Ouch! Gastric Ulcers Are a Pain in the Gut

Transcription

1 Ouch! Gastric Ulcers Are a Pain in the Gut Harold C. McKenzie III DVM, MS, DACVIM Associate Professor of Equine Medicine Marion dupont Scott Equine Medical Center VA/MD Regional College of Veterinary Medicine Leesburg, VA Equine Gastric Ulcer Syndrome! Disease complex! Ulceration of the esophageal, gastric, or duodenal mucosa! Asymptomatic and symptomatic cases! Focal or multifocal lesions of the squamous mucosa, glandular mucosa, or both! Esophageal and duodenal ulceration uncommon Equine Gastric Ulcer Syndrome! Prevalence in the horse population! 40-93% in performance horses! 25-51% in foals Effects of EGUS on Horses! Decreased appetite! Poor body condition! Poor performance! Colic! Severe complications! Duodenal stricture

2 Anatomy of the Stomach Nonglandular region (squamous epithelium) Margo plicatus Glandular region (glandular epithelium) Esophagus Pylorus Duodenum Adapted from Andrews, F. Gastric Squamous Mucosa! Simple stratified epithelium! No secretion or absorption! Highly susceptible to injury! Tremendous proliferative and healing capacity Gastric Glandular Mucosa! Highly resistant to injury! Mucus/ bicarbonate barrier! Mucosal blood flow " Nitric oxide " PGE! Cellular restitution Equine Gastric Acid Secretion! Acid secretion is continuous! Foals secrete hydrochloric acid continuously, even when not nursing! Horses secrete hydrochloric acid continuously, even when not eating! Consumption of milk or roughage decreases gastric acidity

3 Neonatal Gastric Acid Secretion Adult Gastric ph Free Choice Grass Hay ph 4 Recumbent Nursing Sanchez et al Time Adult Gastric ph Feed Withheld ph Equine Gastric Ulcer Syndrome Pathophysiology! Squamous lesions are the result of increased exposure to acid! Glandular lesions are the result of impaired mucosal protection Time

4 EGUS Risk Factors! Illness! Strenuous exercise! Feeding schedule! No ulcers in horses at pasture! Decreased acid when roughage available! Increased acid when fed concentrates! Intermittent feed deprivation = ulcers Prevalence in Adults! Adults! One-third of normal, stall-confined horses can have mild lesions (squamous)! Up to 90% of race horses: half of these lesions are moderate to severe! Up to 60% of show horses! Most horses with colic have gastric lesions (cause and effect?) EGUS Progression in Horses in Race Training Prevalence in Foals Begin Training 3 Months! Up to 50% of normal, asymptomatic foals develop gastric lesions! Most lesions are in squamous mucosa! Most lesions heal without treatment! Up to 40% of foals with clinical disorder develop glandular mucosal lesions

5 Glandular Mucosal Lesions! Impaired mucosal defenses! Impaired blood flow! Physiologic stress! NSAIDs! Impaired nitric oxide synthesis?! Other???! Impaired mucus/bicarbonate barrier?! Inflammation Glandular Mucosal Lesions - Helicobacter?! Traditionally Helicobacter is not considered to be a cause of gastric lesions in horses! There is some evidence that Helicobacter or related organisms are present within the equine stomach! Urease activity! PCR evidence of Urei gene in equine glandular mucosa! Specific to Helicobacter sp.! No causative role established, however Diagnosis of EGUS Gastroscopic Evaluation! Clinical signs! Often non-specific! Laboratory findings! Succeed test for blood and protein in feces! Sucrose absorption test has been described! Gastroscopy! Only reliable method of diagnosis! Treatment of clinical signs! Use appropriate acid suppression! Signs should resolve in 24 to 48 hours

6 Equine Gastroscopy Equine Endoscopy: Normal Stomach Left! Right! Right " Cranial! Caudal! Greater curvature" Lateral view! Caudal to cranial view! Lesser curvature" Equine Endoscopy: Normal Stomach Gastric Lesions: Adults Glandular body Antrum, pylorus! Erosions Severe erosions Pylorus! Bleeding ulcer

7 Gastric Lesions: Adults Gastric Lesions: Foals Desquamation Glandular body! ulceration! Antral ulceration! Hyperemic,! thickened rugae! Erosion in neonate Bleeding Ulceration Gastric Lesions: Foals EGUS Treatment Glandular lesion in sick foal Antral ulcers Pyloric ulceration!! Management! Dietary modification! Limit stressful life events! Drugs! Acid suppressive drugs! H2 antagonists! Proton pump inhibitors! Antacids! Mucosal protectants

8 EGUS Treatment - Management! Dietary modification! Provide roughage at all times! Pasture turnout, free choice hay! Include alfalfa hay in diet up to 25-30% of roughage! Dietary antacid! Corn oil, rice bran or rice bran oil! Minimize impact of stressful life events! Stall confinement, trailering, overcrowding! If cannot minimize then consider prophylactic treatment EGUS Treatment: H2 Antagonists! Ranitidine (Zantac)! Cimetidine (Tagamet)! Famotidine (Pepcid)! Inconsistent! Absorption! Effectiveness Merritt, A.M., ph Dose-Response Variability: H2 Antagonists 2.0 MG/KG FAMOTIDINE IDOL BULLET TIME ph MG/KG RANITIDINE EGUS Treatment Proton Pump Inhibitors! Omeprazole (Gastrogard)! Blocks the pump that produces hydrochloric acid in the stomach! Permanent inhibition! Average turnover time for parietal cells is 24 hours! Once daily treatment X Merritt, A.M., IDOL BULLET TIME

9 Omeprazole (GastroGard )! Dose-confirmation trial in horses in simulated race training! Ulcers healed completely in 78% at a dose of 4 mg/kg/ day x 28 d compared to 4% of control horses! Recurrence of ulcers prevented at 2 mg/kg/day! Post-launch study in racehorses at several tracks showed similar results! Results in non-racehorses even better! Cimetidine not effective in racehorses Omeprazole (GastroGard )! Suppression of acid secretion at a dose of 4 mg/kg/ day:! 99% at 8 hours after dosing! 90% at 24 hours after dosing! GastroGard label dose: 4 mg/kg, once daily x 28 days! May heal in 14 days, but endoscopy needed to confirm! Ulcergard label dose: 1mg/kg once daily! Effective prevention even in heavy training Compounded Omeprazole! Tremendous variation in how they are prepared! And in the source for the active ingredient! There is no testing done to confirm that they actually are effective in reducing stomach acidity! A study done at the University of Florida showed that most of the compounded omeprazole products were ineffective at suppressing acid production! A study at UC Davis showed that compounded products were not effective in healing or preventing gastric ulcers in racehorses What about Antacids?! Temporary effect (30 to 120 minutes)! Neigh-Lox! Mylanta extra strength, Maalox II, Maalox TC! Large dose ( ml)! May be useful on day of performance! I will often use Ulcergard for prevention during stressful events rather than antacids

10 Antacid vs H 2 Antagonist Enhance Mucosal Protection ph ml MAALOX 120 ml MAALOX 6.6 mg/kg RANITIDINE! Sucralfate TIME! Binds to ulcerated glandular mucosa! Not effective for squamous lesions! Does appear to be beneficial in the treatment of glandular ulcers! Can be given concurrently with acidsuppressive drugs. Questions?