Basics of Total Parenteral Nutrition (TPN) Pharmacology

Kerry R. Johnston, R.Ph.

Clinical Pharmacy Specialist, Nutrition/High-Tech Infusion Therapy

Definition: Parenteral nutrition is provision of nutrition through other than the

alimentary tract.

History of Parenteral Nutrition: Many attempts at parenteral nutrition since early in

this century. In late 1960's, techniques had been developed enough to provide for
relatively long periods of time with strict protocols. In the subsequent years,
additional development of techniques, materials, devices etc., allowed for routine
utilization of this sophisticated treatment modality.

Indications for parenteral nutrition:

Short bowel syndrome:

Acute inflammatory bowel disease/pancreatitis

Chronic inflammatory bowel disease/pancreatitis

Trauma

Vascular insufficiency to bowel

Neoplastic disease

Gastrointestinal Fistula- many gastrointestinal fistulas will heal with sole

intervention being parenteral nutrition.

Sepsis

Burns- may be helpful in improvement in healing and maintenance of fluid and

electrolyte status.

Congenital malabsorption syndromes:

Cystic Fibrosis

Developmental failure of villi

Bowel Obstruction/hypomotility- bowel obstruction contraindicates enteral feeding

necessitating intravenous route for nutritional support.

Idiopathic pseudo-obstruction

Chronic small bowel obstructions

Scleroderma
Neoplastic disease- Controversy exists as to place in therapy.

Hyperemesis Gravidarum- intractable nausea and vomiting during pregnancy.

Potential complications of parenteral nutrition:

Metabolic complications:

Hyperglycemia- most common metabolic complication of parenteral nutrition.

Related to rate of dextrose infusion, concentration, level of stress, etc.

Hypoglycemia- most commonly related to abrupt discontinuation of TPN without

tapering, especially with high dextrose concentrations.

Essential fatty acid deficiency- may result from parenteral nutrition regimen devoid
intravenous fat administration. May occur in as little as 2 weeks, particularly in
malnourished patients.

Electrolyte imbalance- inadequate or excess administration of electrolytes in

parenteral nutrition solutions.

Fluid volume disturbances- volume deficit of volume overload (particularly

important in patients with renal impairment or CHF).

Acid/base imbalance- solution design must take into account acid/base status of
patient, i.e. chloride, acetate etc.
Mechanical complications:

Catheter related- examples include pneumothorax, vessel damage, thrombosis,

catheter breakage, etc.

Air embolism- a result of air being introduced into catheter.

Delivery device related- most commonly device failure.

Septic complications- patients with indwelling access devices are at high risk for
catheter related sepsis.

Parenteral nutrition formula design:

Ingredients:

Carbohydrate- functions as a source of non-protein calories:

Dextrose- utilized as primary non-protein oxidative energy substrate in U.S.

Hydrous dextrose provides 3.4 kcal/g. Depresses gluconeogenesis. Nitrogen
sparing effect beneficial in reducing protein catabolism and utilization for energy
source. Primarily utilized in peripheral tissues and requires insulin.

Glycerol- has been used primarily in peripherally administered solutions. Provides

4.3 kcal/g.

Xylitol- has been utilized to provide non-protein calories. An insulin independent

pathway through liver metabolism.
Fructose- Utilized primarily in Europe.

Protein- All available products contain crystalline amino acids. Protein hydrolysates
no longer utilized. Various formulas available to meet a variety of needs. (Specific
disease states, pediatrics etc.). Provides 4.0 kcal/g.

Lipid- usually 10-20% emulsion of safflower or soybean oil. Typically administered

either to prevent essential fatty acid deficiency or to provide non-carbohydrate,
non- protein calories. Provides 1.1-2.0 kcal/mL (9kcal/g fat).

2 in 1 solutions- contain protein and dextrose in base solution (lipid usually

administered separately).

3 in 1 solutions- contains protein, dextrose and fat in base solution.

pros and cons

Additives- many additives are available for utilization in TPN admixture. Extreme
caution must be observed regarding compatibility, stability, etc. especially with 3 in
1 solutions.

Electrolytes:

Single ingredient electrolyte solutions- examples include potassium chloride,

calcium gluconate, magnesium sulfate, sodium phosphate, etc.
Multiple electrolyte solutions- contain fixed combinations of electrolytes in specific
volume. Intended to simplify compounding and standardize electrolyte component
of parenteral nutrition solution.

Vitamins- intended to provide necessary vitamins that patient would otherwise

receive in diet. Contain water soluble and fat soluble vitamins. Examples include
MVC 9+3, MVI-12, etc. Some also available as single entity vitamin injection
solutions. Examples include vitamin K, ascorbic acid, thiamine, etc.

Trace element solutions:

Single trace element solutions- single entity products such as copper sulfate, zinc
sulfate, etc.

Multiple trace element solutions- available in a variety of combinations with fixed

quantities per given volume. Trace elements contained vary from product to
product, manufacturer to manufacturer. Examples include MTE-4, MTE-5 etc.

Mixed electrolyte and trace element formulations- intended for maintenance

parenteral nutrition in stable patients to facilitate ease of solution admixture.

Drugs- in general addition of pharmacologic agents to parenteral solutions should

be avoided due to stability, compatibility, potential for interruption of administration
etc.:

Heparin- some evidence to support use as venoprotective in small doses. May be

beneficial in peripheral administration.

H-2 Blockers- may be useful in prevention of stress ulceration in patients receiving

parenteral nutrition.
Promotility agents- metoclopramide may be helpful in earlier return of normal
gastrointestinal motility while patient receiving parenteral nutrition solutions.

Others- antibiotics, narcotics

Calculation of patient requirements:

Carbohydrate (non-protein calories)- may be calculated using Harris-Benedict

equation to estimate basal energy expenditure, then add stress and activity factors,
or:

basal requirement- 25kcal/kg body weight

non-stressed (ambulatory)- 30 kcal/kg body weight

mild stress (malnourished)- 35-40kcal/kg body weight

severe injury or sepsis- 45-60kcal/kg body weight

severe burns- up to 80kcal/kg body weight

infants up to 200kcal/kg body weight

Protein- requirements usually estimated empirically:

non-stressed 0.5-1g/kg body weight

mild stress 1.2-1.4 g/kg body weight

moderate stress 1.5-2.0g/kg body weight

severe stress 2.0-2.5g/kg body weight

Fluid- two methods to calculate fluid requirements include:

1500mL for first 20 kg body weight, then 20mL/kg thereafter, or

30mL/kg of body weight

Adult electrolyte requirements:

Sodium 60-125 mEq/day

Potassium 60-240mEq/day

Calcium 4.5-9mEq/day

Magnesium 8-24mEq/day

Phosphate 10-60mEq/day

Chloride 3/4:1 or 1:1 ratio with sodium

Acetate requirement varies

Vitamins- requirements are empiric, however commercial multiple vitamin

formulations for parenteral use usually contain in 10mL:

Ascorbic acid 100mg

Vitamin A 3,300IU
Vitamin D 200IU

Thiamine 3mg

Riboflavin 3.6mg

Pyridoxine 4mg

Niacinamide 40mg

Pantothenic acid 15mg

Vitamin E 10IU

Biotin 60_g

Cyanocobalamin 5_g

Folic acid 400_g

Adult trace element requirements-

Zinc 2.5-4mg/day

Copper 0.5-1.5mg/day

Manganese 150-800_g/day

Chromium 10-15_g/day

Selenium 40-80_g/day

Formula Design:
Selected References

Dean RE ed.: Total Parenteral Nutrition: Standard Techniques. Pluribus Press, Inc.,
Division of Teach'Em, Inc. Chicago, 1983.

Mattox TW: Parenteral Nutrition in Dipiro JT, Talbert RL, Yee GC, et al, eds.:
Pharmacotherapy: A Pathophysiologic Approach, 3rd ed. Appleton and Lange,
Stamford, 1997; 2735-2758.

Rombeau JL and Caldwell MD, eds.: Clinical Nutrition: Parenteral Nutrition 2nd ed.
W.B. Saunders Company, Philadelphia, 1993.

Shils ME and Young VR, eds.: Modern Nutrition in Health and Disease, 7th ed. Lea
& Febiger, Philadelphia, 1986.

Weinsier RL, ed.: Handbook of Clinical Nutrition, 2nd ed. C.V. Mosby Company, St.
Louis, 1989.

Basics of Total Parenteral Nutrition (TPN) Pharmacology

Self-Assessment Questions with Answers

1. Parenteral nutrition may be useful for patients with which of the following
diagnoses?

a. Short bowel syndrome of various etiologies.

b. Congenital malabsorption syndromes including cystic fibrosis.

c. Bowel obstruction.

d. Some neoplastic diseases.

e. All of the above.

2. Mechanical complications of parenteral nutrition include all of the following

except:

a. thrombosis.

b. air embolism.

c. dehydration.

d. infusion device failure.

e. catheter breakage.

3. Non-protein calories in parenteral nutrition solutions are usually provided as:

a. anhydrous dextrose.

b. hydrous dextrose.

c. essential fatty acids.

d. crystalline amino acids.

e. fructose.

4. The phrase "3 in 1" as related to parenteral nutirtion solutions relates most
closely to:
a. parenteral nutrition solutions providing 3 liters volume per day.

b. parenteral nutrition orders written for 3 days at a time.

c. parenteral nutrition solutions providing mixtures of carbohydrate, protein and

lipid.

d. parenteral nutrition solutions providing 3 kcal per mL solution.

e. none of the above.

5. Carbohydrate calories may be calculated by:

a. utilization of the Harris-Benedict equation only.

b. relative degree of stress added to basal requirements.

c. utilization of the Henderson-Hasselbach equation.

d. none of the above.

e. all of the above except a.

Basics of Total Parenteral Nutrition (TPN) Pharmacology

Self-Assessment Questions

1. Parenteral nutrition may be useful for patients with which of the following
diagnoses?
a. Short bowel syndrome of various etiologies.

b. Congenital malabsorption syndromes including cystic fibrosis.

c. Bowel obstruction.

d. Some neoplastic diseases.

e. All of the above.

2. Mechanical complications of parenteral nutrition include all of the following

except:

a. thrombosis.

b. air embolism.

c. dehydration.

d. infusion device failure.

e. catheter breakage.

3. Non-protein calories in parenteral nutrition solutions are usually provided as:

a. anhydrous dextrose.

b. hydrous dextrose.

c. essential fatty acids.

d. crystalline amino acids.

e. fructose.
4. The phrase "3 in 1" as related to parenteral nutirtion solutions relates most
closely to:

a. parenteral nutrition solutions providing 3 liters volume per day.

b. parenteral nutrition orders written for 3 days at a time.

c. parenteral nutrition solutions providing mixtures of carbohydrate, protein and

lipid.

d. parenteral nutrition solutions providing 3 kcal per mL solution.

e. none of the above.

5. Carbohydrate calories may be calculated by:

a. utilization of the Harris-Benedict equation only.

b. relative degree of stress added to basal requirements.

c. utilization of the Henderson-Hasselbach equation.

d. none of the above.

e. all of the above except a.