Abstract

Esophageal, gastric and duodenal ulcers are some of the more common intestinal ailments that occur in cetaceans. In humans 70% of gastric ulcers are associated with Helicobacter infection while 25% of the ulcers are associated with non-steroidal anti inflammatory drugs (NSAIDs).¹ Ulcers related to NSAIDs are thought to be secondary to decreases in prostaglandin production. Effects from oral, rectal and parenteral use are similar indicating a systemic effect on the gastrointestinal mucosa.¹ The effect of stress on the development of ulcers is unclear, and the contribution of various etiologic factors involved with ulcer formation in cetaceans has not been determined.

Etiologic considerations for an ulcer in a cetacean may be influenced by the animal's history, the therapeutic use of anti-inflammatory compounds and a high clinical index of suspicion. Clinical evidence of gastrointestinal ulceration may be masked by other ailments and confuse the caretakers and clinicians as to the presence, cause, or location of ulcers. Ulcer signs include depression, self-imposed isolation, decreased or absent appetite, changes in the time of food acceptance, decreased cooperation with training staff when eating, abdominal cramping, floating at or near the surface, and regurgitation or vomiting. Ulcers may occur in one location of the proximal gastrointestinal tract or in multiple areas simultaneously.

While pain relief is becoming a standard approach in veterinary medicine, non-steroidal anti-inflammatory therapy can potentially play a role in the development of gastric ulceration in cetaceans. One of the earlier NSAIDS used in cetacean medicine, flunixin meglumine, has been correlated with increased ulcer incidence including perforation at the level of the connecting chamber or pyloric stomach. Other non-steroidal medications, such as carprofen, have been used for short periods of time (2-3 days) without apparent adverse clinical effects. On the other hand, one female adult dolphin with musculoskeletal problems initially responded very well to carprofen; however, after four weeks of therapy she developed clinical signs of gastric ulceration including the presence of blood in her gastric fluid.

The diagnostic approach to these conditions in cetaceans is similar to that in the human field. Performing a complete blood count and chemistry panel is necessary to clarify the degree of any blood loss and response shown by inflammatory indicators such as white blood cell count, fibrinogen, serum iron, erythrocyte sedimentation rate, alkaline phosphatase, and albumin. Collecting fasting gastric samples either by endoscopy or orogastric tube for cytology, culture, pH and salinity testing is also critical in ulcer diagnostic evaluation of cetaceans.

Initial investigations into Helicobacter sp. and its association with gastrointestinal ulceration in cetaceans was begun in the early 1990's. Polymerase chain reaction techniques have since verified that this organism is present in some cetaceans species with and without ulcers.² The recognition of Helicobacter as a major ulcer etiologic agent in the human field has changed some diagnostic and treatment considerations in cetacean medicine. The standard approaches for diagnosis of ulceration associated with Helicobacter includes gastric fluid sampling with cytology and culture, esophagogastroscopy with biopsy (esophagogastroduodenoscopy in humans), cytology, culture, and rapid urea testing of the biopsy samples. Upper gastrointestinal double contrast barium radiography utilized in humans is not commonly employed in cetaceans. Fecal samples can also be analyzed with cytology, culture, and PCR for Helicobacter. The presence of melena in the stool may be an indication of hemorrhage related to upper intestinal ulceration. Other human-based diagnostic tools for the detection of Helicobacter include serologic testing, urea breath testing, and stool antigen analysis.

By comparison with human, cetacean clinicians are more likely to utilize methods such as gastric sampling with orogastric tubes and less likely to have tools such as endoscopy to aid in ulcer diagnosis. While a gastric sample with obvious cytological evidence of mammalian blood should prompt timely therapy, this does not rule out the other complicating factors such as the location, extent of the lesions, and involvement of foreign materials. When possible it is important to follow this procedure with gastroscopy to confirm a diagnosis and direct appropriate therapy. In cetaceans, however, some endoscopic limitations do exist. Direct visual confirmation of ulcerations is hampered by the anatomic challenges in gaining access to the distal chambers of the stomach and lack of access to the duodenum. Ulcerations can easily be missed in the first stomach chamber if a clinician does not thoroughly scan the region. The second chamber is possible but challenging to access, frequently requiring retroflexion of the scope and retrograde positioning from the first to the second chambers. The second chamber does not expand readily with air which limits visibility. In addition, the architecture of the mucosa with its rugal folds and red color is not as easy to evaluate for ulceration. Culture, biopsy and fluid retrieval may still be performed even with the limited visibility. Access to the third chamber is theoretically possible but the opening from the second to third chamber is very close to the margin between the first and second chambers. If abdominal radiographs are also included in a workup, they should be taken prior to the endoscopic procedure which often introduces a substantial amount of air to the gastrointestinal tract.

The therapeutic approach to esophagogastric ulceration in cetaceans may vary depending on the site involved, the experience of the clinician, and the equipment available. Quite frequently treatment is based on less specific diagnostic methods such as a low hematocrit, an increasing blood urea nitrogen level, and the behavioral changes in food acceptance. Therapy generally involves rehydration either parentally with lactated ringers solution or saline, or orally with warm fresh water or water containing electrolyte solutions. Oral solutions with electrolytes have been shown to increase fluid uptake over plain water use. When sodium retention is a concern, the level of electrolytes can be decreased to avoid further sodium loading but still promote fluid uptake. The latter is thought to be less damaging to ulcerated gastric mucosa. In some cases where frequent oral supplementation is required, cetaceans have been trained to voluntarily accept gastric tubes to ease fluid administration.

Mucosal protectants, such as bismuth, bismuth subsalicylate, and sucralfate, can be part of an effective approach to ulcer therapy. Misoprostol has been shown to be cytoprotective when taken with NSAIDS and has been used with H2 blockers in cetaceans. H2 blockers, such as cimetidine, ranitidine, famotidine and nizatidine, selectively block histamine release and when used twice a day in humans they have a success rate of greater than 70%.¹ Hydrogen pump inhibitors inhibit acid release by binding and inhibiting the H+/K+ adenosine triphosphatase pump. In humans, these products are given once to twice a day for four weeks and have an 80 to 100% healing rate if they are given where Helicobacter is not present. If the clinician thinks Helicobacter to be a factor, antibiotics are strongly encouraged as part of the therapy for gastric ulcers. Multiple drug combinations have been used for the eradication of Helicobacter pylori in humans and five different regimens are approved by the American College of Gastroenterology.¹ Each regime has at least three components, usually with two oral antibiotics such as tetracycline, metronidazole, clarithromycin, or amoxicillin. The combination may also include bismuth and an H2 blocker or a proton pump inhibitor. In cetaceans other antacids such as over-the-counter aluminum hydroxide and magnesium hydroxides have been used to treat gastric ulcer conditions and esophageal reflux disease. It is important to remember that these compounds may interfere with absorption of other medications used in ulcer therapy including antibiotics and iron salts.

Approach to ulcer therapy in cetaceans may differ from therapies for humans. Anorexic cetaceans generally do not take medication voluntarily so there is a need to mix mediations into slurry and deliver them either with water, electrolytes, or fish gruel through a gastric tube. Failure or delay in expected therapeutic response may be related to a mismatch in food presentation and absorption of the ulcer medication. Over-use of ulcer medications may result in poor digestion of fish bones leading to complications such as vomiting and bone impactions. This seems more likely with proton pump inhibitors that have a sustained alkalizing effect than H2 blockers which reduces or inhibits the intermittent acid production needed for fish bone digestion. Choices for the initial therapy for severe ulcers can include some of the following:

1.  No whole fish fed for two to three days. Medications administered parenterally or with electrolyte solution by orogastric tube two to four times daily as needed. Low levels of glucose (2% or less) can be added if needed in the tubed solution.

2.  When using multiple medications that may inhibit digestion of bones, use either gruel made with boneless fish fillets or an electrolyte solution initially and monitor stomach pH several times per day if possible.

3.  If protracted use of multiple ulcer medications is required and a cetacean is voluntarily accepting food, try using fish fillets instead of whole fish as a temporary method until digestion improves or medications are readjusted.

4.  If the animal begins eating whole fish and is receiving multiple oral anti-ulcer medications, a follow-up gastroscopy is warranted within two to three days to determine whether digestion of bones is occurring.

5.  If multiple daily procedures produce abnormal behavioral changes, diazepam can be used at low levels to potentially alleviate some of the anxiety involved. In addition, caretakers should be those familiar to the animal and ideally the animal should be living with compatible, familiar pool mates, as this can greatly improve the chances of a return to voluntary eating.

Another area that deserves more scrutiny and possible use is the application of probiotics during and after therapy. While controversial, there is some data in the human field that has shown a negative effect on helicobacter organisms from addition of appropriate lactobacillus organisms.³

References

1.  Gastric Ulcers, Shrestha, S, Lau, DL. 2007. Emedicine.com/MED/topic 849.htm.

2.  Gueneau, P, Reyes, N, Briceno, S, Bonaventura, C, Dominguez Bello, MG. 2004. Prevalence of Gastric Helicobacter Infection in Two Species of Cetaceans (Tursiops truncatus, and Phocena phocena), Helicobacter. 9: 597.

3.  Mllyluoma, E, Veijola, L, Poussa, T, Vapaataolo, H, Ruatelin, H, Korpela, R. 2003. Effects of Probiotic Mixture in Helicobacter pylori Eradication Therapy, Helicobacter. 9: 5