PRESENTED BY

ROOMA KHALID

M.Phil pharmaceutics(2014-

2016)

Islamia University Bahawalpur

Definition

Objectives

Indications

Administration

Formulation

Compounding

Documentation

DEFINITION:

A method of feeding the patients by

infusing the mixture of all necessary

nutrients into the circulatory system, thus by

passing the GIT.

Also referred to as

Intravenous nutrition

Parental nutrition

Parental nutrition is indicated generally

when there is severe gastro-intestinal

dysfunction (patients who cannot take

sufficient food or feeding formulas by enteral

route)

1:Central or total parental nutrition (TPN)

2:Peripheral parental nutrition (PPN)

1: CENTRAL OR TOTAL PARENTAL NUTRITION:

It is given via central

vein.central route is indicated when long

term feed is anticipated, high tonicity or

large volume formulations are required.

2: PERIPHERAL PARENTAL NUTRITION:

it is given via peripheral vein. It

is indicated for patients which require short

term feeding. Generally 900mOsmol/L is

maximum osmolarity tolerated by the

peripheral veins.

For patients unable to tolerate any form of

enteral feeding, the administration of fluid

and nutrients via a parenteral route is

necessary.

For long-term care a balanced diet

containing all the essential nutrients,

including vitamins and trace elements, must

be provided.

To prevent unwanted weight loss and skinbreak down, promoting positive nitrogenbalance and maintaining visceral and somaticprotein stores.

Illness and injury promote catabolism andhypermetabolism, so the patient is burningcalories faster to keep up with his body'sdemands. If he doesn't get adequatenutrition, his body will break down leanmuscle for glucose, which could slow healingand prolong his recovery (Collins & Navarre,2003).

TPN reduces morbidity and mortality,

promotes tissue repair, and enhances the

immune response (Merck, n.d.)

Johnston at al reported in 1978 that an

undernourished patient whose

gastrointestinal tract is temporarily or

permanently unusable can increase lean body

tissue and also lay down fat if fed a suitable

combination of nutrients intravenously.

With an understanding of the clinical aspects

of TPN, pharmacists can recommend

regimens to fulfil the needs of the patient as

diagnosed by the physician.

Possible interactions with concomintant

medication may be identified and advice

given on suitable administration systems.

TPN is considered necessary in following

conditions:

Patients whose GIT tract is inaccessible, non

functional, perforated.

Undernorished patients who cannot ingest

larger volumes of oral feedings and are being

prepared for surgery, radiation therapy, or

chemotherapy.

Disorders requiring complete bowel rest e.g

ulcerative colitis

Pediatric GI disorders e.g prolonged diarrhea

Powell-Tuck at al reported in 1978 a

technique for administration of the total

daily requirement for TPN via a single

container. This was a significant advance

over the multiple-bottle method of

administration. Three-litre bag therapy,

however, is not ideal for all patients.

In an intensive care unit, for example,

requirements for fluids and electrolytes may

change rapidly throughout the day and

require the careful titration that can only be

obtained with smaller volume fluids and

injections.

For short-term therapy rotation of peripheral

entry sites may provide a simple means of

administering TPN without the complications

of initiating central vein access. Silk at al

reported in 1983 that for longer-term

therapy a catheter placed into the superior

vena cava as being the safest method of

entry providing rapid dilution of the

hypertonic solution.

Adult TPN patients generally receive 2-3

litres of fluids per day. Rapid,uncontrolled

infusion of this amount of fluid would cause

renal overload and would be of no benefit to

the patient. It is thus vital that some form of

flow control device is employed. This may

range from simple clamps through to

electronic drip controllers.

Once TPN has been initiated on a patient it is

essential that routine monitoring is carried

out. The clinical pharmacist should have an

understanding of the relevance of these

routine tests (particularly those such as 24-

hour urine analysis which is the main

determinant of nitrogen requirements) in

order to make adjustment to the TPN

formulation.

Parenteral nutrition solutions are complex

formulations that generally include energy

supplied as dextrose and fat, as well as

protein, electrolytes, trace

elements,vitamins, and water. These

components usually need to be individualized

for patients according to their primary

diagnosis, chronic diseases, fluid and

electrolyte balance,acid-base status, and

specific goals of parenteral nutrition.

1. NITROGEN:

The main objective of parental

nutrition is to supply the undernourished

patient with sufficient utilizable nitrogen to

re-establish nitrogen balance, i.e. where the

amount of nitrogen administered is

approximately equal to that excreted (mainly

as urea).

2.AMINO ACIDS:

The body’s relative requirements of the

individual amino acids is expected as follows:

ESSENTIAL:

Which cannot be synthesized

by man. All the commercially available

solutions contain the eight essential amino

acids in varying proportions.

NON ESSENTIAL AMINO ACIDS:

Those amino acidswhich can normally be synthesized by thebody. These amino acids are used to increasethe amount of nitrogen available from thesolutions.

SEMI ESSENTIAL AMINO ACIDS:

Those amino acidswhich although they can in theory besynthesized by the body, may occasionallyneed to be provided in the TPN solution dueto the patient's age or disease state.

3.ENERGY MACRO NUTIENTS

DEXTROSE:

Dextrose is the primary source of parenteral

carbohydrate.

Dextrose is needed by the central nervous

system, white blood cells, red blood cells,

and renal medulla.

Each gram of hydrated dextrose used in

parenteral nutrition yields 3.4 kcal.

Parenteral nutrition solutions suitable for

peripheral vein administration have dextrose

concentrations of 10% or less.

Parenteral nutrition solutions with final

concentrations of 10% or greater must be

administered by a central vein because of

the high osmolarity.

4. LIPIDS:

Administration of lipid emulsion on a

daily, twice or three times weekly basis

appears to provide a balanced mixture of

nutrients for the patient requiring long-term

feeding. Intravenous fat emulsions are used

in parenteral nutrition as an energy source

and to provide essential fatty acids.

Intravenous fat emulsions are particularly

beneficial as an energy source in patients

suffering from diabetes,stress, respiratory

acidosis, and hepatic steatosis.

5.ELECTROLYTES:

Electrolytes in maintenance or therapeutic

doses need to be added daily to the

parenteral nutrition solution to preserve

electrolyte homeostasis.

Each patient’s requirements for individual

electrolytes depend on the primary disease

state, renal function, hepatic function,

pharmacotherapy, past intake, renal or

extrarenal losses, and nutritional status.

Sodium is of critical importance in the fluid

balance of both of healthy and sick subjects.

Sodium losses and gains are generally

accompanied by similar shifts in chloride ions

and a consequent movement in water.

Severe losses may lead to hypovolaemia,

circulatory failure and shock. Generally a

serum concentration of 135-145 mEq/litre is

throught to be normal.

Potassium is essential for the normal

operation of the cell and is an important

determinant of cell membrane resting

potential.

Thus abnormally high or low levels can result

in poor nerve impulse conduction,

fluctuations in heart rhythm and even death

due to heart failure.

It also plays a vital role in distribution of

body water

Absence of calcium from TPN in the long

term may produce symptoms of

hypocalcaemia such as muscle spasm and

numbness.

The effect of lack of calcium on the growing

child on TPN could understandably have a

dramatic effect of growth and development

of bones and teeth.

Magnesium has many physiological actions.

The most clinically significant effects of

magnesium imbalance are associated with

changes in neuromuscular or cardiovascular

function.

By virtue of its buffering action phosphate

helps maintain body acid-base balance.

If phosphate is not provided in the TPN

solution hypophosphataemia may develop

which can give rise to impaired red blood

cell function of many organs.

Hypophosphataemia may also be induced as

a result of infusion of high glucose loads.

Trace elements are essential micronutrients

that are metabolic cofactors essential for the

proper functioning of several enzyme

systems.

Zinc, Copper, Selenium, Chromium, Iron,

Manganese, Cobalt, Molybdenum.

Zinc requirements are increased in metabolic

stress and in gastrointestinal disease

secondary to diarrheal diseases.

Manganese and copper are excreted through

the biliary tract, whereas Zinc, and

selenium are excreted renally.

Therefore, copper and manganese should be

used with caution in patients with

cholestatic liver disease.

Selenium stores have been shown to be

depleted in patients receiving long-term

parenteral nutrition or in those with thermal

injury, acquired immunodeficiency

syndrome, or liver failure.

Therefore, selenium should be added initially

to the parenteral nutrition solution for

patients with these disease states or

conditions.

7. VITAMINS

Patients on long-term TPN therapy will

generally require some vitamin

supplementation.

The commercial preparations of vitamins

available along with recommended daily

requirements which seem to vary according

to the current available recommendations.

A Retinol

B1 Thiamines

B2 Riboflavine

B6 Pyridoxine

B12 Cyanocobalamin

B Nicotinamide

B Biotin

B Pantothenic acid

B Folic acid

C Ascorbic acid

D Calciferol

E Tocopherol acetate

K Phytomenadione

Vitamins are an essential component of a

patient’s daily parenteral nutrition regimen

because they are necessary for normal

metabolism and cellular function of the

body.

Individual parenteral vitamins are

recommended when the multivitamins

products are not available.

Vitamins that are marketed as single-entity

parenteral formulations include

vitamins A, D, E, K, B1 (thiamine), B2

(riboflavin), B3 (niacin), B6 (pyridoxine),

B9(folic acid), B12 (cyanocobalamin) , and C

(ascorbic acid).

8. FLUIDS

In the human body, water is the predominant

chemical entity, generally accounting for

more than half of the total body weight.

An inverse relationship exists between the

amount of body fat and the amount of body

water present in an individual.

Total water gains and losses in the healthy

adult fall within the range of 1500-3000ml

daily.

Thus, where the patient requires TPN, the

volume administered will fall into this range

and may need to be supplemented by

additional fluids in the special cases of

burns, etc.

Careful patient monitoring is required to

ensure that they do not become dehydrated.

Nutrients are mixed just prior to infusions,by breaking the plastic connectors betweenthe compartments, then vitamins and traceelements are added extemporaneously to thebag.

Shelf –life of these bags is at least 12months, but allow only for standardizedformulas.

The use of three-compartment TPN bags isless expensive in terms of application coststhan separate bottles or hospital-compounded bag systems.

Because of the complexity of parenteral

nutrition products, safe preparation is a

complicated task.

The quality of the final product depends on

the facilities, resources,personnel training

and products used in preparation.

Since the inception of parenteral nutrition,

pharmacists have developed policies and

procedures for parenteral nutrition

compounding based on their training and

interpretation of the literature.

Parenteral nutrition is considered a high-risk

sterile product. Its compounding includes

complex and/or numerous aseptic

manipulations.

Specific guidelines for aseptic processing

include media fill validations of both the

process and the personnel carrying out the

process.

There are specific requirements for facilities,

space and environmental control similar to

those of a Class 100 clean-room

environment.

Sterile product release checks require visual

inspection against a lighted white and black

background for evidence of visible

particulates or other foreign matter.

In addition,compounding accuracy checks of

the addition of all drug products or

ingredients used to prepare the parenteral

nutrition product are ensured by validating

the volume and quantity used in admixture.

Presterilized disposable membrane filtrationdevices, which are sensitive in detecting lowlevels of contamination and easy to use, arecommercially available.

The compounding of parenteral nutritionadmixtures accelerates the rate ofphysicochemical destabilization, resulting inthe recommendation to administerparenteral nutrition as soon after itspreparation as possible certain amino acids,lipids, and multivitamins are mostsusceptible to instability.

Pharmacist involved in TPN should have a

thorough understanding of the potential

stability issues in these mixtures and be able

to advise physicians accordingly.

In general the following information will be

required on the label:

Patient name/number

Ward

Product constituents

Batch (dispensing number)

Expiry date/time

Storage conditions

Other instructions such as guidance on

administration rate or technique, limitations

on further additions etc., may also be

required.

Once the product has been filled and

labelled a pharmacist should perform a final

check against the prescription prior to

sending the product to the ward.

This check should include the patient’s

name, ward, etc. and should once again

compare the constituents requested against

the final label.

Details of further additions, storage,

conditions, expiry date, etc. should also be

confirmed and the batch number or other

reference allocated should be checked to

facilitate traceability in the event of any

difficulties arising subsequent to dispensing,

e.g. precipitation, discoloration, etc.

The hospital pharmacist may be involved in

development of nursing care guidelines with

particular reference to further additions,

storage, etc.

It may also be useful for the ward

pharmacist to check that TPN is being

correctly administered to the patient, i.e.

with correct flow control device, away from

direct sunlight, etc.

Allwood at al recommends in 1984 that

compounded TPN solutions should be stored

at 2-8˚C in light of both microbiological and

chemical considerations.

Should not be stored at room temperature

for periods in excess of the 12-24 hours

required for administration.

Where supplies of compounded product are

to be made to hospitals or home patients

away from the site of manufacture, the

quality of the packaging system to maintain

product temperature during transit should be

validated to the satisfaction of local quality

control standards.

Insulated polystyrene containers may be

useful for this purpose.

Providing a TPN compounding service within

a hospital may be a costly venture for the

pharmacy department.

All the factors must be considered when

developing true service costs and deciding

whether to produce in house or obtain

product from a regional hospital or

commercial source.

Bags made of poly-ethylene and poly-

vinylchloride and of the copolymer

ethylenevinylacetate were used as containers

of perfusion solutions for total parenteral

nutrition.

Injectable solutions for Total Parenteral

Nutrition containing L-

aminoacids,electrolytes and glucose, are

commonly sold as medicinal specialities in

glass containers.

Bags made of plastic materials such as

copolymer ethylene-vinylacetate (EVA), poly-

ethylene (PE) and poly-vinylchloride (PVC)

are being used more and more often in the

manufacture of containers of perfusion

solutions.

A work sheet should be generated for each

TPN-dispensing activity to be carried out for

recording materials, patient name, label

details, etc.

The format for such a work sheet should be

agreed between the production and quality

control departments of the hospital in

accordance with local policy.

Prescribe the nutrient formulation

Recognize the needs of individual patients.

Modification in quantities according to

clinical situation of patients.

Monitor the interactions among various

electrolytes and drugs affect TPN mixture.

Assist the health care team in developing a

cost effective formulary of nutrition

products.