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Review article

Parenteral nutrition in preterm newborns: proposal for a


practical protocol
Parenteral nutrition in preterm infants: proposal of a practical guideline

Fabiola Isabel S. de Souza1 , Marcia Teske2, Roseli Oselka S. Sarni3

Summary ABSTRACT

Objective: To review the literature and concepts related Objective: Review the literature regarding parenteral
to parenteral nutritional therapy for preterm newborns and nutrition of preterm infants in order to propose a practical
propose a practical flowchart for indication, progression of guideline for indication, increase of parameters and
parameters and monitoring for use in neonatal units. monitoring of this nutritional therapy in neonatal units.
Data sources: Articles published in English and Data source: Studies in English and Portuguese from
Portuguese in the Medline, Embase, Lilacs and SciELO the last ten years were retrieved from Medline, Embase,
databases in the last ten years, in addition to classic Lilacs and SciELO using the following key-words: preterm
references and international consensus. The keywords used infants, parenteral nutrition, nutrition therapy and lipid
as a search source were preterm newborn, parenteral emulsions. Also classical studies and consensus on the theme
nutrition, nutritional therapy and lipid emulsions. were manually searched.
Data synthesis: Parenteral nutrition is an essential Data synthesis: Parenteral nutrition is an essential
procedure in the in-hospital treatment of preterm newborns. treatment strategy for preterm infants. Besides progress in
In addition to advances in knowledge and progress in knowledge and legislation, several factors contribute to
legislation, several factors have contributed to reducing the reduce neonatal morbidity and mortality of newborns using
morbidity and mortality of these newborns and increasing parenteral nutrition and to increase the security in its
the safety in the use of parenteral nutrition, such as the prescription such as catheters' quality, training of the
quality of the catheters used, adequate training and multiprofessional team and development of new specific
qualification of the professionals involved, the existence of parenteral nutrition formulations.
teams multidisciplinary teams and the development of new inputs. Conclusions: The practical parenteral nutrition guide
Conclusions: This practical protocol on parenteral line proposed here follows international guidelines and was
nutrition for premature newborns was developed based on based on critical analysis of the studies published in the last
international recommendations from scientific societies and 10 years.
on the critical analysis of scientific studies.

Keywords: parenteral nutrition; newborn; premature; Keywords: parenteral nutrition; infant newborn; infant
nutritional recommendations. early; nutrition policy.

1 Master in Sciences from the Escola Paulista de Medicina of the Federal Mailing address:
University of São Paulo (Unifesp-EPM), collaborating physician in the Roseli Oselka Saccardo Sarni
Nutrology Service of the Department of Pediatrics at the Faculdade de Rua René Zamlutti, 94 – apt. 52 – Vila Mariana
Medicina do ABC (FMABC) and clinical coordinator of the Multidisciplinary CEP 04116 260 – São Paulo/SP
Team of Nutritional Therapy of the Mário Covas State Hospital and São
Bernardo do Campo University Hospital of the ABC Foundation. Santo E-mail: rssarni@unifesp.br / rssarni@uol.com.br
Andre, SP, Brazil
2 Collaborating physician at the Nutrology Service of the Department of Received on: 1/7/2008
Pediatrics at FMABC. Santo Andre, SP, Brazil Approved on: 4/10/2008
3 PhD in Medicine and assistant physician at the Department of Pediatrics
at Unifesp-EPM, assistant professor at the Department of Pediatrics and
coordinator of the Nutrology Service at the Department of Pediatrics at
FMABC. Santo Andre, SP, Brazil

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Fabiola Isabel S. de Souza et al

Introduction parenteral nutrition, regulating the indication, prescription,


pharmaceutical preparation (pharmaceutical evaluation,
Parenteral nutrition (PN) is an essential therapeutic procedure manipulation, quality control, conservation and transport),
in the in-hospital treatment of preterm newborns (PTNB)(1). The administration, clinical and laboratory control.
nutritional therapy of the PTNB represents an enormous In 2005, the Ministry of Health published a series of
challenge, since the lower the weight and gestational age of the ordinances that instituted, within the scope of the Unified Health
newborn (NB), the greater their nutritional needs to achieve System (SUS), the High Complexity in Nutritional Therapy
adequate growth and development(2,3). PTNBs have reduced (Assistance Units and Reference Centers)(12). These ordinances
reserves and greater immaturity of the gastrointestinal tract and include several nutritional therapy procedures for adults and
other organs, systems and devices, which makes it impossible children, including neonatal parenteral nutrition, which
to use the enteral route exclusively, especially in the first weeks represented a great advance in legislation in the recognition of
of life(4-6) . Thus, the advances in procedures related to PN, this therapeutic procedure.
such as the type of catheter used(7,8), the training and
qualification of the professionals involved(9) and the development Recommendation

of new inputs, allied(10) to the progress in legislation(11 ,12),


have greatly contributed to increase safety in the use of this The smaller the PTNB, the earlier the indication for PN should
form of nutritional therapy. be, since the energy reserves of these children are quite
limited(1,16). It is estimated that a 1,000g NB would have
PN is a procedure that is part of the neonatal intensive care enough energy reserves to survive, without nutritional therapy,
routine, and it is important to develop practical protocols that for just four days(17,18).
take into account the advances available in the literature and Children weighing less than 1000g should receive PN in the
proposals for international guidelines. In this context, the first hours of life and, initially, a solution containing amino acids,
objective of this article is, with an adequate review of the glucose and electrolytes is suggested(18,19). PTNB weighing
literature, to present the concepts related to parenteral nutritional 1000 to 1500g also deserve special attention, and the start of
therapy for PTNB and to propose a practical protocol for PN should not be postponed for more than 48 hours. Even in
indication, progression of parameters and monitoring, which can newborns weighing more than 1500g, they should not remain
be used in the training of professionals, such as pediatric for more than 72 hours without effective nutritional therapy(1) (Figure 1).
residents and multidisciplinary teams that work with neonatal Enteral nutrition should preferably be administered with
nutritional therapy. human milk and as early as possible (in the first 48 hours of life),
To carry out the literature review, the guidelines proposed even in small volumes (Figure 1), as it represents a potent
by several international scientific societies such as the American stimulus factor for the maturation of the gastrointestinal tract and
Academy of Pediatrics (APA)(13), American Society for protection against infections, in addition to other advantages(20-22).
Parenteral and Enteral Nutrition (Aspen)(14) and European
Society for Clinical Nutrition were used. and Metabolism (Espen) In Brazil, as well as in European countries, 3:1 solutions are
and European Society for Pediatric Gastroenterology, Hepatology used (dextrose, lipids and proteins in the same container). In
and Nutrition (ESPGHAN)(15) and for articles in English and some countries, such as the United States, lipids are supplied
Portuguese related to parenteral nutritional therapy for PTNB, separately from other nutrients, in order to reduce the risk of
published in Medline, Embase, Lilacs and SciELO databases, in incompatibilities and precipitation.
last ten years. The keywords used as a search source were: Next, the steps and different components of PN will be
preterm newborn, parenteral nutrition, nutritional therapy, lipid discussed individually in order to formulate a practical protocol
emulsions. for the use of PN in PTNB. Reading combined with observation
of Figure 1 is suggested.
Legislation
venous access
Brazil has had specific legislation since 1998. This is
Ordinance No. 272/MS/SNVS, of April 8, 1998(11), which PN solutions with osmolarity above 600mOsm/L
establishes the minimum requirements required for the therapy of (Chart 1), used in peripheral accesses, can lead to

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Parenteral nutrition in preterm newborns: proposal for a practical protocol

preterm newborn

ÿ1000g 1000g¬1500g >1500g

Minimal enteral nutrition in Minimal enteral nutrition in Consider the exclusive use
24 hours or when stable 24 hours or when stable of enteral nutrition

Start NPP <24 hours of life 24¬48 hours of life 24¬72 hours of life

80mL/kg/day 70mL/kg/day 70mL/kg/day

initial volume
Progress daily: according to water needs, weight, clinical conditions, others
infused volumes and fluid balance. Generally, in 7 days it reachesÿ150mL/kg/day

Glucose (VIG) 4mg/kg/min 4mg/kg/min 4mg/kg/min


From the 1st day
*50% glucose solution

Progress VIG daily (4-12mg/kg/min) according to right-handedness (ideal: 70-120mg/dL)

amino acids 1.5g/kg/day 1.5g/kg/day 1.5g/kg/day


From the 1st day
*Amino acids with
10% taurine
Progress: 1g/kg/day (max: 3.5g/kg/day) Progress: 1g/kg/day (max:
3.0g/kg/day)

lipids
>24 hours of life 1g/kg/day 1g/kg/day 1g/kg/day
*20% emulsion with
TCL or TCL/TCM

Progress from 0.5-1g/kg/day to 3g/kg/day (maximum) and monitor triglyceride levels if: <150mg/dL
(progress), 200-250mg/dL (not progress) and >250mg/dL ( stop the infusion
of lipids for 24-48 hours and restart with 1g/kg/day if normalization)

Vitamins
®
>24 hours of life Pediatric Polivit A® : 4ml/kg (max: 10mL) + Pediatric Polivit B pediatric: 2ml/kg (max: 5mL)
MVI 12®: 2ml/kg (max: 5mL)
Frutovitan®: 2mL/kg
*Vitamin K (plus): 1 or 3mg (IM or IV) 1x/week or 1.5 or 0.5mg 2x/week

trace elements
>24 hours of life Oliped 4®: 1mL/kg Ped-Element® : 0.2mL/kg
Ad-Element® : 0.05mL/kg Tracitrans Plus ®: 0.3mL/kg
Politrace 4®: 0.1mL/kg
*Zinc: add 200-400ÿg/day to meet needs

Electrolytes
Electrolyte Onset Dose
Sodium ÿ72 hours 1-3mEq/kg
Potassium ÿ72 hours 1-2mEq/kg
Calcium <24 hours 1-2mEq/kg
Magnesium <24 hours 0.3-0.5mEq/kg
Phosphor >24 hours 1-2mmol/kg

Figure 1 – Algorithm for indication and follow-up of parenteral nutritional therapy in preterm newborns.

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Fabiola Isabel S. de Souza et al

to a series of complications (phlebitis, extravasation, etc.). Cysteine is also a conditionally essential amino acid in the
As, in most cases, the PN of the PTNB exceeds this value neonatal period, especially for those younger than 32
and its use occurs for a prolonged period (>14 days), it is weeks(30). This amino acid is the major substrate for the
preferable, initially, to have a central access. synthesis of the tripeptide glutathione (an integral part of the
The use of peripherally inserted central periphe rally enzyme glutathione peroxidase, with an antioxidant function)
inserted central catheters (PICCs) represented a true revolution and is not part of amino acid solutions due to its low stability.
in the choice of access route for PN due to its safety and ease However, cysteine can be added to the PN solution (30 to
of insertion. Currently, such catheters are considered the first 55mg/
option for PN infusion in neonates(7). PN infusion through kg/day or 200 to 350µmol/kg or 40mg/g protein in the solution)
umbilical catheters is related to a greater number of mechanical to ensure the normalization of plasmatic levels, especially if
and infectious complications, and should be used only in the child is not receiving enteral nutrition with human
exceptional situations and for a short period (artery <5 days milk(13,29).
and vein <14 days)(23) . Thus, the catheter in the umbilical Regarding glutamine, there is no current evidence of
vein can be used in the first hours of life, while the insertion of benefits from its use in PTNB(13,14,30,31). If administered,
the PICC is provided. 20% of the infused amount of amino acids should not be
exceeded (0.4 to 0.5g/kg/day)(14,29).
amino acids Carnitine, used in the transport of long-chain fatty acids
across the mitochondrial membrane, is also not present in
Studies show that the initial infusion of 1.5g/kg/day of currently available amino acid solutions.
amino acids, followed by increases from 0.5 to 1g/kg/day up Its supplementation should be considered in children receiving
to 3 to 3.5g/kg/day, is necessary to promote positive nitrogen PN exclusively for a period longer than four weeks.
balance in PTNB (23.24). The infusion of higher rates of amino The suggested parenteral dose is 10mg/kg/day(29).
acids (3 to 3.5g/kg/day) in the first hours of life, even in
newborns weighing <1000g, does not induce toxicity and lipids
promotes a better immediate nitrogen balance when
compared to lower rates ( 1 to 1.5g/kg/day)(13,25,26), The infusion of lipids in the PN of the PTNB is important to
however, there are still no studies evaluating adverse events provide energy and essential fatty acids, with the
from this practice in the long term(27). In this protocol, it is recommendation of linoleic acid for the PTNB of 0.25g/
recommended to start with 1.5g/kg/day and promote rapid day, and can be started early(32,33) and with improved
increments (1g/kg/day and a maximum of 4g/kg/day), which tolerance if the infusion occurs continuously, within 24
allows reaching the proposed supply in 72 hours (Figure 1) . hours(34).
Protein supply in the early stages of PN in PTNB is much In practice, lipid infusion can be started from the second
higher than that recommended for older children in different day of life (>24 hours of life), with an initial infusion rate of 0.5
clinical situations. Therefore, the calculation of the ratio grams to 1g/kg/day (maximum 4g/kg/day) and increments of 0.5 to 1
of nitrogen/non-protein calories should not be taken into g/kg/day. However, special attention should be paid to the
account in this phase of PN planning(19,24). The energy monitoring of serum triglycerides, requiring a new dosage at
metabolism of PTNB is different, especially in those <1000g, each increase of 1g/kg(34) (Chart 2). It is suggested to
with glucose production from gluconeogenesis and use of interrupt the progression of lipid infusion when triglyceride
protein as an energy substrate, even in conditions of clinical stability(24,28).
levels are above 200mg/dL and suspend it if above 250mg/
Some amino acids are considered conditionally essential dL, returning after 24 to 48 hours with 1g/kg, depending on
for PTNBs and, therefore, the choice of pediatric solutions is the clinical condition. Another important fact to be observed is
essential to ensure safety and meet specific nutritional needs. that the lipid infusion rate should not exceed 0.13 to 0.17g/kg/
Such solutions, specially adapted, contain taurine, tyrosine, h(34) (Figure 1).
histidine, aspartic acid and glutamic acid in amounts similar to Several factors, in addition to the lipid infusion rate, influence
those found in human milk, but contain lower concentrations triglyceridemia, including extreme prematurity, sepsis,
of methionine, glycine and phenylalanine(13,29) (Table 1) . cholestasis, catabolism, renal failure and pancreatitis, among
others.

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Parenteral nutrition in preterm newborns: proposal for a practical protocol

Table 1 - Composition of crystalline amino acid solutions for parenteral use


Composition Travasol® 10% Aminosteril® 10% Primene® 10% Aminoped® 10%
(g/100mL) baxter Fresenius Kabi baxter Fresenius Kabi
leucine 0.73 0.74 1.00 1.07
phenylalanine 0.56 0.51 0.42 0.46
lysine 0.58 0.66 1.10 0.71
Methionine 0.40 0.43 0.24 0.46
Isoleucine 0.60 0.50 0.67 0.64
Valine 0.58 0.62 0.76 0.71
histidine 0.48 0.30 0.38 0.41
threonine 0.42 0.44 0.37 0.52
tryptophan 0.18 0.20 0.20 0.18
Alanine 2.07 1.50 0.80 0.72
Glycine 1.03 1.40 0.40 --

Arginine 1.15 1.12 0.84 0.64


proline 0.68 1.50 0.30 1.61
serine 0.50 -- 0.40 0.90
tyrosine 0.04 -- 0.05 0.55
cysteine -- -- 0.19 0.04
Aspartic acid -- -- 0.60 --

Glutamic acid -- -- 1.00 --

ornithine -- -- 0.25 --

Taurine -- -- 0.06 --

Osmolarity-mOsm/L 998 939 790 848


Travasol® and Aminosteril®=are standard solutions; Primene® and Aminoped®= are pediatric solutions, the latter of which comes with taurine
(conditionally essential amino acid for PTNB).

Recent studies have shown that the use of heparin in PN In practice, prefer 20% lipid emulsions, since their lower ratio
does not improve lipid clearance and therefore, currently, its between phospholipids and triglycerides promotes better
routine use in solutions for this purpose is not recommended. In whitening and, consequently, lower risk of hypertriglyceridemia,
some situations, the use of heparin can be beneficial by compared to 10% emulsions(34) . It is possible to use emulsions
increasing the duration of the catheters and also by reducing the containing only long chain triglycerides or half and half with
risk of obstruction(35). The suggested dose is 0.5U/mL of the PN medium and long chain triglycerides. The latter, despite having a
solution, bearing in mind that its addition increases the risk of lower content of essential fatty acids, are theoretically metabolized
instability in the 3:1 PN solution. more quickly because the medium-chain triglyceride is practically
Huge advances have taken place in recent years regarding independent of carnitine to enter the mitochondria and subsequent
the composition of lipid emulsions for PN. Currently, there are oxidation(33,34) .
emulsions with long-chain and medium-chain fatty acids on the
market, only long-chain (soybean oil), emulsions with olive oil, There is no obvious association between hyperbilirubinemia,
fish oil and structured lipids (soybean, olive, fish and medium- thrombocytopenia and cholestasis with the infusion of lipids,
chain triglycerides ). However, there are few studies using these however, if all other causes related to these diseases, which are
new lipid emulsions in the PN of PTNB, which, unfortunately, quite common in PTNBs, are ruled out, the triglyceride levels
limits their current use(33)(Table 2). should be more rigorously monitored. As a last resort, in
thrombocytopenia and cholestasis, one can temporarily reduce or suspend (2

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Table 2 - Composition of traditional lipid emulsions for parenteral use


Composition (g/100mL) Lipovenos® Lipovenos® Lipovenos® Lipovenos® Lipovenos®
TCL 10% TCL 20% MCT 10% MCT 20% PLR
Fresenius Fresenius Fresenius Fresenius Fresenius
kabi kabi kabi kabi kabi
Soy oil 10 20 5 10 10
TCM --- --- 5 10 ---
Glycerol 2.5 2.5 2.5 2.5 2.5
egg phospholipid 1.2 1.2 0.6 1.2 ---
egg lecithin --- --- --- --- 0.6
alpha tocopherol --- --- --- --- ---

Osmolarity (mOsm/L) 273 273 272 273 272

Composition (g/100mL) Lipofundin® Lipofundin® Ivelip® TCL10% Ivelip®


TCM 10% TCM 20% TCL20%

B.Braun B.Braun baxter baxter

Soy oil 5 10 10 20
TCM 5 10 --- ---
Glycerol 2.5 2.5 2.5 2.5
egg phospholipid --- --- --- ---
egg lecithin 0.8 1.2 1.2 1.2
alpha tocopherol 10 20 --- ---

Osmolarity (mOsm/L) 345 380 265 270

48s) the infusion and observe if there is improvement in the greater number of complications, especially of an infectious
condition(14,34). Regarding cholestasis, fasting is one of the most nature, and increased risk of mortality(39).
important risk factors for its development. Thus, the administration
of enteral nutrition, even with small volumes, is fundamental(36). Vitamins

Glucose The vitamins are added in combination, in ampoules, in the


PN solution. It is important to know the recommendation and
D-glucose (dextrose) is the carbohydrate used in PN solutions composition of the multivitamins available to offer adequate
and provides 3.4kcal/g. Solutions with 5, 10, 25 and 50% amounts(40), bearing in mind that there are no specific products
concentration are available. Glucose plays a fundamental role in for PTNBs. An approximate calculation, taking into account the
the metabolism of the central nervous system. To calculate the recommendations for this age group and the solutions most
amount to be added to the PN, the infusion rate or glucose commonly used in our country, is available in the algorithm
infusion rate (TIG or VIG) is used, expressed in mg/kg/min. proposed at the end of this chapter (Table 3, Figure 1).
Generally, it starts with a VIG of 4mg/kg/min, progressing to 12 Special emphasis can be given to vitamin A, as the solutions
and 14mg/kg/min, depending on the neonate's needs and clinical available on the market often do not meet the needs of the
condition (Charts 1 and 2). In this progression, it is essential to neonate, without leading to an excess supply of other vitamins.
monitor blood glucose, ideally values between 70 and 120mg/ A recent meta-analysis
dL(13,28,37). Episodes of hypoglycemia are associated with concluded that vitamin A supplementation (intramuscular,
worse future neuropsychomotor development(38) and episodes intravenous or oral) in PTNB weighing <1500g is associated with
of hyperglycemia are related to the reduced mortality and the need for oxygen therapy at one month
of life. For neonates <1000g,

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Parenteral nutrition in preterm newborns: proposal for a practical protocol

Chart 1 – Parameters for monitoring parenteral nutritional therapy in preterm newborns.


Expected Meaning

a) Calcium concentration <10mEq/L This is the [Ca] in mEq/L in the PN solution.


Ca (mEq) -------- volume in PN If >10mEq/L, it may destabilize the solution.

x (mEq) -------- 1000 mL

b) Sum of cations [Mg+Ca]<16 mEq/L It is the sum of the mEq of the cations (bi and
Ca (mEq)+Mg (mEq) ---- volume in PN trivalent) in the solution. If >16mEq/L, it may
destabilize the solution.
x (mEq) ------------------------- 1000 mL

c) Ca/P ratio (mg) 1.3:1 to 2:1 (mg) This is the ratio of the amount of Ca and P to
Ca (mg) in PN -------------1.3¬2 1.1:1 to 1.3:1 (molar) maintain solution stability when inorganic
phosphorus salts are used. A level close to 2:1
P (mg) in PN --------------- 1
(mg) is best for bone incorporation.

d) Osmolarity (mOsm/L) <600mOsm/L It is the best parameter to define the route of PN


Osm=(AX8)+(GX7)+(Nax2)+(Px0.2)-50 (peripheral) use: if <600, it is safe to use the peripheral route;
>600mOsm/L 600-900, you can use the peripheral route with
G=Glucose (g/L); A=amino acids (g/L);
care; and >900, it is mandatory to use the central
Na=sodium (mEq/L; P=phosphorus (mg/L) (central) route .

e) Non-protein Kcal/gram N (C/N) 100/1-150/1 Characterization of nutrient distribution.


N/C=g N/kcal Lipid+kcal (glucose) (metabolic stress) Hypercatabolic NBs or under metabolic
150/1-250/1 stress benefit from the 100/1-150/1 ratio. RN in
1g protein=0.16g nitrogen (4kcal)
anabolism need ratios of 150/1-250/1. This
(for anabolism)
1g lipid=9kcal relationship is not so important in PTNB.
1g glucose=3.4kcal

f) Glucose concentration >12.5% It cannot be the only parameter to define whether


[Glucose]=g (glucose)/total volume the solution will be used in the peripheral or central
route.

g) Caloric offer PN calories/weight Calculation to verify that the necessary


OC=kcal (lipids)+kcal (proteins)+kcal (glucose)/ calories are being offered for synthesis/
weight (kg) maintenance of organs, tissues and systems.

such findings were also observed after 36 weeks of corrected suggests that the photoprotection of the PN solution would reduce
gestational age(14,41). by 30% the incidence of chronic lung disease in PTNB(43).
In situations where there is a need for exclusive use of PN,
without using the enteral route or in the presence of cholestasis trace elements
or sepsis, intravenous or intramuscular supplementation with
vitamin K at a dose of 1 to Similar to vitamins, oligoelements are added to the PN solution
3mg/week. in combination, in ampoules, and there are no specific products
Another important care that reduces vitamin losses is the use for PTNB(40,44)
of vials and equipment with photoprotection. Exposure to light (Table 4). An offer suggestion, based on the recommendations
leads to the degradation of photosensitive vitamins and to a and composition of the solutions available on the market, is shown
greater production of lipid peroxides in PN(42). a recent work in Figure 1. There are solutions available only

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Chart 2 – Suggested clinical and laboratory controls in nutritional therapy for preterm newborns.
parameters First period stable period

Clinical (activity, diuresis, blood pressure, heart rate, Daily Daily


respiratory rate, temperature, fluid balance)

Electrolytes and pH (Na, K, Ca, P, Mg) 3-4x week Weekly

urea and creatinine 2-3x week Weekly

Glycemia (dextro) Daily (3 times) Daily (1 time)

glycosuria Daily (3 times) Daily (1 time)

Albumin Weekly Weekly

Liver enzymes (TGO, TGP, Gamma-GT) Weekly Weekly

Hemoglobin and hematocrit Weekly Weekly

glycosuria Daily Daily

Urinary density Daily Daily

Leukogram when indicated when indicated

cultures when indicated when indicated

Triglycerides (total cholesterol and fractions not required) 4 hours after ÿ lipid infusion Weekly

Table 3 - Lipo and water-soluble vitamin requirements kg/day in preterm newborns and composition for each mL of solutions
Daily MVI 12 Polivit ® A Polivit® B frutovitam®
Opoplex®
recommendation (kg/day) Pediatric Pediatric ampoule 10mL
Pediatric ampoule 10mL ampoule 5mL
ampoule 5mL
grossman Inpharma Inpharma crystallia

For each 1mL For each 1mL For each 1mL For each 1mL

fat soluble vitamins


700 122 70 --- 304
A (µg)
2.8 1.4 0.7 --- 5
In G)
80 40 --- --- ---
K (µg)
4 1 1 ---
D (µg) two

water soluble vitamins


25 16 8 --- 50
Ascorbic acid (mg)
0.35 0.3 0.12 --- ---
Thiamine (mg)
0.15 0.35 0.14 --- 0.5
Riboflavin (mg)
0.18 0.25 0.10 --- 1.5
Pyridoxine (mg)
6.8 4.25 1.7 --- 10
Niacin (mg)
2.0 1.25 0.5 --- 2.5
Pathothenic Acid (mg)
6.0 4 --- 4 ---
Biotin (µg)
56.0 28 --- 35 ---
Folate (µg)
0.3 0.2 --- 0.2 ---
Vitamin B12 (µg)
dose/day 2mL/kg 4mL/kg 2mL/kg 2mL/kg

*Conversions: vitamin A, 700µg=2300UI; vitamin E, 7mg of ÿ-tocopherol=7UI; vitamin D, 10µg=400UI.

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Parenteral nutrition in preterm newborns: proposal for a practical protocol

Table 4 – Trace element requirements (kg/day) in preterm newborns and composition for each mL of trace element solutions

Nutrient Recommendation Ped-Element® Oliped 4® Ad-Element® Polytrace®4 Tracitrans® Plus*

(µg/kg/day) (5mL ampoule) (5mL ampoule) (2mL ampoule) (5mL ampoule) (10mL vial)
Manufacturer Darrow Inpharma Darrow Inpharma Fresenius
(µg/mL) (µg/mL) (µg/mL) (µg/mL) (µg/mL)
Zinc (µg) 400 500 100 1250 1000 660

Copper (µg) 20 100 20 400 200 127


2.0 --- --- --- --- 3.2
Selenium (µg)
Chromium (µg) 0.20 1 0.17 5 two 1

Manganese (µg) 1.0 10 6 200 100 27


0.25 --- --- --- ---
Molybdenum (µg) two

1.0 --- --- --- --- 13


Iodine (µg)
dose/day& 0.2mL/kg 1mL/kg 0.05mL/kg# 0.1mL/kg 0.3mL/kg
*Tracitrans® plus: also contains iron 112µg/mL and fluoride 95µg/mL; #Even with the dose adjustment, the supply of manganese is ten times higher
than recommended per day; &The calculation was based on the recommendation for copper and, therefore, some trace elements are above and
others below the recommended level, since an individualized calculation is not possible. In the case of zinc, there is an individualized solution and it
is necessary to add 200 to 400µg in addition to that offered by the trace elements solution to adjust needs.

with zinc in its composition (200µg/mL and 1,000µg/mL), The other electrolytes (sodium, potassium, magnesium) are
which can be used in combination with trace element solutions added to the solution according to the days of life and the
to meet the extra zinc needs in this age group. recommended amounts (Figure 1). Some care should be
taken into account when offering electrolytes in 3:1
Some precautions are important: manganese and copper solutions(44): the amount of calcium in the solution should not
are excreted by the liver. In conditions where there is impaired exceed 10mEq/L and the sum of di- or trivalent cations (calcium
bile excretion (cholestasis), the addition of these oligoelements and magnesium) should remain below 16mEq /L (Table 1).
to PN can be reduced or even excluded. It is possible, even The initial water supply should be 80mL/kg/day for NB
with exclusive PN, to use only the zinc solution for a period of <1,000g and 70mL/kg for the others(13). Volume progression
two weeks, without prejudice to the PTNB(14,44). should take into account the water balance and other fluids
Recent studies indicate that selenium is an important trace infused enterally or parenterally, and at the end of the first
element in the nutritional therapy of preterm infants from the week of life, it should be around 130 to 150mL/kg/day. It is
first days of life, especially to reduce episodes of sepsis(45,46). also important to consider, for water supply, the presence of
Unfortunately, commercially available pediatric trace element diseases that lead to the need for water restriction, such as
solutions do not contain selenium. An option to supplement patent ductus arteriosus.
selenium is to administer the solution of trace elements for
adults (adapting the amounts to be offered by Tracitrans® enteral nutrition
Plus) or the supplementary feeding via enteral route.
Enteral nutrition should be introduced early, preferably
within the first 48 hours of life, in small amounts, with raw
Minerals human milk (1st option) or pasteurized (2nd option). The
One of the great challenges of PTNB nutritional therapy is progression is made, depending on the clinical condition and
to offer large amounts of calcium and phosphorus, with the tolerance of the diet by the PTNB, with increments of 20 to
adequate ratio for bone mineralization (calcium:phosphorus 30mL/kg/day(4,17), however, it should be remembered that
ratio from 1.3:1 to 2:1mg or from 1.1:1 to 1, 3:1 in molar ratio) the use of human milk is associated with better tolerance and ,
and without leading to precipitation of the solution. To facilitate therefore, a faster progression of the enteral diet can be
administration, it is preferred to use phosphorus in organic performed. When it is not possible to use breast milk, the most
form (Table 5). Parenteral needs range from 80 to 100mg/kg/ appropriate option is the use of specific infant formulas for
day of calcium and 43 to 62mg/kg/day of phosphorus(40). preterm infants.

286 Rev Paul Pediatr 2008;26(3):278-89.


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Fabiola Isabel S. de Souza et al

Table 5 - Composition of electrolyte solutions


Product Cation anion
mEq/mL mg/mL mEq/mL mg/mL
10% sodium acetate 0.7 16.9 0.7 43.4
Sodium acetate 2mEq/mL 2.0 46.0 2.0 118.1
Potassium acetate 2mEq/mL 2.0 78.2 2.0 117.9
10% sodium bicarbonate 1.2 27.4 1.2 72.6
Sodium chloride 3% 0.5 13.1 0.5 20.2
Sodium chloride 10% 1.7 39.3 1.7 60.7
Sodium chloride 20% 3.4 78.6 3.4 121.4
Sodium chloride 4mEq/mL 4.0 92 4.0 141.8
Potassium chloride 19.1% 2.6 100.1 2.6 90.9
Potassium chloride 2mEq/mL 2.0 78.2 2.0 70.9
Potassium diacid phosphate 25% 1.8 71.8 1.8 57.0
Potassium Monoacid Phosphate 25% 2.9 112.3 1.9 44.5
Sodium Phosphate 2mEq/mL 2.0 46.0 1.1* 34.2
Potassium phosphate 2mEq/mL 2.0 96 1.1* 34.2
Sodium glycerophosphate 1Mmol/mL 2.0* (Na) 46 1.0* 31.0
Sodium glycerophosphate 0.33Mmol/mL 0.66* (Na) 15.3 0.33* 10.2
Calcium Gluconate 10% 0.5 8.9 0.5 87.0
Magnesium sulfate 10% 0.8 9.9 0.8 39
Magnesium sulfate 20% 1.6 19.8 1.6 78.0
Magnesium sulfate 50% 4.0 49.5 4.0 195.0
Magnesium sulfate 1mEq/mL 1.0 12.2 1.0 48.1
*Mmol/L.

Monitoring Proper maintenance of catheters greatly reduces infectious


complications related to PN.
The implementation of a follow-up and monitoring strategy for For PTNB-associated cholestasis of PN, the most important
the use of PN is essential to prevent and treat early complications risk factors are enteral fasting time, time of use of PN and sepsis.
related to its use. The participation of a multidisciplinary team in Once cholestasis is installed, for its treatment, the use of enteral
the institution of care protocols with catheter, manipulation, drug- nutrition (even in small volumes), the reduction in the supply of
nutrient interaction, installation, photoprotection, nutritional amino acids and the supply of glucose, maintenance of circulating
assessment and metabolic and laboratory follow-up increase the triglyceride levels below 200mg/ dL (if necessary, suspend the
safety and effectiveness of the use of PN in PTNB (Chart 1 and lipid infusion for 24 to 48 hours), temporary suspension (seven
two). to 14 days) of the oligoelement solution, since copper and
manganese are excreted by the liver. In more advanced cases,
Complications cyclic PN can be used (14,47).

The most serious complications associated with the use of


PN in PTNB are hepatobiliary complications (cholestasis) and Final considerations
sepsis(47). Protocols of care and monitoring of the use of PN,
with the involvement of the multidisciplinary team, prevent and This practical protocol on PN for PTNB was developed based
significantly reduce the complications associated with PN(9). on international recommendations from scientific societies and
theand
Measures such as care with the preparation of the solution, positioning critical analysis of scientific papers.

Rev Paul Pediatr 2008;26(3):278-89. 287


Machine Translated by Google
Parenteral nutrition in preterm newborns: proposal for a practical protocol

with appropriate methodology approaching the theme. The and support the development of protocols by multidisciplinary
article intends to facilitate the training of pediatric residents nutritional therapy teams.

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