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TOTAL PARENTERAL
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16
otal parenteral nutrition (TPN) support for
critically ill newborns was first reported four
T
decades ago.44 However, in the modern era
of neonatal care, TPN continues to be a critical
aspect of intensive newborn care. Availability of
TPN has been one of the developments responsible for improved outcome of neonatal surgical
patients.
preterm infants has provided new challenges for
neonatal parenteral nutrition.61 Current evidence
would suggest that early nutritional support is
important to prevent postnatal growth restriction, which has been commonly recognized in
these infants.
results if it includes an experienced “nutrition
team” comprising a neonatologist, surgeon,
nutrition support nurse, pharmacist, dietitian,
and social worker, with each member playing a
vital role to make TPN a safe and effective therapy. This chapter discusses the nutritional needs
of the high-risk newborn, specific indications for
TPN, and guidelines for formulation and administration of intravenous (IV) nutritional solutions. An
overview of mechanical, infectious, and metabolic
complications is also presented with emphasis on
prevention and early identification.
94,100,102
A neonatal service that uses TPN has the best
NUTRITION
STEVEN L. OLSEN, ALEXANDRIA OSCHMAN, AND KELLY TRACY
Increased survival of extremely
40,45,61
glycogen. Stable blood sugar levels are maintained
by hormonal regulation of glycogen production
(glycogenesis) and breakdown to glucose (glycogenolysis). Newborns, particularly those who
are growth restricted or preterm, have low glycogen stores and often have insufficient regulatory
mechanisms.
The body’s greatest energy stores are in
the form of fat, which provides a calorie yield
of 9 kcal/g when metabolized. In addition to
normal deposits of adipose tissue, newborns (and
hibernating adult animals) have unique stores called
brown fat. These stores, which are anatomically
located between the scapulae, in the axillae and
mediastinum, and around the adrenal glands, protect
the body from hypothermia through nonshivering
thermogenesis91 (see Chapter 6).
Protein makes up lean body mass. Although
protein generally is not used as an energy source
postnatally, in fetal life, amino acids are oxidized
apparently for energy.
periods postnatally, but extended periods of pro-
tein catabolism (breakdown of endogenous substrates), such as during times of starvation, may
lead to body dysfunction, as noted later.
118
122
This may be true for brief
The Effects of Insufficient Nutrition
PHYSIOLOGY
Fuel Stores
During periods of fasting, tissue stores of energy
provide the major source of fuel for the body.
Carbohydrate is stored in the liver and muscle as
BLUE type highlights content that is particularly applicable to clinical settings.
The last trimester of gestation is a time of rapid
fetal growth, with active transplacental transport
of most nutritional substrates. Preterm delivery
interrupts the nutritional supply and abruptly
results in a catabolic state, which, if prolonged,
may alter growth potential. It is unclear whether
it is possible to achieve in utero growth rates for
the postnatal preterm infant, but reestablishment
459
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of an anabolic state and maintenance of micronutrient sufficiency is necessary.
40,58,122
During
this period of neonatal life, the rapidly growing
brain is responsible for much of the nutritional
requirements. Inadequate early nutrition may
have irreversible effects on later neurodevelopmental outcomes.
79
Postnatal growth restriction also is associated
with neonatal medical complications, including
apnea, ventilator dependence, and chronic lung
disease.36 Immune responses may be depressed
with increased susceptibility to infection (see
Chapter 22). Protein malnutrition is most fre-
quently seen in extreme preterms and may
contribute to poor growth potential and longterm morbidity in these infants.
36,122,123
Poor
postnatal growth for most extremely low-birthweight (ELBW) infants has emphasized the need
for additional strategies to improve nutrition for this
population.
40,41,42
One strategy is to initiate parenteral nutrition
within the first hours after birth. Even though
the exact benefits and harms are unknown, provid-
ing early, increased energy and protein support
have been associated with improved short-term
growth outcomes.40 Longer-term outcomes, such
as reductions in the incidence of common neonatal
morbidities, increased brain growth, and improved
neurodevelopmental outcomes, are more difficult
to link directly to early parenteral nutrition. There
is no evidence that early parenteral nutrition
increases morbidity or mortality risks, but also
unclear is the influence of early nutritional support
on the incidence of childhood obesity and the risk
for cardiovascular disease and metabolic syndrome
in adults.
88
Nutritional Requirements of
the Neonate
CALORIC
Caloric requirements for preterm infants,
including very-low-birth-weight (VLBW)
and small-for-gestational-age (SGA) infants,
are approximately 110 to 130 kcal/kg/day.
Caloric requirements for near-term and term
infants are 90 to 120 kcal/kg/day. These estimates are based on enteral intake (see Chapter
17). Parenteral requirements are about 20% less,
or approximately 80 to 100 kcal/kg/day. Factors
affecting caloric requirements include the infant’s
141
gestational age, chronologic age, weight, activity level, body temperature, ambient temperature,
underlying disease, and degree of stress. Infections,
including nosocomial, may also contribute to additional caloric needs.
125
Resting energy expendi-
ture is an estimate of the approximate range
of basic energy needs and is approximately 45
kcal/kg/day in infants less than 900 g and 50
kcal/kg/day for infants larger than 1000 g.
141
Physical activity, which usually is infrequent in
preterm infants, contributes less than 10% to the
energy needs.
78
However, in pathologic states, such as with
repetitious seizures or neonatal abstinence syndrome, increased activity may increase caloric needs.
An elevation of body temperature increases
caloric expenditure by approximately 12% for
each degree Celsius above 37.8° C (100° F).
Metabolic demands of surgery and postoperative
healing, or severe cardiac or pulmonary distress,
may increase caloric requirements by as much as
30% and chronic failure to thrive by 50% to 100%.
In addition, postnatal dexamethasone therapy may
slow weight and linear growth rates and potentially
may negatively affect brain growth.
WATER
31,36,90,140
Water requirements vary with gestational and post-
natal age (postconceptual age) and environmental
conditions (e.g., care in an incubator versus radiant
heat warmer, use of phototherapy) (see Chapter 14).
ELECTROLYTE AND MINERAL
Sodium requirements are minimal for the first
days of life. After 1 week, the average requirement is 3 to 4 mEq/kg/day. Large renal losses
(greater than 5 mEq/kg/day) may occur in
very immature infants (less than 28 weeks of
gestation) in the first weeks of life. Potassium
and chloride requirements are approximately 2
mEq/kg/day and 3 to 4 mEq/kg/day, respectively. Glucosuria with resulting osmotic diuresis may increase sodium and potassium urinary
49
losses.
Calcium is an important cofactor in hemostasis, enzyme function, muscle contraction, and cell
membrane stability. In the newborn, 98% of calcium
is stored in the bone. The initial calcium require-
ment is 1 mEq/kg/day to maintain calcium
homeostasis and to avoid irritability and tetany
associated with low serum ionized calcium levels.
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461
In utero, the accretion rate is 4 to 5 mEq/kg/
day, which the growing preterm infant should
receive in addition to adequate phosphorus and
vitamin D to avoid osteopenia, rickets, and
bone fractures.
134
Excess calcium intake may cause
central nervous system (CNS) depression or signs
of renal toxicity.
The phosphorus requirement for the growing
preterm infant is 40 to 60 mg/kg/day (31 mg =
1 mmol). Bone contains 80% of the body’s phos-
phorus. Low phosphorus intake causes increased
renal calcium excretion and a depletion of bone
calcium phosphate. A calcium-to-phosphate ratio
of 1.7:1 (mg:mg) or 1.3:1 (mmol:mmol) is recommended in short-term parenteral nutrition
for preterm neonates.24 Low phosphorus intake
or chronic furosemide diuretic therapy also may
lead to hypercalciuria and nephrolithiasis.29 Because
phosphorus is a major constituent of cellular energy
function (adenosine triphosphate, 2,3-diphosphoglycerate, creatinine phosphate), severe depletion
may result in muscle paralysis, respiratory failure,
and interruption of important cellular functions,
such as the hemoglobin-oxygen dissociation curve
and leukocyte activity.
Magnesium is essential for intracellular
enzyme systems. The requirement is 0.25 to 0.5
mEq/kg/day.7 Magnesium deficiency states mimic
hypocalcemia, manifesting as irritability, tremulousness, tetany, and cardiac dysrhythmias. Magnesium
excess may manifest as lethargy, hypotonia, and
delayed stooling.
CARBOHYDRATE
During fetal life, glucose is the primary source
of energy.
122
At birth, the preterm infant has only a
small supply of glycogen, the storage form of glucose
(equivalent to about 200 kcal of energy). Glucose
is particularly important for the CNS, because
other substrates are not available. Initially, a
glucose infusion rate (GIR) of 6 mg/kg/min is
sufficient to meet metabolic needs of the newborn
infant. Requirements are greater for infants who
are stressed (e.g., from sepsis or hypothermia) or
hyperinsulinemic (e.g., infants of diabetic mothers
or infants with Beckwith-Wiedemann syndrome).
With long-term parenteral nutrition, at least
50% of total caloric requirement should be
provided as carbohydrate (GIR 8 to 10 mg/kg/
min), generally as dextrose (calculated as 3.4
kcal/gm of hydrated carbohydrate). Preterm
infants, especially ELBW patients, who receive
early and higher amino acids in their parenteral
nutrition, have been shown to have a decreased
incidence of hyperglycemia requiring insulin
treatment.2 To avoid metabolic consequences
of excessive glucose loads, a GIR of more than
13 mg/kg/min (19 g/kg/day of glucose) should
be avoided.
PROTEIN
The quantity of daily nitrogen required by a
term newborn infant, based on estimates from
breast milk intake, is approximately 325 mg/
kg/day (approximately 2 g/kg/day of protein).8
Requirements for preterm infants are much higher,
as indicated by in utero accretion rates during the
latter half of pregnancy. At 28 weeks’ gestation, the
fetus requires 350 mg/kg/day of nitrogen. This figure declines to 150 mg/kg/day by term gestation.
When the estimated accretion rate is added to
the obligatory postnatal nitrogen excretion, the
requirement for a 28-week gestation preterm
infant may be calculated to be approximately
495 mg/kg/day (3.1 g/kg/day of protein). If
one assumes parenterally administered amino
acids are converted to body proteins at 75%
efficiency, the estimated parenteral amino acid
requirement would be as high as 3.7 g/kg/
47,125
day.
In fetal life, protein is actively transported from
the mother’s circulation across the placenta in
quantities greater than needed for accretion, with
the excess being oxidized by the fetus or placenta
for energy.
121
Clinicians have found that increasing
protein intake postnatally at all energy intake levels
above 40 kcal/kg/day results in increased protein
accretion. Current evidence indicates that protein
intake up to 4 g/kg/day is safe with no clinically
significant increase in azotemia, acidemia, or
hyperaminoacidemia.95 Although more studies are
looking at higher amino acid administration, further
investigations are needed to determine safe upper
limits for maximum protein administration beyond
that level.
27
Studies have shown that administration of
amino acids shortly after birth decreases protein
catabolism, which is extremely important, particularly for VLBW infants.
47,71,121
Early amino
acid administration is also associated with reductions
in hyperkalemia and hyperglycemia.
21,27,92
Based
on the current evidence, providing VLBW
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infants with 3 g/kg/day of protein on the first
day of life is safe.41 Many NICUs have created
a “stock” or “starter TPN (protein-containing)
solution” to achieve the goal of providing 2 to
3 g/kg/day of protein to promote anabolism
immediately after admission. Although current
studies support the early use of parenteral protein
nutrition, further investigation is needed to document the effect of this supplementation on postNICU long-term growth and development.
88
The quality of the infused amino acid mixture is
important for efficacy and safety.1 Although there
is no formulation specifically for preterm infants,
pediatric solutions provide greater quantities
of essential amino acids and result in plasma
amino acid levels similar to those of postprandial breastfed infants. An essential amino acid is
one that cannot be synthesized in adequate quantity
to meet the requirements for normal growth and
development. The differentiation between essential
and nonessential amino acids is not clear in newborn infants, because the ability to synthesize some
amino acids may vary with the clinical situation or
stage of maturity. Lysine and threonine are essential
in their entirety. There is a high requirement for
branched-chain amino acids (e.g., leucine, isoleucine, valine) in the growing newborn. These are
metabolized primarily in skeletal muscle.
87,123
Methionine is an essential sulfur-containing
amino acid that is metabolized to cysteine and taurine. For preterm infants of less than 32 weeks’
gestation, cystathionase activity is insufficient
for cysteine synthesis. Some investigators have
found that cysteine supplementation results in
greater nitrogen retention, and for this reason
it is recommended for short-term supplementation for high-risk preterm infants, although
the effects of prolonged use have not been fully
investigated.
114
Cysteine is not stable in amino acid
solutions, so cysteine hydrochloride supplements
must be added separately to the parenteral nutrition.
Taurine is a nonprotein amino sulfonic acid that is
converted from cysteine by cysteine sulfonic acid
decarboxylase. Taurine concentrations are low in
infants who have received nonsupplemented TPN
infusions. Taurine deficiency may have a detri-
mental effect on the developing nervous system.
Taurine is present in commonly used pediatric
amino acids and may prevent cholestasis in some
newborns by more effectively conjugating bile
salts and creating soluble end products.
116,130
Tyrosine is another amino acid that appears to be
essential in the newborn period. It is present in small
amounts in most amino acid solutions, although
one manufacturer uses a soluble form, N-acetyl-l-
tyrosine, which infants slowly metabolize to tyro-
101
sine.
Tyrosine is a byproduct of phenylalanine
metabolism, so supplementation has an effect on the
phenylalanine requirement. Histidine is considered
to be an essential amino acid for newborns, with the
lowest levels evident in preterm infants. Arginine may
be essential only for the newborn with reduced arginine synthetase activity. This amino acid is thought
to facilitate clearance of nitrogenous waste products
by “priming the urea cycle.” Use of amino acid infusate with insufficient arginine has been associated
with hyperammonemia.60 Glutamine also has been
considered a conditionally essential amino acid, but
no benefit was shown in randomized trials for parenteral glutamine in relation to mortality, incidence of
necrotizing enterocolitis (NEC), or infection rates.
86
Nonessential amino acids make up the largest
percentage of the amino acid pool in the fetal body.
The desired quantities of these amino acids for parenteral solutions are not known. It is thought that
they should be provided in a balanced formulation.
Pediatric solutions differ from adult solutions by
providing glutamic acid and aspartic acid with lower
glycine concentrations.
FAT
1,9
Long-chain fatty acids are essential in the newborn
for brain development and appear to be important for
gene expression and other molecular mechanisms.73
Essential fatty acids (EFAs) include linoleic and
linolenic and, in the newborn, arachidonic acid.7
Biochemical evidence of EFA deficiency may be
seen in less than 1 week in VLBW infants receiving
a deficient diet, and the administration of parenteral
glucose and amino acids may accelerate these abnormalities.
119
EFA deficiency results in an imbalance
in fatty acid production with an overproduction
of nonessential fatty acids. Clinical manifestations
appearing at variable times after biochemical
changes of EFA deficiency include scaly dermatitis, poor hair growth, thrombocytopenia, failure
to thrive, poor wound healing, and increased
susceptibility to bacterial infection. Clinical manifestations of EFA deficiency can be avoided if 3%
to 4% of caloric intake is supplied as linoleic acid
(approximately 0.5 g/kg/day of soybean-based
IV lipid).
62
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463
In addition to preventing EFA deficiency, lipid
emulsion is a concentrated source of nonprotein calories, which promotes nitrogen retention.
Preterm infants appear to have limited capability to
oxidize fatty acids. This limitation may be related
to deficiency of carnitine, which, in the form of
acylcarnitine, promotes transfer of fatty acids into
mitochondria, where oxidative metabolism occurs.
However, a systematic review of randomized studies
found no benefit for carnitine supplementation on
weight gain, lipid utilization, or ketogenesis, so routine supplementation is not recommended.
VITAMINS
28
The biologic role of vitamins, signs and symptoms
of deficiency states, and recommended oral requirements are available in Chapter 17. Although there
is not a multivitamin formulation specifically for
preterm infants, the American Society for Clinical
Nutrition (ASCN) has suggested that preterm
infants receive 40% to 65% of the daily recommended vitamin doses for term infants and
children.
110
These guidelines may result in excessive intakes of some water-soluble vitamins, particularly pyridoxine and riboflavin. Although preterm
infants have limited stores of lipid-soluble vitamins
because of low body fat, potential toxicity from
excess administration is a concern. Vitamin A is a
lipid-soluble vitamin that is important for tissue
growth, protein synthesis, and epithelial differentiation. Vitamin A may be administered more
effectively in lipid emulsion rather than dextrose
amino acid solutions.
7,38
However, vitamin A sup-
plementation has been proven to be effective in
lowering chronic lung disease rates only when
given by intramuscular injections three times
per week.
39,128
Vitamin E is a lipid-soluble biologic anti-
oxidant that is deficient in preterm infants.
However, daily parenteral intake of 2 to 3 mg/kg
has been associated with serum levels generally
in the recommended range of 1 to 2 mg/dL.
Pharmacologic doses have been tried unsuccessfully for prevention of bronchopulmonary dysplasia
and retinopathy of prematurity, and IV high-dose
vitamin E may increase risk for sepsis.25 Therefore,
aiming for tocopherol levels greater than 3.5 mg/
dL is not recommended. Vitamin K production
by intestinal flora is impaired by insufficient
enteral feedings and use of broad-spectrum antibiotics in infants on long-term TPN. Vitamin K
is provided at the recommended dosage through
parenteral pediatric multivitamin solutions.
TRACE MINERALS
7
Although trace minerals are relatively scarce (less
than 0.01% of the weight of the human body by
definition), they play an important role in normal
growth and development.50 Early supplementation
of selenium has shown a reduction in sepsis events.3
Deficiencies of both zinc and copper have been
identified in infants on long-term TPN not supplemented with trace minerals. Postsurgical infants
with ongoing gastrointestinal losses may have negative zinc balance even if given usual zinc replacement in TPN.
109
Manifestations of deficiency and recommendations for intake are provided in Chapter 17.
Parenteral recommendations are lower than enteral,
which are based on physiologic requirements.
Preterm infants receiving breast milk and not
receiving frequent blood transfusions should
receive 2 mg/kg/day of enteral iron supplementation starting by 1 month of age. For term,
breastfed infants not receiving frequent blood
transfusions, enteral iron supplementation at 1
mg/kg/day may be necessary by 4 months of
age.12 Infants receiving erythropoietin therapy
need additional iron supplementation, given
either enterally or parenterally.
84,98
INDICATIONS
Parenteral nutrition, including protein supplementation and carbohydrate at basal levels, should begin on the first day of life for
preterm infants not being fed, as well as for
other newborns who are not likely to tolerate
enteral feedings within a few days. A preterm
infant has limited nutritional stores and quickly
develops negative protein balance without early
supplementation. TPN continues to be a critical
aspect of long-term management for neonatal
surgical patients.
solutions are administered through a peripheral
vein, caloric intake is limited because the fluid
osmolarity should not exceed 900 mOsm/L,
which results in relatively limited concentrations
of carbohydrate (less than 12.5% dextrose) and
amino acids (less than 3%).24 Some recommend
even more conservative limits on osmolarity
102
When parenteral nutrition
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for peripheral lines (500 mOsm/L).53 When
used with lipid emulsions, peripheral parenteral
nutrition (PPN) allows caloric intake of about
70 to 80 kcal/kg/day and protein intake of 2.5
to 3.0 g/kg/day. This level of nutritional intake
prevents catabolism and, in some cases, results in
moderate growth. PPN usually is adequate for term
newborns with transient bowel disease (such as may
be seen after the repair of a small omphalocele) or
for larger preterm infants whose enteral feedings
are delayed for a few days. PPN is commonly used
to supplement nutrition in newborns who are
receiving partial enteral feedings. When caloric
needs can be met by PPN, this route is preferred
to the central route, because the catheter insertion
risks of central catheters are avoided and generally,
the risk for infection is less.
If parenteral nutritional duration is longer
than 1 week, administration of TPN solution
through a central line is recommended. The
placement of a central line for parenteral nutrition
allows a higher carbohydrate load to be used, giving
more calories with less fluid. In preterm infants at
risk for a patent ductus arteriosus and pulmonary
edema, diminishing fluid intake and improving
nutritional status may be important aspects of
management.
Specific indications for TPN by a central
catheter include the following:
• ELBW infants (less than 1000 g birth weight)
and others who do not tolerate a significant
volume of enteral feeding within the first week
of age or who cannot receive adequate caloric
intake by PPN
• Infants who have had gastrointestinal surgery
and will have a significant delay in enteral nutrition, such as those with a gastroschisis, bowel
resection after NEC, or meconium peritonitis
• Infants with chronic gastrointestinal dysfunc-
tion, such as intractable diarrhea
DATA COLLECTION
Monitoring Growth
Weight loss or insufficient weight gain is the
initial effect of inadequate caloric intake. Linear
growth, although less affected, is diminished
after long periods of poor nutrition. Because
of “brain sparing,” head circumference growth
is the least affected. Measurements should be
obtained in a standardized fashion and recorded
weekly.
Fetal weight gain in utero at each week
of gestation is currently used as the standard
to assess adequacy of postnatal growth. In
the midtrimester (24 to 27 weeks’ gestation),
expected weight gain is 1.5% of body weight.
122
Charts are available to monitor postnatal growth
rates based on data from a large preterm population,
although for long-term monitoring, use of growth
curves from normal populations, which are available
from the World Health Organization (WHO), may
be more appropriate.
133
Minimum monitoring of growth should consist of the following:
• Weigh daily, or more frequently in ELBW
infants with rapidly changing extracellular fluid
status. Maintenance of a thermostable environ-
ment with minimal handling of ELBW infants
can be achieved through the use of in-bed scales.
Strict attention to consistency of technique
during the weighing process is essential to obtain
accurate, reliable measurements.
127
Monitoring
weight gain on a weekly basis in grams
per kilogram of weight gained daily (g/kg/
day) may help in reducing postnatal growth
restriction and positively affect long-term
neurodevelopmental outcome. An ideal rate
of weight gain for ELBW infants appears to
be 18 to 21 g/kg/day.
46
• Measure length weekly.
• Measure head circumference weekly.
Biochemical Monitoring
In addition to anthropometric measurements,
biochemical parameters may be monitored to
assess nutritional adequacy. Periodic assessment
of calcium, phosphorus, and alkaline phosphatase
levels is important to detect metabolic disturbances
associated with osteopenia.
tein malnutrition include serum total protein,
albumin, transferrin, retinol-binding protein,
and transthyretin (prealbumin); the latter two
are suggested primarily for preterm infants.
Routine clinical use of these measurements awaits
greater definition of normal variation and independent effects of systemic illness and medications.
Biochemical monitoring of the infant’s physiologic status is necessary to avoid complications
134
Tests for pro-
8,51
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TABLE
16.1
VARIABLE ACUTE STABLE
Electrolytes, BUN Daily 2×/wk
Calcium, phosphorus Weekly Biweekly
Alkaline phosphatase — Biweekly
Serum glucose screen q8hr Daily
Urine glucose
Hemoglobin/hematocrit Daily Weekly
METABOLIC MONITORING FOR INFANTS
RECEIVING PARENTERAL NUTRITION
FREQUENCY
q8hr Daily
Liver function:
Bilirubin 2×/wk PRN
Transaminase Weekly Biweekly
Triglyceride* — Weekly
*When on lipid emulsion.
BUN, Blood urea nitrogen; PRN, as needed.
of TPN. Usefulness of the laboratory data should
be balanced with the economic costs and risks from
iatrogenic blood losses for the infant (Table 16.1).
When serum electrolyte levels are abnormal,
urinary electrolyte levels may be useful to clarify
sodium and potassium requirements (e.g., if body
sodium is depleted, low urine concentration would
be expected).
TREATMENT
Vascular Access
UMBILICAL ARTERY CATHETERS AND
UMBILICAL VEIN CATHETERS
Umbilical artery catheters (UACs) and umbilical
vein catheters (UVCs) are commonly placed in
sick newborns to provide vascular access for IV
fluids, blood samplings, and blood pressure monitoring. Because of the risks for thromboembolic
and infection complications, these lines generally
are removed as soon as possible when no longer
needed. Optimally UACs should not be left in
place longer than 5 days, although UVCs can be
used up to 14 days if managed aseptically.
15,37,51
PERIPHERAL AND MIDLINE CATHETERS
If continued venous access is necessary after
this time, a peripheral, midline, or peripherally
inserted central catheter (PICC) can be placed.
The type of line used is determined by the anticipated length of time needed and the osmolarity of
the substances to be infused.
53
Peripheral IV lines are indicated for short-term
IV access. A midline catheter, which is threaded to the
proximal portion of an extremity or neck, can provide
longer IV access than a peripheral IV line when prolonged peripheral strength TPN is indicated. Midline
catheters appear to be associated with lower rates of
phlebitis than short peripheral catheters and with
lower rates of infection and cost than central lines.
PERIPHERALLY INSERTED CENTRAL
CATHETERS
77
A PICC line can provide maximal nutritional
intake when long-term parenteral access is necessary.4 Percutaneous placement of a 1.9-Fr to 3.0-
Fr Silastic (silicone) or polyurethane catheter can be
performed routinely in even the smallest of neonatal
patients by trained nurses and physicians.
137
The catheter usually is placed in the antecubital or axillary veins
in the arms, but leg, scalp, or external jugular veins may
be used to achieve central access. Veins that may be
needed for percutaneous central line placement should
not be sites for routine venipuncture (see Chapter 7).
Percutaneous line placement involves stabilization of the vein, maximum barrier precautions
(sterile gloves, gown, large drape, masks), and
antiseptic preparation of the skin with 2% chlorhexidine or povidone-iodine and alcohol prod-
15,72,137
uct.
Infrared vein detectors or ultrasound
may be used as adjuncts to identify appropriate veins
for PICC cannulation.
26,93
Fully equipped prepackaged kits are available for this procedure from
a number of manufacturers. Most kits include an
insertion needle that is used to puncture and tunnel
through the subcutaneous tissue before entering the
vein. Once the needle is within the vein, the catheter, which has been flushed with heparinized saline
solution, is passed through the needle into the vein
and advanced to a premeasured distance, which is
the estimated location of the superior vena cava.54
The catheter tip position should be documented
radiographically. The addition of heparin to IV
fluids is commonly used by practitioners to prevent
occlusion of vascular catheters. However, there is no
indisputable evidence for this practice.
106,107
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BROVIAC CATHETER
Large-bore Silastic catheters (Broviac) are placed
surgically in infants in whom the percutaneous
method is not successful and long-term access
is anticipated. Generally, the catheters are placed in
the internal or external jugular veins or common
facial vein by cutdown and threaded to a central
venous site but can also be placed via the femoral
vein. The distal end is tunneled subcutaneously and
exited through the anterior chest wall or thigh if
placed in the leg.89 The catheter must be secured
and dressed under sterile conditions.
OTHER VASCULAR ACCESS OPTIONS
Other sites that may be used for TPN infusion on
a short-term basis include subclavian, jugular, and
femoral veins. Some centers use a UVC for shortterm parenteral nutrition when another site is not
feasible.
Composition of Infusate
CARBOHYDRATE
The prime source of calories for the neonate
usually is dextrose. Peripherally, dextrose fluids
up to 12.5% solution can be used. When central
access is obtained, more concentrated dextrose
(up to 30%) can be utilized. The glucose load is
increased if either the infusion rate or glucose concentration of the infusate is increased. Too rapid an
increase in glucose load may exceed an infant’s
carbohydrate tolerance and result in hyperglycemia. A rapid decrease in the infusion rate or the
glucose concentration of the infusate may result
in hypoglycemia.
When calculating caloric intake, use the following:
or
lated as follows:
100 mL kg of D W= 34 kcal kg
or
100 mL kg of D W=102 kcal kg
The glucose infusion rate (GIR) can be calcu-
g glucose day 1000
1440 min day
1g dextrose = 3.4 kcal
10
30
weight kg
Endogenous glucose production is approximately 4 mg/kg/min. Parenteral nutrition infusions should start with a GIR between 5 and 6
mg/kg/min for VLBW and ELBW infants.
Daily increases in dextrose concentration or fluid
volume to increase carbohydrate administration by
2 mg/kg/min usually are tolerated. ELBW infants
may be carbohydrate intolerant, and initial GIR
should be lower (4 or 5 mg/kg/min) for these
infants. An insulin infusion may be considered for
ELBW infants experiencing persistent hyperglycemia with physiologic glucose infusion rates.
Glucose infusion rates should not exceed 13
mg/kg/min unless severe hypoglycemia is ensuing. Blood glucose determinations and screening for glucosuria should be performed several
times each day when glucose delivery is initiated or altered.
LIPIDS
Traditionally lipid emulsion products have been
derived from soybean oil. Newer lipid emulsion products contain a mix of soybean oil, fish
oil, medium chain triglycerides, and olive oil.
Soybean oil lipid emulsion at a rate of 0.5 to
1 g/kg/day is sufficient to prevent EFA deficiency, but additional lipids should be provided
to supplement nonprotein caloric intake and
support growth.
sions are used, a minimum of 2 gm/kg/day may
be necessary to prevent EFA deficiency. Lipids
should never make up more than 50% of total
caloric intake. Fat emulsions should be given
cautiously, beginning with 0.5 to 1 g/kg/day
and advanced 0.5 g/kg every 1 to 2 days as
tolerated to 3 g/kg/day maximum. Fat emulsions
are available as either 10% or 20%, but the 20%
concentration is universally used for VLBW infants,
because its lower phospholipid concentration results
in lower plasma levels of triglyceride and cholesterol
and less fluid administration (Table 16.2).
Emulsified fat particles are similar in size and
metabolic rate to naturally occurring chylomicrons.
Most are cleared through passage in the adipose and
muscle tissue. The capillary endothelial lipoprotein
lipase hydrolyzes triglycerides and phospholipids,
generating free fatty acids (FFAs), glycerol, and
other glycerides. Most of the FFAs diffuse into
the adipose tissue for reesterification and storage.
A small portion circulates to be used by other
tissues for fuel or for conversion by the liver into
122
When mixed oil lipid emul-
126
138
96
CHAPTER 16 Total Parenteral Nutrition
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TABLE
16.2
COMPOSITION INTRALIPID (BAXTER) 20% LIPOSYN II (HOSPIRA) 20% SMOF (FRESENIUS KABI) 20%
COMPOSITION OF FAT EMULSIONS
Fatty Acid Distribution (%)
Linoleic acid 53 54.5 19.5
Oleic acid 24.5 22.4 29
Palmitic acid 10.5 10.5 9.5
Linolenic acid 7.5 8.3 2.5
Stearic acid
3.4
4.2 2.8
Components (grams/100 mL)
Soybean oil
Egg phospholipids 1.2 1.2 1.2
Glycerin 2.25 2.5 2.5
Caloric contents (kcal/dl) 200 200 200
Osmolarity (mOsm/L) 260 292 270
20 20 6
467
very-low-density lipoprotein. Extremely preterm
and SGA infants with decreased adipose tissue
have prolonged clearance of fat emulsions. In
general, because complications of lipids are
related to delay in clearance, lipids should be
infused over a 24-hour period to provide the
lowest hourly rate.94 Infusion rates faster than 0.2
g/kg/hr for lipid infusions have been associated
with hyperlipidemia.
126
The rate-limiting step for
lipid clearance is the metabolism by lipoprotein
lipase. The use of heparin stimulates the release of
this enzyme and may enhance clearance of IV lipids.
Carbohydrate also must be administered with fat to
facilitate fatty acid oxidation and to promote FFA
clearance.
AMINO ACID SOLUTION
Multiple amino acid solutions are available for
neonatal and infant parenteral use. Each solution is
sterile, is hypertonic, and contains crystalline amino
acids. Each solution provides a mixture of essential
and nonessential amino acids and may or may not
contain taurine and a soluble form of tyrosine.
The amino acid formulation provides a well-tolerated nitrogen source for nutritional support. The
essential amino acids typically found in formulations are leucine, isoleucine, lysine, valine, histidine,
phenylalanine, threonine, methionine, tryptophan,
and cystine. The nonessential amino acids that are
typically included are alanine, arginine, proline,
glutamic acid, serine, glycine, and aspartic acid. The
composition of amino acid varies by manufacturer.
A minimum quantity of energy substrates
must be provided for effective utilization of
parenteral protein. For ELBW infants, approximately 40 kcal/kg/day of carbohydrates or fat
and 1.5 g/kg/day of protein are necessary for
resting metabolic needs to prevent catabolism.
However, urinary protein losses are greatest for
preterm infants, so additional supplementation is
needed to prevent protein deficits. For each gram
of protein provided above the basal amount,
approximately 10 kcal of nonprotein energy is
needed.
41,47,122
Contraindications to amino acid administration
include untreated anuria, hypersensitivity to the
solution, or inborn errors of metabolism, including those involving branched-chain amino acid
metabolism, such as maple syrup urine disease and
isovaleric acidemia.
ELECTROLYTES
Sodium and potassium may be supplied with
chloride, acetate, or phosphate anions. The
daily chloride requirement is approximately
3 mEq/kg/day and should be balanced with
UNIT THREE Metabolic and Nutritional Care of the Neonate468
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acetate to avoid alkalosis or acidosis (acetate is
converted to bicarbonate). Amino acid prepara-
tions also supply anions that must be recognized to
calculate a balanced anion solution. For example,
TrophAmine and Premasol supplies approximately
1 mEq of acetate per gram of protein. On the other
hand, cysteine addition to the TPN solution reduces
the pH, necessitating buffering with acetate.
MINERALS
Phosphorus may be provided as sodium or
potassium phosphate. Calcium may be provided
as 10% calcium gluconate (9.7 mg of elemental
calcium/100 mg of salt). Both calcium gluconate
and potassium phosphate have relatively high levels of aluminum and should be used judiciously
for chronic TPN in infants with renal dysfunction
(see discussion of aluminum toxicity under Trace
Elements later in this chapter). When preparing a
solution with both calcium and phosphate, care must
be taken to avoid calcium phosphate precipitation,
which may limit the intake of these important minerals. Magnesium is supplied as magnesium sulfate.
If one is using a potassium phosphate solution at pH
7.4, 4.4 mEq of potassium supplies 93 mg of elemental
phosphorus (3 mM). When a solution of sodium phosphate is used at pH 7.4, 4.0 mEq of sodium is given
with each 93 mg of elemental phosphorus.
CALCIUM
• Because of increased risk for precipitation,
calcium chloride generally should not be used
(but may be considered for an infant at risk for
aluminum toxicity).
• An elevation in ambient temperature, increased
storage time, rise in pH, and decrease in protein or glucose concentration may increase
the likelihood of precipitation. The addition
of cysteine, which lowers solution pH, may
enhance calcium and phosphate solubility.
9
• When one is preparing the solution, calcium
and phosphate salts should be added separately, but not in sequence, during the last
stages of solution mixing. The solubility of
the added calcium should be calculated from
the volume at the time the calcium is added,
not the final volume.
• The use of a physiologic ratio of calcium
to phosphorus (1.8:1) in the TPN solution allows increased concentration of these
minerals.
97,114
VITAMINS
A preparation approximating the American Medical
Association’s recommended formulation of IV vitamins is available (MVI-Ped). The daily recom-
mended dose is 1.5 mL/day for infants weighing
less than 1 kg, 3.25 mL/day for those infants
who weigh 1 to 3 kg, and 5 mL/day for infants
weighing greater than 3 kg.
TRACE ELEMENTS
85
Zinc is supplied as zinc sulfate. Serum zinc levels
usually approximate the maternal levels at birth
and decline over the first week of life. Zinc sup-
plementation should be considered from the
time parenteral nutrition is initiated.
139
It may be
important to initiate zinc intake earlier in neonates
with intestinal loss, such as after gastrointestinal
surgery.
Copper is supplied as cupric sulfate. Approximately
two thirds of stored copper is accumulated during the
last trimester. Therefore, a preterm infant may need
early supplementation, but a term infant has adequate
hepatic stores for at least several weeks. Because copper is excreted through the biliary system, this mineral should be decreased by 50% or removed from
parenteral fluids for infants with cholestasis.
85
Selenium, manganese, and chromium salts are commonly provided in long-term parenteral nutrition.
Supplementing very preterm infants with selenium is associated with reduction in sepsis.3
Manganese supplementation should not be provided to infants with cholestasis. The chromium
dose may be reduced or discontinued in an infant
with impaired renal function. Some studies have
suggested that manganese and chromium should
not be provided in parenteral nutrition due to the
degree of cross contamination of these two trace
elements in other parenteral nutrition products.
57,139
Traces of aluminum are incorporated into parenteral solutions during processing.70 Although
aluminum is not known to have a physiologic role
in the body, high aluminum levels have been associated with bone disease, encephalopathy, anemia, and
hepatic cholestasis and may contribute to neurodevelopmental damage in preterm infants on chronic
parenteral nutrition.18 Infants with disturbance of
renal clearance are at greatest risk for aluminum loading. Although the U.S. Food and Drug
Administration (FDA) requires manufacturers to
report the aluminum content of parenteral products,
a recent Canadian study found that TPN remains
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