ESPEN Congress Brussels 2005

Incompatibilities in TPNA Problem not only in bags!

Regina Lourenço

Regina LourençoPharmacy Department

Center of Nutrition and MetabolismUniversity Hospital St Maria

Lisboa, Portugal

Incompatibilities in TPNIncompatibilities in TPN

IV tubingIV tubing

CatheterCatheter

11

MicroMicroorganismsorganisms

AirAir

IncompatiIncompatibilitiesbilities

Particulate Particulate mattermatter

Catheter blockageCatheter blockageARDSARDS

Pulmonary emboliPulmonary emboliInfectionInfection

ChemicalChemical

PhotolysisPhotolysis

OxidationOxidation

PhysicalPhysical

PrecipitationPrecipitation

CrackingCrackinglipid emulsionlipid emulsion

SorptionSorption

Nutrition therapeutic failureIatrogenic complications

22

Flow rate

IV tubing

TPNComposition

Co-infusionof drugs

Light

Temperature

IntrinsecIntrinsecfactorsfactors

ExtrinsecExtrinsecfactorsfactors

Decompositionor rearrange into a

new chemical entity

Catalyseoxidation / reduction

Wavelenghtdaylight > fluorescent

Intensity

Presence oflipid emulsion

LightLight

CoCo--infusioninfusionof drugsof drugs

Decrease

hypoglicaemia

electrolytes disorders

Increase

precipitation

LE instability

infection

Amikacin

Sodium bicarbonate

HEPARIN

DiazepamDiazepamFurosemideFurosemidePhenytoinPhenytoin

Peripheral access Peripheral access limitedlimited

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

33

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

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

44

Electromechanical barrierElectromechanical barrier

oiloil waterwater

-

Phospholipids

Zeta potentialpH 6-9

InterferencePhysical instability

Aggregation Creaming Coalescence Cracking

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)

66

PUFA

O2

1O2 + FA OHº + FAº

PUFAº + H2OPUFAOPUFAO22ºº

PUFA PUFAOPUFAO22HH

+ PUFAº

OxygenOxygen

Light

Temperature

LipidsLipids

Vitamins A / E / C

Copper, iron, selenium

Lipid emulsion

Lipidemulsion

Lipidperoxides

Ascorbicacid

Hydrogenperoxides

OO22Riboflavin

Light

Calcium oxalateCalcium oxalate

Ascorbic acid

Dehydro-Ascorbic acid

Oxalic acid

Ca2+

OO22AdditivesAdditivesInfusionInfusion

PermeationPermeation

TemperatureTemperatureCopperCopper

IronIronManganeseManganese

ZincZinc

77

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

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

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)

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

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.