The ability of non-steroidal anti-inflammatory drugs (NSAIDs) to cause gastrointestinal ulcers is well established in equine practice. These drugs have therapeutic properties for a wide array of conditions but can also elicit toxic side effects. The risk of developing right dorsal colitis (RDC) and indeed, ulceration throughout the gastrointestinal mucosa as well as in the mouth and esophagus, may well occur in response to long duration, high dose treatment plans. However, RDC has been observed in horses receiving the recommended dose (4.4 mg/kg b.i.d) for a duration of less than a week (Cohen 2002).
NSAIDs inhibit cyclooxygenases (COX). Cyclooxygenases mediate the release of a variety of prostaglandins. COX-1 mediates prostaglandin H2 release, a prostaglandin involved in cytoprotection of the intestinal mucosa. COX-2 is responsible for production of prostaglandins associated with inflammation, which is what the therapeutic NSAIDs are targeted at. Phenylbutazone, for example, is a non-specific COX inhibitor – it inhibits both COX-1 and COX-2. By inhibiting COX-1, phenylbutazone decreases the cytoprotective activity of prostaglandin E on the alimentary mucosa (aiding blood flow, mucin secretion and motility) and therefore predisposing the intestinal mucosa to damage and ulceration. Indeed, supplementation of synthetic prostaglandin E1 (Misoprostol) prior to phenylbutazone administration showed a much-reduced prevalence of ulceration and inflammation (Collins, Tyler 1985).
In addition to COX inhibition, NSAIDs can cause injury by microvascular damage, direct local injury, inhibition of cell division, and reduced hydrophobicity of the gastric mucosa. These factors can greatly influence the ability of the intestinal and gastric mucosa to maintain homeostasis, promote cell turnover and repair.
Some evidence shows that pre-existing colonic ulceration, physiologic stress, enterotoxemia, and dehydration increase the risk of horses developing RDC when receiving NSAID therapy. Age, breed, health status, hydration, diet, and stress all factor into a horse’s susceptibility to developing RDC. Toxicosis can develop whether the drugs are administered orally or parenterally. However, it is still poorly understood why a predilection exists for lesions to involve specifically the right dorsal colon.
In order of highest risk, NSAIDs linked to toxicosis include:
- Flunixin meglumine,
- and Ketoprofen.
The COX-2 selective inhibitor firocoxib appears to be much less associated with RDC or other conditions related to NSAID use, resulting in potent anti-inflammatory properties with fewer side effects.
Note that administering two or more NSAIDs concurrently at recommended doses is similar to giving twice the normal dose of one, prolonging their effect and increasing risk of toxicity.
Clinical Signs of NSAID Toxicosis in Horses
Clinical signs of toxicosis can occur within days to weeks of commencing NSAID treatment. Clinical signs vary depending on location of the ulceration but can also be difficult to differentiate as many symptoms overlap:
- Oral lingual ulceration – difficulty in prehension and mastication
- Esophageal ulceration – excessive salivation, pain behaviors (stretching neck, groaning) when swallowing
- Gastric ulceration – slow consumption of feed, loss of appetite, anorexia
Colonic ulceration can occur acutely and cause severe rapid onset colitis, however typically the course of disease is more insidious, with clinical signs such as intermittent colic, sometimes diarrhea, and sometimes weight loss. Protein loss through the damaged colon can be profound and lead to:
- Ventral edema
- Weight loss
When subsequent scarring of the right dorsal colon occurs, it may lead to impactions in the colon. Accompanying oral and lingual ulceration and subsequent difficulty masticating further exacerbate the potential for impactions.
In cases of severe colonic ulceration, lesions provide localized areas where luminal endotoxins and pathogens can easily enter the vascular system, leading to systemic inflammation and septicemia. In severe cases, profuse diarrhea, dehydration, fever, severe colic, tachycardia and even death can result.
The most consistent clinicopathological features of RDC include mild anemia, hypoproteinemia, hypoalbuminemia and hypocalcemia related to protein losses through inflamed and/or ulcerated intestinal mucosa and changes associated with decreased intravascular oncotic pressure.
Diagnosing Right Dorsal Colitis in Horses
A presumptuous diagnosis of right dorsal colitis may be made based on the history of NSAID administration, clinical signs, and the presence of hypoproteinemia and hypoalbuminemia.
Further diagnostics may include:
- Ultrasonography to detect colonic mural thickening (> 5mm) of the right dorsal colon.
- Isotope labeled white blood cell scintigraphy.
- Fecal blood testing to detect albumin loss from mucosal injury.
- Blood work to detect anemia, hypoproteinemia, hypoalbuminemia and hypocalcemia.
Early recognition of RDC and immediate treatment is critical for the horse’s successful outcome. If diagnosis is delayed and the disease is severe, prognosis is poor.
Treatment for NSAID Toxicosis and RDC in Horses
When NSAID toxicosis is suspected, immediate discontinuation of NSAID use should be coupled with therapy to aid gastrointestinal healing and recovery. Further treatment may be determined based on severity of the disease and presenting symptoms.
Depending on severity the following treatment approaches may be beneficial:
- Gastric lavage via administration of one gallon of mineral oil via nasogastric tube, repeated after two hours, to decrease drug absorption.
- Utilization of IV fluid therapy in cases of hypovolemia, especially with concurrent azotemia.
- Transfusion of plasma or synthetic colloids to increase plasma oncotic pressure (the benefits of synthetic colloids are coming under debate, plasma is preferable).
- Feeding of a psyllium mucilloid (1-2oz twice a day) to help promote colonic healing by increasing concentration of short-chain fatty acids.
- Safflower oil – 1 cup added to feed daily.
- Minimize stress.
In some cases, surgery may be required to reduce scarring that has partially obstructed the intestine.
While proton pump inhibitors are often administered to treat gastric ulceration, these are not recommended for RDC as they may have negative side effects for the hindgut. Pharmaceutical therapies to treat colitis resulting from NSAID use should be tailored to the individual horse’s illness and tolerance.
These may include:
- Synthetic analog of PGE2 (Misoprostol) – demonstrated to reduce phenylbutazone-induced ulceration in horses and may promote repair of intestinal mucosa. However, the drug is expensive and side effects include colic.
- Sucralfate – forms a sticky viscous gel, which adheres firmly to the base of ulcers creating an acid resistant layer to protect against acid and pepsin. Found to reduce intestinal discomfort and disturbances in other species and with few side effects.
- Metronidazole and Sulfasalazine – anti-inflammatory effect in the intestinal tract shown in other species. Could also be of benefit in RDC due to limiting adherence of neutrophils to vascular endothelium, a process associated with the pathogenesis of mucosal injury.
- Linoleic acid – may help to modulate pro-inflammatory eicosanoids, and may increase the synthesis of prostaglandin E2 to promote repair.
Dietary Management for Horses with Right Dorsal Colitis
Careful dietary management focused on reducing bulk in the diet is critical to recovery from NSAID toxicosis affecting the colon. The aim is to reduce physiologic and mechanical load on the colon in order to allow it to rest and heal.
Dietary management should:
- Provide a low-bulk diet in the form of an alfalfa-based pelleted concentrate.
- Restrict or eliminate roughage.
- Be fed in many (4-6 at least) small meals throughout the day.
A complete pelleted diet should contain both concentrate and adequate but low roughage. For horses that won’t eat a complete pelleted feed or are inclined to crib bite, allow small amounts of fresh grass frequently throughout the day. Corn oil may be added to increase fat and aid in healing of damaged mucosa by promoting synthesis of PGE2.
The optimal duration for forage restriction is unclear, but should be based on the weeks to months the colon can take to fully recover.
Horses recovering from RDC should undergo dietary changes gradually to reduce risk of additional gut damage and colic.
References & Further Reading
Andrews, F.M. (2006) Gastric and Colonic Ulcers. A Pain in the Gut! Web Presentation. University of Tennessee, College of Veterinary Medicine
Cohen, T. (2002) In. NSAID Toxicosis. 415-417. In. Manual of Equine Gastroenterology. Eds Mair, T.S., Divers, T., Ducharme, N. WB Saunders, Edinburgh, UK
Collins, L.G., Tyler, D.E. (1985) Experimentally induced phenylbutazone toxicosis in ponies: description of the syndrome and its prevention with synthetic prostaglandin E2. Am J Vet Res. 46(8): 1605-15
Galvin, N., Dillon, H., McGovern, F. (2002) Right dorsal colitis in the horse: minireview and reports on three cases in Ireland. Ir Vet J. 57(8): 467–473
Smith, B.P. (2015) Large Animal Internal Medicine. 5th ed. Elsevier Inc. St. Louis, MO.