TOTAL PARENTAL NUTRITION

PRESENTED BYROOMA KHALIDM.Phil pharmaceutics(2014-2016)Islamia University Bahawalpur

CONTENTS Definition Objectives Indications Administration Formulation Compounding Documentation

TOTAL PARENTAL NUTRITION 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

TOTAL 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)

CATEGORIES OF PARENTAL NUTIRITION1:Central or total parental nutrition (TPN)

2:Peripheral parental nutrition (PPN)

CATEGORIES OF TPN1: 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.

OBJECTIVES 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.

OBJECTIVES To prevent unwanted weight loss and

skin break down, promoting positive nitrogen balance and maintaining visceral and somatic protein stores.

Illness and injury promote catabolism and hypermetabolism, so the patient is burning calories faster to keep up with his body's demands. If he doesn't get adequate nutrition, his body will break down lean muscle for glucose, which could slow healing and prolong his recovery (Collins & Navarre, 2003).

OBJECTIVES 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.

CLINICAL ASPECTS 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.

INDICATIONS 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

INDICATIONS Pediatric GI disorders e.g prolonged

diarrhea

ADMINISTRATION 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.

ADMINISTRATION 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.

CHOICE OF ENTRY SITES 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.

FLOW CONTROL 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.

PATIENT ASSESMENT AND MONITORING 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.

FORMULATION OF TPN 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.

COMPONENTS 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).

COMPONENTS2.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.

COMPONENTS NON ESSENTIAL AMINO ACIDS: Those amino acids

which can normally be synthesized by the body. These amino acids are used to increase the amount of nitrogen available from the solutions.

SEMI ESSENTIAL AMINO ACIDS: Those amino acids

which although they can in theory be synthesized by the body, may occasionally need to be provided in the TPN solution due to the patient's age or disease state.

COMPONENTS 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.

COMPONENTS 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.

COMPONENTS 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.

COMPONENTS Intravenous fat emulsions are

particularly beneficial as an energy source in patients suffering from diabetes,stress, respiratory acidosis, and hepatic steatosis.

COMPONENTS5.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.

COMPONENTS 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.

COMPONENTS 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

COMPONENTS 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.

COMPONENTS Magnesium has many physiological

actions. The most clinically significant effects of magnesium imbalance are associated with changes in neuromuscular or cardiovascular function.

COMPONENTS 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.

COMPONENTS 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.

COMPONENTS 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.

COMPONENTS 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.

COMPONENTS7. 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.

COMPONENTS A Retinol B1 Thiamines B2 Riboflavine B6 Pyridoxine B12 Cyanocobalamin B Nicotinamide B Biotin

COMPONENTS B Pantothenic acid B Folic acid C Ascorbic acid D Calciferol E Tocopherol acetate K Phytomenadione

COMPONENTS 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.

COMPONENTS 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).

COMPONENTS8. 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.

COMPONENTS 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.

PREPARATION Nutrients are mixed just prior to

infusions, by breaking the plastic connectors between the compartments, then vitamins and trace elements are added extemporaneously to the bag.

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

The use of three-compartment TPN bags is less expensive in terms of application costs than separate bottles or hospital-compounded bag systems.

COMPOUNDING CONSIDERATIONS 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.

COMPOUNDING CONSIDERATIONS 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.

COMPOUNDING CONSIDERATIONS 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.

COMPOUNDING CONSIDERATIONS 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.

COMPOUNDING CONSIDERATIONS Presterilized disposable membrane

filtration devices, which are sensitive in detecting low levels of contamination and easy to use, are commercially available.

The compounding of parenteral nutrition admixtures accelerates the rate of physicochemical destabilization, resulting in the recommendation to administer parenteral nutrition as soon after its preparation as possible certain amino acids, lipids, and multivitamins are most susceptible to instability.

COMPOUNDING CONSIDERATIONS Pharmacist involved in TPN should have

a thorough understanding of the potential stability issues in these mixtures and be able to advise physicians accordingly.

LABELING 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

LABELING Other instructions such as guidance on

administration rate or technique, limitations on further additions etc., may also be required.

DISPENSING 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.

DISPENSING 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.

DISPENSING 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.

STORAGE 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.

PACAKAGING 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.

COST 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 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 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.

DOCUMENTATION 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.

ROLE OF PHARMACIST 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.