ParenteralNutrition: The Role of the Pharmacist in the Era ... · 2005 Parenteral Nutrition: The...
Transcript of ParenteralNutrition: The Role of the Pharmacist in the Era ... · 2005 Parenteral Nutrition: The...
ESPEN Congress Brussels 2005
bull Parenteral NutritionThe Role of the Pharmacist in the Era of 3-chamber Bags
bull Stefan Muumlhlebach
20052005
ParenteralParenteral NutritionNutritionThe Role of the Pharmacist in the Era of The Role of the Pharmacist in the Era of
33--chamber Bagschamber Bags
Stefan Muumlhlebach Prof DrSwissmedic Berne (Switzerland)
Stefanmuehlebachswissmedicch
20052005
The Swiss Capital BerneThe Swiss Capital BerneView from View from SwissSwissmedicmedic to the to the AlpesAlpes
20052005
The Berner Oberlandafter the heavy rainfalls last week
(Fluids can harm)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)
(Total)(Total)
ParenteralParenteralNutritionNutrition
(Partial)(Partial)
GastrointestinalFailure
GastrointestinalDysfunction
ImpairedEnteral Absorption
Digestion
Assimilation
20052005
PN Characteristics (1)PN Characteristics (1)
Nutrients ivNutrients ivFluids
Electrolytes
Glucose
Amino Acids
Triglycerides
VitaminsTrace Elements
PORT-A-CATH
HICKMANN BROVIAC
iv Accessiv Access
Fat
Protein
Glycogen
N-Loss
TissueTissueMetabolism Metabolism RebuildingRebuilding
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ParenteralParenteral NutritionNutritionThe Role of the Pharmacist in the Era of The Role of the Pharmacist in the Era of
33--chamber Bagschamber Bags
Stefan Muumlhlebach Prof DrSwissmedic Berne (Switzerland)
Stefanmuehlebachswissmedicch
20052005
The Swiss Capital BerneThe Swiss Capital BerneView from View from SwissSwissmedicmedic to the to the AlpesAlpes
20052005
The Berner Oberlandafter the heavy rainfalls last week
(Fluids can harm)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)
(Total)(Total)
ParenteralParenteralNutritionNutrition
(Partial)(Partial)
GastrointestinalFailure
GastrointestinalDysfunction
ImpairedEnteral Absorption
Digestion
Assimilation
20052005
PN Characteristics (1)PN Characteristics (1)
Nutrients ivNutrients ivFluids
Electrolytes
Glucose
Amino Acids
Triglycerides
VitaminsTrace Elements
PORT-A-CATH
HICKMANN BROVIAC
iv Accessiv Access
Fat
Protein
Glycogen
N-Loss
TissueTissueMetabolism Metabolism RebuildingRebuilding
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
The Swiss Capital BerneThe Swiss Capital BerneView from View from SwissSwissmedicmedic to the to the AlpesAlpes
20052005
The Berner Oberlandafter the heavy rainfalls last week
(Fluids can harm)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)
(Total)(Total)
ParenteralParenteralNutritionNutrition
(Partial)(Partial)
GastrointestinalFailure
GastrointestinalDysfunction
ImpairedEnteral Absorption
Digestion
Assimilation
20052005
PN Characteristics (1)PN Characteristics (1)
Nutrients ivNutrients ivFluids
Electrolytes
Glucose
Amino Acids
Triglycerides
VitaminsTrace Elements
PORT-A-CATH
HICKMANN BROVIAC
iv Accessiv Access
Fat
Protein
Glycogen
N-Loss
TissueTissueMetabolism Metabolism RebuildingRebuilding
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
The Berner Oberlandafter the heavy rainfalls last week
(Fluids can harm)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)
(Total)(Total)
ParenteralParenteralNutritionNutrition
(Partial)(Partial)
GastrointestinalFailure
GastrointestinalDysfunction
ImpairedEnteral Absorption
Digestion
Assimilation
20052005
PN Characteristics (1)PN Characteristics (1)
Nutrients ivNutrients ivFluids
Electrolytes
Glucose
Amino Acids
Triglycerides
VitaminsTrace Elements
PORT-A-CATH
HICKMANN BROVIAC
iv Accessiv Access
Fat
Protein
Glycogen
N-Loss
TissueTissueMetabolism Metabolism RebuildingRebuilding
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)
(Total)(Total)
ParenteralParenteralNutritionNutrition
(Partial)(Partial)
GastrointestinalFailure
GastrointestinalDysfunction
ImpairedEnteral Absorption
Digestion
Assimilation
20052005
PN Characteristics (1)PN Characteristics (1)
Nutrients ivNutrients ivFluids
Electrolytes
Glucose
Amino Acids
Triglycerides
VitaminsTrace Elements
PORT-A-CATH
HICKMANN BROVIAC
iv Accessiv Access
Fat
Protein
Glycogen
N-Loss
TissueTissueMetabolism Metabolism RebuildingRebuilding
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)
(Total)(Total)
ParenteralParenteralNutritionNutrition
(Partial)(Partial)
GastrointestinalFailure
GastrointestinalDysfunction
ImpairedEnteral Absorption
Digestion
Assimilation
20052005
PN Characteristics (1)PN Characteristics (1)
Nutrients ivNutrients ivFluids
Electrolytes
Glucose
Amino Acids
Triglycerides
VitaminsTrace Elements
PORT-A-CATH
HICKMANN BROVIAC
iv Accessiv Access
Fat
Protein
Glycogen
N-Loss
TissueTissueMetabolism Metabolism RebuildingRebuilding
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PN Characteristics (1)PN Characteristics (1)
Nutrients ivNutrients ivFluids
Electrolytes
Glucose
Amino Acids
Triglycerides
VitaminsTrace Elements
PORT-A-CATH
HICKMANN BROVIAC
iv Accessiv Access
Fat
Protein
Glycogen
N-Loss
TissueTissueMetabolism Metabolism RebuildingRebuilding
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PN Substrate Admixing PN Substrate Admixing insideinside the Body the Body (Multi(Multi--bottle System)bottle System)
Glucose (additives)
Amino Acids(additives)
Lipid
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Glucose
Muumlhlebach Curr Opin Cin Nutr Metabol Care 20058291
Comp
onen
ts
ErrorsDosingAdministration
ComplicationsComplications(Safety)(Safety)
MetabolicMetabolicMicrobialMicrobialMechanicalMechanicalEconomicEconomic )
Amino acidsGlnhellip
TriglyceridesLCT MCT Ω-3
Trace elements Fe Zn Mn Cu Cr Mo Se F J
ElectrolytesNa K Ca Mg P Cl
VitaminsA B C D E K
PN Characteristics (2)PN Characteristics (2)
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ParenteralParenteral Nutrition (PN)Nutrition (PN)bull Effective when indicatedbull Higher risk of complications
ndash iv accessndash Correct dosingndash Aseptic preparation (individualisation)ndash Stability complex pharmaceutical interactionsndash Higher costs compared to ENndash Patients partly highly fragile (neonates
critically ill)ndash Long-term treatment (HPN)
bull Multi-professional approach (pharmacist)
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Role
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Clinical Nutrition Clinical Nutrition MultiMulti--professional Processprofessional Process
Nutrition Support Team
PatientPatientOutcomeOutcome
Diagnosis
Nutritional state
PatientEvaluation
Malnutritionrisk
Prescription
EnteralParenteral
AdmixingAdministration
GMPHandling
Benefits from NST (Review) JPEN 200428(4)251
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005 Hospital Manufacture and Hospital Manufacture and CompoundingCompounding
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Risk reduction (Safety uarr)
bull Mechanical Documented stability of the admixtures
bull Metabolic Appropriate nutrient administration(individualisation)
bull Infective Aseptic compounding (ready to use)
bull Economic Preparation cost Utilisation review
bull Convenience AIO ready to use single container
PN Pharmaceutical SupportPN Pharmaceutical SupportCompounding AdmixingCompounding Admixing
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limits
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
AIO admixtureLimited stability
DextroseAmino acidsLCT (MCT) fatNa+
K+
Ca++
Mg++
PhosphateFe Zn Mn Cu Cr Mo Se F J(Vit A B C D E K)
Components(gt 50)
DextroseNa K Ca P
Amino acidsNa K Mg
Lipid
Trace elementsVitamins
1
2
3
4
5
Ready to use AIO Admixture Safe PracticesReady to use AIO Admixture Safe Practices
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291 Driscoll JPEN 200327433
IndustrialIndustrialProductionProduction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Lipid Lipid PeroxidationPeroxidation in EVAin EVA--AIO AdmixturesAIO AdmixturesInfluence of Trace Elements (TE) Influence of Trace Elements (TE)
and Storage Conditionsand Storage Conditions
0
1
2
3
4
1 4 8 14 19 29Days of storage
Peroxide values[mmol peroxidesL]
08
Steger Muumlhlebach JPEN 20002437-41
20-30degC daylight with TE20-30degC daylight
2-8degC light-protected with TE2-8degC light-protected
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005 Industrial AIO Premixes Industrial AIO Premixes (Standards)(Standards)The 3The 3--Chamber BagChamber Bag
Injection port
Breakable connectionor seal
Infusion port
Glucose Lipid
Amino acidsCover wrap
(Oxygen protection)
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
Container polymer(Sterilisation)
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005 Standardised PN in HospitalsStandardised PN in HospitalsNutrition 200420528Nutrition 200420528--535535
Switzerland 86 adult standard PN (HP 16 compounded)
France79 adult standard PN(HP 18 compounded )
Belgium86 adult standard PN
(HP 56 compounded)
HospCategory Median Min-
Max Ratio MedianMin-Max
Ratio Median Min-Max Ratio
Univ 6lsquo983(4) 1lsquo874-9lsquo725
60-7lsquo506
4-2lsquo890
51 13lsquo017 (18)
2lsquo419-39lsquo500 154 6lsquo041 (1)
600-41lsquo300
95
Non-Univ 1lsquo351 (12) 39 2lsquo490
(19)350-6lsquo760
49 1lsquo375 (1)20-
16lsquo47268
Regional 651 39 267 (5)30-
3lsquo15932 1lsquo966 (6)
380-3lsquo600
92
Private 2lsquo357 (6)384-
12lsquo62975
Ratio no of PN bags per yearbed in 2000 Home PN proportion 5-7 (CH B) 20 (F)
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Duration of HPNNumber of Regimens [n] Reasons for Adaptations
Regimens per patientRegimens per patient 75 plusmn 6575 plusmn 65
Patient No of regimens [n]
Nutritional requirement
Product requirement
Stability reasons
AB 2 7 BK 4 3 1 BS 5 5 FS 11 16 3 1 JF 4 3 1 KA 4 4 2 RS 24 38 4 1 UM 13 15 3 VE 3 3 VF 8 36 XM 4 7 Total 82 137 14 2 Mean plusmn SD 75 plusmn 65 125 plusmn 130
HPN Need for Individualisation of PNHPN Need for Individualisation of PN
Clin Nutr 200019(suppl1)60
0 12 24 36 48 60 72 84 96 108 120ABBKBSFSJFKARSUMVEVFXM
Mean
Patie
nt
[months]
n=4n=8
n=3n=13
n=24n=4
n=4
n=4n=2
n=5n=11
Mean Mean plusmnplusmn SDSD [month] 526 plusmn 405[month] 526 plusmn 405
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safety
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PN Pharmaceutical TasksPN Pharmaceutical Tasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
X
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Lipid Emulsion DestabilisationLipid Emulsion Destabilisation
reversible irreversible-
Lecithin emulsifierempty 02 - 04 microm
MFTmaxmean max droplet diameter
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Droplet Distribution of iv Lipid EmulsionsDroplet Distribution of iv Lipid EmulsionsNormal Probability Curve Normal Probability Curve
From Driscoll DF Examination of selection of light-scattering and light obscuration acceptance criteria for lipid injectable emulsions Pharm Forum 200430(6)2244-53
Large Diameter Tail bdquoUnstableldquo
Large Diameter Tail bdquoStableldquo
Mean Droplet Size (~03 microm)
Diameter [microm]
20+ microm005 03 5
Fat
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PFAT5 Dose Increase over 24-hour Infusion in Rats (23 mlhr)Half-life of increase 12 hours
0000
0500
1000
1500
2000
2500
3000
3500
0 1 6 12 17 18 19 20 21 22 23 24 25
Time [hrs]
Dos
e R
ate
(PFA
T5 [
] hr
)
0000
0500
1000
1500
2000
2500
3000
3500
PFA
T 5 [
]
Dose Rate (DR) from measuredPFAT5
DR PFAT5(t)= DR PFAT5(0)+10-7e(0573t)DR PFAT5(t) = DR PFAT5(0) + 1610-7 e(0573t)
Dose Rate (DR) from Measured PFAT5
1000
0500
0000
LB027
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Lipid Emulsion Stability Influence of Lipids and Amino Acids
Schmutz CW Werner R Keller U Muumlhlebach SClin Nutr 199312(S2)59
AIO PN 5 g lipidL 6 g NL 144 g dextrose L pH 49-53Na+K+ (60mM) P (19 mM) trace elementsCa++ (75 mM) Mg++ (10mM)
MCT vs Lipovenoumls
Amino Acids
Lipids Amino Acids
X Lipids
Hausmann-Amin vs
Vamin
0002
0111
0594
Vamin vs
Proteinsteril
0786
0241
0026
Hausmann-Amin vs
Proteinsteril
0011
0934
0005
ANOVA of MFTmax with repeated measures and two group factors
Significance over time (10 days) (p-values)
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Lipid Emulsion Stability (Lipid Emulsion Stability (MFTMFTmaxmax) ) Influence of Amino acidsInfluence of Amino acids
Clin Nutr 199312(S2)59
AIO-Stability using Intralipidreg (MFTmax)
Ca++ 75 mM Mg++ 10 mMM
FTm
ax[micro
m]
45
Days after compounding
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005 Bag Plastic Film layers Bag Plastic Film layers Physical Phenomena OccurringPhysical Phenomena Occurring
Desorption
Solution Film Outer side
Permeation
Migration
Adsorption
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Effect of Packaging Container on Effect of Packaging Container on Lipid Emulsion CharacteristicsLipid Emulsion Characteristics
PFAT5 Levels in Various LipidsManufacturer G-Lipids (n) P-Lipids (n) 3C-P Lipids (n)
A 0046plusmn0004 (4) 0120plusmn0023 (2) 0159plusmn0015 (2)B 0028plusmn0011 (3) Not Available 0006plusmn0002 (2)
LB028 The effects of packaging containers and manufacturer on the large-diameter tail of the globule size distribution
of lipid injectable emulsions - Part 2D F Driscoll1 A Thomas2 K Kluetsch2 B R Bistrian1 J Nehne2
1Medicine Harvard Medical School Boston United States 2Hospital Care B Braun Melsungen Germany
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Medication Errors with Medication Errors with ParenteralsParenterals
Taxis K Barber N Taxis K Barber N EurEur J J ClinClin PharmacolPharmacol 200459815200459815--77
Multiple Step Preparation Admixing (Ready to use)
IncompatibilitiesAdmixing incompatible drugs
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
50 microm
Ca2+ + H3PO4Ca(H2PO4)2 + CaHPO4
Solubility (H2O)
RDA iv [mmolkg]Neonates Adults
Calcium 05 - 15 01 - 02Phosphate 06 - 13 01 - 09Vol [mlkg] 120 25 - 30
Calcium phosphate PrecipitationCalcium phosphate Precipitation
April 18 1994 FDA-Alert
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Nutritional Care in HospitalsNutritional Care in Hospitals
Council of Europe (2002)
4Responsibility defined4Education and training4Patient-oriented4Multidisciplinary nutrition support teams4Implementation top down
(Guidelines and recommendations)Clinical Nutrition 200120(5)455-460 Akt Ernaumlhr Med 200328133-136
Aim Prevent treat undernutrition to improve patientlsquos outcomeBest use of clinical nutrition
PhysicianPharmacistDieticianNurse Other healthprofessionals
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PN PN PharmaceuticalPharmaceutical TasksTasks
Acquisition and DeliveryPurchase andor preparation ()Distribution
Drug use and administrationRecommendations and guidelines (dosages interactions iv administration)
Control and ReviewProduct qualityHandling (correctnesslegality CIRS safety)Analysis of indications outcomeCost
Stock management Waste
Selection and Documentation of Products
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
DrugActive ingredientSolvent
VehicleInfusion fluidContainer
Good ManufacturingPractices
AsepsisDocumentation
AdministrationParenteral AccessInfusion time
AIO AdmixtureLipids
GlucoseAmino acidsElectrolytes
Trace elementsVitamins
Drug admixing in PN Drug admixing in PN Pharmaceutical AspectsPharmaceutical Aspects
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005 Lipid Peroxide Formation Vitamins Lipid Peroxide Formation Vitamins (NICU)(NICU)
0
100
200
300
400
500
600
700
0 1 2 4 8 12 24
Fig Trend in peroxide formation in a lipid emulsion with (1 a b ab) and without fat soluble vitamins (contr)
The emulsion was pumped through the orange coloured infusion system at different flow and lighting conditions
pero
xide
con
c [micro
mol
TB
H-e
ql-1
]
time [h]1 07 ml h-1 daylight a 01 ml h-1 daylightb 07 ml h-1 phototherapy light ab 01 ml h-1 phototherapy lightcontr 01 ml h-1 phototherapy light
Graumlflein Muumlhlebach Clinical Nutrition 200423892
Intralipid 20 plusmn Vitalipid Infant (AD2K1E)Light-protecting tubings syringe pumpFOX Assay tert-butyl hydroperoxide (TBH) as reference
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Drug Drug NutrientNutrient Interaction Interaction CiclosporinCiclosporin ((SandimmunSandimmunregreg) admixed to iv ) admixed to iv IntralipidIntralipidregreg
0
1
2
3
4
5
6
7
0 1 2 3 4
CyA-Konzentration [microMolCyAmMol Triglycerid]
FFA-
Relea
se [micro
MolM
in] 100 lipase activity
Ciclosporin CyA
Sandimmun ivCyA+ CremophorEtOH
SolventCremophorEtOH
Fig 1 Lipase inactivation by CyA Sandimmuntradeiv or solvent in lipid emulsion Solvent (CyA-free) is expressed corresponding to the concentration in Sandimmuntradeiv
Clinical Nutrition 200120(S3)27
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
ContentContentbull Parenteral Nutrition Characteristicsbull NST Pharmacistrsquos Rolebull Delivery Systems and their limitsbull Pharmacistrsquos Role in PN Safetybull Conclusions
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PN Delivery Systems 3PN Delivery Systems 3--C C BagsBagsBottles with
singlecomponents
Bottles withcombined
components
Two in oneAdmixtures
All-in-one(3 in 1)
admixturesAmino acids
Glucose
Lipid
Ready-to-use (-) (+) + + +
21
AIO
Adapted from bdquoBasic in Clinical Nutritionldquo 3rd edition Galen (Prague) 2004
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Pharmacistrsquos RolePharmacistrsquos RoleSafe PracticesSafe Practices
Glucose Lipid
Amino acids
Muumlhlebach Curr Opin Clin Nutr Metabol Care 20058291
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Pharmacistrsquos RolePharmacistrsquos RolePN as Drug VehiclePN as Drug Vehicle
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
bull Duration of PN [d] 7-78 (min-max) 14 (mean)12 (median)
bull Indication Guidelines (ASPEN acute93) 77 (7192) fulfilled
bull Chart Review Requirements 50 fulfilled (Check lists) Prescriptions 28 incomplete
Lab tests 64 incomplete
bull Complications Hyperglycaemia 30 ( gt 10mM) Catheter-related 7 ( 23infections)
Akt Ernaehr Med 19982343-49
ResultsResults
Quality of Hospital PN Use Quality of Hospital PN Use Concordance to local guidelinesConcordance to local guidelines
92113 consecutive surgical patients with PN prospective analys92113 consecutive surgical patients with PN prospective analysis over 9 monthsis over 9 months
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Quality Increase of PN TreatmentQuality Increase of PN Treatment
Nutrition Guidelines (Nutrition Support Team)
bull Standardisation of PN treatments (unified concept)bull Less inappropriate treatments (errors )bull Reduced costs
Adapted from Woolf SH Arch Intern Med 1992152946-52
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005 PN Economic Importance PN Economic Importance in Hospitalsin Hospitals
Drug Products Basic iv Fluids for infusion Parenteral Nutrition Dalteparin (LMWH Coagulation disorders) Rituximab (MabTherareg Antineoplastics) Gamma Globulines iv (Immunology) Iopromid (Ultravistreg Constrat media) Trastuzumab (Herceptinreg Antineoplastics) Erythropoetin (Hemodialysis) Docetaxel (Antineoplastics) Piperacillin + Tacobactam Paclitacel (Antineoplastics) Carboplatin (Antineoplastics) Gemcitabin (Antineoplastics) Iomeprol (Iomeronreg Constrat media l) Infliximab (Remicadereg) Cisplatin (Antineoplastics) Hemodialysis Concentrates (Hemodialysis) Amoxicillin + Clavulansaumlure (Anti-Infection) (Pharmacy KSA Acquisition Costs 2004)
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
PharmaconutritionPharmaconutritionDifferent Types of Lipid EmulsionDifferent Types of Lipid Emulsion
bull Soybean Safflower Oil (Ω-6 Ω-3 ~ 7 1)Arachidonic acid PEG24 LT24 (SIRS)
bull MCT LCT (Ω-6 Ω-3 ~ 7 1)Structured Lipid Emulsion
bull SMOF (Ω-6 Ω-3 ~ 25 1)Soybean (30)-MCT (30)-Olive Oil (25)-Fish Oil (15) EPA DHA
Clinical Nutrition 200524 (Supplement 1) 1-30 New Lipid in Parenteral Nutrition
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
iv Drug Errors at Ward Leveliv Drug Errors at Ward LevelAdmixing amp AdministrationAdmixing amp Administration
Identification(prescription)
(3)
Ready to use(0)
1-step(0)
Multi-step(14)
IdentificationPatient(0)
Bolus(73)
Small volumeInfusion
(9)
Large volumeInfusion
(0)
KTaxis N Barber bdquo iv drug errorsldquo BMJ 2003326684
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction
20052005
Incompatibility reactionsIncompatibility reactions
Chemical Incompatibilitiesbull Oxidation Reductionbull Hydrolysisbull Polymerisationbull Decarboxylation
(CO2 formation)bull Racemate formationbull Complexation
bdquoChem-physik Inkompatibilitaumlten parenteral verabreichter Arzneimittelldquo in Grundlagen der Arzneimitteltherapie 16th edition 234-9 Documed Basel 2005
Lipidperoxidation
Maillard-Reaction