Gastroduodenal Ulcers

The occurrence of gastric ulcer disease is not limited to foals treated with non-steroidal anti-inflammatory drugs (NSAIDS). Many foals that have not been treated with NSAIDs have gastric ulcer disease. Endoscopic studies reveal erosions and ulcers in a high percentage of foals without signs of gastric disease.

I. Clinical Syndromes [1]

1. Asymptomatic ulcers are subclinical ulcers usually located in the non-glandular stomach along the margo plicatus.
2. Symptomatic ulcers are usually non-perforating ulcers, unless there is progression to perforation, in the glandular or nonglandular stomach.
3. Perforative ulcers in the gastric wall or duodenum. Clinical signs are associated with acute severe peritonitis and cardiovascular collapse.
4. Pyloric or duodenal stricture secondary to healing and scarring of non-perforating ulcers.

II. Gastro-endoscopic Findings

1. Healthy foals [2,3]

1. Most lesions prevalent in foals < 10 days of age are found in the squamous mucosa immediately adjacent the margo plicatus along greater curvature.
2. Squamous mucosa of fundus lesions less common.
3. Squamous epithelial desquamation observed in 80% of foals < 40 days of age.
4. Glandular mucosal lesions uncommon unless foal has symptoms.
5. Presence of concurrent or recent diarrhea increases prevalence of lesions.

2. Ill foals [2,3]

1. Severe ulceration of stratified squamous mucosal epithelium adjacent to margo plicatus in young foals.
2. Ulceration of glandular mucosa.
3. Ulceration of stratified squamous mucosal epithelium along the lesser curvature and around cardia in older foals.
4. Diarrhea is most frequent clinical sign in foals with gastric ulcers.

III. Clinical Signs

Some of the signs of gastroduodenal ulcers in foals vary with the clinical syndrome.

1. Diarrhea [2,3] is the most common sign according to some studies.
2. Teeth grinding, salivation, gastric reflux (may be hemorrhagic), colic, dorsal recumbency, anorexia, fever, weight loss, diarrhea, "stretching-like" episodes [1].
3. Fever
4. Development of clinical signs may follow a stressful situation such as shipping, surgery, or concurrent illness (respiratory tract disease, diarrhea, or may occur in outbreaks involving a number of foals).
5. Because gastric ulcers frequently develop with other problems, early accurate diagnosis is difficult.

IV. Diagnosis

1. History of foals having diarrhea, an induced stressful situation, i.e., shipping, surgery or other illnesses; history of having been administered NSAIDs; history of farm outbreak of gastroduodenal ulcer disease. Rotavirus thought to have a role in the development of duodenal ulcers.
2. Clinical signs. The observation of diarrhea alone, colic, excessive salivation and teeth grinding (bruxism) is very suggestive of gastroduodenal ulcers. Other signs, as listed above, are nonspecific for gastroduodenal ulcers. Abdominal pain can sometimes be localized to xiphoid region by abdominal palpation.
3. Gastric reflux of foul smelling, hemorrhagic fluid.

1. Fecal occult blood (Hematest™, Ames Co.), while not specific for ulcerative disease, may be positive in diarrheas associated with gastroduodenal ulceration, parasites or mucosal ulceration associated with infectious agents.

4. Gastroscopy may afford direct observation of ulcers but can be hampered by:

1. Ingesta and gastric secretions obscuring visualization.
2. Acute angle between cardia and pylorus.
3. Solid food and milk should be withheld for 12 and 4 hours respectively, before gastroscopy if possible in foals over 20 days of age.

5. Contrast radiographic findings consistent with duodenal stricture include a flaccid esophagus with fluid that refluxes into the esophagus from stomach, large gastric silhouette, and delayed gastric emptying (>2 hours).
6. Sucrose test: this disaccharide has been used experimentally to diagnose gastric ulceration in horses. Sucrose gets hydrolized to glucose and fructose in the small intestine although in gastric ulceration the sucrose gets absorbed through the injured gastric mucosa. Detection of sucrose in the blood or urine indicates gastric ulcers. The test has not been validated yet.
7. Abdominal ultrasound may reveal thickened, edematous (>5 mm) stomach wall. Duodenal wall may also be thickened (>3 mm) and its lumen is dilated (>3 cm). Small intestinal loops are often dilated (>3 cm) with sluggish motility, all suggestive of ileus.

V. Treatment

1. Agents to decrease gastric acid via H2 receptor antagonism

1. Cimetidine (Tagamet™ Glaxo, North Carolina) 4.4-6.6 mg/kg 4-6 times daily IV or 20-25 mg/kg orally QID for minimum of 2 weeks. Not frequently used anymore, because of side effects and short half life.
2. Ranitidine (Zantac™ Glaxo, North Carolina) 6.6 mg/kg BID or TID PO or 1.5 mg/kg IV TID for minimum of 2 weeks. Should be the drug of choice as an H2-blocker.
   Editor's Comment - With higher dose watch for increase in liver enzymes.
3. Famotidine (Pepcid) 0.25-0.5 mg/kg IV TID or 24 mg/kg orally TID. Minimal pharmacokinetic data is available.

2. Agents to decrease gastric acid via proton pump inhibition [4-6]

1. Omeprazole (Gastrogard® Merial) is a very potent proton pump blocker. 1-4 mg/kg orally SID for 2-4 weeks or 0.5 mg/kg IV SID.

1. Omeprazole may disrupt normal GI flora, by increasing gastric pH, and allow the proliferation of pathogens (Salmonella).
2. Some studies suggest that sick neonates actually do not have acidic gastric environment.

2. Pantoprazole has been shown to effectively increase gastric pH, when given iv. at a dose of 1.5 mg/kg SID.

3. Antacids

1. Can be used at end of other therapies to prevent reoccurrence.
2. Mylanta II™, Maalox™.

4. Mucosal protectant

1. Carafate™ (Sucralfate) 22 mg/kg 2 to 4 times daily orally [7]
2. Can administer at same time as H2 blockers; 8 others suggest giving 1 hour before H2 blockers.
3. Did not heal asymptomatic ulcers [9]

5. Therapeutic agents for reflux esophagitis or delayed gastric emptying.

1. Use agents described above.
2. Bethanecol (Urecholine®) 0.025-0.03 mg/kg. subcutaneously q 4 hours to aid gastric emptying.

1. Follow by oral dosages of 0.3-0.75 mg/kg 3 to 4 times daily.
2. Side effects: diarrhea, colic, salivation; decrease dosage.
3. Make sure no GI obstruction is present prior to use.

3. Metoclopramide (Reglan®)

1. 0.10-0.25 mg/kg 3 to 4 times daily orally or 0.04 mg/kg as a CRI
2. May see adverse CNS effects, facial sweating, tachycardia.

4. Cisapride: dose is 0.8 mg/kg orally TID.

6. Prostaglandin E synthetic agents

1. Misoprostol (Cytotec®) (5 ug/kg TID orally) has been used to prevent ulcers in foals receiving NSAIDs and in treatment of ulcers.

1. If colic develops may need to lower dosage.
2. Only drug approved in humans to prevent NSAID associated gastric ulcers.
3. Expense and concern about side effects have limited use.
   Editor's Comment - May be under utilized therapy.

VI. Drugs That May Cause Gastric Ulcers

1. Phenylbutazone

1. 10 mg/kg/day for 10 to 42 days produces severe oral, gastrointestinal ulcers and diarrhea as early as day 3 of treatment [10]

2. Flunixin meglumine

1. 1.1 mg/kg/day for 30 days produces oral and gastric ulcers. (Less ulcerogenic than phenylbutazone [11])
2. Intramuscular route produces less oral ulceration.
3. Dosages of 0.5-1.1 mg/kg/day intravenously in 2 day old foals for 5 days did not produce gastric ulceration [12]

3. Prevention of ulcers when using NSAIDS in foals.

1. Study with ranitidine during phenylbutazone administration -failed to protect against ulcers [10]
2. Misoprostol only drug that has been shown to be effective.