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Flashcards in Parenteral Nutrition Support Deck (66):

Clinical nutrition support routes of supply

Nasogastric (NG)
Nasojejunal (NJ)
Percutaneous endoscopic- gastrostomy (PEG)
Percutaneous endoscopic- jejunal (PEJ)


Parenteral nutrition- ingredients

Amino acids
Trace elements


Indications for parenteral nutrition

Post-operative states where oral or tube feeding is contra-indicated for more than four or five days
Short bowel syndrome
GI fistulae
Acute pancreatitis
Multiple injuries involving viscera
Major sepsis
Severe burns


Nutrition, nutrition science and nutrients definitions

Nutrition: the science of food and its relationship to health
Nutrition science: the nature and distribution of nutrients in foods and their metabolic effects
Nutrients: chemical compounds in foods that are absorbed and utilised to promote health


Essential nutrient

One that is required by an organism, yet cannot be synthesised; failure to do so leading to a deficiency disease


Classifications of nutrients

Can be divided into 2 classes
Macronutrients: proteins, fats, carbohydrates and some mineral salts- supply energy for growth and activity
Micronutrients: vitamins and trace elements- catalyse the utilisation of the macronutrients


Pathophysiology of nutritional disease

Occurs by virtue of:
A dietary inadequacy
GI malabsorption
Abnormal systemic loss of nutrients through haemorrhage, diarrhoea or excessive sweating
Failure to reabsorb and retain nutrients by the kidneys


Primary malnutrition- marasmus

Insufficient energy to match requirements so body draws on its own stores
Severe wasting
No oedema
Subcutaneous fat minimal
Severe muscle wasting
Albumin near normal


Primary malnutrition- kwashiorkor

Insufficient protein intake so decreased visceral protein synthesis
Little wasting, muscle wasting variable
Subcutaneous fat present
Low serum albumin
Enlarged fatty liver
Skin/hair fragility


What are the sequence of events leading to a deficiency disease?

Nutrient not received or retained- plasma and tissue levels decline
Loss of cellular stores of nutrient, followed by reduction in all functions that depend on given nutrient
If deficiency persists, biochemical changes are followed by impairment of physiologic functions in given cells and their organs- leading to mortality


Metabolic pathways in first 24 hours of starvation

Glycogen from the liver is converted into glucose for the heart, muscles, kidney and brain


Metabolic pathways in early/late starvation

Amino acids from muscle and glycerol from fat stores are taken up by the liver and turned into glucose, ketones and fatty acids


The difference between metabolic reactions to short term and long term starvation

Increased glycogenolysis becomes depleted glycogen stored
Glucose oxidation leads to decreased glucose oxidation
Increased lipolysis leads to greatly increased lipolysis
Ketogenesis in the liver leads to greatly increased ketogenesis in the liver
Energy expenditure transiently elevated, becomes decreased


Primary and secondary effects of malnutrition

Increased tendency of infection, delayed wound healing, hypoproteinemia, muscle weakness
Increased morbidity, prolonged hospitalization, prolonged convalescence, increased mortality, increased costs


Effect of malnutrition on respiratory function

Decreased inspiratory force
Reduced vital capacity
Reduced functional residual capacity
Oxygenation decreased


Nutritional assessment



Malnutrition screening

MUST- Malnutrition Universal Screening Tool
Developed by MAG (malnutrition advisory group) or BAPEN (British association of parenteral and enteral nutrition)


Malnutrition tests

Simple tests- patient height and weight
Anthropometric tests- skinfold thickness, mid-arm circumference
Biochemical tests- complete blood tests, urinary and stool output


Nutritionally at risk patients

Gross underweight or overweight
Recent loss of 10% or more of usual body weight
High alcohol intake
Increased metabolic needs e.g. excessive burns, infection, trauma


Amino acid solutions

Comprise of a solution of crystalline L-amino acids
They provide amino acids for protein synthesis
Have a balance of essential and non-essential amino acids
There is no excessive levels of any one particular amino acid



Usually a solution of glucose in water at various concentrations (5-70%)
Major source of energy (minimum requirement of 200g/day for an adult male to avoid ketosis and protein catabolism)
Solutions of fructose, maltose, sucrose, xylitol, sorbitol and even ethanol have been looked at


Definition of an emulsion

A dispersion of one immiscible liquid in another as small droplets. It is a thermodynamically unstable system, which will separate into its original states over time
A barrier to instability can be produced by the use of an emulsifying agent. this generate a mechanical barrier and or an electrostatic barrier.


IV lipid emulsions and chylomicrons

The particle in IV emulsions have similar properties to natural chylomicrons, so that they are cleared from the body with similar kinetics


Fluid and electrolyte balance

Fluid requirements usually in the range of 2-3L/day
Weight increases greater than 1kg/week could be due to water fluid retention


Signs of water depletion

Thirst, dry tongue, low urine volume, concentrated urine, weight loss, inelastic skin, mental confusion


Signs of water intoxication

Drowsiness, loss of concentration, giddiness, confusion, anorexia, loss of muscle power, subcutaneous oedema


Trace elements

Withdrawal leads to a reproducible functional and or structural abnormality
The abnormality is associated with a specific biochemical change
This biochemical change is prevented and or cured along with the observed clinical abnormality by giving the deficient trace element


Essential trace elements

Copper, chromium, iron, magnesium, molybdenum, selenium, zinc, iron, iodine, fluorine, cobalt, nickel, tin, silicon, vanadium, arsenic
These trace elements constitute less than 0.01% of the human body weight


Trace element- uptake and use

Orally obtained trace elements are absorbed usually from the gut in combination with specific carrier proteins
Generally, trace elements are vital components of many of the body's enzyme systems. They act either as integral components called metalloenzymes or as cofactors to enzymes.
The enzyme systems usually being involved in the breakdown of nutrients and the synthesis of biomolecules


IV nutrition and trace elements

Protein hydrolysates- used as the usual source of amino acids until around 1970, provided varying amounts of trace elements as contaminants
The purified crystalline amino acid solutions used today contain much smaller amounts of contaminants and therefore reports of trace element deficiency states were soon reported


UK chambered bags

Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition


Delivery of TPN

Central route: disadvantages- air embolism, pneumothorax, central vein thrombosis, cost of insertion; advantages- rapid and high flow delivery route, long term use
Peripheral route: disadvantages- sepsis, kinked lines, thrombophlebitis, insertion sites; advantages- short use, easy insertion, multiple insertion sites


Responsibilities of the PN pharmacist

To ensure maximum chemical and physical compatibility and stability of all the constituents in a PN admixture
To provide a maximum guarantee of sterility of the finished product
To achieve a cost effective approach to the prescribed formulation


PN stability issues

Immediate use vs stored products
Prescription vs batch production
Home parenteral nutrition (additions)
Industrially or hospital compounded


Complexity of TPN admixtures

More than 50 chemical entities, numerous interactions, precipitation, emulsion breakdown, container materials- PVC, EVA and multi-laminated, environmental conditions- light, oxygen and temperature, drugs


Chemical and physical stability issues

Chemical: component stability, drugs
Physical: precipitation, lipid emulsion, drugs


Vitamins/trace elements stability

Vitamins: effects of light, oxygen, interaction with plastics
Trace elements: reaction with H2S gas and or direct reaction between cysteine and copper ions, ion and phosphate solutions


PN stability checks

Chemical: complex testing in industrial units- extrapolation of testing data from regulatory submission documents, research into groups of components and lipids
Physical: free from precipitated matter, globule size distribution changes- lipid emulsions


Clinical requirements of calcium and phosphate

Transference levels across the placenta near birth can be up to 4mmol of calcium and 1mmol of phosphate/kg/day
Requirements for the premature infant can reach 6mmol of calcium and 2.5mmol of phosphate/kg/day in 100-150ml of fluid


Types of calcium phosphate precipitate

Ca3(PO4)2- immediate precipitate- white and amorphous
CaHPO4- time mediated precipitate- distinct crystal formation


Factors affecting calcium phosphate precipitation

Degree of dissociation and likelihood of calcium phosphate precipitation
Chloride>gluconate>organic salts
Chemical reaction kinetics- warmer environment gives faster reactions
Amino acids: buffer pH changes, forms complexes with calcium
Magnesium: forms complexes with phosphate
Order of mixing: phosphate solutions should be added to glucose solutions, calcium solutions should be added to amino acid solutions, if not possible then phosphate solutions should be added first and calcium last


Assessing compatibility/stability

Theoretical assessment based on: solubility calculations, pH calculations, complexation calculations
Practical experiments


Analysis methods or determining the presence of calcium phosphate precipitates

Visual inspection, fibre optic lighting with light and dark backgrounds, nephelometry, pH measurements, particle counting methods, chemical analysis methods


Compatibility/stability quality criteria

Visual inspection: the admixture should be clear and free from particulate matter
pH measurement: there should be no significant change of the experimental storage period


Calcium phosphate precipitate related clinical problems

Catheter occlusion
Pulmonary deposition of calcium phosphate crystals leading to respiratory distress syndrome which in turn leads to multi organ failure


Organic phosphates used in parenteral nutrition

Sodium glycerophosphate
Calcium glycerophosphate


Organic phosphate metabolism

Glycerophosphates and glucose-1-phosphate have important roles in the carbohydrate metabolism cycle
Plasma alkaline phosphatases are thought to be responsible for the cleavage of the inorganic phosphate from the organic phosphate molecule


Organic phosphate conclusions

Calcium phosphate precipitation is life threatening and it is the responsibility of the pharmacist to ensure its prevention
Organic phosphates have an important role to play in fluid restricted parenteral nutrition situations where high levels of calcium and phosphate are required


Pharmacist role

Judgement of stability issues: impact on clinical need- adult vs neonates etc.
Aware of clinical practice
Critical review of information- be aware of differences in worldwide practice and solutions


IV lipid emulsions and chylomicrons

The particles in IV emulsions have similar properties to natural chylomicrons, so that they are cleared from the body with similar kinetics


Electric double layer

Cations at interface
Cations and anions in diffuse layers
Zeta potential of intralipid = -30mV
Mutual repulsion of globules provides stability


Shielding of the surface charge is affected by:

Availability of ions (ionic strength)
Specific absorption of ions on the surface
Ionisation state of the emulsifiers


Influence of non-lipid components on stability

Glucose: degradation products, variations in pH and pH effects
Amino acids: balance of acidic and basic forms and pH and charge effects
Electrolytes: dependence on valency and charge effects


Instability limits

Blockage of the capillaries of the lungs by large globules
0.5% of particles found in lungs are 1 micrometre in diameter, while 31% were 8 micrometres in diameter
PFAT limit: % of particles greater than 5 micrometres, range of defined instruments to be used to assess the stability


Complexity of PN admixture stability

More than 50 chemical entities- numerous interactions
Precipitation or emulsion breakdown
Container materials- PVC, EVA and multi-laminated
Environmental conditions- light, oxygen and temperature


Advantages of PN drug addition

Increased microbiological safety (if addition made in pharmacy)
Reduction in fluid and electrolyte load for patient
Posible cost savings (reduction in nursing workload, reduced delivery equipment requirements etc. )


Types of PN admixtures

All in one
Aqueous two in one
Two in ones with Y sited lipid emulsion


Drug and PN stability

Adsorption or absorption of drug to the PN delivery container and tubing
e.g. insulin reported losses of 12-30%
Lipid emulsion interference with insulin binding reported in other studies
Bioavailability of drug after administration
Problems with narrow therapeutic drugs
Drug stability in the nutrient solution- possible degradation products


Results of interaction

Addition of long-chain heparin to PN admixtures containing calcium and lipid emulsion
Gross changes in lipid emulsion stability observed in seconds


Structure of heparin

Repeated structure with varying chain length
Method of manufacture- influences molecular size
NB new low molecular weight versions


Options/methods of PN drug addition

Flush techniques
Multiple lumen catheters
Piggy-backing the drug via a Y site
Direct addition to PN container (with and without storage)


Flush techniques

PN administration, stop PN delivery, flush delivery line with neutral solution, restart PN delivery
Disadvantages: increased risk of contamination, fluid and electrolyte load benefits lost, PN administration rate altered


Piggy-back methods

Stability of drug in neutral solution and in PN admixture
Advantage- no storage of system
Disadvantages- risk of contamination, rates of infusion, length of co-mixed infusion


Drug addition to PN container

Advantage: controlled addition under aseptic conditions in pharmacy
Disadvantages: storage/contact times longer, no independent control of delivery rates of PN and drug, problems with patients with constantly changing formulations (wastage)


Testing methods

Visual inspection
Turbidimetric measurements
Particle size analysis and counting methods
HPLC and other chemical analysis methods
Important to reproduce clinical conditions


FDA safety alert 1994

A filter should be used when infusing either central or peripheral nutrition admixtures