Vol. 23, No.

7 July 2001

661

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COMPENDIUM For
Compendium: Equine Edition.
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EDUCATION

FOR

VETERINARIANS

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EQUINE EDITION

Article #4 (1.5 contact hours)

Refereed Peer Review

KEY FACTS
Although bacteria or their
products may be responsible for
initiation of the inflammatory
response, the response itself
results from the activity of hostderived proinflammatory
mediators.
The excessive activity of
antiinflammatory mediators may
result in immunosuppression
during or after a severe
inflammatory response.
Because of the difficulty of
definitively identifying neonates
with bacterial infection, it can be
appropriately assumed that any
high-risk neonatal foal that
presents with clinical illness is
septic.

Equine Neonatal
Sepsis: The
Pathophysiology of
Severe Inflammation
and Infection
Marion duPont Scott Equine Medical Center
Leesburg, Virginia

H. C. McKenzie III, DVM, MS, DACVIM

M. O. Furr, DVM, PhD, DACVIM
ABSTRACT: Although the clinical syndrome of sepsis is a major problem in equine neonates,
the pathophysiology of this condition remains incomplete. Because the term sepsis describes
a broad range of disorders with different underlying causes and often different prognoses, the
understanding of this process is further complicated. Continued progress is being made, however, in defining the syndromes associated with sepsis and in elucidating the mechanisms involved in these processes. Attempts at modulating the septic process by interfering with the
action of bacterial toxins or the production or activity of individual mediators have not been
successful, thereby reinforcing that this is a multifactorial response. Fortunately, the complex
interactions of intra- and extracellular messengers leading to clinical sepsis continue to be defined. An increased understanding of the processes involved in the septic response may aid in
the identification of patients with these syndromes as well as improve the effectiveness of
treatment regimens.

ne of the most challenging problems faced by equine veterinarians is the

management of equine neonates with sepsis. Despite the substantial advances that have been made in the medical management of these foals,
the mortality rate remains high.1 This is due to the fact that sepsis represents a
systemic inflammatory response to infection or injury; therefore, it can rapidly
progress to septic shock and death despite aggressive treatment. Traditionally,
the term septicemia, which is used to refer to this process in equine neonates, describes a systemic disease process involving the presence of pathogenic microorganisms and/or their toxins in the blood.2 The classic presentation of sepsis was
that of disseminated gram-negative bacterial infections; however, it has become
apparent that an identical syndrome occurs in patients with gram-positive bacte-

662 Equine

Compendium July 2001

Bacteremia

Hypoxia

Viremia
Infection

Sepsis

SIRS

Trauma

Fungemia
Parasitemia

Other

vention, a process termed multiorgan

dysfunction syndrome (MODS). 5,8,9
MODS is a progressive syndrome with
initial dysfunction in the cardiovascular
system, followed by involvement of the
respiratory, hepatic, gastrointestinal, renal, cardiac, and neurologic systems.5,11
These processes result in the development
of refractory hypotension, lactic acidosis,
and oliguria, often progressing to
death.9,11

PATHOPHYSIOLOGY OF SEPSIS
Inflammation
Inflammation represents the response
of tissues to either injury or the presence
Figure 1Relationships of systemic inflammatory response syndrome (SIRS), sep- of microorganisms. It serves a vital role
sis, and infection. Infection is not always associated with an inflammatory re- because it enhances the movement of
sponse; and SIRS can occur without infection. When SIRS occurs in association phagocytic cells and defensive molecules
(e.g., immunoglobulin, complement)
with infection, the response may be referred to as sepsis.3
from the bloodstream to the site of infection or injury. The first step in this process is the recognition of tissue injury or microbial invarial infections, viral infections, trauma, hypovolemia,
sion. Injured cells release preformed mediators (e.g.,
hemorrhage, and immunologic and drug reactions (Fighistamine) and synthesize proinflammatory substances,
ure 1).36
including eicosanoids (e.g., prostaglandins, thromboxThe abnormalities associated with the clinical synanes, leukotrienes) and the cytokines (interleukin [IL]-1
drome of sepsis result from a nonspecific innate inflamand tumor necrosis factor [TNF]; Figures 2 and 3).
matory response. This response, which has been termed
These mediators are responsible for the initiation of a
the systemic inflammatory response syndrome
(SIRS), is not necessarily associated with the presence
nonspecific inflammatory response. Microbial invasion
of bacterial infection.7,8 SIRS, which represents a common terminal phase of the inflammatory response charBOX 1
acterized by malignant global activation of multiple
Terms Used to Describe Clinical Syndromes
proinflammatory pathways,4 is defined by the presence
Associated with Systemic Inflammation9,10
of two or more of the following abnormalities: fever or
hypothermia (rectal temperature greater than 39.2C or
Infection: Inflammatory response to the presence of
less than 37.2C), tachycardia (heart rate greater than
microorganisms or the invasion of normally sterile
120 beats/min), tachypnea (respiratory rate greater
host tissue by microorganisms
than 30 breaths/min) or hypocapnia (partial pressure of
Bacteremia/septicemia: Presence of viable bacteria in
arterial carbon dioxide less than 32 mm Hg), leukocythe bloodstream
tosis or leukopenia (leukocyte count greater than
Systemic inflammatory response syndrome (SIRS):
12,500 or less than 4000 cells/l), or increased numSystemic response to an array of severe clinical
bers of immature forms of granulocytes (greater than
insults
10% bands).9,10 These manifestations of disease are the
Shock: SIRS-induced hypotension refractory to fluid
same as those previously used to define sepsis, and the
resuscitation in association with hypoperfusion
appreciation that many different stimuli can induce
Sepsis: SIRS due to infection
this response has resulted in sepsis being redefined as
Severe sepsis: Sepsis associated with organ
SIRS due to infection (Box 1).8
dysfunction, hypoperfusion, or hypotension
The changes associated with SIRS can lead to shock,
Septic shock: Sepsis-induced shock
which is characterized by severe hypotension not reMultiorgan dysfunction syndrome (MODS):
sponsive to intravenous fluid therapy (Figure 2). Shock
Altered organ function in an acutely ill patient
can result in hypoperfusion and organ dysfunction such
requiring intervention to maintain homeostasis
that homeostasis cannot be maintained without interOther

Compendium July 2001

Equine 663

Normal Foal
Intrauterine infection

Postnatal infection

Hypoxia

Other insults: Trauma, hypovolemia,

hemorrhage, drug or immunologic reactions

Recognition of tissue injury

or presence of microorganisms
(see Figure 4)

Proinflammatory cytokines

Proinflammatory enzymes

Macrophage activation

(inducible nitric oxide synthase,

phospholipase A2, cyclooxygenase-2)

Increased vascular
permeability

(see Figures 3 and 4)

Endothelial activation and

local vasodilation

(interleukin-1, tumor necrosis factor,

interleukin-6, interleukin-12, and
interleukin-18)

Neutrophil activation,
chemotaxis, migration

Systemic vasoconstriction
(transient)

Fluid
extravasation

Localized
hemostatic
dysfunction

Impaired cardiac function

Systemic vasodilatation

Systemic hemostatic
dysfunction

Refractory hypotension
(shock)

Multiorgan dysfunction
syndrome

Tissue injury/
cellular dysfunction

Figure 2Schematic representation of the progression of the inflammatory process and associated pathophysiologic changes in a

foal exposed to infectious organisms or other injurious insults.

may result in tissue injury, thereby initiating this process, or specific bacterial cell components may be recognized by immune cells (macrophages), which result in
the production of inflammatory mediators and the initiation of an inflammatory response.12 The bacterial
cellular components that are recognized by the immune
system include endotoxins (lipopolysaccharide; LPS)
and exotoxins from gram-negative bacteria as well as
peptidoglycans (PGs), lipoteichoic acids (LTAs), enterotoxins, and superantigenic exotoxins from grampositive bacteria.7,1315 Although bacterial infection may
be responsible for the initiation of an inflammatory re-

sponse, the inflammatory process itself results solely

from the production of endogenous mediators.
Because of the predominance of gram-negative infection in foals with sepsis, LPS is commonly involved in
the molecular mechanisms described. On entering the
circulation, LPS is avidly bound to the LPS-binding
protein (LBP); the LPSLBP complex then binds to a
receptor present on the surface of the mononuclear
phagocyte (mCD14) or in the circulation (sCD14).16,17
CD14 also binds PG and LTA from gram-positive bacteria.7,13,16 This may represent a route of cellular activation in gram-positive infections.7,13,16 The LPSLBP

664 Equine

Compendium July 2001

Lipopolysaccharide
Trauma

Lipopolysaccharide-binding
protein

Hypoxia

Grampositive
bacteria

Viruses
Mononuclear
phagocyte

+
PROTEIN MEDIATORS
Interleukin-1
Complement
Interleukin-6
system
Interleukin-8
Coagulation
Interleukin-12
system
TNF-
Interferon-
Elastase/cathepsin B
Kinin/kallikreins

+
LIPID MEDIATORS
Platelet activation factor
Thromboxane A2
Prostaglandins
Leukotrienes

Low systemic levels

of mediators

REDUCED OXYGEN SPECIES

Singlet oxygen
Superoxide anion
Hydroxyl radical
Nitric oxide
Hypochloride ion

High systemic levels

of mediators

ANTIINFLAMMATORY
MEDIATORS
Interleukin-4
Interleukin-10
Interleukin-13
Adrenal corticosteroids
Prostaglandin E2
Interleukin-1 receptor
antagonist
Soluble interleukin-1
receptor II
Soluble TNF receptors

BENEFICIAL EFFECTS
Moderate fever
Immune stimulation
Microbicidal effects

DETRIMENTAL EFFECTS
SIRS
Disseminated intravascular
coagulation
Septic shock

Figure 3Interaction of initiating factors and host-derived proinflammatory (+) and antiinflammatory () mediators in the reso-

lution of infection and the development of SIRS and septic shock.14

CD14 or PGLTACD14 complex is then responsible

for cellular activation of the mononuclear phagocyte via
a toll-like receptor (TLR) that transmits the activation
signal across the cell membrane (Figure 4).7 Numerous
types of TLRs have been identified in mammalian
species; evidence suggests that these different types of
TLRs are responsible for recognition of different types
of microbial pathogens.7
Cellular activation may also occur because of the development of a nonspecific oxidative stress reaction
within the mononuclear phagocyte following stimulation by proinflammatory stimuli such as TNF-, endotoxin, or exotoxins (Figure 4).18 The development of an
inflammatory response is dependent on the productionprimarily by the activated mononuclear phagocyteof numerous inflammatory mediators, including
proinflammatory cytokines (e.g., TNF-, IL-1, IL-6),

proinflammatory enzymes (e.g., inducible nitric oxide

synthase, phospholipase A2, cyclooxygenase-2), and adhesion molecules (e.g., selectins, intracellular adhesion
molecules).18 The transcription of many of the genes
encoded for these mediators or the enzymes that produce them is dependent on the transcription activator
nuclear factorB; therefore, this molecule may be a
potential target for intervention in SIRS (Figure 4).1921
The initial changes that occur in an inflammatory response are primarily the result of local vasodilation
and increased vascular permeability caused by the effects
of vasoactive mediators released by the injured or infected cell (Figures 2 and 3). These factors include histamine, serotonin, kinins, eicosanoids, platelet activating factor, fibrin degradation products, and the
complement products, C3a and C5a. Changes occur in
the vascular endothelium under the influence of

Compendium July 2001

Equine 665

molecules arising from the injured tisCD14

sue (e.g., IL-1, TNF-, histamine), reTNF
or IL-1
sulting in neutrophil diapedesis and
receptor
4,22
increased vascular permeability. On
TLR
IB-/nuclear factorB
their arrival at the site of tissue injury,
+
complex
neutrophils and macrophages phago+
cytose foreign material and injured or
+
TLR
dead tissue cells and destroy the
Nuclear factorB
phagocytosed material by oxidative
mechanisms (neutrophils) or by both
oxidative and nonoxidative mechaPhosphorylated
nisms (macrophages). In addition,
IB-
macrophages release a number of fac+
tors that augment the immune reGene
Cytoplasm
transcription
Proinflammatory
sponse, including the proinflammatoProtein
cytokines
synthesis
and enzymes
ry cytokines (e.g., IL-1, TNF-, IL-6,
Nucleus
IL-12, IL-18; Figure 3). The proinflammatory cytokines signal target
cells, primarily neutrophils, to increase
the production of secondary inflam- Figure 4The transcription activator nuclear factor (NF)B is normally retained in
matory mediators, including phospho- the cytoplasm in an inactivated state, preventing the unregulated production of inlipid derivatives (e.g., prostaglandins, flammatory mediators. This inactivation is caused by the binding of NF-B by the
thromboxane A2, leukotrienes) and re- repressor protein IB-.19 Following stimulation of the cell by a proinflammatory
active oxygen species (singlet oxygen, agent, IB- is phosphorylated, freeing NF-B, which is then capable of entering
superoxide anion, hydroxyl radical, the nucleus and activating transcription of genes encoding for inflammatory cyhydrogen peroxide, NO, hypochloride tokines (e.g., tumor necrosis factor, interleukin-1, interleukin-6), proinflammatoion), further increasing the activity of ry enzymes (e.g., inducible nitric oxide synthase, phospholipase A2, cylcooxygenase18
the inflammatory response.23 The sys- 2), and adhesion molecules (e.g., selectins, intracellular adhesion molecules).
temic manifestations of inflammation
and/or infection (e.g., fever, lethargy,
malaise, loss of appetite, cachexia) are primarily due to
flammatory cytokines (e.g., soluble IL-1 receptor type
TNF- and IL-1.
II, soluble TNF receptors).4,21,25 The balance between
these proinflammatory and antiinflammatory components is important in determining the characteristics of
Acute-Phase Response
the inflammatory response because excessive activity of
Interleukin-6, IL-1, and TNF- initiate the acutethe antiinflammatory component may result in imphase response, whereby the liver increases production
munosuppression during or after a severe inflammatory
of acute-phase proteins. These substances are important
response, which has been termed compensatory antiinin many phases of the response to inflammatory stimuli,
flammatory response syndrome by Bone and colincluding complement activation, coagulation, fibrinolysis, transport of substances within the blood stream, inleagues.9
hibition of neutrophil proteases, and modulation of the
Systemic Inflammatory Response Syndrome
inflammatory response (Figure 3).24 The acute-phase reIn moderation, the changes associated with an inflamsponse is critical in inflammation, healing, and adaptamatory response are protective, resulting in enhanced
tion to noxious stimuli.24 Also included in the acutekilling of microbes by antigen-specific and nonspecific
phase response is a counterregulatory antiinflammatory
mechanisms, generalized immune stimulation, and incomponent that normally functions to minimize and recreased activity of the systems required for the healing of
solve the inflammatory response to localized stimuli.
damaged tissue. The excessive, malignant form of the
This counterregulatory response consists of antiinflaminflammatory and acute-phase responses, termed SIRS,
matory mediators that inhibit macrophage activation
is characterized by the systemic activity of numerous
(e.g., IL-4, IL-10, IL-13, adrenal corticosteroids, transproinflammatory mediators, including cytokines (e.g.,
forming growth factor-, prostaglandin-E2), antagonists
IL-1, TNF-, IL-6, IL-8), phospholipid derivatives
to the receptors for proinflammatory cytokines (e.g., IL(e.g., platelet activating factor, prostaglandins, throm1 receptor antagonist), and soluble receptors of proin-

Compendium July 2001

boxane A2, leukotrienes), complement components (e.g.,

C3a, C5a), reactive oxygen species (e.g., superoxide anion, hydrogen peroxide, hydroxyl radical, singlet oxygen,
hypochloride ion), and vasoactive gases (e.g., NO, carbon monoxide).4,25 As previously described, these mediators all represent components of the normal inflammatory response to a localized stimulus, but the systemic
activity of these proinflammatory mediators may result
in an excessive, and often detrimental, response.
One of the first effects that occurs with SIRS is
widespread endothelial activation, resulting in the increased production of vasoactive mediators and alteration of vascular homeostasis. Inflammatory cytokines
(e.g., IL-1, TNF-) are responsible for activation of the
endothelium, and the activated cells produce inflammatory cytokines as well as increased amounts of NO
(via inducible NO synthase), prostaglandins (via inducible cyclooxygenase-2), and endothelin-1.26 Activated endothelial cells retract from one another, increasing
the size of the intercellular pores and allowing for increased vascular permeability. They also increase their
production of tissue factor and von Willebrand factor,
resulting in localized thrombosis and platelet adherence, respectively.26
The initial systemic effect of these changes is pulmonary vasoconstriction leading to pulmonary hypertension 27 likely caused by thromboxane A 2. 28 The
initial hypertensive phase is followed by systemic hypotension caused by decreased arterial tone and results
in decreased left ventricular preload, combined with
venous vasodilation in the large-capacity vessels that
decreases venous return. These effects are likely due to
epoprostenal (PGI2; prostacyclin) and NO26 and can
progress to the syndrome of hyperdynamic shock, with
increases in heart rate and cardiac output developing as
compensatory mechanisms to maintain tissue perfusion.29 This compensatory response is impaired by the
reduction in left ventricular preload, combined with
the decreased cardiac contractility resulting from myocardial depressants (e.g., NO, TNF- , IL-1), decreased myocardial responsiveness to -adrenergic
stimulation, and decreased compliance due to myocardial edema.15
Changes occurring in the microvasculature further
contribute to the impairment of tissue perfusion. Arteriolar vasoconstriction develops due to the impairment
of the normal autoregulatory systems (e.g., NO from
endothelial NO synthase, PGI2 from cyclooxygenase-1)
caused by inflammatory cytokines and endothelin-1
combined with the increased production of vasoconstrictive substances (e.g., endothelin-1, thromboxane
A2). Adherence of neutrophils to the endothelium and
endothelial cell swelling further reduce blood flow. Ac-

Equine 667

cumulation of fibrin and aggregation of platelets and

erythrocytes secondary to activation of the clotting system results in occlusion of the vasculature, leading to
tissue hypoperfusion. Arteriovenous shunting occurs in
some tissues, whereas increased vascular permeability
results in extravasation of fluids into the interstitial
space, further contributing to hypotension and hypovolemia. Progressive alteration of the microcirculation
leading to failure may represent the common final
pathway of SIRS-related injury contributing to or resulting in MODS.30
Activation of coagulation occurs primarily through
the extrinsic pathway because of the production and
surface expression of tissue factor (thromboplastin) on
endothelial cells and mononuclear phagocytes under the
influence of IL-6, the production of which is increased
by proinflammatory stimuli (e.g., endotoxin, TNF-,
IL-1).25,31,32 Endothelial injury secondary to neutrophil
degranulation results in decreased production of PGI2
and NO, leading to increased platelet adhesion.32 In the
normal state, the accumulation of excessive amounts of
fibrin would be prevented by the action of plasmin, the
primary mediator of fibrinolysis. In the presence of
SIRS, the fibrinolytic system is suppressed because of
the increased plasma concentration of plasminogen-activator inhibitor type 1, the primary inhibitor of fibrinolysis.31 The widespread activation of the clotting system,
combined with impairment of fibrinolysis and depression of the inhibitors of coagulation, can result in a consumptive coagulopathy potentially leading to disseminated intravascular coagulation.16,31

Shock
The progression of these processes affecting the cardiovascular system ultimately results in shock. Shock
occurs when cardiovascular function is severely impaired, such that hypotension cannot be corrected with
intravenous fluid administration and requiring the use
of inotropic and/or vasopressor agents.5,11 Shock represents severe cardiovascular dysfunction associated with
SIRS and is a primary component of MODS. Septic
shock is defined as shock associated with infection.
Multiorgan Dysfunction Syndrome
The development of MODS is likely the result of
cardiovascular dysfunction, which leads to tissue hypoperfusion combined with changes in cellular
metabolism that result in impairment of oxygen delivery and uptake, respectively.11 The presence of tissue
hypoxia is manifested by metabolic acidosis and decreased oxygen extraction ratios.11 Pulmonary dysfunction is manifested by refractory hypoxemia, potentially
caused by increased pulmonary vascular permeability,

668 Equine

microthrombi formation, pulmonary epithelial injury,

pulmonary edema, and impairment of surfactant production.33 Renal dysfunction is manifested by the development of azotemia and oliguria; acute renal failure
is likely caused by alterations in the distribution of intrarenal blood flow arising from microvascular alterations with or without systemic hypotension.11
Gastrointestinal dysfunction is primarily manifested
by the presence of ileus but may also result in loss of
the normal barrier function of the gastrointestinal mucosa.34 This loss of the mucosal barrier may further
contribute to the pathogenesis of MODS due to bacterial translocation or endotoxin absorption.34 Hepatic
dysfunction is manifested by the development of hyperbilirubinemia and, in some cases, increased serum activities of hepatic enzymes (sorbital dehydrogenase, aspartate aminotransferase). Hepatic dysfunction may
result from hypoperfusion, particularly because of the
high metabolic demands of this tissue, but may be
heightened by the production of inflammatory mediators by the hepatic Kupffers cells secondary to the actions of systemic mediators or stimuli derived from the
gastrointestinal tract.35 Dysfunction of the central nervous system, which is frequently present, may manifest
as depression but can progress to septic encephalopathy
with extensive neuronal injury.36 The development of
consumptive coagulopathy (disseminated intravascular
coagulation) could also be considered a component of
MODS rather than merely a pathophysiologic process
contributing to the development of organ failure.

NEONATAL SEPTICEMIA
Risk Factors
A number of factors have been identified that increase the likelihood of septicemia and mortality in
equine neonates. The risk factors for septicemia may
include a history of placentitis, prenatal vulvar discharge, dystocia, maternal illness, premature or delayed
parturition, induced parturition, total failure of passive
transfer, prolonged transport of the pregnant mare, and
the presence of localized disease in the neonate (e.g.,
anterior uveitis, diarrhea, pneumonia, infectious arthritis, open wounds).37,38 Partial failure of passive transfer
(serum IgG concentration 200 to 400 mg/dl) has been
considered a risk factor for septicemia. However, this
may not be the case because one study39 reported no
statistical difference in duration or frequency of illness
or survival when comparing foals with IgG concentrations of less than 400 or greater than 800 mg/dl. Risk
factors for neonatal death may include maternal illness,
premature or delayed parturition, induced parturition,
prolonged duration of clinical signs, and decreased
serum IgG concentration.40,41

Compendium July 2001

Routes of Invasion
Pathogenic organisms can infect equine neonates by
numerous routes. While in the intrauterine environment, the fetus may be exposed to organisms that have
invaded the placenta or that cross the placentalchorial
barrier, gaining direct access to the foals bloodstream.
Bacteria associated with placental disease may enter the
amniotic fluid and gain access to the respiratory and gastrointestinal tracts of the fetus. After birth, bacterial infection can be caused by contamination of the umbilical
stump, ingestion or inhalation, or secondary to wounds.2
Organisms Involved in Neonatal Sepsis
Blood culture remains the most definitive test for antemortem identification of septicemia in equine neonates.
Blood culture should be performedideally prior to the
administration of antimicrobial therapywhen any
equine neonate presents with a clinical suspicion of sepsis. This test has been reported to have variable sensitivity in many species, including horses, with false-negative
results obtained in up to 37% of cases of fatal
septicemia.42,43 It is interesting to contemplate how much
higher the false-negative rate might be in the less severely
ill neonate that recovers with antimicrobial therapy.44 It
has been recommended that multiple samples be collected to maximize the sensitivity of this test, but the majority of isolates have been reported to be present in the first
culture sample. The need for immediate antimicrobial
therapy usually results in only one sample being obtained.2 Because of the low sensitivity of blood culture, it
is important to obtain bacterial cultures from suspected
areas of infection during the course of treatment because
the blood culture may be falsely negative or nosocomial
infection may have developed during the course of treatment. The appropriate samples are dependent on the
system affected but would include transtracheal aspirate;
blood; urine; synovial, peritoneal, and cerebrospinal fluid; and umbilical remnants following surgical resection.
Although historically gram-positive organisms were
most commonly associated with neonatal infections,
over the past 20 years the most common bacteria isolated from infected foals have been gram-negative organisms (Table 1).2,42,43,45 Gram-positive organisms isolated
from infected foals are typically present in mixed infections with gram-negative organisms; streptococcal
species are most common.2,42,46 Other organisms associated with severe systemic inflammation in equine
neonates include equine herpesvirus type 1 and Histoplasma capsulatum.6,47,48 It is also possible that severe hypoxia, which leads to hypoxic ischemic encephalopathy
(also known as neonatal asphyxia, dummy foal syndrome), represents a causative factor for induction of
SIRS in equine neonates.49,50

Compendium July 2001

Equine 669

TABLE 1
Organisms Isolated from Infected Neonatal Foals
Organism

Percentage of Isolates

Gram-negative
Escherichia coli 42,43,45
Klebsiella pneumoniae 42,43
Actinobacillus species42,43,45
Enterobacter species42,43,45
Pseudomonas aeruginosa 42,43,45
Citrobacter species43
Pasteurella species42
Salmonella species42,45
Serratia marcescens 42,45

30.656%
3.712.9%
819%
3.55.7%
2.84.7%
4.7%
3.7%
2.83.7%
2.83.7%

Gram-positive
-hemolytic streptococci 43,45
Other streptococci 43
Staphylococcus species42,45
Clostridium species42,43,45

1.25.6%
7.1%
2.83.7%
2.43.7%

Other
Equine herpesvirus type 16,47
Histoplasma capsulatum 48

Not available
Not available

Identification of Septic Neonates

Identification of septic neonates is of clinical relevance in ensuring that appropriate treatment is administered and in determining prognosis for survival. The
identification of septic neonates remains problematic,
however, because neonates that present with clinical abnormalities consistent with sepsis (SIRS) may be negative on blood culture with no evidence of a focal site of
infection. Attempts to identify equine neonates with
septicemia have included the development of a sepsis
scoring system that combines historical information,
objective data, and subjective measures to derive a numerical representation of the patients condition.51 The
sensitivity and specificity of this scoring system were reported to be 93% and 86%, respectively.51 Unfortunately, the specificity and sensitivity may not always be
this high.52 In addition, this scoring system must be
adapted to each intensive care unit in which it is applied to achieve reasonably high levels of sensitivity and
specificity.52
Attempts to create sepsis scoring systems for human
patients have encountered many of the same difficulties, likely resulting from the inherent limitations involved. The primary limitation arises from the fact that
scoring systems strive to incorporate large amounts of
clinically relevant data into a single representative numeric value. Although this may be beneficial in concentrating ones attention on the most important compo-

nents of the clinical situation, it also results in a loss of

information.53 The second limitation arises from the
fact that, as previously discussed, the pathophysiologic
mechanisms operating in equine neonates with SIRS
are consistent, regardless of the primary etiology.
Therefore, the manifestations of disease that are subsequently incorporated into a scoring system inherently
lack the precision required to differentiate various types
of primary disease. As a result, no sepsis score can substitute for clinical judgment, and these scores should be
used as a diagnostic aid in the identification of highrisk individuals with full consideration given to their
limitations.37,53 Because of the difficulty of definitively
identifying neonates with bacterial infection, it is appropriate to make the assumption that any high-risk
neonatal foals presenting with clinical illness are septic.54 Aggressive therapy that includes antimicrobials is
indicated. Although there are some risks associated
with antimicrobial therapy, they are greatly outweighed
by the risks associated with withholding antimicrobial
therapy from a patient with sepsis secondary to bacterial infection.

CONCLUSION
The development of SIRS in equine neonates is a
complex process that involves numerous initiating factors, inflammatory mediators, and variable degrees of
organ dysfunction. Initially, it may be difficult to determine the underlying disease process when presented
with a neonate with SIRS. Treatment of patients with
SIRS requires the same basic supportive therapies (e.g.,
intravenous fluids, antimicrobials, antiinflammatories)
regardless of the etiology, but identification of the specific etiology will allow for more effective and appropriate application of both basic and adjunctive therapies. It
is clear that the treatment of SIRS and its sequelae cannot focus solely on any single component of this process
but must be directed at resolution of the initiating stimulus, modulation of the inflammatory response, and
support and maintenance of organ function.
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ARTICLE #4 CE TEST
The article you have read qualifies for 1.5 contact hours of Continuing Education Credit from
the Auburn University College of Veterinary
Medicine. Choose the best answer to each of the following questions; then mark your answers on the
postage-paid envelope inserted in Compendium.

CE

1. The clinical condition of sepsis results from the activity of

a. bacteria.
b. viruses.
c. fungi.
d. host-derived mediators.
e. all of the above
2. SIRS represents
a. the clinical response to infection.
b. the excessive activity of the antiinflammatory response.
c. the result of cardiovascular dysfunction leading to
tissue hypoperfusion.
d. the excessive, malignant form of the inflammatory
and acute-phase responses.
e. a systemic disease process involving the presence of
pathogenic microorganisms and/or their toxins in
the blood.
3. The organisms most commonly involved in equine
neonatal infections are
a. gram-positive bacteria.
b. gram-negative bacteria.
c. equine herpesvirus type 1.
d. mixed bacterial infections.
e. anaerobic bacteria.
4. The excessive activity of endogenous antiinflammatory
mediators may result in the
a. MODS.
b. SIRS.
c. compensatory antiinflammatory response syndrome.

d. systemic antiinflammatory response syndrome.

e. septic shock.
5. The risk factors for equine neonatal septicemia include
all of the following except
a. unobserved parturition.
b. gestational age.
c. dystocia.
d. induced parturition.
e. maternal illness.
6. Blood culture samples
a. are often contaminated with nonpathogenic bacteria.
b. are rarely useful in guiding the clinical management
of septic foals.
c. must be collected before administration of antimicrobial agents.
d. have very high sensitivity and specificity for septicemia.
e. should be collected in all foals presented with a
clinical suspicion of sepsis.
7. Antimicrobial therapy
a. should be delayed pending the results of bacterial
culture and sensitivity testing.
b. should be initiated early in any high-risk clinically
ill neonatal foal.
c. is without major risk.
d. will prevent the culture of organisms from blood
cultures.
e. should be reserved only for foals with clinically detectable infection.
8. Abnormalities used to define SIRS include all of the
following except
a. fever.
b. tachypnea.
c. leukocytosis.
d. central nervous system depression.
e. hypothermia.
9. Sepsis scoring systems are helpful in
a. deciding if a foal should be treated with antimicrobials.
b. monitoring the response to treatment.
c. identification of high-risk individuals.
d. assessment of passive transfer.
e. determining the most appropriate antimicrobials
for treatment of sepsis.
10. Organ dysfunction in equine neonates with sepsis may
be manifested by all of the following except
a. polyuria.
b. hypotension.
c. hypoxia.
d. ileus.
e. hyperbilirubinemia.