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138 C. di Venosa
The onset of EN can occur regardless of the presence of bowel sounds, unless
ischemia or intestinal obstruction is suspected, as they only give us information on
contractility and are not necessarily related to the integrity of the mucosa, its barrier
function, or absorption capacity [
6]. In this situation, EN could lead to a more rapid
recovery of bowel sounds, fewer vomiting episodes and a shorter intensive care and
hospital stay [7 ].
EN can also be administered during treatment with vasopressor agents at small or
moderate, chronic and stable or decreasing doses, always balancing the potent ial
benefit of early EN against the associated risk due to a high frequency of food
intolerance [
8–12].
There are certain conditions where the initiation of enteral nutrition (EN) should
be delayed until the underlying issues are addressed. In patients with uncontrolled
shock (norepinephrine >1 μg/kg/min) and persistent failure to meet hemodynamic
and tissue perfusion goals (evidenced by persistent hyperlactatemia), the initiation of
EN should be deferred. It is crucial to prioritize the resolution of life-threatening
hypoxemia, hypercapnia, or uncontrolled acidosis before considering the commencement of enteral nutrition. EN initiation should only be contemplated under
conditions of stable hypoxemia and compensated or permissive hypercarbia and
acidosis. This cautious approach ensures that the patient’s immediate physiological
needs are addressed and stabilized before introducing enteral nutrition [13]. In the
presence of active upper gastrointestinal bleeding, resumption of enteral nutrition
(EN) can only occur after the bleeding has stopped. This approach helps reduce the
risk of stress ulcers. For patients with overt intestinal ischemia (occlusive or
non-occlusive), intestinal obstruction (mechanical ileus), abdominal compartment
syndrome, or high-flow intestinal fistula where obtaining distal access to the fistula is
not possible, EN must be suspended.
If a single large volume of gastric aspirate exceeding 500 ml/6 h is detected, the
administration of prokinetics (such as metoclopramide or erythromycin) and
reassessment should be initiated. If the issue persists, postpyloric administration,
rather than prolonged suspension of EN, should be considered.
The use
of neuromuscular blocking agents should not automatically preclude
EN. However, an increased degree of intolerance should always be considered in
deeply sedated patients, whether or not neuromuscular blocking agents are concurrently used. Regular monitoring and adjustments to the nutritional plan may be
necessary to ensure optimal tolerance and safety in these cases [9]. During therapeutic hypothermia, EN can be started at low doses given that energy metabolism
could be significantly reduced with the prevention of shivering [14, 15]; tolerance
to EN is reduced but improves during rewarming [16] phase in which it is possible to
increase the dose administered [9]. Even in the prone position, EN does not need to
be delayed as gastric emptying does not appear to be significantly affected by this
position nor has there been an increase in adverse events in most studies [17–19].
13 Enteral Nutrition Overview and Formula Selection Considerations 139
Components of Enteral Mixtures
The main energy substrates that make up EN mixtures are carbohydrates and lipids
associated with proteins but the content of macro and micronutrients differs between
the various formulations.
Carbohydrates in general they have to cover 50–60% of total energy during
nutritional support and are provided in the form of starches, maltodextrins, disaccharides, and monosaccharides [20]. They are the preferential substrate for energy
production used by many cells in the body, but in critical illnesses stress induces
insulin resistance and hyperglycemia [3].
A maximum rate of glucose infusion has been identified which must not exceed
5 mg/kg/min (0.25–0.3 g/Kg/h), beyond which there are no physiologically significant increases in protein synthesis and of direct oxidation of glucose. Furthermore,
there is a physiological cost to exceeding the optimal glucose infusion rate, as
indicated by increased lipogenesis with increased CO
representing an additional stressor, and by large fat deposits in the liver at autopsy in
patients infused with large quantities of glucose [21].
Lipids play a crucial role in enteral nutrition due to their high caloric content,
serving as a concentrated source of energy. They offer several benefits, allowing for
a reduction in the amount of carbohydrates required as part of nutritional support.
Lipids provide essential fatty acids, serve as the building blocks of cell membranes,
and can modulate metabolic processes at various levels.
The rate of lipid oxidation is influenced not only by energy expenditure but also
by the hormonal state, the clinical situation, and the presence of other energy
substrates, particularly glucose. The intake of lipids should be tailored to cover
20–40% of energy expenditure, taking into account individual tolerance and the
specific clinical circumstances of the patient. This personalized approach ensures
optimal nutritional support and helps meet the energy needs of the critically ill
individual. Regular monitoring and adjustments may be necessary to maintain a
balance and address the dynamic nature of the patient’s met abolic state [22]. They
are present in the mixtures as long-chain triglycerides (LCT), vegetable oils (corn,
sunflower, soybean, coconut, rapeseed, olive), and medium-chain triglycerides
(MCT) often emulsified with soy lecithin. MCTs are a source of medium chain
saturated fatty acids usually derived from coconut oil, they are a good source of
energy while not affecting blood triglyceride levels. They are ketogenic, protein
sparing, and relatively resistant to peroxidation. They do not appear to compromise
liver, immune, or lung function; however, rapid infusion of this lipid emulsion in
patients with acute respiratory distress syndrome may cause deterioration of lung
function and hemodynamics [
Proteins play
a critical role in enteral nutrition, significantly influencing a
23]
.
patient’s clinical recovery and, consequently, the length of hospital stay. When
selecting an enteral mixture, it is essential to assess the protein content in terms of
quantity, quality, and the form in which the proteins are present.
production during infusion,
2
140 C. di Venosa
The caloric intake from proteins typically ranges between 16% and 20% of total
calories. Protein quality is a key factor that affects tolerance, the rate of absorption,
and protein utilization. It is determined by the relative amounts of essential and
nonessential amino acids and the presence of branched-chain amino acids (BCAAs)
for achieving an adequate amino acid balance.
Whey proteins stand out as the most complete protein source because they
contain all essential and non-essential amino acids. Additionally, whey proteins
are rich in BCAAs (valine, leucine, and isoleucine) and sulfur-containing amino
acids (cysteine and methionine). These components contribute to antioxidant properties and improve immune function, enhancing the overall nutritional support
provided by enteral mixtures. The careful consideration of protein quantity and
quality ensures an optimal nutritional profile tailored to the specific needs of the
critically ill patient. Regular monitoring and adjustments may be necessary to adapt
to the dynamic nature of the patient’s clinical condition.
The source of proteins is a crucial consideration in enteral nutrition, with milk or
egg proteins exhibiting greater biological value (BV), protein efficiency ratio (PER),
net protein utilization (NPU), and protein digestibility-corrected amino acid score
(PDCAAS) compared to plant proteins. These metrics indicate the quality and
efficiency of protein utilization by the body.
Proteins in an enteral mixture can be present in various forms, including whole,
concentrated, isolated, hydrolyzed, or as free amino acids. The degree of hydrolysis,
which refers to the extent of protein breakdown into smaller peptides or amino acids,
can impact osmolarity, flavor, absorption, and tolerance of the mixture. However,
it’s important to note that increasing the level of protein hydrolysis also raises the
costs of the mixture. Therefore, hydrolyzed proteins or amino acids should be
administered judiciously and reserved for specific cases, such as severe pancreatic
insufficiency or significantly impaired intestinal absorption. This ensures that the
nutritional support provided aligns with the individual needs and tolerances of the
patient while considering cost-effectiveness. Regular assessment and adjustments
based on the patient’ s response and clinical condition contribute to the overall
success of enteral nutrition [
Vitami
ineral salts, and trace elements are present in the mixtures in quan-
ns, m
24].
tities such as to meet the daily needs according to the Reference Intake Levels of
Nutrients and Energy (LARN) or Recommended Daily Allowance (RDA) for a
minimum quantity of the mixture capable of providing 1200–1500 Kcal. Patients’
needs should be assessed based on deficiencies related to their particular condition
and integrated if necessary. Generally all the hydro and fat-soluble vitamins are
present [20]
The fib
.
ers, when present, affect the density of the mixture. Fermentable fiber
(particularly partially hydrolyzed guar gum PHGG) is effective in preventing and
reducing EN-induced diarrhea in post-surgical patients and in fully resuscitated and
hemodynamically stable critically ill patients. Insoluble fiber should be avoided in all
critically ill patients. Both soluble and insoluble fiber should be avoided in patients at
high risk of intestinal ischemia or severe dysmotility (Table 13.1). An intake of
15–30 g/d of fiber is recommended for patients receiving EN [24].
13 Enteral Nutrition Overview and Formula Selection Considerations 141
Table 13.1 Fibers classification
Soluble
• Acacia gum
• PHGG
• Inulin
• FOS
• Pectin
• Hemicellulose A
• Oat fiber
Insoluble
• Cellulose
• Soy polysaccharide
• Resistant starch
• Hemicellulose B
Table 13.2 Classification of mixtures based on degree of hydrolysis of the substrates
Nutrients Polymeric Oligomeric Monomeric
Carbohydrates Polysaccharides
Oligosacchardes
Maltodextrins
Proteins Polypeptides
Complex proteins
(casein, soy, lactalbumin,
etc.)
Lipids LCT
MCT (rare)
Minimal demolition Maximum demolition
Fibers Sometimes present Always absent Always absent
Micronutrients Second LARN o
Osmolarity Isosmolar
(200–300 mOsm/L)
Palatabilty Acceptable Poor Very
Cost Low High Very high
Fermentable
• Acacia gum
• PHGG
• Inulin
• FOS
• Soy polysaccharide
• Resistant starch
• Pectin
Nonfermentable
• Cellulose
• Outer pea fiber
3—saccharides
2—saccharides
Mono- saccharides
3—peptides
2—peptides
Free amino acids
LCT
MCT
RDA Second LARN o
RDA
Hyper-osmolar
(400–700
Nonviscosus
• Cellulose
• Outer pea fiber
• Soy polysaccharide
• Resistant starch
• PHGG
• Inulin
• FOS
Viscosus
• Pectin
• Some gums (e.g., guar gum)
Mono—saccharides
Free amino acids
MCT
Second LARN o
RDA
mOsm/L)
Hyper-osmolar
(500–900 mOsm/L)
bad
Classification of Mixtures
The enteral mixtures currently on the market can be classified based on some
important factors:
• Degree of hydrolysis of the substrates
• Caloric intake
• Protein intake
The degree of
polymeric, oligomeric, or semielemental and monomeric or elemental. They are all
lactose and gluten free (Table 13.2).
hydrolysis of the substrates differentiates enteral mixtures into
142 C. di Venosa
Table 13.3 Classification of mixtures based on caloric intake and protein intake
Formulas: range
[median] Standard High-calories Hyperprotein
kcal/ml 1–1.1 [1] 1.2–2 [1.5] 1–1.52 [1.3] ± dense
Proteins % kcal g/l 15–20 [15.9] %
Lipids % kcal /g/l 25–28%
CHO % kcal /g/l 47–56%
mOsm/l 200–285 275–487 270–600
Na mEq/l 30–58 25–65 21–76
K mEq/l 35–44 31–58 32–76
Cl mEq/l 21–43 21–52 11–45
Mg mEq/l 12–22 12–37 12–35
mEq/l 35–46 33–60 31–62
Ca
P mMol/l 26–50 31–70 31–70
Oml % 80–85 71–80 75–85
H
2
38–50 [40] g/l
28–35 g/l
123–145 g/l
15–20 [18] %
55–100 [62] g/l
25–45%
37–100 g/l
35–54%
120–204 g/l
20.5–37%
53–100 g/l
14–35%
15–65 g/l
31–64%
73–183 g/l
Polymeric mixtures contain macronutrients in whole form, their administration
presupposes uncompromised digestive and absorption activity. Carbohydrates are
made up of polysaccharides, oligosaccharides, or maltodextrins. Lipids are derived
from vegetable oils containing LCT rich in essential fatty acids (linoleic and
linolenic), and rarely from MCT. The protein component is made up of polypeptides
or complex proteins derived mainly from casein, lactalbumin, soy, and egg. They are
complete with micronutrients and some may contain fibers (soluble and insoluble).
They are isosmolar (200–300 mOsm/L).
Oligomeric or semi-elemental mixtures contain macronutrients in partiall y
hydrolysed form which require minimal digestive processes so they are rapidly
and completely absorbed. Carbohydrates are in the form of oligo or monosaccharides, lipids are present as LCT and MCT, and proteins as tripeptides, dipeptides, and
some free amino acids. They do not contain fiber. They are hyperosmolar
(400–700 mOsm/L). The use of these formulations is recommended in patients
with persistent diarrhea, with suspected malabsorption or lack of response to
fiber [4].
Monomeric or elemental blends contain macronutrients in hydrolyzed form.
Carbohydrates are present as monosaccharides, lipids as MCTs, and proteins as
free amino acids. They do not contain fiber. They have a very high osmolarity
(500–900 mOsm/L) and the cost is very high [20].
Based on the ratio between macronutrients and the variations in caloric and
protein intake, the enteral mixtures were classified and listed on a functional basis
(Table 13.3).
The stand
ard formulas guarantee a physi ological caloric distribution (1 kcal/ml)
between proteins, carbohydrates, and lipids (kcal/gN, kcal np/gN and CHO/lipids),
13 Enteral Nutrition Overview and Formula Selection Considerations 143
the electrolyte content is generally low, the vitamins are standard, and they are
isoosmolar.
High-calorie formulas are concentrated formulas (>1 kcal/ml) obtained by
increasing the lipid quota and reducing the percentage of water, variable CHO/lipid
ratio and osmolarity, protein content more or less similar to the standard ones,
electrolyte range more variable than the standard diet, and lower water content.
High-protein formu
las guarantee a higher protein intake than others, and they can
be normal or high-calorie (kcal/ml and very variable CHO/Lipid ratio), with a wider
electrolyte and water range than the standard diet.
In all these mixtures, the ratio of non-protein Kcal/g of nitrogen is very variable,
42:1 in some oligomeric formulas to 224:1 in some high-calorie formulas. A
from
ratio of 150:1 to 200:1 is considered an adequate intake for stable patients, but for
patients who are critically ill or tend to lose muscle mass, a ratio of 100:1 or less may
be optimal.
Specific Mixtures for Organ Failure
There are mixtures on the market which, due to the addition of particular nutrients
and/or variations in the composition of macronutrients or micronutrients, are specific
for organ failure (renal with or without dialysis treatment, pulmonary, hepatic) or
pathologies such as diabetes in how much their nutritional profile takes into account
the particular metabolic dysfunctions and demands of these organs (Table
Low-electrolyte, low-volume formulas may be used in a small percentage of
patients, more for physiological benefits, such as in renal failure.
13.4).
Table 13.4 Specific mixtures for organ failure
Protein intake Lipids CHO
Nitrogen
g/L
6,4
Kidney failure 4,8 30 6– 43–45 40–
Dialysis patients 11,2 70 14–
Chronic pulmonary
insuf
ficiency
Liver failure 6,4 40 12 33–40
10 62,5 16,5 50–55
Proteins
g/L
40
%
kcal
% kcal
16
33
–
18 51 14–20 g/L
15
–49
8
43–51 40–
(20–30%
MCT)
(35
–50%
MCT)
Caloric
intake
%
kcal
kcal/mL
33
0,9
–
2 Low
51
2 Low
51
28 1,3-1,5 EPA, Vit.E,
33–
1–1,3 BCAA
50
–1
Other
nutrients
FiberDiabetics
electrolyte
electrolyte
Taurine,
C
ω-3, GLA
(36–44%
of total
proteins)
144 C. di Venosa
Special high-fat, low-carbohydrate formulations designed to manipulate respira-
tory quotient and reduce CO
production should not be used in intensive care
2
patients with acute respiratory failure. Rather, care should be taken to prevent total
caloric intake from exceeding energy needs, since CO
production increases signif-
2
icantly with lipogenesis and may be poorly tolerated in patients prone to CO
retention [6].
For patients with acute respiratory failure, calorically dense formulations could be
considered when it is necessary to avoid fluid accumulation and pulmonary edema
common in this type of patients [25].
In patients with diabetes, glycemic control can be facilitated by the use of specific
enteral formulas with a defined nutritional composition consisting of modified
maltodextrin, fructose, fiber, monounsaturated fatty acids (MUFA), soy proteins,
and antioxidants.
Compared to standard formulas, they are typically richer in fat (40–50% of
energy, with a large contribution of MUFA, e.g., >60% fat), with a lower carbohydrate content (approximately 35–40% of energy) and up to 15% energy from
fructose. These nutrients may facilitate glycemic management by delaying gastric
emptying (fat and fiber), delaying intestinal absorption of carbohydrates (fiber), and
producing smaller glycemic responses (fructose). However, particularly formulas
containing a high percentage of fructose should be administered with some caution
to critically ill patients, who are at risk of lactic acidosis [7].
2
Choice of the Enteral Mixture
An important criterion for choosing a mixture for EN must always be linked to the
clinical and metabolic state of the patient, the estimate of needs, and the possible
poor tolerability of fluid intake. When initiating EN in the critical care setting, it is
recommended to start with a standard polymer formula and avoid the routine use of
all specialty formulas in critically ill patients in a medical intensive care unit (MICU)
and disease-specific formulas in surgical intensive care unit (SICU).
For most ICU patients, a standard isoosmolar polymer formula is appropriate and
well tolerated. Once gastric function has been tested, you can move on to diets of
different composition, if indicated.
A structured approach will allow you to provide nutritional support tailored to the
patient.
Oligo o
compromised, allowing faster absorption of macronutrients.
The admin
to increase calorie intake in patients with gastrointestinal dysfunction, reduce volumes in patients with inability to tolerate full volume isocaloric EN or who require
fluid restriction. However, attention must be paid to the greater osmolarity and
higher lipid content of these formulations which can further compromise delayed
gastric emptying through neurohumoral feedback mechanisms and can cause
onomeric mixtures can be used if gastrointestinal function is
r m
istration of a high-calorie formulation is indicated when there is a need
13 Enteral Nutrition Overview and Formula Selection Considerations 145
diarrhea through the stimulation of liquid secretion in the small intestine. Furthermore, the administration of high-energy nutrition at a slower rate may have the
unintended consequence of lower water and protein intake [8].
High-protein formulations can be used in the stable phase
progressive increase in protein administration since a time-dependent effect of
protein intake has been observed in critically ill patients [
of amino acids improves with time, leading to an increase in protein production of
the whole body only after the first period of the acute phase, increasing further in the
post-acute phase [3].
A high-protein isocaloric formula can be administered to obese patients, in whom
protein intake must be guided by urinary nitrogen losses or determination of lean
body mass [2].
of critical illness with
26]. In fact, the conversion
Special Composition Formulas
There are special formulas on the market enriched with substances with immunomodulatory, anti-inflammatory, and antioxidant effects.
Immunomodulatory formulas enriched with arginine, nucleotides, and omega-3
fatty acids are superior to standard enteral formulas in some patient groups, such as
patients undergoing upper gastrointestinal surgery, trauma (head trauma), and
patients with mild sepsis. However, they are not recommended in patients with
severe sepsis, in whom an immunomodulatory formula may be harmful, and they
should not be used routinely in the MICU.
Other special formulations are those enriched with fish oil (FO) with antiinflammatory and immunomodulatory effects which confer further clinical benefits,
particularly in SICU patients, especially if administered in the perioperative period
to reduce the rate of complications and length of stay in intensive care and hospital.
Enteral formulations characterized by an anti-inflammatory lipid profile (omega3-rich FO, borage oil) and antioxidants should be considered for critically ill patients
with acute respiratory distress syndrome (ARDS) and severe acute lung injury
(ALI) [23].
Conclusions
In the nutritional treatment of critically ill patients, it is essential to recognize that not
only the nutritional aspect is being addressed but also that metabolic alterations are
monitored. Therefore, the patient’s current metabolic state must be assessed regularly. This emphasizes the importance of meticulously checking the composition of
the administered mixtures.
When selec
first. In most cases, enteral nutrition (EN) is a feasible option. Initiate EN with the
ting the route of administration, prioritize the most physiological route
146 C. di Venosa
simplest standard solutions and, if necessary, progress to more complex formulations
with a special composition tailored to the pathology. This approach ensures a careful
and stepwise adjustment of nutritional support based on the patient’s evolving needs
and condition.
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