Merilee F. Costello, DVM, DACVECC
Feline pancreatitis is a complex disease that can result in severe and potentially fatal systemic inflammation. This systemic inflammation can result in organ dysfunction or failure and can be fatal in some patients. Pancreatitis in our feline patients can be a challenging disease to both diagnose and treat, and numerous studies have provided information on the unique pathophysiology associated with pancreatitis in these patients. It has also been clearly documented that there are significant differences in the feline response to critical illness and specific concerns when treating these patients. The following will discuss the classification, the unique physiology and pathophysiology related to pancreatitis in the cat, clinical presentation and secondary systemic effects with a focus on the systemic inflammatory response in these patients. In addition, time will be spent discussing diagnostic testing, treatment, monitoring, and prognosis.
Classification and Physiology
Feline pancreatitis has been classified into many different categories. One classification scheme divides pancreatitis into acute, chronic active, and chronic. Within this classification acute is further broken down into acute necrotizing and acute suppurative. Clinically, pancreatitis can be classified as mild or severe based on the severity of secondary systemic effects, pancreatic necrosis and mortality. For the purposes of this talk, the discussion will be geared towards severe pancreatitis and the secondary systemic inflammation, as this is often the form treated in the emergency/intensive care setting.
The unique physiology in cats is also related to the clinical manifestations of pancreatitis. Unlike dogs, the majority of cats (80%) have only one pancreatic duct, as the accessory pancreatic duct generally does not persist after development. The pancreatic duct in the cat enters the duodenum through the major duodenal papilla, alongside the bile duct. Pancreatic secretion is mediated both through neural as well as hormonal mechanisms. In cats, the primary mechanism is thought to be hormonal, mediated by secretin and cholecystokinin (CCK) which are released when food enters the small intestine.
Pancreatitis in cats manifests not only as an underlying cause of severe systemic inflammation, it can also occur secondary to disease in other areas of the body. Determination of the exact inciting event is often difficult, if not impossible. In a study of 40 cases of acute necrotizing pancreatitis and suppurative pancreatitis in the cat, the authors report that most cats had no clear etiology. Pancreatic disease has been associated with dysfunction of numerous organs, including liver/hepatobiliary, endocrine pancreas (diabetes, diabetic ketoacidosis), kidneys, intestines, lungs, and peritoneum (effusion). Traumatic injury, surgery, drugs, toxic (organophosphate) and infectious causes have also been implicated. Regardless of the underlying or inciting event, the development of pancreatitis is generally thought to be secondary to a failure of the inherent protective mechanisms of the pancreas. This failure results in zymogen activation within the pancreas and subsequent entry into the interstitium and peritoneal cavity. This leads to local inflammation, pancreatic tissue damage and cell death. The severity of the local and subsequent systemic inflammation is regulated by plasma protease inhibitors in the circulation. The main circulating inhibitors are α1-protease inhibitor and α-macroglobulin. Exhaustion of these protective mechanisms can lead to systemic inflammation and secondary organ dysfunction. Depending on the organ system affected, the systemic sequelae of pancreatitis may include diabetes/DKA, renal failure, disseminated intravascular coagulation, hepatic dysfunction, bile duct obstruction, acute respiratory distress syndrome, myocardial dysfunction, sepsis or death.
Sirs in the Cat
The term systemic inflammatory response syndrome (SIRS) is used to describe a clinical condition consisting of a generalized inflammatory response that can occur secondary to a number of different disease processes, both sterile as well as infectious causes. The inflammation and potential necrosis within the pancreas as well as the significant inflammation with the peritoneal cavity are a significant cause of SIRS in both dogs and cats. It is important to note, however, that the clinical definition of this syndrome is widely debated in both veterinary as well as human critical care. Based on the definition for SIRS in human patients, clinical definitions for SIRS in canine patients were developed and subsequently evaluated in clinical cases. Recently, newer definitions for SIRS in our feline patients have been proposed taking into account the physiologic differences in this species. The criteria for SIRS in the cat are: Temperature >103.5, <100; heart rate >225, <140; respiratory rate >40; wbc >19,500, <5,000, or >5% bands.
Unfortunately, the clinical signs seen in cases of feline pancreatitis are often vague and non-specific. Clinical signs frequently associated with pancreatitis in cats include lethargy, anorexia, dehydration, tachypnea, hypothermia, and icterus. In one study, only 35% of cats had a history of vomiting, and only 25% had reported abdominal pain. In addition, clinical signs are often confounded by the presence of one or more co morbid conditions (e.g., diabetes, inflammatory bowel disease, hepatic lipidosis). Routine diagnostic testing, although essential for evaluation of other organ systems, often provides little assistance in the diagnosis of pancreatitis. This absence of pathognomonic clinical or clinicopathologic signs may explain the fact that antemortem diagnosis of pancreatitis in the cat is rare.
As previously stated, the clinicopathologic changes seen in these cats are typically indistinguishable from those seen in other diseases associated with critical illness. Despite this lack of sensitivity, routine bloodwork is an essential part of the work-up in these cats. Abdominal ultrasound plays an integral role in evaluating not only the pancreas in affected cats, but also other intraabdominal organs. Although CT is useful in people with pancreatitis, it has limited diagnostic utility in our feline patients. In addition, more specialized testing has been investigated to try and improve antemortem diagnosis.
Despite the numerous studies that have been done to investigate etiology, diagnostic testing and prognostic indicators, there remains a paucity of literature discussing treatment options for these cats. The treatment for the cat with pancreatitis is primarily supportive care, and therapy for organ dysfunction. As with any critical illness, the primary goals in treating the cat with pancreatitis are to maintain perfusion and oxygen delivery to the tissues. Oxygen delivery (DO2) is calculated from the following formula:
DO2 = Cardiac Output x Oxygen Content
Oxygen Content = [(1.34 Hb x SpO2) + (0.003 x PaO2)]
Cardiac output is calculated as heart rate x stroke volume. Stroke volume can be improved by maximizing preload with fluid administration. Dehydration is common in these cats, and hypotension is often present in cats with severe acute pancreatitis. Fluid therapy should be aimed at replacing deficits, providing maintenance requirements, and providing for any ongoing losses. In cats with hypotension, the shock bolus is 50-60 ml/kg of crystalloids or 5 ml/kg of colloids. It is important to remember, though, that fluid therapy must be used judiciously, 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.
Numerous studies have documented the presence of hypothermia in critically ill cats. Hypothermia can lead to compromise of cardiovascular, respiratory, central nervous system and hemodynamic functions. Rewarming of these cats is initially done with warm intravenous fluids, and external heat support (forced air heating, circulating water blankets, or incubator) is often required to maintain normothermia.
In some cats, hypotension remains despite adequate volume recussitation. In these cases, exogenous catecholamine therapy is necessary. Dopamine is a vasopressor with positive inotropic, chronotropic and vasoconstrictive effects (5-15 mcg/kg/min). This drug is often the first line in critically ill cats. Cats with severe acute pancreatitis may not respond to dopamine. In these cats, norepinephrine (0.1-3 mcg/kg/min) or epinephrine (0.1-2 mcg/kg/min) may be more effective. Low-dose dopamine (5mcg/kg/min) has also been shown to diminish the severity of experimentally induced pancreatitis in cats, but has not been investigated in spontaneously occurring disease.
Although not a common finding in cats with pancreatitis, vomiting can occur either due to pancreatitis or dysfunction in other organ systems. In these cats, anti-emetics such as metoclopramide, prochlorperazine or ondansetron should be administered. Gastroprotectants such as H2 blockers or sucralfate should be administered in cats with known or suspected gastrointestinal ulceration.
Unlike dogs, fasting is not recommended in cats with pancreatitis unless the patient is vomiting. Hepatic lipidosis is a common problem in these cases, and alimentary support is an integral component of treatment. Ideally, nutrition is provided enterally. This can be accomplished via a naso-esophageal tube, per-cutaneous gastrotomy tube, or a jejunostomy tube. If the patient is vomiting, total or partial parenteral nutrition is a viable alternative. Recent studies in humans have shown that maintaining normoglycemia significantly improves outcome in critically ill patients. Diabetes and DKA are not uncommon in these cases and can complicate the treatment of the cat with pancreatitis. Even in cats without a previous diagnosis of diabetes, especially patients receiving TPN, the clinician must carefully monitor for hyperglycemia and treat with insulin when appropriate.
Routine use of antibiotics in cats with pancreatitis is quite controversial. Studies in humans have failed to show beneficial effects of routine antibiotic use and have documented increased risk of infections with multi-drug resistance organisms. Based on studies such as this and the low reported incidence of infectious complications, it has been recommended that antibiotic therapy only be administered in cases once an infectious complication has been identified. In contrast, experimental work in cats has documented that bacterial flora are able to colonize an inflamed pancreas from multiple sources, including the colon. This data has resulted in some recommending routine broad-spectrum antibiotic use in cats with pancreatitis. Regardless, antibiotics should be used in all cases with documented or highly suspected infectious disease--either in the pancreas or other organ systems.
Pain can be difficult to assess in these cats, and the severity of clinical signs can sometimes result in a reluctance of clinicians to treat with pain medications. Untreated pain will lead to depression, inappetance/ anorexia, decreased mobility, and an increase in stress hormones. Analgesics such as buprenorphine (5-10 mcg/kg) or butorphanol (0.2-0.4 mg/kg) can be administered to treat abdominal pain associated with pancreatitis and potential peritonitis. Other possible options include fentanyl (continuous rate infusion, fentanyl patch) or epidural analgesia.
Plasma transfusions have been recommended in dogs to replace circulating macroglobulins that are depleted in severe pancreatitis. No studies have been done in cats to determine if plasma therapy in cats has a beneficial effect of the clinical course of pancreatitis. In cats with prolongation of coagulation times, plasma therapy should be given to normalize clotting times. Further studies to determine the effect of plasma therapy in cats with pancreatitis are needed before definitive recommendations can be made.
Cats with acute pancreatitis are dynamic cases and careful monitoring is vital to the management of these cats. This can be challenging in the feline patient due to both their small size as well as the relative lack of clinical studies evaluating monitoring devices in feline subjects. Despite these facts, there are numerous methods to monitor the critically ill cat. Indirect monitoring of blood pressure can be done via Doppler or oscillometric methods. Fluid balance can be challenging in these cats, and central venous pressure monitoring can help guide fluid therapy. Pulmonary complications are common in these cats, and pulse oximetry is a non-invasive method to assess oxygen saturation and monitor respiratory status. Routine laboratory assessment of venous blood gas measurements, PCV/total solids measurement, and lactate should be done on a regular basis to monitor for anemia, acid base abnormalities or evidence of poor perfusion. However, the frequency at which these are monitored should be determined by weighing the benefits of close monitoring against the detriment of repeated blood sampling and the possibility of iatrogenic anemia.
The prognosis for pancreatitis in the cat is directly related to the severity of pancreatic disease as well as the present of concurrent organ dysfunction. In a recent report of 46 cases of acute pancreatitis the fatality rate was 41%. Aggressive supportive care is imperative to maximize the chances for recovery in these cats.
1. Estrin MA, et al. JVIM 2006: 20(6): 1334.
2. Zoran DL. JAAHA 2006: 42(1): 1.
3. Forman MA, et al. JVIM 2004: 18(6): 807.
4. Ferreri JA, et al. JAVMA 2003: 223 (4): 469.
5. Saunders HM, et al. JAVMA 2002: 221(12): 1724.
6. Kimmel SE, et al. JAVMA 2001: 219(8): 1105.
7. Brady CA, et al. JAVMA 2000: 217(4): 531.