It Takes Two to Treat - Pancreatic Disease
World Small Animal Veterinary Association World Congress Proceedings, 2014
Jörg M. Steiner1, DrMedVet, PhD, DACVIM, DECVIM-CA, AGAF; Marge Chandler2, DVM, MS, MANZCVSc, DACVN, DDACVIM, DDECVIM-CA, MRCVS
1Texas A&M University, College Station, TX, USA; 2Royal (Dick) School of Veterinary Studies, Roslin, UK

Exocrine Pancreatic Insufficiency Medical Therapy

Most dogs and cats with EPI can be successfully treated by dietary supplementation with pancreatic enzymes. Dried extracts of porcine pancreas are available. The clinical impression in dogs and cats is that powder is more effective than tablets, capsules, and especially enteric-coated products have also been substantiated in human patients with EPI. Initially, one teaspoon per 10 kg body weight and meal should be given in dogs, and one teaspoon per cat and meal in cats. Oral bleeding has recently been reported in 3 of 25 dogs with EPI treated with pancreatic enzyme supplements. The oral bleeding stopped in all 3 dogs after the dose of pancreatic enzymes was decreased. Moistening the food pancreatic powder mix also appears to decrease the frequency of this side effect.

If the owner has access to fresh pancreas, this may be a viable alternative use of pancreatic powder. However, there is a slight risk of transmission of Aujeszky's disease from raw pork pancreas, BSE from raw bovine pancreas, and Echinococcus multilocularis from raw game pancreas. One to three ounces (30–90 g) of raw chopped pancreas can replace one teaspoon of pancreatic extract. Raw pancreas can be kept frozen for several months without loss of enzymatic activity. Preincubation of the food with pancreatic enzymes, supplementation with bile salts, or concurrent antacid therapy are unnecessary in most canine and feline patients with EPI. When clinical signs have resolved, the amount of pancreatic enzymes given can be gradually decreased to the lowest effective dose, which may vary from patient to patient, and from batch to batch of the pancreatic supplement.

Even though pancreatic enzyme supplementation causes the clinical signs to subside in almost all patients, it has been shown in humans and dogs with EPI that nutrient absorption, and particularly fat absorption, are not normalized by enzyme supplementation. This is thought to be due to the low pH in the stomach leading to irreversible damage of some of the pancreatic lipase contained in the supplement. Even though gastric pH can be raised by administration of antacids, the negative effect of the increased intraluminal gastric pH on fat digestion by gastric lipase appears to cancel much of the positive effect, so that overall there is only a minimal increase in fat absorption, which is clinically not important in most patients. However, the use of omeprazole has recently been shown to be efficacious in human patients with EPI and may be tried at a dose of 0.7–1.0 mg/kg q12h PO if the patient does not respond to routine therapy.

Some dogs and cats do not respond to enzyme supplementation and cobalamin application. These patients likely have concurrent small intestinal disease. In dogs with EPI, small intestinal dysbiosis is common and may need to be treated with antibiotic therapy (antibiotic of choice tylosin at 25 mg/kg q12h PO for 6–8 weeks). In cats with EPI, inflammatory bowel disease can frequently occur concurrently.

Dietary Therapy

Feeding a highly digestible, low fiber diet improves some of the clinical signs, such as flatulence or borborygmus. This also decreases faecal volume and defecation frequency. However, dietary therapy alone is unlikely to improve faecal consistency. Using a highly digestible diet with the addition of pancreatic enzymes increases the amount of energy absorbed from the nutrients and improves faecal consistency. This should improve weight gain, which is important as most of these patients are underweight. Increased dietary fiber impairs pancreatic enzyme activity and decreases calorie density so should be avoided.

Response to enzyme supplementation alone may not be satisfactory in some canine or feline patients with EPI. Many dogs and especially cats with EPI also have a serious depletion of total body cobalamin (vitamin B12) stores. Serum cobalamin and folate concentrations should be routinely evaluated in small animals with suspected EPI, and dogs and cats with decreased serum cobalamin concentrations should be treated with cobalamin parenterally. Hypovitaminoses of other fat- and water-soluble vitamins are also common, but most patients are not routinely treated with vitamin supplements and respond well to therapy otherwise. Also, as indicated, vitamin K deficiency may occur in rare cases and should be anticipated as a potential complication.

Pancreatitis

Treatment of Inciting Cause

Whenever possible, the inciting cause of the disease should be removed or treated. However, this may be difficult to accomplish, as most cases of canine and feline pancreatitis are considered idiopathic.

A serum chemistry profile should be performed to rule out hypertriglyceridemia or hypercalcemia. Exposure to unnecessary drugs, especially those implicated in causing pancreatitis in dogs, cats, or other species, should be avoided. Thus, a careful drug history should be taken, and the clinician should carefully determine whether treatment is still needed.

Supportive Care

Aggressive fluid therapy is the mainstay of supportive therapy for dogs and cats with severe forms of pancreatitis. Fluid, electrolyte, and acid-base imbalances need to be assessed, and corrected as early as possible. This is especially important since systemic complications are associated with a worse outcome and many of the systemic complications, once established, are difficult to treat. Recent studies in humans have shown that minimal differences in blood urea nitrogen concentrations at time of admission to the hospital and also minimal changes of BUN during the first 24 to 48 h after admission to the hospital can have a dramatic impact on the outcome in humans with acute pancreatitis.

Analgesia

Abdominal pain is the key clinical sign in human patients with pancreatitis and is recognized in excess of 90% of all pancreatitis patients. Abdominal pain is much more commonly recognized in dogs than in cats with pancreatitis, but even in dogs, the reported rate of abdominal pain is only approximately 58% and is even lower in cats. It is unlikely that abdominal pain occurs less frequently in dogs and cats than in humans and it is much more likely that abdominal pain remains unidentified in veterinary species. Thus, the presence of abdominal pain should be assumed, and analgesic drugs are indicated in all small animal patients with pancreatitis.

Antiemetics

Until recently, the choices for antiemetic agents for use in dogs and cats with pancreatitis was limited. Metoclopramide, a dopamine inhibitor, was most widely used. However, its effect on splanchnic perfusion remains in question, and the author does not like to use metoclopramide in dogs or cats with pancreatitis. Fortunately, several other antiemetic agents have become available over the last few years.

Maropitant, an NK1 antagonist has become widely available for use in dogs and cats. Maropitant is a highly efficacious antiemetic agent through both peripherally and centrally medicated mechanisms and can be used both parenterally in patients that are actively vomiting and orally in patients that appear mostly nauseous.

Dolasetron and ondansetron are 5HT3 antagonists and are also very effective antiemetic agents in both dogs and cats. The injectable formulation of dolasetron can be used for intravenous, subcutaneous, or oral administration and is being used at 0.3–0.6 mg/kg q12–24h in both dogs and cats. Since maropitant and 5HT3 antagonists work through different mechanisms, both drugs can be combined.

Antibiotics

In contrast to humans, infectious complications of pancreatitis are rare in dogs and cats with pancreatitis. Also, even though such complications occur frequently in human pancreatitis patients and are estimated to be responsible for approximately 25–50% of all deaths associated with acute pancreatitis, a clear advantage of antibiotic use has not been demonstrated to date. Therefore, the use of antibiotic agents should be limited to those cases when an infectious complication can be identified or is strongly suspected.

Other Therapeutic Strategies

Many other therapeutic strategies, such as the administration of trypsin-inhibitors (e.g., Trasylol), platelet activating factor inhibitors (PAFANTs), dopamine, antacids, antisecretory agents (i.e., anticholinergics, calcitonin, glucagon, somatostatin), or selenium and peritoneal lavage all have been evaluated in human patients with pancreatitis. With the exception of PAFANTs and selenium, none of these have shown any beneficial effect at this point.

Mild Chronic Pancreatitis

It should be noted that many small animal patients, both canine and feline, have mild forms of chronic pancreatitis. Often times these patients have concurrent conditions, most notably IBD. Very little is known about appropriate therapy for these patients, and management is often limited to evaluation and treatment of the concurrent condition, and careful monitoring of the pancreatitis.

Serum calcium and triglyceride concentrations should always be evaluated in these patients in order to identify any risk factors that can potentially be addressed therapeutically.

Over the last two decades, a new form of pancreatitis, autoimmune pancreatitis, has been described in humans. Autoimmune pancreatitis is now more commonly recognized in humans and is characterized by a lymphocytic-plasmacytic infiltration of the pancreas. Human patients with autoimmune pancreatitis respond favorably to the administration of corticosteroids. Recently, several clinicians have started to cautiously treat canine and feline patients with chronic pancreatitis with corticosteroids and have found this treatment strategy to be beneficial in a portion of cases. Also, successful treatment of a canine patient with chronic pancreatitis with cyclosporine has been reported in the literature. However, further studies are needed before these treatment strategies can be recommended for more routine use in dogs and cats. Regardless of the management, progress of the disease should always be monitored.

Dietary Therapy for Pancreatitis

Previous dietary recommendations for patients with acute pancreatitis were to withhold food and water. The current recommendations for canine patients with mild pancreatitis is to restrict food and water only if there is significant vomiting, and to return oral intake with a highly digestible, high carbohydrate, low-fat diet as soon as possible. Early feeding in human pancreatitis cases improves survival rates, and appears to be well tolerated in canine patients. Restricting the fat content of the diet is important. Most of the very low-fat diets available for dogs are weight reduction diets, which are often high in fiber, not very digestible, and are low in calories, so they are a poor choice if a patient is losing weight unintentionally. Two low-fat diets that are not high in fiber are available and are a good choice for the convalescent pancreatitis patient. Many dogs with chronic pancreatitis can be managed with a low-fat diet.

In an anorexic patient who is not vomiting, the simplest and most widely used methods of providing enteral nutrition are naso-oesophageal tubes, gastrostomy tubes or oesophagostomy tubes. Most pets appear to tolerate these forms of nutritional support well.

For pancreatitis patients with continued vomiting, oral intake must be curtailed for a longer period of time and aggressive intravenous fluid therapy is required. The feeding options in these patients are using a jejunostomy tube or parenteral nutrition, and these interventions may improve clinical outcome. Parenteral nutrition may be provided by using a central vein, such as the jugular vein, or a peripheral vein such as the cephalic vein may be used if less concentrated formulas are used.

High serum triglycerides are often associated with pancreatitis in dogs. In one study, an elevated post-prandial serum triglyceride concentration was associated with increased canine specific pancreatic lipase immunoreactivity in overweight dogs, although in this study the dogs did not develop overt signs of pancreatitis. Dietary saturated fats induce expression of monocyte chemoattractant protein-1 mRNA, a protein involved in the pathogenesis of obesity-mediated inflammation. A low-fat diet, especially for saturated fatty acids, is the initial treatment for elevated serum triglycerides.

The addition of omega 3 fatty acids at an empiric rate of 40 to 100 mg of eicosapentanoic and docosahexanoic acid (combined) per kg to the diet can also help to lower triglyceride concentrations. Omega-3 fish oil lipids can also decrease the inflammatory response, improve the immune function and restore bowel function in severe acute pancreatitis.

If this is not successful, "no flush" slow-release niacin at 50 to 100 mg given with food may be added. Adding regular niacin to food may also decrease the risk of a vasodilation (flush) sometimes seen with niacin. Finally, gemfibrozil (150–300 mg/dog divided) can be added, but safety is not well established.

As overweight dogs are more prone to developing pancreatitis, control of body weight and body condition is important. As well as an increased risk of disease, pancreatitis is more likely to be severe and necrotizing in obese individuals. Overweight dogs should be put on low fat weight loss diets in a controlled and monitored weight loss programme, ideally through a weight loss clinic. If a dog with pancreatitis has a body condition score of 5/9 (3/5) or less, they should be put on a low-fat diet which is not low in calories.

Pancreatitis in Cats

The use of low-fat diets for cats with pancreatitis does not appear to be as crucial as it is in dogs. Cats with chronic pancreatitis can develop cobalamin malabsorption and deficiency, because the intrinsic factor may be deficient. The intrinsic factor promotes intestinal cobalamin absorption, and is produced only by the pancreas in cats as opposed to the stomach and pancreas in dogs. Cobalamin should be supplemented at 250 µg per cat subcutaneously once a week for one month, and then once every two weeks.

Cats with pancreatitis should be checked for comorbid diseases which often occur with feline pancreatitis, such as inflammatory bowel disease, cholangitis and diabetes mellitus. Dietary therapy for these diseases may be needed.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Marge Chandler, DVM, MS, MANZCVSc, DACVN, DACVIM, DECVIM-CA, MRCVS
Royal (Dick) School of Veterinary Studies
Roslin, UK

Jörg M. Steiner, DrMedVet, PhD, DACVIM, DECVIM-CA, AGAF
Texas A&M University
College Station, TX, USA


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