Critical Care Clinics

Volume 13 • Number 3 • July 1997

Copyright © 1997 W. B. Saunders Company

669

Common Issues in Pediatric and Adult Clinical Care

COMMON NUTRITIONAL ISSUES IN PEDIATRIC AND ADULT

CRITICAL CARE MEDICINE

Gregory J. Schears MD
Clifford S. Deutschman MS, MD, FCCM

Departments of Anesthesiology (GJS, CSD), Critical Care Medicine Pediatrics (GJS),

University of Pennsylvania, School of Medicine; and Children's Hospital of Philadelphia
(GJS), Philadelphia, Pennsylvania

At the core of critical care medicine is a belief that optimization of bioenergetics and
removal of metabolic waste reduce morbidity and improve survival. Thus, ensuring
appropriate metabolic support is essential. Bassili and Deitel, [20] Chandra, [36] and
Reinhardt et al [144] have demonstrated that malnutrition prolongs ventilation and
increases the incidence of sepsis and death. Others [175] [180] have shown that treating
malnutrition improves clinical outcome. Providing the proper substrate to meet
metabolic requirements should curtail catabolism, promote rapid wound healing, and
protect from infection. The nutritional requirements of healthy individuals are well
studied. Relevant information regarding metabolic requirements in specific disorders,
however, is often lacking. Compounding this difficulty is the fact that most human
studies have been conducted in adults. Therefore, pediatric information may be
scarce. This article presents issues common to both pediatric and adult critical care.
Included is a discussion of assessment, substrate, route, nutritional pharmacology,
and disease-specific issues for patients beyond the full-term newborn period.

Address reprint requests to

Gregory J. Schears, MD
Children's Hospital of Philadelphia
Department of Anesthesiology & CCM
34th Street & Civic Center Boulevard
Philadelphia, PA 19104
ASSESSMENT

Delivery of appropriate metabolic support begins with assessment of nutritional status.

Assessment tools also can be used to monitor

670

maintenance and improvement. Recognizing and quantifying protein-energy malnutrition

(PEM) is the first step in identifying patients at risk for increased morbidity and mortality.
The ideal nutritional assessment tool is sensitive, specific, reproducible, relevant in illness
and health, distinguishes lean body mass from fat, is easily applied at the bedside, and is
cost effective. Most methods can meet only two or three of these goals. [38] [121] [194] We
discuss tools that are useful or readily accessible to intensive care unit (ICU) patients.

Anthropometry

Over 50 years ago Studley [172] reported a 33% mortality in patients with a greater than 20%
weight loss on admission for ulcer surgery. Since then, several studies have noted increased
morbidity and mortality in association with weight loss. [26] [119] [151] [159] [189] These observations
probably reflect the impact of disease on weight rather than weight on outcome.

Anthropometry, a population-based comparison of human body measurements, is a

commonly used method and includes weight, height, skinfold thickness, and appendage
circumference. In pediatrics, weight for age, [76] weight for height, [181] weight/height ratio for
age, [125] and growth charts [87] have all been used. Though authors differ on which approach is
most accurate, [126] [182] [194] growth chart analysis can best identify patients at risk. Because
adults have obtained maximum height, growth curves are not useful. Typically, these are
replaced with insurance tables [147] to assess ideal weight for height, age, and gender. Data
indicate that these tables add little to examination by an experienced clinician. [50]

Triceps skinfold thickness [112] attempts to estimate total body fat. This can be extrapolated to
lean body mass. This measurement is simple to perform at the bedside and is inexpensive.
It assumes that body fat is uniformly distributed and that healthy population standards
apply to the critically ill. Neither assumption seems to be valid. [25] [81] [85] [115] Further,
interobserver variation can be significant. [74] Anthropometry is probably more useful in
assessing chronic nutritional support.

Biochemical Markers

A number of biochemical markers have been used in nutritional assessment. Serum

albumin concentration is the most widely used and studied. Hypoalbuminemia has been
associated with increased length of stay [7] and risk of death. [92] [144] Because of its long half-
life (20 days), [150] high rate of intravascular and extravascular exchange, [64] and insensitivity
to starvation, [169] this measurement seems to be a better marker of disease severity than of
nutritional status. [67] [123]
Transferrin, the serum transport protein for iron, has an 8-day half-life and has been shown
to correlate with nitrogen balance. [65] Unlike

671

albumin, it is found almost entirely in the intravascular space. Transferrin synthesis is

induced by iron deficiency and by acute-phase responses. There is a suggestion that
transferrin is a better marker for nutritional status in population studies than in individual
patients. [41] [152]

Prealbumin, [98] or transthyretin, serves as serum thyroxin transport protein. This protein has
a half-life of 2 days and serum concentrations have been shown to respond to dietary
restriction when albumin and transferrin did not. [98] [163] Increases in prealbumin have been
demonstrated to correlate with a positive nitrogen balance [41] and may therefore indicate a
positive response to a nutritional regimen. [168]

Insulin-like growth factor 1, a modulator of growth hormone, has also been shown to
correlate with 24-hour nitrogen balance. [44] [105] Though largely used in research, insulin-like
growth factor-1 may ultimately prove to be the most rapidly responding [72] and accurate
reflection of changes in acute nutritional state. [178]

Multiparameter Tools

Nitrogen balance relates urinary urea excretion with protein intake. Improvement in the
nitrogen balance is considered one of the best markers of the adequacy of nutritional
support. The percentage, however, of total nitrogen excreted as urea can vary. [29] Therefore,
results must be interpreted cautiously in patients receiving crystalline amino acids.

The Subjective Global Assessment (SGA), [38] the Instant Nutritional Assessment, [158] and the
Prognostic Nutritional Index [121] all use more than one variable to identify patients at risk
due to malnutrition. SGA, which uses strictly clinical criteria, has good interoperator
reproducibility. [13] A correlation between malnutrition and infection risk has been identified.
[12]
Subjective Global Assessment, however, is not quantitative and has not been used in the
critically ill. [121] The Instant Nutritional Assessment combines albumin levels and total
lymphocyte counts. A reduction in both values correlated with increased complication and
death rates. [158] Although simple, this index is more likely to indicate severity of illness or
the presence of inflammation than nutritional status. [64] [67] [123] [150] [169] The Prognostic
Nutritional Index uses a combination of clinical and laboratory information. It has been
validated in adult surgical patients and high values correlate with an increased risk of
complication. [95] It probably, however, better reflects severity of illness than PEM.

Indirect Calorimetry

Indirect calorimetry (IC) measures the consumption of oxygen (V O2 ) and the production of
carbon dioxide (V CO2 ) when metabolic substrate is burned. If the patient inspires a known
concentration of O2 and CO2 , measurement of expired V O2 and V CO2 can be used to
calculate metabolic

672

energy expenditure. Resting energy expenditure (REE) can be determined using the
following formula:

Application of this technique in adults and children has both advantages and disadvantages.
Unlike other approximations of REE, such as tables [46] or the Harris-Benedict equation, [88]
IC can provide a real-time measurement of REE on an individual patient. Further, IC data
are accurate and reproducible. [27] IC applied to ventilated patients requires meticulous
attention to several factors. [143] [184] These include system leaks, inconsistent F IO2 delivery, [28]
and IC calibration and drift. For an F IO2 greater than 0.4 there is a potential for increased
error as the inspiratory/expiratory O2 percentage difference decreases [177] and oxygen
analyzers enter a nonlinear, less accurate range. In pediatrics, the use of uncuffed tubes
further adds to sampling error. [42] Attempts have been made to compensate for this effect. [157]

When appropriately applied and interpreted, IC may be the only clinically available tool
that can give real-time accurate information regarding energy expenditure and substrate
utilization. Whether knowing the REE influences outcome remains unproven. Certain
clinical situations, such as sepsis, trauma, burns, and chronic ventilation, make accurate
estimation of REE difficult. IC does offer the advantage of early detection of altered
metabolic states and can be used to monitor the adequacy of support over time. Equations
are being developed to account for disease-specific changes in REE [69] [70] [101] that may reduce
the need for IC.

SUBSTRATE

Metabolism

Humans depend on the hydrolysis of the phosphate bonds in adenosine triphosphate (ATP)
to provide energy. The ATP reserve has been estimated to last only a few minutes, so
adequate substrate for ATP generation is essential. Synthesis of ATP occurs in three sets of
biochemical reactions: (1) glycolysis (Embden-Meyerhof); (2) the tricarboxylic acid cycle
(Krebs); and (3) electron transport. [23] The last two phases generate the majority of ATP.
Both require oxygen as a final electron acceptor.

Glucose, the primary fuel for glycolysis, can be exogenous or supplied via the conversion
of stored glycogen. Glycerol and some amino acids can enter the Krebs cycle directly. Our
need to provide nutritional support in critically ill patients depends on a complex
relationship between intake, disease, and substrate stores.

To classify PEM, it is useful to distinguish between starvation and hypermetabolic stress. [19]
Starvation is the lack of nutrient intake. To compensate, the body attempts to reduce energy
expenditure and directs substrate stores to essential functions like maintaining the central
nervous

673

system. [114] The initial energy sources used are stored glycogen and glucose derived from
amino acids. The fuel source then converts to fatty acids, ketones, and glycerol. Protein
catabolism is reduced to preserve lean body mass. In contrast, hypermetabolic stress is an
activated state in which resting energy needs are increased and catabolism may be
rampant. [61] Potential indicators of this response include neural pathways, hormonal
mediators, and white cell products. Lean body mass wasting may exceed that expected for
comparable starvation (Table 1) . [19]

Both starvation and hypermetabolism result in loss of body cell mass. Critically ill patients
are often on a continuum between these two states. Given adequate caloric intake,
nutritional support spares starvation-mediated loss of lean body mass. For the
hypermetabolic patient, protein catabolism is only partially responsive to exogenesis
substrate. [19]

Caloric Requirements

The nutritional requirements of both healthy adults and children are well established.
Children, however, have the additional need to support growth and development. The US
guidelines, called the recommended daily allowances, are based on the average needs of
healthy people plus a 30% to 50% excess as a margin of error (Table 2) (Table Not
Available) . [45] For healthy adults the Harris-Benedict [88] equation is often used to estimate
REE.

where W is weight in kilograms, H is height in centimeters, and A is age in years.

For critically ill adults and children, disease-specific information to help estimate caloric
needs is limited. Long et al [118] using indirect calorimetry

TABLE 1 -- COMPARISON OF STARVATION AND STRESS HYPERMETABOLISM

From Barton RE: Nutrition support in critical illness. Nutrition in Clinical Practice 9:127,
1994; with permission.
 Stress
Starvation Hypermetabolism
REE Decreased Increased
Respiratory quotient (0.6-0.7) (0.8-0.9)
Mediator activation -- +++
Primary fuels Fat Mixed
Proteolysis + +++
Branched-chain oxidation + +++
Hepatic protein synthesis + +++
Ureagenesis + +++
Urinary nitrogen loss + +++
Gluconeogenesis + +++
Ketone body production ++++ +

674

TABLE 2 -- MEAN HEIGHTS AND WEIGHTS AND RECOMMENDED ENERGY INTAKE

IN INFANTS AND CHILDREN
Reprinted with permission from recommended Dietary Allowances: 10th Edition. Copyright
1989 by the National Academy of Sciences. Courtesy of the National Academy Press,
Washington, DC.
(Not Available)

on adults under varying degrees of stress, modified the Harris-Benedict equation to

account for activity and injury factors, called the actual energy expenditure (AEE): (AEE=
BMR × activity factor × injury factor) (Table 3) (Table Not Available) . For adults and
children, additional information is required to estimate caloric requirements better in the
ICU.

Carbohydrate

Any deficit in glucose availability triggers nitrogen wasting and the mobilization of fat
stores. Exogenous carbohydrate provision should prevent or at least reduce catabolism and
in part meet energy requirements. Ingested polysaccharides are converted in the gut into
oligo- and monosaccharides. Those are further hydrolyzed and transported across the brush
border via ATPase facilitated diffusion. Most glucose is delivered to the liver via the portal
circulation. [83] With parenteral nutrition
 TABLE 3 -- ACTIVITY FACTORS FOR ADJUNCT OF AEE CALCULATION
From Lond CL, Schaffel J, Geiger JW, et al: Metabolic response to injury and illness:
Estimation of energy and protein needs from calorimetry and nitrogen balance. Journal of
Parenteral and Enteral Nutrition 3:452, 1979; with permission.
(Not Available)

675

(PN) glucose may be taken up directly by all tissues and perhaps stored as glycogen.
Current recommendations for percent of total calories from carbohydrate are around 50%
in starvation. Hypermetabolic patients may require slightly more. There is an upper limit to
glucose oxidation (5 mg/kg/min), however, and hypermetabolic patients often exceed this
level. Thus, hyperglycemia is common in stress. [45] [173] [192] Excess carbohydrate
supplementation can result in increased CO2 production, fever, hepatic steatosis,
hyperosmolarity, and osmotic diuresis.

Lipid

The goals of lipid supplementation include providing for essential fatty acids, promoting
nitrogen sparing, and offering a balanced approach to fulfilling energy requirements.
Ingested fat forms chylomicrons in the gut lumen. These enter the mesenteric lymphatics
and drain into the systemic circulation via the thoracic duct. Chylomicra can be stored in
adipose tissue or delivered to the liver. In the liver, lipid can be directed into an energy-
yielding pathway, converted to ketone bodies for transport to remote tissues, or used for the
synthesis of bile salts. Intracellular transfer of lipid requires conversion to glycerol and free
fatty acids. [38] Parenteral lipids are handled similarly to chylomicrons. They also can be
incorporated into apoprotein-C-II. This compound activates lipoprotein lipase and further
promotes metabolism. [91]

To prevent essential fatty acid deficiency in children requires 0.5 g/kg/d. [73] For adults,
essential fatty acid deficiency can be prevented with PN lipids making up 3.2% or greater
of the total calories or with 15% of total enteral calories. [18] Using current balanced
formulations this can easily be achieved. Commonly, between 20% and 40% of total
calories in PN comes from lipids. Above a minimal carbohydrate load, lipids are as protein
sparing as glucose. [17] During stress hypermetabolism, lipid oxidation may be impaired by a
decrease in lipoprotein lipase activity. [146] Halberg, [84] however, has shown that there is
increased clearance of intravenous fat during stress. This fat is not necessarily used as a fuel
source and may help to preserve endogenous fat stores. [77]

A number of complications have been associated with lipid infusion. Significant hepatic
deposition has been found in septic rats. [40] Deposition of lipid in the reticuloendothelial
system has been linked to decreased phagocytosis and bacterial killing. [86] Bolus dosing of
lipid has been associated with reduced pulmonary diffusion capacity. [82] Altered lipid
metabolism in stressed patients has resulted in increased levels of triglycerides and free
fatty acids. [146] Hence, monitoring is particularly important for the hypermetabolic patient.

Protein

The goal of supplemental protein is to provide substrate for cellular protein synthesis and
the maintenance of lean body mass. Ingested

676

protein is broken down by brush border enzymes into amino acids and oligopeptides.
These are transported across the lumen for use in the liver, muscle, and other tissues. [83]
PN for patients with normal organ function contains a mixture of essential and
nonessential amino acids. Modified products are available for some disease states. A
modified product containing high concentrations of branched chained amino acids has
been shown to improve hepatic encephalopathy in some studies. [32] Use of this modified
product in other clinical situations has not been as successful.

For healthy humans, protein requirements decrease with age. Infants require over 2 g/kg/d,
whereas adults need 1 g/kg/d. [60] For critically ill patients the requirements are much more
complex. [91] In a metabolically stressed patient, protein requirements may increase as much
as 300%. [110] Although meeting the protein requirement in the hypermetabolic patient is
essential, prerenal azotemia can develop. Dialysis may be needed. [83]

ROUTE

The majority of information now suggests that the early use of enteral nutrition (EN) is
superior to PN. The use of PN is gradually being reduced to those situations where enteral
intolerance, inadequacy of surface area, or clinical concern regarding competency of the
alimentary tract are present.

A number of studies have identified route-related complications and outcome. Alexander et

al [5] were the first to show the benefits of EN in pediatric burn patients. Patients receiving
EN supplement had a 100% survival. Matched controls receiving PN alone had a 56%
survival. Herndon et al [93] showed similar findings in adult burn patients. Prospective,
randomized, unblinded trials [33] [134] have not documented improved survival. Infectious
complications, however, appear to be reduced. Moore et al, [134] studying adult trauma
patients, were able to show that patients receiving EN had a 3% infectious complication
rate, whereas those maintained on PN had a 20% rate. Early (within the first 24 hours)
initiation of EN may also reduce hypermetabolism and infectious risk. [131] [133]

The negative impact of PN has been shown in several ways. Disruption of the intestinal
barrier has been noted when PN was administered following burn injury and sepsis. [52] [195]
PN in the absence of stress has been associated with intestinal lumen atrophy and increased
permeability. [149] [188] This can yield bacterial and endotoxin translocation [97] [138] and is one
probable explanation for the increased infection rates with PN. Further human studies on
PN have shown impaired neutrophil function [128] and exaggerated production of counter-
regulatory hormones, [66] potentially worsening metabolic derangements seen in sepsis.

Complications and cost need to be considered. [2] The reported risk of complications for a
PN-dedicated catheter was 6%. [2] For needle

677

jejunostomy tubes the reported complication rate is 1.5%. [136] Chellis et al, [39] comparing the
cost of PN versus EN, estimated EN saves $425 per day over PN.

IMMUNONUTRITION

PEM and other specific deficiencies are known to have an impact on immune function. [35]
For example, PEM can reduce essentially all arms of the immune system including B-cell,
T-cell, macrophage, and neutrophil function; complement activation; and delayed
hypersensitivity. Recent research has focused not only on improving nutrition but also on
the effects of individual components on the immune system. This new approach is called
immunonutrition or nutritional pharmacology. [4] [124] [164]

Arginine

Arginine is a nonessential amino acid that functions as a precursor for nitric oxide. [132] In
animals and humans, arginine has been shown to [15] [16] [145] increase production and the
release of natural killer and helper T-cells in healthy volunteers. Barbul et al [14] have shown
that arginine increases thymic cellularity [145] and promotes wound healing in rats. In
humans, Daly et al [47] have shown reduced infection rates and shorter hospital stays in
postoperative cancer patients.

Glutamine

Glutamine is also a nonessential amino acid and a precursor for the synthesis of nucleic
acids. Stored in skeletal muscle, it appears to be the preferred fuel for enterocytes in times
of stress [167] and may prevent translocation of bacteria. [8] It also may serve as a fuel source
for T lymphocytes and macrophages. [106]

RNA

RNA appears to have immunostimulatory properties. [179] RNA-enriched enteral diets

increase the maturation and phenotypic expression of T-cells. Nucleotide free diets have
been associated with reduced cell-mediated immunity and T-cell activation. Restoration of
nucleotides to the diet reverses this process. [68] [142]
 678

Omega-3 Fatty Acids

Two essential fatty acids, linoleic acid and linolenic acid, have a significant impact on the
immune system. Linoleic acid, an omega-6 fatty acid, is found in common cooking oils and
in lipid emulsions used in PN. Linoleic acid is a precursor of arachidonic acid, and thus for
the four-series luekotrienes and the two-series eicosanoids, thromboxane A2 and
prostaglandin E2 . Leukotriene B4 is a potent neutrophil chemotactic agent and has a role in
neutrophil adhesion. [122] Thromboxane A2 is a potent bronchoconstrictor and promotes
platelet aggregation. [176] Prostaglandin E2 contributes to superoxide generation and increases
suppressor T-cell activity, reducing cell-mediated immunity. [55] Thus, the products of
omega-6 fatty acids are proinflammatory but limit the immune system's ability to clear the
insult.

Omega-3 fatty acids (linolenic) are found in fish oils. They are precursors for
docosahexaenoic acid and eicosapentaenoic acid, which in turn are precursors for three-
series prostaglandins and thromboxanes and five-series leukotrienes. These products have
significantly less biologic activity than the omega-6 products. They are less prone to
promote inflammation or immunosuppression. [6] [139] Several groups have shown improved
cell-mediated immunity and increased survival in stressed animals receiving omega-3 fatty
acid supplements. [31] [37] [139] Human data using immunomodulating diets suggest reduced
incidence of wound infections and improved length of stay in burn patients [79] and reduced
length of stay in ICU patients. [21] These results are preliminary but encouraging.

ORGAN SYSTEM AND DISEASE-SPECIFIC ISSUES

When evaluating the relationship between critical illness and nutrition, it is often difficult
to determine if the illness is impacting on nutrition or if nutrition is impacting on the
illness. This section briefly deals with these issues as they apply to specific diseases.

Respiratory Failure

Nutritional issues related to respiratory failure [80] [148] include the impact of malnutrition on
pulmonary structure and function, the consequences of feeding, and considerations with
mechanical ventilation. It has long been recognized that malnutrition may be a cause of
respiratory insufficiency. [24] [108] The development of premature emphysema has been noted
in young adults during periods of starvation [170] and in semistarved rats. [153] Starvation is
associated with reduced numbers of elastic fibers, altered surfactant, [153] a 30% to 40%
decrease in vital capacity, [10] [108] reduced diaphramatic mass, [10] decreased response to
hypoxia, [56] and blunted ventilatory drive. [183] Death from starvation is often due to
pneumonia. This

679
may relate to a reduction in pulmonary IgA production [165] and impaired T-cell function. [34]

Refeeding has been associated with a return of respiratory function [56] [108] [153] [183] but not a
resolution of emphysematous areas. [153] Amount and substrate mix have important
implications for CO2 production in respiratory failure. [49] In respiratory failure, initial
administration of calories to provide 1 to 1.2 times approximated REE per day is
appropriate until response to refeeding can be determined. [148] The commonly used Harris-
Benedict equation adjusted for injury and severity does not account for respiratory failure
and ventilation. [118] Therefore, indirect calorimetry may be helpful because overfeeding with
glucose can increase CO2 production via lipogenesis. If PN is required, a lower percentage
of total calories should be provided by carbohydrates to reduce the risk of hypercapnia. [140]
There has been some concern that high omega-6 lipid content can exacerbate adult
respiratory distress syndrome. [107] Some authors thus recommend that 50% of total calories
be supplied via lipid. [140] [148]

Given the effects of malnutrition on pulmonary function, nutritional status could influence
weaning from the ventilator. Several small retrospective reviews [20] [113] have supported this
association. In addition, micronutrient abnormalities have been implicated in unsuccessful
weaning. Hypophosphatemia has been linked to respiratory failure. [63] This may occur with
use of phosphate-binding aluminum or magnesium antacids or as a result of intracellular
movement of phosphate with glucose during PN. [100] Hypomagnesemia and hypokalemia
have been associated with respiratory failure. Serum magnesium levels may not adequately
reflect intramuscular deficiencies. [9] [59] Provision of concentrated nutrition formula may
also be necessary during weaning to minimize the impact of interstitial lung water.

Cardiovascular Disease

Cardiac cachexia [141] is a term used to describe malnutrition in patients with heart disease.
Starvation has been shown to reduce myocardial and skeletal muscle mass. [94] Nutritional
issues for cardiac patients deal as much with their tolerance of the supplement as the
supplement itself. Refeeding of severely malnourished patients is associated with
arrhythmias and sudden death. [104] This may be caused by intolerance of excess
intravascular volume, increased energy expenditure, or electrolyte abnormalities. [96] [104]
Supplemental nutrition can negatively impact factors determining myocardial oxygen
supply and demand. Heart rate may increase with the demands of increased REE seen with
refeeding. Hence, excess calories can have a negative effect. Indirect calorimetry is
probably the best way to determine the needs of adult patients. For children, 150 kcal/kg/d
has been estimated to meet the requirements for growth and development in infants with
congenital heart disease. More attention

680

may need to be paid to correction of low potassium, calcium, and magnesium to reduce
arrhythmias.
Liver Dysfunction

Patients with liver dysfunction develop protein energy malnutrition from anorexia,
malabsorption, early satiety, and reduced protein synthesis. [75] Nutritional supplementation
is crucial to improve status and to increase the likelihood of successful transplantation, [160] if
needed. Nutritional assessment in liver failure is particularly difficult given that edema and
ascites alter appendage circumferences and weight and that liver failure decreases
production of transport proteins, such as albumin, transferrin, and transthyretin. Clinical
judgment may be the best way to assess PEM severity. In the stable chronic liver failure
patient, protein requirements are generally in the normal range (1 g/kg/d for adults and 2.5
to 3 g/kg/d for infants). [22] [75] In hepatic encephalopathy, the amount of protein may need to
be reduced. Other sources for encephalopathy also need to be excluded, such as sepsis and
gastrointestinal bleeding. The use of formulas substituting branched chain amino acids for
aromatic and sulfhydryl-containing amino acids to improve hepatic encephalopathy is
controversial. In starvation, providing adequate total calories to prevent muscle catabolism
may be all that is needed to prevent the release of aromatic amino acids from skeletal
muscle. For adults, providing 25 to 30 kcal/kg/d (as estimated by the Harris-Benedict
equation) seems reasonable. Infants with liver failure require between 100 and 130
kcal/kg/d to provide for growth and development. [22] Fat-soluble vitamins are often deficient
and need to be supplemented.

Sepsis

The septic patient serves as a model of hypermetabolism. Derangements in carbohydrate,

protein, and lipid metabolism can be significant. [137] [191] REE is elevated and oxygen
consumption is increased. Glucose uptake by peripheral tissues is increased, [161] but the rate
of absolute oxidation is decreased. The increased need for glucose is met by an increased
rate of gluconeogenesis and glycolysis. [161] Catecholamines and glucagon are probably the
most important mediators for this increased synthesis. [116] Catecholamines may also mediate
the insulin resistance seen in sepsis. [116] Plasma free fatty acids may or may not be elevated.
[71]
Factors, such as blood flow and pH in adipose tissue, influence the release of free fatty
acids in the septic patient. [137] Catecholamines appear to be the dominate mediator for
lipolysis in sepsis. [193] Protein loss is due to degradation exceeding synthesis. [117] The net loss
of muscle mass can exceed 0.5 kg of body cell mass each day. [191] Treatment with
nutritional supplementation has been discussed.

681

Burns

Improved survival from extensive burns can be attributed in part to increased attention to
nutritional support. [53] A hypermetabolic response paralleling the extent of injury occurs
with burns. [187] Factors implicated in sustaining this reaction include inflammatory
mediators, counter regulatory hormones, and bacteria and endotoxin from the wound or
intestine. [53] Interestingly, serum interleukin-6 levels appear to correlate with burn size and
the degree of protein catabolism. [51] Mochizuki et al [131] have shown that enteral, but not
parenteral, feeds immediately postburn reduce the hypermetabolic response. This is
probably related to preservation of the intestinal barrier, which has been shown to be lost
after burns. [52]

Caloric requirements for burn victims have been extensively studied. For pediatric burns,
23 methods for predicting energy expenditure can be documented. [185] Mayes and colleagues
[122A]
looked at nine of the most commonly used methods and compared them with indirect
calorimetry. They found the revised Galveston formula to approximate the energy
requirements best for children less than 12 years with greater than 30% burns: kcal/d=
1800 kcal/m2 BSA + 1300 kcal/m2 BSAB, where BSAB= body surface area burned. For
adults, Deitch [53] has devised a burn severity factor, that can be used in conjunction with
the Harris-Benedict equation (Table 4) (Table Not Available) . [24]

The goal of closely approximating the caloric needs of burn victims is to avoid the dangers
of overfeeding and still provide adequate substrate to limit catabolism. Attention to other
issues, such as a thermally neutral environment, treatment of fever, relief of pain and
anxiety, and early coverage of wounds, is crucial to reversing the hypermetabolic state.

Renal Failure

For acute renal failure (ARF) there is no clear evidence that early institution of
hyperalimentation affects outcome. [120] Catabolism is a major cause of muscle mass loss in
ARF and may be related to inflammatory mediators, [186] impaired protein synthesis, [54]
blunted insulin-stimulated

TABLE 4 -- ADJUSTMENTS FOR BURN SEVERITY

From Deitch EA: Nutritional support of the burn patient. Crit Care Clin 11:735, 1995; with
permission.
(Not Available)

682

muscle protein synthesis, [130] and high levels of counter-regulatory hormones. [111] Because
of insulin resistance, there is increased hepatic gluconeogenesis [43] and hyperglycemia.
Lipolysis is impaired and elimination of infused lipid emulsions can be delayed. [57]
Electrolyte abnormalities, such as hyperkalemia, hyperphosphatemia, and hypocalcemia,
may also contribute.

Energy requirements based on the Harris-Benedict equation are generally 20% to 30%
higher for ARF. [155] [166] When PN is necessary, high glucose concentrations are preferred to
minimize fluid intake. Glucose intolerance may necessitate insulin administration.
Triglyceride clearance is reduced in ARF, [58] so decreased dosing and increased monitoring
may be required. The American Society for Parenteral and Enteral Nutrition recommends
a balance of both essential and nonessential amino acids be used. [4] This stems from
literature that initially suggested that an improved renal recovery was seen with a group
treated with essential amino acids exclusively. [1] This study was not supported with
additional studies. [62] [129] It is important to point out that reducing protein intake to limit
blood urea nitrogen generation is not helpful. Meeting protein needs may make dialysis
necessary, but this is preferable to protein malnutrition.

WOUND HEALING

The relationship between nutrition and wound healing seems self evident. Still, objective
human data demonstrating improved wound healing in any but severely malnourished
patients are scant. Albina [3] recently reviewed the evidence, both animal and human, to
support the relationship. The various outcomes assessed dealt with the quality of healing
based on tensile strength; collagen deposition; time; and complications, such as infection.
Several studies have demonstrated reduced anastomotic tensile strength in undernourished
rodents. [48] [102] [103] Whether this represented a lack of overall calories or a selected protein-
free diet as was intended is less of an issue than the fact that these animals had up to a 50%
reduction in wound strength. Most human studies have examined protein deposition in an
implanted tube of polytetrafluoroethylene. [3] [78] [154] The analysis involves measurement of
hydroxyproline, an indicator of collagen deposition, and of DNA as a marker of wound
cellularity. Several studies [89] [90] [156] [190] demonstrate a quantitative difference in the amount of
hydroxyproline recovered from the wounds of malnourished or underfed patients. The
relevance of this method has been questioned. Because there is no evidence that improving
nutrition is detrimental to wound healing, and several studies suggest it could be
beneficial, supplemental nutrition seems justified.

CONCLUSION

We have the ability to supply a wide variety of PN and EN supplements to both adult and
pediatric critically ill patients. Choosing the

683

right kind, amount, and route is very complex and the literature is often vague. The use of
early enteral feeds, whenever possible, is gaining support. Despite many methods of
assessing malnutrition, the best test may be clinical judgment. Estimating energy needs
and response to intervention can be done reliably in health but is unproven in many
diseases. Finally, although there is some disagreement as to the amount of the various
nutrients to be given, it is generally agreed that a balanced approach coupled with careful
monitoring is important. The manipulation of various nutrients may have a significant
impact on certain disease states. Thus, nutrition for the critically ill adult or child is
constantly challenging.

References
1. AbelRM, et al: Improved survival from acute renal failure after treatment with essential amino
acids and glucose: Results of a prospective double blind study. N Engl J Med 288:695, 1973

2. Adul KA, Farr BM: Central venous catheter related infection: A review. Nutrition 12:208, 1996

3. Albina JE: Nutrition and wound healing. Journal of Parenteral and Enteral Nutrition 18:367,
1994

4. Alexander JW: Immunonutrition: An emerging strategy in the ICU. J Crit Care Nutr 1:21, 1993

5. AlexanderJW, MacMillan BG, Stinnelt JD, et al: Beneficial effect of aggressive feeding in severely
burned children. Ann Surg 192:505, 1980

6. Alexander JW, Saxton H, Trocki O, Ogle CK: The importance of lipid type in the diet after burn
injury. Ann Surg 125:86, 1990

7. Anderson CF, Wochas DN: The utility of serum albumin values in the nutritional assessment of
hospitalized patients. Mayo Clin Prac 57:181, 1982

8. AndrassyRJ: Preserving the gut mucosal barrier and enhancing the immune response. Contemp
Surg 42:21, 1987

9. Anonymous: Hypokalemic respiratory arrest in diabetic ketoacidosis. JAMA 257:3363, 1987

10. Arora NS, Rochester DF: Respiratory muscle strength and maximal voluntary ventilation in
undernourished patients. Am Rev Respir Dis 126:5, 1982

11. A.S.P.E.N. Board of Directors: Guidelines for the use of parenteral and enteral nutrition in adult
and pediatric patients. Journal of Parenteral and Enteral Nutrition 17:155A, 1993

12. Baker JP: A comparison of the predictive value of nutritional assessment techniques. Hum Nutr
Clin 36C:233, 1982

13. Baker JP, Detsky AS, Weeson DG, et al: Nutritional assessment: A comparison of clinical
judgement and objective measurements. N Engl J Med 306:969, 1982

14. Barbul A, Rettura G, Levenson SM, Seifer E: Arginine: A thymatropic and wound healing
promoter agent. Surg Forum 28:101, 1977

15. Barbul A, Sisto PA, Wasserkru HL, Efron G: Arginine stimulate lymphocyte immune response in
healthy humans. Surgery 90:244, 1981

16. Barbul A, Wasserkru HL, Reifter E: Immunostimulatory effects of arginine in normal and injured
rats. J Surg Res 29:228, 1980

17. Bark S, Holm I, et al: Nitrogen sparing effect of fat emulsion compared with glucose in the post
operative period. Acta Chir Scand 142:423, 1976

18. Barr LH, Dunn GD, Brennan MF: Essential fatty acid deficiency during total parenteral nutrition.
Ann Surg 193:304, 1980

19. Barton RE: Nutrition support in critical illness. Nutrition in Clinical Practice 9:127, 1994
 684

20. Bassili HR, Deitel M: Effect of nutritional support on weaning patients off mechanical ventilators.
Journal of Parenteral and Enteral Nutrition 5:161, 1980

21. Bauer RH, Lavin PT, LiCari JJ, et al: A modified enteral formula reduces hospital length of stay in
patients in intensive care units. Critical Care Medicine 21:S275, 1993

22. Becht MB, Pedisen SH, et al: Growth and nutritional management of pediatric patients after
orthotopic liver transplantation. Gastro Clin North Am 22:367, 1993

23. Becker WM: Energy and the Living Cell: An Introduction to Bioenergetics. Philadelphia, JB
Lippincott, 1977

24. Benedict FA: A Study of Prolonged Fasting. Washington, DC, Carnegie Institute, 1915

25. Bishop CW, Ritchey SJ: Evaluating upper arm anthropometric measurements. J Am Diet Assoc
84:331, 1984

26. Blackburn GL, Harvey KB: Nutritional assessment as a routine in clinical medicine. Postgrad
Med 71:46, 1982

27. Brondi LS, Grana M, Mazzanti T, et al: Energy expenditure and gas exchange measurements in
postoperative patients: Thermodilution vs. Indirect calorimetry. Critical Care Medicine 20:1273,
1992

28. Browning JA, Lindberg SE, Turney SF: The effects of fluctuating F IO2 on metabolic
measurements in mechanically ventilated patients. Critical Care Medicine 6:162, 1982

29. Burgess EJ, Fleck A: Inadequacy of measuring urea for the estimation of nitrogen balance during
parental nutrition. Ann Clin Biochem 27:163, 1990

30. Carpenter YA, Askanazi J, Elwyn DH, et al: Effects of hypercaloric glucose infusion or lipid
metabolism on injury and sepsis. J Trauma 19:649, 1979

31. Cerra FB, Alden PA, Negro F, et al: Sepsis and exogenous lipid modulation. Journal of
Parenteral and Enteral Nutrition 12:63S

32. Cerra FB, Cheung NK, Fischer JE, et al: Disease specific amino acid infusion in hepatic
encephalopathy. A prospective randomized double blinded controlled trial. Journal of Parenteral
and Enteral Nutrition 9:288, 1985

33. Cerra FB, McPherson JP, Konstantinides FN, et al: Enteral nutrition does not prevent multiple
organ failure after sepsis. Surgery 104:727, 1988

34. Chandra RK: Cell mediated immunity in nutritional imbalance. Fed Proc 39(13):3088, 1980

35. Chandra RK: Immunity and infection. In Kinney JM, Jeejeebhoy KN, Hill GL, Owen OE: Nutrition
and Metabolism in Patient Care. Philadelphia, WB Saunders, 1988

36. Chandra RK: Nutrition, immunology and infection: Present knowledge and future direction.
Lancet 1:688, 1983
37. Chandra RK, Baker M, Whang S, Au B: Effect of two feeding formulas on immune responses
and mortality in mice challenged with listeria monocytogenes. Immun Lett 27:45, 1991

38. Charney P: Nutritional assessment in the 1990's: Where are we now? Nutrition in Clinical
Practice 10:131, 1995

39. Chellis MJ, Sanders SV, et al: Early enteral feeding in the pediatric intensive care unit. Journal of
Parenteral and Enteral Nutrition 20:71, 1996

40. Chen WJ: Utilization of intralipid in septic rats: Effects of sepsis on the clearance of exogenous
fat emulsions from various organs. Journal of Parenteral and Enteral Nutrition 10:482, 1986

41. Church JM, Hill GL: Assessing efficacy of intravenous nutrition in general surgical patients:
Dynamic nutritional assessment using plasma proteins. Journal of Parenteral and Enteral Nutrition
11:135, 1987

42. Chwals WJ, Lally KP, Wooley MM: Indirect calorimetry in mechanically ventilated infants and
children, measurement accuracy with absence of audible airleak. Critical Care Medicine 20:768,
1992

43. Cianciorusi B, et al: Hepatic uptake and release of glucose, lactate and amino acids in acutely
uremic dogs. Metabolism 40:261, 1991

44. Clemmons DR, Underwood LE, Dickinson RN, et al: Use of plasma somatomedin-C/insulin like
growth factor measurements to monitor the response to nutritional repletion in malnourished
patients. Ann J Clin Nutr 41:191, 1985

685

45. Committee on Dietary Allowance Food and Nutrition Board: Washington, DC, National
Research Council, National Academy of Science, 23, 1980

46. Consaluzio CF, Johnson RE, Pecora LJ: Physiological Measurement of Metabolism Functions in
Man. New York, McGraw-Hill, 1963

47. Daly JM, Lieberman MD, Goldfine J: Enteral nutrition with supplemental arginine, RNA, and
Omega-3 fatty acids in patients after operation: Immunologic, metabolic, and clinical outcome.
Surgery 112:56, 1992

48. Daley JM, Vars HM, Dudrick SH: Effects of protein depletion on strength of colonic anastomoses.
Surg Gynecol Obstet 134:15, 1972

49. Dark D, Pingleton SK, Kerby GR: Hypercapnia during weaning: A complication of nutritional
support. Chest 88:141, 1985

50. Dauncey MJ, Gandy G, Gairdner D: Assessment of total body fat in infancy from skinfold
thickness measurements. Arch Dis Child 52:223, 1977

51. DeBondt JP, Chollet-Martin S, Hermann A, et al: Cytokine response to burn injury: Relationships
to protein metabolism. J Trauma 36:624, 1994
52. Deitch EA: Intestinal permeability is increased in burn patients shortly after injury. Surgery
107:411, 1990

53. Deitch EA: Nutritional support of the burn patient. Crit Care Clin 11:735, 1995

54. Delaporte C, Gros F, Anagnastopoulos T: Inhibiting effects of plasma dialysate on protein

syntesis in vitro: Influence of dialysis and transplantation. Am J Clin Nutr 33:1407, 1980

55. Dinarello CA, Marnay SO, Rosenwasser LJ: Role of arachidonic metabolism in
immunoregulatory function in human leukocytic pyrogen/lymphacyte activity factor. J Immunol
130:890, 1983

56. Doekel RC Jr, Zwillich CW, Scoggin CH, et al: Clinical semi-starvation: Depression of hypoxic
ventillary response. N Engl J Med 295:358, 1976

57. Druml W, et al: Post heparin lipolytic activity in acute renal failure. Clin Nephrol 23:289, 1985

58. Druml W, Fischer M, Seth S, et al: Fat elimination in acute renal failure: Long chain vs. medium
chain triglyceride. Am J Clin Nutr 55:468, 1992

59. Faccadori E, DelConale S, Coffini E, et al: Muscle and serum magnesium in pulmonary intensive
care unit patients. Critical Care Medicine 16:751, 1988

60. FAD/WHO/UNU: Energy and Protein Requirements. Geneva, WHO Technical Series 724, 1985,
pp 1-206

61. Fath JJ, Meguid MM, Cerra FB: Hormonal and metabolic responses to surgery and stress. In
Goldsmith HM (ed): Practice of Surgery. New York, Harper and Row, 1985

62. Feinstein EI, Blumenkrantz MJ, Healy M, et al: Clinical and metabolic responses to parenteral
nutrition in acute renal failure. A controlled double blinded study. Medicine 60:124, 1981

63. Fiaccadori E, Caffrini E, Fracchci C, et al: Hypophosphatemia and phosphous depletion in

respiratory and peripheral muscles in patients with respiratory failure due to COPD. Chest
105:1392, 1994

64. Fleck A: Plasma proteins as nutritional indicators in the perioperative period. Br J Clin Pract
42(supp 63):20, 1988

65. Fletcher JP, Little JM, Guest PK: A comparison of serum transfusion and serum prealbumin as
nutritional parameters. Journal of Parenteral and Enteral Nutrition 11:144, 1987

66. Fong Y, Marono MA, Barber A, et al: Total parenteral nutrition and bowel rest modify the
response to endotoxin humans. Ann Surg 210:449, 1989

67. Forse RA, Shizgal HM: Serum albumin and nutritional status. Journal of Parenteral and Enteral
Nutrition 4:450, 1980

68. Fourlow WC, Kulkarni AD, Van Buren CT, Rudolph FB: Effect of nucleotide restriction and
supplementation on resistance to experimental candidiasis. Journal of Parenteral and Enteral
Nutrition 12:49, 1988

69. Frankenfield DC, Omert LA, Badellino MM, et al: Correlation between measured energy
expenditure and clinically obtained variable in trauma and sepsis patients. Journal of Parenteral and
Enteral Nutrition 18:398, 1994

70. Frankenfield DC, Wiles CD, Bagley S, Siegel J: Relationship between resting and

686

total energy expenditure in injured and septic patients. Critical Care Medicine 22:1796, 1994

71. Frayn KN: Hormonal control of metabolism in trauma and sepsis. Clin Endocrinol 24:577, 1986

72. Frayn KN, Price DA, Maycock PR, et al: Plasmasomatomedin activity after injury in man and its
relationship to other hormonal and metabolic changes. Clin Endocrinol 20:179, 1984

73. Friedman Z, Danon A, Stahlman MR, et al: Rapid onset of essential fatty acids deficiency in the
newborn. Pediatrics 58:640, 1978

74. Fuller NJ, Jebb SA, Goldberg GR, et al: Interobserver variability in the measurement of body
composition. Eur J Clin Nutr 45:43, 1991

75. Gecelter FR, Comer GM: Nutritional support during liver failure. Crit Care Clin 11:675, 1995

76. Gomez F, Galvion RR, Ciavioto J, Frenk S: Malnutrition in infancy and childhood with special
reference to Kwaskiorkor. Adv Pediatr 7:137, 1955

77. Goodenough RD, Wolfe RR: Effect of total parenteral nutrition on free fatty acid metabolism in
burned patients. Journal of Parenteral and Enteral Nutrition 8:357, 1984

78. Goodson III WH, Hunt TK: Development of a new miniature method for the study of wound
healing in human subjects. J Surg Res 33:394, 1982

79. Gottschlich MM, Jenins M, Warden GD, et al: Differential effects of three enteral dietary regimes
on selected outcomes variables in burn patients. Journal of Parenteral and Enteral Nutrition
14:225, 1990

80. Grant JP: Nutrition care of patients with acute and chronic respiratory failure. Nutr Clin Pract
9:11, 1994

81. Gray GE, Gray LK: Anthopometric measurements and their interpretation: Principles, practices,
and problems. J Am Diet Assoc 77:534, 1980

82. Greene HL, Hazlett O, Demaree R: Relationship between intralipid induced hyperlipemia and
pulmonary function. Am J Clin Nutr 29:L127, 1976

83. Haber BA, Deutschman CS: Nutrition and metabolism in the critically ill child. In Rodger
Textbook of Pediatric Intensive Care, ed 2. Baltimore, MD, Williams & Wilkins, 1996

84. Halberg D: Studies on the elimination of exogenous lipids from the blood stream. Acta Physiol
Scand 65:151, 1965

85. Hall JC, O'Quigley J, Giles GR, et al: Upper limb anthropometry: The value of measurement
variance studies. Am J Clin Nutr 33:1846, 1980
86. Hamawy KJ, Maldower LL, et al: The effect of lipid emulsion on the reticuloendothelial system
function in the injured animal. Journal of Parenteral and Enteral Nutrition 9:559, 1985

87. Hamill PW, Drizd TA, Johnson CL, et al: Physical growth: National Center for Health Statistics
Percentiles. Am J Clin Nutr 32:607, 1979

88. Harris JA, Benedict TG: Biometric Studies of Basal Metabolism in Man. Publication 279.
Washington, DC, Carnegie Institute, 1919

89. Haydock DA, Hill GL: Impaired wound healing in surgical patients with varying degress of
malnutrition. Journal of Parenteral and Enteral Nutrition 10:550, 1986

90. Haydock DA, Hill GL: Improved wound healing response in surgical patients receiving
intravenous nutrition. Br J Surg 74:320, 1987

91. Heird WC: Amino acid and energy needs of pediatric patients receiving parenteral nutrition.
Pediatr Clin North Am 42:765, 1995

92. Herman F, Safran C, Leukoff S, et al: Serum albumin on admission as a predictor of death,
length of stay and readmission. Arch Intern Med 152:125, 1992

93. Herndon DN, Barrow RE, Stein M, et al: Increased mortality with intravenous supplemental
feeding in severely burned patients. J Burn Care Rehabil 10:309, 1989

94. Heymsfield SB, Bethel RA, Ansley JD, et al: Cardiac abnormalities in cachectic patients before
and during nutritional repletion. Am Heart J 95:584, 1978

95. Hooley R, Levine H, Flores TC, et al: Predicting post operative head and neck complications
using nutritional assessment. Arch Otolargyngol Head Neck Surg 109:83, 1983

687

96. Howard CWH, Fonnera V: Electrolyte disturbances and cardiac failure with hypomagnesium in
anorexia nervosa. BMJ 291:1680, 1985

97. Howeston EE, Kalman SN: The intestinal tract as a portal of entry of Pseudomonas in burned
rats. J Trauma 12:335, 1972

98. Ingelbleek Y, De Visscher M, DeNayer P: Measurement of prealbumin as index of protein calorie

malnutrition. Lancet 2:106, 1972

99. Ingelbleek Y, Von den Schriek HG, DeNayer PH, et al: Albumin, transferin and thyroxin binding
prealbumin/retinol binding protein complex in assessment of malnutrition. Clin Chim Acta 63:61,
1975

100. Ireton-JonesC, Borman K, Turner Jr WW: Nutrition considerations in the management of

ventilator dependent patients. Nutrition in Clinical Practice 8:60, 1993

101. Ireton-JonesCS, Turner Jr WW, Liepa GU, Baxter CR: Equations for estimation of energy
expenditure in patients with burns with special reference to ventilation status. J Burn Care Rehabil
13:330, 1992
102. Irvin
TT: Effect of malnutrition and hyperalimentation on wound healing. Surg Gynecol Obstet
146:33, 1978

103. Irvin TT, Hunt TK: Effect of malnutrition on colonic healing. Ann Surg 180:765, 1974

104. Isner
HM, Robberts WC, Heymfield SB, et al: Anorexia nervose and sudden death. Ann Intern
Med 102:49, 1985

105. Jeejeebhoy KN, Meguid MM: Assessment of nutritional status in the oncological patient. Surg
Clin North Am 66:1077, 1986

106. Kaproth RP, Konstantinides FN, Moga CN, Cerra FB: Free glutamine is available to the
intestinal mucosa from intact protein based enteral diets. Abstract 413, ASPEN, 1991

107. Kelsen SG, Ference M, Kapoor S: Effects of prolonged undernutrition on structure and function
of the diaphram. J Appl Physiol 58:1354, 1985

108. Keyes A, Brozek J, Henschel A: The Biology of Human Starvation. Minneapolis, University of
Minnesota Press, 1950

109. Kinney MM, Zarem HA, Rogers RL: Energy expenditure and utilization of carbohydrate, fat and
protein in hospitalized patients. J Clin Invest 38:1017, 1959

110. Knutrud O: The Water and Electrolyte in the Newborn Child After Major Surgery. Oslo, Norway,
University Forlaget, 1965

111. KokotF, Kuska J: The endocrine system in patients with acute renal insufficiency. Kidney Int
10(suppl 6):526, 1976

112. Krug-Wispe S: Nutrition assessment. In Queen PM, Long CE (eds): Handbook of Pediatric
Nutrition. Gaithersberg, MD, Aspen Publishers, 1993, pp 26-63

113. Larca L, Greenbaum DM: Effectiveness of intensive nutritional regimes in patients who fail to
wean from mechanical ventilation. Critical Care Medicine 10:297, 1982

114. Levenson SM, Sifter E: Starvation: Metabolic and physiologic responses. In Fischer JE (ed):
Practice of Surgery. New York, Harper and Row, 1985

115. Lohman TG: Skinfolds and body density and their relation to body fatness: A review. Hum Biol
25:181, 1981

116. LongCH: Sepsis induced insulin resistance is mediated by a beta-adrenergic mechanism. Am J

Physiol 262:E703, 1992

117. Long CL, Joevonandorn M, Kim BM, et al: Whole body protein synthesis and catobolism in
septic man. Am J Clin Nutr 30:1340, 1977

118. Long CL, Schaffel J, Geiger JW, et al: Metabolic response to injury and illness: Estimation of
energy and protein needs from indirect calorimetry and nitrogen balance. Journal of Parenteral and
Enteral Nutrition 3:452, 1979

119. Makela JT, Kellosalo J, Laitinen SO, Kairabioma MI: Morbidity and mortality after abdominal
operation for cancer. Hepatogastroenterology 39(S):420, 1992
120. Malina MF, Riella MC: Nutritional support in the patient with renal failure. 11:685, 1995

121. Manning EM, Shenkin A: Nutritional assessment in the critically ill. Crit Care Clin 11:603, 1995

122. Mayatepek E, Hoffman GF: Leukotrienes: Biosynthesis, metabolism, and pathophysiologic

significance. Pediatr Res 37:1, 1995

122A. Mayes T, Gottschlich MM, Khoury J, et al: Evaluation of predicted and measured

688

energy requirements in burned children. Journal of the American Dietetic Association 96(1):24-29,
1996

123. McClave S, Mitoraz T, Thielmeier K, et al: Differentiating subtypes of protein calorie

malnutrition: Incidence and clinical significance in a university hospital setting. Journal of Parenteral
and Enteral Nutrition 16:337, 1992

124. McClave SA, Lowen CC, Snider HL: Immunonutrition and enteral hyperalimentation of critically
ill patients. Dig Dis Sci 37:1153, 1992

125. McLaren DS, Reed WWC: Classification of nutritional status in early childhood. Lancet 2:146,
1972

126. McLaren DS, Reed WWC: Weight/length classifications of nutritional status. Lancet 2:219, 1975

127. McMahon MM, Farnell MB, Murray MJ: Nutritional support on critically ill in sepsis patients.
Mayo Clin Proc 68:911, 1993

128. Meyer J, Yurt RW, Duhoney R, et al: Differential neutrophil activation before and after endotoxin
infusion in enterally versus parenterally fed human volunteers. Surg Gynecol Obstet 167:501, 1988

129. Mirtalla JM, et al: A comparison of essential and general amino acids infusion in the nutritional
support of patients with compromised renal function. Journal of Parenteral and Enteral Nutrition
6:109, 1982

130. Mitch WE: Amino acid release by the hind quarter and urea appearance on acute uremia. Am J
Physiol 241:415, 1981

131. Mochizuki H, Trocki O, Dominioni L, et al: Mechanism of post burn hypermetabolism and
catabolism by early enteral feeding. Ann Surg 200:297, 1984

132. Moncada S: The L-arginine nitric oxide pathway. Acta Physiol Scand 145:201, 1992

133. MooreEE, Jones TN: Benefits of immediate jejunostomy feeding after major abdominal trauma:
A prospective randomized study. J Trauma 26:874, 1986

134. Moore FA, Moore EE, Jones TN, et al: TEN vs. TPN following major abdominal trauma-induced
septic morbidity. J Trauma 29:916, 1989

135. MoyesT, Gottschlich MM, Khourg J, Warden GD: Evaluation of predicted and measured energy
requirement in burned children. J Am Diet Assoc 96:24, 1996
136. Myers JG, Page CP, et al: Complications of needle catheter j ejuneostomy in 2022 consecutive
applications. Am J Surgery 170:547, 1995

137. NelsonKM, Long CL: Physiological basis for nutrition in sepsis. Nutrition in Clinical Practice
4:142, 1989

138. O'Dwyer ST, Michie HR, Ziegler TR, et al: A single dose of entotoxin increases intestinal
permeability in healthy humans. Arch Surg 123:1459, 1988

139. Pick MD, Ogle CK, Alexander JW: Composition of fat in enteral diets can influence outcome in
experimental peritonitis. Ann Surg 213:74, 1991

140. Pinard B, Geller E: Nutritional support during pulmonary failure. Crit Care Clin 11:705, 1995

141. Pittman JG, Cohen P: The pathogenesis of cardiac cachexia. N Engl J Med 271:403, 1964

142. Pizzini RP, Kurmar S, Kulkarni AD, et al: Dietary nucleotides reverse malnutrition and starvation
induced immunosuppression. Arch Surg 204:1, 1986

143. Porter C, Cohen NH: Indirect calorimetry in critically ill patients: Role of the clinical dietician in
interpreting results. Journal of American Dietetic Association 96:49, 1996

144. Reinhardt GF, Myscofski, Wilken D: Incidence and mortality of hypoalbuminemic patients in
hospitalized veterans. J Parent Enter Nutr 4:357, 1980

145. Retheria G, Padaver J, Barbul A, et al: Supplemental arginine increases thymic cellularity in
normal and murine sarcoma virus inoculated mice and increases resistance to murine sarcoma
virus tumor. Journal of Parenteral and Enteral Nutrition 3:409, 1979

146. RobinAP, Askanazi J, Greenwood MRC: Lipoprotein lipase activity in surgical patients:
Influence of trauma and infection. Surgery 90:401, 1981

147. Robinett-Weiss N, Hixson ML, Keir B, et al: The Metropolitan height/weight tables: Perspectives
for use. J Am Diet Assoc 84:1480, 1984

148. Rothkopf MM, Stanislous G, Haverstrick L, et al: Nutritional support in respiratory failure.
Nutrition in Clinical Practice 4:184, 1989

689

149. Rothman D, Latham MC, Walker WA: Transport of macromolecules in malnourished animals:
Evidence of increased uptake of intestinal antigens. Nutr Res 2:467, 1982

150. Rothschild MA, Oratz M, Schrieber SS: Albumin synthesis. N Engl J Med 286:748, 1972

151. Roy LB, Edwards PA, Barr LH: The value of nutritional assessment in the surgical patient.
Journal of Parenteral and Enteral Nutrition 9:170, 1985

152. Roza AM, Twitt D, Shizgal HM: Transfusion: A poor measure of nutritional status. Journal of
Parenteral and Enteral Nutrition 8:523, 1984
153. SahebjamiJ, Wirmon JA: Emphysema like changes in the lungs of starved rats. Am Rev Respir
Dis 124:619, 1981

154. Sandberg N, Zederfeldt B: The tensile strength of healing wounds and collagen formation in rats
and rabbits. Acta Clin Scand 126:187, 1963

155. Schneeweiss B, et al: Energy metabolism in acute and chronic renal failure. Am J Clin Nutr
52:596, 1990

156. Schroeder D, Gillandes L, Mahr K, et al: Effects of immediate post-op enteral nutrition and
body composition, muscle function, and wound healing. Journal of Parenteral and Enteral Nutrition
15:376, 1991

157. Selby AM, McCauley JC, Schnell DN, et al: Indirect calorimetry in mechanically ventilated
children: A new technique that overcomes the problem of endotracheal tube leak. CCM 23:365,
1995

158. Seltzer
MH, Bastidas JA, Cooper DM, et al: Instant nutritional assessment. Journal of Parenteral
and Enteral Nutrition 3:157, 1979

159. Seltzer MH, Slocum BA, Cataldi-Betcher EL, et al: Instant nutritional assessment: Absolute
weight loss and surgical mortality. Journal of Parenteral and Enteral Nutrition 6:218, 1982

160. Shaw BW, Wood P, Gordon RD, et al: Influence of selected patient variables and operative
blood loss on 6 mo survival following liver transplantation. Series Liver Dis 5:385, 1985

161. Shaw JHF, Klein S, Wolfe RR: Assessment of alonin, urea, and glucose interrelationships in
normal subjects and in patients with sepsis with stable isotopic traces. Surgery 97:557, 1985

162. Shaw JHF, Wildorne M, Wolfe RR: Whole body protein kinetic in severely septic patients: The
response to glucose infusion and total parental nutrition. Ann Surg 205:288, 1987

163. Shetty PS, Jung RT, Watrasiewicz KE, et al: Rapid-turnover transport proteins: An index of
subclinical protein energy malnutrition. Lancet 2:230, 1979

164. Shronts EP: Basic concepts in immunology and its application to clinical nutrition. Nutrition in
Clinical Practice 8:131, 1993

165. Sirisinha S, Suskind R, Edelman R, et al: Secretory and serum IgA in children with protein
calorie malnutrition. Pediatrics 55:166, 1975

166. Soop M, Forsberg A, Thorne A, et al: Energy expenditure in post operative multi organ failure
with acute renal failure. Clin Nephrol 31:139, 1989

167. Souba WW: The gut as a nitrogen-processing organ in the metabolic response to critical illness.
Nutr Supp Serv 8:15, 1988

168. Spiekerman AM: Proteins used in nutritional assessment. Clinics in Laboratory Medicine,
13(2)353, 1993

169. Starker PM, Gump FE, Askanazi J, et al: Serum albumin levels as an index of nutritional
support. Surgery 91:194, 1982
170. Stein J, Fenigstein H: Anatomie pathologique de la maladie de famine. In Apfilbaum E (ed):
Maladie de Famine. Warsaw, American Joint Distribution Committee, 1946, pp 21-77

171. Strong RM, Condon SC, Solinger MR, et al: Equal aspiration rates from post pylorus and
intragastric placed feeding tubes: A randomized prospective study. Journal of Parenteral and
Enteral Nutrition 16:59, 1992

172. Studley HO: Percentage of weight loss. A basic indicator of surgical risk in patient with chronic
peptic ulcer. JAMA 106:458, 1936

173. Taylor L, O'Neill Jr JA: Total parenteral nutrition in the pediatric patient. Surg Clin North Am
71:477, 1991

690

174. Teabeaut II JR: Aspiration of gastric contents: An experimental study. Am J Pathol 28:51, 1952

175. The Veterans Affairs Total Parenteral Nutritional Cooperative Study Group: Perioperative
nutrition in surgical patients. N Engl J Med 325:525, 1991

176. Thien FCK, Walters EH: Eicosanoids and asthma: An update: Prostaglandins Leukotrienes and
Essential Fatty Acids. 52:271, 1995

177. Ultman JS, Burzstein S: Analysis error in the determination of respiratory gas exchange at
varying F IO2 . J Appl Physiol 50:210, 1981

178. Unterman TG, Vazquez RM, Slas AJ, et al: Nutrition and somatomedin. Usefulness of
somatonein-C in nutritional assessment. Am J Med 78:228, 1985

179. VanBuren CT, Kulkarni AD, Schondle VB: The influence of dietary nucleotides on cell mediated
immunity. Transplantation 63:350, 1983

180. VonMeyenfeldt MF, Meyerink WJHJ, Rouflant MMJ, et al: Perioperative nutritional support: A
randomized clinical trial. Clin Nutr 11:180, 1992

181. Waterlow JC: Classification and definition of protein-calorie malnutrition. BMJ 3:566, 1972

182. Waterlow JC: Some aspects of childhood malnutrition as a public health problem. BMJ 4:88,
1974

183. Weissman C, Askunazi J, Rosenbaum S, et al: Amino acids and respiration. Ann Intern Med
98:41, 1983

184. Weissman C, Kemper M: Metabolic measurements in the critically ill. Crit Care Clin 11:169,
1995

185. Williamson J, Marvin J, Heimbach DM: Actual nutrition care practicies for burn patients: A
national survey. Proc Am Burn Assoc 21:116, 1989

186. Wilmore DW: Catabolic illness: Strategies for enhancing recovery. N Engl J Med 325:695, 1991
187. Wilmore DW, Aulick LH: Metabolic changes in burned patients. Surg Clin North Am 58:1173,
1978

188. Wilmore DW, Smith RJ, O'Dwyer ST, et al: The gut: A central organ after surgical stress.
Surgery 104:917, 1988

189. Windsor
JA, Hill GL: Weight loss with physiologic impairment: A basic indicator of surgical risk.
Ann Surg 207:290, 1988

190. Windsor JA, Knight GS, Hill GL: Wound healing response in surgical patients: Recent good
intake is more important than nutritional status. Br J Surg 75:135, 1988

191. Wojnor MM, Kaukins WG, Long CH: Nutritional support of the septic patient. Crit Care Clin
11:717, 1995

192. Wolfe R, Allsop J, Burke J: Glucose metabolism in man: Responses to intravenous glucose
infusion. Metabolism 28:210, 1979

193. Wolfe RR, Shaw JHF: Glucose and FFA kinetics in sepsis. Role of glucagon and sympathetic
nervous system activity. Am J Physiol 248:E236, 1985

194. Wright JA, Ashenberg CA, Whitaker RC: Comparison of methods to categorize undernutrition in
children. J Pediatr 124:944, 1994

195. Ziegler TR, Smith RJ, O'Dwyer ST, et al: Increased intestinal permeability associated with
infection in burn patients. Arch Surg 123:1313, 1988

MD Consult L.L.C. http://www.mdconsult.com

Bookmark URL: /das/journal/view/N/9881428?ja=67991&PAGE=1.html&ANCHOR=top&source=HS,MI