Memorias Curso Internacional de Medicina y Cirugía en Gatos

AMMVEPE 1968 - 2017

MEMORIAS DE LAS PONENCIAS EN EL CURSO INTERNACIONAL DE MEDICINA Y CIRUGÍA EN GATOS Abril 27 y 28 de 2017 AAPAUNAM Ciudad Universitaria Ciudad de México

Asociación Mexicana de Médicos Veterinarios Especialistas en Pequeñas Especies, S. C. www.ammvepe.com.mx

Asociación Mexicana de Médicos Veterinarios Especialistas en Pequeñas Especies, S. C. www.ammvepe.com.mx

AMMVEPE 1968 - 2017

MEMORIAS DE LAS PONENCIAS EN EL CURSO INTERNACIONAL DE MEDICINA Y CIRUGĂ?A EN GATOS Pancreatitis - Cats are not small Dogs..!

Sussan Little, DVM, DABP (Feline) Current Concepts in Treating Chronic Kidney Disease in Cats Sussan Little, DVM, DABP (Feline)

How to improve the Safety of Anesthesia for Cats Sussan Little, DVM, DABP (Feline)

Investigating Elevated Liver Enzymes in Cats Sussan Little, DVM, DABP (Feline)

Asociación Mexicana de Médicos Veterinarios Especialistas en Pequeñas Especies, S. C. www.ammvepe.com.mx

Pancreatitis – Cats are not small dogs!

Susan Little, DVM, DABVP (Feline) Bytown Cat Hospital, Ottawa, Canada catvet@vin.com Chronic pancreatitis (CP) is proving to be more common than previously thought in cats. It is often difficult to diagnose, although the situation is changing as awareness increases and understanding of the relationship with concurrent diseases improves. Histologically, pancreatitis in cats is classified into three forms: 1) acute necrotizing, 2) acute suppurative (a form unique to cats), and 3) chronic non-suppurative (the most common). In the chronic nonsuppurative form, the inflammation is mononuclear (usually lymphocytic) with disruption of pancreatic architecture due to fibrosis.

In most cases of CP, the disease is considered idiopathic. However, specific underlying causes are occasionally identified (e.g. viral infection, fluke infection, toxoplasmosis, trauma, organophosphate poisoning). There are no specific age, breed or sex predispositions for CP in cats. Unlike the canine, no association has been made with a high fat diet or obesity. The true prevalence of pancreatitis in cats is unknown.

Clinical signs of feline CP are different from those in dogs. Unfortunately, in the cat, clinical signs are vague and non-specific (e.g., lethargy, anorexia, vomiting, weight loss). Physical examination findings may include dehydration, icterus, pallor, signs of abdominal pain, and fever or hypothermia. It is probable that many cases go undiagnosed. In one necropsy study, 45% of apparently healthy cats had some histopathologic evidence of pancreatitis. Vomiting (35% of cases) and cranial abdominal pain (25% of cases) are less common in cats with CP than in dogs with acute pancreatitis. However, it must be noted that assessment of chronic pain in general and cranial abdominal pain in particular is not always easy in cats. Several concurrent diseases are found in cats with CP (inflammatory bowel disease [IBD], inflammatory liver disease, hepatic lipidosis, bile duct obstruction, diabetes mellitus, vitamin B12 deficiency, etc.), causing variable clinical signs. In particular, elevations of liver enzymes are common, thereby misleading the clinician into a diagnosis of liver disease. Interestingly, there is growing evidence that there could be a link between bacterial infection in the liver and in the pancreas. An ascending infection from the duodenum could lead to pancreatitis and cholangitis in at least some cats. Pancreatitis, IBD and cholangitis appear to co-exist in many cats, leading to the term triaditis.

Evaluation of cats suspected to have CP should include a detailed medical history, a thorough physical examination, routine laboratory testing (CBC, serum chemistry panel, urinalysis), abdominal imaging, and assessment of pancreatic function (feline trypsin-like immunoreactivity [fTLI], feline pancreatic lipase immunoreactivity [fPLI]). Although findings of routine laboratory tests are typically non-specific or even normal, these tests are used to diagnose or exclude other diseases and to help confirm the diagnosis of CP. As well, specific abnormalities requiring correction may be discovered (e.g., electrolyte imbalances). Abnormal findings on CBC include nonregenerative anemia, leukocytosis, and mild thrombocytopenia.

Changes on serum chemistries include elevated ALT and ALP, hyperbilirubinemia, hyperglycemia, azotemia, hypokalemia, and hypoalbuminemia. Hypercholesterolemia is common although the cause is unknown. There are few differentials for hypercholesterolemia

in cats, so this finding in a sick cat should raise the possibility of pancreatitis. Hypocalcemia is not common, but when present, may be a poor prognostic sign. Serum lipase and amylase concentrations are less useful in the cat than the dog. However, increased lipase along with pancreatic ultrasound abnormalities may have good positive predictive value. Serum cobalamin should be evaluated as low concentrations can be a sign of pancreatic exocrine disease (extrinsic factor is produced in the pancreas) and/or ileal disease (e.g., IBD or lymphoma).

Increases in fTLI are specific for pancreatic enzyme leakage, but the test is not sensitive for diagnosis of CP (28-40%). Elevations in fTLI may also be seen in cats with IBD or gastrointestinal lymphoma. However, over time, cats with CP may develop exocrine pancreatic insufficiency and fTLI is useful for detection of this complication. The most sensitive and specific assay for CP is fPLI. It is not affected by pre-renal azotemia. One study demonstrated that the magnitude of fPLI concentration is correlated with negative outcomes in cats with acute pancreatitis. However, the more chronic the disease, the less leakage of fPLI is expected to occur, meaning the sensitivity of the test will drop dramatically. It is most useful in cats with moderate to severe disease; cats with mild CP may not have abnormal fPLI values.

Imaging studies are best suited for diagnosis of acute pancreatitis, but even then, findings are not consistent and are subject to operator skill and interpretation. The sensitivity and specificity of radiography for diagnosis of pancreatitis is particularly low, but it is inexpensive and useful to rule out other diseases. In some cases, loss of peritoneal detail is noted in the cranial abdomen. Mild pancreatitis is difficult to diagnose with ultrasound so that a normal examination cannot exclude the diagnosis. As well, the more chronic the disease, the less likely that changes will be detected on ultrasound examination. Findings in moderate to severe cases may include abdominal effusion, hypoechogenicity of the pancreas, a hyperechoic peripancreatic mesentery (due to fat necrosis), pancreatic and biliary duct dilatation, and other pancreatic changes (e.g., enlargement, calcification, cavitation).

Definitive diagnosis of pancreatitis may be accomplished with biopsy and histopathology. It is the only way to differentiate acute from chronic disease. However, biopsy cannot be used in all cases (e.g., due to cost, risk of surgery and anesthesia in a sick patient).

Single biopsy samples may miss focal lesions, so multiple samples should be taken when possible. If biopsy of the pancreas is performed, it appears reasonable to biopsy the liver and small intestinal tract at the same time. Conversely, the pancreas should be evaluated in cats known or suspected to have IBD or cholangitis. Fortunately, the risk of post-surgical acute pancreatitis from exacerbation of underlying disease seems to be uncommon in cats.

In summary, a combination of careful evaluation of the cat’s history, serum fPLI and abdominal ultrasonography, together with pancreatic cytology or histopathology when possible, is considered to be the most practical and reliable means for an accurate diagnosis or exclusion of pancreatitis.

Treatment of cats with CP is controversial as there are no evidence-based studies available to guide therapeutic choices. Dehydration should be treated with fluid therapy (e.g., lactated Ringer’s solution or 0.9% saline) and any electrolyte imbalances (e.g., hypokalemia) should be corrected. Vomiting can be controlled with anti-emetics such as maropitant or dolasetron (see Table 1). Antibiotics are generally not indicated. Anti-inflammatory therapy with corticosteroids (prednisolone, 0.5-1.0 mg/kg, q 12-24h; higher doses if IBD is suspected or confirmed) would seem reasonable when lymphocytic inflammation is present (although this

can only be determined with biopsy). In cats with end-stage disease, inflammation is absent and fibrosis and degeneration are prominent; therefore, corticosteroid treatment would not be appropriate. CP may produce low grade or focal pain, which can be challenging to detect in cats. Clinical signs may include lethargy, hiding and inappetence. A trial treatment with an opioid such as buprenorphine or with gabapentin is reasonable. A non-steroidal antiinflammatory drug could be used if the cat is eating and is well hydrated. Periods of inappetence may be managed with appetite stimulants such as mirtazapine.

‘Resting the pancreas’ by withholding food and water has been a traditional therapeutic strategy, but benefits remain unproven. In fact, evidence in humans and dogs suggests that early nutritional support is important. Daily nutritional requirements should be calculated and the amount of food eaten should be monitored closely to ensure the cat’s nutritional needs are being met. The diet chosen should be highly digestible and palatable. There is no need to choose a low fat diet for cats with CP (as is common in affected dogs). Force-feeding should be avoided to prevent food aversion. If assisted feeding is necessary, such as in cats that have been anorectic for 2 or more d ays, esophagostomy tubes are effective and easy to place.

Recommended reading Abrams-Ogg A, Ruotsalo K, Kocmarek H, et al. Total serum lipase activity for the antemortem diagnosis of feline pancreatitis (abstract). J Vet Intern Med 2013;27:708.

Baral RM. Diseases of the exocrine pancreas. In Little S (editor). The Cat: Clinical Medicine and Management, St. Louis, 2012, Saunders, pp. 513-522.

De Cock HE, Forman MA, Farver TB, et al. Prevalence and histopathologic characteristics of pancreatitis in cats. Vet Pathol 2007;44:39-49.

Pratschke KM, Ryan J, McAlinden A, McLauchlan G. Pancreatic surgical biopsy in 24 dogs and 19 cats: postoperative complications and clinical relevance of histological findings. J Small Anim Pract 2015;56(1):60–6.

Simpson KW. Pancreatitis and triaditis in cats: causes and treatment. J Small Anim Pract 2015;56(1):40–9.

Steiner JM. Diagnosis of pancreatitis. Vet Clin North Am Small Anim Pract 2003;33:1181-1195.

Stockhaus C, Teske E, Schellenberger K, et al. Serial serum feline pancreatic lipase immunoreactivity concentrations and prognostic variables in 33 cats with pancreatitis. J Am Vet Med Assoc 2013;243:1713-1718.

Warren A, Center S, McDonough S, et al. Histopathologic features, immunophenotyping, clonality, and eubacterial fluorescence in situ hybridization in cats with lymphocytic cholangitis/cholangiohepatitis. Vet Pathol 2011;48:627-641.

Washabau RJ: Feline pancreatic disease. In Ettinger SJ, Feldman EC (editors): Textbook of Veterinary Internal Medicine, ed 7, St. Louis, 2010, Elsevier, p 1704.

Twedt DC, Armstrong, P.J., Simpson, K.W. Feline cholangitis. In Bonagura JD and Twedt DC (eds): Current Veterinary Therapy VX , St. Louis, 2014, Elsevier Saunders, pp 614-618.

Xenoulis PG, Suchodolski JS, Steiner JM. Chronic pancreatitis in dogs and cats. Comp Contin Edu Pract Vet 2008;30:166-180.

Zoran DL: Pancreatitis in cats: Diagnosis and management of a challenging disease, J Am Anim Hosp Assoc 42:1, 2006.

Table 1: Common antiemetic drugs used to treat vomiting in cats Drug Metoclopramide Dolasetron

Dosage 0.2 – 0.4 mg/kg SC, PO q 8hr 1 – 2 mg/kg/day CRI 0.5 - 1 mg/kg IV, PO q 24 hrs

Ondansetron Maropitant

0.5 mg/kg PO q 12 hrs 1 mg/kg IV, SC, PO q 24 hrs (up to 5 days)

Phenothiazines:

0.1 – 0.5 mg/kg SC q 8hr

prochlorperazine chlorpromazine Mirtazapine

1.9 – 3.75 mg/cat PO q 48 hrs Often given as ¼ of 15 mg tablet

Comments Also prokinetic Centrally acting?

5-HT3 receptor antagonists

Inhibits substance P binding to NK-1 receptors Use with caution in hepatic disease Centrally acting via multiple mechanisms May cause sedation

5-HT3 receptor antagonist Appetite stimulant Reduce dose by 30% in hepatic or renal impairment

Current Concepts in Treating Chronic Kidney Disease in Cats Susan Little, DVM, DABVP (Feline) Bytown Cat Hospital, Ottawa, Canada catvet@vin.com @catvetsusan http://drsusanlittle.net Facebook.com/DrSusanLittle

Chronic kidney disease (CKD) is the most common renal disease in the cat. The prevalence of CKD seems to be increasing over time; estimates are that it affects about one-third of all cats over 15 years of age.(1) It is an important cause of mortality, especially in older cats. CKD is typically a progressive disease and can be accompanied by a wide range of clinical and pathological changes. However, the clinical presentation is variable from patient to patient.

The International Renal Interest Society (IRIS) has published guidelines for clinical staging and treatment targets for both canine and feline kidney disease (http://www.iris-kidney.com). As well, the International Society of Feline Medicine published Consensus Guidelines on the Diagnosis and Management of Feline Chronic Kidney Disease in 2016 (http://jfm.sagepub.com/site/Guidelines/Guidelines.xhtml). The reader is referred to these documents for a complete discussion of CKD diagnosis and management.

The goals of CKD therapy are to:  Minimize clinical signs of uremia  Minimize disturbances of electrolytes, vitamins, and minerals  Provide adequate nutrition and hydration  Improve quality of life (QOL), especially in IRIS stages 3 and 4  Modify disease progression (IRIS stages 2 and 3) Wherever possible, potential therapies should be evaluated in light of a specific treatment goal and based on available evidence. In some patients, multiple treatments may be indicated, but administration of multiple therapies must be balanced with QOL; prioritizing therapies most likely to benefit each patient is important.

Key management strategies for cats with CKD include: 1) Managing hydration: Cats with CKD are predisposed to dehydration, especially in IRIS stages 3 and 4. Studies confirming the clinical impact of maintaining hydration are lacking, but it is considered a critical part of management. Maintaining hydration may help maintain QOL, address electrolyte and acid-base disturbances, and preserve renal blood flow by preventing dehydration (and potentially affecting disease progression). Unstable or decompensated cats with CKD may require hospitalization and IV fluid therapy, along with management of electrolyte and acid-base disturbances. Owners should also be educated about long term management of hydration, including increasing voluntary water intake and

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home subcutaneous fluid therapy (up to 150 mL every 1-3 days). Fluid choices include balanced electrolyte solutions or 0.45% saline. Potassium chloride can be added as needed.

Managing diet: Renal therapeutic diets are restricted in protein, phosphorus, and sodium compared to maintenance diets. They may be increased in caloric density, are alkalinizing, and have added potassium, B vitamins, antioxidants, and omega-3 fatty acids. In short, they bring many potential benefits to CKD patients. Studies have evaluated the effect of renal therapeutic diets on improving longevity and reduction of clinical signs of uremia with good quality of evidence for a beneficial effect (see Best Bets for Vets evidence-based medicine review: https://bestbetsforvets.org/bet/146).(2-6) Moderate protein restriction is recommended to avoid loss of lean body mass. Evidence that protein restriction alone slows progression of CKD is lacking; however, phosphorus restriction is thought to be the most important factor. Renal therapeutic diets should be considered for cats in IRIS stages 2-4, but the overall nutritional needs of the cat must also be considered as other disease processes may be present. A wide range of renal therapeutic diets is now available, each with different levels of protein restriction, so that diet recommendations can be tailored to the patient’s needs. Even some ‘senior’ cat diets may be appropriate for cats with early CKD, although the nutrient profile must be evaluated before making a recommendation.

Managing serum phosphorus and calcium: IRIS has established target serum phosphorus concentrations that should be reviewed. Maintaining serum phosphorus within the suggested targets may be accomplished in many cats with the use of a renal therapeutic diet. However, as disease progresses, some cats will require both a renal therapeutic diet and an oral phosphate binder. As well, some patients may be unable to eat a renal therapeutic diet and may need earlier use of oral phosphate binders. Commonly used oral phosphate binders include aluminum hydroxide and calcium carbonate. The daily dose is always split into multiple administrations given with food or at the time of eating.

Hyperphosphatemia can be associated with active vitamin D deficiency but supplementation with calcitriol is not well studied in cats. A single published study has failed to show a benefit.(7) Cats receiving calcium-containing phosphate binders should have serum ionized calcium monitored as moderate to severe hypercalcemia is a potential cause of renal injury.

Managing serum potassium: Cats with CKD can become hypokalemic through various mechanisms. Hypokalemia is associated with lethargy, poor appetite, constipation, and muscle weakness but has not specifically been associated with effects on longevity or disease progression in CKD patients. Serum potassium should be routinely monitored and supplementation implemented when the concentration is less than 3.5 mmol/L. Renal therapeutic diets are supplemented with potassium but some cats may need additional oral supplementation with potassium gluconate or citrate (starting dose 1-4 mmol [mEq]/cat every 12 hours). Some clinicians prefer to start supplementation earlier, when serum potassium is less than 4.0 mmol [mEq]/L. Managing blood pressure: Systemic hypertension can be seen in cats with CKD so routine monitoring of systolic blood pressure (SBP) is indicated. The potential for target organ (eyes, heart, cerebrovascular tissue, kidney) damage from hypertension has been well established. In addition, hypertension has been associated with proteinuria in cats (see below). Doppler and high-definition oscillometric devices are the most commonly

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recommended for cats. Measuring SBP in cats can be challenging – Guidelines for the Identification, Evaluation, and Management of Systemic Hypertension in Dogs and Cats have been published and should be consulted (http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2007.tb03005.x/pdf). Drug therapy is indicated in patients with hypertension with the goal of maintaining SBP below 150-160 mmHg. Amlodipine is currently the monotherapy drug of choice; monotherapy with ACE inhibitors or atenolol is not effective in most hypertensive cats. Telmisartan is a new drug in veterinary medicine that is showing promise as an anti-hypertensive.

Managing proteinuria: An increasing degree of proteinuria is associated with reduced longevity in cats so CKD patients should be routinely assessed for proteinuria.(8) Urine protein:creatinine ratio (UPC) is the recommended test. Drug therapy is indicated for cats that are persistently proteinuric without evidence for another cause (such as infection).

The American College of Veterinary Internal Medicine proteinuria guidelines (http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2005.tb02713.x/pdf) should be reviewed and suggest treatment when the UPC is >0.4. However, some clinicians recommend drug therapy when the UPC is >0.2 as cats with UPC <0.2 have better survival times than cats with higher values. Commonly used drugs include benazepril and telmisartan along with a renal therapeutic diet (see Best Bets for Vets review: https://bestbetsforvets.org/bet/389). Patients on drug therapy should be monitored for adverse effects (e.g., worsening azotemia, hypotension) although they are uncommon in cats.

Managing anemia: A non- or poorly regenerative anemia associated with a relative lack of erythropoietin may be seen in some cats with CKD. In addition to the impact on QOL, anemia is an independent risk factor for progression of CKD.(9-12) Treatment of anemia may therefore improve QOL and survival.(13) Darbopoietin (1 µg/kg SC weekly until PCV >25%, then 1 µg/kg SC every 2-3 weeks based on PCV) appears less likely to induce anti-red blood cell antibodies in cats than erythropoietin.(14) Therapy is started when the PCV is persistently <20% and the target for treatment is maintaining the PCV at >25%.

Concomitant iron therapy is recommended with injectable iron dextran (50 mg/cat monthly as needed). Frequent monitoring of PCV, reticulocyte count, and SBP is required, especially in the initial phase of treatment.

Managing urinary tract infections: CKD predisposes cats to urinary tract infection (UTI), especially older female cats. Many infections are subclinical although changes may be evident on urinalysis. The most common isolate is Escherichia coli. The significance of subclinical UTI is unknown, so routine monitoring of urine cultures is controversial. Cats with clinical signs of UTI and/or pyuria (>5 white blood cells/hpf) should have a urine culture performed to guide therapy. Treatment guidelines for UTI published by the International Society for Companion Animal Infectious Diseases (http://www.hindawi.com/journals/vmi/2011/263768/) should be consulted. Therapy can be started with amoxicillin (11-15 mg/kg PO every 8 hours) while results of urine culture and sensitivity are pending.

Managing clinical signs: Cats with CKD may have nausea, vomiting, and inappetance as a result of uremic toxins affecting the central chemoreceptor trigger zone. Owners identify poor appetite as an important QOL concern; it could also result in protein and calorie

malnutrition. A reduction in appetite should be actively investigated and treated; nausea should always be considered as a possible cause even if the cat is not vomiting. Maropitant (2 mg/kg PO every 24 hours) has been shown to reduce vomiting (15) and mirtazapine (1.88 mg/cat PO every 48 hours) has been shown to reduce vomiting and increase appetite and weight gain (16); these drugs are preferred over H2 blockers such as famotidine. Cats that are not responding to drug therapy may benefit from placement of an esophagostomy feeding tube to maintain hydration, administer drugs, and provide nutrition.

SUMMARY For each CKD patient, establish the IRIS stage and develop an individual treatment plan, taking into account what is most appropriate for each patient and owner. Prioritize the options based on the cat’s medical needs and the owner’s preferences and abilities. Review the plan with the owner and confirm commitment. Establish a reassessment and monitoring schedule to assess the patient’s response, make any necessary changes to the treatment plan, ensure the owner understands the treatments, and uncover compliance issues.

References 1. Reynolds BS, Lefebvre HP. Feline CKD: Pathophysiology and risk factors — what do we know? J Feline Med Surg 2013;15(1 suppl):3–14.

2. Plantinga EA, Everts H, Kastelein AM, et al. Retrospective study of the survival of cats with acquired chronic renal insufficiency offered different commercial diets. Vet Rec 2005; 157:185–187.

3. Elliott J, Rawlings JM, Markwell PJ, et al. Survival of cats with naturally occurring chronic renal failure: effect 4. of dietary management. J Small Anim Pract 2000; 41:235–242.

5. Ross SJ, osborne CA, Kirk CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc 2006; 229:949-957.

6. Harte JG, Markwell PJ, Moraillon RM, et al. Dietary management of naturally occurring chronic renal failure in cats. J Nutr 1994; 124: 2660S–2662S. 7. Hostutler RA, diBartola SP, Chew dJ, et al. Comparison of the effects of daily and intermittent dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure. J Vet Intern Med 2006; 20: 1307–1313.

8. Syme HM, Markwell PJ, Pfeiffer d, et al. Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med 2006; 20: 528–535.

9. King JN, Tasker S, Gunn-Moore DA, et al. Prognostic factors in cats with chronic kidney disease. J Vet Intern Med 2007; 21: 906–916.

10. Geddes RF, Elliott J and Syme HM. Relationship between plasma fibroblast growth factor23 concentration and survival time in cats with chronic kidney disease. J Vet Intern Med 2015; 29: 1494–1501.

11. Chakrabarti S, Syme HM and Elliott J. Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med 2012; 26:275-281.

12. Kuwahara Y, ohba Y, Kitoh K, et al. Association of laboratory data and death within one month in cats with chronic renal failure. J Small Anim Pract 2006; 47: 446–450.

13. Chalhoub S, Langston C and Eatroff A. Anemia of renal disease: what it is, what to do and what’s new. J Feline Med Surg 2011; 13: 629–640.

14. Chalhoub S, Langston CE and Farrelly J. The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases. J Vet Intern Med 2012; 26:363–369.

15. Quimby JM, Brock WT, Moses K, et al. Chronic use of maropitant for the management of vomiting and inappetence in cats with chronic kidney disease: a blinded, placebocontrolled clinical trial. J Feline Med Surg 2015; 17: 692–697.

16. Quimby JM and Lunn KF. Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: a masked placebo-controlled crossover clinical trial. Vet J 2013; 197: 651–655.

Asociación Mexicana de Médicos Veterinarios Especialistas en Pequeñas Especies, S. C. www.ammvepe.com.mx

How to Improve the Safety of Anesthesia for Cats Susan Little, DVM, DABVP (Feline) Bytown Cat Hospital, Ottawa, Canada catvet@vin.com @catvetsusan http://drsusanlittle.net Facebook.com/DrSusanLittle Veterinary medicine has no mandatory reporting or investigation of anesthetic-related adverse effects, including death. Until recently, very little data was available to evaluate the risks of anesthesia for cats. A multi-center prospective cohort study in the United Kingdom from 20022004, the Confidential Enquiry into Perioperative Small Animal Fatalities (CEPSAF), has changed that. This study recorded patient outcomes after premedication and within 48 hours of the end of the procedure, and calculated the risks of anesthetic-related death for cats (n=79,178), dogs, rabbits, and other small mammals.

Cats have a higher anesthesia-related mortality rate than dogs; in fact, healthy cats were twice as likely to die compared to healthy dogs (see Table 1). Other studies have had similar findings. ‘Healthy’ and ‘sick’ are based on the American Society of Anesthesiologists (ASA) classification system. Comparable data suggests that mortality rates for humans in developed countries is less than 0.05%.

Table 1: Mortality rates in cats and dogs from the CEPSAF study Mortality Overall Healthy (ASA 1-2) Sick (ASA 3-5)

Dogs 0.17% 0.05% 1.33%

Cats 0.24% 0.11% 1.40%

Adapted from: Brodbelt DC, Blissitt KJ, Hammond RA, et al: The risk of death: the Confidential Enquiry into Perioperative Small Animal Fatalities. Vet Anaesth Analg 35:365-373, 2008.

Most deaths, in cats as well as dogs, occur in the post-operative period. The most common causes of death in the CEPSAF study were cardiovascular or respiratory problems (57%), although the cause was unknown in 20% of feline patients. The most critical time is the first 3 hours after the end of anesthesia, when about 2/3 of all anesthetic-related deaths occur.

Patients are often transitioning from 100% oxygen to room air during this time, while they are cold and shivering, which increases oxygen demand. This is especially risky for cats with cardiac disease and those with other illnesses. It is also the time when monitoring is at the lowest level as equipment has been removed and nursing staff may be distracted with other tasks. Finally, as cats regain consciousness, they may become aware of pain if it has not been adequately prevented or treated, leading to tachycardia and hypertension. Therefore, the immediate postoperative period should be one of diligent monitoring of feline patients.

Factors associated with risk of anesthetic death in cats include overall health status, subclinical disease, body weight, age, hypothermia, intravenous fluid use, anesthetic drugs and techniques, and duration of anesthesia (see Table 2):

Overall health status: Careful attention should be paid to a preanesthetic physical examination and patient history, stabilization of the patient, selection of anesthetic techniques, plans for monitoring, and post-operative care.

Subclinical disease: Some cats deemed to be ‘healthy’ in the CEPSAF study may in fact have had subclinical disease, especially cardiac disease. Clinics should establish pre-anesthetic laboratory testing protocols for feline patients based on age and other risk factors. Preanesthetic testing can range from simple blood and urine panels in young, otherwise healthy patients to more involved testing including blood pressure assessment, radiographs, or diseasebased laboratory testing (e.g., total T4).

Subclinical cardiac disease is especially concerning. The prevalence of cardiomyopathy is about 15% in ‘apparently’ healthy cats and cardiac disease can be present in patients without cardiac murmurs or arrhythmias. The risk of hypertrophic cardiomyopathy increases with increasing age, male sex, certain breeds (e.g., Maine Coon, Ragdoll, Bengal, Persian), and presence of a heart murmur. However, good handling skills are necessary to perform adequate pre-anesthetic examinations on feline patients that are often very stressed. In one shelter study, multiple auscultations were required to detect a heart murmur in some cats. Cardiac biomarkers such as NTproBNP (Feline proBNP, IDEXX) represent an opportunity to detect occult cardiac disease and should be considered for higher risk patients and even older patients without a detectable heart murmur.

Body weight: Cats weighing less than 2 kg (4.4 lb) are at increased risk of death (15 times greater than cats weighing 2-6 kg [4.4-13.2 lb]). Reasons include the high surface area-tobody weight ratio of small cats predisposing them to hypothermia, and inaccurate calculation of drug doses if body weight is not accurately measured (instead of estimated). Obese cats are also at increased risk of death due to respiratory compromise, reduced cardiovascular reserves, and relative drug overdoses if calculations are not based on lean body weight.

Age: Cats older than 12 years are twice as likely to die compared with cats aged 6 months to 5 years, and the risk is independent of ASA status. This increased risk may be due to decreased respiratory and cardiovascular reserve, decreased ability to regulate body temperature, and age-related decrease in anesthetic drug requirements. Health screening of apparently healthy cats over 10 years of age reveals an increased prevalence of problems such as high blood pressure and kidney disease, so pre-anesthetic laboratory data will be helpful in senior cats to assess health status.

Hypothermia: Detrimental effects of hypothermia include increased intraoperative bleeding, increased risk of wound infection, increased oxygen consumption due to shivering in recovery, slower metabolism of drugs, delayed recovery, and decreased perfusion. Shivering may also contribute to increased sensation of pain in cats as it does in humans. The CEPSAF study found that temperature was monitored in only 1-2% of cats during anesthesia, and in only 11-15% of cats during recovery. Another study by Redondo and colleagues found that 97% of cats have a lower body temperature at the end of anesthesia than before. The greater the degree of hypothermia, the greater the risk of mortality (7% with severe hypothermia). Active warming techniques should be used to provide warmth either before premedication or at least at the time of premedication. In addition, chilling should be reduced by avoiding contact with cold surfaces and avoiding the use of cold surgical preparation solutions.

Intravenous fluids: The use of IV fluids increased the risk of death by a factor of 4 in both healthy and sick cats in the CEPSAF study. This is most likely due to inappropriate administration of fluid therapy. The blood volume of cats is about 60 mL/kg body weight compared to 80-90 mL/kg for dogs. Intraoperative fluids rates are often 10 mL/kg/hour and this rate is likely too high for cats. Current recommendations are a more conservative 3 mL/kg/hour as a starting rate for crystalloid fluid administration in cats. As well, infusion or syringe pumps or a Buretrol should be used to ensure accurate volume delivery. This is especially important since a percentage of cats will have undiagnosed cardiac disease and vascular overload could contribute to mortality.

Anesthetic drugs and techniques: Premedication provides sedation that makes cats easier to handle and less stressed, and it reduces the dose of induction and maintenance drugs.

Monitoring: Most of the reduction in the risk of anesthesia for humans is due to improved monitoring. In veterinary medicine, a trained nurse whose primary focus is management of the patient during anesthesia significantly reduces the odds of a complication.

In the CEPSAF study, monitoring pulse rate and quality and monitoring pulse oximetry significantly reduced mortality.

Duration of anesthesia: A duration of anesthesia greater than 90 minutes increases the risk of mortality by a factor of 3 compared with durations less than 30 minutes. Therefore, it is important to ensure that all preparations are made in advance, that all drugs and equipment are on hand, and that procedures are performed efficiently. If several different procedures require anesthesia, it may be more prudent to perform them separately to reduce anesthesia time for each event.

Table 2: Key factors related to morbidity/mortality and how to mitigate the risk Factor Solution Hypothermia Measure body temperature regularly Use passive and active warming early Fluid therapy Use syringe or fluid pump, or Buretrol for accurate measurement Duration of anesthesia Plan in advance, be efficient Airway obstruction, tracheal rupture Intubate carefully, do not overinflate the cuff Use anesthetic masks for short procedures Cardiovascular collapse, hypoxemia Monitor pulse rate and rhythm, monitor pulse oximetry A few topics require special mention. Respiratory obstruction is a more frequent postanesthetic cause of death in cats than dogs. Tracheal injury can occur during intubation if the procedure is not done correctly. Intubation should be performed under the correct plane of anesthesia, with direct visualization of the larynx, and gently with patience. Topical local anesthetics such as lidocaine are helpful if used in appropriate metered aerosol doses. The correct size and length of endotracheal tube should be used for each patient. Endotracheal tube cuffs should not be overinflated; this is a cause of tracheal tears. For short procedures, intubation may not be required and an anesthetic mask can be used instead. Postanesthetic

blindness has occurred in cats related to the use of spring-loaded mouth gags for dental procedures. This is due to cerebral ischemia caused by impaired blood flow in the maxillary artery when the mouth is held open under pressure. For this reason, spring-loaded mouth gags should not be used in cats.

References: Brodbelt DC, Pfeiffer DU, Young LE, Wood JL. Risk factors for anaesthetic-related death in cats: results from the confidential enquiry into perioperative small animal fatalities (CEPSAF). Br J Anaesth 2007;99(5):617–23.

Brodbelt D. Feline anesthetic deaths in veterinary practice. Top Companion Anim Med 2010;25(4):189– 94.

Payne JR, Brodbelt DC, Luis Fuentes V. Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study). J Vet Cardiol 2015;17(Suppl 1):S244–57.

Redondo JI, Suesta P, Gil L, et al: Retrospective study of the prevalence of postanaesthetic hypothermia in cats. Vet Rec 170:206, 2012.

Robertson S. Anesthetic-related morbidity and mortality in cats. In Little S, editor: August’s Consultations in Feline Internal Medicine, vol 7, St. Louis, 2016, Elsevier.

Investigating Elevated Liver Enzymes in Cats Susan Little, DVM, DABVP (Feline) Bytown Cat Hospital, Ottawa, Canada catvet@vin.com @catvetsusan http://drsusanlittle.net

Facebook.com/DrSusanLittle Clinicians are often presented with apparently healthy patients that have liver enzymes elevated above the reference interval on routine health screens. This raises the question â&#x20AC;&#x201C; does the patient have liver disease? In order to answer the question, some key points must be remembered. One is that the liver has a great reserve capacity and clinical signs of hepatic disease may not appear until disease is advanced. Another is that the liver is often the victim of non-hepatic disease (especially diseases of the pancreas and gastrointestinal tract, and hyperthyroidism) so the entire patient must be evaluated to detect secondary reactive hepatopathies (Box 1). Finally, due to the way that reference intervals are established (typically the central 95% of the reference group), 2.5% of the population will have values above or below the reference interval for any given test. In general, 2-fold to 3-fold increases above the upper limit of the reference interval are considered mild, 4-fold to 5-fold elevations are considered moderate, and higher elevations are considered severe. Detection of a single mildly elevated liver enzyme on routine testing of an apparently healthy animal is insufficient for the diagnosis of hepatobiliary disease.

Box 1: Common non-hepatic diseases that can elevate liver enzymes in the cat Diabetes mellitus Congestive heart failure Hyperthyroidism Severe hemolytic anemia Pancreatitis Abdominal trauma Inflammatory bowel disease Systemic infections Neoplasia The prevalence of elevated liver enzymes in both healthy and sick cats is not well described. In one study of routine health screening of 100 apparently healthy cats 6 years of age and older, 6% had elevated ALT results with most being mildly elevated.[1] Only one cat had an elevated AST result. Data on ALP or GGT was not included in the study. By contrast, in a study of 1,022 samples from both healthy and sick dogs, elevated ALT was found in 20% and elevated AST in 12% of samples.[2] The most commonly elevated liver enzymes in apparently healthy cats are the leakage enzymes, ALT and AST. Elevations are associated with damage (reversible or irreversible) to the hepatocyte membrane, allowing leakage of the enzymes from the cytoplasm. Elevations in ALT are most sensitive for inflammation, necrosis, and primary neoplasia and less sensitive for lipidosis, metastatic neoplasia, and portosystemic vascular anomalies. The half-life of ALT in cats is only 3-6 hours (compared with 2.5 days in the dog) so a return to normal values after acute insults occurs rapidly in the cat. ALT can be elevated due to in vitro hemolysis and lipemia.

AST is derived from both liver and non-hepatic sources (skeletal and cardiac muscle) so elevations are considered to be more sensitive but less specific for hepatic disease. One must bear in mind, however, that diseases of muscle are not common in cats and evaluation of serum creatine kinase will assist in discriminating the source of the AST elevation. Hemolysis can cause significant increases in AST. As for ALT, the half-life of AST is shorter in the cat (1.5 hours) than the dog (12 hours); serum AST will return to normal more rapidly than ALT. In primary liver disease, ALT and AST typically increase together, and may be accompanied by increases in ALP and/or GGT, as well as hypoalbuminemia and decreased BUN. Care must be taken in the interpretation of ALT and AST as they do not identify the disease origin and the magnitude of elevations is not a reliable indicator of disease severity. Evaluating ALT and AST every 3-5 days can be helpful in determining whether a disease process is resolving or persistent pathology exists.

ALP and GGT are hepatocyte membrane-associated enzymes and elevations are associated with cholestasis (stimulated by impaired bile flow). ALP is found in hepatocytes that line bile canaliculi and sinusoids and is also present in bone; mild elevations are common in growing animals. GGT is also present in the kidney and pancreas but increases are most commonly associated with cholestasis or biliary hyperplasia. While elevations in ALP and GGT can be induced by corticosteroids in dogs, this does not occur in cats. Phenobarbital is less likely to induce elevations in ALP in cats than in dogs, but has been reported. The half-life of ALP in the cat is only 6 hours (in contrast to 66 hours in the dog) and cats have less hepatocellular ALP than dogs so that elevations are usually considered significant in the cat. GGT may be a more sensitive indicator of hepatobiliary disease in cats as the half-life is longer than ALP. When ALP and GGT are roughly equally proportionately increased, the diagnosis is likely to be one of either pancreatitis, cholangitis, or extra-hepatic bile duct obstruction. In hepatic lipidosis, ALP is typically increased 5-10 fold while GGT is either normal or increased only 1-2 fold.

Investigation of elevated liver enzymes in the apparently healthy cat Given that so many non-hepatic diseases can cause increases in liver enzymes, it is critically important to rule in primary hepatic disease before invasive procedures such as liver biopsy are planned. A systematic investigative approach is outlined in Figure 1. The first steps when an elevated liver enzyme is encountered in an asymptomatic patient are to verify the value and to rule out spurious increases in enzyme activity due to lipemia and hemolysis.

Figure 1: Algorithm for the approach to elevated ALT/AST in apparently healthy cats (adapted from Webster CRL. Interpretation of serum transaminase levels in dogs and cats. Clinicians Brief, Nov 2005, pp 13-18). SBA = serum bile acids

A thorough physical examination and medical history are important â&#x20AC;&#x201C; is the patient truly healthy and asymptomatic? A few key points should not be overlooked in the medical history, such as history of toxin exposure and drug/supplement administration (Box 2), evaluation for hyporexia, and evidence for polyuria/polydipsia. The physical examination should include careful evaluation of the thyroid gland and assessment for jaundice, which can be subtle in the early stages.

Box 2: Some drugs associated with hepatotoxicity in cats Acetaminophen Ketoconazole Anabolic steroids Megestrol acetate Diazepam (oral) Methimazole Results of other laboratory evaluations may also be incorporated in the initial evaluation. Five tests on routine biochemistry panels can be used to assess liver function: cholesterol, bilirubin, glucose, albumin, and BUN. However, they are most likely to be affected in cats with clinical signs of hepatic disease. If no obvious explanation for the abnormal liver enzyme can be found, there are two courses of action. A more in-depth diagnostic evaluation can be undertaken, starting with serum bile acids, or the liver enzymes can be re-evaluated in 2-4 weeks.

Serum bile acids are often used to test hepatic function (in non-icteric cats). There are some caveats to the use of bile acid testing. One is that while increases are associated with hepatic insufficiency, the magnitude of increase cannot be used to assess severity of disease or the type of dysfunction. The second is that paired (12-hour fasting and 2-hour post-prandial) samples are usually recommended, but obtaining post-prandial samples in cats is difficult. Single fasting samples can sometimes give false normal results but if a single bile acid test is abnormal, it does indicate liver dysfunction. An alternative to serum bile acid evaluation is evaluation of urine bile acids with a single sample. Cats with liver disease (especially cholestatic disease) have increased urinary bile acid excretion. Urine bile acids are measured 4-8 hours post-prandial and compared in a ratio to urine creatinine. The post-prandial urine sample can be collected at home, or the cat can be fed at home and brought to the hospital for sample collection. In one study of 54 cats with hepatic disease, 17 cats with non-hepatic disease, and 8 normal cats, the results of a single post-prandial urine bile acid test were highly correlated with health status.[3] Urine bile acid:urine creatinine ratios greater than 4.4 are considered evidence of hepatic dysfunction.

Abnormal liver enzymes should not be ignored in the apparently healthy patient, but care should be taken not to convict a patient of liver disease too hastily. In fact, elevations in liver enzymes are more often associated with non-hepatic disease. A step-wise approach can be taken to investigate elevated liver enzymes in a systematic manner, reserving invasive procedures for those animals with evidence of hepatic dysfunction.

References 1. Paepe D, Verjans G, Duchateau L, et al. Routine health screening: findings in apparently healthy middle-aged and old cats. J Feline Med Surg 2013;15(1):8â&#x20AC;&#x201C;19.

2. Comazzi S, Pieralisi C, Bertazzolo W. Haematological and biochemical abnormalities in canine blood: frequency and associations in 1022 samples. J Small Anim Pract 2004;45:343-349.

3. Trainor D, Center SA, Randolph JF, et al. Urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in cats. J Vet Intern Med 2003;17(2):145â&#x20AC;&#x201C;53.

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