PARENTERAL NUTRITION (PN)
Pharmacotherapy 4 for PharmD
Spring 2013
References
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DiPiro:Parenteral Nutrition
UpToDate:
Nutrition support in critically ill patients: An overview
Nutrition support in critically ill patients: Parenteral
nutrition
Koda-Kimble: Adult Parenteral Nutrition
ESPEN Guidelines on Parenteral Nutrition: Intensive
care. 2009.
espen.info/documents/0909/Intensive%20Care.pdf
Introduction
Pharmacist's role in nutrition-support care requires
knowledge of:
• principles of patient selection,
• initial therapy design,
• preparation & dispensing of nutritional
formulations,
• outcome monitoring.
Desired Outcomes
• 4 steps to providing optimal care:
1.definition of nutrition goals
2.determination of nutrient requirements to
achieve goals
3.delivery of required nutrients
4.assessment of nutrition regimen.
Nutrition support goals
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correction of caloric & nitrogen imbalances,
any fluid or electrolyte abnormalities,
known vitamin or trace element abnormalities.
Additionally: to ↓ metabolic response to injury by
minimizing oxidant stress & favorably modulating
immune response – without causing or worsening
other metabolic complications.
Specific caloric goals
(a) adequate energy intake to promote normal growth &
development in children,
(b) energy equilibrium & preservation of fat calorie stores in
well-nourished adults,
(c) positive energy balance in malnourished patients with
depleted endogenous fat stores.
• Obese patients with excess endogenous fat stores (> 120%
of IBW) may require less caloric support
• Specific nitrogen goals are positive nitrogen balance or
nitrogen equilibrium & improvement in serum
concentration of visceral protein markers such as
transferrin or prealbumin.
Desired Outcomes (cont’d)
• Who will benefit form PN? - patients who have
nonfunctional GI tracts or are otherwise not
candidates for enteral nutrition.
• Routine monitoring: to ensure that nutrition
regimen is suitable as patient's clinical condition
changes & to minimize or treat complications
early.
• Potential risks of initiating therapy: infection &
other metabolic abnormalities
Estimation of Energy Expenditure
Basal Energy Expenditure (BEE) (=BMR, basal metabolic rate)
• Harris-Benedict Equations
BEE men (kcal/day)=66.47 + 13.75 W + 5.0 H – 6.76 A
BEE women (kcal/day)=655.10 + 9.56 W + 1.85 H – 4.68 A,
or 20–25 kcal/kg/day
(A, age in years; H, height in cm; W, weight in kg).
Multiply the BEE by an adjustment factor (stress factor), depending on the level of
metabolic stress and nutritional goal. In patients who are anabolic, hypermetabolic,
critically ill, or are malnourished and/or have a fistula, use a stress factor of about 1.3–
1.5.
Energy Requirements
• Hospitalized patient, mild stress 20–25 kcal/kg/day
• Moderate stress, malnourished 25–30 kcal/kg/day
• Severe stress, critically ill 30–35 kcal/kg/day
The Subjective Global Assessment
Normal or Mild Malnutrition:
• No change in dietary intake or inadequate dietary intake <2 weeks; and/or
• No history or <2-day history of anorexia, nausea, vomiting, or diarrhea;
and/or
• Weight loss of <5% of usual body weight (UBW).
Moderate Malnutrition:
• Inadequate dietary intake 2 weeks; and/or
• History of anorexia, vomiting, or diarrhea 1–2 weeks; and/or
• Weight change of 5–9% of UBW over <6 months.
Severe Malnutrition:
• Inadequate dietary intake for 1 month; and/or
• History of anorexia, vomiting, or diarrhea for 2 weeks; and/or
• Visual evidence of wasting; and/or
• Loss of 10% of UBW over <6 months.
It has also been suggested that an unintentional weight loss of >10% over a 6month period indicates severe malnutrition.
NB: if actual weight is less than his IBW, use actual (admission) weight.
Indications for Adult PN
1. Inability to absorb nutrients via GIT because of
1 or > of the following:
a. Massive small bowel resection
b. Intractable vomiting when adequate EN is not
expected for 7–14 days.
c. Severe diarrhea
d. Bowel obstruction
e. GI fistulae: patients with prolonged inadequate
nutritional intake > 5–7 days who are not
candidates for EN
EN, enteral nutrition; GI, gastrointestinal; HSCT, hematopoietic stem cell transplantation;
PN, parenteral nutrition; SBS, short-bowel syndrome.
Indications for Adult PN (cont’d)
2. Cancer: antineoplastic therapy, radiation therapy, or
HSCT
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may be used in moderately to severely malnourished
patients receiving active anticancer treatment who are
not candidates for EN
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is not routinely indicated for well-nourished or mildly
malnourished patients undergoing surgery,
chemotherapy, or radiation therapy
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is unlikely to benefit patients with advanced cancer
whose malignancy is unresponsive to treatment (may be
appropriate for some carefully selected patients with
estimated life expectancy of > 40–60 days & strong
social & financial support)
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is appropriate for patients undergoing HSCT who are
malnourished & who are anticipated to be unable to
ingest &/or absorb adequate nutrients for 7–14 days.
Indications for Adult PN (cont’d)
3. Pancreatitis: severe pancreatitis with prolonged inadequate
nutritional intake longer than 5–7 days who are not
candidates for EN (if EN exacerbates abdominal pain,
ascites, or fistula output)
4. Critical Care
a. in patients in whom EN is contraindicated or is unlikely to
provide adequate nutritional requirements within 5–10
days
b. organ failure (liver, renal, or respiratory): patients with
moderate to severe catabolism when EN is
contraindicated
c. burns: in patients in whom EN is contraindicated or is
unlikely to provide adequate nutritional requirements
within 4–5 days
ESPEN guidelines:
• All ICU patients who are not expected to be
on normal nutrition within 3 days should
receive PN within 24 to 48 h if EN is
contraindicated or if they cannot tolerate
EN.
Indications for Adult PN (cont’d)
5. Perioperative PN
a. Preoperative: for 7–14 days for patients with moderate to
severe malnutrition who are undergoing major GI surgery,
if operation can be safely postponed
b. Postoperative: in patients in whom EN is contraindicated
or is unlikely to provide adequate nutritional requirements
within 7–10 days
6. Hyperemesis gravidarum: when EN is not tolerated
7. Eating disorders: PN should be considered for patients with
anorexia nervosa & severe malnutrition who are unable or
unwilling to ingest adequate nutrition
Indications for Pediatric PN
1. When EN is unlikely to provide adequate nutritional
requirements
a. Premature infant within 24–48 hours
b. Other pediatric patients within 5–7 days
2. When GIT is not functional or cannot be assessed
a. Massive small bowel resection resulting in short-bowel
syndrome
b. Neonatal necrotizing enterocolitis
c. Severe inflammatory bowel disease
d. Intractable diarrhea &/or vomiting
e. Graft-versus-host disease
f. Postchemotherapy
3. Infants & children requiring extracorporeal membrane oxygenation
4. Organ failure (liver, renal, pulmonary, pancreas) when EN is
contraindicated & child is catabolic
Contraindications to PN (UpToDate)
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hyperosmolality,
severe hyperglycemia,
severe electrolyte abnormalities,
volume overload,
inadequate attempts to feed enterally.
Sepsis or SIRS is a relative contraindication
to parenteral nutrition
Timing of PN
• Adult PN therapy is not emergent intervention & should
not be initiated until patient is hemodynamically stable.
• In general, adults who are not candidates for EN should be
considered candidates for PN after 7-14 days of suboptimal
nutritional intake.
• Children: early PN within the first 24 hours of life for
infants with birth weight < 1,500 grams.
• - within 5 to 7 days in other pediatric patients who are
unable to meet their nutrient requirements with enteral
nutrition.
• earlier intervention should be considered in term infants
(within 2-3 days), critically ill children (within 3-5 days),
& children with preexisting malnutrition.
Components of PN
• PN formulations include IV sources of protein, dextrose,
fat, water, electrolytes, vitamins, trace elements, etc.
• Macronutrients: water, protein, dextrose, & IV fat
emulsion (IVFE).
• Micronutrients: vitamins, trace elements, & electrolytes.
• In general, macronutrients are used for energy (dextrose &
fat) & as structural substrates (protein & fat).
• Micronutrients are required to support enzymatic reactions,
fluid balance, & regulation of electrophysiologic
processes.
Osmolarity of PN
Osmolarity of PN (cont’d)
• The osmolarity of typical peripheral parenteral feedings is
600-900 mOsm/L.
• Osmolarity of a dextrose/amino acid formulation can be
approximated quickly by multiplying the % dextrose
concentration by 50 & the % amino acid concentration by
100.
• ~ 150 mOsm/L should be added for contribution of
electrolytes, vitamins, & trace elements.
• Although concurrent administration of fat emulsions (up to
60% of nonprotein calories) decreases osmolarity, buffers
pH, & improves peripheral vein tolerance, it does not
eliminate the risk of thrombophlebitis
2-in-1 versus 3-in-1
Macronutrient Components of PN Solutions
Macronutrient Components of PN Solutions (cont’d)
AAA, aromatic amino acids (includes phenylalanine and tyrosine); BCAA, branched-chain
amino acids (leucine, isoleucine, and valine); EAA, essential amino acids (leucine, isoleucine,
valine, phenylalanine, tryptophan, methionine, threonine, and lysine); LCT, long-chain
triglycerides; PN, parenteral nutrition.
Amino Acids (AAs)
• Protein in PN solutions is provided as crystalline amino
acids (CAAs), which are used primarily for protein
synthesis.
• When oxidized for energy, 1 g of protein yields 4
calories. However, including caloric contribution from
protein when calculating calories provided by PN regimen
is controversial.
• Standard CAA solutions are designed for use in patients
with "normal" organ function & nutritional requirements.
• Nitrogen concentration of dietary protein is ~16% → 6.25
(100 g protein/16 g nitrogen) is commonly accepted as
conversion figure for calculating nitrogen amount
provided by CAA protein.
Amino Acids (cont’d)
• Electrolytes provided by CAA solutions must be
considered when determining patient's individual
requirements.
• CAA are available in concentrations of 5.5-15%.
• Highly concentrated products (15-20%) are attractive for
use in critically ill patients who typically require fluid
restriction but have large protein needs.
• Modified AA solutions are designed for use in patients
who have altered protein requirements, such as those with
hepatic encephalopathy, renal failure, etc.
• Rationale for & clinical efficacy of modified amino acids
in disease-specific PN regimens is controversial.
Amino Acids (cont’d)
• Some conditionally EAAs, such as cysteine, carnitine, &
glutamine, are not available in commercial CAA solutions
in pharmacologic amounts because they are relatively
unstable or poorly soluble.
• → PN solutions may need to be modified by clinicians to
provide desired amount of supplemental conditionally
essential AAs.
• Cysteine is conditionally EAA in preterm & term infants.
• Carnitine use in neonatal PN regimens is generally
reserved for patients receiving sole PN support for > 2
weeks.
• When PN is indicated in ICU patients the amino acid
solution should contain 0.2–0.4 g/kg/day of L-glutamine
(e.g. 0.3–0.6 g/kg/day alanyl-glutamine dipeptide)
(ESPEN).
Dextrose
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Primary energy source in PN solutions
Dextrose monohydrate, 5-70%.
When oxidized, each gram provides 3.4 kcal.
IV dextrose infusion rates should not exceed 12-14 mg/kg
per minute in infants & 4-7 mg/kg per minute in adults.
• Recommended dextrose dose for routine clinical care
rarely exceeds 5 mg/kg per minute in older critically ill
children (1-11 years old) & adults.
• HW: what happens if dextrose infusion rate exceeds
glucose oxidation rate?
Intravenous Fat Emulsion (IVFE)
• Concentrated source of calories & essential fatty acids.
• Differ in triglyceride source (soybean oil or combination of
soybean oil & safflower oil), fatty acid content, &
commercially available concentrations (10, 20, & 30%).
• These products also contain egg phospholipids as
emulsifying agent & glycerol to make emulsion isotonic.
• Caloric content: 1.1 kcal/mL for 10% emulsion, 2
kcal/mL for 20% emulsion, & 3 kcal/mL for 30%
emulsion
• Emulsions containing soybean oil: ~50-55% linoleic acid
& 4-9% linolenic acid; IVFEs that contain safflower oil are
made of ~66% linoleic acid & 4% linolenic acid.
• Higher amounts of circulating phospholipids are associated
with impaired triglyceride clearance in neonates & infants,
20% IVFE is the preferred product for this population.
• Both IVFE types are effective for treatment or prevention
of essential fatty acid deficiency (EFAD).
IVFE (cont’d)
• EFAD may be prevented by providing 2-5% of total
calories as linoleic acid & 0.25- 0.5% as linolenic acid.
• This may be achieved in most adults by giving ~100 g
IVFE weekly.
• Neonates & infants require minimum of 0.5-1 g/kg daily.
• Risk of hypertriglyceridemia decreases with longer
infusion times.
• Rapid IVFE infusions are reported to contribute to ↓
oxygenation in neonates.
• Adverse pulmonary effects are thought to be caused by
polyunsaturated fatty acid (PUFA)-driven prostaglandin
production, which results in altered vascular tone.
• Rapid infusion of long-chain fatty acid formulations may
have negative impact on immunocompetence by
saturating reticuloendothelial system.
IVFE (cont’d)
• Initiation of IVFE earlier than 4-7 days of life in infants
with birth weight <800 g remains controversial because
of potential ↑ risk of chronic lung disease & death.
• IVFE use may facilitate provision of adequate calories &
minimize complications of nutrition therapy such as
hyperglycemia, hepatotoxicity, or ↑ carbon dioxide
production.
• Patients receiving first IVFE dose should be monitored for
dyspnea, chest tightness, palpitations & chills.
• HA, nausea, & fever might be associated with rapid
infusion rate.
• IVFE use is c/i in patients with impaired ability to clear fat
emulsion, such as patients with pathologic hyperlipidemia
& hypertriglyceridemia associated with pancreatitis.
• Patients with egg allergy should be evaluated carefully for
nature & severity of reaction before deciding to initiate fatbased PN regimen.
IVFE (cont’d)
• 10% & 20% IVFE products may be administered either by
central or peripheral route.
• They may be added directly to PN solution as total nutrient
admixture (TNA) or 3-in-1 system (lipids, protein, glucose,
& additives), or they may be piggybacked with CAAdextrose solution.
• 30% IVFE is only approved for use in preparation of TNA
& is not intended for direct IV administration.
• New lipid sources: medium-chain triglycerides (MCTs)
are available in Europe
• Advantages: MCTs are hydrolyzed & cleared > rapidly
than LCTs, & they do not accumulate in liver.
• MCTs do not require carnitine for entrance into
mitochondria for oxidation.
• However, MCTs are not source of essential fatty acids.
IVFE (cont’d)
• Omega-3 PUFAs (linolenic acid) are metabolized
to cytokines, which may be < inflammatory &
immunosuppressive than those derived from
omega-6 PUFAs (linoleic acid).
• Propofol is delivered in soybean oil-in-water
emulsion that is essentially same as Intralipid
10%.
• It is used commonly for continuous sedation of
ventilated patients & should be considered a
potentially significant source of calories that may
require adjustment of patient's nutrition regimen.
Vitamins
• Adult parenteral multiple-vitamin products are
available commercially.
• There are two commercially available parenteral
vitamin products for use in pediatric patients:
MVI-Pediatric & Infuvite Pediatric for infants
weighing <1 kg to children up to 11 years old.
• There are no commercially available IV
multivitamin products designed to specifically
meet unique requirements of premature infants
(higher vitamin A & lower doses of vitamins B1,
B2, B6, & B12 compared to recommendations for
term infants & older children).
Vitamins (cont’d)
• Parenteral multiple-vitamin formulations for adults contain
13 essential vitamins.
• Supplemental vitamin K may be given IM or SC or added
to PN solution if needed.
• Current recommendations suggest supplemental vitamin K
is unnecessary when vitamin K-containing multiplevitamin product is used.
• Parenteral multiple-vitamin formulation containing no
vitamin K is commercially available for use in patients
receiving home parenteral nutrition & warfarin
anticoagulation.
• Individual & combination products are available to provide
additional or tailored supplementation (to prevent vitamin
toxicities or deficiencies caused by altered metabolism or
drug therapy).
Trace Elements
• IV trace elements are available as single-mineral solutions
& as multiple-mineral combinations ±electrolytes.
• Most products provide daily requirements for zinc, copper,
chromium, & manganese, whereas some also include
iodide, molybdenum, or selenium.
• Higher doses of supplemental zinc likely are necessary in
patients with high-output ostomies or diarrhea because
GIT is predominant excretion route for zinc.
• Manganese & copper are excreted through biliary tract →
should be restricted or withheld from PN solutions in
patients with cholestatic liver disease
• Chromium, molybdenum, & selenium are excreted renally
→ should be restricted or withheld in patients with renal
failure
Electrolytes
• Patients who have "normal" organ function & relatively
normal serum concentrations of any electrolyte should
receive normal maintenance multiple-electrolyte doses
when PN is initiated & daily thereafter.
• Concentrated multiple-electrolyte solutions designed for
addition to PN solutions generally contain only sodium,
potassium, calcium, & magnesium.
• Phosphorus must be added as separate additive.
Designing PN Regimen
• Several factors are important: venous access, fluid status,
& macronutrient & micronutrient requirements.
• Patient's venous access & fluid status determines how
concentrated PN solution may be compounded.
• PN solutions may be administered by central or peripheral
venous access depending on clinical condition.
• PN solutions may be provided as a 2-in-1 formulation that
contains dextrose, CAA, & other necessary micronutrients,
or as TNA that contains dextrose, CAA, & IVFE, as well
as other necessary micronutrients.
• Advantages of TNA solutions: ↓ infusion pumps, tubing,
etc.), ↓ time for compounding & administration, ↓ in
manipulations of infusion line (↓ risk of catheter
contamination), ease of delivery & storage for patients
receiving home PN.
• Potential disadvantages: ↑risk of infections & stability &
compatibility concerns → < desirable in specific patient
populations such as neonates & infants.
Route of PN & infusion type depend on patient's clinical
status & expected length of therapy.
Routes of PN Administration
Peripheral Route (PPN)
• Is option for mild to moderately stressed patients in whom
central access is unavailable or undesirable & function of
their GIT is expected to return within 10 -14 days.
• Lower concentrations of AAs (3-5% final concentration),
dextrose (5-10% final concentration), & micronutrients &
larger volumes compared to central parenteral nutrition
(CPN) are necessary → patient should not be fluid
restricted or require large nutrient amounts.
• Although dilute with nutrients, osmolarity of these
formulations is 600-900 mOsm/L (hypertonic) → are
irritating to peripheral veins & can cause thrombophlebitis
→ necessitates frequent site rotations (at least every 48–72
hours), which may quickly exhaust venous access sites.
• Advantages: lower risk of infectious, metabolic, &
technical complications.
Routes of PN Administration
(cont’d)
Peripheral Route (PPN)
• Factors complicating PPN: multiple courses of
chemotherapy, malnourished patients, premature infants,
elderly patients, & others after multiple venous access.
• Thrombophlebitis is common complication.
• To minimize phlebitis: addition of IVFE to regimen as
possible venous lumen protectant, subtherapeutic heparin
doses (0.5 to 1 unit/mL) to prevent thrombus formation,
&/or small doses of hydrocortisone (5 mg/L) to minimize
access site inflammation.
• Midline catheter use may offer some advantage with
reducing risk of thrombophlebitis (they are longer & infuse
into larger venous vessels which may dilute PN solution to
more tolerable osmolarity.
Central Route
• CPN is the preferred choice for PN delivery & is used for
patients who
- require PN for periods >7–14 days during hospitalization or
indefinitely at home.
- have large nutrient requirements,
- poor peripheral venous access,
- fluctuating fluid requirements (metabolically stressed
patients with extensive surgery, trauma, sepsis, multipleorgan failure, or malignancy).
• CPN solutions are highly concentrated hypertonic
solutions that must be administered through large central
vein.
• Disadvantages: risks associated with catheter insertion,
routine catheter use & care of access site.
Central Route (cont’d)
• Central venous catheters for short-term use in adults are
commonly inserted percutaneously into subclavian (or
peripheral like basilic, cephalic, or brachial) vein &
advanced so that the tip is at superior vena cava.
• If this approach is not possible, internal jugular vein can
be used.
• In neonates: via catheter placed in umbilical vein.
• When therapy is expected to last >4 weeks, catheter
usually is tunneled subcutaneously before entering central
vessel, secured initially with retaining sutures, & anchored
in place with cuff.
• Parenteral nutrient formulations designed for
administration through central veins can contain relatively
high concentrations of dextrose (20%–35%), amino acids
(5%–10%), and lipids providing a caloric density of >1
kcal/mL in a solution with an osmolarity of >2,000
mOsm/L
Adult PN Solutions
2 methods for ordering adult PN:
1. “Standard formula approach" - base formulations with
fixed nonprotein calorie–to-nitrogen ratio.
• usually includes different formulas designed for mild to
moderately stressed patients, renal failure patients, fluidrestricted patients, & liver failure patients.
• Because nonprotein calorie-to-nitrogen ratio is fixed,
amount of nutrient delivered depends solely on infusion
rate.
2. “Individualized formula approach" permits compounding
of patient-specific solutions.
• Compounding of PN solution is limited only by
concentrations of stock solutions & stability of additives.
• Nutrient amount delivered depends on daily volume of PN
solution infused & nutrient concentrations in PN solution.
Calculation of Adult PN Regimen
• Patient case: Patient’s daily nutritional requirements are
100 g protein & 2,000 total kcal.
• Patient has central venous access & reports no history of
hyperlipidemia or egg allergy.
• Patient is not fluid restricted.
• PN solution will be compounded as individualized regimen
using single-bag, 24- hr infusion of 2-in-1 solution with
IVFE piggybacked into PN infusion line.
• Determine total PN volume & administration rate by
calculating macronutrient stock solution volumes required
to provide desired daily nutrients.
• Stock solutions used to compound this regimen are 10%
crystalline amino acids (CAA), 70% dextrose, & 20%
IVFE.
Calculation of Adult PN Regimen (cont’d)
1. Determine daily IVFE calories & volume
• 2,000 kcal/day × 30%–40% of total calories as fat = 600–
800 kcal/day
• Choose IVFE 20% 250 mL/day × 2 kcal/mL = 500
kcal/day
2. Determine 70% dextrose stock solution volume
• Determine dextrose calories
• Dextrose calories = TOTAL − IVFE − Protein
• 2,000 kcal − 500 kcal IVFE − (4 kcal/g × 100 g CAA) =
1,100 kcal
• Calculate required dextrose (grams)
• 1,100 kcal ÷ 3.4 kcal/g dextrose = 324 g dextrose
• Determine 70% dextrose volume
• 70 g/100 mL = 324 g/X mL 70% dextrose; X = 463 mL
70% dextrose
Calculation of Adult PN Regimen (cont’d)
3. Calculate 10% CAA stock solution volume
• 10 g/100 mL = 100 g/X mL 10% CAA; X = 1,000 mL
10% CAA
4. Determine 2-in-1 PN volume & administration rate
• Calculate CAA/dextrose volume
• 463 mL 70% dextrose + 1,000 mL 10% CAA = 1,463 mL
CAA–dextrose
• Add 100–200 mL for additives
• Total 2-in-1 volume = ~1,600–1,700 mL/day
• Calculate administration rate
• 1,600–1,700 mL/day ÷ 24 hours = 67–71 mL/hour; round
to 65–70 mL/hour
Calculation of Adult PN Regimen (cont’d)
5. Choose final 2-in-1 PN regimen & determine provided
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nutrient amounts:
Final 2-in-1 regimen
100 g CAA/324 gm dextrose in 1,680 mL/day to infuse at
70 mL/hour
+ 20% IVFE 250 mL to infuse at 2 mL/hour
Calculate macronutrient calories
20% IVFE calories: 250 mL × 2 kcal/mL = 500 kcal
Dextrose calories: 324 g × 3.4 kcal/g = 1,102 kcal
Protein calories: 100 g × 4 kcal/g = 400 kcal
Total kcal: 2,002 kcal
Nonprotein kcal: 1,602 kcal
Simplifying calculation of PN regimen after
patient's nutritional requirements have been
decided
• Adult patients receiving only PN therapy may need larger
volumes of fluid to provide maintenance requirements &
replace extrarenal losses.
• Patients may receive adequate fluid from additional IV
maintenance solution (e.g., 0.45% NaCl in 5% dextrose)
&/or piggybacked medications.
• Methods for estimated fluid needs for basic maintenance:
1. The simplest method uses 30-35 mL/kg/day as the basis.
2. Another method is to provide 1,500 mL for the first 20 kg
body weight plus additional 20 mL/kg for actual weight
beyond the initial 20 kg.
• Additional fluid must be provided for increased losses
such as vomiting, nasogastric (NG) tube output, diarrhea,
or large open wounds.
Pediatric PN Solutions
• Are typically ordered using individualized approach based
on patient's weight.
• Current safe practice guidelines suggest that pediatric PN
label identify components as "amount per day" with
secondary expression of components as "amount per
kilogram per day.“
• Because infants & children generally receive daily
maintenance fluid from PN regimen, supplemental IV
solutions are rarely needed.
• TNA system is not recommended for use when
compounding neonatal PN because of IVFE instability
with higher calcium & phosphorus concentrations.
Administration Techniques
• PN solutions should be administered with infusion pump.
• IV administration line for CAA-dextrose solutions should
include 0.22-micron inline filter to remove particulate
matter, air, & any microorganisms.
• IVFEs administered separately from CAA-dextrose
solution must be piggybacked into PN line at site beyond
inline filter because average size of IVFE particles is ~0.5
microns.
• FDA recommends for IVFE use of 1.2-micron filter, which
may be effective in preventing catheter occlusion caused
by precipitates or lipid aggregates
• This filter size is also reported to remove Candida
albicans.
Initiating & Advancing PN Infusion
Adult PN
• Patient's nutrition status, current clinical status, history of
glucose tolerance, & dextrose concentration in formula
will dictate infusion rate.
• Stable patients with normal organ function & stable
baseline serum glucose concentrations: abruptly initiating
or discontinuing PN therapy.
• Patients receiving intermittent SC regular insulin, patients
with severe renal or hepatic disease, other disease states
that may ↑ risk of hypoglycemia (severe diabetes or
pancreatic malignancy & patients who are receiving betablockers): begin PN infusion &↑ rate gradually over 12-24
hours to desired rate →↓ in stepwise fashion, e.g., by 50%
for 1 hour prior to discontinuation
Continuous versus Cyclic Infusions
• Continuous infusions are attractive for use in patients with
unstable fluid balance or glucose control.
• Intermittent or cyclic infusion of PN, usually for 12-18
hours each day, is useful in hospitalized patients with
limited venous access in whom administration of multiple
other medications requires interruption of PN infusion.
• Cyclic PN also may prevent or treat hepatotoxicities
associated with continuous PN therapy.
• In addition, this delivery mode allows patients receiving
PN at home ability to resume relatively normal lifestyle.
• Cyclic PN is not optimal for all patients & should be used
with caution in those with severe glucose intolerance or
diabetes, or unstable fluid balance.
Evaluation of Therapeutic Outcomes
• Serum concentrations of electrolytes, hematologic indices,
& biochemical markers for renal function, liver function,
& nutrition status should be measured prior to PN
initiation & periodically thereafter depending on patient's
age, nutrition status, & clinical condition.
• Frequency of blood tests in neonates & infants tends to be
more conservative due to smaller circulating blood
volumes &, in some cases, lack of central vascular access.
• Other important clinical measurements include vital signs,
weight, total fluid intake & losses, & nutritional intakes.
• Weekly height/length & head circumference measurements
are helpful for monitoring nutritional changes in neonates.
Monitoring strategy for patients receiving PN.
• Baseline (prior to initiation of TPN)
↓
Weight
Vital signs
• Temperature
• Pulse
• Respirations
Current nutritional intake
CBC
Serum electrolytes
• Sodium
• Potassium
• Chloride
• Bicarbonate
• Magnesium
• Phosphorous
• Calcium
Serum glucose
Serum albumin
Markers for organ function
• LFT
• AST
• ALT
• Total bilirubin
• PT or INR
RFT
• Blood urea nitrogen
• Creatinine
Fluid balance
- Input
• Oral
• Nasointestinal
• Intravenous
- Output
• Urine
• Gastrointestinal
• Other losses
Special pediatric considerations: height/length, head circumference
Monitoring strategy for patients receiving
parenteral nutrition (PN) (cont’d)
Daily
↓
• Vital signs
• Current nutritional intake
• Fluid balance
- Input
- Output
• Capillary blood glucose
- As necessary; unstable patients may
require measurements every 1–2 h
↓
Serum electrolytes
• Sodium
• Potassium
• Chloride
• Bicarbonate
• Calcium
Serum glucose
↓
↓
Daily for first 3–4 days after initiation
of TPN
• Add magnesium & phosphorous if
patient at risk for refeeding
syndrome or if baseline values are
abnormal
• Serum electrolytes may be
measured less frequently in stable
patients
• Critically ill patients may require
more frequent monitoring
• Special pediatric considerations:
• Total bilirubin—daily in newborns
until normal
Monitoring strategy for patients receiving
parenteral nutrition (PN) (cont’d)
•
Weekly
↓
Nitrogen balance
Prealbumin or transferrin
Serum triglyceride
Liver function tests
• AlkP
• AST
• ALT
• Total bilirubin
• PT or INR (as necessary)
↓
•
Liver function tests may be drawn
less frequently in stable patients
(every 2–4 weeks)
↓
Special pediatric considerations:
• Height/length
• Head circumference
Compounding, Storage, &
Infection Control
• Compounded sterile preparations are defined by risk level
(high, medium, low) based on probability of microbial,
chemical, or physical contamination.
• PN solutions are classified as medium-risk compounded
sterile preparation.
• In general, PN solutions should be prepared using aseptic
technique under properly maintained laminar flow hood.
• Supervision by pharmacist experienced in compounding
IV solutions & knowledgeable about stability,
compatibility, & storage of PN solutions is also necessary.
Compounding, Storage, & Infection
Control (cont’d)
• Quality assurance procedures should be developed to
maintain safe & accurate admixture preparation.
• PN base solutions may be prepared by using gravity-driven
transfer of CAA stock solutions to partially filled bags of
concentrated dextrose stock solutions.
• There are commercially prepared CAA-dextrose products
separated within single bag & then mixed prior to use.
• Advances in compounding technology have facilitated use
of automated compounders for preparing PN solutions perform calculations necessary to determine volumes of
nutrient stock solutions → communicates determined
calculations directly to transfer pump device that delivers
fluid from source container to final container by either
volumetric or gravimetric fluid pumping system.
Compounding, Storage, & Infection
Control (cont’d)
• In spite of acidic pH & hypertonicity, growth of
Pseudomonas aeruginosa, Escherichia coli, & C. albicans
has been reported in CAA-dextrose solutions.
• TNA solutions appear to support growth of bacteria less
than IVFEs, but more than CAA-dextrose solutions.
• CDC recommends that IVFE infusions not exceed 12
hours, unless volume considerations require more time, in
which case IVFE infusions should be completed within 24
hours.
• But FDA-approved guidelines for handling procedures for
IVFE-containing anesthetic agent propofol restrict infusion
time to 12 hours after bottle has been spiked & require
infusion tubing change every 12 hours.
Compounding, Storage, & Infection
Control (cont’d)
• CDC guidelines recommend use of administration sets for
2-in-1 PN for up to 72 hours, but those used for TNA
solutions & IVFE should be changed every 24 hours.
• Frequently neonates require considerably smaller volumes
(e.g., 2 ml/day) of IVFE than are commercially available.
• Some institutions aseptically transfer IVFE into plastic
syringes for syringe pump infusion →↑ risk of bacteremia.
• FDA-approved guidelines for propofol handling
procedures restrict infusion times for doses provided in
syringes to 6 hours.
• Many institutions allow infusion times between 12 & 24
hours.
Stability & Compatibility
• CAA-dextrose solutions generally are stable for 1-2
months if refrigerated at 4°C & protected from light.
• TNA formulations are complex mixtures that are
inherently unstable.
• Several factors affect stability of TNA solutions, including
pH, electrolyte charges, temperature, & time after
compounding.
• US Pharmacopeia 797 standards recommend storage times
of not > 30 hours at controlled room temperature (15°C to
30°C) & not more than 9 days at refrigerated temperatures
(2°C to 4°C) for all medium-risk compounded sterile
preparations, including PN solutions.
Stability & Compatibility (cont’d)
• Because of differences in pH among various CAA
products & differences in phospholipid content among
IVFE products, specific manufacturers should be consulted
for compatibility & stability information prior to routine
mixing of components.
• One approach to compounding TNA formulations
manually is to first combine CAA, dextrose, & sterile
water (if necessary).
• Add electrolytes, vitamins, & trace elements & then
visually inspect solution for precipitate.
• Finally, add IVFE & visually inspect solution to ensure
uniform emulsion exists.
• But: this specific order & time sequence may not be
possible with use of automated compounders.
Stability & Compatibility (cont’d)
• Precipitation of calcium & phosphorus is common
interaction that is potentially life-threatening.
• Factors that enhance risk of precipitate formation include
high concentrations of calcium & phosphorus salts, use of
chloride salt of calcium, decreased amino acid & dextrose
concentrations, increased solution temperature, increased
solution pH, use of improper sequence when mixing
calcium & phosphorus salts, & presence of other additives
including IVFEs.
• Electrolyte stability in TNA solutions is difficult to assess
because of poor visualization of precipitate should one
occur.
• PN solutions for neonates & infants tend to have larger
calcium & phosphorus amounts, as well as other divalent
cations, that limit use of TNA formulations.
• Use of 2-in-1 formulation with separate administration of
IVFEs is recommended for neonates & infants.
Stability & Compatibility (cont’d)
• Addition of bicarbonate to acidic PN solutions → carbon
dioxide gas & insoluble calcium & magnesium carbonates
→ sodium bicarbonate use in PN solutions is not
recommended (use bicarbonate precursor such as acetate).
• Because of variable stabilities of individual vitamins, IV
vitamin solutions should be added to PN solution near to
time of administration, & should not be in PN solution
longer than 24 hours.
• Peroxide formation in dextrose-amino acid solutions
depends on concentration of IV multivitamins, CAA, &
dextrose, & presence of IVFEs.
• Peroxides have negative effects on organ & immune
function: e.g., neonatal hypoxic–ischemic encephalopathy,
intraventricular hemorrhage, chronic lung disease,
retinopathy of prematurity & necrotizing enterocolitis.
• Protecting PN & IVFE solutions from light is
recommended to minimize peroxide formation.
Stability & Compatibility (cont’d)
• Compatibility of IV medications & other IV solutions is an
important concern in delivering safe & effective drug and
nutritional therapy.
• IV medications are infused most often as separate
admixture piggybacked in PN line.
• For adding medications directly to PN solution, specific
criteria should be considered: dosage regimen should be
stable for each 24-hour period & should have
pharmacokinetic properties appropriate for continuous
infusion.
• There should be documented chemical & physical
compatibility of medication with PN mixture.
• PN regimen should be infused continuously over 24 hours.
HW:
• Advantages & disadvantages of PN
admixtures with drugs?
• Examples of drugs frequently used as such
admixtures
Complications of PN
1. Mechanical or Technical Complications
• infusion pump failure,
• problems with administration sets or tubing,
• problems with catheter - potentially life-threatening:
- pneumothorax,
- catheter misdirection or migration into wrong vein or
improperly positioned within cardiac chambers,
- arterial puncture,
- bleeding,
- hematoma formation,
- venous thrombosis,
- air embolism,
- breakage of catheter
Complications of PN (cont’d)
2. Infectious Complications
• Can be major hazard in patients receiving CPN.
• Predisposing factors: compromised immunity,
concomitant infection, frequent use of broad-spectrum
antibiotics, malnutrition
• Sources of infection: improper preparation of solutions,
catheter-related bloodstream infection (defined as presence
of bacterial or fungal growth from catheter tip & peripheral
blood cultures).
• Catheter infection or colonized catheter is defined as
microbial growth from catheter tip or from blood culture
drawn from catheter with no growth of the same organism
in peripheral blood culture.
• Colonization may occur after multiple manipulations of
line used for PN administration (when used to administer
other medications), failure of in-line bacterial filters, poor
placement technique, & poor care of insertion site.
Complications of PN (cont’d)
3. Metabolic & Nutritional Complications
• PN-associated hepatic dysfunction
• Risk factors in children: degree of prematurity, sepsis,
hypoxia, lack of enteral nutrition, small bowel bacterial
overgrowth, GI conditions requiring surgical intervention,
duration of PN therapy, long-term administration of
excessive calories.
• PN-associated hepatic dysfunction in infants is
characterized clinically by serum direct bilirubin
concentration > 2 mg/dL.
• Taurine deficiency has been proposed as etiology of
cholestasis in preterm infants & neonates (essential
amino acid not present in standard CAA solutions but
important in neonatal & infant bile metabolism).
• Risk factors in adults: preexisting liver diseases, sepsis,
preexisting malnutrition, extensive bowel resection,
duration of PN therapy, lack of enteral intake, choline
deficiency, long-term administration of excessive calories
Metabolic Abnormalities Associated with PN
Macronutrients
ALT, alanine aminotransferase (SGPT); AST, aspartate aminotransferase (SGOT); Alk Phos,
alkaline phosphatase; Bili, bilirubin; EFAD, essential fatty acid deficiency; EN, enteral
nutrition; IVFE, intravenous fat emulsion; PN, parenteral nutrition.
Complications of PN (cont’d)
Metabolic & Nutritional Complications (cont’d)
• Hypertriglyceridemia (TG 400-500 mg/dL in adults &
150-200 mg/dL in preterm infants, neonates, & older
pediatric patients) may occur in patients receiving IVFEbased PN.
• Risk factors: preexisting liver or pancreatic dysfunction,
sepsis, multiple-organ failure, degree of prematurity, IVFE
infusion rate, & dose.
• IVFE-associated hypertriglyceridemia generally is thought
to be caused by defective lipid clearance.
• Reducing IVFE infusion rate or dose or withholding IVFE
therapy should be considered when patients present with
hypertriglyceridemia or lipemic serum.
• Use of low-dose heparin to stimulate lipoprotein lipase
activity has been suggested.
Complications of PN (cont’d)
Metabolic & Nutritional Complications (cont’d)
• Severe & rapid ↓ in serum phosphate, potassium &
magnesium concentrations, fluid retention are common
features of refeeding syndrome.
• Individuals at risk: severely malnourished with significant
weight loss who receive aggressive nutritional
supplementation, unfed for 7-10 days with evidence of
stress or nutritional depletion, chronic diseases causing
undernutrition (cancer, cardiac cachexia, COPD or
cirrhosis), & those with previous morbid obesity &
massive weight loss.
• Recommendations for initiating PN in adults at risk for
refeeding syndrome: providing 25-50% of calculated
nonprotein caloric requirements initially.
Complications of PN (cont’d)
Metabolic & Nutritional Complications (cont’d)
• Dextrose dose should be initiated at ~100-200 g/day.
• Calories should be advanced over 3-4 days to desired goal.
• Pediatric PN regimens are usually advanced over several
days as general practice.
• Additional recommendations for minimizing risk of
refeeding syndrome in pediatric patients includes provision
of additional phosphorus & potassium above standard
nutrient requirements at the time PN is initiated
HOMEWORK:
• Hyperglycemia & its
management/prevention (including insulin
doses & glycemic targets in critically ill
patients)
Complications of PN (cont’d)
Metabolic & Nutritional Complications (cont’d)
• Lactic acidosis & other life-threatening complications
associated with severe thiamine deficiency in patients who
received PN solutions without multivitamin
supplementation → at least maintenance doses of vitamins,
trace elements & EAAs should be provided to all patients
with normal age-related organ function receiving PN.
• Patients receiving PN regimens without IVFEs for
extended periods (weeks-months) are at risk for
development of EFAD: hair loss, desquamative dermatitis,
thrombocytopenia, malabsorption & diarrhea resulting
from changes in intestinal mucosa.
• Triene-to-tetraene ratio > 0.4 is biochemical evidence for
EFAD.
• May occur within 72 hours in premature infants.
Complications of PN (cont’d)
Metabolic & Nutritional Complications (cont’d)
• Metabolic bone disease is reported in adults & children
receiving long-term home PN.
• In adults is characterized by osteomalacia with or without
osteoporosis
• Diagnosis may not be made in premature infants until after
development of bone fractures or overt rickets.
• Etiology is likely multifactorial.
• Treatment: calcium & vitamin D supplementation &
exercise.
• Others have recommended removal of vitamin D from PN
in patients with low serum PTH & 1,25-hydroxyvitamin D
concentrations.
• Nutrient-induced toxicities, most commonly as result of
accumulation of fat-soluble vitamins or trace elements
Complications of PN (cont’d)
Metabolic & Nutritional Complications (cont’d)
• Aluminum accumulation may occur during long-term PN
therapy, especially in patients with renal insufficiency, &
is associated with abnormal neurologic & hematologic
function & metabolic bone disease in adults & premature
infants.
• FDA: parenteral doses of 4-5 mcg/kg per day are
associated with CNS & bone toxicity in patients with
impaired renal function, including premature
• In 2004 FDA: restriction of aluminum content in largevolume PN stock solutions (CAA, dextrose, sterile water
for injection, IVFE) to maximum of 25 mcg/L &
requirement for manufacturers to indicate maximum
aluminum concentration at expiration for both large &
small volume parenteral products used for PN.