Recipient Organization
UNIVERSITY OF ILLINOIS
2001 S. Lincoln Ave.
URBANA,IL 61801
Performing Department
Veterinary Research & Extension
Non Technical Summary
Equine gastric ulcer syndrome (EGUS) is a common and significant cause of morbidity in horses, with a range of clinical signs including inappetence, colic, and poor performance. EGUS has several known risk factors, including fasting and non-steroidal anti-inflammatory drug (NSAID) administration. Horses hospitalized for colic are commonly exposed to both of these risk factors, making these patients at particularly high risk for the formation of both squamous (associated with fasting) and glandular (associated with NSAIDs) gastric ulcers. Prophylactic treatment with anti-ulcer medication is often prescribed for these at-risk patients, but appropriate drug selection is complicated by the fact that squamous and glandular ulcers vary both in etiology and response to treatment. Additionally, treatment is costly (omeprazole) and/or time consuming (sucralfate, given three times daily) to administer, making selection of the most effective protocol for a horse's individual situation highly desirable. To our knowledge, evidence-based recommendations are not available for effective prevention of gastric ulceration in patients exposed to multiple risk factors. The aim of this study is to establish the efficacy of omeprazole or sucralfate monotherapy in the prevention of gastric ulceration resulting from the combined stressors of NSAID use and fasting, using an experimental model that mimics conditions commonly experienced by hospitalized equine colic patients. We hypothesize that prophylactic treatment with either omeprazole or sucralfate will be equally effective at the prevention of gastric ulceration in horses under these conditions. Twenty healthy adult horses will undergo a feed-fast protocol and be treated with flunixin meglumine during two seven-day treatment periods. Following a two-way randomized crossover block design, horses will receive either omeprazole (1mg/kg by mouth q24 hours), or sucralfate (20mg/kg by mouth q8 hours), with a minimum eight-week washout between treatments. Gastroscopy will be performed after each of three 24-hour fast periods to document presence and severity of both squamous and glandular gastric ulceration. Upon completion of this study, we expect to have established the utility (or not) of omeprazole and sucralfate for ulcer prophylaxis in fasted horses prescribed flunixin meglumine. This work is an important step towards the development of evidence-based recommendations for the prevention of gastric ulcers in clinical patients exposed to multiple risk factors.
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Goals / Objectives
Establish the efficacy of omeprazole or sucralfate monotherapy in the preventionof gastric ulceration resulting from the combined stressors of NSAID use and fasting. We havefound that the combination of a feed-fast protocol and flunixin meglumine administration rapidly induces clinically significant (ā„ grade 2) glandular and squamous gastric ulcers. In this objective, horses will serve as their own controls following a two-way crossoverdesign, with a minimum eight-week washout period between treatments. Horses will receive either omeprazole (1mg/kg by mouth [PO] q24 hours; Treatment A), or sucralfate (20mg/kg PO q8 hours;Treatment B). Based upon the reliable and severe gastric ulceration induced in our preliminarywork and previously published studiesinclusion of an untreated control group is unnecessary,as the focus of the proposed work is to directly compare efficacy of the two prophylactictreatments. Gastroscopy will be performed following a 24-hour fast on days 2, 4, and 7 of eachtreatment period to document presence and severity (graded 0-4) of both squamous and glandulargastric ulceration.
Project Methods
Twenty healthy horses from the teaching herd maintained at the University of Illinois Veterinary Teaching Hospital (VTH) will be used in a randomized crossover design. Each horse will be kept in a stall with timothy grass/alfalfa mixed hay fed twice daily and water available at all times. Prior to the study and between treatment phases, horses will be maintained on pasture with intermittent stabling as needed. For the study protocol, horses will be placed on a feed-fast protocol to induce gastric ulcers: 24h fast - 24h feed - 24h fast - 48h feed - 24h fast. Starting at the time of the first gastroscopy exam, immediately following the first fasting period, horses will treated with 1.1 mg/kg flunixin meglumine IV via jugular catheter. This treatment will be continued every 12 hours throughout the study protocol period. To evaluate the efficacy of each ulcer prophylaxis protocol, horses will serve as their own controls following a two-way crossover design. Under Treatment A, horses will be administered the labeled preventative dose of omeprazole (GastroGardĀ®, 1mg/kg PO q24 hours) for fivedays, beginning after the initial 24-hour period of fasting and first gastroscopy exam. Omeprazole will be administered 30 minutes prior to a hay meal. Under Treatment B, horses will be administered sucralfate (20mg/kg PO q8 hours) for fivedays, beginning after the initial period of fasting and first gastroscopy exam. The order of the treatment protocols will be randomized according to a Latin Square design. At the completion of each protocol period, horses will be turned out on pasture or otherwise returned to their typical housing environment for at least eightweeks before starting the next protocolGastroscopy will be performed threetimes during each trial: 1) after the initial 24 hours of fasting, establishing a baseline; 2) after 48 cumulative hours of fasting/48 cumulative hours of medication; and 3) after 72 cumulative hours of fasting/120 cumulative hours of medication. Gastroscopy with a 3.5m video endoscope will be performed using routine restraint and standing sedation. Endoscopy images will be reviewed and scored by an investigator blinded to treatment at the conclusion of the study. Complete physical examinations will be performed prior to initiation and twice daily during each protocol. During each study protocol period, horses will be monitored every sixhours by study personnel; attitude, appetite, water consumption, and manure production will be recorded. Every 48 hours PCV, TS, lactate, glucose, and a renal profile will be measured to monitor hydration, NSAID-induced renal injury and colon inflammation. Scanning ultrasounds of the abdomen will be performed at the time of each gastroscopy, with particular emphasis on the kidneys and large colon. Subjective assessments will be made of kidney structure and colonic edema, and objective measurements will be taken of the right dorsal colon wall thickness.