Formulating an HPN Prescription Dr Alison Culkin Research Dietitian St Mark’s Hospital
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Formulating an HPN Prescription Dr Alison Culkin Research Dietitian St Mark’s Hospital
Overview
● To be able to formulate a tailor made PN bag
● To have an understanding of the importance of PN stability
Case
Date Age Problem
1997 Congenital myasthenia syndrome 1997 10 days Tracheostomy on BiPAP 1998 8 months Gastrostomy insertion (later removed) 2002 5 years Nissen Fundoplication 2009 12 years Adhesiolysis (small bowel obstruction) 2012 14 years Adhesiolysis (small bowel obstruction) Jan 2014 16 years Correction of scoliosis June 2015 17 years SB resection due to obstruction from
volvulus leaving 40cm from DJ flexure with 280cm of distal bowel to colon
17 year old male lives with his grandparents
Estimated requirements Energy 1750kcal Nitrogen 9.3g Fluid 3000ml Sodium 207mmol Potassium 31-47mmol Calcium 3.1-4.7mmol Magnesium 3.1-6.2mmol Phosphate 12mmol
Multichamber bag Volume
(ml) N (g)
Energy (kcal)
Na (mmol)
K (mmol)
Ca (mmol)
Mg (mmol)
PO4 (mmol)
Kabiven 9 2400 9 1500 53 40 3.3 6.7 18
Additrace 1 vial
Solivito 1 vial
Vitlipid 1 vial
Requirements 3000 9.3 1250 207 31-47 3.1-4.7 3.1-6.2 12
Prescription 2430 9 1500 53 40 3.3 6.7 18
•Monitor weight and anthropometrics Too much energy
•Request additions to the bag? •Run additional saline Inadequate fluid & sodium
•Monitor blood concentrations Too much phosphate
How to provide this regimen?
• Difficult to provide from MCB
• High fluid / electrolyte requirements
• Lipid free bags
• PN needs to be tailored to individual requirements
• Depends on pharmacy compounding facilities
Tailored/Scratch bags Depends on compounding facilities/cost/storage etc Use when ‘all-in-one’ does not fit:
↓ Fluid/ electrolyte requirements e.g. renal ↑ Fluid/ electrolyte requirement e.g. high output stoma/fistula
More flexibility with amounts but still limited by product selection: i.e. Lipids available in 250 & 500ml bottles (550-1000kcal) Nitrogen may only be as 8.25g, 9.1g, 12.85g, 13.5g
Formulating an HPN Bag
• Choose the amino acid solution
• Choose the glucose solution
• Choose the lipid emulsion
• Electrolytes (min & max)
• Vitamins and trace elements
• Volume
Choose a nitrogen source
Volumeml N (g) Energy
kcal Na
mmol K
mmol Ca
mmol Mg
mmol PO4
mmol
Vamin 18EF 500 9
Requirements 3000 9.3 1250 207 31-47 3.1-4.7 3.1-6.2 12
Total (so far)
500 9 0 0 0 0 0 0
Taurine
• Shown to occur in short bowel patients • Do not reabsorb bile acids normally • ↑ losses of taurine conjugates of bile acids
Deficiency
• Children: LFTs improve (Heird et al, 1987) • Adults: Plasma concentrations restored with
10mg/kg/d (Kopple 1990)
Correcting the deficiency
Bile acid
conjugation Sulfolithocholate Choline (cholestatic)
Taurine (not cholestatic) Bile
Taurine in HPN
• RCT (crossover) • HPN patients with chronic cholestasis given a mean
16mg/kg/day • 11 patients completed both arms of the study
Methods
• No change in Alk Phos, bilirubin or GGT • No adverse events or complications observed • 90% found to be taurine deplete & plasma
concentration restored after IV supplementation Results
• Taurine is safe but no effect on LFTs over 3 months Conclusion
Culkin et al (2008) Eur J Clin Nutr, 62, 575
The aim was to determine if the inclusion of IV taurine as part of the nitrogen source of HPN reduces abnormal LFTs
Glutamine Most abundant amino acid in the body Main source is skeletal muscle (>60%) evidence of
depletion during stress Major fuel for rapidly proliferating tissues, e.g.
enterocytes & immune cells Precursor for glutathione (antioxidant) Substrate for renal ammonia production (regulation of acid-base balance) ‘Conditionally essential’ in times of injury and sepsis Safe IV dose 0.28-0.57g/kg/d
Glutamine in HPN
• 35 HPN patients • RCT (crossover design) Methods
• No difference in infective complications, intestinal permeability, plasma glutamine concentrations
Results
• Glutamine as part of the nitrogen source of HPN can be given to patients for 6 months without any adverse effects
Conclusion Culkin et al (2008) Eur J Clin Nutr, 62, 575
To determine if the inclusion of 10 g of glutamine as part of the nitrogen source of HPN reduces infectious complications.
Choose a lipid source Volume
ml N (g) Energy kcal
Na mmol
K mmol
Ca mmol
Mg mmol
PO4 mmol
Vamin 18EF 500 9
SMOF Lipid 20% 500 1000 7.5*
Requirements 3000 9.3 1250 207 31-47 3.1-4.7 3.1-6.2 12
Total (so far) 1000 9 1000 0 0 0 0 0
Lipid in long term PN Patients Trial Lipid Outcome
Rubin (2000) Nutrition, 16:95
n=20 4/52 on PN
Prospective RCT for 4/52
MCT/LCT vs LCT 2 patients on LCT ↑ LFT → Normal on LCT/MCT
Chambrier (2004) JPEN, 28:7
n=11 >6/12 on HPN
Prospective non randomised for 4/12
LCT →MCT/LCT No difference in LFTs No EFAD ↓ vitamin K
Thomas-Gibson (2004) Clin Nutr 23, 4
n=11 6/12 on HPN
Retro & prospective for 6/12
LCT → Olive Oil No difference in LFTs infection or thrombosis
Reimund (2005) APT, 21:445
n=14 >11/12 on HPN
Prospective non randomised for 3/12
LCT or LCT/MCT → olive oil
No difference in LFTs CRP, IL-6 or TNF-α No EFAD
Vahedi (2005) BJN, 94:909
n=13 >6/12 on HPN
RCT for 3/12 LCT MCT/LCT Olive
No difference in LFTs No EFAD
Klek (2013) Clin Nutr 32:224
n=73 >4/52 on PN & HPN
RCT for 4/52 LCT vs SMOF ↓ ALT, AST & Bili No change in IL-6, CRP ↑ Vitamin E, EPA & DHA
Choose a glucose source Volume
ml N (g)
Energy kcal
Na mmol
K mmol
Ca mmol
Mg mmol
PO4 mmol
Vamin 18EF 500 9
SMOF Lipid 20% 500 1000 7.5*
Glucose 10% 500 200
Glucose 40% 500 800
Requirements 3000 9.3 1250 207 31-47 3.1-4.7 3.1-6.2 12
Total (so far) 2000 9 2000 0 0 0 0 0
Electrolytes
Need to be individually assessed Additions can be added in aseptic unit Maximum amounts vary with fluid/
macronutrient composition Discuss stability with pharmacy
Volume (ml)
Nitrogen (g)
Energy (Kcal)
Na (mmol)
K (mmol)
Ca (mmol)
Mg (mmol)
PO4 (mmol)
Vamin 18EF 500 9
Glucose 10% 500 200
Glucose 40% 500 800
Water 1000
SMOF Lipid 20% 500 1000 7.5*
Sodium chloride 0.9% 500 77
Sodium chloride 30% 18 92
Potassium chloride 15% 30 60
Calcium Chloride 1mmol/ml 5 5
Magnesium sulphate 50% 3 6
Sodium glycerophosphate 21.6%
15 30 15
Requirement 3000 9.3 1250 207 31-47 3.1-4.7 3.1-6.2 12
Total 3571 9 2000 199 60 5 6 22.5*
Electrolytes & fluid
Vitamins ● All patients receiving parenteral nutrition should
receive fat & water vitamins ● Requirements are different to oral/enteral ● Use standard preparations in fixed doses but adjust if:
● Deficiency (acute/chronic) ● Toxicity (acute/chronic) ● Degradation during storage ● Effect of acute phase response on requirements/ plasma
concentrations (CRP <20 for accurate interpretation)
Vitamin preparations
Cernevit Solivito Vitlipid Vitamin A Biotin Folic Acid Vitamin B12 Thiamine Riboflavin Vitamin B6 Pantothenic acid Vitamin C Vitamin D Vitamin E Vitamin K
3500 IU 69 µg
414 µg 6 µg
3.51 mg 4.14 mg 4.53 mg
17.25 mg 125 mg
220 IU (D3) 10.2mg
0 µg
- 60 µg
400 µg 5 µg
3.1 mg 4.9 mg 4.9 mg
16.5 mg 113 mg
- -
3300 IU - - - - - - - -
200 IU 1 IU
150 µg
Vitamin D status in HPN patients 199 patients assessed at St Mark’s Mean vitamin D 62 ± 37nmol/L 8% severely deficient, 37% deficient, 27% insufficient Not associated with gender, age or IF aetiology High dose IM supplementation (150,000IU)
↑concentrations but still below recommended levels
Tee et al 2010, UEGW 2979
Trace elements in PN Requirements are different to oral/enteral Assess patients individually Large amounts needed in short bowel (selenium/zinc) Use standard preparations in fixed doses but adjust if:
• Deficiency (acute/chronic) • Toxicity (acute/chronic) • Effect of acute phase response on requirements / plasma
concentrations(CRP <20 for accurate interpretation)
Review regularly
Shenkin (2001) Clin Nutr, 20:47, Fuhrman (2006) Nut Clin Pract, 21:566, Hardy et al (2009) Nutrition, 25:1073
Trace element preparations • Additrace (10ml) • Decan (40ml) • Nutrylet (10ml) • Addaven (10ml)
Commercially available
• Varies • Selenium content is ↓in Additrace compared to Decan,
Nutrylet and Addaven Composition
• Hepatic: Cu, Mn • Renal: Zn, Cr, Se
Consider clearance
• Give trace elements & water-soluble vitamins daily due to losses during dialysis
• Caution with Vitlipid due to Vitamin A: suggest give x 3/week and monitor
Renal patients
Our lipid HPN Regimen Volume
(ml) Nitrogen
(g) Energy (Kcal)
Na (mmol)
K (mmol)
Ca (mmol)
Mg (mmol)
PO4 (mmol)
Vamin 18EF 500 9
Glucose 10% 500 200
Glucose 40% 500 800
Water 1000
SMOF Lipid 20% 500 1000 7.5*
Sodium chloride 0.9% 500 77
Sodium chloride 30% 18 92
Potassium chloride 15% 30 60
Calcium Chloride 1mmol/ml 5 5
Magnesium sulphate 50% 3 6
Sodium glycerophosphate 21.6%
15 30 15
Additrace 10
Cernevit 5
Requirement 3000 9.3 1250 207 31-47 3.1-4.7 3.1-6.2 12
Total 3586 9 2000 199 60 5 6 22.5
Our aqueous HPN Regimen Volume
(ml) Nitrogen
(g) Energy (Kcal)
Na (mmol)
K (mmol)
Ca (mmol)
Mg (mmol)
PO4 (mmol)
Vamin 18EF 500 9
Glucose 50% 500 1000
Water 1000
Sodium chloride 0.9% 1000 154
Sodium chloride 30% 3 15
Potassium chloride 15% 30 60
Calcium Chloride 1mmol/ml 5 5
Magnesium sulphate 50% 3 6
Sodium glycerophosphate 21.6%
15 30 15
Additrace 10
Cernevit 5
Requirement 3000 9.3 1250 207 31-47 3.1-4.7 3.1-6.2 12
Total 3071 9 1000 199 60 5 6 15
Stability
• It is important to have a basic knowledge of stability
• It is important to be aware of restrictions that exist
• Every PN bag requires a stability check in order to produce a solution safe for administration
• Patient safety is paramount
Basic stability
Complex solutions with >50 chemical components
Environment, storage time and container can also affect stability
Main risks: Calcium/phosphate interaction Lipid Electrolytes Trace elements Vitamins
Stability Ca & Phosphate
•Factors affecting this: •Calcium salt •Phosphate salt •Temperature •Other PN components (amino acid and magnesium)
•Mixing order •Risk: •Catheter occlusion •Pulmonary deposition of calcium phosphate crystals
Lipid •Electrolyte and trace element concentrations
•Volume •Amino acid composition (balance, pH) •Glucose concentration (pH and viscosity) •Buffering agents (PO4, acetate) •Lipid emulsion composition •Light •Temperature & storage/delivery times
Electrolyte •Maximum values that can be added are available from manufacturers
•Related to lipid stability and reactivity between species
•Higher electrolyte content in an aqueous bag than a lipid containing bag
Trace element • Particularly a problem with Vamin®
amino acid solutions • Cysteine interacts with copper to
form copper sulphide precipitate • Additions e.g. Zinc, Selenium, Iron
Vitamin • Vitamins degrade within hours of
addition to PN mixture • Need to protect from light and
oxygen • Oxidation can be reduced by using
multilayer bags and removing air from the bag after filling
• Use light protection bags • What about protecting the giving
sets?
Summary
Advantages & disadvantages of different types of PN
Formulate a PN prescription to meet requirements
The importance of stability & your pharmacist
The importance of working as part of an MDT including aseptic services
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