Incompatibilities in TPN A Problem not only in bags ... · Incompatibilities in TPN A Problem not...
Transcript of Incompatibilities in TPN A Problem not only in bags ... · Incompatibilities in TPN A Problem not...
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ESPEN Congress Brussels 2005
Incompatibilities in TPNA Problem not only in bags!
Regina Lourenço
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Regina LourençoPharmacy Department
Center of Nutrition and MetabolismUniversity Hospital St Maria
Lisboa, Portugal
Incompatibilities in TPNIncompatibilities in TPN
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IV tubingIV tubing
CatheterCatheter
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MicroMicroorganismsorganisms
AirAir
IncompatiIncompatibilitiesbilities
Particulate Particulate mattermatter
Catheter blockageCatheter blockageARDSARDS
Pulmonary emboliPulmonary emboliInfectionInfection
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ChemicalChemical
PhotolysisPhotolysis
OxidationOxidation
PhysicalPhysical
PrecipitationPrecipitation
CrackingCrackinglipid emulsionlipid emulsion
SorptionSorption
Nutrition therapeutic failureIatrogenic complications
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Flow rate
IV tubing
TPNComposition
Co-infusionof drugs
Light
Temperature
IntrinsecIntrinsecfactorsfactors
ExtrinsecExtrinsecfactorsfactors
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Decompositionor rearrange into a
new chemical entity
Catalyseoxidation / reduction
Wavelenghtdaylight > fluorescent
Intensity
Presence oflipid emulsion
LightLight
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CoCo--infusioninfusionof drugsof drugs
Decrease
hypoglicaemia
electrolytes disorders
Increase
precipitation
LE instability
infection
Amikacin
Sodium bicarbonate
HEPARIN
DiazepamDiazepamFurosemideFurosemidePhenytoinPhenytoin
Peripheral access Peripheral access limitedlimited
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CoCo--infusioninfusionof drugsof drugs
MultiMulti--lumenlumencathetercatheter
Y Y -- sitesiteconnectionconnection
Contact timeminimal
Contact time15 – 60 min
incompatibilitiesincompatibilities
TPN / Drug stability data!
PN composition
Drug’s brand name
Drug’s concentration
Contact times
Do notextrapolated
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pH
H3PO4 H2PO4- HPO4
2 - PO4 3 -
2.12.1 7.27.2 12.212.2
Ca2+ Ca2+Ca2+
Ca (HCa (H22POPO44))22 CaHPOCaHPO44 CaCa33(PO(PO44))22
CrystallineCrystallinepppp
Amorphous Amorphous pppp
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FreeFreecalciumcalcium
ionion
Order ofOrder ofmixingmixing
MagnesiumMagnesium
pHpH
TemperatureTemperature
Add phosphate first
Amino acids solutionsbuffering capacity
complexationPhosphates solutions
inorg. vs org. salts
Cysteine addition[glucose]
Chloride vsgluconate/gluceptate
saltsdegree of dissociation
degree of dissociationmonobasic dibasic salt
soluble/stablesalts with phosphate
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Electromechanical barrierElectromechanical barrier
oiloil waterwater
-
Phospholipids
Zeta potentialpH 6-9
InterferencePhysical instability
Aggregation Creaming Coalescence Cracking
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Divalent Divalent cationcation
-
-
CationCation 2+2+
oiloil
Lipid emulsion
Concentration: 10% vs 20%
Hydrocarbon chain length: MCT vs LCT
Fatty acids profile: oleic acid content
sodium oleate amount
pHpH
Phosphate / amino acids sources
Glucose content
TemperatureTemperature
FactorsFactors
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Sunlight (direct) Sunlight (direct) 100%100%
Daylight (shade) Daylight (shade) 90%90%Retinol
RiboflavinSunlight (direct) Sunlight (direct) 100% (8h)100% (8h)Daylight (shade) Daylight (shade) 47%47%Phototherapy Phototherapy 50% (24h)50% (24h)
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PUFA
O2
1O2 + FA OHº + FAº
PUFAº + H2OPUFAOPUFAO22ºº
PUFA PUFAOPUFAO22HH
+ PUFAº
OxygenOxygen
Light
Temperature
LipidsLipids
Vitamins A / E / C
Copper, iron, selenium
Lipid emulsion
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Lipidemulsion
Lipidperoxides
Ascorbicacid
Hydrogenperoxides
OO22Riboflavin
Light
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Calcium oxalateCalcium oxalate
Ascorbic acid
Dehydro-Ascorbic acid
Oxalic acid
Ca2+
OO22AdditivesAdditivesInfusionInfusion
PermeationPermeation
TemperatureTemperatureCopperCopper
IronIronManganeseManganese
ZincZinc
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The pharmacist has valuable expertise inImprove patient careAvoid adverse events
Decrease morbidity and mortality
Identifying issues related to compatibility / stability of TPN solutionsAdministration set tubing
Catheter
Selection of TPN components according to biological age, disease and compatibility data: amino acids solutions, lipid emulsions, calcium and
phosphorus salts, multivitamins formulations
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Minimise the likehood of an interaction
Precaution in evaluating compatibility/stability data
Avoid the administration of medications through the same port of TPN
Interrupt the TPN administration and flush with sterile water or sodium chloride 0,9% before and after administering the drug
Observe the patient for unexpected changes in clinical response
Monitorization of blood concentrations - drugs with narrow therapeutic index
Drug Drug –– Nutrient InteractionNutrient Interaction
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InIn--line filterline filter
Why? Decrease particles matters, microprecipitates, microorganims, air
Who? ICU, immunocompromised, neonates, children, home TPN patients
Where? Place as close to the patient
When to change? 0,2 micron + 1,2 micron: 24 h
0,2 micron endotoxin-retaining: 96 h
Which? 0,2 micron: 2-in-1 vs 1,2 micron: 3-in-1
(if possible, use endotoxin-retaining filters)
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LightLight--protecting administration setsprotecting administration sets
Prevents lipid peroxidation and vitamins degradation
or ensure that:or ensure that:
exposure to direct sunlight is avoided
daylight exposure is minimised by avoiding close proximity to windows
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References
Driscoll DF. Stability and compatibility assesment techiniques for total parenteral nutrition admixtures: setting the bar according to pharmacopeial standards. Curr Opin Clin Nutr Metab Care 2005; 8: 297-303.Muhlebach S. Practical aspects of multichamber bags for parenteral nutrition. Curr Opin Clin NutrMetab Care 2005; 8: 291-295.Gibbons E et al. Degradation of dehydroascorbic acid in parenteral nutrition mixttures. J PharmBiomed Anal 2001; 25: 605-611.Bethune K et al. Use of filters during the preparation and administration of parenteral nutrition: position paper guidelines prepared by a British Pharmaceutical Nutrition Group Working Party. Nutrition 2001; 17: 403-408.Silvers K et al. Lipid peroxide and hydrogen peroxide formation in parenteral nutrition solutions containing multivitamins. JPEN 2001; 25(3): 14-17. Allwood MC et al. Compatibility and stability of additives in parenteral nutrition admixtures. Nutrition 1998; 14: 697-706.Ball PA et al. Particulate contamination in parenteral nutrition solutions: still a cause for concern. Nutrition 2001; 17: 926-929.Allwood MC. Light protection during parenteral nutrition infusion: is it really necessary? Nutrition 2000; 16: 234-235.Parikh et al. Physical compatibility of neonatal total parenteral nutrient admixtures containing organic calcium and inorganic phosphate salts. Am J Health-Syst Pharm 2005; 62(1): 1177- 1183.Driscoll DF. Physicochemical stability assessment of lipid emulsions of varying oil composition. ClinNutr 2001; 20(2): 151-157.