Satellite Symposium - Tony - BAPEN · PDF fileSatellite Symposium SdbSponsored by. ... [Incubator 32 – 34 ... Baby 3: 1 42 Kg Gestational age 29 weeksBaby 3: 1.42 Kg,

Satellite Symposium

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Formulation of a start-up & maintenance PN feedfor the preterm infantp

BAPEN CONFERENCE NOV 2007

T M hTony MurphyPharmacy Department

University College London HospitalsUniversity College London Hospitals

[email protected] p y@

Formulation of standard PN feeds for the preterm infantFormulation of standard PN feeds for the preterm infant

PN administration system• PN administration system

• Historical changes to the standard baby PN feed (1972 – 2007)

• Mini audit on the neonatal unit at UCLH

• Improving the current PN feed p o g t e cu e t eed

• UK working party & Reference Sources

• New ‘start-up’ and ‘maintenance’ PN feeds

• Administration guidelines

• Dose modification in the term baby

F t id ti & d l t• Future considerations & developments

IV Administration system for baby PN (UCH)

Administration System forInfusion of Parenteral NutritionTo Premature Infants at UCLHTo Premature Infants at UCLH

a Amino AcidGlucose Mix & Peditrace 1ml / 150ml [Ward 20 – 25°C]

EVA TPN bagOxford Nutrition

IV Burette (Alaris) Medex 2001Code 72103E Syringe driver

Lipid 20% &Solivito N & Vitlipid InfSolivito N & Vitlipid Inf1ml/Kg

BD AmberSyringeRef 300869

Alaris SE Gold Pump

Pall 0.2 micron IMF light protectedFilter Line (ref MF1641)

Neonatal Y connectorWith anti reflux valvesIMF (ref MF1572)

[Incubator 32 – 34°C] or [Cot 20 – 25°C]

Butterfly line Bore 1mm, Volume 0.2ml

Neonatal Catheter Bore 0.3mm,Volume 0.03ml [catheter 37°C]

Standard baby PN feed at UCLH (1972 – 2007)( iti f i id / l ‘b ’ l ti )(composition of amino acid / glucose ‘base’ solution)

additional Sodium, Potassium & Phosphate (from 1995 onwards) added as required

PN Feed 1970 Oct 1990 Oct 1990 1995 1995 PresentPN Feed 1970 – Oct 1990Per 150 ml

Oct 1990 – 1995Per 150ml

1995 - Present

Nitrogen (g) *Kabi Fresenius

0.33 equivalent to 2.46g AASource: Vamin 9 Glucose*

0.4 equivalent to 2.84g AASource: Vaminolact*

0.4 equivalent to 2.84g AASource: Vaminolact*

Glucose (g) 15 15 15

Sodium (mmol) 4 4 2.25

Potassium (mmol) 2.9 3 2

Calcium (mmol) 0.89 0.9 0.9

Magnesium (mmol) 0.16 0.17 0.17

Phosphate (mmol) 0.98 (inorganic salt) 0.98 (inorganic salt) 1.13 (glycerophosphate)

Chloride (mmol) 4.6 3.19 1.44

Acetate (mmol) - 2.25 1.49

Gluconate (mmol) 1.78 1.8 1.2

Zi ( ) 150 150 250 ( P di )Zinc (µg) 150 150 250 (as Peditrace)

Copper (µg) 45 45 20

Manganese (µg) - - 1

Selenium (µg) 1 5 2Selenium (µg) - 1.5 2

Fluorine (µg) - - 3

Iodine (nanomol) - - 7.9

Mini audit on the neonatal unitBaby 1: 0.604 Kg, Gestational age 23 weeksBaby 1: 0.604 Kg, Gestational age 23 weeks

D f lif 1 2 3 4 5 6 7Day of life 1 2 3 4 5 6 7

PN feedm l / Kg

0 0 0 0 108 114 145

Fat emulsion20% m l / Kg

0 0 0 0 5 10 15g

Oral Feedm l / Kg

0 0 0 0 5.8 1.7 0

Total IV andOral feedm l / Kg

124 143 137 196 209 209 169

IV glucose 7 2 8 7 8 7 7 9 10 10 7 11 6IV glucosem g / Kg / m in

7.2 8.7 8.7 7.9 10 10.7 11.6

Day of life 8* 9 10 11 12 13 14

PN feed 77 0 0 0 108 114 145m l / KgFat emulsion20% m l / Kg

0 0 0 0 5 10 15

Oral Feedm l / Kg

0 0 0 0 5.8 1.7 0

Total IV and 124 143 137 196 209 209 169Total IV andOral feedm l / Kg

124 143 137 196 209 209 169

IV glucosem g / Kg / m in

7.2 8.7 8.7 7.9 10 10.7 11.6

* Line o t infected?* Line out – infected?

Mini audit on the neonatal unitBaby 2: 0 700 Kg Gestational age 25 weeksBaby 2: 0.700 Kg, Gestational age 25 weeks

f lif 1 2 3 4 6Day of life 1 2 3 4 5 6 7

PN feedml / Kg

0 0 146 148 146 150 139

Fat emulsion20% ml / Kg

0 0 6.4 10.8 15 15.4 16.620% ml / KgOral Feedml / Kg

0 0 0 0 0 0 0 ?

Total IV andOral feedml / Kg

90 147 175 169 171 186 160

ml / KgIV glucosemg / Kg / min

6.7 9.3 11 10.3 10.1 10.8 9.6

Day of life 8 9 10

PN feedml / Kg

93 59 16

Fat emulsion20% ml / Kg

16.8 8.3 4

Oral Feedl / K

114 147 191ml / KgTotal IV andOral feedml / Kg

224 215 212

IV glucosemg / Kg / min

6.4 4.1 1.1mg / Kg / min

Mini audit on the neonatal unitBaby 3: 1 42 Kg Gestational age 29 weeksBaby 3: 1.42 Kg, Gestational age 29 weeks

Day of life 1 2 3 4 5 6 7

PN feedml / Kg

0 0 0 0 0 150 150

Fat emulsion 0 0 0 0 0 0 520% ml / KgOral Feedml / Kg

0 5.6 9.1 2.1 0 0 0

Total IV andOral feed

l / K

83 83 123 143 143 150 155

ml / KgIV glucosemg / Kg / min

5.9 5.9 8.6 9.9 9.9 10.4 10.4

Day of life 8 9 10 11 12 13

PN feedml / Kg

150 150 150 150 150 120

Fat emulsion20% ml / Kg

5 10 10 15 15 0

Oral Feed 0 0 0 0 2.1 34Oral Feedml / Kg

0 0 0 0 2.1 34

Total IV andOral feedml / Kg

155 160 160 165 167 155

IV glucose 10.4 4.1 10.4 10.4 10.4 5.9mg / Kg / min

Improving the current PN feed – some objectives:

• Design a start-up intravenous feed to enable earlier introduction of amino acids

• Increase the amino acid content of the current PN feed to deliver3.5g / Kg / day amino acids to ELBW (<1Kg) and VLBW (<1.5Kg) preterm infants [ c rrent feed 2 8g / Kg / da ]infants [ current feed 2.8g / Kg / day ]Tsang (2005) guideline amounts of amino acids g / kg / day:

Day 0 Transition GrowingELBW infants: 2 3.5 3.5 – 4VLBW infants: 2 3.5 3.2 – 3.8

• Increase calcium content of PN feed to provide1.5mmol / Kg / day[ current feed 0.9 mmol / kg / day ]Tsang (2005) guideline amounts (mmol / kg / d)g ( ) g ( g )

Day 0 Transition GrowingELBW infants: 0.5 -1.5 1.5 1.5 - 2VLBW infants: 0.5 -1.5 1.5 1.5 - 2VLBW infants: 0.5 1.5 1.5 1.5 2

Improving the current PN feed – some objectives:

• Ensure non-metabolisable base content of the feed is equal to or higher than current value

• Reduce the volume of the PN feed. [ currently 150ml / kg / day – amino acid, glucose and electrolyte solution

15 l / k / d 20% F t l i TOTAL 165 l / K / d ]+ 15ml / kg / day – 20% Fat emulsion TOTAL 165ml / Kg / day]

• Decide on the daily dose of Vitlipid N Infant (fat soluble vitamins)[ currently 1ml / Kg / day ]

Neonatal PN working party - 20th Nov 2002Neonatal PN working party 20th Nov 2002

I C t ll ( Bi i h Child ’ H it l )• Ian Costello ( Birmingham Children’s Hospital )• Venetia Horn ( Great Ormond Street )

A d F ( St M ’ H it l P t th )• Andy Fox ( St Mary’s Hospital Portsmouth )• Victoria Magnall ( Alderhey Children’s Hospital )• Tony Murphy ( University College Hospital)• Dr John Puntis ( Leeds General Infirmary )• Elaine Smith ( Chelsea & Westminster Hospital )• Rachel & Zac ( Kabi Fresenius )

Neonatal PN - working party – 2006/7Neonatal PN working party 2006/7

• Pamela Cairns – Bristol (St Michaels Maternity Hospital)• Alan Cosslett – Cardiff (University)

• Richard Gant Essex (Colchester Hospital)• Richard Gant – Essex (Colchester Hospital)• Sarah Irwin – Cardiff (University)

• Chris Jarvis – Nottingham (Hospital)• Caroline King – London (Hammersmith Hospital)

• Bruce McElroy – Birmingham• Claire McIntyre – Fresenius Kabi LtdClaire McIntyre Fresenius Kabi Ltd

• Tony Murphy – London (Univ. Coll. Hospital)• Sarah Ryan – London (Guy’s & St Thomas’ Hospital)

I R kill C l Ltd• Ian Rosekilly – Calea Ltd• Stephen Tomlin – London (Guy’s & St Thomas’ Hospital)

• Guy Topping – Calea Ltdy pp g• A Scott – Nottingham (Hospital)

Source references - in paediatric PNSource references in paediatric PN

– Nutrition of the Preterm infant. Scientific basis and practical guidelines.g

Tsang RC, Uauy R, Koletzko B, Zlotkin SH. 2nd edition 2005. Published by Digital Educational Publishing ISBN 1-58352-100-3

– Guidelines of Paediatric Parenteral Nutrition (ESPGHAN)(European Guidelines)

Koletzko B, Goulet O, Shamir R, Hunt J, Krohn KJournal of Paediatric Gastroenterology and Nutrition 2005;41

supplement 2, S1-S87pp ,

Water Soluble Vitamins – Recommended doses in Preterm InfantsPropose no change to UCLH PN feed Solivito N 1ml / KgPropose no change to UCLH PN feed – Solivito N 1ml / Kg

Vitamin ESPGHAN 2005 TSANG 2005 Current UCLH Proposed UCLHInfants. ELBW & VLBW

Infants. PN Feed

Solivito N 1ml / kgPN Feed No Change

Vitamin C (mg) 15 – 25 15 – 25 10 10

Thiamine (µg) 0.35 – 0.5 0.2 – 0.3 0.3 0.3

Riboflavine (mg) 0.15 – 0.2 0.15 – 0.2 0.36 0.36

Pyridoxine (mg) 0.15 – 0.2 0.15 – 0.2 0.4 0.4

Niacin (mg) 4 – 6.8 4 – 6.8 4 4

B12 (µg) 0.3 0.3 0.5 0.5

Pantothenic acid (mg) 1 – 2 1.2 – 1.7 1.5 1.5

Bi ti ( ) 5 8 5 8 6 6Biotin (µg) 5 – 8 5 – 8 6 6

Folic acid (µg) 56 25 – 50 40 40

Fat Soluble Vitamins – Recommended doses in Preterm InfantsPropose to increase Vitlipid N Infant dose from 1ml / Kg to 2ml / Kg

Vitamin ESPGHAN 2005Infants.

TSANG 2005ELBW & VLBW

Infants.

Current UCLHPN Feed

Vitlipid N Infant 1ml / Kg

Proposed UCLHPN Feed

Increase dose to2ml / Kgg g

Vitamin A (µg) 150 – 300[ 500 ]

210 – 450 69 138

Vitamin D (µg) 0 8 1 25 – 4 1 2Vitamin D (µg) 0.8[ 4 ]

1.25 4 1 2

Vitamin E (mg) 2.8 – 3.5[2 8 ]

2.8 – 3.5 0.64 1.28[2.8 ]

Vitamin K (µg) 10[ 80 ]

10 20 40

Figures in [ red ] are original recommendations by Greene HL et al Am J Clin Nutr 1988; 48(5): 976-86

Good ref: re vitamin A & E absorption to PN bag and admin lines:C Haas, O Genzel – Boroviczeny, B Koletzko. European Journal of Clinical Nutrition 2002; 56(9): 906 - 912

Start-up Feed – Jan 2008p

Formula for 100 ml Composition per 100 ml

Vaminolac 46 mlGlucose 50% 20 ml

Composition per 100 ml

Nitrogen (g) 0.42[ i l 3 i id ]Glucose 50% 20 ml

Potassium Acid Phosphate 13.6% 1 mlCalcium Gluconate 10% 4.48 ml

[equivalent to 3 g amino acids]

Glucose (g) 10Sodium (mmol) 0

Magnesium Sulphate 50% 0.1 mlZinc Sulphate 50µmol/ml 0.08 mlWater for Injection 28 34 ml

Potassium (mmol) 1Calcium (mmol) 1Magnesium (mmol) 0 2Water for Injection 28.34 ml

N Base: - 0.8 mmol / 100ml

Magnesium (mmol) 0.2Phosphate (mmol) 1Chloride (mmol) 0Gluconate (mmol) 1Sulphate 0.2

Maintenance PN Feed – Jan 2008

Formula for 135 ml Composition per 135 ml

Vaminolac 53 mlGlucose 50% 30 ml

Composition per 135 ml

Nitrogen (g) 0.49[ i l 3 46 i id ]Glucose 50% 30 ml

Sodium Glycerophosphate 21.6% 1.5 mlPotassium Acetate 49% 0.4 ml

[equivalent to 3.46 g amino acids]

Glucose (g) 15Sodium (mmol) 3

Calcium Chloride 14.7% 1 mlCalcium Gluconate 10% 2.24 mlMagnesium Sulphate 50% 0 1 ml

Potassium (mmol) 2Calcium (mmol) 1.5Magnesium (mmol) 0 2Magnesium Sulphate 50% 0.1 ml

Water for Injection 46.79 mlMagnesium (mmol) 0.2Phosphate (mmol) 1.5Chloride (mmol) 2

N Base: + 2.3 mmol / 135ml

Current PN feed: +1 7 mmol / 150ml

Acetate (mmol) 2Gluconate (mmol) 1Sulphate (mmol) 0 2Current PN feed: +1.7 mmol / 150ml Sulphate (mmol) 0.2

Proposed schedule for using standard PN feeds in Preterm Infants < 2.5 Kg (renal function permitting)

START UP Feed / Kg MAINTENANCE Feed / Kg

Day 1 of life Day 2 Day 3 Day 4 onwardsVolume (ml) AA / glucose solution 50 100 135 135

Amino acids (g) 1.5 3 3.46 3.46

Glucose (g) 5 10 15 15Glucose (g) 5 10 15 15

Sodium (mmol) 0 0 3 3

Potassium (mmol) 0.5 1 2 2

Calcium (mmol) 0.5 1 1.5 1.5

Magnesium (mmol) 0.1 0.2 0.2 0.2

Phosphate (mmol) 0.5 1 1.5 1.5

Chloride (mmol) 0 0 2 2

Acetate (mmol) 0 0 2 2 [ Max 5mmol ]Acetate (mmol) 0 0 2 2 [ Max 5mmol ]

Zinc (µmol) 0.2 0.4 0.4 (from Peditrace) 0.4 (from Peditrace)

Peditrace (trace elements) 0 0 1ml 1ml

Intralipid 20% emulsion 0 5 10 15

Solivito N (ml/kg) 0 0 - 1 1 1

Vitlipid N Infant (ml/kg) 0 0 – 2 2 2

+ ADDITONAL FLUIDS & ELECTROLYTES AS REQUIREDTOTAL FEED VOLUME (ml / kg) 50 107 147 152TOTAL FEED VOLUME (ml / kg) 50 107 147 152

Total Energy (kcal/kg) inc Protein 25.5 61 93 103

Proposed schedule for using standard PN feeds in Term Infants > 2 5 Kg (renal function permitting)Term Infants > 2.5 Kg (renal function permitting)

MAINTENANCE Feed / Kg

Day 1 of PN Day 2 Day 3 onwardsDay 1 of PN Day 2 Day 3 onwards

Volume (ml) AA / glucose solution 60 80 100

Amino acids (g) 1.5 2 2.56

Glucose (g) 6.7 8.8 11(g)

Sodium (mmol) 1.3 1.8 2.2

Potassium (mmol) 0.9 1.2 1.5

Calcium (mmol) 0.67 0.9 1.1

Magnesium (mmol) 0.09 0.12 0.15

Phosphate (mmol) 0.67 0.9 1.1

Chloride (mmol) 0.9 1.2 1.5

Acetate (mmol) 0.9 1.2 1.5

Peditrace (trace elements) 1ml / 100ml feed 1ml / 100ml feed 1ml / 100ml feed

Intralipid 20% emulsion 5 10 15

Solivito N (ml/kg) 1 1 1

Vitlipid N Infant (ml/kg) 1 1 1

+ ADDITONAL FLUIDS & ELECTROLYTES AS REQUIREDTOTAL FEED VOLUME (ml / kg) 66 91 116Total Energy (kcal/kg) inc Protein 42.3 62.7 83.4

Intralipid 20% emulsion (x100)

Lipid aggregation at the interface betweenIntralipid and the amino acid /glucose mixtureIntralipid and the amino acid /glucose mixture

A sample of the PN mixture leaving the catheter tip after 7 hours of a simulated feedsimulated feed

Future considerations & developmentsFuture considerations & developments

• UCLH to start using new PN feeds in Jan 2008• UCLH to start using new PN feeds in Jan 2008

• 6 month audit proposed following implementation

• Stability of emulsion system at interface with amino acid / glucose solution needs to be assessed following increase of calcium concentration in feedconcentration in feed

• A PN feed containing a lower glucose concentration ( providing 10 g/kg vs 15 g/kg/day ) would be useful to manage hyperglycaemia10 g/kg vs 15 g/kg/day ) would be useful to manage hyperglycaemia

• Aluminium load in PN feed should be assessed – particularly that contributed by calcium gluconate additivecontributed by calcium gluconate additive.

• UK working party has been set up to consider the formulation of PN feeds for older infants and childrenfeeds for older infants and children.

Final thought!From Jonathan Shaw’s* 1973 paper

Parenteral Nutrition in the Management of Sick Low Birthweight Infants. Paediatric Clinics of North America Vol 20, No 2, May 1973

‘The technique of parenteral feeding, though promising, has a definite mortality and morbidity which can only be kept at an acceptable level by

obsessional attention to detail’

* Lecturer in Paediatrics, University College Hospital, Medical School, y g p ,