Nutritional support of the critically ill and injured patient Support in the... · method,a standard RQ of 0.85 is assumed.By using the Fick equation to compute VO 2, and using RQ

Crit Care Clin 20 (2004) 135–157

Nutritional support of the critically ill and

injured patient

D. Sue Slone, MDTrauma Critical Care Section, Swedish Medical Center, 499 East Hamden Avenue, Suite 380,

Englewood, CO 80110, USA

Critically injured patients are characterized by hypermetabolism and accelerated

catabolism, leading to rapid malnutrition. The prevalence of malnutrition among

hospitalized patients is as high as 50% [1,2]. Inadequate nutrition is associated with

an increased risk of morbidity, mortality, and longer hospital stays [3]. Most trauma

patients are well nourished before injury. These patients are candidates for

nutritional support because of the hypercatabolic state associated with multiple

trauma. Adjuvant nutritional therapy has developed an expanding role in clinical

intensive care, as the medical community begins to understand the immune system,

sepsis, multiple organ dysfunction, and wound healing. With a better understand-

ing of the endogenous responses to injury, more can be learned about the mediators

of these responses. These mediators can be manipulated through improved insight

into nutritional support, its timing, complications, and its role in the full recupera-

tion of patients from the acute phase to rehabilitation.

Nutritional assessment

Assessment is used to identify patients who would benefit from nutritional

support and suggests a design for that therapy. No patient is more difficult to feed

than one with multiple injuries. As catecholamines, cytokines, and insulin levels

rise in response to these traumatic insults, energy expenditure and protein turnover

increase. Because of the heterogeneity of this patient population, it is difficult to

develop guidelines applicable to all critically injured patients. There is a great need

for clinical judgment. Many authors have provided exhaustive lists of possible

markers for nutritional assessment [4]. The focus of this discussion will define a

practical strategy, using readily available means of assessing nutritional status.

Conditions such as thermal injuries, severe CNS (central nervous system) insult,

0749-0704/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.

doi:10.1016/S0749-0704(03)00093-9

E-mail address: [email protected]

D.S. Slone / Crit Care Clin 20 (2004) 135–157136

sepsis, and certain comorbid conditions (eg, cancer, COPD [chronic obstructive

pulmonary disease], alcoholism, and heart disease) produce added metabolic

challenges and complications. These conditions exacerbate energy expenditure

and protein catabolism brought on by severe injury. This evokes a variation even

among patients with the same disease process [5].

The assessment begins with a thorough history. This is not always practical

during a trauma resuscitation and evaluation. The added challenge of alcohol

intoxication, coma, pharmacologic management of the ventilator, and frequent

anesthesia adds to the inherent challenge. Once the history is attainable, it should

include alcoholic tendencies (associated with malnutrition), history of diabetes,

chronic pulmonary disease, renal failure, weight gains, and weight losses (asso-

ciated with increased morbidity) [6]. The underlying mechanism of injury is

relevant to the assessment. Body weight change in the intensive care unit (ICU)

patient is not a good measure of outcome, because it usually reflects fluid shifts.

Body weight is most useful as serial measurements of the hospitalized patient to

assess fluid status and response to therapy. The largest problemwith body weight is

that it relies on the comparison of a range of normal values that often is limited by

the diversity of the control population [7]. A more optimal nutritional indicator is

body mass index (BMI, body weight in kilograms divided by square of height in

meters). This index overcomes the limitations of changes in body weight and the

need to compare it with expected normal values (Fig. 1).

Clinicians should inspect for body habitus, obesity, muscle mass, pretemporal

wasting, and edema. Although anthropometrics measures, such as triceps, skinfold

thickness, and midarm muscle circumference are objective evaluations of these

energy pools, they add little to the overall clinical plan [8]. These measurements are

safe, simple, and inexpensive. They can be done at the bedside. Because the ratio of

subcutaneous to total body fat may vary from 20% to 70% in normal subjects [9], it

is notoriously inaccurate over a range of body sizes. It is most inaccurate in the

extreme patients. These measures will often overestimate body fat in malnourished

patients. They will underestimate body fat in obese patients. Acute changes are not

detected accurately with anthropometrics [10]. These findings often are very hard

to assess after aggressive fluid resuscitation.

Serum albumin

Albumin remains a useful tool in evaluating nutrition and predicting the

patient’s risk for morbidity [11]. Gibbs et al found this to be a significant predictor

for sepsis and major infections. This clinical trial involved over 54,000 patients,

and the preoperative albumin level was identified as a significant predictor of

mortality and morbidity for patients undergoing surgical procedures. There would

be no baseline albumin in trauma patients. It was a predictor of pneumonia and

wound infections [12], which would be applicable in the critically injured patients.

Clinicians are cautioned that serum albumin can be altered with excessive protein

losses, catabolism, and decreased hepatic protein synthesis. Dilutional effects

Fig. 1. Body mass index calculator.

D.S. Slone / Crit Care Clin 20 (2004) 135–157 137

following massive fluid resuscitation are a very big factor in the trauma care

setting. Transferrin, prealbumin, and other proteins have been studied for pos-

sible improvements over albumin. They did not increase the sensitivity of this

laboratory value. The difference in their usefulness is related to their reduced half-

life. Transferrin (8- to 10-day half-life) and prealbumin (2- to 3-day half-life) have

been accepted as sensitive indicators of acute protein and energy depletion, but

they have not been shown to make a significant difference in the prediction

of outcome [3]. Retinol binding protein has a 20-hour half-life, but it is limited

by the same multifactor concerns.


Objective multi-parameter indices designed to predict clinical outcomes rely on

these values and thus are limited by the same concerns. For example, when tested

clinically, the prognostic nutrition index (PNI) grossly overestimates the risk of

complications and death [13].

Measures of immunocompetence

Immunity is suppressed by malnutrition. Cell-mediated immunity is more

affected than humoral. [3] The total lymphocyte count (TLC) and delayed

hypersensitivity skin testing (DHST) are the two tests most frequently used. A

TLC of less than 3000/mm3 reflects immunodeficiency. It is not useful in patients

who are critically ill, since sepsis, trauma, and disseminated intravascular coagul-

opathy also depress immune function, including TLC. There has been a strong

association between DHST results and morbidity. Mortality rates are higher in

patients with negative skin test reactions when compared with patients with normal

reactivity [14].

Caloric and nitrogen balance studies

Balance studies are used in the ICU to clarify nutritional requirements. They

do not furnish a dynamic picture of the adequacy of current nutritional status.

Balance studies fail to provide an assessment of past deficits and future improve-

ments. Nitrogen balance is an inexpensive, easy, and effective measurement. It is

calculated by subtracting the total excreted nitrogen from the total dietary

nitrogen intake (Box 1).

Box 1. Nitrogen output and balance equations

Nitrogen output

24-hour urine urea nitrogen(UUN)(g/d)=

UUN(mg/d)� urine output(mL/d) �1 g/1000 mg

�1 dL/100 mL

Total nitrogen loss(g/d)24-hour UUN(g/d)

+(0.20� 24-hour UUN g/d)+2 g/d

Nitrogen balance

24-hour intake protein (g)/6.25(g)� urinary nitrogen (g/d)=N/d


The seemingly simple determination of nitrogen balance is fraught with

difficulties. About 80% of nitrogen is eliminated through the urine. Other losses

(purines, ammonia, and others) are estimated at 2 g daily. Twenty percent of urea is

eliminated through feces and various other body fluids. A positive nitrogen

balance, in the range of 2 to 4 g of nitrogen per 24 hours (anabolic state) is very

difficult to achieve in the critically injured patient. This is simply not attainable

when severe hypermetabolism is present [15].

Metabolic requirements

The balance between energy intake and expenditure determines the daily energy

requirements (calories). If measured energy expenditure (MEE) is not readily

available, the estimated caloric requirement is 104.67 to 146.54 kJ/kg of ideal

body weight. Calorie balance can be measured using indirect calorimetry or

calculated by the Harris–Benedict equation (published nearly 85 years ago,

Box 2) [16]. This equation was developed using healthy volunteers and there-

fore dramatically underestimates the energy requirements of trauma patients.

Stress factors evolved for the modification of this formulation and are highly

suspicious for overestimation of caloric requirements (Table 1) [17].

The most accurate measure of BEE is the indirect calorimetry using a metabolic

cart [18]. The basal metabolism can be determined by measuring oxygen con-

sumption (VO2) and carbon dioxide production (VCO2).

Energy expenditure ¼ cardiac output � VO2 þ ð1:11Þ ðVCO2Þ ½19�

The procedure to measure BEE is slightly more labor intensive and sometimes

difficult in the critical care setting. It also provides a respiratory quotient (RQ).

This ratio of the carbon dioxide production (VCO2) to oxygen consumption

(VO2) provides the composition of the oxidized substrate. It is unclear whether

Box 2. Harris–Benedict equation

Men:

basal metabolic expenditure (BEE)=

66+(13.7) (weight kg)+ (5) (height cm)� (6.8) (age years)

Women:

BEE=

655+(9.6) (weight kg)+(1.7) (height cm)� (4.7) (age years)

Table 1

Stress related correction factora

Patient condition Correction factor

Activity Bed rest 1.2 (X RME)

Sitting in chair 1.3

Infection Fever 1.0 + 0.13/�CPeritonitis 1.2 – 1.37

Sepsis 1.4 – 1.8

Trauma Soft tissue trauma 1.14 – 1.37

Closed head injury 1.4 – 1.6

Skeletal trauma 1.2 – 1.37

Burns < 20% BSA 1.0 – 1.5

40% BSA 1.5 – 1.85

100% BSA 1.5 – 2.05

Abbreviation: BSA, body surface area.a Must be adjusted during recovery and convalescence.


the use of this sophisticated measure of calorie expenditures to calculate energy

requirements provides an improvement in outcome [20]. The RQ, when using

glucose as fuel, is 0.9 to 1.0. Mixed substrate combustion has an RQ of 0.8 to

0.9. Fat as a primary fuel source produces an RQ of 0.7 to 0.8. Indirect

calorimetry should be used to measure energy expenditures when the standard

formulas are inaccurate. In a recent review, Brandi et al [21] suggested that

indirect calorimetry is beneficial when the critically ill fail to respond adequately

to estimated nutritional needs, have organ dysfunction and are in need of long-

term nutritional support, and are receiving supplemental feedings simultaneous

with weaning from the mechanical ventilator.

Fick equation

Oxygen consumption also can be determined by using a Swan–Ganz catheter

and the Fick method (Box 3). Because VCO2 is not measured directly by this

Box 3. Fick method (energy expenditure)

Oxygen consumption (VO2)=CO (L/min)� (Cao2�Cvo2)� 10 Cao2 (mL/dL)=Hgb g/dL� 1.37� Sao2+0.003*� Pao2 Cvo2 (mL/dL)=Hgb g/dL� Svo2+0.003*� Pvo2 Energy expenditure=([3.9�Vo2]+1.1 [0.85�Vo2])� 1.44 Energy expenditure=6.96�Vo2

* Blood oxygen solubility coefficient.


method, a standard RQ of 0.85 is assumed. By using the Fick equation to compute

VO2, and using RQ to compute the VCO2, this equation seems to correlate well

with the indirect calorimetry and Harris–Benedict equation [22].

Patient selection

The patient who is a candidate for nutritional support is the healthy uninjured

patient who has been without nutrition for 5 to 7 days. The trauma patient with an

Injury Severity Score (ISS) of greater than 15, burn victim with a Body Surface

Area (BSA) burn of greater than 20%, the patient with severe peritonitis or

septicemia are all hypermetabolic and at risk for malnutrition. The only other

patient who benefits from nutritional support is the malnourished patient who has

by definition lost greater than 10% of the usual body weight. No other patient

groups have been shown to benefit from adjuvant nutritional therapy. This has been

studied carefully and reported by Buzby et al in 1991, among others. The

participants were 395 malnourished patients known as the Veterans Affairs Total

Parenteral Nutrition Cooperative Study Group [23]. The purpose of the study was

to examine the efficacy of perioperative total parenteral nutrition (TPN). In all

instances of poor patient selection, the risk of using TPNmay outweigh the benefits

[24]. The only applicability to the trauma patient population is the frequency with

which they can develop malnutrition. Patient selection may be one of the reasons

well-designed, reproducible nutritional studies with significant outcome differ-

ences are so difficult to develop. The major point of awareness is the importance of

patient selection in the nutritional support for the trauma patient population. It may

be better to wait 1 extra day for adjuvant enteral therapy than the start TPN on the

third or fourth day after injury. The risk of TPN may outweigh the significance of

the benefit and always must be considered in the trauma patient population.

Caloric/energy requirement

The goal of surgical nutrition in the critically injured patient is maintenance,

not repletion. Overfeeding results in lipogenesis and results in a large increase in

carbon dioxide production. It should be suspected when the clinically measured

RQ is 1.1 or greater. The increased CO2 production associated with overfeeding

requires an increase in minute ventilation or respiratory acidosis occurs. Both of

these complications are undesirable in the trauma patient. The clinician should

consider glucose intolerance if the provided nutrition is based on measured

energy expenditures (MEE), but the patient retains an elevated RQ, attendant

respiratory acidosis, or high minute ventilation. The glucose use rate (5 mg/kg per

minute) may have been exceeded. Some patients may have pulmonary physiol-

ogy that does not allow them to handle normal CO2 production. In this situation,

manipulation of the ratio of lipids to carbohydrates may prove to be beneficial.

Lipid calories should not exceed 60% of energy requirements. Dextrose mono-


hydrate in TPN provides 14.24 kJ per gram. Ten percent lipid emulsion provides

5.02 kJ/mL. Twenty percent lipid emulsion provides 8.79 kJ/mL. Lipids are iso-

osmotic, calorie dense, and useful during glucose intolerance. Unfortunately, their

use has been associated with a higher risk of infection [25]. This risk is not huge,

but it is concerning. The minimum calorie requirement that should be delivered as

lipids to prevent fatty acid deficiency is 5% [26]. There has not been an evidence-

based answer concerning the maximal lipid intake or ideal lipid ratio. Serum

triglyceride levels must be maintained within a normal range while the patient

receives intralipids.

Protein requirements

In a healthy patient without protein intake, there is an obligatory loss of 20 to

30 g of protein per day. In hypermetabolic critical trauma patients, protein

degradation and synthesis typically increase in concert with a net loss. Patients

lose up to 1% of their body protein per day. For this reason, 1.5 to 2.0 g of protein

per kilogram of ideal body weight per day is recommended [27]. There is little

doubt that the new mode of postlaparotomy open abdominal wound, increasing

entercutaneous fistulae formation, systemic inflammatory response syndrome

(SIRS), and new modes of mechanical ventilation have an impact on the insensible

protein losses in critically injured patients. Studies of graded protein delivery

demonstrated no significant benefit when providing the trauma patient with more

than 1.5 g/kg ideal body weight [12]. There are no published data suggesting

improved survival for adults with protein supplements that exceed this rate.

Alexander [28], however, showed that children with severe burns had a significant

reduction inmortality when proteins were supplemented with more than 1.5 g/kg of

ideal body weight.

Amino acids

The need for certain amino acids during a stressful critical illness has been

demonstrated by several clinical studies [29]. Glutamine is the most abundant

amino acid in the body, but it shows deficits during episodes of severe stress

(therefore considered semiessential). Glutamine production is up-regulated signifi-

cantly during times of stress, trauma, and sepsis. It serves as a nitrogen donor for

ammonia synthesis in the kidney to increase the excretion of acid. It acts as a

primary fuel for enterocytes and immunologic cells. It is also important in glu-

tathione synthesis [30]. Arginine is another semiessential amino acid that contrib-

utes to the immune system and metabolic function. Branched-chain amino acids

(BCAA) are considered essential and the primary energy source for muscle [31].

There has not been any clinically proven benefit to supplementation with BCAA

[32]. One theoretical nutritional use for BCAA is the reduction of the level of false

transmitters that are caused by aromatic amino acids [33].


Glucose/insulin

The association between hyperglycemia and infectious complications is as-

suming greater importance in the critically ill. Hyperglycemia and insulin re-

sistance are common in critically ill patients, even if patients were not previously

diabetic. The normalization of blood glucose levels with intensive insulin therapy

improves the prognosis of such patients as seen in a large ICU study reported

by Van Den Berghe et al [34]. The use of insulin to maintain blood glucose at

a level that did not exceed 110 mg/dL substantially reduced mortality in this ICU.

The patient group included only 8% (n = 68) major trauma and burn patients.

The applicability of these data to trauma patients has not been determined.

Electrolyte requirements

Phosphorus is a ubiquitous mineral, and approximately 70% to 90% of adult

intake is absorbed [35]. The total stores are 500 to 800 g. It is located mostly

(80%) in bones and teeth. Muscle contains 9% of phosphorus. A small per-

centage is available for synthesis of intracellular energy compounds (ATP). It is

also useful in formation of 2,3 diphosphoglycerate (2,3 DPG) [36]. There are so

many phosphorus-dependent metabolic pathways that maintaining phosphorus

homeostasis is critical for normal body function. Hypophosphatemia can lead

to significant respiratory failure, as it is a major energy component for the

diaphragm. Excessive nutritional support can cause hypophosphatemia, com-

monly known as refeeding syndrome, which will be discussed later.

Trace elements

Copper has multiple effects on immune response, including both T and B cell

defects. Interactions with iron often occur, and low copper may be associated with

reduced nutritional intake. Both anemia and immune suppression are observed in

patients with copper deficiencies. Decreasing copper causes a significant reduc-

tion in proliferative response to reduced interleukin (IL)-2 receptor secretion [37].

The liver stores several vitamins and micronutrients. As liver failure progresses,

its ability to store nutrients is impaired. There is malabsorption of vitamins A,

E, and K because of steatorrhea. Vitamin D levels may be reduced in the blood,

in the presence of impaired renal function. Niacin, folate, and vitamin B12 also

may be deficient in a patient with a history of alcohol abuse. Iron deficiency

anemia may be found in patients with a history of gastrointestinal (GI) bleed.

Bombesin is a tetradecapeptide analogous to mammalian gastrin-releasing

peptide, which stimulates the release of several other GI tract hormones. It has

been shown to increase the levels of intestinal IgA. Bombesin given three times per

day has completely reversed the negative effect of TPN on respiratory tract

immunity and gut associated lymphoid tissue (GALT) [38].


Metabolic responses

The metabolic responses to injury differ significantly from those of starvation.

During starvation, the body attempts to compensate by decreasing its metabolic

rate. Glycogen stores are depleted in the first 24 hours, and fat becomes the chief

energy source. Proteins are conserved until late in the process. In most trauma

patients, numerous metabolic processes join to produce a hypermetabolic state

characterized by a rapid and significant negative nitrogen balance. The net result of

protein tissue and muscle mass loss is two to three times that lost during starvation.

Lipolysis is functionally reduced to the progressive elevation in insulin levels and

relative glucose intolerance. This causes high levels of circulating glucose, which is

not useful energy for the traumatized patient. Substrate delivery in the trauma and

burn patient becomes key to preventing lipolysis and protein degradation. The

overprovision of calories can cause the following hazards: increased metabolic

rate, increased oxygen consumption, hyperglycemia, fluid imbalance and de-

hydration caused by hyperosmotic load, fatty infiltrated liver, fluid overload,

immunosuppression, prolonged ventilator dependence caused by increased CO2production, and electrolyte imbalance. Using graded calorie infusions in patients

with burns, Burke [39] found the level of calorie input, which demonstrated

increased rates of CO2 production and hepatic fat deposition when exceeded. The

ideal level that he identified was 104.67 kJ/kg of ideal body weight per day.

Immunonutrition

The suppressive effect of nutrient imbalance on the immune system is seen

most readily in malnutrition [40]. Nutritional deficits produce significant atrophy

of lymphoid organs and impaired function leading to infections [41,42]. Addi-

tionally, studies suggest that overnutrition, particularly excessive fat intake, can

cause immunosuppression [43]. Because microbes have a direct effect on di-

gestion, these relationships are linked tightly in a mutually interactive fashion

through the function of the GI immune system. Advances in the field of im-

munology over the past 20 years have led to a better understanding of the role

nutrition plays in the immune status of injured patients. It has been apparent that

certain specific nutrients might exert pharmacologic immune-enhancing effects

upon individuals independent of routine nonenergy protein intake. These include

arginine, glutamine, nucleotides, and omega-3 fatty acids.

Arginine

Arginine promotes normal T-cell function and helper T-cell levels. It also

enhances delayed type hypersensitivity and lymphocyte blastogenesis. It has been

shown to stimulate macrophages and natural killer cell function [44]. It also plays a

significant role in wound healing [45]. Most studies have evaluated arginine in

conjunction with n–3 polyunsaturated fatty acids (PUFA) and dietary nucleotides.

Linoleic acid

Linoleic acid is a w–6 PUFA that is a major constituent of cell membranes and aprecursor of prostanoid and leukotriene synthesis. It is considered an essential

amino acid. Deficiency causes dermatitis. These deficiencies can be prevented by

the minimal free fatty acid (FFA) requirement, which is 5% of total calorie intake.

Its role in immune enhancement and as a substrate for the synthesis of prostanoids

and leukotrienes is gaining acceptance quickly. There are no parenteral forms of

linoleic acid available. Enteral immune-enhancing formulas containing w–3 PUFAare commercially available.

Glutamine

Glutamine is an oxidative fuel for rapidly replicating cells, including GI mu-

cosal cells, lymphocytes, and macrophages. It is also a nitrogen shuttle and

precursor of the antioxidant glutathione. During stressed states, the body requires

an exogenous source of glutamine to avoid catabolism and muscle glutamine

depletion [46,47].

Nucleotides

Nucleotides enhance the replication of rapidly growing cells to include im-

mune cells and GI mucosal cells [48], In addition, Good et al [49] were first to

recognize the association between micronutrient deficiencies of vitamins and

trace elements with a depressed immune response. Specifically, Good proposed

that a certain key elemental deficiency, zinc, might be the cause. Primary zinc

deficiency causes intractable and even fatal infections. Zinc is essential, as it

is required for the biologic activity of thymic hormone needed for the matu-

ration of T cells [50]. Copper has multiple effects on immunity, including T- and

B-cell function. Other trace elements included in some of the diets were sele-

nium and taurine, with known antioxidant properties [51]. Antioxidants have

been shown in vitro to modulate the activity of various immune cells such as the

T lymphocyte, endothelial cell, and monocyte/macrophage. Selenium deficiency

also reduces antibody responses.

There have been numerous studies of the clinical, immunologic, nutritional,

and biochemical effects of arginine, glutamine, w–3 FFA and nucleotides. Thereare over 400 citations in the medical and biochemical literature. There were three

meta-analyses [52–54] that determined immune enhancement showed clinical

results such as decreased infection. There was no significant change in mortality

resulting from dietary immunomodulation. Moore et al [55] published the results

of a prospective randomized multi-center trial using isocaloric formulas on

primarily traumatically injured critical care patients. The patients were fed

immediately and received the diet for a week. There were increases in immuno-

logic responses in the study group, with significantly fewer intra-abdominal

abscesses and fewer multiple organ failures. This trial demonstrated similar

findings with most of the many other immunomodulation studies. It showed that



there were some clinical improvements in outcome but no significant reductions in

mortality. It also can be noted that none of the centers studied any of the

components separately. A clinical trial was presented from Seattle, using a trauma

patient population that showed a significant increase in the development of adult

respiratory distress syndrome (ARDS) among those fed Impact (Novartis, Basel,

Switzerland; a commercially developed ‘‘immune-enhancing’’ formula) [56]. This

balance between improved immunity and heightened inflammation could make

the overall response to these enhancing diet harmful. It is potentially unpredictable

in different clinical settings. The danger of extrapolation between disparate groups

is prevalent. This was a very small study and was powered higher in the original

design. It raises interesting concerns about the routine use of immune-enhanced

formulas without further evaluation.

Twenty-two randomized trials (2419 patients) compared the use of various

immune-enhancing formulas. When the data are aggregated, there is no mortality

advantage, although many of the study patients had a reduction in infectious

complications. All studies looked at the additives in combination, making it hard to

evaluate any single component. Animal studies suggested that arginine was dose-

dependent and varied with the timing of administration [57]. Immunonutrition was

effective in elective surgical patients but had no affect on critical care patients in

general. These supplements showed no significant affect on infectious complica-

tions, length of ICU stay, or duration of mechanical ventilation. Immunonutrition

was associated only with a reduction in total hospital length of stay. There were

suggestions of methodologic weakness in some primary studies, sample size

problems, and even some evidence (in one small study) that immune-enhanced

diets may be associated with an increased mortality in critically injured patients.

One wonders about the merit of immunonutrition, it is known today. Further

research needs to define the underlying mechanism by which immunonutrition

may be harmful, to identify which ingredients have a clinical affect, and which

patients are associated with an outcome benefit. Once this study design is

developed, it needs to be applied to trauma patients to evaluate the effect of

immunonutrition on the critically injured patient.

Timing

It has not been established clearly when to initiate nutritional support. Extensive

data-based literature suggests that nutrition will attenuate the hypermetabolic

response to injury, reduce the rate of infectious complications, and maintain the

integrity of the intestinal mucosa along with its immunologic defenses [58,59].

Obviously, a healthy young well-nourished individual with no significant injury

can go several days without nutritional support. This will cause minimal effect on

the patient’s mortality or morbidity. Any variation, such as the infliction of a major

injury, advanced age, or the presence of comorbidities can alter the patient’s

requirement for nutritional support drastically. Although many authors have

defined the patient population requiring this support adequately, the optimal timing


has not been elucidated. The benefits of early feeding in hypermetabolic patients

have not been studied adequately. The heterogeneity of the hypermetabolic group

of patients makes the study designs problematic and flawed. The largest study

group of trauma patients reported by Moore and Jones [60] demonstrated a

decrease in septic complications in patients who received early jejunal feedings,

compared with a control group who received TPN. Because of the mixed route of

administration seen in this study group, one cannot be certain that the significant

difference in outcome was attributable to the early timing of the feeds, the enteral

route of nutrition, or some other unidentified factor. Moore et al were credited with

the first clinical studies that demonstrated a benefit with early enteral nutrition. A

subsequent clinical trial by the same authors showed a reduction in pneumonia and

intra-abdominal abscess formation [61]. A meta-analysis was published by Moore

to clarify the findings from multiple clinical trials [62]. Because of the paucity

of clinical trials to base practice guidelines, a summary report from a panel of

experts sponsored by the National Institutes of Health, The American Society for

Parenteral and Enteral Nutrition, and the American Society for Clinical Nutrition

reviewed all published literature concerning the benefits of perioperative nutrition

[59]. TPN was found to decrease complications in malnourished populations only.

A final statement was made that ‘‘nutritional support should be initiated in patients

who are not expected to resume oral feeding for 7 to 10 days.’’ The panel

also called for more prospective controlled trials with revised designs that would

allow the question of whether the timing of nutritional support affects outcome to

be explored.

One prudent practice is to withhold nutritional support until after achieving

hemodynamic stability even though hypermetabolic state may be present imme-

diately. Shock has been shown clinically to reduce mesenteric perfusion, and it is

presumed that early feeding during the shock state can contribute to mesenteric

ischemia, infarction, and perforation [63]. Furthermore, metabolic derangements

such as glucose intolerance resulting in hyperglycemia and osmotic diuresis can

complicate further an already compromised critically injured patient. Even without

evidence-based literature specific to the timing of nutritional support, most

clinicians agree that early feeding in the severely injured patient is favorable.

Route of administration

Before 1968 [64], the GI tract was the only route available for nutrition. Dudrick

et al revolutionized the management of patients dying from the inability to take

enteral nutrition with a description of TPN. This became the preferred route of

nutrition in the 1970s, because it was relatively safe, convenient, and widely

available in spite of the condition of the digestive tract. In the 1980s, it was

determined that there were compelling advantages to enteral nutrition, including

the improved usefulness of the nutrients with the first pass through the liver [65]. It

was advanced more slowly than TPN, but the nitrogen losses were found to be less.

GI feeding did not cause the glucose intolerance seen in TPN, was felt to be


protective against significant gut atrophy, attenuated the stress response better,

maintained immunocompetence, and preserved the gut flora [66–68]. Thus, by the

end of the 1980s, there was renewed interest in enteral feeding. After being the first

to establish the importance of early feeding for trauma patients, Moore et al were

credited with the first randomized controlled trial in the trauma population

designed to evaluate the advantages offered by enteral nutrition compared with

TPN [62]. Kudsk et al confirmed these observations at Presley Memorial Trauma

Center in Memphis, Tennessee [69]. Investigators argue that enteral nutrition

maintains the integrity of the GI tract and has fewer associated infectious

complications compared with TPN. The problem with these two similar class I

studies was the size, which may have been suboptimal [70]. A meta-analysis done

by Moore and Feliciano [63] found support for early total enteral nutrition (TEN)

versus TPN in the trauma patient but did not find defined support in the nontrauma

population. Just as many trials showed no difference between TPN and enteral

nutrition. Most of these trials were not done on trauma patients, but Pacelli et al

demonstrated that enteral feeding following major abdominal surgery failed to

reduce postoperative complications and mortality when compared with parenteral

nutrition [71]. Was the design flaw, which provided patients in the enteral feeding

arm of the study with TPN during the periods of time when the patient would not

tolerate enteral feeds, the reason for the disparity between these results and the

findings that Moore published when evaluating the trauma patient population?

Many of the comparative trials were characterizedwith inadequate patient selection

(not restricted to patients who required nutritional support), small study size, and

insufficient definitions of complications. Lipman did a thorough review of the

literature as it concerned the route of delivery of nutrition [72]. He evaluated the

common arguments that enteral nutrition is better because it is cheaper, safer, more

physiologic, promotes better GI function, prevents bacterial translocation, and

improves outcome. This comparison of enteral nutrition and TPN on gut–barrier

function and other clinical outcomes did not demonstrate an advantage in patients

with abdominal trauma, except in the reduction of sepsis. This inconsistency

undoubtedly highlights the shortcomings of meta-analyses when used to assess

trials of different quality involving heterogeneous patient groups and diverse

endpoints. If the risks of enteral nutrition were equal to TPN, then enteral nutrition

is better because of its reduction of cost alone. To take a current look at the old

controversial issue of TPN versus TEN, a common theme should become apparent

when initiating support. TPN should be reserved for those patients whose GI tract

will remain unavailable for a prolonged period, resulting in eventual malnutrition.

There is some concern that most of the complications associated with TPN are

caused by the lipid component. Battistella et al suggest lipids be withheld from the

TPN of trauma patients able to tolerate at least 10% of their nutrition enterally. This

group received fewer calories, but no intravenous lipids. They had fewer infections,

shorter LOS, and fewer days on a ventilator [72]. Cerra found no difference in the

potential for multiple organ failure in patients receiving enteral feeds versus TPN

[73]. A logical resolution to the conflict of TPN and TEN is that if the gut is

functional, use it. One should not have a slavish commitment to enteral feeds in the


patient who does not tolerate it. It even has been suggested that the increase in

splanchnic blood flow induced by enteral feeds may be detrimental to the critically

injured patient. The time has come for the TEN versus TPN debate to be laid to rest.

Patients with questionable GI function should be fed using a combination of TEN

and TPN. The enteral feed should be increased or decreased according to tolerance,

with TPN adjusted accordingly. If the patient is going back and forth, with

procedures requiring intermittent deferment of enteral feeds, then TPN should be

used preferentially. Although TPN has infectious implications and is associated

with GI atrophy, it is immediately available and does not require much time and

tolerance to reach full support. Border et al found less sepsis in patients who

received at least 40% of their nutrition by enteral routes [74].

The debate about the route continues to raise controversy, but flawless trials

demonstrating consistent benefits to major outcomes have been rare. There is a

general lack of evidence-based guidelines involving the decisions related to

nutritional timing and route.

Feeding access

The benefits of enteral nutrition in trauma patients are recognized widely. The

optimal method of enteral access in severely injured patients is not established.

Feeding jejunostomy generally is considered to be a safe method of establishing

enteral access in elective surgical patients, but the safety in trauma patients is less

certain. Holmes et al [75] retrospectively evaluated the complication rate of the

jejunostomy feeding tube in trauma patients and found it to be 10%. Although the

value of enteral feeding has been investigated extensively, the safety of feeding

jejunostomy as an adjunct to trauma celiotomy has received less evaluative

investigation. Many centers have become quite discouraged with the use of this

type of access, although this may be premature. With appropriate patient se-

lection, judicious tube feeding regimens, and attention to technical details, the

jejunostomy related complications could be controlled. Alternative enteral ac-

cess techniques should be considered in this population, however. Other such

access can be provided with nasal jejunal feeding tubes and needle catheter

jejunostomy. Nasoduodenal (postpyloric) feeding tubes may be placed easily and

can provide a safer method than surgical jejunal access for feeding the severely

injured patient [76].

Complications

Overfeeding

Overfeeding critically ill patients can cause metabolic complications that are

serious and sometimes fatal. Patients who are very small, very large, or very old are

particularly vulnerable to overfeeding.

Azotemia

Azotemia occurs when the rate of urea production exceeds the excretion. The

rate of synthesis of urea in the liver depends on the protein intake and endogenous

catabolism. Inflammation and infection activate cytokines (eg, IL-1 and IL-6) that

accelerate muscle breakdown. Furthermore, adrenal hormones and catecholamines

such as glucagons, cortisol, and epinephrine, which are elevated after traumatic

injury, stimulate muscle catabolism. Accelerated proteolysis in critically ill and

injured patients, combined with overzealous protein delivery, sets the stage for

azotemia [77].

Fat overload syndrome

Life-threatening complications are rare but can occur because of excessive

amounts of soybean oil emulsions [78]. Respiratory distress, coagulopathies, and

abnormal liver function tests are the primary manifestations of fat overload. Less

commonly reported abnormalities are acute renal failure, fever, rash, depressed

platelet counts, low hemoglobin concentration, hypertension, and tachycardia [79].

Patients who have sustained injury have stimulated cytokine production and

depressed lipoprotein lipase activity [80]. Lipase activity probably further stimu-

lates the cytokine response.

Hypertriglyceridemia

Overfeeding carbohydrates may lead to hypertriglyceridemia within a matter of

days [81]. Infusing lipid in excess of 2 gm/kg per day has been associated with

hypertriglyceridemia in patients receiving propofol, a lipid-based drug used for

sedation [82]. It is not known whether propofol exerts an effect that is independent

of the effect of the lipid carrier. Propofol decreases tissue oxidation and carbon

dioxide production [83].

Hepatic steatosis

More than one mechanism may be responsible for the accumulation of hepatic

fat. Hepatic steatosis during overfeeding derives from exogenous lipid or redistri-

bution of fat from adipose tissue.

Hypercapnia

Carbon dioxide is formed when intracellular substrates are broken down to

produce ATP. With overfeeding, the ratio of carbohydrate to fat in substrate

oxidation continues to increase over time. When and how much fat oxidation is

displaced by carbohydrate oxidation may depend on the patient’s ability to store

glycogen. Eventually, overfeeding will lead to more carbon dioxide production

over time [84]. Plasma triglyceride is elevated in patients with infectious illness,

particularly gram-negative sepsis. This is primarily caused by the effect of tumor

necrosis factor, which decreases the activity of lipoprotein lipase [85].


Table 2

Complications of central venous catheterization

Pneumothorax Catheter occlusion Hydrothorax/hydromediastinum

Air embolism Thoracic duct injury Catheter embolus

Improper location Hemomediastinum Brachial plexus injury

Venous thrombosis Arterial puncture Local hematoma/bleeding

Failure to cannulate Hemothorax Subcutaneous emphysema

Catheter sepsis Local infection Bacteremia


Metabolic acidosis

Metabolic acidosis has been reported recently with excessive protein intake

from an enteral formula [86].

Refeeding syndrome

Initiation of nutrition support to patients with severely depleted nutrient stores is

associated with clinically significant shifts in phosphorus, magnesium, and

potassium from extracellular to intracellular spaces [87]. In the fed state, ATP

production, glycogenesis, and protein anabolism place extra demands on the

supply of these important minerals, whose transport into cells is stimulated by

insulin [88]. Additionally, starvation causes a catabolic release of intracellular

phosphate, which is excreted in the urine. Total body stores of intracellular

electrolytes slowly are depleted, because these constituents of the body cell mass

are lost slowly during catabolism. Refeeding and the early stages of overfeeding are

both cardiovascular demands. Chronically malnourished patients whose cardiac

muscle is depleted are not prepared to deal with the circulatory demands caused by

the initiation of aggressive nutrition support [89]. Approaches for the prevention

and management of refeeding syndrome (also called nutritional recovery syn-

drome) include supplement with vitamins and minerals as soon as possible.

Consider thiamin, folate, B-6, and zinc [90] supplementation. Clinicians may have

to reach the nutritional goals slowly, with close monitoring of cardiac and mineral

status for acute changes. The refeeding syndrome is a complication of nutritional

support that potentially causes considerable morbidity and mortality associated

with sodium retention and expansion of the extracellular space, leading to weight

gain [91].

Central line complications

The complications seen in central venous catheterization associated with TPN

are found in Table 2.

Special problems

Head injuries

This patient profile can portray a significant hypermetabolic/catabolic response.

Sedation, paralytics, and muscle relaxants modulate this. Energy requirements in


the paralyzed or comatose patient are quite difficult to estimate. Indirect calorime-

try or MEE calculations are useful in these patients. Early nutritional support can

be achieved, but special attention must be made to prevent hyperglycemia, which

has been shown to exacerbate ischemic brain injury.

Burn injury

Major burns are the most hypermetabolic/hypercatabolic injuries and can

double the MEE. The profound immunosuppression seen in these patients has

prompted a great deal of work on nutritional approaches to immune-enhancement.

Burn patients require the most calories, the most proteins, and vitamin C, and high

doses of vitamin E.

Obese trauma patients

Nutritional support in critically ill or injured obese patients can pose unique

problems for clinicians. Many of these patients have chronic diseases related to

their obesity such as diabetes, degenerative joint disease, hypertension, respiratory

abnormalities, hyperlipidemia, and hepatobiliary disease. They are more likely

than their nonobese counterparts to develop complications such as nosocomial

infections, wound dehiscence, and cardiorespiratory complications [92–94]. The

MEE of obese patients is widely variable, and their energy needs are difficult to

predict accurately [95]. As a result, nutritional intake very easily could be given in

excess, leading to the complications of overfeeding. This has become a recognized

problem, and alternative hypocaloric, high-protein feeding has been developed for

the critically ill obese patient [96,97]. Dickerson, et al [98] reported results of a

retrospective trial examining 40 obese trauma patients who received enteral tube

feedings. They examined the nutrition and clinical outcomes of critically ill obese

patients who received eucaloric or hypocaloric enteral feeds. Nitrogen balance and

protein responses were similar between groups. Clinical outcomes favored the

hypocaloric group, with a significantly lower number of ICU days, fewer days of

antibiotic therapy, and fewer days on the ventilator. A randomized double blind trial

is warranted to confirm the clinical outcome of the superiority of hypocaloric

enteral feeding over eucaloric enteral feeding in critically ill, obese patients.

Summary

The understanding of the importance of nutrition, particularly in the critically ill

patient, is based on the known physiologic consequences of malnutrition. It

includes respiratory muscle function, cardiac function, the coagulation cascade

balance, electrolyte and hormonal balance, and renal function. Nutrition affects

emotional and behavioral responses, functional recovery, and the overall cost of

health care. The need to identify and treat the malnourished or potentially


malnourished patient is a critical aspect of patient management. Much is known of

catabolic and hypermetabolic state caused by trauma and burns. The response to

injury needs to be mediated. There is much to learn about the intervention of that

response through adjuvant nutritional therapy.

References

[1] Bistrian BR, Blackburn GL, Hallowell E, Heddle R. Protein status of general surgical patients.

JAMA 1974;230(6):858–60.

[2] Hill GL, Blackett RL, Pickford I, Burkinshaw L, Young GA, Warren JV, et al. Malnutrition in

surgical patients: an unrecognised problem. Lancet 1977;1:689–92.

[3] Smith LC, Mullen JL. Nutritional assessment and indications for nutritional support. Surg Clin

North Am 1991;71:449–57.

[4] Abbasi A. Nutrition. In: Duthie EH, editor. Practice of geriatrics. 3rd edition. New York: WB

Saunders Company; 1998. p. 145–58.

[5] McClave SA, Snider HL. Understanding the metabolic response to critical illness: factors that

cause patients to deviate from the accepted pattern of hypermetabolism. New Horiz 1994;2:

139–46.

[6] Studley HO. Percentage of weight loss: a basic indicator of surgical risk. JAMA 1999;106:

2013–9.

[7] Master AM, Lasser RP, Beckman G. Tables of average weight and height of Americans aged

65–94. JAMA 1960;172:658–62.

[8] Baker JP, Detsky AS, Wesson DE. Nutritional assessment: a comparison of clinical judgment

and objective measurements. N Engl J Med 1982;306:969–72.

[9] Svendsen OL, Haarbo J, Heitmann BL, Gotfredsen A, Christiansen C. Measurement of body

fat in elderly subjects. Am J Clin Nutr 1991;53(5):1117–23.

[10] Lohman TG. Skinfolds and body density and their relation to body fatness. Hum Biol 1981;

53:181–225.

[11] Gibbs J, Cull W, Henderson W, Daley J, Hur K, Khuri SF. Preoperative serum albumin level as

a predictor of operative mortality and morbidity. Arch Surg 1999;134:36–42.

[12] Mullen JL, Buzby GP, Waldman MT. Prediction of operative morbidity by preoperative nutri-

tional assessment. Surg Forum 1979;30:80–2.

[13] Buzby GP, Mullen JP, Matthews DC, et al. Prognostic nutritional index in gastrointestinal

surgery. Am J Surg 1980;139:160–7.

[14] Twomey P, Ziegler D, Rombeau JL. Utilization of skin testing in nutritional assessment: a criti-

cal review. JPEN J Parenter Enteral Nutr 1982;6:50–7.

[15] Ishibashi N, Plank L, Sando K, Hill GL. Optimal protein requirements during the first 2 weeks

after the onset of critical illness. Crit Care Med 1998;26(9):1529–35.

[16] Harris JA, Benedict FG. Biometric Studies of Basal Metabolism in Man. Washington, DC:

Carnegie Institute; 1919.

[17] Daly JM, Heymsfield SB, Head CA, Harvey LP, Nixon DW, Katzeff H, et al. Human energy

requirements: Overestimation by widely used prediction equation. Am J Clin Nutr 1985;42(6):

1170–4.

[18] Makk LJ, McClave SA, Creech PW, Johnson DR, Short AF, Whitlow NL, et al. Clinical

application of the metabolic cart to the delivery of total parenteral nutrition. Crit Care Med

1990;18(12):1320–7.

[19] Weir JB. New methods for calculating metabolic rate with special reference to protein metabo-

lism. J Physiol 1949;109:1–9.

[20] Kinney J. Indirect calorimetry: the search for clinical relevance. Nutr Clin Pract 1992;7:203–6.

[21] Brandi LS, Bertolini R, Calafa M. Indirect calorimetry in critically ill patients: clinical applica-

tions and practical advice. Nutrition 1997;13:349.


[22] Cobean RA, Gentilello LM, Parker A, Jurkovich GJ, Maier RV. Nutritional assessment using

a pulmonary artery catheter. J Trauma 1992;33(3):452–6.

[23] Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total paren-

teral nutrition in surgical patients. N Engl J Med 1991;325:525–32.

[24] Buzby GP, Blouin G, Colling CL. Perioperative parenteral nutrition in surgical patients. N Engl

J Med 1991;325:525–31.

[25] Pomposelli JJ, Bistrian BR. Is total parenteral nutrition immunosuppressive? New Horiz 1994;

2:224–9.

[26] Goodgame JT, Lowry SF, Brennan MF. Essential fatty acid deficiency in total parenteral nu-

trition: time course of development and suggestions for therapy. Surgery 1978;84:271.

[27] Rombeau JL, Rolandelli RH, Wilmore DW. Nutritional support. In: Wilmore DW, Cheung LY,

Harken AJ, Holcroft JW, Meakins JL, editors. Scientific American surgery. New York: Scientific

American; 1999. p. 10–5.

[28] Alexander JW, MacMillan BG, Stinnett JD, Ogle CK, Bozian RC, Fischer JE, et al. Bene-

ficial effects of aggressive protein feeding in severely burned children. Ann Surg 1980;192:

505–17.

[29] Garlick PJ, Wernerman J. Protein metabolism in injury. In: Cooper GJ, Dudley HAF, Gann DS,

Little RA, Maynard RL, editors. Scientific foundation of trauma. Oxford (UK): Butterworth

Heineman; 1997. p. 690–728.

[30] Souba WW. Glutamine: a key substrate for the splanchnic bed. Annu Rev Nutr 1991;11:285.

[31] Freund HR, Hanani M. The metabolic role of branched-chain amino acids. Nutrition 2002;18:

287–8.

[32] Meyenfeld MF, Soeters PB, Vente JP. Effect of branched-chain amino acid enrichment of total

parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma. Br J Surg

1990;77:924–9.

[33] Naylor CD, O’Rourke K, Detsky AS, Baker JP. Parenteral nutrition with BCAA in hepatic

encephalopathy: a meta-analysis. Gastroenterology 1989;97:1033.

[34] Van Den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive

insulin therapy in critically ill patients. N Engl J Med 2001;345(19):1359–67.

[35] Peppers MP, Geheb M, Desai T. Hypophosphatemia and hyperphosphatemia. Crit Care Clin

1991;7(1):201–14.

[36] Knochel JP. The pathophysiology and clinical characteristics of severe hypophosphatemia. Arch

Intern Med 1977;137:203–20.

[37] Kelley DS, Daudu PA, Taylor PC, Mackey BE, Turnlund JR. Effects of low copper diets on

human immune response. Am J Clin Nutr 1995;62:412.

[38] Li J, Kudsk KA, Hamidian M, Gocinski BL. Bombesin affects mucosal immunity and gut-

associated lymphoid tissue in IV-fed mice. Arch Surg 1995;130:1164.

[39] Burke JF, Wolfe RR, Mullany CJ, Mathews DE, Bier DM. Glucose requirements following

burn injury. Ann Surg 1979;190:274–85.

[40] Smythe PM, Brereton-Stiles GG, Grace HJ, Mafoyane A, Schonland M, Coovadia HM, et al.

Thymolymolymphatic deficiency and depression of cell-mediated immunity in protein-calorie

malnutrition. Lancet 1971;2:939–43.

[41] Chandra RK. Nutrition and the immune system. Proc Nutr Soc 1993;52:77.

[42] Shronts EP. Basic concepts of immunology and its application to clinical nutrition. Nutr Clin

Pract 1993;8:177.

[43] Lorenz E, Good RA. Nutritional indications for cancer prevention-calorie restriction. In: Cun-

ninghan-Rundles S, editor. Nutrient modulation of the immune response. New York: Marcel

Dekker; 1993. p. 481.

[44] Barbul A, Lazarou SA, Efron DT, Wasserkrug HL, Efron G. Arginine enhances wound healing

and lymphocyte immune responses in humans. Surgery 1990;108:331.

[45] Barbul A, Sisto DA, Wasserkrug HL, Levenson SM, Efron G, Seifler E. Arginine stimulates

lymphocyte immune response in healthy human beings. Surgery 1981;90:244.

[46] Calder PC, Uaqoob P. Glutamine and the immune system. Amino Acids 1999;17:227.


[47] Saito H, Furukawa S, Matsuda T. Glutamine as an immunoenhancing nutrient. JPEN J Parenter

Enteral Nutr 1999;23:S59.

[48] Carver JD. Dietary nucleotides: cellular, immune, intestinal and hepatic system effects. J Nutr

1994;124:144.

[49] Good RA, Fernandes G, Cunningham–Rundles C. The relation of zinc deficiency to immunologic

function in animals and man. In: Seligman M, Hitzig WH, editors. Primary immunodeficiencies.

Amsterdam (Netherlands): Elsevier; 1980. p. 223.

[50] Dardenne M, Savino W, Borrih S, Bach JF. A zinc-dependent epitope of the molecule of thy-

mulin, a thymic hormone. Proc Natl Acad Sci U S A 1985;82:1202.

[51] Grimble RF. Nutritional antioxidants and the modulation of inflammation: theory and practice.

New Horiz 1994;2:412–20.

[52] Heys SD, Walker LG, Smith I, Eremin O. Enteral nutritional supplementation with key nu-

trients in patients with critical illness and cancer: a meta-analysis of randomized control clini-

cal trials. Ann Surg 1999;229:467–77.

[53] Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of

clinical outcome. Crit Care Med 1999;27:2799–805.

[54] Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become

routine in critically ill patients? JAMA 2001;286(8):944–53.

[55] Moore FA, Moore EE, Kudsk KA. Clinical benefit of an immune-enhancing diet for early

postinjury enteral feeding. J Trauma 1994;37:607–15.

[56] Mendez C, Jurkovich GJ, Garcia I, Davis D, Parker A, Maier RV. Effects of an immune-

enhancing diet in critically injured patients. J Trauma 1997;42(5):933–41.

[57] Barbul A, Wasserkrug HL, Goldfine J. Enteral nutrition with supplemental arginine in normal

and injured rats. J Surg Res 1980;29:228–35.

[58] Braga M, Gianotti L, Cestari A, Bignali A, Pellegatta F, Dolei A, et al. Gut function, immune

and inflammatory responses in patients perioperatively fed with supplemented enteral formulas.

Arch Surg 1996;131:1257–65.

[59] Klein S, Kinney J, Jeejeebhoy K, Alpers D, Hellerstein M, Murray M, et al. Nutrition support

in clinical practice. JPEN J Parenter Enteral Nutr 1997;21(3):133–56.

[60] Moore EE, Jones TN. Benefits of immediate jejunal feeding after major abdominal trauma.

J Trauma 1986;26:874.

[61] Moore FA, Moore EE, Jones TN, McCroskey BL, Peterson VM. TEN versus TPN following

major abdominal trauma-reduced septic mortality. J Trauma 1989;29:916–23.

[62] Moore FA, Feliciano DV, Andrassy RJ, McArdle AH, Booth FV, Morgenstein–Wagner TB,

et al. Early enteral feeding, compared with parenteral reduces postoperative septic complications.

Ann Surg 1992;216(2):172–83.

[63] Boley SJ, Brandt LJ, Veith FJ, Kosches D, Sales C. A new provocative test for chronic mesen-

teric ischemia. Am J Gastroenterol 1991;86(7):888–91.

[64] Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long-term parenteral nutrition with growth

and development and positive nitrogen balance. Surgery 1968;64(1):134–42.

[65] Enrione EB, Gelfand MJ, Morgan D, Sperling M, Wagner SC, Popp MB. The effect of rate

and route of nutrient intake on protein metabolism. J Surg Res 1986;40(4):320–5.

[66] Meyer J. Nutrition. Surg Gynecol Obstet 1988;167:50.

[67] Lowry SF. The route of feeding influences injury responses. J Trauma 1990;33:S10–5.

[68] Alverdy J, Chi HS, Sheldon GF. The effect of parenteral nutrition on GI immunity. Ann Surg

1985;202(6):681–4.

[69] Kudsk KA, Croce MA, Fabian TC, Minard G, Tolley EA, Poret HA, et al. Enteral versus

parenteral feeding. Ann Surg 1992;215:503–11.

[70] Battistella FD, Widergren JT, Anderson JT, Siepler JK, Weber JC. A prospective, randomized

trial of intravenous fat emulsion administration in trauma victims requiring total parenteral

nutrition. J Trauma 1997;43:52–60.

[71] Pacelli F, Bossola M, Papa V, Malerba M, Modesti C, Sgadari A, et al. Enteral versus parenteral

nutrition after major abdominal surgery. Arch Surg 2001;136:933–5.


[72] Lipman TO. Grains or veins: is enteral nutrition really better than parenteral nutrition? JPEN J

Parenter Enteral Nutr 1998;22:167.

[73] Cerra FB. Hypermetabolism, organ failure, and metabolic support. Surgery 1987;101:1.

[74] Border JR, Hassett J, LaDuca J, Seibel R, Steinberg S, Mills B, et al. The gut origin septic

states in blunt multiple trauma (ISS = 40) in the intensive care unit. Ann Surg 1987;206(4):

427–48.

[75] Holmes JH, Brundage SI, Pak-chuen Y, Hall RA, Maier RV, Jurkovich GJ. Complications of

surgical feeding jejunostomy in trauma patients. J Trauma 2003;47(6):1009–15.

[76] Myers JG, Page CP, Stewart RM, Schwesinger WH, Sirinek KR, Aust JB. Complications of

needle catheter jejunostomy in 2022 consecutive applications. Am J Surg 1995;170:547–51.

[77] Bessey PQ. Parenteral nutrition and trauma. In: Rombeau JL, Caldwell MD, editors. Clinical

nutrition: parenteral nutrition. 2nd edition. Philadelphia: WB Saunders; 1993. p. 538–65.

[78] Hansen LM, Hardie WR, Hidalgo J. Fat emulsion for intravenous administration: clinical expe-

rience with intralipid 10%. Ann Surg 1976;184:80–8.

[79] Belin RP, Bivins BA, Jona JZ, Young VL. Fat overload with a 10% soybean emulsion. Arch

Surg 1976;111:1391–3.

[80] Roth B, Nilsson–Ehle P, Eliasson I. Possible role of short-term nutrition with fat emulsions

for development of haemophagocytosis with multiple organ failure in a patient with traumatic

brain injury. Intensive Care Med 1993;19:111–4.

[81] Aarsland A, Chinkes D, Wolfe RR. Contributions of de novo synthesis of fatty acids to total

VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man.

J Clin Invest 1996;98:2008–17.

[82] Eddleston JM, Shelly MP. The effect on serum lipid concentrations of a prolonged infusion

of propofol-hypertriglyceridemia associated with propofol administration. Intensive Care Med

1991;17:424–6.

[83] Barr J. Propofol: a new drug for sedation in the intensive care unit. Int Anesthesiol Clin 1995;

33:131–54.

[84] Wolfe RR, O’Donnell Jr TF, Stone MD, Richmond DA, Burke JR. Investigation of factors de-

termining the optimal glucose infusion rate in total parenteral nutrition. Metabolism 1980;29:

892–900.

[85] Beisel WR. Nutrition and infection. In: Linder MC, editor. Nutritional biochemistry with clinical

applications. 2nd edition. New York: Elsevier Press; 1991. p. 507–52.

[86] Bauer B, Gardner L, Holdy K, Kalafer M. Case report: metabolic acidosis associated with

high protein enteral nutrition (EN). Presented at: Nutrition And Metabolic Support: Challenges

in the Age of Managed Care; 21st Clinical Congress of the American Society for Parenteral and

Enteral Nutrition. San Francisco, January 26–29, 1997.

[87] Brooks MJ, Melnik G. The refeeding syndrome: an approach to understanding its complica-

tions and preventing its occurrence. Pharmacotherapy 1995;15:713–26.

[88] Genuth SM. Whole body metabolism and the hormones of pancreatic islets. In: Berne RM, Levy

MN, editors. Physiology. 2nd edition. St. Louis (MO): Mosby; 1988. p. 864.

[89] Heymsfield SB, Bethel RA, Ansley JD, Gibbs DM, Felner JM, Nutter DO. Cardiac abnormali-

ties in cachectic patients before and during nutritional repletion. Am Heart J 1978;95:5884–94.

[90] Cravo ML, Gloria LM, Selhub J, Nadeau MR, Camilo ME, Resende MP, et al. Hyperhomocys-

teinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status.

Am J Clin Nutr 1996;63:220–4.

[91] Weinsier RL, Krumdieck CL. Death resulting from overzealous total parenteral nutrition:

the refeeding syndrome revisited. Am J Clin Nutr 1981;34:393–9.

[92] Pasulka PS, Bistrian BR, Benotti PN, Blackburn GL. The risks of surgery in obese patients. Ann

Intern Med 1986;104:540–9.

[93] Choban PS, Heckler R, Burge JC, Flancbaum L. Increased incidence of nosocomial infections

in obese surgical patients. Am Surg 1995;61:1001.

[94] Printen KJ, Paulk SC, Mason EE. Acute postoperative wound complications after gastric sur-

gery for morbid obesity. Am Surg 1975;41:483–7.


[95] Feurer ID, Crosby LO, Buzby GP, Rosato EF, Mullen JL. Resting energy expenditure in mor-

bid obesity. Ann Surg 1983;197(1):17–21.

[96] Burge JC, Goon A, Choban PS, Glancbaum L. Efficacy of hypocaloric total parenteral nutri-

tion in hospitalized obese patients: a prospective, double-blind randomized trial. JPEN J Parenter

Enteral Nutr 1994;18:203.

[97] Dickerson RN, Rosato EF, Mullen JL. Net protein anabolism with hypocaloric parenteral nu-

trition in obese stressed patients. Am J Clin Nutr 1986;44:747.

[98] Dickerson RN, Boschert MA, Kudsk KA, Brown RO. Hypocaloric enteral tube feeding in

critically ill obese patients. Nutrition 2002;18:241–6.

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Nutritional support of the critically ill and injured patient Support in the... · method,a standard RQ of 0.85 is assumed.By using the Fick equation to compute VO 2, and using RQ