Pathogenesis

Cantharidin is the toxic principle found in beetles of the genus Epicauta, commonly known as blister beetles.^777-779 Ingestion of the beetles in contaminated alfalfa hay results in absorption of cantharidin through the gastrointestinal tract. Blister beetles feed on the flowers of alfalfa and are incorporated into baled alfalfa hay if the hay is cut and processed simultaneously.^777-779 Large swarms of beetles may be found in relatively small portions of hay. The lethal dose of cantharidin is less than 1 mg/kg, but the concentration of cantharidin varies from species to species of blister beetles.^777,778 Therefore as many as 100 to as few as six to eight beetles may be lethal. Often more than one horse will be affected. The fatality rate may be 50% or greater.^777,780

Cantharidin is a potent irritant, causing cell damage and necrosis on contact.^777,779,780 The mucosa of the gastrointestinal tract is most commonly affected in horses because they ingest the toxin. Ulceration throughout the alimentary tract has been observed in natural and experimental cantharidin toxicity. Diarrhea probably results from the severe ulceration and inflammation of the large intestine, causing increased secretion of water, electrolytes, and protein. Large volumes of fluid and protein are lost in the gastrointestinal tract, causing hemoconcentration and profound hypoalbuminemia in some cases.^777,778,780 Cystitis, nephrosis, and myocarditis occur in natural and experimentally produced cases of cantharidin toxicity.^777,779,780 Cystitis and nephrosis occurs from the high concentration of cantharidin in the urine. The cause of the myocarditis and myocardial necrosis is unknown, but they may also be direct effects of the toxin on the myocardium. Elevated plasma CK activity is often observed and has been postulated to arise from the damaged myocardium.^777,778 Horses have a characteristically stiff gait, but histopathologic evidence of skeletal muscle injury that explains the elevated plasma CK activity has not been observed.⁷⁷⁸ Hypocalcemia and hypomagnesemia are characteristic features of cantharidin toxicity in horses that have not been explained.^777,778,780 Hypocalcemia may occur from hypoalbuminemia, but the ionized calcium concentration is often decreased, along with the total calcium concentration, indicating that hypoalbuminemia is not responsible for the hypocalcemia.⁷⁷⁸

ANTIMICROBIAL-ASSOCIATED DIARRHEA

The onset of acute diarrhea in the horse has been associated with the use of several antimicrobial drugs. Lincomycin administered orally and tetracycline administered parenterally have been demonstrated to induce severe diarrhea in horses.^782,783 The oral administration of TMS, erythromycin, metronidazole, and penicillin and parenteral administration of ceftiofur have been implicated with onset of diarrhea, including fatal colitis, in horses. In one report there was no association between TMS and diarrhea.⁷⁸⁴ However, in other reports, prior administration of antimicrobial drugs was positively associated with onset of colitis and negatively associated with prognosis for survival in horses with colitis.⁷⁸⁵

Antimicrobial-associated diarrhea is presumed to be secondary to disruption of normal colonic microflora and the proliferation of an enteropathogen, such as Salmonella species, C. perfringens, and C. difficile. Of interest, it was reported that mares whose foals were treated with erythromycin for Rhodococcus infection developed severe, acute colitis, from which C. difficile and its toxins were isolated.⁷⁸⁶ The mares had erythromycin detected in their feces, and exposure to the erythromycin was presumed to have occurred by the mares licking erythromycin from the foals’ faces.

OTHER CAUSES OF ACUTE DIARRHEA

NSAID toxicity (see p. 754) has been associated with diarrhea secondary to damage to the colonic mucosa. Grain (carbohydrate) overload may cause acute diarrhea resulting from overproduction of lactate in the colon. A combination of hyperosmolarity of the luminal contents and damage to the colonic mucosa account for the pathophysiology of grain overload. The clinical signs are similar to those of other acute diarrheal diseases in horses and depend on the severity of the overload. Hyperlactemia, metabolic acidosis, and sepsis are key features of grain overload, and laminitis is a common sequela. Acute diarrhea in the adult horse has also been associated with conditions such as lymphosarcoma enterocolitis and other IBDs, intestinal lymphosarcoma, peritonitis, heavy metal intoxication, anaphylaxis, and stress.

CLINICAL ASSESSMENTS IN ACUTE DIARRHEA PATIENTS

The diagnostic evaluations performed on horses with acute diarrhea are intended to provide the clinician with information to accurately assess the horse’s condition and thus direct therapy toward specific requirements. The first part of the evaluation is a thorough physical examination, with particular attention paid to the horse’s hydration status (skin turgor, gum moisture, capillary refill time), evidence of sepsis (fever or hypothermia, hyperemic mucous membranes, prolonged capillary refill time), cardiovascular system (heart rate and rhythm, character of peripheral pulse, capillary refill time), and signs of laminitis (lameness, digital pulse, palpable temperature of hoof walls). Horses with colitis are often moderately to severely dehydrated, with either purplish or brick-red mucous membranes. Purple mucous membrane color reflects venous congestion and poor venous return, whereas brick-red membrane color reflects venous congestion and poor venous return plus arteriole and venule shunting and poor tissue oxygen exchange.

Blood pressure should be monitored, and whereas direct measurements via an arterial catheter are most accurate, indirect pressure measurements obtained using a Doppler transducer placed over the coccygeal artery are satisfactory. Hypotension and hypertension each occur in horses with colitis, and the blood pressure status of a patient often is unpredictable. Blood pressure can be monitored as frequently as labor permits and should be done hourly if vasoactive pharmaceutical agents are used.

Laboratory tests that should be performed include CBC and plasma protein and total solids. Total hemoglobin and PCV are used to assess hydration status. Total protein is used to assess hydration status and degree of protein loss through inflamed intestinal mucosa, and in more chronic cases through protein catabolism. Comparison of clinical hydration, PCV, and total protein is useful in determining the extent of protein loss, and daily evaluations can be used to determine the rate of protein loss. Colloid oncotic pressure measurements are useful, particularly if colloidal fluids other than plasma are given.

Total WBC count, WBC differential, and WBC morphology are used to assess severity of sepsis; plasma fibrinogen is used to assess the severity of inflammation. Typically the total WBC and neutrophil counts decrease initially. This is primarily attributable to bacterial endotoxins and the host’s mediators of systemic inflammation and occurs in most cases of acute colitis, not just in those caused by Salmonella species. The morphology of the WBCs reflects the severity of the inflammatory response. “Toxic” changes such as basophilia, granulation, vacuolation of the cytoplasm, and scalloped borders of the cell membrane or adherence of neutrophils to RBCs do not reflect injury to the neutrophils by toxins but reflect the cells’ responses to stimulation by proinflammatory agents (TNF, IL-1) and the production of inflammatory mediators by the neutrophils that are toxic to bacteria. The degree of these changes in circulating neutrophils can be used to assess the severity of disease and also to assess the progress the horse is making. Often the initial sign that the horse is improving is a decrease in the “toxic” appearance to the neutrophils and a regenerative neutrophil response. A horse that continues to have severe neutropenia with a degenerating left shift or neutrophils, with cytoplasmic vacuolation, granulation, and basophilia, for more than 10 days has severe colitis that is unlikely to resolve.

Serum chemistry tests that should be performed include electrolytes (sodium, chloride, potassium, and calcium), BUN and creatinine, blood lactate concentration, and assessment of acid-base status (blood pH and bicarbonate, or total CO₂). Horses with diarrhea often are hyponatremic, hypochloremic, and hypokalemic. With decreased feed intake, hypocalcemia occurs. A high gap metabolic acidosis with hyperlactemia may be noted, particularly in horses with sepsis. The severity of these electrolyte disturbances should be monitored, often daily, to allow for appropriate therapy. Parameters that assess renal function, BUN and creatinine, are frequently increased in horses with diarrhea for several reasons. Prerenal azotemia resulting from dehydration and decreased filtration across the glomerulus accounts for some of the increase in these parameters. Hyponatremia and hypochloremia can cause a decrease in glomerular filtration and an increase in BUN and creatinine secondary to tubuloglomerular feedback. Horses that are adequately hydrated yet moderately hyponatremic (serum sodium 120 to 128 mEq/L) often remain azotemic until sodium levels increase above 130 mEq/L. In addition, horses with toxemic colitis often have damage to renal parenchyma, presumably the result of the effects of inflammatory mediators and alterations in renal blood flow.

The acid-base status can be evaluated by estimating serum bicarbonate on the basis of the total CO₂ or directly from a venous or arterial blood gas analysis. Evaluation of a venous blood gas sample is useful in assessing perfusion and oxygen extraction. An increased venous oxygen partial pressure (>60 mm Hg) is indicative of poor capillary perfusion and oxygen delivery to the tissues. Affected horses usually have brick-red mucous membranes.

PRINCIPLES OF THERAPY FOR ACUTE DIARRHEA

Because the pathophysiology of equine colitis is complex, treatment is often multifaceted. Many of these treatments provide well-documented benefit, whereas with others the efficacy is based on empiric judgment only. Outcome is determined not only by the severity of the primary disease causing colitis but also by complications that may arise from the disease.

In cases of acute colitis, fluid administration remains the treatment of primary importance. Most patients require intravenous administration in the early stages. The fluids used must replace fluid, sodium, chloride, and potassium losses. Often, large volumes are required for several days. More specific guidelines for fluid therapy in colitis patients are covered in the Fluid Therapy for Horses with Gastrointestinal Diseases section (p. 767) and in Chapter 44.

Most horses with colitis become hypoproteinemic secondary to protein leakage through the inflamed colon and catabolism of albumin secondary to negative energy balance. Hypoproteinemia frequently leads to edema formation in several areas of the body, including the intestinal tract, and can compromise the clinician’s ability to keep the patient properly hydrated through fluid administration. Intravenous plasma therapy is often beneficial. Plasma, 3 to 10 L, should be given IV. Other colloidal fluids may be more cost-effective for increasing colloidal oncotic pressures in hypoproteinemic horses but do not have the additional properties of plasma that may be beneficial.

Plasma contains proteins besides albumin and therefore can be of benefit beyond improvement of plasma oncotic pressure. The immunoglobulin present in plasma is of recognized benefit in the treatment of failure of passive transfer in foals. The role of nonspecific immunoglobulin in the treatment of colitis is not known. Fibronectin is essential to the normal function of the monocyte-macrophage system in the processing of a variety of antigens. Other plasma proteins such as elastase and proteinase inhibitors, complement inhibitors, AT-III, and other inhibitors of hypercoagulability may be beneficial to colitis patients.

The nutritional requirements of the colitis patient need to be considered, particularly in a case that may be protracted. Horses with colitis are typically anorectic, and the disruption of normal physiologic processes in the inflamed cecum and colon limits the effectiveness of these organs in the digestion and absorption of nutrients. In addition, several mediators of inflammation and septicemia alter protein and calorie metabolism, resulting in a catabolic state. Therefore even if the horse eats, it is likely to be in a severe caloric deficit for some time. Normally an average horse requires approximately 15 Mcal/day. An endotoxemic horse may require 25 Mcal/day. In a catabolic patient, muscle and fat tissue are mobilized and used in lieu of ingested nutrients. The plasma protein pool, including albumin and immunoglobulins, also is catabolized. In many cases of colitis the decrease in plasma protein may be as much a result of catabolism as of leakage through the inflamed colon. A variety of products can be used for enteral feeding (see Chapter 50).

Colitis is an inflammatory disease, and limiting inflammation is desirable when treating patients, particularly those with severe disease. Moreover, horses with acute colitis, regardless of the cause, have signs compatible with systemic inflammation associated with sepsis. Flunixin (0.25 to 0.5 mg/kg q6–8h) is the most commonly used antiinflammatory therapy in horses with colitis. However, the use of flunixin should be judicious and must be carefully monitored to avoid unwanted side effects on the gut mucosa and kidneys (see p. 754). Other antiinflammatory therapies, such as lidocaine controlled rate infusions, may also be beneficial.

Sepsis is a common clinical feature in horses with acute colitis. Most of the clinical signs of sepsis are likely attributable to the effects of endotoxin. Therefore specific therapy for endotoxemia may be warranted (see p. 719).

The use of antimicrobial drugs in the treatment of colitis is controversial. In cases of colitis caused by N. risticii, the efficacy of tetracycline, 6.6 to 11 mg/kg IV once or twice daily, is documented clinically and experimentally. In other cases of colitis, including Salmonella colitis, in which specific antimicrobial sensitivities to the Salmonella species have been established, the efficacy of antimicrobial administration is less well documented. Many clinicians believe that the use of an antimicrobial for which the Salmonella species have demonstrated sensitivity, such as chloramphenicol, enrofloxacin, gentamicin, amikacin, or a third-generation cephalosporin, does not significantly alter the course of the disease or hasten the elimination of the organism from the body. However, there is no published evidence either supporting or not supporting the efficacy of antimicrobial treatment for salmonellosis, and the use of antibiotic therapy remains a judgment of the clinician. In patients with sepsis the use of broad-spectrum antibiotics is justified to prevent bacteremia or organ colonization by Salmonella species or other enteric organisms.

Medications that minimize or abolish colonic fluid secretion would be of tremendous benefit in the treatment of equine colitis. Medications such as kaolin, bismuth subsalicylate, and activated charcoal are frequently used in cases of colitis in adult horses, but their efficacy as antisecretory agents in this context has not been established. These medications are more effective in foals with diarrhea, probably as a result of an effect on the small intestine rather than the colon. Absorbent powders such as activated charcoal or DTO smectite (Biosponge) may be useful to absorb bacterial toxins, particularly in horses with clostridiosis.

Cecal Impaction

Cecal impaction may develop as a primary condition or may arise as a complication in hospitalized horses, particularly those that have undergone surgery.⁷⁹⁸ Reasons for development of cecal impaction in hospitalized horses are unclear, although motility disturbances arising from postoperative pain may play a role. Cecal impactions may occur as one of two types: impaction of the cecum with firm ingesta or gross distention of the cecum with fluid ingesta. The latter has been termed cecal dysfunction and may be initiated by abnormalities in cecal motility. Evidence in favor of this supposition includes the fact that the right ventral colon is typically empty in horses with cecal dysfunction, suggesting a lack of aborad movement of digesta through the cecocolic orifice. However, clinical differentiation of cecal impaction and cecal dysfunction may be very difficult.⁷⁹⁹ Horses with dry-ingesta—filled cecal impactions tend to be presented with the condition as the primary complaint, and there is often a gradual onset of abdominal pain over a number of days. Such impactions have a propensity to rupture before the development of severe abdominal pain or systemic deterioration and therefore must be closely monitored. In horses with cecal dysfunction, there is frequently an association with surgery, particularly orthopedic surgery. For horses that develop this condition in the postoperative period, it is often very difficult to detect because there is an expectation for horses to show some degree of depression after surgery and because horses are often already on analgesics such as NSAIDs or opiates. The simplest method to detect these cases is to closely monitor fecal output in the postoperative period.⁸⁰⁰ A normal horse should produce six to eight piles of manure per day, whereas an abnormal horse may have no evidence of defection or a marked reduction in fecal production (<three piles of manure per day). These horses should be carefully evaluated for both pain and intraabdominal evidence of an impaction and treated accordingly.

The diagnosis of primary cecal impaction is based on palpation of a firm, impacted cecum or a grossly distended fluid-filled cecum per rectum. According to one study such findings were detected in 89% of horses with cecal impaction that underwent per rectum palpation of the abdomen.⁷⁹⁹ In some cases, cecal impactions may be difficult to differentiate from large colon impactions. However, careful palpation will reveal the inability to move the hand completely dorsal to the impacted viscus because of the cecum’s attachment to the dorsal body wall.

Treatment for horses with dry-ingesta—filled cecal impactions may include initial medical therapy, including aggressive administration of intravenous fluids, judicious use of analgesics, and administration of oral laxatives (e.g., 2 to 4 L of mineral oil per 500 kg).⁸⁰¹ Other oral laxatives have also been recommended, including magnesium sulfate (1 mg/kg in 4 L of water PO up to twice daily for up to 3 days) and psyllium (1 kg q6-8h). However, if the cecum is grossly distended or if medical therapy has had no effect within a reasonable period of time, surgical evacuation of the cecum via a typhlotomy is indicated. In addition, it is advisable to perform an ileocolostomy in order to bypass the cecum, as postoperative cecal motility dysfunction with recurrence of the disease is common.⁸⁰² However, this aspect of surgical treatment remains controversial, and there are cases of cecal impaction if identified early that can be treated via typhlotomy alone.

In horses with cecal dysfunction, immediate surgery is indicated. In addition, cecal bypass is often warranted because it is suspected that motility disturbances initiate the disease, and therefore recurrence in the absence of cecal bypass may occur. However, this decision can be made based on the appearance of the cecum at surgery.

The prognosis depends on the type of cecal impaction encountered. In a recent report in which dry-ingesta—filled cecal impactions were treated by typhlotomy and ileocolostomy or jejunocolostomy, seven of nine horses lived long-term. The cecum of horses in which cecal dysfunction develops have a great propensity to rupture, which is universally fatal. Because these cases can be difficult to identify before surgery, the prognosis for this condition tends to be unfavorable.

Large Colon Impaction

Impactions of the large colon with ingesta occur at sites of anatomic reductions in luminal diameter, particularly the pelvic flexure and the right dorsal colon.⁸⁰³ Although there are a number of reported risk factors, most have not been proven. However, a sudden restriction in exercise associated with musculoskeletal injury appears to be frequently associated with onset of impaction. A further consideration is equine feeding regimens, which usually entail twice-daily feeding of concentrate. Such regimens are associated with secretion of large volumes of fluid into the small intestine, resulting in transient hypovolemia (15% loss of plasma volume).⁸⁰⁴ This leads to activation of the renin-angiotensin-aldosterone system, and because aldosterone stimulates absorption of fluid from the large colon, this may dehydrate colonic contents.^804,805 Large concentrate meals may decrease small intestinal transit time, resulting in increased presentation of soluble carbohydrate to the cecum and large colon. Large shifts of fluid into the colon occur as concentrates are readily fermented in the large intestine, which would be expected to activate the renin-angiotensin-aldosterone system. This in turn triggers net fluid absorption from the large colon. The effects of these large fluid fluxes on development of large intestinal disorders remains to be fully characterized, but undoubtedly they play some role in the syndrome of colic. From a practical standpoint, intestinal fluid fluxes may be reduced with frequent small feedings in those horses requiring concentrate to maintain condition.⁸⁰⁴

Clinical signs of large colon impaction include slow onset of mild colic that is typically well controlled with administration of analgesics but becomes increasingly more severe and refractory if the impaction does not resolve. The diagnosis is based on palpation of a firm mass in the large colon per rectum. However, the extent of the impaction may be underestimated by rectal palpation alone because much of the colon will be out of reach. Adjacent colon may be distended if the impaction has resulted in complete obstruction. Initial medical treatment should be attempted. Intermittent abdominal pain is controlled with administration of analgesics (flunixin meglumine 0.25 mg/kg IV q6h to 1.1 mg/kg IV q12h; butorphanol 0.05 mg/kg IV as needed [prn]; xylazine 0.3 to 0.5 mg/kg IV prn). Detomidine (10 to 20 mg IV prn) can be administered with great caution, since this agent readily masks severe pain. In addition to analgesics, mineral oil (2 to 4 L/500 kg PO), water with dioctyl sodium sulfosuccinate (180 to 240 mL in 4 L of water, PO), or magnesium sulfate (1 mg/kg in 4 L of water PO) may be administered by stomach tube for laxative effects. Access to feed should not be permitted. For impactions that persist, aggressive oral and/or intravenous fluid therapy should be instituted. One study demonstrated the increased efficacy of a continuously administered oral rehydration solution in softening feces as compared with intravenous fluids, which are probably best suited to restoring the systemic extracellular fluid compartment.⁸⁰⁶ If the impaction remains unresolved, the horse becomes uncontrollably pained, or extensive gas distention of the colon occurs, surgery is indicated. At surgery the contents of the colon are evacuated via a pelvic flexure enterotomy. The prognosis is good for those horses in which impactions resolve medically (95% long-term survival in one study) and fair for horses that require surgical intervention (58% long-term survival in the same study).⁷⁹⁵

Enteroliths

These mineralized masses are typically composed of ammonium magnesium phosphate (struvite).⁸⁰⁷ One study has suggested that an increase in magnesium in the diet may predispose to the formation of enteroliths.⁸⁰⁸ Enteroliths almost always form around a nucleus such as a silicon dioxide stone, a nail (Fig. 32-56), or piece of rope that has been ingested and are most commonly found in the right dorsal and transverse colons. Although enterolithiasis has a wide geographic distribution, horses in California have a high incidence. In one California-based study, horses with enterolithiasis represented 28% of the surgical colic population. In addition, Arabians, Morgans, American Saddlebreds, and donkeys are at risk of this disease.⁸⁰⁹ A more recent study performed in California indicated that horses fed a diet composed predominantly of alfalfa hay are at risk for development of enterolithiasis, and allowing horses to graze on pasture was protective against this disease.⁸¹⁰

Fig. 32-56 Cut section of an enterolith. Note the presence of a nail head (arrow) that served as a nucleus for the formation of a struvite enterolith.

Courtesy Dr. David G. Bristol.

Initially, clinical signs include intermittent abdominal pain in mature horses (almost always greater than 4 years of age),⁸¹¹ with few abnormalities on rectal examination. As enteroliths become larger, they may occlude the lumen of the colon and cause acute pain and large colon distention that necessitate surgical exploration. In some cases an enterolith is forced into the small colon, where it causes acute small colon obstruction. Enteroliths may be diagnosed by abdominal radiography or at surgery. On rare occasions, an enterolith may be palpated per rectum, particularly if it is present in the distal small colon.

In general, surgery is required for these cases, although there are reports of enteroliths being retrieved per rectum. In fact, in one study 14% of horses presented for treatment of enterolithiasis had a history of passing an enterolith in the feces.⁸⁰⁹ However, enteroliths are typically located in the right dorsal colon, transverse colon, or small colon. At surgery the enterolith is gently pushed toward a pelvic flexure enterotomy, but removal frequently requires a separate right dorsal colon enterotomy to prevent rupture of the colon. After removal of an enterolith, further exploration must be conducted to determine if other enteroliths are present. Solitary enteroliths are usually round, whereas multiple enteroliths have flat sides. The prognosis is good (92% 1-year survival of horses recovered from surgery in one study of 900 cases) unless the colon is ruptured during removal of an enterolith. In one recent study, rupture occurred in 15% of cases.⁸⁰⁹

Sand Impactions of the Large Colon

Sand impactions of the large colon are common in horses with access to sandy soils, particularly horses whose feed is placed on the ground. Sand accumulates in the large colon, particularly the right dorsal colon and pelvic flexure.^812,813 In addition, sand may trigger diarrhea, presumably as a result of irritation of the colonic mucosa.⁸¹⁴ In horses with sand impactions, clinical signs are similar to those of horses with large colon impactions. In addition, sand may be found in the feces, and auscultation of the ventral abdomen may reveal sounds of sand moving within the large colon.⁸¹⁵ Sand also may be detected on abdominal radiography. The diagnosis is definitively made at surgery but may be tentatively based on clinical signs compatible with a large colon impaction together with evidence of sand in the feces. To determine the presence of sand, several fecal balls are placed in a rectal palpation sleeve or other container, which is subsequently filled with water. If sand is present, it will accumulate at the bottom of the container. In addition, mineral opacity may be detected within the colon on abdominal radiographs.

Initially, medical therapy is warranted. Administration of psyllium hydrophilic mucilloid in water by stomach tube may facilitate passage of sand, although a recent experimental study failed to show a benefit of this treatment.⁸¹⁶ If colic becomes intractable, surgical evacuation of the large colon should be performed. The prognosis is good.

Right Dorsal Displacement of the Large Colon

With right dorsal displacement of the colon, the colon displaces to the right of the cecum. Findings on per rectal palpation typically include colonic bands coursing horizontally across the abdomen, with evidence of colon lateral to the cecum. In the most common configuration of right dorsal displacement, the large colon wraps around the cecum (pivoting counterclockwise around the cecum, looking from above the horse) with the pelvic flexure lying in the left dorsal quadrant. Alternatively, the colon may wrap around the cecum in the opposite direction, with the pelvic flexure lying in the right dorsal quadrant.⁸¹⁹

Nephrosplenic Entrapment (Left Dorsal Displacement) of the Large Colon

On the left side, colon displacements most commonly involve entrapment of the colon over the nephrosplenic ligament, although left dorsal displacements may be detected before the colon is fully entrapped. Clinical signs include gradual onset of mild to moderate colic as the entrapped colon fills with gas. Palpation per rectum will reveal gas-distended ventral colon and displacement of the spleen toward the center of the abdomen. Careful palpation following colonic bands up to the left dorsal quadrant often reveals the presence of colon between the left kidney and the spleen. Diagnosis may be based on palpation per rectum of the colon traversing the nephrosplenic ligament. Alternatively, a tentative diagnosis can be reached using abdominal ultrasonography.⁸²⁰ The spleen can be visualized on the left side of the abdomen, but the left kidney will be obscured by gas-distended bowel. Evaluation of this technique indicates that there are no instances of false-positive results, although false-negative results may occasionally occur. Therefore, as with other examination techniques, ultrasonography is not uniformly reliable. A definitive diagnosis may require surgery. Treatment has traditionally been surgical intervention, during which the colon is gently rocked free of the nephrosplenic space. More recently, nonsurgical intervention has been successful in select cases.^821,822 If such manipulations are to be attempted, the clinician must be certain of a diagnosis. The horse is anesthetized and placed in right lateral recumbency. The horse is rotated up to dorsal recumbency, rocked back and forth for 5 to 10 minutes, and then rolled down into left lateral recumbency.⁸²³ The nephrosplenic space should be palpated per rectum to determine whether or not the entrapment has been relieved. Phenylephrine (3 to 6 mg/kg/min over 15 minutes) may be administered to decrease the size of the spleen.⁸²⁴ If the entrapment remains, further attempts may be tried, but in cases where the displacement is not corrected, the horse should be taken to surgery. More recently, phenylephrine has been used in conjunction with 30 to 45 minutes of light exercise (jogging) to successfully reduce nephrosplenic entrapments in four of six horses. This technique can be used on horses with mild to moderate colonic distention, particularly if signs of colic can be readily controlled.

Regardless of technique, the prognosis is good. In one study, survival was in excess of 90%.⁸²² There are cases in which nonsurgical interventions do not completely correct the problem and others in which nonsurgical manipulations correct the entrapment but result in large colon volvulus or displacement.⁸²⁵ Such patients should be taken to surgery promptly.

Atresia Coli

Atresia of any segment of the colon is a rare congenital abnormality in horses (Fig. 32-57).⁸²⁶ The heritability and causes of the condition are unknown. One potential mechanism for development of the lesion is intestinal ischemia during fetal life, which secondarily results in necrosis of a segment of intestine. Clinical signs include a failure to pass meconium and colic within the first 12 to 24 hours of life. Secondary abdominal distention results from complete intestinal obstruction, and abdominal radiographs may reveal gas-distended colon. The diagnosis is made at surgery. Any portion of the colon may be absent, but the distal segment of the large colon and/or the proximal small colon is usually most severely affected. If sufficient tissue is present, anastomosis to the proximal blind end of the colon may be attempted. The prognosis depends on which segment of the colon is absent but is usually poor because of an absence of distal colon.

Fig. 32-57 Operative view of a foal with atresia coli. Complete atresia of the pelvic flexure has resulted in a blind-ended ventral colon (arrows) resulting in gas distention of the colon. The ventral colon was subsequently anastomosed to the dorsal colon in this foal.

Large Colon Volvulus

Clinical signs include rapid onset of severe, unrelenting abdominal pain.⁸²⁸ Although postparturient broodmares appear to be at risk, this association has not been conclusively determined. Once the large colon is strangulated (>270 degrees volvulus), gas distention is marked, leading to gross distention of the abdomen, compromised respiration as the distended bowel presses against the diaphragm, and visceral pooling of blood as the caudal vena cava is compressed. Horses with this condition are frequently refractory to even the most potent of analgesics. These horses may prefer to lie in dorsal recumbency, presumably to take weight off the strangulated colon. An abbreviated physical examination is warranted in these cases, because the time elapsed from the onset of strangulation to surgical correction is critical. Experimentally the colon is irreversibly damaged with 3 to 4 hours of 360-degree volvulus of the entire colon.⁸²⁹ Despite severe pain and hypovolemia, horses may have a paradoxically low heart rate, possibly related to increased vagal tone. In addition, results of abdominocentesis are often not indicative of the degree of colon compromise,⁸³⁰ and in many cases abdominocentesis should not be done because of extreme colonic distention. Palpation per rectum will reveal severe gas distention of the large colon, often restricting access to the abdomen beyond the pelvic brim. The diagnosis may be tentatively based on signalment, severity of pain, and degree of distention.

At surgery the volvulus is typically located at the mesenteric attachment of the colon to the dorsal body wall, and the most common direction of the twist is dorsomedial using the right ventral colon as a reference point. However, the colon may twist in the opposite direction, twist more than 360 degrees (up to 720 degrees has been reported), or twist at the level of the diaphragmatic and sternal flexures. In all cases the colon should be decompressed as much as possible, and in many cases evacuation of colon contents via a pelvic flexure enterotomy will facilitate correction of the volvulus. A determination must be made after correction of the volvulus as to whether the colon has been irreversibly injured. This is frequently based on mucosal color and bleeding (if an enterotomy has been performed), palpation of a pulse in the colonic arteries, serosal color, and appearance of muscular motility. However, determination of viability based on these parameters is unreliable. Currently, one of the most reliable techniques for determining viability is histologic evaluation of frozen sections of colonic mucosa. Biopsies may be obtained at the pelvic flexure because it has been determined that mucosal changes are uniform throughout strangulated colon. A prediction of viability is based on the degree of crypt epithelial loss and the interstitium:crypt ratio (based on measurements of the crypt width and the width of interstitial space between crypts). In one study, 16 of 18 horses that had >50% loss of crypt epithelium and an interstitium:crypt ratio of >3 typically did not survive, whereas 43 of 46 horses that had less severe mucosal changes survived, suggesting high accuracy.⁸³¹ In addition, it has been suggested that accuracy of viability determination can be increased by combining histologic evaluation with surface oximetry or laser Doppler determination of blood flow.⁸³² Unfortunately, frozen histologic sections are not available at most referral centers on an emergency basis. One recent study assessed intraoperative colonic intraluminal pressure as a more practical potential indicator of outcome in horses with large colon volvulus but found this measurement to be of little benefit in accurately making this determination.⁸³³

If the colon is judged to be irreversibly damaged, the feasibility of a large colon resection can be considered. Although 95% of the colon can be resected (that part of the colon distal to the level of the cecocolic fold), damage from the volvulus usually exceeds what can be resected. In these cases surgeons may elect to resect as much damaged bowel as possible or may advise euthanasia.

The prognosis for survival is guarded to poor because of the rapid onset of this disease. In one study the survival rate was 35%.⁸³⁰ In a more recent report, the survival rate was 36% for horses with 360-degree volvulus of the large colon compared with 71% for horses with 270-degree volvulus.⁸²⁸ However, one study in central Kentucky documented a high success rate, most likely because of early recognition of the disease and the proximity of the hospital to the surgical caseload.⁸³⁴ Postoperative complications include hypovolemic and endotoxemic shock, extensive loss of circulating protein, disseminated intravascular coagulation, and laminitis. In addition, large colon volvulus has a propensity to recur. Although one study documented a recurrence rate of less than 5%,⁸³⁰ some authors believe recurrence may be as high as 50%. Therefore methods to prevent recurrence should be considered.^835,836

Intussusception

The most common intussusception of the large intestine is cecocolic intussusception, although when this is compared with all forms of colic, it is a relatively rare condition of the horse, accounting for 11 of 842 horses (1.3%) taken to surgery because of colic at one hospital.⁸³⁷ The condition tends to occur in young horses (2 to 3 years of age) and may be associated with intestinal parasites, particularly tapeworms. Clinical signs include acute onset of colic that varies in severity according to the degree of intussusception. Initially, the cecal tip inverts, creating a cecocecal intussusception, which does not obstruct flow of ingesta. As the intussusception progresses, the cecum inverts into the right ventral colon (cecocolic intussusception), which obstructs flow of ingesta and often causes severe colic. In one report on cecocolic intussusception, 10 of 11 horses had severe colic.⁸³⁷ The cause of abdominal pain is often difficult to differentiate in these cases, although it is sometimes possible to detect a mass on the right side of the abdomen and the concurrent absence of a palpable cecum. Treatment involves manual surgical reduction by retracting the intussusceptum directly or via an enterotomy in the right ventral colon.⁸³⁸ The prognosis is usually regarded as poor because of severe compromise to the cecum and the risk of cecal rupture or severe contamination during surgery. However, a recent report has indicated that seven of eight horses that underwent right ventral colon enterotomy and cecal resection survived long term.⁸³⁸

Colocolic intussusceptions are rare but have reportedly affected the pelvic flexure and the left colon.^839-842 Although the condition is reportedly more common in young horses, older horses may be affected. Clinical findings may include a palpable mass on the left side of the abdomen. Ultrasonography may also be useful. Treatment requires manual reduction of the intussusception at surgery, or resection of affected bowel.

Pathophysiology and Predisposing Factors

The principal mechanism of the therapeutic and toxic effects of NSAIDs is related to their inhibition of prostaglandin synthesis by inhibition of the COX enzyme. Two isoforms of the COX enzyme have been identified: COX-1 and COX-2.⁸⁴⁶ COX-1 is generally constitutively expressed and is thought to play an important role in maintaining physiologic homeostasis; it is found in such tissues as the gastrointestinal mucosa and kidney and in the endothelium and platelets. In contrast, COX-2 is primarily an inducible enzyme that has a critical role in inflammation and is produced by a variety of cells including monocytes, neutrophils, epithelial cells, fibroblasts, synoviocytes, and chondrocytes.

It has been postulated that drugs that nonselectively inhibit both COX-1 and COX-2 have greater toxic potential because they inhibit prostaglandins necessary for physiologic homeostasis as well as prostaglandins that mediate inflammation and pain.⁸⁴⁶ Both COX-1– and COX-2–dependent prostaglandins play an important role not only in maintaining the epithelial barrier in the gut, but also in healing the epithelium when the mucosa is damaged (e.g., because of ischemic injury or infection). All of the commonly used NSAIDs in horses are considered to be nonselective. NSAIDs that are COX-2 selective are less ulcerogenic in other species and may be so in horses. For example, COX-2 selectivity decreases the adverse effects of NSAIDs in a model of epithelial repair in horses.⁸⁴⁷ COX-2 selective NSAIDs are being developed for use in horses but are not yet approved for use in the United States.

Although the COX-1–versus—COX-2 scheme is currently considered valid, evidence exists that it may be overly simplistic. For example, COX-1 may play an important role in inflammation and is at least partly inducible.⁸⁴⁸ In contrast, COX-2 can be induced physiologically in various organs and tissues and by stimuli other than inflammation.^846,849 In horses, gastric ulcerogenicity of even the nonselective NSAIDs varies (phenylbutazone > flunixin meglumine > ketoprofen).⁸⁵⁰ This difference in toxicity among drugs may relate not only to the COX selectivity, but also on other factors such as tissue distribution.

The gastrointestinal tract and the kidneys are the most common targets for NSAID toxicity. NSAID-induced injury can develop anywhere in the gastrointestinal tract (from the mouth to the rectum). Two well-recognized syndromes may be attributed at least in part to NSAID toxicity. The first is gastric ulceration. In the stomach, inhibition of COX can increase acid secretion, decrease output of mucus and bicarbonate, impair vasodilation, and diminish epithelial restitution, cell division, and angiogenesis.⁸⁵¹ Inhibition of COX also impairs the healing of existing ulcers. A second syndrome attributed to NSAID toxicity is right dorsal ulcerative colitis (RDUC). Although the right dorsal segment of the large intestine is most commonly affected, other segments may also be involved. Ulcerative lesions in the large intestine can be particularly troublesome because they can cause chronic debilitation, are difficult to diagnose, and can be refractory to treatment. In the kidney, PGE₂ and PGI₂ (prostacyclin) produce vasodilation in the autoregulatory response of renal blood flow to hypoperfusion; consequently, hypovolemia, hemorrhage, or renal disease will increase the risk of renal NSAID toxicosis. Damage is greatest at the renal crest (papilla), and papillary crest necrosis may be associated with subsequent nephrolithiasis or ureterolithiasis and chronic renal failure.⁸⁵² In humans the most common side effect of NSAIDs is bleeding, caused in part by reduced function of platelets and in part by gastrointestinal hemorrhage.

Not all of the adverse effects of NSAIDs are attributable to COX inhibition. The NSAIDs also cause injury from a variety of mechanisms, including microvascular damage, increased intracellular concentration of reactive oxygen and other free radicals, direct local injury (particularly with ion trapping in the stomach), inhibition of cell division, and reduced hydrophobicity of the gastric mucous coat.^849,851 Inhibiting COX may shunt arachidonic acid metabolism toward the lipoxygenase pathway, thereby producing other biologically active eicosanoids. The clinical significance of this shunting is unclear, but the potential for deleterious effects exists.

Although the toxicity of NSAIDs is related to the dose and duration of administration, some horses develop toxicosis at recommended doses. Predisposing factors such as dehydration, renal disease, hepatic disease, or sepsis may contribute to the development of NSAID toxicity. Dehydration, renal disease, and hepatic disease predispose to NSAID toxicosis because of reduced tissue perfusion and reduced drug elimination. Sepsis may predispose to NSAID toxicosis because of secondary hypovolemia, decreased tissue perfusion, and direct and indirect effects of various mediators produced in response to sepsis (e.g., platelet aggregating factor). In humans, risk of NSAID-induced ulceration is increased among those with various gastrointestinal disorders (e.g., IBDs). NSAIDs inhibit the ability of injured equine intestinal mucosa to repair, which may increase the risk of ulceration in horses with ischemic damage or intestinal infections. Body weight may be a predisposing factor in that NSAIDs are often administered to ponies, miniature horses, and small horses at doses higher than those recommended for their body weight. Inadvertent overdosing can occur regardless of body weight or size (e.g., administration of a 12-g tube of phenylbutazone paste when administration of an anthelmintic paste was intended).

Some horses may have an idiosyncratic predisposition, particularly for ulceration of the right dorsal colon. Experimentally, arthritic laboratory animals were more susceptible to NSAID-induced gastropathy than healthy animals.⁸⁵³ This finding may have relevance to horses because NSAIDs are often administered to chronically lame horses. Two or more NSAIDs are used concurrently in some situations. It is important to recognize that the effects of combining NSAIDs are additive, such that administering two NSAIDs at each of their recommended doses is similar to giving twice the recommended dose of one NSAID. Combination of two NSAIDs will prolong their pharmacologic effect and increase the risk of toxicity.⁸⁵⁴

Clinical Signs

Clinical signs of NSAID toxicity are usually referable to the alimentary system and vary depending on the segment involved. Oral or lingual ulceration may lead to difficulty in prehension and mastication. Esophageal ulceration may result in excessive salivation and apparent signs of pain (stretching of the neck, groaning) during swallowing. Gastric ulceration may result in slow consumption of feed, inappetence (particularly for grain in some horses), or anorexia. Horses that have gastric outflow obstruction associated with gastroduodenal ulceration may exhibit ptyalism, reflux esophagitis, and, in severe cases, spontaneous nasogastric reflux. Horses with ulceration anywhere in the gastrointestinal tract may exhibit signs of colic, which may be intermittent and varying in severity. Horses with colonic ulceration may have soft stool or diarrhea and ventral edema secondary to enteric protein loss. Diarrhea can be severe, even fatal. Endotoxemia may result from intestinal mucosal damage caused by NSAIDs. Clinical signs of endotoxemia (e.g., tachycardia, altered appearance of mucous membranes, fever, and dehydration) may be seen in some horses with NSAID enteropathy. In some horses, hematuria may be seen.

Horses may have clinical signs days to weeks after having been administered NSAIDs. Such horses typically are presented because of recurring colic, weight loss, or loose manure. It is particularly important in these horses to determine whether there is any history of NSAID administration, even if it was several weeks previous to the time of presentation.

Diagnosis

Diagnosis is usually made on the basis of history of NSAID use, clinical signs, and clinicopathologic findings. The most consistent clinicopathologic abnormalities in horses with NSAID toxicosis are hypoproteinemia and hypoalbuminemia, presumably from loss of protein through inflamed intestinal mucosa. These findings are more commonly observed with damage to the distal intestinal tract and are not reliable for diagnosis of NSAID gastropathy. Some horses have decreased serum concentration of calcium, presumably attributable to intestinal loss of protein-bound calcium. In horses with NSAID-induced diarrhea, hyponatremia, hypochloremia, hypokalemia, acidemia, and hypovolemia may be observed if the diarrhea is severe. In such cases, hypovolemia may make the serum protein concentration appear to be higher than its actual value would be were the horse adequately hydrated.

In chronic cases, horses may be anemic from inflammation, intestinal loss of blood through ulceration, or reduced function of platelets. Occult blood may be found in the feces of horses with lesions in the more distal portions of the intestinal tract. Tests for occult blood often lack sensitivity, and false-positive results may be expected for up to 24 hours after rectal palpation.

The concentration of leukocytes is usually within the reference range, although leukocytosis and hyperfibrinogenemia, associated with inflammation, and leukopenia and neutropenia, presumably caused by endotoxemia, can be seen in some horses with acute NSAID toxicosis affecting the distal intestine. Generally, results of peritoneal fluid analysis are within reference ranges, but increased concentration of nucleated WBCs, total protein, and fibrinogen may be seen when there is advanced intestinal damage or intestinal vascular infarction. When findings of cytologic examination of peritoneal fluid are abnormal, results are more consistent with nonseptic than septic inflammation; however, septic inflammation may be observed when severe intestinal ulceration leads to transmural lesions and septic peritonitis.

Several clinicopathologic changes may accompany NSAID-induced renal damage. The most consistent finding is decreased urine specific gravity, from 1.008 to 1.020. Inability to properly dilute urine can be found with acute NSAID toxicosis for years after the original insult. This results from preferential damage to areas of the kidney that contribute most to concentrating urine (medulla, papilla). In chronic cases urine specific gravity typically ranges from 1.013 to 1.020. Some horses with NSAID toxicosis are azotemic. In acute cases azotemia can result from dehydration, NSAID-induced alterations in renal blood flow, and tubuloglomerular feedback mechanisms. Chronic azotemia, with serum creatinine ranging from 2.1 to 3.5 mg/dL, results from tubuloglomerular feedback mechanisms that reduce glomerular filtration to compensate for reduced reclamation of solutes in the medullary collecting ducts. In acute NSAID toxicosis, there may be overt hematuria. In other cases, urinalysis may reveal occult blood, increased renal cells, and increased WBCs. In chronic cases other than decreased urine specific gravity, urinalysis results are typically normal.

Endoscopy can be useful to visualize the location and extent of esophageal and gastric lesions. NSAID-induced gastric lesions are more common in the glandular epithelium, although nonglandular lesions can be observed. Contrast radiography or scintigraphy may be useful to document delayed gastric emptying in some horses. Lesions of the jejunum, ileum, cecum, and colon can be difficult to identify without celiotomy and enterotomy. Isotope-labeled WBC scintigraphic scans may identify colonic ulceration⁸⁵⁵; the sensitivity and availability of the procedure is limited, however. Ultrasonography may reveal thickening of the right dorsal colon or other colonic segments, but the technique appears to lack sensitivity.⁸⁵⁶ Horses with renal crest necrosis may have increased ultrasonographic echogenicity of the renal crest and echogenic debris in the renal pelvis.

Management

Administration of NSAIDs should be discontinued if NSAID toxicosis is suspected. Gastric lavage and administration of 1 gallon of mineral oil per 450 kg of body weight via nasogastric tube may be of benefit in horses with acute NSAID overdose to reduce the absorption of the administered NSAID. Treatment for gastric ulceration with a proton-pump inhibitor (e.g., omeprazole*), an H₂-receptor blocker (e.g., ranitidine), or sucralfate should be implemented for horses with gastric ulceration.

Regardless of the site of NSAID toxicity, administration of misoprostol† may be of benefit because administration of a synthetic analog of PGE₂ has been demonstrated to prevent phenylbutazone-induced gastrointestinal lesions in horses.⁸⁵⁷ Misoprostol, a synthetic analog of prostaglandin E₁, can be administered orally starting at doses of 5 μg/kg q12h or 2 μg/kg q6h. Some horses will develop signs of abdominal discomfort or diarrhea at these doses; another protocol is starting at 1.5 μg/kg q8h for 2 to 4 days and increasing at increments of 0.5 μg/kg q8h every 2 to 4 days until a maintenance dose of 2.5 to 3 μg/kg q8h is achieved. Because of the paucity of experimental and clinical data for this drug, dosage schedules should be individually tailored for the horse’s illness and tolerance to the drug.

For horses with hypovolemia secondary to colitis, administration of crystalloid fluids is indicated. Infusion of plasma may benefit horses with NSAID-induced enteropathies and signs of endotoxemia. The aim of plasma transfusion in a hypoproteinemic horse with colitis need not be to increase the plasma concentration into the reference range, because this may be cost-prohibitive and infused protein may be rapidly lost via the intestinal tract. Smaller volumes of plasma (1 to 3 L in an average-size horse) may exert beneficial effects by increasing colloid oncotic pressure and perhaps by modulating the effects of endotoxemia. Alternative colloidal fluids may be beneficial as well. Hetastarch (5 to 10 mL/kg IV q48-72h) may maintain plasma colloid oncotic pressure in the acute stages of the NSAID toxicity. Administration of broad-spectrum antimicrobial drugs may be indicated when signs of endotoxemia are observed. Parenteral administration of antimicrobial drugs is preferable to oral administration in horses with colitis because of the presumed increased risk of antimicrobial-associated diarrhea with the oral route. Oral administration of metronidazole (10 to 15 mg/kg PO q8-12h) might be an exception to this guideline, because evidence exists that metronidazole may exert an antiinflammatory effect and enhance healing in NSAID-induced intestinal ulceration.⁸⁵⁸

For horses with RDUC, dietary management directed toward providing a low-bulk diet in the form of a pelleted concentrate and restricting or eliminating ingestion of roughage is recommended. The aims of this approach are to decrease the mechanical and physiologic load of the colon. A complete pelleted diet (i.e., a diet that contains both concentrate and adequate but relatively low dietary roughage) will decrease intestinal fill in the colon. A diet lower in fiber should decrease the physiologic load of the colon because the cecum and large colon are the primary sites in horses of fiber digestion and exchange of fluid and electrolytes. Concentrate should be fed in smaller amounts and frequently (four to six feedings per day). Addition of corn oil may provide additional calories and may also aid in healing of the damaged intestinal mucosa by promoting PGE₂ production. Some horses will not eat complete pellets, and some horses that have roughage withheld will eat bedding or wood as a consequence. These horses should be allowed to eat fresh grass in small amounts on a frequent basis (four to six times daily). The importance of and optimal duration for restriction of roughage is unknown, but it likely requires months for the colon to heal. Horses should be changed from and returned to their usual diet over a period of several days to decrease the risk of inducing other digestive disorders.

Feeding psyllium mucilloid may promote colonic healing in horses with RDUC. In other animal species, psyllium mucilloid has been demonstrated to increase the concentration of short-chain fatty acids of the large bowel, and increased short-chain fatty acids can promote colonic mucosal repair.⁸⁵⁹ The amount and duration of psyllium mucilloid administered orally that is required to alter the colonic concentration of short-chain fatty acids and the role of short-chain fatty acids in repair of RDUC in horses is unknown. Continuous feeding according to manufacturer’s recommendations for 3 to 6 months is suggested, or feeding 1 to 2 oz of psyllium mucilloid once or twice daily for the same duration may be considered.

Horses with strictures of the pylorus, duodenum, jejunum, or colon may require surgical management. Bypass or resection of affected intestinal segments may be necessary.

Limiting the extent of predisposing factors, such as dehydration, should decrease the risk of NSAID toxicosis. Avoiding use of NSAIDs or limiting the dose and duration of treatment to the minimum that is required to control the primary problem is recommended to decrease the risk of NSAID toxicosis. Other approaches to analgesia, such as regional (epidural or perineural nerve blocks of distal limbs) anesthesia or administration of butorphanol,* should be considered.

Atresia Coli and Aganglionosis

Atresia coli is much more rare in foals than it is in calves, with a reported incidence of 0.44%.⁸⁶⁴ There are several theories on the pathogenesis of this disease, but an ischemic vascular accident that results in atrophy of the affected segment is the most widely accepted.⁸⁶⁵ There are four types of atresia,⁸⁶⁶ with type 3, blind end atresia with no connection of the atretic segments, being the most common in foals.^864,867 Atresia coli may be confused with overo lethal white syndrome, in which affected foals have myenteric aganglionosis of the distal intestinal tract resulting from a mutation in the endothelin receptor type B gene.^868,869 However, in this condition the intestinal tract is patent but nonfunctional. Loss of neurons in the myenteric plexus of the small colon can also be found in equine dysautonomia (grass sickness), although it is usually less severely affected than the ileum.⁸⁷⁰

Foals with atresia are usually normal at birth but develop progressive abdominal distention and colic within 24 hours of birth. Atresia can be differentiated from other causes of colic in foals by the lack of feces with no meconium staining even after an enema.⁸⁶⁵ It may be possible to confirm a blind ending rectum or distal small colon by digital palpation or passage of a soft catheter or endoscope. However, the defect is usually too proximal to visualize this way, and perforation of the friable colonic mucosa can easily occur; therefore I do not use this method for diagnosis. Plain radiographs do not usually identify the atresia but can help to differentiate it from a meconium impaction. Retrograde contrast radiography, as described later in this section for meconium impaction, may give a more definitive answer.⁸⁷¹ A large volume of barium sulfate, up to 20 mL/kg, may be needed if the atresia is proximal to the transverse colon. If atresia is present, the contrast agent will be seen to end abruptly at the atretic segment.

The only chance for survival in cases of atresia is early exploratory celiotomy to assess the affected segment and determine if surgical correction is possible. In calves with atresia, the prognosis is vastly improved if the diagnosis is made early and the animal is alert and is stabilized medically before surgery.^872,873 However, in foals, despite attempting surgical resection of the atretic segment and anastomosis, the prognosis is grave, with a 100% mortality rate reported in several studies.^864,867

Simple Impaction

Small colon impaction is the most common abnormal condition of the small colon in adult horses, affecting 1.9% to 2.5% of all horses seen for colic at referral institutes.^874,875 Several studies report a strong association between small colon impaction and diarrhea. The most recent study documents that horses with diarrhea are 10 times more likely to develop a small colon impaction than horses without diarrhea.⁸⁷⁶ In other studies, diarrhea developed during hospitalization in 70% of all horses with small colon impaction, and 43% of those treated surgically cultured positive for Salmonella species.⁸⁷⁴ These studies suggest that impaction of the small colon may be a sequela to colonic inflammation, such as Salmonella infection. Therefore it is advisable to use isolation protocols for all horses with a small colon impaction. Previous reports have documented a dramatic increase in the incidence of small colon impaction in the fall and winter, possibly because of decreased water intake or close housing that increases the incidence of infectious colitis, but a definitive reason is unknown. It is interesting to note that this seasonal incidence was not significant in the most recent study, possibly because of the milder winters in the south.⁸⁷⁶

Diagnosis of a small colon impaction is most easily made by rectal palpation, with an accuracy of 79% to 87%.^874,876 A solid tube of ingesta with loss of the normal sacculations is found. However, great care should be taken when performing a rectal examination because the rectal mucosa may be edematous, and frequently the horse will strain.⁸⁷⁷ It now appears that the best parameter for determining when surgical treatment of these cases is required is the presence of abdominal distention. Recently it has been reported that horses with a small colon impaction and abdominal distention are five times more likely to require surgical correction than horses without abdominal distention.⁸⁷⁶ Unlike other types of colic, this single factor is more significant than heart rate, temperature, or duration of colic when determining the need for surgical intervention.⁸⁷⁶

Medical therapy should consist of aggressive intravenous and enteral fluid therapy, including correction of electrolyte abnormalities, combined with laxatives and lubricants, and analgesics as necessary.^874,875 The length of time for the impaction to resolve with medical treatment is often longer than for large colon impactions, averaging over 2 days.⁸⁷⁶ Surgical correction of the impaction via exploratory celiotomy is usually performed via a high enema combined with extra luminal massage by the surgeon. The impacted small colon is extremely friable, and great care should be taken by the surgeon when manipulating the bowel in order to avoid serosal tears. Application of sterile carboxymethylcellulose to the serosal surface may help lubricate the intestine and reduce the trauma of manipulation. In severe cases, infusion of the impacted contents with isotonic fluids or an enterotomy in the small colon may be necessary to facilitate evacuation of the impaction.⁸⁷⁷ An additional concern is the risk of reimpaction of the small colon as ingesta from the large colon move aborally after surgery. Therefore if there are ingesta in the large colon at the time of surgery, a pelvic flexure enterotomy is recommended to empty the large colon and reduce the risk of recurrence.⁸⁷⁴ Surgical correction of the impaction can be time-consuming; therefore to reduce anesthesia time it is advisable to assemble the items needed for a high enema, such as a stomach tube with a rounded atraumatic end, stomach pump, and buckets of warm water, in the operating room before induction.

The prognosis for medical and surgical treatment appears to be similar in most studies.^874,876 It is interesting to note, however, that overall prognosis appears to have improved in recent years, increasing from approximately 75% in cases from 1986 to 1996⁸⁷⁴ to approximately 95% in cases from 1999 to 2004.⁸⁷⁶ Therefore, overall, the prognosis for small colon impaction is excellent, even if surgical treatment is necessary. However, because of the underlying inflammatory cause of this condition, length of hospitalization and associated costs tend to be higher than those incurred with a simple large colon impaction.⁸⁷⁶

Fecaliths, Enteroliths, and Foreign Bodies

Simple obstruction of the small colon also occurs from inspissated feces (fecaliths), enteroliths, foreign bodies, or, less frequently, concretions of plant material (phytobezoars) or masses of matted hair (trichobezoars).

Fecaliths are improperly formed fecal balls that are larger than normal at 4 to 6 cm diameter in miniature horses.⁸⁷⁸ They are a common cause of colic in young miniature horses,⁸⁷⁸ with an occurrence rate of 63% in a study of surgical colic in miniature horses.⁸⁷⁹ Causes of the formation of fecaliths are probably similar to those of other impactions and include poor-quality roughage, dental disease causing problems with mastication, and reduced water intake.^878,879 Fecaliths that become lodged in the small colon usually cause complete intestinal obstruction and require surgical removal as described later. When managing colic in miniature horses, regardless of the cause, the patient should have serum triglyceride concentration monitored to allow early detection and treatment of hyperlipemia.⁸⁸⁰

Enteroliths are mainly composed of magnesium ammonium phosphate deposited in concentric layers around a nidus such as a small rock.⁸⁸¹ The incidence is very high in certain areas, such as California, where enterolithiasis constitutes 15.1% of all colic seen at the University of California, Davis⁸⁸² compared with less than 2% of colic cases at Texas A&M University.⁸⁸³ Several studies report an increased incidence in Arabians, although the reason for this is unknown. Enteroliths can lodge in the large colon, transverse colon, or small colon, but the last is a relatively common site, with over 45% of cases involving an obstructive enterolith in the small colon.⁸⁸² Horses with enteroliths were found to have certain changes in the composition of their colonic contents, compared with other surgical colic cases, which may predispose them to enterolith formation. These differences included a more alkaline pH, more colonic fluid, and higher mineral concentrations.⁸⁸⁴ Certain management practices may also predispose to enterolith formation, including feeding a high proportion of alfalfa and giving less access to pasture.^883,884 Clinical signs of enterolithiasis are similar to those seen with other nonstrangulating obstructions of the large or small colon. However, many horses with enterolithiasis have a history of intermittent colic, and some may even have passed enteroliths in the feces.⁸⁸² Abdominal radiographs may be a useful aid in diagnosis, although the sensitivity is reduced when the enterolith is in the small colon.⁸⁸⁵ Medical management aimed at reducing colonic pH has been suggested to try and prevent recurrence after surgery. However, when an enterolith lodges in the small colon it usually causes complete obstruction and acute colic that requires surgical intervention as described later. Rupture of the gastrointestinal tract is particularly common if the enterolith is lodged in the small colon and surgery is delayed.⁸⁸² Such cases should therefore be prioritized as requiring emergency surgery, even when there is a history of chronic colic.

Obstruction of the small colon can also occur from ingestion of foreign material such as rope, twine, rubber fencing, cloth, or tires.^886,887 This is usually a problem of younger horses, possibly because they are more inquisitive and will eat nonfood items found in their environment. It is possible for the foreign body to cause signs of small intestinal obstruction first, followed by a period of quiescence while it passes through the large colon before it finally causes complete obstruction of the small colon and acute onset of severe colic⁸⁸⁸ and abdominal distention.⁸⁸⁶ The fibers become covered in crystalline material during their transit through the intestinal tract, and the resulting irregular sharp projections cause mucosal ulceration,⁸⁶⁰ which can be seen during exploratory celiotomy oral to the site where the foreign body has finally become lodged. These sharp projections make it virtually impossible to manipulate the foreign body orally or aborally within the lumen, making removal more complicated.

The majority of these obstructions require exploratory laparotomy and an enterotomy to allow the obstruction to be removed.^878,882,886 Regardless of the cause of the obstruction, the overlying intestine is friable and can easily rupture either during induction of anesthesia⁸⁸⁶ or during surgical manipulation.^882,887 If possible, the mass should be gently manipulated more proximal or distal to the original site at which it lodged, so that the enterotomy can be performed in uninjured intestine.⁸⁶⁰ However foreign bodies in particular may be difficult to manipulate, and the enterotomy may have to be performed directly over the top of the obstruction. The site selected for the enterotomy should be isolated from the abdomen with sterile towels before the enterotomy incision is made. The incision should be made longitudinally through the antimesenteric taenia in order to preserve luminal diameter, reduce hemorrhage, and maximize speed and ease of the procedure.^889,890 The enterotomy can be closed in one layer using an inverting suture pattern.⁸⁹⁰ Problems arise, however, when intraluminal obstructions occur at the proximal portion of the descending colon, where the lumen narrows between the transverse and descending colon. Here, manipulation of the obstruction aborally into a section of small colon that can be exteriorized may be impossible. In such cases an antimesenteric teniotomy, through the seromuscular layer alone, can be performed. This will allow the obstruction to be advanced aborally into a section that can be exteriorized, while the intact mucosa prevents abdominal contamination.⁸⁹¹ The enterotomy and seromuscular incision are then closed as described earlier.

Meconium Retention

Meconium is composed of substances that are present in the intestinal tract at birth, such as glandular secretions, sloughed cells, and swallowed amniotic fluid, and is therefore sterile. It is thick and tarry and is usually passed within 48 hours of birth. Several studies indicate a higher incidence of meconium retention in colts than fillies, presumably because of the longer narrower pelvis in males.^892,893 Any factors that reduce intestinal motility, such as failure to ingest colostrum, and dysmaturity, can result in difficulty passing meconium, which is described as meconium retention. This results in progressive clinical signs of colic such as tail flagging, straining, and reduced suckling. This can progress to more severe signs of colic over time, such as rolling and abdominal distention. These signs are similar to those seen with ruptured bladder, and the two conditions can occur together; therefore a complete examination of the foal is important.

It may be possible to palpate meconium retained at the pelvic inlet by careful digital rectal examination. If the meconium is retained more proximally, it may be identified on a plain lateral radiograph. Confirmation of the obstruction may be provided by retrograde contrast radiography, which provides excellent sensitivity and specificity for evaluation of the transverse and descending colon.⁸⁷¹ After plain radiographs are obtained, a Foley catheter is placed into the rectum and inflated. Up to 20 mL/kg (approximately 1 L) of 30% barium sulfate is carefully allowed to flow in by gravity until it squirts around the catheter or discomfort is observed.⁸⁷¹ Lateral and, more important, ventrodorsal radiographs are then obtained. If a meconium impaction is present, the contrast agent is stopped before it reaches the transverse colon.

Supportive medical management of all foals should be performed first, including correction of fluid and electrolyte imbalances, provision of nutritional support, and correction of failure of passive transfer if indicated.⁸⁹⁴ Judicious use of analgesics such as flunixin meglumine or butorphanol and oral laxatives such as mineral oil may aid resolution of the impaction. However, the most effective treatment is administration of an enema. The enema can be a commercial phosphate enema or simply soap and water administered through a Foley catheter using gravity flow as described previously. In cases that are refractory to simple enemas, an acetylcysteine enema may be effective. Acetylcysteine is a mucolytic, which acts by breaking disulfide bonds to make meconium less viscous. These enemas are available commercially (E-Z Pass Foal Enema Kit, Animal Reproduction Systems, Chino, Calif.) or can be formulated by adding 20 g of baking soda to 200 mL of water, and then adding 8 g of acetylcysteine powder to make a 4% solution.⁸⁹² The solution is infused slowly through a Foley catheter, which is then clamped to allow the solution to be retained for up to 45 minutes to allow maximum activity of the acetylcysteine. Successful resolution of the meconium retention occurred in all acetylcysteine-treated foals in one study, although 5% of foals did require three enemas before resolution.⁸⁹²

Previous reports have indicated that approximately one third of foals with meconium retention require exploratory celiotomy for resolution.⁸⁹³ However, this was before the increased use of acetylcysteine retention enemas, and it is likely that the current rate of surgical intervention is much lower. Considering the high rate of adhesions in neonatal foals undergoing exploratory laparotomy,^893,895 this should result in an improved prognosis for this condition.

Other Causes of Simple Obstruction

Because of the proximity of the descending colon to the urogenital tract, it is possible for the descending colon to be obstructed by structures such as an ovary or retained testicle. Although such conditions occur infrequently, the most common is for the small colon to become entwined around an ovary.⁸⁶⁰ The intestine can be freed and is not usually compromised, but the ovary itself is usually nonviable and requires resection.⁸⁹⁶ A similar problem has been reported from the spermatic cord of a retained teratoma occluding the small colon.⁸⁹⁷

Intramural Hematoma

Intramural hematoma of the small colon is relatively rare, although some cases may not be diagnosed if they do not cause complete obstruction and if they resolve without intervention.⁸⁹⁸ Hemorrhage occurs between the mucosa and muscularis layers, which expand to occlude the lumen and cause complete obstruction. The length affected has been reported to range from 24 to 65 cm. The cause is unknown, although in people, blunt abdominal trauma has been associated with the condition.⁸⁹⁹ In one equine case series, iatrogenic rectal trauma was implicated as the cause.⁹⁰⁰ There is an increased incidence in older horses, with those affected having an average age of 11 years in one study.⁸⁶⁰ Affected cases frequently have blood in the rectum and may show signs of vascular compromise from blood loss.^860,900

Exploratory celiotomy with complete resection of the affected segment and end-to-end anastomosis is necessary. Because of the long length of the affected segment, it may be difficult to exteriorize and resect all damaged intestine. However, if the entire affected segment can be removed, the prognosis is good, with 75% of horses surviving in one study.⁸⁹⁸

Mesocolic Tears and Rectal Prolapse

Tears in the mesentery of the small colon can occur as a complication of parturition, especially in multiparous mares,^901,902 and result in segmental ischemic necrosis of the small colon. Trauma and straining during parturition can result in tearing of the mesocolon and devitalization of the associated descending colon, which may progress to an intussusception of the small colon, which manifests as a type III or IV rectal prolapse. In a type III rectal prolapse the rectal ampulla prolapses, as with a type II prolapse, but in addition a portion of the small colon intussuscepts into the rectum. In type IV rectal prolapse part of the small colon and the rectum intussuscepts through the anus.^901,903 Gentle palpation around the prolapse can help determine the type of prolapse. Although a rectal prolapse is readily identifiable, tears of the mesocolon resulting in devitalization of the small colon result in a more insidious onset of clinical signs, including depression and lack of feces.^901,902

The mesocolic tear is frequently located caudally, resulting in the affected area being inaccessible via a midline celiotomy. Therefore it may be more prudent to first perform standing flank laparoscopy to determine the location and extent of the lesion.⁹⁰⁴ This allows assessment of the lesion to determine if resection and anastomosis of the affected segment via celiotomy is feasible, or if a permanent colostomy is required.⁹⁰⁵

Strangulating Lipoma

Pedunculated lipomas can cause a strangulating or nonstrangulating obstruction of the small colon, but this occurs much less frequently than in the small intestine. In a large retrospective study, lipomas were found to involve the descending colon in less than 10% of cases.⁹⁰⁶ The overall incidence of lipomas affecting any portion of the gastrointestinal tract is increased in older geldings^906,907 and in Saddlebreds and Arabians.⁹⁰⁶ It is therefore likely that lipomas specifically affecting the descending colon have a similar distribution. Fig. 32-58 illustrates a pedunculated lipoma that had strangulated a short section of the small colon. Clinical signs typical of a strangulating obstruction are seen, with a significantly elevated heart rate, abnormal abdominocentesis, and distended large colon on rectal examination.⁸⁶⁰ In addition, on rectal examination a constriction of the lumen of the small colon caused by the lipoma may be felt. Surgery is necessary to free the constricting lipoma, followed by resection and anastomosis if the intestine is nonviable (Fig. 32-59). The prognosis is worse if resection is required, with a 50% survival rate in one study, compared with 100% survival for nonstrangulating lipomas.⁸⁶⁰

Fig. 32-58 A short section of small colon that had been strangulated by a pedunculated lipoma.

Fig. 32-59 The same case as in the previous figure after resection of the ischemic segment and end-to-end anastomosis.

Other Causes of Strangulating Obstruction

Several other causes of strangulating obstruction can occur, but each condition is relatively rare. These include volvulus of the small colon⁸⁸⁸ and strangulation through internal hernias such as a vaginal tear⁸⁶¹ or tears in the gastrosplenic ligament.⁹⁰⁸

Prognosis

A good survival rate was found in two large studies reviewing small colon disorders, with 71% and 91% of patients being discharged from the hospital.^860,861 The main reason for euthanasia at the time of surgery was an inability to completely exteriorize the affected segment to allow adequate resection and anastomosis.⁸⁶⁰ Previous reports have suggested that resection and anastomosis in the small colon may carry a poor prognosis because of a relatively poor blood supply, higher bacterial counts, solid fecal material, and increased collagenase activity compared with the small intestine.⁸⁸⁸ However, if the patients euthanized at surgery are excluded, short-term survival after surgery for a small colon lesion is excellent, with a report of 100% survival in one study.⁹⁰⁹ In addition, horses that required resection and anastomosis did not have a worse prognosis for survival⁸⁶¹ and are less likely to develop the complications associated with small intestinal resection, such as POI.⁹¹⁰

Anatomy and Physiology

The peritoneum is the mesothelial lining of the peritoneal cavity and its contained viscera. It forms a closed sac in males but communicates with the external environment in females via the fallopian tubes. The peritoneum consists of a single layer of mesothelial squamous cells resting on a thin basal lamina, which is attached to a loose connective tissue layer containing collagen, and elastic fibers, allowing a variable degree of motion. The peritoneum is coated with a thin serous film that serves to minimize friction and thus facilitates free movement between abdominal viscera.^911,912 The peritoneum is divided into the visceral peritoneum, which encloses the intraperitoneal organs and forms the omentum and mesenteries, and the parietal peritoneum, which lines the abdominal walls, pelvis, and diaphragm. The visceral peritoneum, mesentery, and omentum are supplied and drained by the splanchnic vasculature.⁹¹³ The parietal peritoneum is supplied by arterial branches of the lower intercostal, lumbar, and iliac vessels and is drained by veins entering into the caudal vena cava. Branches of the spinal nerves supplying the abdominal wall innervate the parietal peritoneum, and the phrenic nerve supplies the diaphragmatic peritoneum. As a result, irritation of the parietal peritoneum gives rise to afferent stimuli that are transmitted by the intercostal and phrenic nerves and perceived as somatic pain.⁹¹³ In contrast, there are no pain receptors in the visceral peritoneum, and afferent stimuli are conducted centrally by the visceral autonomic nervous system.

Peritoneal fluid is constantly being produced and absorbed. The movement of fluid and solutes occurs by passive diffusion across the semipermeable peritoneal membrane.⁹¹⁴ Solutions or drugs administered into the peritoneal cavity equilibrate rapidly with plasma. Transperitoneal fluid movement can be increased during peritoneal inflammation, causing a rapid and massive transudation of fluid into the peritoneal cavity that can lead to hypotension and shock.⁹¹⁴

The peritoneal lymphatics, especially the diaphragmatic lymphatics, play a major role in the removal of fluid and solutes from the peritoneal cavity. The diaphragmatic lymphatic valves provide a unidirectional clearance of peritoneal fluid and debris, which empty primarily into the thoracic duct and are probably the first line of defense in peritoneal contamination. These lymphatics are aided by movements of breathing, which encourage cranial flow and clearance of peritoneal fluid.^915-917 Cellular defenses are provided by peritoneal macrophages, mast cells, and mesothelial cells. Activated peritoneal T lymphocytes and local antibody production have also been demonstrated experimentally.⁹¹⁶ Peritoneal macrophages have antimicrobial activity resulting from their complement receptors, phagocytic ability, and T cell—mediated immune responses. In addition, peritoneal macrophages are important in neutrophil chemotaxis and fibroblast stimulation, which aid in bacteria localization. Peritoneal mesothelial cells are an abundant source of plasminogen activator, which is responsible for normal fibrinolytic activity on peritoneal surfaces.⁹¹⁵

Pathophysiology of Peritoneal Injury

Peritonitis can be induced by a number of infectious (bacterial, viral, fungal, parasitic) and noninfectious (traumatic, chemical, neoplastic) causes. The initial reaction to inflammatory stimulus is the release of histamine and serotonin from peritoneal mast cells and macrophages, resulting in vasodilation and increased vascular permeability with transudation of fibrinogen-rich plasma into the peritoneal cavity. The concurrent loss of mesothelial cells and release of tissue thromboplastin reduce the fibrinolytic capabilities of the peritoneal surface and activate the extrinsic coagulation pathway, thereby shifting the fibrinolysis-coagulation equilibrium toward fibrin formation.^918,919 This response serves to aid in the fibrin seal of the peritoneal defect and provides the framework for fibroblasts to lay down collagen, which produces fibrous adhesions to localize bacteria.

Peritoneal macrophages stimulate neutrophil chemotaxis both directly and indirectly via the release of TNF and IL-1. TNF and IL-1 stimulate neutrophil margination and degranulation and alter the vascular endothelium to promote leukocyte adherence. Metabolism of cell membranes results in phospholipid products such as PAF, prostaglandins, and leukotrienes, which contribute to the vasodilatory response; phospholipase A₂ provides the catalyst for activation of these phospholipid products via the arachidonic acid pathway. Within hours an influx of fluid, protein, and neutrophils enters the peritoneal cavity in response to the inflammatory stimulus.⁹¹⁹

The combination of enlarged diaphragmatic lymphatics and the cellular defenses described earlier result in rapid clearance of debris from the contaminated peritoneal cavity. If the inflammatory response resolves, the mesothelial cell lining is restored from either free-floating macrophages or differentiated subperitoneal connective tissue cells.⁹¹⁹ The normal fibrinolytic activity of the peritoneal mesothelial cells returns, initiating removal of the accumulated fibrin clots. Severe inflammation, foreign bodies, intestinal ischemia, or infection can result in continued fibrin production from proliferating and migrating fibroblasts, causing fibrous scarring and adhesion formation.⁹¹⁸

Peritonitis in the horse is usually secondary to intestinal leakage or degeneration, resulting in the transmural passage of bacteria into the peritoneal cavity. Any disease process that causes gastrointestinal, hepatic, or urogenital inflammation or compromise can lead to the development of peritonitis. The adverse effects of intraperitoneal bacteria can be enhanced by the presence of excessive peritoneal fluid accumulation, hemorrhage,⁹²⁰ fibrin, bile, necrotic tissue, ischemia, anaerobes, and fecal matter. Excessive peritoneal fluid enhances the dissemination of localized bacteria and dilutes opsonic proteins such as complement and immunoglobulins.

Fibrin formation can be beneficial in confining bacteria; however, excessive amounts can result in abscess formation and prevent phagocytes and antimicrobial drugs from reaching the source of contamination. Fibrinous adhesions may also physically occlude diaphragmatic lymphatics and protect bacteria from opsonins, neutrophils, and antibiotics. Necrotic tissue, fecal matter, and bile all prolong the debridement phase of peritoneal healing and interfere with peritoneal defense mechanisms.

Peritonitis is an inflammation of the peritoneum and can result from many causes, which are classified as primary or secondary, acute or chronic, and localized or diffuse. Primary peritonitis is uncommon in adult horses but may occur by hematogenous spread of bacteria in the septic or immunocompromised neonate or in young horses exposed to Streptococcus equi infection.⁹¹⁶ Uroperitoneum and septicemia-induced peritonitis occur predominantly in neonates. Internal abdominal abscesses caused by disseminated S. equi, Streptococcus zooepidemicus, or R. equi infection are usually found in weanlings or young horses.^921,922

Peritonitis secondary to another disease process may be caused by perforating abdominal wounds, chemical irritation (bile, urine), neoplasia, breeding and foaling injuries (uterine or vaginal trauma), intestinal parasitism, hepatitis, nephritis, pancreatitis, ruptured bladder or ureter, urinary infection, ruptured or lacerated abdominal viscera (spleen, ovary, liver, diaphragm), castration complications, and factors directly related to gastrointestinal problems, which are divided into preoperative, intraoperative, and postoperative causes (Box 32-4).

Diagnosis

CLINICOPATHOLOGY

Abnormal laboratory values are dependent on the cause and duration of peritonitis. Hematologic abnormalities seen in acute peritonitis include elevated PCV secondary to transudation of fluid into the peritoneal cavity and endotoxemia. Initially a proportional increase in plasma protein levels occurs, reflecting the degree of dehydration; however, in severe cases protein eventually is sequestered into the abdomen because of increased capillary permeability, resulting in systemic hypoproteinemia. Peripheral blood neutropenia with a degenerative left shift is caused by margination of neutrophils and migration of these cells into the abdomen. Increased plasma fibrinogen levels (up to 1000 mg/dL) can occur after 48 hours. Peritonitis of longer duration and internal abscesses are associated with greater variability in laboratory values, but affected horses often demonstrate a normal or increased systemic neutrophil count, monocytosis, and elevated plasma protein levels as a result of increased immunoglobulin production.⁹²²

Alterations in blood gas analysis and serum chemistry values often depend on the horse’s clinical and hydration status at the time of presentation. Elevations in BUN and creatinine occur secondary to dehydration. Hypokalemia, hypochloremia, and hyponatremia may occur in the anorectic, acidotic patient with gastrointestinal dysfunction. Serum creatinine levels, anion gap, and pH were significantly different between survivors and nonsurvivors at the time of presentation in 67 horses with peritonitis.⁹²⁵

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Abdominocentesis confirms the diagnosis of peritonitis, although the cause may remain unknown. Normal peritoneal fluid is clear, straw colored, and serous in consistency. The total nucleated cell count and total protein in peritoneal fluid of normal horses were reported to be less than 5000 cells/μL and 2.5 g/dL, respectively, with 24% to 60% of the cells being neutrophils.⁹²⁶ We have found that normal horses typically have peritoneal fluid protein less than 1 g/dL. The cytologic appearance of the leukocytes and mesothelial cells should be normal, although activated mesothelial cells are not an unusual observation.

Colorless fluid is very dilute, and, if it is present in large quantities, the possibility of ascites or uroperitoneum must be considered. Serosanguineous fluid indicates an increase in erythrocytes or free hemoglobin that may be caused by intestinal degeneration and transmural erythrocyte leakage, splenic puncture during abdominocentesis, abdominal viscera laceration, or skin contamination. Green fluid results from enterocentesis or intestinal rupture, and brown fluid is associated with late-stage tissue necrosis. Turbid fluid indicates an increased cell count, and opalescence suggests chylous effusion. Flocculent fluid with fibrin strands indicates an inflammatory, exudative process in the abdomen. The quantity of fluid varies among horses and can be increased in acute peritonitis (transudate or exudate) or absent in chronic peritonitis with excessive fibrin production.

Peritoneal fluid parameters consistent with peritonitis vary widely, depending on the disease process. High nucleated cell counts ranging from 15,000 to 800,000 cells/μL with greater than 90% neutrophils having toxic or degenerative changes have been reported for horses with peritonitis^923-926 or internal abscesses.⁹²² Total protein greater than 2.5 g/dL indicates increased capillary permeability of the abdominal viscera or peritoneum resulting in protein exudation and is associated with peritoneal inflammation, intestinal compromise, or blood contamination of the peritoneal fluid. The presence of fibrin and intracellular bacteria is diagnostic for peritonitis. Cytologic evidence of extracellular bacteria can result from skin contamination and should be interpreted in combination with clinical signs.

It may be difficult to distinguish between early and mild septic peritonitis and nonseptic peritoneal inflammation using clinical and clinicopathologic findings alone. In addition, false-negative bacterial cultures in horses with peritonitis are not uncommon, and positive culture results often require several days of incubation. One study investigated peritoneal fluid pH, glucose concentration, and LDH activity in normal horses and horses with either septic or nonseptic peritonitis.⁹²⁷ Horses with septic peritonitis had significantly lower peritoneal fluid pH and glucose concentration than horses with nonseptic peritonitis or healthy horses. Serum-to-peritoneal fluid glucose concentration differences >50 mg/dL were diagnostic for septic peritonitis. Peritoneal fluid pH >7.3, glucose concentration <30 mg/dL, and fibrinogen concentration >200 mg/dL were highly indicative of septic peritonitis. LDH activity was not useful in the detection of septic and nonseptic peritonitis. These measurements may provide early indication of sepsis, especially if cytologic evaluation or bacterial culture results are unavailable. The acidic peritoneal fluid pH likely reflects lactate production by peritoneal fluid neutrophils via glycolysis and acid metabolite production by bacteria. The low peritoneal glucose concentration may be secondary to glucose use by bacteria and phagocytic cells, glycolytic enzymatic activity in the peritoneal fluid, or low transport of glucose from the blood to peritoneal fluid.

Peritoneal fluid must be interpreted carefully in horses after abdominal surgery, foaling, castration, or multiple abdominocentesis. Nucleated cell counts between 85,000 and 418,000 cells/μL and protein values from 4.7 to 6.5 g/dL were found on postoperative day 5 in six normal horses that had undergone abdominal exploration.⁹²⁸ Peritoneal fluid 5 days after open castration (N=24) contained 30,000 nucleated white cells per microliter, with more than 85% being neutrophils. By day 7 after castration the cell counts were normal, with no toxic or degenerative changes.⁹²⁹ Parturition can cause increased nucleated cell and RBC counts, with elevated total protein values in the peritoneal fluid.⁹³⁰ In a recent study, postpartum mares having uneventful foaling or uncomplicated dystocia had normal peritoneal fluid except for elevation in percent neutrophils. Mares having complicated dystocia had bloody peritoneal fluid with increased total protein (median total protein = 4 g/dL) and WBCs (median WBCs = 40,5000) 1 day after foaling.⁹³¹ Schumacher found no significant alterations in peritoneal fluid in normal horses sampled every 24 hours for 5 days; however, 48 hours after enterocentesis, nucleated cell counts were 113,333 in six of nine horses.⁹³² Cytologic examination of the peritoneal fluid should include a Wright and a Gram stain. Macrophages should be examined closely for evidence of cellular engulfment and erythrophagocytosis. The peritoneal fluid cell morphology is an important diagnostic aid and can be evaluated from the Wright stain. The Gram stain demonstrates the presence of bacteria and can guide initial antimicrobial treatments until culture and sensitivity results become available. Microbiologic culture is performed to identify aerobic and anaerobic bacteria, and antibiotic susceptibility testing is done to identify specific antibiotic therapy. Serial cultures of the peritoneal fluid may be necessary to identify emerging or resistant bacterial strains. Optimal bacteria isolation techniques when peritoneal fluid is cultured require the use of an enriching broth, blood culture medium, and, if appropriate, an antimicrobial removal device.*

Bacteria were cultured or cytologically identified in 48 of 67 horses (71.6%) with peritonitis, and E. coli and Staphylococcus epidermidis were the most common bacteria isolated from peritoneal fluid samples.⁹²⁵ Others have reported only a 16% to 25% isolation rate for infective agents.^923,924 Anaerobes have been isolated from approximately 20% of equine peritonitis cases, with Bacteroides fragilis most common.⁹²⁴ Failure to identify or culture bacteria from peritoneal fluid does not rule out septic peritonitis. Ultrasonography may be helpful in obtaining abdominal fluid, detecting fibrin tags, determining if blood is within the abdomen, or finding an abdominal abscess (Figs. 32-60 and 32-61).

Fig. 32-60 Sonogram of adult horse abdomen showing web of fibrin (F) surrounding fluid found in a horse with chronic peritonitis. The wall of the small intestine (SI) is thickened.

Courtesy Dr. David Schmitz, Texas A&M University.

Fig. 32-61 Sonogram of abdomen full of blood. The fluid appears as swirling echogenic fluid.

Courtesy Dr. David Schmitz, Texas A&M University.

Hemoperitoneum is blood in the abdominal cavity caused by intraabdominal hemorrhage. Although rare in horses, it can be life-threatening. Clinical signs are variable and dependent on cause and severity. Affected horses often show signs of anxiety or depression as well as shock and anemia. Clinical signs of abdominal pain result from high intraabdominal pressure or the irritating effect of blood on serosal surfaces. In one study of 67 cases of hemoperitoneum in the horse, 79% were presented with a primary complaint of abdominal discomfort.⁹³³ Other clinical signs were shock and pale mucous membranes in 60% of horses. Mean heart rate was 76 beats/min, respiratory rate was on average 30 breaths/min, and mean hematocrit was 30% with a total protein concentration of 5.8 g/dL. Causes of the hemoperitoneum were trauma (25%); neoplasia (18%); uterine artery rupture (14%); mesenteric injury (12%); disseminated intravascular coagulation (6%); and idiopathic causes (20%). Fifty-one percent survived to hospital discharge, 37% were euthanized, and 12% died. Poor short-term outcome was significantly associated with a high respiratory rate.

Treatment

Horses with peritonitis require early, aggressive therapy. The treatment of peritonitis involves (1) patient stabilization, (2) correction of the inciting cause, and, in most cases, (3) administration of antimicrobial drugs and/or anthelmintic drugs. Surgical intervention may be required to identify or correct the cause of the peritonitis. See the accompanying algorithm for the treatment of peritonitis in horses.

Stabilization includes treatment of systemic hypovolemia and endotoxic shock. Intensive fluid therapy is usually required to replace fluid losses into the peritoneal cavity and combat cardiovascular collapse. Acid-base disorders should be identified and corrected. Electrolytes, especially calcium and potassium, are important for gastrointestinal function and should be supplemented if deficits exist. If intestinal compromise or gram-negative bacterial infections are suspected as the cause of peritonitis, J5 hyperimmune plasma* (4.4 mL/kg) may moderate the degree of endotoxemia. J5 is a mutant strain of E. coli that lacks the variable oligosaccharide side chains and binds to many gram-negative organisms and endotoxins, providing cross-protection.⁹³⁴ If serum hypoproteinemia (total protein less than 4 g/dL) is present, administration of additional plasma should be considered to minimize peripheral edema.

Prognosis

The prognosis depends on cause, severity, duration, and complications of the peritonitis. The mortality rate was 59.7% in a recent retrospective study of 67 horses with peritonitis.⁹²⁵ The prognosis for mortality in that study was dependent on the inciting cause of peritonitis, with postoperative peritonitis having a high mortality rate (56%).

Laminitis, diarrhea, ileus, and coagulopathies can occur after endotoxemia, and abdominal adhesions or abscess formation can have a negative effect on long-term prognosis. There are no specific laboratory parameters that can predict prognosis in affected horses; however, a rapid response to therapy is considered a favorable prognostic indicator. With early diagnosis, correction of the inciting cause, aggressive medical therapy, and peritoneal lavage, a fair-to-good prognosis can be given in acute cases of septic peritonitis in the horse.

Clinical Signs

The clinical signs of hypovolemia and dehydration are listed inTable 32-7. Hypovolemia is an emergency, and the aim of treatment should be to reverse hypovolemia in 1 to 2 hours. Dehydration needs to be addressed in the first 12 to 24 hours of therapy. Unfortunately, attempts to link given clinical signs with a percent fluid dehydration have not proved accurate.⁹⁴⁸ It is important to assess all clinical signs and make a judgment on the fluid status based on the whole patient, including laboratory parameters if available. For example, tachycardia in horses with colic may be a result of pain or hypovolemia. Clinical signs and response to analgesics or fluid loading may help differentiate the two.

Table 32-7 Clinical Signs of Hypovolemia and Dehydration Horses

Not all signs are consistently present in all horses.

From Corley K, Stephen J, eds: Equine hospital manual, Oxford, UK, 2008, Blackwell. Used with permission.

Laboratory Signs of Dehydration

The most commonly used laboratory tests to assess hypovolemia are PCV and plasma total solids. Unfortunately these tests are neither sensitive nor specific. The PCV may be substantially increased by splenic contraction in the horse, making small increases very hard to interpret. A PCV of over 50% in a resting horse usually represents hypovolemia. Plasma total solids (protein measured by refractometer) or total protein (measured by a chemistry analyzer) concentration also increases with hypovolemia. However, significant protein loss can occur in gastrointestinal disease (particularly with colitis), resulting in a low or normal protein concentration despite marked hypovolemia. Furthermore, hypergammaglobulinemia (e.g., in cyathostomiasis) can increase the plasma total protein concentration in the absence of hypovolemia. The PCV and plasma total solids are most useful when greatly increased or when used serially to monitor the response to fluid therapy.

Plasma or serum creatinine concentrations are useful to assess hydration status in the absence of renal dysfunction. High normal (1.5 to 1.8 mg/dL; 130 to 160 μmol/L) creatinine concentrations can be associated with subclinical hypovolemia and should be evaluated in light of the history and clinical signs. Creatinine concentrations up to 3.5 mg/dL (310 μmol/L) are common with moderate to severe hypovolemia, and concentrations as high as 5 mg/dL (450 μmol/L) are possible with prolonged or marked hypovolemia. Even in severe hypovolemia, the creatinine concentration will not increase by much more than 2.3 mg/dL (200 μmol/L) per day.⁹⁴⁹ If the creatinine concentration is higher than would be suggested by the clinical signs and other laboratory parameters and if the creatinine concentration does not decrease appropriately with fluid therapy, renal dysfunction should be suspected.

Increased blood lactate concentrations in the nonexercising horse are sufficient evidence of a metabolic disturbance to initiate fluid therapy. Blood lactate concentrations are an indicator of tissue perfusion. The most common causes of increased lactate in the horse with gastrointestinal disease are endotoxemia, which can increase tissue lactate production by inappropriate anaerobic metabolism, and hypovolemia. Increased blood lactate concentrations were associated with worse outcomes in equine colic.⁹⁵⁰ Lactate can be measured in the field with hand-held blood gas analyzers.* The expected lactate concentration can also be calculated by means of equations based on electrolyte and acid-base measurements. However, when tested in foals, these equations were only moderately accurate.⁹⁵¹ An increased circulating lactate should be suspected in metabolic acidosis (decreased pH, negative base excess) in the absence of hyperchloremia or hyponatremia.⁹⁵² Urine specific gravity can easily be measured in the field. High urine specific gravity (>1.040) indicates probable dehydration and normal renal concentration of urine. Isosthenuria (1.010) indicates possible renal damage or a recent high fluid load. Urine specific gravity is useful to monitor the response to fluid therapy because rising or continually high specific gravities in the face of fluid therapy indicate insufficient fluid is being delivered to the horse.

Cardiac Filling Pressures

Assessment of cardiac filling pressures and the changes in these pressures in response to fluids is the most accurate method of determining fluid requirements in the hospitalized animal. It is moderately easy to measure CVP in the horse. A piece of sterile polyethylene tubing (PE190, outside diameter 1.70 mm, at least 1.5 m long) can be passed through a 12-gauge jugular catheter into the thoracic vena cava or right atrium. Correct positioning of the end of the tubing is estimated by measuring the distance against the horse and confirmed by observing changes in pressure with breathing activity. The catheter is connected to a pressure transducer or manometer at the level of the sternal manubrium.⁹⁵³ The normal CVP of the horse is 5 to 14 mm Hg.⁹⁵³ In a horse with normal cardiac function, a high CVP indicates fluid overloading and a low CVP indicates insufficient circulating volume. Perhaps more accurate is the change in CVP in response to a “fluid challenge” (bolus of fluids),⁹⁵⁴ but this has not been evaluated in the horse. The fluid challenge method of monitoring fluid therapy may prove to be particularly useful when factors such as acute renal failure or pulmonary edema complicate the gastrointestinal disease.

Crystalloids

For most situations in the field, commercial isotonic polyionic crystalloid solutions are the safest fluids to resuscitate hypovolemic or dehydrated adult horses. They increase plasma volume without causing profound electrolyte disturbances, because they contain approximately the same electrolyte concentrations as plasma. It also follows that polyionic crystalloid solutions are often not sufficient to correct electrolyte imbalances. Isotonic (0.9%) sodium chloride has a higher ratio of chloride to sodium than plasma and therefore causes mild hyperchloremic acidosis in normal ponies.⁹⁵⁵ Isotonic sodium chloride should not be used for resuscitation unless indicated by measured electrolyte abnormalities. Sodium chloride solution has been advocated in hyperkalemia in order to avoid the potassium-containing polyionic fluids. In adult horses with gastrointestinal disturbances (with the exception of quarter horses with the hyperkalemic periodic paralysis (HYPP) phenotype), hyperkalemia is likely to reflect acidosis, and polyionic fluids are probably appropriate.

Two classes of polyionic fluids are available, those for resuscitation and those for maintenance. Maintenance fluids (e.g., Normosol-M*, Plasma-lyte M†) contain higher potassium and lower sodium and chloride concentrations than resuscitation fluids (e.g., Normosol-R*, Plasma-lyte 148†, Isolec‡, lactated Ringer’s solution†). However, maintenance fluids are not currently commercially available in sizes greater than 1 L. This has led to the practice of adding potassium chloride (at 10 to 20 mEq/L) to resuscitation formulas to use as maintenance fluids in adult equine patients.

The different alkalizing agents (or “bicarbonate substitutes”) in resuscitation fluids have some clinical relevance. The alkalizing agent in plasma is bicarbonate. Bicarbonate-containing fluids are unstable when stored and may result in profound metabolic alkalosis. Therefore Hartmann, an American pediatrician, replaced the bicarbonate with lactate to make lactated Ringer’s solution (also called Hartmann’s solution). Lactate is metabolized in the liver, but this process is slow enough to avoid the rapid changes in plasma pH seen with bicarbonate. Sodium bicarbonate and sodium lactate both increase the strong ion difference, resulting in metabolic alkalosis. The cation (sodium) remains in the extracellular fluid, whereas the anion (bicarbonate or lactate) is metabolized.⁹⁵⁶ It is the speed of metabolism of the anion and the renal excretion of sodium that determines the ultimate alkalinizing effect. It may seem counterintuitive to administer lactate-containing fluids to a horse with lactic acidosis resulting from poor tissue perfusion. However, clinical trials in human patients in hemorrhagic shock have shown that lactate-containing fluids do not exacerbate the lactic acidosis of hypoperfusion.⁹⁵⁷ It appears that the liver’s capacity for metabolizing lactate is not overwhelmed in shock, but the delivery of lactate by the circulation to the liver is impaired. Restoring the circulating volume, even with fluids containing moderate amounts of lactate, is sufficient to allow the liver to clear the circulating lactate. In horses with liver disease, which may have impaired lactate metabolism, lactated Ringer’s solution should be used with caution. Alternative alkalizing agents to lactate are found in some commercial polyionic fluids (e.g., acetate and gluconate in Normosol-R). Acetate is metabolized by the muscles and gluconate by a variety of tissues throughout the body. Lactated Ringers’ solution contains calcium, whereas Normosol-R contains magnesium. Calcium is incompatible with whole blood and sodium bicarbonate and is contraindicated in hypercalcemia; therefore fluids containing magnesium can be used in more clinical situations than those containing calcium.

Five-percent dextrose (D5W) and 5% glucose (G5W) solutions are used to replace water without accompanying electrolytes and are effectively hypotonic because the dextrose or glucose is rapidly metabolized. They are indicated in cases in which fluid loss exceeds electrolyte loss, which can occur in strangulating intestinal lesions and colitis.⁹⁵⁸ Horses receiving D5W or G5W should be monitored carefully because rapid administration can lead to hyperglycemia. If the plasma glucose concentration exceeds the renal threshold (approximately 180 mg/dL [10 mmol/L]), an osmotic diuresis will result, which can reduce the benefit of the fluid administration. D5W contains 0.17 kcal/mL, and G5W contains 0.19 kcal/mL. They should not be considered a form of parenteral nutrition. In order to provide 11.5 Mcal/day, the maintenance requirement for a 500-kg horse standing in a stall,⁹⁵⁹ it would be necessary to administer 60 to 70 L of these fluids per day, which would result in serious electrolyte abnormalities. Although the glucose in D5W and G5W has been recommended for resuscitation of some foals, these fluids are poor choices for hypovolemia. Thirty minutes after administration, only 10% of these solutions remain in the circulation. It is better to separate fluid and glucose replacement, if possible. If this is not practicable, 10 to 20 mL of 50% glucose solution should be added per liter of balanced electrolyte solution for acute resuscitation of hypovolemic and hypoglycemic foals.

Sodium bicarbonate has been advocated for correction of the acid-base disturbances associated with equine gastrointestinal disease. However, its use in lactic acidosis is highly controversial,⁹⁶⁰ and it should probably be reserved for use in hyponatremia without hypochloremia and for renal tubular acidosis, manifested by hyperchloremia without accompanying hypernatremia.⁹⁵² Both of these electrolyte disturbances occur occasionally in horses with severe colitis. Sodium bicarbonate should be avoided in horses with respiratory dysfunction because the bicarbonate is converted to carbon dioxide that, if it is not excreted by the lungs, leads to an increase in plasma carbon dioxide tension and further acidosis.⁹⁵² Caution is also necessary in patients with hypocalcemia, because sodium bicarbonate administration can result in tetany; in patients with severe hypokalemia that can be worsened by increasing the plasma pH; and in patients with congestive heart failure, in whom the large sodium load may exacerbate fluid retention.

Homemade or “carboy” fluids, although considerably cheaper than commercial fluids, have been associated with clinical signs of endotoxemia in normal horses⁹⁶¹ and a sevenfold increase in the risk of thrombophlebitis⁹⁶² and therefore cannot be recommended.

Hypertonic Saline

The large volumes of isotonic fluids required for resuscitation in the horse and the fact that only approximately 30% of the administered fluid remains in the circulation after 30 minutes⁹⁶³ have prompted the search for alternative fluids. Hypertonic saline and colloid solutions have received the most attention.

Hypertonic saline (2 to 4 mL/kg of 7% to 7.5% NaCl) has been advocated as a method of quickly restoring circulating volume in shock patients. Administration of 7% sodium chloride results in an increase in the extracellular fluid of two to three times the infused volume for at least 60 minutes after it is infused. This is the result of fluid shifts from the interstitial fluid, principally from the muscle and liver,⁹⁶⁴ without significant fluid replacement. Hypertonic saline should always be followed up by large volumes (at least 10 L for each liter of hypertonic saline) of isotonic polyionic crystalloids within 2.5 hours (the point in experimental studies a which cardiac output begins to fall below baseline).⁹⁶⁵ As well as restoring plasma volume, hypertonic saline reduces the capillary endothelial swelling that may occur as part of SIRS and therefore improves tissue microcirculation and oxygen delivery.⁹⁶⁶ Administration of 5 mL of hypertonic saline solution per kilogram immediately after experimental endotoxin infusion in horses attenuated the cardiovascular derangements associated with endotoxemia more effectively than an equivalent volume of isotonic saline.⁹⁶⁵ However, when compared with pentastarch (a colloid) in horses presented because of surgical colic, hypertonic saline resulted in a lower cardiac output for the first 2.5 hours of anesthesia.⁹⁶⁷ Given the beneficial effects of hypertonic saline in experimental endotoxemia and sepsis, it may have a role after initial fluid resuscitation. However, treatment of endotoxic horses with hypertonic saline after fluid resuscitation has not been clinically evaluated.

The combination of hetastarch (10 mL/kg) or pentastarch 10% (10 to 15 mL/kg) with hypertonic saline (4 mL/kg) appears to be an excellent solution for resuscitation of severely hypovolemic horses, especially in severe colitis.

Colloids

Colloids, particularly hetastarch, have recently been advocated for resuscitation and treatment of severe hypoproteinemia in horses.⁹⁶⁸ Colloids contain large branched molecules (450 kD average molecular weight for hetastarch compared with 69 kD for albumin). These molecules exert a large colloidal oncotic pressure and do not readily leak out of the vasculature and thus hold fluid in the circulation. Endotoxin⁹⁶⁹ and ischemia-reperfusion injury⁹⁷⁰ induce capillary damage that allows plasma albumin to leak out into the interstitium. The large colloid molecules may not leak as readily, allowing their oncotic pressure to draw fluid back into the vasculature. They may also plug the gaps in the capillary endothelium. However, if the capillary damage is severe enough, even the larger colloids may leak into the interstitium and exert their oncotic pressure to draw fluid with them.

In normal ponies, hetastarch is safe but prolongs bleeding times at high doses (20 mL/kg).⁹⁷¹ Pentastarch also affects coagulation, but at higher doses than hetastarch.⁹⁷² Although these hydroxyethyl starches have been used extensively in horses,^967,968 it is still unclear whether their use alters morbidity or mortality. Pentastarch appears to be superior to hypertonic saline when given before emergency colic surgery, at least in terms of cardiac output during anesthesia.⁹⁶⁷ When colloids are used, the plasma total solids or total protein concentration is no longer a useful guide to hydration status or plasma oncotic pressure.⁹⁶⁸

Fresh frozen equine plasma has been used extensively in horses with diarrhea. Although classically prescribed for hypoalbuminemia, its utility for replacing protein is unclear. At least 6 to 8 L need to be given to adult horses to treat clinically significant hypoproteinemia,⁹⁷³ and the effects may be short-lived. Plasma administration does not have the advantage of the larger colloids of potentially drawing fluid back into the circulation in damaged capillaries, but it prevents low plasma oncotic pressure, which leads to generalized edema. Plasma may have a role in replacing AT-III and other cofactors that are depleted during the SIRS, and this has led to its continued use in diarrhea cases, with apparently favorable results. Freshly donated, rather than frozen, plasma contains higher concentrations of clotting factors and cofactors and is preferred in diarrhea cases.

Oral Fluid Therapy

It is possible to effectively treat dehydrated (but not hypovolemic) horses with oral replacement solutions.⁹⁷⁴ In horses with gastrointestinal disease but no apparent dehydration, administration of an electrolyte paste and provision of fresh drinking water may be sufficient to supplement water and electrolytes.⁹⁷⁵ Oral fluids do not need to be sterile and are therefore considerably cheaper than intravenous fluids. It is apparently not necessary to add glucose to oral fluids for the horse,⁹⁷⁶ but electrolytes should be added if feasible. It is important to administer hypotonic or isotonic fluids.⁹⁷⁶ A possible isotonic solution consists of 4.9 g of table salt per liter and 4.9 g of Lite salt* per liter to give final concentrations of 123 mmol/L sodium, 34 mmol/L potassium, and 157 mmol/L chloride.⁹⁷⁶ If sodium chloride is used alone, no more than 9 g should be added per liter. An isotonic solution can be made without the use of weight scales by measuring salt crystals in the barrel of a syringe. Fifteen mL of Lite salt and 15 mL of table salt added to 4 L of water will make an approximately isotonic solution. The fluids should be given via a stomach tube to allow measured quantities to be given. The amount given at one time should not exceed 8 to 10 L in a 500-kg horse, with at least 20 minutes between each administration. Before each dose the stomach should be refluxed and the administration delayed if more than 2 L of fluid are recovered. Some horses will show abdominal pain if large volumes of fluids are given, especially if the fluids are cold.

Oral fluids hydrate the colon contents more effectively than intravenous fluids^977,978 and therefore are an ideal treatment for most horses with large colon impactions.⁹⁷⁹ However, oral fluids are not suitable in hypovolemia. The absorption of fluids from the gastrointestinal tract is dependent on its blood supply, and the physiologic response to hypovolemia is to divert blood supply from the gastrointestinal tract to maintain perfusion of other organs.

Parenteral Nutrition

Any therapeutic plan in the horse should include a nutritional plan. An enteral diet based on the horse’s normal diet is the first choice for nutritional support. However, in adult horses with gastric reflux, ileus, esophageal obstruction, or anorexia, parenteral nutrition should be considered if the interruption to enteral feeding is predicted to last at least 3 days.⁹⁸⁰ The use of parenteral nutrition may be especially indicated in acute protein losing enteropathy, where its use may prolong the oncotic effects of exogenously administered plasma, possibly by preventing plasma albumin from being metabolized for energy. Total parenteral nutrition solutions commonly consist of dextrose, amino acids, lipids, and a vitamin-mineral mix. The estimated energy requirement of a normal adult horse standing in a stall is calculated with the following equation⁹⁵⁹:

The protein requirement is calculated with the following equation⁹⁵⁹:

The formulation of parenteral nutrition solutions is described elsewhere.⁹⁸⁰ Parenteral nutrition is widely used in some practices for horses with gastrointestinal disease.⁹⁸¹ Although there is much anecdotal evidence that parenteral nutrition (as opposed to no nutrition) may be beneficial in adult horses with gastrointestinal disorders, it has not been formally studied. The administration of parenteral nutrition increases the risk of thrombophlebitis and sepsis in hospitalized human patients.⁹⁸²

Resuscitation

Reversal of hypovolemia is the most important phase of fluid therapy. Although no specific experiments have been performed in the horse, there is plenty of evidence from human medicine that early reversal of hypovolemia dramatically improves outcome.^987,988 The clinical signs of hypovolemia are given in Table 32-7. There is no good evidence for choosing between balanced electrolyte solutions and colloids for treatment of hypovolemia. Therefore factors such as availability, speed of administration, ease of transport, and clinician preference will determine this choice.

The most common concept used to describe treatment of hypovolemia is the “shock dose.” This describes the maximum dose of fluids to be given acutely, as a bolus, to animals in shock. The shock dose for adult horses is 60 to 80 mL of crystalloids per kilogram. In practice, ¼ to ½ of the shock dose is given as a bolus. The animal is then quickly reassessed. If any evidence of continuing hypovolemia is present, a further ¼ of the shock dose is then given. This process is then repeated, with the animal being reassessed and given further boluses of ¼ of the shock dose as necessary, until hypovolemia has been reversed or a full shock dose has been given. It should be possible to deliver a full shock dose to a foal in 30 to 40 minutes and to an adult horse in 60 to 90 minutes. Delivering fluid this fast requires a large-gauge catheter and a wide-bore delivery system. In my practice, wide-bore tubing designed for delivery of fluid during arthroscopy is used for reversal of hypovolemia in adult horses. Drip sets with inbuilt coils provide a much greater resistance to flow and are reserved for treatment of dehydration and ongoing losses and provision of maintenance needs. In adult horses with severe hypovolemia, both jugular veins may be catheterized with large-bore catheters (10 to 12 gauge) that allow approximately 35 L/hr to be administered by gravity if a wide-bore administration set is used. One of the jugular catheters should be removed immediately after the initial resuscitation phase is over, to reduce the risk of bilateral jugular vein thrombosis. A fluid pump may also be used to achieve high rates of fluid delivery, but the high pressures may cause damage to the intima of the vein and increase the risk of thrombosis. If colloid fluids are being used for initial resuscitation, 1 L should be used to replace each 3 to 4 L of crystalloid. The amount of hetastarch infused should not exceed 10 mL/kg.

In the neonatal foal, there is an alternative method to the shock dose method that is more practical. For this method, give a bolus of 1 L of crystalloids (i.e., approximately 20 mL/kg for a 50-kg foal) and reassess the foal to decide if hypovolemia has been reversed. Up to three further boluses may be given, reassessing the foal after each. Most obviously hypovolemic foals require at least two boluses. In foals in which the body weight is obviously different from 50 kg, the method needs to be adjusted so that the bolus is approximately 20 mL/kg. In pony foals and very premature thoroughbred foals, a bolus of 500 mL is usually appropriate. In large draft foals, the first bolus should be 2 L.

Deciding that hypovolemia has been reversed and that no further fluids are required is not always straightforward. In adult horses the clinical signs of hypovolemia should improve dramatically. Particularly useful to judge are the heart rate, jugular fill, and urination. Heart rate may not return to the normal range (particularly if other factors, such as pain, are also driving heart rate), but it should decrease. Jugular fill may be noticeably quicker. Adult horses often urinate once sufficient acute fluids have been given. In foals the clinical signs of hypovolemia may not have been present. Often there is an improvement in degree of consciousness with administration of fluids. As for adults, foals often urinate once hypovolemia has been reversed. There may also be a change in mean arterial blood pressure with fluid administration in foals, and a MAP that was reduced and now is consistently above 65 mm Hg probably indicates that sufficient acute fluids have been administered.

It is important to remember that reversal of hypovolemia represents the beginning of fluid therapy, and not the end. Almost all horses that have been hypovolemic will also be dehydrated, and this will need to be addressed over the next 12 to 24 hours. Furthermore, these horses may be sufficiently compromised to limit their fluid intake, or increase their losses, resulting in a continued need for fluid therapy.

Uncontrolled Hemorrhage

There is one important exception to aggressive fluid therapy for hypovolemia. This is in the case of uncontrolled hemorrhage (e.g., intraabdominal bleeds).^989,990 Fluids should be given at a rate of 2 to 3 mL/kg/hr until the hemorrhage has been controlled (usually by surgical intervention). When arterial blood pressure can be measured, therapy should be titrated to a moderate MAP (60 mm Hg).

Dehydration

Estimating the degree of dehydration and replacing it with fluid is not as straightforward as it sounds. Although tables relating clinical signs to estimated percent dehydration have been published,⁹⁹¹ it is unlikely that these are sufficiently accurate to be a useful clinical guide. Evidence from dogs and cats demonstrates that similar tables are not accurate in those species,⁹⁹² and clinical experience suggests that the same is true of the tables designed for horses.

This therefore leaves the clinician without a set recipe to treat dehydration, and with a quandary. The key is monitoring. Once the hypovolemia has been treated, the horse should be examined for clinical and laboratory signs of dehydration. The horse should then be given fluids in excess of the ongoing losses plus the maintenance requirements, until the clinical and laboratory signs of dehydration are no longer present. The aim should be for dehydration to be reversed in 12 to 24 hours. In practical terms, dehydration is usually treated by giving fluids at twice the maintenance rate (see later) with the addition of fluids for ongoing losses. Therefore a dehydrated adult horse will receive 5 mL/kg/hr and ongoing losses, and a foal will receive 9 mL/kg/hr and ongoing losses, until dehydration is reversed. In horses with normal renal function, urine specific gravity is probably the most reliable indicator of when dehydration is reversed. Horses with urine specific gravities below 1.020, and foals with urine specific gravities of 1.010 or less, are unlikely to be dehydrated. Adult horses with normal renal function, frequent urination, and a urine specific gravity of 1.012 or below are probably receiving too much fluid. It is important, however, to check the other clinical signs of dehydration, as isosthenuria (urine specific gravity 1.008 to 1.012) can also occur in horses and foals with renal failure. These horses will usually have increased plasma creatinine concentrations. Horses with polyuric renal failure could become markedly dehydrated or hypovolemic, if fluid monitoring were based on urine specific gravity alone. Skin tent is a reasonably reliable clinical sign to use to judge dehydration in adult horses. It is less reliable in neonatal foals and geriatric horses. Tacky mucous membranes are also reasonably reliable indicators of ongoing dehydration, providing the animal is maintaining its mouth shut most of the time.

Ongoing Losses

Excessive fluid losses from horses with acute abdominal disease frequently do not stop when treatment is initiated, and these must be taken into account in the fluid plan. The most dramatic ongoing fluid losses are with severe diarrhea or nasogastric reflux, which may reach 200 mL/kg/day (100 L/day for a 500-kg horse).⁹⁹³ Even without such obvious losses, horses may lose significant amounts of fluid through sweating, inadequate intake or, rarely, polyuric renal failure.

Treatment for ongoing losses is aimed to exactly replace the amount lost to maintain hydration. This is relatively simple when the amount of fluid lost can be measured, as in the case of nasogastric reflux. Reflux is collected in a graduated bucket, and the amount collected over a 4- to 12-hour period is compared with the amount of fluid administered. If the fluid lost is in excess of the amounts given, the fluid rates are adjusted both to replace this over the next 12 to 24 hours and to account for the higher level of ongoing losses than originally estimated. If the excessive losses have resulted in hypovolemia (on the basis of clinical and laboratory evidence), this must be treated acutely. It is much harder to estimate losses from diarrhea, sweating, and urination. In the case of diarrhea and urination, it is possible either to attempt to collect the feces or urine or to use absorbent bedding and measure the increase in weight. These are almost never done in clinical practice, except in the case of recumbent neonatal foals, for which feces or urine may be readily collected and weighed on incontinence pads or urine may be collected with an indwelling Foley catheter and closed collection system. When ongoing losses cannot be collected, they must be estimated. These estimates may be inaccurate, and the amount of ongoing loss can dramatically change; therefore it is important to frequently reassess the adequacy of fluid therapy through clinical examination and relevant laboratory investigations. Horses in which ongoing losses are not adequately replaced will become dehydrated initially, then hypovolemic. Urine specific gravity and the clinical signs of dehydration are the best methods of ensuring sufficient fluid delivery.

Maintenance

The mean daily water intake (including the water content of feed) of normal resting adult horses is 57 to 64 mL/kg/day at ambient temperatures of 41° F to 77° F (5° C to 25° C).^994,995 When mares were restricted to 40 mL/kg/day, they demonstrated significant dehydration.⁹⁹⁶ A useful guideline for maintenance rate in adult horses is 60 mL/kg/day (2.5 mL/kg/hour). Thus, a 500-kg horse requires approximately 30 L/day for maintenance, in addition to any fluids to replace ongoing losses. The maintenance requirement of neonatal foals is significantly higher and is usually taken to be 4 to 5 mL/kg/hr,^997,998 although some authors use a lower estimate.⁹⁹⁹ The fluid intake of nursing foals considerably exceeds this figure.¹⁰⁰⁰ However, clinical experience suggests that use of 4 to 5 mL/kg/hr is appropriate for maintenance in foals receiving no enteral fluids. It should be emphasized that it is important to take into account the fluid component of all infusions when calculating fluid rates to avoid inadvertent volume overload in neonatal foals receiving a number of intravenous infusions. For both horses and foals with normal enteral function, it is possible to meet maintenance requirements with nasogastric fluids, if this is clinically appropriate.

Monitoring of adequacy of fluid delivery is vital even when dehydration has been addressed and there are no major ongoing losses. The fluid requirements of the animal can change during treatment, and it is important to check that they are matched to requirements. Again, this is best done by monitoring urine specific gravity and assessing for the clinical signs of dehydration.

Acid-Base Disturbances

The most common acid-base disturbance in horses with gastrointestinal disease is metabolic acidosis, caused by lactic acidosis (hypovolemia, endotoxemia), hyponatremia (colitis, peritonitis, intestinal torsion), or hyperchloremia (occasionally seen in colitis cases). Metabolic alkalosis, resulting from hypochloremia (high-volume gastric reflux) or hypoalbuminemia (severe enterocolitis, excessive fluid therapy), respiratory alkalosis (hyperventilation from pain), and respiratory acidosis (hypoventilation from extreme abdominal distention, central depression) can also occur.⁹⁵²

Although the predominant clinical signs in horses with acid-base disturbances are likely to result from the cause of the disturbance, clinical signs can arise from the physiologic consequences of the derangement. Metabolic acidosis can result in reduced cardiac contractility, constriction of the peripheral vasculature, inhibition of glycolysis, decrease in oxygen uptake by hemoglobin in the lungs, and CNS depression. Metabolic alkalosis can lead to overexcitability of nervous tissue, blunting of the hypoxic drive, compensatory hypoventilation, susceptibility to cardiac arrhythmias, and inhibition of oxygen release in the tissues.

Treatment of acid-base disturbances should be directed at the underlying cause and the specific plasma constituent imbalance. It is possible to determine the relative contributions of unidentified anions (principally lactate in horses with gastrointestinal disturbances), sodium, chloride, and protein to the measured acid-base status by the use of equations based on the calculated base excess.^952,1003 However, decisions for treatment can often be based on the absolute values of these blood constituents, and it is only in complex disturbances with changes in multiple blood constituents that the equations are usually necessary.

Lactate

As discussed earlier, increased blood or plasma lactate concentrations are usually a result of poor tissue perfusion in gastrointestinal diseases but may also be caused by inappropriate anaerobic metabolism in endotoxemia. The clinical signs of lactemia are those of the accompanying metabolic acidosis, but the signs of the cause of the lactic acidosis (those of shock) may predominate.

Although lactate can be directly measured, its plasma concentration can be accurately predicted by the anion gap in adult horses with normal plasma protein concentrations.¹⁰⁰⁴ The anion gap is calculated from the plasma concentrations of (sodium + potassium) minus the concentrations of (chloride + bicarbonate). The normal range is 7 to 15 mEq/L.¹⁰⁰⁴ At low and high protein concentrations, the equations based on base excess^952,1003 or the simplified strong ion gap (2.24 × total protein [g/dL]/[1 + 10^6.65−pH] − Anion gap)¹⁰⁰⁴ should be used. Any of these calculations may easily be performed on a pocket calculator, but none was accurate in critically ill foals.⁹⁵¹

Lactic acidosis should be treated with large volumes of polyionic crystalloid solutions. The use of sodium bicarbonate in lactic acidosis is highly controversial.^960,1005 It corrects the laboratory value (pH) without addressing the underlying pathophysiology (poor tissue perfusion) by imposing a hypernatremic alkalosis on an already deranged metabolic balance. Although increasing the pH may improve myocardial contractility, this effect may be negated by the myocardial depressant effects of an increased carbon dioxide tension.¹⁰⁰⁶ In endotoxic ponies, administration of sodium bicarbonate resulted in an increased blood lactate concentration, hypernatremia, hypokalemia, and hyperosmolality.¹⁰⁰⁷

Sodium

Low plasma sodium concentrations are most commonly seen in acute colitis, such as salmonellosis, PHF, and clostridiosis. The hyponatremia is usually accompanied by hypochloremia because of an increased loss of electrolytes relative to water.⁹⁵⁸ Other gastrointestinal conditions associated with hyponatremia are those that result in third spacing of sodium (peritonitis, torsion or volvulus of gut) and with sodium-wasting disorders (esophageal obstruction leading to loss of saliva). The clinical signs of hyponatremia are neurologic disturbances, including reduced or absent menace response, intention tremor, and hypermetric gait,¹⁰⁰⁸ but severe clinical signs do not usually occur until the sodium concentration is less than 110 mEq/L.¹⁰⁰⁹ Hyponatremia will also result in metabolic acidosis.⁹⁵²

The fluid choice for hyponatremia depends on whether there is concurrent hypochloremia. If the plasma chloride concentration is also low, sodium chloride should be used. If the chloride concentration is normal or increased (which is rare in gastrointestinal disease), then sodium bicarbonate should be administered. If the hyponatremia is severe, then hypertonic solutions may be administered initially (7% to 7.5% sodium chloride and 5% to 8.4% sodium bicarbonate, respectively). Rapid correction of sodium deficits in other species can cause central pontine myelinosis.¹⁰⁰⁹ It is unclear whether this is a risk in the horse and therefore whether it is necessary to follow the guidelines for sodium restoration in other species. These guidelines state that sodium should be corrected at a rate of 1 mEq/L/hr in acute hyponatremia and at less than 0.5 mEq/L/hr in chronic hyponatremia, in neither case to exceed 8 mEq/L during the first 24 hours.¹⁰⁰⁹

Hypernatremia is rare in horses with gastrointestinal disease^{958,1001,1010} and is usually caused by water loss in excess of electrolytes and accompanied by hyperchloremia. To correct hypernatremia, low-sodium fluids such as 5% dextrose or 2.5% dextrose and 0.45% sodium chloride should be administered. Again, in other species it is recommended not to correct hypernatremia too rapidly; sodium should be lowered by 0.5 mEq/L/hr, not to exceed 12 mEq/L over the first 24 hours.¹⁰⁰⁹

Clinical signs associated with hyponatremia and hypernatremia are caused by changes in plasma osmolality. Sodium is the major cation in plasma, and sodium and glucose concentrations are the main determinants of plasma osmolality.⁹⁵⁸ Changes in plasma osmolality can lead to CNS edema or dehydration, resulting in neurologic signs.¹⁰¹¹ Rapid changes in plasma sodium concentration may also cause CNS edema or dehydration, because the cerebrospinal fluid slowly equilibrates with the plasma, but will rapidly change if osmotic gradients are high.

Chloride

The loss of gastric hydrochloric acid in high-volume reflux (in proximal enteritis and grass sickness) and the secretion and/or lack of absorption of chloride in severe colitis often leads to hypochloremia in gastrointestinal disease.^1001,1010 Hypochloremia in the absence of hyponatremia results in metabolic alkalosis.⁹⁵² The alkalosis associated with hypochloremia may also result in increased cellular uptake of potassium, leading to hypokalemia.¹⁰⁰⁹

Treatment of hypochloremia can usually be achieved with intravenous 0.9% sodium chloride, which contains more chloride relative to sodium than plasma. In horses with high-volume gastric reflux, administration of intravenous H₂-receptor antagonists (e.g., cimetidine at 6.6 mg/kg IV qid) reduces gastric hydrochloric acid secretion and therefore should reduce chloride loss. In humans, intravenous hydrochloric acid has been used to treat severe hypochloremia,¹⁰¹² but carries substantial risks for the patient.¹⁰¹³ Hyperchloremia is rare in horses with gastrointestinal disease but may occur in severe colitis because of water secretion in excess of electrolytes. It should be treated with 5% dextrose if accompanied by hypernatremia and with sodium bicarbonate if severe and accompanied by a low or normal plasma sodium concentration.¹⁰⁰⁹

Potassium

Hypokalemia is commonly seen in horses after surgery for colic¹⁰¹⁰ because of enhanced mineralocorticoid and glucocorticoid release and because of infusion of large amounts of sodium-containing fluids that increase distal tubular flow and renal potassium loss.¹⁰¹¹ Hypokalemia also occurs in colitis and metabolic alkalosis. The most relevant clinical sign of hypokalemia is reduced intestinal motility.^1009,1014 However, the association between hypokalemia and ileus remains undetermined in the horse. Other clinical signs include muscle weakness, lethargy, and inability to concentrate urine.¹⁰⁰⁹ Cardiac conduction abnormalities are rare except in severe hypokalemia and in preexisting cardiac dysfunction.¹⁰¹⁴ The effect of potassium on acid-base status is small and need not be considered clinically.⁹⁵²

Potassium is primarily an intracellular ion, and therefore decreases in whole body potassium may not be detected by plasma measurements.¹⁰¹⁵ Although erythrocyte potassium content has been used to estimate whole body potassium,¹⁰¹⁵ its accuracy is unclear. Moreover, the extracellular potassium concentration (reflected in the plasma) is more relevant to neuromuscular transmission and therefore to the important clinical signs than whole body potassium stores.¹⁰¹¹ The intervention level for treatment of hypokalemia is unclear. In postoperative colic cases and proximal enteritis, the prevention of ileus is a primary goal, and it may be prudent to supplement the plasma potassium concentration below 3.5 mEq/L. In other patients, especially those being fed enterally, it may not be necessary to treat plasma potassium concentration above 3 mEq/L.

Hypokalemia is treated with intravenous potassium chloride solution. The rate of administration is more important than the amount. The rate should not normally exceed 0.5 mEq/kg/hr and should never exceed 1 mEq/kg/hr.¹⁰⁰⁹ The addition of 40 mEq of potassium chloride per liter of crystalloid fluids is safe at rates up to 10 mL/kg/hr (5 L/hr for a 500-kg horse). This amount is usually required only in severe hypokalemia (<2.7 mEq/L), and smaller disturbances can often be successfully treated with 20 mEq of fluid per liter. If hypokalemia does not respond to potassium chloride administration, magnesium should be supplemented.¹⁰¹⁶ Hyperkalemia is not typical in horses with gastrointestinal disease, although it may occur with acidosis, colitis, secondary renal failure, and hyperkalemic periodic paralysis. Artifactual hyperkalemia may be seen in blood samples stored for longer than 2 hours before plasma separation, because of leaching of potassium from the erythrocytes. Clinical signs are due to disruption of neuromuscular transmission and are therefore similar to those of hypokalemia. In the absence of clinical signs, polyionic fluids should be administered. Possible treatments for symptomatic or severe (>7 mEq/L) hyperkalemia include calcium gluconate (1 mL/kg IV over 10 minutes), sodium bicarbonate (1 to 2 mEq/L IV over 15 minutes) and 50% dextrose solution (2 mL/kg IV over 5 minutes).¹⁰⁰⁹

Calcium

Low plasma ionized calcium concentrations are common in horses with surgical colic¹⁰¹⁷ and in colitis cases. Possible causes of this hypocalcemia include lactic acidosis,¹⁰¹⁸ endotoxin-induced changes in calcium homeostasis,¹⁰¹⁹ and functional disturbances to the small intestine (the main site of calcium absorption in the horse¹⁰²⁰). Clinical signs of hypocalcemia reported in the horse include synchronous diaphragmatic flutter, tetany, muscle spasm, and seizures.¹⁰²¹ Of these, only diaphragmatic flutter is seen with any regularity in adult horses. Hypocalcemia has also been associated with POI in the horse,^{1017,1022,1023} but a causal relationship has not been demonstrated.

Approximately 50% of the total calcium in plasma is bound to albumin or complexed with small ligands. The remaining ionized fraction is the biologically active form. Where possible, the plasma ionized calcium concentration should be measured, rather than the total concentration, because the plasma albumin concentration is often decreased in gastrointestinal diseases. If total plasma calcium measurements are used to guide therapy, the calcium concentration should be corrected for changes in albumin concentration. The intervention level for treatment of hypocalcemia is debatable. There is one report of exacerbation of endotoxemia with calcium administration in a rodent model.¹⁰²⁴ Although the relevance of this to the horse has not been determined, aggressive supplementation of calcium in endotoxemic horses may be inadvisable. Even in endotoxic horses, calcium should probably be supplemented if the ionized calcium concentration is less than 4.8 mg/dL (1.2 mmol/L).

Hypocalcemia is treated with intravenous 23% calcium gluconate or 20% to 40% calcium borogluconate solution. A typical volume required is 100 to 300 mL of the 20% to 23% solution,¹⁰¹⁷ but the amount will depend on ongoing losses, and the ionized calcium concentration should be frequently checked during therapy. Calcium solutions are irritating to the veins and should be diluted in crystalloid fluids before administration. They are incompatible with sodium bicarbonate and whole blood. After calcium supplementation, the plasma calcium concentration should be checked after 4 to 8 hours because ongoing losses and redistribution into cells may result in further hypocalcemia. Hypocalcemia can be a sequela to magnesium deficiency, and therefore magnesium should be supplemented in horses with refractory hypocalcemia.

Hypercalcemia occurs in horses with chronic renal failure but is rare in gastrointestinal disease. Clinical signs are usually those of the underlying pathophysiology, but soft-tissue calcification may occur. Treatment for severe hypercalcemia (ionized calcium greater than 9 mg/dL [2.25 mmol/L]) should include non—calcium-containing intravenous fluids (sodium chloride or Normosol-R) and intravenous magnesium sulfate (see treatment of hypomagnesemia, later).

Magnesium

In one report, 44% of horses with gastrointestinal disease had low plasma magnesium concentrations.¹⁰²⁵ Causes of hypomagnesemia include decreased intake, gastrointestinal losses (prolonged nasogastric reflux, malabsorption), alterations in distribution (endotoxemia, parenteral nutrition administration), renal losses (prolonged administration of lactated Ringer’s solution or other magnesium-free fluids, hypophosphatemia, acidemia, renal tubular acidosis),^1026,1027 and excessive sweating.¹⁰²⁸ Severe hypomagnesemia can result in ventricular arrhythmias and also muscle tremors, ataxia, seizures, and calcification of elastic tissue¹⁰²⁹ in the horse. Other clinical manifestations of hypomagnesemia reported in human patients include supraventricular tachycardia, atrial fibrillation, thrombosis, anemia, decreased muscle strength, increased nephrotoxicity of aminoglycoside drugs, increased pulmonary vascular resistance, and sudden death.^{1026,1030-1032} Hypomagnesemia can also result in hypokalemia refractory to potassium supplementation.¹⁰¹⁶

Extracellular fluid contains approximately 1% of the total body magnesium, and therefore the serum magnesium concentration may not reflect the total body magnesium status,¹⁰²⁷ making diagnosis of hypomagnesemia difficult. Fortunately it is safe to administer moderate amounts of magnesium, irrespective of the magnesium status of the horse, providing the horse has normal renal function. Intravenous magnesium sulfate (at 2 mg/kg/min, not to exceed 50 mg/kg) is recommended for ventricular arrhythmias associated with hypomagnesemia.¹⁰³³ Higher doses should be avoided because they cause significant muscle weakness; 140 mg/kg of intravenous magnesium sulfate can induce recumbency in normal horses.¹⁰³⁴ For treatment of hypomagnesemia in the absence of cardiac signs, 2 to 8 mg/kg can be used as an initial dose in horses with normal renal function. Oral supplementation is possible with magnesium oxide, but oral magnesium sulfate should be avoided because of its laxative effects.

In the study by Costa and colleagues, 11% of horses with gastrointestinal disease were hypermagnesemic, but associated clinical signs were not reported.¹⁰²⁵ Severe clinical signs after nasogastric administration of magnesium sulfate were reported in two horses with large colon impactions. The doses given were between 1600 and 2000 mg/kg. Both horses recovered 1 to 6 hours after the onset of clinical signs, which included flaccid paralysis with recumbency, tachycardia, tachypnea, and nondetectable peripheral pulses. The horses were treated with 250 mL of 23% calcium gluconate solution IV, repeated after an hour, and polyionic intravenous fluids to promote diuresis.¹⁰³⁵ The phosphorylation of adenosine diphosphate (ADP) to form ATP is dependent on the intracellular magnesium concentration,¹⁰³⁶ and therefore hypomagnesemia can disrupt ATP-dependent cellular processes. The sodium-potassium ATPase pump, the major mechanism for controlling intracellular and extracellular sodium and potassium concentrations, is ATP dependent and thus magnesium dependent. This may explain the relationship of refractory hypokalemia to hypomagnesemia.¹⁰¹⁶ The relationship between the sodium-potassium ATPase pump and magnesium may also explain the effect of magnesium on calcium flux, because sodium is exchanged down its concentration gradient (controlled by the sodium-potassium ATPase pump) for calcium by the sodium-calcium exchanger.¹⁰³⁷ Because of the interaction of the magnesium concentration with these other electrolytes, a main effect of hypomagnesium is to alter depolarization of nerve and muscle cells.¹⁰³¹ Magnesium also directly competes with calcium for some of its binding sites, allowing greater binding of calcium to enzymes in hypomagnesemia. One such enzyme is phospholipase A₂; increased calcium binding results in greater activity of this enzyme, which leads to the increased formation of eicosanoids, particularly TXA₂,¹⁰³⁰ that may play a role in thrombophlebitis.¹⁰³⁸

Phosphorus

Hypophosphatemia has been reported in horses with either strangulating intestinal lesions or intestinal ileus¹⁰⁰¹ and is also a sequela to renal dysfunction.⁹⁴⁹ Prolonged administration of lactate-containing fluids,¹⁰³⁹ metabolic or respiratory alkaloses, repeated gastric magnesium sulfate administration (because magnesium binds phosphate to form an insoluble complex), and prolonged administration of non—lipid-containing parenteral nutrition solutions¹⁰⁴⁰ may also result in hypophosphatemia. Reduced intestinal phosphate absorption, apparently without hypophosphatemia, is a sequela to large colon resection.¹⁰⁴¹ Clinical signs reported in small animals and humans with hypophosphatemia include hemolysis, skeletal muscle weakness and rhabdomyolysis, leukocyte dysfunction, ventricular arrhythmias, and reduced cardiac output.^1040,1042

Clinical manifestations and treatment of hypophosphatemia have not been reported in the horse, and in humans there is no good evidence for treatment in the absence of clinical signs.¹⁰⁴⁰ Treatment options reported in small animals include intravenous potassium phosphate (0.01 to 0.03 mmol/kg/hr) and oral potassium phosphate (0.5 to 2 mmol/kg/day).¹⁰⁴² The potential effects of potassium phosphate on the plasma potassium concentration must be considered before this treatment is commenced. Intravenous glucose-1-phosphate¹⁰⁴³ and intravenous sodium phosphate have also been reported in humans. The safety of these treatments has not been evaluated in the horse.

Hyperphosphatemia occurs in horses with strangulating intestinal lesions¹⁰⁴⁴ and severe colitis¹⁰⁰¹ without specifically attributable clinical signs. Clinical findings reported in small animals include diarrhea, hypocalcemia, hypernatremia, and an increased propensity to metastatic soft-tissue calcification. Treatment recommended in small animals includes intravenous fluids, to correct any acidosis and promote renal phosphorus excretion, and dextrose-containing fluids, to promote translocation of phosphorus into cells.¹⁰⁴²

The clinical signs of hypophosphatemia result from the wide range of physiologic functions of phosphate. These include storage of energy as ATP, which is used for many processes including muscle contraction, neuronal transmission, and electrolyte transport. Because phosphorus and magnesium deficiencies can both result in reduced availability of ATP, the clinical signs can be similar. Phosphate also acts as a buffer in plasma and is a component of many intracellular compounds including phospholipids, nucleic acids, enzymatic cofactors, and signaling molecules such as cyclic adenosine phosphate. It appears that increased plasma phosphate concentrations are not directly toxic.¹⁰⁴⁵ Hypocalcemia and metastatic soft-tissue calcification caused by hyperphosphatemia result from the calcium-phosphate product exceeding that required for precipitation of calcium phosphate in the tissues.^1042,1045

Albumin

Hypoalbuminemia is common in horses with moderate to severe compromise of the colon. It may also occur with over-aggressive fluid therapy and parasitism. Clinical signs of hypoalbuminemia are peripheral edema (due to reduced plasma oncotic pressure) and tissue and organ edema, leading to reduced oxygen uptake by cells (increased perfusion distance), and in severe cases organ failure. Albumin is a weak acid, and severe hypoalbuminemia may contribute to metabolic alkalosis or mask concurrent metabolic acidosis.⁹⁵² A decrease in albumin concentration of 1 g/dL results in an increase in the base excess of +3.7 mEq/L.¹⁰⁰³

Hypoalbuminemia should be treated when acute or if there are clinical signs. Although it is advisable to treat all horses with a plasma total solids concentration of less than 4 g/dL, a few horses with chronic hypoproteinemia can have plasma total solids concentrations of 3.5 to 4 g/dL with no apparent clinical signs. The treatment options for hypoalbuminemia include fresh or fresh frozen equine plasma, concentrated albumin solutions, and hetastarch. Plasma has the advantage of containing other factors, such as AT-III, that may be depleted in the disease process. Hetastarch has the advantage of large molecular size and long persistence in the circulation⁹⁷¹ but has questionable efficacy in human patients. Albumin solutions were shown to result in neither benefit nor harm in human critically ill patients when compared with saline.¹⁰⁴⁶ At the time of writing, equine albumin solutions are not available commercially, and their role in the treatment of horses is unclear.

Thrombophlebitis

Thrombophlebitis is a common complication of intravenous fluid therapy.⁹⁶² It may be a nidus for infection and may cause mechanical blockage of venous drainage, resulting in local edema. Fatal edematous occlusion of the upper respiratory tract can result from bilateral jugular vein thrombosis. It is therefore advisable not to catheterize the contralateral jugular vein if one jugular vein shows any signs of thrombosis. Bacterial endocarditis, particularly of the tricuspid valve, can occur as a sequela to infectious thrombosis.

Thrombophlebitis can be identified by heat, swelling, or the presence of any exudate around the catheter insertion site or by palpation of a thrombus (“corded” feel) in the catheterized vein. Catheterized veins should be checked at least daily. Ultrasonography of the catheterized vein can help identify thrombus formation. It is prudent to continue to check the vein for 2 to 3 days after catheter removal because thrombophlebitis may develop or become apparent in this time period.

The risk factors for thrombophlebitis include administration of carboy fluids,⁹⁶² presence of diarrhea⁹⁶² or endotoxemia,¹⁰³⁸ polytetrafluoroethylene (Teflon) catheter material, and long duration of catheterization.⁹⁸⁴ Several other risk factors for thrombophlebitis have been identified in humans but not studied in horses. These include inexperienced personnel placing the catheter,¹⁰⁴⁷ administration of total parenteral nutrition,⁹⁸² and larger-bore catheters.¹⁰⁴⁸ Treatment for thrombophlebitis should include topical nitroglycerin ointment¹⁰⁴⁹ and probably also hot-packing and topical DMSO ointment. Catheters from thrombosed veins should be removed aseptically and cultured (preferably by the roll-plate technique¹⁰⁵⁰) to allow in vitro susceptibility directed antimicrobial therapy, if necessary. A fine-needle aspirate of the thrombus can also be used for bacterial culture. Fluid-filled pockets within the thrombus can often be identified by ultrasound¹⁰⁵¹ and should undergo aspiration after surgical preparation of the skin over them. Empirical antimicrobial drugs should be broad spectrum with activity against Streptococci and Staphylococci species¹⁰⁵¹ and have good tissue penetration. Such drugs include ceftiofur, gentamicin, and chloramphenicol.

Overhydration

Clinical signs of overhydration are rare in adult horses with normal cardiac and renal function. The most important clinical sign is pulmonary edema, manifested by dyspnea and a pink-white foamy nasal discharge. Treatment should include furosemide (0.5 to 1 mg/kg IV) and a reduction in the rate of fluid administration. Intranasal oxygen supplementation is indicated when there is significant hypoxemia (detected by arterial blood gas analysis). Further fluid therapy in such horses should be carefully monitored, ideally by means of CVP measurements.

Dobutamine

In the absence of cardiac output measurements, dobutamine should be the first drug used in hypotensive horses (MAP <65 mm Hg) that have not responded to appropriate fluid therapy. Dobutamine is a β₁-adrenergic agonist and increases cardiac output.¹⁰⁵⁸ Dobutamine also has significant β₂ activity, which could cause vasodilation. Dobutamine should be diluted in isotonic saline, 5% dextrose, or lactated Ringer’s solution. The dose should be carefully titrated from a starting dose of 1 to 3 μg/kg/min. The horse should be carefully monitored for tachycardia, which in some cases may indicate inadequate fluid resuscitation, and for dysrhythmias.

In horses with endotoxemia and increased cardiac output, dobutamine is unlikely to improve tissue oxygenation. Despite increasing cardiac output, dobutamine did not ameliorate experimental colon ischemia in the pig.¹⁰⁵⁹

Norepinephrine

In hypotensive horses that either do not respond to dobutamine or have a measured increased cardiac output, norepinephrine (noradrenaline) administration should be considered. Norepinephrine is an α-adrenergic and moderate β₁-adrenergic agonist. It is a powerful vasoconstrictor in the horse.¹⁰⁶⁰ Norepinephrine should be diluted in 5% dextrose. A starting dose is 0.1 μg/kg/min, and effects may be seen in some patients at doses as low as 0.01 μg/kg/min. The highest reported doses are 1.5 μg/kg/min in the horse¹⁰⁶⁰ and 3.3 μg/kg/min in human patients.¹⁰⁶¹ Concurrent infusion of dobutamine (5 μg/kg/min) with norepinephrine has been demonstrated in humans to result in improved tissue perfusion¹⁰⁶² and might be prudent when cardiac output is not being directly monitored. It is important to carefully monitor urine output when using norepinephrine, as inappropriate doses may reduce renal blood flow.

Dopamine

Dopamine has β-adrenergic (inotropic), α-adrenergic (pressor), and dopaminergic effects. In other species the dopaminergic effects predominate at low doses (1-5 μg/kg/min), the β-adrenergic effects at moderate doses (5 to 10 μg/kg/min), and the α-adrenergic effects at high doses (above 10 μg/kg/min),¹⁰⁶³ but these distinctions may be blurred in the horse.¹⁰⁶⁴ In anesthetized horses a dopamine infusion started 5 minutes after endotoxin administration improved cardiovascular variables but did not prevent hypoxemia or metabolic acidosis.¹⁰⁶⁵ Dopamine causes significant vasoconstriction of equine colonic arteries at higher doses in vitro¹⁰⁶⁶ and is associated with reduced gastric mucosal perfusion in human septic patients in vivo.¹⁰⁶⁷ Furthermore, dopamine may disrupt normal equine gastrointestinal activity, even after the infusion is stopped.¹⁰⁶⁸ In normal horses low doses of dopamine (5 μg/kg/min) can cause cardiac arrhythmias.¹⁰⁶⁴

Dopamine is not recommended for horses with gastrointestinal diseases because of the reported deleterious effects on the gastrointestinal system and because the predominant effects vary with the plasma concentration,¹⁰⁶⁴ which cannot be predicted from the infusion rate.^1069,1070 Low-dose dopamine has been demonstrated not to have any efficacy in preventing or treating acute renal failure in human patients,¹⁰⁷¹ and dopamine infusion does not increase creatinine clearance in the normal horse.¹⁰⁶⁴

Nitroprusside

In severely hypertensive horses, sodium nitroprusside administration should be considered.¹⁰⁵⁸ A diastolic blood pressure greater than 110 to 120 mm Hg is considered to be a hypertensive crisis in human medicine.¹⁰⁷² Nitroprusside liberates nitric oxide by a nonenzymatic one-electron reduction that occurs on exposure to tissues such as vascular smooth muscle membranes.¹⁰⁷³ Hypertension, particularly pulmonary hypertension, has been reported in experimental horses and foals treated with a low dose of endotoxin.^{965,1057,1074} Laminitis is also associated with hypertension (MAP up to 158 mm Hg).¹⁰⁷⁵ However, this increase in arterial pressure may be associated with increased cardiac output rather than a generalized increase in vascular tone (systemic vascular resistance).¹⁰⁷⁵ Nitroprusside induces relaxation of palmar digital arteries and veins isolated from carbohydrate-overloaded horses.¹⁰⁷⁶ Treatment of acute laminitis with glyceryl trinitrate applied topically to the pasterns results in some amelioration of clinical signs.¹⁰⁷⁷ Assuming that this response is due to nitric oxide, parenteral nitroprusside administration would represent a method of delivering a more controlled source of nitric oxide. The potential beneficial role of nitroprusside administration in ameliorating laminitis remains to be investigated.

Sodium nitroprusside should be diluted in 5% dextrose solution and wrapped in foil to protect the solution from light. The dose should be carefully titrated from a starting dose of 0.1 to 0.3 μg/kg/min. It is imperative to monitor the blood pressure continuously during the initial titration phase and frequently thereafter. As with all nitric oxide donors, there is a reduced responsiveness with time that may necessitate increasing doses.¹⁰⁷³ Hepatic metabolism of nitroprusside produces thiocyanate and cyanide, which may result in altered neurologic status, acidosis, and death at high concentrations.¹⁰⁷⁸ In human patients, cyanide toxicity has not been reported at doses of less than 2 μg/kg/min.¹⁰⁷⁸ Fenoldopam, a selective dopamine-1 receptor agonist, is a possible alternative antihypertensive agent that has been used experimentally in the horse and foal.^1079,1080 However, the current cost of fenoldopam is likely to prohibit its use in adult horses.