By: Shihaam Cader

Chief Dietitian

Head of Department

RCWMCH

Update on Pediatric Parenteral

Nutrition Guidelines

Introduction

The goal of parenteral nutrition (PN) is to correct or prevent nutritional

deficiencies when unable to provide nutrients via enteral route

Usually considered when unable to feed for 3 – 5 days infants/children

Common conditions in children:

Intestinal failure ( SBS,atresia, NEC)

Enteropathies or malabsorption due to CGE

Choice of suitable parenteral solutions depends on the macronutrients &

micronutrients needs of children – not only quantity but quality of nutrients

Setting the scene….

6 month old girl Poor nutritional status (wt5.5kg,

stunted, wasted) Previous bowel resection (35cm SB)

due to NEC Ileostomy Initially TPN then weaned to enteral /

oral feeds

10 year old boy

Admitted to ICU with

complicated post

appendectomy, abdominal

sepsis

ventilation support

Poor nutritional status (25kg)

BMI 13.7 (Z score -2)

Patient A Patient B

Planned ileostomy closure due

to increased output

For recommencement of TPN

post surgery

Baseline bloods shows normal

electrolytes, CMP but raised

bilirubin levels

NPM for more than 5 days

post surgery

Baseline bloods normal

Guidelines on Pediatric PN

ESPGHAN/ESPEN/ESPR/CSPEN

1 •Guideline development process

2 •Energy

3 •Amino acids

4 •Lipids

5 •Carbohydrates

6 •Fluid & electrolytes

7 •Iron and trace elements

8 •Calcium, Phosphate, magnesium

9 •Vitamins

10 •Venous Access

11 •Organisational aspects

12 •Home parenteral nutrition

13 •Standard vs Individualized parenteral nutrition

14 •Complications

14

Ch

ap

ters

Key points from ESPGHAN 2018

1. Energy & Carbohydrate PN

2. Parenteral Nutrition in critically ill

3. Protein requirements

4. Lipid requirements & lipid emulsions

5. Micronutrients

6. Practical approach

Energy Needs

Hyperglycemia – may increase risk of infection

Hyperlipidemia

Excess fat deposition

Liver steatosis (impairing liver function)

- Hypoglycemia

- Impaired growth

- Tissue catabolism – LBM

- Poor cognitive/ behavioral development

- Impaired immunity

- Increasing risk of mortality/morbidity

Ris

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FINDING THE BALANCE

Energy recommendations

Schofield for REE (kcal/d) 0- 18 years is preferred – least to underestimate.

Add relevant PAL, disease factors & growth to get TOTAL PN requirments

Derived from 2004 FAO/WHO/UNU recommendations (previously 1985)

Lower as does not take into account 5-10% needed for enteral absorption.

Main source of fuel for brain cell metabolism & for

other body functions

Glucose metabolism is influenced by

1. Age

2. Acute illness

3. Nutritional status

4. Provision of other macronutrients

Use of glucose alone is not recommended

because of:

•Hyperglycemia

• fatty liver [steatosis] & increase VLDL

• excess CO2 production

• EFA deficiency [within 2-3 days]

Carbohydrate

Carbohydrate recommendations

Recognizing the different phases of critical ill

Phases of critical illness

Joosten etal Curr Opin Clin Nutr Metb Care 2019

Endogenous production irrespective of

exogenous energy provided

Gradual increase stepwise 2 -3 days

ACUTE phase

First hours – days

Resuscitation phase

- requires vital organ

support – such as

sedation,

mechanical

ventilation,

vasopressors, fluid

resuscitation

STABLE phase

When can be

weaned from

these vital

support

RECOVERY phase

When mobilising

More

Energy/CHO

required to

promote growth

and recovery

Phases of critical illness

Joosten etal Curr Opin Clin Nutr Metb Care 2019

Acute phase energy intake is equal or lower

Thereafter increased to promote tissue repair & growth

Energy : Different phases

Acute phase typically the first 1- 2 days

Recommendations for acute and stable phase can be applied to

critical care setting and recovery for all other patients

Carbohydrate needsNEW

Critical ill

Timing of supplemental PN

PEPaNIC trial : Early vs Late PN

Multicenter RCT in 1440 critically ill infants & children (0-17years)

Compared early initiation of supplemental PN (within 24 hrs) to

late PN (withholding for 8days) in addition to EN

Outcomes:

Reduced number of new infections, ventilation time, kidney

failure and LOS

Limitations:

PN may not have been indicated/needed

Timing of supplemental PN

A) Editorial response…

Mehta, N (2016 New England J Medicine) raised concerns

Appropriate PN indications

Equations used to determine energy requirements

Threshold of EN tolerance less than 80% of target calories

B ) Review article:

Koletzko, B et.al. (Curr Opin Clin Nutr Metab Care 2017)

Indications for PN – if gut works use it

Majority patients had normal BMI

Early PN group average ICU stay was ~4days

Supplemental PN can be delayed for 1 week in those with NORMAL

nutritional status or with low risk of nutritional deficiency

Overfeeding with glucose

During recovery insulin resistance will decrease and metabolism will improve

Lipogenesis & fat deposition

High CHO induces Insulin

resistence

Liver steatosis

Increased CO2

ACUTE phase

Management of Hyperglycaemia

Amino acid requirements

Preterm Infants Children Children Adolescents

2m - 3years 3-12 years >12years

g/kg/day

2005

1.5 - 4.01.5 - 3.0 1.0 - 2.5 1.0 - 2.0 1.0 - 2.0

2016

D1: 1.5 - 2.51.5 - 3.0 (max) 2.5 2.0 2.0

D2: 2.5 - 3.5 Accompanied by >65kcal/kg/d Min 1.0 min 1.0 min 1.0

Strong recommendation - Glutamine should not be supplemented

additionally in infants and children up to the age of two years

Taurine to be included in AA solutions (strong consensus)

AA requirements are lower in PN than EN because bypasses intestine

Pediatric suitable AA solutions

that includes Essential AA

ESPGHAN : Lipid requirements

Preterm Infants Children

g/kg/day

2005 3.0 - 4.0 3.0 - 4.0 1.0 - 3.0

2016 max 4.0 max 4.0 max 3.0

EFAs: 0.25g/kg Linoleic for preterm 0.1g/kg/day linoleic acid term infants and children

Integral part of pediatric PN

Providing high energy needs without CHO overload & increasing the osmolarity

EFAs – critical role in early development

Maximal lipid oxidation rate is

~3g/kg/day in young children

1.7 – 2.5g/kg/day in adults

Excess stored in adipose tissue & increase risk of fat overload Sx and may impair the immune response

ESPGHAN : Types of Lipid emulsions

The choice of ILEs is influenced by:

composition of lipid emulsion ,

Duration of PN,

Clinical setting,

Age,

Disease conditions

NEW

ESPGHAN : Types of Lipid emulsions

Pediatric PN patients at high risk of IFALD – such as :

Premature infants

Long term bowel rest

Ileal resection / enterostomy (loss of hepatic-enteric cycle)

Sepsis

SBS

Use of lipid emulsions

Beneficial than pure SO lipid as less

proinflammatory effects, less

immunosuppression & more antioxidant

effects

Particularly in prems -

decreased LPL and

reduced fat oxidation

Use of Lipid emulsions

STRONG RECOMMENDATION

Management of IFALD

Common complication in long term PN

Is related to patients receiving long term PN [> 14 days]

It can be reversed if detected and monitored closely

It is clinically diagnosed with raised total bilirubin levels

[> 20mg/dL]

It can even persist 2 weeks after PN has stopped

The causes are multifactorial

Multifactorial

Absence of

enteral nutrition

Infection or

sepsis

Lipid

emulsions

Premature

infants

Short bowel

syndrome

reduced bile acid enterohepatic circulation, resulting in

reduce bile flow ----- hepatotoxic

OverfeedingCHO/Lipids

Prolonged PN>14days

Causes of IFALD / PNAC

Management strategies to include

1. Trophic feeding

2. Minimise the lipid dose [g/kg/day]

3. Ensure not overfeeding

4. Treat sepsis

5. Cyclical PN

6. And / Or altering Lipid emulsion

Management IFALD

Management IFALD

Several observational studies shown by changing dose or type of ILEs

has reversed IFALD – but limited RCT

These changes include:

1. Reduction in proinflammatory n6s

2. Reduction in phytosterol supply

3. Provision of alpha- tocopherol

4. Anti-inflammatory n3s

Pure Fish oil

Available studies shown the use of pure FO ILEs to benefit IFALD

However no long term studies (>15days)

Concern of EFA deficiency & aspects related to coagulation

Fish oil role in IFALD

1. ↓ inflammation

2. ↑ antioxidant activity

3. ↓ phytosterols

4. ↑biliary flow

1. ↑ inflammation

2. Provide EFAs

Having right balance between n6 and n3s

Ratio n6:n3

Soya Fish MCT Olive

o Rich in MUFA n9

o ↓ lipid

peroxidation

o Less PUFAs

o ↑ antioxidant

intake

o ↑ vitamin E

status

o Lacks omega3s

o Safe & well

tolerated

o Calorie rich

compound

o Rapidly

available source

of energy

o Not dependent

on carnitine for

mitochondrial

transport

o Safe & well

tolerated

o Rich in n3

o Source EPA/DHA

o Anti-inflammatory

properties

o Safe & well

tolerated

o Rich in n6

o Source of EFA

o Pro-inflammatory

properties

o Contains

Phytosterols

o Lack of

sufficient

antioxidants

o Concerns linked

with PNALD

Types of Lipid emulsions

Combination of lipid emulsions beneficial

List of lipid emulsions available [not all in SA]

Pure Soy*

Soya+MCT* Soya+Olive* Pure Fish

Soya+MCT+

FishSoy+MCT+ Olive+Fish*

Soybean (%) 100 50 20 0 40 30

Coconut(MCT) (%) 0 50 0 0 50 30

Olive (%) 0 0 80 0 0 25

Fish (%) 0 0 0 100 10 15

Phytosterols(mg/L) 348 ? 327 0 ~125 47.6

αtocopherol(µmol/L) 87 395 75 505 455 500

EPA 0 0 0 20.1 3 3

DHA 0 0 0 18.4 2 2

Ratio n6:n3 6.7:1 16:1 9.1:1 1:8.2 2.7:1 2.5:1

Pichler, J. Euro J Clin Nutr 2014;68:1161Seida, JPEN 2013; 37:44Vlaardingbroek Am J Clin Nutr 2012; 96:255

*Only available in SA

Mixed Lipid emulsions

ESPGHAN : Monitoring of lipids

ESPGHAN : Monitoring of lipids

Risk of hypertriglyceridemia:

CHO high

Lipid dose high

Malnourished ( slower rate of clearance)

Sepsis

Prem/ELBW – limited muscle/fat mass &

reduced hydrolytic capacity

When to monitor:

1- 2days after initiation or adjustment of lipid infusion

Thereafter weekly to monthly depending on the

patient

LIPIDS TO BE LOWERED – NEVER STOPPED

Micronutrients

Limited data for last 30 years

However infants and children are at risk of deficiencies

Therefore recommendations are that all children receive micronutrients

daily infusions as part of their PN solution

Water and lipid solutions should be added to lipid emulsions increase

vitamin stability

Fat soluble vitamins

•Adequate supply essential for growth and development

• Vitamin A & E exposure to sunlight is detrimental and can cause degradation

•Administering with lipid helps reduce this risk and at same time protecting the

lipids from peroxidation – antioxidant properties

Vitamins & Trace elements 2005 2018

Infants[per kg] Children [per day] Infants(per kg) Children (per day)

Vitamin C [mg] 15-25 80 same same

Thiamine[B1] [mg] 0.35-0.50 1 same 1.2mg/day

Riboflavin [mg] 0.15-0.2 1.4 same same

Pyridoxine [mg] 0.15- 0.2 1 same same

Niacin [mg] 4 - 6.8 17 same same

B12 [ug] 0.3 1 same same

Pantothenic [mg] 1-2 5 2.5mg/kg same

Biotin [ug] 5 - 8 20 same same

Folic acid [ug] 56 140 same same

Vitamin A[ug] 150-300 150 same same

Vitamin D2[ug] 32 IU 400 IU 40 - 150IU/kg/day 400 - 600IU/day

Vitamin E[mg] 2.8-3.5 7 same 11mg/day

Vitamin K[ug]

10µg/kg -recommended but not

possible 200 same same

copper[ug] 20 20ug/kg upto 0.5mg/day same

Iodine[ug] 1 same same

Selenium[ug] 2-32 - 3ug/kg max

100ug/day same

Zinc[ug]250 for <3m 50µg/kg same same

100 for >3m max 5mg/d

Mn [ug] low dose 1µg/kg 50 max 50ug/daysame

Mo [ug]0.25µg/kg[max

5µg/d]

Vitamin D

Several reports of vitamin D deficiency and decreased bone

mineral disease among pediatric during and after PN

Therefore needs to be monitored

Minerals (Ca/P/Mg)

Parenteral mineral supply :

Ca cations may precipitate with inorganic phosphate

(calcium chloride) anions

To some degree this can be avoided by mixing Ca and

phosphate with amino-acid and glucose solutions

before diluting the solution and by adding phosphate

salt at the end of the process

Energy metabolism & optimal bone mineralization

Malnourished patients – hypoP has been result of refeeding Sx

Extreme hypoP can result in muscle weakness, respiratory

failure, cardiac dysfunction & death

Children on long term PN are at high risk of metabolic bone

disease (MBD)

Therefore close monitoring of Ca, P, vitamin D & bone

mineral status is required

Phosphate needs in long term PN

Added in PN solutions in

different variations as:

CaCl

MgSo4

KPO4

mg /kg / day (mmol/kg/day)

Calcium Preterm 0 - 6months 7 -12months 1 - 13 years 14 - 18 years

2005 32 (0.8) 20 (0.5) 11 ( 0.2) 7 ( 0.2)

2016

First days: 32 – 80

(0.8 - 2.0 ) 30 - 60 (0.8 - 1.5) 20 (0.5) 10 - 16 (0.25 -0.4)

growing: 100 – 140

(1.6 - 3.5)

Phosphate Preterm 0 - 6months 7 -12months 1 - 13 years 14 - 18 years

2005 14 (0.5) 15 (0.5) 6 (0.2) 6 (0.2)

2016 31 - 62 (1.0 -2.0) 20 - 40 (0.7 - 1.3) 15 (0.5) 6 - 22 (0.2 -0.7)

6 - 22

(0.2 -0.7)

77 - 108 (1.6 -3.5)

Magnesium Preterm 0 - 6months 7 -12months 1 - 13 years 14 - 18 years

2005 5 (0.2) 4.2 (0.2) 2.4 (0.1) 2.4 (0.1)

2016 2.5 - 5.0 (0.1 - 0.2) 2.4 - 5 (0.1 - 0.2) 4 (0.15) 2.4 (0.1) 2.4 (0.1)

5.0 - 7.5 (0.2 - 0.3)

Calcium, Phosphorus, Magnesium

PRACTICAL APPROACH

SA perspective

Choice of PN bags based on :

Standardised solutions that has both macro and micronutrients

These macronutrients profile suitable for pediatric such as

appropriate amino acids solutions with essential amino acids

Availability of alternative lipid emulsions – combination of

different types of lipids

Additional micronutrients suited for pediatric population given for

long term PN ( > 2-4 weeks)

Standardised bags is recommended as it minimizes the risk of

compounding errors, reduced cost, reduced wastage

Practical approach

6 month girl Poor nutritional status (wt

5.5kg, stunted and wasted

Previous bowel resection

(35cm SB) due to NEC

Ileostomy

Initially TPN then weaned to

enteral / oral feeds

Planned ileostomy closure

due to increased output

For recommencement of TPN

post surgery

Baseline bloods shows normal

electrolytes, CMP but raised

bilirubin levels

Patient A Energy RQ: Recovery: 75 – 85kcal/kgProtein: 2g/kg/dayLipid: 1-4g/kg/dayCHO: 8.6 – 14g/kg/dayFluid: 120 – 150ml/kg

Pediatric bag 3m-3years (750ml bag)

Fluid 120ml/kg 130ml/kg 150ml/kg

Total Fluid 660ml 715ml 825ml

Energy(per kg)

85kcal 92kcal 107kcal

Protein(per kg

2.5g 2.8g 3.2g

Lipid(per kg)

2.5g 2.8g 3.2g

CHO(per kg)

12.7g 13.8g 16g

Electrolytes met with all volumes

Essential amino acids met

EFAs met

Practical approach

6 month girl Poor nutritional status (wt

5.5kg, stunted and wasted

Previous bowel resection

(35cm SB) due to NEC

Ileostomy

Initially TPN then weaned to

enteral / oral feeds

Planned ileostomy closure

due to increased output

For recommencement of TPN

post surgery

Baseline bloods shows normal

electrolytes, CMP but raised

bilirubin levels

Patient A Administration:

Day 1: half rate i.e 60ml/kg

Day 2: Full 120ml/kg

Due to increase bilirubin

levels and expected long

term use of PN

Complex lipid

emulsion with

soya,MCT,olive,Fish

Maintain same lipid

dose

Trophic feeding

Reassess – if not gaining

adequate weight increase PN

volume to 130 – 140ml/kg

Practical approach

10 year old boy

Admitted to ICU with

complicated post

appendectomy,

abdominal sepsis

ventilation support

Poor nutritional status with

weight of 25kg

BMI 13.7 (Z score -2)

NPM for more than 5 days

post surgery

Patient B

Energy RQ: Acute phase: 30 – 40kcal/kgStable phase: 40 – 55kcal/kgRecovery: 55 – 65kcal/kg Protein: 1- 2g/kgLipid: 1-3g/kgCHO: Acute: 2.9 – 3.6g/kgStable: 2.8 – 5.8g/kgRecovery: 4.3 – 8.6 g/kgFluid: 60 – 80ml/kg

Pediatric bag 6- 12years (1400ml bag)

Fluid 60ml/kg 65ml/kg 70ml/kg

Total Fluid 1500ml 1625ml 1750ml

Energy(per kg)

52kcal 56kcal 60kcal

Protein(per kg)

1.6g 1.7g 1.8

Lipid(per kg)

2.1g 2.3g 2.45g

CHO(per kg)

6.3g 6.8g 7.3g

Practical approach

10 year old boy

Admitted to ICU with

complicated post

appendectomy,

abdominal sepsis

ventilation support

Poor nutritional status with

weight of 25kg

BMI 13.7 (Z score -2)

NPM for more than 5 days

post surgery

Patient B Administration:

D1-D2 (Acute): Rate 36ml/hr

3.6g CHO and 30kcal/kg

D2 – D3 (Stable): Rate 46ml/hr

4.8g CHO and 38kcal/kg

Recovery: Full rate 68ml/hr

Fluid 65ml/kg

Limitation:

To meet this fluid volume – 2

bags required

Early change of PN bag

Summary

New guidelines emphasizes the importance of

recognizing energy requirements during the 3 phases of

critical illness

Encourage the use of composite lipid emulsions as

oppose to pure soya lipid emulsion

Monitoring micronutrients such as Vitamin D as pediatric

population at risk of deficiency

When choosing appropriate PN solutions ensure that

they are suitable for needs of the pediatric patient

THANK YOU

Contact details:

Shihaam.Cader@westerncape.gov.za