Pancreatitis can range from mild cases to severe cases, with some patients requiring aggressive treatment and hospitalization due to systemic complications and organ damage. Photo courtesy Dr. Andrew Linklater Pancreatitis, characterized by the abnormal release of digestive enzymes from acinar cells into pancreatic tissue, triggers a cascade of inflammatory responses leading to clinical signs, such as inappetence, abdominal pain, vomiting, diarrhea, and systemic illness, and this can be quite complex.1 Pancreatitis can present as an acute, chronic, or acute on chronic disease, and the severity of illness varies widely from one patient to the next. Those with mild or recurrent symptoms can often be treated as an outpatient, while more severe patients require hospitalization to help maintain fluid balance, and nutrition, as well as control pain. Additionally, a smaller number of patients may develop severe, systemic consequences resulting in multiple organ injuries and require aggressive medical or, rarely, surgical treatment. Pancreatitis has also been known to be associated with trauma (including surgical manipulation) and occurs concurrently with inflammatory bowel disease and cholangiohepatitis (triaditis)in cats.2 Diagnostic modalities and scoring systems Historically, histopathology was considered the “gold standard” for diagnosing pancreatitis; however, due to the cost, patient risks, invasive nature or surgery, variability in diagnosis (as pancreatitis can be focal and not represented in a small biopsy), and lack of improved outcomes from surgical intervention, histopathology is rarely used as a diagnostic tool for pancreatitis, other than postmortem examination. Diagnosis tends to rely on a combination of clinical signs, physical examinations, and diagnostic tests, which vary in sensitivity and specificity. Routine clinical pathology tests may reveal non-specific changes, such as dehydration (elevated packed cell volume/total solids), hypoproteinemia due to GI losses and the negative acute phase protein, prerenal or renal azotemia, and elevated liver enzymes due to direct hepatic injury, concurrent cholangiohepatitis, or functional biliary obstruction. The neutrophil-to-lymphocyte ratio (NLR) has gained much momentum in a wide variety of critically ill veterinary patients; it is simple to calculate and readily available. Although NLR has been shown to be elevated in patients with acute pancreatitis compared to normal animals, it has not demonstrated a significant relationship to disease severity.3 Another study demonstrated a relationship of NLR to mortality but not the length of hospitalization.4 Specific diagnostic markers, such as amylase and lipase, show variable reliability in diagnosing pancreatitis and, as such, are considered neither specific nor sensitive. Canine- and feline-specific pancreatic lipase tests (PLI), available as either a colorimetric in-house ELISA or through a reference laboratory, have improved diagnostic accuracy compared to amylase and lipase; however, sensitivities of 70-90 percent still leave room for improvement, and false-positives can occur.2 Other biomarkers, such as interleukin (IL)-6 and C-reactive protein (CRP), have been explored but are not widely utilized due to their availability and non-specific nature. Procalcitonin (PCT) has gained some momentum in human medicine to help guide the use of antibiotics and predict outcomes in human and veterinary patients with some (but not all investigated) infectious diseases. However, PCT has not been investigated in pancreatitis;5,6 there is some evidence showing elevated PCT, along with other biomarkers, may correlate with outcome in dogs with systemic inflammatory response syndrome, which is seen in some patients with pancreatitis, but evidence showing that PCT is a useful tool in veterinary patients with pancreatitis is lacking.7 Imaging techniques are critical for diagnosing pancreatitis. Radiographs are limited in sensitivity and specificity but can help rule out other conditions. Ultrasound is increasingly available, has a reasonable sensitivity for pancreatitis, and is much more specific for diagnosing pancreatitis than radiographs. Ultrasonographic changes commonly include pancreatic enlargement or thickening, echogenicity variations (hypoechogenic or mixed echogenic) with a concurrent hyperechogenic mesentery, indicating local inflammation.2 Secondary ileus, free fluid from inflammation, and biliary obstruction are also common findings. Ongoing research has demonstrated some correlation between ultrasound and PLI.8 Scoring systems based on ultrasound findings have been developed but are not universally adopted. Ultrasound-guided aspirates have a low reported complication or adverse event rate but have not been widely adopted due to clinical concern for aggravation of pancreatitis; this is most commonly performed to help rule out neoplasia or to drain pancreatic abscesses without surgical intervention. An ultrasound image of the pancreas shows it to be thickened, irregular, and hypoechogenic, surrounded by hyperechogenic mesentery. Photo courtesy Dr. Andrew Linklater. Computed tomography (CT) is very sensitive for diagnosing pancreatitis and complications thereof, such as portal vein thrombosis.9 However, CT is less available, more expensive, and requires sedation or general anesthesia. Scoring systems, such as the Canine Acute Pancreatitis Score (CAPS), help evaluate the severity of pancreatitis and predict mortality. CAPS assigns a score of 0-2 for most body systems (hepatic, hematopoietic, cardiac, etc.) The goal of this score is primarily to match case selection for the clinical publications of pancreatitis, but it may also be helpful in tracking illness severity10 and has been used as a potential predictor of mortality. The CAPS score uses a weighted sum for each abnormality (1= abnormal, 0 = normal): tachypnea x 3, coagulation disorder x 3, creatinine x 4, iCa x 3, giving a range of 0-13. In one study, a cutoff score of 6 was 100 percent sensitive and 85 percent specific for predicting mortality.10 A primer on four potential causal groups There are a variety of potential predispositions to developing pancreatitis, divided into four categories: Dietary: high-fat diet or ingestion of unusual food items Medications: azathioprine, phenobarbital, sulfonamides, and many others Endocrinopathies or hereditary diseases: hyperadrenocorticism, hypothyroidism, diabetes, SPINK-1 mutation, terrier breeds, etc. Hypertriglyceridemia and various infectious diseases: ehrlichiosis, babesiosis, toxoplasma, etc.).1 The correlation of these predispositions with pancreatitis does not necessarily imply causation, as a specific etiology is not identified for most veterinary patients diagnosed with pancreatitis. Treatment Treating pancreatitis mainly includes fluid therapy to correct hypovolemia and dehydration, analgesia, antiemetics, and early enteral nutrition;2 prokinetics and gastric acid reducers are often complementary. Managing critically ill patients has demonstrated overhydration should be avoided, so judicious use of crystalloids is recommended.11 Nutritional management for critically ill patients is essential, and enteral nutrition is generally preferred. It has been demonstrated to be well-tolerated by patients with pancreatitis, with few complications. Nutrition supplementation may be attempted with appetite stimulants, such as capromorelin or mirtazapine. However, short- or long-term feeding tubes, such as nasogastric/nasoesophageal or esophagostomy tubes, are often chosen due to their ease of placement and use, and minimal cost. Parenteral nutrition is generally avoided unless enteral options are non-viable.11 Surgical treatment of pancreatitis is rarely indicated. However, a recent study examined long-term outcomes in dogs with pancreatitis and biliary obstruction and noted an improved survival rate in dogs treated with surgery.12 Therefore, surgical intervention may benefit some patients with progressive biliary obstruction which is not improving with medical management. Three treatment options remain controversial for patients with pancreatitis: plasma, antibiotics, and steroids. Historically, plasma was recommended for supplementation of alpha-macroglobulin, a protease inhibitor. However, a retrospective study demonstrated no benefit to fresh frozen plasma administration and was negatively associated with outcome.13 Plasma may still provide some benefit in select patients with significant complications of pancreatitis, including hypoproteinemia (and need for colloid support) or coagulopathies, which can develop as a consequence of systemic inflammation. The cost of plasma may also play into the decision if it should be used or not. Antibiotics have commonly been recommended, with the argument of limiting bacterial translocation. However, multiple prospective, randomized human trials have not demonstrated a benefit, so they only considered it in select patients,2 such as those that are immunosuppressed (e.g. neutropenic [<2000/ul], perioperative antibiotics if surgery is performed or when a focal infection is identified); adhering to antibiotic stewardship guidelines is recommended. Glucocorticoids have generally been avoided as historical evidence potentially presented a correlation between their use and the development of pancreatitis. However, a recent literature review examined a wide range of causes of experimental and naturally occurring pancreatitis and concluded steroids may have a benefit on outcomes.14 Large, evidence-based trials have yet to be conducted. Although many clinicians consider anti-inflammatory doses of steroids, particularly in cats, evidence is currently lacking to support this decision. Critically ill patients, which are hospitalized for several days, may also develop critical-illness related corticosteroid insufficiency (CIRCI) and may also benefit from the use of steroids. Still, the diagnosis of CIRCI in veterinary patients has not been standardized. A new leukocyte function-associated antigen-1 (LFA-1) activation inhibitor has recently been available in the market for the treatment of acute pancreatitis in dogs, fuzapladib sodium. The company manufacturing it claims in a pilot field study that patients with acute pancreatitis had improved clinical scores.15 In an experimental study in mice, it did not improve postoperative ileus but did decrease the number of macrophages. Much more is yet to be determined about this new medication, and cost remains a significant factor.16 Conclusion In conclusion, pancreatitis is a common disease diagnosed in dogs and cats. Diagnosis is often based on symptoms, physical exam findings, laboratory tests (including a PLI) and abdominal imaging, such as ultrasound. Standard treatment includes a combination of supportive care, including anti-emetics, analgesics, fluids and nutrition; some patients may develop severe complications, and surgery is rarely indicated unless abscessation or refractory biliary obstruction are present. A novel neutrophil inhibitor may be of use, but more information is needed. The use of scoring systems, steroids, antibiotics and plasma remain controversial with little evidence to support their use. Andrew Linklater, DVM, DACVECC, grew up in Canada and moved to the U.S. to complete a rotating internship in Los Angeles before his residency at the Animal Emergency Center in Milwaukee. He became board-certified by the American College of Veterinary Emergency and Critical Care in 2009. Dr. Linklater has been the lead of the Emergency department at a multispecialty hospital for nearly 15 years in Wisconsin, mentoring more than 100 interns and residents. He has authored more than 50 peer-reviewed publications, including two veterinary textbooks, and has accomplished hundreds of lecture hours at many national and international conferences. Recently, Linklater has moved to Colorado to join Veterinary Specialists of the Rockies. In his free time, he enjoys traveling, curling, outdoor mountain activities, and spending time with his family. References Cridge H, Lim SY, Algul H, Steiner JM. New insights into the etiology, risk factors and pathogenesis of pancreatitis in dogs: Potential impacts on clinical practice. J Vet Intern Med. 2022;36:847-864. Forman MA, Steiner, J, Armstrong PJ, et al. ACVIM consensus statement on pancreatitis in cat. J Vet Intern Med. 2021;35:703723. Neumann S. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ration in dogs and cats with acute pancreatitis. Vet Clin Pathol 2021;50:45-51. Johnson MM, Gicking JC, Keys, DA. Evaluation of red blood cell distribution width, neutrophil-to-lymphocyte ration and other hematologic parameters in canine acute pancreatitis. J Vet Emerg Crit Care. 2023 Sep-Oct;33(5):587-597. Goggs R, Robbins SN, LaLonde-Paul D, Menard JM. Serial analysis of blood biomarker concentration ins dogs with pneumonia, septic peritonitis and pyometra. J Vet Intern Med. 2022 Mar;36(2):549-564. Koho N, Rajamaki MM, Viitanen SJ. Serum procalcitonin as a diagnostic biomarker in dogs with bacterial respiratory disease. Vet clin Pathol 2024 Jun;53(2):273-279. Chardorneshin JR, Khaksar E, Sharif MT, Jahandideh A. The prognostic value of procalcitonin in critically ill cases of systemic inflammatory response syndrome in dogs. Comp Clin Path. 2023;32(1):91-97. Hammes K, Kook PH. Effects of medical history and clinical factors on serum lipase activity and ultrasonographic evidence of pancreatitis: Analysis of 234 dogs. J Vet Intern Med. 2022 May;36(3):935-946. French JM, Twedt DC, Rao S, Marolf AJ. Computed tomographic angiography and ultrasonography in the diagnosis and evaluation of acute pancreatitis in dogs. J Vet Intern Med. 2019 Jan;33(1):79-88. Febres V, Dossin O, Reif C, et al. Development and validation of a novel clinical scoring system for short-term prediction of death in dogs with acute pancreatitis. J Vet Intern Med. 2019 Mar;33(2):499-507. Trikudanathan G, Yazici C, Phillips AE, Rosmark CE. Diagnosis and management of acute pancreatitis. Gastroenterology. 2024 Sep;167(4):673-688. Cleary K, Chong WL, Angles JM. Features, management and long-term outcome in dogs with pancreatitis and bile duct obstruction treated medically and surgically: 41 dogs (2015-2021). J Am Vet Med Assoc. 2023 Jul 14;261(11):1694-1701. Weatherton LK, Streeter EM. Evaluation of fresh frozen plasma administration in dogs with pancreatitis: 77 cases (1995-2005). J Vet Emerg Crit Care 2009 Dec;19(6):617-22. Bjornkaer-Neilsen K-A, Bjornvad CR. Corticosteroid treatment for acute/acute-on-chronic experimental and naturally occurring pancreatitis in several species. Acta Vet Scand 2021 Jul 13;63(1):28. doi: 10.1186/s13028-021-00592-0. Steiner JM, Lainesse C, et al. Fuzapladib in a randomized controlled multicenter masked study in dogs with presumptive acute onset pancreatitis. J Vet Intern Med. 2023. Kajo N, Iwaoka K, Nakamura S, Tsukamoto A. Fuzapladib reduces postsurgical inflammation in the intestinal muscularis externa. J Vet Med Sci. 2023 Nov 2;85(11):1151-1156.
