Neonatal and Perinatal Diseases
Before the 1980s, intensive management of the compromised neonate was unusual and
little was known regarding many of the problems of this special patient population.
Although some specific conditions had been described by astute clinician-researchers,
most notably the “dummy” foal syndrome
1
and respiratory distress syndrome caused by primary surfactant deficiency,
2
little information regarding the diagnosis and management of conditions of the foal
during the neonatal period was available, although at least one active group was investigating
fetal and neonatal physiology of the horse in Great Britain.1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14 When treatment of compromised foals was undertaken, the approach
most commonly resembled treating them as small adults with little understanding of
the different physiology of the equine neonate. The advent of improved management
of reproductive efficiency of mares led naturally to increased interest in preservation
of the conceptus to parturition and the foal thereafter. Interested clinicians, taking
their lessons from the field of human perinatology/neonatology and sometimes working
hand-in-hand with their counterparts in the human field, pioneered investigations
into these small patients and created the fields of equine perinatology and equine
neonatal intensive care.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,
18, 19 Because of the foresight and energy of these early investigators, the field
of veterinary perinatology/neonatology exploded in the 1980s, leading to the creation
of equine neonatal intensive care units throughout the United Sates and the world.
From these units information about the normal and abnormal physiology of foals, the
medical conditions affecting them, and methods for treatment and management of these
problems has been developed through observational, retrospective, and prospective
studies. This veritable explosion of information over the last 20 years has improved
greatly the ability of all practitioners to provide appropriate care for these patients,
whether in the field or at an equine neonatal intensive care unit. The ability not
only to save the lives of these patients but also to treat them in such a manner as
to allow them to fulfill their purposes, whether as pleasure animals or racing athletes,
has improved almost exponentially from those early days.20, 21, 22, 23 This chapter
aims to provide the clinician with some of the most current information regarding
the management of these patients, recognizing that much still remains unknown and
that advances will continue to be made in this dynamic field. The reader is cautioned
that much of this chapter is flavored by the experiences of the author and that variation
in approach and treatment of specific problems exists between neonatal intensive care
units (NICUs) and between clinicians in the same NICU and that each year results in
change. In some cases, information that is presented has been gleaned from human NICU
studies, essentially using the critically ill infant as the experimental model.
Many of the problems of the newborn foal have their genesis in utero. Identification
of high-risk pregnancies is an important component of prenatal care of the foal, and
some of the most commonly encountered problems of the dam resulting in abnormal foals
include previous or concurrent disease, poor reproductive history, poor perineal or
pelvic conformation, poor general health, poor nutritional condition, prolonged transport,
history of previous abnormal foals, placental abnormalities, and twins.
24
Some of the more common causes of abortion can result in the birth of severely compromised
foals of variable gestation lengths (Box 19-1
). These include infectious causes such as equine herpesvirus (EHV) types 1 (most
commonly) and 4 (rarely), equine infectious anemia, equine arteritis virus, bacterial
and fungal placentitis, leptospirosis, equine ehrlichiosis, and gram-negative septicemia/endotoxemia.25,
26, 27 Noninfectious causes of abortion include twinning and noninfectious placental
abnormalities such as extensive endometrial fibrosis, body pregnancy, and abnormal
length (long or short) of the umbilical cord.24, 28
BOX 19-1
CONDITIONS ASSOCIATED WITH HIGH-RISK PREGNANCY
Maternal Conditions
Colic/endotoxemia
Abdominal hernia
Pelvic anatomic abnormalities
Malnutrition
Any debilitating disease
Uterine torsion
Uterine abnormalities
Mare reproductive loss syndrome
Hyperlipemia
Hypogalactia
History of previous abnormal foals
Conceptional Conditions
Placentitis
Twins
Hydrops
Prolonged gestation
Fetal abnormalities
Dystocia
Fescue toxicosis
Umbilical abnormalities
Congenital deformity
To the equine neonatologist opportunities for intervention may appear limited, and
in the case of many of the aforementioned causes of fetal loss, this is true. However,
one can do much in an attempt to preserve the pregnancy and in effect treat the fetus.
When one is faced with a threatened pregnancy, one has various ways of evaluating
the fetus and its environment and may use many potential therapies.
Prepartum Evaluation Of The Fetus And Placenta
Once one identifies a pregnancy as high risk, one should evaluate the fetus for viability.
Evaluation should include as thorough an evaluation as possible of the reproductive
tract, placenta, and fetal fluids. Prepartum disorders in the mare usually are readily
recognizable, but disorders of the fetus and placenta can be more subtle and difficult
to determine. The first step is to take a thorough history of the mare. Of particular
interest is any history of previous abnormal foals, but the history taking should
include questions regarding transportation; establishment of an accurate breeding
date (sometimes more difficult than one would suspect); any pertinent medical history
including any diagnostic testing performed for this pregnancy such as culture, endometrial
biopsy, and cytologic results; and any rectal and ultrasound examination results.
Additionally, one should obtain information regarding possible ingestion of endophyte-infected
fescue or exposure to potential infectious causes of abortion.29, 30 A complete vaccination
and deworming history is requisite, as is a complete history of any medications and
supplements administered during pregnancy.
After obtaining a history, one examines the mare per rectum. This examination should
include palpation of the cervix, uterus, fetus, and all palpable abdominal contents.
One should note any abnormalities. The cervix should be tight throughout gestation;
the late gestation uterus will be large and distended with fluid and usually pulled
craniad in the abdomen. Palpation of the fetus frequently results in some fetal movement;
however, one should interpret lack of movement with caution, for some normal fetuses
do not respond. Ultrasonographic evaluation of the uterus and conceptus per rectum
can provide valuable information, particularly regarding placental thickness if placentitis
is a concern. One may evaluate fetal fluids and estimate fetal size from the size
of the eye later in gestation.
31
In the author's hospital the practitioners choose not to perform vaginal examinations
or speculum examinations because of an association between these examinations and
the subsequent development of placentitis. Unless placentitis is recognized with ultrasonograhic
evaluation per rectum and culture is desirable, these types of examinations are generally
not necessary.
Following examination per rectum, one performs transabdominal ultrasonographic evaluation
of the uterus and conceptus.
28
One can generate a biophysical profile of the fetus from this examination in the late-term
fetus and readily determine viability.32, 33 One also readily can determine the presence
or absence of twins in the late pregnant mare in this manner. One performs the sonogram
through the acoustic window from the udder to the xiphoid ventrally and laterally
to the skinfolds of the flank. Imaging of the fetus usually requires a low-frequency
(3.5-MHz) probe, whereas examination of the placenta and endometrium requires a higher-frequency
(7.5-MHz) probe. A complete description of this examination is beyond the scope of
this chapter, but the reader will find several complete descriptions of the technique
and normal values for specific gestation lengths within the relevant veterinary literature.
33
The utility of this examination lies in its repeatability and low risk to the dam
and fetus. Sequential examinations over time allow the clinician to follow the pregnancy
and to identify changes as they occur.
A companion to transabdominal ultrasongraphy is evaluation of the fetal electrocardiogram
(ECG). One can measure fetal ECGs continuously using telemetry or can obtain them
using more conventional techniques several times throughout the day.24, 28, 34 One
places electrodes on the skin of the mare in locations aimed at maximizing the magnitude
of the fetal ECG. Because the fetus frequently changes position, multiple sites may
be needed in any 24-hour period. To begin, one places an electrode dorsally in the
area of the sacral prominence with two electrodes placed bilaterally in a transverse
plane in the region of the flank. The fetal ECG maximal amplitude is low, usually
0.05 to 0.1 mV, and can be lost in artifact or background noise, so one commonly must
move electrodes to new positions to maximize the appearance of the fetal ECG. The
normal fetal heart rate during the last months of gestation ranges from 65 to 115
beats/min, a fairly wide distribution. The range of heart rate of an individual fetus
can be narrow, however. Bradycardia in the fetus is an adaptation to in utero stress,
most commonly thought to be hypoxia. By slowing the heart rate, the fetus prolongs
exposure of fetal blood to maternal blood, increasing the time for equilibration of
dissolved gas across the placenta and improving the oxygen content of the fetal blood.
The fetus also has altered the distribution of its cardiac output in response to hypoxia,
centralizing blood distribution.35, 36 Tachycardia in the fetus can be associated
with fetal movement, and brief periods of tachycardia should occur in the fetus in
any 24-hour period. Persistent tachycardia is a sign of fetal distress and represents
more severe fetal compromise than bradycardia. The author has recognized dysrhythmias
in the challenged fetus, most commonly as atrial fibrillation but also apparent runs
of ventricular tachycardia.
The ability to monitor the fetus in a high-risk pregnancy inevitably has led to questions
of whether, how, and when to intervene. Most equine neonatologists would agree that
removal of the fetus from the uterus before its attainment of readiness for birth
is not desirable. One of the difficulties in determining fetal preparedness for birth
is that prediction of parturition is difficult in these mares. Many of the parameters
used in normal mares are unreliable in the high-risk pregnant mare. One must have
an accurate history of any previous gestation length in terms of days for the specific
mare in question to allow a more accurate estimate of her usual gestational length.
Evaluation of the usual mammary gland parameters, including size, the presence of
“wax,” and alteration of electrolyte concentrations, is not generally predictive in
the high-risk mare, for in the author's experience many of these mares have changes
predictive of parturition for weeks before actual parturition.37, 38 This circumstance
may be related to the observation that many high-risk pregnant mares, particularly
those with placentitis, are presented for a primary complaint of early onset lactation.
Although pulmonary system maturity in human beings can be assessed with some degree
of accuracy using measurement of lecithin/sphingomyelin ratios, this measurement—along
with sphingomyelin, cortisol, and creatinine concentrations in the amnionic fluid—has
proved to be of no benefit in the horse.39, 40, 41 Amniocentesis carries a high risk
of abortion in the horse, even with ultrasound guidance, and is not a clinically useful
technique at this time.
41
Currently, no clear-cut guidelines are available as to when to intervene, but the
presence of persistent fetal tachycardia or prolonged absence of fetal movements,
including breathing movements, as determined by transabdominal ultrasound evaluation,
should initiate discussion regarding the appropriateness of induction of parturition
or elective cesarean section. The goal of induction or cesarean section is to remove
a pregnancy that is threatening the survival of the dam with no thought to fetal survival
or to remove the fetus from a threatening environment to improve its likelihood for
survival. Preterm induction is ill advised if fetal survival is desirable because
of the limited ability to treat severely immature neonates. Timing of intervention
in these circumstances remains an art, not a science.
The approach to management of the high-risk pregnancy is dictated to some degree by
the exact cause for concern, but for many mares therapy is similar. Many high-risk
mares have placentitis, primarily caused by ascending bacterial or fungal infections
originating in the region of the cervix. These infections can cause in utero sepsis
or compromise the fetus by local elucidation of inflammatory mediators or altered
placental function.42, 43 Premature udder development and vaginal discharge are common
clinical signs. Treatment consists of administration of broad-spectrum antimicrobial
agents and nonsteroidal antiinflammatory drugs (Table 19-1
). In the author's clinic, trimethoprim-sulfonamide drugs have been the antimicrobial
of choice based on unpublished studies performed at the facility demonstrating increased
concentration of these agents in the fetal fluids compared with penicillin and gentamicin.
However, if culture and sensitivity results are available, one should institute directed
therapy. Nonsteroidal antiinflammatory agents such as flunixin meglumine are useful
to combat alterations in prostaglandin balance that may be associated with infection
and inflammation. Although the efficacy of these agents is best when administered
before the development of clinical signs, to date no detrimental effects have been
reported in the fetus or dam when chronically used at low doses in well-hydrated patients.
Tocolytic agents and agents that promote uterine quiescence have been used and include
altrenogest, isoxuprine, and clenbuterol.44, 45, 46, 47, 48 Altrenogest usually is
administered, although its need in late gestation has been challenged. The efficacy
of isoxuprine as a tocolytic in the horse is unproven, and bioavailability of orally
administered isoxuprine appears to be highly variable.
48
The long-term use of clenbuterol is inadvisable because of receptor population changes
associated with chronic use and its unknown effects on the fetus at this time. Clenbuterol
may be indicated during management of dystocia in preparation for assisted delivery
or cesarean section.
46
The intravenous form of clenbuterol is not currently available in the United States.
TABLE 19-1
Drugs Used to Treat High-Risk Pregnancy
DRUG
DOSE/FREQUENCY/ROUTE
REASON
Trimethoprim-sulfonamide
25 mg/kg b.i.d. p.o.
Antimicrobial
Flunixin meglumine
0.25 mg/kg t.i.d. p.o. or IV*
Antiinflammatory
Altrenogest
0.44 mg/kg s.i.d. p.o.
Tocolytic
Isoxuprine
0.4–0.6 mg/kg b.i.d. IM or p.o.
Tocolytic
Clenbuterol
0.8 μg/kg as needed p.o.†
Tocolytic
Vitamin E
6000–10,000 IU s.i.d. p.o.
Antioxidant
*
IV, Intravenously; IM, intramuscularly.
†
Intravenous form currently not available in the United States.
One can use three additional strategies in managing high-risk pregnancy patients.
In mares with evidence of placental dysfunction, with or without signs of fetal distress,
the author provides intranasal oxygen supplementation in the hope of improving oxygen
delivery to the fetus. Intranasal oxygen insufflation of 10 to 15 L/min to the mare
significantly increases Pao
2 and percent oxygen saturation of hemoglobin.
49
Because of the placental vessel arrangement of the horse, improvement of these two
arterial blood gas parameters should result in improved oxygen delivery to the fetus.
Blood gas transport is largely independent of diffusion distance in the equine placenta,
particularly in late gestation, and depends more on blood flow. Information from other
species cannot be extrapolated to the equine placenta because of its diffuse epitheliochorial
nature and the arrangement of the maternal and fetal blood vessels within the microcotyledons.50,
51 Umbilical venous pO2 is 50 to 54 mm Hg in the horse fetus, compared with 30 to
34 mm Hg in the sheep, whereas the maternal uterine vein to umbilical vein pO2 difference
is near 0. Also unlike the sheep, the umbilical venous pO2 values decrease 5 to 10
mm Hg in response to maternal hypoxemia and increase in response to maternal hyperoxia.52,
53, 54
Vitamin E (tocopherol) is administered orally to some high-risk mares as an antioxidant.
Administration of large doses of vitamin E before traumatic brain injury improves
neurologic outcome in experimental models and has been examined as possible prophylaxis
for human neonatal encephalopathy.55, 56, 57 Extrapolation of that information to
the compromised equine fetus suggests that increased antioxidant concentrations in
the fetus may mitigate some of the consequences of uterine and birth hypoxia, but
no evidence is available to date demonstrating that protection occurs or that vitamin
E accumulates in the fetus in response to supplementation of the mare. Finally, many
high-risk mares are anorectic or held off feed because of their medical condition.
These mares are at particularly great risk for fetal loss because of their lack of
feed intake, which alters prostaglandin metabolism.
58
Therefore one should administer 2.5% to 5% dextrose in 0.45% saline or water (5% dextrose)
intravenously at maintenance fluid rates to these patients.
Perhaps the most important aspect of managing high-risk pregnancy mares is frequent
observation and development of a plan. One should observe mares at least hourly for
evidence of early-stage labor and should put them under constant video surveillance
if possible. Depending on the primary problem, the team managing the mare should develop
a plan for handling the parturition once labor begins and for fetal resuscitation
following delivery. Any equipment that might be needed should be readily available
stallside, and a call sheet, listing contact numbers for all involved, should be posted
on or near the stall. The plan should include a decision as to how to handle a complicated
dystocia, should it occur, with permission for general anesthesia and cesarean section
obtained before the event so that time is not wasted. An important question to be
posed to the owner at the outset is which is most important to the owner, the mare
or the foal, for the answer may dictate the direction of the decision tree once labor
begins.
59
Evaluation Of The Newborn Foal
Early recognition of abnormalities is of utmost importance for successful management
of critically ill foals. To recognize the abnormal, one must know the normal. Immediately
following birth, foals effect several important physiologic and behavioral changes.
Chief among these changes is the adaptation of the cardiovascular and respiratory
systems to extrauterine life. The normal transition of the respiratory tract involves
opening closed alveoli and absorption of fluid from the airway, accomplished by a
combination of breathing efforts, expiration against a closed glottis (grunting),
and a change in sodium flux across the respiratory membrane from net secretion to
net absorption.60, 61, 62, 63, 64 The transition from fetal to neonatal circulatory
patterns requires resolution of the pulmonary hypertension present in the fetus, normally
shunting blood flow through the lower resistance ductus arteriosus in the fetal state,
to direct cardiac output to the pulmonary vasculature for participation in gas exchange.
This change is achieved by the opening of alveoli, decreasing airway resistance and
providing radial support for pulmonary vessels, functional closure of the ductus arteriosus,
and increasing the oxygen tension in the lung, reversing pulmonary vasoconstriction
mediated by hypoxia.65, 66 Pulmonary tree vasodilators (prostacyclin, nitric oxide
[NO]) and vasoconstrictors (endothelin-1, leukotrienes) play apparently well-coordinated,
but as yet not fully elucidated, roles. In the normal newborn this change is smooth
and rapid. These critical events are undermined by factors such as inadequate lung
development, surfactant deficiency (primary or secondary), viral or bacterial infection,
placental abnormalities, in utero hypoxia, and meconium aspiration.
Spontaneous breathing should begin in the neonate within 1 minute of birth, many foals
attempt to breathe as their thorax clears the pelvic canal. During the first hour
of life, the respiratory rate of a healthy foal can be as high as 80 breaths per minute
but should decrease to 30 to 40 breaths per minute within a few hours. Similarly,
the heart rate of a healthy newborn foal has a regular rhythm and should be at least
60 beats/min at the first minute.67, 68 One usually can auscultate a continuous murmur
over the left side of the heart, although its loudness may vary with position. This
murmur is thought to be associated with some shunting through the ductus arteriosus.
One may auscultate variable systolic murmurs, thought to be flow murmurs, during the
first week of life.
69
One should investigate more thoroughly murmurs that persist beyond the first week
of life in an otherwise healthy foal, along with any murmur associated with persistent
hypoxia. Auscultation of the thorax shortly after birth reveals a cacophony of sounds
as airways open and fluid is cleared. End-expiratory crackles are consistently audible
in the dependent lung during and following lateral recumbency. For a normal newborn
foal to appear slightly cyanotic during this initial adaptation period is not unusual,
but this should resolve within minutes of birth. The equine fetus, as do all fetuses,
exists in a moderately hypoxic environment, but the equine fetus has a greater partial
pressure of oxygen, around 50 mm Hg.
70
Because the fetus is well adapted to low oxygen tensions, cyanosis is rarely present
in newborn foals once adaption occurs, even those with low oxygen tensions. Although
in many species the fetal blood oxygen affinity is greater than the maternal blood,
in the equine fetus the oxygen affinity of its hemoglobin is only about 2 mm Hg greater
than the maternal blood because of decreased levels of 2,3-diphosphoglycerate compared
with other species.
71
The result is enhanced oxygen unloading in the equine fetus compared with others.
2,3-Diphosphoglycerate concentration increases after birth in the foal and reaches
mature levels by 3 to 5 days of age. The major blood adaptation of the equine fetus
to chronic hypoxia is an increase in packed cell volume of up to 20%, increasing the
oxygen content of the blood as compensation for decreased oxygen delivery at the placenta.
72
A larger than expected packed cell volume in any newborn foal should alert the clinician
for possible sequelae from chronic hypoxia. The presence of significant cyanosis that
persists should prompt the clinician to evaluate the foal thoroughly for cardiac anomalies
resulting in significant right-to-left shunting or separated circulations, such as
transposition of the great vessels.
The chest wall of the foal is compliant, facilitating passage through the pelvic canal
during parturition. This compliance requires that the foal actively participate in
inspiration and expiration with several potential consequences. First, restriction
of the thorax or the abdomen can result in impaired ventilation, which can occur easily
when one restrains a foal and may result in spuriously abnormal arterial blood gas
values (see the discussion on arterial blood gas evaluation, Respiratory Diseases
Associated with Hypoxemia in the Neonate). Second, foals with primary pulmonary parenchymal
disease resulting in poorly compliant lungs develop paradoxical chest wall motion,
with the thorax moving inward during inspiration.73, 74, 75, 76 The work of breathing
can increase greatly, resulting in respiratory failure because of respiratory muscle
fatigue. A foal that appears suddenly to improve a previously abnormal respiratory
rate and pattern may in fact be in greater respiratory difficulty because of fatigue.
One can observe a reduction in respiratory rate or abnormal breathing pattern in premature/dysmature
foals or foals subjected to peripartum hypoxia/asphxia. Although the genesis of these
patterns is not understood fully, Cheyne-Stokes (lengthy periods of apnea interrupted
by short breaths that wax and wane in depth), cluster (short periods of apnea interspersed
with long periods of breathing), and Biot's breathing (periods of apnea and breathing
with no discernible pattern) may occur in these cases. Foals attempting to maintain
an adequate lung volume expire against a partially closed glottis, called Valsalva's
maneuver, producing an audible grunt.
Foals are normally nonresponsive while in the birth canal but should respond to stimulation
immediately after birth.
67
The lack of responsiveness while in the birth canal has lead to presumption of fetal
death during dystocia. Because of this, one should attempt other tests before determining
that a foal is dead intrapartum. One possibly may detect pulses in the tongue, neck,
or any presented limbs or palpate the thorax for a heartbeat. In the author's facility,
nasotracheal intubation of the foal combined with measurement of CO2 tensions in the
exhaled gas aids practitioners in cases where they can reach the nose. Nasotracheal
intubation of foals under these circumstances actually can be performed readily with
minimal practice. Having long endotracheal tubes available of several different diameters
(7 to 12 mm outer diameter) with an inflatable cuff is important. One can pass the
tube blindly using a finger in one nostril for guidance and can check the position
frequently by palpation of the throatlatch region. One inflates the cuff and begins
manual ventilation with 100% oxygen or room air using an Ambu-bag or equivalent. One
can obtain continuous measurement of CO2 tension using a capnograph or single-use
disposable end-tidal CO2 monitor attached to the Ambu-bag or the nasotracheal tube.
In a dead foal the end-tidal CO2 measurement will be negligible after the first 10
to 20 breaths. One must ensure tube placement and seal integrity and allow for multiple
breaths. Some CO2 will “wash out” with the first few breaths and can result in false
hope initially. End-tidal CO2 varies in living intrapartum foals, depending on cardiac
output and ventilation frequency, but should be consistently greater than 20 mm Hg
and is usually closer to 30 mm Hg. Once one establishes manual ventilation of a living
foal, one must continue ventilation until the foal is delivered satisfactorily. The
author has resuscitated and maintained many foals successfully in this manner throughout
induction of general anesthesia in the mare and cesarean section delivery of the foal.
The nasotracheal tube also provides a convenient site for administration of intratracheal
medications such as epinephrine used for extrauterine intrapartum resuscitation of
the foal. The reader is cautioned that intratracheal epinephrine increases end-tidal
CO2 measurements transiently, even in a dead foal, because of local actions on tissues.
One should allow a washout period after intratracheal administration of epinephrine.
The righting reflex is present as the foal exits the birth canal, as is the withdrawal
reflex. Cranial nerve responses are intact at birth, but the menace response may take
as long as 2 weeks to develop fully. One should not consider lack of a menace reflex
diagnostic of visual deficits in the newborn foal. Within an hour of birth the normal
foal will demonstrate auditory orientation with unilateral pinna control. The normal
pupillary angle is ventromedial in the newborn foal; this angle gradually becomes
dorsomedial over the first month of life. Foals should begin attempting to stand shortly
after birth and should be able to achieve this on their own within 2 hours of birth.
67
The normal newborn foal has a suck reflex shortly after birth and should be searching
for an udder even before it stands. The expectation is that a normal foal will be
sucking from the dam unaided by 3 hours post partum; many foals are overachievers
and will be sucking well before this time. The normal foal may defecate shortly after
standing but may not attempt defecation until after it first successfully sucks from
the dam. Urination varies more, with filly foals usually urinating before colt foals,
but both usually do not urinate for several hours following birth, up to 12 hours
for some colts.
67
For colt foals to fail to drop their penises when urinating over the first few days
of life is not unusual.
The gait of the newborn foal is hypermetric and the stance is base wide. Extreme hypermetria
of the forelimbs, usually bilateral but occasionally unilateral, has been observed
in some foals and is associated with perinatal hypoxic/ischemic insults, but this
gait abnormality usually resolves without specific therapy within a few days. Spinal
reflexes tend to be exaggerated, whereas the crossed extensor reflex may not be fully
present until 3 weeks of age.
77
Foals also exhibit an exaggerated response to external stimuli (noise, sudden visual
changes, touch) for the first few weeks of life. Foals are not bonded strongly to
their mother for the first few weeks of life and will follow any large moving object,
including other horses and human beings. Orphan foals bond with surrogate mothers
until they are several months of age; their primary motivation appears to be appetite.
Conversely, mares strongly bond with their foals shortly after parturition; the process
begins once the chorioallantois ruptures and is driven more by olfaction and taste
than by vision or hearing. Interference with this process, by medical intervention
or excessive owner manipulation of the foal, can disrupt normal bonding and result
in foal rejection by the dam.
78
Evaluation Of The Weak Or Depressed Foal
NEONATAL RESUSCITATION
Most newborn foals make the transition to extrauterine life easily. However, for those
in difficulty, recognition of the condition immediately and institution of appropriate
resuscitation is of utmost importance. A modified Apgar scoring system has been developed
as a guide for initiating resuscitation and assessing probable level of fetal compromise
(Table 19-2
).
79
One also must at least perform a cursory physical examination before initiating resuscitation,
for issues of humaneness are associated with with serious problems such as severe
limb contracture, microophthalmia, and hydrocephalus, among others.
TABLE 19-2
Apgar Score in the Foal
Rights were not granted to include this table in electronic media. Please refer to
the printed book.
From Martens RJ: Pediatrics. In Mansmann RA, McAllister ES, Pratt PW, editors: Equine
medicine and surgery, ed 3, vol 1, Santa Barbara, Calif, 1982, American Veterinary
Publications.
© 2004 American Veterinary Publications
2004
Since January 2020 Elsevier has created a COVID-19 resource centre with free information
in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre
is hosted on Elsevier Connect, the company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related research that is
available on the COVID-19 resource centre - including this research content - immediately
available in PubMed Central and other publicly funded repositories, such as the WHO
COVID database with rights for unrestricted research re-use and analyses in any form
or by any means with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
The initial assessment begins during presentation of the fetus. Although the following
applies primarily to attending the birth of a foal from a high-risk pregnancy, one
can perform quiet and rapid evaluation during any attended birth. The goal in a normal
birth with a normal foal is to disturb the bonding process minimally. This goal also
applies to high-risk parturitions, but some disruption of normal bonding is inevitable.
The lead clinician should control tightly the number of persons attending, and the
degree of activity surrounding, the birth.
One should evaluate the strength and rate of any palpable peripheral pulse and should
evaluate the apical pulse as soon as the chest clears the birth canal. Bradycardia
(pulse <40 beats/min) is expected during forceful contractions, and the pulse rate
should increase rapidly once the chest clears the birth canal. Persistent bradycardia
is an indication for rapid intervention.
The fetus is normally hypoxemic compared with the newborn foal, and this hypoxemia
is largely responsible for the maintenance of fetal circulation by generation of pulmonary
hypertension. The fetus responds to conditions producing more severe in utero hypoxia
by strengthening the fetal circulatory pattern, and the neonate responds to hypoxia
by reverting to the fetal circulatory pattern.
80
During a normal parturition, mild asphyxia occurs and results in fetal responses that
pave the way for a successful transition to extrauterine life. If more than mild transient
asphyxia occurs, the fetus is stimulated to breathe in utero; this is known as primary
asphyxia.
81
If the initial breathing effort resulting from the primary asphyxia does not correct
the asphyxia, a second gasping period occurs in several minutes, known as the secondary
asphyxia response. If no improvement in asphyxia occurs during this period, the foal
enters secondary apnea, a state that is irreversible except with resuscitation.
Therefore the first priority of neonatal resuscitation is establishing an airway and
breathing pattern. One should assume that foals not spontaneously breathing are in
secondary apnea and should clear the airway of membranes as soon as the nose is presented.
If meconium staining is present, one should suction the airway before delivery of
the foal is completed and before the foal breathes spontaneously. One should continue
to the trachea if aspiration of the nasopharynx is productive. Overzealous suctioning
worsens bradycardia as it worsens hypoxia. One should stop suctioning once the foal
begins breathing spontaneously, as hypoxia will worsen with continued suction. If
the foal does not breathe or move spontaneously within seconds of birth, one should
begin tactile stimulation. If tactile stimulation fails to result in spontaneous breathing,
one immediately should intubate the foal and manually ventilate the foal using an
Ambu-bag or equivalent. One can use mouth-to-nose ventilation if nasotracheal tubes
and an Ambu-bag are not available. The goal of this therapy is to reverse fetal circulation,
and hyperventilation with 100% oxygen is the best choice for this purpose. However,
recent evidence suggests that no clinical disadvantages are apparent in using room
air for ventilation of asphyxiated human neonates rather than 100% oxygen.82, 83 Human
infants resuscitated with room air recovered more quickly than those resuscitated
with 100% oxygen in one study as assessed by Apgar scores, time to the first cry,
and the sustained pattern of breathing.
84
In addition, neonates resuscitated with 100% oxygen exhibited biochemical findings
reflecting prolonged oxidative stress, present even after 4 weeks of postnatal life,
which did not appear in the group resuscitated with room air. Thus the current accepted
recommendations for using 100% oxygen in the resuscitation of asphyxiated neonates
needs further discussion and investigation.85, 86 Almost 90% of foals requiring resuscitation
respond to hyperventilation alone and require no additional therapy. One can initiate
nasotracheal intubation while the foal is in the birth canal if the foal will not
be delivered rapidly, such as with a difficult dystocia. This technique is “blind”
and requires some practice but may be beneficial and lifesaving. Once spontaneous
breathing is present, one should provide humidified oxygen via nasal insufflation
at 8 to 10 L/min.
One should initiate cardiovascular support in the form of chest compression if the
foal remains bradycardic despite ventilation and a nonperfusing rhythm is present.
One should make sure the foal is on a hard surface in right lateral recumbency with
the topline against a wall or other support. Approximately 5% of foals are born with
fractured ribs and an assessment for the presence of rib fractures is in order before
initiating chest compressions.
87
Palpation of the ribs identifies many of these fractures, which usually are multiple
and consecutive on one side of the thorax and located in a relatively straight line
along the part of the rib with the greatest curvature dorsal to the costochondral
junction. Unfortunately, ribs 3 to 5 frequently are involved, and their location over
the heart can make chest compression a potentially fatal exercise. Auscultation over
the ribs during breathing results in a recognizable click, identifying rib fractures
that may have escaped detection by palpation.
One should initiate drug therapy if a nonperfusing rhythm persists for more than 30
to 60 seconds in the face of chest compression. Epinephrine is the first drug of choice
(Table 19-3
). Practitioners pose various arguments regarding the best dose and the best frequency
of administration for resuscitation. However, most of the data are acquired from human
cardiac arrest studies and are not strictly applicable to the equine neonate because
the genesis of the cardiovascular failure is different.88, 89 Vasopressin is gaining
attention as a cardiovascular resuscitation drug, and although the author has used
this drug in resuscitation and as a pressor, experience is limited at this time.
90
The author does not use atropine in bradycardic newborn foals because the bradycardia
usually is caused by hypoxia, and if the hypoxia is not corrected, atropine can increase
myocardial oxygen debt.
89
The author also does not use doxapram because it does not reverse secondary apnea,
the most common apnea in newborns.
TABLE 19-3
Resuscitation Drugs Used for Cardiopulmonary Resuscitation of Foals*
DOSE
DRUG
HOW SUPPLIED
PER kg
ml/kg
ml/30 kg
ml/40 kg
ml/50 kg
Epinephrine (low dose)
1 mg/ml (1:1000)
0.01–0.02 mg
0.01–0.02
0.3–0.6
0.4–0.8
0.5–1
3–5 minutes
Epinephrine (high dose)
1 mg/ml (1:1000)
0.1–0.2 mg
0.1–0.2
3–6
4–8
5–10
3–5 minutes
Lidocaine
2% (20 mg/ml)
1.5 mg
0.075
2.25
3
3.75
Every 5 minutes for a maximum of 3 mg/kg
Bretylium
50 mg/ml
5–10 mg (30–35 mg/kg maximum dose)
0.1–0.2
3–6
4–8
5–10
10 minutes
Atropine
0.54 mg/ml
0.02 mg
0.037
1.1
1.5
1.8
Maximum of 2 times
CaCl
10% solution
0.5–1.0 mEq
0.2
6
8
10
NaHCO3
1 mEq/ml
0.5–1 mEq
0.5–1
15–30
20–40
25–50
MgSO4
50% (500 mg/ml)
14–28 mg
0.028–0.056
0.8–1.7
1.1–2.2
1.4–2.8
*
Epinephrine is the most commonly used of the drugs.
Because birthing areas are generally cold, one should dry the foal and place it on
dry bedding once resuscitation is complete. The fetus has some homeothermic mechanisms,
but its size in relation to its mother and its position within her body means that
it is in effect a poikilotherm. The body temperature of the foal generally reflects
that of its environment, namely its mother, although the human fetal temperature directly
measured at cesarean section, induction of labor, or during labor is approximately
0.5° C higher than the mothers.91, 92 Adaptation from poikilothermy to homeothermy
normally takes place rapidly following birth. The fetus is capable of nonshivering
thermogenesis, primarily through the oxidation of brown fat reserves, but this type
of thermogenesis is inhibited in utero, probably by placental prostaglandin E2 and
adenosine.93, 94 Immediately after birth the foal must adapt to independent thermoregulation.
Local physical factors, including ambient temperature and humidity, act to induce
cold stress, and the newborn must produce heat by metabolic activity. In response
to the catecholamine surge associated with birth, uncoupling of oxidative phosphorylation
occurs within mitochondria, releasing energy as heat. This nonshivering thermogenesis
is impaired in newborns undergoing hypoxia or asphyxiation and in those that are ill
at birth. Infants born to mothers sedated with benzodiazepines are affected similarly,
a consideration in the choice of sedative and preanesthetic medications in mares suffering
dystocia or undergoing cesarean section.95, 96, 97 Heat losses by convection, radiation,
and evaporation are high in most areas where foals are delivered, resuscitated, and
managed, and one must take care to minimize cold stress in the newborn and the critically
ill foal. Supplementary heat, in the form of radiant heat lamps or warm air circulating
blankets, may be required.
One should use fluid therapy conservatively during postpartum resuscitation, for the
neonate is not volume depleted unless excessive bleeding has occurred. Some compromised
newborn foals are actually hypervolemic. Fluid therapy of the neonate is discussed
in more detail later in this chapter. Because the renal function of the equine neonate
is substantially different from the adult, one cannot simply scale down fluid therapy
from adult therapy.98, 99, 100 If intravenous fluids are required for resuscitation
and blood loss is identified, administration of 20 ml/kg of a non–glucose-containing
polyionic isotonic fluid over 20 minutes (about 1 L for a 50-kg foal) once intravenous
access is established can be effective. The author stresses non–glucose-containing
polyionic intravenous fluids because hyperglycemia, but not hypoglycemia, immediately
after fetal or neonatal asphyxia interfered with the recovery of brain cell membrane
function and energy metabolism in neonatal piglets in one recent study.
101
These findings suggest that post–hypoxic-ischemic hyperglycemia is not beneficial
and might even be harmful in neonatal hypoxic-ischemic encephalopathy. Indications
for this shock bolus therapy include poor mentation, poorly palpable peripheral pulses,
and the development of cold distal extremities, compatible with hemorrhagic shock.
One should reassess the patient after the initial bolus and administer additional
boluses as necessary. Ideally, one should follow up on blood pressures and ECG readings
and initiate appropriate pressor therapy if needed. Again, these procedures are discussed
in detail later in the chapter.
One can administer glucose-containing fluids after resuscitation at a rate of 4 to
8 mg/kg/min (about 250 ml/hr of 5% dextrose or 125 ml/hr of 10% dextrose) to the average
50-kg foal, particularly in the obviously compromised foal. This therapy is indicated
to help resolve metabolic acidosis, to support cardiac output because myocardial glycogen
stores likely have been depleted, and to prevent postasphyxial hypoglycemia. Under
normal conditions, the fetal-to-maternal blood glucose concentration gradient is 50%
to 60% in the horse, and glucose is the predominant source of energy during fetal
development.102, 103 Glucose transport across the placenta is facilitated by carrier
receptors (glucose transporter [GLUT] receptors), and a direct relationship exists
between maternal and fetal blood glucose concentration when maternal glucose is in
the normal range.
102
The GLUT receptors in the placenta are stereospecific, saturable, and energy independent.
104
Although the enzyme kinetics for GLUT isoform 1 suggest that they are not saturable
under conditions of euglycemia, equine maternal hyperglycemia results in increased
fetal glucose concentration to a plateau point, likely caused by GLUT saturation.
At term, the net umbilical uptake of glucose is 4 to 7 mg/kg/min, with most of the
glucose being used by the brain and skeletal muscle.105, 106, 107 The fetus only develops
gluconeogenesis under conditions of severe maternal starvation. A certain percentage
of the delivered glucose is used to develop large glycogen stores in the fetal liver
and cardiac muscle in preparation for birth, and at birth the foal liver produces
glucose at a rate of 4 to 8 mg/kg/min by using these stores. Fetal glycogen stores
also are built using the substrates lactate, pyruvate, and alanine; fetal uptake of
lactate across the placenta is about half that of glucose.102, 108 The transition
to gluconeogenesis, stimulated by increased circulating catecholamine concentration
from birth and by stimulation of glucagon release at the time the umbilical cord breaks
takes 2 to 4 hours in the normal foal, and glycogenolysis supplies needed glucose
until feeding and glucose production are accomplished.
109
In the challenged foal, glycogen stores may have been depleted and gluconeogenesis
delayed, so provision of glucose at rates similar to what the liver would normally
produce during this period is requisite.
PERSISTENT PULMONARY HYPERTENSION
Persistent pulmonary hypertension (PPH) also is known as reversion to fetal circulation
or persistent fetal circulation, and its genesis lies in the failure of the fetus
to make the respiratory and cardiac transition to extrauterine life successfully or
reversion of the newborn to fetal circulatory patterns in response to hypoxia or acidosis.
Differentiating this problem from other causes of hypoxemia in the newborn requires
some investigation, and multiple serial arterial blood gas analyses are necessary
to confirm suspicion of this problem (see the section on arterial blood gas analysis,
Respiratory Diseases Associated with Hypoxemia in the Neonate). However, one should
suspect the condition in any neonate with hypercapnic hypoxemia that persists and
worsens; these foals are in hypoxemic respiratory failure. The fetal circulatory pattern,
with pulmonary hypertension and right-to-left shunting of blood through the patent
foramen ovale and ductus arteriosus, is maintained in these cases.
Pulmonary vascular resistance falls at delivery to about 10% of fetal values, while
pulmonary blood flow increases accordingly.
110
Early in the postnatal period these two changes balance each other, and mean pulmonary
and systolic pressures remain increased for several hours. Systolic pulmonary pressures
can remain equivalent to systemic pressure for up to 6 hours of age in human infants,
although diastolic pulmonary pressures are well below systemic diastolic pressures
by 1 hour.
111
Mean pulmonary artery pressures fall gradually over the first 48 hours.
112
The direct effects of lung expansion and increasing alveolar oxygen tension probably
provide the initial stimulus for pulmonary arteriolar dilation and partly result from
direct physical effects, but vasoactive substances are released in response to physical
forces associated with ventilation, for example prostacyclin.
110
Other vasoactive mediators thought to play a role in regulating pulmonary arteriolar
tone include NO, prostaglandins D2 and E2, bradykinin, histamine, endothelin-1, angiotensin
II, and atrial natriuretic peptide. The increase in alveolar and arterial oxygen tensions
at birth is required for completion of resolution of pulmonary hypertension. Much
of this increase is thought to be mediated by NO, evidence for this being the parallel
increase during gestation of the pulmonary vasodilation response to hyperoxia and
the increase in NO synthesis.
113
However, inhibition of NO synthesis does not eliminate the initial decrease in pulmonary
artery resistance occurring because of opening of the airways.
114
When these mechanisms fail, one can recognize PPH. Right-to-left shunting within the
lungs and through patent fetal conduits occurs and can result from many factors, including
asphyxia and meconium aspiration, but in many cases the precipitating trigger is unknown.
Inappropriately decreased levels of vasodilators (NO) and inappropriately increased
levels of vasoconstrictors (endothelin-1) currently are being examined as potential
mechanisms. Chronic in utero hypoxia and acidosis may result in hypertrophy of the
pulmonary arteriolar smooth muscle.
115
In these cases, reversal of PPH can be difficult and cannot be achieved rapidly.
Treatment of PPH is twofold: abolishment of hypoxia and correction of the acidosis,
for both abnormalities only bolster the fetal circulatory pattern. Initial therapy
is provision of oxygen intranasally at 8 to 10 L/min. Some foals respond to this therapy
and establish neonatal circulatory patterns within a few hours. Failure to improve
or worsening of hypoxemic respiratory failure following intranasal oxygen administration
should prompt intubation and mechanical ventilation with 100% oxygen. This serves
two purposes, one diagnostic and one therapeutic. Ventilation with 100% oxygen may
resolve PPH and, if intrapulmonary shunt and altered ventilation-perfusion relationships
are causing the hypoxic respiratory failure, arterial oxygen tension (Pao
2) should exceed 100 mm Hg under these conditions. Failure to improve Pao
2 suggests PPH or large right-to-left extrapulmonary shunt caused by congenital cardiac
anomaly. The vasodilators prostacyclin and telazoline (an α-blocking vasodilator)
cause pulmonary vasodilation in human infants with PPH, but the effects on oxygenation
vary and the side-effects (tachycardia, severe systemic hypotension) are unacceptable.
116
Recognition of NO as a potent dilator of pulmonary vessels has created a significant
step forward in the treatment of these patients, for inhaled NO dilates vessels in
ventilated portions of the lung while having minimal effects on the systemic circulation.
117
Based on evidence presently available, use of inhaled NO in an initial concentration
of about 20 ppm in the ventilatory gas seems reasonable for term and near-term foals
with hypoxic respiratory failure and PPH that fails to respond to mechanical ventilation
using 100% oxygen alone.117, 118 The author has used this approach in the clinic,
administering a range of 5 to 40 ppm NO with success.
PERINATAL ASPHYXIA SYNDROME
Hypoxic ischemic encephalopathy (HIE), currently referred to as neonatal encephalopathy
in the human literature, is one systemic manifestation of a broader syndrome of perinatal
asphyxia syndrome (PAS), and management of foals with signs consistent with a diagnosis
of HIE requires the clinician to examine other body systems fully and to provide therapy
directed at treating other involved systems.
119
Although PAS primarily manifests as HIE, the gastrointestinal tract and kidneys frequently
are affected by peripartum hypoxia/ischemia/asphyxia, and one should expect complications
associated with these systems. Hypoxic ischemic encephalopathy also may affect the
cardiovascular and respiratory systems, and one also may encounter endocrine disorders
in these patients.
Hypoxic ischemic encephalopathy has been recognized as one of the most common diseases
of the equine neonate for generations.1, 10, 12 In the past HIE has been known as
dummy foal syndrome and as neonatal maladjustment syndrome. The designation HIE, although
not perfect, attempts to describe the syndrome in terms of the suspected underlying
pathophysiology.
A wide spectrum of clinical signs is associated with HIE and can range from mild depression
with loss of the suck reflex to grand mal seizure activity. Typically, affected foals
are normal at birth but show signs of central nervous system abnormalities within
a few hours after birth. Some foals are obviously abnormal at birth, and some do not
show signs until 24 hours of age. Hypoxic ischemic encephalopathy commonly is associated
with adverse peripartum events, including dystocia and premature placental separation,
but a fair number of foals have no known peripartum period of hypoxia, suggesting
that these foals result from unrecognized in utero hypoxia (Box 19-2
). Severe maternal illness also may result in foals born with PAS. In human beings,
ascending placental infection now is suspected of being a major contributor to neonatal
encephalopathy in infants, and the incidence of neonatal encephalopathy increases
with the presence of maternal fever, suggesting a role for maternal inflammatory mediators.
120
BOX 19-2
CAUSES OF HYPOXIA IN THE FETUS AND NEONATE
Maternal Causes
Reduced maternal oxygen delivery
Maternal anemia
Maternal pulmonary disease with hypoxemia
Maternal cardiovascular disease
Reduced uterine blood flow
Maternal hypotension (endotoxemia/colic)
Maternal hypertension (laminitis/painful conditions)
Abnormal uterine contractions
Anything that increases uterine vascular resistance
Placental Causes
Premature placental separation
Placental insufficiency; for example, twins
Placental dysfunction
Fescue toxicity
Postmaturity
Placentitis
Placenta edema
Reduced umbilical blood flow
General anesthesia of the dam
Congenital cardiovascular disease
Inappropriate fetal blood distribution
Fetal hypovolemia
Excessive length of umbilical cord
Intrapartum Causes
Dystocia
Premature placental separation
Uterine inertia
Oxytocin induction of labor
Cesarean section
General anesthesia
Poor uterine blood flow because of maternal positioning
Decreased maternal cardiac output
Reduced umbilical blood flow
Effects of anesthetic drugs on fetus
Anything that prolongs stage 2 labor
Neonatal Period Causes
Prematurity
Recumbency
Musculoskeletal disease
Sepsis
Prematurity
Mild hypoxic ischemic encephalopathy
Pulmonary disease
Meconium aspiration
Milk aspiration
Persistent pulmonary hypertension
Septic pneumonia
Acute respiratory distress syndrome or acute lung injury
Severe disturbance in breathing pattern
Septic shock
Anemia
Neonatal isoerythrolysis
Excessive umbilical bleeding
Fractured ribs (hemothorax) or long bone fracture
Congenital cardiovascular disease
© 2004
2004
Since January 2020 Elsevier has created a COVID-19 resource centre with free information
in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre
is hosted on Elsevier Connect, the company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related research that is
available on the COVID-19 resource centre - including this research content - immediately
available in PubMed Central and other publicly funded repositories, such as the WHO
COVID database with rights for unrestricted research re-use and analyses in any form
or by any means with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Adapted from Palmer JE: Perinatal hypoxic-ischemic disease. Proceedings of the International
Veterinary Emergency Critical Care Symposium, San Antonio, Tex., 1998. p 717-718.
The underlying pathophysiologic details of HIE in the foal are unknown, and to date
accurate experimental models of HIE and PAS in the foal have not been described. However,
a great deal of attention has been paid to peripartum hypoxia/asphyxia by human counterparts
because the effects of adverse peripartum events in the human neonate have far ranging
implications for the affected human neonate and for society. Therefore equine neonatologists
have long looked to human studies and models of the human disease for understanding
of the syndrome in the equine neonate.
Perinatal brain damage in the mature fetus usually results from severe uterine asphyxia
caused by an acute reduction of uterine or umbilical circulation. The fetus responds
to this challenge by activation of the sympathetic adrenergic nervous system, causing
a redistribution of cardiac output that favors the central organs: brain, heart, and
adrenal glands.121, 122 If the hypoxic insult continues, the fetus reaches a point
beyond which it cannot maintain this centralization of circulation, cardiac output
falls, and cerebral circulation diminishes.
122
The loss of oxygen results in a substantial decrease in oxidative phosphorylation
in the brain with concomitant decreased energy production. The Na+/K+ pump at the
cell membrane cannot maintain the ionic gradients, and the membrane potential is lost
in the brain cells. In the absence of the membrane potential, calcium flows down its
large extracellular/intracellular concentration gradient through voltage-dependent
ion channels into the cell. This calcium overload of the neuron leads to cell damage
by activation of calcium-dependent proteases, lipases, and endonucleases. Protein
biosynthesis is halted. Calcium also enters the cells by glutamate-regulated ion channels
as glutamate, an excitatory neurotransmitter, is released from presynaptic vesicles
following anoxic cellular depolarization. Once the anoxic event is over, protein synthesis
remains inhibited in specific areas of the brain and returns to normal in less vulnerable
areas of the brain. Loss of protein synthesis appears to be an early indicator of
cell death caused by the primary hypoxic/anoxic event.
123
A second wave of neuronal cell death occurs during the reperfusion phase and is thought
to be similar to classically described postischemic reperfusion injury in that damage
is caused by production of and release of oxygen radicals, synthesis of NO, and inflammatory
reactions.
124
Additionally, an imbalance between excitatory and inhibitory neurotransmitters occurs.
123
Part of the secondary cell death that occurs is thought to be caused by apoptosis,
a type of programmed cell death termed cellular suicide. Secondary cell death also
is thought be caused by the neurotoxicity of glutamate and aspartate resulting again
from increased intracellular calcium levels.125, 126 In human infants the distribution
of lesions with hypoxic-ischemic brain damage following prenatal, perinatal, or postnatal
asphyxia falls into distinct patterns depending on the type of hypoxia-ischemia rather
than on postconceptual age at which the asphyxial event occurs.
126
Periventricular leukomalacia was associated with chronic hypoxia-ischemia, whereas
the basal ganglia and thalamus were affected primarily in patients experiencing acute
profound asphyxia, providing direct evidence that the nature of the event determines
the severity and distribution of neurologic damage in human beings. These remarkably
selective patterns of injury in children, with differential variability in the damage
caused to regions anatomically located within millimeters of each other, resulted
in the hypothesis that location within neurotransmitter-specific circuitry loops is
important. This hypothesis has important implications in the design of neuroprotective
strategies and therapies for neonates experiencing hypoxic-ischemic-asphyxial events.
Now the evidence is overwhelming that the excitotoxic cascade that evolves during
HIE extends over several days from the time of insult and is modifiable.125, 126
In brain injury, traumatic or hypoxic, the mechanisms underlying delayed tissue injury
still are understood poorly. Many believe that neurochemical changes, including excessive
neurotransmitter release, are pivotal in the pathophysiology of secondary neuronal
death. Excitatory amino acid neurotransmitters and magnesium are known to play at
least a minimal role in secondary cell death following brain injury; a fair body of
literature regarding these factors has been generated over the last 10 years. The
activation of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors is implicated
in the pathophysiology of traumatic brain injury and is suspected to play a role in
HIE.125, 126, 127 Mechanically injured neurons demonstrate a reduction of voltage-dependent
Mg2+ blockade of NMDA current that can be restored partially by increasing extracellular
Mg2+ concentration or by pretreatment with calphostin C, a protein kinase C inhibitor.
128
This finding suggested that administration of Mg2+ to patients with brain injury could
lead to improved outcome. Subsequently, magnesium sulfate solution was shown to improve
dramatically the immediate recovery of rats from hypoxia.
129
However, although pretreatment with magnesium sulfate protected against hypoxic ischemic
brain injury, postasphyxial treatment worsened brain damage in 7-day-old rats, suggesting
an age-related response in the rat.
130
Delayed magnesium treatment of mature rats following severe traumatic axonal brain
injury improved motor outcome when administered up to 24 hours after injury, with
early treatments providing the most benefit.
131
Maternal seizure in rats is associated with fetal histopathologic changes that are
abolished by administration of magnesium sulfate to the mother, and magnesium sulfate
has been demonstrated to protect the fetal brain from severe maternal hypoxia.
132
Clinical trials investigating the efficacy of magnesium treatment following hypoxia
in infants are under way, with few reports currently in the medical literature. Magnesium
sulfate was used to treat nine infants after perinatal asphyxia in one study (no control
group), and all children were neurologically normal at 1 year of age. Seizures did
not occur in any of these children, nor were any adverse side effects noted.
133
Magnesium sulfate administration failed to delay the global impairment in energy metabolism
after hypoxia ischemia, characteristic of severe brain damage, in newborn piglets;
at 48 hours after hypoxia ischemia, no difference could be found in the severity of
injury in piglets treated with magnesium compared with piglets treated with placebo,
suggesting magnesium may not be protective with severe acute injury.
134
In developing countries, birth hypoxia frequently is associated with HIE, and although
this finding is attributed most frequently to inadequate obstetric care, poor nutrition
also may play a role. Red blood cell magnesium levels were measured in more than 500
women in labor at a teaching hospital in South Africa.
135
Fifty five of the women delivered infants with HIE and had significantly lower levels
of magnesium than controls; the infants with HIE also had significantly lower magnesium
levels than controls. The large majority (54 of 55) of the women giving birth to HIE
infants were from poor social circumstances, suggesting nutrition might play a role
in some cases of HIE, with maternal magnesium levels affecting outcome in the infants.
The authors suggested an early pregnancy intervention study may help determine the
role of magnesium in the pathogenesis of HIE in human infants born to at-risk mothers.
Therapy for the various manifestations of hypoxia-ischemia involves control of seizures,
general cerebral support, correction of metabolic abnormalities, maintenance of normal
arterial blood gas values, maintenance of tissue perfusion, maintenance of renal function,
treatment of gastrointestinal dysfunction, prevention and recognition and early treatment
of secondary infections, and general supportive care. Control of seizures is important
because cerebral oxygen consumption increases fivefold during seizures. One can use
diazepam for emergency control of seizures (Table 19-4
). If diazepam does not stop seizures readily or one recognizes more than two seizures,
then one should replace diazepam with phenobarbital given to effect. The half-life
of phenobarbital can be long in the foal (100 hours), and one should keep this in
mind when monitoring neurologic function in these cases after phenobarbital administration
(J.E. Palmer, personal communication, 1998).
136
Early-stage, preseizure administration of phenobarbital has been advocated by some
investigators for prevention of neonatal encephalopathy. However, one recent study
in asphyxiated human infants demonstrated that early phenobarbital treatment was associated
with a threefold increase in the incidence of subsequent seizures and consequently
a trend toward increased mortality. Seizures per se were associated with almost a
twentyfold increase in mortality. Their findings suggest that early phenobarbital
administration may produce adverse rather than beneficial effects following asphyxia.
Because this was an observational study; the results need to be confirmed by appropriate
randomized trials in similar clinical settings.
137
If phenobarbital fails to control seizures, one may attempt phenytoin therapy. In
cases of HIE, one should avoid ketamine and xylazine because of their association
with increased intracranial pressure. One must protect the foal from injury during
a seizure and also ensure the patency of the airway to prevent the onset of negative
pressure pulmonary edema
138
or aspiration pneumonia.
TABLE 19-4
Drugs Used to Control or Prevent Seizures in Foals
DRUG
DOSE
ROUTE
FREQUENCY
COMMENT
Diazepam
5–10 mg per foal
IV*
As needed
Short-term seizure control
Phenobarbital
2–3 mg/kg
IV
Bolus to effect
Bolus over 15–20 minutes. Half-life can be prolonged; decreases thermoregulatory control,
respiratory drive, and blood pressure
Phenytoin
5–10 mg/kg loading; 5 mg/kg maintenance
IV
q4h for first 24 hours; then b.i.d. (?)
Seizure control
Magnesium sulfate†
0.05 mg/kg/hr loading dose; 0.025 mg/kg/hr maintenance‡
IV
Constant rate infusion for first hour and for maintenance
Discontinue if muscle tremors or hypotension occur. Treat for 24–48 hours after hypoxic
insult
Gabapentin
8 mg/kg
p.o.
b.i.d. to t.i.d.
Seizure control
*
IV, Intravenous.
†
To make 0.1 gm/ml solution, add 20 ml 50% MgSO4 to 80 ml 0.9% NaCl.
‡
Loading dose = 25 ml/hr of 0.1 gm/ml solution for 1 hour. Maintenance dose = 12 ml/hr
of 0.1 gm/ml solution.
Probably the most important therapeutic interventions are aimed at maintaining cerebral
perfusion, which is achieved by careful titration of intravenous fluid support, neither
too much nor too little (see Fluid Therapy in Neonates) and judicious administration
of inotropes and pressors to maintain adequate perfusion pressures (see Pressor and
Inotrope Therapy in Neonates). Cerebral interstitial edema is only truly present in
the most severe cases139, 140; in most cases the lesion is intracellular edema and
most of the classic agents used to treat cerebral interstitial edema (e.g., mannitol)
are minimally effective treating cellular edema. Occasionally the author uses thiamine
supplementation in the intravenous fluids to support metabolic processes, specifically
mitochondrial metabolism and membrane Na+,K+-ATPases, involved in maintaining cellular
fluid balance.141, 142 This therapy is rational and inexpensive but unproven in efficacy.
Only if cellular necrosis and vasogenic edema are present are drugs such as mannitol
and dimethyl sulfoxide indicated, and again these cases are usually the most severely
affected. In the author's clinic, practitioners rarely have used dimethyl sulfoxide
in neonates for the last several years and have recognized no change in outcome by
discontinuing its use. When the practitioners use intravenously administered dimethyl
sulfoxide, they do so within the first hour after an acute asphyxial insult and use
it primarily for its hydroxyl radical scavenging effects and its theoretical modulation
of postischemic reperfusion injury.
143
Naloxone has been advocated for treating HIE in human beings and in foals,144, 145,
146 perhaps based on a study suggesting that postasphyxia blood-brain barrier disruption
was related causally to poor neurologic outcome in a lamb model of HIE and that naloxone
prevented disruption and neurologic dysfunction among those survivors with an intact
blood-brain barrier.
145
However, other studies have demonstrated that naloxone exacerbates hypoxic-ischemic
brain injury in 7-day-old rats subjected to unilateral common carotid artery ligation
and hypoxia. Moreover, systemic acidosis and cellular edema were no different in naloxone-treated
animals compared with animals treated with saline solution. The authors concluded
that high doses of naloxone in fact may reduce the resistance of the fetus to hypoxic
stress.
146
The use of naloxone in human neonatal resuscitation remains controversial, for whether
the contradictory effects are related to a reduction in acute neuronal swelling by
osmotic effects or by a more direct receptor-mediated mechanism is currently unknown.
147
Naloxone is most effective in resuscitation of compromised human infants born to mothers
addicted to drugs. Some practitioners are using γ-aminobutyric acid adrenergic agonists
to manage HIE in foals, based on evidence showing neuroprotection when used in ischemia
alone and combined with NMDA antagonists.148, 149, 150 The author currently has no
experience with these compounds and cannot comment regarding their efficacy in foals.
Regional hypothermia also is being investigated as a potential therapy for global
hypoxia/ischemia; published data are consistent with the theory that cooling must
be continued throughout the entire secondary phase of injury (about 3 days) to be
effective.
151
Experimentally, this approach has resulted in dramatic decreases in cellular edema
and neuronal loss; its practical application remains to be demonstrated.
Despite a lack of consensus regarding the use of magnesium to treat infants with HIE,
the author has used magnesium sulfate infusion as part of the therapy for selected
foals with HIE for the past several years. The rationale is based primarily on the
evidence demonstrating protection in some studies and a failure of any one study to
demonstrate significant detrimental effects. The clinical impressions of the author
to date suggest that the therapy is safe and may decrease the incidence of seizure
in patients. The author administers magnesium sulfate as a constant rate infusion
over 1 hour after giving a loading dose. The author has continued the infusion for
up to 3 days without demonstrable negative effect beyond some possible trembling.
Given the current evidence, a 24-hour course of treatment may be effective and all
that is necessary. Postasphyxial treatment certainly may be beneficial in foals with
HIE, and maternal magnesium therapy may be beneficial in certain high-risk pregnancy
patients.
Foals with PAS often have a variety of metabolic problems including hypo- or hyperglycemia,
hypo- or hypercalcemia, hypo- or hyperkalemia, hypo- or hyperchloremia, and varying
degrees of metabolic acidosis. Although one needs to address these problems, one should
not forget the normal period of hypoglycemia that occurs postpartum and should not
treat aggressively so as to avoid worsening the neurologic injury. Foals suffering
from PAS also have frequent recurrent bouts of hypoxemia and occasional bouts of hypercapnia.
Intranasally administered oxygen is generally needed in these cases as a preventative
therapy and as direct treatment, for the appearance of the abnormalities can be sporadic
and unpredictable. Additional respiratory support, particularly in those foals with
centrally mediated hypoventilation and periods of apnea or abnormal breathing patterns,
include caffeine (per os or per rectum) and positive pressure ventilation. Caffeine
is a central respiratory stimulant and has minimal side effects at the dosages used
(10 mg/kg loading dose; 2.5 mg/kg as needed).
152
The author purchases whatever oral form of caffeine is available at the local convenience
store or drug store and administers it dissolved in warm water per rectum. Foals treated
with caffeine have an increased level of arousal and are more reactive to the environment.
Adverse effects generally are limited to restlessness, hyperactivity, and mild to
moderate tachycardia. Mechanical ventilation of these patients can be rewarding and
generally is required for less than 48 hours. One must monitor and maintain blood
pH within the normal range. Metabolic alkalosis can develop in some of these foals
and requires clinician tolerance of some degree of hypercapnia. pH is important in
evaluation and consideration of alternatives for treatment. If the respiratory acidosis
is not so severe as to affect the patient adversely (generally >70 mm Hg), and the
pH is within normal limits, the foal may tolerate hypercapnia.
153
The goal is to normalize pH. Foals with respiratory acidosis as compensation for metabolic
alkalosis do not respond to caffeine. Metabolic alkalosis in critically ill foals
frequently is associated with electrolyte abnormalities, creating differences in strong
ion balance. One handles this pH perturbation best by correcting the underlying electrolyte
problem.
Maintaining tissue perfusion and oxygen delivery to tissues is a cornerstone of therapy
for PAS to avoid additional injury. One should maintain the oxygen-carrying capacity
of the blood; some foals require transfusions to maintain a packed cell volume greater
than 20%. Adequate vascular volume is important, but one should take care to avoid
fluid overload in the foal. Early evidence of fluid overload is subtle accumulation
of ventral edema between the front legs and over the distal limbs. Fluid overload
can result in cerebral edema, pulmonary edema, and edema of other tissues, including
the gastrointestinal tract. This edema interferes with normal organ function and worsens
the condition of the patient. One maintains perfusion by supporting cardiac output
and blood pressure by judicious use of intravenous fluid support and inotrope/pressor
support. The author does not target therapy to a specific systolic, mean, or diastolic
pressure but monitors urine output, mentation, limb perfusion, gastrointestinal function,
and respiratory function as indicators that perfusion is acceptable. For these patients
to require pressor therapy is not unusual, but in some cases the hypoxic damage is
sufficiently severe to blunt the response of the patient to the drugs.
The kidney is a target for injury in patients with PPH, and for renal compromise to
play a significant role in the demise of these foals is not unusual. Clinical signs
of renal disease are generally referable to disruption of normal control of renal
blood flow and tubular edema leading to tubular necrosis and renal failure. These
foals have signs of fluid overload and generalized edema. One must balance urine output
and fluid therapy in these cases to prevent additional organ dysfunction associated
with edema. Although evidence has accumulated that neither dopamine nor furosemide
play a role in protecting the kidney or reversing acute renal failure, these agents
can be useful in managing volume overload in these cases.154, 155, 156 The aim is
not to drive oliguric renal failure into a high-output condition but rather to enhance
urine output.
Overzealous use of diuretics and pressors in these cases can result in diuresis requiring
increased intravenous fluid support and can be counterproductive. The author's approach
is more conservative. Low doses of dopamine administered as a constant rate infusion
of 2 to 5 μg/kg/min are usually effective in establishing diuresis by natriuresis.
One should avoid large doses of dopamine (>20 μg/kg/min) because high doses can produce
systemic and pulmonary vasoconstriction, potentially exacerbating PPH.
157
One can administer a bolus (0.25 to 1.0 mg/kg) or constant rate infusion (0.25 to
2.0 mg/kg/hr) of furosemide, but once furosemide diuresis is established, one must
evaluate electrolyte concentrations and blood gas tensions frequently because potassium,
chloride, and calcium losses can be considerable and because significant metabolic
alkalosis can develop from strong ion imbalances. The author does not aim for urine
production rates of 300 ml/hr, as has been presented by other authors as a urine output
goal for critically ill equine neonates.
158
Rather the author looks for urine output that is appropriate for fluid intake and
does not attempt to drive urine output to an arbitrary goal by excessive fluid administration
or pressor use. Although the average urine output for a normal equine neonate is about
6 ml/kg/hr (∼300 ml/hr for a 50-kg foal), these values were obtained from normal foals
drinking a milk diet with a large free water component.98, 99, 100 The urine of normal
newborn foals is dilute, reflecting the large free water load they incur by their
diet. Expecting critically ill foals to produce such large volumes of urine, particularly
those on restricted diets or receiving total parenteral nutrition, is an exercise
in futility, and manipulating fluid, pressor, or diuretic therapy in attempt to meet
an artificial goal is inappropriate. Fluid therapy in the critically ill neonate is
discussed later in this chapter.
One final caveat regarding renal dysfunction in PAS is that one should perform therapeutic
drug monitoring when it is available. Many antimicrobial agents used to manage these
cases, most notably the aminoglycosides, depend on renal clearance. Aminoglycoside
toxicity occurs in the equine neonate and exacerbates or complicates the management
of renal failure originally resulting from primary hemodynamic causes. The author
monitors aminoglycoside concentrations for 30-minute peak and 23- to 24-hour trough
values in these cases and adjusts dosage and frequency of drug administration based
on these results. The author considers a trough value of less than 2 μg/dl as desirable
for gentamicin and amikacin.
Foals with PAS suffer from a variety of problems associated with abnormalities within
the gastrointestinal tract.
159
Commonly they have ileus, recurrent excessive gastric reflux, and gas distention.
These problems are exacerbated by constant feeding in the face of continued dysfunction
and continued hypoxia. Frequently, enteral feeding cannot meet their nutritional requirements,
and partial or total parenteral nutrition is required. One must give special attention
to passive transfer of immunity (see Failure of Passive Transfer) and glucose homeostasis
in these cases. Although some practitioners use prokinetic agents as therapy for ileus
in these cases, the author's approach is again more conservative. Appearance of damage
to the gastrointestinal tract can be subtle and lag behind other clinical abnormalities
for days to weeks. Low-grade colic, decreased gastrointestinal motility, decreased
fecal output, and low weight gain are among the most common clinical signs of gastrointestinal
dysfunction in these case, but more severe problems, including necrotizing enterocolitis
and intussusception, have been associated with these cases. The return to enteral
feeding must be slow in many of these cases. A currently debated topic is constant
versus pulsed enteral feeding.160, 161, 162 The author uses pulsed feeding through
an indwelling small-gauge feeding tube. In many foals these tubes stay in place for
weeks and cause no problems as the foals are returned to their dams for sucking or
are trained to drink from a bottle or bucket.
Foals with PAS are also susceptible to secondary infection. Treatment of recognized
infection is covered under sepsis in this chapter. If infection is recognized in these
patients after hospitalization, one should give attention to the likelihood of nosocomial
infection and should direct antimicrobial therapy based on known nosocomial pathogens
in the NICU and their susceptibility patterns until culture and sensitivity results
become available. One should make repeat determinations of immunoglobulin G (IgG)
concentration; additional intravenous plasma therapy may be required. Nosocomial infections
are often rapidly overwhelming, and acute deterioration in the condition of a foal
with PAS should prompt a search for nosocomial infection.
The prognosis for foals with PAS is good to excellent when the condition is recognized
early and aggressively treated in term foals. Up to 80% of these neonates survive
and go on to lead productive and useful athletic lives.20, 21, 22, 23 The prognosis
decreases with delayed or insufficient treatment and concurrent problems such as prematurity
and sepsis.
PREMATURITY/DYSMATURITY/POSTMATURITY
In human NICUs the survival rates of low-gestation-length infants has increased dramatically
since the 1980s concurrent with improvements in obstetric and neonatal care. The now
routine, well-validated use of antenatal steroid and artificial surfactant therapies
has contributed greatly to the enhanced survival of this patient population, although
the use of these particular therapies is not common or frequently indicated in the
equine NICU.163, 164 However, with improved care, outcomes in the equine NICU population
have improved also, with survival of premature patients in many NICUs exceeding 80%.
21
In the equine population, gestation length is much more flexible than in the human
population; however, the definition of the term prematurity needs reexamination. Traditionally,
prematurity is defined as a preterm birth of less than 320 days of gestation in the
horse. Given the variability of gestation length in the horse, ranging from 310 days
to more than 370 days in some mares, a mare with a usual gestation length of 315 days
possibly could have a term foal at 313 days, whereas a mare with a usual gestation
length of 365 days may have a premature foal at 340 days, considered the normal gestation
length. Foals that are born postterm but are small are termed dysmature; a postmature
foal is a postterm foal that has a normal axial skeletal size but is thin to emaciated.
Dysmature foals may have been classified in the past as small for gestational age
and are thought to have suffered placental insufficiency, whereas postmature foals
are usually normal foals that have been retained too long in utero, perhaps because
of an abnormal signaling of readiness for birth, and have outgrown their somewhat
aged placenta. Postmature foals become more abnormal the longer they are maintained,
also may suffer from placental insufficiency, and are represented best by the classic
foal born to a mare ingesting endophyte-infested fescue.
165
Box 19-3
compares the characteristics of premature/dysmature foals with those of postmature
foals.
BOX 19-3
CLINICAL CHARACTERISTICS OF PREMATURE/DYSMATURE AND POSTMATURE FOALS
Premature/Dysmature
Low birth weight
Small frame; thin
Poor muscle development possible
Flexor laxity common
Periarticular laxity
Hypotonia more common
High chest wall compliance
Low lung compliance
Short, silky hair coat
Domed forehead
Floppy ears; poor cartilage development
Weak suck reflex
Poor thermoregulation
Gastrointestinal tract dysfunction
Delayed maturation of renal function: low urine output
Entropion with secondary corneal ulcers
Poor glucose regulation
Postmature
Normal to high birth weight
Large frame; thin
Poor muscle development possible
Flexor contraction common
Hypertonia more common
Long hair coat
Fully erupted incisors
Weak suck reflex
Poor thermoregulation
Gastrointestinal tract dysfunction
Delayed maturation of renal function: low urine output
Poor glucose regulation
Delayed time to standing
Hyperreactive
Poor postural reflexes
© 2004
2004
Since January 2020 Elsevier has created a COVID-19 resource centre with free information
in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre
is hosted on Elsevier Connect, the company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related research that is
available on the COVID-19 resource centre - including this research content - immediately
available in PubMed Central and other publicly funded repositories, such as the WHO
COVID database with rights for unrestricted research re-use and analyses in any form
or by any means with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Adapted from Palmer JE: Prematurity, dysmaturity, postmaturity. Proceedings of the
International Veterinary Emergency Critical Care Symposium, San Antonio, Tex., 1998.
pp 722-723.
The causes of prematurity/dysmaturity/postmaturity include the causes of high-risk
pregnancy presented in Box 19-1. Additional causes include iatrogenic causes such
as early elective induction of labor based on inaccurate breeding dates or misinterpretation
of late-term colic or uterine bleeding as ineffective labor. Most causes remain in
the category of idiopathic, with no discernible precipitating factor. Despite lack
of an obvious cause, premature labor and delivery does not just happen, and even if
undetermined, the cause may continue to affect the foal in the postparturient period.
All body systems may be affected by prematurity, dysmaturity, and postmaturity, and
thorough evaluation of all body systems is necessary.
Respiratory failure is common in these foals, although the cause usually is not surfactant
deficiency. Immaturity of the respiratory tract, poor control of respiratory vessel
tone, and weak respiratory muscles combined with poorly compliant lungs and a greatly
compliant chest wall contribute to respiratory failure in these cases. Most require
oxygen supplementation and positional support for optimal oxygenation and ventilation.
One must extend effort to maintain these “floppy foals” in sternal recumbency. Some
foals may require mechanical ventilation. These foals also require cardiovascular
support but are frequently unresponsive to commonly used pressors and inotropes: dopamine,
dobutamine, epinephrine, and vasopressin. Careful use of these drugs and judicious
intravenous fluid therapy are necessary. The goal should not be one of achieving specific
pressure values (e.g., mean arterial pressure of 60 mm Hg) but of adequate perfusion.
Renal function, reflected in low urine output, is frequently poor initially in these
cases because of delay in making the transition from fetal to neonatal glomerular
filtration rates.
166
The delay can result from true failure of transition or from hypoxic/ischemic insult.
One should approach fluid therapy cautiously in these cases; initial fluid restriction
may be in order to avoid fluid overload. Many premature/dysmature/postmature foals
have suffered a hypoxic insult and have all of the disorders associated with PAS,
including HIE. Treatment is similar to that of term foals with these problems. These
foals also are predisposed to secondary bacterial infection and must be examined frequently
for signs consistent with early sepsis or nosocomial infection.
The gastrointestinal system of these foals is not usually functionally mature, which
may result from a primary lack of maturity or from hypoxia. Dysmotility and varying
degrees of necrotizing enterocolitis are common. One commonly encounters hyperglycemia
and hypoglycemia. Hyperglycemia generally is related to stress, increased levels of
circulating catecholamines, and rapid progression to gluconeogenesis, whereas hypoglycemia
is associated with diminished glycogen stores, inability to engage gluconeongenesis,
sepsis, and hypoxic damage.
167
Immature endocrine function is present in many of these foals, particularly regarding
the hypothalamic-pituitary-adrenal axis, and contributes to metabolic derangements.168,
169 One should delay enteral feeding when possible until the foal is stable regarding
metabolic and cardiorespiratory parameters. On intiating enteral feeding, one should
provide small volumes initially and slowly increase the volume over several days.
One frequently encounters musculoskeletal problems, particularly in premature foals,
that include significant flexor laxity and decreased muscle tone. Postmature foals
frequently are affected by flexure contracture deformities, most likely because of
decreased intrauterine movement as they increase in size. Premature foals frequently
exhibit decreased cuboidal bone ossification that predisposes them to crush injury
of the carpal and tarsal bones if weight bearing is not strictly controlled. Physical
therapy in the form of standing and exercise is indicated in the management of all
these problems, but one should take care to ensure that the patient does not fatigue
or stand in abnormal positions. Bandaging of the limbs is contraindicated because
this only increases laxity, although light bandages over the fetlock may be necessary
to prevent injury to that area if flexor laxity is severe. The foals are predisposed
to angular limb deformity and must be observed closely and frequently for this problem
as they mature.
170
The overall prognosis for premature/dysmature/postmature foals remains good with intensive
care and good attention to detail. Many of these foals (up to 80%) survive and become
productive athletes.
21
Complications associated with sepsis and musculoskeletal abnormalities are the most
significant indicators of poor athletic outcome.
SEPSIS
The last 20 years have seen an explosion of new therapeutic agents purportedly useful
for treating sepsis. Unfortunately, clinical trials investigating these new therapies
have failed to demonstrate a positive effect, have shown negative results, or have
resulted in diametrically opposed study results, one showing a benefit and another
showing no benefit or a detrimental effect. On a positive note, the survival rate
of foals being treated for sepsis has improved. Work was done regarding foal diseases
and their treatment in the 1960s, but the field did not attract much serious attention
until the 1980s. Since that time almost every major veterinary college and many large
private referral practices have constructed NICUs or their equivalent. Next to hypoxic
ischemic asphyxial syndromes, sepsis is the number one reason for presentation and
treatment at these facilities. Neonatal septicemia of the horse has been the subject
of three international workshops,171, 172, 173 and a perinatology lecture covering
some aspect of neonatal sepsis has been presented at almost every large continuing
education meeting attended by equine veterinarians.
Concensus criteria conferences
1
in the early 1990s defined sepsis and septic shock for human beings.174, 175
Sepsis was defined as the systemic response to infection manifested by two or more
of the following conditions as a result of infection: a) temperature >38° C or <36°;
b) heart rate >90 beats/min; c) respiratory rate >20 breaths per minute or Paco
2 <32 torr; and d) white blood cell count >12,000 cell/μl, <4,000 cell/μl, or >10%
immature (band) forms. Septic shock was defined as sepsis induced hypotension or the
requirement for vasopressors/ionotropes to maintain blood pressure despite adequate
fluid resuscitation along with the presence of perfusion abnormalities that may include
lactic acidosis, oliguria, or acute alteration in mental status. These definitions
are broadly acceptable and applicable to neonatal sepsis in foals, and many of the
treatment modalities in human medicine have been applied in some manner to the equine
neonatal patient. Additional definitions that have come into vogue that are actually
useful at times, include the following: SIRS, the systemic inflammatory response system;
MODS, multiple organ system dysfuction; and MOFS, multiple organ failure syndrome.
(SIRS is sick, MODS is sicker, and MOFS is dying.) The compensatory response syndrome
(CARS) ideally balances SIRS and keeps it from becoming detrimental. If balance is
achieved, recovery is possible. Imbalance progresses to septic shock, MODS, and MOFS.
In horses, MODS is manifested most commonly as renal failure, hepatic failure, central
nervous system dysfunction, and disseminated intravascular coagulation. Managing the
septic patient involves early recognition of all the potential alphabet combinations
and supporting the patient or intervening in the face of multiple clinical consequences,
termed CHAOS (Cardiovacular compromise; Homeostasis; Apoptosis; Organ dysfunction;
Suppression of the immune system).
176
Inflammatory mediators are involved in all these processes and can be beneficial or
detrimental, depending on timing and opposing responses. Neutrophils, platelets, lymphocytes,
macrophages, and endothelial cells are involved, and the implicated inflammatory molecules
grow daily in numbers.
Sepsis in the foal initially can be subtle, and the onset of clinical signs varies
depending on the pathogen involved and the immune status of the foal. For the purposes
here, the discussion is limited to bacterial sepsis, but the foal also is susceptible
to viral and fungal sepsis, which can appear similar to bacterial sepsis. Failure
of passive transfer (FPT) of immunity can contribute to the development of sepsis
in a foal at risk.177, 178 Testing for and treating FPT has received attention in
the veterinary literature. It remains true, however, that foals presented to NICUs
that have an ultimate diagnosis of sepsis have FPT.16, 19 The current recommendation
is that foals have IgG levels greater than or equal to 800 mg/dl for passive transfer
to be considered adequate. Other risk factors for the development of sepsis include
any adverse advents at the time of birth, maternal illness, or any abnormalities in
the foal. Although the umbilicus frequently is implicated as a major portal of entry
for infectious organisms in the foal, the gastrointestinal tract may be the primary
site of entry.
179
Other possible portals of entry include the respiratory tract and wounds.
Early signs of sepsis include depression, decreased suck reflex, increased recumbency,
fever, hypothermia, weakness, dysphagia, failure to gain weight, increased respiratory
rate, tachycardia, bradycardia, injected mucous membranes, decreased capillary refill
time, shivering, lameness, aural petechia, and coronitis. If sepsis is recognized
early, patients with sepsis may have a good outcome, depending on the pathogen involved.
Gram-negative sepsis remains the most commonly diagnosed, but increasingly gram-positive
septicemia is being recognized.
180
Foals in intensive care units and at referral hospitals have an additional risk of
nosocomial infection. An attempt to isolate the organim involved early in the course
of the disease becomes important. If possible, one should obtain blood cultures, and
if localizing signs are present, one should obtain samples as deemed appropriate.
Cultures should be aerobic and anaerobic. Recently, work has been done evaluating
real-time polymerase chain reaction technology in sepsis in the foal as a means of
identifying causative organisms.181, 182 Until one obtains antimicrobial sensitivity
patterns for the pathogen involved, one should initiate broad-spectrum antimicrobial
therapy (Table 19-5
). Intravenously administered amikacin and penicillin are good first-line choices,
but one should monitor renal function closely. Other first-line antimicrobial choices
might include high-dose ceftiofur sodium or ticarcillin/clavulanic acid. One should
treat failure of passive transfer if present. One should provide intranasal oxygen
insufflation at 5 to 10 L/min even if hypoxemia is not present to decrease the work
of breathing and provide support for the increased oxygen demands associated with
sepsis.
183
Should arterial blood gas analysis reveal significant hypoventilation, one may administer
caffeine orally or per rectum to increase central respiratory drive. Mechanical ventilation
may be necessary in cases of severe respiratory involvement such as with acute lung
injury or acute respiratory distress syndrome. If the foal is hypotensive, one may
administer pressor agents or inotropes by constant rate infusion (Table 19-6
). Inotrope and pressor therapy generally is restricted to referral centers where
these drugs can be given as constant rate infusions and blood pressure can be monitored
closely. Some practitioners use nonsteroidal antiinflammatory agents and, in specific
circumstances, corticosteroids. Use of these drugs should be judicious because they
may have several negative consequences for the foal including renal failure and gastric/dunodenal
ulceration.184, 185, 186
TABLE 19-5
Antimicrobial Drugs Dosages Used in Foals in the Neonatal Intensive Care Unit
DRUG
DOSE
ROUTE
FREQUENCY
COMMENTS
Amikacin sulfate
25–30 mg/kg
IV*
s.i.d.
Requires therapeutic drug monitoring: peak >60; trough <2
Ampicillin trihydrate
20 mg/kg
p.o.
t.i.d.
Poor absorption noted in foals >2–3 weeks of age.
Sodium ampicillin
50–100 mg/kg
IV
q.i.d.
—
Amoxicillin trihydrate
20–30 mg/kg
p.o.
t.i.d.
Poor absorption noted in foals >2–3 weeks of age.
Cefotaxime
50–100 mg/kg
IV
q.i.d.
—
Cefuroxime (Ceftin)
30 mg/kg/day
p.o.
b.i.d., t.i.d.
Total daily dose is divided into 10 mg/kg t.i.d. or 15 mg/kg b.i.d.
Cephalexin
10 mg/kg
p.o.
q.i.d.
—
Ceftiofur (Naxcel)
10 mg/kg
IV
q.i.d.
Give slowly over 20 minutes as double-diluted volume in 0.9% saline.
Chloramphenicol palmitate
50 mg/kg
p.o.
q.i.d.
Public health concerns
Chloramphenicol succinate
10–25 mg/kg
IV
q.i.d.
Public health concerns
Enrofloxacin
2.5–10 mg/kg
IV, p.o.
s.i.d.
Chondropathy and arthropathy reported in foals.
Erythromycin stearate
20–30 mg/kg
p.o.
t.i.d. to q.i.d.
Avoid warm temperatures and high humidity. Colitis reported in dams of foals receiving
this drug.
Erythromycin lactiobionate
∼5 mg/kg
IV
Every 4–6 hours
—
Gentamicin sulfate
8.8 mg/kg
IV
s.i.d.
Requires therapeutic drug monitoring: peak >40; trough <2
Imipenem
10–20 mg/kg
IV
q.i.d.
Seizures reported as adverse reaction.
Metronidazole
15 mg/kg
p.o., as needed
q.i.d.
Anorexia can occur.
25 mg/kg
b.i.d.
Potassium penicillin Sodium penicillin
20,000–50,000 U/kg
IV
q.i.d.
Give potassium penicillin slowly over 5 to 10 minutes.
Rifampin
5 mg/kg
p.o.
b.i.d.
Always administer with second antimicrobial because of rapid development of resistance.
Ticarcillin
50–100 mg/kg
IV
q.i.d.
—
Ticarcillin and clavulonic acid (Timentin)
50–100 mg/kg
IV
q.i.d.
—
Trimethoprim-sulfonamide
30 mg/kg
p.o.
b.i.d.
—
Fluconazole
8 mg/kg loading; 4 mg/kg
p.o.
b.i.d.
—
*
IV, Intravenous.
Adapted from Palmer JE: Neonatal drug doses. Proceedings of the sixth International
Veterinary Emergency Critical Care Symposium, San Antonio, Tex., 2000.
© 2004
2004
Since January 2020 Elsevier has created a COVID-19 resource centre with free information
in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre
is hosted on Elsevier Connect, the company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related research that is
available on the COVID-19 resource centre - including this research content - immediately
available in PubMed Central and other publicly funded repositories, such as the WHO
COVID database with rights for unrestricted research re-use and analyses in any form
or by any means with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
TABLE 19-6
Inotrope and Pressor Medications Used in the Neonatal Intensive Care Unit*
DRUG
DOSE
ROUTE
COMMENT
Dopamine
3–20 μg/kg/min
IV-CRI†
Follow the rule of 6: 6 × mass of foal (kg) = number of milligrams to add to 100 ml
saline (1 ml/hr = 1 g/kg/min)
Dobutamine
3–40 μg/kg/min
IV-CRI
Epinephrine‡
0.2–2 μg/kg/min
IV-CRI
Norepinephrine‡
0.2–3 μg/kg/min
IV-CRI
Data fom Connoly Neonatal Intensive Care Unit, Kennet Square, Penn.
*
One should use these medications to effect and should monitor blood pressure during
their use.
†
IV-CRI, Intravenously at constant rate infusion.
‡
For epinephrine and norepinephrine, apply a “rule of 0.6” where 0.6 × mass of foal
(kg) = number of mg drug to add to 100 ml saline so 1 ml/hr = 0.1 μg/kg/min.
Nursing care is one of the most important aspects of treating septic foals. Foals
should be kept warm and dry. They should be turned at 2-hour intervals if they are
recumbent. Feeding septic foals can be a challenge if gastrointestinal function is
abnormal, and total parenteral nutrition may be needed. If at all possible, foals
should be weighed daily and blood glucose levels monitored frequently. Some foals
become persistently hyperglycemic on small glucose infusion rates. These foals may
benefit from constant rate low-dose insulin infusions (Table 19-7
). Recumbent foals must be examined frequently for decubital sore development, the
appearance of corneal ulcers, and for heat and swelling associated with joints and
physis.
TABLE 19-7
Miscellaneous Drugs Used in the Neonatal Intensive Care Unit
DRUG
DOSE
ROUTE
FREQUENCY
COMMENTS
Aminophylline
2–3 mg/kg
IV*
b.i.d. to q.i.d.
Monitor theophylline levels. Therapeutic: 6–12 μg/l Toxic: >20 μg/l
Caffeine
10 mg/kg loading dose 2.5 mg/kg maintenance
Orally as needed
s.i.d., b.i.d.
Steady state level: 5–20 μg/l Toxic: >50–75 μg/l
Dimethyl sulfoxide
1 g/kg
IV
Once
Administer as 5% to 10% solution; dimethyl sulfoxide is hypertonic.
Heparin
40–100 U/kg
SQ/IV
b.i.d.
—
Insulin (protamine zinc)
0.15 U/kg
IM/SQ
b.i.d.
—
Insulin (regular)
0.00125–0.2 U/kg/hr
IV
Constant rate Infusion
Pretreat lines: insulin adsorbs to lines.
*
IV, Intravenous; SQ, subcutaneous; IM, intramuscular.
Adapted from Palmer JE: Neonatal drug doses. Proceedings of the International Veterinary
Emergency Critical Care Symposium, San Antonio, Tex., 2000.
© 2004
2004
Since January 2020 Elsevier has created a COVID-19 resource centre with free information
in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre
is hosted on Elsevier Connect, the company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related research that is
available on the COVID-19 resource centre - including this research content - immediately
available in PubMed Central and other publicly funded repositories, such as the WHO
COVID database with rights for unrestricted research re-use and analyses in any form
or by any means with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
The prognosis for foals in the early stages of sepsis is fair to good. Once the disease
has progressed to septic shock the prognosis decreases, although short-term survival
rates are as good as those in human critical care units. Long-term survival and athletic
outcomes are fair. Racing breed foals that make it to the track perform similarly
to their age-matched siblings.
21
Other Diseases Causing Weakness In Foals
BOTULISM
Botulism is a neuromuscular disease of foals characterized by flaccid paralysis.
187
Although the disease is discussed in detail elsewhere in this text, the form most
commonly observed in foals, the toxicoinfectious form, deserves some specific comments.
The causative organism is Clostridium botulinum, an anaerobic organism. Although affected
adults usually acquire the disease by ingestion of preformed toxin elucidated from
the organism, in the foal less than 8 months of age the organism can survive and multiply
in the gastointestinal tract and produce necrotic foci within the liver, giving the
foal constant exposure to newly formed toxin. The horse is exquisitely sensitive to
the toxin, and only small quantities of toxin are required to produce clinical signs
and death in affected animals. The ɛ-toxin of C. botulinum binds to the presynaptic
membrane of motor neurons and prevents transmission of impulses by blocking the release
of acetylcholine from the presynaptic vessicles. This block produces the clinical
signs of muscle weakness, manifested in foals as trembling (shaker foals) or acute
recumbency.
188
Pupillary dilation, dysphagia, tremors, recumbency, and terminal respiratory distress
caused by respiratory muscle paralysis occur. Foals can be found acutely dead. In
endemic areas (the Northeast and mid-Atlantic regions of United States), for these
foals to be evaluated first as having colic is not unusual.
Treatment aims to neutralize the toxin by administration of botulinum antitoxin and
to provide antimicrobial treatment of the infection with penicillin, metronidazole,
and/or oxytetracycline.189, 190 At a minimum, feeding of milk replacer via indwelling
nasogastric tube at 20% of the body weight of the foal per day divided into every
2-hour meals is required. Many of these foals require respiratory support (in the
form of intranasal oxygen insufflation), because of respiratory muscle paralysis.
Respiratory acidosis is present on arterial blood gas analysis in most of these foals
because of hypoventilation and lateral recumbency, but they can tolerate some degree
of hypercapnia (Paco
2 ∼70 mm Hg) if the pH is normal and oxygenation (Pao
2 >70 mm Hg; percent oxygen saturation of hemoglobin, >90%) is adequate. Metabolic
alkalosis can accompany the respiratory acidosis, but this is a compensatory change
and resolves once gas exchange is normalized. Some of these patients require mechanical
ventilation, which may be lifesaving. One may discontinue mechanical ventilation as
clinical signs resolve and the respiratory muscles gain strength. Nursing care is
important, and these foals should be turned every 2 hours. They should be maintained
in sternal recumbency if possible and kept warm and dry. With good nursing care, good
nutritional support, and adequate respiratory support, the prognosis for these foals
is good. The limiting factor in the prognosis for life is often financial.
190
Foals that recover from the acute stage of this disease eventually fully recover.
Botulism is an expensive disease to treat and is also an entirely preventable disease.189,
190 All pregnant mares in endemic areas should be vaccinated against C. botulinum.
Vaccination does not prevent all cases of botulism, particularly if the foal has failure
of passive transfer or acquires the disease after maternal immunity wanes and before
its own vaccination.
NUTRITIONAL MUSCULAR DYSTROPHY (WHITE MUSCLE DISEASE)
Nutritional muscular dystrophy or white muscle disease is a vitamin E/selenium–responsive
muscle disease of horses of all ages probably caused by a dietary deficiency of selenium
and vitamin E.
191
The condition occurs most commonly in geographic areas with low selenium levels in
the soil, generally the northeastern, northwestern, Great Lakes and mid-Atlantic regions
of the United States.
Two forms of the disease are described in foals: the fulminant form, in which the
foal is found acutely dead, and the subacute form. In the fulminant form, death usually
is attributed to myocardial lesions resulting in cardiovascular collapse. The subacute
form is characterized by dysphagia and gait abnormalities primarily caused by stiffness
of the muscles of locomotion. Paralysis, if present, is not flaccid as in botulism.
Abnormal function of respiratory muscles may complicate the clinical situation. Aspiration
pneumonia may be present following problems associated with swallowing; the tongue
and pharyngeal muscles frequently are affected in the early stages of disease.
191
Foals with severe disease may have widespread muscle necrosis leading to hyperkalemia,
which can be severe and result in death of the foal. Serum activities of the muscle
enzymes creatine kinase and aspartate aminotransferase may be greatly increased. Diagnosis
is confirmed at necropsy or ante mortem by determination of decreased vitamin E, selenium,
and glutathione peroxidase concentrations in the blood of the foal before supplementation.
Myoglobinuria and acute renal failure are not uncommon in these foals.
Treatment of foals with nutritional muscular dystrophy is primarily supportive. One
should address all metabolic abnormalities. Some foals require intranasal oxygen insufflation.
Affected foals are unable to suck effectively, and one should provide enteral (via
an indwelling nasogastric tube) or parenteral nutritional support. Because of the
high likelihood of aspiration pneumonia, one should administer broad-spectrum antimicrobial
therapy parenterally. The patient should be kept quiet and should be stimulated minimally.
Affected foals should receive parenteral (intramuscular) vitamin E and selenium supplementation.
Selenium is toxic in large doses. The prognosis for severely affected foals is guarded.
For less severely affected foals the prognosis is good with appropriate treatment.
The disease is preventable by ensuring that mares receive sufficient vitamin E and
selenium while pregnant and by supplementing foals with parenteral injections of vitamin
E and selenium at birth in endemic areas. A more complete discussion of the pathophysiology
of this disease and the nutritional management is presented elsewhere in this text.
Diseases Causing Abnormal Mentation Or Other Neurologic Signs In Foals (Other Than
Perinatal Asphyxia Syndrome)
HEPATIC ENCEPHALOPATHY
Primary liver disease is uncommon in the foal and occurs primarily as a sequela to
sepsis. Clinical signs of severe liver disease may include depression, ataxia, and
seizures. In affected foals, increases in serum liver enzyme activities and concentrations
of ammonia and bile acids frequently can be identified. The mechanism(s) underlying
hepatoencephalopathy are not delineated clearly, although increased excitatory neurotransmitters,
or compounds that mimic their activity, are implicated. Hepatoencephalopathy is discussed
in more detail elsewhere in this text.
Tyzzer's disease (Clostridium piliformis infection) rarely causes primary liver disease
in foals from 4 to about 40 days of age. This disease is almost uniformly fatal. The
incubation period is short, and the mare is thought to be the carrier.192, 193, 194,
195, 196 Clinical signs range from acute death to depression, fever, and pronounced
icterus. The feces of affected foals may appear white to grey because of the lack
of bile. Clinicopathologic abnormalities include leukopenia, hyperfibrinogenemia,
metabolic acidosis, and hypoglycemia.197, 198 Liver lesions at postmortem are characterized
microscopically by multiple foci of necrosis. One usually can demonstrate variable
numbers of elongated, slender intracytoplasmic bacilli within hepatocytes bordering
the necrotic foci. Infiltration of the portal triads with inflammatory cells and biliary
duct hyperplasia and degeneration are observable. The bacillus also occurs in association
with myocardial lesions. Lesions in the intestine are characterised by mucosal necrosis
with inflammatory cell infiltration, increased mucus production, submucosal lymphoid
hyperplasia, and submucosal hemorrhage. Necrosis of lymphoid follicles, congestion,
and hemorrhage can be present in the spleen and mesenteric lymph nodes.
196
Affected foals may have a profound metabolic acidosis that is unresponsive to treatment.
The clinical course is short, and most affected foals die within a few hours of developing
neurologic signs.
Primary liver disease has been reported in association with ferrous sulfate administration
in a probiotic compound.
199
The lesion was massive hepatocellular necrosis and liver failure. The product is no
longer commercially available. Portosystemic shunt is rare in the foal but has been
reported in foals as young as 3 months of age.200, 201, 202
INFECTIOUS CAUSES
Most infectious causes of neurologic abnormalities in foals are associated with sepsis.
Although rarely reported, Halicephalobus gingivalis (deletrix) infection has been
reported in three foals; in one case the foal was 3 weeks of age.203, 204 Possibly
transmission in these cases was transmammary; the dam in one case died 1 year later
with confirmed H. deletrix infestation of her udder. Listeria monocytogenes has been
reported as a cause of neurologic disease in foals.
205
Recently, Sarcocystis neurona was identified as the causative agent of central nervous
system disease in a foal, and equine herpes myeloencephalitis has been diagnosed in
individual foals and in herd outbreaks involving foals.206, 207
Neospora also was reported in one foal recently.
208
Rhodococcus equi abscesses can form in the central nervous system or cause neurologic
signs associated with compression, as with vertebral body abscesses.209, 210, 211
OTHER DISEASES
Cerebellar hypolasia, occipitoatlantoaxial malformation, and agenesis of the corpus
callosum with cerebellar vermian hypoplasia have been reported in foals.212, 213,
214, 215, 216, 217 Ivermectin toxicity and moxidectin toxicity have been reported.218,
219 Electrolyte abnormalities such as extreme hypo- or hypernatremia may result in
neurologic manifestations of disease.220, 221 Cervical stenotic myelopathy and degenerative
myelopathy also have been reported in foals, although the age at onset is usually
more than 4 months.
222
Idiopathic epilepsy of Arabian foals usually is associated with another infectious
disease and is thought to be temporary and self-limiting.
Immunologic Diseases Of Foals
FAILURE OF PASSIVE TRANSFER
Causes, diagnosis, and treatment of FPT of immunity are covered in detail elsewhere
in this text. Failure of passive transfer occurs when a foal fails to ingest a significant
quantity of good-quality colostrum. Failure of passive transfer may occur by several
mechanisms: failure of the foal to suck from the dam for any reason and failure of
the dam to produce sufficient quantity of quality colostrum. Box 19-4
presents causes of FPT. Several methods are available for measuring IgG concentration
in blood; the most reliable are enzyme-linked immunosorbent assay and single radial
immunodiffusion technology-based tests.223, 224, 225, 226, 227, 228, 229 Foals usually
are tested at 24 hours of age, but one may test the foal earlier if colostrum ingestion
has occurred and a concern exists regarding the passive transfer of immunity status
of the foal, recognizing that additional increases in IgG concentration may occur
with additional time.230, 231 The concentration of IgG in the blood of the foal has
been used as an indicator of the adequacy of passive transfer, but the actual blood
concentration at which FPT is diagnosed has been challenged in recent years.232, 233,
234 Foals with sepsis commonly have a serum IgG concentration of less than 800 mg/dl.16,
19 Foals with FPT are more likely to die from sepsis.177, 178, 235, 236, 237, 238,
239 One should consider the IgG concentration only as a marker for adequacy of colostral
absorption. All the measured IgG is unlikely to be directed against the specific pathogen
affecting any particular neonate, and IgG is not the only immune protection afforded
the foal by colostrum. Many factors that confer local and more general immunity to
the newborn are present in colostrum; these include growth factors, cytokines, lactoferrins,
CD14, leukocytes, and other yet to be described proteins.240, 241, 242, 243, 244 By
considering IgG a marker of adequacy for passive transfer, similar to γ-glutamyltransferase
in calves, the clinician can make choices for replacement that are more beneficial
to the patient.
245
After one identifies FPT in a foal, treatment depends on the current condition of
the foal and its local environment. Foals not presently ill and on well-managed farms
with low population density and low prevalence of disease may not require treatment
if their IgG concentration is between 400 and 800 mg/dl. Critically ill neonates with
FPT in an equine NICU are by definition ill and in an environment with high disease
prevalence. These patients require immediate treatment of FPT and frequent reassessment
of their passive immunity status. Critically ill foals often fail to demonstrate the
expected increase in blood IgG concentration based on grams of IgG administered per
kilogram of body mass compared with healthy, colostrum-deprived foals.235, 246, 247
Sick foals also demonstrate a more rapid decline in IgG concentration than do healthy
foals because they use and catabolize available protein.
BOX 19-4
CAUSES OF FAILURE OF PASSIVE TRANSFER
Maternal Causes
Premature lactation
Placentitis
Twins
Premature placental separation
Poor colostral quality
Maiden mares
Older mares
Failure of lactation
Aglactia
Fescue toxicosis
Foal Causes
Failure to ingest colostrum
Weakness
Prematurity
Musculoskeletal deformity
Perinatal asphyxia syndrome
Failure to absorb colostrum
Prematurity
Necrotizing enterocolitis
One may treat foals with FPT by oral or intravenous administration of various products
containing IgG. One can attempt oral administration of additional colostrum or IgG-containing
products such as plasma, serum, or lyophilized colostrum in foals less than 12 to
24 hours of age.248, 249, 250 Depending on the age of the foal and the maturity and
function of the gastrointestinal tract, this treatment may be effective. Many NICUs
and large breeding farms maintain colostrum banks for this purpose. One should administer
plasma intravenously if the foal is not expected to absorb additional colostrum or
if the enteral route is unavailable. Commercially available hyperimmune plasma products
designed for use in foals are available and can be stored frozen. Plasma and banked
colostrum should be stored in a non–frost-free freezer to minimize protein loss associated
with freeze-thaw cycling.
251
One should administer plasma through special tubing with an in-line filter and should
monitor patients closely for transfusion reactions.
252
One may use serum and concentrated IgG products, but the practitioner should be aware
that many of these products focus on IgG retention and not on other factors associated
with passive transfer of immunity. One should measure IgG concentration after transfusion
and provide additional plasma as necessary. Administration of plasma to critically
ill foals without FPT may be beneficial through provision of other factors present
in the plasma. In these situations, fresh frozen plasma or fresh plasma may be best,
particularly if transfusion of clotting proteins is desired.
NEONATAL ISOERYTHROLYSIS
Neonatal isoerythrolysis is a hemolytic syndrome in newborn foals caused by a blood
group incompatibility between the foal and dam and is mediated by maternal antibodies
against foal erythrocytes (alloantibodies) absorbed from the colostrum. The disease
most often affects foals born to multiparous mares and should be suspected in foals
less than 7 days of age with clinical signs of icterus, weakness, and tachycardia.
A primiparous mare can produce a foal with neonatal isoerythrolysis if she has received
a prior sensitizing blood transfusion or has developed placental abnormalities in
early gestation that allowed leakage of fetal red blood cells into her circulation.
Many are the causes of jaundice in newborn foals, including sepsis, meconium impaction,
and liver failure, but these usually can be differentiated readily from neonatal isoerythrolysis
by measuring the packed cell volume, which is usually less than 20% in foals with
neonatal isoerythrolysis.
Foals with neonatal isoerythrolysis are born clinically normal then become depressed
and weak and have a reduced suckle response within 12 to 72 hours of birth. The rapidity
of onset and severity of disease are determined by the quantity and activity of absorbed
alloantibodies. Affected foals have tachycardia, tachypnea, and dyspnea. The oral
mucosa is initially pale and then becomes icteric in foals that survive 24 to 48 hours.
Hemoglobinuria may occur. Seizures caused by cerebral hypoxia are a preterminal event.
The salient laboratory findings are anemia and hyperbilirubinemia. Most of the increased
bilirubin is unconjugated, although the absolute concentration of conjugated bilirubin
generally is increased well above normal. Urine may be red to brown and is positive
for occult blood.
Cause and Pathogenesis
The natural development of neonatal isoerythrolysis has several prerequisites. First,
the foal must inherit from the sire and express an erythrocyte antigen (alloantigen)
that is not possessed by the mare. Blood group incompatibility between the foal and
dam is not particularly uncommon, but most blood group factors are not strongly antigenic
under the conditions of exposure through previous parturition or placental leakage.
Factor Aa of the A system and factor Qa of the Q system are highly immunogenic, however,
and nearly all cases of neonatal isoerythrolysis are caused by antibodies to these
alloantigens. The exception is in the case of mule foals in which a specific donkey
factor has been implicated.253, 254, 255 Mares that are negative for Aa or Qa or both
are considered to be at risk for producing a foal with neonatal isoerythrolysis. The
risk involves approximately 19% and 17% of Thoroughbred and Standardbred mares, respectively.
Second, and perhaps most important, the mare must become sensitized to the incompatible
alloantigen and produce antibodies to it. The mechanism for this is not known in many
instances but generally is believed to result from transplacental hemorrhage during
a previous pregnancy involving a foal with the same incompatible blood factor.
255
Sensitization via transplacental contamination with fetal erythrocytes earlier in
the current pregnancy is possible, but an anamnestic response is generally necessary
to induce a pathogenic quantity of alloantibodies.
256
Ten percent of Thoroughbred mares and 20% of Standardbred mares have antibodies to
the Ca blood group antigen without known exposure to erythrocytes.
255
Some common environmental antigen is postulated possibly to lead to production of
anti-Ca antibodies. Data suggest that these natural antibodies may suppress an immune
response to other blood group antigens because mares negative for Aa that have anti-Ca
antibodies often do not produce antibodies to Aa of the erythrocytes in their foals
that also contain Ca antigen. This antibody-mediated immunosuppression is thought
to result from the destruction of fetal cells before the dam mounts an immune response
to other cell surface antigens. Natural alloantibodies have not been associated with
neonatal isoerythrolysis in horses.
After the mare becomes sensitized to the erythrocytes of her foal, alloantibodies
are concentrated in the colostrum during the last month of gestation. Unlike the human
neonate, which acquires alloantibodies in utero and thus is born with hemolytic disease,
the foal is protected from these antibodies before birth by the complex epitheliochorial
placentation of the mare. Thus the final criterion for foal development of neonatal
isoerythrolysis is ingestion in the first 24 hours of life of colostrum-containing
alloantibodies specific for foal alloantigens. Immunoglobulin-coated foal erythrocytes
are removed prematurely from circulation by the mononuclear phagocyte system or are
lysed intravascularly via complement. The rapidity of development and severity of
clinical signs are determined by the amount of alloantibodies that was absorbed and
their innate activity. Alloantibodies against Aa are potent hemolysins and generally
are associated with a more severe clinical syndrome than antibodies against Qa or
other alloantigens. The highest alloantibody titers are likely to be produced by mares
that were sensitized in a previous pregnancy and then subsequently reexposed to the
same erythrocyte antigen during the last trimester of the current pregnancy. Prior
sensitization of a mare by blood transfusion or other exposure to equine blood products
may predispose to neonatal isoerythrolysis.
256
Diagnosis
One can make a tentative diagnosis of neonatal isoerythrolysis in any foal that has
lethargy, anemia, and icterus during the first 4 days of life. Blood loss anemia caused
by birth trauma is attended by pallor. Icterus caused by sepsis or liver dysfunction
would not be associated with anemia. One must base the definitive diagnosis of neonatal
isoerythrolysis on demonstration of alloantibodies in the serum or colostrum of the
dam that are directed against foal erythrocytes. The most reliable serodiagnostic
test for neonatal isoerythrolysis is the hemolytic cross-match using washed foal erythrocytes,
mare serum, and an exogenous source of absorbed complement (usually from rabbits).
5
Although this test is impractical in a practice setting, a number of qualified laboratories
routinely perform this diagnostic service. The direct antiglobulin test (Coombs' test)
may demonstrate the presence of antibodies on foal erythrocytes; however, false negatives
occur frequently. Most human or veterinary hematology laboratories can perform routine
saline agglutination cross-match between mare serum and foal cells. Because some equine
alloantibodies act only as hemolysins, agglutination tests may be falsely negative.
Most field screening tests of colostrum have not proved to be reliable enough for
practical use.
Treatment
If one recognizes neonatal isoerythrolysis when the foal is less than 24 hours old,
one must withhold the dam's milk and feed the foal an alternative source of milk during
the first day of life. One can accomplish this by muzzling the foal and feeding it
via nasogastric tube. The minimum necessary amount of milk is 1% of body mass every
2 hours (e.g., a 50-kg foal should receive 500 ml or 1 pint of mare's milk or milk
replacer every 2 hours). The udder of the mare should be stripped regularly (at least
every 4 hours) and the milk discarded. In most instances, clinical signs are not apparent
until after the foal is 24 hours old, when colostral antibodies have been depleted
or the absorptive capacity of the foal's intestine for immunoglobulin has diminished.
Withholding milk at this point is of minimal benefit.
Supportive care to ensure adequate warmth and hydration is paramount. The foal should
not be stressed and exercise must be restricted. Confining the mare and foal to a
box stall is a best. Intravenous fluids are indicated to promote and minimize the
nephrotoxic effects of hemoglobin and to correct any fluid deficits and electrolyte
and acid-base imbalances. Antimicrobials may be necessary to prevent secondary infections.
One should monitor foals carefully for the necessity of blood transfusion, although
transfusion should be used only as a lifesaving measure. When the packed cell volume
drops below 12%, blood transfusion is warranted to prevent life-threatening cerebral
hypoxia. Erythrocytes from the dam are perfect in terms of nonreactivity with the
blood of the foal; however, the fluid portion of the blood of the mare has to be removed
completely from the cells to prevent administration of additional harmful alloantibodies
to the foal. One can pellet the erythrocytes of the dam from blood collected in acid-citrate-dextrose
solution by centrifugation or gravity and then aseptically draw off the plasma by
suction apparatus or syringe and replace it with sterile isotonic (0.9%) saline. One
thoroughly mixes the cells with the saline and then repeats the centrifugation or
sedimentation, followed by aspiration and discarding of the saline. One should perform
this washing process at least three times. One then can suspend the packed erythrocytes
in an equal volume of isotonic saline for administration. Erythrocyte washing by centrifugation
is more desirable than gravity sedimentation because antibody removal is more complete
and packed cell preparations can be prepared more quickly (each gravity sedimentation
requires 1 to 2 hours). Packed red blood cells are advantageous in overcoming the
problem of volume overload.
When equipment or conditions do not allow the safe use of dam erythrocytes, an alternative
donor is necessary. Because the alloantibodies absorbed by the foal generally are
directed against Aa or Qa and because the latter are highly prevalent among most breeds
of horses, a compatible blood donor is difficult to identify. The odds of finding
a donor without Aa or Qa are higher in Quarter Horses, Morgans, and Standardbreds
than in Thoroughbreds and Arabians. Previously blood-typed individuals negative for
Aa and Qa and free of alloantibodies are optimal. One should give 2 to 4 L of blood
or 1 to 2 L of packed erythrocytes over 2 to 4 hours. These allogeneic cells have
a short life span and represent a large burden to the neonatal mononuclear phagocyte
system, which may cause increased susceptibility to infection. In addition, these
cells sensitize the foal to future transfusion reactions. One must measure all potential
harm against the benefit in each situation.
If a mule foal is the patient, one should not use blood from a female previously bred
to a donkey. In cases in which transfusion will be delayed, one cannot identify a
compatible donor, or the packed cell volume is so low as to be life-threatening (hemoglobin
<5 mg/dl), one may administer polymerized bovine hemoglobin products at a dose of
5 to 15 ml/kg.
257
One may use dexamethasone (0.08 mg/kg) to treat peracute neonatal isoerythrolysis
if the packed cell volume is less than 12% and transfusion may be delayed or is not
fully compatible, but dexamethasone has detrimental effects on blood glucose regulation
in the neonate, and because the antibody in question is of maternal origin, corticosteroid
therapy in immunosuppressive doses probably is not indicated. Intranasal oxygen insufflation
(5 to 10 L/min) may be beneficial. Most foals with neonatal isoerythrolysis have adequate
passive transfer of immunity, but antimicrobial therapy is indicated to protect against
secondary sepsis resulting from the compromised condition of the foal. Supportive
care and good nursing care, including keeping the foal warm and quiet are essential.
One should expect the packed cell volume to decline again 4 to 7 days after transfusion.
258
Client Education
The prognosis for neonatal isoerythrolysis in foals depends on the quantity and activity
of absorbed antibodies and is indirectly proportional to the rate of onset of signs.
In peracute cases the foal may die before the problem is recognized, whereas foals
with slowly progressive signs often live with appropriate supportive care.
Like most diseases, neonatal isoerythrolysis is much more effectively prevented than
treated.
259
Any mare that has produced a foal with neonatal isoerythrolysis should be suspect
for the production of another affected foal; thus one should provide all subsequent
foals with an alternative colostrum source and discard the colostrum of the dam unless
she is bred to a stallion with known blood type compatibility. Mares negative for
Aa and Qa alloantigens are most at risk of producing affected foals, thus they should
be identified by blood-typing. Subsequently, breeding of these mares may be restricted
to Aa- and Qa-negative stallions, thus eliminating the possibility of producing an
affected foal. In breeds with a high prevalence of Aa or Qa alloantigens (e.g., Thoroughbreds
and Arabians), a stallion negative for these and suitable based on other criteria
may be difficult to identify. If these “at risk” mares are bred as desired, their
serum should be screened in the last month of pregnancy for the presence of erythrocyte
alloantibodies. One must test mares with low or equivocal titers closer to the time
of parturition. If one detects alloantibodies, the colostrum of the dam should be
withheld and the foal then should be provided with an alternative colostrum source.
Maternal alloantibodies to Ca do not appear to mediate neonatal isoerythrolysis in
foals and actually may be preventive by removing potentially sensitizing cells from
the circulation
56
; therefore one should not deprive foals of colostrum from mares possessing anti-Ca
antibodies, even when Ca is present on their erythrocytes. Rarely, the antigens De,
Ua, Pa, and Ab have been associated with neonatal isoerythrolysis in foals; however,
to consider mares without these alloantigens to be at risk for neonatal isoerythrolysis
is not practical.
IMMUNE-MEDIATED THROMBOCYTOPENIA AND NEUTROPENIA
These syndromes recently have been recognized and described within the veterinary
literature, although they have been recognized widely in human neonatology for many
years.260, 261, 262, 263 Affected foals demonstrate these hematologic abnormalities
within the first week of life, and the mechanism is similar to neonatal isoerythrolysis
following ingestion of maternal antibody directed against the platelet or the neutrophil.
In general, affected foals are healthy but may demonstrate bleeding tendencies if
thrombocytopenia is severe or they may be more susceptible to sepsis. One confirms
the diagnosis by appropriate testing for platelet- and neutrophil-associated antibody.
264
One must rule out other causes of neonatal thrombocytopenia and neutropenia, particularly
sepsis. Foals born to the mare in the future seem likely to be at risk for developing
similar problems, and one should treat future foals as one treats neonatal isoerythrolysis
foals: prevent sucking from the dam and provide an alternate source of passive immunity
in the form of banked colostrum or intravenous plasma. One should provide an alternative
nutritional source, such as foal milk replacer, to the foal for the first 48 hours
of life and should muzzle the foal while it is in the company of its dam for that
period of time. Treatment is primarily supportive, but in the case of severe thrombocytopenia,
transfusion of platelet-enriched fresh plasma may be indicated. Granulocyte colony-stimulating
factor has been used in foals with neutropenia, but substantial efficacy has yet to
be demonstrated. Broad-spectrum antimicrobial therapy may be prudent in cases of alloantibody-associated
neutropenia. Treatment with immunosuppressive doses of corticosteroids is probably
unwarranted, given the increased risk of infection, because the antibody in question
is of maternal origin.
Other specific diseases of the immune system of foals, severe combined immunodeficiency,
selective IgM deficiency, transient hypogammaglobulinemia, agammaglobulinemia, and
other unclassified immunodeficincies are covered in detail elsewhere in this text.
Diseases Of The Respiratory Tract
RESPIRATORY DISTRESS
The neonate can experience respiratory distress immediately after birth because of
several congenital respiratory tract or cardiac anomalies. Chief among these causes
are bilateral choanal atresia, stenotic nares, dorsal displacement of the soft palate
caused by anatomic deformity or neurologic impairment, accessory or ectopic lung lobes,
lung lobe hypertrophy, lung lobe dysplasia, cardiac anomalies with right-to-left shunting,
and miscellaneous causes such as subepiglotic cysts and severe edema of the larynx.264,
265, 266, 267, 268, 269, 270, 271 One must evaluate and treat these situations immediately
and should consider them true emergencies.
One readily can recognize foals with airway occlusion by the lack of airflow through
the nostrils despite obvious attempts to breathe and by respiratory stridor. These
foals may demonstrate open-mouth breathing and their cheeks may puff outward when
they exhale. One foal with congenital bilateral choanal atresia was recognized during
extrauterine intrapartum resusucitation because of an inability to pass a nasotrancheal
tube. One can establish an effective airway by orotracheal intubation in these cases
under most circumstances, but some foals require an emergency tracheostomy. One diagnoses
the underlying problem by endoscopy or radiography in most cases. Treatment of choanal
atresia and cystic structures is surgical, whereas severe laryngeal edema and laryngeal
paralysis frequently respond to medical management. Until the underlying problem is
resolved in these cases, one should administer broad-spectrum antimicrobial therapy
and feed the foal by intubation or total parenteral nutrition. One can give colostrum,
but these foals frequently develop aspiration pneumonia if allowed to suck from their
dams, so intravenously administered plasma also may be necessary to provide sufficient
passive immunity.
RESPIRATORY DISEASES ASSOCIATED WITH HYPOXEMIA IN THE NEONATE
Arterial blood gas determinations are the most sensitive indicator of respiratory
function readily available to the clinician. The most readily available arteries for
sampling are the metatarsal arteries and the brachial arteries. Portable arterial/venous
blood gas analyzers now are making arterial blood gas analysis more practical in the
field, and the technique is no longer reserved for large referral practices. Managing
a critically ill equine neonate without knowledge of arterial blood gas parameters
is veritably impossible. Pulse oximetry is useful, but these monitors only measure
oxygen saturation of hemoglobin. Desaturation can occur rapidly in critically ill
neonates. The utility of these monitors in the foal has yet to be demonstrated clearly,
particularly in cases of poor peripheral perfusion.
272
The most common abnormalities recognized with arterial blood gas analysis are hypoxemia
with normo- or hypocapnia and hypoxemia with hypercapnia. Hypoxemia is defined as
decreased oxygen tension of the arterial blood (decrease Pao
2), and hypoxia is defined as decreased oxygen concentration at the level of the tissue,
with or without hypoxemia. Hypoxia results from hypoxemia, decreased perfusion of
the tissue bed in question, or decreased oxygen-carrying capacity of the blood resulting
from anemia or hemoglobin alteration.
Five primary means by which hypoxemia may develop are (1) low concentration of oxygen
in the inspired air such as in high altitude or in an error mixing ventilator gas;
(2) hypoventilation; (3) ventilation/perfusion mismatch; (4) diffusion limitation;
and (5) intrapulmonary or intracardiac right-to-left shunting of blood. Hypoxemia
is not an uncommon finding in neonates but must be evaluated in terms of the current
age of the foal and its position.15, 273, 274, 275, 276 One also must consider the
difficulty encountered in obtaining the sample because severe struggling can affect
the arterial blood gas results. Table 19-8
presents normal arterial blood gas parameters for varying ages of foals. The normal
foal has a small shunt fraction (∼10%) that persists for the first few days of life
and contributes slightly to a blunted response to breathing 100% oxygen compared with
the adult. Hypoxemia frequently occurs in foals with prematurity, PAS, and sepsis,
although other conditions also result in hypoxemia in the neonate. In the early stage
of sepsis associated hypoxemia, Paco
2 may be within normal limits or decreased if the foal is hyperventilating for any
reason. If the lung is involved significantly in the underlying pathologic condition,
such as with severe pneumonia, acute lung injury, or acute respiratory distress syndrome,
increased Paco
2 may well be present, representing respiratory failure.
277
TABLE 19-8
Normal Arterial Blood Gas Values for Foals*
GESTATIONAL AGE
POSTNATAL AGE
POSITION
pH
PaCO2 (mm Hg)
PaO2 (mm Hg)
Term†
2 minutes
Lateral
7.31 ± 0.02
54.1 ± 2.0
56.4 ± 2.3
15 minutes
7.32 ± 0.03
50.4 ± 2.7
57.5 ± 3.6
30 minutes
7.35 ± 0.01
51.5 ± 1.5
57.0 ± 1.8
60 minutes
7.36 ± 0.01
47.3 ± 2.2
60.9 ± 2.7
2 hours
7.36 ± 0.01
47.7 ± 1.7
66.5 ± 2.3
4 hours
7.35 ± 0.02
45.0 ± 1.9
75.7 ± 4.9
12 hours
7.36 ± 0.02
44.3 ± 1.2
73.5 ± 3.0
24 hours
7.39 ± 0.01
45.5 ± 1.5
67.6 ± 4.4
48 hours
7.37 ± 0.01
46.1 ± 1.1
74.9 ± 3.3
4 days
7.40 ± 0.01
45.8 ± 1.1
81.2 ± 3.1
Premature‡
0.5–11 hours
Lateral
7.21 ± 0.05
55.3 ± 3.6
53.7 ± 1.5
*
Reported values are assumed to not be temperature corrected. Values are mean ± SEM.
†
Stewart JH, Rose RJ, Barko AM: Respiratory studies in foals from birth to seven days
old, Equine Vet J 16:323, 1984.
‡
Rose RJ, Rossdale PD, Leadon DP: Blood gas and acid-base status in spontaneously delivered
term-induced and induced premature foals, J Reprod Fert Suppl 32:521, 1982.
Hypoxemia usually is treated with intranasal humidified oxygen insufflation at 4 to
10 L/min. Hypercapnia is not a simple matter to treat. One must try to distinguish
between acute and chronic hypercapnia. Acute hypercapnia usually is accompanied by
a dramatic decrease in blood pH of 0.008 pH units for each 1 mm Hg increase in Paco
2. This acidemia can promote circulatory collapse, particularly in the concurrently
hypoxemic and/or hypovolemic patient. The effects of more chronic CO2 retention are
less obvious because the time course allows for adaptation. The pH change is less,
about 0.003 pH units per 1 mm Hg increase in Paco
2, because it is balanced by enhanced renal absorption of bicarbonate by the proximal
renal tubule. Most foals with acute respiratory distress are in the acute stages of
respiratory failure, but chronic adaptation begins to occur within 6 to 12 hours and
is maximal in 3 to 5 days. One will note an increase in bicarbonate, particularly
if the acidemia is primarily respiratory in origin. Intravenous administration of
sodium bicarbonate to correct respiratory acidosis/acidemia should be done cautiously
in these foals because CO2 retention may only be increased. Also, one should remember
that 1 mEq of sodium is administered with each mEq of bicarbonate and hypernatremia
has been seen in foals treated exuberantly with sodium bicarbonate. Foals with hypercapnia
of several days' duration also may develop a blunted respiratory drive to increased
CO2. In these foals, oxygen administration, although essential to treat hypoxemia,
may further depress ventilation and further decrease pH. This effect is caused by
a loss of hypoxic drive following oxygen therapy. One should consider these foals
candidates for mechanical ventilation if the Paco
2 is greater than 70 mm Hg or is contributing to the poor condition of the foal, such
as causing significant pH changes. If hypercapnia is caused by central depression
of ventilation, as frequently occurs in foals with PAS, one can administer caffeine
(10 mg/kg loading dose; then 2.5 mg/kg as needed) per rectum or orally in foals with
normal gastrointestinal function. Other clinicians may recommend continuous rate infusions
of doxapram hydrochoride (Dopram; 400 mg/total dose at 0.05 mg/kg/min) for these foals.
If this therapy fails, one should consider mechanical ventilation. Mechanical ventilation
of foals with central respiratory depression is rewarding and may be necessary only
for a few hours to days. A special category is the foal with botulism exhibiting respiratory
failure caused by respiratory muscle paralysis. These foals do well with mechanical
ventilation, although the duration of mechanical ventilation is more prolonged, frequently
more than 1 week. Foals with primary metabolic alkalosis usually have compensatory
respiratory acidosis. Treatment of hypercapnia is not necessary in these cases because
it is in response to the metabolic condition. These foals do not respond to caffeine,
and they should not be ventilated mechanically if this is the only disorder present.
Bacterial Pneumonia
In the neonate, bacterial pneumonia usually results from sepsis or aspiration during
sucking. Foals with sepsis can develop acute lung injury or acute respiratory distress
syndrome as part of the systemic response to sepsis, and this is frequently a contributor
to the demise of foals in septic shock. The best way to diagnose bacterial pneumonia
is by cytologic examination and culture of a transtracheal aspirate, but blood culture
may aid in early identification of the causative organism and allow for early institution
of directed antimicrobial therapy. A second frequent cause of bacterial pneumonia
in the neonate is aspiration caused by a poor suck reflex or dysphagia associated
with PAS, sepsis, or weakness. One must take care to ensure that aspiration is not
iatrogenic in foals being bottle fed. Auscultation over the trachea while the foal
is sucking helps identify occult aspiration. One should suspect occult aspiration
pneumonia in any critically ill neonate that is being bottle fed or is sucking on
its own that has unexplained fever, fails to gain weight, or has a persistently increased
fibrinogen level.
Older foals develop bacterial pneumonia, frequently following an earlier viral infection.
278
Bacterial pneumonia is discussed in depth elsewhere in this text, but a few comments
specific to the foal are necessary. One should auscultate and percuss the thorax of
the foal, but results may not correlate closely with the severity of disease. The
most commonly isolated bacterial organism in foal pneumonia is Streptococcus zooepidemicus,
and one may isolate it alone or as a component of a mixed infection.278, 279, 280
Transtracheal aspirate for culture and cytologic examination is recommended because
mixed gram-positive and gram-negative infections are common, and antimicrobial susceptibility
patterns can be unpredictable. One should split the obtained aspirate and submit samples
for bacterial culture, virus isolation, and cytologic examination. Additional diagnostics
include radiography, ultrasonography, and serial determination of white blood cell
counts (with differential) and blood fibrinogen concentrations. Treatment includes
administration of appropriate antimicrobial therapy. Some foals may benefit from nebulization
with saline or other local products. Ascarid larval migration through the lung can
mimic bacterial pneumonia.
281
In these cases the foal may not respond to antimicrobial therapy and should be dewormed
with ivermectin. Deworming the mare within 1 month of parturition and frequent deworming
of the foal prevent ascarid migration pneumonia in most foals.
A special category of bacterial pneumonia in foals is Rhodococcus equi bronchopneumonia.
This pneumonia of young foals was described first in 1923.
282
The organism originally was known as Corynebacterium equi and is a gram-positive pleomorphic
coccobacillus usually less than 1 μm in diameter and 2 μm in length. The organisms
frequently are associated in L- and V-shaped clusters that have been termed Chinese
character formations. R. equi has an acid-fast staining characteristic under some
growing circumstances because of the presence of mycolic acid in its cell wall, similar
to Mycobacterium and Nocardia species. Mycolic acid promotes granuloma formation.
The organism is able to multiply in and destroy macrophages as it prevents phagosome
lysosome fusion.283, 284 Much attention has been paid to this organism in recent years,
given its propensity to produce enzootic and epizootic outbreaks of disease. The organism
is thought to be primarily an opportunistic pathogen, and it lives in the soil of
most geographic areas. Foals are affected most frequently between the ages of 1 and
6 months, when maternally derived immunity has begun to wane. The disease is insidious,
and foals may have significant pulmonary involvement before developing noticeable
clinical signs.
Phagocytosis of R. equi by equine macrophages is not associated with a functional
respiratory burst and, at least in human beings, the l-arginine–NO pathway is not
required for intracellular killing of this organism.285, 286 Optimal binding of R.
equi to mouse macrophages in vitro requires complement and is mediated by Mac-1, a
leukocyte complement receptor type 3 (CR3, CD11b/CD18).
287
Opsonisation of R. equi with specific antibody is associated with increased phagosome-lysosome
fusion and enhanced killing of R. equi, suggesting that the mechanism of cellular
entry is important.
283
Neutrophils from foals and adult horses are fully bactericidal, and killing of R.
equi is enhanced considerably by specific opsonizing antibody.
288
The ability of R. equi to induce disease in foals likely depends on host and microbial
factors. Knowledge of the virulence mechanisms of R. equi was speculative until the
discovery of the virulence plasmid.
289
As opposed to most environmental R. equi organisms, isolates from clinically affected
foals typically contain 85- to 90-kb plasmids encoding an immunogenic virulence-associated
protein (VapA) that is expressed on the bacterial surface in a temperature-regulated
manner.
290
Plasmid-cured bacteria lose their ability to replicate and survive in macrophages
and are cleared from the lungs within 2 weeks of intrabronchial challenge without
producing pneumonia.
291
However, expression of VapA alone is not sufficient to restore the virulence phenotype.
Six other genes have approximately 40% overall amino acid identity with VapA, and
the identification of multiple genes with considerable homology suggests these genes
constitute a virulence-associated gene family in R. equi.
292
Other candidates for virulence factors include capsular polysaccharides and cholesterol
oxidase, choline phosphohydrolase, and phospholipase C exoenzymes (“equi factors”),
but their roles have not been defined clearly.
The primary manifestation of disease caused by R. equi infection is severe bronchopneumonia
with granuloma, abscess formation, or both. Up to 50% of foals diagnosed with bronchopneumonia
also have extrapulmonary sites of infection.
293
As the pneumonia progresses, clinical signs may include decreased appetite, lethargy,
fever, tachypnea, and increased effort of breathing characterized by nostril flaring
and increased abdominal effort. Cough and bilateral nasal discharge are inconsistent
findings. A smaller percentage of affected foals may have a more devastating, subacute
form. These foals may be found dead or have acute respiratory distress with a high
fever and no previous history of clinical respiratory disease.
Hyperfibrinogenemia is the most consistent laboratory abnormality in foals with R.
equi pneumonia. Neutrophilic leukocytosis (>12,000 cells/μl), with or without monocytosis,
is common.
294
Thoracic radiography is a useful diagnostic aid, frequently revealing a prominent
alveolar pattern with poorly defined regional consolidation and/or abscessation. Ultrasonography
is a helpful diagnostic tool when the disease involves peripheral lung tissue. Although
a number of serologic tests have been described, serologic diagnosis of R. equi infections
is controversial and difficult because exposure of foals to this organism at a young
age leads to production of antibody without necessarily producing clinical disease.295,
296 Serologic tests may be more useful at the farm level to detect overall exposure
than at the individual level. Bacteriologic culture combined with cytologic examination
of a tracheobronchial aspirate remains the most definitive method for accurate diagnosis
of R. equi pneumonia. However, foals without clinical disease exposed to contaminated
environments may have R. equi in their tracheae from inhalation of contaminated dust;
therefore one should interpret culture results in the context of the overall case
presentation.
297
Culture results in one study were as sensitive as polymerase chain reaction–based
assays and offered the advantage of allowing in vitro antimicrobial susceptibility
testing.
298
However, polymerase chain reaction is likely to be a useful tool, and results from
a second trial suggest the assay is more sensitive and specific than culture of tracheobronchial
aspirates for diagnosis.
299
The combination of erythromycin and rifampin has become the treatment of choice for
R. equi infections in foals, and the combination reduces the likelihood of resistance
to either drug. The recommended dosage regimen for rifampin is 5 mg/kg every 12 hours
or 10 mg/kg every 24 hours orally. The recommended dose of estolate or ethylsuccinate
esters of erythromycin is 25 mg/kg every 8 or 12 hours orally.
300
Recently, azithromycin has been recommended for treatment of R. equi infection at
a dosage of 10 mg/kg orally every 24 hours for 5 to 7 days and then every other day.
301
Alternatively, clarithromycin at 7.5 mg/kg every 12 hours orally, in combination with
rifampin, may be therapeutically effective. Severely affected foals may require intranasal
oxygen insufflation, intravenous fluid support, and nutritional support. Treatment
generally continues for 4 to 10 weeks until all clinical and laboratory evidence of
infection is resolved. Although well tolerated by most foals, erythromycin can result
in soft feces. This diarrhea is generally self-limiting and does not require cessation
of therapy, but one should monitor affected foals carefully. An idiosyncratic reaction
characterized by severe hyperthermia and tachypnea has been described in foals treated
with erythromycin during periods of hot weather.
302
Affected foals should be moved to a colder environment and treated with antipyretic
drugs and alcohol baths if necessary. Clostridium difficile enterocolitis has been
reported in the dams of nursing foals treated with erythromycin given orally.
303
The dam is exposed to active erythromycin by coprophagy or by drinking from a communal
water source where the foal has “rinsed” its mouth.
Prevention of R. equi pneumonia on farms with recurrent problems is problematic. The
most clearly demonstrated prophylactic measure to date has been the administration
of plasma that is hyperimmune to R. equi to foals within the first week of life and
then again when maternal immunity begins to wane at around 30 days of age.304, 305,
306, 307, 308, 309, 310, 311 No effective vaccination protocols for the dam or foal
have been described to date. Farm management is important in preventing disease, and
control measures include frequent manure removal, avoidance of overcrowded conditions,
and planting of dusty or sandy soils.
304
The prognosis for R. equi bronchopneumonia is fair to good in foals with the more
chronic form of the disease. Foals with acute respiratory distress have a more guarded
prognosis, as do foals with sites of significant extrapulmonary infection. The long-term
prognosis for survival for foals with R. equi bronchopneumonia is good, and many foals
perform as expected as athletes.
312
Viral Pneumonia
The most commonly identified causes of viral pneumonia in foals are equine herpesviruses
1 and 4 (EHV-1 and EHV-4), equine influenza, and equine arteritis virus (EVA). Equine
herpesvirus 1 is probably the most clinically important, but outbreaks of EVA in neonates
have occurred and are devastating.27, 313, 314, 315, 316, 317, 318 Adenovirus is reported
sporadically and as a problem in Arabian foals with severe combined immunodeficiency.319,
320, 321
In the neonate, infection with EHV-1 or EVA is almost uniformly fatal and antemortem
diagnosis is difficult, even once an outbreak on a particular farm is identified.
Several factors appear common to foals with EHV-1, including icterus, leukopenia,
neutropenia, and petechial hemorrhage, but these problems also are identified in foals
with severe sepsis.315, 322, 323 The antiviral drug acyclovir (10 to 16 mg/kg orally
or per rectum 4 to 5 times per day) has been used in cases of EHV-1 in neonates, with
some evidence of efficacy in mildly affected foals or foals affected after birth.
323
If viral pneumonia is a possibility, one should collect blood and tracheal aspirates
at presentation for bacterial and virus isolation. The lungs of foals with EHV-1 or
EVA are noncompliant, and pulmonary edema may be present. Mechanical ventilation of
these cases may prolong life, but death is generally inevitable because of the magnitude
of damage to the lungs. Foals suspected of having EHV-1 or EVA should be isolated
because they may be shedding large quantities of virus and pose a threat to other
neonates and pregnant mares. Foals with EVA generally are born to seronegative mares,
and intravenous treatment with plasma with a high titer against EVA may prove beneficial
because passive immunity appears to have a large role in protection against this disease
in neonates.318, 324
Older foals and weanlings may be affected by herpesviruses. Disease is usually mild,
although a fatal pulmonary vasculotropic form of the disease has been described recently
in young horses.325, 326 The clinical signs of disease are indistinguishable from
influenza and include a dry cough, fever, and serous to mucopurulent nasal discharge,
particularly if secondary bacterial infection occurs. Rhinitis, pharyngitis, and tracheitis
may be present. Treatment of affected foals is primarily supportive. Foals also may
become infected with EHV-2. The predominant clinical signs are fever and lymphoid
hyperplasia with pharyngitis.327, 328 Diagnosis is by virus isolation.
OTHER CAUSES OF RESPIRATORY SIGNS IN FOALS
Rib fractures have been recognized in 3% to 5% of all neonatal foals and can be associated
with respiratory distress.
87
Potential complications of rib fractures include fatal myocardial puncture, hemothorax,
and pneumothorax. Rib fractures frequently are found during physical examination by
palpation of the ribs or by auscultation over the fracture sites. One can confirm
the diagnosis by radiographic and ultrasonographic evaluation. Often multiple ribs
are affected on one side of the chest. Specific treatment is generally unnecessary,
but direct pressure on the thorax should be avoided in all cases. Some specific patients
may benefit from surgical stabilization of some fractures, particularly those fractures
overlying the heart.
Pneumothorax can occur spontaneously or following excessive positive pressure ventilation
329
or following tracheostomy surgery or trauma. Any foal being ventilated mechanically
that suddenly has respiratory distress and hypoxemia should be evaluated for pneumothorax.
Diagnosis is by auscultation and percussion of the thorax, but one can confirm the
diagnosis with radiographic and ultrasonographic evaluation of the thorax. Needle
aspiration of air from the pleural space also confirms the diagnosis. Treatment is
required in cases in which clinical signs are moderate to severe or progressive and
involves closed suction of the pleural space. Subcutaneous emphysema can complicate
treatment of this problem.
Idiopathic or transient tachypnea has been observed in Clydesdale, Thoroughbred, and
Arabian breed foals. In human infants, transient tachypnea can be related to delayed
absorption of fluid from the lung, perhaps because of immature sodium channels.
330
In foals, tachypnea generally occurs when conditions are warm and humid and is thought
to result from immature or dysfunctional thermoregulatory mechanisms. Clinical signs
of increased respiratory rate and rectal temperature develop within a few days of
birth and may persist for several weeks. Treatment involves moving the foal to a cooler
environment, body clipping, and provision of cool water or alcohol baths. These foals
frequently are treated with broad-spectrum antimicrobial drugs until infectious pneumonia
can be ruled out.
A syndrome of bronchointerstitial pneumonia and acute respiratory distress has been
described in older foals and appears to be a distinct entity from acute respiratory
distress syndrome in neonatal foals in association with sepsis.
331
The underlying cause has not been identified, but the genesis is probably multifactorial
with several potential pathogens being implicated. Affected foals have acute respiratory
distress with significant tachypnea, dyspnea, nostril flare, and increased inspiratory
and expiratory effort. Auscultation reveals a cacophony of abnormal sounds including
crackles and polyphonic wheezes in all lung fields. Loud bronchial sounds are audible
over central airways, and bronchovesicular sounds are lost peripherally. Affected
foals are cyanotic, febrile, and unwilling to move or eat. Foals may be found acutely
dead. Laboratory abnormalities include leukocytosis, hyperfibrinogenemia, and hypoxemia
with hypercapneic acidosis. Foals can be dehydrated severely and have coagulation
changes consistent with disseminated intravascular coagulation. Hypoxic injury to
other organs, primarily the kidneys and liver, can occur. Chest radiographs reveal
a prominent interstitial pattern overlying a bronchoalveolar pattern that is distributed
diffusely throughout the lung. This syndrome is a respiratory emergency. Treatment
is broad-based and includes administration of oxygen, nonsteroidal antiinflammatory
agents, broad-spectrum antimicrobial therapy, nebulization, judicious intravenous
fluid therapy, nutritional support, and corticosteroid therapy. One must manage hyperthermia
in the foal. Corticosteroid therapy appears to have been lifesaving in most of the
reported surviving foals. Because this syndrome is associated with high environmental
temperatures in some areas, prevention involves control of ambient temperatures, not
transporting foals during hot weather, and keeping foals out of direct sun on hot
days, particularly foals being treated with erythromycin for suspected or confirmed
R. equi infection.
332
Diseases Of The Urinary Tract
UROPERITONEUM
Uroperitoneum has been recognized as a syndrome in foals for more than 50 years.333,
334 Classically, affected foals are 24 to 36 hours old at the time clinical signs
first are recognized.334, 335, 336 Previous reports had a proportionately larger affected
male than female population.334, 335, 337 The hypothesis was that colts were more
at risk because their long, narrow, high-resistance urethra was less likely to allow
bladder emptying, resulting in rupture of a full bladder during parturition when high
pressures were applied focally or circumferentially around the bladder.
333
More recent reports suggest that such extreme sex bias may have been an artifact of
small case numbers in the early reports.
Rupture or disruption of any structure of the urinary tract can occur. The dorsal
wall of the bladder has been reported to be a frequent disruption site, with the ventral
wall less likely to be involved.
336
The urachus appears to be the next most commonly affected structure. A few cases of
ureteral and urethral defects have been reported.336, 337 Sepsis does not appear to
favor one site over the others.
338
The pathophysiology of uroperitoneum is not yet understood fully. The high pressure
exerted on a full bladder during parturition once was thought to be the main cause.
Full bladder and obstruction caused by a partial umbilical cord at parturition, strenuous
exercise, and external trauma have been reported as causes.
339
A few reports describe smooth and noninflamed edges of torn tissue, suggesting the
possibility of congenital bladder wall defects.338, 340, 341 Sepsis leading to urinary
tract rupture and uroperitoneum may occur in foals hospitalized for a variety of unrelated
problems. The onset of clinical signs of uroperitoneum may be insidious in these foals,
and diagnosis may be less obvious.
338
Clinical signs associated with uroperitoneum in the neonatal foal typically include
straining to urinate, dribbling urine, and a stretched-out stance. Weakness, tachycardia,
tachypnea, and not sucking well are also common. A distended abdomen may be evident,
and one may feel a fluid wave on ballottement of the abdomen. Occasionally, urine
accumulates in the scrotum and should not be confused with hernia. Foals also may
show signs of sepsis, including fever, injected mucous membranes, diarrhea, and disease
of other body systems.
Laboratory findings vary depending on the duration of the uroperitoneum and on the
presence and severity of sepsis. Classic findings include hyperkalemia, hyponatremia,
and hypochloremia arising from equilibration of urine electrolytes and water with
blood across the peritoneal membrane.335, 336, 337 The usual foal diet of milk, which
is high in potassium and low in sodium, promotes the electrolyte abnormalities. Foals
that develop uroperitoneum while receiving intravenous fluids may not have classic
electrolyte imbalances at the time clinical signs are recognized.
338
Increased serum creatinine concentration is often present, whereas blood urea nitrogen
concentrations occasionally, but not consistently, are increased.335, 336, 337 Metabolic
acidosis and hypoxemia may be present. Some patients also have serum hypoosmolality.
335
One should test foals for failure of passive transfer. One of the most sensitive laboratory
tests for uroperitoneum is the ratio of peritoneal to serum creatinine. A ratio greater
than or equal to 2:1 is considered diagnostic of uroperitoneum. One should collect
peritoneal fluid and test it for creatinine concentration, as well as for cytologic
findings, culture, and sensitivity. Cytologic evaluation of peritoneal fluid is necessary
to identify concurrent peritonitis or other gastrointestinal compromise. One should
perform an electrocardiogram on initial evaluation of a foal with suspected uroperitoneum
because hyperkalemia may result in bradycardia, increased duration of the QRS complex,
a shortened Q-T interval, increased P-wave duration, prolonged P-R interval, or atrioventricular
conduction disturbances. Other possible cardiac sequelae to hyperkalemia include cardiac
arrest, third-degree atrioventricular block, ventricular premature contractions, and
ventricular fibrillation.337, 340
For any foal exhibiting signs of dypsnea, tachypnea, or hypoxemia, one should have
thoracic radiographs taken before induction of anesthesia to rule out pleural effusion,
pneumonia, or acute respiratory distress syndrome, which could complicate ventilation
and oxygenation during anesthesia and the postoperative period. Ultrasonography has
become the tool of choice in the diagnosis of uroperitoneum and is a useful tool available
to the practitioner.
342
One can image free peritoneal fluid readily, and tears within the bladder are readily
visible. The empty bladder with a significant defect, in a fluid-filled abdomen, will
collapse on itself and often have a U shape. One also can visualize urachal and urethral
lesions. Six of eight foals in one study had urinary tract lesions identified sonographically,
and all 31 foals of another study underwent sonographic evaluation, and a significant
correlation between ultrasonographic findings and location of the lesion at surgery
existed.336, 338
Initial treatment aims to stabilize the patient and correct any electrolyte and acid-base
abnormalities and provide fluid volume replacement. One should use 0.9% or 0.45% saline
with 5% dextrose until laboratory data are available. A potassium concentration of
greater than 5.5 mEq/L can be life threatening. One can manage hyperkalemia by peritoneal
drainage to decrease whole-body potassium stores using teat cannulae, Foley catheters,
large-gauge (16 or 14) intravenous catheters, or human peritoneal dialysis catheters.
Fluid replacement at least should equal the amount of fluid removed from the abdomen
to prevent acute hypotension caused by expansion of previously collapsed capillary
beds. Abdominal drainage also helps ventilation and decreases the work of breathing
by decreasing pressure on the diaphragm. One may administer calcium gluconate, glucose,
sodium bicarbonate, or insulin intravenously to decrease serum potassium concentrations.
These maneuvers do not correct the whole-body potassium overload, however, and once
therapy is discontinued, hyperkalemia can reappear until the urine is removed from
the abdomen. One should correct hyponatremia slowly. Because of the real possibility
of concurrent sepsis, one should obtain blood cultures before preoperative administration
of antimicrobials. Broad-spectrum coverage (penicillin and amikacin or ceftiofur sodium)
is recommended until culture results become available. One should perform therapeutic
drug monitoring when using aminoglycoside therapy. However, the peak value may be
depressed because of the increased volume of distribution represented by the volume
of urine in the abdomen, so one should not make dose adjustment based on a low peak
until obtaining a new peak after surgical correction of the uroperitoneum. One should
treat foals with failure of passive transfer with adequate volumes of intravenously
administered plasma.
After one has addressed the metabolic abnormalities, one may consider surgical management.
Medical management using an indwelling Foley catheter has been described.
343
Preoperative medical stabilization reduces anesthetic risk. Safer inhalant agents
such as isoflurane also have decreased risk. Removal of the internal umbilical remnant
at the time of surgery is usual. One should consider culturing any removed umbilical
remnant and submitting the remnant for histopathologic evaluation. Recurrence of urinary
tract rupture can occur. Sepsis, hypoxemia, pneumonia, peritonitis, and acute respiratory
distress syndrome complicate the management of uroperitoneum. Many affected foals
are persistently oxygen dependent for several days following surgical correction,
and one should perform serial arterial blood gas analyses before discontinuing intranasal
oxygen supplementation.
Prognosis is associated closely with concurrent illness, especially septicemia. Uncomplicated
uroperitoneum from a defect in the bladder has a good prognosis. If the location of
the lesion is other than the bladder, the prognosis is not as favorable.
337
Foals with septicemia have a much poorer prognosis.338, 339
ACUTE RENAL FAILURE
Acute renal failure most often occurs as a complication of prenatal asphyxial syndrome,
sepsis, or aminoglycoside therapy. Acute renal failure also has been reported following
oxytetracycline administration in foals.
344
The dose of oxytetracycline commonly used to treat flexural deformities in foals is
approximately 10 times the antimicrobial dose. Many foals treated in this manner also
have suffered some degree of perinatal asphxia, which also damages the kidney, because
of prolonged parturition precipitated in part by the flexural deformity. Evaluation
of renal function in these foals before the administration of the first dose of oxytetracycline
and continued monitoring of serum creatinine concentrations before administering subsequent
doses of this nephrotoxic compound would seem reasonable. Hemodialysis has been used
as therapy in one of these cases, but prevention is important because these foals
may fail to respond to usual therapy for oliguric renal failure and are euthanized.
344
CONGENITAL RENAL DISEASE
The most commonly reported congenital deformity of the kidney of the foal is renal
hypoplasia and dysplasia, which may have a heritable component.345, 346 Renal arteriovenous
malformations have been reported also.
347
Ectopic ureters and fenestrated ureters have been described in the foal.348, 349,
350 Congenital renal defects, among others, were reported in three weak, recumbent
neonatal foals born to mares being treated for equine protozoal myeloencephalitis.
351
Mares received sulfadiazine or sulfamethoxazole-trimethoprim, pyrimethamine, folic
acid, and vitamin E orally. The foals were anemic, leukopenic, azotemic, hyponatremic,
and hyperkalemic. Serum folate concentrations were lower than those reported in the
literature for clinically normal brood mares. Treatment was unsuccessful. Necropsy
revealed lobulated kidneys with thin cortices and a pale medulla. The authors postulated
that oral administration of sulfonamides, 2,4-diaminopyrimidines (pyrimethamine with
or without trimethoprim), and folic acid to mares during pregnancy is related to congenital
defects in newborn foals.
Umbilical Disorders
The umbilicus serves as the conduit for nutrition and gas exchange between the dam
and the fetal foal. The urine from the foal is expelled via this structure into the
allantoic cavity. The author has recognized cases of in utero bladder distention in
the fetus that were associated with multiple twists decreasing urine flow or focal
stenosis creating the same effect. Foals born with this condition did not have bladder
rupture associated with parturition but did have other severe abnormalities that eventually
resulted in their demise, primarily premature delivery with failure to adapt to extrauterine
life (P.A. Wilkins, J.E. Palmer, and F.T. Bain, unpublished data). At birth the umbilicus
breaks, leaving a small external remnant and a large internal remnant. The umbilicus
long has been regarded as the primary site of entry of pathogens into the neonate,
although this has been challenged recently. Treatment of the umbilicus after birth
involves dipping it (preferably just the most distal component) with various caustic
compounds. The most current recommendation is to treat the umbilicus with dilute chlorhexidine,
povidone-iodine, or dilute iodine solutions for just a few times following birth.
Exhuberant treatment of the umbilical stump with caustic solutions can lead to scalding
of the ventral abdomen and may promote patency of the urachus. The ultrasonographic
appearance and measurements of the umbilical arteries, urachus, and umbilical vein
of foals from 6 hours to 4 weeks of age have been described in detail.
342
A 7.5-MHz sector scanner transducer placed across the midline of the ventral portion
of the abdominal wall of the foal works best because of the superficial location of
these structures. The mean (± SD) diameter of the umbilical vein was 0.61 ± 0.20 cm
immediately cranial to the umbilical stalk, 0.52 ± 0.19 cm midway between the umbilicus
and liver, and 0.6 ± 0.19 cm at the liver. The urachus and umbilical arteries of normal
foals have a mean total diameter of 1.75 ± 0.37 cm at the bladder apex. The umbilical
arteries scanned along either side of the bladder have a mean diameter of 0.85 ± 0.21
cm. One can use these measurements and the ultrasonographic appearance of the internal
umbilical structures from clinically normal foals as references to diagnose abnormalities
of the umbilical structures in neonatal foals.352, 353 The most common abnormalities
of these structures are focal abscess formation, hematoma, and urachal tear.
HERNIA
Herniae traditionally have been thought to develop from failure of closure at the
umbilical stump after birth. However, the closure of the body wall defect at the umbilicus
was studied in relation to the development of umbilical herniae in a large group of
normal foals followed from birth until 5 months of age or from birth until 11 months
of age.
354
At birth, approximately half of these foals had a defect in the body wall at the umbilicus
that was termed a palpable umbilical ring. In 18 foals this defect disappeared within
4 days, but in one foal the ring did not close and a hernial sac with abdominal contents
was palpable. This foal was considered to be the only foal to have a truly congenital
umbilical hernia. Twelve foals developed an umbilical hernia between 5 and 8 weeks
of age. The prevalence of umbilical herniae was much higher than in other studies,
possibly because of the prospective nature of the study. Based on this study, the
large majority of umbilical herniae would appear not to result from failure of closure
but rather to be acquired after birth. One should consider the palpable ring structure
within the body wall at the umbilicus a variant of normal in the foal and should not
call it a hernia until the foal is at least 1 month of age.
In one study of 147 horses treated for umbilical herniae over a 13½-year period, only
8.8% developed complications in association with umbilical defects.
355
Six horses had intestinal incarceration; the incarceration was reduced manually in
3 horses before admission and resolved without treatment in 2 others. The hernia was
surgically reduced in 1 horse. Herniorrhaphy was performed on 4 of the 5 horses in
which the incarceration did not require surgical reduction, and the fifth was managed
conservatively. The study confirmed that complications of umbilical herniae are rare
in horses; however, when they do develop, they may be one of various forms, some of
which are insidious in onset. The primary differential diagnosis for an external swelling
in the umbilical stump region is an external abdominal abscess, which will be firm,
variably painful, warm, and nonreducible. Ultrasonographic evaluation readily can
confirm either possibility.
OTHER CONGENITAL ABNORMALITIES
One report describes a 3-day-old foal that died from intestinal strangulation caused
by a remnant of vitelline vein that extended between the umbilicus and the portal
vein.
356
PATENT URACHUS
Patent urachus frequently is recognized in the abnormal neonate, probably because
of the increased recumbency and decreased movement of these patients. Cauterization
of a patent urachus is no longer recommended except in cases that persist for long
periods of time (>1 month) after the foal becomes more active. Surgical resection
may provide relief in some foals, but most cases resolve without treatment if given
enough time. Foals with a patent urachus may posture and strain frequently to urinate,
some of this may be associated with irritation or local infection of the urachus.
One can alleviate this by administration of broad-spectrum antimicrobial therapy such
that the drug has a high concentration in the urine (e.g., trimethoprim-sulfa drug
combinations) and by oral administration of phenazopyridine hydrochloride (Pyridium),
a dye that anesthetizes the urinary tract epithelial surfaces (see Table 19-7). This
dye turns the urine orange and stains everything yellow-orange that it or the urine
touches but can provide a great deal of relief to foals with this problem.
UMBILICAL REMNANT INFECTION
The umbilicus has been considered the traditional point of entry of bacteria into
the septic neonate, and septic foals have been referred to as having “navel ill” and
“joint ill” in the past. Although current thought suggests that the gastrointestinal
tract may be the route of entry in most septic neonates, infection of the umbilicus—termed
omphalitis, or omphalophlebitis
if the vessels are involved—still occurs as a single focus of infection or along with
more generalized infection. External signs, such as swelling, heat, pain, ventral
edema, or purulent discharge may be present in some foals, but more usually external
signs are minimal and one suspects infection because of infection in another site
(e.g., an infected joint), fever, or otherwise unexplained increased blood fibrinogen
concentration. One confirms the diagnosis by ultrasonographic evaluation of the internal
umbilical remnant. Any of the umbilical structures may be involved. A complete description
of the evaluation is available within the relevant veterinary literature, but the
examination is performed best with the foal standing using a 7.5-MHz probe with a
standoff.
353
The usual finding is that the affected structure is larger than expected. A fluid-filled
core and echogeneic shadows consistent with gas may be apparent in some cases. Interpretation
requires some experience, and the examiner should be familiar with variants of normal,
such as gas shadows associated with a patent urachus and enlarged vessels caused by
hematoma formation, so that treatment is not initiated inappropriately.
Two options for treatment are surgical and medical. Medical treatment is preferable
in cases in which the lesion is well localized and small and in foals with a medical
condition that is not amenable to anesthesia and surgical intervention. One should
institute broad-spectrum antimicrobial therapy, and one may need to continue therapy
for 2 to 3 weeks. Most affected foals respond to medical therapy. Frequent reevaluation
of the abnormality is necessary, every 5 to 7 days initially, and one should measure
blood fibrinogen concentrations at reevaluation because they should stabilize and
decrease with effective treatment. Failure to respond to therapy within 10 days to
2 weeks suggests that an empiric change in the antimicrobial used may be necessary.
In foals that are refractory to medical management or where the lesion is large, surgical
excision of the entire umbilical remnant may be desirable.
Diseases Of The Gastrointestinal Tract
COLIC IN THE NEONATE
Colic in the foal can be difficult to diagnose accurately because one cannot perform
an examination per rectum. However, many diagnostic aids, most importantly ultrasonography,
are available to help differentiate medical from surgical causes of abdominal discomfort
in the foal.
OBSTRUCTION
Intestinal accidents of all types described in adult horses, with the possible exception
of enteroliths, occur in foals. Intussusception, volvulus, displacement, diaphragmatic
hernia, and intra- and extraluminal obstruction have been reported in foals. Abdominal
ultrasonographic and radiographic evaluation greatly aids diagnosis. Treatment is
primarily surgical. Foals with PAS and intestinal dysmotility are at increased risk
of intussusception and displacement, and Miniature breed foals appear to be at increased
risk for fecolith and enterolith formation.
MECONIUM RETENTION/IMPACTION
Meconium retention or impaction is a common cause of abdominal discomfort in newborn
foals. Most foals defecate shortly after their first meal. The usual practice for
most owners or veterinarians attending the birth of a foal is to administer an enema
to aid this process. In the past, phosphate-based commercially available enemata (Fleet)
were used frequently, but if used excessively these types of enemata can create problems
of their own, including rectal irritation and hyperphosphatemia. The best enema is
warm soapy water made with a mild soap such as liquid Ivory soap that can be administered
through soft rubber tubing using gravity flow. Foals with significant meconium retention
become colicky within the first few hours of life as gas accumulates within their
bowel. Frequently, one can palpate the meconium through the abdominal wall. Additional
diagnostics can include abdominal ultrasonography and radiography, particularly if
one must rule out other, more serious types of colic. These foals assume a classic
stance with an arched back. One must differentiate this stance from the stance assumed
by foals with uroperitoneum, which is more extended. Foals with meconium retention
have had simultaneous ruptured bladder, however, so the clinician must be sure to
evaluate the foal fully for both problems. Foals that do not respond rapidly to enema
administration need additional treatment, which can include giving mineral oil (2
to 4 ounces) by nasogastric tube. One can treat persistent meconium retention resulting
in significant abdominal distention by muzzling the foal to prevent further milk intake
and administering intravenous fluids at an appropriate maintenance rate. If continuous
rate infusion is possible, 5% to 10% dextrose is the preferred fluid to use to provide
calories to the foal. One should not use dextrose as a bolus fluid. More aggressive
treatment would include administration of retention enemata made using acetylcysteine,
which serves as an irritant and increases secretion. Extreme cases of meconium retention
may require surgical intervention, but this is usually not necessary and most cases
resolve with medical management alone within 12 to 24 hours. Some foals require pain
managment. One should avoid nonsteroidal antiinflammatory drugs in the neonate because
of their effects on renal function and gastric mucosal blood flow (see Gastric Ulcers).
Many foals respond well to butorphanol administered intramuscularly at a dose of 3
to 5 mg to an average 50-kg foal. Intranasal oxygen insufflation is beneficial in
foals with significant abdominal distention.
One should evaluate foals with meconium impaction/retention for evidence of PAS because
intestinal dysmotility is common in PAS. Colostrum is a laxative, and these foals
also may suffer from failure of passive transfer, with meconium retention resulting
from the lack of adequate colostrum. These foals are also at risk of sepsis because
the mucosal intestinal barrier probably has been disrupted and translocation of bacteria
can occur. One should obtain blood cultures on these foals and should monitor them
closely for signs of sepsis.
CONGENITAL DEFECTS
Atresia within the gastrointestinal system of the foal occurs infrequently, but clinical
signs are characteristic.
357
Acute colic occurs within the first few hours and is accompanied by abdominal distention
similar to meconium retention. Three primary types of atresia are described in the
foal: membrane atresia, cord atresia, and blind-end atresia. Antemortem diagnosis
of atresia, short of abdominal exploratory surgery, is aided by the lack of meconium
staining of the rectum or any administered enema fluids. Additional diagnostic tests
may include administration of a barium enema for a radiographic study, colonoscopy,
and abdominal ultrasonography. Abdominocentesis is usually normal until bowel rupture
is imminent or has occurred. One can make affected foals more comfortable by muzzling
them to prevent further milk intake and by supplying them with fluids and nutrition
intravenously. If one attempts surgical correction, one first should initiate broad-spectrum
antimicrobial therapy and determine passive transfer status. Frequently, these foals
are hypoxemic because of the abdominal distention, and oxygen supplementation is desirable.
LETHAL WHITE SYNDROME
Solid white foals born to overo-overo matings of American Paint Horses may suffer
from congential aganglionosis of the ileum, cecum, and colon. These foals present
similarly to foals with meconium impaction or atresia in that colic develops shortly
after birth and involves progressive abdominal distention with feeding. The inherited
defect is in the endothelin receptor gene.358, 359, 360, 361 No effective treatment
exists, but the clinician should be aware that not all white foals of this mating
are affected, and some simply may have meconium retention, so a short period of treatment
may be warranted.
NECROTIZING ENTEROCOLITIS
Necrotizing enterocolitis is considered the most common acquired gastrointestinal
emergency of human infants.362, 363 The 1500 to 2000 infants that die every year from
this disease in the United States and the large number of infants who develop short
gut syndrome from this disease only represent the tip of the iceberg of the problems
necrotizing enterocolitis causes. The widespread fear of necrotizing enterocolitis
among neonatologists and pediatric surgeons has contributed in large part to the use
of the intravenous route rather than the gastrointestinal tract for nourishing these
infants for long periods. The pathogenesis of necrotizing enterocolitis is unknown
but may result from a disturbance of the delicate balance among gastrointestinal perfusion,
enteric organisms, and enteral feeding. Risk factors for necrotizing enterocolitis
in human infants include prematurity, hypoxic-ischemic insult, and formula or breast
milk feedings. The clinical spectrum of necrotizing enterocolitis is multifactoral
and ranges from temperature instability, apnea, lethargy, abdominal distention, bilious
residuals, septic shock, disseminated intravascular coagulation, and death. Medical
management is usually adequate treatment for necrotizing enterocolitis. In the neonatal
foal, necrotizing enterocolitis is probably one of the most underrecognized causes
of gastrointestinal dysfunction and in the past has been attributed only to infection
with anaerobic organisms including Clostridium perfringens type C and C. difficile.
364
Although a specific form of enteritis is associated with intestinal infection by these
organisms, most necrotizing enterocolitis is associated with prematurity or PAS in
the infant and the foal.
One should suspect necrotizing enterocolitis in any foal that is having difficulty
tolerating oral feeding, demonstrating signs of ileus, or having episodes of colic
and in any foal with occult blood or frank blood in the stool. Foals exhibiting any
of these clinical signs should not be fed orally if possible and should receive parenteral
nutrition until gastrointestinal function returns to near normal. The mucosal barrier
of the intestine is unlikely to be fully intact, and these foals are at risk for sepsis
from bacterial translocation. One should institute broad-spectrum antimicrobial therapy
in these foals and, if any evidence of coordinated gastrointestinal motility is apparent,
should administer sucralfate orally as a protectant.
GASTRIC ULCERS
Gastric ulcer disease has been recognized in foals, and lesions vary in anatomic distribution,
severity, and cause. In clinically normal neonatal foals (<30 days of age), gastric
ulcers and mucosal desquamation have been documented.365, 366, 367, 368 Because of
these reports and other early reports of death following ruptured clinically silent
ulcers in neonatal foals, for years many clinicians felt it necessary to treat critically
ill neonates with antiulcer medication prophylactically.369, 370, 371 Recently, this
paradigm has been challenged.
The pathophysiology of gastric ulcer disease is described most reasonably as an imbalance
in protective and aggressive factors.372, 373, 374 These protective factors are responsible
for maintaining a healthy gastrointestinal tract by promoting adequate mucosal blood
flow, adequate mucus and bicarbonate production, prostaglandin E2 production, epithelial
growth factor production, gastric afferent innervation, epithelial cell restitution,
and gastroduodenal motility. Probably the most important factor is maintenance of
mucosal blood flow. Hypoxia, NO, prostaglandins, and gastric afferent innervation
influence mucosal blood flow. The aggressive factors include gastric acid, bile salts,
pepsin, and enzymes. Few specific causes have been found for gastric ulcer disease
in foals. Excessive administration of nonsteroidal antiinflammatory drugs can result
in ulceration of the glandular and squamous epithelium because of an inhibition of
prostaglandin production, which leads to a decrease in mucosal blood flow and an increase
in acid production. Nonsteroidal antiinflammatory drugs also can impair the healing
of lesions and rarely are indicated in neonatal equine medicine.372, 373
In the critically ill neonate the suspected cause of gastric ulcers has shifted away
from an excessive amount of intraluminal gastric acid toward gastric mucosal ischemia
caused by hypoxia, low blood flow conditions, or both.
375
Perforating gastric ulcers are more likely a manifestation of necrotizing enterocolitis
than of excessive gastric acid. Shock, sepsis, or trauma can result in gastric mucosal
ischemia, allowing for the disruption of epithelial cell integrity and permitting
damage by aggressive factors or providing an environment suitable for the establishment
of bacteria colonization.375, 376 Impairment of mucosal blood flow also may result
in reperfusion injury, allowing the formation of gastric ulcers. In the sick neonatal
foal (<7 days of age) a wide variability in the intragastric pH has been documented
depending on the type of disease, severity, and milk intake frequency and volume,
suggesting that in the critically ill equine neonate, ulcer prophylaxis using histamine
antagonists or proton pump inhibitors is not only unnecessary but unlikely to work.
377
Clinically significant gastric ulcers can occur in the squamous, glandular, or both
portions of the stomach as a primary problem or resulting from another problem. Clinical
signs include diarrhea, abdominal pain, restlessness, rolling, lying in dorsal recumbency,
excessive salivation, and bruxism. In the neonatal foal the only clinical signs present
may be depression or partial anorexia until a more catastrophic event, such as perforation,
occurs. Some lesions in the gastric mucosa extend from the pylorus into the proximal
duodenum and can result in stricture of the pylorus and proximal duodenum. These foals
are usually older (>1 month of age) and have a greater volume of reflux. Bruxism and
ptyalism are also more prominent in these older foals.
The most sensitive and specific method for diagnosing gastric ulcers is visualization
by endoscopic examination.
365
Unfortunately, the use of gastric endoscopy has led to recognition of relative nonlesions
and ulcers resulting from other problems and of clinically significant disease states.
The clinician should not stop simply when ulceration of the stomach is recognized
with endoscopy but should examine that patient fully for other potential sources of
the clinical signs. Other diagnostic tests may help in determining the severity of
the ulcers, including fecal occult blood or gastric blood assessments, contrast radiography,
abdominal ultrasound, and abdominocentesis. Endoscopy of the foal stomach carries
an additional risk of exacerbating colic in the short term, unless the examiner ensures
that as much introduced air as possible is evacuated from the stomach at the end of
the procedure.
The presence of a brown gastric reflux fluid may indicate the presence of bleeding
ulcers. Blood in the feces of the neonate is more consistent with a diagnosis of necrotizing
enterocolitis, which can be associated with gastric ulcers. Contrast radiography is
useful if one suspsects delayed gastric emptying or pyloric or duodenal stricture
in older foals. If a stricture has occurred, one will note a delay in complete emptying
of barium from the stomach (>2 hours).
367
Abdominal ultrasound may be useful to visualize free abdominal fluid and gastric or
small intestinal distention if one suspects a perforation. One can visualize portions
of the descending duodenum, and a thickened duodenum should increase the index of
suspicion for duondenal stricture. Abdominocentesis also may confirm perforation.
Traditional therapy for gastric ulceration includes mucosal adherents, histamine type
2 receptor antagonists, proton pump inhibitors, and antacids.
378
The most widely used mucosal adherent is sucralfate, which is a hydroxy aluminum salt
of sucrose. The main therapeutic action of sucralfate is to bind to the negatively
charged particles in the ulcer crater.378, 379 At a pH less than 2, sucralfate is
converted to a sticky viscous gel, which adheres to the ulcer crater and remains adhered
for 6 hours, but at a higher pH, sucralfate remains in a suspension. Sucralfate is
still effective because it inhibits pepsin and buffers hydrogen ions. Other important
actions of sucralfate include stimulating production of prostaglandin E, which maintains
mucosal blood flow; increasing bicarbonate secretion; stimulating mucous secretion;
decreasing peptic activity; and binding epidermal growth factor. The histamine type
2 receptor antagonists include cimetidine, ranitidine, and famotidine. These compounds
block the interaction of histamine with the histamine type 2 receptor on the parietal
cell, resulting in inhibition of gastric acid secretion. Clinically normal neonatal
foals have a highly acidic gastric fluid that is influenced by sucking. Intravenous
and oral administration of ranitidine increases intragastric pH in normal foals but
critically ill neonatal foals have a blunted response to ranitidine administration.377,
380 One possible conclusion reached from these studies is that in critically ill neonatal
foals, gastric ulcers may not be caused by an increased intraluminal gastric acidity.
The most commonly used proton pump inhibitor is omeprazole. This drug has not as yet
been approved for use in foals under 30 days of age. Omeprazole inhibits the secretion
of hydrogen ions at the parietal cell by irreversibly binding to the H+,K+-ATPase
proton pump of the cell. Most of the lesions in older foals were healed after daily
administration of omeprazole for 28 days according to one report.
381
Table 19-9
summarizes the therapeutic agents for treating gastric ulcers in foals.
TABLE 19-9
Therapeutic Agents for Treating Gastric Ulcers in Foals
DRUG CATEGORY
DRUG
DOSE
ROUTE
FREQUENCY
Mucosal protectant
Sucralfate
10–20 mg/kg
p.o.
t.i.d. to q.i.d.
Histamine type 2 receptor antagonist
Cimetidine
10–20 mg/kg
p.o.
q4h
Ranitidine
6.6 mg/kg
IV*
q4h
5–10 mg/kg
p.o.
b.i.d. to q.i.d.
0.8–2.2 mg/kg
IV
q.i.d.
Proton pump inhibitor
Omeprazole
4 mg/kg
p.o.
s.i.d.
1–2 mg/kg
p.o.
s.i.d. (prophylaxis)
Antacids
Milk of Magnesia
2–4 oz
p.o.
s.i.d. to b.i.d.
Maalox
240 ml
p.o.
q4h
*
IV, Intravenous.
Adapted from Barr B: Gastric ulcer prophylaxis in the critically ill equine neonate.
In Wilkins PA, Palmer JE, editors: Recent advances in equine neonatal care, Ithaca,
NY, 2001, International Veterinary Information Service (A0413.1101).
© 2004 International Veterinary Information Service
2004
Since January 2020 Elsevier has created a COVID-19 resource centre with free information
in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre
is hosted on Elsevier Connect, the company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related research that is
available on the COVID-19 resource centre - including this research content - immediately
available in PubMed Central and other publicly funded repositories, such as the WHO
COVID database with rights for unrestricted research re-use and analyses in any form
or by any means with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Prophylactic treatment of critically ill neonates for gastric ulcers has been standard
therapy for years because of the evidence of clinically silent ulcers. This approach
may not be appropriate for several reasons. An increased incidence of nosocomial pneumonia
and systemic sepsis is associated with high gastric pH in human patients in intensive
care.382, 383, 384 Patients in intensive care units treated prophylactically with
histamine type 2 receptor antagonists are more likely to develop pneumonia during
ventilation therapy and gastric colonization with potentially pathogenic bacteria
or yeast.382, 385 An acidic environment appears to protect against airway colonization
by bacteria of intestinal origin and bacteria translocated across the gastrointestinal
tract. Pathogenesis of ulcers in the neonatal foal most likely does not involve increased
intraluminal gastric acid but instead may be caused by decreased mucosal perfusion
associated with shock, hypoxia, and hypoxic/ischemic insult to the gastric mucosa.
A recent report revealed that gastric ulcer disease in equine NICU patients is independent
of pharmacologic prophylaxis.
386
In this study, despite decreased treatment, the incidence of gastric ulcers found
in these foals at necropsy had decreased significantly. The decrease was attributed
to overall improvement in management of these cases. Similarly, in a human intensive
care unit, the incidence of stress ulcers decreased independent of the use of prophylaxis.375,
387 Early treatment of sepsis, sufficient oxygenation, improved monitoring, institution
of enteral feedings, and improved nursing care may contribute to the reduction in
gastric ulcers in the neonatal patient. Use of histamine type 2 receptor antagonist
and proton pump inhibitors apparently may not be necessary; however, in some instances
sucralfate may be useful. Sucralfate reduced the rate of bacterial translocation in
a rat model during hemorrhagic shock and also may prohibit the generation of acute
gastric mucosal injury and progression to ulcer formation induced by ischemia-reperfusion.388,
389 In a human medical intensive care unit, airway colonization by new pathogens occurred
more frequently in patients receiving agents that increased gastric pH than in those
receiving sucralfate.382, 390 In the critically ill neonatal foal, risk factors for
gastric ulceration have not been identified clearly, although foals treated routinely
with nonsteroidal antiinflammatory drugs may be at increased risk for gastric lesions.
Prophylactic treatment for gastric ulcers in critically ill neonates may not be necessary,
and one should consider carefully the pros and cons of their use before their administration.
DIARRHEAL DISEASES OF FOALS
Foal Heat Diarrhea
Foal heat diarrhea is a mild, self-limiting form of diarrhea that occurs in foals
between 5 and 14 days of age, about the time of the “foal heat” in the dam. The definitive
cause of foal heat diarrhea has yet to be described, but the condition may be associated
with dietary changes or changes in gastrointestinal function that occur around that
time. This form of diarrhea is not caused by Stongyloides westeri infestation as previously
thought.
391
Foals with foal heat diarrhea are not systemically ill and should not require therapy.
One should evaluate fully any foals with diarrhea at this time for other possible
causes of diarrhea, particularly if they are unwell or exhibit anorexia or dehydration.
Viral Diarrhea
Viral diarrhea occurs most commonly in large groups of mares and foals that are housed
together. Rotavirus is an isolate from the feces of up to 40% of foals with diarrhea
worldwide, alone or with another pathogen.392, 393 The virus infects and denudes the
microvilli, resulting in increased secretion combined with decreased absorption. The
virus interferes with disaccharidase function and alters the function of the intestinal
sodium-glucose cotransport proteins. The initial clinical signs are anorexia and depression,
with profuse watery diarrhea occurring shortly thereafter. Severely affected foals
may become significantly dehydrated and have electrolyte abnormalities, primarily
hyponatremia and hypochloremia with metabolic acidosis. These foals generally require
intravenous fluid support, whereas less severely affected foals may require only symptomatic
therapy. Definitive diagnosis is by detection of the virus in the feces of foals with
diarrhea. However, none of the available tests are particularly sensitive, and the
virus also may be found with other intestinal pathogens. Recently, vaccination of
pregnant mares has been suggested as a means of prevention, with preliminary results
suggesting efficacy.394, 395 Although a definitive role for adenovirus has not been
established in the foal, adenovirus is a common co-isolate from foals with rotaviral
diarrhea.
396
A specific equine coronavirus recently has been identified from an immunocompetent
foal with diarrhea, and a second report of cornavirus diarrhea was published recently.397,
398 One case report suggests a parvovirus caused diarrhea in the foal.
399
Treatment of viral diarrhea in foals is primarily supportive. Intravenous fluid and
parenteral nutritional support may be necessary in severe cases. Very young foals
may benefit from intravenous plasma administration and broad-spectrum antimicrobial
coverage to limit bacterial translocation. One can administer sucralfate orally in
these cases as a gastrointestinal protectant and to discourage bacterial translocation.
Foals with moderate to severe metabolic acidosis may benefit from sodium bicarbonate
administration if their ventilatory function is normal. One administers sodium bicarbonate
at half the calculated deficit (0.5 × standard base excess × body mass in kilograms)
as an isotonic solution at the maintenance fluid rate. One should reevaluate sodium
and bicarbonate (or standard base excess) concentrations regularly. Nonspecific therapy
of diarrhea is discussed elsewhere in this text.
Bacterial Diarrhea
Diarrhea is frequently the primary presenting complaint in foals with sepsis, so one
should rule out this differential diagnosis in foals less than 1 week of age. One
should evaluate all neonatal foals with diarrhea for possible sepsis and should include
a blood culture whenever possible.
Clostridium perfringens and C. difficile are recognized increasingly as serious pathogens
of the foal.400, 401, 402, 403 Foals with either pathogen generally have abdominal
pain, dehydration, and profuse watery diarrhea. Some foals may have red-tinged or
frankly bloody feces, which carries a poorer prognosis. Most foals with this type
of diarrhea require intensive care or, at the minimum, intravenous fluid administration.
Outbreaks of this type of diarrhea on farms occasionally occur, and the suggestion
is that the dam has a role in transmission of the bacteria. Diagnosis is by recognition
of the offending organism by Gram stain of the feces, by bacterial isolation from
the feces, and by detecting the presence of toxins associated with the organisms.
Specific treatment includes oral administration of metronidazole and broad-spectrum
antimicrobial coverage as prophylaxis for bacterial translocation associated sepsis
in younger foals. Foals with severe blood loss in their feces may require transfusion
of whole blood.
Salmonella spp., Escherichia coli, Bacteroides fragilis, and Aeromonas hydrophila
have been implicated in diarrhea in foals. Salmonella generally is associated with
septicemia in foals, and although some convincing evidence exists for a role for E.
coli in foal diarrheal disease, the extent of E. coli as a pathogen of the gastrointestinal
tract in foals has yet to be described fully.371, 404, 405, 406, 407
Proliferative enteropathy is a transmissible enteric disease caused by Lawsonia intracellulare.
408, 409 Most foals have been weaned before the appearance of clinical signs of depression,
rapid and significant weight loss, subcutaneous edema, diarrhea, and colic. Poor body
condition with a rough hair coat and a pot-bellied appearance are common in affected
foals. Clinicopathologic abnormalities included hypoproteinemia, leukocytosis, anemia,
and increased serum creatine kinase concentration. Postmortem reveals characteristic
intracellular bacteria within the apical cytoplasm of proliferating crypt epithelial
cells of the intestinal mucosa. Antemortem diagnosis of equine proliferative enteropathy
is based on clinical signs, hypoproteinemia, and the exclusion of other common enteric
pathogens. Fecal polymerase chain reaction analysis may be positive for the presence
of L. intracellulare, and affected foals develop antibodies against L. intracellulare.
410
Treatment with erythromycin estolate alone or combined with rifampin for a minimum
of 21 days is recommended with additional symptomatic treatment when indicated.
Protozoal Diarrhea
Cryptosporidium spp. cause gastroenteritis and diarrhea in many animal species and
are not host-specific. Cryptosporidium has been implicated as the casual agent of
diarrhea in foals, but the organism is isolated from the feces of diarrheic foals
and normal foals with the same frequency and concentration, making a clear role for
the organism difficult to elucidate.411, 412, 413 Diarrhea caused by Cryptosporidium
in other species and that described for foals is generally self-limiting, with a clinical
course of between 5 to 14 days. Immunosuppressed patients, including foals compromised
by concurrent disease, are thought to be at increased risk for complications resulting
from infection with this organism.411, 412 Treatment is symptomatic. Cryptosporidiosis
is a disease with zoonotic potential, and one should take appropriate precautions,
including use of gloves and frequent hand washing, if organisms are identified in
the feces of any patients so as to prevent spread to other patients and personnel.
Eimeria leukarti, Trichomonas equi, and Giardia equi have been identified in the feces
of normal horses and horses with diarrhea. Transmission studies have failed to produce
reliable clinical signs, and the prevalence and significance of these organisms in
the genesis of foal diarrhea remain unknown.
Parasitic Diarrhea
Strongyloides westeri is a common parasitic infection of foals.392, 414, 415 Transmission
is transmammary, and patent infection is recognizable in the foal by 8 to 12 days
of age. This nematode previously was associated anecdotally with foal heat diarrhea,
but the association has not been demonstrated clearly. The diarrhea is generally mild
and is treated effectively by deworming with benzimidazole or ivermectin anthelmintics.
391
Strongylus vulgaris fourth-stage larvae cause diarrhea in young foals during migration
through the arterioles of the cecum and descending colon. Clinical signs may resemble
thromboembolic colic.
414
The prepatent period is about 6 months, and diagnosis is based on clinical examination,
clinicopathologic changes, and farm deworming history. Patients with diarrhea associated
with this parasite may have peripheral leukocytosis, neutrophilia, eosinophilia, and
hypoproteinemia. Appropriate deworming with ivermectin (label dose), fenbendazole
(10 mg/kg/day orally for 5 days), or thiabendazole (440 mg/kg/day orally for 2 days)
is recommended, with the last two drug dosages being larger than the label dose.
Cyathostomiasis, or diarrhea resulting from the sudden emergence of encysted cyathostome
larvae, is an unusual cause of diarrhea in the foal.
Neonate Therapy
FLUID THERAPY IN NEONATES
The clinician managing critically ill neonates must recognize that intravenous fluid
therapy simply cannot be scaled down from adult management approaches. Fluid management
of the ill neonate, particularly over the first few days of life, must take into consideration
that the neonate is undergoing a large transition from the fetal to the neonatal state
and that important physiologic changes are taking place.
166
These transitions include shifts in renal handling of free water and sodium and increased
insensible losses because of evaporation from the body surface area and the respiratory
tract. The newborn kidney has a limited ability to excrete excess free water and sodium,
and the barrier between the vascular and interstitial space is more porous than that
of adults. Water and sodium overload, particularly in the first few days of life,
can have disastrous long-term consequences for the neonate.416, 417 In the equine
neonate, excess fluid administration frequently manifests as generalized edema formation
and excessive weight gain, frequently equivalent to the volume of excess fluid administered
intravenously. In cases in which antidiuretic hormone secretion is inappropriate,
as in some foals with PAS, generalized edema may not form, but the excess free water
is maintained in the vascular space. This syndrome of inappropriate antidiuretic hormone
secretion is recognized in the foal that gains excessive weight not manifested as
edema generally, with decreased urine output and electrolyte abnormalities such as
hyponatremia and hypochloremia.
418
The foal manifests neurologic abnormalities associated with hyponatremia. The serum
creatinine concentration varies in these cases, but urine always is concentrated compared
with the normally dilute, copious amounts of urine produced by foals more than 24
hours of age on a milk diet. If measured, serum osmolarity is less than urine osmolarity.
The treatment for this disorder is fluid restriction until weight loss occurs, electrolyte
abnormalities normalize, and urine concentration decreases. If the clinician is unaware
of this differential diagnosis, the neonate can be assumed mistakenly to be in renal
failure, and the condition can be exacerbated by excessive intravenous fluid administration
in an attempt to produce diuresis.
The problem of appropriate fluid management in critically ill neonates has been recognized
by medical physicians for years and has resulted in changes in fluid management of
these patients. The approach taken has been one of fluid restriction, in particular
sodium restriction but also free water restriction, and has resulted in improved outcome
and fewer complications, such as patent ductus arteriosus and necrotizing enterocolitis.416,
417 The calculations used for maintenance intravenous fluid support in these patients
takes into consideration the ratio of surface area to volume and partially compensates
for insensible water losses. Maintenance fluids are provided as 5% dextrose to limit
sodium overload and provide sufficient free water to restore intracellular and interstitial
requirements. The calculation for maintenance fluid administration is as follows:
First 10 kg body mass
100 ml/kg/day
Second 10 kg body mass
50 ml/kg/day
All additional kilograms of body mass
25 ml/kg/day
As an example, the average 50-kg foal would receive 1000 ml/day for the first 10 kg
of body mass, 500 ml/day for the next 10 kg of body mass, and 750 ml/day for the remaining
30 kg of body mass for a total of 2250 ml/day. This translates to an hourly fluid
rate of about 94 ml/hr.
One should adjust the fluid and sodium requirements for ongoing losses exceeding the
maintenance requirements. These losses can take the form of diarrheal losses and excessive
urine output, such as those with glucose diuresis and renal damage resulting in an
increased fractional excretion of sodium. The normal fractional excretion of sodium
in neonatal foals is less than that of adult horses, usually less than 1% (J.E. Palmer,
unpublished data). In the critically ill foal the sodium requirement can be met with
as little as 140 mEq of sodium per day, about that administered in a single liter
of normal equine plasma. One can address sodium deficits by separate infusion of sodium-containing
fluids, although this may not be necessary if one considers the sodium being administered
in other forms, including drugs administered as sodium salts and any constant rate
infusions (pressors, inotropes, etc.) that are being provided as solutions made with
0.9% sodium chloride.
The author has used this approach to fluid therapy in her NICU for the last few years
and believes that the percentage of foals suffering from generalized edema and related
problems has decreased. If one takes this approach to fluid therapy, one should take
the weight of the patient once daily, or even twice daily, and monitor the fluid intake
and output as closely as practical. One should evaluate any larger than anticipated
weight gains or losses. One should not expect urine output to approach the reported
normal of 300 ml/hr for a 50-kg foal because the free water administered is limited,
unless the patient is experiencing diuresis (glucosuria, resolution of the syndrome
of inappropriate antidiuretic hormone secretion, resolution of previous edematous
state, renal disease). One should obtain the urine specific gravity several times
daily and should determine fractional excretion of sodium at regular intervals. If
the volume of urine produced by the patient is measured accurately, one can determine
sodium losses accurately and can obtain creatinine clearance values. One should obtain
blood pressure measurements at regular intervals throughout the day because hypotension
can be a problem in these patients, particularly in septic foals and foals suffering
from PAS, and one may need to increase fluid therapy to maintain adequate vascular
volume. Patients with hypotension may need inotrope and pressor support.
PRESSOR AND INOTROPE THERAPY IN NEONATES
Inotrope and pressor therapy generally is restricted to referral centers where these
drugs can be administered as constant rate infusions and blood pressure can be monitored
closely. Blood pressure can be monitored directly or indirectly by the use of cuffs
placed on the base of the tail. Both techniques have advantages and disadvantages.
Although direct blood pressure measurements are considered the gold standard and are
generally more accurate, the difficulty in placing and maintaining arterial catheters
and lines in these patients severely restricts the utility of this method. Indirect
techniques can be inaccurate and are affected by cuff size and placement. However,
indirect techniques are easier to use in the NICU and can be useful if trained staff
are using the equipment. In the author's NICU, once practitioners identify the appropriate
cuff size, they dedicate that cuff to that patient for the duration of the hospitalization
to decrease variability caused by using different cuffs. One should monitor the blood
pressure of all recumbent patients at regular intervals, and trends upward or downward
should prompt the clinician to make necessary adjustments.
Foals suffering from PAS and sepsis are the patients most at risk for significant
hypotension and perfusion abnormalities. Perfusion is maintained by supporting cardiac
output and blood pressure with judicious use of intravenous fluid support and inotrope/pressor
support. The author does not aim for any specific target systolic, mean, or diastolic
pressure. Instead the author monitors urine output, mentation, limb perfusion, gastrointestinal
function, and respiratory function as indicators that perfusion is acceptable. For
NICU patients to require inotrope and pressor therapy is not unusual, but in some
cases hypoxic and septic damage is sufficiently severe to blunt the response of the
patient to the drugs. One must approach each patient as an individual, and no single
inotrope/pressor protocol will suffice for all patients.
Dobutamine is a β-adrenergic inotrope that is frequently used as first choice therapy
in NICU patients. Its effects are β1 at the lower dose range. Neonates have a limited
ability to increase stroke volume in an effort to maintain cardiac output, and one
may observe tachycardia in these patients as heart rate increases to maintain cardiac
output and vascular pressure. Dobutamine is useful after patients are volume replete
for support of cardiac output. The dose range is between 2 to 20 μg/kg/min provided
as a constant rate infusion.
Dopamine has dopaminergic activity at low doses, β1 and β2 activity at moderate doses,
and α1 activity at high doses. Dopamine causes norepinephrine release, which has lead
to the suggestion that this is its major mode of action at higher doses. At doses
greater than 20 μg/kg/min, intrapulmonary shunting, pulmonary venous vasoconstriction,
and reduced splanchic perfusion may occur. Dopamine also produces natriuresis at lower
doses through a direct effect on renal tubules. For these reasons, dopamine has fallen
out of favor at some referral institutions.
Norepinephrine has α1 and β1 activity but variable β2 activity, resulting in potent
vasopressor effects; it has inotropic and chronotropic effects, but its chronotropic
effect usually is blunted by vagal reflexes slowing the heart rate induced by the
increase in blood pressure. In many critical care units, norepinephrine has become
a pressor of choice and frequently is used along with dobutamine. Evidence suggests
that splanchic perfusion is maintained better with norepinephrine than with some other
pressors.
419
The dose range is 0.2 to 2.0 μg/kg/min, although larger doses have been used when
necessary in certain patients.
Epinephrine has α1, α2, β1, and β2 activity; β activity predominates and results in
increased cardiac output and decreased peripheral resistance at low doses. Epinephrine
has been associated with hyperglycemia, hypokalemia, lipolysis, increased lactate
concentration, and increased platelet aggregation. The effect on renal function is
controversial. Use of epinephrine usually is limited to those patients not responding
to other pressors.
Vasopressin (antidiuretic hormone) is a pressor gaining a great deal of attention
in the critical care literature. Vasopressin appears to be depleted from the neurohypophysis
in septic shock,
420
and short-term administration of vasopressin spares conventional vasopressor use,
in addition to improving some measures of renal function.
421
Low-dose vasopressin infusion increases mean arterial pressure, systemic vascular
resistance, and urine output in patients with vasodilatory septic shock that are hyporesponsive
to catecholamines. These data indicate that low-dose vasopressin infusions may be
useful in treating hypotension in patients with septic shock.
422
The author has been using low-dose vasopressin in patients in her NICU for the past
few years and has the clinical impression that blood pressure is defended more readily
using this agent in concert with other management strategies. The author commonly
uses low-dose vasopressin constant rate infusion with dobutamine constant rate infusion
as the initial inotrope/pressor therapy in cases requiring pressure defense, although
no prospective studies are yet available regarding this drug in veterinary medicine.
REFERENCES
1
Rossdale
PD
Clinical studies on 4 newborn throughbred foals suffering from convulsions with special
reference to blood gas chemistry and pulmonary ventilation
Res Vet Sci
10
3
1969
279
291
5388662
2
Rossdale
PD
Pattle
RE
Mahaffey
LW
Respiratory distress in a newborn foal with failure to form lung lining film
Nature
215
109
1967
1498
1499
5183154
3
Rossdale
PD
Clinical studies on the newborn thoroughbred foal. 2. Heart rate, auscultation and
electrocardiogram
Br Vet J
123
12
1967
521
532
6076666
4
Rossdale
PD
Blood gas tensions and pH values in the normal thoroughbred foal at birth and in the
following 42h
Biol Neonat
13
1
1968
18
25
5753166
5
Rossdale
PD
Measurements of pulmonary ventilation in normal newborn thoroughbred foals during
the first three days of life
Br Vet J
125
4
1969
157
161
5814054
6
Rossdale
PD
Some parameters of respiratory function in normal and abnormal newborn foals with
special reference to levels of paO2 during air and oxygen inhalation
Res Vet Sci
11
3
1970
270
276
5532266
7
Rossdale
PD
Modern concepts of neonatal disease in foals
Equine Vet J
4
3
1972
117
128
4568905
8
Nathanielsz
PW
Rossdale
PD
Silver
M
Studies on fetal, neonatal and maternal cortisol metabolism in the mare
J Reprod Fertil Suppl
23
1975
625
630
9
Arvidson
G
Astedt
B
Ekelund
L
Surfactant studies in the fetal and neonatal foal
J Reprod Fertil Suppl
23
1975
663
665
10
Palmer
AC
Rossdale
PD
Neuropathology of the convulsive foal syndrome
J Reprod Fertil Suppl
23
1975
691
694
11
Kitchen
H
Rossdale
PD
Metabolic profiles of newborn foals
J Reprod Fertil Suppl
23
1975
705
707
12
Palmer
AC
Rossdale
PD
Neuropathological changes associated with the neonatal maladjustment syndrome in the
thoroughbred foal
Res Vet Sci
20
3
1976
267
275
935662
13
Rose
RJ
Rossdale
PD
Leadon
DP
Blood gas and acid-base status in spontaneously delivered, term-induced and induced
premature foals
J Reprod Fertil Suppl
32
1982
521
528
6820066
14
Rossdale
PD
Ousey
JC
Dudan
FE
Studies on equine prematurity. 1. Methodology
Equine Vet J
16
4
1984
275
278
6479124
15
Kosch
PC
Koterba
AM
Coons
TJ
Developments in management of the newborn foal in respiratory distress. 1. Evaluation
Equine Vet J
16
4
1984
312
318
6383813
16
Koterba
AM
Brewer
BD
Tarplee
FA
Clinical and clinicopathological characteristics of the septicaemic neonatal foal:
review of 38 cases
Equine Vet J
16
4
1984
376
382
6479139
17
Koterba
AM
Drummond
WH
Kosch
P
Intensive care of the neonatal foal
Vet Clin North Am Equine Pract
1
1
1985
3
34
3878189
18
Koterba
AM
Drummond
WH
Nutritional support of the foal during intensive care
Vet Clin North Am Equine Pract
1
1
1985
35
40
3935294
19
Brewer
BD
Koterba
AM
Carter
RL
Comparison of empirically developed sepsis score with a computer generated and weighted
scoring system for the identification of sepsis in the equine neonate
Equine Vet J
20
1
1988
23
24
3284743
20
Baker
SM
Drummond
WH
Lane
TJ
Follow-up evaluation of horses after neonatal intensive care
J Am Vet Med Assoc
189
11
1986
1454
1457
3804838
21
Axon
J
Palmer
J
Wilkins
PA
Short-term and long-term athletic outcome of neonatal intensive care unit survivors
Proc Am Assoc Equine Pract
45
1999
224
225
22
Freeman
L
Paradis
MR
Evaluating the effectiveness of equine neonatal intensive care
Vet Med
87
Sept 1992
921
926
23
Lester GD: Short and long term evaluation of neonatal intensive care. Proceedings
of the fourteenth annual meeting of the American College of Veterinary Internal Medicine,
San Antonio, Tex, 1996. pp 547-548.
24
LeBlanc
MM
Identification and treatment of the compromised equine fetus: a clinical perspective
Equine Vet J Suppl
24
1997
100
103
25
Donahue
JM
Williams
NM
Emergent causes of placentitis and abortion
Vet Clin North Am Equine Pract
16
3
2000
443
456
11219342
26
Janosi
S
Huszenicza
G
Kulcsar
M
Endocrine and reproductive consequences of certain endotoxin-mediated diseases in
farm mammals: a review
Acta Vet Hung
46
1
1998
71
84
9704512
27
Del Piero
F
Equine viral arteriti
Vet Pathol
37
4
2000
287
296
10896389
28
Vaala
WE
Sertich
PL
Management strategies for mares at risk for periparturient complications
Vet Clin North Am Equine Pract
10
1
1994
237
265
8039034
29
Putnam
MR
Bransby
DI
Schumacher
J
Effects of the fungal endophyte Acremonium coenophialum in fescue on pregnant mares
and foal viability
Am J Vet Res
52
12
1991
2071
2074
1789525
30
Redmond
LM
Cross
DL
Strickland
JR
Efficacy of domperidone and sulpiride as treatments for fescue toxicosis in horses
Am J Vet Res
55
5
1994
722
729
8067624
31
Kahn
W
Leidl
W
[Ultrasonic biometry of horse fetuses in utero and sonographic representation of their
organs]
Dtsch Tierarztl Wochenschr
94
9
1987
509
515
3319485
32
Adams-Brendemuehl
C
Pipers
FS
Antepartum evaluations of the equine fetus
J Reprod Fertil Suppl
35
1987
565
573
3316646
33
Reef
VB
Equine diagnostic ultrasound
1998
WB Saunders
Philadelphia
34
Buss
DD
Asbury
AC
Chevalier
L
Limitations in equine fetal electrocardiography
Am Vet Med Assoc
177
2
1980
174
176
35
Jensen
A
Garnier
Y
Berger
R
Dynamics of fetal circulatory responses to hypoxia and asphyxia
Eur J Obstet Gynecol Reprod Biol
84
2
1999
155
172
10428339
36
Cohn
HE
Piasecki
GJ
Jackson
BT
The effect of fetal heart rate on cardiovascular function during hypoxemia
Am J Obstet Gynecol
138
8
1980
1190
1199
6778215
37
Leadon
DP
Jeffcott
LB
Rossdale
PD
Mammary secretions in normal spontaneous and induced premature parturition in the
mare
Equine Vet J
16
4
1984
256
259
6479122
38
Ousey
JC
Delclaux
M
Rossdale
PD
Evaluation of three strip tests for measuring electrolytes in mares' pre-partum mammary
secretions and for predicting parturition
Equine Vet J
21
3
1989
196
200
2731508
39
Williams
MA
Goyert
NA
Goyert
GL
Preliminary report of transabdominal amniocentesis for the determination of pulmonary
maturity in an equine population
Equine Vet J
20
6
1988
457
458
3063523
40
Williams
MA
Schmidt
AR
Carleton
CL
Amniotic fluid analysis for ante-partum foetal assessment in the horse
Equine Vet J
24
3
1992
236
238
1606938
41
Schmidt
AR
Williams
MA
Carleton
CL
Evaluation of transabdominal ultrasound-guided amniocentesis in the late gestational
mare
Equine Vet J
23
4
1991
261
265
1915224
42
Cottrill
CM
Jeffers-Lo
J
Ousey
JC
The placenta as a determinant of fetal well-being in normal and abnormal equine pregnancies
J Reprod Fertil Suppl
44
1991
591
601
1795302
43
Giles
RC
Donahue
JM
Hong
CB
Causes of abortion, stillbirth, and perinatal death in horses: 3,527 cases (1986-1991)
J Am Vet Med Assoc
203
8
1993
1170
1175
8244867
44
Daels
PF
Stabenfeldt
GH
Hughes
JP
Evaluation of progesterone deficiency as a cause of fetal death in mares with experimentally
induced endotoxemia
Am J Vet Res
52
2
1991
282
288
2012339
45
McKinnon
AO
Lescun
TB
Walker
JH
The inability of some synthetic progestagens to maintain pregnancy in the mare
Equine Vet J
32
1
2000
83
85
10661391
46
Gastal
MO
Gastal
EL
Torres
CA
Effect of oxytocin, prostaglandin F2 alpha, and clenbuterol on uterine dynamics in
mares
Theriogenology
50
4
1998
521
534
10732144
47
Niebyl
JR
Johnson
JW
Inhibition of preterm labor
Clin Obstet Gynecol
23
1
1980
115
126
6102498
48
Harkins
JD
Mundy
GD
Stanley
S
Absence of detectable pharmacological effects after oral administration of isoxsuprine
Equine Vet J
30
4
1998
294
299
9705111
49
Wilkins
PA
Seahorn
TL
Intranasal oxygen therapy in adult horses
J Vet Emerg Crit Care
10
3
2000
221
50
Samuel
CA
Allen
WR
Steven
DH
Studies on the equine placenta. 1. Development of the microcotyledons
J Reprod Fertil
41
2
1974
441
445
4452985
51
Bjorkman
N
Fine structure of the fetal-maternal area of exchange in the epitheliochorial and
endotheliochorial types of placentation
Acta Anat Suppl (Basel)
61
1973
1
22
4585764
52
Comline
RS
Silver
M
pO2 levels in the placental circulation of the mare and ewe
Nature
217
123
1968
76
77
5635637
53
Silver
M
Comline
RS
Fetal and placental O2 consumption and the uptake of different metabolites in the
ruminant and horse during late gestation
Adv Exp Med Biol
75
1976
731
736
1015452
54
Fowden
AL
Forhead
AJ
White
KL
Equine uteroplacental metabolism at mid- and late gestation
Exp Physiol
85
5
2000
539
545
11038405
55
Inci
S
Ozcan
OE
Kilinc
K
Time-level relationship for lipid peroxidation and the protective effect of alpha-tocopherol
in experimental mild and severe brain injury
Neurosurgery
43
2
1998
330
335
9696087
56
Clifton
GL
Lyeth
BG
Jenkins
LW
Effect of D, alpha-tocopheryl succinate and polyethylene glycol on performance tests
after fluid percussion brain injury
J Neurotrauma
6
2
1989
71
81
2769771
57
Daneyemez
M
Kurt
E
Cosar
A
Methylprednisolone and vitamin E therapy in perinatal hypoxic-ischemic brain damage
in rats
Neuroscience
92
2
1999
693
697
10408617
58
Fowden
AL
Ralph
MM
Silver
M
Nutritional regulation of uteroplacental prostaglandin production and metabolism in
pregnant ewes and mares during late gestation
Exp Clin Endocrinol
102
3
1994
212
221
7995343
59
Freeman
DE
Hungerford
LL
Schaeffer
D
Caesarean section and other methods for assisted delivery: comparison of effects on
mare mortality and complications
Equine Vet J
31
3
1999
203
207
10402132
60
Jain
L
Alveolar fluid clearance in developing lungs and its role in neonatal transition
Clin Perinatol
26
3
1999
585
599
10494466
61
Folkesson
HG
Norlin
A
Baines
DL
Salt and water transport across the alveolar epithelium in the developing lung: correlations
between function and recent molecular biology advances
Int J Mol Med
2
5
1998
515
531
(review).
9858647
62
Dukarm
RC
Steinhorn
RH
Morin
FC
3rd
The normal pulmonary vascular transition at birth
Clin Perinatol
23
4
1996
711
726
8982566
63
Tessier
GJ
Lester
GD
Langham
MR
Ion transport properties of fetal sheep alveolar epithelial cells in monolayer culture
Am J Physiol
270
6 pt 1
1996
L1008
L1016
8764227
64
Lakshminrusimha
S
Steinhorn
RH
Pulmonary vascular biology during neonatal transition
Clin Perinatol
26
3
1999
601
619
10494467
65
Shaul
PW
Regulation of vasodilator synthesis during lung development
Early Hum Dev
54
3
1999
271
294
10321793
66
Steinhorn
RH
Millard
SL
Morin
FC
3rd
Persistent pulmonary hypertension of the newborn: role of nitric oxide and endothelin
in pathophysiology and treatment
Clin Perinatol
22
2
1995
405
428
7671545
67
Rossdale
PD
Clinical studies on the newborn thoroughbred foal. 1. Perinatal behavior
Br Vet J
123
11
1967
470
481
6070620
68
Rossdale
PD
The adaptive processes of the newborn foal
Vet Rec
87
2
1970
37
38
69
Lombard
CW
Evans
M
Martin
L
Blood pressure, electrocardiogram and echocardiogram measurements in the growing pony
foal
Equine Vet J
16
4
1984
342
347
6479130
70
Silver
M
Comline
RS
Transfer of gases and metabolites in the equine placenta: a comparison with other
species
J Reprod Fertil Suppl
23
1975
589
594
71
Comline
RS
Silver
M
A comparative study of blood gas tensions, oxygen affinity and red cell 2,3 DPG concentrations
in foetal and maternal blood in the mare, cow and sow
J Physiol
242
3
1974
805
826
4475693
72
Werner
EJ
Neonatal polycythemia and hyperviscosity
Clin Perinatol
22
3
1995
693
710
8521689
73
Koterba
AM
Kosch
PC
Respiratory mechanics and breathing pattern in neonatal foals
J Reprod Fertil Suppl
35
1987
575
585
3479610
74
Algren
S
Lynam
LE
Mechanics of ventilation: compliance
Neonatal Netw
12
4
1993
63
67
75
Stewart
JH
Rose
RJ
Barko
AM
Respiratory studies in foals from birth to seven days old
Equine Vet J
16
4
1984
323
328
6479127
76
Stewart
JH
Young
IH
Rose
RJ
The distribution of ventilation-perfusion ratios in the lungs of newborn foals
J Dev Physiol
9
4
1987
309
324
2821098
77
Adams
R
Mayhew
IG
Neurological examination of newborn foals
Equine Vet J
16
4
1984
306
312
6479126
78
Crowell-Davis
SL
Houpt
KA
Maternal behavior
Vet Clin North Am Equine Pract
2
3
1986
557
571
3492245
79
Martens
RJ
Pediatrics
ed 3
Mannsmann
RA
McCallister
ES
Pratt
PW
Equine medicine and surgery
vol 1
1982
American Veterinary Publications
Santa Barbara, Calif
80
Soifer
SJ
Kaslow
D
Roman
C
Umbilical cord compression produces pulmonary hypertension in newborn lambs: a model
to study the pathophysiology of persistent pulmonary hypertension in the newborn
J Dev Physiol
9
3
1987
239
252
3112213
81
Gupta
JM
Tizard
JP
The sequence of events in neonatal apnoea
Lancet
2
7506
1967
55
59
4165460
82
Tarnow-Mordi
WO
Room air or oxygen for asphyxiated babies?
Lancet
352
9125
1998
341
342
9717918
83
Saugstad
OD
Resuscitation with room-air or oxygen supplementation
Clin Perinatol
25
3
1998
741
756
9779345
84
Vento
M
Asensi
M
Sastre
J
Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately
asphyxiated term neonates
Pediatrics
107
4
2001
642
647
11335737
85
Vento
M
Asensi
M
Sastre
J
Six years of experience with the use of room air for the resuscitation of asphyxiated
newly born term infants
Biol Neonat
79
3-4
2001
261
267
86
Saugstad
OD
Resuscitation of newborn infants with room air or oxygen
Semin Neonatol
6
3
2001
233
239
11520188
87
Jean
D
Laverty
S
Halley
J
Thoracic trauma in newborn foals
Equine Vet J
31
2
1999
149
152
10213427
88
Kattwinkel
J
Niermeyer
S
Nadkarni
V
An advisory statement from the Pediatric Working Group of the International Liaison
Committee on Resuscitation
Middle East J Anesthesiol
16
3
2001
315
351
11789468
89
Ushay
HM
Notterman
DA
Pharmacology of pediatric resuscitation
Pediatr Clin North Am
44
1
1997
207
233
9057791
90
Holland
P
Hodge
D
Vasopressin and epinephrine for cardiac arrest
Lancet
358
9298
2001
2081
2082
11755643
91
Walker
D
Walker
A
Wood
C
Temperature of the human fetus
J Obstet Gynaecol Br Commonw
76
6
1969
503
511
5785672
92
Macaulay
JH
Randall
NR
Bond
K
Continuous monitoring of fetal temperature by noninvasive probe and its relationship
to maternal temperature, fetal heart rate, and cord arterial oxygen and pH
Obstet Gynecol
79
3
1992
469
474
1738532
93
Ball
KT
Gunn
TR
Gluckman
PD
Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis
J Appl Physiol
81
6
1996
2393
2398
9018484
94
Gunn
TR
Gluckman
PD
Perinatal thermogenesis
Early Hum Dev
42
3
1995
169
183
7493585
95
Gunn
TR
Ball
KT
Power
GG
Factors influencing the initiation of nonshivering thermogenesis
Am J Obstet Gynecol
164
1 pt 1
1991
210
217
1986610
96
Gunn
TR
Ball
KT
Gluckman
PD
Reversible umbilical cord occlusion: effects on thermogenesis in utero
Pediatr Res
30
6
1991
513
517
1805145
97
Cree
JE
Meyer
J
Hailey
DM
Diazepam in labour: its metabolism and effect on the clinical condition and thermogenesis
of the newborn
Br Med J
4
5887
1973
251
255
4753234
98
Brewer
BD
Clement
SF
Lotz
WS
Renal clearance, urinary excretion of endogenous substances, and urinary diagnostic
indices in healthy neonatal foals
J Vet Intern Med
5
1
1991
28
33
1673477
99
Edwards
DJ
Brownlow
MA
Hutchins
DR
Indices of renal function: values in eight normal foals from birth to 56 days
Aust Vet J
67
7
1990
251
254
2393372
100
Brewer
BD
Clement
SF
Lotz
WS
A comparison of inulin, para-aminohippuric acid, and endogenous creatinine clearances
as measures of renal function in neonatal foals
J Vet Intern Med
4
6
1990
301
305
2074554
101
Park
WS
Chang
YS
Lee
M
Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy
metabolism during the immediate reoxygenation-reperfusion period after acute transient
global hypoxia-ischemia in the newborn piglet
Brain Res
901
1-2
2001
102
108
11368956
102
Fowden
AL
Forhead
AJ
White
KL
Equine uteroplacental metabolism at mid- and late gestation
Exp Physiol
85
5
2000
539
545
11038405
103
Fowden
AL
Silver
M
Glucose and oxygen metabolism in the fetal foal during late gestation
Am J Physiol
269
6 pt 2
1995
R1455
R1461
8594949
104
Takata
K
Hirano
H
Mechanism of glucose transport across the human and rat placental barrier: a review
Microsc Res Tech
38
1-2
1997
145
152
9260845
105
Kalhan
SC
D'Angelo
LJ
Savin
SM
Glucose production in pregnant women at term gestation: sources of glucose for human
fetus
J Clin Invest
63
3
1979
388
394
429559
106
Kalhan
SC
Bier
DM
Savin
SM
Estimation of glucose turnover and 13C recycling in the human newborn by simultaneous
[1-13C]glucose and [6,6-1H2]glucose tracers
J Clin Endocrinol Metab
50
3
1980
456
460
7358831
107
Cowett
RM
Oh
W
Pollak
A
Glucose disposal of low birth weight infants: steady state hyperglycemia produced
by constant intravenous glucose infusion
Pediatrics
63
3
1979
389
396
440840
108
Levitsky
LL
Paton
JB
Fisher
DE
Precursors to glycogen in ovine fetuses
Am J Physiol
255
5 pt 1
1988
E743
E747
3189544
109
Kawai
Y
Arinze
IJ
Activation of glycogenolysis in neonatal liver
J Biol Chem
256
2
1981
853
858
6256371
110
Leffler
CW
Hessler
JR
Green
RS
The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis
Pediatr Res
18
10
1984
938
942
6387607
111
Emmanouilides
GC
Moss
AJ
Duffie
ER
Pulmonary arterial pressure changes in human newborn infants from birth to 3 days
of age
J Pediatr
65
1964
327
333
14210853
112
Evans
NJ
Archer
LN
Postnatal circulatory adaptation in healthy term and preterm neonates
Arch Dis Child
65
1 spec no
1990
24
26
2306130
113
Shaul
PW
Farrar
MA
Magness
RR
Pulmonary endothelial nitric oxide production is developmentally regulated in the
fetus and newborn
Am J Physiol
265
4 pt 2
1993
H1056
H1063
8238393
114
Fineman
JR
Soifer
SJ
Heymann
MA
Regulation of pulmonary vascular tone in the perinatal period
Annu Rev Physiol
57
1995
115
134
7778860
115
Murphy
JD
Rabinovitch
M
Goldstein
JD
The structural basis of persistent pulmonary hypertension of the newborn infant
J Pediatr
98
6
1981
962
967
7229803
116
Noerr
B
Tolazoline HCl (Priscoline)
Neonatal Netw
7
3
1988
74
75
3205245
117
Finer
NN
Barrington
KJ
Nitric oxide for respiratory failure in infants born at or near term
Cochrane Database Syst Rev
4
2001
CD000399
118
Lester
GD
DeMarco
VG
Norman
WM
Effect of inhaled nitric oxide on experimentally induced pulmonary hypertension in
neonatal foals
Am J Vet Res
60
10
1999
1207
1212
10791931
119
Whitelaw
A
Systematic review of therapy after hypoxic-ischaemic brain injury in the perinatal
period
Semin Neonatol
5
1
2000
33
40
10802748
120
Nelson
KB
Willoughby
RE
Infection, inflammation and the risk of cerebral palsy
Curr Opin Neurol
13
2
2000
133
139
10987569
121
Rudolph
AM
The fetal circulation and its response to stress
J Dev Physiol
6
1
1984
11
19
6707438
122
Goetzman
BW
Itskovitz
J
Rudolph
AM
Fetal adaptations to spontaneous hypoxemia and responses to maternal oxygen breathing
Biol Neonat
46
6
1984
276
284
123
Evrard
P
Pathophysiology of perinatal brain damage
Dev Neurosci
23
3
2001
171
174
11598315
124
Andine
P
Jacobson
I
Hagberg
H
Enhanced calcium uptake by CA1 pyramidal cell dendrites in the postischemic phase
despite subnormal evoked field potentials: excitatory amino acid receptor dependency
and relationship to neuronal damage
J Cereb Blood Flow Metab
12
5
1992
773
783
1324252
125
Sebastiao
AM
de Mendonca
A
Moreira
T
Activation of synaptic NMDA receptors by action potential-dependent release of transmitter
during hypoxia impairs recovery of synaptic transmission on reoxygenation
J Neurosci
21
21
2001
8564
8571
11606644
126
Vexler
ZS
Ferriero
DM
Molecular and biochemical mechanisms of perinatal brain injury
Semin Neonatol
6
2
2001
99
108
11483016
127
D'Souza
SW
McConnell
SE
Slater
P
Glycine site of the excitatory amino acid N-methyl-D-aspartate receptor in neonatal
and adult brain
Arch Dis Child
69
2
1993
212
215
8215523
128
Zhang
L
Rzigalinski
BA
Ellis
EF
Reduction of voltage-dependent Mg2+ blockade of NMDA current in mechanically injured
neurons
Science
274
5294
1996
1921
1923
8943207
129
Nakajima
W
Ishida
A
Takada
G
Magnesium attenuates a striatal dopamine increase induced by anoxia in the neonatal
rat brain: an in vivo microdialysis study
Pediatr Res
41
6
1997
809
814
9167193
130
Sameshima
H
Ota
A
Ikenoue
T
Pretreatment with magnesium sulfate protects against hypoxic-ischemic brain injury
but postasphyxial treatment worsens brain damage in seven-day-old rats
Am J Obstet Gynecol
180
3 pt 1
1999
725
730
10076154
131
Heath
DL
Vink
R
Improved motor outcome in response to magnesium therapy received up to 24 hours after
traumatic diffuse axonal brain injury in rats
J Neurosurg
90
3
1999
504
509
10067920
132
Hallak
M
Kupsky
WJ
Hotra
JW
Fetal rat brain damage caused by maternal seizure activity: prevention by magnesium
sulfate
Am J Obstet Gynecol
181
4
1999
828
834
10521737
133
Maroszynska
I
Sobolewska
B
Gulczynska
E
Can magnesium sulfate reduce the risk of cerebral injury after perinatal asphyxia?
Acta Pol Pharm
56
6
1999
469
473
10715892
134
Greenwood
K
Cox
P
Mehmet
H
Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn piglet
does not protect against cerebral damage
Pediatr Res
48
3
2000
346
345
10960501
135
Ilves
P
Blennow
M
Kutt
E
Concentrations of magnesium and ionized calcium in umbilical cord blood in distressed
term newborn infants with hypoxic-ischemic encephalopathy
Acta Paediatr
85
11
1996
1348
1350
8955464
136
Spehar
AM
Hill
MR
Mayhew
IG
Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal
Equine Vet J
16
4
1984
368
371
6479136
137
Ajayi
OA
Oyaniyi
OT
Chike-Obi
UD
Adverse effects of early phenobarbital administration in term newborns with perinatal
asphyxia
Trop Med Int Health
3
7
1998
592
595
9705195
138
Tute
AS
Wilkins
PA
Gleed
RD
Negative pressure pulmonary edema as a post-anesthetic complication associated with
upper airway obstruction in a horse
Vet Surg
25
6
1996
519
523
8923732
139
Kortz
GD
Madigan
JE
Lakritz
J
Cerebral oedema and cerebellar herniation in four equine neonates
Equine Vet J
24
1
1992
63
66
1555546
140
Kempski
O
Cerebral edema
Semin Nephrol
21
3
2001
303
307
11320499
141
Watanabe
I
Tomita
T
Hung
KS
Edematous necrosis in thiamine-deficient encephalopathy of the mouse
J Neuropathol Exp Neurol
40
4
1981
454
471
7252527
142
Wilkins
PA
Vaala
WE
Zivotofsky
D
A herd outbreak of equine leukoencephalomalacia
Cornell Vet
84
1
1994
53
59
8313709
143
Brayton
CF
Dimethyl sulfoxide (DMSO): a review
Cornell Vet
76
1
1986
61
90
3510103
144
Chernick
V
Craig
RJ
Naloxone reverses neonatal depression caused by fetal asphyxia
Science
216
4551
1982
1252
1253
7200636
145
Ting
P
Pan
Y
The effects of naloxone on the post-asphyxic cerebral pathophysiology of newborn lambs
Neurol Res
16
5
1994
359
364
7870275
146
Young
RS
Hessert
TR
Pritchard
GA
Naloxone exacerbates hypoxic-ischemic brain injury in the neonatal rat
Am J Obstet Gynecol
150
1
1984
52
56
6548084
147
Kattwinkel
J
Niermeyer
S
Nadkarni
V
Resuscitation of the newly born infant: an advisory statement from the Pediatric Working
Group of the International Liaison Committee on Resuscitation
Resuscitation
40
2
1999
71
88
10225280
148
Bain FT: Neurologic disorders in foals other than hypoxic-ischemic encephalopathy.
Proceedings of the International Veterinary Emergency Critical Care Symposium, San
Antonio, Tex, 1998. pp 691-692.
149
Lyden
PD
Lonzo
L
Combination therapy protects ischemic brain in rats: a glutamate antagonist plus a
gamma-aminobutyric acid agonist
Stoke
25
1
1994
189
196
150
Madden
KP
Effect of gamma-aminobutyric acid modulation on neuronal ischemia in rabbits
Stroke
25
11
1994
2271
2274
7974555
151
Gunn
AJ
Cerebral hypothermia for prevention of brain injury following perinatal asphyxia
Curr Opin Pediatr
12
2
2000
111
115
10763759
152
Bhatia
J
Current options in the management of apnea of prematurity
Clin Pediatr (Phila)
39
6
2000
327
336
10879934
153
Ambalavanan
N
Carlo
WA
Hypocapnia and hypercapnia in respiratory management of newborn infants
Clin Perinatol
28
3
2001
517
531
11570152
154
Filler
G
Acute renal failure in children: aetiology and management
Paediatr Drugs
3
11
2001
783
792
11735664
155
Rudis
MI
Low-dose dopamine in the intensive care unit: DNR or DNRx?
Crit Care Med
29
8
2001
1638
1639
11505148
156
Kellum
JA
M Decker
J
Use of dopamine in acute renal failure: a meta-analysis
Crit Care Med
29
8
2001
1526
1531
11505120
157
Cheung
PY
Barrington
KJ
The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic
anesthetized piglets
Crit Care
5
3
2001
158
166
11353933
158
Corley
KTT
McKenzie
HC
Amoroso
LM
Initial experience with norepinephrine infusion in hypotensive critically ill foal
J Vet Emerg Crit Care
10
2000
267
276
159
Martin-Ancel
A
Garcia-Alix
A
Gaya
F
Multiple organ involvement in perinatal asphyxia
J Pediatr
127
5
1995
786
793
7472837
160
Jawaheer
G
Shaw
NJ
Pierro
A
Continuous enteral feeding impairs gallbladder emptying in infants
J Pediatr
138
6
2001
822
825
11391323
161
McClure
RJ
Trophic feeding of the preterm infant
Acta Paediatr Suppl
90
436
2001
19
21
11332950
162
Premji
S
Chessell
L
Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature
infants less than 1500 grams
Cochrane Database Syst Rev
1
2001
CD001819
163
McEvoy
C
Bowling
S
Williamson
K
Functional residual capacity and passive compliance measurements after antenatal steroid
therapy in preterm infants
Pediatr Pulmonol
31
6
2001
425
430
11389574
164
Suresh
GK
Soll
RF
Current surfactant use in premature infants
Clin Perinatol
28
3
2001
671
694
11570160
165
Putnam
MR
Bransby
DI
Schumacher
J
Effects of the fungal endophyte Acremonium coenophialum in fescue on pregnant mares
and foal viability
Am J Vet Res
52
12
1991
2071
2074
1789525
166
Berry
LM
Ikegami
M
Woods
E
Postnatal renal adaptation in preterm and term lambs
Reprod Fertil Dev
7
3
1995
491
498
8606960
167
Zanardo
V
Cagdas
S
Golin
R
Risk factors of hypoglycemia in premature infants
Fetal Diagn Ther
14
2
1999
63
67
10085501
168
Broughton Pipkin
F
Ousey
JC
Wallace
CP
Studies on equine prematurity. 4. Effect of salt and water loss on the renin-angiotensin-aldosterone
system in the newborn foal
Equine Vet J
16
4
1984
292
297
6383811
169
Webb
PD
Leadon
DP
Rossdale
PD
Studies on equine prematurity. 5. Histology of the adrenal cortex of the premature
newborn foal
Equine Vet J
16
4
1984
297
299
6479125
170
Livesay-Wilkins
PA
Angular limb deformities in premature/dysmature foals
Mod Vet Pract
67
Oct-Nov 1986
808
911
171
Neonatal Septicemia Workshop 1
1995
Dorothy Havemeyer Foundation
Westminster, Massachussets
172
Neonatal Septicemia Workshop 2
1998
Dorothy Havemeyer Foundation
Boston
173
Neonatal Septicemia Workshop 3
2001
Dorothy Havemeyer Foundation
Talliores, France
174
Muckart
DJ
Bhagwanjee
S
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference
definitions of the systemic inflammatory response syndrome and allied disorders in
relation to critically injured patient
Crit Care Med
25
11
1997
1789
1795
9366759
175
Matot
I
Sprung
CL
Definition of sepsis
Intensive Care Med
27
suppl 1
2001
S3
S9
11307368
176
Dellinger
RP
Bone
RC
To SIRS with love
Crit Care Med
26
1
1998
178
179
9428563
177
Tyler-McGowan
CM
Hodgson
JL
Hodgson
DR
Failure of passive transfer in foals: incidence and outcome on four studs in New South
Wales
Aust Vet J
75
1
1997
56
59
9034501
178
Robinson
JA
Allen
GK
Green
EM
A prospective study of septicaemia in colostrum-deprived foals
Equine Vet J
25
3
1993
214
219
8508750
179
Steinmetz
OK
Meakins
JL
Care of the gut in the surgical intensive care unit: fact or fashion?
Can J Surg
34
3
1991
207
215
1905191
180
Marsh
PS
Palmer
JE
Bacterial isolates from blood and their susceptibility patterns in critically ill
foals: 543 cases (1991-1998)
J Am Vet Med Assoc
218
10
2001
1608
1610
11393374
181
Madigan JE, Leutenegger CM: Development of real-time TaqMan PCR systems to facilitate
the diagnosis and research of septicemia in foals. Proceedings of the Neonatal Septicemia
Workshop 3, Boston, 2001. pp 35-36.
182
Alcivar-Warren A, Pascual I, Dhar AK et al: Expressed sequence TAGS (ESTs) isolated
from blood of a septic thoroughbred foal. Proceedings of the Neonatal Septicemia Workshop
3, Boston, 2001. pp 37-40.
183
Rivers
E
Nguyen
B
Havstad
S
Early goal-directed therapy in the treatment of severe sepsis and septic shock
N Engl J Med
345
19
2001
1368
1377
11794169
184
Traub-Dargatz
JL
Bertone
JJ
Gould
DH
Chronic flunixin meglumine therapy in foals
Am J Vet Res
49
1
1988
7
12
3354970
185
Carrick
JB
Papich
MG
Middleton
DM
Clinical and pathological effects of flunixin meglumine administration to neonatal
foals
Can J Vet Res
53
2
1989
195
201
2713784
186
Rebhun
WC
Dill
SG
Power
HT
Gastric ulcers in foals
J Am Vet Med Assoc
180
4
1982
404
407
7061324
187
Swerczek
TW
Experimentally induced toxicoinfectious botulism in horses and foals
Am J Vet Res
41
3
1980
348
350
7369606
188
Swerczek
TW
Toxicoinfectious botulism in foals and adult horses
J Am Vet Med Assoc
176
3
1980
217
220
6988376
189
Whitlock
RH
Buckley
C
Botulism
Vet Clin North Am Equine Pract
13
1
1997
107
128
9106347
190
Galey
FD
Botulism in the horse
Vet Clin North Am Equine Pract
17
3
2001
579
588
11780288
191
Lofstedt
J
White muscle disease of foals
Vet Clin North Am Equine Pract
13
1
1997
169
185
9106350
192
Harrington
DD
Naturally-occurring Tyzzer's disease (Bacillus piliformis infection) in horse foals
Vet Rec
96
3
1975
59
63
1119056
193
Carrigan
MJ
Pedrana
RG
McKibbin
AW
Suspected Tyzzer's disease in two foals
J S Afr Vet Assoc
56
2
1985
107
108
4020811
194
Whitwell
KE
Four cases of Tyzzer's disease in foals in England
Equine Vet J
8
3
1976
118
122
954720
195
Turk
MA
Gallina
AM
Perryman
LE
Bacillus piliformis infection (Tyzzer's disease) in foals in northwestern United States:
a retrospective study of 21 cases
J Am Vet Med Assoc
178
3
1981
279
281
7228786
196
Pulley
LT
Shively
JN
Tyzzer's disease in a foal: light- and electron-microscopic observations
Vet Pathol
11
3
1974
203
211
4463569
197
Humber
KA
Sweeney
RW
Saik
JE
Clinical and clinicopathologic findings in two foals infected with Bacillus piliformis
J Am Vet Med Assoc
193
11
1988
1425
1428
3209457
198
Brown
CM
Ainsworth
DM
Personett
LA
Serum biochemical and haematological findings in two foals with focal bacterial hepatitis
(Tyzzer's disease)
Equine Vet J
15
4
1983
375
376
6641687
199
Acland
HM
Mann
PC
Robertson
JL
Toxic hepatopathy in neonatal foals
Vet Pathol
21
1
1984
3
9
6710809
200
Fortier
LA
Fubini
SL
Flanders
JA
The diagnosis and surgical correction of congenital portosystemic vascular anomalies
in two calves and two foals
Vet Surg
25
2
1996
154
160
8928393
201
Hillyer
MH
Holt
PE
Barr
FJ
Clinical signs and radiographic diagnosis of a portosystemic shunt in a foal
Vet Rec
132
18
1993
457
460
8517006
202
Buonanno
AM
Carlson
GP
Kantrowitz
B
Clinical and diagnostic features of portosystemic shunt in a foal
J Am Vet Med Assoc
192
3
1988
387
389
3356582
203
Wilkins
PA
Wacholder
S
Nolan
TJ
Evidence for transmission of Halicephalobus deletrix (H gingivalis) from dam to foal
J Vet Intern Med
15
4
2001
412
417
11467602
204
Spalding
MG
Greiner
EC
Green
SL
Halicephalobus (Micronema) deletrix infection in two half-sibling foals
J Am Vet Med Assoc
196
7
1990
1127
1129
2329083
205
Clark
EG
Turner
AS
Boysen
BG
Listeriosis in an Arabian foal with combined immunodeficiency
J Am Vet Med Assoc
172
3
1978
363
366
413818
206
Gray
LC
Magdesian
KG
Sturges
BK
Suspected protozoal myeloencephalitis in a two-month-old colt
Vet Rec
149
9
2001
269
273
11558662
207
Whitwell
KE
Blunden
AS
Pathological findings in horses dying during an outbreak of the paralytic form of
equid herpesvirus type 1 (EHV-1) infection
Equine Vet J
24
1
1992
13
19
1313358
208
Lindsay
DS
Steinberg
H
Dubielzig
RR
Central nervous system neosporosis in a foal
J Vet Diagn Invest
8
4
1996
507
510
8953546
209
Chaffin
MK
Honnas
CM
Crabill
MR
Cauda equina syndrome, diskospondylitis, and a paravertebral abscess caused by Rhodococcus
equi in a foal
J Am Vet Med Assoc
206
2
1995
215
220
7751225
210
Olchowy
TW
Vertebral body osteomyelitis due to Rhodococcus equi in two Arabian foals
Equine Vet J
26
1
1994
79
82
8143672
211
Giguere
S
Lavoie
JP
Rhodococcus equi vertebral osteomyelitis in 3 Quarter horse colts
Equine Vet J
26
1
1994
74
77
8143671
212
Cudd
TA
Mayhew
IG
Cottrill
CM
Agenesis of the corpus callosum with cerebellar vermian hypoplasia in a foal resembling
the Dandy-Walker syndrome: pre-mortem diagnosis by clinical evaluation and CT scanning
Equine Vet J
21
5
1989
378
381
2776727
213
Dungworth
DL
Fowler
ME
Cerebellar hypoplasia and degeneration in a foal
Cornell Vet
56
1
1966
17
24
5950937
214
Palmer
AC
Blakemore
WF
Cook
WR
Cerebellar hypoplasia and degeneration in the young Arab horse: clinical and neuropathological
features
Vet Rec
93
3
1973
62
66
4748678
215
Rosenstein
DS
Schott
HC
2nd
Stickle
RL
Imaging diagnosis: occipitoatlantoaxial malformation in a miniature horse foal
Vet Radiol Ultrasound
41
3
2000
218
219
10850870
216
de Lahunta
A
Hatfield
C
Dietz
A
Occipitoatlantoaxial malformation with duplication of the atlas and axis in a half
Arabian foal
Cornell Vet
79
2
1989
185
193
2924582
217
Wilson
WD
Hughes
SJ
Ghoshal
NG
Occipitoatlantoaxial malformation in two non-Arabian horses
J Am Vet Med Assoc
187
1
1985
36
40
4019299
218
Godber
LM
Derksen
FJ
Williams
JF
Ivermectin toxicosis in a neonatal foal
Aust Vet J
72
5
1995
191
192
7661821
219
Johnson
PJ
Mrad
DR
Schwartz
AJ
Presumed moxidectin toxicosis in three foals
J Am Vet Med Assoc
214
5
1999
678
680
10088018
220
Lakritz
J
Madigan
J
Carlson
GP
Hypovolemic hyponatremia and signs of neurologic disease associated with diarrhea
in a foal
J Am Vet Med Assoc
200
8
1992
1114
1116
1607318
221
Brown
WD
Caruso
JM
Extrapontine myelinolysis with involvement of the hippocampus in three children with
severe hypernatremia
J Child Neurol
14
7
1999
428
433
10573464
222
Tomizawa
N
Nishimura
R
Sasaki
N
Relationships between radiography of cervical vertebrae and histopathology of the
cervical cord in wobbling 19 foals
J Vet Med Sci
56
2
1994
227
233
8075209
223
Erhard
MH
Luft
C
Remler
HP
Assessment of colostral transfer and systemic availability of immunoglobulin G in
new-born foals using a newly developed enzyme-linked immunosorbent assay (ELISA) system
J Anim Physiol Anim Nutr (Berl)
85
5-6
2001
164
173
11686785
224
Bertone
JJ
Jones
RL
Curtis
CR
Evaluation of a test kit for determination of serum immunoglobulin G concentration
in foals
J Vet Intern Med
2
4
1988
181
183
3148029
225
LeBlanc
MM
McLaurin
BI
Boswell
R
Relationships among serum immunoglobulin concentration in foals, colostral specific
gravity, and colostral immunoglobulin concentration
J Am Vet Med Assoc
189
1
1986
57
60
3733502
226
Kent
JE
Blackmore
DJ
Measurement of IgG in equine blood by immunoturbidimetry and latex agglutination
Equine Vet J
17
2
1985
125
129
2580703
227
Watson
DL
Bennell
MA
Griffiths
JR
A rapid, specific test for detecting absorption of colostral IgG by the neonatal foal
Aust Vet J
56
11
1980
513
516
7247883
228
Buening
GM
Perryman
LE
McGuire
TC
Practical methods of determining serum immunoglobulin M and immunoglobulin G concentrations
in foals
J Am Vet Med Assoc
171
5
1977
455
458
409701
229
McGuire
TC
Crawford
TB
Passive immunity in the foal: measurement of immunoglobulin classes and specific antibody
Am J Vet Res
34
10
1973
1299
1303
4355952
230
Jeffcott
LB
Studies on passive immunity in the foal. 1. Gamma-globulin and antibody variations
associated with the maternal transfer of immunity and the onset of active immunity
J Comp Pathol
84
1
1974
93
101
4137211
231
MacDougall
DF
Immunoglobulin metabolism in the neonatal foal
J Reprod Fertil Suppl
23
1975
739
742
232
Baldwin
JL
Cooper
WL
Vanderwall
DK
Prevalence (treatment days) and severity of illness in hypogammaglobulinemic and normogammaglobulinemic
foals
J Am Vet Med Assoc
198
3
1991
423
428
2010335
233
Clabough
DL
Levine
JF
Grant
GL
Factors associated with failure of passive transfer of colostral antibodies in standardbred
foals
J Vet Intern Med
5
6
1991
335
340
1779427
234
Baldwin
JL
Failure of passive transfer in foals
J Vet Intern Med
6
3
1992
197
198
1619597
235
Stoneham
SJ
Digby
NJ
Ricketts
SW
Failure of passive transfer of colostral immunity in the foal: incidence, and the
effect of stud management and plasma transfusions
Vet Rec
128
18
1991
416
419
1853533
236
Raidal
SL
The incidence and consequences of failure of passive transfer of immunity on a thoroughbred
breeding farm
Aust Vet J
73
6
1996
201
206
8893988
237
McGuire
TC
Crawford
TB
Hallowell
AL
Failure of colostral immunoglobulin transfer as an explanation for most infections
and deaths of neonatal foals
J Am Vet Med Assoc
170
11
1977
1302
1304
863776
238
Norcross
NL
Secretion and composition of colostrum and milk
J Am Vet Med Assoc
181
10
1982
1057
1060
6816773
239
Sheoran
AS
Timoney
JF
Holmes
MA
Immunoglobulin isotypes in sera and nasal mucosal secretions and their neonatal transfer
and distribution in horses
Am J Vet Res
61
9
2000
1099
1105
10976743
240
Takahata
Y
Takada
H
Nomura
A
Interleukin-18 in human milk
Pediatr Res
50
2
2001
268
272
11477214
241
Hossner
KL
Yemm
RS
Improved recovery of insulin-like growth factors (IGFs) from bovine colostrum using
alkaline diafiltration
Biotechnol Appl Biochem
32
pt 3
2000
161
166
11115387
242
Zablocka
A
Janusz
M
Rybka
K
Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine
colostrum and its active nonapeptide fragment analogs
Eur Cytokine Netw
12
3
2001
462
467
11566627
243
Bastian
SE
Dunbar
AJ
Priebe
IK
Measurement of betacellulin levels in bovine serum, colostrum and milk
J Endocrinol
168
1
2001
203
212
11139784
244
van Hooijdonk
AC
Kussendrager
KD
Steijns
JM
In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum
involved in non-specific defence
Br J Nutr
84
suppl 1
2000
S127
S134
11242457
245
Zanker
IA
Hammon
HM
Blum
JW
Activities of gamma-glutamyltransferase, alkaline phosphatase and aspartate-aminotransferase
in colostrum, milk and blood plasma of calves fed first colostrum at 0-2, 6-7, 12-13
and 24-25 h after birth
J Vet Med A Physiol Pathol Clin Med
48
3
2001
179
185
11379391
246
Wilkins
PA
Dewan-Mix
S
Efficacy of intravenous plasma to transfer passive immunity in clinically healthy
and clinically ill equine neonates with failure of passive transfer
Cornell Vet
84
1
1994
7
14
8313712
247
Liu
IK
Brown
C
Myers
RC
Evaluation of intravenous administration of concentrated immunoglobulin G to colostrum-deprived
foals
Am J Vet Res
52
5
1991
709
712
1854093
248
Burton
SC
Hintz
HF
Kemen
MJ
Lyophilized hyperimmune equine serum as a source of antibodies for neonatal foals
Am J Vet Res
42
2
1981
308
310
6266291
249
Lavoie
JP
Spensley
MS
Smith
BP
Absorption of bovine colostral immunoglobulins G and M in newborn foals
Am J Vet Res
50
9
1989
1598
1603
2508519
250
Klobasa
F
Goel
MC
Werhahn
E
Comparison of freezing and lyophilizing for preservation of colostrum as a source
of immunoglobulins for calves
J Anim Sci
76
4
1998
923
926
9581912
251
O'Rielly
JL
A comparison of the reduction in immunoglobulin (IgG) concentration of frozen equine
plasma treated by three thawing techniques
Aust Vet J
70
12
1993
442
444
8117209
252
Hunt
E
Wood
B
Use of blood and blood products
Vet Clin North Am Food Anim Pract
15
3
1999
641
662
10573816
253
Traub-Dargatz
JL
McClure
J
Kock
C
Neonatal isoerythrolysis in mule foals
J Am Vet Med Assoc
206
1995
67
70
7744666
254
McClure
J
Koch
C
Traub-Dargatz
J
Characterization of a red blood cell antigen in donkeys and mules associated with
neonatal isoerythrolysis
Anim Genet
25
1994
119
120
8010529
255
Bailey
E
Prevalence of anti-red blood cell antibodies in the serum and colostrum of mares and
its relationship to neonatal isoerythrolysis
Am J Vet Res
43
1982
1917
1921
7181190
256
Whiting
J
David
JB
Neonatal isoerythrolysis
Compend Cont Educ Pract Vet
22
10
2000
968
976
257
Perkins
GA
Divers
TJ
Polymerized hemoglobin therapy in a foal with neonatal isoerythrolysis
J Vet Emerg Crit Care
11
2
2001
141
146
258
Smith
JE
Dever
M
Smith
J
Post-transfusion survival of 50Cr-labeled erythrocytes in neonatal foals
J Vet Intern Med
6
3
1992
183
187
1619595
259
McClure
J
Strategies for prevention of neonatal isoerythrolysis in horses and mules
Equine Vet Educ
9
3
1997
118
122
260
Ramirez
S
Gaunt
SD
McClure
JJ
Detection and effects on platelet function of anti-platelet antibody in mule foals
with experimentally induced neonatal alloimmune thrombocytopenia
J Vet Intern Med
13
6
1999
534
539
10587252
261
Buechner-Maxwell
V
Scott
MA
Godber
L
Neonatal alloimmune thrombocytopenia in a Quarter horse foal
J Vet Intern Med
11
5
1997
304
308
9348499
262
Roberts
IA
Murray
NA
Neonatal thrombocytopenia: new insights into pathogenesis and implications for clinical
management
Curr Opin Pediatr
13
1
2001
16
21
11176238
263
Sellon
DC
Thrombocytopenia in horses
Equine Vet Educ
10
1998
133
139
264
Ramirez
S
Gaunt
SD
McClure
JJ
Detection and effects on platelet function of anti-platelet antibody in mule foals
with experimentally induced neonatal alloimmune thrombocytopenia
J Vet Intern Med
13
6
1999
534
539
10587252
265
Reef
VB
Cardiovascular disease in the equine neonate
Vet Clin North Am Equine Pract
1
1
1985
117
129
3907765
266
Hong
CB
Congenital polyalveolar lobe in three foals
J Comp Pathol
115
1
1996
85
88
8878754
267
Hinchcliff
KW
Adams
WM
Critical pulmonary stenosis in a newborn foal
Equine Vet J
23
4
1991
318
320
1915237
268
Riley
CB
Yovich
JV
Bolton
JR
Bilateral hypoplasia of the soft palate in a foal
Aust Vet J
68
5
1991
178
179
1883297
269
Hultgren
BD
Pulmonary lobar hypertrophy in a foal
J Am Vet Med Assoc
188
4
1986
422
423
3949621
270
Crowe
MW
Swerczek
TW
Equine congenital defects
Am J Vet Res
46
2
1985
353
358
3994101
271
Aylor
MK
Campbell
ML
Goring
RL
Congenital bilateral choanal atresia in a standardbred foal
Equine Vet J
16
4
1984
396
398
6479141
272
Chaffin
MK
Matthews
NS
Cohen
ND
Evaluation of pulse oximetry in anaesthetised foals using multiple combinations of
transducer type and transducer attachment site
Equine Vet J
28
6
1996
437
445
9049492
273
Yamamoto
K
Yasuda
J
Too
K
Electrocardiographic findings during parturition and blood gas tensions immediately
after birth in thoroughbred foals
Jpn J Vet Res
39
2-4
1991
143
157
1821437
274
Hodgson
DR
Blood gas and acid-base changes in the neonatal foal
Vet Clin North Am Equine Pract
3
3
1987
617
629
3322529
275
Rossdale
PD
Blood gas tensions and pH values in the normal thoroughbred foal at birth and in the
following 42h
Biol Neonat
13
1
1968
18
25
5753166
276
Madigan
JE
Thomas
WP
Backus
KQ
Mixed venous blood gases in recumbent and upright positions in foals from birth to
14 days of age
Equine Vet J
24
5
1992
399
401
1396517
277
Palmer
JE
Ventilatory support of the neonatal foal
Vet Clin North Am Equine Pract
10
1
1994
167
185
8039030
278
Report of foal pneumonia panel
AAEP Newslett
2
1978
76
279
Hoffman
AM
Viel
L
Prescott
JF
Association of microbiologic flora with clinical, endoscopic, and pulmonary cytologic
findings in foals with distal respiratory tract infection
Am J Vet Res
54
10
1993
1615
1622
8250386
280
Hoffman
AM
Viel
L
Prescott
JF
Microbiologic changes during antimicrobial treatment and rate of relapse of distal
respiratory tract infections in foals
Am J Vet Res
54
10
1993
1608
1614
8250385
281
Srihakim
S
Swerczek
TW
Pathologic changes and pathogenesis of Parascaris equorum infection in parasite-free
pony foals
Am J Vet Res
39
7
1978
1155
1160
677534
282
Magnusson
H
Spezifische infektiose Pneumonie beim Fohlen. Ein neuer Eiterreger beim Pferd
Arch Wiss Prakt Tierheilkd
50
1923
22
283
Hietala
SK
Ardans
AA
Interaction of Rhodococcus equi with phagocytic cells from Rhodococcus equi-exposed
and non-exposed foals
Vet Microbiol
14
1987
307
320
3672873
284
Zink
MC
Yager
JA
Prescott
JF
Electron microscopic investigation of intracellular events after ingestion of Rhodococcus
equi by foal alveolar macrophages
Vet Microbiol
14
1987
295
305
3672872
285
Brumbaugh
GW
Davis
LE
Thurmon
JC
Influence of Rhodococcus equi on the respiratory burst of resident alveolar macrophages
from adult horses
Am J Vet Res
51
1990
766
771
2337275
286
Vullo
V
Mastroianni
CM
Lichtner
M
Rhodococcus equi infection of monocytes/macrophages from human immunodeficiency (HIV)-infected
patients and healthy individuals: evaluation of intracellular killing and nitric oxide
production
FEMS Immunol Med Microbiol
21
1998
11
17
9657316
287
Hondalus
MK
Diamond
MS
Rosenthal
LA
The intracellular bacterium Rhodococcus equi requires Mac-1 to bind to mammalian cells
Infect Immun
61
1993
2919
2929
8514396
288
Martens
RJ
Martens
JG
Renshaw
HW
Rhodococcus (Corynebacterium) equi: bactericidal capacity of neutrophils from neonatal
and adult horses
Am J Vet Res
49
1988
295
299
3358541
289
Takai
S
Koike
K
Ohbushi
S
Identification of 15- to 17-kilodalton antigens associated with virulent Rhodococcus
equi
J Clin Microbiol
29
1991
439
443
2037660
290
Takai
S
Iie
M
Watanabe
Y
Virulence-associated 15- to 17 kilodalton antigens in Rhodococcus equi: temperature-dependent
expression and location of the antigens
Infect Immun
60
1992
2995
2997
1612765
291
Giguère
S
Hondalus
MK
Yager
JA
Role of the 85-kilobase plasmid and plasmid-encoded virulence-associated protein A
in intracellular survival and virulence of Rhodococcus equi
Infect Immun
67
1999
3548
3557
10377138
292
Byrne
BA
Prescott
JF
Palmer
GH
Characterization of avirulence-associated gene family in Rhodococcus equi.
Wernery
U
Wade
JF
Mumford
JA
Kaaden
OR
Equine Infectious Diseases VIII
1999
R & W Publications
Newmarket, England
293
Zink
MC
Yager
JA
Smart
NL
Corynebacterium equi infections in horses, 1958-1984: a review of 131 cases
Can J Vet Res
27
1986
213
217
294
Giguere
S
Prescott
JF
Clinical manifestations, diagnosis, treatment, and prevention of Rhodococcus equi
infections in foals
Vet Microbiol
56
3-4
1997
313
334
9226845
295
Hietala
SK
Ardans
AA
Sansome
A
Detection of Corynebacterium equi-specific antibody in horses by enzyme-linked immunosorbent
assay
Am J Vet Res
46
1985
13
15
3918488
296
Wilkins PA, Lesser FR, Gaskin JM: Rhodococcus equi pneumonia in foals: comparison
of ELISA and AGID serology on a commercial thoroughbred breeding farm. Proceedings
of the eleventh ACVIM Forum, Washington, DC, 1993. pp 957.
297
Ardans
AA
Hietala
SK
Spensley
MS
Studies of naturally occuring and experimental Rhodococcus equi (Corynebacterium equi)
pneumonia in foals
Proc Am Assoc Equine Pract
32
1986
129
144
298
Takai
S
Vigo
G
Ikushima
H
Detection of virulent Rhodococcus equi in tracheal aspirate samples by polymerase
chain reaction for rapid diagnosis of R. equi pneumonia in foals
Vet Microbiol
61
1998
59
69
9646466
299
Sellon
DC
Besser
TE
Vivrette
SL
Comparison of nucleic acid amplification, serology, and microbiologic culture for
diagnosis of Rhodococcus equi pneumonia in foals
J Clin Microbiol
39
4
2001
1289
1293
11283043
300
Hillidge
CJ
Use of erythromycin-rifampin combination in treatment of Rhodococcus equi pneumonia
Vet Microbiol
14
1987
337
342
3314109
301
Jacks
S
Giguere
S
Gronwall
PR
Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar
cells in foals
Am J Vet Res
62
12
2001
1870
1875
11763173
302
Traub-Dargatz
J
Wilson
WD
Conboy
HS
Hyperthermia in foals treated with erythromycin alone or in combination with rifampin
for respiratory disease during hot environmental conditions
Proc Am Assoc Equine Pract
42
1996
243
244
303
Baverud
V
Franklin
A
Gunnarsson
A
Clostridium difficile associated with acute colitis in mares when their foals are
treated with erythromycin and rifampicin for Rhodococcus equi pneumonia
Equine Vet J
30
1998
482
488
9844966
304
Giguère
S
Prescott
JF
Strategies for the control of Rhodococcus equi infections on enzootic farms
Proc Am Assoc Equine Pract
43
1997
65
70
305
Becu
T
Polledo
G
Gaskin
JM
Immunoprophylaxis of Rhodococcus equi pneumonia in foals
Vet Microbiol
56
1997
193
204
9226834
306
Hurley
JR
Begg
AP
Failure of hyperimmune plasma to prevent pneumonia caused by Rhodococcus equi in foals
Aust Vet J
72
1995
418
420
8929188
307
Martens
RJ
Martens
JG
Fiske
RA
Rhodococcus equi foal pneumonia: protective effects of immune plasma in experimentally
infected foals
Equine Vet J
21
1989
249
255
2767025
308
Madigan
JE
Hietala
S
Muller
N
Protection against naturally acquired Rhodococcus equi pneumonia in foals by administration
of hyperimmune plasma
J Reprod Fert Suppl
44
1991
571
578
309
Muller
NS
Madigan
JE
Methods of implementation of an immunoprophylaxis program for the prevention of Rhodococcus
equi pneumonia: results of a 5-year field study
Proc Am Assoc Equine Pract
38
1992
193
201
310
Higuchi
T
Arakawa
T
Hashikura
S
Effect of prophylactic administration of hyperimmune plasma to prevent Rhodococcus
equi infection on foals from endemically affected farms
Zentralbl Veterinarmed B
46
1999
641
648
10605374
311
Hooper-McGrevy
KE
Giguere
S
Wilkie
BN
Valuation of equine immunoglobulin specific for Rhodococcus equi virulence-associated
proteins A and C for use in protecting foals against Rhodococcus equi-induced pneumonia
Am J Vet Res
62
8
2001
1307
1313
11497456
312
Ainsworth
DM
Eicker
SW
Yeager
AE
Associations between physical examination, laboratory, and radiographic findings and
outcome and subsequent racing performance of foals with Rhodococcus equi infection:
115 cases (1984-1992)
J Am Vet Med Assoc
213
1998
510
515
9713534
313
Burrell
MH
Endoscopic and virological observations on respiratory disease in a group of young
thoroughbred horses in training
Equine Vet J
17
2
1985
99
103
2985380
314
Gilkerson
JR
Whalley
JM
Drummer
HE
Epidemiology of EHV-1 and EHV-4 in the mare and foal populations on a Hunter Valley
stud farm: are mares the source of EHV-1 for unweaned foals?
Vet Microbiol
68
1-2
1999
27
34
10501159
315
McCartan
CG
Russell
MM
Wood
JL
Clinical, serological and virological characteristics of an outbreak of paresis and
neonatal foal disease due to equine herpesvirus-1 on a stud farm
Vet Rec
136
1
1995
7
12
7900264
316
Frymus
T
Kita
J
Woyciechowska
S
Foetal and neonatal foal losses on equine herpesvirus type 1(EHV-1) infected farms
before and after EHV-1 vaccination was introduced
Pol Arch Weter
26
3-4
1986
7
14
317
Hartley
WJ
Dixon
RJ
An outbreak of foal perinatal mortality due to equid herpesvirus type 1: pathological
observations
Equine Vet J
11
4
1979
215
218
232044
318
Del Piero
F
Wilkins
PA
Lopez
JW
Equine viral arteritis in newborn foals: clinical, pathological, serological, microbiological
and immunohistochemical observations
Equine Vet J
29
3
1997
178
185
9234009
319
Webb
RF
Knight
PR
Walker
KH
Involvement of adenovirus in pneumonia in a thoroughbred foal
Aust Vet J
57
3
1981
142
143
6266384
320
Moorthy
AR
Spradbrow
PB
Adenoviral infection of Arab foals with respiratory tract disease
Zentralbl Veterinarmed B
25
6
1978
469
477
212906
321
Thompson
DB
Spradborw
PB
Studdert
M
Isolation of an adenovirus from an Arab foal with a combined immunodeficiency disease
Aust Vet J
52
10
1976
435
437
189745
322
Perkins
G
Ainsworth
DM
Erb
HN
Clinical, haematological and biochemical findings in foals with neonatal equine herpesvirus-1
infection compared with septic and premature foals
Equine Vet J
31
5
1999
422
426
10505959
323
Murray
MJ
del Piero
F
Jeffrey
SC
Neonatal equine herpesvirus type 1 infection on a thoroughbred breeding farm
J Vet Intern Med
12
1
1998
36
41
9503358
324
Hullinger
PJ
Wilson
WD
Rossitto
PV
Passive transfer, rate of decay, and protein specificity of antibodies against equine
arteritis virus in horses from a standardbred herd with high seroprevalence
J Am Vet Med Assoc
213
6
1998
839
842
9743724
325
Del Piero
F
Wilkins
PA
Timoney
PJ
Fatal nonneurological EHV-1 infection in a yearling filly
Vet Pathol
37
6
2000
672
676
11105961
326
Del Piero
F
Wilkins
PA
Pulmonary vasculotropic EHV-1 infection in equids
Vet Pathol
38
4
2001
474
11467487
327
Borchers
K
Wolfinger
U
Ludwig
H
Virological and molecular biological investigations into equine herpes virus type
2 (EHV-2) experimental infections
Virus Res
55
1
1998
101
106
9712516
328
Murray
MJ
Eichorn
ES
Dubovi
EJ
Equine herpesvirus type 2: prevalence and seroepidemiology in foals
Equine Vet J
28
6
1996
432
436
9049491
329
Marble
SL
Edens
LM
Shiroma
JT
Subcutaneous emphysema in a neonatal foal
J Am Vet Med Assoc
208
1
1996
97
99
8682714
330
O'Brodovich
HM
Immature epithelial Na+ channel expression is one of the pathogenetic mechanisms leading
to human neonatal respiratory distress syndrome
Proc Assoc Am Physicians
108
5
1996
345
355
8902878
331
Lakritz
J
Wilson
WD
Berry
CR
Bronchointerstitial pneumonia and respiratory distress in young horses: clinical,
clinicopathologic, radiographic, and pathological findings in 23 cases (1984-1989)
J Vet Intern Med
7
5
1993
277
288
8263846
332
Stratton-Phelps
M
Wilson
WD
Gardner
IA
Risk of adverse effects in pneumonic foals treated with erythromycin versus other
antibiotics: 143 cases (1986-1996)
J Am Vet Med Assoc
217
1
2000
68
73
10909450
333
Bain
AM
Disease of foals
Aust Vet J
30
1954
9
12
334
Du Plessis
JL
Rupture of the bladder in the newborn foal and its surgical correction
J S Afr Vet Assoc
29
1958
261
263
335
Behr
MJ
Hackett
RP
Bentinick-Smith
J
Metabolic abnormalities associated with rupture of the urinary bladder in neonatal
foals
J Am Vet Med Assoc
178
1981
263
266
7228782
336
Adams
R
Koterba
AM
Cudd
TC
Exploratory celiotomy for suspected urinary tract disruption in neonatal foals: a
review of 18 cases
Equine Vet J
20
1988
13
17
3366099
337
Richardson
DW
Kohn
CW
Uroperitoneum in the foal
J Am Vet Med Assoc
182
1983
267
271
6681809
338
Kablack
KA
Embertson
RM
Bernard
WV
Uroperitoneum in the hospitalized equine neonate: retrospective study of 31 cases,
1988-1997
Equine Vet J
32
2000
505
508
11093624
339
Pascoe
RR
Repair of a defect in the bladder of a foal
Aust Vet J
47
1971
343
344
5106537
340
Hackett
RP
Rupture of the urinary bladder in neonatal foals
Compend Cont Educ Pract Vet
6
1984
S488
S492
341
Wellington
JKM
Bladder defects in newborn foals
Aust Vet J
48
1972
426
(letter).
4655395
342
Reef
VB
Ultrasound of the urinary tract
Reef
VB
Equine diagnostic ultrasound
1998
WB Saunders
Philadelphia
343
Lavoie
JP
Harnagel
SH
Nonsurgical management of ruptured urinary bladder in a critically ill foal
J Am Vet Med Assoc
192
1988
1577
1580
3410776
344
Vivrette
S
Cowgill
LD
Pascoe
J
Hemodialysis for treatment of oxytetracycline-induced acute renal failure in a neonatal
foal
J Am Vet Med Assoc
203
1
1993
105
107
8407440
345
Andrews
FM
Rosol
TJ
Kohn
CW
Bilateral renal hypoplasia in four young horses
J Am Vet Med Assoc
189
2
1986
209
212
3744981
346
Brown
CM
Parks
AH
Mullaney
TP
Bilateral renal dysplasia and hypoplasia in a foal with an imperforate anus
Vet Rec
122
4
1988
91
92
3354168
347
Schott
HC
2nd
Barbee
DD
Hines
MT
Clinical vignette: renal arteriovenous malformation in a Quarter horse foal
J Vet Intern Med
10
4
1996
204
206
8819044
348
Tomlinson
JE
Farnsworth
K
Sage
AM
Percutaneous ultrasound-guided pyelography aided diagnosis of ectopic ureter and hydronephrosis
in a 3-week-old filly
Vet Radiol Ultrasound
42
4
2001
349
351
11499712
349
Cutler
TJ
Mackay
RJ
Johnson
CM
Bilateral ureteral tears in a foal
Aust Vet J
75
6
1997
413
415
9247689
350
Stickle
RL
Wilcock
BP
Huseman
JL
Multiple ureteral defects in a Belgian foal
Vet Med Small Anim Clin
70
7
1975
819
821
1041091
351
Toribio
RE
Bain
FT
Mrad
DR
Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis
during pregnancy
J Am Vet Med Assoc
212
5
1998
697
701
9524643
352
Reef
VB
Collatos
C
Ultrasonography of umbilical structures in clinically normal foals
Am J Vet Res
49
12
1988
2143
2146
3071195
353
Reef
VB
Collatos
C
Spencer
PA
Clinical, ultrasonographic, and surgical findings in foals with umbilical remnant
infections
J Am Vet Med Assoc
195
1
1989
69
72
2668242
354
Enzerink
E
van Weeren
PR
van der Velden
MA
Closure of the abdominal wall at the umbilicus and the development of umbilical hernias
in a group of foals from birth to 11 months of age
Vet Rec
147
2
2000
37
39
10955891
355
Freeman
DE
Orsini
JA
Harrison
IW
Complications of umbilical hernias in horses: 13 cases (1972-1986)
J Am Vet Med Assoc
192
6
1988
804
807
3356601
356
De Bosschere
H
Simoens
P
Ducatelle
R
Persistent vitelline vein in a foal
Vet Rec
145
3
1999
75
77
10460028
357
Young
RL
Linford
RL
Olander
HJ
Atresia coli in the foal: a review of six cases
Equine Vet J
24
1
1992
60
62
1555545
358
Santschi
EM
Purdy
AK
Valberg
SJ
Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses
Mamm Genome
9
4
1998
306
309
9530628
359
Yang
GC
Croaker
D
Zhang
AL
A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal
white foal syndrome (LWFS): a horse variant of Hirschsprung disease
Hum Mol Genet
7
6
1998
1047
1052
9580670
360
Metallinos
DL
Bowling
AT
Rine
J
A missense mutation in the endothelin-B receptor gene is associated with lethal white
foal syndrome: an equine version of Hirschsprung disease
Mamm Genome
9
6
1998
426
431
9585428
361
Santschi
EM
Vrotsos
PD
Purdy
AK
Incidence of the endothelin receptor B mutation that causes lethal white foal syndrome
in white-patterned horses
Am J Vet Res
62
1
2001
97
103
11197568
362
Hostetler
MA
Schulman
M
Necrotizing enterocolitis presenting in the emergency department: case report and
review of differential considerations for vomiting in the neonate
J Emerg Med
21
2
2001
165
170
11489407
363
Caplan
MS
Jilling
T
New concepts in necrotizing enterocolitis
Curr Opin Pediatr
13
2
2001
111
115
11317050
364
Jones
RL
Adney
WS
Alexander
AF
Hemorrhagic necrotizing enterocolitis associated with Clostridium difficile infection
in four foals
J Am Vet Med Assoc
193
1
1988
76
79
3262102
365
Murray
MJ
Endoscopic appearance of gastric lesions in foals: 94 cases (1987-1988)
J Am Vet Med Assoc
195
1989
1135
1141
2808108
366
Murray
MJ
Grodinsky
BS
Cowles
RR
Endoscopic evaluation of changes in gastric lesions of thoroughbred foals
J Am Vet Med Assoc
196
1990
1623
1627
2347755
367
Murray
MJ
Gastroduodenal ulceration in foals
Equine Vet Educ
11
1999
199
207
368
Murray
MJ
Murray
CM
Sweeney
HJ
Prevalence of gastric lesions in foals without signs of gastric disease: an endoscopic
survey
Equine Vet J
22
1990
6
8
2298194
369
Rebhun
WC
Dill
SG
Power
HT
Gastric ulcers in foals
J Am Vet Med Assoc
180
4
1982
404
407
7061324
370
Traub-Dagartz
J
Bayly
W
Riggs
M
Exsanguination due to gastric ulceration in a foal
J Am Vet Med Assoc
186
3
1985
280
281
3972690
371
Palmer
JE
Gastrointestinal diseases of foals
Vet Clin North Am Equine Pract
1
1
1985
151
168
3907766
372
Murray
MJ
Pathophysiology of peptic disorders in foals and horses: a review
Equine Vet J Suppl
29
1999
14
18
373
Andrews
FM
Nadeau
JA
Clinical syndromes of gastric ulceration in foals and mature horses
Equine Vet J Suppl
29
1999
30
33
374
Becht
JL
Byars
TD
Gastroduodenal ulceration in foals
Equine Vet J
18
1986
307
312
3758011
375
Navab
F
Steingrub
J
Stress ulcer: is routine prophylaxis necessary?
Am J Gastroenterol
90
1995
708
712
7733073
376
Mertz
HR
Walsh
TH
Peptic ulcer pathophysiology
Med Clin North Am
75
1990
799
814
377
Sanchez
LC
Lester
GD
Merritt
AM
Intragastric pH in critically ill neonatal foals and the effect of ranitidine
J Am Vet Med Assoc
218
2001
907
911
11294316
378
MacAllister
CG
A review of medical treatment for peptic ulcer disease
Equine Vet J Suppl
29
1999
45
49
379
Borne
AT
MacAllister
CG
Effect of sucralfate on healing of subclinical gastric ulcers in foals
J Am Vet Med Assoc
202
1993
1465
1468
8496102
380
Sanchez
LC
Lester
GD
Merritt
AM
Effect of ranitidine on intragastric pH in clinically normal neonatal foals
J Am Vet Med Assoc
212
1998
1407
1412
9589127
381
MacAllister
CG
Sifferman
RL
McClure
SR
Effects of omeprazole paste on healing of spontaneous gastric ulcers in horses and
foals: a field trial
Equine Vet J Suppl
29
1999
77
80
382
Kappstein
I
Schulgen
G
Frienrich
T
Incidence of pneumonia in mechanically ventilated patients treated with sucralfate
or cimetidine as prophylaxis for stress bleeding: bacterial colonization of the stomach
Am J Med
91
1991
125S
131S
383
Dinsmore
JE
Jackson
RJ
Smith
SD
The protective role of gastric acidity in neonatal bacterial translocation
J Pediatr Surg
32
1997
1014
1016
9247224
384
Crill
CM
Hak
EB
Upper gastrointestinal tract bleeding in critically ill pediatric patients
Pharmacotherapy
19
1999
162
180
10030767
385
Ortiz
JE
Sottile
FD
Sigel
P
Gastric colonization as a consequence of stress ulcer prophylaxis: a prospective,
randomized trial
Pharmacotherapy
18
1998
486
491
9620099
386
Barr BS, Wilkins PS, DelPiero F et al: Is prophylaxis for gastric ulcers necessary
in critically ill equine neonates? A retrospective study of necropsy cases 1995-1999.
Proceedings of the eighteenth annual meeting of the Veterinary Medical Forum, Seattle,
Wash, 2000. p 705.
387
Devlin
JW
Ben-Menachem
T
Ulep
SK
Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation to
the incidence of endoscopically proven stress ulceration
Ann Pharmacother
32
1998
869
874
9762371
388
Georgopoulos
A
Feistauer
SM
Makristathis
A
Influence of stress ulcer prophylaxis on translocation of bacteria from the intestinal
tract in rats
Wien Klin Wochenschr
108
1996
321
325
8767984
389
Wada
K
Kamisaki
Y
Kitano
M
Effects of sucralfate on acute gastric mucosal injury and gastric ulcer induced by
ischemia-reperfusion in rats
Pharmacology
54
1997
57
63
9088038
390
Devlin
JW
Ben-Menachem
T
Ulep
SK
Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation to
the incidence of endoscopically proven stress ulceration
Ann Pharmacother
32
1998
869
874
9762371
391
Ludwig
KG
Craig
TM
Bowen
JM
Efficacy of ivermectin in controlling Strongyloides westeri infections in foals
Am J Vet Res
44
2
1983
314
316
6687517
392
Netherwood
T
Wood
JL
Townsend
HG
Foal diarrhoea between 1991 and 1994 in the United Kingdom associated with Clostridium
perfringens, rotavirus, Strongyloides westeri and Cryptosporidium spp
Epidemiol Infect
117
2
1996
375
383
8870636
393
Dwyer
RM
Rotaviral diarrhea
Vet Clin North Am Equine Pract
9
2
1993
311
319
8358646
394
Powell
DG
Dwyer
RM
Traub-Dargatz
JL
Field study of the safety, immunogenicity, and efficacy of an inactivated equine rotavirus
vaccine
J Am Vet Med Assoc
211
2
1997
193
198
9227750
395
Barrandeguy
M
Parreno
V
Lagos Marmol
M
Prevention of rotavirus diarrhoea in foals by parenteral vaccination of the mares:
field trial
Dev Biol Stand
92
1998
253
257
9580371
396
Corrier
DE
Montgomery
D
Scutchfield
WL
Adenovirus in the intestinal epithelium of a foal with prolonged diarrhea
Vet Pathol
19
5
1982
564
567
6293145
397
Guy
JS
Breslin
JJ
Breuhaus
B
Characterization of a coronavirus isolated from a diarrheic foal
J Clin Microbiol
38
12
2000
4523
4526
11101590
398
Davis
E
Rush
BR
Cox
J
Neonatal enterocolitis associated with coronavirus infection in a foal: a case report
J Vet Diagn Invest
12
2
2000
153
156
10730946
399
Baker
JC
Ames
TR
Total parenteral nutritional therapy of a foal with diarrhoea from which parvovirus-like
particles were identified
Equine Vet J
19
4
1987
342
344
3040389
400
Jones
RL
Clostridial enterocolitis
Vet Clin North Am Equine Pract
16
3
2000
471
485
11219344
401
East
LM
Savage
CJ
Traub-Dargatz
JL
Enterocolitis associated with Clostridium perfringens infection in neonatal foals:
54 cases (1988-1997)
J Am Vet Med Assoc
212
11
1998
1751
1756
9621884
402
Netherwood
T
Binns
M
Townsend
H
The Clostridium perfringens enterotoxin from equine isolates: its characterization,
sequence and role in foal diarrhoea
Epidemiol Infect
120
2
1998
193
200
9593490
403
Jones
RL
Adney
WS
Shideler
RK
Isolation of Clostridium difficile and detection of cytotoxin in the feces of diarrheic
foals in the absence of antimicrobial treatment
J Clin Microbiol
25
7
1987
1225
1227
3112178
404
Browning
GF
Chalmers
RM
Snodgrass
DR
The prevalence of enteric pathogens in diarrhoeic thoroughbred foals in Britain and
Ireland
Equine Vet J
23
6
1991
405
409
1663866
405
Walker
RL
Madigan
JE
Hird
DW
An outbreak of equine neonatal salmonellosis
J Vet Diagn Invest
3
3
1991
223
227
1911993
406
Eugster
AK
Whitford
HW
Mehr
LE
Concurrent rotavirus and Salmonella infections in foals
J Am Vet Med Assoc
173
7
1978
857
858
213413
407
Ward
AC
Sriranganathan
N
Evermann
JF
Isolation of piliated Escherichia coli from diarrheic foals
Vet Microbiol
12
3
1986
221
228
2877521
408
Lavoie
JP
Drolet
R
Parsons
D
Equine proliferative enteropathy: a cause of weight loss, colic, diarrhoea and hypoproteinaemia
in foals on three breeding farms in Canada
Equine Vet J
32
5
2000
418
425
11037264
409
Williams
NM
Harrison
LR
Gebhart
CJ
Proliferative enteropathy in a foal caused by Lawsonia intracellularis-like bacterium
J Vet Diagn Invest
8
2
1996
254
256
8744752
410
Cooper
DM
Swanson
DL
Gebhart
CJ
Diagnosis of proliferative enteritis in frozen and formalin-fixed, paraffin-embedded
tissues from a hamster, horse, deer and ostrich using a Lawsonia intracellularis-specific
multiplex PCR assay
Vet Microbiol
54
1
1997
47
62
9050170
411
Mair
TS
Taylor
FG
Harbour
DA
Concurrent cryptosporidium and coronavirus infections in an Arabian foal with combined
immunodeficiency syndrome
Vet Rec
126
6
1990
127
130
2156372
412
Snyder
SP
England
JJ
McChesney
AE
Cryptosporidiosis in immunodeficient Arabian foals
Vet Pathol
15
1
1978
12
17
625861
413
Cole
DJ
Cohen
ND
Snowden
K
Prevalence of and risk factors for fecal shedding of Cryptosporidium parvum oocysts
in horses
J Am Vet Med Assoc
213
9
1998
1296
1302
9810386
414
Brown
CA
MacKay
RJ
Chandra
S
Overwhelming strongyloidosis in a foal
J Am Vet Med Assoc
211
3
1997
333
334
9262674
415
DeLay
J
Peregrine
AS
Parsons
DA
Verminous arteritis in a 3-month-old thoroughbred foal
Can Vet J
42
4
2001
289
291
11326632
416
Kavvadia
V
Greenough
A
Dimitriou
G
Randomised trial of fluid restriction in ventilated very low birthweight infants
Arch Dis Child Fetal Neonatal Ed
83
2
2000
F91
F96
10952699
417
Bell
EF
Acarregui
MJ
Restricted versus liberal water intake for preventing morbidity and mortality in preterm
infants
Cochrane Database Syst Rev
2
2000
CD000503
and 3:CD000503, 2001 (update).
418
Bussmann
C
Bast
T
Rating
D
Hyponatraemia in children with acute CNS disease: SIADH or cerebral salt wasting?
Childs Nerv Syst
17
1-2
2001
58
62
(discussion 63); erratum in Childs Nerv Syst 17(9):575, 2001.
11219625
419
Yang
Y
Qiu
HB
Zhou
SX
Comparison of norepinephrine-dobutamine to dopamine alone for splanchnic perfusion
in sheep with septic shock
Acta Pharmacol Sin
23
2
2002
133
137
11866873
420
Sharshar
T
Carlier
R
Blanchard
A
Depletion of neurohypophyseal content of vasopressin in septic shock
Crit Care Med
30
3
2002
497
500
11990905
421
Tsuneyoshi
I
Yamada
H
Kakihana
Y
Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory
septic shock
Crit Care Med
29
3
2001
487
493
11373409
422
Patel
BM
Chittock
DR
Russell
JA
Beneficial effects of short-term vasopressin infusion during severe septic shock
Anesthesiology
96
3
2002
576
582
11873030
Santschi
Elizabeth M.
19.1—Musculoskeletal Disorders of Foals
The advances in medical care of equine neonates in the last 20 years have resulted
in the survival of many foals that previously would have died from sepsis, asphyxia,
and prematurity; and the successful management of their musculoskeletal system can
be a major challenge. Major factors adding to the challenge are the immaturity of
components of the musculoskeletal system and the demands placed on them by a growing
and active foal. Additional pressures to treat orthopedic conditions in foals have
come from an overall increase in the demand for quality health care for animals, advances
in medical science, and in some breeds the increasing value of the juvenile equine
athlete. Equine veterinarians that encounter pediatric orthopedic problems are only
beginning to get the information needed to make appropriate treatment decisions.
NEONATAL MUSCULOSKELETAL SYSTEM
The equine neonate has specific differences in structure and physiology from adults
that one must consider when designing an optimal therapeutic or management strategy.
Few investigations have focused on the equine neonatal musculoskeletal system,1, 2,
3, 4, 5, 6 but a large body of clinical information exists, and one can make cautious
extrapolations from work in other species.
7
Neonatal equine bones have accelerated modeling and remodeling processes
5
that result in accelerated fracture healing and an increased susceptibility to deformation
caused by excessive loading. Contralateral limb varus deformities of the growth centers
(most commonly distal radius and metacarpus/metatarsus) are common in overloaded limbs.
The increased plasticity of the skeletal structure also is mirrored in the soft tissue
support system, for these units become flaccid within 2 weeks of immobilization.
4
This laxity is important, because it further compromises the use of the fractured
limb and can last as long as the coaptation was in place. Additional divergences from
adult physiology include musculoskeletal immaturity (generalized or focal) and immune
system differences. Finally, foals are lighter and can tolerate and will assume recumbency
more readily than adults. The net results of these differences are that one must consider
the use of external coaptation carefully, fractures heal quickly, one must consider
damage to the contralateral limb from overstress, reducing weight bearing is possible,
and infection is always lurking.
TRAUMA
Long Bone Fractures
Stresses can affect the musculoskeletal system of the foal at any time, including
in utero. Although rare, reports describe in utero fractures (K. Sprayberry, personal
communication, 2003) that result in foal locomotor problems and even maternal uterine
damage from sharp bone ends. The cause is presumably from vigorous muscular activity
of the foal, but one cannot rule out direct trauma. The fractures result in foal lameness
and can increase the likelihood of dystocia and caused colic in one mare when the
broken bones damaged the uterus. Treatment depends on how long the fracture has been
present and on the fracture location and configuration, but if the fracture is repairable,
internal fixation probably is necessary. Fractures occurring during foaling result
from aggressive obstetric manipulation (mandibles) or chest compression. One should
stabilize unstable mandibular fractures. Appendicular fractures usually do not occur
during parturition because of the robust character of the bones of the foal.
After birth, foals are susceptible to external trauma from many sources. The dilemma
is that younger foals with fractures are more likely to heal but also are more likely
to develop contralateral limb problems because of excessive weight bearing and affected
limb flexor tendon laxity if the limb is immobilized fully. As a result, internal
fixation is often the best choice for neonatal fractures to keep the fractured limb
in use.
Small Bone and Avulsion Fractures
Proximal sesamoid bone fractures result from hyperextension of the fetlock joint.
Foals are lame after the fracture, but the lameness can be mild and often diminishes
quickly. Soft tissue swelling occurs over the sesamoids. Fractures are usually simple,
can occur uniaxially or biaxially, and can be apical, midbody, or basilar. Fractures
can occur in any joint and can affect multiple sesamoids in one foal. However, they
most commonly are single forelimb fractures
8
and in Thoroughbreds are most frequent in the left front medial proximal sesamoid
(J.P. Morehead, personal communication, 2003). Of particular interest to neonatologists
is that proximal sesamoids fractures often occur in recovered neonatal patients that
are allowed too much exercise too soon. Foals from the NICU need a gradual introduction
to pasture turnout to allow their musculoskeletal system to adjust. Mares are often
in need of turnout, but in the interest of their foals, they must wait.
Treatment of proximal sesamoid fractures in foals is stall confinement with support
bandaging. Healing occurs, albeit with some distortion of the shape of the sesamoid.
Severely displaced fragments result in large and misshapen sesamoids, and surgery
may be considered for these foals, because restriction of fetlock flexion can occur
after conservative therapy.
Third phalangeal fractures are also common in foals. These foals have a lameness that
worsens with hoof compression. Hoof abscesses are uncommon in young foals but should
be considered. Most commonly, radiographs reveal nonarticular small fractures on the
wings on the third phalanx. The fractures are associated with hard ground and exercise.
The fractures heal with stall confinement, and unlike adults, leave no discernable
radiographic fibrous union.
Avulsion fractures of the proximal insertion of the peroneus tertius and the origin
of the long digital extensor tendon have been reported.9, 10 Both soft tissue structures
attach to the extensor fossa of the distal femur. The two affected foals had lameness
of a hindlimb associated with swelling, pain, and crepitation. Radiographs revealed
multiple avulsion fractures of the extensor fossa. Because of the intraarticular fragments
in the femoropatellar joint, and the fear of later degenerative joint disease, fragments
were removed arthroscopically. Both foals were juveniles at last follow-up; one foal
was considered normal, and one had a mild residual lameness.
Tendon and Ligament Damage
Tendon and ligament damage is uncommon in neonates probably because of their low body
weight. Extensor tendon damage following flexural deformities is the most common tendon
problem and is discussed in Congential Flexural Deformities of Foals. Gastrocnemius
ruptures are one of the most devastating problems and have occurred after forced extraction
because of a breech presentation, severe flexor tendon laxity, and tarsal contracture.
Loss of gastrocnemius function usually results in a non–weight-bearing limb, although
an intact superficial digital flexor tendon may make some weight bearing possible.
Complete loss of support is difficult to treat successfully. Coaptation of the limb
is logical but difficult to obtain. Schroeder-Thomas splints have been used but are
difficult to manage. Tube casts also are used but must be changed frequently, and
cast sores are inevitable (L.R. Bramlage, personal communication, 2003). The prognosis
for athletic function is guarded.
Treatment for ligamentous injuries is usually some form of coaptation, although surgical
repairs have been performed when coaptation was unworkable.
11
Coaptation in proper limb alignment allows the ligaments to heal and should be used
if the injury will destabilize a joint and cause damage to growing epiphyses or cuboidal
bones. One can achieve coaptation with casts or splints under a bandage. Casts are
initially a greater expense, and cast sores and their resulting white hairs are a
risk, but the rigid immobilization and the lack of the requirement for daily adjustment
makes them preferable. Important to musculotendinous health is some measure of weight
bearing to avoid laxity after coaptation removal, which one can achieve by using tube
casts and splints that allow weight bearing. Following coaptation, bandaging and a
gradual return to exercise are recommended for ligamentous injuries.
LUXATING PATELLAE
Patellar luxation can affect foals in one or both hindlimbs, and the luxation can
vary from a laxity in the medial attachments to complete luxations that cannot be
replaced in the patellar groove of the distal femur.12, 13 Medial luxations have not
been reported. Clinical signs vary from a slight discontinuous motion during stifle
flexion to an inability to stand. Many foals have a crouching stance on the affected
limb because of an inability to extend the stifle. The pathophysiology of patellar
luxations is unknown. Congenital bilateral luxations are common in Miniature horse
foals and are believed to be genetic. Luxations are rarer in other breeds and are
occasionally traumatic. The affected limbs are usually not grossly abnormal except
for effusion of the femoropatellar joint and the luxation. A shallow trochlear groove
has been reported to be a cause of patellar luxation, but objective evidence is lacking.
One should evaluate foals for the ability to stand. Once the appropriate supportive
care is provided, if a foal cannot stand, euthanasia is recommended. Most bilateral
luxations in horses fit in this category. However, Miniature horse foals often can
stand sufficiently to nurse despite bilateral luxations, and one may consider treatment.
Treatment consists of replacing and stabilizing the patella and sometimes surgically
deepening the patellar groove. Delaying surgical repair until the foal is approximately
30 days old is recommended to avoid neonatal problems, allow the musculoskeletal system
to mature, and provide good anchors for suture. Some surgeons worry that delay may
cause further femoropatellar developmental abnormalities, but in a small number of
cases, this has not been an issue. The prognosis for Miniature horse foals appears
to be good because of their low body weights and modest performance expectations.
Too few reports about the correction of unilateral luxations in light horses exist
to make a definitive statement about prognosis except that success and failure have
been experienced.12, 13
CONGENITAL FLEXURAL DEFORMITIES
Congenital flexural deformities in foals can be classified as severe (rarely correctable),
moderate (correctable with therapy), or mild (self-correctable). Examples of severe
flexural deformities include arthrogryposis (deformities of multiple limbs and often
the head and neck), severe carpal deformities (flexor angle of the carpus less than
90 degrees), and tarsal contractures (rare). Extraordinary methods have been used
to correct severe deformities
14
but are often unsuccessful.
Mild flexural deformities are those that result in an upright conformation to the
limb, but the foal can bear weight on the limb and load the flexor structures. These
foals require no specific treatment and will self-correct with controlled exercise.
Moderate flexural deformities are those that make bearing weight on the limb and loading
the flexor structures and ligaments difficult for the foal. When these deformities
occur bilaterally (most common), the foals cannot rise to suckle or does so with great
difficulty, and the lack of weight bearing worsens the flexural deformity. Examples
of moderate flexural deformities include carpal and forelimb fetlock flexural deformities
that usually occur together, hindlimb fetlock flexural deformities with coronopedal
flexion or hyperextension, and the uncommon coronopedal flexural deformity alone.
Treatment of moderate flexural deformities aims to place the solar surface of the
foot on the ground so that the weight of the foal can stretch the flexor structures.
Splints are useful for restoring the limb to normal orientation but require attention
to detail because the splints often exert an extreme amount of tension on the soft
tissues, and the skin of the foal is thin. Pressure sores are easy to create and at
a minimum result in an extended convalescence.
The first step in splint application is to apply a separate heavy bandage to the limb,
which should be reapplied as necessary because the bandage can slip and cause focal
constriction. Commercial gauze over cotton bandage material works better than sheet
cotton as a bandage. The splint is made of polyvinyl chloride pipe cut in half or
thirds. Using 50% of the diameter of the pipe results in less splint rotation but
is bulkier and leaves more splint exposed to cause trauma. One cuts off the corners
of the splint and pads the ends with gauze or roll cotton covered with tape. Palmar
or plantar placement of the splint is preferable, but severe deformities may require
initial dorsal placement. As the limb straightens, one can bend the splint to tape
the fetlock into the bend to extend it. One can tape the splint tightly to the limb
over the bandage with nonelastic (white or duct) tape. This procedure requires at
least two persons, one to extend the limb firmly and hold the limb and one to tape.
One should leave the splint on for 8 to 12 hours and then remove it for 8 to 12 hours.
One can reapply splints as necessary.
In addition to splints, some medications are of value for treating flexural deformities.
Oxytetracycline (40 to 50 mg/kg) given intravenously appears to relax the soft tissues.
15
The mechanism of action is unknown, and the drug is most efficacious when given in
the first 3 days of life. This dose is high but appears to be safe for healthy foals
and can be repeated at 24-hour intervals. Foals should be normovolemic during tetracycline
administration. One should use the drug with caution in foals with renal impairment.
Foals should be urinating and have reasonable urinary parameters (serum urea nitrogen,
creatinine, and urinalysis) before tetracycline use. Diarrhea is an uncommon sequela
to tetracycline use. One should monitor the unaffected limbs closely because all limbs
experience a relaxation of the palmar/plantar support.15, 16 Discontinuation of tetracycline
therapy before affected limbs are normal but after they can bear weight is common
because of worsening laxity in the “normal” limbs. One also can use phenylbutazone
(4 mg/kg) for a short time when the splints are used. Some analgesia appears to help
the foals use the limbs and stretch the soft tissues. One should not use phenylbutazone
for long periods of time because of the potential of inducing gastric ulcers.
Surgical treatment of congenital flexural deformities rarely is indicated. Severely
affected foals rarely respond favorably to surgery, and mildly affected foals do not
need it. Surgery is most appropriate for foals with moderate flexural deformities
that are neglected or have not responded to splinting and tetracycline. The most common
surgical therapy performed for congenital flexural deformities is the inferior check
ligament desmotomy for fetlock or coronopedal flexural deformities.
Ruptures of the extensor tendons commonly occur with congenital flexural deformities
and result from the foal overloading the extensor tendons. No specific therapy for
the ruptures is necessary. If the rupture is extensive, it can interfere with the
ability to extend the fetlock and to place the foot flat. These foals then tend to
knuckle over, even after correction of the flexural deformity. A firm fetlock bandage
extends the digit and assists in foot placement until the extensor tendons heal.
CONGENITAL EXTENSION DEFORMITIES
Foals commonly are born with hyperextension deformities of the fetlock of varying
degrees of severity. All but the worst deformities self-correct as muscle tone improves.
A deeply bedded stall is all that is usually necessary to protect the soft tissues,
but one can apply a light bandage to the coronary band and pastern if trauma is a
problem. Severe deformities are more problematic but rare, so therapeutic recommendations
are not available. Hyperextension of the carpus occasionally occurs and usually is
treated conservatively. However, a tube cast to align the limb may be necessary to
protect the dorsal surface of developing carpal bones.
CONFORMATIONAL DEVIATIONS
Neonatal foals exhibit three categories of forelimb conformational deviations: angulation,
rotation, and carpal offset. Angular deviations most commonly are centered in the
metaphysis and epiphysis, but their location is described by the closest joint, usually
the carpus and fetlock. When the deviation of the distal limb is lateral to the long
axis, the deviation is valgus, and when the deviation is medial, the deviation is
varus. More than one joint can be affected, and although rare in neonates, valgus
and varus can occur in different joints in one limb.
Rotational deformities appear to originate most commonly in the diaphysis or metaphysis
of the radius or the metacarpus. In neonates the direction of rotation of the distal
limb at both sites is almost exclusively outward. Associated angular and rotational
deviations occur.
17
In neonates, limb deviations occur in foals with narrower chests and less developed
pectoral muscles than in straight foals, and they appear to have an initial greater
overall weakness in the musculoskeletal system because it first interacts with gravity,
body mass, and ground reaction forces. However, after the first few days of life,
the asymmetric loading of the growth centers does affect limb deviations. Angulation
results from a compressive load that is asymmetric in a frontal plane but is uniform
in the sagittal plane, and rotation occurs when the compressive load is asymmetric
in both planes and the limb develops around an overloaded axis point. Considered this
way, valgus and outward rotation deviations in young foals are coupled, as are varus
and inward rotation in older foals. The loading asymmetry for valgus/outward rotation
foals is accentuated as foals assume a base-wide posture that is more stable side-to-side
but promotes a lateralization of the limb load. The specific effects of intermittent
versus static loads, strain magnitude versus strain rate, and shear and hydrostatic
stress on growing bones is only beginning to be understood. However, clinical experience
supports the general observation that excessive cartilage compression is deleterious
to bone growth.
Offset carpal conformation describes a joint that appears to deviate outwardly and
then inwardly, all within the carpus. The deformity is thought to be centered at the
radiocarpal joint, but the specific structural cause of offset has not been determined.
This conformation is more common in older foals but occasionally occurs in neonates.
The deviation is particularly common when incomplete ossification of the carpal bones
is present.
The causes of conformational deviations are a matter of some debate. As always, the
major factors are genetics or environment. Genetic influences include the assortment
of alleles that controls bone form and growth and the assortment that modulates bone
remodeling. Many in the horse industry believe that genetics is a strong determiner
of limb conformation. Environmental influences are many and include the intrauterine
environment, the postnatal limb load, nutrition, and bad luck. Suffice to say, the
situation is complex, but one must consider biologic and mechanicobiologic influences
when evaluating the growth of long bones.
18
Several factors may contribute to the common occurrence of deviations in the carpus.
First, the carpus is in the middle of the limb and is subject to the greatest bending
forces. Second, the carpal anatomy is complex and perhaps is not understood completely.
The carpus has seven cuboidal bones, two long bones, and two epiphyses (distal radial
and lateral styloid); and cartilage surrounds all. The ligamentous support includes
collateral ligaments, innumerable intracarpal ligaments, and a palmar carpal soft
tissue ligament. The distal radial physis is not flat transversely, but undulates
in the frontal and sagittal planes.
3
A separate center of ossification for the lateral styloid process is found at its
palmar-lateral aspect. Because of this separate center of ossification, more cartilage
and less bone are in the lateral aspect of the distal radial growth center, suggesting
it may be more susceptible to growth alterations from load.
Less common conformation deformities in young foals include hindlimb deformities,
windswept conformation, diaphyseal deviations (usually of the metacarpus/metatarsus),
gross congenital malformations such as agenesis and polydactyly, and acquired varus
deformities of the carpus and fetlock. Hindlimb conformational deviations can manifest
as tarsal and fetlock angular deformities and external limb rotation, usually centered
above the tarsus. Windswept foals have limbs (usually both forelimb or both hindlimbs)
that are curved in the same direction in the frontal plane. Diaphyseal deviations,
agenesis, and polydactyly are rare and have various presentations. Acquired varus
deformities are caused by excessive loading, which appears to be focused medially
on the growth plates.
Evaluation
One should evaluate the limbs to determine the location, extent, and potential cause
of the deviation. Evaluation consists of observation and then palpation for heat,
swelling, or ligament laxity. Ligamentous laxity of the medial carpal ligaments is
an important cause of carpal valgus and should be evaluated carefully. Lameness is
not a characteristic of uncomplicated angular limb deformities and suggests further
evaluations are necessary. Radiography is indicated for foals with severe deviations
(all tarsal valgus), ligamentous laxity, lameness, or joint effusions. Ultrasonography
may be valuable for selected soft tissue evaluations.
Nonsurgical Treatments
Conservative therapy is by far the most commonly used therapy in foals less than 30
days of age.
19
Mild to moderate carpal valgus and external rotation of the carpus and fetlock are
common and normal in neonates, particularly light breed horses. Most congenital limb
deviations improve with age, if the developing musculoskeletal system is protected
from overuse and abnormal loads. Approximately 90% of Thoroughbred foals with congenital
carpal valgus self-correct. Those foals that do not most often have abnormal bone
(incomplete ossification) with normal stress or normal bone with abnormal stress (ligamentous
laxity or contralateral limb lameness). Correction continues for several months, and
on average, foals reach their straightest conformation (regarding angulation) at approximately
10 months of age (E.M. Santschi, unpublished data).
Determination of the appropriate treatment for foals with angular limb deformities
is based on the age of the foal, the severity and location of the deviation, and its
causes. One must evaluate the entire foal and the affected limb. If the carpal collateral
ligaments have no laxity and carpal incomplete ossification is not suspected, one
may use an exercise program such as in Table 19-10
, assuming that the foal has no contradicting additional problems. Exercise is essential
for the robust development of almost every body system for neonates, and fresh air
and good ventilation reduce the occurrence of respiratory disease. Appropriate limb
loading along with growth and maturity is what straightens limbs, but excessive amounts
of loading can be deleterious. For example, one should use exercise cautiously in
foals with very asymmetric deviations. When one limb is much more deviated than the
other, it appears to be loaded excessively and compromised more than if both limbs
were affected similarly. And finally, limb deviations are additive. Foals with external
rotation and carpal valgus improve more slowly than those with one type of deviation.
TABLE 19-10
Exercise Recommendations for Foals With Uncomplicated Carpal Valgus*
TIME
MILD (4°–10°)
MODERATE (11°–16°)
SEVERE (>16°)
Initial exercise
Paddock turnout
Stall confinement; playing while mare is walked in hand daily
Large stall confinement; limited walking in hand
After 1–2 weeks
Pasture turnout
Paddock turnout
Stall confinement; playing while mare is walked in hand
Maintenance
Pasture turnout
Pasture turnout
Paddock turnout
*
Increasing levels of exercise are allowed as the angulation decreases; static and
worsening deviations are indications for further evaluation.
Incomplete ossification of cuboidal bones and focal ligamentous laxity are complicating
matters of great potential impact on adult conformation. They generally manifest as
a moderate to severe limb deviation. Physical examination indicates laxity because
angular limb deviations are reducible. Radiographs are the best way to evaluate the
extent of carpal bone ossification. Incomplete ossification of the cuboidal bones
can be focal or widespread. Focal immaturity is not common but can result in severe
angulation. Generalized immaturity is more frequent and initially often manifests
as an offset conformation with valgus angulation. When the foal becomes heavier, assumes
a base-wide stance, and is allowed exercise, crushing of the bones of the lateral
carpus (usually the lateral styloid process of the radius, the ulnar, the fourth and
the intermediate facet of the third carpal bone) results in a permanent intracarpal
valgus deviation. The same result occurs when significant medial carpal ligament laxity
goes untreated.
In the forelimb, foals with collateral ligamentous laxity and moderate to severely
immature cuboidal bones should have external coaptation placed on the affected limb
to maintain axial orientation. Tube casts that allow weight bearing on the digit are
preferred to splints. Ligamentous laxity in the carpus usually responds to tube casting
for 7 to 10 days followed by bandaging and cautious exercise. The duration of similar
coaptation necessary for immature carpal bones depends on the degree of immaturity
and the speed with which the bones mature. Because casts cannot be left on neonatal
limbs for more than 7 to 10 days because of their fast growth, more than one cast
may be necessary.
Treatment of tarsal valgus and rotational deformities is much less common than in
the forelimbs because deviations are less common than in the forelimb, because some
breeds prefer an outward position to the hindlimb, and perhaps because owners recognize
it less frequently.
20
Hindlimbs generally are unaffected by ligamentous laxity, but tarsal incomplete ossification
is common and often is associated with tarsal valgus. Treatment of tarsal incomplete
ossification is important because tarsal crushing results in an unfavorable prognosis
for athletic performance.20, 21 Hindlimbs require a slightly different approach to
coaptation than forelimbs because of their anatomy. Foals can rise to stand if their
forelimbs are fixed in extension but cannot do so if their hindlimbs are extended.
The multiple bony protuberances of the hock make cast sores more likely than in the
forelimb, so casts are problematic. Gutter splints are not useful because of the angle
of the hock. Severely limiting exercise is part of allowing the tarsus to mature without
cartilage crushing, but foals cannot always be recumbent. Extra small articulated
anterior cruciate ligament splints for human beings (Playmaker Wraparound, dj Orthopedics,
Vista, California) have given the best results. For small foals, a padded bandage
is necessary under the splint, which is reversed to conform to the angle of the hock.
The splints allow enough flexion in the hock for the foal to rise but appear sufficient
when combined with stall rest to protect the cartilage from crushing. Splints are
left on the hocks until the cuboidal bones have ossified as shown by radiography.
Fetlock conformational deviations in neonates that are treated best conservatively
are rare. Outward rotation is the most common deviation but is thought to have minimal
effect on the performance and improves with maturity. The only therapy used is to
rasp the toe square to promote central breakover. Severe outward rotation can promote
a fetlock valgus conformation, so one can use a medial hoof wall extension of epoxy
to bring the limb load medially. The most commonly treated fetlock deviations are
inward but usually occur in foals older than 30 days. However, if the deviation is
noticed in neonates, one can use small lateral hoof wall extensions that generally
are made of epoxy with fiberglass cloth embedded to prevent chipping.
Windswept foals are born with multiple deviations. Evaluating the foal as a whole
is best rather than focusing on individual joints. Most of these foals become straight
over time with conservative therapy.
Surgical Treatment
No surgical procedures are commonly accepted for direct treatment of rotational or
carpal offset deviations, so angular deviations are described. Surgical procedures
to correct carpal and fetlock valgus include periosteal transection and elevation
and transphyseal bridging. Periosteal elevation is thought to accelerate growth on
the concave side of the metaphysis, and transphyseal bridging is used to restrict
the growth on the convex side of the physis. Studies indicate an approximately 80%
improvement of carpal valgus foals after periosteal transection and elevation, but
unfortunately they do not compare foals that had surgery with controls that did not.22,
23 Recently, some have suggested that most of the correction was unrelated to the
surgery,
24
and one experimental study supports that conclusion.
25
As a result, at this time making firm recommendations about the indications for periosteal
transection and elevation is difficult. However, periosteal transection and elevation
has a low likelihood of complications and may be effective. The procedure is inexpensive
and can be done in the field and therefore may be an option for clients with foals
with carpal valgus in which a transphyseal bridging is undesirable or unnecessary.
One indication is the very young foal born with a notably asymmetric epiphysis that
results in a severe carpal valgus. This distal radial appearance is not particularly
common, but the lack of ossification in the epiphysis can make a firm hold with a
transphyseal bridging difficult to achieve. However, one can use distolateral radial
periosteal elevation at an early age in an attempt to accelerate correction of the
valgus and protect developing carpal bones.
Often a degree of anxiety exists about correction of fetlock angulations because of
the much shorter time period for physeal growth. Most fetlocks are in their final
conformation by 60 days of age, so correction is best accomplished with earlier treatment,
usually by 4 weeks of age. One can perform periosteal elevation on the medial (for
varus deviations) or lateral (for valgus deviations) aspect of the distal metacarpus/metatarsus.
The definitive treatment of limb angulation at a growth plate is transphyseal bridging.
One should consider using the procedure at about 3 weeks of age for all moderate to
severe fetlock deviations, at about 4 weeks for severe carpal deviations, and 6 to
8 weeks for mild fetlock deviations, moderate carpal deviations, and any worsening
angular deformities. One must perform bridge removal when the limb straightens to
prevent overcorrection.
Diaphyseal deviations are rare but can occur in varying degrees of severity. If the
foal can bear weight on the limb, a conservative approach is indicated. One can consider
periosteal elevation of the length of the concave surface of the long bone. If the
foal cannot bear weight on the limb because of the severity of deviation, euthanasia
is probably the best option. However, a revision osteotomy and internal fixation may
be appropriate for selected foals.
26
Polydactyly is also rare and sometimes can be corrected surgically. The outcome is
based on the degree of articular involvement.
ORTHOPEDIC INFECTIONS IN NEONATAL FOALS
Bacteria may invade the foal musculoskeletal system and cause orthopedic infection
after delivery by the circulation, by direct extension from another system, or by
direct inoculation. Hematogenous delivery is by far the most common and results in
infection of synovial structures (joints, tendon sheaths, bursae) and bone. Extension
from another site without hematogenous delivery is rare. Direct inoculation almost
exclusively results from traumatic rather than surgical wounds.
Much is still to be learned about the pathophysiology of orthopedic infection, including
the source of the infecting bacteria. The umbilicus commonly is accepted as a possible
source of bacteria,
27
but many believe that the gastrointestinal and respiratory tracts are at least equally
responsible. Associated conditions in foals with septic arthritis include failure
of passive transfer, pneumonia, and enteritis.
28
The classification of orthopedic sepsis in foals into infection of bones and joints
is probably irrelevant because most foals with septic arthritis also have infectious
osteitis or osteomyelitis.27, 29 Septic arthritis is more readily recognizable because
the reactivity of the synovium to the bacteria causes joint effusion and lameness
and because early radiographic signs of bone infection in foals are equivocal.
Also unclear are the reasons for the apparent site predilection for orthopedic infection
in foals. The femoropatellar joint and the tarsocrural joint are affected most frequently,
followed by the carpal and fetlock joints, and finally an assortment of miscellaneous
joints such as the elbow, shoulder, and hip.
28
The common association of osteomyelitis of the distal femoral, tibial, and metacarpal/metatarsal
physes with a newly recognized septic arthritis suggests that the infection in that
area started at the growth center (epiphysis, physis, or metaphysis). The localization
of the apparent initial site of infection to the growth center has been suggested
to result from “looping” metaphyseal vessels with sluggish blood flow that allow pathogens
more time to escape the circulation.29, 30 However, transmission electron microscopy
indicates that osteogenic cells and the vascular endothelium are a continuous network
in developing embryos,
31
indicating that the relationship between circulation and bone is more intimate than
previously suspected.
A possible association between osteomyelitis and thickened or traumatized cartilage
exists. Focal osteomyelitis lesions occur commonly at the bone cartilage junction27,
29 and particularly in areas where cartilage is attached at an angle to the long axis
or where thickened.
29
An association also exists between incomplete ossification of the central and third
tarsal bones and osteomyelitis.
32
Trauma to the metaphysis is a known predisposing cause of osteomyelitis in young bacteremic
rabbits.
33
A trend exists for foals with more than one joint affected to be affected bilaterally
in the same joint, rather than in random joints. This trend suggests that a “window”
exists when a joint may be more susceptible to infection and that trauma to the developing
cartilage may be a contributing factor. In neonates, cartilage is vascular,
34
and possibly small traumatic cartilage lesions with associated hemorrhage and exposure
of bacterial binding sites might be the inciting cause for the location of infection.
The pathogens most commonly associated with septic arthritis in young foals are also
those that frequently are implicated in neonatal sepsis. The most commonly isolated
gram-negative organisms are Escherichia coli and other Enterobacteriaceae, Actinobacillus
equuli, and Salmonella spp. Frequently isolated gram-positive organisms include Streptococcus
spp., Staphylococcus spp., and Rhodococcus equi.
28
Anaerobic bacteria and fungi are rare but should be considered in refractory cases.
The diagnosis of orthopedic sepsis can be challenging. The most common clinical sign
is lameness, followed by swelling around a joint or metaphysis. Joint effusion alone
may cause the swelling, but edema is also common, especially if metaphyseal osteomyelitis
is present. But effusion and edema can be difficult to detect because of the tissue
surrounding the focus of infection in the shoulder, elbow, hip, and coffin joints.
One should evaluate lame foals carefully by palpation to localize pain and swelling.
If one can find no pain or swelling, one should obtain a complete blood count and
fibrinogen level. Although a complete blood count is not always abnormal in foals
with septic arthritis, abnormalities should raise the index of suspicion of infection.
Elevations in fibrinogen are fairly common in septic arthritis,
28
and fibrinogen almost always is elevated if the infection involves bone. If hematologic
values are normal, the lameness could be caused by trauma, but the foal should be
monitored closely for improvement, and closer evaluation is indicated if improvement
is not rapid.
An arthrocentesis is the diagnostic test of choice for confirmation of septic arthritis.
One should perform joint puncture in a sterile fashion, and sedation is indicated
to get an atraumatic tap. Short-term anesthesia is preferable when joints have effusion
because one may perform joint lavage at the same time. Normal joint fluid should be
clear to slightly yellow, should be viscous, and should contain less than 2500 nucleated
cells per deciliter. The cell ratio should be roughly 50:50 polymorphonuclear and
mononuclear. The total protein content should be less than 2.5 mg/dl. One should consider
joints to be infected if the nucleated cell count is greater than 10,000 cells/dl.
For joints falling between 2500 and 10,000 cells/dl, if the polymorphonuclear cell
count is >90%, one should consider the joints infected. Cytologists are often reluctant
to diagnose infection when nuclear degeneration or bacteria are not visible. This
is overly conservative and results in delay in treating infections because bacteria
and nuclear degeneration are rare in early cases of joint infection. Out of an abundance
of caution, one should treat lame foals with suspicious joints as infected unless
they are clearly normal. One should always culture joint fluid in an attempt to identify
the offending organisms, but because of difficulties in culturing pathogens from joint
fluid samples, absence of growth does not mean absence of infection. One obtains the
best culture results if the foal has not been treated with antimicrobial agents beforehand.
One should obtain as much joint fluid as possible for culture and should incubate
it overnight in blood culture media before plate inoculation. As always in potentially
septic foals, blood culture may assist in the isolation of the organism.
Other orthopedic infections that do not involve the joint may be more difficult to
detect. Often these are not apparent until infection breeches the joint and causes
lameness. However, astute caretakers may notice early clinical signs such as mild
lameness, fever, or edema centered at a growth center. Radiography and advanced imaging
modalities such as magnetic resonance imaging are the best diagnostic tools for the
localization of areas of osteitis and osteomyelitis. One should examine the area of
concern carefully, giving particular attention to the growth centers and subchondral
bone. Interpretation of radiographs may be difficult because these areas are complex
and normally have irregular bone margins in the growing foal. If a normal contralateral
joint is available, comparison radiographs may be useful. Because of the high metabolic
turnover in growing foal bone, changes occur faster than with adults, so radiographs
at the earliest sign of potential infection of bone and joint are recommended. If
evidence of osteolysis is clear, aspiration of the area may yield material for culture.
The goals of treatment are to eliminate infection immediately and then resolve inflammation.
Bacteria and products of inflammation elicited by infection are responsible for destruction
of bone and cartilage. The ultimate aim of treatment is to protect the structures
critical to athletic performance such as subchondral bone and cartilage in weight-bearing
areas. Advances in the treatment of sepsis have resulted in hospital discharge rates
of 78% for foals with septic arthritis, but their rate of high performers is 30%,
28
indicating a need for improvement. Equine veterinarians cannot replace what has been
destroyed, so early identification and aggressive therapies are presently the best
methods to improve performance rates.
One achieves the goals of treatment by physical removal of bacteria, products of inflammation,
and debris and by medications to kill the bacteria and reduce inflammation. One should
optimize the physiology and general health of the foal to assist this process; one
should include other treatments and supportive therapies for septic foals, especially
treatment of failure of passive transfer, in the therapeutic plan. Intravenous administration
of antimicrobials (see Chapter 4) is the cornerstone of treatment of orthopedic infection,
and if the drug is administered early in the course of infection and bacteria are
susceptible, intravenous administration may be sufficient to eliminate the organisms.
However, treatment of many foals does not begin until disease is advanced. If treatment
begins after bacteria have had a chance to establish themselves, one should bring
all appropriate methods to bear to end the infection.
Additional therapies for septic arthritis include joint lavage, arthrotomy (for drainage),35,
36 debridement (arthroscopically or arthrotomy),
37
intraarticular administration of antimicrobials, intravenous regional perfusion,
38
and antimicrobial beads.39, 40 One can use any sterile isotonic solution to flush
a joint, and additives do not appear to give significant additional benefit. If radiographs
do not indicate osteomyelitis, lavage, intraarticular antibiotics, and if possible,
regional perfusion are recommended. If osteitis or osteomyelitis is present, debridement
is indicated arthroscopically or via arthrotomy (one should culture the debris if
the pathogen is unknown). If the joint is closed, one may use antibiotics intraarticularly.
If the joint is left open to drain, regional perfusion is useful. Antimicrobial beads
theoretically are best to use if the wound is closed, but they appear to give benefit
even if the wound is open under a bandage. Because of concerns about the use of beads
in a joint,
41
beads often are used in tissue defects and the surrounding tissues. The major goal
is to remove material that is compromising healthy tissues and to obtain high concentrations
of antimicrobials in infected tissues.
High antimicrobial concentrations are necessary because adhered bacteria are difficult
to kill and may require many times the in vitro bacterial minimum inhibitory concentration.
Intraarticular administration of antimicrobials has been used for many years and has
great value.
35
Regional perfusion of diluted antimicrobials recently has come into use and may be
administered intraosseously
42
or intravenously. Intravenous perfusion is preferable because no special equipment
is needed, but intraosseous perfusion may be valuable where intravenous access is
impossible. The concept behind both procedures is to fill the venous vasculature in
the area of the infection with antimicrobials diluted by a sterile balanced electrolyte
solution. One isolates the anatomic area of interest using one or two tourniquets.
The perfusate diffuses into all tissues and achieves much higher concentrations than
are possible using intravenous therapy. This technique has shown excellent results
as an adjunct therapy for orthopedic infection.
43
For foals, 12 to 20 ml total of perfusate containing 250 mg amikacin is useful for
most single joint sites. Amikacin has given consistently good results without complication
and is a good choice based on its concentration-dependent activity. One may use a
higher volume for the stifle, but the thigh musculature makes an effective tourniquet
difficult to achieve. Because of concerns that perfusion might dislodge bacteria and
renew systemic sepsis, high concentrations of systemic antimicrobials are recommended
at the time of the perfusion.
If joint lavage and intraarticular administration of antimicrobials are not sufficient
to resolve infection, one may perform arthrotomy to assist the joint to drain. Passive
and active drains add foreign material and so are not useful. Maintaining the joint
under a sterile bandage is critical and can be difficult to do in proximal joints
such as the stifle and elbow. Tie-over bandages can be useful in this application.
The best measure of success is the resolution of lameness and local inflammation.
Radiographs may be helpful, but the most common sign of success is a failure of the
infection to progress, rather than radiographic healing. One should continue intravenously
administered antimicrobials for at least 1 week after the resolution of lameness.
If an appropriate drug is available, one should give foals antimicrobials orally for
at least 2 weeks more. A total of at least 4 weeks of antimicrobials is recommended
for most foals with orthopedic infection.
Treatment failures usually result from an inability to kill bacteria adhered to isolated
tissue (usually dead bone). Sometimes this failure is caused by incomplete debridement
or an inability to access a known site of infection, but more frequently it is because
infection has flourished in an unknown site. For this reason, multiple imaging modalities
(radiographs, ultrasound, computed tomography, and magnetic resonance imaging) used
multiple times are recommended for all refractory cases of septic arthritis.
Osteomyelitis not associated with a joint still involves a growth center. The ideal
treatment for these infections is surgical debridement, systemic antimicrobial therapy,
and some form of local antibiotic delivery.44, 45 Even in the face of large initial
osseous defects, infection may resolve, the defect may heal, and the foal may regain
normal limb anatomy and function with appropriate therapy.
REFERENCES
1
Firth
EC
Poulos
PW
Blood vessels in the developing growth plate of the equine distal radius and metacarpus
Res Vet Sci
33
1982
159
166
6755592
2
Firth
EC
Poulos
PW
Microangiographic studies of metaphyseal vessels in young foals
Res Vet Sci
34
1983
231
235
6856996
3
Firth
EC
Hodge
H
Physeal form of the longbones of the foal
Res Vet Sci
62
3
1997
217
221
9300537
4
Kelly
NJ
Watrous
BJ
Wagner
PC
Comparison of splinting and casting on the degree of laxity induced in thoracic limbs
in young horses
Equine Pract
9
1987
10
15
5
Stover
SM
Pool
RR
Martin
RB
Histological features of the dorsal cortex of the third metacarpal bone mid-diaphysis
during postnatal growth in thoroughbred horses
J Anat
181
1992
455
469
1304584
6
Madison
JB
Garber
JL
Rice
B
Effect of oxytetracycline on metacarpophalangeal and distal interphalageal joint angles
in newborn foals
J Am Vet Med Assoc
204
1994
246
249
8144385
7
Wirth
T
Syed Ali
MM
Rauer
C
The blood supply of the growth plate and the epiphysis: a comparative scanning electron
microscopy and histological experimental study in growing sheep
Calcif Tissue Int
70
2002
312
319
12004336
8
Ellis
DR
Fractures of the proximal sesamoid bones in thoroughbred foals
Equine Vet J
11
1
1979
48
52
428364
9
Blikslager
AT
Bristol
DG
Avulsion of the origin of the peroneus tertius tendon in a foal
J Am Vet Med Assoc
204
1994
1483
1485
8050977
10
Holcombe
SJ
Bertone
AL
Avulsion fracture of the origin of the extensor digitorum longus muscle in a foal
J Am Vet Med Assoc
204
10
1994
1652
1654
8050948
11
Sanders-Shamis
M
Gabel
AA
Surgical reconstruction of a ruptured medial collateral ligament in a foal
J Am Vet Med Assoc
193
1988
80
82
3417534
12
Kobluck
CN
Correction of patellar luxation by recession sulcoplasty in three foals
Vet Surg
2
1993
298
300
13
Engelbert
TA
Tate
LP
Richardson
DC
Lateral patellar luxation in miniature horse foals
Vet Surg
22
1993
293
297
8351812
14
Trout
DR
Lohse
CL
Anatomy and therapeutic resection of the peroneus tertius in a foal
J Am Vet Med Assoc
179
1981
247
251
7287548
15
Lokai
MD
Meyer
RJ
Preliminary observations on oxytetracycline treatment of congenital flexural deformities
in foals
Mod Vet Pract
66
1985
237
239
16
Madison
JB
Garber
JL
Rice
B
Effect of oxytetracycline on metacarpophalangeal and distal interphalangal join angles
in newborn foals
J Am Vet Med Assoc
204
1994
246
249
8144385
17
Turner
AS
Torsion in quadrapeds and its impact on mammalian joints
Clin Orthop
302
1994
11
16
18
Stevens
SS
Beaupre
GS
Carter
DR
Computer model of endochondral growth and ossification in long bones: biological and
mechanobiological influences
J Orthop Res
17
1999
646
653
10569472
19
Bramlage
LR
Embertson
RM
Observations on the evaluation and selection of foal limb deformities for surgical
treatment
Proc Am Asoc Equine Pract
36
1990
273
279
20
Dutton
DM
Watkins
JP
Honnas
CM
Treatment response and athletic outcome of foals with tarsal valgus deformities: 39
cases (1988-1997)
J Am Vet Med Assoc
215
1999
1481
1484
10579047
21
Dutton
DM
Watkins
JP
Walker
MA
Incomplete ossification of the tarsal bones in foals: 22 cases (1988-1996)
J Am Vet Med Assoc
213
1998
1590
1594
9838959
22
Auer
JA
Martens
RJ
Periosteal transection and periosteal stripping for correction of angular limb deformities
in foals
Am J Vet Res
43
9
1982
1530
1534
7149399
23
Bertone
AL
Turner
AS
Park
RD
Periosteal transection and stripping for treatment of angular limb deformities in
foals: clinical observations
J Am Vet Med Assoc
187
1985
145
152
4030448
24
Slone
DE
Roberts
CT
Hughes
FE
Restricted exercise and transphyseal bridging for correction of angular limb deformities
Proc Am Assoc Equine Pract
46
2000
126
127
25
Read
EK
Read
MR
Townsend
HG
Effect of hemi-circumferential periosteal transection and elevation in foals with
experimentally induced angular limb deformities
J Am Vet Med Assoc
221
2002
536
540
12184705
26
White
KK
Diaphyseal angular limb deformities in three foals
J Am Vet Med Assoc
182
1983
272
279
6826451
27
Firth
EC
Current concepts of infectious polyarthritis in foals
Equine Vet J
15
1
1983
5
9
6825649
28
Steel
CM
Hunt
AR
Adams
PLE
Factors associated with prognosis for survival and athletic use in foals with septic
arthritis: 93 cases (1987-1994)
J Am Vet Med Assoc
215
1999
973
977
10511863
29
Firth
EC
Goedegebuure
SA
The site of focal osteomyelitis lesions in foals
Vet Q
10
2
1988
99
108
3413976
30
Bennett
D
Pathological features of multiple bone infection in the foal
Vet Rec
103
1978
482
485
373223
31
Palazzini
S
Palumbo
C
Ferretti
M
Stromal cell culture and relationships in perimedullary spaces of chick embryo shaft
bones
Anat Embryol
197
1998
349
537
9623668
32
Firth
EC
Goedegebuure
SA
Dik
KJ
Tarsal osteomyelitis in foals
Vet Rec
116
10
1985
261
266
3992822
33
Shingleton
WD
Mackie
EJ
Cawston
TE
Cartilage canals in equine articular/epiphyseal growth cartilage and a possible association
with dyschondroplasia
Equine Vet J
29
1997
360
364
9306061
34
Whalen
JL
Fitzgerald
RH
Morrisey
RT
A histological study of acute hematogenous osteomyelitis following physeal injuries
in rabbits
J Bone Joint Surg
70-A
1988
1383
1392
35
Schneider
RK
Bramlage
LR
Mecklenburg
LM
Open drainage, intra-articular and systemic antibiotics in the treatment of septic
arthritis/tenosynovitis in horses
EquineVet J
24
1992
443
449
36
Bertone
AL
McIlwraith
CW
Jones
RL
Comparison of various treatments for experimentally induced equine infectious arthritis
Am J Vet Res
48
1987
519
529
3565909
37
Schneider
RK
Bramlage
LR
Moore
RM
A retrospective study of 192 horses affected with septic arthritis/tenosynovitis
Equine Vet J
24
6
1992
436
442
1459056
38
Murphey
ED
Santschi
EM
Papich
MG
Regional intravenous perfusion of the distal limbs of horses with amikacin sulfate
Vet Pharmacol Ther
22
1999
68
71
39
Booth
TM
Butson
RJ
Clegg
PD
Treatment of sepsis in the small tarsal joints of 11 horses with gentamicin-impregnated
polymethylmethacrylate beads
Vet Rec
148
12
2001
376
380
11321553
40
Holcombe
SJ
Schneider
RK
Bramlage
LR
Use of antibiotic-impregnated polymethyl-methacrylate in horses with open or infected
fractures or joints: 19 cases (1987-1995)
J Am Vet Med Assoc
211
7
1997
889
893
9333094
41
Farnsworth
KD
White
NA
Robertson
J
The effect of implanting gentamicin-impregnated polymethylmethacrylate beads in the
tarsocrural joint of the horse
Vet Surg
30
2001
126
131
11230766
42
Whitehair
KJ
Blevins
WE
Fessler
JF
Regional perfusion of the equine carpus for antibiotic delivery
Vet Surg
21
1992
279
285
1455636
43
Santschi EM, Adams SB, Murphey EM: How to perform equine digital intravascular perfusion.
Proceedings of the fortyfourth annual meeting of the American Association of Equine
Practitioners, Baltimore, 1998. pp 198-201.
44
Desjardins
MR
Vachon
AM
Surgical management of Rhodococcus equi metaphysitis in a foal
J Am Vet Med Assoc
197
5
1990
608
612
2211310
45
Kettner
N-U
Parker
JE
Watrous
BJ
Intraosseous regional perfusion for treatment of septic physitis in a 2-week-old foal
J Am Vet Med Assoc
222
2003
346
350
12564599