Neonatal and Paediatric Total Parenteral Nutrition Workshop
A special report

Dr Gert Kirsten
E-mail: gfk@sun.ac.za

Contents

1. Introduction
2. Key problems/areas of concern
3. Neonatal TPN
1. Current Guidelines
2. Nutrient Sources Available in South Africa
3. Comparison of Pre-Mixed TPN Regimens Currently Available in South Africa
4. Discussion and Recommendations
5. Proposed Regimens
4. Pediatric TPN
1. Introduction
2. Current Guidelines
3. Comparison of Pre-mixed Pediatric TPN Regimens Currently Available in South Africa
4. Discussion and Recommendations

1.   Introduction

A special TPN workshop was hosted by the University of Stellenbosch Medical School and sponsored by Isotec Nutrition. The workshop was held at Tygerberg Hospital, Cape Town (South Africa) in February 1999. The delegates included neonatologists, pediatricians, pharmacists and dietitians.

The delegates recognised that often parenteral nutrition is used as an adjunct to enteral feeding and is not constitute the total nutrition of the child.

The purpose of the workshop was to bring the key opinion leaders in he field of Neonatal and Pediatric TPN together to discuss current trends in TPN solutions as well as proposed research into the development of improved TPN regimens for local (South Africa) use.

2. Key problems/areas of concern

1. South Africa requires an amino acid solution that contains Taurine, and that is suitable [specifically designed] for neonatal and pediatric TPN.
2. A 20% lipid emulsion should preferably be used in neonatal and pediatric TPN [versus a 10% solution] is preferred and should be used routinely.
3. The calcium, phosphorus, magnesium and sodium content in some of the pre-mixed regimens currently used in South Africa, are inadequate and could potentially result in clinical deficiencies [especially in neonates].
4. In-line filters [1,2u] should be used in neonatal and pediatric TPN.
5. Stability of neonatal TPN regimens in environmental temperatures greater than 24 degrees C [the majority of special and high care neonatal units are heated above 24 degrees C].
6. The importance of standardized labeling on Regimen bags. There is a lack of standardized labeling of TPN bags in South Africa. This can lead to the misinterpretation of information given on the bag. It has been suggested that certain regimens should carry warnings, for example: fat-free regimens should not be used for more than 3 days.
7. Additive free regimens labels’ should carry a warning that the regimen should not be used for more than 4 days, and such regimens should only be used in TPN experienced units in which appropriate administration, monitoring and protocols are followed.

3. Neonatal TPN

3.1 Current guidelines

Children are not miniature adults, and there are important differences, which should be taken into account when providing parenteral nutrition for them. Children differ from adults in that they require nutrients for growth. Consequently, the requirements for water, electrolytes, protein, fat and carbohydrate and vary considerably with age. In addition, qualitative differences are present, in particular in the requirement for amino acids. Histidine is an essential amino acid in infancy and additional proline, cystine and/or cysteine, and alanine should be added as the latter cannot be synthesized in adequate amounts in the young infant and therefore are considered "semi-essential".

TPN regimens should be designed to meet the estimated nutrition requirements for each patient. However, pharmacists need to be able to recognize when specified nutrients are not within acceptable, stable ranges. The specified quantity of protein, carbohydrate, fat, electrolytes, fluid, vitamins, and trace elements should all be assessed for appropriateness before they are compounded. Acceptable ranges for each of these nutrients should be based on compatibility, stability, and normal clinical requirements.

3.1.1 Daily protein and energy requirements for he pre-term infants

• Maintenance with + ve N₂ balance but no weight gain:
  • NPE: 50-60 kcal//kg/day
  • Protein: 2-2,5 g/kg/day
• Maintenance with + ve N₂ balance and weight gain (15 g/kg/day)
  • NPE: 80-90 kcal/kg/day 
  • Protein: 3 g/kg/day
• ESPEN guidelines
  • Energy (kcal/kg) 90-100
  • Protein (g/kg) 2,5-3,5
  • CHO (g/kg) 10-15
  • Fat (g/kg) 2-3,5
  • Na (mmol/kg) 2-3,5
  • Cl (mmol/kg) 2-3,5
  • K (mmol/kg) 2-3
  • Ca (mmol/kg) 1,5-2,25
  • PO4 (mmol/kg) 1,1-2,3
  • Mg (mmol/kg) 0,15-0,25

3.2 Nutrient sources available in South Africa

3.2.1 Amino Acid Solutions: Vamin G

Currently Vamin G is the only amino acid solution registered in South Africa, which is suitable for administration to neonatal and paediatric patients. The meeting requested that Isotec assist where possible to facilitate the importation of Vaminolact or similar product which contains Taurine and is more suitable for neonatal and paediatric TPN.

3.2.2 Carbohydrate Solutions: Glucose 10%, 20%, 35% and 50% 

The available solutions are all suitable for use in neonatal and paediatric TPN patients provided that they are diluted in the requisite quantities and the final concentration is suitable for IV infusion as a component of TPN.

3.2.3 Fat Emulsions: Intralipid 10%, 20%

Owing to the lower phospholipid content in Intralipid 20%, it is the preferred emulsion for use in neonatal and paediatric TPN regimens. In all cases Intralipid 20% must be used as the source of fat energy and essential fatty acids.

3.3 Comparison of the pre-mixed TPN regimens currently available in South Africa

Product: ITN 1005

Comments/ Recommendations

1. Na, Mg, Ca and P should be increased (Ref. ESPEN 1997 Guidelines-see pt 3.1.1).
2. This regimen is unlikely to result in weight gain, but it will maintain a positive nitrogen balance.
3. Adjust Ca/PO4 ratio to 1,5:1.
4. ITN 1005 should not be used for more than 3 days without the addition of fat to prevent EFAD (at least 0,5g/kg/day of fat should be given either enterally or intravenously).

Product: ITN 1006

Comments/ Recommendations

1. Same protein and electrolyte profile as Product : ITN 1005, except that the glucose content is lower, and hence provides less energy.
2. This regimen may be used when glucose intolerance is evident.

Product: ITH 1501

Comments/ Recommendations

1. Administration of fat containing regimens should be via an in-line 1,2u filter to remove any micro-aggregates that may be present.
2. This regimen contains a high level of fat compared to RDA.
3. Discontinue this regimen (ref. ITN 1601).

Product : ITN 1601

Comments/ Recommendations

1. Adjust electrolytes to 1997 ESPEN Guidelines.
2. Adjust ratio of Ca: PO4 to 1,5:1 and increase to 1997 ESPEN Guidelines pending stability).

Product: T11

Composition	Per 100ml	Per 150ml	RDA/100ml	Ratio to rda
Na (mmol/kg)	2,2	3,3	3,25	1,015
Ca (mmol/kg)	1,2	1,8	1,8	1
P (mmol/kg)	0,7	1,05	1,5	0,7
Mg (mmol/kg)	0,13	0,2	0,15-0,25	1,3
Protein (g/kg)	2	3	3,5	0,857
K (mmol/kg)	1,59	2,38	2	1,19
Energy (kcal/kg)	44	66	100	0,66

Comments/ Recommendations

1. Compare to ITN 1005
2. Fat [lipid emulsion] should be added/ given no later than 3 days following the initiation of the parenteral feeding.
3. Owing to the relatively high calcium concentration of the solution, the IV sites should be monitored closely for any tissue infiltration and drugs should not be administered through the line [due to the high risk of precipitation and incompatibility.

3.4  Discussion and recommendations

Calcium and Phosphate Ratio
Discussion largely revolved around the issue of Ca²⁺ and PO₄ and the general consensus was that Isotec should investigate adjusting the Ca²⁺ and PO₄ to the RDA guidelines if stability permits, failing which, at least change the composition to represent a ratio of Ca²⁺ and PO₄ of 1,5:1. This may be achieved by:

Increasing Ca²⁺
Increasing PO₄
Adjusting Glucose to alter pH of solution to enhance Ca²⁺ and PO₄ solubility.

Electrolyte Content 
The other electrolytes should be adjusted to more closely compare to that of Neonatalyte (or 1997 ESPEN Guidelines).

Regimen Stability at 32 ° C
Most Neonatal ICU’s [high and special care units] have an environmental temperature higher than 24 ° C [the temperature at which TPN regimens stability have been established]. Recommend that Isotec Nutrition conduct stability studies at 32-35 ° C to closely simulate the conditions under which the regimens are administered.  

Standardized Labeling
The importance of appropriate and standardized labeling was discussed. It was recommended that Isotec Nutrition investigate the inclusion of specific warnings which could be incorporated on the product labels, and redesign the labeling format as per the 1997 ESPEN Guidelines (to prevent misinterpretation/s). Every precaution should be taken to make Doctors and Nurses aware of the effective and safe use of TPN.

3.5 Proposed regimens

Isotec Nutrition will review and conduct stability studies of the proposed adjustments to the TPN regimens as listed below:

Product: ITN 1005 (Adjusted)

Composition	Per 100ml	Per 150ml	RDA/100ml	Ratio to rda
Na (mmol/kg)	2,15	3,2	3.25	1
Ca (mmol/kg)	1,18	1,8	1,8	1
P (mmol/kg)	0,9	1,35	1,5	0,9
Protein (g/kg)	1,81	2,72	2,5-3,5	1
Mg (mmol/kg)	0,18	0,27	0,15-0,25	1,08
K (mmol/kg)	1,92	2,8	2-3	1
Glucose (g/kg)	9,65	14,5	20	0,75

Product: ITN 1006 (Adjusted)

Composition	Per 100ml	Per 150ml	RDA/100ml	Ratio to rda
Na (mmol/kg)	2,15	3,2	3,25	1
Ca (mmol/kg)	1,18	1,8	1,8	1
P (mmol/kg)	0,9	1,35	1,5	0,9
Protein (g/kg)	1,81	2,72	2,5-3,5	1
Mg (mmol/kg)	0,18	0,27	0,1-0,25	1,08
K (mmol/kg)	1,92	2,8	2-3	1
Glucose (g/kg)	6,43	9,65	20	0,5

Product: ITN 1601 (Adjusted)

Composition	Per 100ml	Per 150ml	RDA/100ml	Ratio to rda
Na (mmol/kg)	2,2	3,3	3,25	1
Ca (mmol/kg)	1,16	1,74	1,8	1
P (mmol/kg)	0,87	1,31	1,5	0,9
Protein (g/kg)	1,98	2,97	2,5-3,5	1
Mg (mmol/kg)	0,19	0,29	0,15-0,25	1,14
K (mmol/kg)	1,75	2,6	2	1,3
Glucose (g/kg)	10,5	15,75	20	0,8
Fat (g/kg)	1,76	2,6	3,5	0,75

4. Pediatric TPN

4.1 Introduction

Ideally the nutritional requirements for a pediatric patient should be calculated individually and compounded accordingly. Logistically this is not possible, as there are many factors affecting the choice of individualised regimens including cost, availability and stability of the regimen.

The pediatric TPN regimens, which are commercially available from Isotec Nutrition at present, were originally derived from the neonatal formulae and supplied in proportionately larger volumes. These regimens are suitable for children under one year of age, but the requirements of older pediatric patient differ from those for neonates. The aim of this meeting was to propose new regimens, which would be more suitable for patients between the ages of 1 year to 12 years.

It was agreed that pediatric patients should be divided into two groups:

Those between > 1 year and 3 years of age
Those between 4 and 12 years of age

There should only be 2 regimens per age group, a fat-free (lipid-free) regimen and a regimen that contains lipid. The lipid containing formula should aim to supply 100ml per Kg of body weight per 24 hours.

4.2 Current guidelines

4.2.1 TPN Requirements for Pediatric Patients

Standard nutrient requirement ranges for infants and children receiving TPN have been established. Rapidly changing organ function, metabolic immaturity, and normal but rapid weight gain, particularly in neonates and infants, are age-related descriptors of nutrient need.

Requirements for fluids, protein, and energy are substantially higher on a unit-of-weight basis for children than in adults. The distribution of parenteral nutrition non-protein calories for pediatric patients does not vary significantly from that of the adult receiving TPN; however it is worth noting that the typical enteral diet of the neonate or infant derives approximately 50% of non-protein calories from fat.

Calcium and phosphate requirements of the neonate and infant are substantially different from those of the older child and are dramatically different from the requirements for the adult. When one attempts to meet these increased requirements in pediatric TPN regimens, problems may arise because calcium and phosphate salts are incompatible in aqueous solution and may also cause instability in lipid containing regimens.

1 Year to 3 years	4 years to 12 years
Protein = 2,5 g – 3 g / 100ml	Protein = 2 g / 100ml
Energy = 100 kcal /100ml	Energy = 100 kcal /100ml
Glucose=15 g/100ml	Glucose=15 g/100ml
Lipid = 3,5 g/100ml	Lipid = 3,5 g/100ml
Na = 2-3 mmol/100ml	Na = 2-3 mmol/100ml
K = 1,5-2 mmol/100ml	K = 1,5-2 mmol/100ml
Ca = 1,2 mmol/100ml	Ca = 0,6 mmol/100ml
HPO4 = 1 mmol/100ml	HPO4 = 0,5 mmol/100ml
Mg = 0,1 mmol/100ml	Mg = 0,1 mmol/100ml

4.3 Comparison of premixed pediatric TPN regimens currently available in South Africa

Product: ITN 1602

Composition	Per 100ml	RDA (per 100ml)	Ratio to RDA
Protein (g/kg)	2,53	2,5-3	1
Energy (kcal/kg)	66,8	100	0,668
Glucose (g/kg)	10,8	15	0,72
Fat (g/kg)	1,76	3,5	0,82
Na (mmol/kg)	1,8	2-3	0,9
K (mmol/kg)	1,42	1,5-2	0,95
Ca (mmol/kg)	0,82	1,2	0,68
P (mmol/kg)	0,63	1	0,63
Mg (mmol/kg)	0,05	0,1	0,5

Comments/ Recommendations

When administered at 100ml/Kg/24 hours, this regimen supplies approximately 70% of the required energy needs of the patient.   

Protein requirements are adequately met and would maintain a positive nitrogen balance.

Product: ITN 1502

Composition	Per 100ml	RDA (per 100ml)	Ratio to RDA
Protein (g/kg)	2,53	2,5-3	1,01
Energy (kcal/kg)	66,8	100	0,668
Glucose (g/kg)	10,8	15	0,72
Fat (g/kg)	2,7	3,5	0,77
Na (mmol/kg)	1,8	2-3	0,9
K (mmol/kg)	1,42	1,5-2	0,95
Ca (mmol/kg)	0,8	1,2	0,66
P (mmol/kg)	0,68	1	0,68
Mg (mmol/kg)	0,05	0,1	0,5

Comments/ Recommendations

As for Product ITN 1602.
Product: ITN 1700

Composition	Per 100ml	RDA (per 100ml)	Ratio to RDA
Protein (g/kg)	2,77	2	1,38
Energy (kcal/kg)	118,3	100	1,18
Glucose (g/kg)	17,26	15	1,15
Fat (g/kg)	4,93	3,5	1,41
Na (mmol/kg)	2,47	2-3	1,23
K (mmol/kg)	0,99	1,5-2	0,66
Ca (mmol/kg)	0,12	0,6	0,2
P (mmol/kg)	0,37	0,5	0,74
Mg (mmol/kg)	0,075	0,1	0,75

Comments/ Recommendations

This regimen supplies adequate energy in the form of fat and glucose, if administered at a rate of 100ml for 24 hours.

The protein is slightly higher [supplying 1,38 of RDA] than the 1997 ESPEN Guidelines.

K, Ca, P and Mg are inadequate and require adjusting to the 1997 ESPEN Guidelines.

4.4 Discussion and recommendations

The proposal that Isotec Nutrition should evaluate the recommendations and conduct stability studies on the newly proposed regimens, was accepted by all the delegates present.

Indications 
The indications for parenteral nutrition in pediatrics at Red Cross Childrens Hospital [Cape Town] were presented (by Prof A Sive). It was reported that most parenteral nutrition was administered on a short-term basis (usually less than 4 days). Twenty five percent of the TPN indicated, was for medical cases. A reduction in the prescription of TPN was due to a change in approach to more aggressive enteral feeding. However, it was mentioned that parenteral nutrition was occasionally used in combination with enteral nutrition [when nutrient requirements could not be adequately met per enteral nutrition]. It was recommended that appropriate selection criteria [protocol] should be used for the indication of TPN. It should be stressed that the majority of children requiring intravenous nutrition are undernourished at the outset and that in the South African situation, energy dense formulae are required. However, special care to prevent the refeeding syndrome is necessary.

Additive-Free Regimens
The possibility of regimens without additives for short-term parenteral nutrition was discussed [to make short-term parenteral nutrition more cost-effective]. It was felt, however that use of such "additive-free" formula should be limited to units experienced in the administration of parenteral nutrition [in which strict and thorough monitoring practices are followed].

Age Specific Nutrient Requirements
After discussion of the nutritional requirements for the different age groups, it was decided that at least two regimens should be available, namely, one for the young child (1-3 years) and one for the older child (4-12 years). The following requirements were identified:

The suggested compositions proposed regimens for the two age groups are given below. (Composition per 100 ml)

Regimen	Protein (g)	Energy (kcal)	Fat (g)	Glucose (g)	Na (mmol)	K (mmol)	Cl (mmol)	Mg (mmol)	Ca (mmol)	P (mmol)
1-3 years	2,5	100	3,5	15	2,5	1,5	1,8	0,25	1,2	0,9-1
4-12 years	2	100	3,5	15	3	2	2	0,2	0,5-0,7	0,5-0,7

Energy 
Energy content of approximately 1 kcal/ml.

Protein
Some delegates felt that protein should be provided at the upper limit of RDA’s as most of the patients treated [in the South African context] were malnourished. The dangers of excess protein were also stressed [re-feeding syndrome].

Fat
Fat should not provide more than 50% of the non-protein energy. It was recommended that 20% Intralipid should preferably be used [versus 10% Intralipid]. The fat intake is at the upper permissible level and lipaemia should be monitored

Amino Acid Solutions 
Vamin G is currently the only pediatric [appropriate] amino acid solution available in South Africa. It was recommended that Industry source a more pediatric specific amino acid solution that contains glutamine and / or taurine.

Fat-free Regimens
"3-in-1" regimens are used most frequently, however, it was agreed that lipid free regimens are sometimes required. It was thus recommended that a "3-in-1" and a lipid free regimen should be available for both age groups.

Definition of terms
The term "regimen" has been used synonymously with the terms "TPN formulae" and "TPN mixtures"

Disclaimer
The information provided in this document is a summarised outcome of a workshop. The content of the document does NOT imply that it is official SASPEN policy and neither SASPEN or any other party involved in any way in the production or distribution of this document can be held responsible for the accuracy, completeness or relevance of its content. Neither does the inclusion of this document in the Society’s web site implies that SASPEN endorses the contents of the document.
The document is intended for information only and for health professionals experienced in this field of nutrition.

© SASPEN 1999

Last updated: 12-Mar-2004