AACN Advanced Critical Care
Volume 23, Number 4, pp.451-464
© 2012, AACN
Neonatal and Pediatric Parenteral
Nutrition
Anne Gargasz, PharmD, BCPS
ABSTRACT
Parenteral nutrition is one of the most
important therapeutic modalities invented
in the last several decades. Since its introduction in the 1960s, this modality has
saved thousands of lives by providing nutrients parenterally to sustain growth in premature neonates with severe intestinal
immaturity and other pediatric patients with
intestinal failure, such as a gastrointestinal
fistula or short bowel syndrome. Although
P
arenteral nutrition (PN) is one of the most
important therapeutic modalities invented
in the last several decades. Parenteral nutrition, also known as hyperalimentation, was
first introduced in the 1960s and used in beagle puppies and then later in a neonate with
resection of 95% of her small bowel, with
good nutritional outcomes.1 Since then, thousands of lives have been saved by the process
of providing nutrients parenterally. It has
helped sustain growth in premature neonates
with severe intestinal immaturity and pediatric
patients with intestinal failure as a result of
gastrointestinal fistula or short bowel syndrome. In 2009, the National Center for
Health Statistics reported that patients received
PN in almost 360 000 hospital stays; 33% of
the patients who received PN were children.2
Parenteral nutrition solutions are made either
in a 2-in-1 (amino acids, carbohydrates, and
electrolytes) solution with intravenous (IV) fat
emulsion provided separately through a Y connector or in a 3-in-1 solution containing everything in a 2-in-1 formula plus lipids. This
review discusses the nutritional requirements,
common complications, medication additives,
parenteral nutrition can be a lifesaving
treatment, it is not benign. Many complications can result from either short- or longterm usage. This review discusses the
nutritional requirements, common complications, medication additives, and special
considerations for pediatric patients requiring parenteral nutrition.
Keywords: neonatal, nutrition, parenteral nutrition, pediatric.
and special considerations for neonatal and
pediatric patients requiring PN.
Goal of PN
Goals for nutrition support in the pediatric
population include obtaining body composition
similar to age-matched children and maximizing long-term growth and neurodevelopment.
In preterm neonates, the goal is to match the in
utero human fetal growth rate of approximately 15 g/kg per day.3 The use of growth
curves such as the one shown in Figure 1 for
preterm infants is the standard rule of measure
for determining appropriate height and weight
gain in children.4 The Centers for Disease Control and Prevention (CDC) recommends the use
of the World Health Organization growth
standards to monitor growth for infants and
children 0 to 2 years of age and the use of the
Anne Gargasz is Pediatric Clinical Pharmacist, Tampa General
Hospital, 1 Tampa General Circle, Tampa, FL 33606 (annegargasz
@tgh.org).
The author declares no conflicts of interest.
DOI: 10.1097/NCI.0b013e31826e8f8b
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Figure 1: Fenton growth chart for preterm infants. Reprinted with permission from Fenton TR. A new
growth chart for preterm babies: Babson and Benda’s chart updated with recent data and a new format.
BMC Pediatr. 2003;3:13–22. http://www.biomedcentral.com/1471-2431/3/13. Copyright 2003 Fenton;
licensee BioMed Central Ltd.
CDC growth charts for children 2 years of age
and older (http://www.cdc.gov/growthcharts).
Initial Considerations
When writing or reviewing PN orders, clinicians
should consider 3 things: the specific indication
for PN for the patient, the patient’s current IV
fluids, and whether the patient is at risk for
refeeding syndrome (defined later). The specific
indication for PN for a patient will determine his
or her need for more or less fluid, macronutri-
ents, or micronutrients. For example, if the
patient has small bowel syndrome, has increased
ostomy output, and is lagging behind on the
growth chart, the clinician should provide more
volume, protein, and calories. Next, the patient’s
current IV fluids can be a helpful starting point
in writing the PN formula. For example, if a
5-year-old patient weighing 23 kg has been
receiving 5% dextrose in water and 0.45%
sodium chloride with 20 mEq/L potassium
chloride at 65 mL/h for the past 24 hours and
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his laboratory values were within normal limits,
PN can be started with 10% dextrose, 5 mEq/kg
per day sodium chloride, and 1.3 mEq/kg per
day potassium chloride at 65 mL/h. Finally, if
this patient was at risk for refeeding syndrome,
the clinician should use a lower caloric starting
point, increase calories toward the goal more
slowly, and consider adding more potassium,
magnesium, and phosphorus than for a patient
not at risk.
Before starting PN, clinicians should obtain
laboratory levels including a complete metabolic panel, magnesium, phosphorus, triglycerides, and prealbumin. Then a daily basic
metabolic panel with magnesium and phosphorus should be ordered until laboratory values
are within normal limits; once this goal has been
achieved, weekly basic metabolic panel, magnesium, phosphorus, prealbumin, and triglyceride
levels should be monitored. Although obtaining
these laboratory values as specified is helpful, it
may not always be practical in neonatal patients
for whom the volume of blood required for
these laboratory tests is large in comparison
with their total blood volume. The need for laboratory tests must be weighed against the risk of
making the patient anemic from blood draws.
Indications for PN
Although PN can be a lifesaving treatment, it is
not benign. Many complications can result
from either short- or long-term PN; therefore,
one must carefully consider the initiation of
PN for a patient. Outcomes consistently favor
the use of enteral feeding over PN; therefore,
enteral feeding is preferred whenever possible.
Common indications for pediatric PN
include pancreatitis, small bowel syndrome,
severe malnutrition/failure to thrive, and an
inability to tolerate oral or nasogastric feeds as
well as other clinical scenarios in which the
pediatric patient is expected to take nothing by
mouth for more than 5 to 7 days. In the neonatal population, PN is indicated in premature
patients and those with either very low birth
weight (VLBW) (⬍ 1500 g) or extremely low
birth weight (⬍ 1000 g). Full enteral feeds are
not expected to be tolerated for some time in
these populations as a result of gut immaturity,
and withholding nutrition for even 1 day may
lead to poor outcomes.
Refeeding Syndrome
Refeeding syndrome refers to the metabolic
and clinical changes that occur as a result of
providing aggressive nutritional support to a
malnourished patient. Malnourished patients
can have depleted intracellular phosphate
stores. Refeeding causes a shift from fat and
protein metabolism to carbohydrate metabolism. Hypophosphatemia, hypokalemia, and
hypomagnesemia result from insulin secretion
in response to a carbohydrate load, which
shifts these electrolytes intracellularly. Medical complications that occur as a result of
these fluid and electrolyte shifts can include
tremors, seizures, cardiopulmonary abnormalities, and coma. At-risk patients generally
include those who have been underfed for at
least 10 to 14 days or who have had an acute
weight loss of greater than 10% in the past 1
to 2 months. The greatest risk may occur during the first 2 to 3 weeks of aggressive nutritional augmentation to the patient; therefore,
daily laboratory tests are recommended for
the first 1 to 2 weeks and then twice weekly.
These patients require a lower caloric starting
point, calories are increased toward the goal
more slowly, and more potassium, magnesium, and phosphorus may be required in
their PN.
Calculating Maintenance IV
Fluid Volume and Other Fluid
Considerations
Total body water decreases dramatically from
intrauterine life to adulthood: water constitutes 90% of body weight in the preterm
infant, 71% to 83% of body weight in fullterm infants, and 50% to 60% of body
weight in adults.5 The maintenance IV fluid
(MIVF) volume for a pediatric patient may be
determined by using either the HollidaySegar Method 100-50-20 rule (calculating the
total daily volume) or the 4-2-1 rule (calculating an hourly rate) (Table 1).6 Patients with
the following conditions may have increased
fluid requirements: fever, burn, diabetes
insipidus, diarrhea, ileostomy or biliary
drainage, and hyperbilirubinemia. Patients
with hypothermia, syndrome of inappropriate antidiuretic hormone, oliguric renal failure, or patent ductus arteriosus may have
decreased volume requirements. Once the
patient’s daily fluid requirement has been
determined, the following equation can be
used to calculate the actual volume that may
be allotted to PN: PN volume ⫽ MIVF ⫺
lipid volume ⫺ drip/IV medication volumes
⫺ oral/nasogastric feeds.
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Table 1: Calculations for Maintenance Fluid Requirements in Pediatric Patientsa
Weight, kg
Total Maintenance Fluids (mL/kg per day)
Holliday-Segar Method “100-50-20 Rule”
Fluid Rate (mL/kg per hour)
Holliday-Segar Estimate “4-2-1 Rule”
100 mL/kg per day
4 mL/kg per hour
0-10
10-20
1000 mL ⫹ 50 mL/kg for every kg ⬎10
40 ⫹ 2⫻ every kg ⬎10
⬎20
1500 mL ⫹ 20 mL/kg for every kg ⬎20
60 ⫹ 1⫻ every kg ⬎20
a
Data from Holliday and Segar.6
Calculating Daily Energy
Needs and Caloric
Requirements
The nutritional needs of pediatric patients are
determined by their basal metabolic rate, physical activity, growth, and preexisting malnutrition. Caloric supply should aim at covering
these needs. The preferred method to assess
caloric needs in children is to measure total
energy expenditure or resting energy expenditure.7 Equations for calculating specific basal
metabolic rate or resting energy expenditure
are shown in Table 2. In lieu of these equations, total parenteral energy needs may be
roughly estimated using the ranges in Table 3.8
Patient conditions that require increased
caloric needs may include fever, sepsis, burn,
cardiac or pulmonary disease, major complicated surgery, and patients requiring “catch
up” growth. Patients requiring fewer calories
are those who are sedated, in a pentobarbital
coma, being treated with mechanical ventilation, or paralyzed.
Macronutrients
Caloric needs are met by a proper balance of
carbohydrates, proteins, and fats, which are
supplied as follows: dextrose, amino acids, and
lipids in the PN. Generally 40% to 60% of a
patient’s caloric needs are derived from dextrose, 10% to 15% from amino acids, and
20% to 40% from intralipids.
Dextrose
Dextrose is the main source of calories in PN
and usually comprises most of the osmolality
of the solution. Each gram of dextrose provides
3.4 kcal. Normally when initiating PN in a
pediatric patient, one would begin with either a
5% or 10% dextrose concentration and, based
on the patient’s serum glucose levels, titrate the
dose daily toward the patient’s goal dextrose in
increments of 2.5% to 5%. For neonates, carbohydrate delivery should begin between 4 and
8 mg/kg per minute (4-6 mg/kg per minute for
those weighing ⬍ 500 g and limited to 5 mg/kg
per minute in critically ill children) of dextrose
Table 2: Equations Recommended by the European Society for Clinical Nutrition and
Metabolism for Calculating Basal Metabolic Rate or Resting Energy Expenditure in
Childrena
Age, y
0-3
Source
WHO
Schofield (WH)
3-10
WHO
Schofield (WH)
10-18
Harris-Benedict
Gender
Equation
Male
REE ⫽ (60.9 ⫻ Wt) ⫺ 54
Female
REE ⫽ (61 ⫻ Wt) ⫺ 51
Male
BMR ⫽ (0.167 ⫻ Wt) ⫹ (1517.4 ⫻ Ht) ⫺ 617.6
Female
BMR ⫽ (16.25 ⫻ Wt) ⫹ (1023.2 ⫻ Ht) ⫺ 423.5
Male
REE ⫽ (22.7 ⫻ Wt) ⫹ 495
Female
REE ⫽ (22.4 ⫻ Wt) ⫹ 499
Male
BMR ⫽ (19.6 ⫻ Wt) ⫹ (130.3 ⫻ Ht) ⫹ 414.9
Female
BMR ⫽ (16.97 ⫻ Wt) ⫹ (161.8 ⫻ Ht) ⫹ 371.2
Male
REE ⫽ 66.47 ⫹ (13.75 ⫻ Wt) ⫹ (5 ⫻ Ht) ⫺ (6.76 ⫻ age)
Female
REE ⫽ 655.1 ⫹ (9.56 ⫻ Wt) ⫹ (1.85 ⫻ Ht) ⫺ (4.68 ⫻ age)
Abbreviations: BMR, basic metabolic rate; Ht, length in meters (Schofield (WH) equations); Ht, length in cm (Harris-Benedict equation); REE,
resting energy expenditure; WHO, World Health Organization; Wt, body weight in kilograms.
a
Data from Koletzko et al.7
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Table 3: Estimation of Parenteral
Nutrition Caloric Needsa
Age
Table 4: Estimates of Protein Requirements
for Healthy Pediatric Patientsa
Caloric Needs,
kcal/kg per day
Age
Protein Requirements,
g/kg per day
Preterm neonate
90-120
⬍6 mo
Low birth weight/
preterm neonate
3-4
85-105
6-12 mo
80-100
Infant (1-12 mo)
2-3
1-7 y
75-90
Children (⬎10 kg or
1-10 y)
1-2
7-12 y
50-75
⬎12-18 y
30-50
a
Adolescents (11-17 y)
a
0.8-1.5
Reprinted with permission from Mirtallo et al.8
Reprinted with permission from Mirtallo et al.8
to maintain adequate glucose levels and then
advance to a goal of 10 to 13 mg/kg per minute
as tolerated.3,7 Because of osmolarity reasons,
most institutions have a peripheral IV catheter
maximum limit of 10% to 12.5% dextrose
(~900 mOsm/L) and a central venous catheter
limit of 25% to 30% dextrose. Potential complications occurring from the IV administration
of dextrose include hyperglycemia or hypoglycemia, glycosuria and potential osmotic diuresis,
cholestasis, and hepatic steatosis (usually from
long-term high-concentration infusion). Often
difficulty may arise with patients who become
hyperglycemic as a result of abnormal glucose
tolerance yet have not reached their dextrose or
nutritional goals. For these patients, especially
those in the intensive care unit setting, adult
studies have shown that the use of insulin to
maintain a blood glucose level between 80 and
110 mg/dL can reduce overall mortality rate
and blood-stream infections.7
Amino Acids
Amino acids are crucial to making the structural components of all cells in the body and
are essential for tissue turnover and repair.
Each gram of amino acid is equal to 4 kcal. The
protein requirements of neonates and children
depend on age and weight (Table 4). The protein needs of pediatric patients are higher than
those of the adult population when compared
by body weight. Neonates also have higher
demands as they are not able to fully synthesize
all amino acids, making certain amino acids
conditionally essential. To maintain growth
rates similar to those in utero, low-birth-weight
neonates need 2 to 4 g/kg per day of protein.9
Other populations requiring an increased
amount of amino acids include patients with
short bowel syndrome, stress, surgery, and
wound healing. Potential complications and
risks of providing IV amino acids include acidosis, elevated blood urea nitrogen, hyperammonemia, and cholestasis with prolonged
administration. Inadequate supplementation of
energy from carbohydrates and lipids results in
protein breakdown for energy instead of
growth. Generally, amino acids are started at 1
to 1.5 g/kg per day and advanced or weaned,
depending on the serum blood urea nitrogen
level and protein goals.
Lipids
Fats are provided in PN in the form of long-chain
fatty acid emulsions. Several concentrations of
lipid emulsion are available commercially; however, to conserve volume in the pediatric population and improve tolerance, clinicians use a 20%
concentration. Twenty percent lipids are calorically dense, with each gram providing 10 kcal,
and have a low osmolarity. In addition, they provide essential fatty acids, help decrease carbon
dioxide production (compared to carbohydrates), and help maintain a net-nitrogen
balance.7 The lipid requirements of neonates and
children depend on age and weight (Table 5).
Lipid needs are increased in the first 2 years of
life, and enteral fat intake should be unrestricted
in the infant diet. After the second year, many
organizations recommend a slow transition from
unrestricted dietary fat to a goal of less than 30%
total fat and less than 10% saturated fat. Generally, lipids are initiated in PN at 1 g/kg per day
and titrated toward the goal as tolerated by
serum triglyceride levels. In the critical care
patient, concomitant medications containing lipids must be considered in calculating caloric
intake. For example, propofol provides 1.1 kcal/
mL from fat, and patients receiving propofol
infusions should have that fat intake calculated
into total fat intake.
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Table 5: Estimates of Lipid Requirements
for Healthy Pediatric Patientsa
Age
Lipid Requirements,
g/kg per day
Neonates and infants
3-4
Children aged ⬎1 y
2-3
a
Data from Koletzko et al.7
A lipid intake of 0.1 to 0.25 g/kg per day is
required to prevent essential fatty acid deficiency.7 However, complications can result
from IV administration of lipids, such as
hyperlipidemia, cholestasis, lipid overload syndrome with coagulopathy and liver failure, and
potentially kernicterus in premature infants.
Triglyceride levels (drawn via venipuncture, at
the end of a lipid infusion after flushing the
catheter, or from a separate central catheter)
must be tested at least weekly to prevent or
provide early identification of these complications. When triglyceride levels become elevated
(⬎ 200 mg/dL), consider decreasing the daily
dose and, if severely elevated (⬎ 300 mg/dL),
omit lipids until levels return to normal.
Micronutrients: Electrolytes,
Vitamins, and Minerals
In considering electrolytes provided in PN, a
review of how the body uses them and what
affects their serum values is warranted. Table 6
shows common starting ranges for varying age
groups when initiating or reviewing electrolytes in PN.
Electrolytes
Sodium is pivotal to fluid and electrolyte balance and homeostasis of all systems in the
body. It constitutes 90% to 95% of all solutes
in extracellular fluid. Potassium is the main
intracellular cation. It is required for neuromuscular function, metabolic activity, protein synthesis, and resting membrane potential.
Acidosis shifts potassium out of the cell, and
alkalosis will shift potassium into the cell.
Calcium is important for normal blood clotting, cell membrane permeability, secretory
behavior, and neuromuscular excitability. Calcium is bound to albumin. In patients with low
album levels, either a corrected calcium value
should be calculated ([4 ⫺ plasma albumin in
g/dL] ⫻ 0.8 ⫹ serum calcium) or an ionized
calcium level should be obtained. When converting a patient’s home PN to an inpatient
order, occasionally a conversion from mEq to
mg is required (1 mEq elemental calcium ⫽ 20
mg elemental calcium). Another important
consideration with calcium in regard to PN is
its precipitation with phosphate. Most hospitals use PN computer systems that will calculate the calcium and phosphorus curve or
product to ensure that precipitation does not
occur. The equation for determining calcium
phosphorus ratio manually is as follows: calcium (mEq/L) ⫻ phosphorus (mmol/L) ⱕ 300.
In the neonatal period, the optimal ratio of calcium to phosphorus in a range of 1.3 to
1.7 (mol/mol) should be provided to achieve
adequate bone mineralization.7
Half of the body’s magnesium is in the skeleton, with the other half being intracellular in
the heart, liver, and skeletal muscle. Magnesium activates coenzymes needed for carbohydrate and protein metabolism. In addition,
normal magnesium levels are required to
achieve calcium and potassium homeostasis.
Phosphate is the major intracellular anion
and is required for cell function and integrity.
Normal values are age related as a result of
Table 6: Daily Electrolyte and Mineral Requirements for Pediatric Patientsa,b
Preterm Neonates
Infants/Children
Adolescents and
Children, ⬎50 kg
Sodium
2-5 mEq/kg
2-5 mEq/kg
1-2 mEq/kg
Potassium
2-4 mEq/kg
2-4 mEq/kg
1-2 mEq/kg
Electrolyte
Calcium
2-4 mEq/kg
0.5-4 mEq/kg
10-20 mEq
Phosphorus
1-2 mmol/kg
0.5-2 mmol/kg
10-40 mmol
Magnesium
0.3-0.5 mEq/kg
0.3-0.5 mEq/kg
10-30 mEq
Acetate and chloride
a
As needed to maintain acid-base balance
Reprinted with permission from Mirtallo et al.8
b
Assumes normal age-related organ function and normal losses.
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Table 7: Phosphate Normal Ranges
by Agea
Age
Normal Values, mg/dL
Newborns
4.2-9
6 wk to 19 mo
3.8-6.7
19 mo to 3 y
2.9-5.9
3-15 y
3.6-5.6
⬎15 y
a
2.5-5
Data from Taketomo et al.
10
differences in the maturation of the renal system and the rate of bone growth and turnover
(Table 7).10 Often laboratory test results report
only the normal range for adults; therefore,
pediatric normal ranges should be referenced,
as normal ranges change with age.
Trace Elements
Trace elements are often included in standard
PN formulas unless otherwise written to be
omitted. Although the American Society for
Parenteral and Enteral Nutrition (ASPEN)
guidelines state that the recommended intakes
of trace elements can be achieved only through
the use of individualized trace element products, most institutions use commercially available combination products.8 The recommended
daily intake of trace elements for pediatric
patients (Table 8) can generally be obtained by
providing the following amounts of the neonatal
or pediatric parenteral trace element products:
0.25 mL/kg (neonatal product) for neonates
weighing less than 1.5 kg, 0.2 mL/kg (neonatal
product) for neonates weighing 1.5 kg to 10 kg,
2 mL (pediatric product) for pediatric patients
weighing 10 kg to 20 kg, and 4 mL (pediatric
product) for patients weighing more than
20 kg (Table 9).3 Trace elements commonly
provided in PN include chromium, copper,
manganese, and zinc. Selenium is not provided
in most commercially available neonatal or
pediatric trace element products and therefore
must be provided either separately or by diluting the adult product. Current practice standards are to supplement 1 to 3 mcg/kg per day in
infants and children who are exclusively being
fed via PN for greater than 4 weeks or lowbirth-weight infants.7,8,13
Chromium mediates insulin reactions and is
important for peripheral nerve function. Copper is important for transferrin and leukocyte
production, as well as bone formation. Manganese is a cofactor in the production of many
enzymes. As both copper and manganese are
eliminated hepatically, serum levels should be
obtained in patients with liver dysfunction, as
these trace elements can accumulate and
become toxic. Selenium helps prevent oxidative
tissue damage and is important in thyroid
metabolism.
Finally, zinc is a cofactor in many enzymes,
is critical for normal growth and immune functions, and maintains the integrity of skin and
gastrointestinal tract mucosa. Premature and
term infants often require extra supplementation of zinc in addition to what is provided via
commercial trace element preparations (450500 mcg/kg per day for premature infants, 250
mcg/kg per day for infants younger than 3
months, 100 mcg/kg per day for infants 3
months and older) because of their rapid
growth.7 In addition, zinc may need to be
added for those patients with zinc losses from
diarrhea or increased ostomy output.
Vitamins
Similar to trace elements, multivitamins are
often standard in PN unless requested otherwise.
The recommended daily intake of vitamins can
Table 8: Trace Element Daily Requirements for Pediatricsa
Preterm Neonates
⬍3 kg
(mcg/kg per day)
Term Neonates
3-10 kg
(mcg/kg per day)
Infants/Children
10-40 kg
(mcg/kg per day)
Zinc
400
50-250
50-125
2-5 mg
Copper
20
20
5-20
200-500 mcg
Trace Element
Adolescents
⬎40 kg
(per day)
Manganese
1
1
1
40-100 mcg
Chromium
0.05-0.2
0.2
0.14-0.2
5-15 mcg
Selenium
1.5-2
2
1-2
40-60 mcg
a
Reprinted with permission from Mirtallo et al.8
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intramuscularly 3 times weekly for 4 weeks in
addition to what is provided in the PN solution
for the VLBW infant.
Table 9: Content of Neonatal/Pediatric
Parenteral Trace Element Productsa
Content per 1 mL (mcg)
Trace Element
Neonatal Trace
Pediatric Trace
Chromium
0.85
1
Copper
100
100
Manganese
Zinc
a
25
30
1500
500
Additional Additives
A limited number of medications may be
added directly to the PN formulation based on
the needs of patients as well as stability and
compatibility information in the PN solution.
The medications most commonly added to
2-in-1 PN solutions are iron dextran, H2
antagonists, insulin, cysteine, carnitine, and
heparin.
Data from Multitrace-4 Neonatal11 and Trace elements injection 4.12
generally be obtained by providing the following amounts of the pediatric parenteral multivitamin product: 1.5 mL for patients weighing
less than 1 kg, 3 mL for those weighing 1 kg to
less than 3 kg, and 5 mL for those weighing 3
kg or more (Table 10).14 Vitamins included in
PN include both fat-soluble vitamins (A, D, E,
K) and water-soluble vitamins (C, B1,2,3,6,7,9,12).
Some adult multivitamin products (generally
used in patients older than 11 years) do not
contain vitamin K, and therefore it must be
added separately. Also, studies have shown a
reduction in death and oxygen requirement in
VLBW infants when additional vitamin A is
supplemented (the number needed to treat to
benefit is 13-20).15 On the basis of these studies, some centers provide 5000 U of vitamin A
Iron Dextran
Iron is not a current component of trace
elements and is not routinely added to PN
formulations.7–9 However, patients receiving
long-term PN who are unable to tolerate or
unable to absorb oral formulations (eg, short
bowel syndrome) often require IV supplementation for iron-deficiency anemia. Intravenous
iron in the form of iron dextran is the most
common form used in PN because of its compatibility information, although literature is
increasing about iron sucrose compatibility at
certain concentrations in PN formulations.
Iron dextran cannot be added to lipid emulsions
or all-in-one mixtures because it destabilizes
the emulsion. Dosing can be estimated on the
Table 10: Content of Pediatric Parenteral Multivitamin Productsa
Vitamin
Content per 5 mL
A
2300 IU
D
400 IU
E
7 IU
K
Importance/Function
Immune function, respiratory benefits
Maintains calcium and phosphorus homeostasis
Antioxidant
200 mcg
Regulates coagulation factors (VII, IX, X, II)
B1 (thiamine)
1.2 mg
Lipid synthesis, carbohydrate metabolism
B2 (riboflavin)
1.4 mg
Assists in energy metabolism
B3 (niacin)
17 mg
Involved with electron transport and metabolism
B5 (pantothenic acid)
5 mg
Precursor to coenzyme A, energy metabolism
B6 (pyridoxine)
1 mg
Metabolism of carbohydrates and amino acids, immune and
neurological function
B7 (biotin)
20 mg
Cell growth, fatty acids, metabolism of lipids and amino acids
140 mcg
Amino acid metabolism, synthesis of purines and pyrimidines,
catabolism of histidine
B9 (folic acid)
B12 (cyanocobalamin)
1 mcg
Synthesis of DNA nucleotides
C (ascorbic acid)
80 mg
Cofactor and antioxidant
Abbreviation: IU, international unit.
a
Data from Infuvite Pediatric.14
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basis of either weight and hemoglobin concentration or age and weight.10 A test dose must be
given prior to the infusion to evaluate susceptibility to potential anaphylactic and other
adverse reactions. Serum ferritin levels should
be obtained every 1 to 3 months when providing ongoing IV supplementation to minimize
the risk of iron overload.
A theoretical concern with IV iron administration is that it may stimulate bacterial growth
and impair immune function, thereby increasing the risk of infection by iron-requiring pathogens (Klebsiella, Pseudomonas, Salmonella,
Yersinia, Listeria, Haemophilus influenzae,
and Staphylococcus species).7,14 Iron facilitates
viral replication and reverses the bactericidal
effect of lactoferrin and lysozyme. However,
certain aspects of the immune response, such
as the generation of oxidative burst, are suppressed in iron deficiency, and numerous clinical studies have found no correlation between
iron therapy and risk of death or infection.7,16
Heparin
Catheter occlusion, dislodgement, and thrombosis are common complications associated
with central venous catheters in the pediatric
population, and these risks are even greater in
neonates.7,17 Risk factors for these complications include younger age, wrist and scalp IV
insertions, small-gauge catheters, low flow
rates, turbulent flow, blood stasis, blood
hyperviscosity, hypercoagulability, and the
composition of the catheter.7,18 Heparin has
been used prophylactically at a dose of 0.25 to
1 U/mL of PN solution by some centers to prolong the duration of catheter patency and prevent the incidence of catheter-related venous
thrombosis in neonates with umbilical and
central venous catheters.9,19,20 Several Cochrane
Database reviews have investigated the use of
continuous heparin infusion to prevent catheter occlusion and thrombosis. One review
examined 3 randomized trials including 267
neonates with central venous catheters and
found a reduced risk of catheter occlusion but
no statistically significant decrease in thrombosis or catheter-related sepsis with a heparin
dose of 0.5 U/kg per hour.17 Another review
focusing on 10 studies involving peripheral IV
catheter use in neonates found varying effects
on catheter patency and therefore found no
basis to recommend heparin usage for peripheral catheters.21 The European Society for
Parenteral and Enteral Nutrition guidelines
specifically recommend against heparin use in
peripheral catheters.7 Heparin is also recommended at a dose of 1 U/mL of PN solution in
the neonatal population to enhance the clearance of lipid emulsions. Heparin has been
shown to increase lipoprotein lipase levels and
lipolytic activity, thereby stabilizing triglyceride levels.9
Cysteine
As recommended by manufacturers of neonatal and infant amino acid formulations, the
current practice is to add cysteine (40 mg/g of
amino acids) to 2-in-1 PN solutions just prior
to administration for the first year of life
because of immaturity of the synthesis pathway in this age group. The addition of cysteine
decreases the pH, therefore improving the solubility of calcium and phosphorus.8 The European Society for Parenteral and Enteral Nutrition
guidelines recommend a minimum intake of 30
to 55 mg/kg per day in infants and young children to maintain redox potential and calcium
homeostasis.7
Carnitine
Carnitine plays a role in the transport of longchain fatty acids to mitochondria for oxidation, thereby aiding fat metabolism.13 Primary
carnitine deficiency has been associated with
cholestasis and steatosis. Carnitine may be
conditionally essential in neonates on longterm PN because of their low plasma and
tissue concentrations at birth, immature conservation mechanisms, and biosynthetic capabilities.9,22 Carnitine also has been shown to
increase lipid clearance and prevent hypertriglyceridemia in the neonatal population.9 Supplementing carnitine in the PN solution of
patients receiving long-term PN can help mobilize hepatic fat stores and prevent steatosis and
cholestasis.22 Typical dosing is either a bolus of
50 mg/kg per day for 3 days given when measured levels are low or prophylactically at a
dose of 10 to 30 mg/kg per day.9,13,23
Insulin and H2 Antagonists
Patients not at their goal dextrose caloric
intake because of hyperglycemia may require
the addition of insulin to their PN treatment
regimen to continue to provide appropriate
nutrition as well as avoid the complications
associated with elevated glucose levels in
patients with cardiac and infectious diseases.
Caution is advised when determining the
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amount of insulin to be added; Marcoud et al24
report that a higher percentage of insulin
added to PN solution reaches the patient than
previously published. Subcutaneous sliding
scale insulin supplementation or a separate
insulin infusion is always an option.
For patients requiring stress ulcer prophylaxis or gastroesophageal reflux treatment with
an H2 antagonist such as famotidine or ranitidine, clinicians may choose to discontinue the
separate IV injection and instead add it to the
PN solution to save nursing administration
time. The benefits of these agents as well as
proton pump inhibitors must be weighed
against the growing literature for increased risk
of pneumonia, necrotizing enterocolitis, and
other infections associated with their use.
Complications
Hypertriglyceridemia and Essential
Fatty Acid Deficiency
Essential fatty acid deficiency, which causes
platelet dysfunction, hair loss, poor wound
healing, and dry scaly skin, can occur 2 to 4
weeks after the administration of a fat-free PN
solution. It results from a failure to provide at
least 2% to 4% of the total caloric intake as
linoleic acid and 0.25% to 0.5% as ␣-linoleic
acids.8 The European Society for Parenteral
and Enteral Nutrition recommendations are to
provide a minimum of 0.25 kg/kg per day of
lipids to preterm infants and 0.1 g/kg per day
to term infants and older children.7
Conversely, excessive or too rapid lipid intake
can result in lipid overload syndrome. This
syndrome is characterized by coagulopathies,
elevated liver enzymes, hyperbilirubinemia,
hepatomegaly, thrombocytopenia, and respiratory distress. In preterm neonates, tolerance of
lipid emulsions is improved by infusing them
over a 24-hour period. Parenteral nutrition–
associated hypertriglyceridemia can also occur
in pediatric patients with low birth weight and
sepsis, which is usually due to excessive administration of lipids or uncontrolled hyperglycemia.9 As mentioned previously, the addition of
heparin and carnitine to the PN solution can
facilitate the clearance of lipids, therefore stabilizing serum triglyceride levels.
Hyperglycemia in Neonates
Hyperglycemia (plasma glucose ⬎ 150 mg/dL)
occurs frequently in VLBW and premature
neonates, especially during the first days of life.25
Physiological factors such as immaturity of the
liver and pancreas, as well as saturation of insulin receptors, predispose the premature neonate
to hyperglycemia. Other contributing factors,
such as surgery, respiratory distress, and sepsis,
can worsen hyperglycemia.9 Complications
associated with hyperglycemia include retinopathy of prematurity, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, bacterial
and fungal infections, intraventricular hemorrhage, longer hospital stays, and death.25 Treatment of hyperglycemia during PN use is targeted
toward avoiding excess dextrose and providing
IV fat emulsion, as insufficient evidence exists to
show a higher versus lower glucose infusion rate
has an impact.25,26 A recent Cochrane Database
review evaluated 2 trials comparing insulin infusion with standard care and determined that the
evidence did not support the routine use of insulin infusions to prevent hyperglycemia.25 The
ASPEN guidelines also recommend against insulin use to prevent hyperglycemia; however, these
guidelines state that insulin may be indicated for
treatment of persistent hyperglycemia due to
sepsis and medications.26
Metabolic Bone Disease
Although more data exist in adults, metabolic
bone disease has been reported in premature
neonates and infants receiving long-term PN.
This disorder is thought to be due to a combination of phosphorus, calcium, and vitamin D
deficiencies, as well as aluminum accumulation. Patients with malabsorptive disorders, as
well as those taking glucocorticoids and antineoplastic medications, may be at increased risk
for metabolic bone disease. Although no specific treatment is available for this disorder,
ASPEN guidelines suggest providing adequate
amounts of calcium and phosphate in a ratio
of 1:2 and measuring serum aluminum concentrations whenever unexplained metabolic bone
disease is present.9
PN-Associated Cholestasis
With a prevalence of 30% to 70% in infants,
PN-associated cholestasis is diagnosed by a progressive rise in alkaline phosphatase and/or conjugated bilirubin (direct bili ⬎ 2 mg/dL).22 The
exact cause is unknown, although several theories have been proposed, including a continuous
PN maintaining a high insulin level and promoting a fatty liver, lipid intake greater than
1 g/kg per day, excessive or an imbalance of
amino acids, and excess carbohydrates that
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stimulate insulin. Insulin then stimulates
enzymes involved in fatty acid synthesis.
Cholestasis may progress to cirrhosis and liver
failure if left untreated. Treatment of PN-associated liver disease or cholestasis includes cycling
the PN over 12 to 20 hours, adding carnitine to
the PN solution, initiating oral ursodiol, and
providing as much enteral nutrition as tolerated.
Cycling the PN by alternating periods of fasting
and feeding allows for mobilization of fat during periods of fasting.23 Carnitine at a dose of
10 to 30 mg/kg per day, as discussed previously,
can theoretically help mobilize fat stores. Ursodiol at a dose of 30 mg/kg per day works by
reducing the secretion of cholesterol from the
liver, reducing the cholesterol content of bile. It
then becomes the predominant biliary acid, thus
displacing potentially hepatotoxic bile salts.
Catheter-Related Blood
Stream Infections
Because of the osmolarity of PN solutions, a
central venous catheter is often required. Unfortunately, having a long-term central venous
catheter predisposes patients to infection, especially those with short bowel syndrome and
neonates with a birth weight of less than 1000 g.3
Emphasis should be placed on prevention of
catheter-related infections by using aseptic technique, changing the infusion sets for amino acid
and glucose infusions at least every 72 hours,
and having a hang time of no more than 12
hours for IV fat emulsion.3,7 For patients on
long-term cycled PN, ethanol locks may be more
effective than heparin locks in preventing catheterrelated blood stream infections (CRBSIs) and
possibly decrease the need for catheter replacement as well. A meta-analysis of ethanol locks
for the prevention of CRBSIs including 53
patients aged 4 months to 21 years found that,
compared with heparin locks, ethanol locks
reduced the CRBSI rate by 81% and catheter
replacements by 72%. The CDC recommends
the use of ethanol locks in patients with longterm catheters who have a history of multiple
CRBSIs despite aseptic technique.27
Further Considerations and
Concerns
Extracorporeal Membrane
Oxygenation
Extracorporeal membrane oxygenation (ECMO)
is a treatment using an extracorporeal heart-lung
machine with a membrane oxygenator provid-
ing both cardiac and respiratory support. Indications for ECMO use in pediatric patients
include congenital heart disease, persistent pulmonary hypertension, meconium aspiration,
and congenital diaphragmatic hernia failing
conventional ventilatory support. The patient
being treated with ECMO typically receives
fluid volume from multiple IV medications and
infusions and may also require fluid restriction
because of underlying pathophysiology, thereby
leaving minimal volume available to provide
the PN solution. Calcium supplementation
may need to be reduced by half because of an
alteration in calcium and vitamin D regulation
in those receiving ECMO.3 In addition, ASPEN
guidelines recommend that nutrition support
be initiated expeditiously in ECMO patients,
providing up to 3 g/kg per day protein and
allowing the same caloric requirements as recommended for healthy neonates. Enteral feedings should be initiated when the patient is
clinically stable. Care must be taken for the
provision up to 3 g/kg per day protein for up to
3 weeks after a patient has been successfully
weaned from ECMO as a result of a persistent
catabolic state.3,28
Compatibility
Patients receiving PN are frequently unable to
tolerate oral feeds and oral medications, necessitating IV administration of medications. For
patients with multiple-lumen catheters, this
limitation is not a problem; however, for those
patients with only 1 lumen, clinicians must
consider the compatibility of the medication
running via Y site into the same catheter as the
PN solution. Table 11 lists compatibility information for many common medications coinfused via the Y site for both 2-in-1 and 3-in-1
PN solutions.29
Photoprotective Covering for
Neonatal PN
Exposure of PN solutions to light generates
peroxides, which can cause oxidative stress in
neonates, potentially leading to lung remodeling and an increased incidence of BPD. Shielding the PN solution from light may help
decrease levels of peroxides and thus decrease
the incidence of premature neonate complications such as BPD. One post hoc analysis,
including 77 patients randomized to either
light-protected or light-exposed PN, found a
30% reduction in BPD in those receiving
light-protected PN, although results were not
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Table 11: Y-Site Medication Compatibility
With 2-in-1 and 3-in-1 PN Solutionsa
(Continued)
Table 11: Y-Site Medication Compatibility
With 2-in-1 and 3-in-1 PN Solutionsa
PN Solution
Medication
Acyclovir
Amphotericin B
Ampicillin
Bumetanide
PN Solution
2-in-1
3-in-1
I
I
Medication
I
I
Mannitol
C/I
C
Meperidine HCL
C
Meropenem
C
2-in-1
3-in-1
C
C
C
C
NA
C
C
C
Calcium gluconate
C
C
Mesna
Cefazolin
C/I
C
Methotrexate
I
C
Methylprednisolone
sodium succinate
C
C
Metoclopramide
I/C
C
Metronidazole
C
C
Micafungin sodium
C
NA
Midazolam
I/C
I
Milrinone
C
NA
Cefepime
C
NA
Cefotaxime
C
C
Ceftazidime
C
C
Ceftriaxone
C
C
Cefuroxime
C
C
Ciprofloxacin
I
C
Cisplatin
I
C
Clindamycin
C
C
Morphine sulfate
(concentration 1 mg/mL)
C
C
Cyclophosphamide
C
C
Norepinephrine bitartrate
C
C
Dexamethasone sodium
phosphate
C
C
Octreotide acetate
C
C
Digoxin
C
C
Ondansetron HCl
C
I
Diphenhydramine
C
C
Pentobarbital sodium
C
I
Dobutamine
C
C
Phenobarbital sodium
C
I
Dopamine
C
C/I
Phenytoin sodium
I
NA
Epinephrine
C
NA
Piperacillin sodium–
tazobactam sodium
C
C
Epoetin alfa
C
NA
Potassium chloride
C
C
Famotidine
C
C
Potassium phosphate
I
I
Fentanyl citrate
C
C
Propofol
C
NA
Fluconazole
C
C
Ranitidine
C
C
5-Fluorouracil
C/I
C/I
Sodium bicarbonate
I/C
C
Furosemide
C/I
C
Sodium nitroprusside
C
C
Gentamicin sulfate
C
C
Sodium phosphate
I
I
Heparin sodium
C
I
Tacrolimus
C
C
Hydrocortisone sodium
phosphate
C
C
Tobramycin sulfate
C
C
Hydromorphone
C
I/C
Trimethoprimsulfamethoxazole
C
C
Ifosfamide
C
C
Vancomycin
C
C
Imipenem-cilastatin
C
C
Vecuronium bromide
C
NA
Indomethacin
I
NA
Zidovudine
C
C
Insulin regular
C
C
Leucovorin calcium
C
C
Linezolid
C
NA
Lorazepam
C
Magnesium sulfate
C
I
C
(continues)
Abbreviations: C, compatible; C/I, conflicting compatibility, but
strength of evidence supports compatibility; I, incompatible; I/C,
conflicting compatibility and strength of evidence supports
compatibility; IU, international units; NA, compatibility data not
available; PN, parenteral nutrition, Y-site injection; drug
administration via piggyback, IV push, or other IV methods at the
Y-site injection port or other access port (ie, stopcock) between the
PN solution and the central venous catheter.
a
Modified with permission from Mirtallo.29
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statistically significant.30 Another study (retrospective analysis) reviewed the charts of 866
infants from 26 neonatal intensive care units
comparing those receiving light-exposed PN
and partial light-protected PN (bag covered,
but tubing exposed). The incidence of BPD or
death was 66% with the partial light-protected
group versus 59% with the light-exposed
group, revealing no association between lightprotected PN solution and BPD.31 Further
studies are needed to adequately assess whether
the cost associated with this practice is justified
by the possible benefits.
Aluminum Content
Despite the Food and Drug Administration’s
restriction of aluminum contamination of
large-volume commercially available parenterals to less than 25 mcg/L, aluminum is found
in small amounts in several components of the
PN solution: amino acids, lipids, calcium,
phosphate, heparin, vitamins, and trace elements. In addition, compounding bags and
administration sets can contribute another
40% to these commercial products as a result
of leaching.32 Accumulation from these sources
can occur in the neonatal population as a result
of impaired kidney function causing metabolic
bone disease as well as central nervous system
toxicity. Studies have shown that neonates
receiving more than 5 mcg/kg per day of
parenteral aluminum can have accumulations
of toxic levels, leading to these complications.
Although avoiding the administration of
greater than 5 mcg/kg per day aluminum to
neonates may be impossible, caution must be
taken to minimize the amounts contained in
the PN solution as much as possible. Suggested
strategies include purchasing products with
the lowest aluminum content (ie, calcium acetate instead of calcium gluconate) and washing
out or flushing bags, burettes, and catheters
with a few milliliters of sterile water before
compounding.9,32,33
has published standards of practice for nutrition-support nurses that have the potential to
be applied to critical care nursing as well.35
Some of these standards include participating
in nutrition screening, assessment, management, and/or placement of appropriate enteral
or vascular access devices; participating in the
development of the patient’s individualized
nutrition care plan; evaluating the patient’s
nutritional goals and possible complications of
care, and integrating research findings into
practice.35
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