Colitis

OMEGA 3 FATTY ACIDS FOR ENDOTOXEMIA Speaking at the 1997 ACVIM Medical Forum, in Florida, Dr. Joan B Carrick described her studies of the effects of omega 3 fatty acids on endotoxemia in horses. A diet rich in omega 3 fatty acids can reduce the severity of endotoxemia, but ingestion of omega 3 fatty acids does little to improve the clinical situation, where the animal is ill prior to treatment. She explained that, "The major mediators of endotoxemia include the cytokines, tumor necrosis factor, interleukin-1, interleukin-6, interleukin-10 and interleukin-12, and the lipid mediators, platelet activating factor and eicosanoids, thromboxane A z, prostacyclin, prostaglandin E e, and leukotrienes. The eicosanoids are derived from 20 carbon fatty acids, arachidonic acid (f~-6) or eicosapentanoeic acid (f~-3), located in the phospholipids of cell membranes and in the neutral lipids, primarily triglycerides. Inhibition of thromboxane and prostaglandin synthesis using cyclooxygenase inhibitors reduces the pathophysiological changes associated with endotoxemia and are beneficial in the early stages of equine endotoxic shock." Fish oil is a good source of ~-3 fatty acids. The observation that Greenland Eskimos have a low incidence of athrosclerotic disease has resulted in intense interest in dietary

Volume 17, Number 7, 1997

modification of cell membrane fatty acid composition with f~-3 fatty acids, according to Dr. Carrick. She pointed out that Incorporation of f~-3 fatty acids into cell membranes reduces the quantity of arachidonic acid available for eicosanoid synthesis. Although reduction of eicosanoid synthesis is the principal effect of ingestion of f2-3 fatty acid enriched diets, other physiological and cellular responses occur. These responses include changes in cytokine synthesis, expression of procoagulant activity, lymphocyte proliferation, phagocytosis, antibody production, natural killer cell activity, chronic inflammation, reduction of hypertension, prolonged bleeding times and platelet aggregation. Eicosanoid synthesis is reduced further by ingestion of these diets because eicosapentaenoic acid competitively inhibits cyclooxygenase activity. Metabolism of eicosapentaenoic acid yields the 3-series prostaglandins and 5-series leukotrienes which frequently have anti-inflammatory effects thereby moderating the effects of the naturally occurring eicosanoids. Because eicosanoids are important in the pathophysiology of endotoxic or septic shock, ingestion of diets enriched with f~-3 fatty acids should reduce the detrimental effects of endotoxin.

COLITIS Dr. Noah D. Cohen said, "The causes of equine colitis are manifold and it is often difficult to identify the cause(s) for a case of acute colitis. Infectious causes are often considered first, but non-infectious etiologies should be considered. Infectious agents most often associated with colitis in

horses include Salmonella spp, Ehrlichia risticii, and Clostridium difficile; however, other bacteria and viruses may cause colitis in horses. Larval c y a t h o s t o m i a s i s is often implicated in cases of colitis in Europe, and may be an under-recognized cause of colitis in the United States. Although equine colitis is considered most often to result from an infectious cause, efforts to identify an enteropathogen often fail. Non-infectious causes of colitis include changes in dietary composition or quantity, toxic causes (e.g., p h e n y l b u t a z o n e or cantharadin toxicosis), and antibiotic-associated diarrhea." He described the clinical signs of colitis: " D i a r r h e a is c o m m o n l y observed. The consistency and color of diarrhea does not indicate the cause of diarrhea. Hemorrhagic diarrhea is uncommon but can be seen with some cases of salmonellosis, clostridial enterocolitis/colitis X, antibioticassociated colitis, and cantharidin toxicosis. Onset of diarrhea can be variable, regardless of cause; some horses progress from semi-formed stool to a cow-pie consistency to a watery stool, while others have an acute onset of profuse, projectile diarrhea. The volume of stool may vary. Colic (sometimes severe) often precedes diarrhea. Although c o m m o n l y observed, it is important to remember that not all cases of equine colitis develop diarrhea. Diagnosis of such cases can be difficult, and some horses with non-diarrhetic colitis can be severely ill." Treatment of colitis is often laborintensive and expensive, according to Dr. Cohen. Regardless of the cause, certain aspects of treatment will be shared by all horses with colitis. Horses

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with diarrhea require fluid therapy. Pending results of serum electrolyte concentrations, horses should receive polyionic fluids that contain potassium (except in renal failure). Generally, IV therapy is needed for horses with acute colitis. Although acidemia often is corrected by restoring adequate circulatory volume, an alkalizing solution such as lactated Ringer's is preferred. If large volumes are needed, NaC1 solutions should be avoided because they can be acidifying and may worsen edema. Hypertonic saline can be used to restore circulatory volume in horses without total body water deficits, but must be followed by administration of isotonic fluids, according to Dr. Cohen. Other forms of treatment for colitis were described by Dr. Cohen: "Nonsteroidal antiinflammatory drugs (NSAID) may be indicated for analgesic and anti-endotoxic effects. Use of these drugs should be avoided in horses with NSAID toxicity and it is important that recipients be well hydrated. Flunixin meglumine (0.25 to 0.5 mg/kg q. 8 hrs or 1.0 mg/kg q. 12 hrs; IV) is often used. Pentoxifylline (8.4 mg/kg; q. 12 hrs; PO), a rheologic agent, has been demonstrated to decrease platelet aggregation and activity of TNF and IL-1 of endotoxin-stimulated equine macrophage in vitro; these cytokines are important mediators of endotoxemia. D i m e t h y l s u l f o x i d e (DMSO) is often administered to horses with colitis for purported effects of decreasing colonic edema by diuresis and free-radical scavenging. The benefits of DMSO are unsubstantiated and recommended doses range from 0.02 to 1.0 g/kg; q. 12 to 24 hrs; IV diluted to 10% solution in polyconic fluids). Administration of aspirin (10 to 20 mg/kg or 60 to 90 grains/450 kg bwt; q. 48 hrs; PO) may help to avoid thrombotic disorders associated with colitis and endotoxemia. Polymyxin B is an antimicrobial that also binds

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endotoxin and has been demonstrated to diminish detrimental responses from experimental endotoxemia in foals. We have used doses ranging from 2,500 to 6,000 units/kg (IV as a bolus; q. 12 hrs); clinical evidence of efficacy is lacking and caution should be used when administering this agent to azotemic patients." Other therapies which are often used include oral administration of activated charcoal (1 to 3 g/kg as a slurry once or twice daily), bismuth subsalicylate (2 to 4 L of commercial preparations), and mineral oil (2 to 4 L) may help to bind lipid soluble toxins such as endotoxin, and bismuth subsalicylate also may have antidiarrheal properties. If no benefit is observed after 48 hours, use of bismuth products should be discontinued. Feeding or oral administration of psyllium mucilloid (2 to 4 oz q 6 to 8 hrs) may increase fecal bulk, and promote colonic healing. Use of loperamide has not been systematically evaluated in horses; use of 4 to 12 mg of loperamide ("Immodium AD", q 6 to 12 hrs) in adult horses has not been associated with adverse effects. Use of antidiarrheal agents, especially opioids, has been eschewed by some; however, because of concern that their administration may prolong transit time, providing greater opportunity for establishment of bacterial pathogens and absorption of their toxins. Use of a prostaglandin E 2 analog (Cytotec; 2 gg/kg; q. 6 hrs; PO) may be of benefit for horses with NSAID-induced (and possibly other causes of) colitis. While the use Of antimicrobials to treat colitis is controversial, Dr. Cohen said they are sometimes used when clinical or laboratory evidence suggest bacteremia, septicemia, or immunosuppression to prevent seeding of other tissues with bacteria. "Metronidazole should be used for clostridial colitis (15 mg/kg; q. 8 to 12 hrs; PO)," he said. "Evidence exists

that metronidazole also has antiinflammatory effects in indomethacin induced intestinal lesions; this agent may be of benefit for many types of colitis. Tetracycline is recommended for PHF. Bacitracin has been recommended for undifferentiated colitis (5 to 6 g/450 kg bwt; q. 12 to 24 hrs; PO/NO) Ceftiofur can be used; it has good lipid solubility and a broad-spectrum. Although anecdotal reports have linked this agent to diarrhea, and various beta-lactam antibiotics have been associated with diarrhea in people, we have successfully used ceftiofur ("Naxcel", Upjohn; 2 to 4 mg/kg; IV; q 12 hrs) in horses with salmonellosis without causing undesirable side-effects. Specific treatment should be based on results of antimicrobial susceptibility testing because resistance is quite variable among isolates."

DRY COAT, NON-SWEATER, ANHYDROSIS... ...if this describes your horse or that of a friend or client, then we really should talk before the hot and humid weather gets here...

PLEASE CALL (602) 866-7701 ... our feed product may help/ See Equine Veterinary Data Vols. 14(17):406 and 15(11):171.

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