A 6-year-old castrated male Boxer weighing 23.9 kg (52.6 lb) with a body condition score of 4/9 was admitted to the University of Tennessee Small Animal Emergency Service with a chronic history of intermittent vomiting. Approximately 5 weeks prior to admission, the dog had accidentally ingested 5 to ten 15-mg meloxicam tablets that had been prescribed for its owner (approx ingested dose, 3.1 to 6.2 mg/kg [1.4 to 2.8 mg/lb]). The owner had not sought veterinary care at that time because no clinical signs of toxicosis had been observed.
Three days after meloxicam ingestion, the dog had begun to vomit and was brought to its primary care veterinarian for evaluation. There, the dog had received supportive treatment with crystalloid fluid administered IV over a 12-hour period, and a 2-week course of omeprazole (0.8 mg/kg [0.36 mg/lb], PO, q 24 h) and sucralfate (41.8 mg/kg [19 mg/lb]), PO, as a slurry, q 8 h) had been prescribed. Despite these treatments, the dog had developed melena and had continued to vomit almost daily 3 to 4 hours after eating. In addition, it had begun to intermittently assume a prayer posture, presumably to relieve abdominal pain. During the third week of treatment, omeprazole administration had been discontinued and tramadol had been prescribed (50 mg, PO, q 8 h, representing a dose of 2 mg/kg [1 mg/lb]). By that point, the dog had developed intermittent anorexia, was drinking less than usual, and had lost approximately 4 kg (8.8 lb) of body weight. On the fifth week of treatment, the dog was referred to the University of Tennessee Small Animal Emergency Service for evaluation.
Initial physical examination by the Emergency Service revealed mild hyperthermia (rectal temperature, 39.3°C [102.8°F]; reference range, 38.3° to 39.2°C [101.0° to 102.5°F]) and tacky mucous membranes, but no other noteworthy abnormalities. A CBC and serum biochemical analysis were performed, with results within reference intervals. Ultrasonographic evaluation of the abdomen revealed a focal hyperechoic area with distal acoustic shadowing that measured approximately 0.8 cm in width and was strongly suspected to be an ulcer within the pyloric antrum or proximal portion of the duodenum. The immediately adjacent gastroduodenal wall was mildly thickened with disruption of normal wall layering. Esophagogastroduodenoscopy revealed multifocal hyperemia of the gastric mucosa and severe ulceration of the proximal aspect of the duodenum approximately 1 cm aboral to the pyloric sphincter (Figure 1).
Esophagogastroduodenoscopic image of hemorrhage in the proximal portion of the duodenum (asterisk) and ulceration approximately 1 cm aboral to the pyloric sphincter in a 6-year-old castrated male Boxer 5 weeks after accidental ingestion of 5 to ten 15-mg meloxicam tablets (approx dose, 3.1 to 6.2 mg/kg [1.4 to 2.8 mg/lb]).
Citation: Journal of the American Veterinary Medical Association 250, 5; 10.2460/javma.250.5.530
Because of concern for impending perforation and the desire to achieve maximal and sustained gastric acid suppression, a radiotelemetric pH-monitoring capsulea was placed in the gastric fundus under endoscopic guidance as previously described1–3 for continuous monitoring of intragastric pH. Treatment was continued with sucralfate as previously prescribed and omeprazole at an increased administration frequency (0.8 mg/kg, PO, q 12 h). In addition, the owner was provided with three 48-hour pH-monitoring receivers that were calibrated to the pH capsule used in the dog. This setup provided for a 6-day period of continuous monitoring at home with near real-time data acquisition, allowing for tailoring of treatment, if needed, and monitoring of client compliance.
Results of at-home pH monitoring on day 1 indicated that a pH ≥ 3.0 was achieved during 73% of the day, ≥ 4.0 during 60% of the day, ≥ 5.0 during 47% of the day, and ≥ 6.0 during 31% of the day (Figure 2). On day 2, a pH ≥ 3.0 was achieved during 85% of the day, ≥ 4.0 during 79% of the day, ≥ 5.0 during 71% of the day, and ≥ 6.0 during 50% of the day. On day 3, a pH ≥ 3.0 was achieved during 79% of the day, ≥ 4.0 during 73% of the day, ≥ 5.0 during 64% of the day, and ≥ 6.0 during 45% of the day. On day 4, pH range data could not be calculated because of intermittent signal loss. On day 5, a pH ≥ 3.0 was achieved during 79% of the day, ≥ 4.0 during 75% of the day, ≥ 5.0 during 67% of the day, and ≥ 6.0 during 53% of the day. On day 6, continuous pH monitoring led to detection of a rapid drop in intragastric pH following an inadvertent missed dose of omeprazole; a pH ≥ 3.0 was achieved during 52% of the day, ≥ 4.0 during 40% of the day, ≥ 5.0 during 31% of the day, and ≥ 6.0 during 25% of the day. Overall results of pH monitoring were summarized (Figure 3).
Portions of intragastric pH recordings for the dog in Figure 1 on days 1 (A), 3 (B), and 6 (C) during twice-daily omeprazole administration (0.8 mg/kg [0.36 mg/lb], PO). Recordings were obtained via a pH monitoring capsule that had been placed in the gastric fundus under endoscopic guidance and monitored via dedicated receivers. Vertical gray bars represent periods when data readings failed because of excessive distance between the transmitter and receiver. In panel A, the asterisk signifies the first dose of omeprazole. In panel C, the dagger represents a missed dose of omeprazole. A gastric pH ≥ 3.0 (horizontal bar) was achieved during approximately 73% of the day on day 1 (first day of administration), 85% of the day on day 2, 79% of the day on day 3, 79% of the day on day 5, and 52% of the day on day 6 (after the owner missed administering one of the twice-daily doses of omeprazole). Time gastric pH was ≥ 3.0 could not be calculated on day 4 because of signal loss.
Citation: Journal of the American Veterinary Medical Association 250, 5; 10.2460/javma.250.5.530
Mean overall percentage of time that intragastric pH was within various pH ranges throughout the 120-hour monitoring period for the dog of Figure 1. Data from day 4 were not included in the analysis because of signal loss during monitoring. See Figures 1 and 2 for remainder of key.
Citation: Journal of the American Veterinary Medical Association 250, 5; 10.2460/javma.250.5.530
With the exception of a single day of vomiting 2 weeks later, the condition of the dog improved markedly and vomiting otherwise resolved. Appetite and water consumption returned to normal amounts, and the dog gained 0.2 kg (0.44 lb) of body weight within 2 weeks after monitoring began. Esophagogastroduodenoscopy was repeated, and although mild gastric hyperemia persisted, mucosal proliferation was evident in the region of the previous duodenal ulcer with no appreciable ulceration remaining (Figure 4). Continued twice-daily omeprazole administration was recommended for an additional month. The owner reported resolution of clinical signs with continued weight gain during follow-up communications, but further imaging was not pursued.
Follow-up esophagogastroduodenoscopic image of the dog in Figure 1 after 2 weeks of twice-daily omeprazole administration (0.8 mg/kg, PO). The proximal aspect of the duodenum is shown, approximately 1 cm aboral to the pyloric sphincter. The previously identified ulcer appears completely resolved (asterisk). See Figure 1 for remainder of key.
Citation: Journal of the American Veterinary Medical Association 250, 5; 10.2460/javma.250.5.530
Discussion
Peptic ulceration is caused by distinctive, but often overlapping, mechanisms, including diminished mucosal defenses (eg, invasive tumor or exposure to bile salts from duodenal reflux) or excessive acid secretion. Reported causes of peptic ulceration in dogs include neoplastic (eg, mast cell tumor4) and nonneoplastic conditions (eg, intervertebral disk disease in combination with high-dose corticosteroid administration,5 extreme physical activity,6 and NSAID administration7). Failure to recognize and implement treatment for peptic ulceration may lead to gastrointestinal hemorrhage, anemia, gastroduodenal perforation, pneumoperitoneum, septic peritonitis, and death.8
Gastric pH is closely associated with acid-related mucosal injury and healing in people. In vitro and in vivo findings in people with peptic ulcers suggest that an acidic environment activates plasminogen and inhibits adequate platelet aggregation and fibrin clot formation, leading to delayed healing.9,10 Plasmin-mediated fibrinolysis and acid-dependent proteases are believed to lead to clot degradation and subsequent rebleeding. Goals established for the medical treatment of esophageal mucosal erosion in people indicate that optimal healing occurs when an intragastric pH ≥ 3.0 is maintained for approximately 75% of the day.11 This goal has been accepted in human medicine as the minimal target for acid suppression in people with gastric acid-induced injury. Additional, more aggressive pH goals have been established to promote hemostasis and healing of bleeding peptic ulcers.12,13 Thus, acid-suppressant treatment is imperative and commonly prescribed for people with acid-related disorders and with bleeding peptic ulcers in particular.10 Although it is reasonable to suspect that ideal intragastric conditions for hemostasis in dogs may be similar, it is unknown whether therapeutic goals established for people may be extrapolated to other species. As such, a target intragastric pH ≥ 3.0 for ≥ 75% of the day was established as a therapeutic goal for the dog of the present report.
Recent use of accurate, continuous, radiotelemetric esophageal and intragastric pH monitoring has furthered understanding of acid suppressant pharmacodynamics and digestive physiology and disease in companion animals. Effects of orally administered acid suppressants have been evaluated in healthy dogs1 and cats2,3 by use of this technology, resulting in revised dosage recommendations for acid suppressants. Additionally, results of these studies1–3 indicated considerable variability in intragastric pH within seconds of any single measurement, suggesting that intermittent collection of gastric content samples for measurement of pH is unreliable and insufficient. Another study14 of intragastric pH in dogs with a presumptive diagnosis of gastroesophageal reflux disorder allowed for diagnosis of their true disease process and determination that the clinical signs were actually attributable to food-responsive inflammatory enteropathies in a large proportion of study subjects. No reports exist regarding intragastric pH in dogs with naturally occurring peptic ulceration or whether high intragastric pH may promote healing of these lesions.
In the present report, we describe the novel use of continuous radiotelemetric pH monitoring in an in-home setting to evaluate intragastric pH in response to treatment in a dog with naturally occurring peptic ulceration. Acid-suppressant treatment to achieve an intragastric pH ≥ 3.0 for ≥ 75% of the day resulted in resolution of the ulceration. The pH-monitoring system provided easily interpretable data for ongoing assessment of acid suppressant effects and adjustment of dose administration, and it also allowed easy identification of the inadvertent missed dose of medication on day 6. These findings would suggest that this procedure may be useful for assessing owner compliance with treatment recommendations and possibly tailoring of treatment to individuals.
Administration of PPIs is a cornerstone of treatment for peptic ulceration in people,15 and twice-daily administration is recommended for those in hypersecretory states.16 In addition to sucralfate, the dog of the present report received twice-daily administration of a PPI. The increase in the frequency of omeprazole administration, which resulted in achievement of pH goals and resolution of the duodenal ulcer, was the only change made to the prescribed treatment. Although to the authors' knowledge, no reports exist regarding the response to once-daily PPI treatment in dogs with naturally occurring peptic ulceration, this finding is consistent with previously reported failure of once-daily administration of PPIs to improve endoscopic appearance of gastric ulceration in dogs with intervertebral disk disease5 or to promote ulcer healing in dogs with mechanically created gastric ulcers.17
Although gastric pH goals have been established for the medical treatment of mucosal injury in people, more research is necessary to develop clinical goals for companion animals. The resolution of clinical signs in the dog of the present report after an intragastric pH ≥ 3.0 had been achieved for at least 18 h/d suggested that goals for medical treatment of peptic ulcers in people may be applicable to dogs. The findings reported here support the potential for use of continuous radiotelemetric pH monitoring to establish intragastric pH goals for the treatment of individual companion animals with peptic ulceration and the need for research into appropriate pH goals for the treatment of acid-related tissue injury in these species.
Acknowledgments
The authors report that there were no conflicts of interest. No financial support for case management was received from grants or third-party sources.
The authors thank Dr. Sam Parkinson for her care of this patient.
ABBREVIATIONS
| PPI | Proton-pump inhibitor |
Footnotes
Bravo pH-monitoring system, Given Imaging Ltd, Yoqneam, Israel.
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