Parenteral Nutrition

RS Torrinhas and DL Waitzberg, University of Sao Paulo, Sao Paulo, Brazil

2016 Elsevier Ltd. All rights reserved.

Definition
Parenteral nutrition (PN) therapy can be defined as a set of
therapeutic procedures for the maintenance or recovery of
nutritional status in malnourished patients or in those suffering from malnutrition risk either in hospital, ambulatory, or
home settings. PN is provided through the intravenous administration of sterile and pyrogen-free solutions or emulsions
composed of water, electrolytes, carbohydrates, amino acids,
lipids, vitamins, and minerals, and packaged in a glass or
plastic container, designed to support the synthesis or maintenance of tissues, organs, or systems.

History
The routine use of PN in clinical practice was initiated in 1968,
after Dudrick and collaborators demonstrated the safety and
efficacy of the prolonged central vein administration of a parenteral solution containing 50% glucose and 10% amino
acids, combined with electrolytes, minerals, and vitamins, in
achieving growth and body weight gain in children. Later on, it
was found that the PN solution IV-infused with highly concentrated solutions of glucose could cause hyperglycemia, particularly in severely ill patients. This intercurrence was associated
with adverse events such as immunosuppression and an
increase in complications related to infection. Accordingly,
the energy provided by glucose was replaced, in part, by the
addition of parenteral fat emulsions. The parenteral administration of fat as a lipid emulsion (LE) formula, in combination
with glucose and amino acids in a single bag constitutes the so
called all-in-one PN.

Indication
PN is of utmost importance for the nutritional recovery of
patients who cannot eat, should not eat, or may not be sufficiently fed by the enteral route. Providing PN perioperatively
can reduce the morbidity of seriously malnourished surgical
patients, and a meta-analysis of nine randomized clinical trials
showed that PN can significantly decrease mortality in critically ill patients. However, the intestinal disuse due to the
exclusive use of the parenteral route for nutrients supply can
lead to the atrophy of the mucosa, and it can promote increased gut permeability and sometimes bacterial translocation.
Exclusive PN regimens or PN solutions complementary to
enteral nutrition (EN) therapy are usually prescribed when oral
or EN feeding is impossible, contraindicated, or insufficient.
These indications apply to malnourished patients and those at
risk of malnutrition with no gastrointestinal tract function,
disorders requiring complete bowel rest, or those unable to
achieve their energy targets by oral/enteral feeding after 28

Encyclopedia of Food and Health

days, respectively (see Table 1 for absolute and relative indications, and contraindications of PN). While used as a unique
food source, the PN solution must contain all necessary macro
and micronutrients to ensure the patients homeostasis.
Indications of PN should also consider its possible negative
influence on the evolution of the patients disease or treatment,
and the wishes and needs of patients and their families in
critical situations such as terminal cancer without a clear prospect of improved survival or quality of life by using PN. For
patients requiring PN for long periods without the need for
hospitalization, home PN (HPN) is recommended and should
be used in conjunction with EN whenever possible, in order to
maintain the intestinal tropism. Indications for HPN have
increased worldwide as an alternative to improve the life quality of patients with intestinal failure or insufficiency, but it
implies adequate patient, family, and caregiver training, to
avoid HPN-related complications, such as metabolic abnormalities, organ dysfunction, and derived infection of the central venous catheter, which is largely responsible for morbidity
and mortality in these patients.

Planning
The formulation of the PN must meet the patients
energyprotein requirements and provide essential nutrients
in adequate amounts to maintain life, cell, and tissue growth.
These nutritional requirements may vary according to
nutritional status, the disease, and the metabolic condition of
patient, as well as the length of nutritional therapy. Therefore,
the planning of PN therapy must calculate the energy and
nutrient requirements on an individual basis, according to
the patients clinical condition.
The American Society of Parenteral and Enteral Nutrition
(ASPEN) states that adult patients should receive 2035 kcal
kg 1 day 1, divided into carbohydrates, proteins, and fats (see
Figure 1 for a step-by-step guide). Vitamins, trace elements,
and electrolytes for parenteral infusion in adults are offered
based on the recommendations of the Dietary Reference
Intakes (DRIs), which are accepted as a reference point to
find the individual estimation of these micronutrients. As
DRIs were formulated based on the needs of healthy subjects,
patients with specific diseases may require increased amounts
of certain micronutrients for wound healing, tissue recovery,
and anti-free-radical production, which may be provided by
diluting in saline and infusing these micronutrients through a
peripheral vein.
In addition, beside standard formulas of PN, which are
composed mostly of amino acids, glucose, lipids, and
electrolytes, there are special formulations developed to
address the specific needs of morbid conditions that involve
metabolic disorders, such as liver and kidney diseases. The
special solution for liver failure is rich in branched chain

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Parenteral Nutrition

Considering the remained 709.6 kcal/kg/day and 1g fat ~9kcal:

709.6/9 = 78.84 g/day or 1.13 g/kg/day (~390 mL of LE 20%)
Considering 2,100kcla/kg/day of total calories:
2,100 kcal - 326 kcal from protein = 1,774 kcal/kg/day

FAT
CARBOHYDRATE
4565% of non-proteic
calculated calories:
up to 7 g/kg/day

Considering 30 kcal/kg/day supply of total calories:

70kg x 30 kcal/kg=2,100 kcal/day

2535% non-proteic
calculated calories:
Maintenance-up to 2.5
g/kg/day
Catabolismup to 1
g/kg/day

STEP 2

STEP 1
Total caloric value
calculation

Protein calculation

STEP 3

STEP 4

STEP 5

Remaining calories
calculation

Carbohydrate
calculation

Fat calculation

PROTEIN
1035% of total calculated calories:
Maintenace- 0.8 to 1 g/lg/ day
Catabolism- 1.2to 2 g/kg/day

Considering 1.2g protein /kg body weight:

1.2 g x 70 kg = 84 g/day or 326 kcal/day (1 g protein ~4 kcal)

Considering 60% of non-proteic calories:

1,064.4 kcal/day or 266,1 g/day(1 g glucose ~ kcal)

Figure 1 Steps for calorie distribution between carbohydrates, proteins, and lipids during parenteral-nutrition planning. Calculated based on a male
patient with a 70-kg body weight and without specific restrictions regarding macronutrients and micronutrients.

Table 1

Indications and contraindications for prescribing parenteral nutrition

Absolute indications

Relative indications

Contraindications

Impossibility for enteral access due to

gastrointestinal obstruction or prolonged ileus
Inability to absorb nutrients through the
gastrointestinal tract due to massive intestinal
resection (early stage)
Inability to absorb nutrients through the
gastrointestinal tract due to severe short bowel
syndrome
Inability to absorb nutrients through the
gastrointestinal tract due to active inflammatory
bowel disease (requiring 57 days of bowel rest)

Gastrointestinal bleeding requiring

prolonged gastrointestinal rest
Anorexia or severe mucositis due to
chemotherapy, radiotherapy, or
bone marrow transplantation
Extensive surgery with a prediction
of postoperative prolonged ileus
for more than 5 days
Severe diarrhea by malabsorption
Severe pancreatitis requiring bowel
rest for more than 5 days

Functional gastrointestinal tract

amino acids (BCAAs), to increase the BCAA/aromatic amino

acids (AAAs) ratio. In this condition, the decreased hepatic
metabolism increases plasma levels of AAAs and peripheral
metabolism, resulting in a decrease in BCAAs. This situation
allows AAA and its metabolites to enter the brain, potentially
favoring hepatic encephalopathy.
Special formulations for patients with renal failure are characterized by the highest amount of essential amino acids and
histidine; one of them stands out by the addition of arginine,
and another by containing small amounts of nonessential
amino acids. The design of these formulations is based on
the principle that the treatment of patients with chronic renal
failure is benefited by offering low-protein diets and essential
amino acid supplementation. However, due to metabolic differences between acute and chronic renal failure, offering solutions containing only essential amino acids cannot meet the
protein needs of the patient.
Different formulations of LEs are also available as sources of
fat in PN therapy and can be infused alone or associated to
amino acids and glucose (3:1 system), as the source of nonglucose high-calorie energy and essential fatty acids. The different available LEs are distinguishable by the type and amount
of fatty acids present in their composition, based on the availability of essential fatty acids and the property that certain fatty
acids have to influence the immune response. Therefore,
understanding the biological properties of the different fatty

Hemodynamic instability

Allergy to any of its components

Severe hyperlipidemia, blood clotting disorders, acute

shock, and other unstable conditions (e.g., acute
myocardial infarction, stroke, and severe sepsis),
when their lipid component is used

acids that comprise LEs is required to determine those that will

contribute to the clinical evolution of the patient.
Critically ill patients are more susceptible to oxidative
stress, alterations in cell-mediated immunity, inflammation,
and thrombosis. Therefore, these patients may benefit from
LEs based on fish oil containing adequate amount of the
antioxidant alpha-tocopherol, as source of the potentially antiinflammatory and antithrombotic omega-3 fatty acids,
eicosapentaenoic and docosahexaenoic. On the other hand,
LEs based on soybean oil should be avoided in this patient
population, because they provide larger amounts of potentially
proinflammatory and prothrombotic omega-6 fatty acids.
Another nutrient with pharmacologic functions available
for PN is glutamine, which is considered to be an essential
amino acid in some clinical conditions (i.e., a conditionally
essential amino acid). Glutamine plays a key role in various
stages of human metabolism, such as the transport of nitrogen
and protein synthesis, and it serves as the energy source for
rapidly proliferating cells such as enterocytes and immunologic cells. Due to its low water solubility, the parenteral use
of glutamine is commercially available as dipeptides, in which
glutamine may be associated with another amino acid, such as
alanine (alanil-glutamine) and glycine (glycil-glutamine).
Recommendations suggest a dose of 0.30.5 g kg 1 of body
weight for parenteral supplementation of glutamine; however,
this dose may vary according to the individual condition and

Parenteral Nutrition

patient needs. According to the Canadian Guidelines (2013),

when the PN is prescribed to a critically ill patient, glutamine
supplementation should be considered. However, the authors
strongly recommend that glutamine should not be used for
patients with shock or multiple organ failure.
Finally, when planning PN solutions, we must consider
that, independent of the formulation, the nutrients are
dissolved in water. Therefore, PN can also influence the
patients hydration. Considering that some clinical conditions
can increase (i.e., fever, sunburn, and diarrhea) or decrease
(i.e., renal and cardiovascular failure, respiratory disorders)
the need for water, water content is part of the PN planning
in order to provide adequate water amounts based on the
patients metabolic condition.

Administration
After planning the PN, in order to start, the patient must have
an adequate central or peripheral venous access. The PN solution is usually administered into a large-diameter venous
vessel, accessed via the jugular or subclavian vein. The peripheral route for the infusion of PN should be limited to the
administration of PN solutions with low osmolarity (<850 mOsmol l 1) to cover only part of the nutritional needs and
mitigate negative energy balances.
PN should not be initiated before unstable conditions, such
as hypokalemia, hyperhydration, hypotonic dehydration, metabolic acidosis, and hemodynamic instability, are corrected. There
is no definitive available indication to define the ideal moment
to start PN infusion, except for critically ill patients, but still
without consensus between the available nutrition international
societys guidelines. For these patients, the European Society for
Clinical Nutrition and Metabolism (ESPEN) guidelines recommend starting PN after 2448 h in subjects, with EN intolerance,
who are not expected to achieve adequate nutrition within 3
days. On the other hand, ASPEN guidelines recommend PN
before reaching 8 days of hospitalization, with the exception of
patients who have malnutrition on hospital admission.
The infusion of PN is the individual responsibility of the
nursing staff, who must be trained to properly attend the
medical recommendations and follow the good hygiene protocols to ensure adequate and safe infusion. On both the first
and last day of PN infusion, a half of the prescribed volume
should be infused to allow metabolic, enzymatic, and hormonal adjustment and to avoid the occurrence of abnormalities, such as hyperglycemia and hypoglycemia, and electrolyte
disturbances, among others.

Monitoring
During the period of PN infusion, the treatment efficacy
should be monitored closely. PN is a complex procedure subject to complications that may jeopardize its benefits. The
occurrence of adverse events (mechanical, metabolic, and
infectious) and clinical changes that may require changes in
the PN formulation should be controlled during PN infusion.
In addition to specific laboratory tests to identify the risk of
metabolic complications (see the main population risk for

227

metabolic complications in Table 2, as well as the key laboratory tests to identify its risk in Table 3), it is necessary to
periodically observe the degree of patient hydration; clinical
signs of electrolyte disturbances; the occurrence of edema;
changes in consciousness level; the thermal curve; the number
Table 2
Main population risk for developing metabolic complications
related to parenteral nutrition

Population

Metabolic
complication

Main consequence

Patients undergoing
prolonged partial
fast, whose body
has adapted to the
use of free fatty
acids and ketone
bodies as energy
sources
Patients with preexisting diabetes or
significant
physiological stress

Hypophosphatemia
Hypomagnesemia
Hypokalemia

Refeeding syndrome,
with impairment of
hematologic,
neuromuscular, and
respiratory
functions

Hyperglycemia

Patients receiving
parenteral lipid
emulsions, either
alone or in 3-in-1
systems

Hypertriglyceridemia

Impairment of
immune functions,
with an increased
risk of infectious
complications
Development of
pancreatitis and
altered pulmonary
function

Table 3
Laboratory tests to measure the potential risk in developing
metabolic complications related to parenteral nutrition (PN)
Monitoring from the beginning of PN
Laboratory test

Stable patients

Critically ill patients

Sodium, potassium, and

chlorine
Ionized calcium,
phosphorus, and
magnesium
Glucose
Capillary blood glucose

Three times per

week
Twice weekly

Daily or at
physician criteria
Daily or at
physician criteria

Daily
Daily

At physician criteria
Each 6 hours or at
physician criteria
Daily
Twice weekly
Weekly
Weekly

Plasma osmolarity
Plasma urea and creatinine
Total protein and fractions
Total bilirubin and
fractions
Plasma ALT, AST, GGT,
and alkaline
phosphatase
Hemoglobin, hematocrit
pH and blood gas
Plasma triglycerides

Urinary glucose
Density or urine osmolality
Hydrous balance

Weekly
Weekly
Weekly

Twice weekly

Weekly or as
required

Weekly

Weekly when
using lipid
emulsion
46 times per day
24 times per day
Each 12 hours

Daily
Daily
Weekly

46 times per day

24 times per day
Each 6 hours

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Parenteral Nutrition

of bowel movements; the abdominal workup; the introduction

of nutrients; concomitant pharmacological treatments; signs of
PN intolerance; and anthropometric, hematological, and
hemodynamic changes, as well as functional changes in organs
and systems. Whenever possible, the urine-output monitoring
and calculation of water balance should be accessed.

Table 4

Table 4 summarizes the main PN-related complications,

with an emphasis on etiology, symptoms, treatment, and prevention. Complications associated with PN include the risk of
developing infections in the central venous catheter. The control of common infection symptoms, such local changes, leukocytosis, fever, and hyperglycemia, may support the early

Complications related to parenteral nutrition (PN)

Complications

Possible etiology

Symptoms

Treatment

Prevention

Inadequate catheter
insertion

Tachycardia, dyspnea,
persistent cough, and
diaphoresis

Catheter placement by
experienced professional

Air embolism

Air entering in central

venous system by
inadequate opening of the
infusion system

Cyanosis, tachypnea,
hypotension, and heart
murmur

Venous thrombosis

Mechanical vein trauma,

hypotension, highosmolality solution,
hypercoagulopathy,
sepsis, trauma

Edema or pain in neck, in

one or both arms, or in
shoulders

Small pneumothorax can

resolve spontaneously;
larger pneumothorax may
require a thorax drain
Immediately turn the patient
to his left side and lower
the headboard,
encouraging the air to
remain in the right
ventricular apex until
reabsorbed
Anticoagulation therapy with
urokinase or streptokinase;
remove CVC

Peripheral administration of
hypertonic solution
(osmolality
900 mOsm kg 1),
infiltration of venous
access
Improper CVC placement or
maintenance care;
contaminated solution

Redness, swelling, and

pain in peripheral
locations

Change the place of

peripheral access

Systemic fever, chills,

redness and swelling
around the site of
catheter insertion

Change the catheter

placement

Minimize osmolarity of
peripheral solution by using
lipids as the primary source
of calories and reducing the
addition of electrolytes and
other additives, if possible
Development of strict
protocols for CVC
placement and care

Rapid infusion of
concentrated glucose
solution, sepsis,
pancreatitis,
postoperative stress,
chromium deficiency,
steroid use, advanced age
Supply of lipids exceeds the
capacity of the
bloodstream
(>4 mg kg 1 min 1);
sepsis, multiple organ
failure, severe
hyperlipidemia
Excessive administration of
carbohydrates and/or
proteins in severely
malnourished patients

Blood glucose
>200 mg dl 1, metabolic
acidosis, polyuria,
polydipsia

Use insulin, reduce the

concentration of glucose in
NP

Start slowly and advance the

infusion of NP

Serum triglycerides
300350 mg dl 1 6 h
after beginning lipid
infusion; high triglyceride
levels in previously stable
patients (e.g., sepsis)

Decrease the volume and

time of lipid infusion;
simultaneous infusion with
glucose

Hyperlipidemia history before

NP infusion; avoid lipid
administration
>2.5 g kg 1 day 1 or
>60% of total calories

Excess carbohydrates, CO2

retention, cardiac
tamponade, hepatic
dysfunction
Excess protein; blood
urea nitrogen (BUN),
excessive nitrogen
excretion; high
BUN/creatine ratio

Reduction of excessive
supply of
carbohydrate/protein

Avoid excessive
administration of
carbohydrate/protein

Mechanical
Pneumothorax

Infectious
Phlebitis

Catheter-related
sepsis

Matabolic
Hyperglycemia

Hypertriglyceridemia

Refeeding syndrome

Placing and maintenance of

CVC and the extreme care of
the entire infusion system
by an experienced
professional

Silicone catheter use, addition

of heparin to PN when
possible, low-dose warfarin
therapy

Parenteral Nutrition

recognition of an infection episode related to the central

venous catheter, and compliance with best practice during
installation and the infusion of PN can reduce this risk.

Final Comments
Currently, PN therapy, for the specific treatment of malnourished patients who cannot use their oral and enteral routes for
nutrient supply, provides more benefit than harm when
performed according to the available guidelines. The new allin-one concept, in which nutrients are premixed in a single
bag, greatly promotes the safety, efficacy, tolerance, and convenience of PN. However, if done at the hospital pharmacy,
this preparation must be carried out on demand, due to the
limited stability of this mixture (24 h).
New commercial multichannel PN bags were designed to
overcome this limitation and to ensure the PN solution stability by separating its reactive components in different chambers.
The individual components of the PN are mixed in a closed
aseptic system only at the time of their use, through the breaking of the seals separating these chambers. It is noteworthy,
however, that multichannel PN formulations have the disadvantage of not being designed to meet every single patients
needs, mainly infants, in a personalized way, as traditional
formulations can be. Therefore, multichannel PN bags must
be used based on specific criteria.
PN therapy should not be seen as an emergency intervention and therefore must be designed to adequately meet the
individual energy and nutrient needs of patients. PN planning
and execution must be performed by qualified professionals
from the very beginning, meaning parenteral route access, to a
proper ending. Different clinical and biochemical markers
should be closely monitored for these professionals to avoid
potential mechanical, metabolic, and infectious complications
related to PN throughout the infusion period. They also must
consider the PN, for most patients, as a temporary treatment
that should be discontinued as soon as conditions for oral or
enteral diet reintroduction are achieved.

See also: Amino Acids: Determination; Amino Acids: Metabolism;

Carbohydrate: Digestion, Absorption and Metabolism; Diarrheal
Diseases; Dietary Fiber: Determination; Dietary Practices; Dietary
References: US; Energy: Intake and Energy Requirements; Energy
Metabolism; Fatty Acids: Determination and Requirements; Fatty Acids:
Essential Fatty Acids; Fatty Acids: Fatty Acids; Fatty Acids: Metabolism;
Fish Oils: Composition and Health Effects; Malnutrition: Concept,

229

Classification and Magnitude; Malnutrition: Prevention and

Management; Nutrition and Infection; Protein: Digestion, Absorption
and Metabolism; Protein Quality and Amino Acids in Maternal and
Child Nutrition and Health; Protein: Requirements; Proteins: Chemistry,
Characterization, and Quality; Storage Stability: Mechanisms of
Degradation; Storage Stability: Shelf Life Testing; Vitamins: Overview.

Further Reading
Boullata J, Gilbert K, Sacks G, et al. (2014) A.S.P.E.N. clinical guidelines: parenteral
nutrition ordering, order review, compounding, labeling, and dispensing. Journal of
Parenteral and Enteral Nutrition 38(3): 334377.
Bozzetti F, Gavazzi C, Miceli R, et al. (2000) Perioperative total parenteral nutrition in
malnourished, gastrointestinal cancer patients: a randomized, clinical trial. Journal
of Parenteral and Enteral Nutrition 24(1): 714.
Braga M, Ljungqvist O, Soeters P, Fearon K, Weimann A, and Bozzetti F (2009) ESPEN
guidelines on parenteral nutrition: surgery. Clinical Nutrition 28(4): 378386.
Casaer MP, Mesotten D, Hermans G, et al. (2011) Early or late parenteral nutrition in
critically ill adults. New England Journal of Medicine 365(5): 506517.
Dhaliwal R, Cahill N, Lemieux M, and Heyland D (2013) The Canadian critical care
nutrition guidelines in 2013: an update on current recommendations and
implementation strategies. Nutrition in Clinical Practice 29(1): 2943.
Dudrick S (2003) Early developments and clinical applications of total parenteral
nutrition. Journal of Parenteral and Enteral Nutrition 27(4): 291299.
Guglielmi F, Boggio-Bertinet D, Federico A, et al. (2006) Total parenteral nutritionrelated gastroenterological complications. Digestive and Liver Disease 38(9):
623642.
McClave S, Martindale R, Vanek V, et al. (2009) Guidelines for the provision and
assessment of nutrition support therapy in the adult critically ill patient: Society of
Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral
Nutrition (A.S.P.E.N.). Journal of Parenteral and Enteral Nutrition 33(3): 277316.
Simpson F and Doig G (2004) Parenteral vs. enteral nutrition in the critically ill patient:
a meta-analysis of trials using the intention to treat principle. Intensive Care
Medicine 31(1): 1223.
Singer P, Berger M, den Berghe V, et al. (2009) ESPEN guidelines on parenteral
nutrition: intensive care. Clinical Nutrition 28(4): 387400.
Staun M, Pironi L, Bozzetti F, et al. (2009) ESPEN guidelines on parenteral nutrition:
home parenteral nutrition (hpn) in adult patients. Clinical Nutrition 28(4): 467479.
Van Gossum A, Cabre E, Hebuterne X, et al. (2009) ESPEN guidelines on parenteral
nutrition: gastroenterology. Clinical Nutrition 28(4): 415427.
Waitzberg D, Torrinhas R, and Jacintho T (2006) New parenteral lipid emulsions for
clinical use. Journal of Parenteral and Enteral Nutrition 30(4): 351367.

Relevant Websites
http://www.espen.org/ ESPEN - The European Society for Clinical Nutrition and
Metabolism.
http://www.nutritioncare.org/About_Clinical_Nutrition/What_is_Parenteral_Nutrition/
ASPEN - The American Society for Parenteral and Enteral nutrition.
https://www.nutritioncare.org/ ASPEN - The American Society for Parenteral and
Enteral Nutrition.