key: cord-023528-z9rc0ubj
authors: Wilkins, Pamela A.
title: Disorders of Foals
date: 2009-05-18
journal: Equine Internal Medicine
DOI: 10.1016/b0-72-169777-1/50021-4
sha: 
doc_id: 23528
cord_uid: z9rc0ubj

nan

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

Pa m e l a A . Wi l k i n s 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 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.

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 lowfrequency (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.

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 pO 2 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 pO 2 difference is near 0. Also unlike the sheep, the umbilical venous pO 2 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

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 1384 PART II Disorders of Specific Body Systems 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 CO 2 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 CO 2 tension using a capnograph or single-use disposable end-tidal CO 2 monitor attached to the Ambu-bag or the nasotracheal tube. In a dead foal the end-tidal CO 2 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 CO 2 will "wash out" with the first few breaths and can result in false hope initially. End-tidal CO 2 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 endtidal CO 2 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

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.

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 Apgar Score in the Foal 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.

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 E 2 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 1388 PART II Disorders of Specific Body Systems 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 (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 D 2 and E 2 , 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 sideeffects (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.

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 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 Mg 2+ blockade of NMDA current that can be restored partially by increasing extracellular Mg 2+ concentration or by pretreatment with calphostin C, a protein kinase C inhibitor. 128 This finding suggested that administration of Mg 2+ 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 hypoxiaischemia 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 Earlystage, 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.

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 cases 139, 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 highoutput 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.

In human NICUs the survival rates of low-gestationlength 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 endophyteinfested fescue. 165 Box 19-3 compares the characteristics of premature/dysmature foals with those of postmature foals.

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.

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, 171-173 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] 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.

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 

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 ε-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 2~7 0 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 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.

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] 

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] 

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.

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] 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.

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 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.

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 antibodymediated 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 colostrumcontaining 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

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.

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

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.

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.

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.

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 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 CO 2 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 CO 2 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 CO 2 . 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.

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

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.

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

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 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

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 sulfamethoxazoletrimethoprim, 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.

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.

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 13 1 / 2 -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.

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 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.

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.

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.

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 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.

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.

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 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 broadspectrum antimicrobial therapy in these foals and, if any evidence of coordinated gastrointestinal motility is apparent, should administer sucralfate orally as a protectant.

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 E 2 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.

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.

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 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.

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. 400-403 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.

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. 411-413 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.

Strongyloides westeri is a common parasitic infection of foals. 392, 414 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.

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.

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 β 1 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, β 1 and β 2 activity at moderate doses, and α 1 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 α 1 and β 1 activity but variable β 2 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 α 1 , α 2 , β 1 , and β 2 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. 20 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.

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, 1-6 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.

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

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 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.

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 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.

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 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.

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.

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.

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.

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.

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.

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.

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 junction 27, 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.

Clinical studies on 4 newborn throughbred foals suffering from convulsions with special reference to blood gas chemistry and pulmonary ventilation

Respiratory distress in a newborn foal with failure to form lung lining film

Clinical studies on the newborn thoroughbred foal. 2. Heart rate, auscultation and electrocardiogram

Blood gas tensions and pH values in the normal thoroughbred foal at birth and in the following 42h

Measurements of pulmonary ventilation in normal newborn thoroughbred foals during the first three days of life

Some parameters of respiratory function in normal and abnormal newborn foals with special reference to levels of paO2 during air and oxygen inhalation

Modern concepts of neonatal disease in foals

Studies on fetal, neonatal and maternal cortisol metabolism in the mare

Surfactant studies in the fetal and neonatal foal

Neuropathology of the convulsive foal syndrome

Metabolic profiles of newborn foals

Neuropathological changes associated with the neonatal maladjustment syndrome in the thoroughbred foal

Blood gas and acid-base status in spontaneously delivered, term-induced and induced premature foals

Developments in management of the newborn foal in respiratory distress. 1. Evaluation

Clinical and clinicopathological characteristics of the septicaemic neonatal foal: review of 38 cases

Intensive care of the neonatal foal

Nutritional support of the foal during intensive care

Comparison of empirically developed sepsis score with a computer generated and weighted scoring system for the identification of sepsis in the equine neonate

Ion transport properties of fetal sheep alveolar epithelial cells in monolayer culture

Pulmonary vascular biology during neonatal transition

Regulation of vasodilator synthesis during lung development

Morin FC 3rd: Persistent pulmonary hypertension of the newborn: role of nitric oxide and endothelin in pathophysiology and treatment

Clinical studies on the newborn thoroughbred foal. 1. Perinatal behavior

The adaptive processes of the newborn foal

Blood pressure, electrocardiogram and echocardiogram measurements in the growing pony foal

Transfer of gases and metabolites in the equine placenta: a comparison with other species

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

Neonatal polycythemia and hyperviscosity

Respiratory mechanics and breathing pattern in neonatal foals

Mechanics of ventilation: compliance

Respiratory studies in foals from birth to seven days old

The distribution of ventilation-perfusion ratios in the lungs of newborn foals

Neurological examination of newborn foals

Maternal behavior

Equine medicine and surgery

Umbilical cord compression produces pulmonary hypertension in newborn lambs: a model to study the pathophysiology of persistent pulmonary hypertension in the newborn

The sequence of events in neonatal apnoea

Resuscitation with room-air or oxygen supplementation

Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates

Six years of experience with the use of room air for the resuscitation of asphyxiated newly born term infants

Resuscitation of newborn infants with room air or oxygen

Thoracic trauma in newborn foals

An advisory statement from the Pediatric Working Group of the International Liaison Committee on Resuscitation

Pharmacology of pediatric resuscitation

Vasopressin and epinephrine for cardiac arrest

Temperature of the human fetus

Continuous monitoring of fetal temperature by noninvasive probe and its relationship to maternal temperature, fetal heart rate, and cord arterial oxygen and pH

Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis

Perinatal thermogenesis

Factors influencing the initiation of nonshivering thermogenesis

Reversible umbilical cord occlusion: effects on thermogenesis in utero

Diazepam in labour: its metabolism and effect on the clinical condition and thermogenesis of the newborn

Renal clearance, urinary excretion of endogenous substances, and urinary diagnostic indices in healthy neonatal foals

Indices of renal function: values in eight normal foals from birth to 56 days

A comparison of inulin, para-aminohippuric acid, and endogenous creatinine clearances as measures of renal function in neonatal foals

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

Equine uteroplacental metabolism at mid-and late gestation

Glucose and oxygen metabolism in the fetal foal during late gestation

Mechanism of glucose transport across the human and rat placental barrier: a review

Glucose production in pregnant women at term gestation: sources of glucose for human fetus

Estimation of glucose turnover and 13C recycling in the human newborn by simultaneous [1-13C]glucose and [6,6-1H2]glucose tracers

Glucose disposal of low birth weight infants: steady state hyperglycemia produced by constant intravenous glucose infusion

Precursors to glycogen in ovine fetuses

Activation of glycogenolysis in neonatal liver

The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis

Pulmonary arterial pressure changes in human newborn infants from birth to 3 days of age

Postnatal circulatory adaptation in healthy term and preterm neonates

Pulmonary endothelial nitric oxide production is developmentally regulated in the fetus and newborn

Regulation of pulmonary vascular tone in the perinatal period

The structural basis of persistent pulmonary hypertension of the newborn infant

Tolazoline HCl (Priscoline)

Nitric oxide for respiratory failure in infants born at or near term

Effect of inhaled nitric oxide on experimentally induced pulmonary hypertension in neonatal foals

Systematic review of therapy after hypoxic-ischaemic brain injury in the perinatal period

Infection, inflammation and the risk of cerebral palsy

The fetal circulation and its response to stress

Fetal adaptations to spontaneous hypoxemia and responses to maternal oxygen breathing

Pathophysiology of perinatal brain damage

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

Activation of synaptic NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs recovery of synaptic transmission on reoxygenation

Molecular and biochemical mechanisms of perinatal brain injury

Glycine site of the excitatory amino acid N-methyl-D-aspartate receptor in neonatal and adult brain

Reduction of voltagedependent Mg2+ blockade of NMDA current in mechanically injured neurons

Magnesium attenuates a striatal dopamine increase induced by anoxia in the neonatal rat brain: an in vivo microdialysis study

Pretreatment with magnesium sulfate protects against hypoxic-ischemic brain injury but postasphyxial treatment worsens brain damage in seven-day-old rats

Improved motor outcome in response to magnesium therapy received up to 24 hours after traumatic diffuse axonal brain injury in rats

Fetal rat brain damage caused by maternal seizure activity: prevention by magnesium sulfate

Can magnesium sulfate reduce the risk of cerebral injury after perinatal asphyxia

Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn piglet does not protect against cerebral damage

Concentrations of magnesium and ionized calcium in umbilical cord blood in distressed term newborn infants with hypoxic-ischemic encephalopathy

Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal

Adverse effects of early phenobarbital administration in term newborns with perinatal asphyxia

Negative pressure pulmonary edema as a post-anesthetic complication associated with upper airway obstruction in a horse

Cerebral oedema and cerebellar herniation in four equine neonates

Cerebral edema

Edematous necrosis in thiamine-deficient encephalopathy of the mouse

A herd outbreak of equine leukoencephalomalacia

Dimethyl sulfoxide (DMSO): a review

Naloxone reverses neonatal depression caused by fetal asphyxia

The effects of naloxone on the post-asphyxic cerebral pathophysiology of newborn lambs

Naloxone exacerbates hypoxic-ischemic brain injury in the neonatal rat

Resuscitation of the newly born infant: an advisory statement from the Pediatric Working Group of the International Liaison Committee on Resuscitation

Neurologic disorders in foals other than hypoxicischemic encephalopathy

Combination therapy protects ischemic brain in rats: a glutamate antagonist plus a gamma-aminobutyric acid agonist

Effect of gamma-aminobutyric acid modulation on neuronal ischemia in rabbits

Cerebral hypothermia for prevention of brain injury following perinatal asphyxia

Current options in the management of apnea of prematurity

Hypocapnia and hypercapnia in respiratory management of newborn infants

Acute renal failure in children: aetiology and management

Low-dose dopamine in the intensive care unit: DNR or DNRx?

Use of dopamine in acute renal failure: a meta-analysis

The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets

Initial experience with norepinephrine infusion in hypotensive critically ill foal

Multiple organ involvement in perinatal asphyxia

Continuous enteral feeding impairs gallbladder emptying in infants

Trophic feeding of the preterm infant

Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams

Functional residual capacity and passive compliance measurements after antenatal steroid therapy in preterm infants

Current surfactant use in premature infants

Effects of the fungal endophyte Acremonium coenophialum in fescue on pregnant mares and foal viability

Postnatal renal adaptation in preterm and term lambs

Risk factors of hypoglycemia in premature infants

Studies on equine prematurity. 4. Effect of salt and water loss on the reninangiotensin-aldosterone system in the newborn foal

Studies on equine prematurity. 5. Histology of the adrenal cortex of the premature newborn foal

Angular limb deformities in premature/ dysmature foals

Neonatal Septicemia Workshop 1, Dorothy Havemeyer Foundation

Dorothy Havemeyer Foundation

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

Definition of sepsis

To SIRS with love

Failure of passive transfer in foals: incidence and outcome on four studs in New South Wales

A prospective study of septicaemia in colostrum-deprived foals

Care of the gut in the surgical intensive care unit: fact or fashion?

Bacterial isolates from blood and their susceptibility patterns in critically ill foals: 543 cases (1991-1998)

Development of real-time TaqMan PCR systems to facilitate the diagnosis and research of septicemia in foals

Expressed sequence TAGS (ESTs) isolated from blood of a septic thoroughbred foal

Early goal-directed therapy in the treatment of severe sepsis and septic shock

Chronic flunixin meglumine therapy in foals

Clinical and pathological effects of flunixin meglumine administration to neonatal foals

Gastric ulcers in foals

Experimentally induced toxicoinfectious botulism in horses and foals

Toxicoinfectious botulism in foals and adult horses

Botulism in the horse

White muscle disease of foals

Naturally-occurring Tyzzer's disease (Bacillus piliformis infection) in horse foals

Suspected Tyzzer's disease in two foals

Four cases of Tyzzer's disease in foals in England

Bacillus piliformis infection (Tyzzer's disease) in foals in northwestern United States: a retrospective study of 21 cases

Tyzzer's disease in a foal: light-and electron-microscopic observations

Clinical and clinicopathologic findings in two foals infected with Bacillus piliformis

Serum biochemical and haematological findings in two foals with focal bacterial hepatitis (Tyzzer's disease)

Toxic hepatopathy in neonatal foals

The diagnosis and surgical correction of congenital portosystemic vascular anomalies in two calves and two foals

Clinical signs and radiographic diagnosis of a portosystemic shunt in a foal

Clinical and diagnostic features of portosystemic shunt in a foal

Evidence for transmission of Halicephalobus deletrix (H gingivalis) from dam to foal

Halicephalobus (Micronema) deletrix infection in two half-sibling foals

Listeriosis in an Arabian foal with combined immunodeficiency

Suspected protozoal myeloencephalitis in a two-month-old colt

Pathological findings in horses dying during an outbreak of the paralytic form of equid herpesvirus type 1 (EHV-1) infection

Central nervous system neosporosis in a foal

Cauda equina syndrome, diskospondylitis, and a paravertebral abscess caused by Rhodococcus equi in a foal

Vertebral body osteomyelitis due to Rhodococcus equi in two Arabian foals

Rhodococcus equi vertebral osteomyelitis in 3 Quarter horse colts

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

Cerebellar hypoplasia and degeneration in a foal

Cerebellar hypoplasia and degeneration in the young Arab horse: clinical and neuropathological features

Imaging diagnosis: occipitoatlantoaxial malformation in a miniature horse foal

Occipitoatlantoaxial malformation with duplication of the atlas and axis in a half Arabian foal

Occipitoatlantoaxial malformation in two non-Arabian horses

Ivermectin toxicosis in a neonatal foal

Presumed moxidectin toxicosis in three foals

Hypovolemic hyponatremia and signs of neurologic disease associated with diarrhea in a foal

Extrapontine myelinolysis with involvement of the hippocampus in three children with severe hypernatremia

Relationships between radiography of cervical vertebrae and histopathology of the cervical cord in wobbling 19 foals

Assessment of colostral transfer and systemic availability of immunoglobulin G in new-born foals using a newly developed enzyme-linked immunosorbent assay (ELISA) system

Evaluation of a test kit for determination of serum immunoglobulin G concentration in foals

Relationships among serum immunoglobulin concentration in foals, colostral specific gravity, and colostral immunoglobulin concentration

Measurement of IgG in equine blood by immunoturbidimetry and latex agglutination

A rapid, specific test for detecting absorption of colostral IgG by the neonatal foal

Practical methods of determining serum immunoglobulin M and immunoglobulin G concentrations in foals

Passive immunity in the foal: measurement of immunoglobulin classes and specific antibody

Gammaglobulin and antibody variations associated with the maternal transfer of immunity and the onset of active immunity

Immunoglobulin metabolism in the neonatal foal

Prevalence (treatment days) and severity of illness in hypogammaglobulinemic and normogammaglobulinemic foals

Factors associated with failure of passive transfer of colostral antibodies in standardbred foals

Failure of passive transfer in foals

Failure of passive transfer of colostral immunity in the foal: incidence, and the effect of stud management and plasma transfusions

The incidence and consequences of failure of passive transfer of immunity on a thoroughbred breeding farm

Failure of colostral immunoglobulin transfer as an explanation for most infections and deaths of neonatal foals

Secretion and composition of colostrum and milk

Immunoglobulin isotypes in sera and nasal mucosal secretions and their neonatal transfer and distribution in horses

Interleukin-18 in human milk

Improved recovery of insulin-like growth factors (IGFs) from bovine colostrum using alkaline diafiltration

Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs

Measurement of betacellulin levels in bovine serum, colostrum and milk

In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum involved in non-specific defence

Activities of gammaglutamyltransferase, alkaline phosphatase and aspartateaminotransferase in colostrum, milk and blood plasma of calves fed first colostrum at 0-2, 6-7, 12-13 and 24-25 h after birth

Efficacy of intravenous plasma to transfer passive immunity in clinically healthy and clinically ill equine neonates with failure of passive transfer

Evaluation of intravenous administration of concentrated immunoglobulin G to colostrumdeprived foals

Lyophilized hyperimmune equine serum as a source of antibodies for neonatal foals

Absorption of bovine colostral immunoglobulins G and M in newborn foals

Comparison of freezing and lyophilizing for preservation of colostrum as a source of immunoglobulins for calves

A comparison of the reduction in immunoglobulin (IgG) concentration of frozen equine plasma treated by three thawing techniques

Use of blood and blood products

Neonatal isoerythrolysis in mule foals

Characterization of a red blood cell antigen in donkeys and mules associated with neonatal isoerythrolysis

Prevalence of anti-red blood cell antibodies in the serum and colostrum of mares and its relationship to neonatal isoerythrolysis

Polymerized hemoglobin therapy in a foal with neonatal isoerythrolysis

Post-transfusion survival of 50Cr-labeled erythrocytes in neonatal foals

Strategies for prevention of neonatal isoerythrolysis in horses and mules

Detection and effects on platelet function of anti-platelet antibody in mule foals with experimentally induced neonatal alloimmune thrombocytopenia

Neonatal alloimmune thrombocytopenia in a Quarter horse foal

Neonatal thrombocytopenia: new insights into pathogenesis and implications for clinical management

Thrombocytopenia in horses

Detection and effects on platelet function of anti-platelet antibody in mule foals with experimentally induced neonatal alloimmune thrombocytopenia

Reef VB: Cardiovascular disease in the equine neonate

Congenital polyalveolar lobe in three foals

Critical pulmonary stenosis in a newborn foal

Bilateral hypoplasia of the soft palate in a foal

Pulmonary lobar hypertrophy in a foal

Equine congenital defects

Congenital bilateral choanal atresia in a standardbred foal

Evaluation of pulse oximetry in anaesthetised foals using multiple combinations of transducer type and transducer attachment site

Electrocardiographic findings during parturition and blood gas tensions immediately after birth in thoroughbred foals

Blood gas and acid-base changes in the neonatal foal

Blood gas tensions and pH values in the normal thoroughbred foal at birth and in the following 42h

Mixed venous blood gases in recumbent and upright positions in foals from birth to 14 days of age

Ventilatory support of the neonatal foal

Report of foal pneumonia panel

Association of microbiologic flora with clinical, endoscopic, and pulmonary cytologic findings in foals with distal respiratory tract infection

Microbiologic changes during antimicrobial treatment and rate of relapse of distal respiratory tract infections in foals

Pathologic changes and pathogenesis of Parascaris equorum infection in parasite-free pony foals

Spezifische infektiose Pneumonie beim Fohlen. Ein neuer Eiterreger beim Pferd

Interaction of Rhodococcus equi with phagocytic cells from Rhodococcus equi-exposed and non-exposed foals

Electron microscopic investigation of intracellular events after ingestion of Rhodococcus equi by foal alveolar macrophages

Influence of Rhodococcus equi on the respiratory burst of resident alveolar macrophages from adult horses

Rhodococcus equi infection of monocytes/macrophages from human immunodeficiency (HIV)-infected patients and healthy individuals: evaluation of intracellular killing and nitric oxide production

The intracellular bacterium Rhodococcus equi requires Mac-1 to bind to mammalian cells

Rhodococcus (Corynebacterium) equi: bactericidal capacity of neutrophils from neonatal and adult horses

Identification of 15-to 17-kilodalton antigens associated with virulent Rhodococcus equi

Virulence-associated 15-to 17 kilodalton antigens in Rhodococcus equi: temperature-dependent expression and location of the antigens

Role of the 85-kilobase plasmid and plasmid-encoded virulence-associated protein A in intracellular survival and virulence of Rhodococcus equi

Characterization of avirulence-associated gene family in Rhodococcus equi

Corynebacterium equi infections in horses, 1958-1984: a review of 131 cases

Clinical manifestations, diagnosis, treatment, and prevention of Rhodococcus equi infections in foals

Detection of Corynebacterium equi-specific antibody in horses by enzyme-linked immunosorbent assay

Rhodococcus equi pneumonia in foals: comparison of ELISA and AGID serology on a commercial thoroughbred breeding farm

Studies of naturally occuring and experimental Rhodococcus equi (Corynebacterium equi) pneumonia in foals

Detection of virulent Rhodococcus equi in tracheal aspirate samples by polymerase chain reaction for rapid diagnosis of R. equi pneumonia in foals

Comparison of nucleic acid amplification, serology, and microbiologic culture for diagnosis of Rhodococcus equi pneumonia in foals

Use of erythromycin-rifampin combination in treatment of Rhodococcus equi pneumonia

Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals

Hyperthermia in foals treated with erythromycin alone or in combination with rifampin for respiratory disease during hot environmental conditions

Clostridium difficile associated with acute colitis in mares when their foals are treated with erythromycin and rifampicin for Rhodococcus equi pneumonia

Strategies for the control of Rhodococcus equi infections on enzootic farms

Immunoprophylaxis of Rhodococcus equi pneumonia in foals

Failure of hyperimmune plasma to prevent pneumonia caused by Rhodococcus equi in foals

Rhodococcus equi foal pneumonia: protective effects of immune plasma in experimentally infected foals

Protection against naturally acquired Rhodococcus equi pneumonia in foals by administration of hyperimmune plasma

Methods of implementation of an immunoprophylaxis program for the prevention of Rhodococcus equi pneumonia: results of a 5-year field study

Effect of prophylactic administration of hyperimmune plasma to prevent Rhodococcus equi infection on foals from endemically affected farms

Valuation of equine immunoglobulin specific for Rhodococcus equi virulenceassociated proteins A and C for use in protecting foals against Rhodococcus equi-induced pneumonia

Associations between physical examination, laboratory, and radiographic findings and outcome and subsequent racing performance of foals with Rhodococcus equi infection: 115 cases (1984-1992)

Endoscopic and virological observations on respiratory disease in a group of young thoroughbred horses in training

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?

Clinical, serological and virological characteristics of an outbreak of paresis and neonatal foal disease due to equine herpesvirus-1 on a stud farm

Foetal and neonatal foal losses on equine herpesvirus type 1(EHV-1) infected farms before and after EHV-1 vaccination was introduced

An outbreak of foal perinatal mortality due to equid herpesvirus type 1: pathological observations

Equine viral arteritis in newborn foals: clinical, pathological, serological, microbiological and immunohistochemical observations

Involvement of adenovirus in pneumonia in a thoroughbred foal

Adenoviral infection of Arab foals with respiratory tract disease

Isolation of an adenovirus from an Arab foal with a combined immunodeficiency disease

Clinical, haematological and biochemical findings in foals with neonatal equine herpesvirus-1 infection compared with septic and premature foals

Neonatal equine herpesvirus type 1 infection on a thoroughbred breeding farm

Passive transfer, rate of decay, and protein specificity of antibodies against equine arteritis virus in horses from a standardbred herd with high seroprevalence

Fatal nonneurological EHV-1 infection in a yearling filly

Pulmonary vasculotropic EHV-1 infection in equids

Virological and molecular biological investigations into equine herpes virus type 2 (EHV-2) experimental infections

Equine herpesvirus type 2: prevalence and seroepidemiology in foals

Subcutaneous emphysema in a neonatal foal

Immature epithelial Na+ channel expression is one of the pathogenetic mechanisms leading to human neonatal respiratory distress syndrome

Bronchointerstitial pneumonia and respiratory distress in young horses: clinical, clinicopathologic, radiographic, and pathological findings in 23 cases (1984-1989)

Risk of adverse effects in pneumonic foals treated with erythromycin versus other antibiotics: 143 cases (1986-1996)

Disease of foals

Du Plessis JL: Rupture of the bladder in the newborn foal and its surgical correction

Metabolic abnormalities associated with rupture of the urinary bladder in neonatal foals

Exploratory celiotomy for suspected urinary tract disruption in neonatal foals: a review of 18 cases

Uroperitoneum in the foal

Uroperitoneum in the hospitalized equine neonate: retrospective study of 31 cases

Repair of a defect in the bladder of a foal

Rupture of the urinary bladder in neonatal foals

Bladder defects in newborn foals

Ultrasound of the urinary tract

Nonsurgical management of ruptured urinary bladder in a critically ill foal

Hemodialysis for treatment of oxytetracycline-induced acute renal failure in a neonatal foal

Bilateral renal hypoplasia in four young horses

Bilateral renal dysplasia and hypoplasia in a foal with an imperforate anus

Clinical vignette: renal arteriovenous malformation in a Quarter horse foal

Percutaneous ultrasound-guided pyelography aided diagnosis of ectopic ureter and hydronephrosis in a 3-week-old filly

Bilateral ureteral tears in a foal

Multiple ureteral defects in a Belgian foal

Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis during pregnancy

Ultrasonography of umbilical structures in clinically normal foals

Clinical, ultrasonographic, and surgical findings in foals with umbilical remnant infections

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

Complications of umbilical hernias in horses: 13 cases

Persistent vitelline vein in a foal

Atresia coli in the foal: a review of six cases

Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS): a horse variant of Hirschsprung disease

A missense mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome: an equine version of Hirschsprung disease

Incidence of the endothelin receptor B mutation that causes lethal white foal syndrome in white-patterned horses

Necrotizing enterocolitis presenting in the emergency department: case report and review of differential considerations for vomiting in the neonate

New concepts in necrotizing enterocolitis

Hemorrhagic necrotizing enterocolitis associated with Clostridium difficile infection in four foals

Endoscopic appearance of gastric lesions in foals: 94 cases

Endoscopic evaluation of changes in gastric lesions of thoroughbred foals

Gastroduodenal ulceration in foals

Prevalence of gastric lesions in foals without signs of gastric disease: an endoscopic survey

Gastric ulcers in foals

Exsanguination due to gastric ulceration in a foal

Gastrointestinal diseases of foals

Pathophysiology of peptic disorders in foals and horses: a review

Clinical syndromes of gastric ulceration in foals and mature horses

Gastroduodenal ulceration in foals

Stress ulcer: is routine prophylaxis necessary?

Peptic ulcer pathophysiology

Intragastric pH in critically ill neonatal foals and the effect of ranitidine

A review of medical treatment for peptic ulcer disease

Effect of sucralfate on healing of subclinical gastric ulcers in foals

Effect of ranitidine on intragastric pH in clinically normal neonatal foals

Effects of omeprazole paste on healing of spontaneous gastric ulcers in horses and foals: a field trial

Incidence of pneumonia in mechanically ventilated patients treated with sucralfate or cimetidine as prophylaxis for stress bleeding: bacterial colonization of the stomach

The protective role of gastric acidity in neonatal bacterial translocation

Upper gastrointestinal tract bleeding in critically ill pediatric patients

Gastric colonization as a consequence of stress ulcer prophylaxis: a prospective, randomized trial

Is prophylaxis for gastric ulcers necessary in critically ill equine neonates? A retrospective study of necropsy cases 1995-1999

Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation to the incidence of endoscopically proven stress ulceration

Influence of stress ulcer prophylaxis on translocation of bacteria from the intestinal tract in rats

Effects of sucralfate on acute gastric mucosal injury and gastric ulcer induced by ischemiareperfusion in rats

Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation to the incidence of endoscopically proven stress ulceration

Efficacy of ivermectin in controlling Strongyloides westeri infections in foals

Foal diarrhoea between 1991 and 1994 in the United Kingdom associated with

Prevalence of and risk factors for fecal shedding of Cryptosporidium parvum oocysts in horses

Overwhelming strongyloidosis in a foal

Verminous arteritis in a 3-month-old thoroughbred foal

Randomised trial of fluid restriction in ventilated very low birthweight infants

Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants

Hyponatraemia in children with acute CNS disease: SIADH or cerebral salt wasting?

Comparison of norepinephrinedobutamine to dopamine alone for splanchnic perfusion in sheep with septic shock

Depletion of neurohypophyseal content of vasopressin in septic shock

Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock

REFERENCES 1. Firth EC, Poulos PW: Blood vessels in the developing growth plate of the equine distal radius and metacarpus

Microangiographic studies of metaphyseal vessels in young foals

Physeal form of the longbones of the foal

Comparison of splinting and casting on the degree of laxity induced in thoracic limbs in young horses

Histological features of the dorsal cortex of the third metacarpal bone mid-diaphysis during postnatal growth in thoroughbred horses

Effect of oxytetracycline on metacarpophalangeal and distal interphalageal joint angles in newborn foals

The blood supply of the growth plate and the epiphysis: a comparative scanning electron microscopy and histological experimental study in growing sheep

Fractures of the proximal sesamoid bones in thoroughbred foals

Avulsion of the origin of the peroneus tertius tendon in a foal

Avulsion fracture of the origin of the extensor digitorum longus muscle in a foal

Surgical reconstruction of a ruptured medial collateral ligament in a foal

Correction of patellar luxation by recession sulcoplasty in three foals

Lateral patellar luxation in miniature horse foals

Anatomy and therapeutic resection of the peroneus tertius in a foal

Preliminary observations on oxytetracycline treatment of congenital flexural deformities in foals

Effect of oxytetracycline on metacarpophalangeal and distal interphalangal join angles in newborn foals

Torsion in quadrapeds and its impact on mammalian joints

Computer model of endochondral growth and ossification in long bones: biological and mechanobiological influences

Observations on the evaluation and selection of foal limb deformities for surgical treatment

Treatment response and athletic outcome of foals with tarsal valgus deformities: 39 cases

Incomplete ossification of the tarsal bones in foals: 22 cases

Periosteal transection and periosteal stripping for correction of angular limb deformities in foals

Periosteal transection and stripping for treatment of angular limb deformities in foals: clinical observations

Restricted exercise and transphyseal bridging for correction of angular limb deformities

Effect of hemicircumferential periosteal transection and elevation in foals with experimentally induced angular limb deformities

Diaphyseal angular limb deformities in three foals

Current concepts of infectious polyarthritis in foals

Factors associated with prognosis for survival and athletic use in foals with septic arthritis: 93 cases (1987-1994)

The site of focal osteomyelitis lesions in foals

Pathological features of multiple bone infection in the foal

Stromal cell culture and relationships in perimedullary spaces of chick embryo shaft bones

Tarsal osteomyelitis in foals

Cartilage canals in equine articular/epiphyseal growth cartilage and a possible association with dyschondroplasia

A histological study of acute hematogenous osteomyelitis following physeal injuries in rabbits

Open drainage, intra-articular and systemic antibiotics in the treatment of septic arthritis/tenosynovitis in horses

Comparison of various treatments for experimentally induced equine infectious arthritis

A retrospective study of 192 horses affected with septic arthritis/tenosynovitis

Regional intravenous perfusion of the distal limbs of horses with amikacin sulfate

Treatment of sepsis in the small tarsal joints of 11 horses with gentamicin-impregnated polymethylmethacrylate beads

Use of antibioticimpregnated polymethyl-methacrylate in horses with open or infected fractures or joints: 19 cases (1987-1995)

The effect of implanting gentamicin-impregnated polymethylmethacrylate beads in the tarsocrural joint of the horse

Regional perfusion of the equine carpus for antibiotic delivery

How to perform equine digital intravascular perfusion

Surgical management of Rhodococcus equi metaphysitis in a foal

Intraosseous regional perfusion for treatment of septic physitis in a 2-week-old foal