Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5224_Библиотеки_им_академика_М_И_Перельмана.pdf
230 C. Iacovazzo et al.
Since hypermetabolism in one of the factors most affecting energy requirements,
the most accurate tool to estimating energy requirements is indirect calorimetry;
however, predictive equations are still often used. Initial estimates of energy expenditure in burn patient provide a particular challenge due to the heterogeneity of the
metabolic response. Even more challenging is the determination of protein needs.
Once the nutritional targets have been calculated, other key aspects such as the
timing, composition, and route of administration of nutritional support to this patient
population are of paramount importance. Eventually, given the hyperinflammatory
response, the modulation of immune system activity with specific nutrients, termed
immunonutrition, has shown beneficial effects. Three potential targets have been
identified for immunonutrition: mucosal barrier function, cellular defense, and local
or systemic in flammation.
The following paragraphs will present the main pathophysiological aspects of
these severe conditions, and the key elements to supply a practical approach,
according to the major recommendations currently available.
Specific Considerations for Patients with Burn Injury
While several aspects of nutrition therapy are similar in major burns and other
critical care conditions, the pathophysiology of burn injury with its major endocrine,
inflammatory, metabolic, and immune alterations requires some specific nutritional
interventions.
Major burn injuries, i.e., those affecting more than 20% total burn surface area
(TBSA) with or without inhalation injury, represent a specific condition when
compared to the general intensive care pathologies. Critically ill burned patients
are characterized by a strong oxidative stress, an intense inflammatory response, and
a prolonged months-long hypermetabolic and catabolic response, all of which are
proportional to the severity of injury [1 ].
Severe b
increased metabolic rate that can persist for years after injury. Trauma and sepsis also
result in hypermetabolism, although to a much lesser degree and for a significantly
shorter duration [2]. This hypermetabolic state reflects an increase in whole-body
oxygen consumption >10% above normal [3]. In the acute postburn injury phase,
patients with a burn that covers greater than 40% TBSA have a REE between 40%
and 100% above normal [4, 5]
support the significantly increased metabolic needs of the patient as unchecked
hypermetabolism results in an enormous loss of lean muscle mass, immune compromise, and delayed wound healing.
The underlying mechanisms of this vast metabolic, hormonal, and inflammatory
dysregulation are still being actively investigated. At a cellular level, increased
whole-body oxygen consumption supports greater ATP turnover and thermogenesis.
ATP-consuming reactions represent an estimated 57% of the hypermetabolic
response to burns, including ATP turnover for protein synthesis, ATP production
ause a profound pathophysiological stress response and a radically
urns c
t is important to mitigate this stress response and
. I
21 Nutrition in Trauma and Burns 231
for hepatic gluconeogenesis, and the cycling of glucose and fatty acids [6]. Because
ATP turnover does not completely account for burn-induced hypermetabolism, it
implies that mitochondrial oxygen consump tion exceeds ATP production after
severe burn. This likely occurs via the uncoupling of mitochondrial respiration
from ADP phosphorylation resulting in heat production [
by the finding that uncoupling protein-1, the principal mediator of thermogenesis, is
more abundant in the adipose tissue of burn patients compared to healthy individuals
8, 9].
[
Nutrition therapy constitutes an inte
of the initial resuscitation [1]. Nutritional support must be individualized, monitored,
and adjusted throughout recovery. Adequate and prompt nutrition is extremely
important for preventing numerous complications, although nutrition has a complex
relationship with the hypermetabolic state.
gral part of the treatment, from the early start
7]. This theory is supported
Timing and Route of Nutritional Support
Time-to-treatment, including time-to-nutrition, is an important factor for patient
outcome after severe burn. Resuscitation of the severely burned patient can have
profound detrimental effects on the gastrointestinal tract. Large volume crystalloid
resuscitation can cause intestinal edema, potentially leading to paralytic ileus and the
mucosal damage, and resultant increased intestinal permeability allows for bacterial
translocation and decreased nutrient absorption. Enteral nutritional support should
be initiated within 2 h of injury [2, 10]. At the start, enteral feeding is initiated in a
continuous and low volume manner with slow titration to the goal to ensure patient
tolerance.
Early enteral nutrition has been shown to decrease circulating catecholamines,
cortisol, and glucagon and preserve intestinal mucosal integrity, motility, and blood
flow [11]. Early enteral feeding in humans has also shown to result in improved
muscle mass, wound healing, decreased risk of Curling ulcer formation, and shorter
ICU stay [12].
On the other side, parenteral nutrition (PN), alone or in conjunction with EN, is
associated with overfeeding, liver dysfunction, decreased immune response, and
threefold increased mortality [13]. PN also appears to increase the secretion of
proinflammatory mediators, including TNF, and also can aggravate fatty infiltration
of the liver [14].
The superi
accepted, and a parenteral route should only be used in burn patients with contraindication to enteral feeding [15].
ority of enteral nutrition over parenteral nutrition is unanimously
232 C. Iacovazzo et al.
Initial Assessment of the Burn Patient
From a nutritional standpoint, the initial assessment should comprise the evaluation
of nutritional status, and the determination of calorie and protein needs. Since the
intravascular concentration of any molecule reflects the balance hepatic synthesis,
distribution, and degradation, which are all simultaneously and variably altered in
burns, the utility of the measurement of visceral proteins, such as albumin,
prealbumin, transferrin, and fibronectin is limited. The negative nitrogen balance
(from 5 to -30 g/day) reflects the significant protein catabolism.
Estimation of Energy Expenditure
The primary goal of nutritional support in burn patients is to fulfill the increased
caloric requirements caused by the hypermetabolic state while avoiding overfeeding.
The gold standard for establishing caloric needs is indirect calorimetry. In the
absence of such equipment, various formulas can be used, the most accepted of
which for major burn patients is the Toronto formula [10]:
EE =-4343 þ 10:5
þ 0:84
þ 114
*
Unadjusted Harris - Benedict½
*
rectal temperature ° CðÞ½]– 4:5*day post - burn½ :
*
%TBSA½]þ 0:23*caloric intake½
]
]
]
Macronutrients and Micronutrients
Proteins
In critically burn patients,
proteins to maintain lean body mass. Predicted protein requirements are 1.5–2.0 g/
kg/day for burned adults and 2.5–4.0 g/kg/day for burned children [16].
rotein s
The p
ource must be chosen with particular attention, since gastrointestinal
intolerance is common. It is therefore necessary to choose a type of protein with high
biological value while at the same time high enteral tolerability.
In the
acute phase or during sepsis, whey proteins are preferred over caseinates or
proteins with a lower biological value such as soy or other legumes [
“fast” proteins thanks to their speed of absorption and lack of precipitation under
acidic conditions, whey proteins are more effective in promoting muscle growth
[17, 18], given their high content in leucine and the consequent positive effects on
muscle trophism [19]. Whey proteins are also more effective in reducing hyperglycemia and increasing the insulin response [
it is extremely important to provide the correct amount of
10]. Defined as
20].
Furthermore, their high cysteine
21 Nutrition in Trauma and Burns 233
content (the limiting amino acid for the synthesis of glutathione) gives them antioxidant properties, promoting the clearance of free-radicals, and modulation of the
inflammatory state and the immune response [21]. In case of gastrointestinal intolerance and gastric residual, it is preferable to prefer small peptides such as protein
hydrolysates.
In the recovery phase, it is preferable to
choose protein mixtures enriched with
immunonutrients in order to promote healing and immunocompetence.
Carbohydrates
Carbohydrates are the favored energy source for burn patients as high-carbohydrate
diets promote wound healing and may exert a protein-sparing effect. Current evidence recom mends a blood glucose target of 80–140 mg/dL for critically ill, burned
patients (which is increased to 110–180 mg/dL for diabetic patients).
Since hypoxemia, poor perfusion, and tissue edema can alter the results of
capillary point-of-care tests, blood sampling is generally recommended. Diets rich
in carbohydrates with a low glycemic index and proteins promote the reconstitution
of lean mass by increasing protein synthesis and releasing endogenous insulin
[22]. If glucose is given in excess of what can be utilized, it leads to hyperglycemia,
the conversion of glucose to fat, glucosuria, dehydration, and respiratory failure [22].
Fat
It is now widely recognized that essential fatty acids play a key role in the inflammatory response, immune function, and blood coagulation. Changes in the amount
of ω6 and ω3 fatty acids can modulate inflammation and the body immune response,
as ω3 fatty acids reduce the production of inflammatory cytokines and eicosanoids
by competing with arachidonic acid as a substrate for eicosanoids and, indirectly,
altering the expression of inflammatory genes. Thus, n-3 PUFAs are potentially
useful anti-inflammatory agents and may produce beneficial effects in critically burn
patients. It is recommended [10, 23]
obtain a ω6/ω3 ratio >0.70. phase. In a
to
prospective randomized study on 92 burn patients, ω3 supplementation led to a
lower incidence of severe sepsis and septic shock compared to the control
group [24].
Vitamin
The meta
s a
nd Trace Elements
bolism of numerous micronutrients is beneficial after burn as they are
important in immunity and wound healing. Severe burn leads to an intense oxidative
stress, which combined with the substantial inflammatory response adds to the
depletion of the endogenous antioxidant defenses, which are highly dependent on
micronutrients [25]. Vitamin A decreases time of wound healing via increased
234 C. Iacovazzo et al.
epithelial growth, and vitamin C helps collagen creation and cross-linking [26]. Vitamin D is deficient after burns [27], but its exact role and optimal dose remains
unclear [28]. The trace elements Fe, Cu, Se, and Zn are imp ortant for cellular and
humoral immunity, but they are lost in large quantities with the exudative burn
wound losses. Cu is crucial for wound healing and collagen synthesis [29]. Zn is
critical for wound healing, lymphocyte function, DNA replication, and protein
30]. R
synthesis [
the morbidity of severely burned patients [2].
eplacement of these micronutrients has been shown to improve
Immunonutrients
Arginine
L-arginine is an indispensable amino acid; it is part of the urea cycle which is
converted into citrulline, ornithine, and agmatine. It is synthesized endogenously,
but its additional intake is essential during the growth phases and after an injury,
including burns. After trauma, the activation of arginase-1 causes a further reduction
in the availability of arginine, which becomes then conditionally essential. Each
gram of diet ary protein provides approximately 54 mg of arginine. The administration of arginine exerts numerous effects: it improves blood flow, stimulates the
release of growth hormone and insulin-like growth factor-1 (both improving
healing), promotes vasodilation and improves perfusion through the production of
NO, stimulates the proliferation of T-lymphocytes, and increases the levels of
hydroxyproline, the main precursor of collagen, therefore playing an important
role in wound healing [30–34]. The use of arginine in sepsis is controversial and
currently not recommended, because it acts as an intracellular substrate for nitric
oxide, which causes vasodilation.
Nucleotides
Nucleotides support the replication of rapidly dividing cells of the immune system,
such as T-lymphocytes, by providing a source of purine and pyrimidine bases for
DNA/RNA production; similarly, they promote the regeneration of intestinal villi
and are often administered alongside other substrates such as arginine and omega-3
fatty acids to support rapidly turning cells.
Clinical studies
and demonstrated an improved outcome of critically ill, trauma/burn patients [35]. In
a multicenter, prospective, double-blind RCT on 296 critically ill trauma patients,
early enteral immunonutrition (arginine, RNA, and ω3 fatty acids) reduced hospital
stay and the incidence of infectious complications [36].
have evaluated nutritional formulations containing nucleotides
21 Nutrition in Trauma and Burns 235
ω3 Fatty Acids
Cyclooxygenase-mediated fatty acid metabolism is significantly increased in burn
patients and leads to an increased production of pro-inflammatory prostaglandins
(such as PGE and thromboxanes). These can cause immunosuppression and vasoconstriction which further adds to the already occurring immunosuppressed and
reduced wound perfusion of severely burn patients.
The administration of ω3 fatty acids can be helpful since they modulate the
synthesis of cytokines by reducing the product ion of pro-inflammatory/
immunosuppressive mediators; the reduced synthesis of inflammatory prostaglandins leads to a lower induction of arginase-1, which in turn can lead to greater
availability of arginine [
A meta-analysis conducted on 35 clinical trials for a total of 3438 patients showed
how arginine supplementation reduced infectious complications (-41%, p < 0.001)
and hospital stay (-2.38 days, p < 0.001). Immunonutrition based on arginine,
nucleotides, and omega-3 fatty acids reduces the risk of infections by 50% compa red
to standard enteral nutrition [38].
Glutamine
Glutamine is an essential amino acid with numerous functions: it is an important
element for the biosynthesis of ATP, it promotes the integrity of the intestinal
mucosa and stimulates the proliferation of cell s with rapid turnover, and it counteracts the production of pro-inflammatory cytokines. According to the ESPEN 2019
Guidelines [39], enteral glutamine supplementation (0.3–0.5 g/kg/day) is
recommended in burn patients with >20% of TBSA. Supplementation must be
started as soon as possible and maintained for 10–15 days. Nevertheless, studies
of glutamine supplementation in major burn patients are limited; Mamhoud et al.
[40] in a prospective, double-blind, placebo-controlled study on adults with major
burns (30–50% TBSA) demonstrated how enteral supplementation with glutamine
and ω3 fatty acids lowered the incidence of infections and hospital stay.
11, 16, 37].
Monitoring of Nutritional Support
The overall goal of nutritional support is to reestablish normal body composition and
metabolic equilibrium, and commonly measured variables include body weight,
nitrogen balance, imaging of lean body mass, and measurement of serum proteins.
Body weigh
citation routinely adds >10–20 kg, and patients can have increased total body water
for weeks after injury, which can mask the concomitant loss of lean body mass.
Nitrogen balance is an important part of monitoring nutritional support for burn
t can be misleading in severely burn patients: the initial fluid resus-
236 C. Iacovazzo et al.
patients, while measurement of serum proteins such as albumin and prealbumin is
often limited.
Nutritional Support for Trauma Patients
The critically ill trauma patient represents a very complex, multifactorial example of
mixed pathologies that significantly increase mortality [41–43]. Both primary hit and
secondary, posttraumatic injuries lead to a worsening of the clinical and biological
status of these patients, presenting a real challenge for intensivists [44, 45].
Trauma patients are well known for being at high risk of developing malnutrition
during their illness. In fact, a high degree of malnutrition or an inadequate nutrition
strategy can significantly increase the rate of secondary, posttraumatic complications, leading to a vicious cycle in which inflammation, infections, and increased
oxygen consumption are strongly correlated [46].
However, there is still a lack of consensus regarding the optimal timing and
components of nutritional support for critically ill patients after significant trauma.
The major challenge is represented by patients that are generally younger than other
hospitalized subjects, often have fewer comorbidities, and are usually well nourished
at the time of their injury [47–49]. In order to limit severe malnutrition and its
associated complications, several authors described how any attempts at early enteral
nutrition in the first week rarely meet energy and protein requirements due to
frequent pauses of feedings for interventions and procedures and/or feeding intolerance, thus providing <50% of calorie/protein needs [50, 51]. Ideally, the suggested
protein requirements for critically ill patients are approximately 1.5 g/day, with
higher intakes (2–2.5 g/day) in some categories, such as with severe burns
[52, 53]. These intakes are rarely achiev ed in the first week post injury [54–57].
Indirect calorimetry is the gold standard for determining energy requirements of
critically ill patients [58–60], since predictive equations have demonstrated low
sensitivity/specificity. As for the metabolic derangements of critically ill trauma
patients, the key features are represented by hyperglycemia and increased insulin
resistance, rapid loss of muscle mass, and negative nitrogen balance [61, 62]. Hence,
nutrition should be considered as one of the most important therapeutic actions in the
case of critically ill trauma patients. Recent studies have shown important implications of nutrition both in the modulation of the patients’ responses to metabolic stress
and in their clinical outcome [3, 63].
There i
[64]. It remains unclear, however, whether, and if so why, generally well-nourished
trauma patients benefit from early nutrition support and which components of
nutrition are primarily responsible for these benefits.
A significant proportion of trauma patients is represented by patients with traumatic brain injury (TBI) [42, 65, 66]. A different aspect, in the case of these patients,
is represented by the hemodynamic instability and secondary complications that they
develop. From a metabolic point of view, patients with TBI present a hypermetabolic
trong evidence that early enteral feeding leads to improved outcomes
s s
21 Nutrition in Trauma and Burns 237
Table 21.1 Issues, answers, and clinical implications related to nutrition support of trauma patients
Issue to address Answer Clinical implications
Route of access Preferred:
Timing to
initiate
Position Post-pyloric
Type Enteral nutrition:
REE
determination
Calories Initially: 50–65% of energy
Protein 1.5–2.0 g/kg/day Equilibrate nitrogen balance
REE resting energy expenditure, GI gastrointestinal, GALT gut-associated lymphoid system, IC
indirect calorimetry
Enteral (gastric, jejunal—
transpyloric)
Parenteral
Early: 24–48 h of admission Improved survival
Ligament of Treitz and over
standard vs. immune-enhancing
Formula estimation vs.
indirect calorimetry
needs
First 2 weeks:
25–30 kcal/kg/day
(IC)
Better GI integrity
GALT stimulation
. Gastric: not recommended—formation of
residuals
. Jejunal transpyloric: preferred
May worsen hyperglycemia
Immunosuppressive
3rd portion of duodenum
Optimal placement
Best GI tolerance
Lower nutritional/inflammatory/immune
responses
Better
visceral proteins
modulation of inflammatory
Better
response
Lower rates of
Gold standard: IC preferred
Permissive early mild underfeeding:
With stabilization: meet energy needs
Decrease fat free mass catabolism (skeletal
muscle)
infection
status, with elevated catabolism regardless of proteins or calories administered.
Table 21.1 summarizes issues, answers, and clinical implications related to trauma
patient nutrition.
Timing of Initiation: “The Sooner the Better”
In the presence of an acute catabolic state, it is mandatory to avoid delays in starting
nutrition therapy to preserve, as much as possible, the skeletal muscle mass, organ
function, and cerebral homeostasis. Following this important corollary, nutrition
therapy should be initiated early, ideally within the first 24 h after injury, and provide
>50% of resting energy expenditure (REE) with 1–1.5 g protein/kg, for the 2 weeks
subsequent to the injury [67, 68].
This inte
intensity of the inflammatory response to trauma and improving the outcome. Hart
rvention is probably of the most important approach able to limit the
238 C. Iacovazzo et al.
and collaborators showed that patients who were not fed within 5 to 7 days after TBI
had a 2–4 times increase in the likelihood of death, respectively; nutrition, together
with the prevention of arterial hypotension, hypoxia, and intracranial hypertension,
is one of the few therapeutic interventions that can directly affect TBI outcome
[
69]. In a systematic review including 13 RCTs and 3 non-randomized prospective
studies on nutritional support for TBI patients, the beneficial effects of early nutrition
on reducing mortality, improving functional outcomes, and decreasing infectious
complications were demonstrated, as well as the use of small bowel feeding and
immune-enhancing formulae to reduce infectious complications [
this recommendation, the ESICM Expert Panel on gastrointestinal function suggests
delaying enteral nutrition only in critically ill patients with uncontrolled shock,
uncontrolled hypoxemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischemia, bowel obstruction, abdominal compartment
syndrome, and high-output fistula without distal feeding access [71].
70]. Corroborating
Route of Feeding: Digestive Tract (Enteral Nutrition) Versus Intravenous (Parenteral Nutrition)
Results coming from large trials showed clearly that most of the patients [72] are
underfed and that the nutrition deficit persists even after discharge [73]. Kompan
et al. [74] compared early EN through a nasogastric tube to early PN followed by EN
in multiple trauma patients and found a significant decrease in pneumonia and ICU
stay, but not in hospital stay and mortality. Justo Meirelles et al. [75], in moderate
traumatic brain injury, compared EN to PN after resuscitation and did not show any
significant outcome difference. Fan et al. [76] compared three groups: early EN,
early PN, and EN followed by supplemental PN. Mortality and complications were
decreased, and nutritional status and clinical outcomes were improved in the early
EN plus supplemental PN group [
early EN was associated with reduced mortality. Higher protein intake reachi ng
1.5–2 g/kg/day may be considered in this population, given the large protein
losses [79].
uidelin
The G
Foundation state that early transgastric jejunal feeding is recommended to reduce
the incidence of ventilator-associated pneumonia [80].
The advant
defined. Classically, PN is frequently associated with higher rates of infection,
immunosuppression, hyperglycemia, hepatic steatosis, and diminished gastrointestinal integrity. On the other hand, EN stimulates post-prandial hyperemia, enhancing
mucosal blood flow, which counterbalances the alterations in GI blood flow due to
situations of increased intrathoracic pressure during vasopressor use. Furthermore,
EN provides a better quality of macro- and micronutrients such as medium-chain
triglycerides and fiber, leading to the production of short-chain fatty acids [
es for the Management of Severe TBI from the Brain Trauma
ages and disadvantages of PN and EN are well-documented and
77]. An earlier meta-analysis [78] showed that
68, 70,
21 Nutrition in Trauma and Burns 239
81]. Based on this rationale and the data available, the recently ESPEN guidelines
agreed that early EN is the best approach to nutrition therapy in patients with
trauma [40].
Standard or Immune-Enhancing Enteral Nutrition
More recently, based on the concepts of immunonutrition, a retrospective analysis of
patients with isolated, severe TBI randomized to an immune-enhancing formula
(IEN) had higher prealbumin levels reflecting improved nutritional status during
hospitalization and had less bacteremia during hospitalization [82]. While evaluating
the impact of specific nutrients on the lung microbiota and the variation of lung
microbiota in TBI patients developing VAP, during ICU stay, Cotoia et al. found this
category of patients having different structures of bronchoalveolar lavage (BAL)
microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richne ss and evenness. Authors concluded that these findings suggest
to target the lung microbiota as promising approach for preventing infections in
critically ill patients with TBI [
administration of conventional EN enriched with 50 mg/kg of glutamine (alanylGLN 20%) intravenously was associated with an improvement in humoral and cellmediated immunity [84].
83]. Moreover, in a similar cohort of patients, the
Estimation or Measurement of Energy Requirements
TBI itself causes an intrinsic increase in metabolism, which would lead to an
equivalent increase in caloric support. However, applying current routine
neurocritical care measures, most TBI patients are on mechanical ventilation,
under controlled normothermia, under deep sedation, and sometimes with a neuromuscular blockade that may partially reduce this response [85–87].
Thus, indi
critically ill patients, and the clinical application of a measured resting energy
expenditure (mREE) to target nutritional requirements or monitor nutritional support
is already established. Based on the diversity of the data on this specific matter, the
Committee on Nutrition, Trauma, and the Brain Food and Nutrition Board of the
Institute of Medicine suggests that permissive underfeeding (initially 50% of energy
needs, progressing up to 25–30 kcal/kg/day in the first 2 weeks) is probably an
appropriate feeding strategy to be initiated within the first 24 h. Moreover, the Brain
Trauma Foundation proposes feeding TBI patients to attain basal caloric replacement at least by the 5th day and at most, by the 7th day post-injury to decrease
mortality [80, 88].
rect calorimetry is the gold standard by which to measure REE in