Building a Chronic Pain Management Pyramids for Cats Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP the Downing Center for Animal Pain Management Windsor, CO

Building a Chronic Pain Management Pyramids for Cats Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

When building the chronic pain management pyramid, begin at the beginning with a thorough examination, including a neurologic exam, soft tissue palpation, joint ROMs, and gait assessment. Perform a metabolic profile so as not to miss important co-morbidities. And don’t forget radiographs when they are indicated so as not to miss an obvious OSA and treating it as an OA. Be sure to treat the treatable - - and treat all the treatable. Make a plan and work the plan because chronic pain is best addressed from a MULTIMODAL approach. It is no longer appropriate simply to throw an NSAID at the patient. We need to break the pain cycle as quickly and effectively as possible before initiating physiotherapy and/or tissue manipulation. Multimodal management of chronic pain means multi-tasking - - think “plate spinning” or juggling. The client is an absolutely essential partner in the process, or the process is doomed to fail. There is no one right answer, but we need to set priorities (and there may be multiples) based on the needs of each individual patient. Perform your pain palpation systematically and the same way each time. Use 4kg of pressure at each palpation site, and use the fleshy part of P3 (NOT the fingertip). Begin in the paraspinals at the base of the occiput and proceed to the base of the sacrum. Palpate the paraspinals at approximately each spinal segment. Palpate the circumference of the body at the base of the neck by the hands of the clock - - 10 & 2, 9 & 3, 8 & 4. Palpate caudal to the scapulae at those same “clock” points. Palpate at the T/L junction as well. Next palpate the lateral lumbar muscles segment by segment. Then palpate the iliopsoas muscle bundle starting at the T/L and proceeding to the L/S. Squeeze the proximal quadriceps between the flat of the thumb and the lateral index finger. Perform joint ROMs from toes to torso. Once through the whole body, return to the areas exhibiting a reaction and evaluate with additional palpation and/or ROM to better identify and characterize the presence and nature of pain. Teach/drill/practice and include the entire staff. Most chronic pain patients are less active, and consequently are overweight. Dr. Denis Marcellin-Little does a great presentation articulating that the most important physiotherapy treatment for chronic pain patients is normalizing body condition. Make a long- term nutritional plan right at the beginning. If a co-morbidity exists, plan for appropriate therapeutic nutrition once weight loss is achieved. Therapeutic nutrition is best achieved with a fixed formulation and consistency of feeding. Break the pain cycle pharmacologically. NSAIDs remain one cornerstone of chronic pain management, particularly in the initial stages. They decrease inflammation and provide analgesia by acting at various locations within the nervous system. Once pain is controlled, we can (and should) titrate the dose to lowest effective dose, and that may be 0. Once removed, the NSAID can then be reserved for use as an inflammatory pain flare. Do not “mix & match” NSAIDs. Chronic pain is “maladaptive” pain (see Clifford Woolf) or “maldynic” pain (see James Giordano). Maladaptive pain demands we target the dorsal horn of the spinal cord. “Targeted therapy” is a relatively new concept in human pain management, and a REALLY new concept in veterinary medicine. Gabapentin affects α-2-δ subunit of the calcium channel in the dorsal horn of the spinal cord. It is an important gold standard for chronic, maladaptive pain management in humans, and it is emerging with a perioperative role. We need to dose appropriately at 5 – 15 mg/kg BID – TID to start. You will see drug activity within just a few days and maximal effects within 7 – 10 days. DO NOT reduce the dose too quickly or you will risk rebound pain. Begin your dose reduction following at least several months of stability. Long-term dosing is fine - - there are no liver or kidney issues to worry about. Sedation is the dose-limiting side effect. If sedation occurs, do not discontinue gabapentin - - simply reduce the dose and proceed with your plan. This drug has non-linear pharmacokinetics which makes the dose escalation very different from any other drugs we generally reach for. Evaluate the patient, calculate the dose, and begin with the BID dose given ONCE daily in PM for 3 days, then give the dose BID (e.g. 50mg PO once in PM for 3 days, then 50mg PO BID). Reassess the cat in 10 – 14 days. If it is still painful, increase the dose (e.g. 50mg PO TID). Reassess again in 10 – 14 days. If the cat is still painful, increase the dose again (e.g. 100mg PO BID). Once the cat is comfortable stick to that dose for a minimum of 4 – 6 months before beginning de-escalation of the dose, and DO NOT be in a hurry to de-escalate. I actually NAEVER do… The first dose de-escalation should come a MINIMUM of 4 - 6 months after stabilizing the cat’s pain at the lowest level. Decrease the dose, then recheck in 2 – 3 weeks to look for breakthrough pain. The next de-escalation should come in 2 – 4 months, recheck in 2 – 3 weeks for breakthrough pain, etc. Repeat the cycle on this interval. If the pain returns, simply increase the dose - - e.g. 100mg PO BID, then decrease the dose to 50mg PO TID, then decrease to 50mg PO BID, etc. Just a reminder, I NEVER decrease or eliminate gabapentin in my chronic feline pain patients. Amantadine is an NMDA receptor antagonist that complements NSAIDs and gabapentin. We only have data for dogs, but I use this drug as an adjunct in cats routinely. We use 2 – 5 mg/kg/day. It is exceptionally well tolerated long-term compounding works great.

261

Tramadol is useless and should not be used… period. Adequan® is VERY useful in cats with OA. This reflects extra-label usage. Give the injections SQ and NOT IM. Teach clients to dose this at home. Use the canine dosing for cats - - 2 mg/# SQ twice weekly for 4 weeks, then once weekly for 4 weeks, then twice monthly for long-term maintenance. Start using as soon as OA is diagnosed. Long-term use works very well. As for nutrition and nutraceuticals, follow the evidence - - HPD j/d® Feline, glucosamine/LMW chondroitin/ASU, Omega 3 FA’s, Microloactin®. Microlactin® (Duralactin® by VPL) is a milk protein concentrate from the milk of hyper-immunized cows. Hyper-immune milk factor (HIMF) inhibits inflammation in many animal models. It appears to be effective regardless of the etiology of inflammation and demonstrates no evidence of GI irritation. It works by a different mechanism than NSAIDs or corticosteroids. The first data about the anti-inflammatory activity in milk was disclosed in 1981. The novel activities illuminated from pharmacological studies on THIS molecule include the following:  Activate macrophages  Inhibit neutrophil migration  Inhibit neutrophil adhesion  Inhibit infection-induced inflammation  Inhibit arthritis  Suppress edema (rat model)  Inhibit auto-immune disease Microlactin® exhibits a very selective mechanism by blocking cytokines which contribute to the perpetuation of inflammation. It modifies the biological response to inflammation and changes the response of cytokines and neutrophils. It alters the signaling to neutrophils that “calls” them to the sites of inflammation. The neutrophils then do not release the destructive enzymes that perpetuate the inflammatory process. We see much same efficacy profile as NSAID, but the action happens by a different mechanism, so there is no NSAID adverse event profile. Microlactin® can be used safely in dogs, cats, and horses. The dose in cats (per Dr. James Gaynor) is 30 - 50 mg/kg PO BID. It takes time for maximal effects. We see initial effects within 4 – 7 days and maximal effects in 10 – 14 days. This is why Microlactin® is not well positioned for acute pain. For chronic pain, during weeks 1 – 3, overlap with the NSAID, steroid, etc. After week 3, continue Microlactin® for long-term anti-inflammatory activity. Physiotherapy/physical medicine modalities:  Heat  Cold  Therapeutic Laser  NMES  TENS  Therapeutic U/S  Tissue mobilization  Medical massage Tui Na (Chinese medical massage)  Acupuncture  Chiropractic/osteopathic manipulation  Myofascial trigger point therapy  Hydrotherapy  E-stim whirlpool  Swimming  UWT Be as specific as possible when making your pain management plan. Write everything down and have clients keep an “activities of daily living” (ADLs) diary. Conduct a medication, feeding, nutraceutical review at each visit. Once the patient is comfortable/stable, functional, and strong, you can consider removing some elements of the pain management pyramid. Change only one thing at a time. Consider at least 1 – 3 months of stability before adjusting medication doses. Begin by reducing the drug with the greatest potential to cause adverse events (generally, this is the NSAID). Titrate dose down to lowest effective dose, and you may want to consider stopping the NSAID and reserving it for acute pain episodes. Reassessments should happen at regular intervals during NSAID dose reductions - - we choose every 2 – 4 weeks. If we reduce/remove the NSAID and pain returns, we return to the next higher dose for long-term use. Next, target gabapentin reduction (see gabapentin details above). Most human patients never eliminate gabapentin, so don’t sweat this. We never remove gabapentin, Adequan®, nutritional joint support, or omega 3 FA’s.

262

Keys to success  Create as detailed and personalized a plan as possible  Write everything down  Create realistic expectations in dialogue with the client  Schedule the next reassessment +/- treatment appointment before the client leaves  Review all medications/dosing, feeding/nutrition at each visit  Track medication refills (compliance)  Relish the challenges of chronic pain  Involve the entire healthcare team These will be your most rewarding cases and your most committed clients.

Resources Veterinary Anaesthesia Support Group www.vasg.org American Academy of Pain Management www.aapainmanage.org American Society of Pain Educators www.paineducators.org AAHA/AAFP Pain Management Guidelines for Dogs & Cats 2015 Download at: www.aahanet.org ISFM & AAFP Consensus Guidelines: Long-term Use of NSAIDs in Cats Task Force Members: Andrew H Sparkes, BVetMed, PhD, DECVIM, MRCVS Reidun Heine, DVM, PhD, MRCVS B Duncan X Lascelles, BSc, BVSc, PhD, MRCVS, CertVA, DSAS(ST), DECVS, DACVS Richard Malik, DVSc, DipVetAn, MVetClinStud, PhD, FACVSc, FASM Llibertat Real Sampietro, DVM Sheilah Robertson, BVMS (Hons), PhD, CVA, DACVA, DECVAA, MRCVS Margie Scherk, DVM, DABVP (Feline Practice) Polly Taylor, MA, VetMB, PhD, DVA, MRCVS Download at: http://jfm.sagepub.com/content/12/7/521.full.pdf+html

263

CRIs for Cats: Yes You Can! Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

Examples from real life CRI fentanyl Use this drug pre-op, intra-op, and post-op. The standard concentration is 0.05 mg/ml (50 μg/ml). The pre-op bolus is drawn from the standard concentration vial. Pre-op bolus dose Dogs & cats – 0.005mg/kg (5 μg/kg) IV For intra-op and post-op CRI, create a STANDARD DILUTION in small bags of saline (0.9%), and then simply vary the flow rate according to the patient’s size and need. Intra-op dosing Dogs & cats – 20 - 40 μg/kg/hr May go as high as 60 μg/kg/hr or more depending upon the patient’s need. Remember that pure mu opiates are given to effect. Post-op dosing Dogs & cats – 2 - 4 μg/kg/hr using the same standard dilution solution Adjust the dose up if needed (we have had patients who needed 15 – 20 µg/kg/hr post-op - - remember to effect) Create a STANDARD DILUTION of fentanyl (and other drugs) for CRI use and then simply vary the flow rate as needed.  Fentanyl standard dilution: o mg/ml

Case example for fentanyl CRI  6.6# cat = 3 kg  Pre-op bolus: o 5 μg/kg X 3 kg = 15 μg o 15 μg / 50 μg/ml = 0.3 ml of standard concentration fentanyl Intra-op 20 μg/kg/hr X 3 kg = 60 μg/hr Using the standard dilution of 0.01 mg/kg, a 100ml bag contains 10 μg/ml (the bigger the patient - - dog or cat - - the bigger the bag you will need), so 60 μg/hr / 10 μg/ml = 6 ml/hr. Increase the flow rate if the cat needs more fentanyl to achieve the desired analgesic result. Post-op 2 μg/kg/hr X 3 kg = 6 μg/hr

264

We use the standard dilution, 100 ml bag which contains 10 μg/ml, so 6 μg/hr / 10 μg/ml = 0.6 ml/hr. Again, adjust the flow rate as needed.

Case example for ketamine CRI The standard concentration is 100 mg/ml. Create a STANDARD DILUTION of 0.5 mg/ml. The pre-op bolus dose is generally taken from the DILUTED ketamine.  Bolus dose: o Dogs & cats – 0.5 mg/kg  Intra-op dose: o Dogs & cats – 10 μg/kg/minute  Post-op dose: o Dogs & cats – 2 μg/kg/minute

Case example for ketamine CRI  13.2# cat = 6 kg  Use the 0.5 mg/ml STANDARD DILUTION (1 mg = 1000 μg) Pre-op bolus  0.5 mg/kg X 6 kg = 3 mg  Standard dilution bag contains 0.5 mg/ml ketamine, therefore 3mg = 6 ml bolus Intra-op  10 μg/kg/min X 6kg = 60 μg/min; 60 μg/min X 60 min/hr = 3600 μg/hr;  3600 μg/hr / 1000 μg/mg = 3.6 mg/hr;  3.6 mg/hr / 0.5 mg/ml = 7.2 ml/hr Post-op  2 μg/kg/min X 6kg = 12 μg/min; 12 μg/min X 60 min/hr = 720 μg/hr;  720 μg/hr / 1000 μg/mg = 0.72 mg/hr;  0.72 mg/hr / 0.5 mg/ml = 1.44 ml/hr  Simply adjust flow rate up or down as needed to modify dose

CRI lidocaine (dogs, NOT cats) The standard concentration is 20 mg/ml. Create a standard dilution of 4 mg/ml. There is no bolus dose, and the intra-op and post-op doses are the same:  50 μg/kg/min  This is ½ the CRI dose to control cardiac dysrhythmias We use lidocaine CRI during any abdominal procedure in dogs as it seems to be especially useful for visceral pain. Combine it with fentanyl (or morphine) CRI and ketamine CRI

Practice tips 1. Create spread sheets in Excel to lower the risk for miscalculations of flow rates 2. Use increments of 0.2# (or kg), use the standard dilutions described above, and have Excel calculate flow rates based on the appropriate intra-op and post-op dosing 3. Simply multiply flow rates to increase the delivered dose if needed

CRI standard bag dilutions Fentanyl 0.01 mg/mL 25mL Bag 25mL X (0.01mg/mL) = 0.25mg / (0.05mg/mL) = 5.0mL Remove 5.0mL of saline and replace with 5.0mL Fentanyl. 50mL Bag 50mL X (0.01mg/mL) = 0.50mg / (0.05mg/mL) = 10.0mL Remove 10.0mL of saline and replace with 10.0mL Fentanyl. 100mL Bag 100mL X (0.01mg/mL) = 1.0mg / (0.05mg/mL) = 20.0mL Remove 20.0mL of saline and replace with 20.0mL Fentanyl. 250mL Bag 250mL X (0.01mg/mL) = 2.5mg / (0.05mg/mL) = 50.0mL Remove 50.0mL of saline and replace with 50.0mL Fentanyl. 500mL Bag 500mL X (0.01mg/mL) = 5.0mg / (0.05mg/mL) = 100.0mL Remove 100.0mL of saline and replace with 100.0mL Fentanyl. 1000mL Bag 1000mL X (0.01mg/mL) = 10.0mg / (0.05mg/mL) = 200.0mL Remove 200.0mL of saline and replace with 200.0mL Fentanyl.

265

Ketamine 0.5 mg/mL 25mL Bag 25mL X (0.5mg/mL) = 12.5mg / (100mg/mL) = 0.125mL Remove 0.12mL of saline and replace with 0.12mL Ketamine. 50mL Bag 50mL X (0.5mg/mL) = 25.0mg / (100mg/mL) = 0.25mL Remove 0.25mL of saline and replace with 0.25mL Ketamine. 100mL Bag 100mL X (0.5mg/mL) = 50.0mg / (100mg/mL) = 0.50mL Remove 0.50mL of saline and replace with 0.50mL Ketamine. 250mL Bag 250mL X (0.5mg/mL) = 125mg / (100mg/mL) = 1.25mL Remove 1.25mL of saline and replace with 1.25mL Ketamine. 500mL Bag 500mL X (0.5mg/mL) = 250mg / (100mg/mL) = 2.50mL Remove 2.50mL of saline and replace with 2.50mL Ketamine. 1000mL Bag 1000mL X (0.5mg/mL) = 500mg / (100mg/mL) =5.00mL Remove 5.00mL of saline and replace with 5.00mL Ketamine. Lidocaine 4 mg/mL 25mL Bag 25mL X (4mg/mL) = 100mg / (20mg/mL) = 5.0mL Remove 5.0mL of saline and replace with 5.0mL Lidocaine. 50mL Bag 50mL X (4mg/mL) = 200mg / (20mg/mL) = 10.0mL Remove 10.0mL of saline and replace with 10.0mL Lidocaine. 100mL Bag 100mL X (4mg/mL) = 400mg / (20mg/mL) = 20.0mL Remove 20.0mL of saline and replace with 20.0mL Lidocaine. 250mL Bag 250mL X (4mg/mL) = 1000mg / (20mg/mL) = 50.0mL Remove 50.0mL of saline and replace with 50.0mL Lidocaine. 500mL Bag 500mL X (4mg/mL) = 2000mg / (20mg/mL) = 100.0mL Remove 100.0mL of saline and replace with 100.0mL Lidocaine. 1000mL Bag 1000mL X (4mg/mL) = 4000mg / (20mg/mL) = 200.0mL Remove 200.0mL of saline and replace with 200.0mL Lidocaine. Morphine 0.9 mg/mL 25mL Bag 25mL X (0.9mg/mL) = 22.5mg / (15mg/mL) = 1.5mL Remove 1.5mL of saline and replace with 1.5mL Morphine. 50mL Bag 50mL X (0.9mg/mL) = 45.0mg / (15mg/mL) = 3.0mL Remove 3.0mL of saline and replace with 3.0mL Morphine. 100mL Bag 100mL X (0.9mg/mL) = 90.0mg / (15mg/mL) = 6.0mL Remove 6.0mL of saline and replace with 6.0mL Morphine. 250mL Bag 250mL X (0.9mg/mL) = 225mg / (15mg/mL) = 15mL Remove 15mL of saline and replace with 15mL Morphine. 500mL Bag 500mL X (0.9mg/mL) = 450mg / (15mg/mL) = 30mL Remove 30mL of saline and replace with 30mL Morphine. 1000mL Bag 1000mL X (0.9mg/mL) = 900mg / (15mg/mL) =60mL Remove 60mL of saline and replace with 60mL Morphine.

266

Finding Feline Pain Where it Lives: Perfecting Your Pain Palpation Plan Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

Study after study consistently reports that more than 80% of pet owners think of their pets as children. There are more cats than dogs as pets now, and this means job security for us! Our moral imperative is to advocate on behalf of a being that cannot advocate for itself. Pain, according to the IASP definition, is an unpleasant and emotional experience associated with actual or potential tissue damage. The definition goes on to state that the inability to communicate in no way negates the possibility that an individual is experiencing pain and is in need of appropriate pain relieving treatment. Pain is a complex and multifaceted experience. There is a sensory-informational component, an emotional dimension (suffering aspect), and a cognitive-evaluative component (attention, previous experience, perceived threat to individual). In people, pain is what THE PATIENT says it is because humans can self-report. As for pain in animals, pain is what WE say it is - - we assess our patients by proxy. There is tremendous individual variability both among patients and observers. There is no one “right” answer. Nociceptive pain is transient pain in response to a noxious stimulus. Inflammatory pain is spontaneous pain and hypersensitivity to pain in response to tissue damage and inflammation. These are both considered “adaptive” pain. “Maladaptive pain”, on the other hand, is represented by neuropathic pain - - spontaneous pain and hypersensitivity to pain in association with damage to or a lesion of the nervous system - - and functional pain - - hypersensitivity to pain resulting from abnormal central processing of normal input. It was Clifford Woolf in the Annals of Internal Medicine who articulated these two overarching categories of pain. It is important to understand that pain is a spectrum and that pain can (and will) morph from adaptive to maladaptive if it is not appropriately managed. Wind-up involves sensitization of nociceptors, and peripheral and central pain pathways, in response to a barrage of afferent nociceptive impulses resulting in expanded receptive fields and an increased rate of discharge. This is what we need to try to avoid. Patient pain assessment is highly individual and variable for both the patient and for the observer. In our assessment, we must consider the reason and context for the patient’s pain. A good pain scoring system must be based on behavior, species specific, and must be influenced by the type and intensity of pain the animal is experiencing. The ideal pain scoring system would have the following characteristics:  Clearly defined assessment criteria  Suitable for all observers  Simple and quick to use  Sensitive  Useful tools for intervention  Identified strengths and weaknesses  Validated in the cat (because cats are NOT small dogs!!!)

For the record, we still do not have an ideal pain assessment system… Pain induced behavioral changes include:  Loss of normal behaviors  Lack of grooming  Decreased appetite  Decreased water intake  Lack of movement  Decreased interactive behaviors Are you dealing with an aggressive cat? Think about pain! Data suggest that @20% of cats across all ages are dealing with OA, yet 20% of cats in veterinary practices are not being treated for OA. You can’t treat what you don’t see, so we must look for pain, keep an open mind, localize it, identify the source if possible, and make a treatment plan. This pain palpation examination is adapted from the human pain arena, referenced and refereed, and is part of the training of human practitioners as the technique for identifying tender points in a diagnosis of fibromyalgia. It appears in the veterinary literature in an article titled, “Managing chronic maladaptive pain” in Clinician’s Brief, August 2011 (Downing). This is a technique we have used at The Downing Center for nearly 10 years with excellent reproducibility. Perform your pain palpation systematically and the same way each time. Use 4kg of pressure at each palpation site. Use the fleshy part of P3 (NOT the fingertip). Begin in the paraspinals at the base of the occiput and proceed to the base of the sacrum. Palpate the paraspinals at approximately each spinal segment, and don’t forget the base of the tail. Palpate the circumference at base of neck by 267

the hands of the clock - - 10 & 2, 9 & 3, 8 & 4. Palpate caudal to scapulae and at the T/L junction the same way. Next palpate the lateral lumbar muscles segment by segment, and then the iliopsoas muscle bundle starting at the T/L and proceeding to the L/S. Squeeze the proximal quadriceps between the flat of the thumb and the lateral surface of the index finger (P2 & P3). Perform joint ROM from toes to torso, and then finish with the head and face. Return to the areas generating a reaction and evaluate them with additional palpation and/or ROM to better identify and characterize the presence and the nature of the pain. Teach, drill, and practice, practice, practice and include your entire staff. It IS possible to create consistency of assessment within your practice!

Resources ISFM & AAFP Consensus Guidelines: Long-term Use of NSAIDs in Cats Task Force Members: Andrew H Sparkes, BVetMed, PhD, DECVIM, MRCVS Reidun Heine, DVM, PhD, MRCVS B Duncan X Lascelles, BSc, BVSc, PhD, MRCVS, CertVA, DSAS(ST), DECVS, DACVS Richard Malik, DVSc, DipVetAn, MVetClinStud, PhD, FACVSc, FASM Llibertat Real Sampietro, DVM Sheilah Robertson, BVMS (Hons), PhD, CVA, DACVA, DECVAA, MRCVS Margie Scherk, DVM, DABVP (Feline Practice) Polly Taylor, MA, VetMB, PhD, DVA, MRCVS Download at: http://jfm.sagepub.com/content/12/7/521.full.pdf+html AAHA/AAFP Pain Management Guidelines for Dogs & Cats Download at: www.aahanet.org

268

Non-Pharma Options for Feline Pain: Nutrition, Nutraceuticals, and Rehabilitation Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

Food/nutrition Putting together a multi-modal pain management strategy for a cat is like building a pyramid with a firm, broad foundation. Our patients need to eat something every single day, so nothing is easier than prescribing daily intake that makes a positive contribution to medical care and patient well-being. Weight loss and management are the single most important adjunctive pain management tools for chronic/maladaptive pain, and are acknowledged as the most critical physical rehabilitation techniques as well. Overweight and obesity impact joints with OA and increase the severity of OA symptoms. Weight loss alone has been demonstrated to decrease the risk of OA development, slow the progression of existing OA, and to relieve pain from OA - - excellent studies in humans, and ongoing studies in animal patients. Clinically, these ideas ARE being born out in canine and feline patients. For weight loss success we MUST follow the science to recommend the best nutrient profile for the job. Clients need to be educated that over-the-counter pet foods will NOT do the job. Clients do NOT understand that OTC diets labeled “light” are NOT significantly calorie-restricted. This means well-intentioned pet owners are seduced by marketing to believe they are doing something useful for the pet. Our obligation is to educate our clients so that they may make FACT-based decisions, not FANTASY-based decisions. At the moment, Hill’s Prescription Diet Advanced Metabolic Weight Solution provides the strongest science coupled with the strongest/best results for body condition normalization. Prescribe SPECIFIC meal size AND frequency, and DO NOT BE DECEVED BY THE “FEEDING GUIDE” PORTIONS! The portions therein are ALWAYS too high to achieve the necessary results. Prescribe a SPECIFIC snack list. Clients WILL “snack” their pets, so consider green beans, broccoli, cauliflower – fresh or frozen (NOT canned). These are Point® value “0” in the Weight Watchers® point system. Schedule no-charge weigh-in appointments with the client and pet at 3 – 4 week intervals. Make the next weigh-in appointment at each scheduled weigh-in or other assessment. Pain patients will be presented for regular pain reassessments, so their weight should be recorded at each of these visits as well. Consider interactive food toys and dishes for kibble delivery to slow down eating. Have your long-term nutritional profile in mind when embarking on this weight-loss strategy to transition once weight is normalized. Muffin tins make GREAT and CHEAP interactive food toys for cats. Remember that our genetic profile lays the foundation for our physical reality, health, wellness, and potential to develop disease. The EXPRESSION of a genetic trait is influenced by interaction between the genome and environmental factors. We now know that food/nutrition is one of the most important environmental factors that influence genomic expression. Nutrogenomics is the science of how nutrients affect health at the genomic level, and nutrients serve as dietary signals to the systems that influence gene and protein expression. Step one is to determine the genomic expression difference between healthy and diseased individuals, and step two is to identify nutrients/nutritional profiles that alter genomic expression in the diseased individuals to more closely resemble the healthy individuals. Controlled studies can confirm the anticipated outcomes. The future of nutrogenomics promises identifying genomic differences in aging and certain disease processes. Research is underway to identify which nutrients can influence genomic expression in beneficial ways. Think of these as “functional foods”. This science raises interesting questions/possibilities about our future ability to manage or even prevent disease via “functional foods”. Will drugs become obsolete? We also have a nutritional opportunity to interrupt the progression of OA. OA progression creates a cascade of events and effects: Physical stress on joint – chondrocyte damage – activates degradative enzymes – cartilage matrix damage – structural failure

269

We need to interrupt the degradation. EPA helps control joint inflammation & blocks degradative enzymes. Research demonstrates the down-regulation of the genes responsible for cartilage degradation with high levels of EPA. A low ratio of omega- 6/omega-3 FAs reduces inflammation in and around joints. A joint support nutrient profile should have several important characteristics including:  High levels of EPA  High levels of ALA (EPA precursor)  Low omega-6/omega-3  L-carnitine (maintain optimum body weight) Make a long-term nutritional plan at the beginning and articulate the plan in the medical record and to the client right away. Keep these patients on the radar to keep them on track nutritionally. Follow the science and evidence when choosing nutritional profiles for painful patients, and don’t forget to consider any and all relevant co-morbidities when choosing your nutrient profile. Some painful patients have metabolic issues that “trump” their joint disease. Should the patient have a metabolic profile that precludes using a joint- support food, you can still pay attention to joint health via nutraceuticals and a disease modifying agent (e.g. PSGAGs)

PSGAGs Adequan® remains the gold standard (NOT the equine formulation) of PSGAGs. PSGAGs are DMAOs – disease modifying agents of osteoarthritis – made from an extract of cow lung and trachea that is then sulfated. They provide the body with the building blocks of cartilage – molecules that bind to cartilage components. The exact mechanisms of action are not completely known, but PSGAGs have indirect anti-inflammatory effects. They assist the body in the repair of cartilage damaged by the consequences by OA and work best when the body is still in motion and the joints are still in use. This reflects extra-label use in cats - - 2 mg/# SQ 2 X per week for 4 weeks, weekly for 4 weeks, then twice per month indefinitely.

Omega 3 FAs There is clear evidence that high levels of EPA accomplish two important functions in the joint – decreasing inflammation in and around the joints, and down-regulating the genes responsible for the degradative enzymes that lead to cartilage damage. Flax seed oil is NOT an effective source of EPA for cats. EPA and DHA are both found in fish oil. We need to supplement EPA/DHA (both are omega-3s) at a high enough level to “bottom-load” the omega-6/omega-3 ratio to reduce inflammatory mediators. There is a wide range of canine doses quoted - - 20 – 75 mg/kg/day EPA - - I use the same dosing range for cats because we do NOT yet have the same level of high quality data for cat joints. Based on OA studies, we use 50 - 75mg/kg/day PO of EPA divided BID. Both Nordic Naturals® Omega-3 Pet oil (138 mg/ml EPA) and Nutramax® Welactin (125 mg/ml EPA) are manufactured in alignment with pharmaceutical standards. We need to be able to count on specific mgs of EPA and DHA per dosing unit (capsule or ml). Currently no capsules are available for pets with a high enough concentration of EPA/DHA to make dosing reasonable. Most cats are willing to have these liquids top-dressed on their portion-fed kibbles. The research is very compelling about the general anti-inflammatory effects of omega-3 FAs, although the human research is more advanced and broad-based than the current published studies in dogs/cats. In human arena, cardiovascular benefits, immune system support, joint health, renal disease, cancer, dermatology, allergies, cognitive function, neuropathy, and possibly diabetes mellitus. Check out www.omega-research.com Please forgive the canine emphasis of the following studies: Roush J, Dodd C, Fritsch D, et al. Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc. 2010;236(1):59-66. Conclusion: Ingestion of the test food raised blood concentrations of omega-3 fatty acids and appeared to improve the arthritic condition in pet dogs with osteoarthritis. Roush J, Cross A, Renberg W, et al. Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. J Am Vet Med Assoc. 2010;236(1):67-73. Conclusion: At least in the short term, dietary supplementation with fish oil omega-3 fatty acids resulted in an improvement in weight bearing in dogs with osteoarthritis. Fritsch DA, Allen TA, Dodd CE, et al. A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. J Am Vet Med Assoc. 2010 Mar 1;236(5):535-9. Conclusion: Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage. Budsberg SC, Bartges JW. Nutrition and osteoarthritis in dogs: does it help? Vet Clin North Am Small Anim Pract. 2006 Nov;36(6):1307-23, vii - - “…nutrition has become an integral part of (OA) management. This article focuses on the role and dietary ingredients in OA, evaluating current evidence for obesity management, omega-3 fatty acids, and chondromodulating agents…” Hansen RA, Harris MA, Pluhar GE, et al. Fish oil decreases matrix metalloproteinases in knee synovia of dogs with inflammatory joint disease. J Nutr Biochem 2008;19(2):101-8. Conclusion:

270

…results suggest that dietary fish oil may exert beneficial effects on synovial fluid matrix metalloproteinases (MMP) and tissue inhibitors of MMP-2 (TIMP-2) equilibrium in the uninjured stifle of dogs with unilateral CCL injury. The future of omega-3 FAs remains ahead, and nearly daily, new studies are published about the importance of omega-3 FAs in both wellness and preventing illness. There is more research in store for animals patients.

Microlactin Microlactin is a milk protein concentrate from the milk of hyper-immunized cows – hyper-immune milk factor (HIMF) – and inhibits inflammation in many animal models. It appears to be effective regardless of the etiology of inflammation with no evidence of GI irritation. It works by a difference mechanism than NSAIDs or corticosteroids, and the first data about the anti-inflammatory activity of milk was disclosed in 1981. Pharmacological studies have illuminated the following microlactin actions: Activate macrophages, inhibit neutrophil migration, inhibit neutrophil adhesion, inhibit infection-induced inflammation, inhibit arthritis, suppress edema (rat model), inhibit auto-immune disease Microlactin appears to have a very selective mechanism that blocks cytokines which contribute to the perpetuation of inflammation. It modifies the biological response to inflammation by changing the response of cytokines and neutrophils. It alters the signaling to neutrophils that “calls” them to the sites of inflammation. Neutrophils then do not release the destructive enzymes that perpetuate the inflammatory process. While it exhibits much the same efficacy profile as NSAIDs, it employs a different mechanism, so it does not share the NSAID AE profile. Microlactin can be used safely in dogs, cats, and horses, and the dose range in dogs and cats is 30 - 50 mg/kg PO BID. It takes time for maximal effects – initial effects are generally seen within 4 – 7 days with maximal effects at 10 – 14 days. During weeks 1 – 3, overlap it with the NSAID or steroid. After week 3, continue microlactin for long-term anti-inflammatory activity.

Glucosamine/Low molecular weight chondroitin We are still waiting for evidence of definitive benefits from glucosamine to be demonstrated in controlled, well-designed clinical trials. Low molecular weight chondroitin may have a positive effect in a percent of patients, but unfortunately, we cannot predict who will and who will not respond. In 2006, the results were published from the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) - - see the NIH website. This was the first large-scale, multicenter clinical trial in the US to test glucosamine and chondroitin sulfate for knee osteoarthritis. It evaluated glucosamine and chondroitin sulfate separately and in combination and was coordinated by the University of Utah, School of Medicine. The study was designed to test short-term (6 months) effectiveness of glucosamine and chondroitin sulfate in reducing knee OA pain in a large number of participants. Key results - - the positive control (celecoxib) provided statistically significant relief. Overall, there were no significant differences between other treatments and placebo. A subset of subjects with moderate-to-severe pain reported statistically significant relief with glucosamine combined with chondroitin sulfate compared with placebo. Researchers considered these findings preliminary and recommended confirmation through further studies. For participants with mild pain, glucosamine and chondroitin sulfate together or alone were not effective. This reflects the veterinary experience as some patients some seem to benefit, others do not. Be mindful of your recommendations. Low molecular weight chondroitin may be the key for the “responders”. Provide follow-up to modify your plan if this tool is not effective.

Avocado unsaponifiables (ASU) ASU is an extract made from avocado and soybean oils and has been shown in clinical studies to have beneficial effects on OA. In two studies over 3 months (knee & hip OA), the results revealed that patients who took ASU daily decreased their NSAID use. ASU took at least two months for improvement, but in the long-term studies there were no positive results. Are we seeing improved joint structure versus pain relief? Clearly more long-term studies are needed. ASU seems to complement effects of other ingredients. For example, ASU plus LMW chondroitin may be more effective than glucosamine and LMW chondroitin sulfate alone at decreasing the expression of several inflammatory mediators. Pro-inflammatory gene expression in chondrocytes and monocyte/macrophages is inhibited by the combination of avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate, Au RY, Au AY, Rashmir-Raven AM, Frondoza CG, Proceedings, 34th Annual Conference Veterinary Orthopedic Society 2007,57. There has been an explosion of information within past decade, yet our understanding of all these complex factors still in its infancy. The preliminary science is very exciting because it means more and more “tools” for our pain toolboxes! Be careful to make data-driven recommendations, and stay tuned!

Rehabilitation Fortunately for cats, ALL of the rehabilitation techniques that we use in dogs can (and SHOULD) be adapted for use in cats. This INCLUDES the use of hydrotherapy in the underwater treadmill. Don’t be bashful about utilizing any and all of the most commonly 271

leveraged rehabilitation techniques - - cryotherapy, moist heat, stretching, ROM, joint mobilization, hydrotherapy, therapeutic laser - - for painful cats who can benefit. Tailor your treatments to fit the cat’s needs and the cat’s preferences.

272

Pain and Fear in Felines: Linked More Often Than You Think Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

Divinum Est Opus Sedare Dolorem (Divine is the Work to Subdue Pain) -Galen Always approach feline pain from a comprehensive perspective. Begin at the beginning with a thorough examination that includes a neurologic exam, soft tissue palpation, joint ROMs, and gait assessment. Include a metabolic profile so as not to miss important co- morbidities. Treat the treatable - - and treat all the treatable. Make a plan and work the plan, and recognize that chronic pain is best addressed from a MULTIMODAL approach, and it is no longer appropriate simply to throw an NSAID at the patient. Break the pain cycle as quickly and effectively as possible before initiating physiotherapy/tissue manipulation. Multimodal management of chronic pain means multi-tasking, and the client is an absolutely essential partner in the process, or the process is doomed to fail. Creating a fear-free experience for cats is a huge part of our obligation to them!

Pre-exam medication options Buprenorphine  0.05mg/kg  Delivered by owner at home @ 1 hour before the visit  Be sure to explain HOW to deliver it into the cheek pouch  It will NOT mask chronic cat pain! Gabapentin  100mg PO @ 1 – 2 hours pre-exam  It will NOT mask chronic cat pain! Some cats do best with BOTH gabapentin AND buprenorphine. Acepromazine (1mg/ml) – 0.01mg/kg + hydromorphone (2mg/ml) – 0.05mg/kg - - same syringe & delivered SQ Deliver as cat arrives, wait 20 minutes, will NOT mask chronic pain! So, what is the relationship among pain, stress, and distress? While animals do not anticipate or fear their own DEATH, they most certainly DO anticipate and fear PAIN, rightly attempting to avoid pain whenever possible. The pain cats may choose to avoid may include the fowllowing:  IBD  OA  Periodontal disease Pain, anxiety, stress, and distress can become a self-perpetuating cycle.

Let me share some cases Coco Chanel  Ragdoll, FS, 5kg, 10 yrs  Reclusive, impossible to pet, non-interactive with other cats  Never seen when company came to the house  Veterinary visits under general anaesthesia  Biopsy confirmed IBD  Liquid, projectile diarrhea  Occasional vomiting  Easily angered Sybil  DMH, FS, 3.2kg, 15 yrs  Chronic herpes  HATED car travel  Poop, pee, and puke in the carrier with every veterinary visit Ganache  Siamese cross, MC, 6kg, 5 yrs  Should weigh 5kg  Aggressive with other cats in household

273

 Anxious/aggressive at veterinary visits Flower  At rescue:  DSH, FS, 7.3 kg (16# !!!), 9 yr  Could not be touched  Attacked visitors to home  Mats over 80% of body  Excoriated perianal/perivulval areas  Now:  3.4 kg (7.9#) (Hills Metabolic Advanced Wt Sol®)  Gregarious, interactive, playful Rooney  DMH, MC, 2.8kg  CRD  OA – lowback, L/S, SI joints  21½ YEARS OLD!  Pain, Anxiety, & Fear (oh my!) With unacceptable behaviors (“bad actors”), ALWAYS think about pain FIRST! Remember that anxiety exacerbates pain, and pain exacerbates anxiety. Look at the WHOLE patient. Ask LOTS of questions and LISTEN carefully to clients for clues. Ask for pictures and videos. Adequate resources are paramount, but comfort is critical. It is not enough to offer one or two fear-free techniques. Reducing fear may require reducing pain.

274

Palliative Care and Hospice Care for Cats Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

Palliative care and hospice for pets is a relatively young discipline in veterinary medicine. The very first guidelines for end-of-life care were just created in late 2015. The foundational principles have been extracted from human hospice and palliative care. There are critical differences between human and pet hospice and palliative care - - specifically, the option/obligation for humane euthanasia for our animal companions. Humane euthanasia should NEVER be withheld from a dying companion animal who deserves it. Palliative care, hospice, end of life care, and death (either via euthanasia or death without intervention) is a spectrum, and it may take hours to complete the arc from beginning to end. It may actually take weeks to months to complete the journey to death. Human “hospices” were originally charitable places for travelers to find rest and shelter, most commonly travelers heading to shrines and holy places. Hospice for the terminally ill emerged during the 11th century and was overseen by religious orders (most commonly nuns/sisters). The focus really shifted to the dying in the 19th century thanks to Dame Cicely Saunders, an activist nurse who founded the St. Christopher’s Hospice in south London. Now, more than 100 countries offer hospice care to their citizens. Hospice is supportive care in final phases of terminal disease. Hospice recognizes that death is a part of life and it avoids aggressive interventions. The prime directives of hospice and palliative care are pain management, comfort care, and quality of life. Hospice is a philosophy of caring and NOT necessarily a place. Hospice can be delivered anywhere. Palliative care is considered an aspect of hospice care. Recently there has been a greater emphasis in human medicine on palliative care. Hospice in pets was first formally discussed and articulated in the 1980’s by Dr. Eric Clough. Dr. Alice Villalobos, who created the QoL Scale for pets, calls this “pawspice”. There has been a development of multiple formal pet hospice programs and facilities since 2000. Hospice for pets is NOT a substitute for humane euthanasia. A so-called “natural” death is often an agonizing and painful struggle. Ongoing QoL evaluation INVOLVING A VETERINARIAN is a fundamental key to the successful delivery of hospice, palliative, and end-of-life to care for cats. Much planning, forethought, and honest communication is needed. The overarching pet hospice priorities include:  Provide the dying cat with most reasonable and acceptable QoL as end of life approaches  Support and sustain the family-cat relationship until the very end  Remain in relationship with the family throughout and beyond the cat’s death Life-limiting disease brings us to the end-of-life. The concept of “hospice” kicks in as life draws to a close. Before the actual end- of-life, it is “palliative care” that we consider. To palliate means to focus on and mitigate the symptoms of disease without intention to cure the particular condition. Technically, many different diseases are “palliated” rather than cured:  Diabetes mellitus  Diabetes insipidus  CRD  CHD/CHF  Addison’s Disease  Cushing’s Disease  Systemic cancers As soon as life-limiting disease is diagnosed, it is time to open the dialogue about the arc on the way to the end of life, addressing prognosis, treatment options, and the potential adverse events associated with various treatment and management options. Most cats will experience multiple morbidities as they age, so the key to high-quality palliative care and end of life experience is achieving balance among various conditions. Be sure to diagnose ALL of the relevant conditions, set priorities among them, and create a management plan that addresses all the issues. It is important to target synergy among the chosen treatment modalities. Pain management is always the number one priority, and the goal is neither to hasten death nor prolong the dying process. Recognize and respect the significance of quality, meaningful time between the cat and the family. Honor the cat’s will to live (and respect when that will is no longer present). Advanced treatment options are now commonplace which is generally a boon for older cats, but is certainly a complication for cat owners. Delivery of cat hospice (and palliative care) is as individual as the family involved, and there is no one “right” answer. It begs the question, “Is there a difference among palliative care, hospice care, and end-of-life care?” Not really… Think of this as a continuum of care, and the care options will change over time. Patient needs will escalate over time, and the best palliative care is flexible at its core. When we apply palliative care techniques, we need to create a personalized plan for the patient that is based on current illnesses, considers any and all co-morbidities, is based on anticipated symptom progression and emergence, and considers client circumstances and resources.

275

Arrange for 24 hour care for these families. What will happen if there is an after-hours emergency? Create a document for the client that explains the palliative care/hospice focus. We want to avoid unnecessarily heroic interventions. Articulate, outline, and prioritize treatment and management options. It is critical to provide alternatives and options whenever possible and practical. The dying process is disempowering to the family, so providing choices is VERY empowering. Discuss all appropriate management and treatment options independent of finances and allow the client the freedom to choose what they can afford. Consider the cat’s willingness to cooperate with oral medication and provide alternatives whenever they are needed (e.g. injectable meds vs. oral). Anticipate and minimize medication side effects whenever possible. Pay attention to nutrition. E-tubes are NOT heroic measures for most patients who need them! E-tubes make nutritional support and medication easy by providing easy access to the GI tract. Help the client modify the home environment appropriately. This means careful questioning and careful listening to the answers. Create non-skid floor surfaces - - area rugs are often more trouble than they are worth. Interlocking foam floor squares may be more effective. Modify access to stairs, modify access to slick floors, provide mobility devices, and maintain access to family activities. In the home environment, provide easy access to water and food. Use low-sided litter pans or potty pads sprinkled with litter. “Stay-dry” bedding/fabric, orthopedic or memory foam, and temperature regulation are all important considerations. Allow the cat to choose favorite locations, including both indoor as well as outdoor “hang-outs”. The cat should be contained at night or when no one is home. This is all about keeping the cat safe. Provide demonstration of various techniques - - video or in person, and with the actual patient whenever possible. Match the team member to the client, and supplement written information with pictures whenever possible. Have the client repeat the technique in front of a veterinary team member. If needed, have medications compounded for ease of delivery. Do your homework! Some medications cannot be compounded (e.g. amlodipine). Provide a list of medications, how they are supplied, how they are given, the frequency, and how medications should be stored. Provide a list of potential side effects for each medication. Use “pill minders” when possible. Create for clients a medication checklist to prevent medication errors. Perform a medication review at every single visit. End-of-life care does not end at the “end of life”. Emotional support for the client/family is critical, and emotional support must BEGIN at the diagnosis of life-limiting disease. We need to recognize and address the grief of remaining pets. Be able to recognize need for referral to a grief/bereavement specialist. Palliative care is not about giving up nor is it care of “last resort”. It is a kinder, gentler, modified approach to standard care. Be mindful of palliative care techniques that have the potential to undermine the HAB. It may be appropriate to consider having veterinary team members make house-calls for some treatments. For cats who resent or resist travel to the veterinary practice, consider home visits by trained staff. Also, veterinarians can evaluate some of these patients by way of video streaming, Skype, etc. You may want to consider partnership with a local housecall veterinarian. A key to success is consistency of ongoing care coordination. Therapeutic nutrition means using food as medicine. Nutrition may prolong and improve the quality of day-to-day life. Positive nitrogen balance enhances medication efficacy. Most of the time it is better to eat something than nothing. Some palliation is more aggressive in the short-term - - e.g. tumor-reduction surgery, palliative radiation, placement of feeding tube, short hospitalizations to re-stabilize. Short-term interventions can lead to very long-term benefits. Prepare for the worst, and expect the best. Some palliative care/hospice patients will only live a short time after their life-limiting diagnosis. Other cats may actually “graduate” from hospice. Be knowledgeable and enthusiastic about alternatives to death whenever appropriate. Help the client to make fact-based decisions rather than fear-based decisions. Help clients to make guilt-free decisions about care as well as about the timing of euthanasia.

Resource Veterinary Clinics of North America: Small Animal Practice Palliative Medicine and Hospice Care May 2011, Volume 41, Number 3

276

Pharma and Feline Pain: Making the Best Choices Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

Our Moral Imperative: To advocate on behalf of a being that cannot advocate for itself...

Acute pain Acute pain may be planned (surgery) or unplanned (trauma), varies in severity (which dictates the intensity of our pain management strategy), may ALSO involve dealing with chronic/maladaptive pain, and we MUST recognize that a multi-modal approach provides us the opportunity to create a rational plan based on specific tissue targets. Surgery patients These patients provide the greatest opportunity for us to make a difference, and we now know that the best pain management strategy begins BEFORE the surgical insult. This decreases the need for induction agents, inhalant agents, and post-op pain medications. This provides greater comfort for the patient, sets the stage for optimal healing, and using targeted therapy means making rational choices about the areas of the nervous system we need to address and how to get there. We need to prevent the unrelenting afferent barrage of nociceptive signals which leads to peripheral and central sensitization, and “windup”. General anaesthesia ONLY causes unconsciousness and does NOTHING to move us toward the goal of analgesia. Without proper intervention (e.g. pre-emptive analgesia), the pain experience upon awakening, will be WORSE than before becoming unconsciousness. Preventing windup Local anesthetics prevent windup by blocking pain signals completely. In addition, opioids obtund windup and N-methyl-D-aspartic acid (NMDA) receptor antagonists block central sensitization e.g. ketamine as a CRI Pre-op Combining a sedative and opioid (hydromorphone & acepromazine) potentiates the effects of the opioid (but ace is NOT analgesic - - this is VERY important!). Consider carefully the use of anticholinergics (we use ONLY PRN). Keep your feline patient warm! Butorphanol has NO PLACE in a perioperative protocol!  Pre-med, the analgesic effects are GONE just in time for the first stroke of the scalpel  Diminishes effectiveness of any subsequent delivery of pure mu opiate  Expensive (by comparison) to “real” analgesics  Still in use due to complacency Immediately pre-op: Position your patient to have an optimal surgical experience, with minimal pain and optimal healing, so at induction, take 5 – 10 minutes to help your patient by pre-oxygenating @ 4 – 6 L/min via mask while you are placing the catheter & then during induction. Create a SMOOTH induction with propofol + midazolam. It is PAST time to retire ketamine/valium! It creates a ghastly experience for cats! Last step pre-op - - local anaesthesia Place your local anaesthetic BEFORE the surgery begins! Infusing local anaesthesia AFTER a surgery/after an incision is made, is precisely like locking the barn door after the horse is gone. Depending upon the nature of the procedure, the local may be best administered via epidural, intra-articular injection, specific nerve block, etc.

Continuous rate infusion (CRI) This is “continuous” rather than “constant”, and in fact, it changes with the patient’s needs as well. It is an extremely effective way to manage pain intra- and post-op. CRI dramatically reduces the inhalant concentration needed for maintenance. CRI is really the only place for ketamine any longer (not for induction) Intra-op Inhalant anaesthesia DOES NOT provide analgesia. Our pre-meds need a long enough duration to cover our surgery time, but for longer procedures, consider an epidural and/or CRI. Good surgical techniques assist with pain management by minimizing the trauma to tissues. Whatever you do, don’t forget to keep your patient warm! Post-op Continue CRI’s if they are in place, and titrate the dose over time as the cat recovers and regains strength. Do not stop CRIs abruptly. Begin your NSAID at this time if appropriate for the patient. There is NO compelling evidence to support giving the NSAID BEFORE the surgical event. Regularly assess patients and revise the pain plan accordingly. Opioids post-op can be pulse-dosed for patients who do not need or receive CRIs. Until now – regular injectable buprenorphine was used IV or TM, and the doses quoted in the literature are:  0.03mg/kg – 0.05mg/kg 277

The dosing interval depends in large measure upon level of pain, and this formulation requires a fairly frequent dosing interval. Simbadol® (Zoetis) is really a game-changer. It is an excellent complement to an NSAID.  Dose: o 0.24mg/kg SQ ONCE daily for 24 hours of pain relief o Can administer the first dose 1 hour pre-op (label) o We deliver it at the end of our procedures o For use once daily for up to 3 days  Be careful - - o Do not get it on your mucous membranes o Do not use in moribund cats o Be careful in cats with hepatic disease o If cats are sensitive to buprenorphine or other opioids, they may be sensitive to Simabol®  Do NOT dispense for client administration at home  Give the patient the benefit of the doubt when assessing for pain.  Pain is easier to prevent than to reverse.  An NSAID paired with an opioid better than an NSAID alone.  The therapeutic & side-effects of opioids are dose-dependent.  Don’t be afraid to let the patient sleep post-op provided they have stable vital signs.  Reduce any potential adverse side effects by choosing drugs and doses to meet the patient’s needs.  Transition to oral meds for going home.

NSAIDs  Choose according to the best fit for the patient  Determine how long the patient will benefit from their use  If using meloxicam in cats be sure to PRECISION dose  There is NOT compelling evidence to demonstrate that NSAID should be given BEFORE the anaesthetic event.  NSAIDS can increase the risk of complications.

Tramadol NO SAFETY OR EFFICACY DATA IN CATS! Do not use this drug!

Gabapentin This molecule affects α-2-δ ligand of the calcium channel in the dorsal horn of the spinal cord, and post-op can help prevent central sensitization. It decreases consumption of morphine and improves functional recovery in humans with total knee arthroplasty (Pain Res Manage 2009;14(3):217- 222). Compared with placebo, perioperative administration of gabapentin produced significantly better postoperative analgesia (Reg Anesth Pain Med 2006;31:237-247). Sedation is the dose-limiting side effect - - non-linear pharmacokinetics. So far there is only one post-operative study about gabapentin in veterinary medicine (canine amputees), and the drug failure was predictable due to the very low and the very short time it was used… opioids will also fail if the dose is too small. Clinically, in “big pain” cases, gabapentin improves outcomes in pain scores and function – both short and mid-term. The dose range is quite wide - - 5 – 20 mg/kg PO BID – TID. There will be effects within 24 hours – consistent effects within 3 – 5 days – post-op for 14 – 21 days. Remember to use physical medicine options to enhance pain management post-op. You can use these techniques immediately post-op as well as at home when appropriate. Don’t forget general nursing care - - keep the patient warm, turn regularly, keep bladder empty, keep clean of soiling. Use cryotherapy over the surgery site to decrease pain & swelling. Build your “pain management pyramid” based on several factors:  The anticipated pain resulting from the procedure  Routine castration < routine OHE or cryptorchid castration < toe amputation < large tumor removal < total ear ablation < limb amputation or other orthopedic procedure  Give the patient the benefit of the doubt  Layer your modalities to meet the patient’s needs both immediately post-op and as recovery proceeds

Resources Veterinary Anaesthesia Support Group www.vasg.org 278

American Academy of Pain Management www.aapainmanage.org American Society of Pain Educators www.paineducators.org Resource AAHA/AAFP Pain Management Guidelines for Dogs & Cats - 2015 Download at: www.catvets.com

279

They Don’t Deserve to Hurt: The Fundamentals of Feline Pain Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

When considering pain sensation, we MUST remember that all pain is not created equal!!! Nociception is where it all begins. The reception, conduction, and central nervous system processing of nerve signals is generated by the stimulation of nociceptors. This is the first step in the physiological process that leads to the perception of pain. We are taught to consider “types” of pain.

Transient/physiologic pain This is pain that is elicited by activation of nociceptive transducers in the absence of any tissue damage. Transient/physiologic pain plays a protective role, occurs on a daily basis, and does not require medical attention. It actually protects us and preserves us. It [plays an important evolutionary role.

Acute pain This is pain that is elicited by substantial injury and includes surgery, trauma, chemical insult, radiation. This is the normal, predicted physiological response to an adverse chemical, thermal or mechanical stimulus, and is the initiation phase of an extensive, persistent nociceptive and behavioral cascade triggered by tissue injury. If either unmitigated or UNDER=managed, it can set the stage for a perpetual state of self-sustaining pain. This is pain that demands our careful attention.

Chronic pain This is pain that persists for longer than the expected time frame for healing or pain associated with progressive, non-malignant disease. We have been taught to consider it to be a distinct category of pain.

Finally, we consider maladaptive pain This is pathologic pain - - pain that has exceeded its protective usefulness. It can be an overwhelming experience and is often associated with tissue injury incurred at the time of a surgery or injury that is either untreated or UNDER-treated. The results can include hyperalgesia and allodynia. Another type of specific pathologic pain can occur in the cancer patient, and may be the result of a primary tumor, metastatic disease, or the toxic effects of chemotherapy and radiation. It is time to consider the fact that pain is a spectrum from adaptive to maladaptive pain - - “good” pain vs “bad” pain - - pain that helps the patient survive vs pain as disease. (Clifford J Woolf, Annals Intern Med 2004) Maladaptive pain includes neuropathic pain (spontaneous pain and hypersensitivity to pain in association with damage to or a lesion of the nervous system) and functional pain (hypersensitivity to pain resulting from abnormal central processing of normal input). Maladaptive pain is associated with “wind-up”, the sensitization of nociceptors, and peripheral and central pain pathways, in response to a barrage of afferent nociceptive impulses resulting in expanded receptive fields and an increased rate of discharge. Patient pain assessment is highly individual/variable both for the patient and for the observer. We must consider the reason and context for the patient’s pain. AND, of course we must remember that cats are NOT small dogs! One important way to make pain a priority in your practice, educate your team, educate your clients, become members of the IVAPM. The next step is to pursue pain management certification as a Certified Veterinary Pain Practitioner.

280

Building and Charging for a Pain Treatment Pyramid for Cats Robin Downing, DVM, DAAPM, DACVSMR, CVPP, CCRP The Downing Center for Animal Pain Management Windsor, CO

Karen Felsted, DVM, MS, CVPM, CPA PantheraT Veterinary Management Consulting Dallas, TX

For pain in animals, pain is what WE (humans) say it is. There is tremendous individual variability among both patients and observers. There is not one “right” answer. Pain is complex and scientifically intriguing, clinically challenging, and easy to overlook (especially in cats). To improve the treatment of feline pain, we MUST make changes - - never an easy task. The fundamentals of acute pain management mean understanding that treating pain is good medicine, that providing peri-operative analgesia means before, during, and after the surgery, and that multi-modal analgesia is the strategy of choice. We need to update our previous training about different “types” of pain - - acute vs. chronic, cancer pain, acute on chronic, etc. We now understand that pain is a spectrum that transitions and transforms from “adaptive” pain to “maladaptive” pain. If we deal with pain aggressively early on, we prevent the transformation to maladaptive pain. Maladaptive pain gives us more targets to treat. Wind-up involves the sensitization of nociceptors, and peripheral and central pain pathways, in response to a barrage of afferent nociceptive impulses resulting in expanded receptive fields and an increased rate of discharge. While general anaesthesia causes unconsciousness, thus preventing the cortical experience of pain, it does not prevent wind-up. Without proper intervention (e.g. pre- emptive analgesia), the pain experience upon recovery from anaesthesia will be worse upon awakening. Local anesthetics prevent windup by blocking pain signals. Opioids obtund windup. N-methyl-D-aspartic acid (NMDA) receptor antagonists block central sensitization (e.g. ketamine CRI). Part of the therapeutic approach means to minimize tissue damage when possible. The pharmacological approach means blending medications:  Opioids  (+/-)Alpha-2 agonists  Local anaesthetics  NSAIDs  Ketamine (CRI)  Sedation (acepromazine is NOT analgesic) Other strategies include good nursing care, interaction with care-givers, ice packs, supportive bandages, lubricating eyes, emptying the bladder, removing dried blood and soap, providing plastic sheets with absorbent liners, supporting head and limbs, turning regularly. Complementary techniques may also help (acupuncture, therapeutic laser, etc.). Keep your patient warm before during and after the procedure, provide an IV fluid bolus before surgery, provide IV fluids during every anaesthetic event, and pre-oxygenation before beginning. Multimodal therapy utilizes multiple actions on the CNS to prevent and treat pain. Sedatives and opioid analgesics are the most common combination of drugs used prior to general anaesthesia.  Acepromazine as a pre-med: o Excellent tranquilizer o NO analgesic effects o Potentiates opioid effects (synergistic) in the pre-med o Use very low doses o Cats – 0.01 mg/kg SQ o Dilute to 1 mg/ml solution  Benzodiazepines (e.g. diazepam, midazolam): o Few cardiopulmonary effects o Not a good anxiolytic when used alone o Can cause paradoxical excitement (diazepam) o We use midazolam for INDUCTION, and NOT as part of the pre-op protocol o Induction dose – 0.25 mg/kg IV (BOTH dogs & cats)  α2-agonists (e.g. dexmedetomidine): o Dose-dependent sedation, cardiopulmonary depression, and analgesia o Pick your patients carefully!!!  Opioids: o μ-agonists: morphine, hydromorphone, fentanyl 281

o Cornerstone of perioperative pain management o Given to effect o Possible bradycardia, respiratory depression, nausea, but ONLY when the need for pain relief is exceeded by the dose o Good for moderate to severe pain Morphine is not as effective an analgesic for cats as dogs, so it will not be discussed here.  Hydromorphone: o Moderate to severe pain o Similar in action and duration to morphine w/ no histamine release o Less vomiting than morphine in non-painful patients o Duration 4 hr IV, IM, SQ o Possibly better efficacy in cats than morphine, but hyperthermia at analgesic doses in many cats o Pre-op with low-dose (1mg/ml) acepromazine: . 0.05 mg/kg SQ o Post-op: . 0.05 mg/kg SQ or IV  Fentanyl: o Moderate to severe pain (similar to morphine) o Rapid onset (minutes), VERY short duration (minutes) o IV, IM, SQ, epidurally (transdermal – no good) o Best as IV CRI for balanced anesthesia or for unremitting pain o Loading dose, then infusion o Pre-op bolus: . 5 µg/kg o Intra-op CRI: . 20 µg/kg/hr o Post-op CRI: . 2 – 10 µg/kg/hr  Buprenorphine: o Partial μ-agonist, mild to moderate pain, drowsiness (little sedation), duration 6 to 12hr Post-op: . 0.03-0.05 mg/kg o NOT absorbed via SQ o Use IV or TM (can use IM if needed) o NOW we have Simbadol® from Zoetic (1.8mg/ml) . VERY DIFFERENT dosing than conventional, human formulation, buprenorphine . This formulation MUST NOT be sent home with clients!!!  Butorphanol: o Mixed μ-agonist/antagonist with a ceiling effect and an EXTREMELY short duration (@20 min analgesia) o Attenuates the efficacy of subsequently administered μ-agonists (long blockage of μ-receptors) to PREVENT effective analgesia o NOT AN EFFECTIVE ANALGESIC! o ONLY good for smoothing out dexmedetomidine  Ketamine: o NMDA receptor antagonist o No longer has a place for anaesthesia induction . Dissociative (induction) dose merely creates dissociation, no long-lasting pain relief . Rough to sleep, rough to consciousness o Best in CRI application for balanced anaesthesia (prevents wind-up) o Can also use as CRI to “ramp-down”/”break cycle” of chronic pain o Pre-op bolus: . 0.5 mg/kg o Intra-op CRI: . 10 µg/kg/minute o Post-op CRI: 282

. 2 µg/kg/minute  Creating the acute pain plan/general anaesthesia: o Pre-med (Hydro+ace, no anticholinergic) + EMLA o Pre-oxygenation during induction o Induction (propofol + midazolam) followed by loco-regional blocks o Inhalant maintenance o +/- adjuncts (CRI)  Post-op pain management: o Opioid o Hydromorphone (careful about feline hyperthermia) o Buprenorphine . IV or TM . Mild – moderate pain . Don’t forget Simbadol® o NSAID (if appropriate for the patient) o +/- Adjuncts - - CRI, cryotherapy, therapeutic laser o Other consideration: . Gabapentin  Gabapentin: o Neuromodulator at the α-2-δ ligand of Ca channel in dorsal horn of spinal cord o Alters calcium permeability & raises firing threshold o Like resetting a pain thermostat o Standard for chronic maladaptive pain – new in perioperative setting – in C-section & knee arthroplasty, decreased need for opioid (human studies) o No good studies yet in dogs or cats – anecdotally, great results o Some good response within 24 – 48 hrs, max effects within o 5 – 7 days o 5 – 15mg/kg PO BID for 10 – 14 days, q 24hr for 7 – 10 days, then discontinue

Pain summary  LOOK for pain and you will find it  Remember the risk factors (age, breed, size, history of injury, etc.)  Learn how to “ask” your patients if they hurt  Learn how to respond when they say “yes”

Resources Veterinary Anaesthesia Support Group www.vasg.org American Academy of Pain Management www.aapainmanage.org American Society of Pain Educators www.paineducators.org

283

Respectful Handling vs. Rude Wrangling Margie Scherk DVM, DABVP Cats Only Veterinary Clinic Vancouver, Canada

While the number of cats kept as companions in North American homes is increasing, the number of feline visits to clinics has been declining since 2001. Based on the AVMA’s 2007 pet ownership and demographics survey, there are 13% more cats than dogs, yet cats fail to receive the same degree of veterinary attention. In small-animal practices, dogs represented 59% of office visits, cats only 39%. The 2011 Bayer Brakke study further noted three client-driven factors that limited the number of feline visits. 1. Inadequate understanding of the need for regular preventive health visits other than for vaccination. 2. Resistance to bringing a cat to the clinic because of the distress caused by placing a cat into a carrier and making the trip to the clinic. 3. The cost of veterinary care, in particular the frequency and size of price increases. (The economy is a separate, external factor.) In November 2012, an online survey of 401 veterinary practice owners was conducted across the USA. The Bayer Veterinary Care Usage Study III: Feline Findings noted that 78% of veterinarians believed that better care for cats represented one of the most significant, missed opportunities for the profession. Yet, while 70% of veterinarians were familiar with the earlier Bayer-Brakke studies, and while most veterinarians recognize that cat owners consider a clinic visit to be stressful for themselves and their cats, nearly one-third of practices do not have staff trained on how to make visits less stressful for clients. Additionally, relatively few practices have adopted procedures such as: exam rooms used only for cats (35%); cat-only waiting areas that are physically and visually separated from dogs (18%); and cat- only days and appointment hours (11%) The study found that 46% of veterinary clinics surveyed had recently started taking specific steps to increase visits among current feline patients, attract more cat-owning clients, and make their practices more "cat friendly. Part of the lack of awareness (at best) or reluctance (at worst) for making simple, inexpensive changes in attitude and facility is that many veterinarians and veterinary staff members prefer, or feel more comfortable, working with dogs than cats. Veterinarians also indicated that dogs are easier to diagnose. The goal of this presentation is to look at practical steps to overcome these obstacles to routine veterinary care for cats in order to benefit cats and their human companions with resulting benefit of clinic growth.

Improving client compliance The verb “to comply” means to act in accordance with a wish or command (Oxford), to conform, submit, or adapt (as to a regulation or to another's wishes) as required or requested (Miriam-Webster). For clients to comply with our recommendations, they have to fully understand and be able to perform desired actions. We need to engage them in the importance of these actions. Thus, understanding (education) and on-going caring communication are needed to enhance client compliance. Many clients believe that cats are self-sufficient, have very few needs, and are low maintenance pets. They don’t understand that cats live as solitary hunters because they eat small prey; this means that they lack the supportive resources of a society. To avoid showing weakness, they hide signs of illness very well. The first opportunity we have to improve compliance is to teach people to recognize the subtle signs of sickness. Everyone on the veterinary team also has to recognize that any admission of illness by a cat may signal a problem that has been going on for a longer time than one believes. The following clinical signs are things that clients can be taught to look for through newsletters, the clinic website, Facebook and other social media as well as direct client emails. Subtle signs of sickness (http://www.haveweseenyourcatlately.com/Health_and_Wellness.html) Clients need to know what to look for and how significant minor changes such as the following can be: 1. Inappropriate Elimination: Regardless of how “deliberate” it may seem to be, when a cat is avoiding or not using the litter box, they are trying to tell you something. This message may be of physical discomfort or psychological distress. Physical causes include inflammation of the bladder or bowel, arthritis, hyperthyroidism, diabetes, dementia. Psychological distress may be from social disturbance, boredom, the lack of opportunity to act the repertoire of cat behaviours, anxiety due to other animals, children or adults. 2. Changes in Interaction: Changes in how a cat interacts with people, other animals or his/her environment may indicate pain or distress. 3. Changes in Activity: A decrease in energy may be abrupt or gradual. The latter is often attributed to “just getting older”, however, as there is no medical reason that a healthy individual should “slow down” due to increasing age, a cause should be sought. Dehydration, pain from anything, including arthritis, hypokalemia ate some of the problems that should be evaluated. The reverse is also true: an increase in energy in a previously normal cat may be an indicator of incipient illness, most notably, hyperthyroidism or hypertension.

284

4. Changes in Sleeping Habits: This refers both to pattern of sleeping (times of the day and night) as well as postures. A cat with pain or with dementia may either sleep for longer or for shorter periods than previously. With FIV infection, the latter may occur. Night-time yowling suggests a decline in vision or hearing, hypertension, hyperthyroidism, pain or dementia. 5. Changes in Food and Water Consumption: As with sleep, this refers not just to quantity, but also to changes in behaviours associated with these activities (where, how often, amount at each instance, body posture, etc.). 6. Unexplained Weight Loss or Gain: As gratifying as it is to see rapid weight loss in a previously obese patient, even for those on appropriate dietary regimes, it isn’t often a dramatic change. Oral pain may result in inappetence. Gradual weight loss may be related to ageing but should be monitored and investigated. Weight gain is most often from excess calories but could also be due to abdominal or thoracic fluid accumulation. Helpful tools include repeated body weight, body condition score and percentage weight change assessments. 7. Changes in Grooming: Excessive grooming may be due to a skin irritation (allergy, fleas, dryness), a neuropathy, or psychogenic (as a way to release endorphins and reduce stress). A decrease in grooming is often associated with pain, often arthritic or oro-dental. Hairballs may be a sign of dermatologic, psychogenic, altered digestive motility or pain. 8. Signs of Stress: Along with aforementioned inappropriate elimination and overgrooming, signs of distress include hiding, chewing on non-food items, a flicking tail, ear placement further back than normal. 9. Changes in Vocalization: Night-time yowling is but one example. Others include a change in tone, pitch, urgency and frequency of vocalizing. 10. Bad Breath: Numerous oral and dental conditions result in halatosis: periodontal disease is extremely common in cats but infected ulcers, tumours, sialoadenitis, abscesses and spread through grooming of odour from anal sacs or an infected body region. Yet, even recognizing that their cat has a problem may not be enough to get the client to bring them in to the veterinarian. Screening to proactively identify disease early and to provide solid medicine can be an even harder sell because people do not like bringing their cats in to the clinic. Many cat owners would rather provide care at home or even skip any form of consultation unless there is something serious going on! This offers us the second significant opportunity to improve the lives of our patients and be of help to our clients. Getting cats to your clinic It is no fun taking a cat to a veterinary clinic (for the owner or the cat)! All veterinary team members should be trained in teaching clients how to make the trip less stressful, starting at home, while in transit, and once they arrive at the clinic. This conversation begins when the client calls to make an appointment or at the first visit with their cat. The American Association of Feline Practitioners (AAFP) has a free downloadable client handout entitled: Getting Your Cat to the Veterinarian (catvets.com/uploads/PDF/2011FelineFriendlyClientHandout.pdf). Clicker training can be used to help create positive associations. Catalyst Council (www.catalystcouncil.org) has created excellent videos that clinic teams and clients can watch to facilitate learning. The frightening experience begins at home. Imagine the scenario from the cat’s point of view: The carrier comes out, your caregiver is nervous, she chases you around and tries to force you into the carrier. You resist and may resort to self-defense. There are smells of human sweat, fear, maybe even blood. You may feel so anxious that you soil yourself! Eventually you are in the carrier. Everyone is exhausted. Then you are moved into a “car” that moves without you moving. You may be a bit nauseated; certainly you are scared. You cry out repeatedly. You may vomit or soil yourself. Then the “car” stops and you get carried on a noisy and unfamiliar street and into a place with overwhelming smells and sounds! Help! And you are already aroused and anxious….look out! We can reduce the stressors the cat encounters, or, in the case of a new cat, prevent the stressors from occurring by teaching or habituating the cat to associate positive experiences with the carrier, the car, and even the clinic. By leaving the carrier out (or using a Hide Perch Go box/carrier) so that the cat sees it routinely and enters it for treats or other rewards, we dampen the initial tension and fight. Taking the cat on short car rides that are unassociated with the clinic helps recondition the cat’s negative associations with the clinic. Finally, taking the kitty to the clinic to be fussed over or only to get a treat will help teach the cat that the clinic isn’t necessarily a horrible place. Taking the household cat inventory While there are a lot of cats who never get taken to the vet, there are a lot of cats living with existing clients we never see. We don’t even know that they exist! If the cat is well or if the client has had a really bad experience in the past with a cat (or anticipates “bad behavior” from a cat), they are unlikely to voluntarily bring them in for preventive care. We need to ask whether they have any cats or any other pets when they bring their dog or cat in for whatever reason will help to identify the un-served patients.

285

Improving the clinic experience From the client’s point of view: It wasn’t fun to bring her, she isn’t happy about being in the clinic and it isn’t fun watching her be “manhandled”. Once at the clinic, with fear and stress already in place, minimizing or eliminating any further perceptions of threats is extremely important. This requires trying to see the clinic from the point of view of a cat.

Improving a cat’s clinic experiences In many clinics, some veterinarians and other team members do not enjoy working with cats because they may feel anxious about getting hurt. This fear can be reduced by understanding why cats feel that they need to defend themselves, learning to identify the cues, managing the interactions in a positive manner, and making relatively minor changes to what the cat is exposed to. The basis for working cooperatively with cats is being empathic to their nature and behaviors and trying to imagine what their experience is like. Cats are a species with a social structure unlike ours. We need to look at cats differently and adjust our interactions as well as the physical facility to reduce the strangeness and threats that cats experience in the veterinary clinic. Making the environment more “feline friendly” can be as simple as having visual barriers in the seating/waiting area to prevent cats from seeing dogs. Covering the carriers with a towel will also help so that cats don’t see each other. If possible, have separate cat-only waiting area. Reserve at least one examination room only for cats to reduce the smells of predators and to be able to furnish it with cat exam and comfort in mind. Train all staff in respectful cat handling. An excellent and comprehensive resource is the AAFP and International Society of Feline Medicine (ISFM)’s Feline Friendly Handling Guidelines, downloadable at: www.isfm.net/wellcat/UK/FFHG.pdf. It is well worth reviewing and refining cat examination techniques with the goal of making them less threatening. Because value is “perceived worth” and because every visit is a valuable opportunity to educate the client, communicate with the client and the cat throughout the entire procedure. Source and provide feline friendly medications, being sure to follow up one or more times with the client to find out how the patient is doing and if the client needs a refresher course on how to administer the medications. Be sure to send home an exam report with home care instructions for the client to refer to. Schedule recheck appointments or the next wellness visit before the client leaves the practice. The AAFP has created the Cat Friendly Practice program through which any interested clinic can raise its cat care IQ. (catfriendlypractice.catvets.com)

Why cats respond the way they do Relying on the “fight or flight” response, cats attempt to escape situations they view as dangerous. From the perspective of a cat, humans are, (and what we do is), dangerous. As a result, we see frightened and defensive cats every day. Cats try to avoid physical confrontation through the use of intimidating sounds and posture. This small creature feels more threatened than we do, so we need to refrain from becoming frightened ourselves. Ideally, they would like to flee. When they can’t they fight (self-defense) or freeze. Reading and understanding the cues and signals that cats use is important to reducing their fear. It also allows us to respond respectfully. We can learn to avoid using signals that are hostile (e.g., scruffing, making shushing/hissing sounds, looking into their faces). In the wild, the number of feral cats living together depends on the availability of resources: food, water, privacy and safety, latrine availability, and sexual partners. This results in little competition and a social structure that does not require sharing or taking turns. Stress is minimal unless there is a lack of resources. Aggressive communication signals developed in order to keep distance between individuals and prevent contact with outsiders. Physical injury is to be avoided as a cat must be able to hunt and protect herself. If there are enough resources, the natural grouping consists of a colony of related female cats with their young, who they jointly defend and nurse. Males are relegated to the periphery and vie for the prime breeding spot, only one mature tom usually living with the group.

Feline signaling: Reading their cues Tactile sense Touch is very important to cats. They rub against each other (allorubbing), against us, and against inanimate objects. Whether full body rub or a flank, tail, cheek or other body part, this is believed to be an affiliative behavior and is seen between members of the same social group, feline or human. Rubbing is not only tactile, but is also a means of depositing scent. Cats often rub against us; unfortunately, we often misinterpret it as a request to be fed. Allogrooming (mutual grooming) may precede a playful attack, follow a stressful interaction, and appear to be conciliatory or may simply be grooming. Kneading and treading occurs in adults either as a kitten-regressive behavior or as a component of sexual interaction. The neck bite/scruffing is a signal that is used in three contexts: transportation young kittens, sexual, and dominating another cat in a fight. Our use of scruffing fits most closely with the last and probably does not belong in a conciliatory, respectful cooperative setting. (See AAFP and ISFM feline-friendly handling guidelines.)

286

Olfactory cues The role of smell and scent in feline communication is something we human beings are ill-equipped to appreciate. It has been estimated that the size of the olfactory epithelium in cats can be up to 20 cm2, whereas people have only 2 to 4 cm2 of olfactory epithelium. While olfactory signals may be left by several methods, the one that is most problematic for people is urine spraying. This is a potent communication method that we fail to appreciate. Other forms of olfactory messaging are cheek marking an object or individual, scratching to leave scent from glands below the footpads, and midden, (i.e., leaving a deposit of feces uncovered in a strategic place). All of these have several advantages over visual cues. The message exists over time and in the absence of the sender, allowing for remote communication without the potential for conflict that direct interaction risks. This is especially useful in areas with poor visibility and at night. In this way, these signals help cats spread out over space as well as time-share territory. The disadvantage of this form of communication is that the sender cannot change the message once it has been deposited; it cannot be altered or removed and no adjustments can be made in response to the recipient’s reaction. So, urine marking in the home is an attempt to signal to the other cats when “I was ‘here’” and to establish a routine so that the cats can keep a distance by time-sharing the same space without needing to come into conflict. Every time we remove the urine, we interfere with this communication! Because of our less developed olfactory sense, we fail to “read” the cues a patient may be giving us and are unable to fathom the overwhelming olfactory messages from previous patients and substances used in the hospital that the clinic experience must present to cats. Visual cues: Body language (posture, face, tail) Body language and facial expression are extremely effective at maintaining or increasing distance between hostile individuals. This requires an unobstructed view, adequate ambient light, and, unlike olfactory cues, that the two individuals are in the same space together. Body posture gives the big picture of emotional state (see Figure 1), but facial expression (eyes, ears, whiskers, mouth, visibility of teeth) provides the finer details and changes more rapidly. In a clinic setting, for us to appreciate the mental/emotional state of an individual, to avoid provoking them and getting hurt, it is extremely important to watch and interpret facial changes. As a species that generally leads a solitary existence, survival depends on speed, stealth, self-reliance, and outsmarting others. As a consequence, cats may “bluff,” When they act aggressively, they are generally hiding fear; “stoicism” hides vulnerability; subtle changes in behavior mask significant illness. Body postures communicate confidence and physical prowess that may not be present. Keeping a threat at a distance may eliminate the need for a physical confrontation. The arched back “Halloween cat” typifies this façade of confidence. Making oneself smaller, on the other hand, to minimize threat and evade attention is portrayed by a crouch and withdrawal. In these postures, the weight remains on all four paws so that flight or chase remains possible. A cat feeling less fearful does not need to be on his or her feet. However, an extremely fearful threatened cat will roll exposing his or her abdomen with all four feet ready for self-defense. This cat will also be showing all of its weapons (nails and teeth) and be screaming. Cats have extremely mobile ears. (See Figure 2.) When the ears are forward, a cat is listening and is generally relaxed or alert but not emotionally aroused. Turned laterally, flat “airplane ears” indicate that the cat is more fearful or feels threatened. When ears are back and tight to the head, the cat is feeling very threatened and frightened. This cat will have a partially or fully open mouth and be hissing, spitting, yowling, or screaming. The cat will protect itself if we fail to reduce the perceived threat level. Ears turned back but erect indicates the most reactive and aggressive state. In this case, the mouth will be closed and the cat will be emitting a low growl with or without swallowing. This is the cat to be apprehensive of. Vocalization This form of communication requires that the recipient is present; it has the benefit of being easy to adjust from moment to moment. As with other signals, cats have a well-developed repertoire of sounds to convey a need or wish to increase the distance between individuals. The sounds made for encouraging socialization are a trill/chirrup, purr, puffing, prusten, chatter, miaow, and sexual calling. The cat that is open-mouth screaming is highly aroused but is probably less aggressive than the cat that is close-mouthed growl/wah-wah/mowling. Cats use a combination of these different signals in any situation. We have to learn to look for all of them and interpret them together.

From a cat’s point of view Reducing threats in your clinic We need to reduce exposure to predators (dogs, people, other cats) and other perceived threats. Looking over our clinic/hospital environment, what can we do to reduce the stress and threat level of the physical and social environment? What things or events assault the five senses of a cat? How can we make positive changes to these? Table 1 shows a chart that can be completed by the clinic team. Handling (examination, hospitalization, diagnostics, and treatments) The goal is to handle our patients respectfully and provide an appeasing environment to build positive, long-term relationships. This is achieved by reducing threat and, thus, the cat’s need to react defensively. Avoid doing things in a way that use threatening feline body language or tone. The aggressive cat is upright, stiff-legged, large; sit down to examine him. 287

Never stare a frightened cat in the eyes: examine cats from behind and, other than for ophthalmic evaluation, avoid direct facial viewing. Look at the cat’s face using a sideways glance with hooded eyelids. A slow blink is a reassuring signal to a cat similar to a human smile. The aggressive cat growls and uses low tones; use light, upper register tones, perhaps chirruping as cats do when they are relaxed with conspecifics. Shushing a cat to try to calm her as we might a child is the equivalent to hissing at her. Short repetitive sounds should be avoided, since these may resemble spitting rhythms. Purrs, chuffing, trills, and chirrups are welcoming sounds. When cats feel secure and safe, even just able to hide their faces in an elbow or a towel, they allow most procedures. Try to keep all four of their paws on the floor and avoid changing their body position as much as possible. A comprehensive examination, blood and urine collection, body temperature and blood pressure evaluation can all be done without changing the cat’s position. Examine her in the base of her own carrier if the lid can be removed. Don’t hang a cat’s forelimbs over the edge of a table for jugular venipuncture. For the frightened individual, additional lack of support under the paws is not reassuring. Reaching into a kennel to pick up a patient blocks the light; to the cat you appear as a looming frightening stranger. Instead approach the opening of a kennel from the side so that some light still enters. Do not block every chance for escape; if the possibility to have some control over her environment and situation exists, she will be much more cooperative. Because cats rely on flight and fight for survival and are not reliant on others, when it comes to restraint, the mantra holds true: Less is more! Cats inherently resist intimate handling and restraint. By restraining them, we take away their sense of control and cause them to react. It is very easy to condition negative emotional responses. Scruffing is strongly discouraged as it is an act of dominance that cats may resent. Cat bags, masks, and gloves all carry the scents of similarly terrified patients plus other sundry smells (anal gland secretion, pus, blood, halitosis, etc.) A towel is all that is needed to wrap a cat in, in order to protect the handler. Remember, a cat would rather flee than attack. Similarly, stretching is an inappropriate and unnecessary way to apply restraint. Meeting environmental needs improves health Recently, it has been recognized that emotional well-being is highly dependent on meeting the environmental needs of cats. These include those relating to the indoor and outdoor physical environment, as well as a cat’s social interactions, human and otherwise. In the AAFP and ISFM Feline Environmental Needs Guidelines, five pillars are described that form the basis of a healthy feline environment (Ellis, 2013). These pillars are: 1. A safe space 2. Multiple and separated resource stations (food, water, toileting areas, scratching areas, play areas, resting and sleeping areas) 3. Opportunity for play and expression of predatory behaviors 4. Positive, consistent and predictable interactions with humans 5. An environment that respects the importance of a cat’s sense of smell When these are not met, cats become stressed to varying degrees. Some may express illness (such as inflammatory bowel disease, lower urinary tract inflammation), while others will manifest their distress through inappropriate elimination.

Other considerations As cats age, they tolerate less time in the clinic. Siamese cats are especially prone to becoming depressed. Three days is about as long as a cat can stand the indignities and anxieties of hospitalization, even with daily visits from the owner. Consider capping intravenous catheters and send patients home, having them return for outpatient care. Even for in-hospital care, capping catheters off overnight avoids alarms, which can keep patients awake, and allows greater ease of movement. In either case, administer the overnight fluid volume subcutaneously. Because cats “see” the world in overlapping clouds of smells, we should strive to provide familiar smells and reduce foreign, medicinal smells. Client-worn shirts or toys from home are helpful in cages. Feline facial pheromone can help to reduce stress. Because cats’ sense of hearing is tuned more finely than ours, a quiet and reassuring environment is desirable. Cats should not be exposed to the sounds of predators, namely barking dogs. Reducing noises should be addressed when using certain induction agents as some enhance hearing (e.g., ketamine). Avoid changing a cat’s diet during hospitalization as is likely to result in inappetence and possibly the development of an aversion. If a change in diet is required for therapeutic reasons, try to make that change gradually at home. Taking a thorough history is especially important given cats’ tendency to hide illness. Listening carefully to clients and their concerns is extremely important. Often clients detect changes that represent real problems. This is probably more common than the client who is blissfully unaware of significant health problems. By asking open-ended questions, we elicit a more detailed history than using only specific questions. For example, asking, “Have you noticed any changes in the contents of the litter box?” will probably evoke a yes or no answer. Asking something like, “What does his stool look like? Initially, followed by: Would you describe it as hard pellets, moist logs, cowpie, or colored water? When did you first notice this?” will probably provide more useful answers. “Is there anything else?” is a very valuable question.

288

Schedule a recheck appointment to evaluate the effect of any medical or nutritional therapy. Reassessing important variables (e.g., body weight, body condition score, previously abnormal laboratory results) and updating the patient history allows us to provide better care for our feline patients. Care of the client is essential to providing complete patient care. It is only through listening to, educating, and working with the client that we are able to offer the very best veterinary care. Examples of practical applications 1. If a cat is uncooperative, a comprehensive physical examination can usually be done using a towel as a protective barrier. Facing the cat away from you is less threatening for her. Confining the cat between your legs as you sit on the floor provides adequate persistent firm restraint that is reassuring rather than frightening. 2. Swaddling a cat’s forelimbs and torso may help with blood and urine collection, placing the cat in lateral recumbency for cystocentesis and making the medial saphenous vein. This vein is also a superb choice for catheter placement and administration of intravenous medications. If the cat is allowed to have her front end in a sternal position while the back end is in lateral recumbency, she may struggle less. 3. Allow the client to be with the kitty as much as, and whenever, possible. 4. Recognize that a persistently elevated systolic value above 170 or 180 mm Hg probably represents true hypertension rather than the stress response. If in doubt, repeat the value later during the visit. 5. Feliway™ (Ceva Animal Health), a synthetic analog of a feline facial pheromone, generally has a calming effect on cats. Spray (or wipe) it into kennels and carriers and even on your clothing before handling an anxious cat. Let the substance evaporate for a few minutes before placing the cat into the sprayed space. Feliway diffusers plugged into treatment and hospitalization areas as well as reception and consultation rooms can help patients relax. (www.feliway.com) 6. Elevated blood glucose and glucosuria may be a result of persistent stress. A diagnosis of diabetes, therefore, should be confirmed by finding an elevated serum fructosamine.

Facilitating finances The Bayer study showed that clients want costs spread out over time. Fear of large bills is another significant factor preventing owners from bringing their cats to the clinic. Many practices have wellness plans. Additionally, directing clients toward pet health insurance for both preventive and accident/illness coverage before their cats need it is sound medical advice. This could save lives otherwise lost because the owner hesitated to seek care or decided to euthanize the pet because of financial concerns.

Facilitating compliance at home Having a library of YouTube links or making your own clinic “how-to” videos is extremely helpful. YouTube videos made by lay people may have the advantage of being more convincing rather than those by healthcare professionals. Find ones that your staff and you as well as a client think are best. There are many good links. Examples of useful illustrative clips to have on hand include how to:  Give your cat a pill (see below)  Give subcutaneous fluids: www.youtube.com/watch?v=OLOVw35w4Ns  Administer insulin: http://www.youtube.com/watch?v=XeZgKLfIJn4  Measure blood glucose: www.veterinarypartner.com/Content.plx?A=605  Use an inhaler for asthma medications: www.youtube.com/watch?v=INF1W8uaPEA  Feeding with a feeding tube: contact me at [email protected]  Change a KittyKollar (video) and Living with an E-tube (handout): www.kittykollar.com Syringe feeding, brushing teeth, etc are also available. Cat caregivers like to show their skills and help others. Similarly, having a selection of web resources that you have vetted and feel comfortable with guides clients to reading materials when they want to learn more about their companion’s medical condition. Cornell University has a series of videos on a number of procedures and diseases at www.partnersah.vet.cornell.edu. They include: Brushing your cat’s teeth, Giving your cat a pill or capsule, Giving your cat Liquid Medication, Taking your Cat’s Temperature, Trimming your Cat’s Nails. Other free videos include: Caring for your Diabetic Cat, Gastrointestinal Diseases in Cats, Cat Owner’s Guide to Kidney Disease, Managing Destructive Scratching Behaviour in Cats and A Pet Owner’s Guide to Cancer. Everything on the icatcare website has been created by the ISFM and is excellent: http://icatcare.org/advice/general-care. They have an extensive library of handouts on medical conditions as well as general cat care, including several videos. Feline Chronic Kidney Disease: www.felinecrf.org Feline Diabetes: www.felinediabetes.com, www.petdiabetes.com, and one with humour: http://sugarcats.com. Summary By not seeing cats because we don’t know they live with clients or because clients are unwilling to bring them in, we lose the opportunity to:  Provide wellness care, 289

 Detect disease early when we can prevent or alleviate suffering and save expense.  Protect life and enhance welfare.  Build trust with our clients,  Increase clinic visits.

TABLE 1. Chart for evaluating a clinic’s perceived threats to cats Sense Threat Reduce threat by Smell

Hearing

Sight

Taste

Touch

Recommended reading Buffington CAT. Cat Mastery – e book from iTunes AVMA. US pet ownership and demographics sourcebook. Schaumburg, Ill: AVMA, 2007. Volk JO, Felsted KE, Thomas JG, et al. Executive summary of the Bayer veterinary care usage study. J Am Vet Med Assoc 2011;238:1275–1282. Volk JO, Felsted KE, Thomas JG, et al. Executive summary of phase 2 of the Bayer veterinary care usage study. J Am Vet Med Assoc 2011;239(10):1311-1316. The domestic cat: The biology of its behaviour. 2nd ed. Turner DC, Bateson P (eds.). Cambridge, U.K.: Cambridge University Press, 2000. Crowell-Davis SL, Curtis TM, Knowles RJ. Social organization in the cat: a modern understanding. J Feline Med Surg 2004:6:19–28. Hide Perch Go and Cat Sense: www.spca.bc.ca/welfare/professional-resources/catsense/ Gourkow N, Fraser D. The effect of housing and handling practices on the welfare, behaviour and selection of domestic cats (Felis sylvestris catus) by adopters in an animal shelter. Anim Welfare 2006;15:371-377. Rodan I, Sundahl E, Carney H, et al. AAFP and ISFM feline-friendly handling guidelines. J Feline Med Surg 2011;13:364-375. Ellis SL, Rodan I, Carney H, et al. AAFP and ISFM Feline Environmental Needs Guidelines J Feline Med Surg 2013 15: 219-230

Figure 1. Interpreting a cat’s body posture.

Figure 2. Interpreting a cat’s ear position and facial expression.

290

The Complicated Geriatric Cat: Scores of Disorders Margie Scherk DVM, DABVP Cats Only Veterinary Clinic Vancouver, Canada

Elderly cats often present with multiple concurrent conditions. "Age-associated” or “age-appropriate” illnesses that we expect to see in older cats include problems related to the urinary tract (chronic kidney disease (CKD), pyelonephritis, calcium oxalate ureteronephroliths, bacterial cystitis), endocrine system (hyperthyroidism, diabetes mellitus, hyperaldosteronemia), degenerative joint disease (DJD) and other musculoskeletal conditions, dental diseases and neoplasia. Constipation may become an ongoing concern. Certain infectious diseases become more likely in the older individual (e.g., FIP). A decline in functioning of the special senses occurs frequently and behaviour changes suggestive of cognitive dysfunction may be seen in some individuals. Making management recommendations may be challenging as treatments, at first glance, may appear to be in conflict. Thankfully, the body is complex and all systems relate to one another. The four most important therapeutic considerations that must be incorporated in caring for every patient, especially those who are older, are optimizing comfort through analgesia, hydration, nutrition and ensuring that the environmental needs are met so they can perform normal behaviours.

Managing a cat with stage 2-3 chronic kidney disease, hyperthyroidism, hypertension and degenerative joint disease Renal disease is fairly common in untreated hyperthyroid cats. It may be masked due to increased cardiac output, renal blood flow and glomerular filtration rate (GFR). The effects of muscle wasting exacerbate the lower Cr concentrations. Monitoring renal parameters and muscle condition during therapy is advised. Similarly, hypertension may become evident only during the course of therapy or even after the patient is euthyroid. It is well recognized that amelioration of the hyperthyroid state by any method (i.e., medical therapy, 131I treatment or surgery) can result in decreased GFR, elevations in serum urea nitrogen and creatinine (Cr), and, in some cases, overt azotemia. The decline in GFR stabilizes by approximately four weeks (Adams, Becker, Boag, DiBartola, Graves). Numerous studies have attempted to identify parameters that predict declining renal function before correcting hyperthyroidism. Glomerular filtration rate can be measured using plasma clearance of exogenous creatinine exo-iohexol or endo-iohexol; N-acetyl- beta-D-glucosaminidase index and retinol-binding protein have been assessed as possible biomarkers (Lapointe, Riensche, Slater). Symmetric dimethylarginine (SDMA) is a promising biomarker for estimating GFR (Hall JA). It has been shown to be an accurate and precise biomarker for calculating estimated GFR in humans. It is a more sensitive biomarker than serum Cr for assessing early renal dysfunction. By reducing the lower limit of the Cr reference interval and monitoring this parameter longitudinally to look for upward trends, earlier detection in GFR decline can be achieved. False positive elevations occur with SDMA just as they do with Cr with prerenal azotemia, therefore pre-renal causes of decreased GFR and causes of acute kidney injury have to be eliminated before interpreting the result. What role it, or any other early predictive biomarker, will play in the management of CKD in cats is uncertain. Using common clinical measures, cats with hypertension and/or an increase urine protein: creatinine ratio (UPC) are more likely to develop problems while cats with elevated plasma globulins, a high urine specific gravity (usg) and hematocrit are less likely to. A practical approach to a patient with concurrent hyperthyroidism and CKD is to treat medically until the serum T4 is adequately controlled at which time the effect of permanent therapy may be predicted. If renal decline becomes apparent once euthyroidism has been achieved, exogenous thyroid hormone can be supplemented to support the kidneys. A balance must then be struck between creating iatrogenic hyperthyroidism and maintaining renal function as iatrogenic hypothyroidism appears to contribute to azotemia and decreased survival. (Peterson 2013, 2013, 2014, Williams, Aldridge) It is recommended to monitor serum TSH levels post radioiodine or during medical therapy to avoid iatrogenic hypothyroidism (Peterson ACVIM 2014, Peterson Enrollment in Clinical Study, 2016). These cats should either receive a lower dose of medication or be supplemented with thyroxine before the develop overt disease or CKD. The foundation of any treatment plan includes attending to hydration, nutrition, analgesia, and addressing environmental comfort. In this scenario, maintaining euvolemia will be reflected in coat and stool character as well as subjective measures of well-being including grooming, interaction and posture. Daily subcutaneous fluids (warmed to body temperature) may be appropriate. A client handout is included at the end of these notes. Appetite may be negatively affected by renal disease from uremic toxins or, less likely, uremic gastritis. Unlike humans and dogs, cats with CKD are more likely to have gastric fibrosis rather than uremic gastropathy (McLeland)). Nausea associated with uremic acidosis may be alleviated with famotidine 5 mg PO q24h or another H2 antagonist. However, the proton pump inhibitor omeprazole has been shown to provide better acid suppression than famotidine in cats (Parkinson). Additionally, twice-daily omeprazole is more efficacious at suppressing acid production than once daily dosing or ranitidine therapy (Šutalo). Appetite stimulation with mirtazapine (1.88 mg PO q48h) has been shown to benefit cats with CKD (Quimby 2013). Interestingly, maropitant, while effective in palliating vomiting, did not significantly improve appetite or support weight gain in cats with Stage II

291

and III CKD (Quimby 2015). Cats with untreated hyperthyroidism may have an increased appetite yet, due to increased metabolism, lose weight and muscle. Once euthyroid, their appetites generally normalize. It is generally recommended to feed cats with Stage 3 kidney disease, a protein-restricted, renal diet. We must consider several questions when treating each individual. Do cats at every stage of CKD have identical nutritional needs? Do all cats at the same stage have the same etiologic cause for their decline in renal function? Could this cat, perhaps, benefit from being fed a protein enhanced diet, a recuperative diet, a growth diet, a senior diet or a maintenance diet? Protein: calorie malnutrition results from ingesting adequate (or excessive) total calories, but insufficient protein calories. Weight loss may or may not be occur, however there will be muscle wasting as well as a deterioration in the hair coat quality. Additionally, because antibodies are protein, immune function may be compromised; anemia may be exacerbated due to the lack of building components for hemoglobin; albumin levels may decrease and tissue healing may be affected. If a cat is inappetant, restricting protein may result in inadequate intake of all nutrients, because amino acids are key in palatability, resulting in the protein intake falling below that required for normal function. It appears that some loss of weight and lean body mass (LBM) is part of normal aging (Armstrong, Dora-Rose, Bellows), and is not caused by illness but we may be able to address it nutritionally, potentially improving longevity as well as quality of life. In part this is associated with decreased digestion of fat and protein, (Perez-Camargo) in part due to increased requirements for protein and calories that may not be met. (Perez-Camargo, Harper, Laflamme X2, Villaverde) Maintenance of weight and condition prolongs life. (Cupp) Given that cats with CKD often live for a long time, (King 2007, Boyd) the nutritional needs of older cats should be taken into consideration in treatment of those with CKD. Weight loss with poor muscle condition is common among cats with CKD. Weight loss begins before 1 to 3 years before a diagnosis of CKD has been made (Freeman) and is associated with decreased survival. (Boyd, Freeman) A decrease in muscle mass is associated with increased morbidity and mortality in human CKD patients (Wang). Protein synthesis is reduced in these individuals compared to healthy human patients. While inadequate calorie intake contributes to weight, fat and LBM loss, reduction in dietary protein exacerbates the CKD-related muscle loss (Wang) in attempts to meet the needs for protein turnover and ongoing metabolic needs. Increasing dietary protein helps to regulate acid-base balance through excretion of hydrogen ions associated with ammonium. (Remer) This is of clinical relevance when we try to design the optimal nutritional regime for our older feline patients: protein and fat restriction may well be contraindicated. Especially if underweight, older cats will benefit from a more energy-dense, highly digestible diet to help offset these age-related digestive and metabolic changes. As obligate carnivores, cats have evolved to manage a high dietary protein load (Hewson-Hughes X2, Plantinga), but adapt to various intake as long as their minimum needs are met. (Green) Dietary protein is not toxic to kidneys. Creatinine and urea result from metabolizing ingested protein as well as from turnover of endogenous stores in health or in protein deficiency. In excess of 60 purported uremic toxins are reported. (Vanholder 2003) Interactions between many endogenous metabolites (Lisowaska-Myjak) resulting from inflammation, malnutrition, increased concentrations of protein-bound solutes and hypoalbuminemia as well as non- nutritional toxins contribute to the clinical spectrum of uremia. (Vanholder X2, Stenvinkel) Thus, while uremic toxins can result in malnutrition, malnutrition itself results in inflammation, morbidity and mortality in human patients with CKD. (Vanholder 2002) Despite numerous experimental studies and clinical trials, questions about feeding and managing the cat with CKD remain. Some of these are: 1. Do we over-rely on diet? Are there other approaches we could utilize to reduce uremic toxin production or absorption? The renal effects of endogenous protein breakdown have not been studied but may potentially be no different than those of dietary protein. 2. Do different types of kidney disease require different dietary therapies? Fibrosis associated with interstitial changes is the end-point for most cats, however what etiology initiates the process is generally unknown in an individual cat. 3. At what point in disease progression should dietary therapy be implemented, if at all? In theory, would it be better to address acid-base balance initially, and then phosphorus binding, or vice versa? 4. What is the optimal amount of protein for cats with CKD? How much restriction, if any, is necessary? Similar to cats, protein malnutrition, sarcopenia, and iron deficiency are clinical problems in human CKD patients following low protein regimes. 5. Does the type of protein, or the amino acid composition of the protein, make a difference in cats? There is evidence in humans and rats that types of protein can differentially influence the effect of protein on GFR, acid-base and other effects. (Williams, Kontessis, Pecis) 6. Will a cat in IRIS stage 3 or 4 benefit adequately if phosphorus is restricted by means other than diet? No controlled clinical trials address this question. 7. Might some cats with advanced disease benefit from increased dietary protein levels? As discussed earlier, regular reassessment of the patient enables evaluation of muscle and body condition, which is helpful in changing dietary treatment recommendations if warranted. As loss of lean mass is detrimental as well as predictive of progression, 292

increasing dietary protein and using alternate methods to restrict phosphorus or uremic toxins should be considered. When patients fail to eat adequate calories (protein, fat or carbohydrate), then feeding support is required. 8. What are the actual uremic toxins that cause adverse effects in cats and what can we do about them? 9. Should we be investigating phosphatonins (e.g., fibroblast growth factor-23 [FGF-23]) and their role in phosphate homeostasis in cats and potentially seeking ways to block or correct FGF-23 as GFR declines? Finch et al (2013) reported an inverse relationship between FGF-23 concentrations and GFR and demonstrated that FGF-23 is increased in cats that go on to become azotaemic before phosphate concentrations increase. PTH also changes before serum phosphorus. Would these make better markers of progression of renal dysfunction? 10. Progression of renal fibrosis is thought to be related to the ongoing production of pro-inflammatory and pro-fibrotic cytokines. Proteinuria, hypoxia, hyperphosphatemia, ageing and chronic inflammation have been investigated and are believed to maintain this state (Lawson). Should the focus of early identification (e.g., SDMA) and treatment be modification of the inflammatory mediators? 11. Is it appropriate to restrict protein in cats with proteinuria? While protein in urine may initiate an inflammatory response that ultimately progresses to interstitial fibrosis (Lawson), muscle wasting and a perceived decreased quality of life may result in an earlier death, either due to general decline in health or earlier requested euthanasia. Would this be better addressed pharmacologically rather than risking malnutrition? Malnutrition also results in inflammation and mortality, therefore preventing malnutrition, (as well as sarcopenia), is critically important when managing the feline CKD patient. Protein-restricted therapeutic diets are not identical; there are some marked differences in their composition, not just in protein sources and quantities, but also in the calorie source, in their phosphorus, potassium, and sodium content. They are variably supplemented with potassium and fatty acids, restricted in phosphorus. Every patient’s response to a given diet may differ and each cat should be rechecked to assess the effects and suitability of the recommended diet. Table 1 compares reduced protein and phosphorus foods as of December 2012: composition of these diets will have changed since this time. With muscle wasting, Cr levels decrease making it difficult to know how much of a Cr decrease seen in a cat fed a renal diet is from improvement in renal function and how much is because there is less functional muscle producing Cr. Given the smaller number and size of the studies in veterinary medicine, we are unable to perform meta-analysis. It seems prudent to make the following recommendation: when prescribing restricted protein renal diets practitioners must carefully monitor their patients' protein and energy intake and nutritional status, as evidenced by body and muscle condition as well as enjoyment of meals/quality of life. If deterioration in any of these is noted with no other apparent reason, alternate diets or means to reduce phosphorus should be considered. The WSAVA nutrition tools are a useful resource for the BCS and MCS. http://www.wsava.org/sites/default/files/Body%20condition%20score%20chart%20cats.pdf http://www.wsava.org/sites/default/files/Muscle%20condition%20score%20chart-Cats.pdf The MCS may be found at the end of the notes. Because of inherent progression of CKD, IRIS staging focuses on factors which, when managed, are known to slow progression: azotemia, metabolic acidosis, hyperphosphatemia, proteinuria and hypertension. Control of hypertension is important for its negative effects on cardiac function as well as progression of CKD. Amlodipine is the first choice (0.625 mg PO q24h, titrate as needed). In cats with proteinuria, telmisartan may be the best therapeutic choice (Jenkins) especially in cats that are also hypertensive (1 mg/kg PO q24h). (Sent) Addressing the degenerative joint disease in a patient with CKD requires thought but is not insurmountable. The most common concern regarding drug therapy are side effects of using NSAIDs in a dehydrated patient and their effects on gastric mucosal health or on renal function. Opioids are safe for pain relief in any age group and are excellent when used at the same time as other agents, especially NSAIDs. They are not, however, a first drug of choice for cats with arthritic pain as they are not very effective for DJD. This is not to suggest that they shouldn’t be used for “break-through” pain or for comfort during diagnostic testing. If they produce adverse side-effects (e.g., euphoria, constipation and inappetence) in an individual patient they may be reserved for palliative hospice care. Pharmacokinetic data is lacking for safe, long-term use of many NSAIDs in cats. Carprofen half-life varies from nine to over 40 hours in cats (Taylor, Parton). As most NSAIDs have long half-lives in cats when compared to other species, one precaution to avoid toxicity is to reduce the frequency of administration. Interestingly, despite having a short half-life of under 2 hours in blood, robenacoxib (Onsior) its effect persists for 24 h in clinical studies. Metacam 0.5 mg/ml oral suspension has been granted a licence in the EU for the alleviation of inflammation and pain in chronic musculoskeletal disorders in cats. The registered dose is 0.1 mg/kg on the first day followed by 0.05 mg/kg orally once daily. This is the first NSAID licensed for long-term use in cats. Numerous efficacy studies have been performed regarding both of these NSAIDs. Two studies have evaluated long-term safety of this agent in older cats; one concluded that this agent is safe, efficacious and palatable for musculoskeletal pain at 0.01-0.03 mg/kg PO 293

q24h for a mean treatment duration of 5.8 months; no deleterious effect on renal function was detected in cats studied. Gastrointestinal upset in 4% of cats was the only adverse effect noted (Gunew). The second, reviewed the medical records of cats over seven years of age treated for a minimum of 6 months with a daily maintenance dose of 0.02 mg/kg meloxicam and concluded that this dose does not hasten progression of renal disease in aged cats or aged cats with pre-existent stable IRIS stage 1-3 renal disease (Gowan). A paper published in 2015 reported on the safety of robenacoxib (1–2.4mg⁄kg) for daily, month long treatment of DJD in cats including 40 with chronic kidney disease IRIS stages 2-4. There was no evidence of increased risk in the frequency of reported adverse events, or in deterioration in renal variables in the subgroup of cats with concurrent CKD (King 2015). Despite being similar to meloxicam (class and mechanism of action), at this time (September 2016) it is licensed only for short-term use. A comprehensive review of the long-term use of NSAIDs in cats was published in 2010. This document may be accessed free-of- charge at: http://www.catvets.com/guidelines/practice-guidelines/nsaids-in-cats A suitable protocol for a cat with pain from DJD might be baseline NSAID (such as meloxicam or robenacoxib) with intermittent use of an opioid (such as burprenorphine) when break-through pain is evidenced by a decrease in appetite or mobility or social withdrawal. A recent study by King et al has shown that robenacoxib (1.0–2.4 mg/kg PO q24h) is safe in cats with, or without, CKD when administered for DJD for 30 days. Disease-modifying osteoarthritis agents Over the past two decades, research has been aimed at attempts to slow the progression of cartilage degradation as well as to promote rebuilding of healthy matrix. Products have been developed that, in research on humans and dogs, have been shown to be beneficial in enhancing hyaluronic acid production, inhibiting catabolic enzymes in osteoarthritic joints, and encouraging normalization of the synovial fluid and joint cartilage matrix. There is no evidence for efficacy in cats. Studies using radio-labeled compounds have shown that 87% of orally administered glucosamine is absorbed and is incorporated into the cartilage matrix. Glucosamine provides raw materials for synthesis of glycosaminoglycans. Since chondrocytes obtain preformed glucosamine from the circulation (or synthesize it from glucose and amino acids), adequate glucosamine levels in the body are essential for synthesis of glycosaminoglycans in cartilage. Glucosamine is required for the production of hyaluronic acid by synoviocytes. In vitro studies indicate that administration of glucosamine may normalize cartilage metabolism and stimulates the synthesis of proteoglycans. In one study, glucosamine stimulated synthesis of glycosaminolgycans, prostaglandin and collagen by chondrocytes and fibroblasts, suggesting it may actually up-regulate their synthesis. Chondroitin Sulfate (CS) is a long chain polymer of repeating disaccharide units. It is the predominant glycosaminolycan found in articular cartilage and can be purified from bovine, whale, and shark cartilage sources. Bioavailibilty studies in rats, dogs and humans have shown that 70% of orally administered CS is absorbed, some of it intact. Studies in rats and humans using radiolabeled CS have shown that CS reaches synovial fluid and articular cartilage. Hyaluronate concentrations and viscosity were increased, and collagenolytic activity was decreased, in the synovial fluid of human osteoarthritis patients treated with CS for 10 days. Both oral preparations (Cosequin) and parenterally injected preparations (Adequan) have been shown to have therapeutic benefit in in vivo studies. One caution is that a polysulfated glycosaminoglycan, such as Adequan, is a heparin analog, resulting in a transient prolonged partial thromboplastin time. Avoid using it in cats with bleeding disorders or pre-operatively and do not use it concurrently with either omega 3 fatty acids or NSAIDs. Diet Weight loss should be encouraged in the obese, arthritic cat to reduce the pressure on joints. The addition of omega 3 fatty acids may be beneficial by blocking the production of prostaglandins from arachadonic acid in the inflammatory cascade. Dietary modulation should be considered in the therapy of cats with DJD-associated pain (Lascelles). A therapeutic prescription diet for joint health: Hill’s j/d with omega 3 fatty acids is available in both a canned and a dry formulation (504 kcal/cup; 152 kcal/156g can); to date the author is not aware of peer-reviewed papers on this diet. Royal Canin has developed Mobility Support (391 kcal/cup) for cats. Both of these diets may not have sufficient protein for some older patients. A recently published study comparing the Royal Canin diet to the identical diet without the added high levels of eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and supplemented with green-lipped mussel (GLM) extract and glucosamine/chondroitin sulfate. Forty cats with no detectable systemic disease but with radiographic evidence of at least one affected joint and who showed an aversive response to manipulation of that joint were fed one of the two diets (control or test diet) for nine weeks. Cats on the test diet showed significantly greater improvements including an increased ability to jump, increased time spent eating, less time sleeping, increased playing and interacting with other pets. In an earlier study that looked at efficacy and tolerance of an extract of GLM in dogs with DJD, a similar subjective improvement was noted by clients whether the dogs were receiving placebo extract or GLM extract. Therapeutic exercise Moderate exercise has benefits in maintaining range of motion in the face of joint capsule fibrosis, to maintain/build muscle mass and maintain/build healthy articular cartilage. In acute flare-ups, restricting activity may be warranted.

294

Additional therapeutic considerations It is important to make environmental changes in the home as well as having empathic awareness in order to make appropriate changes in handling in a clinic setting. Decreased mobility can result in constipation due to retention, positional stiffness resulting in elimination outside of the litter box, falling when jumping onto or off the bed, inability to climb stairs, inability to crouch to eat resulting in weight loss. Raising bowls for cats with lumbosacral and hip DJD makes it easier to eat. Trimming nails regularly helps to maintain proper joint relationships. Ramps and steps onto favourite sleeping spots gives the cat access to safe places for sleeping and observation. Warm, soft, padded beds for stiff, painful, possibly bony joints should be considered. Adding a litter box so that kitty doesn’t have to walk as far may reduce inappropriate elimination as well as encourage regular voiding and defecation. Making sure that the rim of the litter box is not too high, and that the opening into the box is not too small is helpful. Scooping the litter several times a day and making sure that the litter isn’t too deep or too sparse will encourage regular use. Regular nail trimming helps by maintaining proper joint relationships. Ramps and steps to favourite sleeping spots may be helpful. Warm, soft, padded sleeping places for stiff, painful, possibly bony joints should be considered. Adding a litter box to reduce the distance between boxes may reduce accidents as well as encourage regular voiding and defecation. The rim of the box mustn’t be too high, nor the opening into the box too small. It should be scooped several times a day to encourage use. Acupuncture may be considered and can safely be combined with pharmacologic approaches. While efficacy has been shown for acupuncture in a few conditions in humans, there is no solid scientific evidence at the time of writing that clearly supports its efficacy in cats. Peer-reviewed publications for efficacy of laser therapy and stem cell therapy are also lacking.

Managing a cat with stage 2 chronic kidney disease stage, diabetes mellitus, periodontal disease and inflammatory bowel disease One of the challenges with these comorbidities is nutritional (protein quantity and source, meeting all nutritional requirements). Another is achieving immunomodulation for IBD in the face of glycemic instability. Treatment with corticosteroids takes priority over glycemic effects because inflammation is recognized as a predisposing factor for susceptible individuals to develop diabetes. Franchini has shown at a molecular level that the inflammation induced by bacterial or viral infection can, via molecules recognized by toll gate receptors, damage endocrine pancreatic tissue. In some individuals, IBD can be managed using chlorambucil and metronidazole without corticosteroids. The oral disease adds to difficulties controlling the diabetes. Inflammation and/or infection at any site (dental, urinary tract, etc.) interferes with the ability of all cell receptors to interact with insulin. Anaesthesia for dental care should be performed before the diabetes or IBD are controlled. Before the procedure, ½ of the current dose of insulin is given on the morning of the procedure. The cat should only be fasted for 4 hours with water freely available. Blood glucose measurements should be made during and after the anaesthetic until the cat is able to eat on his own. Concern regarding safety of performing anaesthesia in elderly cats should not be over-emphasized. Two studies have verified that in cats, as in people, age is not a risk factor and should not be a limiting factor in determining whether or not to undertake a medically beneficial procedure. (Hosgood, Brodbelt) The American Society of Anesthesiologists (ASA) characterizes risk using the following physical status classification system that is based on the physical status of the patient. Five categories are defined as follows:  Class 1: Normal, healthy patient  Class 2: A patient with a mild systemic disease  Class 3: A patient with severe systemic disease  Class 4: A patient with a severe systemic disease that is a constant threat to life  Class 5: A moribund patient not expected to survive without the operation Feeding strategies for diabetes include a high protein, low carbohydrate diet or a high fiber diet. However, a diabetic cat can be controlled with insulin as long as any diet and treats fed remain consistent from day to day. Neither carbohydrates nor dry extruded diets are cause of diabetes or obesity. However, exchanging dietary carbohydrate for protein appears to be useful for weight loss treatment and management of non-insulin dependent diabetes in cats. In a prospective, randomized, double blinded 10-week study (Hall TD), 12 cats (7/12 obese) of whom six were newly diagnosed and six were poorly controlled diabetics evaluated standard maintenance diet vs. lower carbohydrate, higher protein (LCHP) diets. The cats ate dry or canned based on their preference. All were treated with glargine and assessed at weeks 1, 2, 4, 6, and 10 with fructosamine, BG curve and clinical signs. One cat from each diet group achieved remission by week 10. All cats improved clinically, increased weight and achieved good glycemic control. Those fed the LCHP had a significantly greater decrease in fructosamine. The conclusion, based on this small study was that using insulin, “frequent monitoring is key to achieving glycemic control in diabetic cats; potential benefits of dietary modification require further evaluation”. The author summarizes all of the preceding studies and approaches: high fiber & low fat, high insoluble fiber vs. low fiber, LCHP canned, low carbohydrate diet vs.

295

low carbohydrate diet plus acarbose, low carbohydrate & low fiber diet vs. moderate carbohydrate & high fiber diet. None of these approaches appears to make a meaningful difference in the small numbers of cats in any of the reviewed studies. Diet recommendations for a cat with a sensitive gastrointestinal tract and a diagnosis of “IBD” are either a limited antigen, a “hypoallergenic” or a hydrolyzed protein diet. Some cats may tolerate a highly digestible, low residue intestinal diet. Omega-3 fatty acids may be beneficial in small quantities. Unless the GI disease is extremely mild, this condition has dietary priority as the diabetes can be regulated on any diet if used consistently and protein restriction may be unnecessary or contraindicated. Regardless of nutritional recommendation made, we are performing a feeding trial with one subject (n=1). We need to reassess the patient to determine how suitable the diet is for him. How is his weight? How is his coat? Does he eat with enjoyment or vigour? What are his stools like (moist logs or dry pellets, cow patties or coloured water)? How energetic is he since he has been on this diet? Has there been a change in his hematocrit and proteins? Have biochemistries or usg changed? Is he proteinuric and potentially protein deficient? What about his blood pressure? Ultimately, quality of life is more important than quantity.

References Adams WH, Daniel GB, Legendre AM et al: Changes in renal function in cats following treatment of hyperthyroidism using 131I, Vet Radiol Ultrasound 1997; 38: 231. Aldridge C, Behrend EN, Martin LG, et al Evaluation of thyroid-stimulating hormone, total thyroxine, and free thyroxine concentrations in hyperthyroid cats receiving methimazole treatment. J Vet Intern Med 2015; 29: 862-868. Armstrong PJ, Lund EM. Changes in body composition and energy balance with aging. Vet Clin Nutr 1996; 3: 83-7. Becker TJ, Graves TK, Kruger JM et al: Effects of methimazole on renal function in cats with hyperthyroidism, J Am Anim Hosp Assoc 2000; 36: 215. Bellows J, Center S, Daristotle L et al: Aging in cats Common physical and functional changes. Journal of Feline Medicine and Surgery. 2016 Jul 1;18(7):533-50. Boag AK, Neiger R, Slater L et al: Changes in the glomerular filtration rate of 27 cats with hyperthyroidism after treatment with radioactive iodine, Vet Rec 2007; 161: 711. Boyd LM, Langston C, Thompson K, et al. Survival in cats with naturally occurring chronic kidney disease (2000-2002). J Vet Intern Med 2008; 22: 1111–1117. Brodbelt DC, Pfeiffer DU, Young LE, et al. Risk factors for anaesthetic-related death in cats: results from the confidential enquiry into perioperative small animal fatalities (CEPSAF). Br J Anaesth 2007; 99: 617-623. Chalhoub S, Langston C, Eatroff A. Anemia of renal disease: what it is, what to do and what's new. J Feline Med Surg. 2011; 13: 629-640. Cook AK, Suchodolski JS, Steiner JM, et al. The prevalence of hypocobalaminaemia in cats with spontaneous hyperthyroidism. J Small Anim Pract. February 2011: 52 (2): 101-6. Cupp CJ, Kerr WW, Jean-Philippe C, et al. The role of nutritional interventions in the longevity and maintenance of long-term health in aging cats intern. J Appl Res Vet Med 2008; 6: 69–81. Cupp CJ, Kerr WW. Effect of diet and body composition on life span in aging cats. Proc Nestle Purina Companion Animal Nutrition Summit, Focus on Gerontology. Mar 26-27, 2010. Clearwater Beach, FL. p. 36-42. DiBartola SP, Broome MR, Stein BS et al: Effect of treatment of hyperthyroidism on renal function in cats, J Am Vet Med Assoc, 208:875,1996. Dora-Rose VP, Scarlett JM. Mortality rates and causes of death among emaciated cats. J Am Vet Med Assoc 2000; 216: 347-351. Finch NC, Geddes RF, Syme HM, et al. Fibroblast growth factor 23 (FGF-23) concentrations in cats with early nonazotemic chronic kidney disease (CKD) and in healthy geriatric cats. J Vet Intern Med 2013; 27: 227–233. Franchini M, Zini E, Osto M, et al. Feline pancreatic islet-like clusters and insulin producing cells express functional Toll-like receptors (TLRs) Vet Immunol Immunopathol. 2010;138(1-2):70-8. Freeman LM. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. J Vet Intern Med 2012; 26: 3-17. Freeman LM, Lachaud MP, Matthews S, et al. Evaluation of weight loss over time in cats with chronic kidney disease [Research report] [abstract]. J Vet Intern Med 2015; 29: 935. Geesaman BM, Whitehouse WH, Viviano KR. Serum Cobalamin and Methylmalonic Acid Concentrations in Hyperthyroid Cats Before and After Radioiodine Treatment. J Vet Intern Med. 2016; 30: 560-565. Gowan R, Lingard A, Johnston L, et al. Retrospective case control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease. J Feline Med Surg 2011 13, 752-761 Graves TK, Olivier NB, Nachreiner RF et al: Changes in renal function associated with treatment of hyperthyroidism in cats, Am J Vet Res 1994; 55: 1745. Green AS, Ramsey JJ, Villaverde C, et al. Cats are able to adapt protein oxidation to protein intake provided their requireme nt for dietary protein is met. J Nutr 2008; 138: 1053–60. Grude ́ P, Guittard J, Garcia C, et al. Excretion mass balance evaluation, metabolite profile analysis and metabolite identif ication in plasma and excreta after oral administration of [14C]-meloxicam to the male cat: preliminary study. J. Vet. Pharmacol. Therap. 2010; 33, 396–407. Gunew MN, Menrath VH, Marshall RD. Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03 mg/kg for treatment of osteoarthritic pain in cats. J Feline Med Surg 2008;10(3):235-41. Hall JA, Yerramilli M, Obare E, et al. Comparison of Serum Concentrations of Symmetric Dimethylarginine and Creatinine as Kidney Function Biomarkers in Cats with Chronic Kidney Disease. J Vet Int Med 2014; 28: 1676-1683. Hall TD. Effects of diet on glucose control in cats with diabetes mellitus treated with twice daily insulin glargine. J Feline Med Surg.11(2):2009. Harper EJ. Changing perspectives on aging and energy requirements: aging, body weight and body composition in humans, dogs an d cats [expanded abstract]. J Nutr 1998; 128: 2627S–31S. 296

Hewson-Hughes AK, Hewson-Hughes VL, Miller AT, et al. Geometric analysis of macronutrient selection in the adult domestic cat, Felis catus. J Exp Biol 2011; 214:1039–51. Hewson-Hughes AK, Hewson-Hughes VL, Colye A, et al. Consistent proportional macronutrient intake selected by adult domestic cats (Felis catus) despite variations in macronutrient and moisture content of foods offered. J Comp Physiol B 2013; 183: 525–536. Hosgood G, Scholl DT. Evaluation of Age and American Society of Anesthesiologists (ASA) Physical Status as Risk Factors for Perianesthetic Morbidity and Mortality in the Cat. J Vet Emerg Crit Care 2002; 12: 9-15 Jenkins TL, Coleman AE, Schmiedt CW, et al. Attenuation of the pressor response to exogenous angiotensin by angiotensin receptor blockers and benazepril hydrochloride in clinically normal cats. Am J Vet Res 2015; 76: 807-813. King JN, Tasker S, Gunn-Moore DA, et al, BENRiC (Benazepril in Renal insufficiency in Cats) Study Group. Prognostic factors in cats with chronic kidney disease. J Vet Intern Med 2007; 21: 906–916. King JN, King S, Budsberg SC, Lascelles BDX, et al. Clinical safety of robenacoxib in feline osteoarthritis: results of a ran domized, blinded, placebo- controlled clinical trial. J Feline Med Surg. Epub June 9, 2015 DOI: 10.1177/1098612X15590870 Kontessis P, Jones S, Dodds R, et al. Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int 1990; 38: 136–144. Laflamme DP, Gunn-Moore D. Nutrition for aging cats. Vet Clin North Am Small Anim Pract 2014; 744: 7761–7774. Laflamme DP. Sarcopenia and weight loss in the geriatric cat. In: Little S, editor. August’s consultations in feline internal medicine, vol. 7. St Louis (MO): Elsevier; 2016. p. 951–6. Laflamme DP, Hannah SS. The effect of protein intake on changes in lean body mass in aging cats. J Fel Med Surg 2016, in pres s. Landsberg G, Denenberg S, Araujo J. Cognitive dysfunction in cats: A syndrome we used to dismiss as ‘old age’. J Fel Med Surg. 2010; 12: 837-848. Lapointe C, Belanger M-C, Dunn M, et al. N-acetyl-beta-D-glucosaminidase index as an early biomarker for chronic kidney disease in cats with hyperthyroidism, J Vet Intern Med, 22: 1103, 2008 Lascelles BDX, Depuy V, Thomson A, et al. Evaluation of a therapeutic diet for feline degenerative joint disease. J Vet Intern Med 2010; 24: 487-495. Lascelles BDX, Henry JB, Brown J, et al. Cross-Sectional Study of the Prevalence of Radiographic Degenerative Joint Disease in Domesticated Cats. Vet Surg 2010; 39: 535–544. Lawson J, Elliott J, Wheeler-Jones C, et al. Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury. Vet J 2015; 203: 18–26. Lisowaska-Myjak B. Uremic toxins and their effects on multiple organ systems. Nephron Clin Pract 2014; 128: 303–311. McLeland SM, Lunn KF, Duncan CG, et al. Relationship among Serum Creatinine, Serum Gastrin, Calcium- phosphorus Product, and Uremic Gastropathy in Cats with Chronic Kidney Disease. J Vet Intern Med 2014; 28: 827-837. Parkinson S, Tolbert K, Messenger K, et al. Evaluation of the effect of orally administered acid suppressants on intragastric pH in cats. J Vet Intern Med 2015; 29: 104-112. Parton K, Balmer TV, Boyle J et al. The pharmacokinetics and effects of intravenously administered carprofen and salicylate on gastrointestinal mucosa and selected biochemical measurements in healthy cats. J Vet Pharmacol Ther 2000; 23: 73-79. Pecis M, DeAzevedo MJ, Gross JL. Chicken and fish diet reduces glomerular hyperfiltration in IDDM patients. Diabetes Care 1994; 17: 665–672. Perez-Camargo G, Young L. Nutrient digestibility in old versus young cats. Compendium 2005; 27(3A): 84. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compendium 2013; 35: E4. Peterson ME. Diagnosis and management of iatrogenic hypothyroidism. In Little SE (ed): August's Consultations in Feline Internal Medicine Volume 7, St. Louis, 2014, Elsevier, 260-269. Peterson ME. Advances in the Treatment of Feline Hyperthyroidism: A Strategy to Slow the Progression of CKD Proceedings ACVIM Forum 2014, 1083-1085. Peterson ME. Clinical Study: Information for veterinarians regarding enrolling cats into study - Monitoring the Effects of Radioiodine Treatment with a Complete Thyroid Panel (T4, T3, Free T4, TSH): http://www.animalendocrine.com/wp-content/uploads/2012/09/Vets—Complete- Thyroid-Panel-T4-T3-Free-T4-TSH-to-Diagnose-Iatrogenic-Hypothyroidism-in -Cats-.pdf Accessed September 3, 2016. Plantinga EA, Bosch G, Hendriks WH. Estimation of the dietary nutrient profile of free-roaming feral cats: possible implications for nutrition of domestic cats. Br J Nutr 2011; 106: S35–48. Remer T. Influence of nutrition on acid-base balance - metabolic aspects. Eur J Nutr 2001; 40: 214–220. Riensche MR, Graves TK, Schaeffer DJ. An investigation of predictors of renal insufficiency following treatment of hyperthyro idism in cats, J Feline Med Surg 2008; 10: 160. Ruaux CG, Steiner JM, Williams DA. Early biochemical and clinical responses to cobalamin supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia. J Vet Intern Med. 2005;19: 155-160. Scherk MA, Ford RB, Gaskell RM, et al. 2013 AAFP Feline Vaccination Advisory Panel Report Journal of Feline Medicine and Surgery (2013) 15, 785–808 Supplementary file Immune Response to Vaccination Fact Sheet http://jfm.sagepub.com/content/suppl/2013/08/14/15.9.785.DC2/10_Immune_response_to_vaccination.pdf Accessed September 2, 2016 Scherk MA, Laflamme DP. Controversies in Veterinary Nephrology: Renal Diets are Indicated for Cats with International Renal Interest Society Chronic Kidney Disease Stages 2 to 4: THE CON VIEW Vet Clin North Am Small Anim Pract 2016; 46: 1067-1094. Sent U, Gössl R, Elliott J, et al. Comparison of Efficacy of Long-term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease J Vet Intern Med 2015; 29: 1479-1487. Simpson KW, Fyfe J, Cornetta A, et al. Subnormal Concentrations of Serum Cobalamin (Vitamin B12) in Cats with Gastrointestina l Disease. J Vet Intern Med 2001; 15: 26–32 Slater MR, Geller S, Rogers K: Long-term health and predictors of survival for hyperthyroid cats treated with iodine 131, J Vet Intern Med, 15: 47, 2001. Sparkes AH, Helene R, Lascelles BCX et al. ISFM and AAFP consensus guidelines: Long-term use of NSAIDs in cats. J Fel Med Surg 2010: 12 (7): 521-538. 297

Stenvinkel P, Heimbürger O, Lindholm B, et al. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000; 15: 953–960. Šutalo S, Ruetten M, Hartnack S, et al. The Effect of Orally Administered Ranitidine and Once‐Daily or Twice‐Daily Orally Administered Omeprazole on Intragastric pH in Cats. J Vet Intern Med 2015; 29: 840-846. Taylor PM, Delatour P, Landoni FM, et al. Pharmacodynamics and enantioselective pharmacokinetics of carprofen in the cat. Res Vet Sci 1996; 60: 144-151. Quimby JM, 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(3): 651-655. Quimby JM, Brock WT, Moses K, et al. Chronic use of maropitant for the management of vomiting and inappetence in cats with ch ronic kidney disease: a blinded, placebo-controlled clinical trial. J Feline Med Surg 2015; 17: 692-697. Vanholder R, Glorieux G, Lameire N. The other side of the coin: Impact of toxin generation and nutrition on the uremic syndrome. Semin Dial 2002; 15 :311–314. Vanholder R, Glorieux G, De Smet R, et al. New insights in uremeic toxins. Kidney Int 2003; 63: S6–10. Villaverde C, Fascetti AJ. Macronutrients in feline health. Vet Clin North Am Small Anim Pract 2014; 44: 699–717. Wang XH, Mitch WE. Mechanisms of muscle wasting in chronic kidney disease. Nat Rev Nephrol 2014; 10: 504–516. Williams AJ, Walls J. Metabolic consequences of differing protein diets in experimental renal disease. Eur J Clin Invest 1987; 17: 117–122. Williams TL, Elliott J, Syme HM. Effect on renal function of restoration of euthyroidism in hyperthyroid cats with iatrogenic hypothyroidism. J Vet Intern Med 2014; 28: 1251-1255. WSAVA Nutrition Toolkit for Body Condition Scoring: http://www.wsava.org/sites/default/files/Body%20condition%20score%20chart%20cats.pdf Accessed September 3, 2016. WSAVA Nutrition Toolkit for Muscle Condition Scoring: http://www.wsava.org/sites/default/files/Muscle%20condition%20score%20chart-Cats.pdf Accessed September 3, 2016. Yu S, Melendez L, Ahle N, et al. Dietary Supplementation of Vitamin B12 Improves Vitamin B12 Status in Geriatric Cats ACVIM Forum 2011

298

When Do Cats with Chronic Kidney Disease Need Protein Restriction? Margie Scherk DVM, DABVP Cats Only Veterinary Clinic Vancouver, Canada

Since the 1950’s, dietary therapy has been the cornerstone for the treatment of chronic kidney diseases (CKD) in dogs and cats. It continues to be the most common recommendation made for affected feline patients and is credited with the highest strength and quality of evidence.1 In addition to protein restriction, dietary modifications include reduced phosphorus and sodium, increased omega-3 polyunsaturated fatty acids, adaptations to promote neutral acid-base balance and possibly increased caloric density, B- vitamins, and fiber. Combined, they provide a beneficial “renal effect”, however evaluation of the effect of individual components remains untested. Assessing these components individually remains an important goal in order to optimize outcome and reduce detrimental effects.

Evaluating the evidence for protein restriction Conclusions regarding dietary therapy for feline CKD come from: 1) pathophysiologic reasoning (e.g., inflammatory attributes of protein in renal tubules2); 2) extrapolation from other species (rodent or canine models and human clinical trials, e.g., phosphate restriction prevented renal mineralization in nephrectomized rats3); 3) observations from renal ablation studies in cats (e.g., caloric rather than protein restriction resulted in fewer nonglomerular lesions4); and 4) trials in naturally occurring CKD in cats (e.g., cats fed renal diet have fewer uremic episodes and renal related deaths compared to cats fed maintenance diet5). Results from these different studies have not however been consistent or have been limited by study design or size. Critical to this presentation is that there are no clinical studies in cats with naturally occurring disease selectively comparing protein levels. A retrospective study (321 cats) comparing cats fed a variety of renal diets to those fed uncontrolled and varied maintenance diets found longer survival in the group fed any renal diet.6 A non-randomized prospective study (50 cats) compared 29 that willingly ate a dry or wet renal diet to those that wouldn’t and were fed an uncontrolled variety of diets. This study found a survival benefit in the renal diet group. It must also be noted that the renal group received phosphorus binders to control hyperphosphatemia as needed; this group had lower serum phosphorus and parathyroid hormone levels.7 Two randomized, controlled prospective trials have been conducted. In one, 74% of 35 cats were fed a renal diet with the balance being fed a control maintenance diet for 24 weeks.8 Those fed the renal diet had less clinical deterioration and less increase in serum creatinine and urea nitrogen (SUN). In the other study, 45 cats (IRIS Stage 2 or 3) were randomly assigned to eat a renal or control maintenance diet. Results revealed fewer uremic episodes and renal related deaths in those eating the renal diet. 5 Despite these studies, because protein has not been parsed out specifically and the diets fed are too dissimilar, it remains unclear what if any role protein restriction plays in the composite effect of dietary therapy. Similarly, optimal levels of dietary protein in treatment of proteinuria in cats is unknown. While proteinuria is recognized as a negative prognostic factor, dietary restriction of this nutrient has not been shown to be beneficial either in angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker trials in naturally occurring disease.9-11 In the nephrectomy model, proteinuria appeared to be associated with hypokalemia12 and did not develop in cats fed a high protein, potassium replete diet.4 In the randomized, controlled prospective study of Stage 2 and 3 cats, dietary protein level did not result in a difference in proteinuria.5 As obligate carnivores, cats have evolved to manage a high dietary protein load13-15 but adapt to various intake as long as their minimum needs are met.16 Dietary protein is not toxic to kidneys. Creatinine and urea result from metabolizing ingested protein as well as from turnover of endogenous stores in health or in protein deficiency. In excess of 60 purported uremic toxins are reported.17 Interactions between many endogenous metabolites18 resulting from inflammation, malnutrition, increased concentrations of protein- bound solutes and hypoalbuminemia as well as non-nutritional toxins contribute to the clinical spectrum of uremia.17,19,20 Thus, while uremic toxins can result in malnutrition, malnutrition itself results in inflammation, morbidity and mortality in human patients with CKD.20 Despite having greater resources and the ability to perform significant meta-analysis, the question of whether or not protein restriction is beneficial in human CKD remains controversial.21-23 Similar to cats, protein malnutrition, sarcopenia, and iron deficiency are clinical problems in human CKD patients following low protein regimes. A prospective study in human CKD patients contrasting protein and phosphorus restriction concluded that the risks associated with protein restriction may outweigh the benefits from phosphorus restriction, and suggested that protein restriction as a means to control phosphorus intake is not justified. 24 A meta- analysis regarding the effects of dietary protein restriction in human CKD concludes that the relatively weak effect on progression of disease suggests that better therapies are needed.25

299

Evaluating the evidence for other aspects of renal diets Phosphorus Numerous studies using the remnant kidney model have verified that controlling serum phosphorus levels with resultant modulation of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23), results in reduced renal pathology, morbidity and mortality in rats as well as in cats. Lumlertgul and Koizumi both showed that restriction of phosphorus arrested progression of CKD in nephrectomized rats independent of dietary protein intake.26,27 Several studies in naturally occurring feline CKD have similarly shown that when phosphorus was controlled in addition to feeding a protein and phosphorus restricted diet, reductions in serum phosphorus,5 PTH, 6,7,28 and FGF-2329 are seen along with increased survival.30-32 Lacking are studies that isolate phosphorus restriction from protein content in naturally occurring feline disease. Acidosis Acidosis stimulates numerous endocrine responses33 contributing to protein catabolism, decreased protein synthesis, loss of lean body mass (LBM),34 increased calcium and potassium excretion. Correction of acid-base imbalance results in improvement in clinical signs that include nausea, anorexia, vomiting, weight loss, weakness, and lethargy. Additionally, it reduces the loss of LBM and may slow the progression of CKD. In retrospective studies of humans with CKD on dialysis, as well as a prospective controlled clinical trial of non-dialysis CKD patients, correction of acidosis not only normalized protein catabolism, but also improved markers of nutritional status, and resulted in less deterioration of creatinine clearance compared to the control group.35 Net nitrogen balance, SUN and total body protein synthesis are positively affected by ensuring a neutral serum pH.36 Potassium Hypokalemia is both a cause, as well as a result, of CKD. Metabolic acidosis results in an extracellular shift of potassium that masks the severity of the intracellular and total body potassium level. Independent of acid-base, potassium supplementation has been shown to reduce serum creatinine.37,38 In another small study, potassium supplementation in normokalemic cats with CKD, resulted in improvement in creatinine, SUN and increased, or no decline, in GFR, when compared to cats supplemented with sodium gluconate.39 These findings lack power to recommend potassium supplementation, per se, however provision of adequate potassium in a non- acidifying diet does appear to be relevant.

Evaluating the evidence for maintaining body condition As cats age, they tend to lose weight and LBM. In part this is associated with decreased digestion of fat and protein,40 in part due to increased requirements for protein and calories that may not be met.40-44 Maintenance of weight and condition prolongs life.45 Given that cats with CKD often live for a long time,10,31 the nutritional needs of older cats should be taken into consideration in treatment of those with CKD. Weight loss with poor muscle condition is common among cats with CKD. Weight loss begins before 1 to 3 years before a diagnosis of CKD has been made46 and is associated with decreased survival.31,46 A decrease in muscle mass is associated with increased morbidity and mortality in human CKD patients.47 Protein synthesis is reduced in these individuals compared to healthy human patients. While inadequate calorie intake contributes to weight, fat and LBM loss, reduction in dietary protein exacerbates the CKD-related muscle loss47 in attempts to meet the needs for protein turnover and ongoing metabolic needs. Increasing dietary protein helps to regulate acid-base balance through excretion of hydrogen ions associated with ammonium.48

Summary While feeding a renal diet is accepted as a core part of therapeutic management, each patient’s response to the disease and to nutritional intervention varies dramatically, and individualizing therapy is required, especially as different pathologic processes may underlie the CKD. At the present time, there are no studies that evaluate the independent effects of restricting protein, controlling acidosis, potassium, or reducing phosphorus. There is, however, sufficient evidence showing that low weight and reduction in LBM is detrimental to quality of life, progression and survival of cats with CKD. In order to ascertain the role (benefit or not) of protein restriction, randomized, controlled prospective studies need to be performed in cats with naturally occurring renal disease comparing diets that are as identical as possible with one having a higher proportion of calories from protein than the other. Until such time, we need to consider that not all cats from IRIS Stage 2 onward be offered a renal diet and focus on the risks of inadequate dietary protein. It is critical to monitor every patient closely for the subtle changes associated with protein deficiency that can shorten life. (Adapted from chapter by Scherk MA, Laflamme DP: Renal Diets are Indicated for Cats with IRIS CKD Stages 2-4: The Con View. Vet Clin N Am Small 2016; 46: 1067)

300

References Roudebush P, Polzin DJ, Ross SJ, Towell TL, Adams LG, Forrester SD. Therapies for feline chronic kidney disease What is the e vidence?. J Feline Med Surg. 2009;11:195-210. Lawson J, Elliott J, Wheeler-Jones C, et al. Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury. Vet J 2015;203:18–26. Ibels LS, Alfrey AC, Haut L, et al. Preservation of function in experimental renal disease by dietary restriction of phosphat e. N Engl J Med 1976;298:122–6. Finco DR, Brown SA, Brown CA, et al. Protein and calorie effects on progression of induced chronic renal failure in cats. Am J Vet Res 1998;59:575– 82. 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;229:949–57 Plantinga EA, Everts H, Kastelein AMC, et al. Retrospective study of the survival of cats with acquired chronic renal insufficiency offered different commercial diets. Vet Rec 2005;157:185–7. Elliott J, Rawlings JM, Markwell PJ, et al. Survival of cats with naturally occurring chronic renal failure: effect of dietary management. J Small Anim Pract 2000;41: 235–42. Harte JG, Markwell PJ, Moraillon RM, et al. Dietary management of naturally occurring chronic renal failure in cats. J Nutr 1994;124:26660S–2S. King JN, Gunn-Moore DA, Tasker S, et al, Benazepril in Renal insufficiency in Cats Study Group. Tolerability and efficacy of benazepril in cats with chronic kidney disease. J Vet Intern Med 2006;20:1054–64. King JN, Tasker S, Gunn‐Moore DA, Strehlau G. Prognostic factors in cats with chronic kidney disease. J Vet Intern Med. 2007;21:906 -16. Sent U, Gössl R, Elliott J, et al. Comparison of efficacy of long-term oral treatment with telmisartan and benazepril in cats with chronic kidney disease. J Vet Intern Med 2015;29:1479–87. Adams LG, Polzin DJ, Osborne CA, et al. Influence of dietary protein/calorie intake on renal morphology and function in cats with 5/6 nephrectomy. Lab Invest 1994;70:347–57. Hewson-Hughes AK, Hewson-Hughes VL, Miller AT, et al. Geometric analysis of macronutrient selection in the adult domestic cat, Felis catus. J Exp Biol 2011; 214:1039–51. Hewson-Hughes AK, Hewson-Hughes VL, Colye A, et al. Consistent proportional macronutrient intake selected by adult domestic cats (Felis catus) despite variations in macronutrient and moisture content of foods offered. J Comp Physiol B 2013;183:525–36. Plantinga EA, Bosch G, Hendriks WH. Estimation of the dietary nutrient profile of free-roaming feral cats: possible implications for nutrition of domestic cats. Br J Nutr 2011;106:S35–48. Green AS, Ramsey JJ, Villaverde C, et al. Cats are able to adapt protein oxidation to protein intake provided their requireme nt for dietary protein is met. J Nutr 2008;138:1053–60. Vanholder R, Glorieux G, De Smet R, et al. New insights in uremeic toxins. Kidney Int 2003;63:S6–10. Lisowaska-Myjak B. Uremic toxins and their effects on multiple organ systems. Nephron Clin Pract 2014;128:303–11. Stenvinkel P, Heimbürger O, Lindholm B, et al. Are there two types of malnutrition in chronic renal failure? Evidence for relationships b etween malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000;15:953–60. Vanholder R, Glorieux G, Lameire N. The other side of the coin: Impact of toxin generation and nutrition on the uremic syndrome. Semin Dial 2002;15:311–4. Levey AS, Greene T, Beck GJ, et al. Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study group. J Am Soc Nephrol 1999;10:2426–39. Levey A, Greene T, Sarnak M, et al. Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis 2006;48:879–88. Kopple JD, Kalantar-Zadeh K, Mehrotra R. Risks of chronic metabolic acidosis in patients with chronic kidney disease. Kidney Int Suppl 2005;95:S21–7. Shinaberger CS, Greenland S, Kopple JD, et al. Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease? Am J Clin Nutr 2008;88:1511–8. Kasiske BL, Lakatua JD, Ma JZ, et al. A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function. Am J Kidney Dis 1998;31:954–61. Lumlertgul D, Burke TJ, Gillum DM, et al. Phosphate depletion arrests progression of chronic renal failure independent of protein intake. Kidney Int 1986;29: 658–66. Koizumi T, Murakami K, Nakayama H, et al. Role of dietary phosphorus in the progression of renal failure. Biochem Biophys Res Commun 2002;295:917–21. Barber PJ, Rawlings JM, Markwell PJ, et al. Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. J Small Anim Pract 1999;40:62–70. Geddes RF, Elliott J, Syme HM. The effect of feeding a renal diet on plasma fibroblast growth factor 23 concentrations in cats with stable azotemic chronic kidney disease. J Vet Intern Med 2013;27:1354–61. 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; 47:446–50. Boyd LM, Langston C, Thompson K, et al. Survival in cats with naturally occurring chronic kidney disease (2000-2002). J Vet Intern Med 2008;22:1111–7. Chakrabarti S, Syme HM, Elliott J. Clinicopathological variables predicting progres sion of azotemia in cats with chronic kidney disease. J Vet Intern Med 2012; 26:275–81. Franch HA, Mitch WE. Catabolism in uremia: the impact of metabolic acidosis. J Am Soc Nephrol 1998;9:S78–81. 301

Franch HA, Raissi S, Wang X, et al. Acidosis impairs insulin receptor substrate- 1-associated phosphoinositide 3-kinase signaling in muscle cells: consequences of proteolysis. Am J Physiol Renal Physiol 2004;287:F700–6. de Brito-Ashurst I, Varagunam M, Raftery MJ, et al. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 2009;20:2075–84. Mehrotra R, Bross R, Wang H, et al. Effect of high-normal compared with low- normal arterial pH on protein balances in automated peritoneal dialysis patients. Am J Clin Nutr 2009;90:1532–40. Dow SW, Fettman MJ, LeCouteur RA, et al. Potassium depletion in cats: renal and dietary influences. J Am Vet Med Assoc 1987;191:1569–75. Dow SW, Fettman MJ, Smith KR, et al. Effects of dietary acidification and potassium depletion o n acid base balance, mineral metabolism and renal function in adult cats. J Nutr 1990;120:569–78. Theisen SK, DiBartola SP, Radin MJ, et al. Muscle potassium content and potassium gluconate supplementation in normokalemic c ats with naturally occurring chronic renal failure. J Vet Intern Med 1997;11:212–7. Perez-Camargo G. Cat nutrition: what’s new in the old? Comp Cont Edu Small Anim Pract 2004;26(Suppl 2A):5–10. Harper EJ. Changing perspectives on aging and energy requirements: aging, body weight and body composition in humans, dogs and cats [expanded abstract]. J Nutr 1998;128:2627S–31S. Laflamme DP, Gunn-Moore D. Nutrition for aging cats. Vet Clin North Am Small Anim Pract 2014;44:761–74. Laflamme DP. Sarcopenia and weight loss in the geriatric cat. In: Little S, editor. August’s consultations in feline internal medicine, vol. 7. St Louis (MO): Elsevier; 2016. p. 951–6. Villaverde C, Fascetti AJ. Macronutrients in feline health. Vet Clin North Am Small Anim Pract 2014;44:699–717. Cupp CJ, Kerr WW. Effect of diet and body composition on life span in aging cats. In: Proceedings of the nestle Purina companion animal n utrition summit: focus on gerontology. St. Louis (MO): Nestle ́ Purina PetCare; 2010. p. 36–42. Freeman LM, Lachaud MP, Matthews S, et al. Evaluation of weight loss over time in cats with chronic kidney disease [Research report] [abstract]. J Vet Intern Med 2015;29:935. Wang XH, Mitch WE. Mechanisms of muscle wasting in chronic kidney disease. Nat Rev Nephrol 2014;10:504–16. Remer T. Influence of nutrition on acid-base balance – metabolic aspects. Eur J Nutr 2001;40:214–20.

302