Equine gastric ulcer syndrome: Observer reliability in ulcer grading and investigation of pharmacological and clinical influences on gastric pH.

Jessica Wise

Research output: ThesisDoctoral Thesis

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Abstract

Equine gastric ulcer syndrome (EGUS) is the most common condition of the equine stomach, with reported prevalence of up to 90% in racehorses and 51% in foals. Gastroscopy and subjective grading of observed mucosal lesions, is the only accurate way to diagnose EGUS and assess severity ante mortem. There are several grading systems proposed for grading of the severity of EGUS at the time of gastroscopy. A 5 point ordinal grading systems is frequently used in clinical and research settings, and has been recommended by the Equine Gastric Ulcer Council (EGUC). There has been little investigation into the reliability of this grading system.
Ulcerative disease of the squamous mucosa is due to exposure to the acidic gastric contents. Omeprazole, a substituted benzimidazole, is the mainstay treatment of EGUS, and administration of this drug has been demonstrated to increase intragastric pH. Omeprazole is acid labile and for oral administration, protection from degradation by gastric acidity is achieved by suspension in buffered solutions or enteric coating, to improve bioavailability. Enteric-coated omeprazole is typically administered as granules suspended in a paste formulation, and has been demonstrated to have greater bioavailability than other formulations of omeprazole.
Due to the previously reported high prevalence of EGUS in foals, and the potential for complications associated with EGUS in neonatal foals, foals admitted to the intensive care unit (ICU) are frequently administered acid-suppressive treatment, empirically, without confirmation of EGUS. The pathophysiology of EGUS in foals is largely incompletely understood, and the role of gastric acidity in the pathogenesis is unknown. Administration of acid suppressive therapy to foals admitted to ICU has been associated with increased risk of undifferentiated diarrhoea.
The aims of this thesis were to: (1) investigate the interobserver and intraobserver reliability of the EGUC grading system and a novel visual analogue scale (VAS) for assessment of squamous and glandular gastric mucosal lesions, and the influence of observer experience on the outcomes for both systems, (2) characterise the pharmacokinetic and pharmacodynamic parameters of omeprazole in horses by comparative studies of an existing enteric-coated oral paste formulation and a novel, in-feed, enteric-coated dry granule formulation, and (3) to determine the intragastric pH profiles of systemically-ill foals admitted to the neonatal intensive care unit and identify clinical and clinicopathological parameters associated with intragastric pH <4.
The results of this thesis determined that the EGUC system for grading EGUS lesions has acceptable intraobserver and interobserver reliability and performs well regardless of clinician experience. A VAS may offer advantages in ease of use for rating of squamous mucosa, but observers should be practiced in the use of this system. Glandular lesions in horses may be more difficult to grade than squamous lesions.
The results of the in-feed omeprazole study demonstrated that the administration of the novel, in-feed, enteric-coated omeprazole product increased gastric pH relative to untreated horses, and to the same magnitude as the commercially available product. Mean pH and the percent of time that gastric pH >4 were increased by treatment, and bioequivalence was demonstrated between preparations, indicating that pharmacodynamic effects were the same regardless of dose rate for both preparations. The findings of this study confirm that plasma concentrations of omeprazole and omeprazole dose do not predict drug pharmacodynamics.
The results of the foal intragastric pH study demonstrated that the majority of the foals included within this study had an intragastric pH of > 4 for > 80% of the recording time, which does not support the indiscriminate use of acid-suppressive medications in critically-ill foals. Our results suggest that non-surviving foals, foals with a history of placentitis, and foals presenting with respiratory insufficiency, had higher intragastric pH. Conversely, foals presenting with diarrhoea had more acidic intragastric profiles. The intragastric pH profiles of critically-ill neonatal foals admitted to the ICU were variable and further research is required to better understand the clinical importance of different pH measurements.
This thesis provides contributions to the understanding the reliability of grading systems for EGUS, as well as adding to the body of literature in understanding the pharmacokinetic and pharmacodynamics of enteric coated omeprazole in the horses. The thesis also provides a contributions to the body of evidence that the non-selective administration of acid suppressive therapy to foals admitted to the ICU is unnecessary, as well as providing a platform for further investigation into the relationship of clinical and clinicopathological parameters and the intragastric pH of neonatal foals.
Original languageEnglish
QualificationDoctor of Veterinary Studies
Awarding Institution
  • Charles Sturt University
Supervisors/Advisors
  • Hughes, Kris, Principal Supervisor
  • Raidal, Sharanne, Co-Supervisor
Place of PublicationAustralia
Publisher
Publication statusPublished - 12 Jul 2021

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