and may cause respiratory distress. In designing a PN formulation for B.B., it is

important to provide a moderate calorie dose and to limit her dextrose dose to less

than 4 mg/kg/minute.

40,41 For adults, the daily lipid intake should not exceed 2.5

g/kg/day. However, current literature supports a maximum of 1 g/kg/day. It is also

important to monitor serum triglyceride levels to assess tolerance to this dose of

IVFE. If the blood sample is obtained while the triglycerides are infusing, as with the

TNA formulation, a serum triglyceride concentration of 400 mg/dL, although

elevated, is acceptable.

42 Hypertriglyceridemia can sometimes be noted quickly by

gross observation of turbidity in the blood sample.

CASE 38-2, QUESTION 4: After hydration with IV fluids, B.B.’s weight is 51.5 kg. PN therapy was

delayed because within 24 hours after admission, B.B. experienced severe abdominal pain and distension and

required surgery. An exploratory laparotomy was performed, and 25 cm of ileum was resected to remove an

area of bowel with severe disease and a stricture that was causing the obstruction. Bowel sounds are absent.

She has a right Port-A-Cath CVC and PN is to begin on postoperative day 1. Calculate energy and protein

goals for B.B.

Energy requirements may be estimated with predictive equations, simplistic

formulas (25–30 kcal/kg/day) or measured by indirect calorimetry, the most accurate

method. Over 200 predictive equations have been published in the literature,

including the Harris–Benedict equation. Using the Harris–Benedict equation for

women (see Table 35-3 in Chapter 35, Basics of Nutrition and Patient Assessment)

and her current weight of 51.5 kg, height of 167.6 cm, and age of 64 years, B.B.’s

basal energy expenditure (BEE) is 1,158 kcal/day. To estimate her total energy

expenditure, the BEE should be modified with an activity factor of 1.2 for being

confined to bed and a stress factor of 1.2 for surgery. These modifications result in an

estimated energy expenditure of 44% greater than her BEE, or 1,668 kcal/day.

Therefore, an energy goal of 1,600 kcal/day is reasonable. In a similar manner, her

protein goal (see Table 35-4 in Chapter 35, Basics of Nutrition and Patient

Assessment) for moderate stress is 62 to 77 g/day of protein (1.2–1.5 g/kg/day).

CASE 38-2, QUESTION 5: Design a TNA parenteral nutrient formulation as a single daily PN bag for B.B.

that provides 1,600 kcal and 70 g of amino acids with a non-protein calorie distribution of 75% carbohydrate and

25% lipid. The macronutrients available on the formulary for compounding the parenteral nutrient formulations

are 70% dextrose, 30% lipid emulsion, and 10% amino acids.

Amino acids calculation

2.

3.

4.

Dextrose calculation

Lipid emulsion calculation

Calculation of final volume of energy substrates

B.B.’s goal PN formulation will provide 291 g of dextrose and approximately 33 g

of lipids daily. If the PN is infused continuously over 24 hours, B.B. will receive 3.9

mg/kg/minute of dextrose and 0.6 g/kg/day of lipids. Both dextrose and lipid doses

comply with the limitations recommended in question 3. Other additives such as

electrolytes, vitamins, and trace elements are included in the parenteral nutrient

formulation and slightly increase the final volume to 1,680 mL/day. The infusion rate

for this formulation can be calculated as follows:

B.B.’s parenteral nutrient formulation of 1,680 mL/day will not meet her

maintenance fluid needs of 2,130 mL/day (see Case 38-1, Question 5). She will

require extra fluid to meet the remainder of her basic fluid needs. These additional

fluids should be provided through another IV or added as sterile water to the TNA

solution.

CASE 38-2, QUESTION 6: What are the advantages and disadvantages of combining the dextrose, fat, and

amino acids in one container?

PN formulations may be prepared in one of two ways: a dextrose–amino acid (2-

in-1) mixture in which IVFE is administered separately as a piggybacked infusion or

a total nutrient admixture (TNA or 3-in-1) in which the dextrose, amino acids, and

IVFE are combined in solution in the same bag.

43

While the use of TNAs have been widely embraced by home care providers and

many institutions for convenience and cost advantages, the addition of IVFE to the

traditional mixture of dextrose and amino acids converts the mixture into a complex

emulsion with physiologic differences that alter the stability of the product.

44 The

differences between these two methods of compounding PN formulations must be

considered. Specific advantages and disadvantages of each are summarized in Table

38-4.

CASE 38-2, QUESTION 7: How stable are the TNA parenteral feeding formulations compared to 2-in-1

formulations? Why is an infusion filter necessary?

IVFE gradually deteriorates over time because of increased formation of free fatty

acids and a resultant decrease in pH. When lipids are mixed with dextrose and amino

acids, this process is accelerated. IVFE consists of an interior oil phase dispersed

within an external water phase. Stability of the IVFE is maintained by polar and

nonpolar regions on the same fat droplet. The surface of the polar region of the fat

droplet is negatively charged and repels other lipid droplets of the same charge.

When the surface loses its negativity, fat droplets aggregate into larger globules and

the emulsion becomes unstable and unsafe for use, risking occlusion of pulmonary

vasculature. Commercially available IVFEs in the United States use an anionic egg

yolk phosphatide emulsifier to stabilize the lipid droplets and maintain dispersion.

Destabilization of the emulsion occurs in phases that begin with creaming and ends

with the coalescence of the lipid particles, or “cracking” of the emulsion. A decrease

in pH and the addition of divalent cations (Mg

2+

, Ca

2+

) alter the electrical charge on

the fat droplet surface and pose a risk to the integrity of the emulsion. Although

dextrose decreases the pH, the addition of amino acids provides an adequate buffer

for this variable. The amount of divalent cations added to TNAs should be limited to

minimize the risk of emulsion instability. Trivalent cations such as iron should never

be added to a TNA parenteral nutrient formulation. PN formulations containing lipid

must be assessed visually for signs of phase separation, in which the instability of the

emulsion is manifested by “oiling out,” indicated by a continuous layer of oil or

individual fat droplets. Fat emulsion particles have an average size of 0.5 μm. A

destabilized emulsion is not visibly apparent until the lipid particles are 40 to 50 μm.

Fat particles as small as 5 μm may occlude pulmonary capillaries.

43,44 Therefore, the

use of a 1.2-μm filter is recommended to protect against the infusion of enlarged lipid

particles.

12,43

p. 797

p. 798

Table 38-4

Advantages and Disadvantages of 2-in-1 and 3-in-1 Parenteral Nutrition

2-in-1 3-in-1

Advantages Improved overallstability

Increased flexibility in

concentrating dextrose and

amino acids

Allows more flexibility to add

higher concentrations of

electrolytes

Better medication compatibility

Reduced risk of bacterial growth

because of high osmolarity and

acidic pH

Better visualization of precipitant

of particulate matter. Enables

the use of bacterial retention

filter (0.22-micron)

Lower risk of catheter occlusion if

IVFE is not used daily

All components are aseptically

compounded by the pharmacy

Simplified regimen for the patient

especially at home

Less supply and equipment costs

Less nursing time needed for

administration

Decreased preparation cost

Decreased risk of contamination

Inhibited bacterial growth versus

separate IVFE

Minimize infusion-related reactions

from IVFE because of slower

infusion rate

May improve lipid clearance

because of slower infusion rate

Decreased risk of phlebitis with

PPN

Disadvantages Increased administration costs and

time when lipids are infused

separately

Increased risk of touch

contamination

Increased risk of phlebitis,

particularly if PPN is not coinfused with IV lipid emulsion

IVFE given in a piggyback

manner is limited to a maximum

hang time of 12 hours.

45

Impaired visualization of particulate

matter or precipitate because of

opacity of IVFE admixture

IVFE is less stable—more prone to

lipid separation. Admixture is

less stable with concentrated

electrolyte additives

Larger particle size of IVFE

admixture. Must use 1.2-micron.

Cannot use 0.22-micron bacterial

retention filter.

Limited compatibility with

medications

Containers with diethylhexyl

phthalate should be avoided

because this toxic material may

be extracted by the lipid and may

harm patients.

Using dual-chamber bags may extend the shelf life of TNAs because they allow the

lipid to be physically separated from the dextrose, amino acids, and other additives

until it is time to administer the feeding. The use of dual-chamber bags has the

greatest advantage for home care settings, where up to a week’s supply of parenteral

feedings are prepared at one time.

43

After preparation, TNAs should be refrigerated (4°C) to preserve stability. Once

the bag is removed from the refrigerator, it may be warmed to room temperature and

the contents mixed well before administration. Mixing is best accomplished by gently

inverting the container up and down to ensure top-to-bottom transfer of the fluid.

Vigorous shaking should be avoided because it introduces air, which can destabilize

the emulsion.

43,44

CASE 38-2, QUESTION 8: How does microbial growth differ between 2-in-1 and TNA (3-in-1)

formulations?

Dextrose–amino acid PN formulations are not conducive to growth of most

organisms because of their high osmolarity (>2,000 mOsm/L) and acidic pH. Lipid

emulsions alone, however, are isotonic and have a physiologic pH, providing an

optimal growth medium. Combining these three substrates in a TNA provides a

formulation with a microbial growth potential that is intermediate between the

two.

43,44 The number of CVC violations or manipulations correlates strongly with the

incidence of catheter-related infections. From an infection-control perspective, the

use of a single daily bag of PN formulation limits the number of manipulations of the

CVC to one per day, thereby minimizing touch contamination. The Centers for

Disease Control and Prevention guidelines allow TNA formulations to hang for up to

24 hours. However, because of concerns about the potential of lipid emulsions to

support microbial growth, the hang time for IVFE when administered alone in a

piggyback manner with 2-in-1 PN formulations is 12 hours.

43

CASE 38-2, QUESTION 9: Design a plan to monitor the adequacy of B.B.’s specialized nutrition support

and to identify and prevent adverse complications.

Routine monitoring and evaluation of nutritional status and the metabolic effects of

therapy are required for patients receiving PN therapy. Nutritional goals established

in the patient care plan are estimates of a patient’s nutritional requirements and must

be evaluated regularly to assess adequacy of therapy. Daily monitoring parameters

include vital signs, body weight, temperature, serum chemistries, hematologic

indices, nutrition intake, and fluid intake and output.

The adequacy of nutrition therapy should be assessed weekly. This may be

accomplished through measuring serum concentrations of visceral proteins (see

Table 35-2 in Chapter 35, Basics of Nutrition and Patient Assessment) such as

prealbumin and albumin. Because prealbumin has a half-life of only 2 to 3 days,

serum concentrations of this protein should increase weekly with adequate nutrition

and improving clinical status. Albumin has a much longer half-life of 14 to 20 days

that renders it less useful in reflecting an anabolic response to PN therapy. It is,

however, a good indicator for morbidity and mortality.

46

Indirect calorimetry, if

performed correctly, is the most accurate way to reassess energy expenditure. A

method to assess adequacy of protein intake is to evaluate nitrogen balance which

compares the amount of nitrogen administered to the amount of nitrogen excreted

(amount “in” vs. amount “out”). The nitrogen “in” is provided by the AA component

of the PN formulation. Each commercially available amino acid formulation has a

slightly different amount of nitrogen per gram of amino, so the manufacturer’s product

information should be consulted to obtain this value. On average about 16% of amino

acid is nitrogen or 1 g of nitrogen for every 6.25 g of protein. Most of the nitrogen is

excreted in the urine as urea, a byproduct of protein breakdown for energy. Renal

excretion of urea nitrogen increases with increasing stress. To determine the nitrogen

balance, urine must be collected for 24 hours and the amount of urine urea nitrogen

(UUN) measured. Some laboratories have the capability of measuring total urine

nitrogen, which measures all nitrogen entities in the urine. In addition, some nitrogen

lost via skin, respiration, and stool is not measurable but is estimated to be between

2 and 4 g/day.

p. 798

p. 799

Table 38-5

Routine Monitoring Parameters for Parenteral Nutrition

Suggested Schedule for TPN Monitoring

Parameter Initial

Daily

(Critically

Ill)

2-3 ×

Weekly

(Stable) Weekly

Monthly

(Home

Health)

As

Indicated

Weight X X X

BUN, Creatinine, Glucose X X X

Na, K, Cl, HCO3

–, Ca, P, Mg X X X

Albumin, AST, ALT, LDH, Alk

Phos, Total Bili, Conj Bili

X X X

Prealbumin X X X

Triglycerides X X X

RBC count, Hgb, Hct, WBC

count, Platelets

X X X

Achieving a positive nitrogen balance is difficult, if not impossible, in critically ill

patients; therefore, the calculation may result in a negative number or zero. For

convalescing patients, a nitrogen balance of plus 2 to 4 g is acceptable. A negative

nitrogen balance prompts a reevaluation of the amount of protein and energy a patient

is receiving. For patients with a negative nitrogen balance, it may be helpful to

increase intake of both calories and protein.

As with all tests, assessment should include monitoring several parameters,

including the patient’s clinical status. Most important is the identification of trends

that may alert clinicians to impending complications. A suggested schedule for

monitoring is provided in Table 38-5.

CASE 38-3

QUESTION 1: C.C., a 56-year-old man, is admitted to the hospital complaining of increasing abdominal pain

and vomiting. He is diagnosed with acute pancreatitis. This is his third admission for pancreatitis during the past

year. His past medical history is significant for ethanol abuse, chronic obstructive pulmonary disease, and type

II diabetes. His social history is significant for 2 packs/day smoking history. A NG tube is inserted, and he is to

receive nothing by mouth (NPO). IV fluids are begun for hydration. During the next 5 days, C.C.’s abdominal

pain subsides, his pancreatitis resolves, and he is started on an oral diet. Two days after beginning an oral diet,

C.C. complains of severe abdominal pain and is vomiting. He is febrile, his WBC count has increased to

21,000/μL, and he is hypotensive, requiring large volumes of IV fluids. Furthermore, he experiences respiratory

distress and requires endotracheal intubation and mechanical ventilation. His most recent arterial blood gas

(ABG) is notable for pH, 7.44; Pco2

, 40 mm Hg; Po2

, 88 mm Hg; and HCO3

−

, 28 mEq/L. C.C.’s clinical

presentation is consistent with severe pancreatic necrosis. A small-bore nasojejunal feeding tube is placed, and

enteral nutrition therapy is begun. However, C.C. experiences severe abdominal pain and distension, and bowel

sounds are absent, so the enteral feeding is discontinued. The decision is made to begin PN because C.C. is not

expected to have a functional GI tract in the near future and his nutrient intake has been inadequate during his

hospitalization. C.C. is 5 feet 8 inches tall, and his usual weight is 215 lb.

What adjustments should be made in determining C.C.’s energy goals?

First, C.C. is considered obese, and an adjusted body weight should be calculated

and used in nutrition calculations. Obesity is defined as weight exceeding 120% of

ideal body weight or a body mass index (BMI) of greater than 30 kg/m2

. C.C. weighs

215 lb, or 98 kg, which is 142% of his ideal body weight of 69 kg. BMI is

determined as shown by Equation 38-9.

Obese patients should have their weight adjusted because adipose tissue is not

metabolically active. However, about one-fourth of the adipose tissue is composed

of some supporting tissue that is metabolically active. Adjusted weight for obesity is

calculated using Equation 38-10.

47

Using an adjusted weight will decrease the risk of overfeeding, which can further

increase adipose tissue and complicate glucose management, especially in a patient

with a history of diabetes mellitus. Another approach is to use the Ireton-Jones

predictive equation that includes a factor for obesity. Using indirect calorimetry to

obtain a measured energy expenditure may more accurately assess energy expenditure

and avoid overfeeding.

C.C. is considered to be a critically ill patient. Guidelines from the American

Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) support permissive

underfeeding (80% of estimated energy requirements) for critically ill patients to

minimize the

p. 799

p. 800

risk of insulin resistance, infectious morbidity, and prolonged mechanical

ventilation. As the patient stabilizes, the PN regimen may be increased to meet a

100% of estimated energy requirments.

21 For critically ill obese patients, the

A.S.P.E.N. guidelines go a step further to support that if BMI is in excess of 30, goal

caloric intake should not exceed 60% to 70% of target energy requirements or 11 to

14 kcal/kg actual body weight per day (or 22–25 kcal/kg ideal body weight per day).

Protein should be provided at >2.0 g/kg IBW for BMI classes I and II and at >2.5

g/kg IBW for BMI class III.

21,48

In the case of C.C., his BMI is 32.7 (BMI Class I) so

his energy goal is estimated at 22 kcal/kg of ideal body weight or approximately

1,500 kcal/day.

CASE 38-3, QUESTION 2: Is the use of lipid emulsion contraindicated in patients with pancreatitis?

Several observations have raised concern about the use of IVFE in patients with

pancreatitis. The oral ingestion of fats may stimulate pancreatic exocrine function and

should be restricted in patients with pancreatitis. Although hyperlipidemia has been

well described in patients with alcohol-induced pancreatitis, it is unlikely that it is

primarily responsible for initiating the pancreatitis. Acute pancreatitis associated

with hypertriglyceridemia is most often seen in patients with hereditary or acquired

defects in lipid metabolism. Furthermore, pancreatitis alone may be associated with

hypertriglyceridemia.

49

Several investigators have evaluated the effects of PN formulations containing

IVFE’s in patients with acute pancreatitis and have found no stimulation of pancreatic

exocrine function. Furthermore, IVFE did not result in abdominal pain or relapse in

patients with a history of pancreatitis. Available data suggest that IVFE are a safe

and efficacious form of calories for patients with pancreatitis.

49

While consensus has not been reached regarding the optimal composition of lipid

emulsions, recent guidelines from the Society of Critical Care Medicine (S.C.C.M.)

and the A.S.P.E.N. recommend that during the first week of stay within an intensive

care unit, patients should receive PN formulations that do not contain soy-based

lipids.

49 The addition of n-3 fatty acids, eicosapentaenoic acid and docosahexaenoic

acid, to lipid emulsions is recommended because of positive effects on cell

membranes and inflammatory processes.

50

Monitoring serum triglyceride concentrations should be part of routine

management for patients with pancreatitis and those receiving parenteral nutrient

formulations containing lipids. Serum triglyceride concentrations should be

maintained at less than 400 mg/dL with a continuous infusion of lipids and less than

250 mg/dL when checked 4 hours after the infusion for patients receiving intermittent

IVFE infusions.

1,42,49

If serum concentrations exceed these parameters, consideration

must be given to decreasing or eliminating the IVFE from the parenteral nutrient

regimen.

CASE 38-3, QUESTION 3: What are other considerations regarding PN therapy initiation and formulation

design for C.C.?

Patients with mild-to-moderate pancreatitis do not generally require nutrition

support therapy. Patients with severe acute pancreatitis should have a nasoenteric

tube placed and feedings initiated as soon as the volume resuscitation is complete. If

tube feeding is not feasible, PN therapy should be considered and initiated after the

first 5 days of hospitalization (after the peak of the inflammatory response).

21 Acute

pancreatitis is a complex condition and its severity is highly variable. Severe acute

pancreatitis can cause systemic inflammatory response syndrome affecting multiple

organ systems often times resulting in organ failure. Compromised or failing organs

may necessitate macronutrient and micronutrient adjustments in the PN formula.

Hyperglycemia is the most common complication associated with PN therapy and

can be caused by a variety of factors. Patients without a history of diabetes mellitus

may exhibit hyperglycemia under conditions of stress. Even greater alterations in

glucose metabolism may be observed in patients with diabetes mellitus during

critical illness. Stress-induced hyperglycemia may develop as a result of insulin

resistance, suppressed insulin secretion, and increased gluconeogenesis and

glycogenolysis.

51 Dextrose should be limited to 150 g during the first 24 hours of

therapy, the amount of dextrose should not be increased until serum glucose

concentrations are consistently less than 180 mg/dL, and capillary blood glucose

concentrations should be monitored frequently. With a history of diabetes, coupled

with acute pancreatitis, it is anticipated that C.C. will need supplemental insulin

when his parenteral nutrient regimen is infused. Insulin therapy may be administered

subcutaneously, intravenously with an insulin infusion, or directly in the PN

formulation.

52,53 Regular insulin may be added to the PN formulation at a dose of 0.1

units per gram of dextrose as a reasonable starting point and should be adjusted to

achieve serum glucose levels between 140 and 180 mg/dL.

54 Alternatively, a

separate insulin infusion may be used for more aggressive glucose control. Capillary

glucose monitoring is required during PN therapy at least every 6 hours and more

frequently in hyperglycemic patients, and it may be necessary to provide additional

subcutaneous insulin.

53,55,56

CASE 38-3, QUESTION 4: C.C.’s current laboratory values are as follows:

Na, 137 mEq/L

K, 4.5 mEq/L

Cl, 102 mEq/L

HCO3

−

, 26 mEq/L

BUN, 9 mg/dL

Creatinine, 0.8 mg/dL

Glucose, 148 mg/dL

Ca, 8.9 mg/dL

Mg, 1.9 mg/dL

P, 2.8 mg/dL

Albumin, 3.0 mg/dL

Which electrolytes should be included in C.C.’s parenteral nutrient formulation?

Once macronutrient goals are achieved and tolerance is established, the daily

management of PN therapy revolves around maintaining the patient’s fluid and

electrolyte needs. All concurrently administered IV fluids and medications must be

considered and accurate records of volume intake and output reviewed. Electrolytes

added to PN formulations are sodium, potassium, chloride, acetate (which is

metabolized to bicarbonate), magnesium, calcium, and phosphate. Electrolyte

requirements can vary widely and should be added to the PN formulation based on

individual patient needs. However, patients without significant fluid and electrolyte

losses, hepatic or renal dysfunction, or acid–base disturbances do well with standard

maintenance doses of electrolytes. Electrolytes may be added individually or as

commercially available combination products for maintenance doses. General

guidelines for electrolyte requirements for parenteral feedings are included in Table

38-6.

CASE 38-3, QUESTION 5: What doses of multiple vitamins and trace elements should C.C. receive in his

parenteral nutrient formulation?

Vitamins and trace elements should be included in PN regimens and are essential

for normal metabolism and effective nutrient utilization. Guidelines for the 13

essential vitamins have been established by the Nutrition Advisory Group of the

American Medical Association

57

(Table 38-7).

p. 800

p. 801

Table 38-6

Guidelines for Daily Electrolyte Requirements

Electrolyte Amount

Sodium 80–100 mEq

Potassium 60–80 mEq

Chloride 50–100 mEq

a

Acetate 50–100 mEq

a

Magnesium 8–20 mEq

Calcium 10–15 mEq

Phosphorus (phosphate) 20–40 mmol

aAs needed to maintain acid–base balance.

Table 38-7

Recommended Adult Daily Doses of Parenteral Vitamins

Vitamins Dose

Fat-Soluble Vitamins

A 3,300 IU (990 retinol equivalents)

D 200 IU (5 mg cholecalciferol)

E 10 IU (6.7 mg/dL-α-tocopherol)

K 150 mcg

Water-Soluble Vitamins

Thiamine (B1

) 6 mg

Riboflavin (B2

) 3.6 mg

Niacin (B3

) 40 mg

Pyridoxine (B6

) 6 mg

Cyanocobalamin (B12

) 5 mcg

Folic acid 600 mg

Pantothenic acid 15 mg

Biotin 60 mcg

Ascorbic acid (C) 200 mg

Guidelines for daily doses of the trace elements, such as chromium, copper,

manganese, and zinc, have also been developed.

58

In addition to these trace elements,

many practitioners provide selenium on a daily basis. Recommended doses of the

trace elements are listed in Table 38-8. As with vitamins, trace elements are

available as single entities or combination products. Molybdenum and iodine are

also available commercially.

CASE 38-3, QUESTION 6: C.C.’s initial PN infusion is started at a rate of 40 mL/hour. Why is this slow

infusion rate selected?

Standard practice for administering PN formulations containing hypertonic

dextrose is to begin at a slow infusion rate of less than 250 g of dextrose during the

first 24 hours for most patients and less than 150 g of dextrose for patients with

known diabetes mellitus or hyperglycemia. The infusion is increased slowly during

the next 24 to 48 hours to the goal infusion rate as of 1,800 mL/day as tolerated. This

initial period allows the clinician to assess tolerance to the nutrient formulation

components and to avoid metabolic complications, primarily hyperglycemia.

37

If

C.C.’s serum glucose level consistently remains less than 180 mg/dL, the PN

formulation infusion rate can be increased to his goal rate.

CASE 38-3, QUESTION 7: During the next 24 hours, a comparison of his intake and output reveals an

overall negative fluid balance because a high volume of gastric fluid is being removed via the NG tube.

Laboratory values at this time are the following:

Na, 138 mEq/L

K, 3.1 mEq/L

Cl, 91 mEq/L

HCO3

−

, 33 mEq/L

BUN, 28 mg/dL

Creatinine, 0.9 mg/dL

Glucose, 279 mg/dL

Ca, 7.8 mg/dL

Mg, 1.4 mg/dL

P, 1.8 mg/dL

Albumin, 2.8 g/dL

Arterial blood gas (ABG) results are pH, 7.46; PO2

, 98 mm Hg; PCO2

, 47 mm Hg; and HCO3

−

, 31 mEq/L.

What factors contribute to these metabolic abnormalities?

Table 38-8

Recommended Daily Adult Doses of Parenteral Trace Elements

Trace Element Dose

Chromium 10–15 mcg

Copper 0.3–0.5 mg

Manganese 60–100 mcg

Selenium 20–60 mcg

Zinc 2.5–5 mg

PN therapy may be associated with multiple metabolic complications. The most

common abnormalities are hypokalemia, hypomagnesemia, hypophosphatemia, and

hyperglycemia. The plan for PN therapy should include routine monitoring of these

serum chemistries to identify complications early and institute methods to manage or

prevent complications.

Hypokalemia

Hypokalemia, a common metabolic abnormality associated with the initiation of PN,

usually occurs within the first 24 to 48 hours. Potassium moves, along with dextrose,

from the extracellular to the intracellular space. Furthermore, building lean body

mass (i.e., anabolism) requires approximately 3 mEq of potassium per gram of

nitrogen provided by the amino acids. Administering dextrose promotes repletion of

glycogen stores, which also requires potassium.

37,39,59

C.C.’s decreased serum potassium concentration is compounded by metabolic

alkalosis. With metabolic alkalosis, the renal excretion of potassium is increased.

Additional potassium should be administered and can be provided in C.C.’s

parenteral feeding or through another IV.

Hypomagnesemia

Magnesium, like potassium, is primarily an intracellular cation and is considered an

anabolic electrolyte. It is common to observe decreases in magnesium serum

concentrations during the administration of parenteral nutrient formulations. Synthesis

of lean tissue requires 0.5 mEq of magnesium per gram of nitrogen.

37,39,59 Additional

magnesium can be added to the PN formulation. However, when a TNA formulation

is used, the amount of magnesium must stay within the guidelines for the cation

content to maintain the stability of the lipid emulsion.

Hypophosphatemia

Hypophosphatemia occurs when phosphorus moves into the cells for the synthesis of

adenosine triphosphate (ATP), an important

p. 801

p. 802

energy carrier. Phosphorus is depleted quickly with the administration of hypertonic

dextrose, especially in malnourished patients (see Case 38-2, Question 3, for

discussion of refeeding syndrome). Phosphorus is used for ATP synthesis, primarily

in the liver and skeletal muscle. Alkalosis also decreases phosphate stores by

stimulating the phosphorylation of carbohydrates. As a component of 2,3-

diphosphoglycerate, found in red blood cells (RBCs), phosphorus is necessary for

the disassociation of oxygen from hemoglobin.

59

Clinical signs and symptoms of hypophosphatemia usually occur when serum

concentrations fall to less than 1.0 mg/dL. They include lethargy, muscle weakness,

impaired WBC function, glucose intolerance, rhabdomyolysis, seizures, hemolytic

anemia, reduced diaphragmatic contractility, and death. Moderate to severe,

complicated hypophosphatemia can be managed by administering up to 0.625

mmol/kg of phosphate IV.

39,59–61 Although C.C.’s serum phosphorus is not less than

1.0 mg/dL, it is low (1.8 mg/dL), and he should receive 15 to 30 mmol of phosphate

in the parenteral nutrient formulation per day. Additional supplements may be

necessary to replete his phosphorus stores.

60

Metabolic Alkalosis

C.C. has evidence of a metabolic alkalosis based on his ABG results,

hypochloremia, and elevated bicarbonate level. The continued loss of fluid and

hydrochloric acid from the NG tube is the most probable cause of his metabolic

alkalosis. Management of this type of metabolic alkalosis is to replace the fluid and

chloride through another IV. Because acetate is converted to bicarbonate and can

further contribute to the alkalosis, the acetate salts in the parenteral nutrient

formulation can be changed to chloride salts.

59 Nevertheless, the PN formulation

generally is not the primary vehicle for adjusting and supplementing electrolytes and

fluids. Instead, the fluid and electrolyte balance may be adjusted with maintenance IV

fluid and electrolyte supplements.

Hyperglycemia

Hyperglycemia is the most common metabolic complication of PN therapy,

especially in stressed patients. Metabolic stress increases gluconeogenesis and

glycogenolysis. This increase in endogenous glucose production coupled with the

administration of hypertonic dextrose in PN formulations increases the potential for

hyperglycemia.

62 C.C. is at particular risk for hyperglycemia because he is diabetic,

experiencing pancreatitis, and recovering from the stress of surgery.

Persistent hyperglycemia may lead to glucosuria and osmotic diuresis, resulting in

dehydration and electrolyte abnormalities. Hyperglycemia compromises the immune

response altering chemotaxis and phagocytosis and impairing complement function,

thereby increasing risk of infection. In extreme cases, hyperglycemia progresses to

hyperosmolar, non-ketotic acidosis and coma, a condition associated with 40%

mortality.

Hyperglycemia can be minimized by limiting the dextrose infusion rate to less than

4 mg/kg/minute (20 kcal/kg/day).

63 Clinical evidence suggests that treatment of

hyperglycemia and maintenance of euglycemia may reduce morbidity and mortality,

length of stay, and hospital costs.

53,55,64–66

CASE 38-3, QUESTION 8: In response to these serum chemistries, the electrolytes in C.C.’s parenteral

nutrient formulation are changed to the following per liter: NaCl, 160 mEq; KCl, 140 mEq; phosphate as K salt,

60 mmol; MgSO4

, 54 mEq; and calcium gluconate, 30 mEq. How do the doses of calcium and phosphate

compare with maintenance doses? What calcium and phosphate incompatibilities should be anticipated? Will the

calcium and magnesium content alter the lipid stability?

Calcium and phosphate solubility is a safety concern with PN formulations. The

dose of calcium ordered for C.C. is more than 3 times the usual maintenance dose

(Table 38-6). This amount of calcium is not necessary because the observed

hypocalcemia merely reflects C.C.’s low serum albumin concentration; therefore,

less calcium is bound to albumin. C.C. probably does not have true hypocalcemia

because his free (or ionized) calcium, which is critical for physiologic function, has

not changed. If available, obtaining an ionized calcium concentration is advised.

However, some laboratories do not have this test available. In this situation, a

“corrected” calcium formulation may be used. For every 1-g/dL decrease in serum

albumin concentration, there will be about a 0.8-mg/dL reduction in the serum

calcium concentration.

67 For C.C., a serum calcium of 7.8 mg/dL will correct to a

serum concentration of 8.8 mg/dL ([4.0–2.8 g/dL albumin][0.8] + 7.8 mg/dL

calcium).

The amount of phosphate prescribed for C.C. at this time exceeds the usual

recommended dose of 20 to 40 mmol/day (Table 38-7). Although C.C. has a low

serum phosphorus concentration and needs additional phosphate, increasing the

dosage in the parenteral nutrient formulation to 60 mmol/day may be incompatible

with the calcium content, resulting in calcium–phosphate precipitation.

Numerous factors affect calcium–phosphate solubility, and caution is warranted

when preparing PN formulations to ensure that solubility limits are not exceeded. If

solubility is compromised, microprecipitates can occur and may cause diffuse

pulmonary emboli, resulting in respiratory distress or death. Calcium and phosphate

precipitation curves have been developed to assist practitioners in safe compounding

practices. These guidelines help predict the points at which calcium–phosphate

precipitation is likely to occur. The solubility of calcium and phosphate must be

determined based on the volume of the formulation at the time the calcium and

phosphate are mixed together, not the final volume. For example, if the electrolytes

including calcium and phosphate are added to 1,000 mL of a dextrose–amino acid

mixture and then 300 mL of IV fat is added, the calcium–phosphate solubility is

based on the 1,000 mL, not the final 1,300 mL volume. In addition, some amino acid

products contain phosphate ions, and these should be considered when determining

calcium–phosphate solubility.

12,68

The in vitro precipitation of calcium–phosphate depends on the type of calcium

salt used in compounding, concentrations of calcium and phosphate, amino acid

concentration, temperature, pH of the formulation, and infusion time. Calcium

gluconate rather than the chloride salt offers enhanced calcium phosphate solubility.

In solution at equimolar concentrations, calcium chloride dissociates more than

calcium gluconate, thereby increasing the yield of free calcium available for binding

with phosphate. Calcium and phosphate should not be added to the PN formulation in

close sequence. It is recommended to add phosphate first and calcium last, thereby

taking advantage of the maximal parenteral volume. The PN formulation should be

agitated periodically during preparation and inspected for precipitates.

69 Other

guidelines for improving the solubility of calcium are a final amino acid

concentration of greater than 2.5% and a pH less than 6. An increase in the ambient

temperature, such as that found in the heated isolettes within neonatal intensive care

units, can facilitate the precipitation of calcium–phosphate. PN formulations should

be infused within 24 hours after compounding if stored at room temperature; if

refrigerated, it should be infused within 24 hours after rewarming. Increasing

temperature and slow infusions may result in calcium–phosphate precipitation in the

IV catheter, even if precipitation has not occurred in the infusion container.

12

The amount of divalent cations, calcium (20 mEq) and magnesium (30 mEq),

exceeds the general guidelines for maximal amounts that can be added safely to a

TNA without disrupting the stability of the lipid emulsion. A limit of 20 divalent

cations per liter is a general guideline. The amount prescribed for C.C.’s

p. 802

p. 803

regimen is excessive because it provides 50 divalent cations in 1.8 L (28 divalent

cations/L) and may result in a potentially unstable admixture.

Last, a 1.2-μm air-eliminating filter should be used when infusing TNA PN

formulations, and a 0.22-μm air-eliminating filter should be used for non–lipidcontaining admixtures.

12

CASE 38-3, QUESTION 9: C.C. is recovering from his pancreatitis, and a small-bore nasojejunal enteral

feeding tube is reinserted. Tube feeding is considered because he cannot eat by mouth because of the

endotracheal tube and mechanical ventilation. How should he be transitioned from parenteral to enteral

feedings?

Tube feedings can begin with a full-strength isotonic enteral feeding formulation at

a slow continuous infusion rate (10-50 mL/hr and advanced by 10-25 mL/hr every 4

to 24 hours) (see Chapter 37, Adult Enteral Nutrition). Concurrently, the PN

formulation should be decreased to avoid fluid overload and to keep the calorie and

protein intake constant. It can be anticipated that C.C. can transition from parenteral

to enteral feedings in 24 to 48 hours.

CASE 38-4

QUESTION 1: D.D., is a 43-year-old man with a 17-year history of Crohn’s disease (CD). He has had

several hospital admissions over the past 2 years with exacerbations of Crohn’s Disease. D.D. has experienced

an unintentional weight loss of 12% over the past year. He is admitted to the hospital for increasing abdominal

pain, nausea, and vomiting for 9 days, and no stool output. Prior to admission D.D.’s condition was managed

with mesalamine 1 gm QID and prednisone 10 mg QD. On physical examination, D.D. appears thin and his

abdomen is distended. Baseline labs are as follows:

Na, 142 mEq/L

K, 4.2 mEq/L

Cl, 99 mEq/L

HCO3

−

, 15 mEq/L

BUN, 12 mg/dL

Creatinine, 0.9 mg/dL

Glucose, 114 mg/dL

Ca, 9.1 mg/dL

Mg, 1.9 mg/dL

P, 5.8 mg/dL

Albumin, 2.8 g/dL

Prealbumin, 28 g/dL

Interpret D.D.’s prealbumin level.

Although D.D.’s prealbumin level indicates his nutritional status is adequate,

caution must be exercised with its interpretation. In the 1960s it was shown that

prednisone administration may elevate prealbumin levels.

70 Despite his prealbumin

level, D.D. has other indicators of chronic malnutrition. His albumin level is low at

2.8 g/dL. He has experienced an unintentional weight loss of 12 lbs over the past

year and appears thin. Corticosteroid therapy is fairly common in patients likely to

use PN solutions. These patients include patients with inflammatory bowel disease,

patients being treated for cancer, and respiratory patients.

CASE 38-4, QUESTION 2: D.D. has a prolonged hospital course complicated by intra-abdominal abscesses,

poor wound healing, and necrotic bowel, requiring removal of all but 82 cm of his small intestine but leaving his

ileocecal valve and colon intact. D.D. is given a diagnosis of short bowel syndrome (SBS). What is the clinical

significance of the presence of D.D.’s ileocecal valve and colon?

The presence of the terminal ileum and colon following small bowel resection is

critical in nutritional and hydrational management as the patient may be able to

tolerate a very short small intestine without TPN support. The presence of the

ileocecal valve is thought to prolong intestinal transit time and serve as a barrier to

bacterial reflux into the small intestine. Deficiencies of electrolytes, trace elements,

and vitamins are common in Crohn’s disease and influenced by the presence of the

terminal ileum and colon. Deficiencies are often reflective of chronic blood loss

(e.g., iron deficiency), chronic diarrhea (e.g., magnesium, selenium, zinc

deficiencies), or loss of specific absorptive sites (e.g., vitamin B12

). There is a high

prevalence of vitamin D deficiency in patients with Crohn’s disease.

CASE 38-4, QUESTION 3: What issues should be addressed in the nutrition and metabolic management of

this patient?

SBS occurs from extensive intestinal resection that results in inadequate bowel

function to support nutrient and fluid requirements. SBS becomes clinically apparent

when about 75% of the small bowel is removed. Recent studies suggest that the

average length of the small intestine may be shorter than previously thought

(approximately 11 feet), so SBS is best defined using a patient’s symptoms and

findings rather than solely on remaining length of small bowel.

71 SBS patients

frequently experience diarrhea, dehydration, and nutritional deficiencies of minerals,

trace elements, and vitamins (see Chapter 28, Lower Gastrointestinal Disorders). In

adults, this syndrome is commonly seen in Crohn’s disease, radiation enteritis,

mesenteric artery infarction, adhesive obstruction, and trauma.

72 Severe malnutrition

will develop without adequate nutrition support.

To maintain adequate nutrition status, D.D. will require PN until his remaining

intestine begins to adapt. This adaptive period may take several weeks to months to

years, with the majority of intestinal adaptation occurring within the first 2 years

following massive bowel resection. Gut adaptation is enhanced by stimulation of the

enterocytes with nutrients, which is best provided by small, frequent oral meals or

tube feeding.

1,73,74 Sometimes the remaining intestine may never adapt, and SBS may

necessitate lifelong PN therapy for survival.

A potential complication of SBS is hypersecretion of gastric fluids. The volume

and acid content of gastric secretions is directly proportional to the amount of bowel

resected.