R cally associated with administration of phenylbutazone

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1 Medical Management of Right Dorsal Colitis in 5 orses: A Retrospective tudy ( ) Noah D. Cohen, G. Kent Carter, Robert. Mealey, and Tex. Taylor Right dorsal colitis in horses has been associated with administration of phenylbutazone. Although reports of right dorsal colitis in this species have described surgical treatment associated with a poor prognosis, we have had success treating this condition medically. This report describes 5 horses with right dorsal colitis confirmed during celiotomy that were initially managed medically. All horses had a history of intermittent abdominal pain; weight loss was noted in only 1 horse. The doses (.0 to 4.6 mg/kg PO bid) and duration (5 to 30 days) of administration of phenylbutazone were not unusually high relative to those recommended (4.4 mg/kg PO bid). ypoproteinemia and hypoalbuminemia were observed in all horses at the time of admission; packed cell volume was low in 4 horses, and hypocalcemia was also observed in 4 horses. Three ight dorsal colitis has been experimentally and clini R cally associated with administration of phenylbutazone to horses. Clinical signs associated with right dorsal colitis include anorexia weight loss, intermittent or sporadic episodes of acute abdominal pain, and diarrhea. 3 urgical treatment is advocated in prior reports; however, the prognosis for affected horses is poor. At the Texas Veterinary Medical Center (TVMC), some horses with right dorsal colitis identified during celiotomy have been managed medically. The purpose of this retrospective study is to review the signalment, history, physical examination, clinicopathologic findings, and response of treatment in horses with right dorsal colitis managed medically. Materials and Methods All horses with right dorsal colitis managed medically at the TVMC between January I, 1985, and December 31, 1993, were included in the study. Five horses were identified by reviewing the medical records. All horses were used for athletic performance. The diagnosis of right dorsal colitis was made on the basis of surgical findings in 4 horses and at necropsy in 1 horse. Diagnosis of right dorsal colitis was based on gross findings of marked edema, thickening, or reduction in diameter of the intestinal tract restricted to the right dorsal colon. In each case, other gross intestinal lesions were absent, and the cause of abdominal pain was attributed to abnormalities of the right dorsal colon. orses that had right dorsal colitis, but that were not managed medically, and horses that had other visible intestinal abnormalities accompanying right dorsal colitis were excluded from the study. The medical record of each horse was reviewed to abstract the following information: ( I) date of admission; () age; (3) breed; (4) From the Department of Large Animal Medicine and urgery, College of Veterinary Medicine, Texas 4&M University, College tation, TX. Accepted February 13, Reprint requests: Noah D. Cohen, 0 VM, Department of Large Animal Medicine and urgery, College of Veterinary Medicine, Texas A&M University. College tation, TX Copyright 0 I995 by the American College of Veterinary Internal Medicine 089 I6640/95/ $3.00/0 of 5 horses (60%) appeared to respond to dietary management and discontinuation of administration of nonsteroidal antiinflammatory drugs. Dietary management consisted of feeding pelleted feed, and restricting or eliminating roughage for a period of at least 3 months. Two horses developed strictures of the right dorsal colon. One horse that developed a colonic stricture, possibly because its owners did not comply with recommendations for management, was subsequently treated surgically. The remaining horse that developed a stricture of the right dorsal colon was euthanked. These data indicate that some horses with right dorsal colitis can be successfully managed with medical treatment. J Vet intern Med 1995;9:776. Copyright by the American College of Veterinary internal Medicine. gender; (5) character and duration of clinical signs prior to admission; (6) history and duration of treatment with nonsteroidal antiinflammatory drugs (IDs); (7) history of training and performance; (8) hematologic and serum biochemical data obtained at the time of admission; (9) results of cytological and biochemical analysis of peritoneal fluid obtained at the time of admission; (10) results of microbiologic culture of feces during hospitalization; (1 1) treatment administered at the TVMC; and (1) response to treatment. Results The 5 horses ranged in age from to 7 years. Four were Quarter orses and 1 was a Thoroughbred; 3 were males ( geldings) and were females. Four horses with right dorsal colitis identified during celiotomy were initially managed medically. One horse, diagnosed presumptively with right dorsal colitis based on history and clinicopathologic findings and managed medically, was later euthanized because of recurrent episodes of abdominal pain; at necropsy, a stricture of the right dorsal colon was identified and determined to be the cause of these episodes. A biopsy specimen for microscopic examination was collected from l horse only (horse I). The biopsy specimen from this horse was not a fullthickness specimen and consisted of tunica muscularis but no mucosa; the muscularis contained fibrinopurulent exudate between muscle bundles, with necrosis and degeneration of many muscle fibers. The duration of clinical signs before admission ranged from 10 to 30 days (median, 11 days; Table 1). All horses had a history of repeated episodes of abdominal pain, and the number of episodes ranged from to 6 (median, ). Two of 5 horses had a history of diarrhea that developed while they were receiving a combination of trimethoprim and sulfonamide (unknown dose), and resolved after the drug was discontinued. One horse had history of weight loss. Four of 5 horses had a known history of treatment with phenylbutazone. The dose and duration of treatment with phenylbutazone was recorded for 3 ofthese 4 horses; the doses were 4.0, 4.5, and 9.1 mg/kg, and the durations of treatment ranged from 5 to 30 days. All horses were hypoproteinemic and hypoalbuminemic 7 Journal of Veterinaly Internal Medicine, Vol9, No 4 (JulyAugust), 1995: pp 7 76

2 RIGT DORAL COLITI IN ORE 73 Table I. ignalment, istory, and Clinicopathologic Findings in 5 orses With Right Dorsal Colitis Treated Medically at the Texas Veterinary Medical Center orse Age (v) Gender Breed Number of colic episodes Duration of clinical signs before admission (d) Duration of administration of phenylbutazone (d) Approximate dose of phenylbutazone (mg/kg/d) Method of diagnosis Diarrhea almonella isolated from feces Fecal occult blood Packed cell volume (%) Total protein (g/dl) Albumin (g/dl) erum calcium (mg/dl) erum creatinine (mg/dl) White blood cells (X 103/pL) Polymorphonuclear cells (x 1 o/,l) Peritoneal white blood cells (x 1 o/,l) Peritoneal total protein (g/dl) Response to medical treatment 5 M O ' 4.5'.1' 8.3' Reference Ranae 9.5' 77.6'.1 F Q ' 4.7' 9.7' G TB ' 10.8' G Q 4 1 N 31' 4.1' 1.6' 10.6*.5' 17.3" 15.7' E M O ' 4.3' ' O Abbreviations. not applicable, M, male, F, female, G, gelding, Q, Quarter orse, TB, Thoroughbred, 7, unknown,, surgery, N, necropsy,, apparently healthy at followup. E, euthanized., surgery performed (owners did not comply with recommended management) Values outside reference range <10.0 <.5 (Table l), 4 horses were hypocalcemic, and 1 was azotemic. Four horses were anemic, had neutrophilia, and 1 was neutropenic upon admission (Table 1). No consistent abnormalities were noted during analysis of peritoneal fluid; the fluid was a transudate in 4 horses and a suppurative exudate in 1 horse. almonella spp were isolated from the feces of of 5 horses, and occult blood was identified in the feces of 1 of 3 horses tested. Only I horse (horse ) underwent gastroscopy, which was normal. All horses were initially treated with dietary management consisting of frequently feeding a complete (Purina orse Chow 00; Purina Mills, Inc, t Louis, MO) or incomplete (Purina Pure Pride 00; Purina Mills, Inc) pelleted concentrate ("lowbulk" diet), changing management to decrease stress, and avoiding treatment with IDs. A complete pelleted feed was defined as a feed that contained at least 30% dietary fiber and that could be fed without requiring additional roughage in the diet; an incomplete pelleted feed was defined as a pelleted feed that required additional roughage in the diet. Pelleted concentrate was fed according to the manufacturer's recommendations (Purina Mills, Inc). Both types of pellets were guaranteed to contain no less than 14% protein and to meet or exceed the recommended energy requirements suggested by the National Research Council when fed as directed. The transition to a diet comprised exclusively or mostly of pelleted concentrate was made gradually. After determining the recommended amount of pellets to be fed, approximately 5% of the recommended amount was fed on the 1 st day. The amount of pellets was increased by approximately 5% every 1 or days, such that all horses were eating the recommended amount of pellets by 8 days after starting the new diet. The total amount of pellets fed was divided into equal amounts fed every 4 to 6 hours. After discharge, owners were advised to feed pellets in equal amounts 4 or more times daily, to monitor their horse's body weight and condition, and to increase the amount of pellets fed, if needed. Roughage was eliminated or restricted to small amounts of fresh grass for a minimum of 3 months. Owners of horses that were fed an incomplete pelleted feed were encouraged to provide small amounts of fresh grass (5 minutes of grazing several times daily). Owners of horses fed a complete pelleted feed were requested to eliminate roughage from the diet. orses 1,, and 5 were fed a complete pelleted diet, and horses 3 and 4 were fed an incomplete pelleted diet. orses 1,3, and 4 were also allowed to ingest small amounts of fresh grass. In horse, dietary management included addition of psyllium mucilloid (Equisyl; Animal ealth Care Products, Vernon, CA) to the diet (4 ounces added to the feed every other day). Management to decrease stress included discontinuing or decreasing the frequency of performance, strenuous exercise, and trailering.

3 74 COEN ET AL Followup information was obtained for all 5 horses; the duration of followup ranged from 8 months to 4 years (median, years). Three horses (horses 1 to 3) were managed successfully with medical treatment; 1 horse (horse ) experienced an episode of abdominal pain months after discharge but was reportedly well 10 months later. At followup, all horses had been able to return to their intended use, and all horses were able to consume what their owners considered to be normal amounts of roughage (> flakes of coastal grass hay for each horse). orse 4 was later euthanized for recurrent colic by the referring veterinarian approximately 8 months after discharge, and was found to have a stricture of the right dorsal colon. orse 5 was readmitted 5 months after discharge and was treated surgically for a stricture of the right dorsal colon. urgical treatment consisted of bypassing the affected portion of the right dorsal colon, which could not be exteriorized, by a sidetoside anastomosis of the right dorsal colon proximal to the lesion and the descending colon approximately 30 cm caudal to the duodenocolic ligament. This horse had been used athletically, treated with phenylbutazone, and fed a hay diet after discharge. The duration of signs before admission was longer for the horses with strictures than for the horses that were successfully managed medically (Table 1). Because of the small number of horses, the statistical significance of this difference in duration of signs was not compared using inferential statistical methods. Discussion Previous reports describe surgical management and poor prognosis for horses with right dorsal colitis.'3 We describe 5 horses with right dorsal colitis, 3 of which were successfully managed medically. Medical management consisted of feeding a lowbulk, lowroughage diet (complete or incomplete pelleted feed), avoiding use of IDs, and in 1 horse, administration of psyllium mucilloid. The rationale for administration of a pelleted diet was to decrease the mechanical and physiologic load of the colon. Feeding pellets decreases intestinal fill, particularly in the colon, thereby decreasing its mechanical load.4 Because the cecum and large colon are the major sites of fiber digestion and exchange of water and electrolyte^,^ a diet lower in fiber might decrease the physiologic load of the colon. We recommended feeding smaller amounts of concentrate frequently (4 to 6 feedings per day), rather than feeding concentrate twice daily. orses fed a pelleted diet were allowed to eat fresh grass in small amounts (approximately 5 minutes of grazing 4 to 6 times daily). The importance and optimal duration of restriction of roughage could not be determined from these horses. Based on our clinical experience, we believe that eliminating or restricting roughage for 3 to 6 months is beneficial. In species other than horses, shortchain fatty acids are known to influence colonic mucosal reair. Psyllium mucilloid has been shown to increase the concentration of shortchain fatty acids of the large bowel in other species.".' ' The rationale for including psyllium mucilloid in the diet of horse was that it might increase the colonic concentration of shortchain fatty acids and might thereby promote colonic healing. The amount and duration of psyllium mucilloid administered PO that is required to alter the colonic concentration of shortchain fatty acids, and the role of shortchain fatty acids in the resolution of right dorsal colitis in horses is unknown. Although the pathogenesis of right dorsal colitis is unknown, the condition has been induced in horses by administration of phenylbutazone (6 g PO sid for 5 days) and restriction of water intake to approximately one half maintenance requirements (30 ml/kg/4 hr for 5 days).' Four of the 5 horses reported here had known history of administration of phenylbutazone; use of IDs was strongly suspected by the referring veterinarian in the 5th horse, but could not be documented. Therefore, avoiding administration of IDs in horses with right dorsal colitis seems advisable. The doses and duration of administration of phenylbutazone in the horses reported here (Table 1) were not unusually high relative to those recommended (4.4 mg/kg PO bid); dehydration and physiological stress associated with performance may have increased the risk of right dorsal colitis induced by IDs in these The finding that most of the horses were young adults is probably a reflection of their use for performance rather than an agerelated predisposition. Alternatively, it has been hypothesized that idiosyncratic or genetic predisposition, protein composition of the diet, or concurrent administration of drugs may contribute to the development of right dorsal colitis.' For example, concurrent administration of phenylbutazone and flunixin meglumine prolonged their pharmacologic effect in mares." Another possible explanation for toxicity associated with the doses reported is that owners or refemng veterinarians may have reported lower doses than those actually administered. Regardless of the pathogenesis of right dorsal colitis, it is important for equine clinicians to recognize that colonic inflammation or ulceration may develop in horses receiving doses of phenylbutazone tolerated by many other horses. Minimizing physiological stress and avoiding dehydration may help decrease the risk of toxicoses caused by IDs. Although we lacked gross or histopathologic evidence of healing after treatment, 3 horses responded clinically to this altered diet. Lack of compliance with dietary and other recommendations for management may have contributed to the failure of medical management in horse 5, which required surgical management of right dorsal colitis. In a previously reported case, a diet comprised exclusively of hay was recommended for management of a horse with recurrent abdominal pain later determined to have right dorsal colitis resulting from inadvertent administration of a high dose of phenylbutazone for 10 days. This horse continued to experience abdominal pain when fed exclusively hay and was eventually treated surgically. The finding that the horses that developed colonic strictures in our study had signs for a longer duration may indicate that the condition progresses to stricture of the right dorsal colon. Colonic stenosis has been described in horses with chronic, severe right dorsal colitis.' Loss of protein induced by intestinal inflammation caused by IDs in horses can develop before development of visible ulceration ofthe gastrointestinal

4 RIGT DORAL COLITI IN ORE 75 tract.16 Conceivably, early recognition of the problem before the development of irreversible lesions, and institution of dietary management with elimination or restriction of roughage may enable recovery in some horses, thereby obviating the need for surgical intervention. Anamnesis and clinicopathologic data may facilitate recognition of horses with right dorsal colitis. The most consistent findings among the horses reported here were intermittent abdominal pain, hypoproteinemia, and hypoalbuminemia. All horses were used for performance and had a history of intermittent abdominal pain. Causes of intermittent abdominal pain are numerous"; suspicion of right dorsal colitis should be increased in performance horses with a known or suspected (eg, chronic lameness) history of administration of IDs. Two horses had a history of diarrhea. The association of the diarrhea with right dorsal colitis, however, was ill defined. Although toxicity from IDs has been associated with diarrhea in horses and foals,",19 the diarrhea in the cases reported here appeared to be associated with PO administration of potentiated sulfonamides (ie, it resolved when the antimicrobial drug was discontinued), as previously reported.*' Infectious causes of the diarrhea could not be excluded completely; almonella sp was isolated from the feces of horses, 1 of which had diarrhea. The clinical importance of isolating almonella was unclear because apparently healthy horses may shed salmonellae in feces," and gastrointestinal disease is a risk factor for equine salmonellsis. almonellosis, however, can cause abdominal pain and proteinlosing enteropathy in horses.1 almonella was isolated from of 9 horses with right dorsal colitis,' but this prevalence was not considered unusually high for horses admitted to that clinic. Loss of body weight, described in previous reports,'" was reported in only 1 of the horses seen at our clinic. The extent or duration of disease may have been less severe in the horses described in our report, such that weight loss was an uncommon feature. ypoproteinemia and hypoalbuminemia were consistent findings in the horses included in this study (Table 1). They may be caused by insufficient ingestion, reduced production, increased metabolism, or extravascular loss of protein. Based on results of anamnesis, physical findings, urinalysis, peritoneal fluid analysis, and serum biochemistry, hypoproteinemia and hypoalbuminemia were attributed to gastrointestinal loss. Because albumin is the most abundant protein in equine plasma and because it has a smaller molecular weight than globulins, its concentration is often decreased in erum of horses with inflammatory disease of the gastrointestinal tract, including phenylbutazone toxicsis.'''* Because the proportion of free, active form of a proteinbound drug will be increased, hypoprotenemia can predispose to phenylbutazone toxicity. ypoproteinemia and hypoalbuminemia may exacerbate hypovolemia (because of decreased intravascular oncotic pressure), further predisposing to intestinal damage induced by IDs. The cause of the anemia in 4 horses was not determined, because further evaluation (eg, total iron binding capacity [TIBC], serum iron concentration, bone marrow aspiration) was not performed. Probable causes include colonic blood loss and anemia associated with chronic inflammatory disease. In humans, blood and protein loss via small intestinal inflammation can be induced by administration of ID. Feces from 3 horses were examined for occult blood, and horse 1 had a positive result (Table I). In our clinical experience, tests for fecal occult blood are not highly sensitive, and a negative result does not preclude the possibility of blood loss via the intestinal tract. The cause of hypocalcemia was not determined. Inadequate dietary intake associated with abdominal pain, gastrointestinal loss of proteinbound calcium, and decreased proteinbound calcium associated with hypoalbuminemia and hypoproteinemia were considered likely causes, but other causes of hypocalcemia such as sepsis, endotoxemia, hypoparathyroidism, and pancreatic disease could not be excluded. igns of tetany were not observed in any horse, indicating that the ionized fraction of calcium was not markedly decreased. Azotemia in horse 5 was attributed to prerenal causes. None of the clinical or clinicopathologic findings observed was specific for right dorsal colitis. imilar findings can be seen in horses with gastric and small intestinal ulcer ation caused by ID.',',', If possible, gastroscopy should be performed in all horses with history of intermittent abdominal pain, weight loss, diarrhea, hypoproteinemia, hypoalbuminemia, and anemia. Only 1 horse included in this study underwent gastroscopy. Consequently, gastric ulceration could not be excluded from the differential diagnosis of the other horses in this study. The presence of gastric ulceration, however, does not preclude the possibility of inflammation or ulceration of the distal gastrointestinal tract. Because the pathophysiology of right dorsal colitis is unknown and because of anatomic considerations, specific drug therapy for the condition cannot be currently recommended. It has been suggested that sucralfate may promote healing of colonic ulcers in horses.9 The rationale for this recommendation is that sucralfate has been shown to diminish intestinal discomfort and reduce intestinal disturbances after radiotherapy for pelvic cancer in humans.30 The extent to which sucralfate influences colonic disease induced by IDs in horses has not been determined. Because the drug is relatively inexpensive and has few adverse effects, administration of sucralfate does not appear to be contraindicated for treating right dorsal colitis. In humans, enteropathy induced by IDs has been treated with sulfasalazine and metronidazole, with varying success.31 To our knowledge, evaluation of these agents for management of colonic lesions induced by IDs in horses has not been reported. Misoprostol, a synthetic analog of prostaglandin E, decreases gastric acid secretion in horses3 and may provide mucosal prtection.'. It is unknown, however, if the drug is cytoprotective for the colonic mucosa in horses. For these reasons, misoprostol cannot be recommended at this time for treatment or prevention of right dorsal colitis. A limitation of this study was that the diagnosis of right dorsal colitis was based on gross anatomic findings during celiotomy or necropsy. The gastric and intestinal mucosae of those horses diagnosed during celiotomy were not exam

5 76 COEN ET AL ined. Thus, the possibility that inflammation or ulceration of gastrointestinal mucosa caused by ID treatment had developed in other areas in these horses could not be excluded. In previous reports, however, gastrointestinal lesions in horses with spontaneously occumng and experimentally induced right dorsal colitis were limited to the right dorsal colon. Although ulceration of the gastric mucosa can develop in adult horses treated with ID,,, similar gastric lesions may be seen in adult horses without clinical signs.35 Because feeding concentrate can increase gastric acidity,35 one could speculate plausibly that the diet we recommended would have exacerbated rather than alleviated clinical signs caused by gastric ulceration. Although previous reports describe surgical management and poor prognosis for horses with right dorsal colitis, our experience indicates that some horses can be successfully managed medically. Medical management consisted of feeding a lowbulk, lowroughage diet for at least 3 months; avoiding use of IDs; and administration of psyllium mucilloid (in 1 horse). Early recognition of the condition and compliance with recommendations may be important for its successful management. References 1. Karcher LF, Dill G, Anderson WI, et al. Right dorsal colitis. J Vet Intern Med 1990;4: immonstr, Gaughan EM, Ducharme NG, et al. Treatment of right dorsal ulcerative colitis in a horse. J Am Vet Med Assoc 1990; Andrews FM, Robertson JT. Diagnosis and surgical treatment of functional obstruction of the right dorsal colon in a horse. J Am Vet Med Assoc 1988; 193: Lewis LD. Feedstuffs, in Lewis LD. Feeding and Care of the orse. Philadelphia, PA, Lea & Febiger, 198: intz F. Digestive physiology of the horse. J Afr Vet Assoc 1975;46: Argenzio RA. hortchain fatty acids and glutamine: influence on mucosal transport and repair. 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