Feline pancreatitis is an often thought of diagnosis in the sick cat. Cats suspected of pancreatitis commonly present with non-specific signs such as lethargy, anorexia, and dehydration.
Feline pancreatitis is an often thought of diagnosis in the sick cat. Cats suspected of pancreatitis commonly present with non-specific signs such as lethargy, anorexia, and dehydration. Examination findings also tend to be non-specific. Diagnosing feline pancreatitis is not as straight forward compared to diagnosing canine pancreatitis. Frequently, the feline patient with suspected pancreatitis has concurrent disease, making the diagnosis of pancreatitis more difficult. Most common diagnostic modalities are not as sensitive for feline pancreatitis and/or need to be sent to an outside laboratory, delaying definitive diagnosis. Although supportive therapy for feline patients with acute pancreatitis is similar to those for canine patients, there are some therapeutic recommendations that differ. The goals of this lecture are to help the veterinarian differentiate pancreatitis from the other disease processes, both concurrent and those with similar presentations, and then determine what traditional and ancillary therapies are warranted in treating the feline patient with acute pancreatitis.
Many different inciting causes have been postulated to cause feline acute pancreatitis. Several infectious agents have been shown to cause feline pancreatitis; feline parvovirus, Toxoplasma gondii, feline herpesvirus I, Eurytrema procyonis (a fluke), feline infectious peritonitis (FIP), and, rarely, Amphimerus pseudofelineus have been implicated. Concurrent metabolic/inflammatory diseases such as diabetes mellitus, inflammatory bowel disease, cholangiohepatitis, and hepatic lipidosis have been noted to be risk factors for developing pancreatitis, although a cause and effect relationship has not been established. Scientific support for the ingestion of a high fat meal or concurrent use of Glucocorticoids as causative agents of feline pancreatitis is lacking. Blunt and penetrating trauma to the abdomen, and the pancreas specifically, can lead to severe acute pancreatitis. Hypoperfusion of the pancreas during anesthesia or shock can also lead to the development of acute pancreatitis. Despite this long list of potential causes, more than 90% of all cases of feline pancreatitis are classified as idiopathic.
Irrespective of the initiating cause, pancreatitis is generally believed to occur when digestive enzymes are activated prematurely within the pancreas. In the normal pancreas, safeguards are present to ensure that harmful pancreatic enzymes are not activated until they reach the intestinal lumen. Enzymes are stored in zymogen granules within the acinar cell in the presence of pancreatic secretory trypsin inhibition and are released at the apical surface directly into the duct system. They are only activated in the intestine, by trypsin, following the cleavage of trypsinogen by enterokinase. In clinical pancreatitis, it is thought that inappropriate premature activation of trypsin from trypsinogen in the acinar cells initiates a cascade of early activation of zymogens, especially pro-elastase and pro-phospholipase, leading to auto-digestion of the pancreas. Often pancreatic inflammation is a self-limiting process, but in some animals reduced pancreatic blood flow and leukocyte and platelet migration into the inflamed pancreas may cause progression to pancreatic necrosis. Secondary infection may arise by bacterial translocation from the intestine. Release of active pancreatic enzymes and inflammatory mediators from the inflamed pancreas amplifies the severity of pancreatic inflammation, and adversely affects the function of many organs (systemic inflammatory response), and cause derangement in fluid, electrolyte and acid-base balance. It is the development of multi-systemic abnormalities that separates mild from severe, potentially fatal pancreatitis.
Pancreatitis tends to occur in any age, neutered cats with no gender preference. Siamese cats are over-represented. In contrast to people and dogs, obesity has not been reported to be a risk factor for pancreatitis in cats. Clinical signs of pancreatitis in cats differ markedly from that in the dog. Cats are far less inclined to have vomiting and diarrhea as presenting complaints. Indeed the most commonly reported clinical signs in the cat are lethargy and anorexia. About 64% of cases are jaundiced. Often cases have only a vague history of weight loss and behavioral change and few abnormalities are consistently detected upon examination, with dehydration and changes in body temperature most commonly reported. Abdominal discomfort, an abdominal mass, respiratory difficulty, and ataxia are inconsistently reported.
Routine laboratory testing, although essential for evaluation of other organ systems, often provides little assistance in the diagnosis of pancreatitis. Serum amylase and lipase activities have no clinical value for the diagnosis of feline pancreatitis. Radiographic changes seen in some feline patients with pancreatitis include a decreased contrast in the cranial abdomen and displacement of abdominal organs. However, these changes are rather subjective and abdominal radiography is non-specific for feline pancreatitis.
Abdominal ultrasound was, and remains, a standard test for diagnosing acute pancreatitis. The sonographic features of feline pancreatitis include hypoechogenicity of the pancreatic parenchyma, hyperechoic peri-pancreatic mesentery, pancreatic enlargement, peritoneal effusion, pancreatic mass and dilation of the pancreatic duct. It has been established that the appearance of the pancreatic duct changes with age in healthy cats. Pancreatic pseudocysts and abscesses are occasionally found by ultrasonography, and should be aspirated for cytology and aerobic culture. However, ultrasonography is not perfect: it is very operator dependent, and false positive and false negative results are possible, even in the hands of an experienced operator. Ultrasonography has been reported to have sensitivity in diagnosing feline pancreatitis of 25-80% with better results noted with more severe pancreatic inflammation. Mild cases of feline pancreatitis may appear normal on ultrasound examination.
The presence of other disease processes is frequent and emphasizes the utility of abdominal ultrasound in patients suspected pancreatitis. Hepatic lipidosis is reported in 38% of cats with acute pancreatitis, and aspiration of the liver via ultrasound guidance is warranted if suspicion is present. Another study found that 14% of cats with lymphocytic portal hepatitis and 39% of cats with cholangiohepatitis had IBD and mild pancreatitis. Many of these cases require biopsy of all three organs for definitive diagnosis as they frequently have negative, non-specific or equivocal ultrasonographic findings.
Trypsinogen and trypsin are pancreas-specific in origin and leakage into the vascular space of both is noted with pancreatitis. A test for trypsin-like immune-reactivity in cats (fTLI) was developed to detect these. FTLI has been shown to be diagnostic for severe acute pancreatitis. However, this test is not very good in detecting milder forms of pancreatitis. A confounding factor in this test is that trypsin has been located in extra-hepatic peri-biliary glands and significant hepatic disease may lead to an increase in fTLI independent of pancreatic inflammation. Because of these limitations, the use of fTLI has fallen out of favor.
More recently, a test to measure pancreatic lipase immuno-reactivity has been developed. This test evaluates the serum for the specific lipase produced and released by the pancreas. Because of the short half-life of pancreas-specific lipase (90 minutes), continuous secretion of high levels of this enzyme into the circulation is needed for a diagnosis of pancreatitis. A quantitative assay for feline pancreatic lipase immuno-reactivity (fPLI) should be performed. Measurement of increased fPLI has been demonstrated to be a very sensitive test for detection of moderate to severe acute feline pancreatitis in cats, in which sensitivities approaching 100% have been documented. The fPLI is less sensitive in cats with mild pancreatitis, and additional studies are warranted to further evaluate the performance characteristics of this assay in cats with mild disease. Therefore, a combination of clinical suspicion, elevated fPLI, and abnormal abdominal ultrasound should be used to non-invasively diagnose acute pancreatitis
Surgery or laparoscopic biopsy for histopathology is the gold standard for diagnosis of feline acute pancreatitis. There are advantages to obtaining surgical biopsy specimens. The pancreas and peri-pancreatic area can be evaluated for abscesses and necrosis and debridement can be performed. During the procedure, a jejunostomy feeding tube can be placed, thus providing the ability to enterally feed the patient but bypassing the pancreas for digestion. The concern regarding obtaining biopsy samples from the pancreas can worsen the disease process is unfounded. However, just like other diagnostic tests for pancreatitis, biopsy has its drawbacks. The use of general anesthesia can lead to hypoperfusion of the splanchnic circulation, exacerbating the pancreatic inflammatory response. Also, pancreatitis can be a segmental disease and, since typically only 1 or 2 samples are obtained, the biopsy sample may not be representative of the process. Unless there is absolute proof of an infectious complication, which is rare, the benefit of the procedure rarely outweighs the perils of surgical intervention.
Fluid, electrolyte, and acid-base imbalances need to be assessed, and corrected as early as possible in the course of acute pancreatitis. This is especially important since systemic complications are associated with a worse outcome. Decreased intravascular perfusion and dehydration are common in these cats, and hypotension is often present in cats with severe acute pancreatitis. Fluid therapy should be tailored to replace deficits of intravascular volume and interstitial fluid, to provide for the patient's maintenance requirements, and replace any ongoing losses. The crystalloid fluids are the mainstay of fluid therapy for the pancreatitis patient. Crystalloid fluids consist primarily of water with a sodium or glucose base, plus the addition of other electrolytes and/or buffers. Replacement crystalloid solutions contain dissolved solutes that approximate the solute concentration found in plasma water. These solutions are indicated for the rapid replacement of intravascular volume and electrolytes as seen with severe volume depletion secondary to the losses associated with vomiting and diarrhea. With replacement crystalloid fluids, only 20-25% of the infused volume of fluid remains within the intravascular space 1 hour after infusion. Therefore, large volumes of replacement crystalloids need to be administered initially to replace intravascular volume and are continued to replace the ongoing losses from the vomitus and diarrhea. These fluids are often supplemented with potassium and/or magnesium to replace the intra-vascular and interstitial deficits found in patients affected with severe acute pancreatitis.
Colloidal fluids are high molecular weight compounds that do not readily leave the intravascular space. They exert their effect of expanding intravascular volume by holding and potentially drawing water into the vasculature. Colloid fluid solutions are indicated for the treatment of hypovolemia, sepsis, and other inflammatory conditions where crystalloid fluids may leak from the vasculature, all potentially present in the patient with pancreatitis. They are also used to improve colloid oncotic pressure in patients with low albumin from protein loss secondary to gastro-enteric losses. Common colloidal solutions used in pancreatitis patients include plasma and synthetic compounds such as hydroxyethyl starch and Oxyglobin™ .
In the feline patient with acute pancreatitis, intravenous is the preferred route of fluid therapy administration. Although convenient, the use of fluid therapy via a multiple of "maintenance needs" is inappropriate as most patients do not lose or require fluid therapy in these multiples. In this situation, fluid therapy is administered as an initial bolus followed by a constant rate infusion. Initial bolus fluid therapy is indicated in the severely volume depleted patient (absolute or relative) and the severely dehydrated patient. In the intravascular volume depleted patient, the volume of the bolus is determined based on resolution of clinical signs (slower heart rate and respirations, improved pulse quality, improved mucus membrane color). Therefore, frequent reassessment of the volume depleted patient is required. Fluid rates as high as 50-60ml/kg/hr of crystalloid fluids may be required. Colloids can also be administered as boluses. Colloids are administered in boluses of 2-3ml/kg up to 10ml/kg. Again, the patient should be re-assessed after each bolus to determine if the bolus has been effective in resolving the volume depleted state or if additional boluses are needed. Crystalloid fluids are often administered along with colloids to augment their vascular volume expanding effect. Smaller doses of crystalloids than those listed above are necessary with the concomitant use of colloid. In the dehydrated patient, the quantity of a fluid bolus is based on the estimated degree of dehydration. The dehydration deficit can be calculated as body weight (kg) x estimated degree of dehydration (%) x 100 = ml of fluid required. It is recommended that one-half of the dehydration deficit be given as a bolus and the remainder replaced as a constant rate infusion over 12-24 hours.
Once vascular volume and some of the dehydration deficits have been replaced, constant rate fluid administration is initiated. As described above, it is used to replace dehydration deficits. It is also necessary to account for a patient's maintenance fluid requirements, as patients with pancreatitis are not consuming sufficient quantities of fluid on their own. Daily maintenance needs for patients varies on the age and size of the patient. Most of us were taught that the maintenance crystalloid fluid needs of a patient are approximately 54-66ml/kg/day. With the use of colloid fluid therapy, infusions at rates of up to 10ml/kg/day have been used to provide continuous intravascular volume support. With the use of infusions of colloid fluids, lower infusion rates of crystalloid fluids are necessary. If a patient has ongoing losses due to vomiting, diarrhea, or third spacing (ascites, pleural effusion), these losses should be replaced on a 2 milliliter replaced per estimated 1 milliliter lost.
It is important to remember, though, that fluid therapy must be used judiciously and monitored carefully, as critically ill cats are predisposed to fluid overload, pulmonary edema and pleural effusion. This occurs for multiple reasons, including vascular leak secondary to systemic inflammation and decreased colloid oncotic pressure due to hypoalbuminemia. Dysfunction in other organ systems such as the heart and kidneys can also impair the ability of the patient to adequately handle fluid therapy. Proper monitoring of the patient receiving fluid therapy is a hands-on endeavor. Much of the information we need is gained through serial examinations. No single parameter evaluated will necessarily provide all the information required to guide fluid therapy. Physical examination parameters that should be evaluated include a patient's weight, mentation, skin turgor, pulse rate and quality, respiratory rate and effort, serial lung auscultation for rales, mucus membrane color, and capillary refill time. Skin turgor allows for gross assessment of hydration status- prolonged skin turgor will be noted with 6-8% dehydration, markedly prolonged skin turgor will be noted with > 8% dehydration. Limitations of this method are that obesity may mask decreases in skin turgor. If an indwelling urinary catheter is in place, serial evaluation of fluid input and urine output can provide significant information regarding whether too little or too much fluid therapy is being administered. Renal chemistry parameters (BUN, creatinine) in conjunction with urine specific gravity measurement provide additional information. Increased renal parameters and/or increasing urine specific gravity may provide clues that a patient is receiving too little fluid therapy. Serum lactate measurement can provide information regarding tissue perfusion. Increased serum lactate concentrations indicate that tissues are not receiving adequate oxygen for metabolism and are instead relying on anaerobic metabolism to provide energy.
The administration of fresh frozen plasma has been advocated for the treatment of severe acute pancreatitis in dogs. No studies have been done in cats to determine if plasma therapy in cats has a beneficial effect of the clinical course of pancreatitis. Aside from the colloidal effects of the albumin in plasma, albumin is also necessary for the transportation of highly protein bound drugs and helps maintain normal serum calcium levels. It also supplies anti-thrombin III and coagulation factors needed for the therapy of disseminated intravascular coagulation. Most important, although of theoretical benefit, are the α-macroglobulins fresh frozen plasma contain, which include α2-antitrypsin and other α-proteases. Once trypsinogen is activated into trypsin, it goes on to activate a whole cascade of other enzyme activation, including but not limited to kallikrein, chymotrypsin, elastase, carboxypeptidase, phospholipase and inflammatory cells via PAR-2 (trypsin receptor). By administering fresh frozen plasma, this cascade may be ameliorated.
Abdominal pain is the key clinical sign in human and canine patients with pancreatitis and is recognized in excess of 90% of all human pancreatitis patients. Abdominal pain is only recognized in approximately 25% of all cats with pancreatitis. However, it is unlikely that abdominal pain occurs less frequently in cats than in humans and it is much more likely that abdominal pain remains unidentified in many cats. The release of proteases and inflammatory mediators into the abdominal cavity causes peritonitis and significant pain. Thus, the presence of abdominal pain should be assumed and analgesic drugs are indicated in all cats with pancreatitis. The most commonly used analgesics include parenteral opiate analgesia and transdermal patches. Parenteral analgesia can be supplied as intermittent injections or continuous rate infusions. Transdermal patches may or may not provide adequate analgesia due to variations in perfusion at the site of application and release of drug into the circulation. Epidural analgesia using a pure opioid and local anesthetic can be performed by single lumbar puncture or placement of an epidural catheter.
Although not a common finding in cats with pancreatitis, vomiting can occur either due to pancreatitis or dysfunction in other organ systems. Antiemetic therapy is indicated if the vomiting is persistent or severe. The α2 adrenergic antagonists and serotininergic antagonists appear to be the most effective anti-emetic agents in the cat. Cats may be treated with an α2 adrenergic antagonist such as chlorpromazine or the serotoninergic antagonists ondansetron (Zofran™), or dolasetron (Anzemet™). Maropitant (Cerenia™) is a newer broad spectrum antiemetic that works both centrally and peripherally and is very effective. However, one of the contraindications for the use of maropitant is liver dysfunction. Metoclopramide, which is a dopamine inhibitor, has routinely been used in these patients. However, the effect of dopamine inhibition on perfusion of the pancreas has not been evaluated and may be detrimental.
There is no proven benefit in using antibiotics in cats with pancreatitis, but they are commonly administered. Cats very seldom get infected local necroses and it may be that by using early enteral nutrition alone we will reduce the risk of sepsis by reducing bacterial translocation. If antibiotics are indicated based on suspected infection, then selection of a broad spectrum antibiotic effective against gram-positive and gram-negative bacteria given parenterally is recommended, pending culture results.
The traditional therapy of withholding food from patients with acute pancreatitis may not be beneficial and in some ways may be harmful. Enteral nutrition was avoided with the concern that it would stimulate vomiting as well as pancreatic secretions, exacerbating the disease process. In cats, hepatic lipidosis is a common problem and alimentary support is an integral component of treatment. Also, enteral nutrition is essential to promote enterocyte health. When the gastro-intestinal tract does not receive sufficient nutrients, several pathologic consequences can occur. These include villous atrophy leading to increased mucosal permeability, decreases in gut-associated lymphoid tissue (GALT), and decreased surface area for absorption of nutrients for systemic use. This may lead to gut barrier failure, allowing translocation of bacterial and endotoxin into the portal and, sometimes, systemic circulation, which may lead may lead to a systemic inflammatory response (SIRS). Several human clinical trials have shown that early enteral nutrition is associated with improved outcomes with regard to infectious complications, length of hospital stay, and cost compared to the use of parenteral nutrition and NPO. A jejunostomy tube may be ideal to minimize pancreatic stimulation but there is evidence to support use of the naso-gastric or naso-esophageal feeding tubes without increased complications.
Patients with pancreatitis that are actively vomiting are candidates for micro-enteral nutrition. Micro-enteral nutrition is the delivery of small amounts of water, electrolytes, and readily absorbed nutrients directly to the gastro-intestinal tract to maintain mucosal cell integrity. Microenteral nutrition is commonly delivered by naso-gastric feeding tubes. Naso-gastric tubes are among the easiest and least expensive forms of feeding tubes available for use. Argyle infant feeding tubes are ideal, are soft and pliable, and are well tolerated after placement by most patients. Red rubber feeding tubes are a viable alternative, although they can more reactive with the nasal mucosa. Aside from being able to provide nutrition to the cells lining the gastro-intestinal tract, a naso-gastric feeding tube can allow the removal of residual air. Removal of residual air in the stomach can decrease gastric distention, making the patient more comfortable, decreasing the chance of emesis, and increasing gastric motility. The removal of residual fluid/food will also decrease gastric distention as well as prevent food from stagnating within the stomach if limited motility is present
Dopamine has been proposed as a therapy for pancreatitis. Dopamine in low doses (~ 5 µg/kg/min) may maintain mesenteric blood flow and may also limit increases in microvascular permeability due to beta-adrenergic effects. Research studies have supported attenuation of multiple organ damage by dopamine in rats and diminished severity of pancreatic injury in cats if given very early in the course of disease. While this time limit would preclude dopamine to be effective in routine therapy of spontaneous pancreatitis, it is possible that feline patients with pancreatitis that have to undergo anesthesia may benefit from treatment with dopamine during the procedure. Still, clinical studies in people or animals have evaluated the use of dopamine in pancreatitis.
Feline acute pancreatitis is a complex disease. Cats often have concurrent organ dysfunction. Cats with concurrent acute pancreatitis and hepatic lipidosis have a much poorer prognosis compared to cats with hepatic lipidosis alone. Many recent advances have been made regarding the pathophysiology and diagnosis of this disease. Yet, underlying causes for pancreatitis remain elusive and therapy primarily remains supportive. Still, aggressive supportive care is imperative to maximize the chances for recovery in these cats.
References furnished upon request