key: cord-0040385-9cxrixcx
authors: McConnico, Rebecca S.
title: Acute Colitis in Horses
date: 2014-06-25
journal: Robinson's Current Therapy in Equine Medicine
DOI: 10.1016/b978-1-4557-4555-5.00068-6
sha: c45b1ec9c49a3f4d2877bfcff0d3571592be9edb
doc_id: 40385
cord_uid: 9cxrixcx

nan

A cute colitis is a common cause of rapid debilitation and death in horses. More than 90% of untreated horses with this condition die or are euthanized, but horses that are treated appropriately usually respond and gradually recover over a 7-to 14-day period. Colitis-associated diarrhea is sporadic in occurrence and is characterized by intraluminal sequestration of fluid, moderate to severe colic, and profuse watery diarrhea, with resultant endotoxemia, leukopenia, and hypovolemia. The condition can affect adult horses of all ages but usually affects horses 2 to 10 years of age. Disease onset is sudden, and progression is rapid. The condition is often preceded by a stressful event. A definitive diagnosis is made in only about 20% of cases. Most antemortem and postmortem tests to determine etiology do not yield a definitive diagnosis.

Treatment of colitis can be extremely costly because of the substantial volumes of intravenous replacement fluids required. At present, there is no curative treatment, and treatment strategies are directed at rehydration, electrolyte and plasma protein replacement, prevention or amelioration of the effects of endotoxemia, provision of nutritional support, and administration of antimicrobials when indicated.

Diarrhea associated with acute colitis is a result of abnormal fluid and ion transport by cecal and colonic mucosa, with fluid loss resulting from a combination of both malabsorption and hypersecretory processes. Under normal conditions, water and electrolytes are secreted by epithelial cells in the intestinal crypts, and most of this fluid is reabsorbed by the surface epithelial cells. Abnormal rates of secretion and absorption result in massive secretion and malabsorption by large intestinal mucosal epithelial cells, leading to severe dehydration and death.

Acute colitis is a general term referring to inflammation of the cecum (typhlitis), colon (colitis), or both (typhlocolitis), with subsequent rapid onset of diarrhea in the adult horse. In contrast to other domestic animals and humans, horses have sudden, massive fluid loss and severe electrolyte imbalances that can result in death in hours. This distinctive clinical presentation in horses may result from several unique features of the large bowel of Equidae. Some of these include the large population of gram-negative endotoxin-bearing bacteria that reside in the large intestine and the markedly high mucosal prostaglandin concentrations, manifested by a marked chloride secretory response, compared with other species. Another possible reason for the distinctive clinical signs is the intense inflammation that results from activation of resident intestinal mucosal and submucosal phagocytic granulocytes by intestinal bacterial products after mucosal barrier disruption.

The causes of acute colitis are reviewed in the fourth edition of Current Therapy in Equine Medicine, (pp 197 to 203).

There is some agreement that certain distinctive clinical, pathologic, or diagnostic characteristics may help in differentiating between specific acute colitis-associated conditions (Table 68 -1). Regardless of the initiating cause, common clinical and pathologic features suggest a common pathophysiologic pathway. Typical hematologic findings include hypovolemia, dehydration, metabolic acidemia, electrolyte derangements, leukopenia with a left shift, toxic neutrophils, lymphopenia, and azotemia. Clinical features include depression, inappetence, fever, tachycardia, dry mucous membranes, skin tenting, prolonged capillary refill time, colic, and watery, often fetid, diarrhea.

Gross necropsy findings usually reveal edematous, sometimes hemorrhagic, typhlitis-colitis with intraluminal sequestration of fluid ingesta (Figure 68 -1). Common microscopic abnormalities include superficial mucosal injury affecting the distal portion of the ileum and the cecum and large colon. Injury is characterized by mucosal epithelial ulceration and erosion, mucosal and submucosal edema, and various degrees of mucosal inflammation. These lesions may enhance net fluid movement into the intestinal lumen by decreasing net solute absorption, increasing mucosal permeability, and stimulating prostaglandin-mediated ion secretion. Disrupted epithelium allows transmural migration of endotoxin.

In horses with impending colitis, lethargy, inappetence, and colic are frequently noticed several hours before the appearance of liquid feces. Physical examination during this early period may reveal high respiratory and heart rates secondary to abdominal discomfort from intraluminal sequestration of fluid or gas, or secondary to inflammatory mediator activity. Rectal temperature may also be high as a result of the inflammatory response to toxin absorption through a disrupted intestinal mucosal barrier. Signs of abdominal discomfort can range from mild, such as recumbency or inappetence, to severe, with the horse rolling and thrashing. Abdominal distension is often evident. These cases may be confused with other large bowel disorders, such as large colon torsion.

Acute equine colitis should be considered a potentially life-threatening emergency, and early evaluation and treatment by a veterinarian are critical. Horses with sudden onset of colitis will sequester a large volume of fluid intraluminally and begin to pass the liquid material within several hours. The volume of fluid lost from the intestinal tract can equal the horse's entire extracellular fluid volume; hence, signs of dehydration and hypovolemia may be severe. Mucous membranes may be brick colored and sticky, capillary refill time is prolonged, and skin turgor is reduced. Progressively severe hypovolemia and subsequent circulatory shock lead to purple mucous membranes and a weak peripheral pulse. Horses with acute colitis are prone to laminitis and may develop Acute Colitis in Horses signs of this additionally life-threatening complication (e.g., lameness, bounding digital pulses, high hoof temperature) any time during the course of disease.

Assessment of data from the horse's blood tests is important for determining the degree of systemic illness and plasma volume replacement needs. Packed cell volume (PCV) and total plasma protein (TPP) values are often high initially and indicate the severity of dehydration. Total protein values that are in or below reference range in a clinically dehydrated horse with a high PCV indicate overall protein loss. Daily PCV and TPP assessment is useful for monitoring daily fluid and protein needs.

Total and differential white blood cell (WBC) counts usually reveal neutropenia with a left shift, and granulocytes often have toxic morphologic changes, including cytoplasmic vacuolation, basophilia, "toxic" granule formation, and Döhle bodies. Signs of overall improvement usually correlate with a decrease in abnormal WBC features, including morphologic changes. Horses in the later stages of acute colitis may have high fibrinogen concentration and neutrophilic leukocytosis, indicating a generalized inflammatory response. Horses with colitis usually have metabolic acidemia; electrolyte derangements including hyponatremia, hypochloremia, hypocapnia, hypokalemia, and hypocalcemia; and azotemia.

Patient history is extremely useful for determining the possible causes of acute colitis, especially if it includes treatment with drugs such as nonsteroidal antiinflammatory drugs (NSAIDs), antimicrobials, or anthelmintics; changes in diet; inadequate deworming history; or a stressful event. It is important to rule out Salmonella spp-associated colitis because these organisms pose a risk for infection to other animals and constitute a potential zoonotic hazard. Because Salmonella organisms are often shed intermittently, five consecutive fecal samples (weighing 5 g or more) for culture and sensitivity or three consecutive fecal samples for polymerase chain reaction (PCR), 1 collected at 24-hour intervals, should be submitted. Neorickettsia risticii, the causative agent of Potomac horse fever, causes biphasic fever, laminitis, and colitis of variable severity. The disease is widespread in many parts of the United States, especially California and the mid-Atlantic states, and in Canada and Europe, with the highest prevalence of disease observed in horses residing in proximity to freshwater ponds and streams. In temperate climates, disease is most common during late spring through early fall. The diagnosis of N risticii-associated colitis may be supported by comparing paired serum titers using immunofluorescence assay testing 2 techniques, but diagnosis is confirmed using antigen detection by (1) identification of N risticii morulae in WBCs during the acute phase of the disease, (2) isolation of the organism from WBCs, or (3) PCR testing of WBCs or feces.

Clostridium difficile has been implicated as a cause of acute colitis in horses treated with antimicrobials, in mares with foals undergoing treatment for Rhodococcus equi pneumonia, and in untreated horses with diarrhea. Commercially available cytotoxin assays for C difficile toxin (A and B) 3 and cytotoxin genes can be used to diagnose C difficile-associated diarrhea. These tests are based on enzyme-linked immunosorbent assay or PCR technology. At least 5 g of feces should be submitted immediately after collection or transported frozen or on ice in airtight containers.

Mounting evidence indicates that equine coronavirus can be a cause of acute equine colitis, and fecal PCR for equine coronavirus should be included in the screening process.

Intestinal parasites, especially encysted cyathostomes, may play a role in causing acute colitis, although more effective deworming products and practices have made this less of a concern. Development of resistance to available anthelmintic products by some intestinal parasites prohibits clinicians from entirely ruling out this cause. Although fecal egg counts are useful in determining the role of parasites, immature encysted larvae can still be causing intestinal inflammation even if fecal egg counts are very low.

Investigators recently have begun to study the microbiome of horses with and without colitis. These investigations suggest that colitis may be a disease of dysbiosis, rather than one that occurs simply through overgrowth of an individual pathogen.

Care of the horse with acute colitis is aimed at restoring plasma volume, providing analgesia, reducing inflammation, blocking the effects of endotoxin and microbes, and supporting patient nutrition.

Intravenous polyionic fluids 4 should be administered at a volume based on total fluid deficit calculated from the clinical assessment of dehydration (e.g., for 8% or moderate dehydration, the calculated volume deficit would be 0.08 × 450 kg body weight = 36 L). This fluid deficit should be replaced rapidly (up to 6 to 10 L per hour in a 450-kg adult horse). After plasma volume has been restored and the horse is well hydrated, the volume of fluids administered can be adjusted but may still be as high as 120 mL/kg daily, depending on ongoing losses. In emergency situations, blood volume can be rapidly expanded and cardiac output increased by intravenous administration of a small volume of hypertonic saline (1 to 2 L of 7% saline). The resulting increase in blood tonicity causes fluid to move rapidly from the extracellular fluid space into the vascular compartment, which improves microcirculatory perfusion and helps prevent complications such as sepsis and multiple-system organ failure. Hypertonic saline administration also has immunomodulatory effects, antiinflammatory effects, and cardiac inotropic effects. Whereas polyionic crystalloids induce only a modest increase in intravascular volume and quickly leave the intravascular space for the interstitium, hypertonic saline increases plasma volume by three to four times the volume administered, and this volume expansion may last for up to 60 minutes. However, it is important to remember that hypertonic saline does not replace the fluid lost in the diarrhea. For this reason, a large volume of balanced polyionic fluid solution should be administered intravenously (at least 2 L per hour) after the hypertonic saline has been administered, until the hydration deficit has been corrected.

Many horses with colitis-associated dehydration and electrolyte imbalances voluntarily consume various types of electrolyte supplements. In addition to offering a fresh clean-water source, offering mixtures of electrolytes in water in a separate pail may be beneficial. Mixtures to consider include (1) water with baking soda (10 g/L), (2) water with NaCl-KCl (i.e., Lite salt; 6 to 10 g/L), and (3) water mixed with a commercial electrolyte solution.

Decreased colloid oncotic pressure leads to decreased effective circulating fluid volume and tissue edema. In horses with acute colitis, total plasma protein may decline to 2 to 3 g/ dL, and albumin concentration may decrease to less than 2.0 g/dL. Intravenous administration of plasma or a combination of plasma and synthetic colloid 5 should be considered as soon as there is evidence of a consistent decline in total plasma protein concentration, if the concentration of albumin is less than 2.0 g/dL, or the horse develops dependent edema.

A 450-kg horse requires 6 to 10 L of plasma or synthetic colloid to improve plasma oncotic pressure. Fresh or fresh frozen plasma is ideal. In addition to albumin, which is the major colloidal component in blood, plasma contains other components that provide systemic support, including fibronectins, complement inhibitors, elastase and proteinase inhibitors, and antithrombin III.

Hetastarch (6%) may be administered at a dosage of 5 to 10 mL/kg. Because of the large size of the starch molecules, this solution is an effective plasma volume expander and results in sustained dose-dependent decreases in PCV and plasma protein concentration accompanied by increased oncotic pressure. Administration of a combination of hetastarch and plasma is more effective for resuscitation in emergency situations in which clinical signs suggest severe hypovolemic shock (6 to 10 L of total colloid solution per 450-kg standard sized adult horse).

Horses with acute colitis absorb large quantities of endotoxin across the disrupted intestinal mucosal barrier, putting them at high risk for developing laminitis, thrombophlebitis, and NSAIDs against the possibility of further bowel damage induced by blocking the protective effects of intestinal mucosal prostaglandins. Endogenous prostaglandins are important inhibitors of intestinal inflammation, and blocking these agents with nonselective NSAIDs may slow recovery and healing of inflamed intestinal mucosa. An alternative potential analgesic combination that has minimal effects on gastrointestinal motility is butorphanol (0.06 to 0.1 mg/kg, IM) with detomidine (0.01 to 0.02 mg/kg, IM), administered every 6 to 8 hours. Alternatively, a constant butorphanol infusion (13 µg/kg per hour, IV) can be conveniently administered by adding 15 mg butorphanol to 5 L of lactated Ringer's solution or other crystalloid, and infusing at a rate of 2 L per hour to a 450-kg horse.

In horses for which geographic risk, clinical and clinicopathologic data, or organism identification creates high suspicion of N risticii-associated colitis, treatment with oxytetracycline (6 to 10 mg/kg, IV, every 12 hours) can be effective. Intravenous broad-spectrum antimicrobials should be used judiciously in horses with acute colitis of unknown etiology and are not always indicated. Mild and transient neutropenia or fever may not justify the use of broadspectrum antimicrobials, but these agents should be considered when the horse has profound or persistent neutropenia and is at risk for complications associated with sepsis, such as peritonitis, pneumonia, cellulitis, thrombophlebitis, and disseminated intravascular coagulation. Potassium penicillin G (22,000 IU/kg, slow IV, every 6 hours) in combination with gentamicin (4.4 to 6.6 mg/kg, IV or IM, every 24 hours) is a commonly used treatment regimen in horses with ongoing systemic disease. Oral broad-spectrum antimicrobial medications are not recommended because of the potential for further disruption of the intestinal microbial population. Orally administered metronidazole (10 to 15 mg/kg, every 8 hours) may be indicated in horses in which Clostridium spp are suspected to play a pathogenic role in the disease. The latter drug may have local antiinflammatory effects and can cause loss of appetite in some horses.

Effective antisecretory medications targeting the large colon in horses have not been identified. It is unlikely that bismuth subsalicylate or similar protectant agents are effective for treating large bowel diarrhea in adult horses because of the large volume of large intestine contents. Di-tri-octahedral smectite adsorbs substances such as endotoxins and exotoxins and binds equine-origin C difficile toxins A and B and C perfringens enterotoxin. This natural hydrated aluminomagnesium silicate is used with the same rationale as activated charcoal, a universal enteral adsorbent. Smectite should be administered early at a dose of 0.5 kg; the powder is mixed with water and administered through a nasogastric tube. The loading dose should be followed by doses of 0.25 to 0.5 kg given every 6 to 12 hours.

Most horses with acute colitis are partially or completely inappetent and lose protein as a consequence of cachexia and protein-losing enteropathy. Partial or total parenteral nutrition may be indicated in horses that remain inappetent for more than 3 to 4 days. Horses with colitis often have some appetite and should be encouraged to continue eating good-quality hay, fresh green grass, and highly digestible disseminated intravascular coagulation. Digital pulses should be monitored three or four times daily until systemic signs of colitis abate. Along with intravenous fluids and general supportive care measures, treatment specifically aimed at combatting endotoxemia is crucial for patient survival.

The primary target areas for managing and treating endotoxemia in horses with acute colitis include (1) neutralization of endotoxin before it interacts with inflammatory cells;

(2) prevention of the synthesis, release, or action of mediator activity; and (3) general supportive care measures.

Endoserum 6 is hyperimmune serum obtained from horses vaccinated against Salmonella typhimurium Re mutant (1.5 mL/kg, IV, diluted 1 : 10 or 1 : 20 in sterile isotonic saline or lactated Ringer's solution). Dilution at this ratio is recommended to minimize the risk for immune-mediated hypersensitivity reactions. Polymyxin B (1000 to 6000 IU/kg, IV, every 8 to 12 hours for up to 3 days) binds and neutralizes endotoxin at the lipid A region of the endotoxin molecule. Because of the potential for nephrotoxic effects, polymyxin B should be used judiciously, and its use in azotemic horses is not recommended.

Low-dose administration of flunixin meglumine (0.25 mg/ kg, IV, every 6 to 8 hours) is recommended to prevent endotoxin-induced prostanoid synthesis in horses. Compared with other regimens involving NSAIDs, flunixin meglumine has a lower risk for adverse effects, including gastrointestinal ulceration, ileus, and renal papillary necrosis. The cyclooxygenase-2 inhibitor drug firocoxib has fewer adverse effects and can be used as an alternative to the nonselective NSAIDs. Administration of corticosteroids inhibits arachidonic acid pathway mediator activity in vitro, but clinical use of these drugs may be associated with increased risk for laminitis. A single dose of short-acting corticosteroid (e.g., prednisolone sodium succinate at 1 mg/kg, IV) may be helpful during the acute stage of endotoxemia without increasing the risk for laminitis.

Administration of dimethylsulfoxide (0.1 g/kg, IV, as a solution of 10% or less) may be useful in blocking lipid peroxidation. Higher doses have been associated with exacerbation of intestinal reperfusion injury in horses. Allopurinol (5 mg/kg, IV) also has been administered to block lipid peroxidation. Pentoxifylline (8 mg/kg, PO or IV [as sterile powder given diluted in fluids], every 8 hours), a phosphodiesterase inhibitor, may be useful in horses that are at risk for developing laminitis because it blocks endotoxin-induced cytokine, thromboxane, and thromboplastin production.

Nonsteroidal antiinflammatory drugs are the most frequently used group of drugs for treating abdominal pain in horses. Typical drugs used include flunixin meglumine (1.1 mg/kg, IV, every 12 hours) and phenylbutazone (2.2 mg/kg, IV, every 12 hours); because phenylbutazone may contribute to further damage of the intestinal epithelial barrier, lower and less frequent doses should be considered. The selective cyclooxygenase-2 inhibitor firocoxib is safer in horses and has similar beneficial antiinflammatory effects; its use should be considered in lieu of nonselective NSAIDs. Veterinarians must weigh the beneficial analgesic effects of nonselective 6 Endoserum, Immvac, Inc., Columbia, MO.

12% to 14% protein concentrate feeds. Horses that continue to eat usually have a better chance of recovery.

Probiotic administration may be useful in restoring colonization resistance in the colon, which is disrupted with antimicrobial-induced C difficile-associated colitis. Adverse effects may arise when unapproved products are used. Veterinarians must educate themselves and their clients in methods of safe practice by using safe and approved equine biotherapeutic products. Transfaunation with fecal liquor from a healthy horse has been used, but it is extremely important to confirm disease-free status in the donor horse because salmonellosis has been transmitted by this route and results of this procedure are equivocal with regard to benefit to the patient.

Rapid institution of appropriate treatment measures improves the prognosis for horses with acute colitis. However, affected horses can deteriorate rapidly, even in the face of aggressive medical treatment. Horses that continue to have frequent, profuse, watery diarrhea and ongoing systemic signs of endotoxemia and septicemia have a poorer prognosis for recovery. Diarrheic horses that are azotemic and have clinicopathologic findings consistent with ongoing hemoconcentration and hypoproteinemia also have a poor prognosis for survival. Antimicrobial administration may induce diarrhea, and horses with antimicrobial-associated diarrhea may have a worse prognosis than those with other types of acute diarrhea. Frequent complications of acute equine colitis include laminitis, thrombophlebitis, debilitation, and marked weight loss.

Characteristics and risk factors for failure of horses with acute diarrhea to survive: 122 cases (1990-1996)

Comparison of the fecal microbiota of healthy horses and horses with colitis by high throughput sequencing of the V3-V5 region of the 16S rRNA gene

Enteritis and colitis in horses

Physicochemical interpretation of acid-base abnormalities in 54 adult horses with acute severe colitis and diarrhea

The effect of nonsteroidal antiinflammatory drugs on the equine intestine

Pathophysiologic effects of phenylbutazone on the right dorsal colon in horses

Antimicrobial therapy for gastrointestinal diseases

Emerging outbreaks associated with equine coronavirus in adult horses

Role of nonsteroidal antiinflammatory drugs in gastrointestinal tract injury and repair