VI. Parenteral Nutrition

A. Access Routes and Catheter Placement

1. Access Routes
A variety of locations can serve as sites for catheter insertion including subclavian, internal jugular, external iliac, and cephalic veins. Due to the hypertonicity of parenteral solutions, the catheter tip must always be positioned into the superior vena cava so that the solutions are immediately diluted to tolerable concentrations. Solutions containing 10% or less dextrose (final concentration) plus amino acids (750-900 mOsm/L) can be infused into a peripheral vein (peripheral parenteral nutrition, PPN). However, this practice is associated with a high risk of phlebitis and is therefore reserved for short-term therapy in individuals with robust veins. Simultaneous infusion of lipid emulsions will dilute the osmotic load and thereby improve tolerance to peripherally administered parenteral nutrition. PPN is useful for preserving somatic and visceral protein reserves in patients with limited tolerance of enteral nutrition support.

2. Catheter Placement Requests

Central catheter placement for parenteral nutrition administration is never an emergency and, to minimize risk of complications, should only be done under planned circumstances by experienced personnel using strict aseptic technique.

UWMC: A variety of catheters can be placed to provide parenteral nutrition. For inpatients, Hohn and Triple Lumen Catheters can be placed by most medical and surgical services. Peripheral Inserted Centeral Catheters (PICC) are placed by PICC nurses. To schedule a PICC line, phone 548-8702. *HICKMAN ™ and Porta Catheters can be placed in Interventinal Radiology or by the General Surgery Service if necessary. For outpatients, catheter placement can be scheduled by the referring physician. PICC lines can be placed if an advanced clinic visit is scheduled with a PICC nurse (548-8702). For other catheters, complete the " Long-term Central Venous Access Request" form and page the General Surgery Nurse Coordinator. A pre-anesthesia testing clinic visit may be required and labs including a coagulation profile and CBC are necessary before catheter placement. (* HICKMAN is a registered trademark of C.R. Bard, Inc. and its related company, BCR, Inc.)

HMC: Central catheter placement is performed and/or supervised by a medical house staff member with the exception of peripherally inserted central catheters (PICC lines) which are placed by Interventional Radiology. HMC does not use a standardized ordering form for catheter placements.

B. Initiating Parenteral Nutrition (PN)

1. Formula Determination

Determine energy requirement (see Section IIIB)
Determine protein requirements (see Section IIIC).
Determine fluid requirements (see Section IIID).

Determine the proportion of calories to be provided as intravenous fat.

Fat emulsion is used as a concentrated calorie source and to prevent essential fatty acid deficiency in patients receiving PN. When used as a source of calories for critically ill patients, 15 to 50 percent of total calories may be supplied as fat. However, to avoid the fat overload syndrome, maximum intravenous fat intake should not exceed 2.5 g/kg/day. The fat overload syndrome is a potentially lethal syndrome, consisting of lipemic serum, massive fat deposition in the lungs and liver, spleen and reticuloendothelial blockade, sepsis, and thrombocytopenia. In order to prevent fatty acid deficiency, linoleic acid must be provided as 2 to 4 percent of total caloric intake (500 mL 10% lipid emulsion 2 to 3 times/week will supply adequate linoleic acid for most patients). The following maximum infusion rates are recommended: 500cc of 10% lipids over 8 to 12 hours; 500cc of 20% lipids over 12 to 16 hours. For critically ill patients with respiratory compromise, continuous 24 hours fat infusion provides stable energy intake. Due to potential intolerance, plasma triglyceride level should be checked prior to initial infusion and repeated 6 hours after lipid infusion is completed.

Fat emulsion should be used cautiously in patients with severe liver disease or dysfunction, or history of hyperlipidemia (e.g. AIDS) as these patients have a decreased capacity to clear the infused fat.

e. Determine carbohydrate tolerance.

Some studies have demonstrated that the rate at which the body can oxidize glucose as energy is limited. Exceeding this limit results in the excess glucose calories being converted into fat which requires energy and places additional stress on the patient. In order to prevent overfeeding with glucose and the resulting complications of hyperglycemia, weight gain, and fatty liver, a "maximum" carbohydrate utilization or tolerance rate should be calculated for all patients who are on total parenteral nutrition. A reasonable estimate is 5 mg CHO/kg/min. For critically ill patients, 3-4 mg CHO/Kg/Min is recommended. The following formula is used to calculate maximum daily CHO tolerance:

Maximum CHO (g/d) = 5 mg CHO/kg/min x IBW* x 1.44**
* IBW = Ideal body weight in kg
** 1.44 = (60 min/hr x 24 hr/day) / (1000 mg/g)

f. Determine electrolyte requirements.

The daily electrolyte requirements for most patients can be met by adding one to three standard electrolyte packages to the PN (See Section III, Table II). The standard electrolyte package available provides the following:

Standard Parenteral Electrolyte Package

Electrolyte Amount

sodium 25 mEq

potassium 40.6 mEq

calcium 5 mEq

magnesium 8 mEq

acetate 33.5 mEq

gluconate 5 mEq

chloride 40.6 mEq

Phosphorus is NOT included in the standard electrolyte package and must be added separately. PN solutions typically contain more phosphate than calcium (as great as 6:1 molar ratio). Cramps may result from excessive phosphate administration. The solubility of calcium in PN solutions is limited by formation of calcium phosphate and carbonate, as well as magnesium salts. Unfortunately, calcium solubility is unpredictable because it depends upon factors such as the commercial sources of the PN components, the order of mixing the PN components, the solution pH, and temperature and storage conditions. In clinical practice, adherence to pharmacy recommendations on the PN order sheets rarely results in precipitation of calcium salts. Furthermore, infusion of large doses of calcium in PN solutions may cause precipitate formation.

Single electrolyte formulations are available in injectable form for individualizing patient prescriptions. Non-standard electrolyte formulations need to be designed with a balance of cations and anions. Acetate is not a "routine" component of a PN prescription as it may result in iatrogenic metabolic alkalosis. Clinical Pharmacists are available to assist with determining electrolyte requirements of individual patients. Potassium replacement in patients with renal impairment must be done cautiously.

g. Determine vitamin requirements.

It is recommended that all adult PN patients, except those in renal failure, be supplemented daily with a standard multivitamin package. The standard vitamin package available provides the following:
Standard Parenteral Multivitamin Package*

Vitamin

Amount

Vitamin A 3300 IU

Vitamin D 200 IU

Vitamin E 10 IU

Vitamin C 100 mg

Thiamine (B₁) 3 mg

Riboflavin (B₂) 3.6 mg

Niacin (B₃) 40 mg

Pyridoxine (B₆) 4 mg

Pantothenic acid 15 mg

Folic Acid 400 mcg

Biotin 60 mcg

Vitamin B₁₂ 5 mcg

* Meets AMA Nutritional Advisory Group and FDA Recommended Allowances

In chronic renal failure, intake of vitamins A and D should be restricted. A vitamin B + C complex is available for PN administration to patients with chronic renal failure. Additional ascorbic acid (500 - 1000 mg) may be added directly to PN solutions for meeting the increased vitamin C requirements of wound healing during critical illness or in the post-op period. Additional folic acid (1 mg/day) can be added directly to PN solutions to meet the increased requirements of pregnancy, or of accelerated red blood cell production in patients with macrocytic anemia. Vitamin K (phytonadione) at 10 mg/week should be given to maintain prothrombin times within the normal range. Vitamin K may be given orally, IM, IV, SQ, or added to PN solution. Patients who are currently receiving warfarin should not be given vitamin K supplementation.

h. Determine trace element requirements.

The trace elements zinc, copper, chromium, manganese, iodine, iron, and selenium must be provided in PN to prevent clinical deficiency. It is recommended that all adult PN patients be supplemented daily with a standard trace element package. The standard trace element package available provides the following:

Standard Parenteral Trace Elements Package

Trace
element
Amount

zinc 5 mg

copper 1 mg

manganese 0.5 mg

chromium 10 mcg

selenium 60 mcg

iodide 75 mcg

Iron is not included in the standard trace element package. Iron is not routinely added to PN solutions because it may alter the stability of other PN components. Furthermore, iron stores are usually sufficient to avoid the need for supplementation during short term use of PN. A parenteral form of iron (iron dextran) is available for intramuscular or intravenous administration to iron-deficient patients who are unable to be supplemented enterally. Iron dextran has caused adverse reactions in a few patients requiring interruption or discontinuation of the infusion. Call the Pharmacy for intravenous iron dextran administration guidelines.

Additional individual trace elements may be added to PN solutions for patients with high metabolic or replacement needs and to treat suspected or diagnosed single trace element deficiencies. Patients with gastrointestinal fluid losses may have increased zinc requirements and should receive additional zinc in their PN. Add to PN daily 5 to 10 mg zinc/L of small bowel fluid loss and 15 to 20 mg zinc/kg stool or ileostomy output. An additional 10 to 20 mg of chromium may be added daily to PN for patients with intestinal losses in excess of one liter. The following trace elements are routinely available to addition to PN solutions:

Single Parenteral Trace Element Formulations

Trace
element
Amount

chromium 0.004 mg/mL

copper 0.4 mg/mL

manganese 0.1 mg/mL

selenium 0.04 mg/mL

iodide 0.1 mg/mL

zinc 1 mg/ml

Trace element supplementation for patients with liver failure or biliary obstruction should be limited to zinc, since copper and manganese are eliminated from the body by biliary excretion. Zinc and chromium are eliminated by renal excretion and should be administered cautiously to patients with renal dysfunction to avoid toxicity.
i. Determine if additional additives are necessary, considering especially:

H2-antagonist (e.g. ranitidine)
insulin-should be given preferably by separate drip until calorie delivery is stable and insulin requirements are known.

2. Writing Parenteral Nutrition Orders

Confirm central catheter placement by X-ray before writing PN orders
Order baseline and routine labs (see Section VII)
Order routine nursing monitoring parameters (see Section VII)
Complete PN order form by checking appropriate boxes to select solution components and additives to meet the patient's estimated requirements. Note that orders for PN at the UWMC and HMC are written based on initial concentrations of the dextrose and amino acid solutions used. For PN solutions, all components including calorie, protein, fat, fluid, mineral, vitamin, electrolyte, and trace element intakes must be prescribed daily.

An Example for Writing the PN Prescription

A patient requires 2200 kcal and 100 g of protein.
For the protein requirements simply check off one liter of 10 percent crystalline amino acids (CAA). This provides 100 g protein and 400 kcal, leaving a caloric balance of 1800 kcal to be provided by carbohydrate and fat.

The minimal fat requirement should be considered next. This is 8 percent of total kcal (4 percent is linoleic acid)- that is, 2200 kcal x 0.08 = 176 kcal/day, or 7 x 176 = 1232 kcal/week. One bottle of 10 percent lipid is 550 kcal. Therefore, the fat requirement can be met approximately with two bottles of percent lipid/week (i.e., 2 x 550 kcal = 1100 kcal/week). Keep it simple! Check off the appropriate lipid order in the box on the request form.

The caloric balance is now 1800 minus 176 kcal = 1624 kcal to be provided as glucose. The caloric density of dextrose is 3.4 kcal/g. Thus, 1624 kcal/3.4 kcal/g dextrose = 478 g dextrose. Again, keep it simple! This is approximately one liter of 50 percent dextrose ("dextrose" is actually glucose monohydrate). Check to verify that this amount of glucose is within the patient's calculated maximum carbohydrate tolerance (see Section VI part B). For example, if the patient's IBW is 70 kg, their carbohydrate tolerance is approximately 70 kg x 5 mg CHO/kg/min x 1.44 (min/d)/(mg/g) = 504 gm/d. Check off one liter of 50 percent dextrose on the order sheet.

Complete the remaining parts of the order sheet, checking off trace elements and vitamins, as well as 10 mg vitamin K/week. If additional volume is required, add sterile water to the prescription. Electrolytes should be added as 1 package/L. Custom additions can be made as necessary. Phosphate should be the final item ordered; in a patient with normal renal function, phosphate should be added as 10 mmol/1000 kcal dextrose. Select the appropriate volume bag (1, 2, or 3 liters) and rate, keeping in mind that the prescription is to cover a 24 hour period.

C. Administration Guidelines and Formulations

PN (dextrose and amino acid) should be initiated at a rate of 25 to 50 mL per hour and advanced at 8 to 12 hour intervals as tolerated, until fluid volume and caloric goals are attained. In the hospitalized patient, PN is generally administered by continuous infusion over 24 hours. Cyclic PN, in which the entire volume of daily PN solution is infused over a period of 8 to 16 hours, is typically used to prepare patients for home PN administration. Advantages include an infusion-free period for the patient to resume other activities and access for administration of incompatible medications.

At both UWMC and HMC, dextrose (glucose) is the major calorie source for PN solutions. It is available in 5, 10, 20, 25, 35, 50, and 70 percent concentrations. Most patients will tolerate 1 L of D5O/24h without complications. Glucose tolerance is highly variable, however, and difficult to predict from clinical criteria. D70W is the most calorically dense dextrose solution currently available(1190 kcal/500 cc VS 1000 kcal/500 cc 20% lipid emulsion) and is useful as a calorie source in fluid-restricted patients and patients with high metabolic (energy) demands such as trauma/burns.

Lipid emulsion is an alternative calorie source in patients with glucose intolerance or poor CO₂ clearance (CO₂ production from fat oxidation is only 70 percent that of glucose oxidation; however, avoiding excessive calorie delivery is typically more effective than adjusting carbohydrate intake).

Protein is supplied in PN as 5.5, 8.5, 10 or 15 percent solutions of crystalline amino acids (CAA). Routine use of special amino acid products such as branched chain amino acids and essential amino acids is discouraged because they are of unproven efficacy in most clinical situations and they are expensive. The caloric density of crystalline amino acids is 4 kcal/g. The nitrogen content of crystalline amino acids is 5 percent higher than that found in the typical diet due to the select mixture of amino acids. At UWMC and HMC, the g nitrogen in 1L of 15, 10, 8.5, and 5.5 percent amino acids solutions is 25.2 g, 16.8 g 14.3 g, and 9.3 g, respectively.

D. Medications and Parenteral Nutrition

Administration of medications via PN may be beneficial when there is limited venous access and/or the patient is fluid restricted. The major problem associated with the addition of medications to PN is the potential for incompatibilities. The following issues should be considered if a medication is to be added to PN.

Certain medications should not be mixed with any PN if intermittent infusion is necessary to achieve therapeutic serum levels (i.e. antibiotics).
Medications that require a precise rate of infusion (i.e. cardiovascular agents) are not recommended to be added to PN solution.
Doses of a medication cannot be readily adjusted once combined with the PN.
Adding alkaline medications to PN admixtures may increase the potential for calcium-phosphate incompatibilities.
Medication must be chemically stable in PN solution for over 24 hours.

Medications routinely added to PN solutions include: H-2 antagonists (e.g. ranitidine) and insulin.

The use of Y-site or piggyback drug delivery has helped prevent or avoid drug compatibility problems. The contact time of multiple solutions being administered via Y-site is short, often in the range of 15-20 minutes. There are many studies documenting the compatibility of PN and medications when administered via Y-site injection. Call the IV pharmacy for a complete list of medications that are compatible with PN and lipids.

E. Complications of Parenteral Nutrition

In spite of improvements in the delivery of PN, this mode of nutrition support is associated with technical, septic and metabolic complications that warrant pursuit of enteral nutrition support when feasible. Technical complications associated with PN include: air embolism, subclavian artery puncture/hemotoma/laceration, pneumothorax, hemothorax, carotid artery injury, thromboembolism, catheter embolism, catheter malposition, Hormer's syndrome, brachial plexus injury, and phrenic nerve paralysis. Septic complications associated with PN include: catheter infection, catheter tunnel infection, and sepsis. Table IV lists potential metabolic complications of PN and offers suggestions for intervention.

Table IV: Metabolic Complications of PN

Complication Possible Cause Suggested Management

Dehydration Inadequate fluid support; unaccounted fluid loss (e.g. diarrhea, fistulae, persistent high fever). Start second infusion of appropriate fluid, such as D5W, 1/2NS, NS. Reestimate fluid requirement and adjust PN accordingly.

Overhydration Excess fluid administration; compromised renal or cardiac function. consider D70 (can't use with PPN) or 20% lipid as calorie Initiate diuretics. Source. Limit volume.

Alkalosis Inadequate K to compensate for cellular uptake during glucose transport; excessive GI or renal K losses. Inadequate Cl in patients undergoing gastric decompression. Add KCl to PN. Assure adequate hydration. Discontinue acetate.

Acidosis Excessive renal or Gl losses of base; excessive Cl in PN Rule out DKA and sepsis. Add acetate to PN

Hypocalcemia Excessive PO₄salts, low serum albumin. Inadequate Ca in PN. Slowly increase calcium in PN prescription.

Hypercalcemia Excessive Ca in PN or administration of vitamin A in patients with renal failure. Can lead to pancreatitis. Decrease calcium in PN. Ensure adequate hydration. Limit vitamin supplements in patients with renal failure to vitamin C and B vitamins.

Hypomagnesemia Inadequate Mg in PN; excessive Mg losses; cellular uptake with induction of anabolism (Refeeding Syndrome). Gradually increase Mg content of PN

Hypophosphatemia Excess losses (urinary PO₄; in alkalosis, Mg, diabetes mellitus, steroid and diuretic therapy); cellular uptake with induction of anabolism ( Refeeding Syndrome). Increase PO₄; content of PN

Hyperglycemic, hyperosmolar nonketotic coma Sustained untreated glucose intolerance. Easily prevented by frequent glucose monitoring. 40% mortality rate. Stop PN. Initiate adequate hydration and insulin drip.

Hyperglycemia Stress response. Occurs in approximately 25% of cases. Rule out infection. Decrease carbohydrate in PN. Provide adequate insulin.

Hypoglycemia Sudden withdrawal of concentrated glucose. More common in children. Taper PN. Start D10.

Hypercarbia Excessive calorie or carbohydrate load. Decrease total calories or CHO load.

Essential fatty acid Inadequate provision of linoleic acid in PN; release of linoleic deficiency acid from adipose stores prevented by continuous dextrose infusion and associated hyperinsulinemia. Provide i.v. lipids (minimum 500 mL 10% lipid two times a week). Alternatively, hold dextrose infusion for 24 hours.

Hyperammonemia Excessive protein load; arginine deficiency (urea cycle); hepatic dysfunction; preformed ammonia in amino acid solution. More common in children. Decrease protein content of PN. Prescribe lactulose.

Hepatic tissue damage and fat infiltration Unclear etiology. Maybe be related to excessive glucose or energy administration; L-carnitine deficiency. Rule out all other causes of liver failure. Increase fat intake relative to CHO.

Cholestasis Lack of GI stimulation. Sludge present in 50% of patients on PN for 406 weeks; resolves with resumption of enteral feeding. Promote enteral feeding.

Table of Contents | VII. Monitoring Nutritional Therapy

Electrolyte	Amount
sodium	25 mEq
potassium	40.6 mEq
calcium	5 mEq
magnesium	8 mEq
acetate	33.5 mEq
gluconate	5 mEq
chloride	40.6 mEq

Vitamin	Amount
Vitamin A	3300 IU
Vitamin D	200 IU
Vitamin E	10 IU
Vitamin C	100 mg
Thiamine (B₁)	3 mg
Riboflavin (B₂)	3.6 mg
Niacin (B₃)	40 mg
Pyridoxine (B₆)	4 mg
Pantothenic acid	15 mg
Folic Acid	400 mcg
Biotin	60 mcg
Vitamin B₁₂	5 mcg

Trace element	Amount
zinc	5 mg
copper	1 mg
manganese	0.5 mg
chromium	10 mcg
selenium	60 mcg
iodide	75 mcg

Complication	Possible Cause	Suggested Management
Dehydration	Inadequate fluid support; unaccounted fluid loss (e.g. diarrhea, fistulae, persistent high fever).	Start second infusion of appropriate fluid, such as D5W, 1/2NS, NS. Reestimate fluid requirement and adjust PN accordingly.
Overhydration	Excess fluid administration; compromised renal or cardiac function.	consider D70 (can't use with PPN) or 20% lipid as calorie Initiate diuretics. Source. Limit volume.
Alkalosis	Inadequate K to compensate for cellular uptake during glucose transport; excessive GI or renal K losses. Inadequate Cl in patients undergoing gastric decompression.	Add KCl to PN. Assure adequate hydration. Discontinue acetate.
Acidosis	Excessive renal or Gl losses of base; excessive Cl in PN	Rule out DKA and sepsis. Add acetate to PN
Hypocalcemia	Excessive PO₄salts, low serum albumin. Inadequate Ca in PN.	Slowly increase calcium in PN prescription.
Hypercalcemia	Excessive Ca in PN or administration of vitamin A in patients with renal failure. Can lead to pancreatitis.	Decrease calcium in PN. Ensure adequate hydration. Limit vitamin supplements in patients with renal failure to vitamin C and B vitamins.
Hypomagnesemia	Inadequate Mg in PN; excessive Mg losses; cellular uptake with induction of anabolism (Refeeding Syndrome).	Gradually increase Mg content of PN
Hypophosphatemia	Excess losses (urinary PO₄; in alkalosis, Mg, diabetes mellitus, steroid and diuretic therapy); cellular uptake with induction of anabolism ( Refeeding Syndrome).	Increase PO₄; content of PN
Hyperglycemic, hyperosmolar nonketotic coma	Sustained untreated glucose intolerance. Easily prevented by frequent glucose monitoring. 40% mortality rate.	Stop PN. Initiate adequate hydration and insulin drip.
Hyperglycemia	Stress response. Occurs in approximately 25% of cases.	Rule out infection. Decrease carbohydrate in PN. Provide adequate insulin.
Hypoglycemia	Sudden withdrawal of concentrated glucose. More common in children.	Taper PN. Start D10.
Hypercarbia	Excessive calorie or carbohydrate load.	Decrease total calories or CHO load.
Essential fatty acid	Inadequate provision of linoleic acid in PN; release of linoleic deficiency acid from adipose stores prevented by continuous dextrose infusion and associated hyperinsulinemia.	Provide i.v. lipids (minimum 500 mL 10% lipid two times a week). Alternatively, hold dextrose infusion for 24 hours.
Hyperammonemia	Excessive protein load; arginine deficiency (urea cycle); hepatic dysfunction; preformed ammonia in amino acid solution. More common in children.	Decrease protein content of PN. Prescribe lactulose.
Hepatic tissue damage and fat infiltration	Unclear etiology. Maybe be related to excessive glucose or energy administration; L-carnitine deficiency.	Rule out all other causes of liver failure. Increase fat intake relative to CHO.
Cholestasis	Lack of GI stimulation. Sludge present in 50% of patients on PN for 406 weeks; resolves with resumption of enteral feeding.	Promote enteral feeding.