bs_bs_banner
92
Review Article
Pathophysiology, diagnosis and treatment of neonatal sepsis
B. Dunkel* and K. T. T. Corley†
Department of Clinical Science and Services, Equine Referral Hospital, The Royal Veterinary College, North Mymms,
UK; and †Anglesey Lodge Equine Hospital, The Curragh, Ireland.
*Corresponding author email: bdunkel@rvc.ac.uk
Keywords: horse; equine neonate; foal; sepsis; inflammation; antimicrobials
Summary
Sepsis is a major cause of death in neonatal foals and, in
recent years, significant progress in the understanding of the
underlying pathophysiology has been made. To achieve a
successful outcome, early diagnosis and treatment focusing
on supporting vital functions and neutralising the effects of the
causative organisms are essential. The pharmacokinetics of
many drugs differ in neonatal foals and more information for
appropriate dosing of antimicrobial and anti-inflammatory
drugs for neonatal foals is now available to guide clinicians in
choosing the best dosages. Prevention remains difficult and
focuses on early recognition while prophylactic use of
antimicrobials is discouraged.
Introduction
Sepsis is a major cause of death in foals aged <7 days (Cohen
1994). Understanding the pathophysiology helps design both
effective diagnostic tests and treatments. With early
appropriate intervention, the survival rate for neonatal foals
can be quite good (72.5% of 120 hospitalised septic foals
survived to discharge between 2002 and 2012, K. Corley,
unpublished data).
Pathophysiology
Much of the pathophysiology and clinical signs of sepsis reflect
the immune response to infection, rather than direct actions of
the infective organism on the body. One manifestation of this
is the systemic inflammatory response syndrome (SIRS). SIRS
refers to changes in the foal’s heart rate, respiratory rate,
temperature and/or white cell count in the face of infection
or inflammation, which are taken to be manifestations of
cytokine activation.
These cytokines are chiefly the product of leucocytes and
therefore the focus of much research into the pathophysiology
of SIRS and sepsis has been leucocyte activation.
Endotoxaemia, which induces SIRS and can be part of sepsis
(when it is due to Gram-negative organisms), has been
extensively researched. For this reason, events in mature horses
are reasonably well described although several assumptions
are still extrapolated from research in man or laboratory
animals (McKenzie and Furr 2001; Sanchez 2005; Sykes and
Furr 2005; Werners et al. 2005; Werners and Bryant 2012).
However, the concept of sepsis is ever expanding and
it is now understood that leucocytes are only one aspect
of an increasingly complex process and that endothelial
cells, platelets, the coagulation system and endocrine
dysregulation all contribute to the disease (Seeley et al. 2012;
De Backer et al. 2014). In essence, molecular patterns
expressed by bacteria (pathogen-associated molecular
© 2014 EVJ Ltd
EQUINE VETERINARY EDUCATION
Equine vet. Educ. (2015) 27 (2) 92-98
doi: 10.1111/eve.12234
patterns) or associated with tissue damage (damage-
associated molecular patterns or alarmins) are recognised by
the immune system (Gando et al. 2011) and cause activation
of the innate and adaptive immune response. This results in
production of a myriad of pro- and anti-inflammatory
substances and cytokines. Overactivation or -suppression of
the immune response can lead to systemic inflammation or
immunosuppression and, if uncontrolled, to progressive
cardiovascular compromise and ultimately death (Werners
and Bryant 2012). Extensive cross-talk between the
inflammatory and coagulation system leads to reciprocal
activation of both systems. Systemic coagulopathies with
formation of microthrombi during severe illness are thought to
play a major role in the pathogenesis of multiple organ
dysfunction (Levi 2010). Coagulopathies and subclinical or
clinical disseminated intravascular coagulation (DIC) are
common in critically ill equine cases of all ages (Monreal et al.
2000; Dolente et al. 2002; Dallap et al. 2003; Dallap 2004;
Cotovio et al. 2007; Armengou et al. 2008; Cotovio et al. 2008;
Dallap Schaer et al. 2009). In one study, fibrin deposits were
detected in 88% of septic nonsurviving equine neonates, with
the lungs being most frequently affected (Cotovio et al. 2008).
Organ failure, although statistically not associated with fibrin
deposition, occurred in 56% of these foals and respiratory
failure accounted for 25% of the organ failure cases (Cotovio
et al. 2008). Functional failure of the microvasculature is
assumed to be another reason for end-organ damage in
human patients. Endothelial dysfunction with impaired intercell
communication, disrupted barrier function with increased
permeability leading to extravascular leak of protein-rich
oedema, altered glycocalyx, enhanced adhesion and rolling
of white blood cells and platelets, and impaired distribution of
blood flow in microvascular beds are the main mechanisms
contributing to these alterations (De Backer et al. 2014; Gill
et al. 2014).
Changes in hormonal concentrations and metabolism
have been documented during sepsis. The changing nature of
these fluctuant and temporal profiles makes it difficult to
interpret or manage hormonal alterations, and cause and
effect are often not clear. Changes can be adaptive to
protect tissues or be the consequence of toxin and cytokine
release or of the treatments initiated by the attending clinician
(Khardori and Castillo 2012). Hormonal profiles of septic foals
have been extensively researched in recent years. There is
increasing evidence that hypothalamus-pituitary-adrenal axis
dysregulations are common in sick, and particularly septic,
neonatal foals. Mounting evidence indicates that relative
adrenal insufficiency (RAI) exists and might be associated with
nonsurvival (Hurcombe et al. 2007, 2008; Hart et al. 2009;
Hurcombe 2011). Plasma cortisol levels increase in response
B. Dunkel and K. T. T. Corley
to critical illness and are essential for maintaining vascular
responses to catecholamines and angiotensin and
modulation of the immune response. During RAI, the foal is not
able to mount a cortical response adequate for the degree
of illness experienced by the body. Although cortisol levels
may be within the normal range, concentrations are relatively
too low for the demands of the patient. Symptoms in man
include haemodynamic instability and refractory hypotension
unresponsive to fluid and vasopressor therapy (Langer et al.
2006). However, whether foals with RAI could benefit from
corticosteroid administration requires further investigation.
Low-dose hydrocortisone treatment in healthy foals aged <7
days old ameliorates endotoxin-induced proinflammatory
cytokine expression without impairing neutrophil phagocytosis
and reactive oxygen species production (Hart et al. 2011),
which could argue for its use.
Other hormonal dysregulations observed in septic foals
include high arginine vasopressin concentrations, nonthyroidal
illness syndrome in sick and premature foals and abnormalities
in energy metabolism, including the somatotropic axis, all
thought to be associated with nonsurvival (Gold et al. 2007;
Hurcombe et al. 2008; Barsnick et al. 2011, 2014; Himler et al.
2012; Dembek et al. 2013).
Diagnosis
The definition of sepsis in man and foals is still evolving. Most
equine clinicians would probably agree that sepsis represents
systemic illness caused by a disseminated or localised
infection. Systemic activation of the inflammatory system is
usually used as evidence that an infection is affecting the
entire body. SIRS is frequently defined as presence of at least 2
of the following criteria: hyper- or hypothermia; tachycardia;
tachypnoea; and an abnormal white blood cell count or
increase in band neutrophils (McKenzie and Furr 2001). For
human neonatal sepsis, the definition was adapted in 2005
(Goldstein et al. 2005) and is now defined as SIRS as a result of
proven or suspected infection. Evaluation of the criteria for
sepsis in a retrospective study showed that of 30 human
neonates with culture proven sepsis (positive blood or
cerebrospinal fluid culture) only 14 (53%) fulfilled SIRS and sepsis
criteria, highlighting the difficulties with the current
classifications. This illustrates the fact that infection in neonates
can be clinically relatively silent and none of the classification
systems are perfect. In foals, no uniform definition for sepsis has
been adopted but, most commonly, a modification of the
human definition (SIRS and infection), a positive blood culture
or a sepsis score ≥12, developed by Brewer et al. (Brewer and
Koterba 1988) is used. The initial report (Brewer and Koterba
1988) demonstrated 93% sensitivity and 86% specificity for the
sepsis score. In subsequent studies on different populations, a
considerably lower sensitivity and specificity were found
(Corley and Furr 2003) and the score failed to predict sepsis in
49% (29/59) of bacteraemic foals in another investigation
(Stewart et al. 2002). A recent study suggested a new cut off
point of >7 for the score resulting in a sensitivity and specificity
of 84.4% and 41.8%, respectively, compared with 56.4% and
73.4% using a cut off of >11 (Weber et al. 2014). Many clinicians
have hoped that serum amyloid A (SAA) might be a good
marker of sepsis in neonatal foals due to its fast response and
short half-life (Tape and Kisilevsky 1990; Belgrave et al. 2013). In
a recent study a cut-off point of >100 mg/l for SAA
concentrations to predict sepsis had a sensitivity and
specificity of 68.6% and 68.5%. The negative predictive value
93
of SAA concentrations >100 mg/l as indicator of sepsis in foals
on admission was 87%. However, in the same study 11 and 9
out of 36 foals considered to be septic had SAA
concentrations <25 mg/l and <10 mg/l, respectively, indicating
that low SAA concentrations do not rule out the presence of
sepsis (Jokisalo et al. unpublished data).
Treatment
The major goals of treatment are to maintain homeostasis
and attempt to neutralise the causative organism and
exaggerated immune responses. Many organ systems are
affected, and treatment often has to be prioritised to support
those immediately vital for life (cardiovascular system,
respiratory system and central nervous system).
Fluid resuscitation and cardiovascular support
Acute hypovolaemia should be corrected as soon as possible
to ensure adequate end-organ perfusion. Balanced
electrolyte solutions given as 10–20 ml/kg bwt boluses over
10–20 min may be used initially. After each bolus, the foal
should be reassessed and boluses repeated as necessary until
peripheral perfusion is improved (Palmer 2004; Magdesian
2005). Signs reflecting successful fluid resuscitation may include
improved pulse quality, capillary and jugular refill time, mucous
membrane colour, warming of the distal limbs, increased urine
output and borborygmi and improved mental status. Of these,
improved mentation and urine output are often the first signs
of improving cardiovascular status. Increasing mean arterial
pressure (MAP) and decreasing blood lactate concentrations
over time are also favourable signs. If no progress has been
achieved after rapid administration of 60–80 ml/kg bwt,
corresponding to 3–4 boluses, additional haemodynamic
support in form of inotropes and/or vasopressors might be
necessary (Palmer 2004). Although MAP is used as a measure
of circulatory status, decisions should not be made on the basis
of MAP alone and it is important to evaluate end-organ
perfusion through lactate concentrations, urine output and
mentation.
Dobutamine (DOB) augments cardiac output by its
primary action on β1-adrenoreceptors. Starting doses of
3–5 μg/kg bwt/min with subsequent titration to effect have
been used in foals while closely monitoring for tachycardia,
arrhythmia and other adverse reactions (Corley 2004;
Valverde et al. 2006; Craig et al. 2007). In some foals, at high
doses of DOB (>15 μg/kg bwt/min), increasing the dose further
appears to have little extra effect on β1-adrenoreceptors
but can cause vasodilatation, presumably mediated via
β2-adrenoreceptors, resulting in falling blood pressure.
Some severely affected foals are in hyperdynamic shock
after initial fluid resuscitation, resulting in decreased peripheral
perfusion and low MAP despite adequate intravascular
volume and administration of inotropes. In these foals it is
necessary to try to restore a sufficient vascular tone to establish
a pressure gradient and promote blood flow through the
peripheral organs. However, as not all organ systems are
uniformly affected by either vasodilation or the administered
vasopressors, their use always carries the risk of excessive
vasoconstriction in some vascular beds, mainly the splanchnic
circulation, thereby decreasing, rather than increasing,
perfusion to those tissues. Norepinephrine (noradrenaline; NE)
is a strong α1-adrenergic agonist with some activity on β1 and
minimal β2 receptor activity (Sakr et al. 2006). Norepinephrine
© 2014 EVJ Ltd
94
(0.01–1.0 μg/kg bwt/min) in combination with DOB might be
useful as a vasopressor in hypotensive foals unresponsive to
fluid resuscitation and inotropes alone. Negative effects of NE
on either renal function or splanchnic circulation were not
detected in the 2 studies (Hollis et al. 2006; Valverde et al.
2006) but close monitoring remains essential. Arginine
vasopressin (anitdiuretic hormone) has received attention due
to its importance in maintaining blood pressure during critical
illness. Doses of 0.1–2.5 mu/kg bwt/min have been used in
neonatal foals (Dickey et al. 2010). Findings in the
experimental setting were suggestive of arginine vasopressin
infusions (0.3 and 1.0 mu/kg bwt/min) causing gastric and
possibly splanchnic hypoperfusion at the higher dose, which
was not observed with either DOB or NE infusions (Valverde
et al. 2006). Based on this information, NE may currently be
regarded as the safer option for vasopressor support in
neonatal foals.
Fluid maintenance
Critically ill foals receiving fluid therapy are prone to oedema
formation, which may be associated with differences in
sodium handling, renal compromise and increased capillary
permeability induced by the primary disease process.
Traditionally, 80–120 ml/kg bwt/day, depending on the age of
the foal, has been used to estimate maintenance fluid
requirements for equine neonates. Other clinicians favour a
‘dry’ maintenance rate based on the Holliday-Segar formula:
for the first 10 kg of body weight, 100 ml/kg are administered,
then 50 ml for each kg from 11–20 kg and 25 ml for each kg of
body weight >20 kg. Using this calculation, maintenance fluids
for a 50 kg foal are 2250 ml/day or a maintenance rate of
94 ml/h (Palmer 2004) (10 kg × 100 ml/kg bwt/day + 10 kg ×
50 ml/kg bwt/day + 30 kg × 25 ml/kg bwt/day) plus fluids
received with parenteral nutrition and medication infusions. It
is important to note that parenteral nutrition, although strictly
speaking not representing i.v. fluids, adds free water to the
total fluid volume administered and that this maintenance
formula is not intended to be used in foals with increased fluid
losses, such as diarrhoea. As no controlled study has
compared the 2 fluid regimes and both have been used
clinically with success, the clinician may choose either
protocol as a starting point from which fluid therapy can be
tailored to the individual case. Whichever formula is used, it is
important to recognise that the high-sodium resuscitation fluids
(such as lactated Ringer’s solution or Normosol-R) are not an
ideal maintenance fluid and can result in high sodium
concentrations in many foals (Buchanan et al. 2005). For this
TABLE 1: Recommended antimicrobial dosages for neonatal foals based on published pharmacokinetic studies in foals
Gentamicin Amikacin Cefquinome Ceftiofur sodium
(Burton et al. (Bucki et al. (Smiet et al. (Meyer et al. 2009;
2013) 2004) 2012) Hall et al. 2011)
Neonatal 12.0 mg/kg bwt 25 mg/kg bwt 4.5 mg/kg bwt 5.0 mg/kg bwt i.v.
foals i.v. q. 36 h i.v. or i.m. i.v. q. 12 h or subcut. q.
q. 24 h 12 h
Notes
© 2014 EVJ Ltd
Sepsis in neonatal foals
reason, either commercially available maintenance fluids
(e.g. Normosol-M) or resuscitation fluids with potassium and
magnesium added and diluted with sterile water (and either
coadministered with glucose or parenteral nutrition to
maintain tonicity) may be more suitable fluids for many foals.
Antimicrobials
The majority of organisms obtained from blood cultures of
neonatal foals are comprised of enteric Gram-negative
bacteria but the percentage of Gram-positive isolates has
increased significantly over the years (Marsh and Palmer 2001;
Corley et al. 2007; Russell et al. 2008; Sanchez et al. 2008). In a
recent study, Enterococcus spp. were cultured more
frequently in recent years. This is concerning due to the
unpredictable antimicrobial susceptibility pattern and the
ability of the organism to act as donor of antimicrobial
resistance genes to other bacteria (Theelen et al. 2014a).
Antimicrobial treatment should be initiated as soon as possible,
ideally after samples for culture have been obtained.
However, it may be detrimental to delay antimicrobial therapy
for the sake of obtaining culture material (Kumar et al. 2006).
Choosing broad-spectrum antimicrobials with the least likely
resistance against suspected pathogens is paramount.
Frequently used combinations include β-lactams and
aminoglycosides or third or fourth generation cephalosporins
as monotherapy. Several drugs require dose adaptations in
neonates due to the larger content of body water and
differences in drug handling (Fielding et al. 2011) and ideally,
pharmacokinetics established in neonates should direct
dosing whenever available. Dose recommendations based on
pharmacokinetic studies in foals are listed in Table 1.
In the UK, cefquinome (Cobactan) is licensed for
treatment of ‘severe bacterial infections with a high risk of
septicaemia in which Escherichia coli is involved’ in foals at a
dose of 1.0 mg/kg bwt i.v. or i.m. q. 12 h for 6–14 days. Based
on pharmacokinetic studies, higher doses of 4.5 mg/kg bwt q.
12 h are recommended for the treatment of bacterial
pathogens with minimal inhibitory concentration (MIC)
≤0.125–0.5 g/l for neonatal foals (Smiet et al. 2012). Time of
plasma concentrations above MIC and drug concentrations
at different body sites might vary depending on administration
mode in time dependent antimicrobials. Continuous rate
infusions (CRI) of β lactam antimicrobials in critically ill people
showed improved pharmacodynamics profiles compared to
bolus administrations (Angus et al. 2000; Cousson et al. 2005)
and CRIs of ceftiofur and cefotaxime have been investigated
in healthy foals (Hewson et al. 2013; Wearn et al. 2013).
Marbofloxacin
Ceftiofur infusion Cefotaxime infusion (Tohamy and
(Wearn et al. 2013) (Hewson et al. 2013) El-Gendy 2013)
Loading dose Loading dose 5 mg/kg bwt i.v. or
2.2 mg/kg bwt i.v. 40 mg/kg bwt i.v. i.m. q. 24 h
followed by followed by
12 μg/kg bwt/min as 160 mg/kg bwt/24 h
continuous rate as continuous rate
infusion infusion
Dose equals 20 mg/kg Safety studies have
bwt/day; plasma not been
steady state performed in foals
concentration of
approx. 8.6 µg/l
B. Dunkel and K. T. T. Corley
Cefotaxime administered as bolus (40 mg/kg bwt i.v. q. 6 h)
achieved significantly lower concentrations in synovial fluid of
neonatal foals than administration by infusion (loading dose of
40 mg/kg bwt i.v. followed by CRI of 160 mg/kg bwt/day;
0.78 mg/l vs. 5.02 mg/l). Cerebrospinal fluid concentrations did
not differ and were low with either administration form
(Hewson et al. 2013). Some antimicrobials that are cost
prohibitive or cannot be used due to risk of colitis in mature
horses might offer an alternative option in foals should
bacteria resistant to first line antimicrobials be identified
(Corley and Hollis 2009).
Antimicrobial sensitivity is changing over time and the
aforementioned study identified worrying trends (Theelen
et al. 2014a,b), although another study identified decreasing
susceptibility only for enrofloxacin over a similar time period
(Sanchez et al. 2008). A decrease in the percentage of isolates
susceptible to gentamicin was noted from 1979–2010 and
several bacteria including Enterobacteriacea, showed an
increase in MIC values for amikacin. A decreased susceptibility
to ceftiofur or increased MIC values for the drug were
also observed; increasing MIC values are often viewed as
first sign of resistance development (Theelen et al. 2014b).
The decrease in in vitro activity of ceftiofur against
Enterobacteriaceae is of concern and it remains to be seen
whether a similar pattern could emerge with use of
cefquinome as monotherapy. Trends for changing sensitivities
in the UK need to be established and then monitored on a
regular basis (Haggett 2014).
Respiratory support
Pulmonary dysfunction is a common problem in critically ill
equine neonates and may include pulmonary immaturity
and surfactant dysfunction, bacterial pneumonia, often
associated with sepsis or aspiration, viral pneumonia,
meconium aspiration or acute respiratory distress syndrome
(Peek et al. 2004; Wilkins 2004; Wilkins et al. 2007). Intranasal
oxygen supplied via uni- or bilateral cannulas allows delivery of
flow rates up to 20–30 l/min, which corresponds to an inspired
oxygen fraction of 70–78% and greater (Wong et al. 2010). As
oxygen toxicity is a threat with administration of a high FiO2
for longer than 24 h, the lowest possible flow rate should
be chosen. Treatment options for centrally mediated
hypoventilation include pharmacological stimulation of the
respiratory centre using caffeine or doxapram or mechanical
ventilation. Orally or rectally administered caffeine (10 mg/kg
bwt loading dose dissolved per os or per rectum; then
2.5–5.0 mg/kg bwt as needed) has been used clinically (Wilkins
2004; Palmer 2005) but doxapram (loading dose 0.5 mg/kg
bwt followed by 0.02–0.08 mg/kg bwt/min) seems to be
superior in stimulating breathing (Giguere et al. 2007, 2008).
The principles of mechanical ventilation in foals have been
reviewed in detail elsewhere (Palmer 2005).
Nutritional support
If a foal is unable to stand or nurse, enteral nutrition is best
provided via an indwelling nasogastric feeding tube.
Pharyngeal dysfunction is common in compromised neonates
and tube feeding minimises the substantial risk of aspiration
(Holcombe et al. 2012). A healthy foal consumes 25–30% of its
bodyweight in milk/day but initial volumes for sick foals should
be smaller (5–10% bwt/day in frequent, small quantities) until
the function of the intestinal tract has been established.
95
Although enteral nutrition is preferable in theory, feeding of
moderately to severely compromised neonates may result in
abdominal distension, colic, diarrhoea and nasogastric reflux.
Enteral feeding of a foal with diarrhoea can greatly prolong
the duration of the disease. The resting energy requirements of
critically ill neonates are approximately 40–50 kcal/kg bwt/day
(Paradis 2001; Jose-Cunilleras et al. 2012) which can be
provided by intravenous glucose (4–8 mg/kg bwt/min) or
parenteral nutrition.
Treatment of systemic inflammation
and coagulopathies
The differences between the mature and neonatal equine
immune and coagulation systems are being increasingly
explored but remain incompletely understood. While in mature
horses with SIRS and sepsis the importance of anti-
inflammatory treatment is emphasised (Kelmer 2009)
treatment recommendations for sepsis in neonatal foals
focus on maintaining normal cardiovascular and respiratory
function, electrolyte and acid base balance and initiating
effective antimicrobial therapy. However, recent
investigations suggest that use of anti-inflammatory and anti-
endotoxic treatment could also be beneficial in neonates.
Significantly lower blood lactate, tumour necrosis factor-α and
thromboxane B2 concentrations, higher blood glucose
concentrations and better attitude scores were noted in
neonatal foals with experimental endotoxaemia after
administration of polymyxin (6000 u/kg bwt i.v. q. 8 h)
compared with the control group (Wong et al. 2013). No
evidence of nephrotoxicity was detected. Meloxicam at
0.6 mg/kg bwt per os q. 12 h is well tolerated in healthy foals
and no adverse effects were noted using 3 times this dose for
7 days (Raidal et al. 2013). Whether septic foals would benefit
from use of polymyxin B or meloxicam and their safety in sick
foals, particularly in regards to renal function, remains to be
established.
Very few effective treatments are available to combat
coagulopathies in any species, particularly DIC. The
concomitant presence of hyper- and hypocoaguable states
with risk of thrombi formation and bleeding demands use of
often opposing treatments. Substitution of platelets and
coagulation factors in form of fresh platelet-rich plasma or
fresh-frozen plasma is recommended for hypocoagulable
patients at risk of bleeding (Gando et al. 2011). In
hypercoaguable patients treatment with either unfractionated
or, ideally, low-molecular weight heparin (LMWH) might aid in
prevention of clot formation. Low-molecular weight heparin
has fewer side effects than unfractionated heparin and one
study suggests that it may have superior anticoagulant
properties in mature horses (Feige et al. 2003). In another study
in mature horses, use of LMWH was linked by the authors with a
better outcome (Cotovio et al. 2007). Heparin has not only
antithrombotic but also anti-inflammatory properties, which
could be useful in the treatment of sepsis (de la Rebiere et al.
2008). Recommended doses are 100 iu/kg bwt subcut. q. 24 h
for neonatal foals, twice as high as the mature dose (Feige et al.
2003; de la Rebiere de Pouyade et al. 2009; Armengou et al.
2010). Fresh or fresh frozen plasma, with or without the addition
of heparin (1500 u/l used anecdotally), could also be used in
hypercoagulation as antithrombin concentrations, one of the
main anticoagulants, are frequently low in septic foals (Barton
et al. 1998). Other treatments including pentoxifylline,
aminophylline or clopidogrel aimed at modifying platelet
© 2014 EVJ Ltd
96 Sepsis in neonatal foals

TABLE 2: Recommended dosages of anti-inflammatory, analgesic and anticoagulant drugs for neonatal based on published
pharmacokinetic studies in foals

Butorphanol
Polymyxin B Meloxicam (Arguedas et al. Fentanyl Firocoxib Dalteparin
(Wong et al. (Raidal et al. 2008; McGowan (Eberspacher et al. (Hovanessian et al. (Armengou et al.
2013) 2013) et al. 2013) 2008) 2011) 2010)

Neonatal 6000 iu/kg bwt i.v. q 0.6 mg/kg bwt per os 0.05–0.1 mg/kg bwt 10.2 mg patch 0.1 mg/kg bwt per 100 iu/kg bwt
foals 8h q. 12 h; i.v. or i.m. releasing 100 μg/h os q. 24 h subcut. q. 24 h
foals <6 weeks old for 72 h
Notes Nephrotoxicity has not No adverse effects 0.1 but not 0.05 mg/kg Variable peak plasma
been investigated in using 3× dose for 7 bwt increased concentrations
sick foals days; toxicity not thermal nociceptive (0.1–28.7 μg/l) after
investigated in sick threshold without 14.3 ± 7.6 h; return to
foals adverse effects baseline 12 h after
removal

function have no or only very limited effects on equine platelets
and coagulation and clinical effects on the coagulation system
still need to be established (Brainard et al. 2011). Doses for
anti-inflammatory, analgesic and anticoagulant drugs are
listed in Table 2.
Prognosis
The prognosis for survival to discharge of hospitalised septic
foals has improved over time (Sanchez et al. 2008) and ranges
in recent studies from 44–71% (Armengou et al. 2008;
Hurcombe et al. 2008; Barsnick et al. 2014; Borchers et al. 2014;
Toth et al. 2014). Prognosis for athletic performance is
considered to be good with surviving septic foals performing
similar to age matched controls. However, most studies have
identified some differences in some performance-related
parameters (Axon et al. 1999; Sanchez et al. 2008). Foals
treated for septic arthritis are considered to have a more
guarded prognosis for successful athletic performance,
particularly if multiple joints are involved (Steel et al. 1999;
Smith et al. 2004; Neil et al. 2010). However, recent large scale
studies are lacking. No differences in sales prices were
identified between foals treated in a hospital and controls
(Corley and Corley 2012).
Prevention
Unfortunately, little can be done to prevent sepsis beyond
well-established measures such as early identification of risk
factors during pregnancy (placentitis, premature placental
separation), meticulous birth hygiene and ensuring complete
passive transfer of immunity has taken place by measuring IgG
concentrations. Prophylactic antimicrobial treatment of
healthy neonatal foals did not show any benefits in regards to
development of infectious diseases and is no longer
recommended (Wohlfender et al. 2009). However, early
recognition of compromised neonates and rapid instigation of
treatment seem to be the key in achieving a positive outcome
and client education in this regard is of utmost importance.
Authors’ declaration of interests
No conflicts of interest have been declared.
References
Angus, B.J., Smith, M.D., Suputtamongkol, Y., Mattie, H., Walsh, A.L.,
Wuthiekanun, V., Chaowagul, W. and White, N.J. (2000)
Pharmacokinetic-pharmacodynamic evaluation of ceftazidime
continuous infusion vs intermittent bolus injection in septicaemic
melioidosis. Br. J. Clin. Pharmacol. 50, 184-191.
Arguedas, M.G., Hines, M.T., Papich, M.G., Farnsworth, K.D. and Sellon,
D.C. (2008) Pharmacokinetics of butorphanol and evaluation of
physiologic and behavioral effects after intravenous and
intramuscular administration to neonatal foals. J. Vet. Intern. Med.
22, 1417-1426.
Armengou, L., Monreal, L., Delgado, M.A., Rios, J., Cesarini, C. and
Jose-Cunilleras, E. (2010) Low-molecular-weight heparin dosage in
newborn foals. J. Vet. Intern. Med. 24, 1190-1195.
Armengou, L., Monreal, L., Tarancón, I., Navarro, M., Rios, J. and Segura,
D. (2008) Plasma d-dimer concentration in sick newborn foals. J. Vet.
Intern. Med. 22, 411-417.
Axon, J.E., Palmer, J. and Wilkins, P. (1999) Short- and long-term athletic
outcome of neonatal intensive care unit survivors. Proc. Am. Ass.
Equine Practnrs. 46, 224-225.
Barsnick, R.J., Hurcombe, S.D., Dembek, K., Frazer, M.L., Slovis, N.M.,
Saville, W.J. and Toribio, R.E. (2014) Somatotropic axis resistance and
ghrelin in critically ill foals. Equine Vet. J. 46, 45-49.
Barsnick, R.J., Hurcombe, S.D., Smith, P.A., Slovis, N.M., Sprayberry, K.A.,
Saville, W.J. and Toribio, R.E. (2011) Insulin, glucagon, and leptin in
critically ill foals. J. Vet. Intern. Med. 25, 123-131.
Barton, M.H., Morris, D.D., Norton, N. and Prasse, K.W. (1998) Hemostatic
and fibrinolytic indices in neonatal foals with presumed septicemia.
J. Vet. Intern. Med. 12, 26-35.
Belgrave, R.L., Dickey, M.M., Arheart, K.L. and Cray, C. (2013)
Assessment of serum amyloid A testing of horses and its clinical
application in a specialized equine practice. J. Am. Vet. Med. Ass.
243, 113-119.
Borchers, A., Magdesian, K.G., Schenck, P.A. and Kass, P.H. (2014) Serial
plasma vasopressin concentration in healthy and hospitalised
neonatal foals. Equine Vet. J. 46, 306-310.
Brainard, B.M., Epstein, K.L., LoBato, D., Kwon, S., Papich, M.G. and
Moore, J.N. (2011) Effects of clopidogrel and aspirin on platelet
aggregation, thromboxane production, and serotonin secretion in
horses. J. Vet. Intern. Med. 25, 116-122.
Brewer, B.D. and Koterba, A.M. (1988) Development of a scoring system
for the early diagnosis of equine neonatal sepsis. Equine Vet. J. 20,
18-22.
Buchanan, B.R., Sommardahl, C.S., Rohrbach, B.W. and Andrews, F.M.
(2005) Effect of a 24-hour infusion of an isotonic electrolyte
replacement fluid on the renal clearance of electrolytes in healthy
neonatal foals. J. Am. Vet. Med. Ass. 227, 1123-1129.
Bucki, E.P., Giguere, S., Macpherson, M. and Davis, R. (2004)
Pharmacokinetics of once-daily amikacin in healthy foals and
therapeutic drug monitoring in hospitalized equine neonates. J. Vet.
Intern. Med. 18, 728-733.
Burton, A.J., Giguere, S., Warner, L., Alhamhoom, Y. and Arnold, R.D.
(2013) Effect of age on the pharmacokinetics of a single daily dose
of gentamicin sulfate in healthy foals. Equine Vet. J. 45, 507-511.
Cohen, N.D. (1994) Causes of and farm management factors
associated with disease and death in foals. J. Am. Vet. Med. Ass.
204, 1644-1651.
Corley, K.T. (2004) Inotropes and vasopressors in adults and foals. Vet.
Clin. North Am.: Equine Pract. 20, 77-106.

© 2014 EVJ Ltd

B. Dunkel and K. T. T. Corley
Corley, K.T. and Corley, M.M. (2012) Hospital treatment as a foal does
not adversely affect future sales performance in Thoroughbred
horses. Equine Vet. J. 44, Suppl. 41, 87-90.
Corley, K.T., Pearce, G., Magdesian, K.G. and Wilson, W.D. (2007)
Bacteraemia in neonatal foals: clinicopathological differences
between Gram-positive and Gram-negative infections, and single
organism and mixed infections. Equine Vet. J. 39, 84-89.
Corley, K.T.T. and Furr, M.O. (2003) Evaluation of a score designed to
predict sepsis in foals. J. Vet. Emerg. Crit. Care 13, 149-155.
Corley, K.T.T. and Hollis, A.R. (2009) Antimicrobial therapy in neonatal
foals. Equine Vet. Educ. 21, 436-448.
Cotovio, M., Monreal, L., Armengou, L., Prada, J., Almeida, J.M. and
Segura, D. (2008) Fibrin deposits and organ failure in newborn foals
with severe septicemia. J. Vet. Intern. Med. 22, 1403-1410.
Cotovio, M., Monreal, L., Navarro, M., Segura, D., Prada, J. and Alves, A.
(2007) Detection of fibrin deposits in tissues from horses with severe
gastrointestinal disorders. J. Vet. Intern. Med. 21, 308-313.
Cousson, J., Floch, T., Vernet-Garnier, V., Appriou, M., Petit, J.S., Jovenin,
N., Lamiable, D. and Hoizey, G. (2005) Pharmacodynamic interest of
ceftazidime continuous infusion vs intermittent bolus administration
in patients with severe nosocomial pneumonia. Pathol. Biol. (Paris)
53, 546-550.
Craig, C.A., Haskins, S.C. and Hildebrand, S.V. (2007) The
cardiopulmonary effects of dobutamine and norepinephrine in
isoflurane-anesthetized foals. Vet. Anaesth. Analg. 34, 377-387.
Dallap, B.L. (2004) Coagulopathy in the equine critical care patient.
Vet. Clin. North Am. Equine Pract. 20, 231-251.
Dallap, B.L., Dolente, B. and Boston, R.C. (2003) Coagulation profiles in
27 horses with large colon volvulus. J. Vet. Emerg. Crit. Care 13,
215-225.
Dallap Schaer, B.L., Wilkins, P.A., Boston, R. and Palmer, J. (2009)
Preliminary evaluation of hemostasis in neonatal foals using a
viscoelastic coagulation and platelet function analyzer. J. Vet.
Emerg. Crit. Care 19, 81-87.
De Backer, D., Orbegozo Cortes, D., Donadello, K. and Vincent, J.L.
(2014) Pathophysiology of microcirculatory dysfunction and the
pathogenesis of septic shock. Virulence 5, 73-79.
De la Rebiere, G., Franck, T., Deby-Dupont, G., Salciccia, A., Grulke, S.,
Péters, F. and Serteyn, D. (2008) Effects of unfractionated and
fractionated heparins on myeloperoxidase activity and interactions
with endothelial cells: possible effects on the pathophysiology of
equine laminitis. Vet. J. 178, 62-69.
De la Rebiere de Pouyade, G., Grulke, S., Detilleux, J., Salciccia, A.,
Verwilghen, D.R., Caudron, I., Gangl, M. and Serteyn, D.D. (2009)
Evaluation of low-molecular-weight heparin for the prevention of
equine laminitis after colic surgery. J. Vet. Emerg. Crit. Care 19,
113-119.
Dembek, K.A., Onasch, K., Hurcombe, S.D., MacGillivray, K.C., Slovis,
N.M., Barr, B.S., Reed, S.M. and Toribio, R.E. (2013) Renin-angiotensin-
aldosterone system and hypothalamic-pituitary-adrenal axis in
hospitalized newborn foals. J. Vet. Intern. Med. 27, 331-338.
Dickey, E.J., McKenzie, H. 3rd, Johnson, A. and Furr, M.O. (2010) Use of
pressor therapy in 34 hypotensive critically ill neonatal foals. Aust.
Vet. J. 88, 472-477.
Dolente, B.A., Wilkins, P.A. and Boston, R.C. (2002) Clinicopathologic
evidence of disseminated intravascular coagulation in horses with
acute colitis. J. Am. Vet. Med. Ass. 220, 1034-1038.
Eberspacher, E., Stanley, S.D., Rezende, M. and Steffey, E.P. (2008)
Pharmacokinetics and tolerance of transdermal fentanyl
administration in foals. Vet. Anaesth. Analg. 35, 249-255.
Feige, K., Schwarzwald, C.C. and Bombeli, T. (2003) Comparison of
unfractioned and low molecular weight heparin for prophylaxis of
coagulopathies in 52 horses with colic: a randomised double-blind
clinical trial. Equine Vet. J. 35, 506-513.
Fielding, C.L., Magdesian, K.G. and Edman, J.E. (2011) Determination of
body water compartments in neonatal foals by use of indicator
dilution techniques and multifrequency bioelectrical impedance
analysis. Am. J. Vet. Res. 72, 1390-1396.
Gando, S., Sawamura, A. and Hayakawa, M. (2011) Trauma, shock, and
disseminated intravascular coagulation: lessons from the classical
literature. Ann. Surg. 254, 10-19.
97
Giguere, S., Sanchez, L.C., Shih, A., Szabo, N.J., Womble, A.Y. and
Robertson, S.A. (2007) Comparison of the effects of caffeine and
doxapram on respiratory and cardiovascular function in foals with
induced respiratory acidosis. Am. J. Vet. Res. 68, 1407-1416.
Giguere, S., Slade, J.K. and Sanchez, L.C. (2008) Retrospective
comparison of caffeine and doxapram for the treatment of
hypercapnia in foals with hypoxic-ischemic encephalopathy. J. Vet.
Intern. Med. 22, 401-405.
Gill, S.E., Taneja, R., Rohan, M., Wang, L. and Mehta, S. (2014) Pulmonary
microvascular albumin leak is associated with endothelial cell death
in murine sepsis-induced lung injury in vivo. PLoS ONE 9, e88501.
Gold, J.R., Divers, T.J., Barton, M.H., Lamb, S.V., Place, N.J., Mohammed,
H.O. and Bain, F.T. (2007) Plasma adrenocorticotropin, cortisol, and
adrenocorticotropin/cortisol ratios in septic and normal-term foals.
J. Vet. Intern. Med. 21, 791-796.
Goldstein, B., Giroir, B., Randolph, A. and International Consensus
Conference on Pediatric Sepsis (2005) International pediatric sepsis
consensus conference: definitions for sepsis and organ dysfunction
in pediatrics. Pediatr. Crit. Care Med. 6, 2-8.
Haggett, E.F. (2014) Antimicrobial use in foals: do we need to change
how we think? Equine Vet. J. 46, 137-138.
Hall, T.L., Tell, L.A., Wetzlich, S.E., McCormick, J.D., Fowler, L.W. and
Pusterla, N. (2011) Pharmacokinetics of ceftiofur sodium and
ceftiofur crystalline free acid in neonatal foals. J. Vet. Pharmacol.
Ther. 34, 403-409.
Hart, K.A., Barton, M.H., Vandenplas, M.L. and Hurley, D.J. (2011) Effects
of low-dose hydrocortisone therapy on immune function in
neonatal horses. Pediatr. Res. 70, 72-77.
Hart, K.A., Slovis, N.M. and Barton, M.H. (2009) Hypothalamic-
pituitary-adrenal axis dysfunction in hospitalized neonatal foals. J.
Vet. Intern. Med. 23, 901-912.
Hewson, J., Johnson, R., Arroyo, L.G., Diaz-Mendez, A., Ruiz-López, J.A.,
Gu, Y. and del Castillo, J.R. (2013) Comparison of continuous infusion
with intermittent bolus administration of cefotaxime on blood and
cavity fluid drug concentrations in neonatal foals. J. Vet. Pharmacol.
Ther. 36, 68-77.
Himler, M., Hurcombe, S.D., Griffin, A., Barsnick, R.J., Rathgeber, R.A.,
MacGillivray, K.C. and Toribio, R.E. (2012) Presumptive nonthyroidal
illness syndrome in critically ill foals. Equine Vet. J. 44, Suppl. 41, 43-47.
Holcombe, S.J., Hurcombe, S.D., Barr, B.S. and Schott, H.C. II (2012)
Dysphagia associated with presumed pharyngeal dysfunction in 16
neonatal foals. Equine Vet. J. 44, Suppl. 41, 105-108.
Hollis, A.R., Ousey, J.C., Palmer, L., Stoneham, S.J. and Corley, K.T. (2006)
Effects of norepinephrine and a combined norepinephrine and
dobutamine infusion on systemic hemodynamics and indices of
renal function in normotensive neonatal thoroughbred foals. J. Vet.
Intern. Med. 20, 1437-1442.
Hovanessian, N., Crisman, M., Hodgson, D.R., McKenzie, H.C., and Davis,
J.L. (2011) Pharmacokinetics of firocoxib in neonatal foals. J. Vet.
Intern. Med. 25, 677.
Hurcombe, S.D. (2011) Hypothalamic-pituitary gland axis function and
dysfunction in horses. Vet. Clin. North Am. Equine Pract. 27, 1-17.
Hurcombe, S.D., Toribio, R.E., Slovis, N., Kohn, C.W., Refsal, K., Saville, W.
and Mudge, M.C. (2008) Blood arginine vasopressin,
adrenocorticotropin hormone, and cortisol concentrations at
admission in septic and critically ill foals and their association with
survival. J. Vet. Intern. Med. 22, 639-647.
Hurcombe, S.D.A., Toribio, R.E., Slovis, N., Kohn, C.W. and Mudge, M.C.
(2007) Vasopressin, ACTH and cortisol concentrations in septic foals:
correlates with survival and nonsurvival. J. Vet. Intern. Med. 21, 582.
Jose-Cunilleras, E., Viu, J., Corradini, I., Armengou, L., Cesarini, C. and
Monreal, L. (2012) Energy expenditure of critically ill neonatal foals.
Equine Vet. J. 44, Suppl. 41, 48-51.
Kelmer, G. (2009) Update on treatments for endotoxemia. Vet. Clin.
North Am.: Equine Pract. 25, 259-270.
Khardori, R. and Castillo, D. (2012) Endocrine and metabolic changes
during sepsis: an update. Med. Clin. North Am. 96, 1095-1105.
Kumar, A., Roberts, D., Wood, K.E., Light, B., Parrillo, J.E., Sharma, S.,
Suppes, R., Feinstein, D., Zanotti, S., Taiberg, L., Gurka, D., Kumar, A.
and Cheang, M. (2006) Duration of hypotension before initiation of
effective antimicrobial therapy is the critical determinant of survival
in human septic shock. Crit. Care Med. 34, 1589-1596.
© 2014 EVJ Ltd
98
Langer, M., Modi, B.P. and Agus, M. (2006) Adrenal insufficiency in the
critically ill neonate and child. Curr. Opin. Pediatr. 18, 448-453.
Levi, M. (2010) The coagulant response in sepsis and inflammation.
Hamostaseologie 30, 10-12, 14-16.
Magdesian, K.G. (2005) Neonatal foal diarrhea. Vet. Clin. North Am.:
Equine Pract. 21, 295-312, vi.
Marsh, P.S. and Palmer, J.E. (2001) Bacterial isolates from blood and their
susceptibility patterns in critically ill foals: 543 cases (1991-1998). J.
Am. Vet. Med. Ass. 218, 1608-1610.
McGowan, K.T., Elfenbein, J.R., Robertson, S.A. and Sanchez, L.C. (2013)
Effect of butorphanol on thermal nociceptive threshold in healthy
pony foals. Equine Vet. J. 45, 503-506.
McKenzie, H.C. 3rd and Furr, M.O. (2001) Equine neonatal sepsis: the
pathophysiology of severe inflammation and infection. Comp.
Cont. Educ. Pract. Vet. 23, 661-670.
Meyer, S., Giguere, S., Rodriguez, R., Zielinski, R.J., Grover, G.S. and
Brown, S.A. (2009) Pharmacokinetics of intravenous ceftiofur sodium
and concentration in body fluids of foals. J. Vet. Pharmacol. Ther. 32,
309-316.
Monreal, L., Anglés, A., Espada, Y., Monasterio, J. and Monreal, M.
(2000) Hypercoagulation and hypofibrinolysis in horses with colic
and DIC. Equine Vet. J. 32, Suppl. 32, 19-25.
Neil, K.M., Axon, J.E., Begg, A.P., Todhunter, P.G., Adams, P.L., Fine, A.E.,
Caron, J.P. and Adkins, A.R. (2010) Retrospective study of 108 foals
with septic osteomyelitis. Aust. Vet. J. 88, 4-12.
Palmer, J.E. (2004) Fluid therapy in the neonate: not your mother’s fluid
space. Vet. Clin. North Am.: Equine Pract. 20, 63-75.
Palmer, J.E. (2005) Ventilatory support of the critically ill foal. Vet. Clin.
North Am.: Equine Pract. 21, 457-486, vii-viii.
Paradis, M. (2001) Nutrition and indirect calorimetry in neonatal foals. In:
Proceedings of the 19th American College of Veterinary Internal
Medicine Forum, Lakewood, Colorado, pp 245-247.
Peek, S.F., Landolt, G., Karasin, A.I., Slack, J.A., Steinberg, H., Semrad,
S.D. and Olsen, C.W. (2004) Acute respiratory distress syndrome and
fatal interstitial pneumonia associated with equine influenza in a
neonatal foal. J. Vet. Intern. Med. 18, 132-134.
Raidal, S.L., Edwards, S., Pippia, J., Boston, R. and Noble, G.K. (2013)
Pharmacokinetics and safety of oral administration of meloxicam to
foals. J. Vet. Intern. Med. 27, 300-307.
Russell, C.M., Axon, J.E., Blishen, A. and Begg, A.P. (2008) Blood culture
isolates and antimicrobial sensitivities from 427 critically ill neonatal
foals. Aust. Vet. J. 86, 266-271.
Sakr, Y., Reinhart, K., Vincent, J.L., Sprung, C.L., Moreno, R., Ranieri, V.M.,
De Backer, D. and Payen, D. (2006) Does dopamine administration
in shock influence outcome? Results of the Sepsis Occurrence in
Acutely Ill Patients (SOAP) Study. Crit. Care Med. 34, 589-597.
Sanchez, L.C. (2005) Equine neonatal sepsis. Vet. Clin. North Am.: Equine
Pract. 21, 273-293.
Sanchez, L.C., Giguere, S. and Lester, G.D. (2008) Factors associated
with survival of neonatal foals with bacteremia and racing
performance of surviving Thoroughbreds: 423 cases (1982-2007). J.
Am. Vet. Med. Ass. 233, 1446-1452.
Seeley, E.J., Matthay, M.A. and Wolters, P.J. (2012) Inflection points in
sepsis biology: from local defense to systemic organ injury. Am. J.
Physiol. Lung Cell. Mol. Physiol. 303, L355-L363.
Smiet, E., Haritova, A., Heil, B.A., Fink-Gremmels, J. and Wijnberg, I.D.
(2012) Comparing the pharmacokinetics of a fourth generation
cephalosporin in three different age groups of New Forest ponies.
Equine Vet. J. 44, Suppl. 41, 52-56.
Smith, L.J., Marr, C.M., Payne, R.J., Stoneham, S.J. and Reid, S.W. (2004)
What is the likelihood that Thoroughbred foals treated for septic
arthritis will race? Equine Vet. J. 36, 452-456.
© 2014 EVJ Ltd
Sepsis in neonatal foals
Steel, C.M., Hunt, A.R., Adams, P.L., Robertson, I.D., Chicken, C., Yovich,
J.V. and Stick, J.A. (1999) Factors associated with prognosis for
survival and athletic use in foals with septic arthritis: 93 cases
(1987-1994). J. Am. Vet. Med. Ass. 215, 973-977.
Stewart, A.J., Hinchcliff, K.W., Saville, W.J., Jose-Cunilleras, E., Hardy, J.,
Kohn, C.W., Reed, S.M. and Kowalski, J.J. (2002) Actinobacillus sp.
bacteremia in foals: clinical signs and prognosis. J. Vet. Intern. Med.
16, 464-471.
Sykes, B.W. and Furr, M.O. (2005) Equine endotoxaemia – a
state-of-the-art review of therapy. Aust. Vet. J. 83, 45-50.
Tape, C. and Kisilevsky, R. (1990) Apolipoprotein A-I and apolipoprotein
SAA half-lives during acute inflammation and amyloidogenesis.
Biochim. Biophys. Acta 1043, 295-300.
Theelen, M.J., Wilson, W.D., Edman, J.M., Magdesian, K.G. and Kass, P.H.
(2014a) Temporal trends in prevalence of bacteria isolated from
foals with sepsis: 1979-2010. Equine Vet. J. 46, 169-173.
Theelen, M.J., Wilson, W.D., Edman, J.M., Magdesian, K.G. and Kass, P.H.
(2014b) Temporal trends in in vitro antimicrobial susceptibility
patterns of bacteria isolated from foals with sepsis: 1979-2010.
Equine Vet. J. 46, 161-168.
Tohamy, M.A. and El-Gendy, A.A.M. (2013) Some pharmacokinetic
aspects and bioavailability of marbofloxacin in foals. Beni-Suef Univ.
J. Basic Appl. Sci. 2, 46-50.
Toth, B., Slovis, N.M., Constable, P.D. and Taylor, S.D. (2014) Plasma
adrenomedullin concentrations in critically ill neonatal foals. J. Vet.
Intern. Med. doi:10.1111/jvim.12358. Epub ahead of print.
Valverde, A., Giguere, S., Sanchez, L.C., Shih, A. and Ryan, C. (2006)
Effects of dobutamine, norepinephrine, and vasopressin on
cardiovascular function in anesthetized neonatal foals with induced
hypotension. Am. J. Vet. Res. 67, 1730-1737.
Wearn, J.M., Davis, J.L., Hodgson, D.R., Raffetto, J.A. and Crisman, M.V.
(2013) Pharmacokinetics of a continuous rate infusion of ceftiofur
sodium in normal foals. J. Vet. Pharmacol. Ther. 36, 99-101.
Weber, E.J., Sanchez, L.C. and Giguère, S. (2014) Re-evaluation of the
sepsis score in equine neonates. Equine Vet. J. doi:10.1111/evj.
12279. Epub ahead of print.
Werners, A.H. and Bryant, C.E. (2012) Pattern recognition receptors in
equine endotoxaemia and sepsis. Equine Vet. J. 44, 490-498.
Werners, A.H., Bull, S. and Fink-Gremmels, J. (2005) Endotoxaemia: a
review with implications for the horse. Equine Vet. J. 37, 371-383.
Wilkins, P.A. (2004) Disorders of Foals, W.B. Saunders, St Louis. 63146.
Wilkins, P.A., Otto, C.M., Baumgardner, J.E., Dunkel, B., Bedenice, D.,
Paradis, M.R., Staffieri, F., Syring, R.S., Slack, J., Grasso, S. and Pranzo,
G. (2007) Acute lung injury and acute respiratory distress syndromes
in veterinary medicine: consensus definitions: the Dorothy Russell
Havemeyer Working Group on ALI and ARDS in Veterinary Medicine.
J. Vet. Emerg. Crit. Care 17, 333-339.
Wohlfender, F.D., Barrelet, F.E., Doherr, M.G., Straub, R. and Meier, H.P.
(2009) Diseases in neonatal foals. Part 1: the 30 day incidence of
disease and the effect of prophylactic antimicrobial drug treatment
during the first three days post partum. Equine Vet. J. 41, 179-185.
Wong, D.M., Alcott, C.J., Wang, C., Hay-Kraus, B., Buchanan, B.R. and
Brockus, C.W. (2010) Physiologic effects of nasopharyngeal
administration of supplemental oxygen at various flow rates in
healthy neonatal foals. Am. J. Vet. Res. 71, 1081-1088.
Wong, D.M., Sponseller, B.A., Alcott, C.J., Agbedanu, P.N., Wang, C.
and Wsu, W.H. (2013) Effects of intravenous administration of
polymyxin B in neonatal foals with experimental endotoxemia. J.
Am. Vet. Med. Ass. 243, 874-881.