9.0000000000000007. Chronic Recurrent Multifocal Osteomyelitis in Pediatric Crohn Disease, A Paradoxical Effect to Antitumor Necrosis Factor Alpha) reported on paradoxical Chronic Recurrent Multifocal Osteomyelitis (CRMO) which I have seen in one of my patients as well.

Key points:

  • In patients receiving anti-TNF agents which are usually effective for CRMO, CRMO may develop paradoxically and may be associated with a psoriaform reaction.
  • At the time of diagnosis of paradoxical reaction, all patients were in remission due to anti-TNFα efficiency. Trough levels of anti-TNFα were in the expected range, and there were no anti–anti-TNFα antibodies.
  • All patients recovered after discontinuation of infliximab (n = 2) or adalimumab (n = 1). 

My take: This study describes a rare adverse effect of anti-TNFα agents. If CRMO develops while on one of these agents, an alternative treatment is needed.

Hellebores

More Data Supporting Lactated Ringers for Acute Pancreatitis

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A Lee et al. Gastroenterol 2021; 160: 955-957. Lactated Ringers vs Normal Saline Resuscitation for Mild Acute Pancreatitis: A Randomized Trial

PK Garg et al. Gastroenterol 2021; 160: 655-59. Full text (editorial) Optimum Fluid Therapy in Acute Pancreatitis Needs an Alchemist

Key findings from this double-blind randomized controlled trial (n=121):

  • ICU admissions were 9.8% in LR group compared with 25% of NS group (RR 0.4, CI 0.2-0.9)
  • Quicker discharge with 44% at 72 hrs in LR group compared with 28% in NS group
  • Median length of stay was 3.5 days (LR group) compared with 4.6 days (NS group)

Critique of study from editorial: “The strengths of their study include a well-designed protocol, reasonable sample size and inclusion of patients within 8 hours of diagnosis; thus, fluids were administered during the critical period when there is a window of opportunity to restore the intravascular volume and maintain adequate tissue perfusion. However, the study included patients with mild pancreatitis. Another issue is that the benefit shown was for secondary outcomes and, thus, these results should be taken as exploratory and hypothesis generating.”

My take: For now, lactated ringer’s is the fluid of choice in individuals with acute pancreatitis.

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Stratifying Risk of Clots in Inflammatory Bowel Disease

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T Naito et al. Gastroenterol 2021; 160: 771-780. Full text: Prevalence and Effect of Genetic Risk of Thromboembolic Disease in Inflammatory Bowel Disease

Background: 10% of healthy subjects are genetically at high risk for thromboembolic disease (TED). For adults with inflammatory bowel disease, TED is “largest cause of mortality in
patients”

Key findings:

  • In total, this retrospective study had 792 IBD patients who had both whole-exome sequencing and genotyping data to identify thrombophilia pathogenic variants. 122 of 792 IBD patients (15.4%) as genetically high risk for TED.
  • Genetic TED risk was significantly associated with increased TED event (odds ratio,2.5; P ¼ .0036).
  • Patients with high TED genetic risk more frequently had thrombosis at multiple sites (78% vs 42%, odds ratio, 3.96; P ¼ .048)

“Our analyses demonstrate that approximately 1 in 7 patients with IBD have odds 2.5 times higher than nongenetically high-risk patients with IBD for experiencing TED.” The risk of TED in IBD is generally 3- to 4-fold higher than the general population

My take: In children, the risk of clots is much lower than in adults. Thus, the potential to identify those at highest risk would be useful in order to target interventions. Also, patients at higher risk for TED may affect choice of treatment (eg. avoiding JAK inhibitors).

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From The Onion:

From The Onion

How a Gluten Challenge Could Change

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A recent randomized double-blind study (MM Leonard et al. Gastroenterol 2021; 160: 720-733. Full Text: Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial) provide evidence that a gluten challenge could detect evidence of celiac disease in hours, not weeks.

This study consisted of 14 adults with biopsy-proven celiac disease (CD) who were randomized to 3 g or 10 g gluten/day intake for 14 days. Each participant underwent extensive studies to detect histological, visible, and biochemical changes associated with gluten introduction. Data required multiple endosopic duodenal biopsies, VCEs and blood collection.

Key findings:

  • Symptoms and plasma interleukin-2 levels “increased significantly or near significantly at both doses.”
  • Interleukin-2 appeared to be the earliest, most sensitive marker of acute gluten
    exposure. IL-2 increases were observed 4 hours after exposure in patients with CD but not in healthy controls.
  • Intestinal damage is more complex and requires a longer duration and higher dose of gluten exposure. In this study, the higher dose (10 g) of gluten exposure was required for enteropathy within the study time frame.

My take: These study findings need to be confirmed in a broader patient cohort. However, in patients needing a gluten challenge, IL-2 response after a single-dose (measured at 4 hours) could be helpful. Those without IL-2 response are unlikely to have CD. Those with an IL-2 response at 4 hours, could confirm CD by completing a gluten challenge.

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Polyurethane vs Silcione with Ethanol Locks

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Prior recommendations for ethanol locks have favored silicone central lines over polyurethane due to concerns of increased breakage rates when ethanol locks are used with polyurethane catheters. However, a recent small study indicates that this may be incorrect.

K LaRusso et al. JPEN https://doi.org/10.1002/jpen.2056. Prolonged Use of Ethanol Lock Prophylaxis With Polyurethane Catheters in Children With Intestinal Failure: A Single‐Center Experience (Reference from Conrad Cole’s twitter feed)

A 10‐year retrospective study with 10 children comprising 85 CVCs and 13,227 catheter days

Key findings:

  • Breakages were the most common complication: polyurethane 1.46/1000 vs silicone 3.76/1000 catheter days. Silicone catheters had a significantly higher breakage rate (adjusted rate ratio [RR], 2.86; 95% confidence interval [CI], 2.84–2.88; P < .001)
  • Polyurethane catheters had higher rates of occlusion (adjusted RR, 0.14; 95% CI, 0.07–0.28; P < .001) and displacements.
  • There were no differences in the overall catheter replacement rates and any other catheter‐related outcomes.

Related blog post: Central Line Pointers

From The Onion:

from The Onion

1. When You Are Fully Vaccinated 2.Outcomes of Duodenal Atresia and Stenosis

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  1. CDC Recommendations: When You’ve Been Fully Vaccinated
  2. GS Bethell et al. JPGN 2021; 72: 239-243. One-year Outcomes of Congenital Duodenal Obstruction: A Population-based Study

This prospective observational study provides helpful outcome data for infants (n=80) born with congenital duodenal obstruction (CDO).

Key findings (also see infographic below):

  • Though there was an 8.4% overall mortality, there were no deaths directly attributed to CDO. 69% had associated anomalies.
  • Median length of stay after repair was 20 days; at 28 days following repair, 76% had been discharged home
  • Failure to achieve full enteral feeds was NOT related to CDO (due instead to other gastrointestinal anomalies). Mean time for full feeds was 13 days post-op; 90% reached full enteral feeds at 28 days.
  • Repair type: 80% had duodenoduodenostomy, 14% had duodenojejunostomy, the others: membrane incision (n=1), membrane resection (n=2), and duodenoplasty (n=2)

My take: This data will inform clinicians of expected outcomes in this population. I hope this cohort is followed long-term to provide more information about long-term outcomes including frequency of pancreatitis.

Must-Read: How to Handle Post-Procedure Fevers

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A recent study (JM Boster, M Iwanowski, RE Kramer. JPGN 2021; 72: 250-254. Management of Pediatric Postendoscopy Fever: Reducing Unnecessary Health Care Utilization With a Clinical Care Guideline) provides clear guidance for how to handle post-procedure fevers.

Using a prospective database with 27,100 endoscopies, the authors evaluated a clinical care guideline to reduce unnecessary medical care following endoscopy.

Key findings:

  • Post-endoscopy fever (PEF) occurred in 0.55% (n=150)
  • ONLY 6 of these 150 PEFs (0.4%) were attributed to a procedure complication: 3 had perforations (all with abdominal pain), 2 had aspiration (both had emesis at time of endoscopy) and 1 had a positive blood culture (though had undergone a liver biopsy as well as endoscopy)
  • The authors published their care guideline (Figure 1) which stratifies risk based on whether the procedure was an interventional (high risk) vs diagnostic (low risk), ASA class, duration of fever, concomitant immunosuppression (eg. steroids), and associated symptoms including vomiting, diarrhea, bleeding, new abdominal pain, impact on activities of daily living, and hydration
  • Interestingly, the authors note that their cohort had a total of 23 perforations, but only 3 presented with fever
  • Using the care guideline resulted in a “significant shift in the prevalence of Grade 2 and above (requiring hospital use) to Grade 1 (clinical observation and reassurance) adverse events, dropping ED visits and admissions by 43.6% and 76.4% respectively for the post-endoscopy fever patients.” This shift was not associated with any observed negative patient outcomes or missed diagnoses.

My take: The authors note that fever is often related to release of inflammatory cytokines which can occur with endoscopy in the absence of complications. The authors methodical guideline to post-procedure fever provides a logical approach to this common problem.

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Short Bowel Syndrome -YouTube Information

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Some good patient educational videos for short bowel syndrome:

Related article: AE Wiskin et al. Clin Nutrition 2021; https://doi.org/10.1016/j.clnesp.2020.12.029. Prevalence of Home Parenteral Nutrition in children Key finding: In 2019, 389 children received HPN (home parenteral nutrition) in the UK; this is nearly double the number last reported in 2012 and is a prevalence of 30 per million children (Thanks to Kipp Ellsworth for this reference)

Other resources:

Related blog posts for Short Bowel Syndrome: