The gut as an immune organ Science supporting better nutrition In this issue

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ISSN 1815-7262
Science supporting
better nutrition
2008 • Volume 4, Issue 2
In this issue
The gut as an immune organ
Clinical nutrition abstracts
Highlights of Clinical Nutrition Week 2008
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CLINICAL
NUTRITION
HIGHLIGHTS
Science supporting
better nutrition
2008 • Volume 4, Issue 2
Feature article
2
The gut as an immune organ
Yoshifumi Sano, Joshua L Hermsen and Kenneth A Kudsk
Clinical nutrition abstracts
Cancer
Cardiovascular disease
Critical care nutrition
Diabetes
Gastrointestinal disorders
Hepatic disease
Nutrition support
Pediatrics
Highlights of Clinical Nutrition Week
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10-14 February 2008
Conference calendar
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24
Feature article
{
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The gut as
an immune organ
Yoshifumi Sanob MD, PhD, Joshua L Hermsenb MD and Kenneth A Kudska,b MD
a
Veterans Administration Surgical Services,
William S Middleton Memorial Veterans Hospital,
Madison, Wisconsin, USA
b
Department of Surgery,
University of Wisconsin-Madison College of Medicine and Public Health,
Madison, Wisconsin, USA
Source of support: NIH grant R01 GM53439
Introduction
}
overall mucosal-associated lymphoid tissue (MALT). Because of, or
more likely as a result of, this arrangement, all mucosal surfaces of
Humans share the environment with huge numbers of micro-
the body are immunologically linked. This can be demonstrated
organisms. According to Whitman et al. 4–6 x 10 prokaryotic
clinically, as immunization at one mucosal surface provides anti-
cells exist on earth.1 All animals ingest food and water for energy,
body against that antigen at other non-immunized mucosal sites.5
30
while living in contact with a significant bacterial burden in nearly
Maintenance of mucosal immune integrity minimizes or
every environment. Food is usually clean in industrialized cultures
eliminates microbial invasion and infection. Since the gut contains
but may not be in non-industrialized parts of the world. Regardless
the largest collection of mucosal immune tissue/cells, the GALT, it
of the food source and/or processing, the gut processes the food
is not surprising that integrity of mucosal immunity depends upon
and water in our daily life for digestion and absorption. The gut
the type and route of nutrition. Clinically, trauma patients fed
also functions as an immune organ to protect us from any ingested,
parenterally (without any enteral stimulation) become more
potentially pathogenic bacteria.
susceptible to infectious complications than injured patients fed
A single layer of epithelium lines the gut. Beneath this layer
enterally.6-9 Current recommendations in critical care call for early
lies a complex immunologic mucosal defense system, the mucosal
enteral nutrition support as tolerated by the intestine.10 This review
immune system. Mucosal immunity and mucosal immune system
discusses some of the major mechanisms involved in providing
components exist not only in the gut but also extend and interact
innate and adaptive gut and mucosal immunity, and the influence
with other mucosal/epithelial surfaces in extra-intestinal sites such
of type and route of nutrition on this system.
as the respiratory tract, the genitourinary tract, and the mammary
and salivary glands. The gut is immunologically interconnected
Innate mucosal immunity
with these extra-intestinal sites but is considered the ‘command
Intestinal innate mucosal immunity protects the host against
CLINICAL NUTRITION HIGHLIGHTS • 2008 • Volume 4, Issue 2
center’ and hub of mucosal immunity.2,3
2
The mucosal immune system consists of innate and adaptive
potential microbial pathogen invasion. Features of the innate
immune mechanisms. Innate mechanisms are ‘built in’ to the struc-
immune system include physical barriers such as tight junctions
ture and/or function of the gut and are not aimed specifically
between epithelial cells, intraluminal secretions, gastric acid,
against any individual pathogen. The adaptive arm of mucosal
digestive enzymes, glycocalyx and mucus proteins, defensins,
immunity generates immunoglobulin A (IgA) at mucosal surfaces.
lysozyme, lactoferrin and physiomechanical barriers such as
IgA provides antigen-specific, antibody-mediated immunity at
peristalsis (Figure 1).11,12
mucosal body-environment interfaces through immune exclusion.
The basic tubular structure of the gastrointestinal (GI) tract
IgA binds to surfaces of potential pathogens, preventing their
consists of epithelial cells, a connective tissue-derived lamina
adherence to, and invasion through, the epithelial barrier.
propria (LP) layer containing a large quantity of immunocytes, and
In mice, at least 80% of total body immunoglobulin-
a purely muscular layer enclosed in a thin serosal covering. A
secreting cells are located in the small intestine. These
simple columnar epithelium lines the tube from the stomach to
immunoglobulin-producing plasma cells are programmed to
rectum. This thin, single-cell thickness layer separates us from the
produce predominately IgA. The plasma cells, co-localized T
environment and works in conjunction with other complex, co-
lymphocytes (CD4+ predominately) and other immune cells such as
ordinated protective strategies. The mucosal epithelia adhere
dendritic cells, constitute the gastrointestinal-associated lymphoid
through cell-to-cell junctions primarily via tight junctions. Tight
tissue (GALT). GALT comprises a significant portion of the body’s
junctions maintain epithelial cell orientation as specific proteins
4
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such as claudin and occludin cooperate to
form these tight junctions between adjacent
epithelial cells. These junctions act as an
Figure 1. Schema of epithelial action against microbes
in gut innate immunity
innate paracellular barrier to microorganMicrobes
ingested
Stomach
ions and solutes.
Small intestine
Large intestine
13
Mucus/glycocalyx
Each part of the GI tract has specific
defenses against bacteria. The stomach
secretes gastric acid and digestive enzymes
to kill most swallowed microorganisms.
Gastric acid
Bile
Pancreatic juice
α-defensins
Lysozyme
Group II A PLA2
Only a few organisms, extremophiles (such
TLRs
NODs
as acidophiles), survive the strong acid pH
Parietal
cells
(~2.0) in the stomach. Just distal to the
14
Papilla of
Vater
Paneth
cells
β-defensins
Columnar
epithelial
cells
Mucin
Trefoil factor
Feature article
isms while controlling passive transport of
Cathelicidins
Goblet
cells
stomach, bacteriostatic bile and pancreatic
Inflammatory or immune
response
juices also hinder bacterial colonization of
the upper GI tract.
15
Digestion and absorption of nutri-
, commensal microflora;
, damaged microbe;
PLA, phospholipase A; TLR, Toll-like receptor
, ingested microbe; NOD, nucleotide-binding oligomerization domain;
ents occurs in the jejunum and ileum. Its
huge surface area of approximately 300 m2 is also covered by a
covered by the dense overlying mucus, remains a generally sterile
single-cell layer of epithelium. Because of its relative delicacy and
environment.21
critical function, a more precise immunologic innate mechanism
Certain bacteria protect the host. Commensal microflora,
with which the host has a symbiotic relationship, are a constituent
protects this region of the GI tract.
Structurally, the intestinal epithelium forms villi and crypts
of health. But how does the body sense which bacteria are
that overlie stem cells capable of differentiating into epithelial
commensal – and normal – and which are potential or overt
cells. Two specialized intestinal epithelial cells, goblet and Paneth
pathogens? Intestinal epithelial cells possess and rely upon several
cells, play important roles in providing innate immunity. These cells
kinds of sensors to make such determinations. Pattern recognition
secrete nonspecific antimicrobial peptides and bacteriolytic
receptors (PRRs), such as Toll-like receptors (TLRs) and
enzymes. Accordingly, Paneth cells possess an abundance of cyto-
nucleotide-binding oligomerization domain (NOD) proteins, detect
plasmic secretory granules. Most of these antimicrobial molecules
conserved microbial molecules called pathogen-associated
are cationic to facilitate binding to anionic bacterial surface poly-
molecular patterns (PAMPs). When stimulated by PAMPs, the
mers. Paneth cells produce α-defensins, which damage microbial
PRRs activate inflammatory or immune responses through
cell membranes,11,18 lysozymes, which hydrolyzes peptidoglycans on
cellular signaling systems such as nuclear factor, NFκB.22,23
16
17
bacterial cell walls, and group IIA phospholipase A2 (PLA2), which
Through these different mechanisms innate immunity pres-
disrupts cell integrity through rapidly degrading bacterial
ents a standardized, stalwart defense against pathogenic disruption
membrane phospholipids. Paneth cells are also found near collec-
of homeostasis in the gut, one of our most vital and vulnerable
tions of epithelial stem cells at the bottom of epithelial crypts. This
organ systems.
arrangement seems designed to let stem cells, which are critical for
continued regeneration of the epithelium, specifically guard against
Adaptive mucosal immunity
bacterial attack and injury. Goblet cells produce mucus constituent
Oral vaccination with oral polio vaccine proved the existence of
surface provides protection by creating a significant physical barrier
significant, active gut involvement in mucosal adaptive immune
to invasion. Goblet cells also produce trefoil factor, which is
responses. Observations that immunization induced production of
involved in epithelial growth and repair.
anti-polio secretory IgA in the feces by oral, but not parenteral,
20
The intestinal columnar epithelial cells themselves produce
immunization highlighted a key gut function in generating an
nonspecific antimicrobial weapons against pathogenic micro-
immune response; ie, the gut ‘sees’, captures and initiates immune
organisms that threaten the integrity of the intestinal epithelium.
responses against luminal antigen.24 In the United States oral polio
β-defensins are expressed by epithelial cells throughout the intes-
vaccine is no longer used, not because it is ineffective, but because
tine, while cathelicidins are produced by epithelial cells lining the
the incidence of spontaneous polio from killed virus vaccination is
colon. Both of these antimicrobial molecules provide bactericidal
now lower than the risk of developing polio from mutation of live
defenses by disrupting bacterial membrane integrity.11 As a result of
oral virus vaccination.
these multiple innate defense strategies, intestinal microflora
Adaptive mucosal immune responses generate plasma cells
remain in the intestinal lumen, while the direct epithelial surface,
which produce secretory IgA for antigenic specific antibody-
proteins.19 The robust mucus layer that overlies the epithelial
3
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Page 4
specialized endothelium found within PPs. Cognate antigen
Figure 2. Peyer’s patch
presented to the naive lymphocytes by DCs or other antigenpresenting cells activates them against that antigen.25,35 Changes in
cell surface adhesion molecules identifies them as activated lympho-
Feature article
cytes. Activated cells maintain L-selectin but upregulate α4β7 and
lymphotoxin (LT) αβ expression.36-38 Most activated B cells switch
immunoglobulin class and differentiate to IgA-producing cells;
naive T cells mature into effector/memory T cells. During this time
lymphotoxin β receptor (LTβR, the receptor activated by LTαβ
ligands) expressed on DCs and stromal cells in the PPs stimulates
more MAdCAM-1 expression to recruit more naive cells.39 LTβR
mediated defenses at epithelial surfaces. Division of the mucosal
signaling is involved in PP organization prenatally as well.40 In vivo
immune system into inductive and effector sites is based upon the
experiments which blockade LTβR function affirm its role in adap-
function of the immune cell complement at specific locations.
tive mucosal immune function.41 After activation in PPs, these
Small intestinal Peyer’s patches (PPs) are the prototypical inductive
lymphocytes migrate via efferent lymph channels, mesenteric lymph
site and the LP under all mucosal surfaces serves as the effector site
nodes (MLN) and the thoracic duct (TD) into the blood stream.
(Figure 2).
Maturation and further differentiation occurs between PPs and the
2,3,25
systemic circulation as evidenced by the increasing percentage of
Inductive sites
IgA-forming B cells at each site (PP < MLN < TD).42 Cells may
Adaptive immune responses start at inductive sites such as PPs and
remain in systemic circulation until called back to an effector site.
isolated lymphoid follicles (ILFs) in the small intestine. PPs and
26
ILFs consist of a specialized follicle-associated epithelium (FAE)
Effector sites
including microvillus (M) cells, dendritic cells (DCs) within the
Circulating sensitized lymphocytes home to LP effector sites
subepithelial dome area and B lymphocyte follicles possessing
through interactions between LTβR located on stromal cells in the
germinal centers (Figure 3). PPs are a major inductive site for
LP,38 endothelial-expressed MAdCAM-1 on the HEV, and a vari-
mucosal immune responses and are formed independent of anti-
ety of tissue-specific chemokines.43 These non-naive lymphocytes
gen stimulation before birth. ILFs on the other hand, appear after
are LTαβ+ which interacts strongly with stromal cells expressing
birth, are dependent on antigenic stimulation and function similar
LTβR. The α4β7 ligand interacts with MAdCAM-1 (Figure 4).34
to PPs to recognize antigen and initiate a mucosal immune
The complete and exact mechanisms of homing to any mucosal site
response.
remain under active investigation; however, this process is multi-
DCs underlying FAE take up luminal antigens, such as whole
factorial and very site specific. In the gut, retinoic acid, a vitamin A
pathogenic microorganisms or individual peptide antigens. The
metabolite, enhances expression of α4β7 on T cells during activa-
DCs take the antigen up through M cells or directly through
tion and ‘imprints’ them to preferentially home back to the gut.44
dendrites projecting into the lumen. M cells possess several char-
Following recruitment to effector sites, B cells terminally
acteristics that enable them to effectively capture and transcytose
differentiate into IgA-producing plasma cells, encouraged by the
27
antigen. A thinner mucus layer covers their
apical surface because the FAE contains fewer
Figure 3. Adaptive mucosal immunity: Inductive site
goblet cells than non-FAE epithelial areas. M
M cell
cells are shorter than normal columnar
epithelium and have smaller and irregular
IEL
microvilli, specific receptors against common
DC
antigenic epitopes, and receptors for antigen
4
LTβR
Antigen presentation
opsonized by secretory IgA.20-23
M cells and the surrounding FAE
capture and present antigen to the PPs, specific
mechanisms to attract naive lymphocytes.
28-32
HEV
Naive
T/B
α4β7++
T/B
LTβR
MAdCAM-1
α4β7+
L-selectin ++
Sensitized
T/B
PP
L-selectin ++
LTαβ+
Naive lymphocytes bearing the ligands, Lselectin and α4β7, are recruited into the PP
MLN
through their interaction with the receptor
mucosal addressin cellular adhesion molecule1
(MAdCAM-1)
expressed
on
high
endothelial venules (HEV).33,34 The HEV is a
Effector sites
Thoracic duct
Blood stream
DC, dendritic cell; HEV, high endothelial venule; IEL, intraepithelial lymphocyte; LTβR, lymphotoxin β receptor; MAdCAM-1, mucosal
addressin cellular adhesion molecule-1; MLN, mesenteric lymph node, PP, Peyer’s patch
6/23/08
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Figure 4. Adaptive mucosal immunity: Effector
site
Page 5
Figure 5. Cytokines in Th1 and
Th2 subset
Th1
Secretory IgA
Cytokine
Inflammatory
plgR
Th-cytokines
Th2
Dimeric IgA
B cells
Cytokine
Plasma cell
βR -1
LT CAM
d
MA
LTαβ+
Inflammatory
TGF-β
IL-4
IL-5
IL-6
IL-10
L-selectin ±
Sensitized
T/B
X
X
X
X
IgA-plgR complex
T cells
α4β7++
Anti-inflammatory
Feature article
INF-γ
TNF-α
IL-1
IL-2
LT, lymphotoxin; LTβR, lymphotoxin β receptor; MAdCAM-1, mucosal addressin
cellular adhesion molecule-1; plgR, polymeric immunoglobulin receptor
X
Anti-inflammatory
X
X
X
X
X
cytokine environment provided by Th2 lymphocytes.35,45,46
lower intestinal tract (Figure 6). This symbiotic population
Cytokines drive secretory IgA production and provide an integral
prevents overgrowth and invasion of pathogenic bacteria through
component of adaptive mucosal immunity (Figure 5).
mucosal surfaces. The total number of normal intestinal
Transforming growth factor-β (TGFβ), along with interleukin-4,
microflora in the human approximates 1014 organisms, with
-5, -6, and -10 (IL-4, IL-5, IL-6, IL-10), belong to the family of T
bacterial densities within the stomach/duodenum, jejunum/ileum
helper type 2 (Th-2) cytokines which stimulate IgA production. T
and large intestine of 101–103, 104–107 and 1011–1012 colony form-
helper type 1 (Th-1) cytokines such as interferon-γ (IFNγ) counter-
ing units/mL respectively.55 Most intestinal commensal microflora
balance their action by inhibiting IgA production.46,47 The mutual
are anaerobic due to low oxygen tension in the gut lumen.
action of T and B cells, modulated largely by cytokine balance,
Facultative anaerobes colonize the more proximal gut due to
regulate production and transport of secretory IgA.
slightly higher oxygen levels, while obligate anaerobes colonize the
Dimeric IgA produced by plasma cells in the LP binds to the
distal bowel.56,57 Although comprehensive culture and identifica-
polymeric immunoglobulin receptor (pIgR) expressed on the baso-
tion techniques for all commensal flora do not exist, the estimated
lateral surface of epithelial cells.48,49 The IgA-pIgR complex is
number of commensal bacterial species in humans is ≥500.58
endocytosed and transported from basal to apical within the
The host mucosal immune system requires tolerance to these
epithelial cell. After reaching the apical surface, the IgA-bound
bacteria to co-exist, since the host recognizes intestinal microflora
extracellular domains of the pIgR molecule (known as secretory
as foreign microorganisms. The host possesses a system of toler-
component), are cleaved as one unit from the pIgR protein and
ance against intestinal commensal microflora to maintain the
released into the lumen as secretory IgA. The presence of secretory
‘normal’ mucosal health status.
TLRs are actively involved in sensing intestinal microflora
enhancing both the stability and effectiveness of IgA as a pathogen
but must be counterbalanced to not react against commensal
neutralizer.50,51 Free secretory component is also released onto the
species. Subtypes of TLRs include TLR2, which recognizes pepti-
mucosal surface following transcytosis of ‘empty’ pIgR (pIgR not
doglycan and lipotecoic acids, and TLR4, which is directed against
bound to dimeric IgA). Free secretory component also neutralizes
lipopolysaccharide. Both are expressed weakly in the intestine
antigen through independent binding action directed against select
where they are likely to encounter many commensal organisms
antimicrobial peptide epitopes.52,53 Moreover, commensal and path-
bearing such markers. TLR downregulating proteins like Toll-
ogenic microorganisms upregulate expression of pIgR by means of
interacting protein on epithelial cells act to balance TLR activity
sensors of the innate immune system, such as TLRs.54 Therefore,
and quiescence to maintain tolerogenic balance.22,59 Regulatory T
synergism and cooperation between adaptive and innate mucosal
cells under the direction of dendritic cells attenuate TLR signaling
immune systems enables more robust and rapid protection.48
as well.60
Intestinal microflora
health by supplying nutrients to intestinal epithelial cells.
Besides the innate and adaptive mucosal immune strategies, the
Commensal microflora ferment undigestable dietary fibers and
presence of intestinal commensal microflora is a co-factor impact-
starches in food in the lower intestine yielding fatty acid products.
ing the gut as an immune organ. Commensal microflora inhabit
These fatty acids stimulate blood flow and electrolyte uptake in
the entire gut, with the largest burden of microorganisms in the
the large intestine.61,62
Intestinal commensal microflora directly promote gut
55
component protects secretory IgA from proteolytic degradation
5
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Page 6
into the PP, drops within hours of stopping enteral
Figure 6. Commensal microflora of the digestive
system
stimulation due to drops in LTβR levels (which
control MAdCAM-1 expression).66-68 As a result of
reduced cell entry into the system, lymphocyte
Feature article
numbers drop quickly in the PP and LP,69 as well as
in the lung. This effectively reduces the number of
cells present to produce IgA by over 60%.
Simultaneously, the remaining T cells decrease
production of Th-2 cytokines such as IL-4 and IL-10,
which are the key cytokine stimulators of IgA
production.70 In addition, expression of intestinal
pIgR, the principal protein in IgA transport from the
LP to the gut lumen also decreases without enteral
feeding.71 As a cumulative consequence of these
changes associated with decreased enteral stimulation, levels of IgA drop at both intestinal and
respiratory mucosal surfaces, rendering them susceptible to microbial invasion.70,72
The drops in mucosal IgA due to reduced
Adapted from Simon GL, Gorbach SL. Intestinal flora in health and disease. Gastroenterology 1984;86:174-193.
enteral stimulation has functional implications for
animals. These mice become unable to effectively
Although the gut remains sterile throughout fetal life, bacte-
generate new mucosal immune responses to infectious challenges,
rial population of the gut begins immediately after childbirth with
particularly in the respiratory tract.73 They also cannot maintain
initiation of oral intake. The type of diet, hygienic milieu and
normal respiratory immunologic defenses against either bacteria
medications affect this bacterial population process. Intestinal
(in an model of pneumonia) or viral upper respiratory infection,
commensal microflora contributes to establishment and develop-
which would normally keep them immune from infection by these
ment of the mucosal immune system. As stated earlier, PPs first
organisms.74,75 However, if animals receive subsequent enteral
appear during gestation but grow with exposure to luminal anti-
feeding, these defenses return to normal, demonstrating that
gens. Experiments in germ-free animals support this notion that PP
immune ‘memory’ remains intact, just ineffective without enteral
growth requires antigen exposure since these animals generate
stimulation. In conjunction with reestablished immunity, re-feed-
smaller PPs than normal. However, introduction of intestinal
ing also restores MAdCAM-1 levels, and PP and LP lymphocyte
microflora into germ-free mice restores normal mucosal immune
populations.66,67,76
63
64
parameters.65 Moreover, ILFs, which function within the intestinal
The reduction in mucosal IgA has potential clinical implica-
epithelial layer like PPs, form only after birth, but not in germ-free
tions. Several human studies have demonstrated a protective role of
newborns.26
IgA in preventing pneumonia.77,78 Current work in trauma patients
is underway to determine whether parenteral feeding impairs
Enteral feeding and mucosal immunity
airway IgA (similar to that seen in animal models) in efforts to
explain the increased incidence of infectious complications demon-
6
Although the gut is the largest immune organ in the body, the type
strated in clinical trials.79 It is known that type and route of
and route of nutrition alters mucosal immune ‘homeostasis’.
nutrition affects commensal intestinal microflora as well.
Results from prospective, randomized clinical trials in trauma
Parenterally fed patients experience decreases in the number of
patient populations support this observation. Severely injured
fecal microflora compared with enterally fed patients.80
trauma patients fed via the gut incur significantly less infectious
The active variable in these experimental situations is likely
morbidity in the form of pneumonia and intra-abdominal abscess
the absence of enteral stimulation and not the presence of
than individuals fed exclusively parenterally.6-9 Investigative work
parenteral nutrition. Mice die after 2–3 days of starvation but
using animals exposed to varying types and routes of nutrition
parenteral feeding maintains them by eliminating the variable of
shows that these variables dramatically influence the mucosal
protein/calorie malnutrition. Evidence suggests that as little as
immune system and the host’s resistance to infections.
25%–50% of calories supplied via the gut (or as little as ¼ of
Mice fed with only parenteral nutrition (PN) experience
normal enteral stimulation) suffice to maintain at least some of the
significant downregulation of multiple mucosal immune para-
‘enterally fed’ mucosal immune morphology.81 However, such a
meters from inductive to effector sites. Levels of MAdCAM-1, the
threshold or cutoff point for maintaining functional mucosal
crucial ‘gatekeeper’ molecule which attracts naive lymphocytes
immunity has not been determined.
6/23/08
Conclusions
3:13 PM
Page 7
with decreased enteral stimulation indicates not only the GALT, but
also the MALT is affected by type and route of nutrition.
While the changes in adaptive mucosal immunity and
virtue of its massive and nearly constant exposure to environ-
commensal microflora induced by decreased enteral stimulation
mental antigen at body/world interfaces, constitutes the largest
have been explored, the relationship between changes in microflora
secondary immune organ in the body. Under normal conditions it
and mucosal immune status provides a fertile ground for investi-
responds appropriately by producing large amounts (~3 g/day) of
gation. Additionally the relationship between enteral stimulation
protective antibody predominately in the form of IgA. Enteral stim-
and innate mucosal immune measures remain relatively unstudied.
ulation seems a key component of maintaining the health of the
Finally, because of the known causal relationships between
mucosal immune system. The changes in extra-intestinal mucosal
type and route of nutrition and infectious morbidity, enteral feed-
immune parameters, such as decreased IgA in the respiratory tract,
ing should be aggressively pursued in the critically injured patient.
Feature article
It seems evolutionarily proper that the mucosal immune system, by
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Page 8
CLINICAL NUTRITION ABSTRACTS
CANCER
Computational modeling of cancer cachexia
Clinical nutrition
abstracts
Curr Opin Clin Nutr Metab Care 2008 May;11(3):214-221.
Hall KD, Baracos VE.
Laboratory of Biological Modeling, National Institute of Diabetes,
Digestive, and Kidney Diseases, National Institutes of Health, Bethesda,
Maryland, USA.
PURPOSE OF REVIEW: Measurements of whole-body
energy expenditure, body composition and in vivo metabolic fluxes are required to quantitatively understand
involuntary weight loss in cancer cachexia. Such studies
are rare because cancer cachexia occurs near the end of
life when invasive metabolic tests may be precluded.
Thus, models of cancer-associated weight loss are an
important tool for helping to understand this debilitating
condition. RECENT FINDINGS: A computational model
of human macronutrient metabolism was recently developed that simulates the normal metabolic adaptations to
semi-starvation and re-feeding. Here, this model was
used to integrate data on the metabolic changes in
patients with cancer cachexia. The resulting computer
simulations show how the known metabolic disturbances
synergize with reduced energy intake to result in a
progressive loss of body weight, fat mass and fat-free
mass. The model was also used to simulate the effects of
nutritional support and investigate inhibition of lipolysis
versus proteolysis as potential therapeutic approaches for
cancer cachexia. SUMMARY: Computational modeling is
a new tool that can integrate clinical data on the metabolic changes in cancer cachexia and provide a
conceptual framework to help understand involuntary
weight loss and predict the effects of potential therapies.
Nutritional support in multimodal therapy for
cancer cachexia
and metabolic change. Thus, alterations in both energy
intake and components of energy expenditure may
contribute to progressive weight loss. Increased resting
energy expenditure related to the systemic inflammatory
response is common and a sustained hypermetabolism
over a long period of disease progression can make a
large contribution to negative energy balance and wasting if not compensated for by an increase in energy
intake. Hypermetabolism and diminished energy intake
due to anorexia may thus constitute a vicious circle in the
development of cancer cachexia. DISCUSSION: Though
nutritional support alone can improve energy intake to a
variable extent and for a variable period of time, it will
not address the underlying catabolic metabolism and is
thus likely to be of limited efficacy if attempts to attenuate the tumor-induced catabolic response are not carried
out at the same time. Concomitant drug treatments for
cancer cachexia may slow down the wasting process by
reducing anorexia, attenuating the systemic inflammation, the skeletal muscle catabolism or stimulating the
muscle protein anabolism. Thus, improved management
of cancer cachexia may require a multimodal approach
by a multidisciplinary team and is best commenced
earlier rather than later. Early start of therapy also facilitates the use of oral nutritional supplementation, which
is preferable to parenteral nutrition in the majority of
cases. Once a patient is severely wasted it may be neither
practical nor ethical to intervene with anything else than
supportive care. CONCLUSION: An improvement in the
condition of all patients with cachexia may not be possible, however, the goal must be to stabilize cachexia and
prevent or delay further decline. There is currently no
single or combined treatment strategy which is successful
in all patients. However, strategies to counteract both
hypermetabolism and reduced dietary intake have been
demonstrated to be of importance for the survival, function and quality of life of cancer patients, and should be
further explored in interventional studies.
Support Care Cancer 2008 May;16(5):447-451.
Bosaeus I.
Department of Clinical Nutrition, Sahlgrenska University Hospital,
Göteborg, Sweden.
8
INTRODUCTION: Malnutrition has since long been
known to be associated with adverse outcomes in cancer
patients. The wasting in cancer cachexia involves loss of
muscle and fat and reflects a catabolic metabolism
induced by an abnormal host response to tumor presence
and/or tumor factors. Patients with cancer cachexia
frequently develop a chronic negative energy and protein
balance driven by a combination of reduced food intake
Refeeding syndrome in cancer patients
Int J Clin Pract 2008 Mar;62(3):460-465.
Marinella MA.
Wright State University School of Medicine, Division of HematologyOncology, Dayton, Ohio, USA.
BACKGROUND: Refeeding syndrome (RFS) is a
common, yet underappreciated, constellation of electrolyte derangements that typically occurs in acutely ill,
malnourished hospitalized patients who are administered
glucose solutions or other forms of intravenous or enteral
nutrition. DISCUSSION: The hallmark of RFS is
The abstracts included in this section were selected from a search on clinical nutrition and related topics of the PubMed database of the United States National
Library of Medicine. PubMed may be accessed via the National Library of Medicine Web site at www.nlm.nih.gov.
6/23/08
hypophosphatemia, but hypokalemia and hypomagnesemia are also common. Patients with various types of
malignancies are at-risk for RFS, but very little exists in
the oncologic literature about this disorder. CONCLUSIONS: As RFS can have many adverse metabolic,
cardiovascular, hematologic and neurologic complications, practicing oncologists need to be aware of the
pathophysiology, risk factors and clinical manifestations
to promptly recognize this important, and potentially
fatal, metabolic disorder.
Clin J Oncol Nurs 2007 Dec;11(6):875-880.
Cady J.
The Radiation Oncology Department, The Virginia Mason Medical Center,
Seattle, Washington, USA.
Significant weight loss and resultant malnutrition in
patients undergoing radiotherapy for head and neck
carcinomas are recognized and preventable clinical
concerns. Morbidity related to weight loss during treatment may include dehydration, hospitalization,
compromised treatment efficacy and reduced quality of
life, and may impact survival. Malnutrition effects on
wound healing may prolong recovery following treatment and increase the risk of morbidity for those
undergoing subsequent salvage surgery. Multiple interventions have been implemented to help ameliorate the
impact of treatment on weight loss and nutritional
status, including the use of percutaneous endoscopic
gastrostomy (PEG) tubes. The value of prophylactic PEG
tube placement at treatment initiation increasingly is
being recognized, and evidence suggests that patients
experience better outcomes. Criteria for patient selection
have not been defined completely, and a great deal of
variation in clinical practice exists, contributing to
underuse of this supportive intervention. According to a
literature review, patients who require therapeutic PEG
tube placement in response to significant weight loss
during treatment suffer greater morbidity than patients
who receive PEG tubes prophylactically. Understanding
patient-, tumor-, and treatment-related risk factors to
systematically identify patients most likely to benefit
from prophylactic PEG tube placement is an important
aspect of nursing care.
The nutritional and metabolic support of heart
failure in the intensive care unit
Curr Opin Clin Nutr Metab Care 2008 Mar;11(2):140-146.
Meltzer JS, Moitra VK.
Division of Critical Care Medicine, Department of Anesthesiology, College
of Physicians and Surgeons of Columbia University, New York, USA.
PURPOSE OF REVIEW: Heart failure and cardiovascular
disease are common causes of morbidity and mortality,
contributing to many ICU admissions. Nutritional deficiencies have been associated with the development and
worsening of chronic heart failure. Nutritional and metabolic support may improve outcomes in critically ill
patients with heart failure. This review analyzes the role
of this support in the acute care setting of the ICU.
RECENT FINDINGS: Cardiac cachexia is a complex
pathophysiologic process. It is characterized by inflammation and anabolic-catabolic imbalance. Nutritional
supplements containing selenium, vitamins and antioxidants may provide needed support to the failing
myocardium. Evidence shows that there is utility in intensive insulin therapy in the critically ill. Finally, there is an
emerging metabolic role for HMG-CoA reductase inhibition, or statin therapy, in the treatment of heart failure.
SUMMARY: Shifting the metabolic milieu from catabolic
to anabolic, reducing free radicals and quieting inflammation in addition to caloric supplementation may be the
key to nutritional support in the heart failure patient.
Tight glycemic control with intensive insulin therapy
plays an expanding role in the care of the critically ill.
Glucose-insulin-potassium therapy probably does not
improve the condition of the patient with heart failure or
acute myocardial infarction.
CRITICAL CARE NUTRITION
Early nutrition support in critical care: A
European perspective
Kreymann KG.
Department of Intensive Care, University Medical Centre, HamburgEppendorf, Germany.
PURPOSE OF REVIEW: Today, early nutrition support is
considered standard care in most intensive care units. The
recommended method is the enteral route, although there
is only minor evidence for this. Often inadequate delivery
of energy and a cumulative energy deficit are implied. The
purpose of this paper is to evaluate the indication for early
enteral nutrition or immunonutrition and to discuss the
application of additional parenteral nutrition. RECENT
FINDINGS: The indication for early enteral nutrition is
also supported by guidelines for enteral nutrition recently
published by the European Society for Clinical Nutrition
and Metabolism. Some more recent results strengthen the
indication for a special formula in acute respiratory
distress syndrome and septic patients. A recent metaanalysis has shown that parenteral nutrition is superior to
delayed enteral nutrition. Additional parenteral nutrition
thus seems to be the way to avoid cumulative energy
deficit associated with insufficient or no enteral nutrition.
SUMMARY: Early enteral nutrition is recommended for
critically ill patients, with special formulas indicated in
specific subgroups of patients. If enteral nutrition is insufficient or fails, parenteral nutrition should be instituted,
respecting the often reduced demand for exogenous
substrates in critically ill patients.
CARDIOVASCULAR DISEASE
Page 9
Clinical nutrition
abstracts
Nutritional support during radiotherapy for head
and neck cancer: The role of prophylactic
feeding tube placement
3:13 PM
9
6/23/08
3:13 PM
Fish oil in critical illness
Clinical nutrition
abstracts
Mayer K, Seeger W.
Department of Internal Medicine, Pulmonary and Critical Care Medicine,
Justus Liebig University Giessen, Germany.
PURPOSE OF REVIEW: The aim of this review is to
discuss recent advances in the role of n-3 lipids derived
from fish oil in clinical nutrition in an intensive care
setting. RECENT FINDINGS: Fish oil supplies n-3 fatty
acids which compete with arachidonic acid (n-6) for the
conversion to lipid mediators, influence lipid-bound
second-messenger generation and dependent cellular
functions, and are a source for resolvins necessary for
the resolution of inflammation. Enteral nutrition with
n-3 fatty acids improved ventilation time in patients with
acute lung injury and in one study reduced mortality in
septic patients. Using a high-dose, short-term infusion of
fish oil-based lipid emulsion, rapid immunologic changes
and effects on the endotoxin-induced stress response
may be achieved. Inclusion of n-3 fatty acids in
parenteral nutrition improved immunologic parameters
and length of stay in surgical patients. SUMMARY:
Inclusion of fish oil in nutrition may influence the
immune response and clinical outcomes by balancing the
negative effects of n-6 fatty acids. Application as a part
of enteral immunonutrition in surgical or acute respiratory distress syndrome patients and in lipid emulsions in
surgical patients has beneficial effects. In septic patients,
data on enteral use are highly controversial. Prospective
data from randomized trials, however, are lacking.
Treatment of mild malnutrition and reduction of
morbidity in abdominal surgery: A trial on 153
patients [article in Italian]
Clin Ter 2008 Jan-Feb;159(1):13-18.
Pronio A, Di Filippo A, Aguzzi D, Laviano A, Narilli P, Piroli S, Vestri A,
Montesani C.
Cattedra di Chirurgia Generale, Policlinico Umberto I, Università La
Sapienza, Roma, Italy.
10
OBJECTIVES: Severe malnutrition (defined as weight
loss more than 10% in a period of 6 months) is considered an important risk factor in major abdominal
surgery, because of a higher post-operative mortality
and morbidity. The aim of our study is to assess the role
of mild malnutrition (weight loss low than 10% in a
period of 6 months) as a risk factor in major abdominal
surgery and to evaluate the efficacy of therapy in order
to improve outcomes in terms of in-hospital mortality,
length of hospital stay and post-operative complications. Moreover, we evaluated serum albuminemia and
lymphocyte count, important nutritional indices, as
predictive risk factors. MATERIALS AND METHODS:
We performed a randomized prospective trial, and
admitted in our institution 153 adult patients, 43 with
mild malnutrition and 110 without. The malnourished
patients were randomized in two groups: the first one
received oral immunonutrition (Impact Oral) for 7–10
days before surgery (22 patients), the second one
received no nutritional support. RESULTS: We observed
a higher number of complications in the nontreated
Page 10
malnourished patients (57%) versus both the treated
malnourished patients (13.6%) and the normal group
(19%) (p < 0.001). Increased morbidity was observed in
patients with serum albuminemia <2.8 g/dL (69.2%)
and with lymphocyte count <1.500 mm 3 (57%).
CONCLUSIONS: Nutritional enriched support demonstrated efficacy in reducing morbidity and length of
hospital stay. Pre-operative oral immuno-nutrition
might be suggested and established in all the patients
with mild malnutrition that will be operated on major
abdominal surgery.
Early enteral supplementation with key
pharmaconutrients improves Sequential Organ
Failure Assessment score in critically ill
patients with sepsis: Outcome of a randomized,
controlled, double-blind trial
Crit Care Med 2008 Jan;36(1):131-144.
Beale RJ, Sherry T, Lei K, Campbell-Stephen L, McCook J, Smith J,
Venetz W, Alteheld B, Stehle P, Schneider H.
Department of Adult Critical Care Medicine, Guy’s and St. Thomas’
Hospital, London, United Kingdom.
OBJECTIVE: To assess the safety and efficacy of an
early enteral pharmaconutrition supplement containing
glutamine dipeptides, antioxidative vitamins and trace
elements, and butyrate in critically ill, septic patients.
DESIGN: A prospective, randomized, controlled,
double-blind clinical trial. SETTING: Adult intensive
care unit in a university hospital. PATIENTS: Fifty-five
critically ill, septic patients requiring enteral feeding.
INTERVENTIONS: Patients received either an enteral
supplement (500 mL of Intestamin, Fresenius Kabi)
containing conditionally essential nutrients or a control
solution via the nasogastric route for up to 10 days.
Inclusion occurred within 24 hours of intensive care
unit admission. Additionally, patients received enteral
feeding with an immunonutrition formula (experimental group) or standard formula (control group) initiated
within 48 hours after enrollment. MEASUREMENTS
AND MAIN RESULTS: Organ dysfunction was assessed
by daily total Sequential Organ Failure Assessment
(SOFA) score over the 10-day study period in both
patient groups. Patients receiving the experimental
supplement showed a significantly faster decline in the
regression slopes of delta daily total SOFA score over
time compared with control. The difference between the
regression coefficients of the two slopes was significant
irrespective of the level of analysis: intent to treat -0.32
vs -0.14, p < 0.0001; per protocol -0.34 vs -0.14, p <
0.0001; and completers (patients receiving ≥80% of the
calculated caloric target over a period of 6 days), -0.26
vs -0.16, p = 0.0005. Vitamin C, as a marker of supplement absorption, increased from 10.6 (1.9–59.4)
μmol/L (normal range 20–50 μmol/L) on day 1 to 58.7
(5.4–189.9) μmol/L by day 3 (p = 0.002) in the intervention group but remained below the normal range in
the control group 17.0 (2.8–78.5) on day 1 and 14.3
(2.4–179.6) on day 3. Serum levels of glycine, serine,
arginine, ornithine, vitamin E and beta-carotene
all increased significantly with treatment in the
6/23/08
supplementation group. CONCLUSIONS: In medical
patients with sepsis, early enteral pharmaconutrition
with glutamine dipeptides, vitamin C and E, betacarotene, selenium, zinc and butyrate in combination
with an immuno-nutrition formula results in significantly
faster recovery of organ function compared with control.
Brussels 2007 roundtable on metabolism in
sepsis and multiple organ failure
JPEN J Parenter Enteral Nutr 2008 Jan-Feb;32(1):1-5.
Herndon DH, Wernerman J.
Department of Surgery, Shriners Hospital for Children, Galveston, Texas,
USA.
Gastric motility function in critically ill
patients tolerant versus intolerant to gastric
nutrition
BACKGROUND: Administration of gastric enteral
nutrition (EN) in the intensive care unit (ICU) is
commonly impeded by high gastric residual volumes
(GRV). This study evaluated gastric emptying in patients
with limited GRV (tolerant group) vs volumes ≥150 mL
(intolerant group) and whether prokinetic therapy
improves gastric motility in intolerant patients. METHODS: To assess gastric motility, mechanically ventilated
patients received acetaminophen 975 mg, and peak
plasma concentration (Cmax), concentration at 60
minutes (C 60), time to Cmax (Tmax) and area under the
concentration-time curve from 0 to 60 minutes (AUC 0-60
were determined. This evaluation was repeated in intolerant patients after 24 hours of either erythromycin 250
mg or metoclopramide 10 mg therapy, both administered intravenously every 6 hours. RESULTS: Ten
tolerant and 20 intolerant patients were studied.
Tolerant patients had significantly greater Cmax (14.12
± 7.25 vs 9.28 ± 5.22 mg/L; p < 0.05), C60 (9.62 ± 4.65
vs 6.08 ± 4.00 mg/L; p < 0.001) and AUC0-60 (10.01 ±
5.97 vs 3.93 ± 2.84 mg/h/L; p < 0.01), and shortened
Tmax (0.81 ± 0.61 vs 1.98 ± 1.26 hours; p < 0.001)
compared with intolerant patients. After prokinetic
therapy, Cmax (15.26 ± 8.85 mg/L), C60 (11.96 ± 5.99
mg/L) and AUC0-60 (10.90 ± 6.57 mg/h/L) increased and
Tmax (1.07 ± 1.01 hours) decreased in the intolerant
group to values similar to the tolerant group. CONCLUSIONS: ICU patients with elevated GRV during gastric
EN have delayed gastric motility. Initiating prokinetic
therapy accelerates gastric emptying to resemble that of
ICU patients tolerating EN.
Nutrition support in the critically ill:
A physician survey
JPEN J Parenter Enteral Nutr 2008 Mar-Apr;32(2):113-119.
Behara AS, Peterson SJ, Chen Y, Butsch J, Lateef O, Komanduri S.
Department of Internal Medicine, Rush University Medical Center,
Chicago, Illinois, USA.
BACKGROUND: Current clinical practice guidelines
delineate optimal nutrition management in the intensive
care unit (ICU) patient. In light of these existing data,
the authors identify current physician perceptions of
nutrition in critical illness, preferences relating to initiation of feeding and management practices specific to
nutrition after initiation of feeding in the ICU patient.
METHODS: The authors electronically distributed a 12question survey to attending physicians, fellows and
residents who routinely admit patients to medical and
surgical ICUs. RESULTS: On a scale ranging from 1 to 5
(1 = low, 5 = high), the attending physician’s mean
rating for importance of nutrition in the ICU was 4.60,
the rating for comfort level with the nutrition support at
the authors’ institution was 3.70, and the rating for the
physician’s own understanding of nutrition support in
critically ill patients was 3.33. Attending physicians,
fellows and residents reported waiting an average of
2.43, 1.79 and 2.63 days, respectively, before addressing
nutrition status in an ICU patient. Fifty-two percent of
attending physicians chose parenteral nutrition as the
preferred route of nutrition support in a patient with
necrotizing pancreatitis. If a patient experiences enteral
feeding intolerance, physicians most commonly would
stop tube feeds. There was no significant difference in
responses to any of the survey questions between attending physicians, fellows and residents. CONCLUSIONS:
This study demonstrates a substantial discordance in
physician perceptions and practice patterns regarding
initiation and management of nutrition in ICU patients,
indicating an urgent need for nutrition-related education
at all levels of training.
Landzinski J, Kiser TH, Fish DN, Wischmeyer PE, MacLaren R.
Department of Pharmacy, Georgetown University Hospital, Washington,
DC, USA.
Page 11
Clinical nutrition
abstracts
At the 2007 International Symposium on Intensive Care
and Emergency Medicine (ISICEM) in Brussels, a roundtable conference on "Metabolic Support in Sepsis and
Multiple Organ Failure" was held. The roundtable was
endorsed by the European Society of Intensive Care
Medicine, the Society of Critical Care Medicine, the
European Society for Clinical Nutrition and
Metabolism, and the American Society for Parenteral
and Enteral Nutrition. Metabolic support in intensive
care has become an exciting topic in recent years, with
improved understanding of the effects of compromised
mitochondrial function, studies demonstrating outcome
benefits of tight glucose control, new insights into the
mechanisms behind insulin resistance, recognition of
glutamine and antioxidants as key nutrients, and emerging knowledge concerning the interactions between
metabolism and endocrinology. Together, these aspects
have generated an increased interest in the importance
of metabolism in intensive care medicine, reflected in the
programs and abstracts at international congresses of
the past few years. This roundtable’s participants each
gave a presentation within their specific area of expertise, and each was followed by general discussion.
Discussions became heated as new concepts and ideas
were debated. New data will be discussed in this
summary, which reveals metabolic and nutrition interventions that could lead to major improvements in
clinically relevant outcomes.
3:13 PM
11
6/23/08
3:13 PM
Effect of calorically dense enteral nutrition
formulas on outcome in critically ill trauma and
surgical patients
Clinical nutrition
abstracts
Bryk J, Zenati M, Forsythe R, Peitzman A, Ochoa JB.
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
BACKGROUND: Surgical and trauma patients are traditionally provided with calorically dense dietary formulas to
deliver high amounts of nutrients. The benefits of these
formulas remain unproven and may be associated with
significant side effects and even increased mortality. We
studied outcomes on surgical and trauma patients receiving
either a calorically dense dietary formula or a normocaloric
dietary formula. METHODS: A retrospective analysis
comparing outcomes in intensive care unit (ICU) surgical
and trauma patients receiving either a calorically dense
dietary formula or a normocaloric dietary formula was
performed at the University of Pittsburgh Medical Center.
RESULTS: One hundred seventeen patients met study criteria. Surgical and trauma patients were analyzed separately.
Despite receiving different calorically dense diets, caloric
intake was not significantly different in surgical patients
receiving either diet. However, surgical patients receiving a
normocaloric formula exhibited decreased length of stay
(14.7 ± 10.1 vs 25.0 ± 11.3 days; p = 0.01), ventilator days
(14.3 ± 12.9 vs 21.3 ± 10.5 days; p = 0.04) and average daily
glucose levels (129.8 ± 4.1 vs 157.9 ± 13.6 mg/dL; p = 0.01),
and were more likely to be directly discharged home
compared with those receiving a calorically dense dietary
formula. Trauma patients receiving a calorically dense
dietary formula were on average 17 years younger (p =
0.01). However, trauma patients receiving a normocaloric
formula exhibited decreased length of stay (15.3 ± 1.6 vs
18.7 ± 1.6 days; p = 0.02) and a greater likelihood of direct
discharge home. CONCLUSIONS: The data generated
suggest that what a patient is fed affects both short- and
long-term outcomes. A prospective study should be designed
to determine the ideal calories needed in surgical and trauma
patients.
DIABETES
12
Effects of high-monounsaturated fatty acid enteral
formula versus high-carbohydrate enteral formula
on plasma glucose concentration and insulin
secretion in healthy individuals and diabetic
patients
J Int Med Res 2008 Jan-Feb;36(1):137-146.
Page 12
aged 20.8 ± 1.2 years and 12 diabetic patients with good
glycemic control (glycosylated hemoglobulin <7%) aged
58.6 ± 7.7 years were randomly assigned to take highMUFA or high-carbohydrate formula after a 12-hour
overnight fast. The patients switched to the other formula
after 7 days. Postprandial plasma glucose and insulin
response were significantly lower in all subjects after taking
high-MUFA formula compared with high-carbohydrate
formula. No differences were observed in free fatty acids,
triglycerides and plasma glucagon between the two diet
groups. In conclusion, a high-MUFA enteral formula
suppresses postprandial hyperglycemia without exaggerated
insulin secretion compared with a high-carbohydrate enteral
diet in patients with type 2 diabetes and healthy subjects.
GASTROINTESTINAL DISORDERS
Nutritional support in acute pancreatitis
Thomson A.
Gastroenterology and Hepatology Unit, The Canberra Hospital and The
Australian National University, Canberra, Australia.
PURPOSE OF REVIEW: This review explores the role of
enteral and parenteral nutrition in severe acute pancreatitis
and discusses the potential benefits of glutamine, omega-3
fatty acids, arginine and selenium together with probiotics
and prebiotics in these patients. In addition, the method of
refeeding during the convalescent period is also examined.
RECENT FINDINGS: A complex picture is emerging in
which enteral nutritional support may be important early in
the course of the disease with parenteral nutrition being
used more as a backup and possibly only after the systemic
inflammatory response has peaked. Nasogastric feeding,
sometimes supplemented by parenteral nutrition, is as efficacious as nasojejunal feeding. An individualized approach,
in which strategies of nutritional support are tailored to
patient response, is gaining currency. Data regarding specialized formulae are mixed but the use of prebiotics is showing
promise and is worthy of further exploration. In the convalescent period, preliminary data also indicate that the risk of
pain developing is no greater if a light diet is instituted
rather than clear fluids. SUMMARY: Nutritional support in
acute pancreatitis remains challenging and controversial
with a number of different and unexpected approaches,
including the use of nasogastric feeding and dual enteral and
parenteral nutrition support, being adopted in recent clinical
trials.
Yokoyama J, Someya Y, Yoshihara R, Ishii H.
Division of Diabetes and Endocrinology, Department of Internal Medicine, Jikei
Daisan University Hospital, Komae City, Tokyo, Japan.
Covert assessment of concurrent and construct
validity of a chart to characterize fecal output and
diarrhea in patients receiving enteral nutrition
We investigated the effects of high-monounsaturated fatty
acid (MUFA) versus high-carbohydrate enteral formula on
postprandial plasma glucose concentration and insulin
response in Japanese patients with type 2 diabetes mellitus
and healthy Japanese volunteers. Ten healthy volunteers
Whelan K, Judd PA, Preedy VR, Taylor MA.
Diet and Gastrointestinal Health, Nutritional Sciences Division, King’s College
London, London, United Kingdom.
JPEN J Parenter Enteral Nutr 2008 Mar-Apr;32(2):160-168.
BACKGROUND: An accurate and convenient method for
6/23/08
HEPATIC DISEASE
Malnutrition in end stage liver disease:
Recommendations and nutritional support
J Gastroenterol Hepatol 2008 Apr;23(4):527-533.
Tsiaousi ET, Hatzitolios AI, Trygonis SK, Savopoulos CG.
First Medical Propedeutic Department of the Aristotle University of
Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece.
and Metabolism, simple bedside methods such as
Subjective Global Assessment and anthropometric parameters are reliable in assessing the nutritional state of
cirrhotic patients. Correcting the nutrient deficit of the
affected patients is mandatory. Avoidance of alcohol and
excess fat and ingestion of 4–6 meals/day containing
carbohydrates and protein are the most common recommendations. In severe malnutrition, initiation of enteral
feeding and/or use of special formulae such as branchedchain, amino acid-enriched nutrient mixtures are often
recommended. Enteral nutrition improves nutritional
status and liver function, reduces complications, prolongs
survival and is therefore indicated.
NUTRITION SUPPORT
Early nutritional therapy: The role of enteral and
parenteral routes
de Aguilar-Nascimento JE, Kudsk KA.
Department of Surgery, Federal University of Mato Grosso, Cuiaba, Brazil.
PURPOSE OF REVIEW: Early nutrition is defined as the
initiation of nutritional therapy within 48 hours of either
hospital admission or surgery. However, optimal timing for
initiation of nutritional therapy through either enteral or
parenteral routes remains poorly defined with the existing
data. We reviewed the recent literature investigating the
role of early enteral and parenteral nutrition in critical
illness and perioperative care. RECENT FINDINGS:
Recent studies in both trauma/surgical and nonsurgical
patients support the superiority of early enteral over early
parenteral nutrition. However, late commencement of
enteral feeding should be avoided if the gastrointestinal
tract is functional. Both prolonged hypocaloric enteral
feeding and hypercaloric parenteral nutrition should be
avoided, although the precise caloric target remains
controversial. SUMMARY: Early enteral nutrition remains
the first option for the critically ill patient. However, there
seems to be increased favor for combined enteralparenteral therapy in cases of sustained hypocaloric enteral
nutrition. The key issue is when the dual regimen should
be initiated. Although more study is required to determine
the optimal timing to initiate a combined enteralparenteral approach, enteral nutrition should be initiated
early and parenteral nutrition added if caloric-protein
targets cannot be achieved after a few days.
Role of enteral nutrition in the incidence of
diarrhea among hospitalized adult patients
Nutrition 2008 Apr 14; [Epub ahead of print].
Luft VC, Beghetto MG, de Mello ED, Polanczyk CA.
Post-Graduate Program in Epidemiology, Universidade Federal do Rio
Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
OBJECTIVE: This study examined the risk of diarrhea as
a result of providing enteral nutrition in the hospital
setting, adjusting for other clinical and therapeutic
factors. METHODS: Adults admitted to a general tertiary
Malnutrition has increasingly been acknowledged as an
important prognostic factor which can influence the clinical outcome of patients suffering from end-stage liver
disease (ESLD). Despite the fact that malnutrition is not
included in the Child-Pugh classification, its presence
should alert clinicians to the same extent as do other
complications, such as ascites and hepatic encephalopathy.
The pathophysiological mechanisms and the clinical conditions that drive cirrhotic patients to an ill-balanced
metabolic state are multiple and they intertwine.
Inadequate offer of nutrients, the hypermetabolic state in
cirrhosis, the diminished synthetic capacity of the liver and
the impaired absorption of nutrients are the main reasons
that disrupt the metabolic balance in ESLD. Identifying
patients that are approaching the state of malnutrition by
simple and easily applied methods is necessary in order to
provide nutritional support to those that need it most.
According to the European Society for Clinical Nutrition
Page 13
Clinical nutrition
abstracts
characterizing fecal output and a consistent threshold for
classifying diarrhea in patients receiving enteral nutrition are
required. The aim of this study is to covertly assess the
construct and concurrent validity of a chart for characterizing fecal output and classifying diarrhea in patients receiving
enteral nutrition. METHODS: The chart was used to monitor fecal output in patients receiving enteral nutrition for a
total of 280 patient days. Nurses characterized 291 fecal
samples, of which 84 underwent measurement of fecal water
using lyophilization and 60 underwent Clostridium difficile
enterotoxin analysis using enzyme-linked immunosorbent
assay. Construct and concurrent validity was assessed
covertly to measure the true performance of the chart in a
real-life clinical and research context. RESULTS: Use of the
chart demonstrated higher fecal frequency (p ≤ 0.04), heavier stools (p ≤ 0.167), more unformed stools (p ≤ 0.001),
higher daily fecal scores (p ≤ 0.001) and higher incidence of
diarrhea (p ≤ 0.002) on days when patients had severe
hypoalbuminemia, were receiving antibiotics, or had a
recent positive C difficile assay, demonstrating construct
validity. The water content of samples assigned to hard and
formed (62.0%), soft and formed (72.1%), loose and
unformed (79.3%) and liquid (87.9%) categories was significantly different (p < 0.001), demonstrating concurrent
validity. CONCLUSIONS: Under covert assessment, the
chart demonstrated construct validity for characterizing
fecal output, daily fecal score and diarrhea, together with
concurrent validity for characterizing fecal consistency. Use
of the chart in clinical practice and research will standardize
the characterization of fecal output and classification of
diarrhea in patients receiving enteral nutrition.
3:13 PM
13
Clinical nutrition
abstracts
6/23/08
3:13 PM
care university hospital, in clinical or surgical units, were
enrolled in the study between June 2004 and May 2005
and prospectively followed during their hospital stay. For
each patient treated with enteral nutrition (n = 302), a
comparable nontreated patient from the same ward, (who
also received antibiotics previously) and was similarly
cared for by the same hospital staff was included in the
study (n = 302), constituting a double-cohort study. All
patients were seen three times per week, on alternating
days, until the occurrence of diarrhea or hospital
discharge. Cox’s regression analyses were applied for
adjustments. RESULTS: The incidence of diarrhea was
18% for patients receiving enteral nutrition and 6% for
nontreated patients (p < 0.01). In multivariate analyses,
enteral nutrition was independently associated with diarrhea (hazard ratio 2.7, 95% confidence interval 1.6–4.7),
even adjusting for age (hazard ratio 1.02, 95% confidence
interval 1.00–1.03) and hospitalization during the
summer months (hazard ratio 2.4, 95% confidence interval 1.5–3.9). Patients for whom strict adherence to
delivery-set washing-and-changing procedures was
observed (on >75% of days) presented a lower incidence
of diarrhea (6.5% vs 20.3%, p = 0.02; and 5.9% vs
19.8%, p = 0.05, respectively). CONCLUSION: Providing
enteral nutrition to the hospitalized elderly during the
summer months is associated with a higher risk of diarrhea. Strategies aimed toward improvement in the quality
of enteral nutrition practices should be evaluated to minimize this deleterious clinical outcome.
Death resulting from overzealous total parenteral
nutrition: The refeeding syndrome revisited
Nutr Clin Pract 2008 Apr;23(2):166-171.
Miller SJ.
University of Montana, Department of Pharmacy Practice, Missoula,
Montana, USA.
14
Commentary is provided on the pivotal paper by Weinsier
and Krumdieck from 1981 describing two patients who
developed profound and fatal refeeding syndrome following initiation of aggressive total parenteral nutrition. This
classic description was among the first to describe the
overwhelming cardiovascular and pulmonary manifestations that can accompany parenteral refeeding with
carbohydrate in chronically malnourished patients. The
syndrome has also been described with oral and enteral
nutrition. One of the hallmarks of the syndrome is
hypophosphatemia. Since 1981, dosing schemes for
addressing hypophosphatemia have been refined. Other
manifestations of the syndrome include other electrolyte
abnormalities such as hypokalemia and hypomagnesemia,
hyperglycemia, fluid and sodium retention, and neurologic
and hematologic complications. Case reports of refeeding
syndrome continue to be published, particularly in the
anorexia nervosa population. Stressed, critically ill patients
may be at risk of refeeding following short periods of
fasting; hypophosphatemia is commonly encountered in
this situation. It behooves the current nutrition support
practitioner to keep in mind the types of patients at risk
of refeeding syndrome and to approach refeeding of such
patients with caution and careful monitoring.
Page 14
Diagnosis and treatment of simple acid-base
disorders
Nutr Clin Pract 2008 Apr;23(2):122-127.
Ayers P, Warrington L.
Mississippi Baptist Medical Center, Department of Pharmacy, Jackson,
Mississippi, USA.
The ability to diagnose and treat acid-base disorders is
an important component in the practice of the nutrition
support clinician. A complete understanding of the basic
principles of metabolic and respiratory disorders allows
the practitioner to formulate educated decisions regarding fluids, parenteral nutrition salts, and the
management of electrolytes. This review will discuss the
diagnosis and treatment of common metabolic and respiratory disorders encountered in nutrition support
practice.
Factors contributing to the development of
hypophosphatemia when refeeding using
parenteral nutrition
Pharm World Sci 2008 Mar 30; [Epub ahead of print].
Marvin VA, Brown D, Portlock J, Livingstone C.
Pharmacy Department, Royal Surrey County Hospital, Guildford, Surrey,
United Kingdom.
AIM: To identify individual attributes or risk factors
which predispose to the development of refeeding
hypophosphatemia in patients on parenteral nutrition
(PN). SETTING: The Royal Surrey County Hospital
(RSCH) a 530-bed, non-teaching Trust with a cancer
center, medical and surgical inpatients and intensive care
unit (ICU). Subjects were recruited prospectively from
all adult inpatients referred for initiation of PN.
METHOD: Seventy patients (cases) with refeeding
hypophosphatemia were matched with controls who had
not experienced a fall in phosphate levels when
commenced on PN. Their nutritional requirements,
nutrition intake and biochemical test results were
compared and statistical analyses performed to show if
any differences between cases and controls were due to
chance. RESULTS: Independent risk factors for developing refeeding hypophosphatemia were: significant
malnutrition measured as a Nutrition Risk Screening
(NRS) score of three or more; less than 12 mmol total
phosphate in the first day’s PN regimen; and an initial
rate of infusion of PN of more than 70% of calculated
requirements. In addition increasing amounts of nonlipid phosphate in the first day’s PN regimen were found
to be protective. Hypomagnesemia prior to starting
PN was nonsignificantly associated with refeeding
hypophosphatemia. Other biochemical markers included
in the study: albumin, calcium, C-reactive protein,
glucose and urea, did not show an association. ICU,
cancer and postoperative patients were not found to be
more at risk. CONCLUSION: Patients with a high NRS
score prior to commencing nutrition support may be
more at risk than others of refeeding hypophosphatemia.
The first 24 hour PN regimen should be run slowly
providing less than 70% of calculated protein and
calorie requirements but containing more than 12 mmol
phosphate.
6/23/08
Glutamine: Role in critical illness and ongoing
clinical trials
Curr Opin Gastroenterol 2008 Mar;24(2):190-197.
Wischmeyer PE.
Department of Anesthesiology, University of Colorado Health Sciences
Center, Denver, Colorado, USA.
Enteral feeding
Curr Opin Gastroenterol 2008 Mar;24(2):184-189.
DeLegge MH.
Medical University of South Carolina, Charleston, South Carolina, USA.
Multiple small clinical trials, observational studies and
retrospective reviews must be analyzed to develop ‘best
practice’ guidelines with enteral nutrition.
Vitamin K-independent warfarin resistance after
concurrent administration of warfarin and
continuous enteral nutrition
Pharmacotherapy 2008 Mar;28(3):308-313.
Dickerson RN, Garmon WM, Kuhl DA, Minard G, Brown RO.
Department of Clinical Pharmacy, University of Tennessee Center for the
Health Sciences, Memphis, Tennessee, USA.
STUDY OBJECTIVE: To assess the influence of withholding continuous enteral nutrition for 1 hour before
and after warfarin administration compared with the
coadministration of warfarin with continuous enteral
nutrition on changes in international normalized ratios
(INRs). DESIGN: Retrospective, crossover case series.
SETTING: Intensive care units of a university-affiliated
medical center. PATIENTS: Six adults who required
nutritional support for at least the first 10 consecutive
days of warfarin therapy; during that 10-day period,
they had a period of at least 3 consecutive days during
which the enteral feeding was withheld for 1 hour before
and after warfarin administration, and had a period of at
least 3 consecutive days when feedings were not withheld during warfarin administration. Patients with
advanced liver disease and those who received therapies,
during the observation period, that significantly alter
warfarin metabolism were omitted from the study.
MEASUREMENTS AND MAIN RESULTS: The change
in INR during the 3-day observation period when feedings were withheld for 1 hour before and after warfarin
administration was significantly different versus the
change in INR during coadministration of warfarin with
continuous feeding (mean ± SD 0.74 ± 0.66 vs -0.13 ±
0.81, p ≤ 0.05). This difference in INR response
occurred despite the administration of similar dosages of
warfarin (5.6 ± 2.1 vs 5.7 ± 2.1 mg/d, p > 0.05). Also
noted was a clinically irrelevant, but statistically significant, difference in vitamin K intake between treatment
periods (77 ± 36 µg/d when feedings were withheld vs
102 ± 28 µg/d when feedings were not withheld, p ≤
0.05). CONCLUSION: Continuous enteral nutrition
should be withheld for 1 hour before and after warfarin
administration to prevent enteral nutrition-associated
warfarin resistance.
Estimating resting energy expenditure in
patients requiring nutritional support: A survey
of dietetic practice
Eur J Clin Nutr 2008 Jan;62(1):150-153.
Green AJ, Smith P, Whelan K.
Department of Nutrition and Dietetics, St George’s Healthcare NHS Trust,
London, United Kingdom.
Estimation of resting energy expenditure (REE) involves
predicting basal metabolic rate (BMR) plus adjustment for
metabolic stress. The aim of this study was to investigate
the methods used to estimate REE and to identify the
PURPOSE OF REVIEW: Enteral nutrition is a widely used
therapy for nutritional treatment of patients with multiple
pathologies. The present review selects important
evidenced-based papers from 2006 and 2007 and critically reviews them for the reader. RECENT FINDINGS:
Use of synbiotics and probiotics is gaining acceptance.
Supplements such as glutamine may be important for
wound healing. Enteral feeding in malnourished patients
may result in rapid growth of gut mucosal protein.
Antibiotics are important for reduction of postpercutaneous endoscopic gastrostomy infections. Early enteral
nutrition in burn patients blunts the hypermetabolic
response. Polymeric enteral formulations in vitro have a
direct anti-inflammatory effect on enterocytes. Enteral
nutrition, however, does not appear better than steroid
use for induction of remission in Crohn’s disease. Longterm (12-week) infusion of immune-enhancing enteral
formulas in a nonsurgical patient group is well tolerated
and safe. Finally, large reviews of enteral nutrition and
their efficacy for specific disease states continue to
demonstrate the difficulty in interpreting multiple small
clinical studies. SUMMARY: Enteral nutrition continues
as a highly used medical therapy, usually as an adjuvant
for other pharmacologic and supportive therapies.
Page 15
Clinical nutrition
abstracts
PURPOSE OF REVIEW: This review will assess recent
clinical and mechanistic data examining glutamine’s ability
to reduce morbidity and mortality in critical illness.
RECENT FINDINGS: Updated meta-analysis data reveal a
significant benefit of glutamine supplementation on
mortality, length of stay and infectious morbidity in critical illness. Recent data support glutamine’s use in critically
ill patients requiring parenteral nutrition and new data
reveal safety and efficacy in head-injured patients. Further,
new findings on glutamine’s beneficial effect on insulin
resistance in critical illness will be reviewed. Recent laboratory data have clarified a number of key mechanistic
pathways by which glutamine may improve outcome in
critical illness. SUMMARY: Severe glutamine deficiencies
occur rapidly in critical illness. The magnitude of glutamine deficiency is correlated with ICU mortality. Further,
meta-analysis reveals glutamine reduces morbidity and
mortality in critical illness. It is likely that our new understanding of the molecular pathways by which glutamine
acts will lead to insight on how best to utilize glutamine as
a nutritional therapy. Presently, randomized, multicenter
clinical trials utilizing glutamine as both nutritional
replacement and pharmacologic intervention, independent
of nutritional needs, are ongoing.
3:13 PM
15
Clinical nutrition
abstracts
6/23/08
3:13 PM
impact of the patient’s clinical condition and the dietitians’
work profile on the stress factor assigned. A random
sample of 115 dietitians from the United Kingdom with an
interest in nutritional support completed a postal questionnaire regarding the estimation of REE for 37 clinical
conditions. The Schofield equation was used by the majority (99%) of dietitians to calculate BMR; however, the
stress factors assigned varied considerably with coefficients
of variation ranging from 18.5 (cancer with cachexia) to
133.9 (HIV). Dietitians specializing in gastroenterology
assigned a higher stress factor to decompensated liver
disease than those not specializing in gastroenterology
(19.3 vs 10.7, p = 0.004). The results of this investigation
strongly suggest that there is wide inconsistency in the
assignment of stress factors within specific conditions and
gives rise to concern over the potential consequences in
terms of under- or overfeeding that may ensue.
Enteral glutamine during active shock
resuscitation is safe and enhances tolerance of
enteral feeding
McQuiggan M, Kozar R, Sailors RM, Ahn C, McKinley B, Moore F.
Department of Surgery, University of Texas Medical School Houston,
Houston, Texas, USA.
16
BACKGROUND: Feeding the hemodynamically unstable
patient is increasingly practiced, yet few data exist on its
safety. Because enteral glutamine is protective to the gut
in experimental models of shock and improves clinical
outcomes, it may benefit trauma patients undergoing
shock resuscitation and improve tolerance if administered early. This pilot study aimed to evaluate
gastrointestinal tolerance and safety of enteral feeding
with glutamine, beginning during shock resuscitation in
severely injured patients. METHODS: In a prospective
randomized trial, 20 patients were randomly assigned to
either an enteral glutamine group (n = 10) or a control
group (n = 10). Patients with severe trauma meeting standardized shock resuscitation criteria received enteral
glutamine 0.5 g/kg/d during the first 24 hours of resuscitation and 10 days thereafter. Immune-enhancing diet
began on postinjury day 1, with a target of 25 kcal/kg/d.
Control patients received isonitrogenous whey powder
plus immune-enhancing diet. Tolerance (vomiting, nasogastric output, diarrhea and distention) was assessed
throughout the study. RESULTS: Glutamine was well
tolerated and no adverse events occurred. Treated
patients had significantly fewer instances of high nasogastric output (5 vs 23; p = 0.010), abdominal distention
(3 vs 12; p = 0.021), and total instances of intolerance (8
vs 42; p = 0.011). Intensive care unit (ICU) and hospital
length of stay were comparable. Control patients
required supplemental parenteral nutrition (PN) to meet
goals at day 7. CONCLUSIONS: Enteral glutamine
administered during active shock resuscitation and
through the early postinjury period is safe and enhances
gastrointestinal tolerance. A large clinical trial is
warranted to determine if enteral glutamine administered
to the hemodynamically unstable patient can reduce
infectious morbidity and mortality.
Page 16
Emergency high-loop jejunostomy as enteral
nutrition access: A simple and safe method
Pacelli F, Rotondi F, Rosa F, Bossola M, Papa V, Tortorelli AP, Sollazzi L,
Doglietto GB.
Department of Surgical Sciences, Digestive Surgery Unit, Catholic
University, School of Medicine, Rome, Italy.
BACKGROUND: Emergency high-loop jejunostomies
are seldom used for nutrition access in the clinical practice. METHODS: This paper describes the results of a
simple and safe technique that uses emergency high-loop
jejunostomy as an enteral feeding access. A feeding tube
is inserted into the efferent loop of the jejunostomy and
then subcutaneously tunneled. In this way, whenever it
becomes necessary, the bag collecting fluids from the
afferent loop can be changed without removing the tube,
which remains permanently inserted into the efferent
loop and secured to the skin in order to avoid displacements. RESULTS: Twenty-nine patients with high-loop
jejunostomy were consecutively treated with the
described technique during the period 2000–2006. The
mean distance between the ligament of Treitz and tube
was 38.3 ± 16.2 cm. After an induction period, all
patients received full-strength enteral nutrition and were
discharged after a mean of 25.1 ± 19.5 days of treatment. All patients were subsequently readmitted to our
unit, and their ostomies were successfully closed. No
major early and late complications were observed;
particularly, no patient experienced local or systemic
septic complications. CONCLUSION: From the analysis
of our results, the described method for delivering
enteral nutrition through an emergency high-loop
ostomy proves easy to apply and clinically effective.
Enteral nutrition can be started as soon as possible after
operation through the efferent loop of the ostomy; the
management of the jejunostomy is simple and safe, with
no additional discomfort for the patients.
PEDIATRICS
Guidelines for the management of growth failure
in childhood inflammatory bowel disease
Inflamm Bowel Dis 2008 Feb 11; [Epub ahead of print].
Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A.
Royal Free Hampstead NHS Trust, Centre for Paediatric Gastroenterology,
Hampstead, London, United Kingdom.
Around 1 in 4 patients with inflammatory bowel disease
(IBD) present in childhood, the majority around the time
of their pubertal growth spurt. This presents challenges
over and above those of managing IBD in adults, as this
period is a time of dramatic psychological and physical
transition for a child. Growth and nutrition are key
priorities in the management of adolescents and young
adults with IBD. Growth failure in IBD is characterized
by delayed skeletal maturation and a delayed onset of
puberty, and is best described in terms of height-for-age
standard deviation score (Z score) or by variations in
6/23/08
Page 17
Long-term outcome, growth and digestive
function in children 2 to 18 years after intestinal
transplantation
Gut 2008 Apr;57(4):455-461; [Epub 2007 Dec 13].
Lacaille F, Vass N, Sauvat F, Canioni D, Colomb V, Talbotec C, De Serre NP,
Salomon J, Hugot JP, Cézard JP, Révillon Y, Ruemme FM, Goulet O.
Pediatric Gastroenterology-Hepatology-Nutrition Unit, Necker-Enfants
malades Hospital, Paris, France.
OBJECTIVE: Small bowel (SB) transplantation (Tx), long
considered a rescue therapy for patients with intestinal
failure, is now a well recognized alternative treatment
strategy to parental nutrition (PN). In this retrospective
study, we analyzed graft functions in 31 children after
SBTx with a follow-up of 2–18 years (median 7 years).
PATIENTS: Twelve children had isolated SBTx, 19 had
combined liver-SBTx and 17 received an additional colon
graft. Growth, nutritional markers, stool balance studies,
endoscopy and graft histology were recorded every 2–3
years post-Tx. RESULTS: All children were weaned from
PN after Tx and 26 children remained PN-free. Enteral
nutrition was required for 14/31 (45%) patients at 2
years post-Tx. All children had high dietary energy
intakes. The degree of steatorrhoea was fairly constant,
with fat and energy absorption rates of 84%–89%.
Growth parameters revealed at transplantation a mean
height Z-score of -1.17. After Tx, two thirds of children
had normal growth, whereas in one third, Z-scores
remained lower than -2, concomitant to a delayed
puberty. Adult height was normal in 5/6. Endoscopy and
histology analyses were normal in asymptomatic patients.
Chronic rejection occurred only in noncompliant
patients. Five intestinal grafts were removed 2.5–8 years
post-Tx for acute or chronic rejection. CONCLUSIONS:
This series indicates that long-term intestinal autonomy
for up to 18 years is possible in the majority of patients
after SBTx. Subnormal energy absorption and moderate
steatorrhoea were often compensated for by hyperphagia,
allowing normal growth and attainment of adult height.
Long-term compliance is an important prerequisite for
long-term graft function.
Clinical nutrition
abstracts
Probiotics and other preventative strategies for
necrotizing enterocolitis
Semin Fetal Neonatal Med 2008 Feb;13(1):35-43; [Epub 2007 Oct 31].
Embleton ND, Yates R.
Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle upon Tyne,
United Kingdom.
Necrotizing enterocolitis (NEC) remains one of the
commonest causes of death and significant morbidity in
preterm infants after the first few postnatal days. NEC
affects approximately 5%–10% of infants born at < or =
28 weeks; about a third will die. Although there do not
appear to be any 'simple fixes', it is clear that there are
many clinical strategies that affect NEC. There is
controlled trial evidence for breast milk, fluid regimes,
enteral antibiotics, immunonutrients and probiotic supplements. This paper will review the evidence relevant to
current populations of preterm infants and determine
which, if any, can be safely and effectively introduced into
current clinical practice.
growth velocity over a period of 3–4 months. Growth
failure is common at presentation in Crohn’s disease
(CD), but less common in ulcerative colitis (UC). The
etiology of growth failure is multifactorial. Principal
determinants, however, include the inflammatory
process per se, with proinflammatory cytokines (eg, IL1β, IL-6) being directly implicated. Furthermore, poor
nutrition and the consequences of prolonged corticosteroid use also contribute to the significant reduction in
final adult height of almost 1 in 5 children. Initially a
prompt, where possible steroid-free, induction of remission is indicated. The ideal is then to sustain a
relapse-free remission until growth is complete, which is
often not until early adulthood. These goals can often be
achieved with a combination of exclusive enteral nutrition (EEN) and early use of immunosuppressants. The
advent of potent and efficacious biological agents
considerably improves the range of growth-sparing
interventions available to children around puberty,
although well-timed surgery remains another highly
effective means of achieving remission and significant
catch-up growth. We carried out a systematic review of
publications to identify the best available evidence for
managing growth failure in children with IBD. Despite
the paucity of high-quality publications, sufficient data
were available in the literature to allow practical,
evidence-based where possible, management guidelines
to be formulated. Although there is clear evidence that
exclusive enteral nutrition achieves mucosal healing, its
effect on growth has only been assessed at 6 months. In
contrast to corticosteroids, EEN has no negative effect
on growth. Corticosteroids remain the key therapy
responsible for medication-induced growth impairment,
although the use of budesonide in selected patients may
minimize the steroid effect on dividing growth plates.
Immunosuppressants have become a mainstay of treatment in children with IBD, and are being used earlier in
the disease course than ever before. However, there are
currently no long-term data reporting better growth
outcome if these agents are introduced very soon after
diagnosis. In comparison, recent data from a large
prospective trial of infliximab in children with moderate
to severe CD suggested significant catch-up growth
during the first year of regular infusions. The only other
intervention that has documented clear catch-up growth
has been surgical resection. Resection of localized CD, in
otherwise treatment-resistant children, early in the
disease process achieves clear catch-up growth within
the next 6 months. There are no data available that
growth hormone improves final adult height in children
with CD. In conjunction with expert endocrinological
support, pubertal delay, more common in boys, may be
treated with parenteral testosterone if causing significant
psychological problems. The optimal management of
children and adolescents requires a multidisciplinary
approach frequently available within the pediatric
healthcare setting. Dedicated dietetic support, along
with nurse-specialist, child psychologist, and with
closely linked medical and surgical care will likely
achieve the best possible start for children facing a lifetime of chronic gut disease.
3:13 PM
17
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Page 18
Highlights of
Clinical Nutrition Week
10–14 February 2008 • Chicago, Illinois, USA
Emerging interests and controversies
in clinical nutrition and critical care –
State of the art lecture: Where have
we been and where are we going?
Highlights of the
G Jensen
State College, PA, USA
changes in their bodies, taste and the manner in which they
must eat can lead to embarrassment, social stigma and selfisolation, and contribute to a learned aversion to food and
reduced food intake.
Recent studies show a proactive approach can lessen
side effects. Pre-treatment swallowing exercises improve post-
After a period of decline in nutrition support teams that para-
treatment swallowing and quality of life in H&N cancer
lleled an emphasis on cost containment in health care, nutrition
patients undergoing radiation or chemotherapy (Kulbersh BD,
support is emerging as a key part of individual medical treatment
et al. Laryngoscope 2006;116:883-886). Prophylactic percuta-
plans for specific patient conditions and phenotypes. Identifying
neous endoscopic gastrostomy (PEG) tube placement that
and treating undernutrition continues to be a keystone in nutri-
allows tube feedings to start earlier in patients with advanced
tion support practice, due to the continued high prevalence of
H&N cancer receiving chemoradiotherapy has been shown to
undernutrition in hospital and acute care settings. However, the
limit weight loss and results in few complications (Wiggenraad
obesity epidemic has broad implications for nutrition support.
RG, et al. Clin Otolaryngol 2007;32: 384-390).
Considerable overlap exists among malnutrition
While nutritional counseling and close follow-up helps
syndromes. Sarcopenia and micronutrient deficiencies arise in
to mitigate the nutritional compromise so often seen with
both undernourished and overnourished patients, and demon-
H&N cancer, cancer cachexia is a chronic systemic inflamma-
strate that undernutrition and overnutrition can occur
tory state that also requires anti-cachexia agents, such as
simultaneously. Inflammation permeates cachexia, protein
corticosteroids and megesterol acetate, to reverse its damaging
energy malnutrition, sarcopenia, failure to thrive and obesity.
effects. Future strategies may include nutraceuticals, omega-3
The lack of standardized definitions is confusing and may
negatively impact therapeutic choices, pointing to the need for a
fatty acids, inflammatory antagonists and other targeted treatments (Couch M, et al. Head Neck 2007;29:401-411).
common nutrition language for malnutrition syndromes
(Thomas DR. Clin Nutr 2007;26:389-399). A new international
effort that builds on earlier attempts to define malnutrition terms
is underway (Roubenoff R, et al. Am J Clin Nutr 1997;66:
192-196).
Research priorities in nutrition support include further
development and testing of screening and assessment tools, and
identification and validation of new laboratory indices for nutri-
18
Nestlé Nutrition Satellite
Symposium – Setting up for success:
Nutrition best practices for patients
with impaired GI function
S McClave (Louisville, KY, USA)
R Martindale (Portland, OR, USA)
J Lacy (Cincinnati, OH, USA)
tion. Well-conceived nutrition intervention studies are needed
Evidence supports the use of early enteral nutrition (EN) as
that tie to clinically relevant outcome studies. Research is also
primary therapy in severe acute pancreatitis (SAP), but its
needed on nutritional modulation of inflammatory conditions
success requires clinicians to be persistent in advancing the
using specific nutrients and functional foods, and on the effect of
feeding and to recognize symptoms of intolerance that would
individualized interventions that are tailored to genetic poly-
limit its use. In a patient with pancreatitis an APACHE II score
morphisms.
of ≥10 or ≥3 Ransom criteria suggests SAP.
Enteral nutrition in SAP maintains gut integrity, sets the
Nutrition challenges in head and
neck cancer
tone for systemic immunity, attenuates the stress response and
JS Magnuson, JL Locher, CS RItchie
Birmingham, AL, USA
and results in fewer complications than parenteral nutrition
disease severity, promotes faster resolution of the disease process
(PN). More importantly, EN reduces mortality by 60%.
Compared with other types of cancer, patients with head and
An immune-modulating formula with arginine, fish oil
neck (H&N) cancer report much lower quality of life and have
and antioxidants is the formula of choice. Gastric feedings are
a higher suicide rate. Alterations of self-identify related to
well tolerated and should be started within 2 days to avoid
6/23/08
3:13 PM
Page 19
delays due to ileus. Although gastric feedings carry a higher
MAdCAM-1 expression in the PP, and are accompanied by
risk for aspiration than small bowel feedings, the link to pneu-
similar decreases in lymphocyte mass. IgA levels in the mucosa
monia is tenuous. Placing the tube 40 cm below the ligament
and the respiratory cell drop concomitant with decreases in
of Treitz may improve tolerance.
total intestinal levels of the IgA-stimulating cytokines IL-4 and
Complicated cases of pancreatitis that require surgical
IL-10. The system is highly dynamic and recovers following
debridement for infected necrosis may need jejunal feedings
introduction of enteral feedings (Zarzaur BL, et al. Shock
and a more elemental formula. Postoperatively, attempts to
2001;15:411-420).
feed patients by the enteral route should continue, but if intolerance persists PN is indicated.
In the clinical setting, the absence of EN reduces the
number of GALT cells in patients with colon cancer (Okamoto
Patients with open abdomens can be fed enterally after
K, et al. JPEN J Parenter Enteral Nutr 2005;29:56-58). The
adequate resuscitation is achieved; however, clinicians must be
lack of enteral feeding also impairs established mucosal immu-
keenly aware of any signs of intolerance and should withhold
nity and the immunologic response to new infectious challenges
feedings if a patient shows any signs of distention, pain, low
(King BK, et al. Ann Surg 1999;229:272-278. Johnson CD, et
urine output or hemodynamic instability.
al. Ann Surg 2003;237:565-573). Parenteral feeding may
contribute to systemic inflammation and increase lung and liver
permeability, leading to multiple organ dysfunction following
arginine, and glutamine. Vitamins E and C and selenium are
severe traumatic injuries (Fukatsu K, et al. Ann Surg
also beneficial. At least 5–7 days of providing a minimum of
2001;233:660-668).
50% of estimated needs are required for immune-modulating
formulas to show benefit.
No data supports withholding jejunal feedings for
Clearly there are immunologic benefits gained at the
mucosal surface when nutrients are delivered via the GI tract
that are not gained with parenteral feeding.
surgery or holding patients with nothing by mouth (NPO)
longer than 3 hours prior to surgery. However, if the patient
Feeding the complex trauma patient
develops pneumotosis postoperatively, enteral feedings should
B Collier
Nashville, TN, USA
be stopped for 3–5 days to avoid nonocclusive bowel necrosis.
Highlights of the
For severely injured trauma patients, data clearly
support using immune-modulating formulas with fish oil,
In complex trauma patients, the presence of persistent systemic
Rhodes Research Lecture:
Of mice and men . . . and a few
hundred mice
inflammatory response syndrome (SIRS), characterized by the
KA Kudsk
Madison, WI, USA
quent immune system impairment. Compounding the
systemic release of proinflammatory mediators, leads to
increased catabolism, acute protein malnutrition and subseproblem, trauma patients who receive inadequate early nutrition can starve, accumulating large energy deficits that cannot
Dr Kudsk hypothesizes that the route and type of nutrition
be made up later on (Todd SR, et al. Nutr Clin Pract
influence mucosal immunity when a lack of enteral stimulation
2006;21:421-429).
creates a defect in mucosal immunity resulting in loss of IgA-
The value of aggressive glucose control in the trauma
mediated defenses in the respiratory tract and increased
patient is unclear. Using an aggressive protocol to maintain
susceptibility to pneumonia.
tight glucose control in trauma patients resulted in no differ-
The small intestine is the principal anatomic site for
ence in outcomes (Collier B, et al. JPEN J Parenter Enteral
immunologic sensitization. Sensitization of most B and T cells
Nutr 2005;29:353-358). Although hyperglycemia is clearly
for mucosal immunity occurs in the Peyer’s patches (PP), aided
proinflammatory, the ideal goal for blood glucose in trauma
by mucosal addressin cellular adhesion molecule-1 (MAdCAM-
patients is unknown and an upper limit of 145 mg/dL may
1), a gateway molecule on the PP. Once sensitized, the cells move
be ideal.
During the resuscitative phase the focus should be on
to the linings of the gastrointestinal (GI) tract, the mammary
appropriate crystalloid and blood use for resuscitative efforts,
tract of lactating females, the respiratory tract and the geni-
early enteral feeds, glucose control, glutamine and early
tourinary tract.
antioxidants. In the early nutrition phase that begins on day 2,
Experimental work has shown alterations in gut-
trauma patients need hypocaloric feedings, immune-enhancing
associated lymphoid tissue (GALT) impairs host defense. Lack
diets, beta blockers and mitochondrial support. By day 7 the
of enteral stimulation decreases T and B cells within PPs and the
trauma patient enters the late anabolic phase of nutrition and
intestinal lamina propria. These alterations occur with
emphasis should be placed on reaching positive nitrogen
decreases in the lymphotoxin-beta receptor (LTßR) signaling
balance by giving adequate nutrition, oxandrolone and beta
pathway (Kang W, et al. Ann Surg 2006;244:392-399) and in
blockers.
out of the PP into the thoracic duct, where they are transported
19
6/23/08
3:13 PM
Feeding the hypotensive patient
Highlights of the
R Kozar
Houston, TX, USA
Page 20
It remains unclear at what volume of gastric residual
aspiration risk increases. In general feedings should not be
held for residual volumes less than 250 mL, although a
Feeding the hemodynamically unstable patient is gaining
promotility agent should be considered for residual
acceptance; yet the practice is not without danger.
volumes persistently greater than 250 mL (McClave SA, et
Nonocclusive bowel necrosis (NOBN) is a rare but serious
al. Gastrointestinal Dis 2003;14:2-10).
complication thought to be caused by metabolic stress when
The inadvertent connection between an enteral
the demand for oxygen during nutrient absorption exceeds
feeding system and a non-enteral system, such as an
supply. The resulting oxygen deprivation places further
intravascular line or peritoneal dialysis catheter, often
stress on the hypoperfused gut and leads to microvasular
results in fatal complications when enteral formula acci-
ischemia and necrosis.
dentally infuses into intravenous lines or catheters. The
Glucose and glutamine are metabolized by the gut and
design of invasive access devices and human error
contribute to energy production. Thus, unlike other nutri-
contribute to enteral misconnections (Guenter P, et al. Jt
ents, they abrogate metabolic stress in the hypoperfused gut,
Comm J Qual Improv 2008;34:285-292). Solutions
enhance gut blood flow and provide a protective effect, via
involve staff and manufacturers, and include education
activation of peroxisome proliferator-activated receptor
and awareness, better purchasing strategies and design
gamma (PPARγ), following mesenteric ischemia (Kozar RA,
changes (Pratt N. Mater Manag Health Care 2006;15:
et al. Gastroenterology 2002;123:810-816).
36-39).
A recently published pilot study demonstrated that
enteral glutamine supplementation during active shock
resuscitation and throughout the early post-injury period is
safe and enhances GI tolerance in severely injured patients
(McQuiggan M, et al. JPEN J Parenter Enteral Nutr
2008;32:28-35). Glutamine supplementation was well
Enteral feeding in the critically ill
patient: Considerations in acute
renal failure
IF Btaiche
Ann Arbor, MI, USA
tolerated compared to protein supplementation and no
Acute renal failure (ARF) is a highly catabolic state and
adverse events occurred. Treated patients had significantly
presents a specific and independent risk factor for poor
fewer instances of GI intolerance. Intensive care unit and
prognosis (Metnitz PG, et al. Crit Care Med 2002;30:
hospital length of stay were comparable. The study was too
2051-2058. Cano N, et al. Clin Nutr 2006;25:295-310).
small to evaluate differences in infectious morbidity or
Similarly to end-stage renal disease, required treatment
mortality.
options compound nutrient losses.
Although data is scarce, available studies indicate
Safe practices for enteral
nutrition: In search of evidence to
support best practice
enteral tube feeding (ETF) is the preferred route for nutri-
MA Corkins (Indianapolis, IN, USA)
S Brantley (Knoxville, TN, USA)
J Boullata (Philadelphia, PA, USA)
P Guenter (Silver Spring, MD, USA)
shown to significantly improve outcomes in critically ill
tional support in patients with ARF when oral feeding
and nutritional supplements are inadequate. ETF was
adult patients treated with chronic renal replacement
therapy (CRRT), even after adjusting for predicted risk of
death (Scheinkestel CD, et al. Nutrition 2003;19:909-
20
This session highlighted ASPEN’s progress to date on devel-
916). Another study compared complications and
oping evidence-based Safe Practices for Enteral Nutrition
nutrient intake in ARF patients receiving tube feedings to
with publication expected later this year. There is a lack of
patients with normal renal function and found that all
evidence to support commonly used methods to check
groups received well above 90% of prescribed nutrition,
enteral feeding tube placement, including auscultation, aspi-
and except for high gastric residual volumes, there were
ration and pH, and capnography. X-rays are the only
no differences in GI or mechanical complications
verified method to confirm placement; however, there are
(Fiaccadori E. Kidney Int 2004;65:999-1008).
concerns with the use of radiation in children.
Direct jejunostomy placement requires significantly
less intervention and is a better option than passing a jejunal feeding tube through the gastrostomy site (Raval MV, et
al. J Pediatr Surg 2006;41:1679-1682). Feedings can begin
Oral nutrition interventions in
end-stage renal disease
TA Ikizler
Nashville, TN, USA
within 48 hours in postoperative patients, even in those with
Patients with end-stage renal disease (ESRD) frequently
open abdominal wounds.
have protein-energy malnutrition plus muscle wasting.
6/23/08
3:13 PM
Page 21
Poor dietary intake, the hemodialysis (HD) process,
2007;17:341-347). A follow-up study is examining the
chronic inflammation and insulin resistance have been
effect of providing 10 g of ALA daily for 12 weeks.
implicated as contributing factors (Ikizler TA. Am J
Initial results show a favourable response with proba-
Physiol
ble effects on hypercoagulability and hyperfibrinolysis
Endocrinol
Metab
2002;282:E107-116).
Intradialytic parenteral nutrition (IDPN) reverses the
in subjects with defined inflammation.
catabolic effects of dialysis, but it is costly and its use
Given its low cost, good tolerance and absence of
is restricted by Medicare and other payers (Pupim LB,
side effects, additional studies using flaxseed powder
et al. J Clin Invest 2002;110:483-492).
are recommended. Nonetheless, patients with normal
An initial study comparing IDPN and oral supple-
or nearly normal inflammatory markers show no bene-
mentation providing 60 g protein, 100 g carbohydrate
fits from omega-3 fatty acid supplementation, even in
and 40 g fat in malnourished ESRD patients showed
those who are overweight or mildly obese, suggesting
oral supplementation was as effective as IDPN in
prophylactic use of omega-3 fatty acids is not indi-
reversing HD-associated protein catabolism and main-
cated for this population (Nelson TL, et al. Cytokine
taining positive protein balance during HD. The
2007;38:101-106).
anabolic effects of oral supplementation persisted
beyond the HD period, providing an additional positive
effect above and beyond what is observed with IDPN
3157).
E Brett, J Mechanick
New York City, NY, USA
The French Intradialytic Nutrition Evaluation
Enteral nutrition helps maintain tight glucose control
Study (FINEs), a large, long-term study in malnour-
during sepsis and should start as soon as the patient is
ished patients with chronic renal failure (CRF),
hemodynamically stable. Goals are ≤100% measured
demonstrated that the route of administration of
resting energy expenditure (MREE) during the shock
nutritional supplementation has no significant effect
and catabolic phases of sepsis, and 100%–130%
on survival or the observed improvements in most
MREE during the anabolic phase of critical illness
nutritional markers. Nutritional supplementation
(McClave SA, et al. JPEN J Parenter Enteral Nutr
providing 1.2 g protein/kg/d and >30 kcal/kg/d
2003;27:16-20).
improved nutritional markers (Cano NJ, et al. J Am Soc
Hyperglycemia in hospitalized patients may be
Nephrol 2007;18:2583-2591). Considering the finan-
due to pre-existing type 1 or type 2 diabetes, or it may
cial advantages, oral supplementation should be the
result
treatment of choice for all chronic renal disease
Regardless of the cause, the adverse effects of acute
patients requiring nutritional intervention.
hyperglycemia, including impaired immune function,
from
stress
or
steroid-induced
Highlights of the
(Pupim LB, et al. J Am Soc Nephrol 2006;17:3149-
Managing diabetes in nutrition
support patients
diabetes.
fluid and electrolyte imbalance, erythrocyte and
Supplementation of flaxseed
powder in morbid obesity
platelet aggregation, endothelial dysfunction and
J Faintuch
Sao Paulo, Brazil
(Cheung NW, et al. Diabetes Care 2005;28:2367-
increased oxidative stress, result in worse outcomes
2371. Lin LY, et al. Am J Med Sci 2007;333:261-265).
Morbid obesity is frequently associated with chronic
Therefore, hyperglycemia is treated the same whether
microinflammation, which carries potentially adverse
or not there is an underlying diagnosis of diabetes.
Compared to patients with diabetes who are
inflammation usually improves after weight loss, even
eating, those on tube feedings have higher peak
minor elevations in C-reactive protein (CRP) have
glucose loads and higher insulin requirements due to
negative prognostic implications and predict mortality
more rapid absorption of continuous low volume
(Kushner I, et al. Am J Med 2006;166:e17-28).
liquid formulas compared to solid food taken in bolus
Flaxseed is the most abundant vegetable source
feedings. However, enterally fed patients have a more
of the omega-3 fatty acid alpha-linolenic acid (ALA)
predictable caloric intake, making control of blood
and is used in coronary disease. A 2-week study in
glucose easier compared to patients who are eating.
obese patients with elevated inflammatory markers
Diabetes-specific formulas have been shown to
showed that adding flaxseed powder to the diet to
result in lower peak glucose, lower insulin requirements
provide 5 g ALA a day alleviated inflammation. Levels
and fewer complications than standard formulas in
of CRP and serum amyloid A (SAA), another inflam-
patients with diabetes. (Peters AL, et al. JPEN J
matory marker, fell (Faintuch J, et al. Obes Surg
Parenternteral Nutr 1992;16:69-74).
metabolic and cardiovascular consequences. Although
21
6/23/08
3:13 PM
Nestlé Nutrition Satellite
Symposium – Clinical studies that
have changed practice: Do you
know them? Do you like them?
Did you implement them?
Highlights of the
RG Martindale (Portland, OR, USA)
R Meier (Liestal, Switzerland)
C Pichard (Geneva, Switzerland)
Page 22
Selenium supplementation in the
ICU – Have we found the magic
bullet?
A Shenkin
Liverpool, England
While good theoretical evidence exists that Se supplements
improve the antioxidant state in critical illness, clinical trials
have shown variable results. In patients with SIRS, Se supple-
This session was designed to assist clinicians in analyzing the
mentation significantly lowered mortality and reduced the
quality of research when deciding whether to implement
incidence of acute renal failure (Angstwurm MW, et al. Crit
new findings into current practice. Presenters demonstrated
Care Med 1999;27:1807-1813). A later meta-analysis of
a systematic approach to evaluating clinical studies
eleven studies showed Se supplementation may be associated
considering the type of study, randomization, blinding of
with a reduction in mortality in critically ill patients and
investigators, percent of follow-up, intention to treat,
concluded Se supplementation is safe (Heyland DK, et al.
sample size for power analysis, patient demographics and
Intensive Care Med 2005;31:327-337). More recently, a pilot
primary endpoints vs ad hoc analysis.
study to reduce deaths from oxidative stress (REDOX) showed
In GI cancer strong evidence supports preemptively
that higher doses of Se (300 μg given enterally plus 500 μg
loading the cell with arginine, omega-3 fatty acids and RNA
given parenterally) reduced oxidative stress and improved clin-
prior to surgery, to reduce perioperative complications and
ical outcomes.
length of hospital stay (Gianotti L, et al. Gastroenterology
Conversely, other studies have found no benefit, espe-
2002;122:1763-1770). Fourteen papers support the use of
cially those using high loading doses. In a multicenter study of
pre- or perioperative immune-modulating formulas.
ICU patients with severe SIRS, higher doses of Se replacement
In another surgical arena, a well-done study showed
showed a strong but not statistically significant trend toward
fish oil given perioperatively reduced the relative risk of
reduced mortality (Angstwurm MW, et al. Crit Care Med
postoperative atrial fibrillation after coronary artery bypass
2007;35:118-126). High loading doses of Se (4,000 μg) had no
surgery by 54.4% and was associated with a shorter
effect on mortality or adverse events and did not reduce oxida-
hospital stay (Calò L, et al. J Am Coll Cardiol 2005;45:
tive damages (Forceville X, et al. Crit Care 2007;11:R73.
1723-1728).
Mishra V, et al. Clin Nutr 2007;26:41-50).
Good evidence also exists for using synbiotics to
Se supplementation is clearly beneficial in select patient
improve outcomes in patients undergoing major abdominal
populations. In burn patients Se supplementation to replace
surgery. In another well-done study, EN using fiber-
losses from the surface results in significantly decreased
containing solutions plus Lactobacillus reduced the rate of
bronchopneumonia infections and shortened hospital stays
postoperative infections compared to parenteral nutrition
(Berger MM, et al. Am J Clin Nutr 1998;68:365-371).
(PN) or fiber-free EN (Rayes N, et al. Nutrition 2002;18:
609-615).
Recent work challenges the practice of hypocaloric
feedings and showed that energy deficits of more than
10,000 Kcal accumulating after only one week are associ-
ated with increased infection rate or impaired wound
22
Supplementation of vitamin C and
vitamin E in the critically ill patient:
Re-examining the evidence
L-N Chan
Seattle, WA, USA
healing. The deficits are impossible to compensate for later
Critically ill patients have low circulating concentrations of
on and call for more aggressive measures to meet energy
vitamins C and E, which could considerably compromise
needs (Villet S, et al. Clin Nutr 2005;24:502-509).
antioxidant defense. Seemingly, vitamin E and C supplementa-
Supplemental PN combined with EN could be an
tion would be beneficial, but most studies have been
effective alternative to achieve energy targets when EN goals
disappointing (Quasim T, et al. Clin Nutr 2003;22:459-462).
are not met by day 4, but controversy surrounds its use in
Chan postulates that failure of vitamin E and C supplementa-
critical illness. A recent meta-analysis investigated the effect
tion to show an expected dose-response may be due to the
of trial quality on the overall conclusions reached when
formulation, dose, route, and time and duration of vitamin
comparing EN and PN. It showed that PN is not related to
therapy.
excess mortality and may even be associated with improved
The optimal formulations and doses of vitamin C and E
survival. (Simpson F, et al. Intensive Care Med 2005;31:12-
required to produce a positive clinical outcome remain
23. Heidegger CP, et al. Intensive Care Med 2007;33:
unknown. The many different available salt forms of vitamins
963-969).
C and E could account for the variable responses seen with
6/23/08
3:13 PM
Page 23
supplementation. In several studies, large doses of oral vitamin
2001;29:2075-2080. Garrel D, et al, Crit Care Med
C (up to 10-fold increase) and oral and intravenous vitamin E
2003;31:2444-2449), reduce Gram-negative infections in
(up to 15-fold increase) produced relatively small increases in
patients with multiple trauma (Houdijk AP, et al. Lancet
serum concentrations, suggesting cellular uptake of vitamins is
1998;352:772-776) and decrease nosocomial infections in
limited (Nathens AB, et al. Ann Surg 2002;236:814-822. Long
patients with SIRS (Conejero R, et al. Nutrition 2002;18:716-
CL, et al. J Surg Res 2003;109: 144-148).
721). A combination of enteral and parenteral glutamine
The route of administration affects the dose-response
relationship. Very high levels of oral vitamin C produce only
probably maximizes benefits in the critically ill patient by
providing both a local and systemic effect.
slightly elevated plasma concentrations, whereas intravenous
administration of vitamin C produces substantially higher
concentration levels. This suggests the intravenous route
bypasses a tight oral control (Padayatty SJ, et al. Ann Intern
Med 2004;140:533-537). A meta-analysis indicated parenteral
Improving outcomes in critically ill
patients: Glycemic control
G Jensen
State College, PA, USA
antioxidants are associated with more favorable clinical
Although Van den Berghe’s landmark study on the use of inten-
outcomes than enteral antioxidants (Heyland DK, et al.
sive insulin therapy (IIT) in cardiac surgery patients showed
Intensive Care Med 2005;31:327-337).
dramatic improvements in outcomes and has changed practice
(Van den Berghe G, et al. N Eng J Med 2001;345:1359-1367),
recent studies raise concern about the routine implementation
weeks of supplementation were required to achieve a dose
of IIT intervention.
response relationship (Devaraj S, et al. Arterioscler Thromb
A subsequent study by Van den Berghe in a medical ICU
Vasc Biol 1997;17:2273-2279). On the other hand, more recent
yielded confusing results; mortality was higher with IIT for
studies on long-term supplementation of vitamin C and E found
patients who stayed in the ICU less than 3 days and lower if
significantly higher increases of vitamin concentrations in the
they stayed longer than 3 days (Van den Berghe G, et al. New
organs than in the serum, suggesting sequestering of vitamins to
Engl J Med 2006;354:449-461). In a trauma population,
protect the organs. This implies that serum or plasma concen-
Collier et al found no differences in pneumonia, surgical infec-
trations may not be a reliable marker for total body
tion or mortality between patients who were managed with an
concentration and calls into question the practice of long-term
IIT protocol compared to the control group (Collier B, et al.
supplementation to increase serum concentration (Mustacich
JPEN J Parenter Enteral Nutr 2005;29:353-359). A more
DJ, et al. Free Radic Biol Med 2007;43:610-618).
recent study found IIT during cardiac surgery did not reduce
Highlights of the
The time and duration of supplementation also influences
the effectiveness of vitamin supplementation. In some studies
perioperative death or morbidity compared with conventional
Improving outcomes in critically ill
patients: Glutamine
supplementation
intraoperative glucose management. The IIT group had an
P van Leeuwen
Amsterdam, The Netherlands
Med 2007;146:233-243).
increased incidence of death and stroke, suggesting a potential
for harm with routine use of IIT (Gandhi GY, et al. Ann Intern
A study comparing the effect on survival among patients
with septic shock using IIT vs conventional insulin therapy and
by closing the paracellular channels on the apical side, thereby
crystalloids vs colloids for fluid resuscitation showed no signif-
decreasing gut permeability (Kouznetsova L, et al. JPEN J
icant difference in mortality or organ failure between groups.
Parenter Enteral Nutr 1999;23:136-139. Le Bacquer O, et al.
However, rates of severe hypoglycemia and serious adverse
Am J Physiol Gastrointest Liver Physiol 2003;285:G128-
events were higher in the IIT group than in the conventional-
G136). Glutamine supports the gut-associated immune system
therapy group, prompting researchers to stop the trial early.
by serving as respiratory fuel for the small intestine and
They concluded that IIT placed critically ill patients with sepsis
substrate for the synthesis of glutathione (Manhart N, et al.
at increased risk for serious adverse events related to hypo-
Ann Surg 2001;234:92-97. Pithon-Curi TC, et al. Am J Physiol
glycemia (Brunkhorst FM, et al. N Engl J Med 2008;
Cell Physiol 2003;284:C1355-1361). Glutamine also stimu-
358:125-139).
lates de novo synthesis of arginine, the precursor of nitric oxide,
which regulates blood flow through the gut during stress.
In the clinical setting, glutamine supplementation reduces
The views expressed in this newsletter are of the
presenters and participants, not Nestlé Nutrition.
morbidity and mortality in critically ill patients, and low plasma
levels significantly predict mortality. Glutamine supplementation has been shown to reduce Gram-negative bacteremia and
death in burn patients (Wischmeyer PE, et al. Crit Care Med
The next Clinical Nutrition Week will be held on 1–4 February
2009 in New Orleans, Louisiana, USA. Further information may
be found at www.nutritionweek.org.
Experimental evidence shows glutamine maintains gut integrity
23
6/23/08
3:13 PM
Page 24
Conference Calendar 2008
August 2008
International Academy of Nutrition
and Aging (IANA) 3rd International
Meeting
1–2 August 2008
Albuquerque, New Mexico, USA
Organizer:
University of New Mexico,
School of Medicine Clinical Nutrition Program,
Aging Process Study
Tel: +1 505 272 3942
Fax: +1 505 272 8604
E-mail: [email protected]
Web site: www.serdi-fr.com/ABQ.htm
3rd World Congress of Pediatric
Gastroenterology, Hepatology and
Nutrition (WCPGHAN 3)
16–20 August 2008
Iguassu Falls, Brazil
Conference calendar
Organizer:
LASPGHAN
Tel: +55 41 3342 7175
Fax: +55 41 3342 7175
Web site: www.wcpghan2008.com
September 2008
44 Annual Meeting of the
European Association for the
Study of Diabetes (EASD)
7–11 September 2008
Rome, Italy
th
Organizer:
EASD Secretariat
Tel: +49 211 758 46920
Fax: +49 211 758 46929
Web site: www.easd.org
21st European Society of Intensive
Care Medicine (ESICM) Annual
Congress
Lisbon, Portugal
Organizer:
ESICM Congress Manager
Tel: + 32 2 559 03 55
Fax: + 32 2 527 00 62
Web site: www.esicm.org
8th Advances in Pediatric Nutrition
Baltimore, Maryland, USA
Organizer:
The Johns Hopkins University School of Medicine
Tel: +1 410 502 9634
Web site: www.hopkinscme.net
October 2008
ADA Food & Nutrition Conference &
Expo (FNCE) 2008
25–28 October 2008
Chicago, Illinois, USA
Organizer:
American Dietetic Association
Tel: +1 800/877 1600 4862
Web site: www.eatright.org/fnce
November 2008
British Association for Parenteral
and Enteral Nutrition (BAPEN)
Conference 2008
4–5 November 2008
Harrogate, United Kingdom
Organizer:
24
30th European Society for Clinical
Nutrition and Metabolism (ESPEN)
Congress
Florence, Italy
Organizer:
MCI Suisse SA
Tel: +41 22 33 99 580
Fax: +41 22 33 99 601
Web site: www.espen.org/npages/florence
Sovereign Conference
Tel: +44 1527 518 777
Web site: www.bapen.org.uk
NASPGHAN-CDHNF Partnership:
A Decade of Progress
13–15 November 2008
San Diego, California, USA
Organizer:
North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition
Children’s Digestive Health and Nutrition Foundation
Tel: +1 215 233 0808
Web site: www.naspghan.org
6/23/08
3:13 PM
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The gut as an immune organ Science supporting better nutrition In this issue

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