Appetite-stimulating effects of once-daily omeprazole in cats with chronic kidney disease: Double-blind, placebo-controlled, randomized, crossover trial.

BACKGROUND: Cats with moderate to advanced chronic kidney disease (CKD) often display clinical signs such as vomiting and decreased appetite, and frequently receive omeprazole or other acid suppressants despite a lack of evidence to support their use. HYPOTHESIS/OBJECTIVES: To evaluate the effect of once-daily PO omeprazole on appetite in cats with CKD. We hypothesized that omeprazole would improve subjective appetite assessments in cats with CKD. ANIMALS: Fourteen client-owned cats with International Renal Interest Society (IRIS) stage 2 or 3 CKD and hyporexia. METHODS: Cats were prospectively enrolled in a multi-institutional, double-blinded, randomized, crossover study to evaluate the effect of a 14-day trial of once-daily PO omeprazole (1 mg/kg) or placebo (lactose gel capsule) on vomiting frequency and appetite. A daily log was completed by the owner during all treatment and rest periods to assess appetite using a subjective, qualitative, and 5-point scoring system. Mixed model analyses of variance were performed to determine if average daily percentage food consumed or appetite score, as measured by subjective owner assessment, differed between treatments. RESULTS: Compared to placebo, a negligible but statistically significant difference in percentage of food consumed was observed between treatments (P = .04) with once-daily omeprazole treatment resulting in a 2.7% increase in food consumption compared to placebo. No significant difference, however, was found in appetite score, body weight, or serum creatinine concentration between treatments. CONCLUSIONS AND CLINICAL IMPORTANCE: Once-daily omeprazole does not markedly increase appetite in cats with CKD and should not be used as a first-line treatment in the absence of evidence of gastrointestinal ulceration.

Evaluation of the effect of a famotidine continuous rate infusion on intragastric pH in healthy dogs.

BACKGROUND: Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4. ANIMALS: Nine healthy Beagle dogs. METHODS: Randomized 2-way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance. RESULTS: There was a statistically significant difference (P < .05) in MPT ≥3 and ≥4 between the CRI and IV q12h groups on all treatment days. On days 1, 2, and 3, the MPTs ± SD for which pH was ≥3 were 92.1 ± 8.5, 96.3 ± 6.2, and 90.0 ± 15.7 for the CRI treatment group and 49.3 ± 27.3, 42.2 ± 19.6, and 45.8 ± 10.1, respectively, for the twice-daily group. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that a famotidine CRI, but not standard doses of famotidine, achieves the clinical goals established in people to promote healing of gastric tissue injury and offers an alternative to intravenous treatment with proton pump inhibitors in dogs.

Postmortem evaluation of renal tubular vacuolization in critically ill dogs.

OBJECTIVE: To describe the frequency of renal tubular vacuolization (RTV) as a surrogate of osmotic nephrosis and assess hyperosmolar agents as predictors of RTV severity. DESIGN: Retrospective study (February 2004-October 2014). SETTING: Veterinary teaching hospital. ANIMALS: Fifty-three client-owned, critically ill dogs that had a postmortem examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency, severity, and location of RTV were determined in small group of critically ill dogs postmortem. Logistic regression was performed to assess cumulative 6% HES (670/0.75) and mannitol dose as predictors for RTV severity with presenting serum creatinine concentration, cumulative furosemide dose, and duration of hospitalization as covariates. RTV was noted in 45 (85%) of 53 critically ill dogs and was most commonly located to the medullary rays (68%). Cumulative 6% HES (670/0.75) dose (P = 0.009) and presenting serum creatinine concentration (P = 0.027) were significant predictors of RTV severity. For every 1 mL/kg increase in 6% HES (670/0.75) dose that a dog received, there was 1.6% increased chance of having more severe RTV (OR 1.016; 95% CI 1.004-1.029). In addition, for every 88.4 µmol/L (1 mg/dL) increase in presenting serum creatinine, there was a 22.7% increased chance of having more severe RTV (OR 1.227; 95% CI 1.023-1.472). Cumulative mannitol (P = 0.548) and furosemide (P = 0.136) doses were not significant predictors of RTV severity. CONCLUSION: In a small group of critically ill dogs, there was a high frequency of RTV identified on postmortem examination. Administration of 6% HES (670/0.75) and presenting serum creatinine concentration were significant predictors of RTV severity. Larger prospective studies are needed to determine the etiology and significance of RTV in dogs.

Omeprazole Minimally Alters the Fecal Microbial Community in Six Cats: A Pilot Study.

Although they have historically been thought of as safe medications, proton pump inhibitors such as omeprazole have been associated with an increased risk of enteric, particularly Clostridium difficile, infections in people. In cats, omeprazole is often the first choice acid suppressant prescribed for the treatment of upper gastrointestinal (GI) ulceration and bleeding. Despite this, no studies to date have explored the effect of omeprazole on the feline fecal microbiome and metabolome. Therefore, the purpose of this pilot study was to evaluate the effect of prolonged omeprazole administration on the fecal microbiome and metabolome in healthy cats to identify targets for analysis in a larger subset of cats with GI disease. A within-subjects, before and after, pilot study was performed whereby six healthy adult cats received 60 days of placebo (250 mg lactose PO q 12 h) followed by 5 mg (0.83-1.6 mg/kg PO q 12 h) omeprazole. On days 0, 30, and 60 of placebo and omeprazole therapy, the fecal microbiome and metabolome were characterized utilizing 16S ribosomal RNA sequencing by Illumina and untargeted mass spectrometry-based methods, respectively. Omeprazole administration resulted in no significant changes in the global microbiome structure or richness. However, transient changes were noted in select bacterial groups with omeprazole administration resulting in an increased sequence percentage of Streptococcus, Lactobacillus, Clostridium, and Faecalibacterium spp. and a decreased sequence percentage of Bifidobacterium spp. Significance was lost for all of these bacterial groups after adjustment for multiple comparisons. The fecal concentration of O-acetylserine and aminomalonate decreased with omeprazole therapy, but significance was lost after adjustment for multiple comparisons. The results of this pilot study conclude that omeprazole has a mild and transient impact on the fecal microbiome and metabolome when orally administered to healthy cats for 60 days. Based on the findings of this pilot study, evaluation of the effect of omeprazole specifically on Streptococcus, Lactobacillus, Clostridium, Faecalibacterium, and Bifidobacterium spp. is warranted in cats with primary GI disease.