Meningitis

Although bacterial meningitis may occur as a primary entity, it more commonly is a result of generalized sepsis in neonates with failure of passive transfer (FPT). Agents that cause meningitis are the same as those that cause septicemia, most commonly bacteria such as Escherichia coli, Enterobacter species, Salmonella species, and Streptococcus species. Because clinical signs of meningitis are easily confused with hypoxic ischemic encephalopathy (HIE) and septicemia without localization in the CNS, diagnosis depends on CSF analysis (see Chapter 35). Treatment recommendations for treating bacterial CNS infections may be found in Chapter 35. Although there is one report on the successful treatment of two neonatal foals with suspected meningitis using third-generation cephalosporins,⁵⁸ in many cases, once the diagnosis is made the infectious process is often well advanced both in the brain and in other tissues, resulting in a poor outcome.

Upper Respiratory Tract Disorders

Upper respiratory tract disorders are relatively uncommon in neonates. Conditions affecting pharyngeal and laryngeal function are important, as they predispose to aspiration pneumonia. Dyspneic neonates also have difficulty nursing and are subsequently likely to become malnourished. Congenital defects of the upper respiratory tract include collapsed trachea, stenotic nares, choanal atresia, epiglottal cyst, and guttural pouch tympany (foal). There have also been recent reports of dorsal displacement of the soft palate (DDSP) as a cause of acute dyspnea, stridor, and dysphagia in neonatal foals.^62,63 Endoscopic examination of the upper airways of these foals revealed that the dorsally displaced soft palate was edematous, flaccid, and redundant. To varying degrees, flaccidity and swelling of other pharyngeal and laryngeal structures (e.g., arytenoid cartilages, epiglottis, or palatopharyngeal arch) were also noted.⁶³ Both medical⁶³ and surgical⁶² treatment of the condition have been suggested. In one study, medical management with antiinflammatory drugs, enteral feeding via nasogastric tube, and broad-spectrum antibiotics (for the coexisting aspiration pneumonia) resulted in dramatic and permanent resolution of the problems within 2 to 4 days. The cause of these abnormalities remains unknown at this time but may involve primary pharyngeal and palatal muscular laxity.⁶³

Impaired pharyngeal and laryngeal function may result from physical deformation or neuromuscular disorders. Pharyngeal and laryngeal injuries are often associated with improper application or use of damaged feeding tubes and oral medication equipment. Compression of the larynx by a retropharyngeal abscess or mass tends to cause inspiratory dyspnea; aspiration pneumonia is a common sequela. Partial occlusion of the upper airway induces turbulent airflow and subsequently mucosal edema. Placement of a tracheostomy tube provides an alternate, sometimes lifesaving, airway and rests the inflamed mucosa.

NMD, hyperkalemic periodic paralysis, and botulism may induce laryngeal paresis. Dysphagia and subsequent aspiration pneumonia are common sequelae of pharyngeal and laryngeal dysfunction associated with NMD and botulism. Exercise- and excitement-induced respiratory stridor has been described in foals with hyperkalemic periodic paralysis.⁶⁴

Collapsed trachea is a rare congenital or acquired condition. Clinical signs include an intermittent honking cough, stridor, and dyspnea with mild exercise. There is no stenosis of the trachea; rather, a dynamic dorsoventral collapse during inspiration. The caudal cervical and cranial thoracic sections of the trachea in the area of the thoracic inlet are most frequently affected. Acquired tracheal collapse is commonly associated with fractured ribs and compression of the trachea at the thoracic inlet by the subsequent bony callus.

Diagnosis of most upper airway disorders can usually be made with a combination of radiography and endoscopy. A 7-mm outside diameter (OD) endoscope is usually small enough to pass through the ventral meatus of horse and pony foals that weight over 30 lb. An integral part of the diagnostic approach to the neonate with suspected upper airway obstruction is assessment of the lungs for aspiration pneumonia. If the primary upper respiratory problem is not corrected and normal nursing is allowed, the pneumonic process will likely persist and become chronic.

Respiratory Infection

Bacterial infection of the lower respiratory tract most commonly occurs during or shortly after birth but can also take place before parturition through aspiration of contaminated amniotic fluid. This may take place in mares with bacterial placentitis. In the newborn foal, pneumonia can result from direct aspiration or inhalation of bacteria or from the hematogenous spread of organisms in foals that are bacteremic. The most common bacterial organisms that have been associated with pulmonary disease in foals are identical to those that cause systemic sepsis. The most common isolates include E. coli, Klebsiella pneumoniae, Pasturella species, Actinobacillus species, and Streptococci species. Less common isolates include, but are not limited to, Salmonella species, Enterobacter species, Pseudomonas species, Serratia marcescens, Staphylococcus species, and Yersinia pseudotuberculosis.

The diagnosis of pneumonia involves identification of the causative organism. Isolation of bacteria can be attempted from blood culture or from culture of amniotic fluid or placental tissue if in utero infection is suspected. Lower airway culture can be difficult, as a tracheal aspiration can be dangerous in a compromised neonate. An alternative method involves passage of a guarded swab through a nasotracheal tube into the lower airway. The tip of the nasotracheal tube can also be cultured if it has been present in the airway for a prolonged period. A CBC and measurement of an acute phase protein, such as fibrinogen, may support a diagnosis of infection but will not be helpful in localization of infection to the respiratory tract. The treatment of bacterial lung disease involves a combination of respiratory support techniques and antibiotic therapy. The neonatal foal readily develops dependent atelectasis in lateral recumbency. Consequently, positioning in sternal rather than lateral recumbency results in improved ventilatory capacity and higher arterial oxygen tension. Broad-spectrum antibiotic therapy should be commenced as soon as lung disease is suspected. A good choice is a β-lactam antibiotic, such as penicillin or ampicillin, combined with an aminoglycoside. The emergence of E. coli resistance to gentamicin in certain regions may limit its future use. The third-generation cephalosporins, such as ceftiofur, ceftazidime, ceftriaxone, and cefotaxime, have distinct advantages over aminoglycosides in the treatment of bacterial pneumonia. They have superior penetration into the lung, and effective tissue concentrations are easily achieved by intravenous or intramuscular routes. Because premature discontinuation of antibiotic therapy has resulted in relapse in a number of cases, repeat radiographs and hematology (complete blood cell count and plasma fibrinogen) are highly recommended before discontinuation of antibiotic therapy. A minimum course of therapy of 3 to 4 weeks’ duration is not unusual in cases of severe pneumonia. Premature foals with pneumonia should be monitored particularly closely for the development of bacterial pneumonia resistant to the antibiotics being used.

Several viruses have been documented as causes of pneumonia in the neonatal foal. These include equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4), equine influenza, equine viral arteritis virus, and adenovirus. Of these, EHV-1 is the most common. Herpesviral pneumonia is frequently fatal, even in the face of aggressive supportive therapies such as mechanical ventilation. The antiviral drug acyclovir has been used. The difficulty is establishing a diagnosis early in the course of treatment. Several factors appear common to EHV-1–infected foals, but none should be considered pathognomonic. These include leukopenia with neutropenia and lymphopenia, and depletion of the myeloid cell lines on cytologic examination of bone marrow aspirates. The presence of dilated retinal vessels and a red discoloration to the optic disc on fundic examination has also been suggested as a common antemortem finding. Infection with adenovirus can be a problem in any immunocompromised foal, especially Arabian foals with severe combined immunodeficiency (SCID) syndrome.

In utero infection with Histoplasma capsulatum can result in placentitis, abortion, or birth of an infected foal with multiple organ disease, including granulomatous pneumonia. An antemortem diagnosis can be difficult to establish but is aided by tracheal aspirate and bronchoalveolar lavage when characteristic yeastlike organisms (3 to 5 μm in diameter) are seen within macrophages. Neonatal and maternal serum should be positive for anti-Histoplasma antibodies using an agar gel immunodiffusion test. The disease has been successfully treated in adults using amphotericin B, but reports of neonatal survival are lacking. Infection with Candida species (especially Candida albicans) is an infrequent complication in foals with chronic bacterial infection. Lengthy antimicrobial use is an apparent risk factor for infection, and many cases begin with oral candidiasis. The diagnosis is based on a history that often includes persistent low-grade fever, worsening respiratory disease or the development of synovitis, and isolation of the organism through blood culture. Successful treatment of neonatal candidiasis has been achieved with ketoconazole, amphotericin B, or fluconazole.

Meconium Aspiration Syndrome

In utero asphyxia or umbilical cord occlusion can result in fetal passage of meconium into amniotic fluid. Hypoxia induces a redistribution of blood flow away from less vital organs, including the gastrointestinal tract, resulting in mesenteric vasoconstriction and secondary intestinal ischemia. Transient hyperperistalsis and anal sphincter relaxation occur, thereby allowing passage of meconium. Meconium aspiration may occur before, during, or immediately after delivery as a result of fetal gasping. Meconium can produce a variety of clinical signs including mechanical airway obstruction (ball-valve effect) and regional air trapping, chemical pneumonitis and alveolitis, alveolar edema, and displacement of surfactant by free fatty acids in meconium, leading to decreased lung compliance, small airway obstruction, and focal atelectasis.^65-67 These events lead to increased pulmonary vascular and airway resistance and ventilation-perfusion mismatching. Meconium may also enhance the growth of bacterial species within the respiratory tract, resulting in secondary bacterial pneumonia. It may be difficult to differentiate meconium aspiration from bacterial pneumonia, especially if the birth was unattended. Occasionally, chronic placentitis is associated with both bacterial pneumonia and meconium aspiration.

If meconium has been aspirated into the pharynx, then gentle suctioning of the nasal and oral cavities is recommended. The ideal time to suction the airways is while the animal is still in the birth canal, before it has taken its first breath. If the foal shows signs of meconium aspiration below the vocal cords, nasotracheal intubation and careful, aseptic suctioning are recommended. Intranasal oxygen should be administered during suctioning. ABG analysis dictates what long-term respiratory and metabolic support is necessary. Mild to moderate hypoxemia can be treated with humidified intranasal oxygen (2 to 10 L/min). Severe hypoxemia with accompanying hypercapnia requires positive pressure ventilation (PPV) and is associated within increased mortality. If surfactant displacement and secondary atelectasis is contributing to hypoxemia, continuous positive airway pressure (CPAP) alone may improve oxygenation while avoiding any unnecessary increase in peak airway pressure. Exogenous surfactant administration has been advocated to treat the surfactant dysfunction, although efficacy data are lacking. Intravenous dimethyl sulfoxide (DMSO) (0.5 to 1 gm/kg) administered as a 10% solution may help reduce alveolar and interstitial edema. Systemic antibiotic therapy is recommended to prevent secondary bacterial pneumonia. Good airway hygiene and coupage are crucial.

A diagnosis of meconium aspiration is based on a history of meconium-contaminated amniotic fluid and a meconium-stained newborn. Radiographs typically show a ventrocranial distribution of pulmonary infiltrate characteristic of aspiration. Clear, brownish fluid may drip from the nose.

Milk Aspiration

Aspiration of milk into the lower airway may occur as a complication of a wide range of conditions. Most foals that aspirate milk also demonstrate nasal regurgitation of milk. Unfortunately the decreased sensitivity of the upper and lower airway to foreign material may make diagnosis of milk aspiration difficult. Aspiration can occur in foals with cleft palate, persistent DDSP, botulism, HIE, or generalized weakness resulting from sepsis or prematurity. Iatrogenic contamination of the airway can occur when bottle-feeding is forced or if the foal is too weak or sleepy to receive feeding. Substantial and sometimes fatal pneumonia can result from inappropriate placement of a nasogastric tube.

The diagnosis of milk aspiration is supported by historical data (nasal regurgitation of milk), physical examination findings (abnormal lung and tracheal sounds), and laboratory data (inflammatory leukogram, elevated fibrinogen, hypoxemia). Radiographic examination commonly reveals a heavy, perihilar, and/or ventrally located interstitial density with or without air bronchograms.

The treatment of milk aspiration involves long-term, broad-spectrum antimicrobial therapy and prevention of further contamination of the airway. The underlying cause should be pursued diagnostically and treated. This may necessitate the use of further diagnostic tests, including endoscopy and plain and contrast radiography. Enteral feeding through a nasogastric or esophagostomy tube is indicated until the underlying problem has been resolved. Persistent or intermittent DDSP in the neonate frequently resolves over time, but this may take weeks to months.

Pneumothorax⁶⁸ and Hemothorax

Pneumothorax is usually an iatrogenic sequela of PPV of diseased lungs, but it may occur spontaneously or as a result of birth trauma or from ruptured bullae within the lung parenchyma. During mechanical ventilation uneven alveolar ventilation leads to alveolar rupture and dissection of air into the interstitium. The air moves along bronchioles and other lung structures to pleural surfaces, forming blebs. This air may rupture into the pleural space. The condition should be strongly suspected if the respiratory condition suddenly worsens while an animal is being ventilated. Clinical signs may include respiratory distress, shift of cardiac point of maximum impulse, cyanosis, and hypotension. Although auscultation may reveal decreased breath sounds, it may be misleading because of the wide referral of breath sounds. Percussion is usually fairly unremarkable, unless the condition is very severe. Radiographs are indicated to confirm the diagnosis, but, if radiology is unavailable or the animal is very distressed, a direct needle aspiration is diagnostic and therapeutic.

Pneumothorax may be treated conservatively if no distress is associated with the air leak and the condition appears stable. Stress should be minimized. Chest tube insertion is indicated in human infants with continuing air leak, if underlying pulmonary disease is causing respiratory distress, and in those patients receiving mechanical ventilation. A trocar catheter is sterilely introduced into the chest cavity, and the catheter is secured, with the suture material crisscrossed tightly around the catheter. Suction is applied at −15 cm H₂O after confirmation of chest tube position by chest radiograph. Suction is discontinued when the tube has drained no air for 24 to 48 hours and when extrapulmonary air has been resolved radiographically for 24 to 48 hours. The tube may then be placed under a water seal for an additional 24 hours, and if no air accumulates the tube may be removed.

Hemothorax is occasionally noted in the large animal neonate. It has occurred secondary to unstable fractured ribs, with puncture of the lung parenchyma resulting in hemorrhage into the pleural space. Occasionally hemothorax may remain undiagnosed until clinical signs of anemia, hypovolemia, or shock appear in the young animal.

Idiopathic or Transient Tachypnea in the Neonate

A syndrome observed in Clydesdale, thoroughbred, and Arabian neonatal foals has been the combination of fever and tachypnea. The condition appears to be more frequent during hot, humid weather conditions. The pathogenesis of the condition is unknown, but it is speculated that it results from a transient problem in central or peripheral control of thermoregulation and/or respiratory rate and pattern.

Affected foals are usually of normal gestation and experience a normal birth. Most display normal activity for a variable period after birth, with a sudden onset of clinical signs. Occasionally a foal may show mild signs of CNS derangement (e.g., lack of affinity for the mare, wandering). There are usually no signs of pulmonary abnormalities as assessed by thoracic radiographs or ABG analysis. Body temperature is variable among foals, ranging from 102° F to 108° F (39° C to 42.2° C). A generally poor response to antipyretics has been noted. The respiratory rate and breathing pattern often resemble panting (respiratory rate >80 breaths/min). The condition usually resolves spontaneously within a few days to weeks.

Before idiopathic tachypnea is diagnosed, it is extremely important to rule out a pneumonic process or other pulmonary abnormality, other forms of infection, metabolic acidosis, and other causes of an increased respiratory rate. Hematology, chest radiographs, and arterial blood gases should be within normal limits, and bacterial cultures should be negative.

Treatment is directed at controlling the body temperature; body clipping, alcohol baths, and maintenance of a cool environment are the most effective methods. If infection cannot be entirely ruled out, antibiotic therapy should be used.

Meconium Impaction

Meconium impaction is the most common cause of colic in the newborn foal. This condition is more common in colts because of the narrow pelvic canal. Many foals show some degree of straining and discomfort while passing meconium, but in most instances it is passed uneventfully by 24 to 48 hours of age. The meconium most commonly becomes impacted in the rectum or small colon. The clinical signs associated with meconium impaction in the otherwise normal foal include repeated attempts to defecate, straining with the back arched, swishing of the tail, and restlessness. Nursing stimulates defecation through an oral-anal reflex, so signs of discomfort may appear shortly after each milk meal. If left untreated, meconium impactions lead to varying degrees of abdominal distention. The foal’s abdomen becomes gas distended, with tympany detected over the paralumbar fossa. Digital examination often reveals a rectum packed with hard fecal balls. Occasionally, the impaction is located more proximally (large or small colon) and radiography or ultrasonography is required for diagnosis.

Low doses of analgesics such as dipyrone (10 to 22 mg/kg IV), flunixin meglumine (0.25 to 1 mg/kg IV), and butorphanol (0.01 to 0.1 mg/kg IV) may be required to prevent self-trauma during colicky episodes. Xylazine may exacerbate gut stasis and can cause respiratory depression, and it should be used with caution in newborn foals. A gravity enema with mild soap and warm water or a commercial Fleet enema usually results in prompt evacuation of the meconium. Refractory meconium impactions may respond to acetylcysteine retention enemas.⁸² The supplies and procedure for a retention enema are as follows: Mix together 150 mL water, 6 g of acetylcysteine powder, and 20 g of sodium bicarbonate (baking soda). Insert a well-lubricated 12 or 14 French, cuffed Foley urinary catheter into the rectum and inflate the cuff. Slowly infuse 120 to 180 mL of the retention enema solution. Plug the end of the catheter. Tape the catheter loosely to the foal’s tail. Leave in place a minimum of 15 minutes, then deflate the cuff and remove the catheter. This procedure can be repeated several times. Care must be taken to avoid traumatizing the rectal mucosa by stiff tubing or multiple enemas with harsh detergents. Clinical signs associated with meconium impaction in the compromised foal may be absent. In asphyxiated or premature individuals that are receiving little or no enteral feeding, meconium may remain in the large colon for days, gradually forming into hard concretions that are diagnosed by palpation or radiographs or at postmortem examination. In these cases the routine administration of an enema is often ineffective in mobilizing the impaction because it is high in the large colon. Additional therapy includes intravenous fluids, oral fluids, and laxatives (60 to 120 mL of mineral oil with ½ to 1 oz of psyllium, 60 to 120 mL of milk of magnesia). If the gas distention becomes severe, transcutaneous bowel trocarization can be pursued. We avoid the use of Dioctyl sodium sulfosuccinate (DSS) as an oral cathartic because it can cause excessive irritation, resulting in diarrhea and colic. Analgesics may also be helpful in controlling the neonate’s discomfort and in reducing the risk of self-trauma. Although most meconium impactions can be successfully treated with aggressive medical therapy, those few foals that are refractory to treatment or display uncontrollable pain are candidates for surgical intervention.

Uroperitoneum

Uroperitoneum is a relatively common cause of abdominal distention and depression in the neonatal foal. The condition predominates in males but may occur in females as well. Uroperitoneum may be congenital or acquired. The congenital form occurs as a result of failure of the dorsal wall of the bladder to close during development.⁸³ The most common cause of uroperitoneum is a ruptured urinary bladder, but other sites in the urinary tract may also leak, including the ureters, urachus, and urethra. Most cases of ruptured bladders are presumed to occur during parturition because of external pressure on a distended bladder. This form occurs most commonly in colts. Uroperitoneum can also occur secondary to ischemic necrosis or infection of the urinary bladder or urachus in the compromised foal.⁷⁸ Critically ill, recumbent foals may rupture their bladders while being lifted and turned with a full bladder or as a result of chronic overdistention associated with the generalized disease state. Foals with botulism may also rupture their bladders secondary to bladder atony and chronic overdistention. Older foals of either sex may experience bladder rupture secondary to focal infection of the umbilical arteries and/or urachus, or ischemic necrosis of the apex of the bladder.

Clinical signs of uroperitoneum are rarely noticed before 48 to 72 hours of age, particularly if the foal is not being watched closely. The first signs may be urinary incontinence or frequent attempts to urinate, with only small amounts voided. Sometimes, particularly in those animals that experience rupture sometime after birth, there is a history of a period of normal urination, which at some point stopped or became abnormal. Loss of suckle, mild colic, and increasing abdominal distention are usually accompanied by worsening depression and increasing heart and respiratory rate. If the condition is allowed to persist, foals become increasingly weak and dyspneic and may be presented in cardiovascular collapse. Fillies with ruptured ureters have been reported to have a characteristic protruding perineum, presumably as a result of retroperitoneal accumulation of fluid.⁸⁴

Laboratory findings commonly associated with uroperitoneum are elevated serum creatinine and blood urea nitrogen (BUN), hyperkalemia, hyponatremia, hypochloremia, and metabolic acidosis. These changes are probably a result of the normal diet of the foal (milk being relatively high in potassium [25 mEq/L] and low in sodium [12 mEq/L]) and the third spacing of urine in the peritoneal cavity. With urine potassium concentration relatively higher than serum levels, and with urine sodium concentration lower than serum levels, the net effect of partial equilibration of serum with peritoneal fluid across a semipermeable membrane is hyponatremia and hyperkalemia, along with an inability to excrete the waste products of metabolism. Hyperkalemia may be severe enough to induce potentially fatal bradyarrhythmias. In hospitalized foals that developed uroperitoneum as a secondary complication, these typical electrolyte abnormalities are not consistently observed. Because most of those foals were receiving replacement intravenous fluids (high in sodium, low in potassium) and very little milk, it was theorized that intake has a great influence on the electrolyte abnormalities associated with uroperitoneum.⁸⁵ On the other hand, the electrolyte abnormalities typically associated with uroperitoneum are not pathognomonic for that disorder. Foals with renal failure, blocked urethra, white muscle disease, and enteritis have shown the same electrolyte changes.

A diagnosis of uroperitoneum often can be made quickly using transabdominal ultrasound and a 5- or 7.5-MHz transducer to visualize large volumes of free, nonechogenic fluid within the abdomen and a small, irregularly shaped, collapsed bladder. Abdominocentesis usually produces a free flow of peritoneal fluid that has a low cell count, low specific gravity, and at least twice the creatinine concentration of peripheral blood. If the creatinine is the same in both serum and peritoneal fluid, other explanations for the clinical signs should be investigated. The WBC count, total protein, and cytology of the fluid should also be determined. Most uncomplicated cases of ruptured bladders have fairly normal values for peritoneal fluid. In some cases, however, an increased WBC count and total protein and the presence of bacteria may suggest peritonitis. This may be a result of the urine in the abdomen, but more commonly there is a primary ongoing infectious problem (necrotic urachus or bladder, enteritis), and the prognosis becomes worse. If laboratory facilities are not available, new methylene blue can be injected into the bladder using a urinary catheter, and a few minutes later a sample of peritoneal fluid should have a blue discoloration if a ruptured bladder is present. However, this technique may not allow detection of other causes of uroperitoneum such as a ruptured ureter or distal urachus. Positive contrast cystography using a 10% solution of water-soluble media may be helpful in detecting the location of the urinary tract leakage. The ability to obtain urine on catheterization of the urinary bladder does not rule out uroperitoneum. Hematology and blood cultures should be performed to detect primary or secondary sepsis.

Treatment of uroperitoneum is surgical repair. However, the foal with uroperitoneum should not be rushed to surgery without first carefully stabilizing it. Serum electrolytes and blood gases should be run to determine the extent of hyperkalemia, hyponatremia, and acidosis present. Although the total amount of water in the body is usually grossly increased by the peritoneal accumulation of urine, effective circulating volume may be drastically reduced. If the eyeballs are sunken and the pulse quality and capillary refill time are poor, aggressive fluid therapy is indicated to support the circulation. This is best performed by concurrently removing as much fluid as possible from the abdomen with a teat cannula, 14G catheter, or peritoneal dialysis catheter to avoid worsening fluid overload and respiratory distress. The fluids of choice to treat the typical electrolyte alterations associated with uroperitoneum are saline, dextrose, and possibly sodium bicarbonate solutions, depending on the degree of acidosis present. In most instances continuous dextrose infusion is effective in decreasing the serum potassium level to an acceptable level, but values should be rechecked before anesthesia is induced. Insulin and dextrose may also be used to treat hyperkalemia, but the patient must be monitored for hypoglycemia. One suggested regimen is regular insulin at 0.1 to 0.2 U/kg subcutaneously (SC) or IV accompanied by a continuous intravenous dextrose infusion (4 to 8 mg/kg/min). Some individuals also have pleural fluid accumulation and atelectasis secondary to the abdominal distention, so oxygenation and ventilation during and after surgery should be closely monitored. Broad-spectrum antibiotics should be started immediately after samples are taken for culture if infection is suspected.

The prognosis for uncomplicated ruptured urinary bladders is usually good (>80% survival), provided the animal is stabilized before anesthesia. The presence of concurrent septicemia carries with it a considerably poorer prognosis.⁸⁵ In one retrospective study among foals with uroperitoneum, 100% of those foals with a negative sepsis score lived and only 57% of foals with a positive sepsis score survived.⁸⁵

Gas or Fluid Accumulation in the Gastrointestinal Tract: Ileus

Abdominal distention and colic secondary to excessive gas and/or fluid accumulation in all or a portion of the GI tract are common complications in the compromised neonate undergoing intensive care. The exact mechanisms responsible for the presumably altered GI motility are not well defined. Ileus is associated with the absence of intestinal sounds, abdominal distention, and intolerance of oral feeds characterized by gastric reflux. Auscultation of reduced GI borborygmi does not always correlate with the degree of intestinal compromise and decreased motility. Transabdominal ultrasonography helps identify absence of intestinal motility and the location and degree of intestinal distention. Ileus and the attending abdominal distention can cause severe colic and can induce respiratory distress in a weak or premature foal with preexisting pulmonary compromise.

Metabolic and infectious causes of ileus in the foal include hypokalemia, hypocalcemia, hypoxic-ischemic bowel injury, bowel obstruction, peritonitis, enterocolitis, and endotoxemia. Hypokalemia is associated with anorexia, diarrhea, and renal loss. Hypocalcemia is associated with prematurity, decreased dietary intake, excessive bicarbonate administration, diuretic therapy, and those conditions such as asphyxia, toxemia, and sepsis that stimulate release of cortisol and catecholamines. Peripartum hypoxia results in a preferential decrease in blood flow to the gut and kidneys. Poor perfusion of the intestines leads to varying degrees of mucosal damage and decreased motility. Severely damaged bowel requires a period of gut rest to allow healing to occur before oral feeds are resumed. Premature resumption of enteral feeding is associated with colic, maldigestion, diarrhea (often bloody), and translocation of intraluminal bacteria across damaged bowel wall into the bloodstream. Some of the more common causes of bowel distention in the neonate include meconium retention, intussusception, ascarid impaction, and small intestinal volvulus. Peritonitis may be associated with intraabdominal abscessation, severe enteritis or GDUD, and generalized septicemia. The most common causes of enteritis in foals include rotavirus, Clostridia species, Salmonella species, and dietary changes. Endotoxemia is usually part of generalized septicemia. Chronic bowel distention, regardless of the cause, further impedes return of normal gut motility. In the foal, aerophagia, particularly in the struggling or hypoxic neonate, often results in gas distention that is not easily removed through a nasogastric tube, because gas tends to move quickly through the GI tract (Fig. 19-8). Abdominal distention is also commonly observed during mechanical ventilation in the foal and as a result of overfeeding in the calf. Foals with botulism are often intolerant of enteral feeding, probably because of altered GI motility. Use of certain milk replacers can result in bloat, colic, and diarrhea, even in the apparently healthy orphan neonate. Discontinuation of or a decrease in the amount of enteral feeding and, if possible, increased activity of the patient usually result in resolution of the problem.

Fig. 19-8 Marked gastric and generalized small intestinal gas distention in a septic, collapsed, 3-day-old thoroughbred colt. There is no evidence of obstruction. The patient was treated with supportive therapy and recovered.

Abdominal radiographs reveal gas-distended loops of small or large intestine and may identify bowel obstruction. Sonographic examination permits evaluation of bowel wall thickness, peritoneal fluid volume and echogenicity, gut patency, intramural gas accumulation, location and degree of intestinal distention, and presence or absence of motility. An abdominal sonogram should be performed to rule out the presence of an intussusception or other obstructive lesion before any prokinetic therapy is initiated.

Management of ileus includes nasogastric decompression, cessation or reduced volume and frequency of enteral feeds if gastric reflux is present, parenteral alimentation if enteral feeding cannot be maintained at a rate of at least 10% of body weight per day, enema administration to relieve distal meconium or fecal retention, correction of any underlying electrolyte abnormalities, exercise for ambulatory foals, and judicious use of prokinetic agents. The gut -atrophies without enteral feeding. Glutamine and butyrate are essential fuels for the small and large bowel respectively and have been added to enteral formulas for people and some oral fluid replacement formulations for animals to help maintain and restore enterocyte health.⁸⁶ Prokinetic drugs should not be used when bowel obstruction or compromised bowel integrity is suspected. Prokinetic agents that have been used include metoclopramide, bethanechol, and erythromycin. There have been anecdotal reports of small intestinal intussusception after prokinetic use in neonatal foals.

Surgical Gastrointestinal Lesions

Most types of displacement, torsion, volvulus, and entrapments that occur in the adult horse may also occur in the neonatal foal, although probably at a lower frequency (Fig. 19-9). Large colon displacement, intussusception, and small intestinal volvulus have also been observed secondary to enteritis and colitis.

Fig. 19-9 Standing abdominal radiograph of a 3-week-old foal that was presented with signs of severe pain. Note the multiple, erectile loops of distended small intestine with fluid lines. Obstructive disease was suspected. On surgical exploration of the abdomen, obstructing adhesions secondary to a previous surgery were found.

Surgical correction of congenital GI defects may be attempted. Atresia ani, atresia recti, and atresia coli have been well documented in the foal, and intestinal aganglionosis has been observed in association with recessive lethal white foals, which are usually the products of mating between two overo paint horses.⁷⁶ Acute colic, progressive abdominal distention, and lack of meconium staining after repeated enemas have been the most common findings in newborn foals with atresia coli. Barium enemas may be of use in identifying foals with a short small colon but may also be misleading.⁸⁷ Surgical exploration of the abdomen offers definitive diagnosis of the severity of the malformation and the possibility of correction, but the owner should be informed before surgery of the high frequency of inoperable lesions and the high failure rate after reattachment.⁸⁷ Before any surgery is contemplated, a thorough physical examination should be performed to identify any other congenital malformations. Surgical correction of atresia ani is often successful, particularly if the atresia is limited only to a persistent membrane blocking the anus and the anal sphincter is normal. The prognosis for atresia coli is guarded. Poor intestinal motility, technical difficulties of attaching bowel segments that are so different in size, anastomosis breakdown, and peritonitis after surgery are common complications.⁸⁷ An inguinal hernia is another congenital lesion occasionally requiring surgical intervention. Such hernias occur in colts and may be caused by compression during parturition. Most congenital inguinal hernias are handled conservatively because the condition is often self-limiting by the time the foal is 3 to 6 months old. Treatment includes daily manual reduction of the hernia and frequent observation to detect possible bowel strangulation. Indications for surgical intervention in foals with congenital hernias include rupture of the common vaginal tunic, persistent colic, severe edema of the prepuce and scrotum, and trauma to the skin overlying the hernial sac. Surgical hernias are difficult to reduce manually, and loops of intestines are often palpable in the subcutaneous tissues of the scrotum and medial thigh.⁸⁸ Unilateral castration is usually performed on the affected side.

Other GI lesions in foals that may require an exploratory laparotomy include intussusception, small or large intestinal volvulus, and mechanical obstruction (e.g., food or ascarid impaction, phytobezoar, fecalith). Intussusceptions are reported in young horses less than 3 years of age. An intussusception is formed when one segment of intestine and its mesentery invaginates into the lumen of the adjacent bowel immediately aboral to it. The invaginated segment is called the intussusceptum, and the enveloping segment is called the intussuscipiens. Small intestinal intussusceptions can involve the jejunum, ileum, or ileocecal junction. Other sites of obstruction include cecocecal and cecocolic junctions. Intussusceptions are most common in foals less than 6 weeks old.⁸⁹

Causes of intussusception include segmental motility differences (e.g., a hypermotile section of bowel adjacent to an atonic segment of bowel) and local changes in the bowel wall (e.g., abscessation). Causes of altered peristalsis include -enteritis, heavy ascarid infestation, mesenteric arteritis, and sudden dietary changes.⁹⁰ Changes in the bowel wall have included granulomas, papillomas, and intramural leiomyoma. Anoplocephala perfoliata has been associated with ileocecal intussusceptions. Clinical signs include varying degrees of discomfort depending on the site of obstruction and its duration. Abdominal pain can be severe but is often low grade and intermittent, accompanied by decreased manure production. Ultrasonography is a useful diagnostic aid. Sonographically the cross-sectional view of the intussusception reveals a target-like pattern with a thick hypoechoic rim. The outer rim is created by severe edema of the entering and returning bowel walls of the intussusceptum.

Treatment involves surgical exploration. Early cases can be manually reduced, followed by surgical resection. Because of the ileum’s tenuous blood supply and the inaccessibility of the ileocecal junction, intussusceptions involving the ileum are usually treated with a side-to-side jejunostomy or ileocecostomy. Ileoileal intussusceptions have been reported to have a better prognosis than jejunal or ileocecal intussusception. Foals that have multiple sites of intussusception have a poor prognosis.

Volvulus may involve the small or large intestines. Small intestinal volvulus is the most common, especially among foals between 2 and 4 months of age. Signs include abdominal distention, gastric reflux, persistent tachycardia, severe pain, and sonographic evidence of uniform, severe bowel distention with bowel wall edema (>3 to 4 mm) and absence of motility. As expected, survival is poorer following correction of strangulating versus nonstrangulating lesions. Strangulating lesions of the small intestines are associated with poor survival compared with large intestinal lesions and have a higher incidence of fatal complications. Parasitic migration and abrupt dietary changes are among conditions thought to predispose to volvulus development.

Surgical colic in foals carries a poorer long-term prognosis than in adult horses. One study⁹¹ examined the survival rate among 67 foals <150 days of age that underwent colic surgery. The most common lesions requiring a celiotomy were small colon impaction, large colon impaction, jejunal volvulus, and ascarid impaction. A poor prognosis was associated with strangulating lesions. Foals less than 14 days of age experienced more early postoperative complications and suffered poor long-term survival because of adhesion formation. Only 25% of foals less than 14 days of age survived in the short term compared with a survival rate of 71% in foals older than 14 days of age.

Another study⁹² examined the outcome among 119 young horses less than 1 year of age that underwent exploratory celiotomy. Among all foals the most common cause for surgery was small intestinal strangulation. Uroperitoneum and meconium impaction were the most common conditions in neonatal foals, and intussusception and enteritis were more common among older foals. Significant elevations in packed cell volume (PCV) (37% to 54%), heart rate (80 to 134 bpm), nucleated cell counts, total protein in peritoneal fluid (3.1 to 32.8 × 10³/μL, 2.9 to 4.9 g/L), and rectal temperature (38.2° C to 39.2° C) were observed in nonsurvivors compared with survivors. Nonsurvivors had significantly decreased serum bicarbonate, chloride, sodium, and venous pH values. Thirty-three percent of foals that survived surgery had evidence of intraabdominal adhesions.

Necrotizing Enterocolitis

NEC has been described in equine neonates.⁹³ It is a syndrome of acute intestinal necrosis.⁹⁴ In human infants, prematurity is the single greatest risk factor, with only a small percentage of affected infants being full term. The causes of NEC are not well defined, but predisposing factors include ischemic hypoxic gut injury, presence of intraluminal bacteria, and enteral feeding. After GI ischemia, mucosal cell metabolism diminishes and the protective mucous layer is lost. This allows enzymes to break down the mucosal barrier, and intraluminal bacteria can then invade and multiply within the bowel wall. Enteral feeding provides substrate for the bacteria. Pneumatosis intestinalis develops, and the bowel frequently ruptures. Abdominal signs include abdominal distention, tenderness, ileus, and ascites. The condition may appear as a fulminant, rapidly progressive disease or progress at a much slower pace.^94,95 One affected equine neonate was premature and was undergoing treatment for respiratory distress when the abdominal crisis occurred. Another was a term foal that had experienced a prolonged delivery and was presented at 24 hours of age because of weakness and abdominal pain. Abdominal distention and abdominal pain, followed by ventral colon rupture, were noted in both foals.⁹³

Clinical signs associated with varying degrees of hypoxic, ischemic gut injury include ileus, gastric reflux, colic, lethargy, abdominal distention, and diarrhea. Reflux and feces may be positive for blood. Generalized sepsis often accompanies NEC. NEC should be distinguished from intestinal ileus secondary to other neonatal diseases, other surgical GI lesions, bacterial or viral enterocolitis, and intolerance to a milk diet. Although no single laboratory test is specific for NEC, the abdominal radiograph often reveals pneumatosis cystoides intestinalis, bowel wall edema, and an abnormal gas pattern consistent with ileus. Ultrasonography may reveal intramural gas accumulation. If intestinal perforation has occurred, pneumoperitoneum and septic peritonitis may also be noted.^93,94 Intestinal perforation is associated with a poor prognosis.

Gastrointestinal Ulceration

GDUD in the older suckling foal is covered in greater detail in Chapter 32. GI ulceration has also been associated with a number of neonatal diseases, including asphyxiation, enteritis, and septicemia.⁹⁶ The most significant form of the disease in this age group is cardiac gland disease—ulceration in the cardiac gland mucosa immediately beneath the margo plicatus. Ulceration presumably occurs in response to altered perfusion and may result in perforation and fatal peritonitis. In endoscopic surveys of neonatal foals in the United States, England, and Ireland, approximately one half of foals less than 3 months of age had evidence of gastric squamous mucosal ulceration.^97,98 The prevalence of lesions was greatest in 2- to 9-day-old foals and 30- to 59-day-old foals. In the young foals, typical lesions were golden-colored crusts in the squamous mucosa next to the margo plicatus along the greater curvature in association with diffuse ulceration and erosion and, commonly, squamous epithelial desquamation.⁹⁸ In one of these studies, foals that had a previous disorder (e.g., diarrhea, illness, transport) were more likely to have a glandular mucosal lesion than those that had not (9% vs 4%).⁹⁸

The clinical signs of bruxism, excessive salivation, and colic that are commonly associated with GDUD in the 1- to 4-month-old foal are rarely observed in the neonatal foal. Frequently, gastric perforation is the first indication of the problem. Perforated and bleeding gastric ulcers have been diagnosed as early as 24 hours of age. There is also a high incidence of abomasal ulceration in calves, but rarely do they become symptomatic unless perforation occurs. Currently the cause and pathophysiology of the condition in the neonatal period is not known. Because of the difficulty of diagnosing the condition without specialized endoscopic equipment and the often catastrophic consequences of subsequent perforation or pyloric or duodenal stricture formation, antiulcer medications are often used prophylactically in the compromised neonatal foal. Foals at highest risk for ulcers are sick neonates that are not recumbent and foals with hypoxic gut damage, enterocolitis, and painful orthopedic conditions. Foals that are chronically recumbent frequently maintain a high pH that may a result of ileus and enterogastric reflux.⁹⁹ In normal foals the mean hourly baseline gastric pH ranged from 3.2 to 3.7. Milk intake had a dramatic but transient alkalinizing effect on pH. H₂ blockers including ranitidine and omeprazole significantly raised gastric pH. Ranitidine administered IV at 2 mg/kg or orally at 6.6 mg/kg significantly raised gastric pH.

Initial therapy includes the use of H₂ blockers (cimetidine 15 to 20 mg/kg orally [PO] q6h; ranitidine 6 to 8 mg/kg PO q8h), cytoprotective agents (sucralfate 20 mg/kg PO q6h), and a new class of drugs, proton pump inhibitors (omeprazole 4 mg/kg PO q24h). Omeprazole is highly effective and has the advantage of once-daily administration. Treatment regimens should continue for a minimum of 21 to 28 days. In acute stages some foals receive additional pain relief from over-the-counter antacid solutions (10 to 20 mL q3-4h). Some foals are in too much pain to nurse and benefit from withholding enteral feeds temporarily and maintaining them on a brief course of parenteral alimentation using a mixture of amino acids, lipids, dextrose, electrolytes, and vitamins. Currently recommended dosages for antiulcer medications are listed in Chapter 32.

Hemoperitoneum

Hemoperitoneum is a relatively uncommon cause of abdominal distention in the large animal neonate. The structures most commonly responsible for the hemorrhage are the umbilical vessels and the liver or spleen when ruptured secondary to trauma. Occasionally other structures such as a ruptured granulosa cell tumor may bleed.¹⁰⁰ Depending on the cause and severity of the hemorrhage, clinical signs relating to hypovolemia and anemia may be mild or severe and may appear shortly after birth or in the older foal. Diagnosis of hemoperitoneum is based on the retrieval of free-flowing blood on peritoneal tap and the detection of free fluid in the abdomen. Ultrasound examination may be of benefit in detecting the source of the bleeding. Of critical importance, regardless of the source of the hemorrhage, is prevention of hypovolemic shock, and intensive patient monitoring and intervention are often indicated. Whole blood replacement may be necessary. If an internally bleeding animal with an unstable cardiovascular system is rushed to surgery without prior stabilization, profound shock may occur, and a poor outcome usually results.

Bacteria

E. coli is the most important mediator of systemic sepsis in newborn foals but is not a common primary cause of diarrhea in this age group. Some reports implicate an association between E. coli and diarrhea in foals. Enterotoxigenic E. coli was isolated from a 3-day-old diarrheic foal from Virginia.¹⁰³ The isolate was of the 0101 serotype, was heat labile-like—toxin positive, but negative for heat stabile. Earlier inoculation studies indicated that F4 (formerly K88)-positive E. coli was not likely to cause diarrhea in foals, although it may have a synergistic role in foals infected with other potential pathogens, such as rotavirus.^104,105

Intestinal disease mediated by clostridial toxins occurs in foals worldwide. The toxins are most commonly derived from biotypes A and C of Clostridium perfringens or from Clostridium difficile. Classic intestinal clostridiosis of foals is caused by C. perfringens biotype C and is characterized by colic, rapid dehydration, cardiovascular collapse, and hemorrhagic diarrhea. The disease occurs most commonly in foals less than 10 days of age, and often less than 36 hours of age. It is associated with a high mortality, and outcomes are rarely influenced by treatment.¹⁰⁶ Death may occur rapidly, and occasionally it occurs before any diarrhea has been passed. Biotype C produces both alpha- and beta-toxins, along with variable amounts of enterotoxin. Cases can occur sporadically or as outbreaks and on some farms occur annually, presumably associated with carriage in specific mares. Biotype A of C. perfringens has become well recognized as a specific cause of foal diarrhea over the past decade. Biotype A produces alpha-toxin and enterotoxin and is associated with a slightly lower mortality rate than biotype C. Affected foals are more likely to respond to directed or supportive care.¹⁰⁶ The development of clinical signs is rapid, and diarrhea may or may not contain blood; in ‘our experience passage of bloody diarrhea is common but usually very transient. Reported risk factors for C. perfringens diarrhea in neonatal foals in Colorado include breed (stock horse type); birth on dirt, sand, or gravel; housing in stalls or on dry lots during the first 3 days of life; and maternal feeding practices. Feeding a low-grain diet prepartum was associated with a decreased risk of neonatal disease.¹⁰⁷ Hematologic findings are consistent with toxemia. This includes hemoconcentration; an initial leukopenia, characterized by a neutropenia with a left shift to immature forms and toxicity; and a lymphopenia. In chronic cases a rebound leukocytosis and hyperfibrinogenemia may develop. Altered coagulation may be evident clinically through prolonged bleeding or spontaneous hemorrhage or through a propensity to develop thrombosis.

A definitive diagnosis of C. perfringens diarrhea is rarely established in practice. The diagnosis is usually based on signalment, clinical features, and outcome, rather than on detection of specific clostridial toxins. Positive fecal culture is strongly supportive, noting that healthy foals may shed low numbers of C. perfringens. Identification of toxin is ideal but is limited because of availability of appropriate commercial assays. Fecal enterotoxin detection assays are available but lack sensitivity, particularly with biotype C isolates. Biotyping of C. perfringens isolates after culture can be achieved using polymerase chain reaction (PCR) analysis for toxin gene sequences. This may be helpful in increasing the accuracy of the diagnosis but again falls short in establishing a definitive cause. Fecal Gram stain is easy to perform and may support an early clinical suspicion of disease if there are abundant numbers of large gram-positive organisms or spores present.

Clostridium difficile can produce an identical clinical syndrome to C. perfringens, although it appears to be more variable with respect to fecal blood. It also occurs as sporadic cases or as clusters or outbreaks. It is important to recognize that clostridial infection can produce a severe inflammatory syndrome that is restricted to the small intestine and may not cause diarrhea. Affected foals can present with signs that mimic strangulating small bowel disease including severe abdominal pain, gastric reflux, and sanguineous peritoneal fluid. Two principal toxins can be liberated from C. difficile, an enterotoxin (toxin A) and a cytotoxin (toxin B). Both nontoxigenic and toxigenic strains exist and can be differentiated only after culture using molecular techniques. Consequently, commercial toxin tests (available for both toxin A and toxin B) are recommended in addition to fecal culture to establish a diagnosis. As with C. perfringens cases, a fecal Gram stain can also increase suspicion. Hematologic changes associated with C. difficile infection can mimic those associated with C. perfringens disease.

Most cases of clostridial enterocolitis require aggressive medical intervention, irrespective of clostridial type. Antimicrobial therapy should be both specific and broad spectrum. Targeted antimicrobial treatment typically includes both metronidazole and penicillin. The majority of affected foals require, at minimum, intravenous crystalloid solutions; some also benefit from plasma or synthetic colloids and inotrope and vasopressor therapy. Additional therapies include C. perfringens biotype C and D antitoxin, di-tri-octahedral smectite clay, and lactase enzyme replacement.^108,109 The use of C. perfringens antitoxin and toxoid is off-label and not without some risk. Pretreatment with antihistamines before antitoxin has been suggested.¹⁰⁸ Prevention of clostridial enterocolitis centers on hygienic housing practices and avoidance of overfeeding of late pregnant mares. Affected foals and their mares should be isolated and strict protocols instituted to limit cross-contamination. Administration of C. perfringens type C and D toxoid to pregnant mares has been used with anecdotal success on farms with recurrent problems with C. perfringens biotype C. The use of prophylactic metronidazole is highly controversial but understandable on properties with a high disease prevalence. Some isolates of C. difficile are reportedly resistant to metronidazole,¹⁰⁸ and although this appears to be dependent on geographic location, the widespread prophylactic use could promote resistance. Prophylactic use of probiotic preparations has also been commonly recommended but is difficult to justify on the basis of limited and conflicting efficacy data.^110,111

Bacteroides fragilis is a gram-negative anaerobic rod and occurs in both enterotoxigenic and nonenterotoxigenic forms. Enterotoxigenic strains of B. fragilis have been incriminated with diarrhea in several species including lambs, calves, pigs, humans, and foals.¹¹² Enterotoxigenic B. fragilis was isolated from young foals (aged 2 to 60 days) with diarrhea.¹¹³ Half of these foals had other potential pathogens detected, including Salmonella or rotavirus. In a study reviewing 20 isolates of B. fragilis from hospitalized foals with diarrhea, only four had the enterotoxin gene.¹¹² The most common isolate from foal feces was a nonenterotoxigenic strain, casting doubt as to clinical relevance.

Enterococcus (group D Streptococcus) durans has also been implicated as a cause of diarrhea in several species including foals.¹⁰⁴ Similarly, Aeromonas hydrophila was isolated more commonly from foals with diarrhea than from control animals, suggesting a potential role in foal diarrhea.¹¹⁴

R. equi is an important cause of pulmonary disease in foals. Although abdominal involvement appears common, the relevance of R. equi as a significant primary enteric pathogen in terms of number of animals affected is likely small. An intestinal syndrome has been directly attributed to R. equi that involves necrosis of the small intestinal Peyer’s patches and multifocal thickening and necrosis of the cecum and large intestine.¹¹⁵ The changes include multiple areas of intestinal ulceration with a thin covering of fibrin and neutrophils. There is also an associated mesenteric lymphadenopathy. The diagnosis of R. equi ulcerative colitis is difficult for a variety of reasons. In contrast to Salmonella infection, in which recovery of the organism from the feces has significance, the recovery of R. equi is common in asymptomatic animals. Up to 100% of foals older than 2 weeks of age may shed large numbers of the bacteria (>10⁴ colony-forming units [cfu] per gram of feces).¹¹⁶

Salmonella infection of neonatal foals is also associated with high mortality. As with clostridial infection, cases can occur sporadically or as part of an outbreak. Mares provide the most important source of Salmonella to newborn foals, but it is rare that both mare and foal develop clinical disease. Clinical signs can become apparent by 24 hours of age but are more common in older foals. The severity of signs is related to virulence of the serotype involved, inoculation dose, and level of host immunity. In contrast to adult infections, detectable bacteremia occurs commonly in affected foals. Consequently foals that may survive the initial intestinal or systemic disease remain at risk for secondary complications that include osteomyelitis, synovitis, meningitis, uveitis, hepatitis, or pyelonephritis. In some foals these complications may not become clinically apparent until days or weeks after resolution of enteric disease. Therefore appropriate and sustained broad-spectrum antibiotic therapy is important in foals known to be affected. The selection of antibiotic should be based on known sensitivity patterns, understanding that in vitro sensitivity may not accurately translate into clinical efficacy because of the intracellular location of Salmonella. For example, the limited distribution of aminoglycosides can lead to therapeutic failure despite often promising in vitro sensitivity.

Viruses

Rotavirus is generally considered to be the most common cause of infectious diarrhea in foals. There are seven known groups of rotavirus (A through G), and many different serotypes within each group. Group A is the primary cause of rotaviral diarrhea in foals, with G3 being the most common serotype. Rotaviruses have the ability to change their surface proteins over time, and this rearrangement of gene segments takes place during co-infections with other strains. This leaves the possibility for many variations of the virus.

Transmission may be direct from animal to animal or indirect through fomites. Disease occurs after a short incubation period. Experimentally, this period may be as brief as 48 hours.¹¹⁷ Rotavirus replicates within the intestine and invades the lining of the proximal small intestine, causing villous cell death and a resultant loss of absorptive area. Diarrhea may result from several mechanisms: (1) a loss of absorptive capacity coupled with a decrease in lactase production can lead to an osmotic load of undigested lactose delivered to an immature hindgut; (2) a compensatory crypt cell proliferation may cause an increase in intestinal secretion; and (3) the virus produces an enterotoxin that causes or contributes to the development of diarrhea. The putative viral enterotoxin and cytotoxin, NSP4, is a nonstructural glycoprotein of rotavirus that is released from virus-infected enterocytes.¹¹⁸ NSP4 is a noncompetitive inhibitor of the Na-glucose symporter and also enhances intestinal chloride secretion.

Disease can be seen between 2 and 160 days of age but is most common in foals less than 60 days old. Indeed, most clinical infections probably occur between 5 and 35 days of age. The presence and severity of diarrhea are highly dependent on the degree of hindgut maturation. Consequently, infection in foals less than 2 weeks of age may result in life-threatening watery diarrhea, whereas infected older foals may have minimal or no diarrhea because of effective colonic compensation of osmotic and fluid loads. Diarrhea when present is often watery but is nonfetid in odor.

There is serologic evidence that broodmares may have an important role in propagation of the virus within a herd. Infections can occur as isolated cases or as outbreaks following periods of overcrowding and stress. Shedding after infection is usually complete by 10 days after the cessation of clinical signs but may occur intermittently for up to 9 months.¹¹⁹ The virus can persist in the environment for up to 9 months, and disinfection usually necessitates the use of substituted phenolic compounds.

The diagnosis of rotaviral diarrhea is based on an appropriate signalment, clinical signs, and detection of the virus in feces. Tests include electron microscopy and commercial immunoassays (latex agglutination or enzyme-linked immunosorbent assay [ELISA]). Virus is shed in large concentration early on during infection.¹²⁰ Central to the management of affected foals is maintenance of hydration through enteral and/or intravenous fluid therapy. Bismuth subsalicylate is commonly administered to foals with diarrhea, irrespective of the underlying cause.

Prevention involves good hygiene and reduction in crowding. Vaccination of mares during pregnancy has yielded variable results in terms of efficacy.^121,122 Some evidence suggests that vaccination may at a minimum delay the onset of disease, thereby reducing both the severity and duration of diarrhea. Limited data from Japan indicate a potential benefit of bovine colostral immunoglobulin powder in the prevention of rotaviral diarrhea.¹²³ A commercial egg-protein—derived supplement has also been used in foals to reduce the prevalence of neonatal diarrhea, but controlled research data are lacking.

Coronavirus can also cause diarrhea in foals during the neonatal period, although it appears to be very uncommon.^124-127 The few reports of clinical disease indicate that disease caused by coronavirus can be very severe. Antemortem diagnosis can be made using electron microscopy, serology, or commercial fecal-capture ELISA. As with rotaviral infection, shedding is greatest in the early stages of disease. Adenovirus is unlikely to play an important role in foal diarrhea, with the exception of foals with severe, combined immunodeficiency syndrome.¹²⁸

Parasites

Strongyloides westeri is a common parasite of foals, with early infection of the foal occurring through mare’s milk. Experimental studies have indicated that higher numbers of infective larvae than are found in milk are needed to produce diarrhea.¹²⁹ In addition, foals with high egg counts (prepatent period 8 to 14 days) are often asymptomatic. S. westeri is susceptible to a variety of anthelmintics, including ivermectin.¹³⁰ Eimeria leuckarti is commonly found in feces of foals from approximately 30 to 125 days of age.¹³¹ It is unlikely to be a cause of diarrhea in foals.¹³²

Cryptosporidium parvum is not considered to be an important pathogen of foals in terms of numbers of animals diseased. Based on epidemiologic studies the parasite appears to be concentrated in some breeding operations.¹³³ Foals diseased with Cryptosporidium shed enormous numbers of infective oocysts into the environment. The parasite is considered to be coccidian-like but differs from coccidia in terms of size (4 to 6 μm diameter compared with 23 to 34 μm for other coccidia), host specificity (not host specific), pathogenesis (invades only epithelium), and drug sensitivity (resistant to many drugs). Infection is by the fecal-oral route. The oocysts can survive in the soil or water for months. They do not require a period of sporulation outside of the host to become infective. In a study of asymptomatic foals in Ohio and Kentucky, it was reported that between 15% and 31% of foals were shedding Cryptosporidium and that shedding began between 4 and 19 weeks of age and persisted no more than 14 weeks.¹³⁴ All shedding had ceased by weaning and was not identified in adult horses. Each generation of the Cryptosporidium lifecycle is brief, with maturation occurring in as little as 12 hours. Consequently, the prepatent period is very short, approximately 72 to 96 hours. Although not determined in foals, a heavily infected calf can shed approximately 50 billion oocysts within a 7-day period.

The diagnosis is usually made through microscopic examination of the feces. Acid-fast or Ziehl-Neelsen stains are required to detect oocysts. Immunofluorescence assays and flow cytometry techniques have also been described. C. parvum infection may be seen with concurrent enteric or systemic infections. The disease is generally self-limiting in immunocompetent animals. Historically the pharmacologic control of Cryptosporidium has been difficult, but paromomycin, nitazoxanide, or azithromycin may be efficacious.

Giardia may be found in normal foals, with infection rates reported to be 17% to 35%. Giardia is present in all age groups, and it is believed foals acquire infection from nursing mares. Concurrent infection with Cryptosporidium and Giardia may be observed. Disease should be suspected if large numbers of parasites are seen on fecal analysis. Affected animals should respond within a few days to treatment with metronidazole; failure to respond should alert to other pathogens.

Nutrition

Nutritional causes of diarrhea include overingestion of milk (as might occur when the mare and foal are separated and rejoined) or overfeeding orphaned or sick foals. Overwhelming the ability of the small intestine to digest and absorb results in presentation of milk to the colon, where it is fermented and produces osmotically active sugars and acids.¹³⁵ In a controlled study of foals less than 5 days of age, an elemental isotonic diet (Osmolyte) produced diarrhea in healthy foals when fed as the sole source of nutrition. Older foals fed a similar diet apparently did not develop diarrhea.* Caution should be exercised in using elemental diets designed for humans in the foal without adequate prior testing of tolerance to the diet. Orphan foals and foals fed commercial mare milk replacer may experience diarrhea associated with these diets. Foals that are fed raw cow’s milk frequently experience diarrhea and failure to thrive. Cow milk replacer uncommonly causes diarrhea but remains a less than ideal replacement. In contrast, foals fed goat’s milk grow well and rarely develop diarrhea, although they may develop a metabolic alkalosis of minimal to no clinical significance.

Transient lactase deficiency has been proposed in foals.^137-139 An oral lactose tolerance test is conducted by a 4-hour fast and administration of 1 g/kg of body weight in a 20% solution of α-lactose powder and observation of an increase of plasma glucose of 35 mg/dL by 90 minutes.¹³⁹ It has been postulated that agents such as rotavirus that damage epithelial cells may cause prolongation of the diarrhea because of temporary lactase deficiency (lactase is produced in mucosal cells). Lactase and cellulobiase are present at birth and decline after 4 months of age.¹⁴⁰

Foal Heat Diarrhea

Diarrhea developing during days 5 to 14 of life has been termed “foal heat diarrhea” because of the time relationship to the occurrence of postfoaling estrus in the mare. Diarrhea has developed in foals in this age group that have been raised separated from the dam on a consistent diet and isolated from pathogens, so it does not appear to be causally related to estrus. There is no demonstrable change in the composition of mare’s milk during this time period.¹⁴¹ S. westeri has been investigated and is not the causative agent of foal heat diarrhea.¹²⁹ The most likely cause of foal heat diarrhea is the establishment of normal flora in the hindgut. Foal heat diarrhea is typically preceded by coprophagy 2 to 3 days before the onset of diarrhea.¹⁴² Classic foal heat diarrheas are mild and require no specific therapy. Continued diarrhea, fever, or depression with signs of reduced sucking activity on the mare should raise concern about other causative agents and should prompt appropriate diagnostic testing and treatment.

Etiology

Septic arthritis, septic physitis, and osteomyelitis as a complication of or sequel to bacteremia produce lameness and reluctance to move. Terminology to describe this condition has included “joint-ill,” “navel-ill,” septic physitis, septic polyarthritis, and septic epiphysitis.¹⁴⁵ Blood-borne bacteria from a previous illness or concurrent with an active nidus of infection produce infection in synovial membranes, growth plates, or periarticular bone. Sources of infection include primary bacteremia with or without FPT¹⁴⁶ (see Chapter 53), pneumonia, umbilical infection, enteritis, and extension of local infection from penetrating wounds. Thirty eight of 140 foals with confirmed septic arthritis demonstrated evidence of umbilical disease. In foals, bacteria that produce septic arthritis include the causative agents of systemic sepsis: E. coli, Klebsiella species, Actinobacillus equuli, Salmonella species, R. equi, and Streptococcus species.¹⁴⁶ A review of 78 foals with septic arthritis ranked the frequency of isolation of bacterial agents. Gram-negative bacteria were cultured from 51 of 78 foals. In addition, the probability of susceptibility of these isolates to various antibiotics was determined. Blood culture produced more bacterial isolates, although joint aspiration yielded bacteria in 69% of foals sampled.¹⁴⁷ Bacterial species cultured from blood and synovial fluid were identical in 16 of 88 foals. Negative cultures occurred in 31% of foals with later confirmed septic arthritis.¹⁴⁷ Gram-negative bacteria were more common in younger foals, and gram-positive infections became increasingly more common with advancing age of the foal.¹⁴⁷

Clinical Signs and Differential Diagnoses

Signs may be extremely variable. Sudden onset of lameness in one leg in an apparently healthy neonate with or without joint distention, pain, or edema may be noted. Other presentations may be observed, consisting of sudden onset of lameness with systemic signs of illness or evidence of multiple joint distention, pain, and edema in a neonate with obvious illness and a diagnosis of septicemia. Prematurity or FPT should raise the index of suspicion. The chief differential diagnosis is trauma; lameness is often attributed by the owner to the dam’s stepping on the newborn. Any neonate less than 45 days of age with sudden onset of lameness should be considered infected until proven otherwise.

Clinical Pathology and Radiology

Diagnosis may be obvious, with signs of septicemia, a positive sepsis score, and a swollen, hot, and painful joint. Peripheral leukocyte counts, rectal temperature, level of alertness, and appetite may be normal with localized infections. Joint aspiration may reveal normal synovial fluid if the infection is in the early stages of synovial membrane inflammation or physeal or bone involvement.¹⁴⁵ Synovial fluid with greater than 10,000 WBCs/μL and greater than 70% neutrophils indicates that infection is likely.¹⁴⁶ Cytology and Gram stain of the synovial fluid may further aid diagnosis. Thin, turbid, or brown synovial fluid with increased leukocytes is considered evidence of infection.¹⁴⁵ Culture of synovial fluid is often negative, even when infection is present. Improved recovery of bacteria may be obtained with thioglycolate broth or brain-heart broth with an agar slant and sodium polyanethole sulfonate (SPS) to prevent clotting and inhibit aminoglycoside and trimethoprim antibiotics.¹⁴⁸ Normal synovial fluid does not rule out septic physitis or osteomyelitis.¹⁴⁵ Careful examination of high-quality radiographs is important for the detection of bone lysis in cases of osseous infection. Initial radiographs may be normal because the degree of damage is often not detectable for 10 to 14 days after initial infection occurs.¹⁴⁵ Radiographic features of septic arthritis include soft-tissue swelling, widening or collapse of the joint space, osteoporosis, and osteosclerosis. Repeat radiographs taken at 3- to 7-day intervals are valuable for assessing the degree of damage if lameness persists.¹⁴⁵ Ultrasound may be used to confirm involvement of the joint and rule out periarticular or tenosynovial infection to avoid iatrogenic contamination of the joint during arthrocentesis. Joint distention and hyperechogenic fragments in the synovial fluid are suggestive of septic arthritis. Normal synovial fluid is anechoic. Bone scans or CT may facilitate early detection.

Pathophysiology

Hematogenous spread of bacteria resulting in bone infection may follow a variety of pathways.¹⁴⁵ A nidus of infection may develop at the junction of cartilage and subchondral bone. The low pressure, slow flow, and reduced oxygen pressure of the blood supply at cartilage-bone junctions may predispose to establishment of infection in these areas. Level of immunity and degree of maturation of bone of the foal may be additional predisposing factors.¹⁴⁵ Destruction of the epiphysis and extension of infection into the joint may be primary in some cases, rather than starting as a primary synovial membrane infection that spreads to the epiphysis and physis. A classification has been proposed to reflect the various pathogeneses of infection (see Box 19-2). Infection of the small bones of the tarsus has been reported to be more common than that of the carpus,¹⁴⁹ and the metaphysis of ribs and vertebral bodies may be involved.¹⁴⁶ Synovitis produces severe inflammation and depletion of the cartilage matrix and collagen framework, which can cause irreversible damage.^145,146 Eburnation of cartilage leads to exposure of subchondral bone and extension of infection in bone.¹⁴⁵

Treatment

Aims of treatment are to remove the infectious agent, protect and minimize cartilage damage, and minimize secondary osteoarthrosis. If partial or complete FPT has occurred, an additional aim is to provide immunoglobulins through plasma transfusion (volume dependent on IgG concentration, but 2 or more liters IV may be required).¹⁴⁵ Treatment described for bacteremia should be used promptly. Umbilical ultrasound should be performed, because many infections may be not be visible externally. Systemic antibiotics provide adequate levels of antibiotic in normal and inflamed joints.^145,150 Antibiotics or antibiotic combinations with both gram-negative and gram-positive spectrum should be used initially, with selection modified by culture results. Ampicillin or a first-generation cephalosporin in conjunction with amikacin or gentamicin has had a good probability of antimicrobial sensitivity.¹⁴⁷ The third-generation cephalosporin ceftiofur may be used as monotherapy. Antimicrobials (antibiotics) should be continued for at least 3 weeks. Joint lavage with 1 to 3 L of balanced polyionic buffered (pH-adjusted) fluids helps to remove bacteria and inflammatory mediators that damage cartilage and improves outcome.¹⁴⁷ An infected joint is a medical emergency, and treatment should be carried out immediately after clinical diagnosis of probable sepsis, even before all cultures and clinical pathology test results are back. Arthrotomy or arthroscopic lavage for joints with fibrin and debris has been advocated and appears effective.^148,151 Delivery of antibiotics to chronically infected tissues via regional limb perfusion or intraosseous infusion has been described.¹⁵² Confinement and limb immobilization may decrease pain, inflammation, and cartilage damage. Short-term use of nonsteroidal antiinflammatory drugs such as flunixin or phenylbutazone at prescribed dosages may be indicated, although the risk that these agents will induce gastric ulceration in foals is well described.

Prognosis

Duration, extent of bone involvement, and degree of damage affect the prognosis. A recent study determined that 79% of foals with septic arthritis had IgG levels less than 8 g/L (800 mg/dL). Infection of multiple joints, delay in onset of treatment, and presence of concurrent bony lesions on radiographs were associated with a poorer prognosis.¹⁴⁷ In one study, 67% of foals with septic arthritis were discharged when treatment was initiated within 24 hours of the onset of clinical signs.¹⁴⁷ Better outcomes were observed when treatment included joint lavage. Of foals treated for septic arthritis, 26% went on to perform their intended function.

If FPT has occurred and multiple joints are involved, the prognosis is poor because, in foals with FPT and lameness, multiorgan involvement is common.¹⁴⁶ Initial detection should warrant a guarded prognosis. The long duration of treatment and sometimes costly multiple therapeutic modalities should be discussed with the owner at the outset. Reevaluation of the patient at regular intervals is indicated. Recurrence after cessation of therapy sometimes occurs.

Developmental Causes

Incomplete ossification of the cuboidal bones (see Fig. 19-1) of the carpus and tarsus of newborn foals is considered to be related to the development of flexural and angular deformities of the foal.¹⁵⁶ Twins, premature foals, foals that are small for gestational age, and foals with in utero acquired infection are likely to have incomplete ossification of cuboidal bones at birth.^156,157 Radiographic analysis and grading of the degree of ossification have been suggested for these foals.¹⁵⁷ Foals with substantially reduced ossification may damage bone with limb loading. Limited exercise may be prudent until ossification begins to increase radiographically, which can be within 7 days. Hypothyroidism (see Chapter 41) has been identified in foals with angular limb deformities, contracted tendons, and tarsal bone collapse.^158,159

Etiology

Various causes have been suggested for failure of the urachus to close and completely involute. Early severance or ligation of the umbilical cord, inflammation, infection, and excessive physical handling of the neonate have been implicated.¹⁶⁰ Rather than being the original cause for hospital admission, patent urachus develops as a complication of hospitalization in a significant percentage of foals in neonatal intensive care. Weakness of abdominal musculature may contribute to the problem in sick foals.

Clinical Signs and Differential Diagnosis

Differential diagnoses include concurrent infection of the navel (omphalophlebitis). Ultrasound may assist the diagnosis and determine the involvement of umbilical arteries or vein.¹⁶¹ Moist hairs around the umbilicus and visualization of fluid coming from the navel are diagnostic. Ultrasound examination of the internal structures of the umbilicus is strongly recommended.

Clinical Pathology

Identification of concurrent infection is essential. A complete physical examination should be performed. If abnormalities are noted, serum IgG, CBC, and urinalysis are helpful for detecting susceptibility to infection and presence of systemic or urinary tract infection.

Pathophysiology

Congenital patent urachus caused by excessive torsion on the umbilical cord in utero occurs in 6% of normal foals.¹⁶² The obstruction of the urachus caused by the torsion causes retention of urine in the bladder and overdistends the proximal urachus, which interferes with normal involution.¹⁶² Infection of umbilical structures or the urachus itself may result in inflammation and failure to completely involute. In a review of 16 cases of umbilical cord infections in foals, 13 of the foals had patent urachus.¹⁶³ The majority of these foals had acquired patent urachus after birth, with the youngest age of onset being 3 days and the mean age of onset being 12 days. Excessive manipulation and improper lifting of the foal’s abdomen in the presence of high urethral sphincter tone may force urine within the bladder out into the involuting urachus. In our experience, farms have experienced outbreaks of patent urachus when procedures (such as tests for FPT) have been implemented that require handling of foals in the first 12 to 24 hours of life. A similar cause may be responsible for the increased incidence of patent urachus in hand-reared calves.

Treatment and Prognosis

Therapy consists of either conservative management through monitoring or medical treatment for infection and cauterization of the urachus with iodine, phenol, or silver nitrate sticks applied into the urachus. Persistence of urine dribbling despite cauterization, the detection of involvement of other umbilical structures through ultrasound, and a rent in the urachus that produces subcutaneous swelling are indications for surgery. Not all foals that have persistent patent urachus have an infected umbilicus. Use of general anesthesia and removal of the entire urachus to the tip of the bladder are performed in foals with an infected or enlarged urachus. Associated arteries and veins should be ligated and removed if they are infected or necrotic. Merely ligating the exterior stump can trap organisms and cause infection. In our neonatal unit the majority of patients with acquired patent urachus respond to conservative therapy. Late-onset patent urachus (5 days of age) may be more refractory to conservative therapy.¹⁶³ Complications are uncommon but may include bladder necrosis and uroperitoneum caused by extension of infection and inflammation of the urachus.

Prevention

Allowing the umbilical cord to rupture without ligation or the careful use of specific umbilical clamps after birth has been suggested to decrease the incidence of patent urachus. Minimum handling of neonates and careful restraint may prevent pressure buildup in the bladder and subsequent patent urachus.

Definition and Etiology

Omphalitis is inflammation of umbilical structures that may include the umbilical arteries, umbilical vein, urachus, or tissues immediately surrounding the umbilicus. The umbilicus consists of three types of structures and undergoes functional and anatomic changes at birth. Two umbilical arteries connect internal iliac arteries to the placenta. These later regress and become the round ligaments of the bladder. One umbilical vein connecting the placenta to the liver and porta cava regresses to become the round ligament of the liver within the falciform ligament. The urachus connects the fetal bladder to the allantoic cavity.

Umbilical abscess or infection of any of the three components of the umbilicus may produce local infection or be a source of septicemia. The source of infection is most commonly the external environment, coupled with FPT. Omphalophlebitis may extend the length of the umbilical vein into the liver and result in liver abscessation.

Clinical Signs and Differential Diagnosis

When the umbilicus is enlarged and draining purulent material, infection is easily noted. In other cases the umbilicus may be dry and larger in diameter than expected. In addition, neonates may have a completely normal-appearing, dry external navel and be severely ill from infection of the urachus, umbilical arteries, or vein. In a neonate with sepsis without external signs of infection, involvement of the umbilicus can be difficult to determine. The presence of pain on palpation of the umbilicus indicates inflammation. Ultrasound aids in the detection of involvement of the urachus or arteries and vein.¹⁶¹ The umbilical area of neonates less than 20 days of age with fever of unknown origin should be scanned. Hematoma developing after umbilical rupture may produce distention of the umbilical stump shortly after birth.

Overt signs of infection include heat, swelling, purulent discharge, or pain. Concurrent signs of systemic infection such as joint infection, pneumonia, diarrhea, meningitis, or uveitis may be noted. Infection in more than one umbilical vessel in the neonate is common, and urachal involvement is frequent. Umbilical abscessation that is walled off and does not involve deeper structures is a less severe problem and may be treated with drainage without surgical removal of the entire umbilicus. The depth of involvement may be determined by standing behind the neonate and pressing the hands together above the umbilicus to detect internal masses and painful areas.

Diagnostic Methods

In addition to detection of overt umbilical inflammation as described, ultrasonography may aid in evaluating a normal-appearing navel.¹⁶⁴ The umbilical vein, arteries, and urachus may be imaged in the newborn (see Chapter 18). The umbilical arteries leave the umbilical stalk and course on the outer edges of the urachus in a parallel fashion.¹⁶⁴ In the foal the urachus connects the apex of the bladder with the umbilicus and is located along the midline immediately adjacent to the body wall. Persistent dilation of the umbilical vein or arteries with a hypoechoic-to-echogenic fluid is seen with infection. If ultrasound is performed by a skilled ultrasonographer familiar with normal ultrasonographic findings of the umbilicus, there is an excellent correlation between surgical and ultrasound findings.¹⁶⁴

Treatment and Prognosis

Early treatment with antibiotics and supportive care as described for the septicemic foal (see Chapter 18) may allow resolution before development of abscessation and distention of the urachus or the umbilical arteries and vein. Established infection, which may occur within 24 hours, may necessitate surgical removal of involved structures in addition to medical therapy.¹⁶³ When omphalophlebitis extends into the liver, the umbilical vein may be marsupialized to facilitate drainage and flushing. The prognosis is very good when adequate passive transfer of colostral immunoglobulins has occurred and when joints or other structures are not involved. Sequelae such as renal abscessation, joint or bone infection, peritonitis, and other complications described for septicemia may develop if therapy is started too late or discontinued prematurely.

Definition and Etiology

Anemia in the neonate should be interpreted in the context of the realization that normal hematologic values of the neonate may vary from those of the adult. In foals, values of hemoglobin and PCV are similar to those in adult horses but decrease during the first weeks and months of life to below those in adults.¹⁶⁵ Foals have low iron stores during the first 5 months of life; this is reflected in decreased serum ferritin concentration, increased serum total iron binding capacity, and decreasing mean corpuscular hemoglobin concentration.¹⁶⁶ Microcyte production is observed rapidly after birth.¹⁶⁶ Absolute RBC and total blood volume decrease at between 2 days and 2 weeks of age and then progressively increase.¹⁶⁷

In addition to frank blood loss from an injury, diseases causing anemia in the neonate include NI, non-NI immune-mediated hemolytic anemia, blood loss caused by gastric ulcer or ovarian cyst rupture producing hemoperitoneum, anemia of chronic disease associated with localized infections, piroplasmosis, and equine infectious anemia.

Clinical Signs and Differential Diagnosis

Rapidly developing anemias such as those associated with NI produce signs of weakness, pale or jaundiced mucous membranes, fever, and depression. Hemoperitoneum produces weakness and pale mucous membranes. Suspected drug-induced, immune-mediated hemolytic anemia and thrombocytopenia have been reported in the foal.¹⁶⁸ Intestinal parasitism does not normally lead to anemia during the neonatal period. Chronic localized infection may produce anemia of chronic disease.

Clinical Pathology

Intravascular hemolysis may produce hemoglobinuria and hemoglobinemia. Icterus develops when the ability of the liver to conjugate bilirubin is exceeded. Mainly, indirect bilirubin is elevated. Anisocytosis is observed in responsive anemias. Nonspecific stimulation of bone marrow may produce a leukocytosis.

Therapy

Determination of the nature of the anemia may allow specific treatment. NI is discussed in Chapter 53. Drug-induced or autoimmune anemias may be treated with corticosteroids (0.05 to 0.1 mg of dexamethasone per kilogram twice a day IM or IV). Blood transfusion after cross-match may be indicated when anemia develops rapidly or PCV drops below 14%. Massive red cell destruction may trigger disseminated intravascular coagulation, and the actual cause of death may be a result of activation of the clotting system by RBC destruction and reticuloendothelial system removal.¹⁶⁹ Associated conditions such as metabolic acidosis and hypoglycemia should be corrected. Anemia of chronic disease requires correction of the primary disease condition.

Definition and Etiology

Fever (rectal temperature >38.9° C [102° F]) as a clinical sign must be interpreted differently in neonates than in the adult because of the variations of anticipated response to systemic illness, temperature regulation control differences, and susceptibility to environmental changes in temperature. In foals with septicemia, fever (> 38.9° C [102° F]) was present in fewer than 30% of cases, and hypothermia was noted in approximately 20%.⁵⁶ Consequently fever is considered an unreliable clinical sign for determination of sepsis in neonates. Older foals with localized infection such as in joints or bone are more likely to have fever.

Differential Diagnosis

The chief differential diagnoses for fever in neonates are fever caused by infections with viral or bacterial pathogens, seizures with subsequent generation of heat by muscular overactivity, pyrogens generated from hemolysis in NI, and environmentally induced hyperthermia. The condition of transient tachypnea of the newborn may produce significantly elevated temperatures in warm environments.¹⁷⁰ Neonatal foals have a rapid respiratory rate that appears to be an attempt at heat loss through a panting type of mechanism. Extreme care must be used in attributing the pyrexia and fever to transient tachypnea syndrome alone by ruling out the presence of infection through physical examination, chest radiographs, blood gases, and computation of a sepsis score. Pathophysiology is similar to that in the adult and is discussed thoroughly in Chapter 4.

Treatment and Prognosis

Although a conservative approach to fever in older animals may be appropriate, the presence of a fever in a neonate warrants rigorous diagnostic evaluation and aggressive therapeutic intervention. The immaturity of the neonatal immune system, the high fatality rate, and the frequency of devastating sequelae to bacterial infection warrant a complete examination of the neonate.

Because fever may be beneficial to the animal, the need to administer antipyretics to the febrile neonate is controversial. Body temperatures lower than 40.8° C (105.4° F) are not considered detrimental unless they are associated with heat stroke or seizures,¹⁷¹ in which case cooling and antipyretics are indicated. Because many antipyretics are antiprostaglandins that can cause deleterious GI and renal effects, these agents should be used judiciously. Dipyrone is often used in neonates in our clinic for antipyretic response because it lacks most of the adverse GI side effects found with most nonsteroidal antiinflammatory drugs. Correction of the initiating cause and maintenance of fluid balance are also important. Prognosis depends on immunoglobulin status and stage of disease when treatment is initiated. Significant fatality rates occur in neonates with bacterial infections. Transient tachypnea has an excellent prognosis, with neonates becoming normothermic within 2 to 3 weeks of age. Clipping a long and thick haircoat, using fans in stalls, and removing the animal from direct sunlight may reduce heat stress to the neonate.

Definition and Etiology

Cyanosis is the purple-blue coloration observed on mucous membranes or skin caused by reduced or poorly oxygenated hemoglobin in blood.¹⁷² Causes for this condition include congenital heart disease, respiratory impairment, or any circulatory condition that produces a right-to-left shunt. The degree of cyanosis depends on the arterial oxygen saturation, hemoglobin concentration, pH, peripheral circulation, and temperature of the neonate.¹⁷² Shock and hypothermia are important causes of peripheral cyanosis (see Box 20-4).

Pathophysiology

The affinity of hemoglobin for oxygen is reflected in the standard oxyhemoglobin dissociation curve. This curve is similar for neonates but is affected by the amount of 2,3-diphosphoglycerate (DPG) in the erythrocyte. The foal does not have a fetal hemoglobin but has decreased amounts of 2,3-DPG, which causes oxygen to bind more tightly to hemoglobin and thus to be released in lesser amounts to the tissues.¹⁷³ Severe hypothermia and acidosis cause the oxygen dissociation curve to shift to the right and therefore contribute to tissue hypoxia. Cyanosis can be either central or peripheral.¹⁷² Peripheral cyanosis results from increased peripheral extraction of oxygen from normally saturated blood or a significant decrease in the perfusion to an extremity.¹⁷² In the neonate, causes include septic shock and severe hypothermia. Central cyanosis is more common in neonates and is related to congenital heart disease that causes right-to-left shunting or severe respiratory conditions that result in hypoxia. Paroxysmal atrial fibrillation in three foals with cyanosis shortly after birth is described.¹⁷⁴

Treatment

Examination and clinical pathologic evaluation for metabolic causes of cyanosis, hypothermia, and cardiac abnormalities should be conducted. History, medication use, auscultation, thoracic radiographs, and arterial blood gases are useful in determining the degree of the respiratory component of cyanosis. Therapy for respiratory causes is discussed in the sections on respiratory distress. Electrocardiography and echocardiography may be required for identification of cardiac anomalies. Circulatory compromise caused by hypothermia, hypoglycemia, and shock requires aggressive fluid therapy, respiratory support, and environmental temperature correction.

Definition and Etiology

In the neonate, urination is usually observed within 6 to 10 hours after birth. Frequency of voiding is every few hours. Urine volume produced in the foal is approximately 148 mL/kg/day.¹⁷⁵ Urine specific gravity is low (1.001 to 1.012) because of the high water content of milk. Specific gravity readings of 1.018 to 1.025 are approaching maximum in concentrated urine.¹⁷⁶

The major causes of slow or painful discharge of urine (stranguria) in neonatal foals are ruptured bladder, bacterial cystitis, urachitis, and reduced urine production (oliguria) resulting from reduced renal perfusion. Pollakiuria, dysuria, and cystitis are complications occasionally observed with urachal abscesses.¹⁷⁶

Pathophysiology

Ruptured bladder (see also Chapter 34) occurs most frequently in male foals and is believed to be caused by occlusion of the male urethra during birth, a full bladder, and great pressures during birth when the mare pushes to expel the fetus. Inadequate pressure flow to the kidney producing oliguria may be caused by congenital cardiac anomalies, asphyxia, sepsis, diarrhea, or endotoxemia. Straining from cystitis can be severe and can mimic meconium impaction. Infection of the bladder may be associated with urachal infection. Inappropriate antidiuretic hormone (ADH) secretion occurs in stressed human infants, resulting in decreased urine production and electrolyte abnormalities. During periods of reduced glomerular filtration rate (GFR), drugs excreted by the kidney may accumulate, resulting in toxicity. Inability to excrete a water load associated with excessive fluid therapy may result in fluid accumulation and pulmonary or generalized edema. Uroperitoneum may result in stranguria or oliguria. Postrenal obstruction syndromes are rare in the neonate. Ectopic ulcers have been reported in foals¹⁷⁷ as a cause of incontinence and hydronephrosis. A syndrome of apparent pain on attempting the first urination is observed in some male foals; urinary bladder catheterization for 1 to 3 days may resolve the problem.

Clinical Signs

A carefully obtained history of events of the birth and neonatal period is important. Observation of defecation, posture during urination, frequency, and estimated amounts of urination should be noted. Excessive stretching of the front legs, dorsoventral flexion of the back, and colic may be observed with uroperitoneum. Detection of oliguria requires careful observation or catheterization of the bladder to determine presence of urine and amount of urine production. Free catch of urine and examination for WBCs aid in diagnosis of cystitis.

Azotemic neonates with oliguria have signs of depression, dehydration, poor pulse quality, prolonged capillary refill, reduced jugular distensibility, and retracted eyeballs. Elevated levels of serum urea and creatinine may be observed with uroperitoneum, often with concurrent electrolyte abnormalities of hyponatremia, hyperkalemia, and hypochloremia. If the presence of uroperitoneum is suspected, abdominocentesis should be performed. The fluid can be analyzed for potassium and creatinine and compared with serum values. Urea rapidly equilibrates between abdominal fluid and serum. Peritoneal fluid creatinine levels will be 1.8 to 2 times those of serum with uroperitoneum. A syndrome of high creatinine in newborn foals associated with maternal conditions or events of birth and without renal disease has been reported. Serial creatinine determinations reveal a gradual decline toward normal values over several days. Consequently a single serum creatinine determination should not be used to determine prerenal, renal, or postrenal uremia in the foal.

Treatment

Administration of balanced electrolyte solutions such as lactated Ringer’s solution or saline and determination of urine production are important. Specific electrolyte and acid-base disturbances should be corrected slowly. Prolonged ischemia of the kidneys may result in permanent renal parenchymal damage. Lack of urine production after restoration of fluid balance should be an indication for diuretic therapy with furosemide (0.5 to 2 mg/kg IV) or osmotic diuresis with mannitol (0.25 to 0.5 mg/kg IV over 20 minutes and repeated in 4 hours if no response occurs). If adequate urine production has not developed, administration of dobutamine (2 to 10 g/kg/min) or dopamine (2 to 5 μg/kg/min) may be attempted. Treatment of concurrent sepsis, endotoxemia, hypoproteinemia, respiratory distress, or other abnormality should be attempted. If adequate urine flow is not produced, maintenance levels of fluids should be administered to prevent fluid overload. Body weight determinations three to four times a day help to prevent overhydration by detecting fluid accumulation. Urinalysis and clearance calculations may add further insight to the origin and degree of primary renal involvement. Progressive development of uremia and generalized edema is associated with a poor prognosis. When oliguria is present, serial BUN and creatinine determinations should be performed and urine production monitored. Recumbent neonates may be catheterized and urine production quantitated.

Definition and Etiology

Heart murmurs in the neonate may be heard normally before physiologic closing of the ductus arteriosus during the first 1 to 5 days of life. Other causes of murmurs include congenital anomalies, severe anemia, and infectious valvular disease.

Clinical Signs and Differential Diagnosis

Physical examination for other signs of heart disease helps determine the severity of the murmur. Jugular pulse, weak or irregular arterial pulse, and palpable thrill indicate a serious condition. Signs of weakness, cyanosis, and tachypnea are indications of poor cardiac performance. Timing and location of the heart murmur should be determined. The electrocardiogram (ECG) may reveal atrial or ventricular enlargement. Thoracic radiography may aid in determining heart size and in detecting pulmonary edema or distended pulmonary vessels. Echocardiography may reveal atrial or ventricular enlargement, thickened ventricular walls, anomalous orientations of outflow tracts, or ventricular septal defects (VSDs).¹⁷⁸

Patent ductus arteriosus (PDA) produces a continuous murmur localized over the left heart base.¹⁷⁹ The diastolic component may not be heard with auscultation over other parts of the heart. As pulmonary hypertension develops, the murmur is shortened to a holosystolic type with normal arterial pulse. Large shunting of blood produces a bounding arterial pulse caused by wide fluctuations of systolic and diastolic pressures.¹⁷⁹ The ECG is normal unless atrial enlargement is present and increasing QRS amplitudes are observed.¹⁷⁸ Radiographs may reveal an enlarged heart with increased vascularity caused by left-to-right shunting of blood. Echocardiography may reveal an increased left atrial and left ventricular diastolic dimension or volume and hyperdynamic septal and left ventricular wall systolic motion (depending on the degree of right-to-left shunt).¹⁷⁸ Catheterization and angiography may further delineate the degree of shunting.¹⁸⁰ Recent studies have indicated the ductus architecture changes days before birth, which prepares the ductus for closure. Triggering factors for closure include increased blood oxygenation and lower pressures resulting from vasodilation of pulmonary vasculature at birth.

VSD produces a large, harsh, holosystolic murmur that is loudest on the right cranial region of the thorax and is softer over the left heart base.¹⁸¹ The ECG may be normal or may show increased amplitude of the QRS, with larger shunts and alterations in chamber size. Radiography may reveal heart size increase, left atrial enlargement, and dilated pulmonary vasculature.¹⁷⁸ Two-dimensional echocardiography may show aortic and septal discontinuity.¹⁷⁸ Injection of saline bubbles into the left ventricle and observation of bubbles in the right atrium or ventricle document a left-to-right shunting of blood.¹⁷⁸ Tetralogy of Fallot or other types of complex malformations often produce loud murmurs and are associated with cyanosis, weakness, fatigue, and stunted growth.¹⁸² Tetralogy of Fallot produces a systolic ejection murmur heard at the left heart base.¹⁷⁸ Electrocardiography may reveal negative QRS complexes in leads I, II, and aVF, suggesting right ventricular hypertrophy.¹⁷⁸ Echocardiography may reveal a thickened right ventricular wall, septal echo dropout in the area of the VSD, rightward displacement of the aortic root, and an abnormal pulmonary outflow region.¹⁷⁸ Saline injection into the jugular vein demonstrates right-to-left flow from the right ventricle to the left ventricle or the aorta.

Treatment

PDA has been treated by chemical closure using indomethacin in human neonates, but it has not been used in veterinary medicine.¹⁸³ Other global antiprostaglandins, including flunixin meglumine, have been used in attempts to assist with chemical closure of the ductus arteriosus in foals. The efficacy of this procedure has not been determined. Minimal fluid administration is also suggested to be of assistance. VSDs may pose few problems if the degree of shunting is small. Other complex cardiac anomalies producing murmurs may be treated symptomatically for a short time, but the long-term prognosis is extremely poor.