Vet Clin Small Anim 32 (2002) 1165–1178

Bacterial translocation:
clinical implications and prevention
Douglass K. Macintire, DVM, MS*,
Ted L. Bellhorn, DVM
Department of Small Animal Surgery and Medicine, College of Veterinary Medicine,
Auburn University, Auburn, AL 36849, USA

Sepsis is the most common cause of death in human trauma patients sur-
viving more than 48 hours after an initial traumatic insult [1]. In many crit-
ically ill patients dying of sepsis, however, no source of infection can be
found. Gram-negative bacteria are the most common organisms cultured
from these patients. In the late 1980s and early 1990s, these observations led
many researchers to suspect that the gut is the reservoir of pathogenic bac-
teria and endotoxins that initiate the systemic host response leading to shock
and organ failure [2].

Definition and background

Bacterial translocation (BT) is defined as the passage of viable indigenous
bacteria from the gastrointestinal (GI) tract to the mesenteric lymph nodes,
liver, spleen, and bloodstream [1]. Numerous animal and human studies
have clearly documented that microorganisms and toxins normally present
in the GI tract can translocate from inside the lumen to extraintestinal sites
[3–5].
In the 1980s and 1990s, various researchers employed a rodent hemorrha-
gic shock model to demonstrate that hemorrhagic shock causes BT to mes-
enteric lymph nodes [6]. With increasing severity of shock, they showed that
bacteria could also be cultured from the liver and spleen [3] and, ultimately,
that bacteria and endotoxin could be detected in systemic blood [4,5].
Because of these findings, many researchers saw the gut as the originator
of multiple organ failure [7–10].

* Corresponding author.
E-mail address: macindk@vetmed.auburn.edu (D.K. Macintire).

0195-5616/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved.
PII: S 0 1 9 5 - 5 6 1 6 ( 0 2 ) 0 0 0 3 7 - 2
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Pathogenesis
A simple hypothesis was proposed to explain the occurrence of multiple
organ dysfunction in animals or human beings without a known septic focus
[9]. It was believed that shock or trauma resulted in reduced perfusion and
impaired oxygen delivery to the gut. The ensuing mucosal damage owing to
ischemia/reperfusion injury and oxygen stress resulted in gut barrier dys-
function, allowing translocation of bacteria, endotoxins, and cytokines into
the systemic circulation. These mediators were thought to induce a massive
proinflammatory response, thus affecting distant organs [11]. A rodent model
of nonlethal gut ischemia/reperfusion supported the role of BT in contri-
buting to distant organ failure [12]. Occlusion of the superior mesenteric
artery for 45 minutes followed by 6 hours of reperfusion resulted in acute
lung injury in rats.
Despite the considerable mass of evidence supporting the existence of BT
in experimental animals, the clinical significance of BT was called into ques-
tion when researchers were unable to culture bacteria from the portal or sys-
temic blood in a series of human trauma victims [13,14]. In addition, the
results of a multicenter trial in critically ill human patients evaluating selec-
tive gut decontamination in which antimicrobial agents were used aggres-
sively to depopulate the gut of pathogenic gram-negative bacteria and
fungi were somewhat disappointing [15]. No improvement in length of sur-
vival was noted, although there was a 50% reduction in the number of infec-
tious complications in these patients.
The inability to culture bacteria from the portal vein of animals or people
with shock of recent onset led to some modifications in the original concept
of BT [16]. It is now believed that the gut-derived factors contributing to dis-
tant organ injury are found in the mesenteric lymph nodes rather than in the
portal blood and that actual bacteria are not necessary to initiate the sys-
temic inflammatory response [17–19].
Presumably, many bacteria that translocate to the intestinal lymphatic
tissue are killed by the host, thereby initiating a massive proinflammatory
response characterized by the release of cytokines, vasoactive substances,
complement, and other immunomodulators [1]. Furthermore, gut-derived
endotoxemia may be the signal that triggers, perpetuates, or exacerbates the
hypermetabolic response seen in the systemic inflammatory response syn-
drome (SIRS) [20]. Endotoxins are known to stimulate cytokine release and
can cause impairment of the immune system, coagulation system, and GI
mucosal barrier [6,21,22]. It is therefore not necessary to culture viable bac-
teria from the bloodstream or distant organs to implicate the gut as the most
probable cause of SIRS.
One theory that has been proposed to explain the relation between the gut
and multiple organ dysfunction has been referred to as the ‘‘two-hit’’ theory
[23]. According to this concept, an initial event, such as trauma or shock, acts
to ‘‘prime’’ the immune system by activating neutrophils and macrophages.
 D.K. Macintire, T.L. Bellhorn / Vet Clin Small Anim 32 (2002) 1165–1178 1167

When a second insult occurs, such as translocation of endotoxins or bacteria

from damaged GI mucosa, an exaggerated host response follows in which
massive quantities of cytokines are produced and released into the systemic
circulation [24]. These cytokines, including tumor necrosis factor-a (TNFa),
interleukin (IL)-6, and IL-1B, cause hemodynamic instability and tissue injury
[12,25–27]. Neutrophils are activated such that their release of mediators is
amplified into a generalized systemic inflammatory response [28].
The systemic inflammatory response consists of complement activation,
oxidant activation, and endothelial-leukocyte interaction with adhesion
molecules [29]. Neutrophils are recruited to the site of injury via complement
and cause tissue damage through the release of proteolytic enzymes, reactive
oxygen species, and vasoactive substances. The endothelial-leukocyte inter-
action can lead to disseminated intravascular coagulation, microvascular
thrombi, and organ damage.
Recent studies also indicate that there is excessive synthesis of nitric oxide
associated with shock [30]. Excess nitric oxide causes vasodilation, hypoten-
sion, and decreased cardiac contractility. Nitric oxide is converted to perox-
ynitrite in macrophages. This mediator can cause cellular damage through
lipid peroxidation, glutathione depletion, ATP depletion, and mitochondrial
dysfunction [31].
Another mechanism contributing to organ damage is selective transcrip-
tion failure in which proinflammatory cytokines are produced in excess and
anti-inflammatory mediators are decreased [11]. A transcriptional failure of
acute-phase proteins has been shown to occur in animal models of fulminant
sepsis, likely contributing to organ failure [32,33].
TNFa is an important mediator of SIRS and multiple organ dysfunction
syndrome (MODS). A rodent model of hemorrhagic shock documented
translocation of GI microorganisms to the mesenteric lymph nodes within
1 hour after the onset of shock [34]. In addition, investigators documented
the expression of the TNFa gene in the ileum, mesenteric lymph nodes, and
white pulp of the spleen but not in the liver, kidney, or lung. Translocation
of microorganisms to the mesenteric lymph nodes seems to trigger the
expression of TNFa in the gut-associated lymphatic tissue, leading to a gen-
eralized host response through altered signal transduction.
Further evidence that BT involves mesenteric lymph nodes rather than
portal blood has been provided by other studies. Acute lung injury after
hemorrhagic shock or thermal injury in rats can be prevented or ameliorated
by diverting mesenteric lymph flow, because the lung is the first organ
exposed to mesenteric lymph [19]. It has also been shown that mesenteric
lymph (but not portal blood) collected after a shock episode activates neu-
trophils, increases endothelial cell permeability, and even causes cell death in
vitro [19]. Mesenteric lymph nodes drain into the thoracic duct, which
bypasses the reticuloendothelial system and goes directly to the lungs. High
levels of endotoxins have been found in lymphatic fluid after shock [18],
whereas blood cultures are often negative [35].
1168 D.K. Macintire, T.L. Bellhorn / Vet Clin Small Anim 32 (2002) 1165–1178

The liver also plays a role in the pathogenesis of BT and gut-induced sep-
sis. BT was increased almost fourfold in human patients with severe liver
disease and cirrhosis compared with noncirrhotic patients [36]. In addition,
selective decontamination of the gut reduced the level of BT for patients
with advanced cirrhosis to that found in noncirrhotic patients [38]. In rats,
experimentally induced ligation of the common bile duct caused significant
BT to the mesenteric lymph nodes and liver. Sucralfate and/or gentamicin
reduced the degree of BT in these rats [39].
Another factor that has recently been shown to be important in the
pathogenesis of BT is bacterial virulence [38–40]. Some types of bacteria,
such as Pseudomonas aeruginosa, or strains of specific bacteria, such as
Escherichia coli, are more virulent than others. They have the ability to sense
when the host is most vulnerable to infection by detecting changes in tem-
perature, pH, osmolality, oxygen, carbon dioxide, nitrogen compounds,
oxygen free radicals, and norepinephrine. The sensing mechanism occurs
through diffusable molecules and allows communication among the bacte-
ria. The signaling induces gene transduction for such processes as adhesion,
colonization, and proliferation. The PA-1 adherence gene causes injury to
the tight epithelial junctions and allows cytotoxins from bacteria to enter the
host. The type III protein secretory system injects secreted invasion protein
(SIP) into cells, allowing bacteria to enter host cells. Inside the host cell, bac-
teria are able to live within macrophage vacuoles and survive oxidative
agents, DNA damage, increased osmolality, starvation, and acid pH
through macrophage gene transduction. The bacteria can then be trans-
ported to more distant sites within the host.
Bacterial overgrowth also contributes to BT [37,41–43]. Studies have
shown that use of antacids in critical patients may lead to proximal gut col-
onization by virulent bacteria because of increased gastric pH. Colonization
of the proximal gut has been associated with an increase in BT and septic
morbidity [41].
Many researchers believe that splanchnic ischemia plays a central role in
the development of multiple organ failure [43–45], because there is a strong
correlation between decreasing intramucosal pH and morbidity and mortal-
ity [46]. It is believed that intestinal ischemia leads to loss of barrier func-
tion, which results in exposure of the gut-associated lymphoid tissue
(GALT) to bacteria and toxins and the ensuing release of massive amounts
of cytokines and endotoxins. If the reticuloendothelial system is over-
whelmed, systemic endotoxemia and/or bacteremia may result.

Gastrointestinal mucosal barrier

Under normal conditions, the gut provides an effective mechanical and
functional barrier to systemic absorption of intraluminal bacteria and toxins
[47]. For BT to occur, bacteria must first adhere to the intestinal mucosa.
Adherence is reduced by intestinal peristalsis and mucus production.
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Enhanced BT has been shown to occur in conditions associated with

decreased peristalsis, such as intestinal ileus and obstruction. Administra-
tion of vasopressors, corticosteroids, and nonsteroidal anti-inflammatory
drugs (NSAIDS) can result in decreased mucus production and loss of the
protective mechanical barrier. Conditions of poor perfusion, such as the
splanchnic ischemia associated with shock, also result in decreased epithelial
cell turnover, cell death, and enhanced potential for mucosal breakdown.
Stress gastritis and ulceration are common in critical patients.
The gut is the largest immunologic and endocrine organ in the body [48].
The GALT consists of Peyer’s patches, lymphoid follicles, lamina propria
lymphocytes, intraepithelial lymphocytes, and mesenteric lymph nodes.
Secretory IgA is produced by the antigen-primed lymphocytes that line the
intestinal mucosa. These immune defenses are critical in defending the host
against bacterial invasion. Immunosuppressed patients are therefore pre-
disposed to BT. Poor nutrition of enterocytes can result in decreased IgA
production and impaired GI immune defenses.
A final factor that helps to maintain the normal GI mucosal barrier is the
protective role of the normal indigenous microflora [49]. Anaerobes are the
most numerous bacteria in the GI tract. They compete with potential patho-
gens for nutrients and mucosal attachment sites, thereby inhibiting bacterial
overgrowth with gram-negative bacteria. Antibiotic therapy often upsets the
delicate balance of the GI microflora by selecting for gram-negative and
resistant organisms while suppressing the more sensitive indigenous anae-
robes [3]. Other interventions that may disrupt the normal flora in critical
patients include the use of H2 blockers, which can result in bacterial over-
growth and colonization of the stomach [50], and the use of hyperosmolar
enteral diets [51].

Importance of nutrition
For many years, the GI tract was ignored in the management of critically
ill patients. The primary function of the GI tract was seen as the absorption
of nutrients, which was considered necessary to support adequate wound
healing and host response to injury or infection. Concern about possible
aspiration, vomiting, ileus, or lack of enteral access led many clinicians to
pursue a course of ‘‘bowel rest.’’ We now know that bowel rest can lead
to mucosal atrophy, altered permeability, and loss of the trophic effects of
GI hormones. It has been shown in experimental models that starvation and
malnutrition alone do not induce BT but may predispose to mucosal dam-
age and the development of a potentially lethal gut origin septic state during
periods of systemic inflammation [52]. Currently, there is significant interest
and ongoing research to identify individual nutrient effects and to use nutri-
tion as a modulator of metabolic and inflammatory processes.
Early studies in rodents showed the superiority of enteral nutrition over
parenterally administered nutrition [53]. BT and mucosal atrophy were seen
1170 D.K. Macintire, T.L. Bellhorn / Vet Clin Small Anim 32 (2002) 1165–1178

in rats administered total parenteral nutrition (TPN) but not in those fed
enterally. In human beings, the adverse effects of TPN have not been pro-
ven. Mucosal atrophy does not occur with short-term TPN, and in perioper-
ative patients, there was no difference in morbidity, mortality, preservation
of gut barrier function, or development of infectious complications in
patients receiving either parenteral or enteral nutrition [54]. Early enteral
nutrition has been advocated to improve splanchnic blood flow and modu-
late the immune response, especially in trauma and burn patients. Enteral
nutrition can be associated with some complications in critically ill patients,
however, such as diarrhea, bloating, vomiting, or ileus [55]. A combination
of enteral and parental nutrition may be the best method to meet the needs
of critically ill patients.
The type of diet fed may also be important. In mice, feeding a liquid diet
results in BT, whereas feeding a solid diet of rat chow does not result in BT
[50]. Another nutrient that has received considerable study is glutamine [56].
Glutamine is the preferred metabolic fuel for cells lining the small intestine
and has been considered a ‘‘conditionally essential’’ nutrient in critically ill
patients. It is essential for lymphocyte mitogenesis and enhances gut barrier
function. Many studies in rodents have shown beneficial effects of adding
glutamine to enteral or parenteral solutions (reduced BT, thicker GI muco-
sa, and increased survivability) [57,58]. In cats, however, a glutamine-
enriched diet was unable to prevent BT or attenuate permeability defects
secondary to methotrexate-induced enterocolitis [59].
The preferred fuel of colonocytes is short-chain fatty acids. These are
produced through fermentation of nondigestible carbohydrates, commonly
referred to as fermentable fibers (pectin, b-glycan, and lactulose). Insoluble
fibers, such as cellulose, have trophic effects on the GI mucosa by promoting
mucus production, stimulating epithelial cell growth, and preserving growth
of normal microflora. Insoluble fiber is thought to stimulate release of tro-
phic gut hormones, which enhance gut barrier function. Current recommen-
dations regarding optimal fiber type and dose are lacking, but research is
ongoing. Preliminary animal studies have shown decreased BT, prevention
of mucosal atrophy, and avoidance of cecal bacterial overgrowth after the
addition of bulk fiber additives to enteral diets [60]. Other dietary additives
that may reduce BT include x3 fatty acids (fish oil products), arginine,
nucleic acids, and antioxidants. Other research is focusing on hormones,
such as bombesin, which exert protective trophic effects on the GI mucosa.
Definitive dietary recommendations await the results of this exciting area of
research.

Clinical significance
Based on experimental studies in animal models, three primary mecha-
nisms leading to enhanced BT have been identified: intestinal bacterial
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overgrowth, deficiencies in host immune defenses, and damage to the GI

mucosal barrier. Aggressive prevention of BT must therefore address these
three concerns as well as provide nutritional support of the gut.
Animal research models and human clinical reports have shown that BT
can be promoted by thermal injury, immunosuppression, trauma, hemor-
rhagic shock, endotoxin, acute necrotizing pancreatitis, TPN, neutropenia,
intestinal obstruction, and intestinal ischemia. These same conditions would
be likely to promote BT in critically ill veterinary patients. In addition, dogs
with severe parvoviral enteritis are uniquely predisposed to developing BT,
sepsis, and endotoxemia because of the combination of neutropenia and
breakdown of the GI mucosal barrier. E. coli has been cultured from the
lungs and liver of dogs that have died from parvoviral enteritis [61], and
endotoxemia has also been documented in affected dogs [62].

Prevention and treatment

Prevention of BT, sepsis, and multiple organ failure is an area of ongoing
research. The most important factor for preventing BT is preservation of an
intact GI mucosal barrier, because experimental studies have shown that BT
can largely be prevented by limiting mucosal injury [63]. For this reason,
therapeutic measures are aimed at (1) decreasing the likelihood of mucosal
disruption, (2) limiting the consequences of disruption if it occurs, and (3)
supporting the gut so that mucosal defects can be rapidly repaired. The fol-
lowing recommendations can be made.

Improving gut oxygenation

It seems that most mucosal damage in critical patients is initiated by ische-
mia and potentiated by reperfusion injury [1,12,44]. Oxygen delivery to the
gut should be maximized with effective aggressive hemodynamic resuscita-
tion. Adequate fluid therapy with crystalloid and/or colloid fluids should
be administered to maintain adequate blood pressure and GI perfusion.
Early resuscitation is important in curbing ischemia and reperfusion
injury. Most cells deprived of oxygen for 5 to 10 minutes can become tem-
porarily or permanently damaged [16]. Simply supplying oxygen to the ani-
mal via a mask, ‘‘flow by,’’ or nasal tubes can double the fractional inspired
oxygen concentration. Red blood cells or oxygen-carrying hemoglobin solu-
tions can also improve oxygen delivery (DO2) to the tissues and are indi-
cated if the hemoglobin concentration drops below 10 to 12 g/dL. Fresh
whole blood or blood stored less than 14 days has a higher concentration
of 2,3-diphosphoglycerate (DPG) compared with stored blood. Red blood
cells not only carry oxygen but act as antioxidants through endogenous sub-
stances, such as catalase and glutathione.
Another advantage of fresh whole blood given within 8 hours of collec-
tion is that it provides coagulation factors as well as having oxygen-carrying
1172 D.K. Macintire, T.L. Bellhorn / Vet Clin Small Anim 32 (2002) 1165–1178

capacity. Hemoglobin substitutes have enhanced uptake of oxygen in the

lungs and may even facilitate offloading of oxygen in tissue [64]. They are
also nitric oxide scavengers, a property that may improve blood pressure
in animals with hypotension secondary to hemorrhagic shock. Supplemental
oxygen should definitely be administered if the pulse oximetry reading drops
below 90% to 95%, but there is also evidence to support hyperoxygenation
of shock patients even when oxygen saturation is normal [65]. In one study
of experimentally induced hemorrhagic shock in rats, administration of
100% oxygen prevented BT and TNFa gene expression compared with that
in rats breathing room air [66]. If available, gastric tonometry is an effective
method for monitoring intramucosal pH and determining whether GI per-
fusion is adequate [46].
Positive inotropes, such as dobutamine or dopamine, may be necessary to
maintain blood pressure and restore perfusion in septic patients [46]. b-Ago-
nists also have anti-inflammatory effects that may reduce ischemia/reperfu-
sion injury. By increasing cyclic AMP, they are thought to stabilize white
blood cells and reduce oxidant release.
Recent studies performed in rodents with hemorrhagic shock have shown
a beneficial effect of hypertonic saline (HTS) [67,68]. Rats treated with HTS
showed attenuation of lung injury and reduced BT compared with rats
resuscitated with lactated Ringer’s solution [68]. HTS was shown to attenu-
ate platelet activating factor and postinjury priming of neutrophils, thereby
reducing the cytotoxic response [69]. Timing may be important, because
early use may suppress neutrophil activation, thereby preventing or reduc-
ing lung damage [70]. Although the effects of HTS are relatively short-lived,
they can be prolonged by adding a colloid, such as hetastarch, which has
also been shown to decrease inflammation by attenuating neutrophils [71].
Broad-spectrum bactericidal antibiotics should be administered to any
animal exhibiting clinical signs of sepsis. Early diagnosis and surgical correc-
tion of areas of devitalized gut or abscess drainage are paramount to suc-
cessful case management.
Reperfusion injury may be prevented with allopurinol [72] or superoxide
dismutase [73]. Vitamins C, E, and A; selenium; and b-carotene as well as
the amino acids cystine, glycine, and glutamine are all involved in the body’s
antioxidant defense network. Dietary supplementation with antioxidants
may be beneficial. Deferoxamine is an iron chelator shown to reduce oxi-
dant damage in experimental studies, but its use has been limited because
of side effects related to hypotension [74]. Recent efforts to combine deferox-
amine with hetastarch have shown improved hemodynamics and reduced
oxidant damage while avoiding toxic side effects [75].
Pentoxifylline and lisofylline have been shown to attenuate lung injury and
reduce BT in rats with hemorrhagic shock [76,77]. These agents decrease tissue
injury by inhibiting neutrophil adherence and decreasing cytokine release.
Research is currently underway to identify agents that selectively improve
GI perfusion. To date, none has been found. Catecholamines, such as
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norepinephrine and epinephrine, which induce splanchnic vasoconstriction,

should be avoided.

Limiting the consequences of mucosal injury

The use of antacids and H2 receptor blockers to reduce stress ulcers and
gastritis in critical patients may result in bacterial overgrowth and an
increased incidence of hospital-acquired pneumonia in ventilated patients
[78]. The use of sucralfate and nasogastric suctioning has been recom-
mended to decrease gastric injury without increasing the gastric pH
[79,80]. Sucralfate has also been shown to decrease BT in a rat model.
The use of selective gut decontamination seems to reduce the incidence
of hospital-acquired infections but has not been shown to increase length
of survival in critically ill human patients [81]. Although not often used in
veterinary patients, a combination of amikacin, amphotericin B, and poly-
myxin B is commonly used in human patients to depopulate the gut of
pathogenic organisms. Selective gut decontamination was shown to decrease
BT in human patients with cirrhosis [36]. In rats, orally administered neo-
mycin or gentamicin alone prevented mortality and reduced BT after ther-
mal injury [37]. A combination of oral polymyxin B, charcoal, and kaolin
has been used to bind lipopolysaccharide (LPS) endotoxin. In addition, the
use of dilute chlorhexidine or povidone-iodine enemas in puppies with par-
voviral enteritis has been anecdotally reported. The use of broad-spectrum
oral antibiotics in animals that are not septic is controversial, as it may
destroy normal flora and allow overgrowth of pathogenic bacteria.
Prokinetic drugs, such as metoclopramide and cisapride [82], are helpful
in decreasing bacterial overgrowth by improving gastric motility. Other
drugs that may be helpful in reducing BT are dopexamine, dobutamine, pen-
toxifylline, and angiotensin converting enzyme inhibitors.
A polyvalent equine origin antiserum against LPS endotoxin is available
for use in small animals (SEPTI-serum; Immvac, Inc., Columbia, MO). The
dosage is 4.4 mL/kg diluted 1:1 with intravenous crystalloid fluids and admin-
istered slowly over 30 to 60 minutes. Although clinical trials are lacking with
this product, it should be most effective if administered before antibiotic ther-
apy, because circulating endotoxin concentrations increase dramatically when
bacteria are killed [83]. Patients receiving equine origin antiserum must be
observed closely during administration for signs of anaphylaxis.

Supporting the gut with enteral nutrition

The importance of providing nutrition to critically ill patients is well
documented. In recent years, however, the importance of ‘‘feeding the gut’’
through early enteral nutrition has become more apparent.
Studies in rodents have shown that compared with enteral nutrition, TPN
was associated with increased mortality and infection rates [53]. It resulted
1174 D.K. Macintire, T.L. Bellhorn / Vet Clin Small Anim 32 (2002) 1165–1178

in mucosal atrophy, and the lipid emulsions were shown to promote immu-
nosuppression through depressed lymphocyte blastogenesis. In addition,
x6 fatty acids are precursors of prostaglandin and leukotrienes and can
promote inflammation. More recent studies in human beings have not
documented the proposed adverse effects of TPN [54]. The current recom-
mendation is to provide nutrition to critical patients by whatever method
is best tolerated by the patient. Even suboptimal caloric replacement is more
beneficial than none at all.
Enteral nutrition exerts its beneficial effects on gut function by strength-
ening the immune system (lymphocytes and macrophages), increasing IgA
and mucin secretion, and maintaining gut mass through its trophic effects
[84]. Even though the beneficial effects of glutamine have not been proven
in species other than rodents, it is safe and may prove beneficial in patients
with extensive mucosal injury. It is unstable and must be added to solutions
immediately before feeding. It is available as a powder (Cambridge Neutra-
ceuticals Baxter Health Care, Boston, MA [1-800-265-2202]) and can be
given at a dosage of 10 mg/kg/d. Glutamine can be added to the drinking
water of recovering animals or added to the enteral diet and administered
through a nasoesophageal, gastrostomy, or jejunostomy tube. Vitamins, x3
fatty acids, and antioxidants have also been used to promote a healthy gut.

Summary
The occurrence of BT has been well documented in experimental animal
models of hemorrhagic shock, trauma, severe burns, cirrhosis, pancreatitis,
and bacterial overgrowth. Translocation of viable bacteria and endotoxins
into mesenteric lymph nodes and other gut-associated lymphatic tissue is
thought to activate a complex interplay of mediators that initiates the SIRS.
Multiple humoral and cellular systems cause synthesis, expression, and
release of inflammatory mediators, such as toxic oxygen radicals, proteolytic
enzymes, adherence molecules, and various cytokines. A massive sustained
proinflammatory response can ultimately result in irreversible multiple
organ dysfunction.
Because BT is associated with splanchnic hypoperfusion, the cornerstone
of therapy involves rapid resuscitation and restoration of tissue perfusion. If
a septic focus can be identified, it should be removed. Gut protectants, pro-
motility agents, antioxidants, and immune-enhancing diets have shown
promise in improving length of survival in these critically ill patients.

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