NAVIGATING PARENTERAL

NUTRITION:

UPDATES ON THE LATEST

Amy Sacapano, MS RD CSPCC CNSC

Bone Marrow Transplant RD, Clinical Dietitian III

Children’s Hospital Los Angeles

Disclosures

• None to declare

1

Learning Objectives

1. View available electronic PN resources

2. Review PN components - Concerns for deficiencies

- How to deal with shortages

3. Discuss differences in Injectable Lipid

Emulsions (ILE)

4. Discuss gut microbiome changes

associated with PN

2

3

PROFESSIONAL RESOURCES

AT YOUR FINGERTIPS

4

5

A.S.P.E.N. Clinical App

https://apps.apple.com/us/app/a-s-p-e-n-clinical-app/id1081990652 Accessed July 2019

6

7

Pediatric RD app

https://www.med.umich.edu/pfans/services/umhspediatricapp.html Accessed July 2019

8

Pediatric RD app

https://www.med.umich.edu/pfans/services/umhspediatricapp.html Accessed July 2019

ASPEN Website: nutritioncare.org

9

10 http://www.nutritioncare.org/PNResources/ Accessed July 2019

ASPEN Website: nutritioncare.org

11

SmartPN Education Resources

12 http://www.nutritioncare.org/smartpn/ Accessed July 2019

PN Nutrition Care Pathway

13 https://www.nutritioncare.org/SmartPN_Pathway.aspx Accessed July 2019

14

PN Care Pathway

https://www.nutritioncare.org/SmartPN_Pathway.aspx Accessed July 2019

Disease States

15

Neonate Pediatrics Adolescents/Adults

In the critical care

setting regardless of

diagnosis

When EN is unable

to meet energy

expenditure and

growth

When intestinal

tract is not

functional

When intestinal

tract cannot be

accessed

When nutrient

needs for growth

are greater than

what can be

provided by oral

intake or EN

support alone

• Do not use PN

based solely on

medical diagnosis

or disease state

Worthington, P. et al “When Is Parenteral Nutrition Appropriate?” JPEN Vol 41 No 3 March 2017. pp 324-377. DOI:

10.1177/0148607117695251

When is PN Preferred?

Neonate and Pediatrics Adolescents/Adults

When EN is not feasible or

insufficient to meet total nutrient

needs

When EN is contraindicated or

patient unable to tolerate

adequate EN or lacks sufficient

bowel function to maintain or

restore nutrition status for

patient who are

Malnourished

At risk for malnutrition

16

Worthington, P. et al “When Is Parenteral Nutrition Appropriate?” JPEN Vol 41 No 3 March 2017. pp 324-377. DOI:

10.1177/0148607117695251

When is EN not feasible?

Neonate and Pediatrics Adolescents/Adults

A clear contraindication to EN,

such as intestinal injury and

perforation

Assess intestinal function and

perfusion, as well as overall

hemodynamic stability

Evaluate clinical factors derived

from history, physical examination

and diagnostic evaluations

17

Worthington, P. et al “When Is Parenteral Nutrition Appropriate?” JPEN Vol 41 No 3 March 2017. pp 324-377. DOI:

10.1177/0148607117695251

Timing of PN

Neonate Pediatrics Adolescents/Adults

Very Low Birth Weight

(VLBW) infant,

birthweight <1500g

Begin PN promptly after

birth

More mature preterm

infants or critically ill

term neonates

Use clinical judgement

assessing:

- hemodynamic

stability

- intestinal function

- intestinal perfusion

- Nutritional status

When evident that patient

will not tolerate full oral or

EN intake for an extended

period

Infants:

Within 1-3 days

Older children:

4-5 days

For patients

Well-nourished and stable

unable to receive 50% or

more of estimated

requirements PO or by EN

After 7 days

Nutritionally-at-risk and

unlikely to achieve

desired oral or EN intake

Within 3-5 days

Baseline moderate or

severe malnutrition when

oral or EN intake is not

possible or sufficient

As soon as feasible

Severe metabolic

instability

Delay until condition

has improved 18

Worthington, P. et al “When Is Parenteral Nutrition Appropriate?” JPEN Vol 41 No

3 March 2017. pp 324-377. DOI: 10.1177/0148607117695251

Elements of Appropriate PN Use

• Identify clinical indication of PN, including manifestations of acute and

chronic intestinal failure

• Recognize situations in which PN is not likely to be of benefit

• Initiate PN based on gastrointestinal function, nutrition status, and clinical

status

• Select the vascular access device best suited to the therapy planned

• Implement measures to promote safety and reduce adverse outcomes

• Evaluate response to therapy

• Adjust in the therapeutic plan based on ongoing monitoring

• Assess continued need for PN

• Transition promptly to oral or enteral nutrition as feasible

• Collaborate across disciplines and departmental boundaries

19

ASPEN DOSING GUIDE

20

Appropriate Dosing for PN

21 http://www.nutritioncare.org/PNResources/ Accessed July 2019

ASPEN Dosing Guide

22

ASPEN Recommendations 2012 vs Available MTE

Trace

Element

MULTI-TE PRODUCTS AVAILABLE IN U.S.

(Manufacturer Dosing Recommendations)

ASPEN

Recommendations

TEMPORARY

U.S.

IMPORTATION

Multitrace4

Neonatal®

(per 1 mL)

Multitrace-4

Pediatric®

(per1 mL)

Trace Elements

Injection 4, USP-

Pediatric ®

(per 1 mL)

Peditrace®

(per 1 mL

Zinc 1.5 mg

(0.1 mg/kg/d,

0.3 mg/kg/d

premature infants

<3 kg)

1 mg

(0.1 mg/kg/d)

0.5 mg

(0.1 mg/kg/d)

No changes (0.3 mg/

kg/d premature infants

<3 kg and 0.1 mg/kg/d

for infants/children >3

kg)

0.25 mg (0.25

mg/kg/d ≤15 kg

3.75 mg/d >15

kg)

Copper 0.1 mg

(0.02 mg/kg/d)

0.1 mg

(0.02 mg/kg/d)

0.1 mg

(0.02 mg/kg/d)

0.02 mg/kg/d 0.02 mg (0.02

mg/kg/d ≤15 kg

0.3 mg/d >15 kg)

Manganese 25 mcg

(2–10 mcg/kg/d)

25 mcg

(2–10 mcg/kg/d)

25 mcg

(2–10 mcg/kg/d)

Decrease to 1 mcg/

kg/d in neonates with

maximal daily dose in

pediatrics to 55 mcg/

day

1 mcg (1

mcg/kg/d ≤15 kg

15 mcg/d >15 kg)

Chromium

(mcg)

0.85 mcg

(0.14–0.20

mcg/kg/d)

1 mcg

(0.14–0.20

mcg/kg/d)

1 mcg

(0.14–0.20

mcg/kg/d)

Reduce dose to

recommended values and

have product available

without Cr for patients

at increased risk of

toxicity

0 mcg

23

Recommended Chromium Changes

24

Age Male Female

0–6 months 0.0006 mcg/kg/day

7–12 months 0.012 mcg/kg/day

1–3 years 0.22 mcg/day

4–8 years 0.30 mcg/day

9–13 years 0.5 mcg/day 0.42 mcg/day

14–18 years 0.7 mcg/day 0.48 mcg/day

A.S.P.E.N., American Society for Parenteral and Enteral Nutrition. Adapted from Moukarzel A, Chromium in parenteral

nutrition: too little or too much? Gastroenterology, 2009;137(5)(suppl):S18–S28, with permission from Elsevier.

ASPEN Recommendations vs. Available MTE

Trace

Element

MULTI-TE PRODUCTS AVAILABLE IN U.S.

(Manufacturer Dosing Recommendations)

ASPEN

Recommendations

TEMPORARY U.S.

IMPORTATION

Multitrace4

Neonatal®

(per 1 mL)

Multitrace-4

Pediatric®

(per1 mL)

Trace Elements

Injection 4,

USP-Pediatric ®

(per 1 mL)

Peditrace®

(per 1 mL)

Selenium 0 mcg 0 mcg 0 mcg Add with dose of 2 mcg/

kg/d

2 mcg (2 mcg/kg/d

≤15 kg

Iron -- -- -- Routine supplementation

of PN could be beneficial, but

more research is needed

especially with lipid-containing

PN

--

Molybdenum -- -- -- Insufficient data to recommend

routine administration

--

Iodide -- -- -- Routine supplementation

of PN could be beneficial, but

more research is needed

1 mcg

(1 mcg/kg/d ≤15 kg

15 mcg/d >15 kg)

Fluoride -- -- -- Routine supplementation

of PN could be

beneficial, but more

research is needed

57 mcg

(57 mcg/kg/d ≤15

kg

855 mcg/d >15

kg)

25

Vanek, V. W. et al. “A Call to Action to bring Safer Parenteral Micronutrient Products to the U.S. Market” Nutrition in

Clinical Practice. Vol. 30 No. 4. August 2015. pp 559-569. DOI: 10.1177/0884533615589992

ESPGHAN/ESPEN Recommendations

Iodine R 7.12 Iodine should be provided with PN at a daily dose of 1-10 g/kg

daily in preterms and at least 1 g/kg/day in infants and

children. (LoE 4, RG 0, strong recommendation, strong consensus)

R 7.13 Patients on long-term PN should be regularly monitored for

iodine status by measuring at least thyroid hormone concentrations

(LoE 4, RG 0, conditional recommendation, strong consensus)

Molybdenum R 7.19 Molybdenum should be provided in long term PN at a dose of

1 g/kg per day in LBW infants and 0.25 mg/kg per day (up to a

maximum of 5.0 g/day) in infants and children. (LoE 4, RG 0,

conditional recommendation, strong consensus)

26

ASPEN Recommendations 2012 Position Paper

Parenteral MVI products: Meets requirement for most PN patients.

Separate vitamin D required for patient who on standard therapy continue to be vitamin D depleted and are unresponsive to oral vitamin D supplements.

Pediatric/Neonatal Multi-trace Element (TE) products:

• Decrease manganese to 1 mcg/kg/d in neonates

• Product with no chromium

• Add selenium 2 mcg/kg/d

Parenteral carnitine products: • No change in the product but should provide 2-5

mg/kg/d to all neonates

27

ASPEN Recommendations 2012 Position Paper

Parenteral choline product: • None currently available; requires commercial development

with doses shown below Pediatric/Neonatal:

• 0-6 mo: 125 mg/d

• 7-12 mo: 150 mg/d

• 1-3 y: 200 mg/d

• 4-8 y: 250 mg/d

• 9-13 y: 375 mg/d

• >13 y 550 mg/d

Adults:

• 550 mg/d

TE contamination in all PN components combined: • Limit manganese contamination to <40 mcg/d in final PN

volume

• Limit copper contamination to <0.1 mg/d in final PN volume

28

ASPEN’s Future Research Recs

In Order of Priority

1. Parenteral chromium requirements in adult, pediatric, and neonatal PN patients

2. Research and development of appropriate monitoring strategies for trace element (TE) and vitamin deficiency and toxicity in PN patients

3. Studies on TE contamination of PN products need to be updated, particularly manganese and chromium contamination of neonatal and pediatric formulas

4. Feasibility of adding parenteral iron to PN formulas to include fat emulsion stability and other potential incompatibilities

5. Benefits of carnitine supplements of PN in adult and pediatric patients

6. Benefits of fluoride supplementation of PN in all age groups

7. Benefit of iodide supplementation of PN in all age groups

29

Vanek, V.W., et al. “A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market”

Nutrition in clinical Practice. Vol 30 No 4. August 2015. DOI: 10.1177/0884533615589992

Injectable Lipid Emulsions

30

http://www.nutritioncare.org/PNResources/ Accessed July 2019

31

Injectable Lipid Emulsions

Comparison of Available ILE Component Intralipid Omegaven SMOFlipid

Soybean oil% 100 30

MCT % 30

Olive Oil % 25

Fish Oil % 100 15

Glycerol, g/100 mL 2.25 2.5 2.5

Egg phospholipid g/100 mL 1.2 1.2 1.2

Phytosterols, mg/L 439 + 5.7 3.66 207

Vitamin E, mg/100 mL 3.8 15-30 16-23

LA,% 50 4.4 21.4

ALA, % 9 1.8 2.5

EPA % 0 19.2 3

DHA, % 0 12.1 2

ARA, % 0 1-4 0.15-0.6

32

ALA, α-linolenic acid; ARA, arachidonic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; LA, linoleic acid;

Anez-Bustillos, L. et al. “Intravenous Fat Emulsion Formulations for the Adult and Pediatric Patient: Understanding the

Differences” Nutrition in Clinical Practice. Vol. 31 No 5 October 2016 pp 596-609. DOI: 10.1177/0884533616662996

Omegaven

33

https://omegavenusa.com/home/ Accessed July 2019

https://omegavenusa.com/wp-content/uploads/2018/11/fullpi.pdf Accessed July 2019

FDA approved for pediatrics July 2018

SMOFlipid

34

https://smoflipid.com/characteristics-of-smoflipid/smoflipid-composition/ Accessed July 2019

Awaiting FDA approval for pediatrics

ILE Generation 1

35

Generation 1 (Soybean Oil based) Pros:

– Robust amount of EFA content allows smaller volume to prevent EFAD. To prevent EFAD: LA > 1% of total calories; α-linolenic acid requirements are even less at 0.2-0.5% of total calories

Cons:

– High ratio of n-6 to n-3 PUFA may give rise to pro-inflammatory eicosanoids

– Leads to reduced clearance of reticuloendothelial system (RES), a key player in the phagocytosis of microorganisms, tissue debris, and particulate matter.

– Increased LDL and triglyceride levels, decrease in HDL levels

– May contribute to intestinal failure associated liver disease (IFALD)

Mundi, M.S. et al. “Parenteral Nutrition – Lipids Emulsions and Potential Complications” Nutrition Issues in

Gastroenterology, Series #166. Practical Gastroenterolgy, August 2017

ILE Generation 4

Generation 4 (Fish-Oil Containing)

Pros:

– Improvement or reversal of IFALD

– Higher -tocopherol (antioxidant from Vitamin E family)

– Less pro-inflammatory profile

Cons:

– Concern for development of EFAD given the lower ratio of n-6 PUFAs

.

36

What about EFAD?

Essential Fatty Acid Deficiency

• Biochemical marker – a reduction of ARA 9a tretraenoic -6 fatty acid, resulting in the increase of trienoic nonessential -9 Mead acid

Holman index (triene:tetraene ratio) at >0.2 is considered biochemical EFAD - May appear as early as 7-10 days of EFAs restriction

S/S are detected at >0.4 Presents with growth retardation, reproductive failure, eczematous dermatitis and alopecia

An LA intake of 2%–4% of total energy, and an ALA intake of 0.25%–0.5% of total energy, are recommended to prevent EFAD.

ILE with Lower levels of LA and ALA raised concerns about their ability to prevent EFAD

37

Gramlich, L. et al. “Essential Fatty Acid Requirements and Intravenous Lipid Emulsions” Journal of

Parenteral and Enteral Nutrition. Vol. 00 No.0 pp 1-11. 2019 DOI: 10.1002/jpen.1537

What about EFAD?

38

What about EFAD?

• Possible retro-conversion pathways

and mobilization from body stores?

• Do DHA and ARA have a role in

preventing EFAD independently of LA

and ALA?

• New biomarker standards?

39

Anez-Bustillos, L. et al. “Redefining essential fatty acids in the era of novel intravenous lipid emulsions.”

Clinical Nutrition. June 2018. 37(3): 784-789. doi:10.1016/j.clnu.2017.07.004

ASPEN ILE Recommendations

“SMOF is not available in the United States. Until it is approved for use, no recommendation can be made for use in the United States.”

40

Wales, P.W. et al. “A.S.P.E.N. Clinical Guidelines: Support of Pediatric Patients with Intestinal Failure at Risk of

Parenteral Nutrition-Associated Liver Disease” Journal of Parenteral and Enteral Nutrition. Vol 38 No 5. July

2014. pp 538-557. DOI: 10.1177/0148607114527772

41

European 2018 Recommendations

R 4.5 In order to prevent essential fatty acids (EFA) deficiency in preterm

infants a lipid emulsion dosage providing a minimum linoleic acid (LA)

intake of 0.25 g/kg/day can be given. This lipid emulsion dosage ensures

an adequate intake of linolenic acid (LNA) with all 20% ILEs currently

registered for paediatric use. (LoE 2¡,RG 0, strong recommendation for,

strong consensus)

R 4.6 In order to prevent EFA deficiency in term infants and in children a lipid

emulsion dosage providing a minimum LA intake of 0.1 g/kg/day can be

given, which also provides an adequate intake of LNA with all 20% ILEs

currently registered for paediatric use.(LoE 3e4, RG 0, conditional

recommendation for, strong consensus)

R 4.7 In preterm infants, newborns and older children on short term PN, pure

soybean oil (SO) ILEs may provide less balanced nutrition than composite

ILEs. For PN lasting longer than a few days, pure SO ILEs should no

longer be used and composite ILEs with or without fish oil (FO) should

be the first choice treatment (LoE 1, RG A, conditional recommendation

for)

WHAT TO DO DURING A

SHORTAGE

42

Reasons for Shortages

43

Holcombe, Beverly. “Appropriate Parenteral Nutrition Prescribing in the Age of Drug Shortages: Introduction” ASPEN

Webinar, June 19, 2019

44

http://www.nutritioncare.org/ProductShortageManagement/ Accessed July 2019

45 https://www.nutritioncare.org/public-policy/product-shortages/ Accessed July 2019

Resources

Resources for Managing Shortages of PN Components

Organization Drug Shortage Resources

U.S. Food and Drug Administration

American Society of Health-System

Pharmacists

American Society for Parenteral and

Enteral Nutrition

The Joint Commission

The Center for Medicare and Medicaid

Services

https://www.fda.gov/Drugs/DrugSafe

ty/DrugShortages/default.htm

https://www.ashp.org/Drug-

Shortages

https://www.nutritioncare.org/public

-policy/product-shortages/

http://www.jointcommission.org/ass

ets/1/18/Revision_to_

MM.02.01.01_HAP_20111222.pdf

https://www.cms.gov/Regulations-

and-Guidance/Guidance/

Manuals/downloads/som107ap_a_hos

pitals.pdf

46 Holcombe, B., Mattox, TW. “Drug Shortages: Effect on Parenteral Nutrition Therapy.” Nutrition in Clinical

Practice. February 2018. Vol. 33 No. 1 pp 53-62. DOI: 10.1002/ncp.10052

Practical Steps

I. Stay Informed

o Drug shortage websites

o Institution

o Outside of institution

II. Do not panic…Instead Assess Situation

o How much medication is on hand

o How long with the shortage last

o Where is it located in the hospital

o Possible sources of alternative medications

III. Come up with Plan

IV. Keep Others Impacted informed

V. Return to Practice as Usual

47

Cober, M. Petrea. “Appropriate Parenteral Nutrition Prescribing in the Age of Drug Shortages: Appropriate PN

Prescribing in Pediatrics: What is Best Practice During and After Shortages?” ASPEN Webinar, June 19, 2019

What to do during a shortage

48

Topline Recommendations

• Do not ration nutrient for PN if the supply of those

components is sufficient to provide the full daily dose

• During component shortages, follow PN management

recommendations available on the ASPEN website at http://www.nutritioncare.org/ProductShortageManagement

• Return to appropriate dosing as soon as the component

shortage has resolved

• Rationing and conservation strategies are intended to be

used only during shortages

• The lack of observed adverse events/deficiencies and the

potential cost savings associated with “partial” dosing

should not be impetus to continue less than optimal dosing http://www.nutritioncare.org/uploadedFiles/Documents/Guidelines_and_Clinical_Resources/PN%20Dosing%201-Sheet-

FINAL.pdf Accessed July 2019

PN AND GUT MICROBIOME

49

Changes to GI Immunity with PN

Changes to GI following PN:

• Gut atrophy – decrease of gut-associated lymphoid tissues (GALT)

• Decrease of innate immune cells

• Loss of of mucosal sIgA release

• Impaired epithelial barrier function and chemical secretions

• Up-regulation of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and

• interferon-γ (IFN-γ)

50

Pierre, JF. “Gastrointestinal immune and microbiome changes during parenteral nutrition” Am J

Pysiol Gastrointest Liver Physiol 312: G246-G256. 2017

Changes to the microbiome

51

Demehri, FR, Barrett, M, Teitelbaum, DH. “Changes to the Intestinal Microbiome With Parenteral Nutrition: Review of

Murine Model and Potential Clinical Implications” Nutrition in Clinical Practice Vol.30 No. 6. 2015

52

Demehri, FR, Barrett, M, Teitelbaum, DH. “Changes to the Intestinal Microbiome With Parenteral Nutrition: Review of

Murine Model and Potential Clinical Implications” Nutrition in Clinical Practice Vol.30 No. 6. 2015

Changes in the gut microbiome of infants on PN

53

Dahlgren, A.F. et al. “Longitudinal changes in the gut microbiome of infants on total parenteral nutrition” Pediatric

Research (2019) 86:107–114; https://doi.org/10.1038/s41390-019-0391-y

Future Studies?

o Factors contributing to microbial shifts

o Intestinal metabolome (ie, the metabolic

composition of the intestinal lumen in driving

changes in the microbiome.)

o Explorations of administering microbial

metabolites, such as Ahr ligands, SCFAs, and

polyamines

54

Demehri, FR, Barrett, M, Teitelbaum, DH. “Changes to the Intestinal Microbiome With Parenteral Nutrition: Review

of Murine Model and Potential Clinical Implications” Nutrition in Clinical Practice Vol.30 No. 6. 2015

Summary

• Electronic PN resources

– Smart phone apps

– ASPEN Website

• PN Component reviews

– Concerns for deficiencies, toxicities

– Strategies during Shortages

• Injectable Lipid Emulsions

• Gut Microbiome and PN

55

References

Anez-Bustillos, Lorenzo, et al. “Redefining essential fatty acids in the era of novel intravenous lipid emulsions.” Clinical Nutrition . Vol. 37 No. 3. pp 784-789. June 2018. DOI:10.1016/j.clnu.2017.07.004

Cober, M. Petrea. “Appropriate PN Prescribing in Pediatrics: What is Best Practice During and After Shortages?” ASPEN Webinar, June 19, 2019

Crill, Catherine M. and Gura, Kathleen M, “Parenteral Nutrition Support.” The ASPEN Pediatric Nutrition Support Core Curriculum 2nd Edition. Ed. Mark R. Corkins: American Society of Parenteral and Enteral Nutrition. 2015

Dahlgren, Allison, et al. “Longitudinal changes in the gut microbiome of infants on total parenteral nutrition” Pediatric Research. April 2019 Vol 86 pp.107–114; https://doi.org/10.1038/s41390-019-0391-y

Demehri, Farokh R. et al. DH. “Changes to the Intestinal Microbiome With Parenteral Nutrition: Review of Murine Model and Potential Clinical Implications” Nutrition in Clinical Practice Vol.30 No. 6. December 2015 pp. 798-806. DOI: 10.1177/0884533615609904

Domell€of M, et al., ESPGHAN/ESPEN/ESPR guidelines on pediatric parenteral nutrition: Iron and trace minerals, Clinical Nutrition (2018), https://doi.org/10.1016/j.clnu.2018.06.949

Gramlich, L. et al. “Essential Fatty Acid Requirements and Intravenous Lipid Emulsions” Journal of Parenteral and Enteral Nutrition. Vol. 00 No.0 pp 1-11. 2019 DOI: 10.1002/jpen.1537

56

References

Holcombe, B., Mattox, TW. “Drug Shortages: Effect on Parenteral Nutrition Therapy.” Nutrition in Clinical Practice. February 2018. Vol. 33 No. 1 pp 53-62. DOI: 10.1002/ncp.10052

Lapillonne, A et al. “WSPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Lipids.” Clinical Nutrition. 2018. https://doi.org/10.1016/j.clnu.2018.06.946

Mundi, M.S. et al. “Parenteral Nutrition – Lipids Emulsions and Potential Complications” Nutrition Issues in Gastroenterology, Practical Gastroenterolgy, August 2017 Series #166

Pierre, JF. “Gastrointestinal immune and microbiome changes during parenteral nutrition” Am J Pysiol Gastrointest Liver Physiol 312: G246-G256. 2017. doi:10.1152/ajpgi.00321.2016.

Vanek, Vincent W., et al. “A.S.P.E.N. Position Paper: Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi-Trace Element Products” Nutrition in Clinical Practice. Vol. 27 No. 4. August 2012. pp. 440-491. DOI: 10.1177/0884533612446706

Vanek, Vincent W., et al. “A Call to Action to Bring Safer Parenteral Micronutrient Products to the US Market.” Nutrition in Clinical Practice. Vol. 30 No.4. August 2015. pp. 559-569. DOI: 10.1177/0884533615589992

Wales, P.W. et al. “A.S.P.E.N. Clinical Guidelines: Support of Pediatric Patients with Intestinal Failure at Risk of Parenteral Nutrition-Associated Liver Disease” Journal of Parenteral and Enteral Nutrition. Vol 38 No 5. July 2014. pp 538-557. DOI: 10.1177/0148607114527772

Worthington, Patricia, et al. “When Is Parenteral Nutrition Appropriate?” Journal of Parenteral and Enteral Nutrition. Vol. 41 No. 3. 2017 pp 324-377. DOI: 10.1177/0148607117695251

57

58