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A Few of My Favorite Things for Cat Anesthesia and Analgesia … · 310 A Few of My Favorite Things...

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310 A Few of My Favorite Things for Cat Anesthesia and Analgesia Tamara Grubb, DVM, PhD, DACVAA Washington State University Pullman, WA These are a few of my favorite things. Some you will have, some you won’t, some might surprise you. The list encompasses equipment, drugs and techniques. Equipment and ‘stuff’ Esophageal stethoscope One of the least expensive pieces of equipment you can buy. More accurate for counting heart rate than the ECG monitor (sometimes the monitor doesn’t know which spikes to count on the ECG tracing) and more useful for indicating that the heart is actually beating (because sound = contraction/flow) than the ECG (electrical activity can occur without any cardiac function). Advantages: EASY, cheap. Can hook up to a speaker so everyone in the room can help monitor the patient. Disadvantages: MIGHT cause reflux esophagitis if inserted into the stomach; patient could bite it off if not removed before the patient wakes up. Source: Multiple companies Bain ‘block’ or ‘mount Block or mount for attachment of a pressure manometer and scavenging system to the rebreathing system. This allows the pressure generated by a delivered breath to be MEASURED, which decreases likelihood of barotrauma (pressure too high) or inadequate ventilation (pressure too low). Also decreases contamination of room with waste gas because of attachment to scavenging system. Source: Multiple companies ‘Pop-off’ occlusion valve (or ‘occlusion button’) Instead of completely closing the pop-off (or ‘pressure relief’) valve to give the patient a breath, just push this button for temporary closure of the valve. When you release the pressure on the button, the valve is automatically open. This prevents accidental prolonged closure of the valve – which can cause rapid pressurization of the breathing system and patient’s the airway. Over-pressurization can cause cardiovascular collapse, pulmonary barotrauma, and death in a very short time (minutes). Advantages: EASY, cheap. Can help to prevent a problem with dire consequences Disadvantages: Takes two hands to give a patient a breath (small price to pay for safety); some models supposedly leak inhalant anesthetic (might be due to failure to close all the way). Source: Multiple companies, eg, Surgivet and JD Medical. Anything to prevent hypothermia!!! Hypothermia develops rapidly in patients under anesthesia and causes a variety of complications including clotting dysfunction, increased risk of infection, tissue hypoxia, acidosis, abnormal cardiac electrical conduction, myocardial ischemia, etc... (Noble 2006). Hypothermia also causes cerebral effects that decrease the patient's anesthetic needs. Unfortunately, the decreased anesthetic need is not always recognized and the delivery of anesthesia is not changed, resulting in an over dosage of anesthetic drugs. Although shivering in recovery may increase the body temperature, the intensive muscle movements associated with shivering causes discomfort and increases oxygen consumption by as much as 200% (Sessler 2002). In fact, in human medicine, an active area of research centers on prevention of shivering in the postoperative period. Finally - and importantly - hypothermia is the main cause of prolonged recoveries from anesthesia, and most anesthetic deaths occur in recovery. Baja silver heat products These little ‘blankets’ are made from a ‘special, aluminum-coated reflective nonwoven material that bounces up to 80% of your patient’s radiant heat loss back towards the animal, providing what we like to call “patient-powered” warming’ (quoted from Baja website). Advantages: Easy to use; can use in places where you can’t plug in a warming blanket; really help maintain body temperature! Disadvantage: Also need active warming devices for most patients. TIP: Start warming as soon as patient is induced. Body temperature starts dropping (quickly!) at induction since muscles relax (muscle activity helps produce body heat) and the thermoregulatory system is ‘anesthetized’ along with the patient. Source: Animal Hospital Supply (animalhospitalsupply.com). Adapters for end-tidal carbon dioxide (ETCO2) monitoring in small patients The side-stream ETCO2 monitor often underestimates the true end-tidal CO2 value in small patients with high respiratory rates and low tidal volumes. By sampling lower in the airway, a more accurate value can be obtained. Advantages: EASY, cheap. Improves accuracy of respiratory monitoring.
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A Few of My Favorite Things for Cat Anesthesia and Analgesia Tamara Grubb, DVM, PhD, DACVAA

Washington State University Pullman, WA

These are a few of my favorite things. Some you will have, some you won’t, some might surprise you. The list encompasses equipment, drugs and techniques. Equipment and ‘stuff’

Esophageal stethoscope One of the least expensive pieces of equipment you can buy. More accurate for counting heart rate than the ECG monitor (sometimes the monitor doesn’t know which spikes to count on the ECG tracing) and more useful for indicating that the heart is actually beating (because sound = contraction/flow) than the ECG (electrical activity can occur without any cardiac function).

• Advantages: EASY, cheap. Can hook up to a speaker so everyone in the room can help monitor the patient. • Disadvantages: MIGHT cause reflux esophagitis if inserted into the stomach; patient could bite it off if not removed

before the patient wakes up. • Source: Multiple companies

Bain ‘block’ or ‘mount Block or mount for attachment of a pressure manometer and scavenging system to the rebreathing system. This allows the pressure generated by a delivered breath to be MEASURED, which decreases likelihood of barotrauma (pressure too high) or inadequate ventilation (pressure too low). Also decreases contamination of room with waste gas because of attachment to scavenging system.

• Source: Multiple companies ‘Pop-off’ occlusion valve (or ‘occlusion button’)

Instead of completely closing the pop-off (or ‘pressure relief’) valve to give the patient a breath, just push this button for temporary closure of the valve. When you release the pressure on the button, the valve is automatically open. This prevents accidental prolonged closure of the valve – which can cause rapid pressurization of the breathing system and patient’s the airway. Over-pressurization can cause cardiovascular collapse, pulmonary barotrauma, and death in a very short time (minutes).

• Advantages: EASY, cheap. Can help to prevent a problem with dire consequences • Disadvantages: Takes two hands to give a patient a breath (small price to pay for safety); some models supposedly leak

inhalant anesthetic (might be due to failure to close all the way). • Source: Multiple companies, eg, Surgivet and JD Medical.

Anything to prevent hypothermia!!! Hypothermia develops rapidly in patients under anesthesia and causes a variety of complications including clotting dysfunction, increased risk of infection, tissue hypoxia, acidosis, abnormal cardiac electrical conduction, myocardial ischemia, etc... (Noble 2006). Hypothermia also causes cerebral effects that decrease the patient's anesthetic needs. Unfortunately, the decreased anesthetic need is not always recognized and the delivery of anesthesia is not changed, resulting in an over dosage of anesthetic drugs. Although shivering in recovery may increase the body temperature, the intensive muscle movements associated with shivering causes discomfort and increases oxygen consumption by as much as 200% (Sessler 2002). In fact, in human medicine, an active area of research centers on prevention of shivering in the postoperative period. Finally - and importantly - hypothermia is the main cause of prolonged recoveries from anesthesia, and most anesthetic deaths occur in recovery.

Baja silver heat products These little ‘blankets’ are made from a ‘special, aluminum-coated reflective nonwoven material that bounces up to 80% of your patient’s radiant heat loss back towards the animal, providing what we like to call “patient-powered” warming’ (quoted from Baja website).

• Advantages: Easy to use; can use in places where you can’t plug in a warming blanket; really help maintain body temperature!

• Disadvantage: Also need active warming devices for most patients. • TIP: Start warming as soon as patient is induced. Body temperature starts dropping (quickly!) at induction since

muscles relax (muscle activity helps produce body heat) and the thermoregulatory system is ‘anesthetized’ along with the patient.

• Source: Animal Hospital Supply (animalhospitalsupply.com). Adapters for end-tidal carbon dioxide (ETCO2) monitoring in small patients

The side-stream ETCO2 monitor often underestimates the true end-tidal CO2 value in small patients with high respiratory rates and low tidal volumes. By sampling lower in the airway, a more accurate value can be obtained.

• Advantages: EASY, cheap. Improves accuracy of respiratory monitoring.

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• Disadvantages: You have to make the adapter so it is a little work;-). Occupies space in the ET tube so not recommended in REALLY small patients (anything that would need a size 3 or less ET tube).

• Source: You. • TIP: Make this little tool by placing a urinary catheter down into the endotracheal tube (not beyond the tip of the

endotracheal tube!) and sample gases from the catheter. • TIP: Another alternative is to use mainstream ETCO2 monitors, which are more expensive and more likely to be

damaged (because the sensor must be placed between the patient and the breathing system with each patient, rather than never handled because the sensor is in the machine [side stream monitors]) but will provide a more accurate ETCO2 reading in most patients. Mainstream monitors also increase deadspace and cause some rebreathing of exhaled gases. But they are excellent ETCO2 monitors!

Vetcorders One of the most convenient and progressive little monitors that we have ever used. It fits right at cage side (or on halter if you are out on a farm treating cats and someone asks you to look at their horse; -) ). Great technology in the unit and it both displays the data and transmits the data thru Bluetooth so you can monitor several patients at once from a location that isn’t right in front of the cage.

• Source: The company is www.sentierconnect.com, but several distributors also carry the monitor. Masimo pulse oximeters

These pulse oximeters perform better than most other pulse oximeters in low flow situations (hypothermia, shock) and in small patients. Also, which may prove useful when we learn to use it better is the pleth variability index (PVI), which can be used to guide fluid therapy in many Advantages: More likely to get a reading in low flow and small patients and can use to guide fluid therapy.

• Disadvantage: Expensive when compared to other pulse oximeters (but not necessarily expensive when compared to other monitors)

• Source: Massimo manufactures them but multiple companies carry them. Other stuff I like

Foam hair curlers as cat mouth gags We don’t use mouth gags for anesthesia but, of course, mouth gags are commonly used in anesthetized patients. Unfortunately, opening the mouth of a cat too wide causes decreased blood flow in the maxillary arteries (Martin-Flores et al. Vet J. 2014 Apr;200(1):60-4), which are the main blood source for the retinae and brain in the cat. The decreased blood flow secondary to mouth gag use has been implicated in blindness and neurologic deficits. These deficits may resolve, but may be permanent and may result in euthanasia (Stiles et al. Vet J. 2012;193(2): 367-73).

• Advantages: CHEAP! Doesn’t force the mouth open excessively wide. • Disadvantages: May not open the mouth wide enough for some procedures in the caudal oral cavity. Can still open the

mouth wider – but don’t leave it that way too long! • TIP: Curlers can be rinsed off and re-used but just throw them away if the cat’s mouth is particularly nasty or if the cat

has any communicable disease. They are cheap! • Source: Any place that sells foam curlers!

Syringe pumps or other volume-limiting devices I use these for administration of drugs (analgesic CRIs, dopamine, etc…) but just as often use them for delivery of IV fluids to cats. A great way to avoid under- or over-hydration (the latter is a fairly common problem in really small patients). Over-hydration can lead to edema in a variety of tissues, most notably pulmonary edema.

• Advantages: EASY to titrate drugs and fluids at an accurate dose. • Disadvantage: Some pumps are expensive; you have to learn to program them – which isn’t all that hard but is

something else to learn. • TIP: Have the technicians learn to program the pump and pretend you don’t know how so that you don’t have to do it;-

). The technicians will be the ones using it most often anyway. • TIP: If you don’t want syringe pumps, use buretrols (or any other fluid limiting device) when administering fluids to

really small patients. OR, my favorite, just pull up the amount of fluid that the patient needs over the expected surgery duration into a syringe and have the anesthetist titrate it in a couple of mls at a time while they are monitoring the patient. Not a continuous method of delivery but close enough to continuous, and avoids overhydration. So for example, a 3 kg cat that needs 5 ml/kg/hour IV fluids that will be anesthetized for 2 hours, we draw up 3 kg x 5 ml/kg/hr x 2 hours = 30 mls of fluid into a syringe.

• Source: Multiple companies

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Drugs and techniques Gabapentin

One of the best drugs for cats! Used for pre-visit calming (50-200 mg/cat 2 hours before leaving home for vet visit) and for treatment of chronic pain and any other pain syndrome that has a neuropathic component (nerve damage, etc…). The main adverse effect is sedation, although diarrhea and/or ataxia can occur (not common).

Although no research manuscripts are available regarding the use of gabapentin in cats for the treatment of chronic pain, this is a common recommendation:

• The dosage generally ranges from 1-10 mg/kg PO BID to QID but dosages as high as 50 mg/kg have been anecdotally reported.

• Generally, gabapentin therapy is initiated at 3-10 (depending on the level of pain and the health of the patient) mg/kg PO BID and dosages increased as necessary.

• Increase by about 25% every 3 days until the patient gets relief or gets sedate. IF THE PATIENT DOESN’T GET RELIEF OR SEDATION, YOU HAVEN’T REALLY TRIED GABAPENTIN!

• If the patient becomes sedate with the first 1-3 doses, decrease the dose and start again. Gradually increasing the dose over time often decreases the incidence of sedation.

• If the patient is to be removed from gabapentin therapy (eg, the patient is ‘cured’ or the gabapentin is not working), the drug should be gradually withdrawn over a period of one to three weeks (depending on the duration of therapy) to prevent rebound hyperalgesia.

• Source: Any pharmacy, most distributors Simbadol®

FDA-approved buprenorphine for CATS! The drug can be administered subcutaneously (SQ) and analgesia lasts 24 hours. Regular buprenorphine has really poor absorption when administered SQ and the compounded ‘extended release’ buprenorphine that supposedly lasts 72 hours has NO PHARMACOKINETIC DATA to support this claim. The duration of Simbadol is supported by FDA-approved data.

• Advantages: It’s buprenorphine – which we know and love in cats! PROVEN 24 hour duration. FDA approval. • Disadvantages: Label dose may be a bit high if you are using good multimodal analgesia (causes sedation). I routinely

decrease the dose by 25%. • Source: Zoetis Animal Health and distributors.

Alpha-2 agonists (medetomidine, dexmedetomidine) If you aren’t using these sedative-analgesic, reversible drugs, you are missing out on an excellent drug class! Especially in cats. The alpha-2 induced drop in heart rate is actually a good thing because it is a normal physiologic response to increased blood pressure – and maintenance of adequate blood pressure is extremely important. The pale mucous membranes are annoying but not indicative of trouble, it just so happens that the greatest concentration of alpha-2 receptors on vessels is in the periphery (including the mucous membranes) so the greatest vasoconstriction (and subsequent pale mucous membranes) are right where we want to assess patient color.

Dopamine Our patient population has changed over the last several decades from predominately young and healthy to more and more often aged or sick. These patients are more likely to experience adverse effects during anesthesia and one of the most common of those effects is hypotension. Of all of the drugs we use, the inhalants are one of the biggest contributors to hypotension. Fortunately, the effects are often dose-dependent so decreasing the anesthetic concentration generally improves blood pressure – at least in young, healthy patients. Older patients or patients with some concurrent diseases may be more susceptible to the inhalant-induced decrease in myocardial contractility, or may have disease that decreases contractility. In these patients, a positive inotropic drug like dopamine (or dobutamine) is the most effective and rapid way to improve blood pressure.

• Advantages: CHEAP, effective, easy to administer as an infusion. • Disadvantages: You have to make an infusion. • Source: Most pharmacies and distributors. • TIP: See infusion guidelines at the end of this document.

Ketamine Of course, ketamine is an old drug (over 50 years old!) and you probably already have it, but are you using it as a constant rate infusion (CRI)?

Painful impulses cause N-methyl-D-aspartate (NMDA) receptors (among others) in the dorsal horn of the spinal cord to depolarize and prolonged depolarization of these receptors can lead to an amplification of the pain stimulus, resulting in what we commonly refer to as central sensitization, 'wind-up' or 'hypersensitization'. When this occurs, the patient may feel more pain than expected (hyperalgesia) or even feel pain in response to a non-painful stimulus (allodynia). By administering drugs that antagonize these receptors (like ketamine), we are able to alleviate this exaggerated response and make the pain easier to control. The NMDA receptor

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antagonist effects are achieved when ketamine is used as a low-dose CRI. Ketamine must be administered in conjunction with true analgesic drugs (eg, opioids or NSAIDs).

• Advantages: CHEAP! Easy to use as an infusion, treats pain in a very unique way so great part of multimodal analgesia. • Disadvantages: Can cause dysphoria if the dose is too high; controlled drug – which is really just something to

remember, not a disadvantage. • Source: Multiple companies • TIP: See dosing charts at the end of this document.

Local/regional blocks If you aren’t doing local/regional analgesia, you are missing out on one of the best (but cheap!) analgesic modalities.

• Advantages: GREAT analgesia, easy, cheap, decreases chance of central sensitization • Disadvantages: Few adverse effects • Two of my favorite blocks in cats: Testicular block and sacro-coccygeal epidural

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Anesthesia Overview: Cat-Specific Maintenance and Recovery Drugs and Techniques

Tamara Grubb, DVM, PhD, DACVAA Washington State University

Pullman, WA

Maintenance • As with other species, inhalant anesthetic drugs are commonly used for procedures lasting > 30 mins.

o Isoflurane, sevoflurane, desflurane o Easily cleared from the body, minimal metabolism, easy to change anesthetic depth o Dose-dependent cardiovascular and respiratory depression

• Injectable drugs are also commonly used in cats for short procedures. These are often administered IM since really small cat veins can make IV injection difficult. Common protocols include:

o Ketamine + an opioid + an alpha-2 agonist Common combination: 0.1-0.2 MLS per 4.5 kg of cat of the following 3 drugs: dexmedetomidine,

ketamine, buprenorphine (or 10 mg/ml butorphanol). Combine all 3 drugs in same syringe and administer IM. Use low-end of dose for deep sedation and high-end for anesthesia. Increase or decrease the dose if cat is larger/smaller than roughly 4.5 kg. This combination (‘kitty magic’) takes effect in 5-10 mins and provides 20-30 mins of anesthesia.

o Telazol alone (not ideal – no sedation or analgesia) o Telazol + an opioid + an alpha-2 agonist

Common combination: Reconstitute the Telazol with 2.5 mls butorphanol (10 mg/ml) and 2.5 mls ketamine (sometimes called ‘TTDex’). Dose the combination at 0.005 mls/kg for mild sedation, 0.01 ml/kg for moderate sedation, 0.02 ml/kg for profound sedation and 0.035-0.04 ml/kg for surgical anesthesia (Ko and Berman. Top Comp Anim Med 2010;25(2):92-97.

• Analgesia o To decrease the dose-dependent impact on cardiovascular and respiratory function, keep the inhalant DOSE

LOW! The best way to do that is to use analgesia. Analgesic drugs/techniques commonly used during the maintenance phase of anesthesia include: Boluses of opioids or alpha-2 agonists Local anesthetic blocks Constant rate infusions (opioids, lidocaine, ketamine, alpha-2 agonists, combinations)

Monitoring Anesthesia causes depression of ALL organ systems

◦ CNS, cardiovascular & respiratory depression most immediately life threatening so our monitoring is focused on these systems

Monitor the basics ◦ MM color, CRT, jaw tone, body temperature, etc…

Use monitoring equipment Monitors & cat specific concerns ECG Can be hard to detect the small complexes. Increase the amplitude of the tracing.

Blood pressure - oscillometric Can be hard to get a reading. Blood pressure is the same as in the dog, but the really small vessels are hard to detect.

Blood pressure - Doppler Usually the best way to get a blood pressure reading in really small patients. Systolic blood pressure as determined by the Doppler may be closer to MAP than SAP in cats (Caulkett et al. Vet Surg 1998;27:370-377). WSU note: Assume it as systolic and carefully assess the cat. Treat if necessary.

SpO2 Great! But cats very likely to get cold (small body size) and vasoconstriction decreases likelihood of getting a reading.

ET CO2 Sidestream may provide average rather than true end-tidal reading in patients with small tidal volumes and high resp. rate.

Support – if it isn’t right – FIX IT! Hypotension (MAP<60 mmHG)

o Decrease the vaporizer setting.

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o Give a bolus of crystalloids or colloids. o Utilize positive inotropic drugs (eg, dopamine, dobutamine). o May need vasopressors (eg, norepinephrine, vasopressin)

Hypoventilation (ETCO2>45-50 mmHg) o Occurs more often than we think o Has many causes o Breathe for the patient!

Hypothermia o Start warming at induction. o ACTIVELY WARM the patient!!! o Minimize anesthesia time.

Cat specific support • Be careful with fluids!

o Administration of fluids was listed as a risk factor for anesthesia-related death (Brodbelt 2009). But it isn’t the fluid that kill cats – it’s the amount of fluid that kills cats!

o Calculate – and administer – the volume of fluids very carefully. Best to draw up the desired amount in a syringe vs trying to deliver a small volume from a fluid bag.

• Cats are very likely to be hypothermic – be aggressive with warming o Prevention easier than rewarming

o Temperature starts dropping AT INDUCTION o Forced air blanket most effective o Warm patient’s environment

o Surgery room, recovery cage, etc… o Use warm fluids, warm scrub solution (and MINIMAL scrub solution), warm lavage solution, etc… o MINIMIZE ANESTHESIA TIME

Recovery Most unexpected anesthetic deaths occur in recovery (Brodbelt D, Vet J 2009;182:152-161).

Timing of Death % of cats that died (number of cats)

After Premedication 1% (14) Induction 8% (53) Maintenance 30% (30) Recovery 61% (106) 0-3 hours after Recovery 66 total cats

We need to keep monitoring and supporting the patients until they are safely awake! MAKE SURE CATS ARE WARM!! Also need to address pain and dysphoria. A rough recovery is NOT acceptable. Think pain first and re-dose the opioids. May need to include a sedative. Alpha-2 agonists are excellent because they provide both sedation AND analgesia.

Of course, we can also reverse the effects of the reversible drugs if necessary – but be sure to address analgesia! Discharge drugs: NSAIDs, buprenorphine, maybe gabapentin or other drugs

Common anesthetic protocol examples

Healthy cat (ASA I-II) inhalant drug based protocol • Preanesthesia: 0.1mg/kg hydromorphone OR 0.2-0.3 mg/kg morphine IM PLUS 10-15 microg/kg of dexmedetomidine

OR 0.03-0.05 mg/kg acepromazine IM. Start NSAIDs now if appropriate. • Induction: Any of the injectable drugs are good choices • Maintenance: Isoflurane, sevoflurane or desflurane administered to effect; provide analgesia appropriate for the

procedure (local blocks, CRI, etc…); monitor and support • Recovery: Sedation and analgesia as indicated by the procedure and patient. Commonly, administer another bolus of the

opioid used for premedication +/- sedation if the patient is stressed or excited. Start or continue NSAIDs. Healthy cat (ASA I-II) injectable drug based protocol

• Preanesthesia: Any opioid at the appropriate dose PLUS 10 microg/kg dexmedetomidine PLUS 5-10 mg/kg ketamine all combined in the same syringe and administered IM. Start NSAIDs now if appropriate. Telazol protocols are also commonly used.

• Induction: The ketamine (or Telazol) in the combination listed above is the induction drug, if the patient is deeply sedated but not asleep, a bolus of any of the injectable drugs are good choices

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• Maintenance: The ketamine (or Telazol) in the combination listed above can be the maintenance drug for SHORT (eg, castration) procedures. If the anesthesia is inadequate or the procedure is prolonged, more ketamine can be administered IM or IV or an inhalant can be used. Isoflurane, sevoflurane or desflurane administered to effect; provide analgesia appropriate for the procedure (local blocks, CRI, etc…); monitor and support

• Recovery: Sedation and analgesia as indicated by the procedure and patient. Commonly, administer another bolus of the opioid used for premedication +/- sedation if the patient is stressed or excited. Start or continue NSAIDs.

ASA III cat • Preanesthesia: 0.1 mg/kg hydromorphone OR 0.1-0.2 mg/kg morphine IM. Opioids aren’t particularly sedating in cats

so probably need to add 0.2 mg/kg diazepam or midazolam (if very calm cat), 1-5 microg/kg dexmedetomidine or 0.01-0.02 mg/kg acepromazine IM (if anxious or stressed but not too sick cat) or 0.5-1.0 mg/kg alfaxalone (if really sick cat)

• Induction: Any of the injectable drugs are good choices. Propofol or alfaxalone would be ideal because they can most easily be titrated ‘to effect’.

• Maintenance: Isoflurane, sevoflurane or desflurane administered to effect; provide analgesia appropriate for the procedure (local blocks, CRI, etc…); monitor and support

• Recovery: Sedation and analgesia as indicated by the procedure and patient. Commonly, administer another bolus of the opioid used for premedication +/- sedation if the patient is stressed or excited. Continue support and monitoring for at least several hours. Start NSAIDs, if appropriate.

ASA IV-V cat • Preanesthesia: The patient should have a catheter in place and should be on IV fluids as part of stabilization.

Administer 2-5 microg/kg fentanyl through the catheter. IF NO CATHETER, try 0.2 mg/kg butorphanol (not great analgesia but decent sedation in these cats) PLUS 0.2 mg/kg diazepam or midazolam.

• Induction: Any of the injectable drugs are good choices and should be administered within 1-5 minutes of the premed fentanyl bolus. Can also administer 0.2 mg/kg diazepam or midazolam to decrease dose of induction drug. Some patients are sick enough that they can be intubated with the opioid and benzodiazepine alone. If not, propofol or alfaxalone would be ideal because they can most easily be titrated ‘to effect’.

• Maintenance: Isoflurane, sevoflurane or desflurane administered to effect – LOW DOSE; provide analgesia appropriate for the procedure (local blocks, CRI, etc…); monitor and support

• Recovery: Analgesia as indicated by the procedure and patient. Continue support and monitoring for as long as it takes to insure that the patient is stable. NSAIDs are generally not used in this category of patients because of the potential for NSAIDs to exacerbate disease effects (eg, renal compromise, GI ulceration, etc…).

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Anesthesia Overview: Cat-Specific Premedications, Sedatives, and Induction Drugs

Tamara Grubb, DVM, PhD, DACVAA Washington State University

Pullman, WA

Cats facts Often nervous or fractious

◦ Increased circulating catecholamines = Increased dose of anesthetic drugs required Small body size

◦ May be difficult to dose, to fit to monitoring & anesthetic equipment & to keep warm Species-specific drug metabolism

◦ May not metabolize drugs the same as dogs do (eg, NSAIDs) Species-specific response to drugs

◦ May respond differently than dogs do (eg, opioids) These differences add to the fact that cats are at higher risk than dogs for anesthesia-related deaths (risk factor of 0.11% vs 0.05%, respectively, in healthy patients and 1.33% vs 1.4%, respectively; Brodbelt 2009). Preanesthesia As with other species, patients should be stabilized prior to anesthesia and premedication should be utilized to improve the safety of anesthesia by allowing a decrease in the dosages of induction and maintenance drugs. Preoperative drugs or drug classes and key points Opioids Excellent choice for all cats. Moderate to profound analgesia, minimal adverse effects, reversible

effects. Many drug and delivery options.

Alpha-2 Agonists Excellent choice for many cats. Mild to profound sedation with analgesia. Effects are reversible. Contraindicated in some forms for cardiovascular disease, but may be beneficial in left ventricular outflow tract obstruction. Causes emesis.

Acepromazine Often a good choice. Provides 4-8 hours of light to moderate sedation, which is nice for many hospitalized cats. No analgesia, effects not reversible.

Benzodiazepines Minimal adverse effects, minimal sedation in young, active patients. Can be effective, especially when combined with an opioid, in very young/very old/sick cats. Midazolam would be the most likely benzo to be used as a premed since it can be administered IM.

Ketamine Often administered IM as part of an anesthetic protocol – so not really a premed but administered concurrently with premeds (usually dexmedetomidine and an opioid).

Alfaxalone Can be used at a low dose (0.5-1.0 mg/kg) IM for moderate sedation of 20-45 mins in very young/old or sick cats (in general, not enough sedation for healthy or excited cats). Better sedation when combined with an opioid.

Cat specific information on premedications

• Full opioid agonists (bind to mu and kappa) receptors are more likely to cause excitement in cats (and horses!) than in dogs (and ruminants!). This class of opioids may be used alone for premedication in some dogs but is almost always combined with a sedative in cats.

o Opioids (primarily full agonists) can cause hyperthermia in cats (Posner LP, et al.VAA 2010;37(1):35-43). The hyperthermia is usually mild and self-limiting but body temperature should be monitored postoperatively and any cat that seems agitated in recovery should be checked for hyperthermia.

• Buprenorphine and butorphanol are unlikely to cause excitement but also don’t provide analgesia as profound as that provided by the full agonists.

• Butorphanol only lasts about 90 minutes in the cat (Lascelles BD, Roberston SA. AJVR 2004;65(8):1085-1089); buprenorphine lasts 4-8 hours.

• Transmucosally administered buprenorphine (this is just the regular buprenorphine applied on the oral mucosa at the standard dose) is a great way to allow owners to provide analgesia for cats at home. Buprenorphine serum concentration after administration by this route was once thought to be equal to serum concentration after IV administration but this was because of a sampling error. In that study, blood from the jugular vein was analyzed for drug concentration. If a drug is administered for absorption from the oral mucosa, guess where it will be in the highest concentration – the jugular vein

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(Hedges AR, et al. J Vet Pharm Therap 2014;37(2):145-150)! So this route is still good, just not as brilliant as we thought it was.

• Simbadol® is buprenorphine in a higher concentration than regular buprenorphine that is FDA-approved for cats. It is labeled for subcutaneous administration (regular buprenorphine is very poorly absorbed after SQ administration) that provides analgesia for 24-hours. It is a DEA Class III drug, just like regular buprenorphine (which is not FDA-approved in animals).

• Dexmedetomidine (specifically Dexdomitor®) is one of the few drugs FDA-approved for use in cats. Alpha-2 agonists are one of my favorite drug classes in cats! They provide analgesia and a range of sedation levels (depending on the dose), can be administered IM and the effects are reversible with atipamezole. If you aren’t using alpha-2 agonists in cats, you are missing out on a great drug class!

• Alpha-2 agonist mediated vasoconstriction causes increased cardiac work, which is why these drugs are contraindicated in many types of cardiovascular disease. However, the slowed heart rate can be beneficial in relieving left ventricular outflow tract obstruction (Lamont et al. JAVMA 2002;221(9):1276-81).

• Alpha-2 agonist mediated bradycardia is a reflex that occurs secondary to vasoconstriction mediated hypertension. This allows decreased cardiac work and is a beneficial reflex. Don’t increase the heart rate unless the patient is bradycardic AND hypotensive!

• Midazolam can be administered IM (0.2 mg/kg) so is often included in premedication protocols for cats (or can be used as part of induction – see information in the induction section). The benzodiazepines are reversible with flumazenil.

• No cat-specific pros or cons for acepromazine used as a premedicant.

• No cat-specific pros or cons for anticholinergics used as premedicants. Atropine or glycopyrrolate should be used to treat/prevent vagally-mediated bradycardia.

• Should NSAIDs be administered to cats as premedications? Cats have pain of inflammation! But we do have to dose NSAIDs carefully. Both meloxicam and robenacoxib are approved for preoperative use in cats and NSAIDs are generally most effective if used preemptively. However, NAIDs block the prostaglandin effect of vasodilation that occurs in some organs (eg, kidneys) during states of low-flow. Cats seem to be more likely than dogs to suffer NSAID-related adverse renal effects so administration of NSAIDs postoperatively, after turning off the inhalant so hypotension is unlikely, is also a good option.

Induction drugs and key points Propofol Can easily be titrated ‘to effect’. Cleared by multiple routes. Causes mild to moderate dose-dependent

cardiovascular and respiratory depression. Can be administered with a benzodiazepine or ketamine (‘ketafol’) to further decrease the propofol dose.

Alfaxalone Can easily be titrated ‘to effect’. Cleared by multiple routes. Causes mild to moderate dose-dependent cardiovascular and respiratory depression. Can be administered with a benzodiazepine to further decrease the alfaxalone dose.

Ketamine Can be administered IM or IV. Minimal to no respiratory changes, provides mild to moderate increase in heart rate and blood pressure (through stimulation of the sympathetic nervous system). Cleared in part unchanged in the urine. MIGHT contribute to sympathetically-driven seizures or arrhythmias? No muscle relaxation, administer with a benzodiazepine or alpha-2 agonist. CRI for analgesia.

Telazol Physiologic effects similar to ketamine/benzo. Very potent, small volumes easy to dose – and to overdose if not careful.

Etomidate No cardiovascular changes – primarily used for patients with profound cardiovascular disease. Without appropriate level of sedation, can cause muscle fasciculations, paddling, vocalization, etc…

Inhalants Not the best idea for routine induction. Dose is very high. Staff are exposed to gases so human health concerns as well as cat health concerns.

Cat specific information on induction drugs

• Propofol causes Heinz bodies with repeat administration (meaning repeated over several days) and was once thought to be a limiting factor for propofol. However, the same thing happens with repeat dosages of ketamine (Bley CR, et al. JAVMA 2007;231(9):1347-53). Turns out it is probably just a cat response, maybe not so much a propofol problem.

• Propofol can be safely used in cats with hepatic lipidosis (Posner LP, et al. JAVMA 2008;232(12):1841-3), even though propofol itself is a lipid.

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• The preservative in the newer version of propofol (Propoflo28) is NOT toxic to cats (Taylor PM, et al. J Feline Med Surg 2012;14(8):516-26). This type of propofol is preferred to the old propofol because the preservative allows the bottle to be used for 28 days after opening whereas the old propofol without a preservative could only be used for 6 hours after opening. This propofol CAN BE USED IN CATS! It isn’t FDA approve in cats, but most drugs aren’t.

• REVIEW: Inhalant induction (mask or chamber induction) is a risk factor for anesthesia-related death and should NOT be the routine method of induction to anesthesia in cats (Brodbelt 2009).

After induction comes intubation. Cat specific information on intubation • Intubate carefully. • Apply a drop of lidocaine on each arytenoid. Cats are more prone than dogs to laryngospasm. The lidocaine reduces the

likelihood of laryngospasm. • Inserting an endotracheal tube was a risk factor for anesthesia-related death in cats (Brodbelt 2009) – but it isn’t the tube that

is a risk factor, it is poor intubation technique that is a risk factor. • Disconnect patients from breathing systems before repositioning them – especially cats. The twisting of the tube in the

trachea as the patient is repositioned can cause tracheal damage. • Don’t use a rigid mouth gag for intubation (or for dentistry, or anything else) in cats. These mouth gags cause excessive

opening of the mouth which can cause occlusion of the maxillary artery, which is the main source of blood supply to the retina and brain in cats (Martin-Flores M, et al. Vet J 2014;200:60-64). Occlusion of this artery secondary to mouth gag use has been linked to blindness and neurologic dysfunction, some of which led to euthanasia (Stiles J, et al. Vet J 2012: 2012;193(2): 367-73).

Common anesthetic protocol examples

Healthy cat (ASA I-II) inhalant drug based protocol • Preanesthesia: 0.1mg/kg hydromorphone OR 0.2-0.3 mg/kg morphine IM PLUS 10-15 microg/kg of dexmedetomidine

OR 0.03-0.05 mg/kg acepromazine IM. Start NSAIDs now if appropriate. • Induction: Any of the injectable drugs are good choices • Maintenance: Isoflurane, sevoflurane or desflurane administered to effect; provide analgesia appropriate for the

procedure (local blocks, CRI, etc…); monitor and support • Recovery: Sedation and analgesia as indicated by the procedure and patient. Commonly, administer another bolus of the

opioid used for premedication +/- sedation if the patient is stressed or excited. Start or continue NSAIDs. Healthy cat (ASA I-II) injectable drug based protocol

• Preanesthesia: Any opioid at the appropriate dose PLUS 10 microg/kg dexmedetomidine PLUS 5-10 mg/kg ketamine all combined in the same syringe and administered IM. Start NSAIDs now if appropriate. Telazol protocols are also commonly used.

• Induction: The ketamine (or Telazol) in the combination listed above is the induction drug, if the patient is deeply sedated but not asleep, a bolus of any of the injectable drugs are good choices

• Maintenance: The ketamine (or Telazol) in the combination listed above can be the maintenance drug for SHORT (eg, castration) procedures. If the anesthesia is inadequate or the procedure is prolonged, more ketamine can be administered IM or IV or an inhalant can be used. Isoflurane, sevoflurane or desflurane administered to effect; provide analgesia appropriate for the procedure (local blocks, CRI, etc…); monitor and support

• Recovery: Sedation and analgesia as indicated by the procedure and patient. Commonly, administer another bolus of the opioid used for premedication +/- sedation if the patient is stressed or excited. Start or continue NSAIDs.

ASA III cat • Preanesthesia: 0.1 mg/kg hydromorphone OR 0.1-0.2 mg/kg morphine IM. Opioids aren’t particularly sedating in cats

so probably need to add 0.2 mg/kg diazepam or midazolam (if very calm cat), 1-5 microg/kg dexmedetomidine or 0.01-0.02 mg/kg acepromazine IM (if anxious or stressed but not too sick cat) or 0.5-1.0 mg/kg alfaxalone (if really sick cat)

• Induction: Any of the injectable drugs are good choices. Propofol or alfaxalone would be ideal because they can most easily be titrated ‘to effect’.

• Maintenance: Isoflurane, sevoflurane or desflurane administered to effect; provide analgesia appropriate for the procedure (local blocks, CRI, etc…); monitor and support

• Recovery: Sedation and analgesia as indicated by the procedure and patient. Commonly, administer another bolus of the opioid used for premedication +/- sedation if the patient is stressed or excited. Continue support and monitoring for at least several hours. Start NSAIDs, if appropriate.

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ASA IV-V cat • Preanesthesia: The patient should have a catheter in place and should be on IV fluids as part of stabilization.

Administer 2-5 microg/kg fentanyl through the catheter. IF NO CATHETER, try 0.2 mg/kg butorphanol (not great analgesia but decent sedation in these cats) PLUS 0.2 mg/kg diazepam or midazolam.

• Induction: Any of the injectable drugs are good choices and should be administered within 1-5 minutes of the premed fentanyl bolus. Can also administer 0.2 mg/kg diazepam or midazolam to decrease dose of induction drug. Some patients are sick enough that they can be intubated with the opioid and benzodiazepine alone. If not, propofol or alfaxalone would be ideal because they can most easily be titrated ‘to effect’.

• Maintenance: Isoflurane, sevoflurane or desflurane administered to effect – LOW DOSE; provide analgesia appropriate for the procedure (local blocks, CRI, etc…); monitor and support

• Recovery: Analgesia as indicated by the procedure and patient. Continue support and monitoring for as long as it takes to insure that the patient is stable. NSAIDs are generally not used in this category of patients because of the potential for NSAIDs to exacerbate disease effects (eg, renal compromise, GI ulceration, etc…).

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Chronic Pain in Cats (Part 1): Why Must We Treat It? Where Do We Start?

Tamara Grubb, DVM, PhD, DACVAA Washington State University

Pullman, WA

Acute versus chronic pain Acute and chronic pain differ in ways other than their duration. Acute pain typically follows some tissue insult such as surgery or trauma and the pain resolves as the injury heals. Acute pain is called ‘protective pain’ because its role is to protect the patient from further tissue damage by limiting use of injured tissues. Acute pain tends to be responsive to treatment with conventional drug therapy including NSAIDs, alpha-2 agonists, and opioids. Chronic pain can exist after the original injury has healed as a result of pathophysiologic changes in the central nervous system. Since there is no longer an injury to ‘protect’, chronic pain serves to no purpose and is called ‘pathologic’ or ‘maladaptive’ pain. Chronic pain can be difficult to treat and poorly responsive to conventional analgesic therapy. Effective treatment may require multiple pharmacologic and non-pharmacologic treatment modalities (i.e., various analgesic drugs, acupuncture, massage, physical therapy, weight control, etc...). Left untreated, chronic pain causes a deterioration of the animal's quality of life and may result in adverse behavioral changes, including aggression.

As is the case in human medicine, osteoarthritis (OA) is the main cause of chronic pain in cats. Based on radiographic evidence, 22% of our general cat population (Godfrey DR. J Small Anim Pract. 2005;46(9):425-9) and 90% of cats over 12 years old (Hardie EM, et al. J Am Vet Med Assoc. 2002;220(5):628-32) may have OA.

Cancer is the second most common cause of chronic pain in animals. Although geriatric pets are most frequently affected, cancer can occur at any age. Patients will almost always require a multi-modal approach to pain therapy and may also require a variety of non-pharmacologic analgesic therapies (eg, acupuncture) as well as a number of analgesic adjunctive medications (e.g. NMDA antagonists). Neuropathic pain, a type of pain caused by a true lesion in the nervous system, is increasingly recognized in veterinary patients. Unfortunately, neuropathic pain can be extremely severe and is also quite difficult to control. Often there is no relief of neuropathic pain from traditional analgesic drugs like NSAIDs and opioids. Assessing chronic pain Cats are the masters at hiding pain. Well, cats are the masters at hiding in general, so why would pain be any different. There are a variety of mobility, postural and facial changes that often occur with chronic pain. Unlike dogs, mobility changes described as ‘lameness’ are not that common in cats but changes in how cats jump up or down or how cats traverse stairs can be indicative of pain. The most useful indicator of chronic pain is generally change in behavior. Examples include: previously friendly, gregarious cats that are now spending all of their time hiding; previously fastidious cats that have stopped grooming; cats with a favorite high-up perch that they no longer jump to; and cats that suddenly start urinating and defecating right outside the litter box. Of course, these can all be signs of other medical issues so a full medical assessment is necessary to rule in (or rule out) pain as the cause. The owners play a major role in assessing chronic pain since cats are much more likely to exhibit signs of pain at home than in the vet clinic. Table 1: Analgesic assessment for the owners of pets in chronic pain to fill in at home. (modified from ‘Pain Management for the Small Animal Practitioner’ by Tranquilli et al; published by Teton New Media, Jackson, WY)

DATE PAIN INTENSITY How bad was your pet’s pain today?

Severe Moderate Mild None

Severe Moderate Mild None

Severe Moderate Mild None

Severe Moderate Mild None

PAIN RELIEF How much pain relief was achieved by the medication?

Complete Good Moderate Slight None

Complete Good Moderate Slight None

Complete Good Moderate Slight None

Complete Good Moderate Slight None

SIDE EFFECTS Did the medication upset your pet in any way? Please describe.

Treatment of chronic pain As stated, treatment of chronic pain is not always easy and often requires a combination of therapies. This combination may include multiple pharmaceuticals, pharmaceuticals plus non-pharmacologic therapy (eg, acupuncture, massage, etc..) or both. Often, finding an effective treatment takes time and must proceed on a 'trial and error' basis. It is important to remember – and important to explain to

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the client - that chronic pain is a very individual disease and treatment protocols almost always require modification for each individual patient. Treatment of chronic pain is most effective when the clinic staff operates as a pain management team. However, a pain management strategy for treating chronic pain will not work unless the pet's owner is also a part of the team. The owner should be educated as to the underlying condition that causes pain, as well as to the effects and side effects of the analgesic therapy. Furthermore, the owner must be committed to long-term therapy and to assessing the extent of their pet's pain and relief of pain from analgesics. Various pain assessment forms are available for the owner to use at home and one is included in Table 1. Also, owners should be advised that adequate pain control involves more than just treatment of the pain itself. Weight loss is extremely important in overweight patients and alteration of the pet’s environment (eg, eliminate need for pet to climb stairs, cover slick floors with mats or rugs to provide better footing, etc…) and activity level (eg, more controlled activity like leash walking is often the best for a pet in pain) are often part of the treatment plan. Analgesic drugs A good review of the pharmacokinetics of oral analgesics used for the treatment of chronic pain in cats (and dogs) has been published (Kukanich B, Papich MG. Am J Vet Res. 2011;72(2):256-62.).

Multimodal therapy Effective treatment of moderate to severe chronic pain almost always requires multimodal therapy. What options are available when the patient is unable to take NSAIDS or, more commonly, when the pain advances to a pain state that is uncontrollable by NSAIDs used alone? In that instance, opioids, N-methyl-D-aspartate (NMDA) antagonists, and novel drugs like gabapentin should all be considered as potential therapies. In addition, non-pharmacologic therapies (eg, acupuncture, massage, physical therapy, TENS, etc…) should be strongly considered. Dosages for drugs used to treat chronic pain, along with considerations for the use of the drugs, are listed in Table 2 in the companion proceedings.

NSAIDs The non-steroidal anti-inflammatory drugs (NSAIDs) are among the few drugs available that actually treat the source of the pain (inflammation)

The meloxicam dose for chronic pain is 0.03-0.05 mg/kg/SID. This can be administered daily or less frequently, if possible. Dosages as low as 0.01 mg/kg/SID may be effective (Gunew MN, etl. J Feline Med Surg. 2008;10(3):235-41) and perhaps even beneficial – or at least not harmful - in some cats with chronic kidney disease (Gowan RA, et al. J Feline Med Surg. 2012;14(12):876-81; Gowan RA, et al. J Feline Med Surg. 2011;13(10):752-61). There are no studies on the use of robenacoxib for chronic pain but there is a published study reporting safety when the drug was used for 42 days (King JN, et al. J Vet Pharmacol Ther. 2012;35(3):290-300.). Anecdotally, the label dose is commonly used SID or less frequently for treatment of chronic pain in cats.

as well as the pain itself. Because of this impact on the pathology that is causing the pain, NSAIDs should be considered any time that pain of inflammation is present – and most of the pain we treat involves some degree of inflammation (eg, surgery, trauma, osteoarthritis, cancer, etc…). Good resource: ISFM and AAFP consensus guidelines: long-term use of NSAIDs in cats. Sparkes AH, et al. J Feline Med Surg. 2010 Jul;12(7):521-38. Although we don’t know everything about NSAIDs and cats, what we do know is that cats have pain of inflammation and NSAIDs are approved for use in cats.

Piprants Piprants are prostaglandin receptor antagonists and grapiprant is currently the only drug in this class.

Grapiprant antagonizes the EP4 receptor of PGE2. This receptor mediates pain and inflammation associated with OA. Because other prostaglandins are not blocked, those involved in homeostasis are not affected and the adverse effects commonly associated with traditional NSAIDs (eg, gastrointestinal upset & ulceration and renal & kidney damage) are minimal to nonexistent. At the time this manuscript was written, grapiprant was not yet FDA-approved in cats but a safety study has been published (Rausch-Derra LC, Rhodes L. Am J Vet Res. 2016;77(7):688-92.).

NOT DRUGS, but added early in treatment plan: Special diets, dietary supplements, nutraceuticals & other disease-modifying compounds

Most of the diets and food supplements are designed to modify the disease progression of OA and are thus called ‘disease modifying osteoarthritis agents’ (DMOAA). Because any improvement that does occur is fairly slow, these compounds should be used as adjunctive therapy to NSAIDs or other rapidly-acting, more potent analgesic drugs when pain is moderate to severe. There are diets and products with some efficacy data and these should be preferred over the many products with no data. Select oral glucosamine products have shown some efficacy, are safe and are easy to administer since most cats will eat them on some food. An injectable compound, Adequan®, is commonly used in cats at the same dose used in dogs. An advantage of this compound is that it can be administered SQ by the owner at home, which means that the cat is more likely to get treated since the cat doesn’t have to come to the hospital.

Gabapentin Gabapentin is commonly used to control seizures in both human and veterinary patients. In addition to the antiseizure activity, gabapentin has been shown to be effective in treating neuropathic pain. Neuropathic pain is pain from nervous system pathology and includes conditions that cause direct pathology of the nervous system (eg, herniated discs, nerve root tumors), pressure on nerves (eg,

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osteophytes near nerves) or nerve damage (eg, trauma, surgery – especially when large nerves are cut). In addition, the pathologic changes that occur in the pain pathway in response to chronic pain stimulation cause neuropathic pain. Although no research manuscripts are available regarding the use of gabapentin in cats for the treatment of chronic pain, many practitioners are using the drug for control of various pain syndromes. The dosage generally ranges from 1-10 mg/kg PO BID to QID but dosages as high as 50 mg/kg have been anecdotally reported. Generally, gabapentin therapy is initiated at 3-10 mg/kg PO BID and dosages increased as necessary. The most common side effect is sedation and the dose of gabapentin should be reduced in patients that become sedate. Gradually increasing the dose over time generally eliminates the chance of sedation. If the patient is to be removed from gabapentin therapy (eg, the patient is ‘cured’ or the gabapentin is not working), the drug should be gradually withdrawn over a period of one to three weeks (depending on the duration of therapy) to prevent rebound hyperalgesia. Gabapentin has a variety of uses in chronic pain and scenarios for addition of gabapentin should include:

• Patients with painful backs/necks • Any patient with known nerve damage • Patients with long standing chronic pain

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Chronic Pain in Cats (Part 2): Digging Deeper into Treatment

Tamara Grubb, DVM, PhD, DACVAA Washington State University

Pullman, WA

If NSAIDs, joint health modifiers and gabapentin aren’t controlling chronic pain in cats, keep digging! Opioids Buprenorphine (Class III) can be administered bucally for both acute and chronic pain in cats but new information has shown that absorption is not as good as was once thought (Giordano, et al. 2010), so recommended dosages have been increased for this route of delivery to 0.03-0.05 mg/kg BID-QID.

Tramadol is a centrally acting analgesic drug that is structurally related to both codeine and morphine and does have some opioid effects. However, tramadol also inhibits both serotonin and norepinephrine uptake. These varied activities are complementary and synergistic for analgesia and have led to the classification of tramadol as a ‘nontraditional centrally acting analgesic’. However, tramadol provides analgesia that is moderate at best and the drug should be used as part of a multimodal protocol rather than as a stand-alone drug. When compared to dogs, bioavailability was greater (93±7%) and the t½ was longer (204±8 mins) in cats following 5 mg/kg tramadol administered orally (Pypendop & Ilkew, 2008; Papich & Bledsoe, 2007). Cats also produced a significant concentration of the active M-1 metabolite, which also had a long t½. Thus, there are more opioid mediated effects, including analgesia and dysphoria, from administration of oral tramadol in cats. And cats vehemently resent the taste of tramadol! The tramadol dose in cats is 1-2 mg/kg BID. Amantadine Amantadine is an antiviral drug that also antagonizes the N-methyl-D-aspartate (NMDA) receptors, an action which prevents or reverses the development of central sensitization but does not provide direct analgesia. In humans, the NMDA-receptor antagonists are being extensively researched and have been used for treatment of acute, chronic and ‘specialized’ (eg, neuropathic and phantom limb) pain conditions. Newer NMDA-receptor antagonists (eg, memantine) are available in human medicine. The dose of amantadine is 5-7 mg/kg PO SID-BID for at least 3 weeks. Amantadine has a variety of uses in chronic pain and scenarios for addition of amantadine include:

• Anytime pain of ‘wind-up’ could be an issue • NSAIDs suddenly ‘not working’ after controlling pain long-term • Any long standing untreated pain • Moderate to severe cancer pain

Ketamine Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist and plays a role in both anesthesia & analgesia. Activation of the NMDA receptors in the dorsal horn of the spinal cord are, in large part, responsible for the pain of central sensitization (or ‘wind up). By antagonizing these receptors, the pain pathway can be returned to ‘normal’. Meaning that the patient may still feel pain (thus ketamine must be part of a multimodal protocol) but that the pain is not exaggerated and is more likely to be controlled by traditional analgesic drugs like NSAIDs and opioids. To achieve this effect, ketamine must be administered as an infusion. The analgesic effects in chronic pain have been well-documented in humans (Remerand et al. 2009; Sigtermans et al. 2009), although, as with any treatment of any chronic condition, a ketamine infusion does not always produce analgesia (Sen et al. 2009). This may be because the pain in those patients is not caused or augmented by central sensitization. In veterinary medicine, ketamine improved postoperative analgesia after forelimb amputation for up to 3 days (Wagner et al. 2002). There are no publications to guide ketamine infusions in cats but an infusion of 2-4 microg/kg/min is fairly common. The duration of the infusion is not known. Ideally, the infusion would be administered until the patient demonstrates decreased pain but this is unlikely to be practical. Anecdotal reports include everything from 2 to 24 hours but the common range is 2-6 hours. The infusion is repeated ‘as needed’ – generally every 30 days. As stated, this is part of a multimodal protocol and the goal is to return quality of life to the patient but not necessarily to eliminate any other analgesic therapies. Other drugs Because chronic pain is so difficult to treat, new drugs – or new applications for old drugs – are continually being investigated. Currently, other drugs to consider for treatment of chronic pain include antidepressant drugs (eg, the tricyclic antidepressants, SNRIs, SSRIs, etc.), bisphosphonates and newer generations of currently used drugs like pregabalin (newer generation of gabapentin) and tapentadol (newer generation of tramadol).

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Nonpharmacologic therapy Techniques reported useful for treatment of OA-mediated pain include everything from simple heat/cold therapy to more advanced techniques like physical therapy/rehabilitation, acupuncture and massage. In addition to the modalities just listed, modalities like therapeutic ultrasound, transcutaneous electrical nerve stimulation (TENS), pulsed radio frequency and low-level laser may all contribute to pain relief but, as with nutraceuticals, most of the evidence of efficacy is weak at best. However, physical therapy/rehabilitation and acupuncture have more positive evidence than the other modalities and many pain practitioners incorporate these techniques into their OA treatment plans. An advantage of the more simple nonpharmacologic therapies is that owners can often be trained to utilize basic techniques at home and the pet can then benefit from more consistent therapy. Owners can be taught to utilize ice packs, heat compresses, basic exercise and physical therapy maneuvers, basic massage, and acupressure. As stated with nutraceuticals, lack of evidence of efficacy does not mean that these treatment modalities are ineffective in all patients and the modalities should be considered as a viable part of multimodal analgesia, especially in patients where other therapies have failed, or as stand-alone treatment when pharmacologic therapy is inappropriate for the patient or when the nonpharmacologic therapy is effective when used alone. Conclusion Chronic pain can drastically alter a patient’s quality of life and can, unfortunately, be difficult to treat. In order to obtain adequate pain control, multimodal therapy should be utilized in every patient with moderate to severe pain. Also unfortunately, the number of drugs and techniques that are available to treat chronic pain is fairly limited and knowledge of the use of these drugs and techniques in cats is even more limited. However, because chronic pain is a major problem in human medicine as well as veterinary medicine, research into the relief of chronic pain is extensive. Hopefully, new drugs and techniques developed for humans will rapidly become available to our veterinary patients. Some common scenarios with treatment recommendations (see table for dosing info)

1. A cat with mild OA has been on an NSAID for an extended duration of time and the NSAID was controlling pain adequately until recently. Now, despite the fact that the disease doesn't seem to be worsening, the patient is fairly painful. Solution: Add amantadine to the current therapy. The most common explanation for this scenario is that the chronic stimulation of the NMDA receptors in the dorsal horn of the spinal cord has produced central sensitization. The NSAID should remain to treat the inflammatory component of OA.

2. A cat with moderate OA or cancer pain is painful even on an NSAID. Solution: Add gabapentin to the NSAID and send home tramadol (or another opioid), either on a continuous basis or an 'as needed' basis. The opioids in cancer patients are generally administered on a continuous basis. If this is a cat, consider using OTM buprenorphine as the opioid.

3. A cat with nerve injury is very painful but is not a candidate for surgery. Solution: Add gabapentin to the NSAID (or steroid) treatment and use tramadol (or another opioid) either as continuous therapy or on an 'as needed' basis. For severe pain, hospitalize the patient for several hours of a ketamine infusion.

4. A cat has pain of OA and elevated renal enzymes but the owner would like to try to improve the cat’s quality of life. Try a joint health modifier like Adequan or Cosequin. These are often very successful in cats. NSAIDs may also be appropriate as evidenced by cats with confirmed renal failure receiving meloxicam for chronic OA pain with no detrimental renal effects (Gowan et al 2012).

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Table 2: Dosages for drugs used to treat chronic pain in cats. Not all drugs / dosages are approved for use. PO=oral administration, SC=subcutaneous, IM=intramuscular, IV=intravenous. SID=once daily, BID=twice daily, TID=three times daily, QID=four times daily. Most dosages in this chart are from: Lascelles D, Robertson S. J Fel Med Surg 2010;12:200-212.

Drug Cat Dose Comments NSAIDs Most commonly used drug class for chronic pain. Meloxicam 0.1 mg/kg ONCE

followed by 0.05 mg/kg daily or less frequently

Dose at left is UK-labeled dose. The drug is often effective at dosages as low as 0.01 mg/kg OR at frequencies of every 2nd-3rd day. Titrate to lowest effective dose or longest effective dosing interval.

Robenacoxib 1-2 mg/kg daily or less frequently

There have been no studies evaluating long-term administration of robenacoxib but the dose at left is fairly commonly used. Titrate to lowest effective dose or longest effective dosing interval.

Opioids May cause constipation with chronic administration. Buprenorphine 0.01-0.03 mg/kg SC, IM,

IV, 0.01-0.05 buccal Used for both acute and chronic pain. May cause anorexia after several days at higher dosages. If this occurs, try decreasing the dose or increasing the dosing interval. May cause mild sedation or excitement.

Fentanyl, transdermal

2-5 ug/kg/hr Apply a 25 microg/hr patch to cats 3.5-5.5 kg. Provides 5-7 days of analgesia. May induce sedation or dysphoria. Use as part of multimodal therapy to decrease impact of varying drug levels that may occur.

Tramadol 1-2 mg/kg PO SID-TID Tramadol is an 'opioid like' drug that has other mechanisms of action. Best used as multimodal therapy with NSAIDs or other analgesic drugs. Cats may experience dysphoria. Cats HATE the taste of tramadol.

Other drugs Amantadine 2-5 mg/kg PO SID-BID Does not provide analgesia directly but helps prevent / treat wind-up due to

NMDA receptor antagonist activity. Use as part of a multimodal protocol. Only comes in 100 mg capsules, need compounding for cats.

Amitriptyline 0.5-2.0 mg/kg PO SID May provide mild analgesia. Administer as part of a multimodal protocol. Ketamine 2-4 microg/kg/min for

several hours. Optimal duration is of infusion is unknown.

Can be used to ‘break’ the cycle of severe pain. Does not provide analgesia directly but helps prevent / treat wind-up due to NMDA receptor antagonist activity. Use as part of a multimodal protocol.

Gabapentin 3-10 mg/kg PO BID-QID; up to 40 mg/kg (start with 3-10 mg/kg)

Effective for treatment of neuropathic pain, which can be a component of chronic pain through changes in the pain pathway. Best used as part of a multimodal protocol.

Joint Health Modifiers

May provide increased comfort level through improved joint health/function, some may have mild anti-inflammatory effects.

Glucosamine based products

Label dose Several products are manufactured specifically for cats. Many experts feel that these products are more effective in cats than in dogs. Use as part of a multimodal protocol.

Polysulfated Glycosaminoglycan (eg, Adequan)

5 mg/kg SC twice week x 4 weeks, then once a week for 4 weeks, then once monthly

Licensed by the FDA for control of OA pain in dogs (not licensed in cats). May provide some analgesia, use as part of a multimodal protocol.

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Don’t CRY, CRI: Constant Rate Infusions in Cats

Tamara Grubb, DVM, PhD, DACVAA Washington State University

Pullman, WA

Constant rate infusions (CRI) of analgesic drugs are an excellent way to manage pain in cats. A CRI of analgesic agents has several advantages over multiple repeated injections for pain relief, including:

1. A more stable plane of analgesia with less incidence of break-through pain (which can be difficult to treat); 2. A lower drug dosage delivered at any given time, resulting in a lower incidence of dose-related side effects; 3. Greater control over drug administration (easy to change the dose); 4. Decreased need for stimulation of resting patients to administer drugs; and 5. Decreased cost (when compared to technician time, needles and syringes required for repeat injections).

Drugs that are useful for CRIs include fentanyl, hydromorphone, morphine, methadone, butorphanol, ketamine, lidocaine and a myriad of combinations of these drugs. Dosages are available in the tables below. Opioids The opioid class of drugs includes some of the most potent analgesic drugs available and opioids should be considered for any patient experiencing moderate to severe pain. Opioids can cause excitement in cats. Fortunately, the low dose of opioids delivered in a CRI rarely results in sedation or excitement. However, if excitement does occur, a light dose of a sedative (eg, acepromazine or dexmedetomidine) can be administered to the cat and the CRI rate maintained (if excitement is mild) or reduced (if excitement is moderate). If sedation occurs, the dose of the CRI can be decreased. Fentanyl, hydromorphone, morphine and methadone are potent full agonist opioids that provide profound dose-related analgesia. These full agonists are the most commonly used opioids but butorphanol, an agonist-antagonist, has an advantage in that this drug is more likely to provide sedation than excitement in cats. However, butorphanol provides only moderate analgesia and has a ceiling effect for pain relief (ie, a point is reached where higher dosages result in more sedation but not more analgesia). Thus, butorphanol is only appropriate for short-term mild to moderate pain and should be used as part of a multi-modal protocol rather than as a sole agent. Lidocaine Lidocaine can be administered systemically to provide analgesia. In addition to pain relief, lidocaine CRIs are anti-inflammatory, antiarrhythmic and improve postoperative GI function (proven in humans and horses – work still to be done in small animals). The mechanism of action of systemic lidocaine is not entirely clear. Proposed mechanisms include blockade of sodium channels or potassium currents in the dorsal horn of the spinal cord and direct inhibition of abnormal electrical charges from injured or inflamed peripheral nerves. Lidocaine CRIs are controversial in cats because: 1) cats appear to be more sensitive to the lidocaine-induced side effects than other species are, and 2) there is evidence that lidocaine may cause excessive cardiovascular depression in cats. Point 1 is potentially (although not unequivocally) true and a lower dosage of lidocaine is recommended for cats. Point 2 is reported in anesthetized cats and the cardiovascular depression could result from a physiologic interaction between lidocaine and anesthetic agents. Also, some argue that lidocaine CRI has been used successfully for anti-arrhythmic therapy in cats without undue cardiovascular depression and should be appropriate for analgesia, especially since the dose for analgesic therapy is actually on the low end of the dose used for anti-arrhythmic therapy. Because of the uncertainty of lidocaine effects in cats, some veterinarians feel that lidocaine CRI is not warranted in the cat at all while others feel that it is an appropriate means to treat pain, especially in patients where other options may be limited. If lidocaine CRI is chosen, using low dosages in conscious cats (ie, not under anesthesia) is recommended. Ketamine Painful impulses cause N-methyl-D-aspartate (NMDA) receptors (among others) in the dorsal horn of the spinal cord to depolarize and prolonged depolarization of these receptors can lead to an amplification of the pain stimulus, resulting in what we commonly refer to as 'wind-up' or 'hypersenstization', and technically called ‘central sensitization’. When this occurs, the patient may feel more pain than expected (hyperalgesia) or even feel pain in response to a non-painful stimulus (allodynia). By administering drugs that antagonize these receptors (like ketamine), we are able to alleviate this exaggerated response and make the pain easier to control. Ketamine is the NMDA-receptor antagonist most commonly used in veterinary medicine and NMDA receptor antagonist effects are achieved when ketamine is used as a low-dose CRI. A single high-dose bolus of ketamine (eg, like the anesthetic induction dose) can serve as a loading dose for a CRI but is unlikely to provide analgesia when used alone. Furthermore, the NMDA receptor antagonists strictly mediate central sensitization and do not provide true analgesia, thus, these drugs must be administered in conjunction with true analgesic drugs (eg, opioids or NSAIDs).

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Alpha-2 agonists Alpha-2 agonists provide both sedation and analgesia and the effects are reversible. Sedation is only minimal when using the CRI but the light level of sedation makes this CRI excellent for patients that are excited or distressed. The alpha-2 agonists are generally added to an opioid CRI (or any other CRI) at the same dosage as that listed in the table for solo use. Combinations of opioids, ketamine, and (possibly) lidocaine CRIs that include multiple drugs are often more effective than CRIs of single drugs because the effects of analgesic agents from different drug classes are generally additive or synergistic. Combinations include opioids + ketamine or opioids + ketamine + lidocaine. However, infusions of a single drug are also effective, especially if the patient is receiving other drugs (eg, NSAIDs and/or local anesthetic via tissue blockade) and the choice of multiple or single drug infusions is more personal preference than science. Calculations of CRI dosages Generally, dosing tables or individualized spread sheets (eg, there are very useful spreadsheets available at multiple websites, including one of my favorites at www.vasg.org

• A = desired dose in microg/kg/min

) should be used for constant rate infusions. These sheets greatly improve the speed at which CRIs can be initiated and greatly decrease the chance of mathematical errors. However, CRI dosages can also be easily calculated using the formula:

• B = body wt in kg • C = Diluent volume in mls • D = Desired fluid rate in mls/hr • E = Drug concentration in mg/ml

A x B x C x 60 / D x E x 1000 = mls of drug to add to diluent NOTE: If the dose at A is in mg/kg/hr, the two conversion factors in the formula (60 in the numerator and 1000 in the

denominator) should be removed from the formula and the mg/kg/hr dose be used instead of the microg/kg/min dose. Loading doses Administering loading doses of the drugs to be infused is important since the loading dose provides a rapid increase in the serum concentration of the drug. The serum concentration of the drug will slowly increase with the infusion, but this may delay time to onset of analgesia. A separate loading dose for opioids may not be necessary if an opioid was used as a premedicant and a separate loading dose for ketamine may not be necessary if ketamine was used as the induction drug. However, if a long delay (>30 mins) occurred between administration of the opioid and/or ketamine and the start of the infusion, repeat the loading dose. The loading dosages are very low and extremely unlikely to cause adverse effects so, if in doubt, re-dose. When to start/stop Start as soon as possible! As soon as a painful patient has an IV catheter in place, consider a CRI. For patients with pain from trauma (eg, hit-by-car or attacks from other animals) or medical conditions (eg, pancreatitis), pain relief is a component of stabilization and infusions can be started immediately after triage. For patients undergoing surgery, start the infusion prior to anesthesia if possible since pre-emptive analgesia is more effective than analgesia that is administered after pain has started. Often surgical patients do not have an IV catheter prior to induction so for these patients, start right after induction or when the patient has been moved into the operating room. Infusions can be started postoperatively if the need for an infusion was not recognized until the postoperative period. It is never too late to start! However, infusions should be started pre- or intra-operatively whenever possible so that the patient can benefit from infusion-delivered intraoperative analgesia and infusion-mediated decreases in the dosage of inhalant drugs necessary to keep the patient anesthetized.

The infusion can be stopped at the end of surgery if appropriate on-going analgesia (eg, NSAIDs, local blocks, etc….) has been administered, or the infusion can be continued for several hours, overnight, or even several days. The infusion duration should be based on the continued analgesic need of the patient. Patients with severe medical (eg, from pancreatitis) or trauma pain often remain on infusions for several days. If the analgesic level of the patient is questionable, the infusion can be slowly weaned off by cutting the dose in half every 1-2 hours and carefully assessing the patient for pain. Summary Constant rate infusions are extremely easy to use and extremely beneficial to the patient. A variety of drugs can be used in the CRI and drug choice should be based not only on what is best for the patient (eg, analgesic potency and safety) but also on what is best for the hospital (eg, comfort level with and availability of drugs). Because calculating CRI dosages can be cumbersome, math is often the only limitation to using these valuable tools. Thus, rather than calculating drug dosages for each CRI, a 'cheat sheet' or computer program is recommended.

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Table 1: Dosages for constant rate infusions (CRIs) used in cats Drug Loading Dose CRI dose Quick Calculation Comments Morphine (M)* 0.10 mg/kg IM 0.03 mg/kg/hr

(0.5 mic/kg/min) Add 15 mg to 500 ml fluid & run at 1 ml/kg/hr

Cat may need light sedation; can be combined with K &/or L

Hydromorphone (H) 0.025 mg/kg IV 0.01 mg/kg/hr Add 5 mg to 500 ml fluid & run at 1 ml/kg/hr

May cause hyperthermia; can be combined with K &/or L

Fentanyl (F) 0.001-0.003 mg/kg IM or IV (1-5 mic/kg IV)

0.002-0.005 mg/kg/h (0.03-0.08 mic/ kg/m) post-op 0.005-0.02 mg/kg/h (0.08-0.3 mic/ kg/m intra-op

For 0.005 mg/kg/h, add 2.5 mg to 500 ml fluid & run at 1 ml/kg/hr

2.5 mg=50 ml F, remove 50 ml LRS before adding F; can be combined with K &/or L.

Methadone 0.1-0.2 mg/kg IV 0.12 mg/kg/hr Add 60 mg to 500 ml fluid & run at 1 ml/kg/hr

MAY cause sedation; can be combined with K &/or L.

Butorphanol 0.1 mg/kg IV 0.1-0.2 mg/kg/hr

Add 50 mg to 500 ml fluid & run at 1 ml/kg/hr for 0.1 mg/kg/hr

Only moderately potent & has ceiling effect - use as part of multimodal protocol

Ketamine (K)* 0.25-0.5 mg/kg IV 0.12-0.6 mg/kg/hr (2 -10 mic/kg/ min)

Add 60 mg to 500 ml fluid & run at 1 ml/kg/hr for 0.12 mg/kg/hr

Generally combined with opioids; may cause dysphoria

Lidocaine (L) 0.25 mg/kg IV 1.5 mg/kg/hr (25 mic/kg/min) Some sources recommend no more than 10 mic/kg/min in cats

Add 750 mg to 500 ml fluid & run at 1 ml/kg/hr 10 mic/kg/min would be 300 mg lidocaine in 500 ml fluid with a rate of 1 ml/kg/hr

750 mg=37.5 ml, remove 37.5 ml LRS before adding L; can be combined with opioid &/or K; Lidocaine MAY be contraindicated in the cat due to cardiovascular effects.

Medetomidine (Med) or Dexmedetomi-dine(D)

1-5 mic/kg Med 1-2 mic/kg D Can be IV or IM May not be necessary

0.001-0.004 mg/kg/hr Med (1-4 mic/kg/hr) 0.0005-0.002 mg/kg/hr D

Add 500 mic Med or 250 mic D (0.5 ml of either) to 500 ml fluid and run 1-4 ml/kg/ hr

Provides analgesia and light sedation. Excellent addition to opioid CRI, or can be administered as solo drug CRI.

Morphine* / Ketamine*

M: 0.10 mg/kg IM K: 0.25-0.5 mg/kg IV

0.03 mg/kg/hr M & 0.12 mg/kg/hr K

Add 15 mg M & 60mg K to 500 ml fluid & run at 1 ml/kg/hr

Can be administered up to 3 ml/kg/hr but dysphoria MAY occur. Can substitute, F, or methadone for M.

Morphine / Ketamine / Lidocaine (MLK)

M: 0.10 mg/kg IM K: 0.25-0.5 mg/kg IV L: 0.25 mg/kg IV

0.03 mg/kg/hr M, 0.12 mg/kg/hr K; 1.5 mg/kg/hr L

Add 15 mg of M, 60 mg K and 750 mg (or 300 mg) L to 500 ml fluid & run at 1 ml/kg/hr

Can substitute H, F or methadone for M.

*Any of the drug amounts in the bag of fluids can be decreased and the fluids administered at a higher rate if necessary. For example, for morphine, ketamine and morphine/ketamine infusions, 7.5 mg of morphine & 30 mg of ketamine can be used and the CRI administered at 2 ml/kg/hr if more fluids are needed.

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Everything You Need to Know About Opioids in Cats Tamara Grubb, DVM, PhD, DACVAA

Washington State University Pullman, WA

The opioid class of drugs includes some of the most potent analgesic drugs available in medicine. Opioids bind to stereospecific presynaptic and postsynaptic opioid receptors, primarily mu and kappa receptors, that are located in the central and peripheral nervous systems. Opioids provide analgesia primarily by decreasing the release of excitatory neurotransmitters presynaptically and inhibition of evoked activity postsynaptically. These effects occur mainly through an increase in potassium conduction (causing hyperpolarization), calcium channel inactivation, or both. Opioids can be used to treat both chronic and acute pain. Opioids can be administered by a wide variety of routes including IV (as boluses or infusions), IM, SQ, PO, transdermally, intra-articularly and perineurally as part of local blockade. Opioids are a very safe class of drugs with adverse effects that are more annoying than truly problematic. If anything bad does happen, the adverse effects of opioids are reversible. If the patient doesn’t respond well, administer an opioid antagonist. However, the analgesia will also be reversed so other analgesic drug classes should be used. Also, butorphanol is an agonist-antagonist and can be used to reverse the mu-mediated effects while allowing the kappa-mediated effects to remain. Kappa-receptor mediated analgesia is not as potent as mu-receptor mediated analgesia so, again, analgesia may need to be provided using other drug classes.

The opioids most commonly used in veterinary medicine fall under the ‘full’ agonist category (morphine, hydromorphone, fentanyl, oxymorphone, methadone), ‘partial’ agonist category (buprenorphine) or ‘agonist-antagonist’ category (butorphanol). Full opioid agonists activate both mu and kappa receptors, thereby providing the most profound analgesia but also the highest likelihood of adverse effects (although it is important to remember here that the adverse effects are not generally clinically significant). In cats, morphine, hydromorphone, oxymorphone and methadone produce analgesia that begins roughly 1-5 minutes after IV injection or 5-10 minutes after IM injection. The duration of analgesia is approximately 2-4 hours, depending on the dose of the drug and the intensity of the pain. These opioids can be administered by a wide variety of routes. Morphine is the prototypical opioid against which all other opioids are measured. Morphine is less effective in cats than in some other species since cats don’t make much of the main intermediate metabolite that is responsible for a portion of the morphine-mediated analgesia (morphine-6-glucuronide. However, it is a myth that morphine is not effective in cats. It is also a myth that morphine cannot be administered IV because it causes histamine release. The drug can indeed cause histamine release if administered rapidly IV, but this is not likely to occur when the drug is administered slowly.

Hydromorphone is one of the most commonly used opioids in cats but has been implicated in causing hyperthermia. However, several opioids (and ketamine) all caused some degree (usually mild and self-limiting) of hyperthermia in cats (Posner et al., VAA 2010;37:35-43), but hydromorphone may contribute more than other opioids (Wegner & Robertson, VAA 2007;34(2):132-138). However, it is a misconception that hydromorphone is contraindicated in cats and many cats receive hydromorphone without complications. Oxymorphone is very similar to morphine and hydromorphone but is less popular than the other two opioids because of its higher cost and fluctuating availability. Methadone is the most commonly used full opioid agonist in Europe but is less popular in the US due to its higher cost. However, the high cost is minimal in cat-sized doses and methadone does have some advantages over the other full mu opioids. Methadone has a higher bioavailability when administered buccally than morphine, hydromorphone or oxymorphone (Pypendop BH, Ilkiw JE, Shilo-Benjamini Y. J Vet Pharmacol Ther. 2014;37(3):295-300). Methadone has some N-methyl-D-aspartate antagonist activity which could lead to anti-hyperalgesic properties. Of the full mu opioids listed here, methadone is the least likely to cause vomiting.

Fentanyl is 80x more potent than morphine, is even less likely to cause adverse effects than the opioids just listed, has a short duration of action (20-30 minutes from a single bolus) and is highly lipid soluble so it is absorbed across the skin. Fentanyl can be administered as a bolus for a short boost in analgesia or as part of an anesthetic induction protocol, as a constant rate infusion, or as a transdermal patch or transdermal solution. Fentanyl is my favorite opioid in critical patients & cats love fentanyl!

Buprenorphine is a partial agonist at the mu receptors (thus evokes only a ‘partial’ response) and an antagonist at the kappa receptors, thus the analgesia provided is not as profound as that provided by the full agonist opioids. Buprenorphine has a slow onset of action (10-30 minutes) regardless of the route of administration and a long duration of action (4-6 for moderate pain – longer for mild pain). Buprenorphine binds tightly to opioid receptors and is difficult to reverse but, fortunately, reversal is rarely necessary since buprenorphine is the least likely of the listed opioids to cause adverse effects. The most effective dose is 0.02-0.04 mg/kg IM or IV Steagall PV, et al. J Vet Intern Med. 2014;28(3):762-70). Buprenorphine administered buccally or ‘oral transmucosally (OTM; this is just the regular buprenorphine applied on the oral mucosa at the standard dose) is a great way to allow owners to provide analgesia for cats at home. Buprenorphine serum concentration after administration by this route is not quite as good as once thought (Hedges AR, et al. J Vet Pharm Therap 2014;37(2):145-150) so don’t be afraid to increase the dose if the cat is still painful. We routinely use 0.03-0.05 mg/kg by this rouge. Simbadol® is buprenorphine in a higher concentration than regular buprenorphine that is FDA-approved for

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cats. It is labeled for subcutaneous administration (regular buprenorphine is very poorly absorbed after SQ administration) that provides analgesia for 24-hours. It is a DEA Class III drug, just like regular buprenorphine (which is not FDA-approved in animals). When using multimodal analgesia, Simbadol may cause sedation in cats. We routinely add the drug to our protocols but decrease the dose by 25%.

Butorphanol is an agonist at the kappa receptors and an antagonist at the mu receptors. Butorphanol produces moderate sedation and analgesia of about 90 minutes duration in the cat (Lascelles BD, Robertson SA. Am J Vet Res. 2004;65(8):1085-9). This duration is not adequate for most surgical procedures.

Tramadol does have some opioid effects and is also a norepinephrine and serotonin reuptake inhibitor. When compared to dogs, bioavailability was greater (93±7%) and the t½ was longer (204±8 mins) in cats following 5 mg/kg tramadol administered orally (Pypendop & Ilkew, 2008; Papich & Bledsoe, 2007). Cats also produced a significant concentration of the active M-1 metabolite, which also had a long t½. Thus, there are more opioid mediated effects, including analgesia and dysphoria, from administration of oral tramadol in cats. But dysphoria occurs fairly commonly and cats vehemently resent the taste of tramadol! Opioid myths Myth: The adverse effects of opioids preclude their use in many patients. Not true! The primary adverse effects of the opioids include nausea, vomiting, slowing of GI motility, constipation, dysphoria, pruritis and respiratory depression. The actual incidence of clinically significant adverse effects is highly overstated. Nausea and vomiting are common but short-lived and not likely to occur in painful patients. Thus, patients premedicated with opioids are likely to vomit but patients treated with opioids post-operatively or post-trauma are highly unlikely to vomit. Slowing of gastrointestinal (GI) motility may occur, but slowed motility is not the same as ileus and the occurrence of ileus is rare. Furthermore, moderate to profound pain causes sympathetic overdrive, which can itself cause slowing of GI motility. Constipation may occur with opioids used for chronic pain but unlikely to occur with acute use. If using opioids for chronic pain, increase the fiber in the patient’s diet.

Myth: Opioids cause profound respiratory depression. Not true! In animals, the respiratory depression caused by opioids is minimal and is generally related to the degree of sedation and to the adverse effects of concurrently administered drugs. Thus, respiratory depression may occur in patients under general anesthesia since the inhalants are also respiratory depressants. However, the dose-sparing effects of the opioids will allow a reduction in the dose of isoflurane, which is a more potent respiratory depressant than the opioids. In conscious patients, the respiratory depression is rarely clinically significant.

Myth: Opioids cannot be used in horses and cats because they cause profound excitement. It is true that this can happen, but it usually means that the opioids weren’t used at the right dose in the right patient. Nonpainful horses and cats can experience excitement but excitement is extremely uncommon in painful patients. Since much of the research was done in nonpainful patients, the literature is replete with frightening reports of cat and horse excitement following opioid administration. In truth, cats and horses respond very well to post-operative or post-trauma opioids. And pre-operative opioids can be administered with a tranquilizer to alleviate excitement.

Opioid infusion dosages for cats

Drug Loading Dose CRI dose Quick Calculation Comments Morphine (M)* 0.10 mg/kg IM 0.03 mg/kg/hr

(0.5 mic/kg/min) Add 15 mg to 500 ml fluid & run at 1 ml/kg/hr

Cat may need light sedation; can be combined with K &/or L

Hydromorphone (H)

0.025 mg/kg IV 0.01 mg/kg/hr Add 5 mg to 500 ml fluid & run at 1 ml/kg/hr

May cause hyperthermia; can be combined with K &/or L

Fentanyl (F) 0.001-0.003 mg/kg IM or IV (1-5 mic/kg IV)

0.002-0.005 mg/kg/h (0.03-0.08 mic/ kg/m) post-op 0.005-0.02 mg/kg/h (0.08-0.3 mic/ kg/m intra-op

For 0.005 mg/kg/h, add 2.5 mg to 500 ml fluid & run at 1 ml/kg/hr

2.5 mg=50 ml F, remove 50 ml LRS before adding F; can be combined with K &/or L.

Methadone 0.1-0.2 mg/kg IV 0.12 mg/kg/hr Add 60 mg to 500 ml fluid & run at 1 ml/kg/hr

MAY cause sedation; can be combined with K &/or L.

Butorphanol 0.1 mg/kg IV 0.1-0.2 mg/kg/hr

Add 50 mg to 500 ml fluid & run at 1 ml/kg/hr for 0.1

Only moderately potent & has ceiling effect - use as part of multimodal protocol

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mg/kg/hr Dosages of opioids used to treat acute pain in cats

Opioid Analgesia Onset / Duration

Cat Dose in mg/kg unless otherwise indicated

Comments and Adverse Effects

Morphine 10mg/mL

Profound analgesia; Full mu and kappa opioid receptor agonists; all are DEA Class II opioids

1-5 mins IV or 10-20 mins IM / 2-4 hours

0.1-0.3 IM or slowly IV

Adverse effects are minimal; nonpainful animals may vomit following IM injection; May cause histamine release if administered fast IV; May cause excitement in cats – use with a tranquilizer; inexpensive.

Hydromorphone 2mg/mL

Similar to morphine

Cat: 0.1 IM or IV

Similar to morphine but no histamine release. May cause hyperthermia in cats, especially at doses >0.1 mg/kg; inexpensive.

Methadone 10mg/mL

Similar to morphine

0.2-0.4 mg/kg IV; 0.2-0.6 IM Cat: 0.6 mg/kg oral transmucosal (OTM).

Similar to morphine but no histamine release and little to no vomiting; is also an N-methyl-D-aspartate antagonist but clinical significance is not known; EXPENSIVE

Fentanyl 50mcg/mL

More potent than the drugs listed above; mu and kappa agonist; DEA Class II

<1-2 min / 20-30 minutes

1-5 micrograms/kg IV, Can administer up to 20 microg/kg. Most commonly used as a CRI. Typical starting dose for CRI: 0.2 microg/kg/min, loading dose 1-2 microg/kg (if needed)

Less likely to cause adverse effects than other full opioid agonists; Duration of action is short so most commonly used as bolus for brief painful stimulus, as an infusion or in a transdermal patch; moderately expensive.

Butorphanol 10mg/mL

Moderate analgesia; kappa agonist, mu antagonist; DEA Class IV opioid

3-5 mins IV or 5-15 mins IM /20- 90 minutes

0.2-0.4 mg/kg IM or IV

SHORT DURATION OF ACTION; Decent sedative, especially if combined with a tranquilizer; same adverse effects as other opioids but effects are generally mild; Unlikely to cause excitement; moderately expensive.

Buprenorphine 0.3mg/mL

Moderate analgesia; partial mu agonist; DEA Class III opioid

10-30 mins / 4-8 hours, depending on pain intensity & dose

0.02-0.04 mg/kg IM, IV; 0.03-0.05 mg/kg BID-TID for oral transmucosal (OTM) . Simbadol is an FDA-approved buprenorphine for cats only that provides analgesia for 24-hrs. Use 75% of label dose (0.24 mg/kg) if using good multimodal analgesia.

Long duration of action but slow onset of action and minimal to no sedation; same adverse effects as other opioids but effects are generally mild or nonexistent; moderately expensive. Commonly used transmucosally to administer postop at home or for chronic pain in cats.

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Local Anesthetic Blocks for Cats: Stop Pain in its Tracks Tamara Grubb, DVM, PhD, DACVAA

Washington State University Pullman, WA

Local anesthetic drugs are extremely effective, inexpensive and easy to use. When local anesthetic drugs are administered, pain impulses originating in the periphery are blocked and prevented from reaching the central nervous system. This blockade has several positive consequences:

• The sensation of pain is alleviated or even eliminated for the duration of the block. Local anesthetic drugs work by blocking sodium channels in nerve membranes. Decreased permeability to sodium slows the rate of depolarization so that the threshold potential is not achieved and an action potential is not propagated, thus the pain impulse is not propagated. Local anesthetics bind more readily to ‘open’ channels, thus rapidly firing nerves are more susceptible to blockade.

• The analgesia allows the patient to be maintained under a lighter plane of anesthesia and this makes the anesthetic episode safer for the patient. In fact, local anesthetic drugs decrease the minimum alveolar concentration (MAC) of all anesthetic gases.

• The likelihood that ‘wind-up’ or hypersensitization will occur is greatly decreased because the portion of the pain pathway called ‘transmission’ is blocked. Transmission involves the conductance of pain impulses from the peripheral nociceptors to the dorsal horn neurons in the spinal cord. The neurons in the dorsal horn are responsible for central sensitization. By blocking input to these neurons, central sensitization (or ‘wind up’) is less likely to occur.

Furthermore, local anesthetic blocks are extremely cost effective and can increase profits to the clinic. Commonly used local anesthetic drugs in veterinary medicine include

• Lidocaine o Onset of action: rapid; approximately 1-2 mins (less than 5 minutes) o Duration of action: 60-120 minutes o CAT DOSE: 2-4 mg/kg

• Bupivacaine o Onset of action: approximately 5-10 minutes (up to 20 minutes) o Duration of action: 4 to 6 hours o CAT DOSE: 1 mg/kg

• Mepivacaine o Onset of action: 2-5 minutes (up to 10 minutes) o Duration of action: 2-3 hours o CAT DOSE: 2-3 mg/kg

• Nocita (liposome-encapsulated bupivacaine) o Onset of action: within 30 minutes o Duration of action: 72 hours o CAT DOSE: 5.3 mg/kg (0.4 ml/kg)

Adverse events caused by local anesthetic drugs • Adverse events are extremely rare but can include any of the following: • Local tissue effects – swelling, bleeding, inflammation, ‘tingling’? (unknown if this occurs in animals) • Anaphylaxis – rare, more common with esters (but still rare) • Central nervous system – muscle tremors, seizure, coma

• At lower concentrations, depression of inhibitory neurons occurs and can cause cerebral excitation, which may lead to seizures. At higher concentrations, profound CNS depression with subsequent coma, respiratory arrest and death can occur. The latter is more likely following IV boluses of large doses.

• Cardiovascular system – the myocardial conduction system is sensitive to local anesthetics and IV boluses can result in cardiovascular collapse. ONLY LIDOCAINE CAN BE ADMINISTERED IV.

• Methemoglobinemia – rare, but can occur in cats.

Commonly used local anesthetic blocks in veterinary medicine For many of the blocks listed below, a suggested volume of drug is listed based on the amount of drug that can physically be injected into the site. However, with all blocks, the total dose that the patient can receive should be calculated and the cumulative dose (add up the dose or volume injected for each block) should not exceed this total dose.

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A. General blocks • ‘Field’ block (also called incisional block or line block)

o Blocking the ‘field’ of surgery. Local anesthetic drugs can be administered around the incision or directly into the incision. It is NOT true that lidocaine in an incision causes a delay in healing.

• Indwelling catheter block (long duration field block) o Indwelling, or ‘soaker’, catheters should be considered for large wounds or incisions that may be difficult to block or

that may require continuous or intermittent delivery of drug for several days. The catheters can be buried in or near incisions and local anesthetic infused through the catheter to provide more

long-term analgesia. Very useful for surgeries with large incisions, eg: amputations, mastectomies, etc… Local anesthetic drugs can be infused via a pump or administered by intermittent injection (eg, q 6-8 hour

injections of bupivacaine at 1-2 mg/kg). The catheter is generally removed in 48-96 hours but can be left in longer.

B. Blocks on the Head • Oral blocks

Blocks listed below will cause unilateral desensitization from the site of injection rostrally to midline. o Maxillary or infraorbital nerve block – cranial approach

The infraorbital nerve exits the infraorbital foramen, which can be palpated as a depression in the buccal mucosa dorsal to the root of the maxillary 3rd premolar (just cranial to the root of the 4th premolar or carnassial tooth in the area where the gingiva on the maxillary bone and the gingiva on the lip join together).

Block the nerve by injecting local anesthetic under the gingiva just rostral to the foramen or insert JUST THE TIP of the needle into the infraorbital canal and inject. Injecting into the foramen insures more caudal spread of the block but is not necessary if the oral surgery site is rostral to the foramen. Also, the foramen can be difficult to locate or to enter in some cats & infusion rostral to the canal is still useful as there will be some caudal migration of the local anesthetic into the canal.

A vessel runs with this nerve so aspirate, then slowly infuse drug Volume that can be injected is approximately 0.1 ml in an average-sized cat.

o Mandibular nerve block

The mandibular foramen or the mandibular nerve can often be palpated on the lingual side of the mandible just rostral to the angle of the mandible and just caudal to the last molar in approximately the middle 1/3rd of the mandible (as measured from top to bottom).

Regardless of whether or not the nerve or foramen can be palpated (often difficult to palpate in very small patients), the landmarks described above will be utilized for deposition of local anesthetic drug.

The nerve ENTERS the mandible at the mandibular foramen and cannot be blocked between the mandibular foramen and the mental foramen.

Intraoral technique: • With the patient’s mouth supported in the open position (ie, use a mouth gag, roll of tape or some other

method to ensure that the patient doesn’t close its mouth while your hand is in the oral cavity), direct the tip of the needle to the site described above. o REMEMBER: Rigid mouth gags should NOT be used in cats. They can cause occlusion of the

maxillary artery with resultant blindness and/or neurologic complications. • Aspirate, then slowly infiltrate (0.2 mls in the average sized cat). The foramen cannot be entered so the

drug is merely infused under the gingiva at the site of the nerve. Extraoral technique:

• Landmarks are the same as those described above but the approach is from the outside, through the skin at the angle of the mandible.

• Pass the needle through the skin along the medial aspect of the mandible to a point where the tip of the needle is at the site of the foramen (again, aiming for a site just caudal to the last molar on the lingual side of the mandible).

This technique is easier than the intraoral technique in cats.

• With a finger in the oral cavity the needle can be felt under the gingiva. • When the site near the mandibular foramen is reached, aspirate and inject the local anesthetic drug (0.2

mls in the average sized cat). C. Blocks of the thorax, abdomen and genital-urinary system • Testicular block

o Isolate the body of the testicles o Inject lidocaine or bupivacaine into the body of the testicle until you feel ‘pressure’ or until the ‘dose’ (see below) has

been injected The drug will migrate up the spermatic cord.

o The dose will be volume limited due to the size of the testicular tissue

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Calculate 1 mg/kg bupivacaine or 4 mg/kg lidocaine and the volume that will ‘fit’ is about ½ of the calculated volume

This will generally be 0.1-0.2 mls per testicle in the average sized cat o For an incision directly over the testicle (cats), continue infiltrating as the needle exits the testicular body to block the

skin and subcutaneous tissue. • Ovarian block or peritoneal ‘block’

o The mesovarium can be infiltrated with lidocaine. o The volume will be about 0.5 mls per side in a cat o Elevate ovary, infiltrate mesovarium, elevate opposite ovary, infiltrate mesovarium, remove first ovary, remove the

second ovary and proceed with the ovariohysterectomy.

o Alternatively, the peritoneal cavity can be ‘bathed’ with local anesthetic. After completing the OHE, dilute 2-4 mg/kg lidocaine OR 1-2 mg/kg bupivacaine to 2-3 times the volume with

sterile saline and ‘bathe’ the peritoneal cavity with the mixture by instilling it into the abdomen. Close the incision as usual.

• Lumbosacral epidural analgesia o Opioids are most commonly used but local anesthetic drugs can be used in conjunction with opioids.

0.1 mg/kg morphine (preservative-free is gold standard but morphine with preservative is commonly used in veterinary medicine)

Dilute to 1 ml/4.5 kg with bupivacaine, sterile saline or sterile water o Provides up to 24 hours of analgesia with little to no systemic effects. The opioids will cause sensory blockade but will

not cause motor blockade. The local anesthetics can cause motor blockade, however, the motor effects are generally minimal or absent by the time the patient recovers from anesthesia to the point that it is ambulatory.

o Consider for any pain in caudal half of patient. Examples include, rear limb soft tissue or orthopedic surgery, abdominal exploratory and bladder surgeries, surgeries on the tail or perineal region, etc…

o Technique: Place the anesthetized patient in sternal or lateral recumbency

o Legs can be placed forward or to the back. I prefer forward in cats. Locate the wings of the ilium and palpate the lumbo-sacral (LS) space (almost directly in line with the wings

of the ilium on the mid-line). Clip and scrub this region. Wear gloves and use a small drape or glove wrapper. Insert an epidural needle into the caudal portion of the LS site with the needle angled at approximately 45o

from vertical. Slowly advance the needle until the epidural space is entered.

o ‘Hanging’ drop often works (aspiration of fluid in the hub of the needle as the epidural space is entered).

o Several ‘pops’ will be felt. o ‘Walking off’ the bone is the most definitive determination of proper placement of the needle in

between vertebrae. STOP as soon as the space is entered and slowly inject the drug.

o The drug should inject easily if the needle is in a space. o Stop injecting and take your thumb off the plunger. the fluid should momentarily

continue to flow if the tip of the needle is in the epidural space. This is the most definitive determination that the needle is in the lumbosacral space.

o If the drug does not inject easily, back up a VERY tiny amount and try again. Once drug has been injected, remove needle and proceed with surgery.

o If local anesthetic drugs have been used, may want to lay patient with surgical side down for about 5 minutes.

Opioid epidurals do NOT affect motor function of the rear limb or diaphragm. Local anesthetic drugs can affect motor function but rarely do (volumes that are described here do not migrate far enough cranially to affect the diaphragm so ventilation is not impaired).

o Complications include ineffective or incomplete block (by far the most common complication), epidural hematoma or abscess, hyperalgesia (VERY rare). Contraindications include bleeding disorders (to prevent hematomas) and skin disease over the LS space (to prevent abscesses). Abnormal pelvic anatomy (either from congenital lesions or trauma) may make epidurals difficult.

• Sacrococcygeal or intercoccygeal epidural o This block is often used to provide analgesia for tail amputations, perineal urethrostomies, and placement of urinary

bladder catheters for urethral obstructions. o Move the tail up and down in a ‘pumping’ motion while palpating the sacrococcygeal region of the patient. The first

movable space at the caudal end of the sacrum is either the sacrococcygeal or intercoccygeal space. Either site is appropriate for injection.

o Insert a 22-G needle through the skin ON MIDLINE at a 45-degree angle to the skin surface.

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o Proceed slowly until needle enters the space (generally hit bone and ‘walk off’ the bone). o Hanging drop technique often works. Should have no resistance on injection. o Use lidocaine for rapid onset (0.1-0.2 ml/kg 2% lidocaine), can add an opioid (same as for lumbosacral epidural) for

long-term analgesia. Don’t inject air, air bubble may cause incomplete block since this is a very small space. • Intercostal block

o Inject local anesthetic in the tissues caudal to the proximal portion of the ribs. Inject local anesthetic in 2-3 rib spaces in front of and 2-3 rib spaces behind the area that needs to be desensitized.

D. Blocks of the limbs • Metacarpals/metatarsals/digits block

o Four different ways to block Three point (or four point)

• Locate the carpus and the accessory carpal pad • Inject 0.1-0.3 mls subcutaneously at three sites: • 1) medial to the accessory carpal pad (blocks median nerve and palmar branch of the ulnar nerve); • 2) lateral and proximal to the accessory carpal pad (blocks dorsal branch of the ulnar nerve); and • ) on the dorsal-medial portion of the carpus (blocks superficial branches of the radial nerve).

Ring block • Similar to three-point block but use a subcutaneous ‘line’ of local anesthetic all the way across the

dorsum of the paw and another ‘line’ all the way across the ventrum of the paw just above the location of the accessory carpal pad to provide a ‘ring’ of local anesthesia that desensitizes the nerves described above.

Interdigit or ‘digital’ block • Block between each toe

‘Splash block’ • ‘Splash’ local anesthetic into incision • Not as effective as other methods

• Brachial plexus block Locate the point of the shoulder, the first rib and the transverse processes of the cervical vertebrae. Insert a 2-3-inch needle (an epidural needle will work) at the point of the shoulder to the point where the tip of the

needle is even with the first rib. Keep the needle horizontal during placement so that the tip does not enter the thoracic cavity.

Aspirate, then inject 1/3 of the local anesthetic (1 mg/kg bupivacaine) diluted with saline to a total 1 ml solution per 4.5 kg body weight) at this site, slowly withdraw the needle to the middle of the area to be blocked, aspirate and inject 1/3 of the local anesthetic. Withdraw the needle to a site just before it exits the skin, aspirate and inject the remaining 1/3 of the local anesthetic.

D. Other uses of local anesthetic drugs • Lidocaine patches have been used over incisions or painful cutaneous lesions in veterinary patients. In humans, lidocaine

patches are used for deeper muscle pain and they may be effective for this type of pain in our patients too. But our patients would likely have to be shaved to get patch contact with the skin and this isn’t usually practical. Uptake from lidocaine patches is slow, resulting in low plasma concentrations, and appear to be safe in cats (Ko et al. J Vet Pharmacol Ther. 2008;31(4):359-67).

• There are a variety of creams & gels that may or may not work. Some of the local anesthetic creams work on the skin if they are placed on the skin and covered with a bandage for 30-45 minutes. These can be used to desensitize the skin for IV catheter placement. Lidocaine gel (you can make your own by just mixing some lidocaine into sterile lubricant) is an excellent lubricant for passing a urinary catheter.

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Feline Eosinophilic Granuloma Complex Edmund Rosser, DVM, DACVD

Michigan State University Lansing, MI

Three reactions: Eosinophilic Ulcer, Eosinophilic Plaque, and Linear Granulomas (may occur in various combinations)

This also represents a symptom response in cats and is NOTMany etiologies believed to be contributory: FeLV, FIV, FIP, allergy (atopic dermatitis, food allergy, flea allergy dermatitis),

insect bite hypersensitivity (mosquitoes), bacteria, genetic predisposition.

a specific disease entity.

Eosinophilic ulcer (indolent ulcer, rodent ulcer, lip ulcer)

Etiology Symptom of an underlying allergic disease - food allergy, atopic dermatitis, flea allergy dermatitis; Occasionally responsive to systemic antibiotics or alpha interferon (latent viral infection, herpes or calici virus); Chronic forms of this reaction have been observed in FIP and FeLV positive cats.

Clinical features Reddish brown erosion or ulcer, slightly raised, with a well-demarcated border; Usually unilateral on upper lip (may be multiple and affect upper and lower lips, nose, periorbital area, and oral mucosa or any combination); Non-painful and non-pruritic; Can be severely erosive lesions; Hemogram normal; Watch progression; may change to squamous cell carcinoma or a plasma cell ulcerative dermatitis.

Diagnosis • History and physical exam • Histopathology: true ulcer, and perivascular infiltration of neutrophils, lymphocytes, plasma cells and fibroblasts. Very

nonspecific • In-vitro serum testing (ELISA tests) for allergen-specific IgE to aeroallergens and insects (not Intradermal testing) • Hypoallergenic diet trials • Response to antibiotics • FeLV tests, FIP titer, PCR for herpes, calici virus isolation • Pedigree review • Macerated tissue culture • True ulcer, not associated with blood eosinophilia and not a granuloma.

Treatment Identify and treat any underlying problem

Herpes or calici viral associated • Pure lysine granules (78.8% lysine) - ¼ teaspoon (~570 mg) q12h for life; L-lysine tablets (no propylene glycol!) - 250-

500 mg/cat for life; L-lysine gel or powder (VIRALYS™) - 250 mg/cat for life • Imiquimod (Aldara®) 5% cream – 3 times weekly • Alpha interferon - 30-1000 units orally SID • Famciclovir (Famvir®) – 90 mg/kg TID

Underlying allergic diseases • Flea treatment protocol • Allergen-specific immunotherapy (ASIT) • Hypoallergenic treatment diets

Systemic antibiotics Cephadroxil - 22 mg/kg BID x 30 days, Trimethoprim/Sulfadiazine - 30 mg/kg BID x 30 days, Amoxicillin/Clavulanic Acid - 12.5 mg/kg BID x 30 days

Corticosteroids Methylprednisolone acetate (DepoMedrol®): 10-15 mg/cat IM or SQ Prednisolone - 1 mg/kg BID to induce remission; decrease to lowest alternate day dose (or eliminate, if possible)

Progesterones Only if the above treatments have failed - Megestrol acetate (Ovaban®): 2.5-5 mg/cat q 48 h to induce remission, then reduce to every 3-7 days to maintain; Repositol progesterone 2-20 mg/kg IM or SQ; lasts 4-6 weeks; Medroxyprogesterone acetate 50-175 mg/cat; lasts 4-6 weeks

Side Effects - Polyuria, polydipsia, polyphagia, Diabetes mellitus, Pituitary-adrenal suppression, Iatrogenic Cushing’s disease, Mood alteration, weight gain, Pyometra, mammary gland hyperplasia/neoplasia, Decreased libido, infertility in males.

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Omega 3 and 6 fatty acids As last resort, try 0.5 cc triamcinolone/lesion (Vetalog®), 6 mg/ml concentration, intralesionally

Cyclosporine 7 mg/kg SID Eosinophilic plaque

Etiology See eosinophilic ulcer (esp. Flea allergy, food allergy, and atopic dermatitis)

Clinical features Raised, well-circumscribed, plaque-like lesions which are frequently moist and erythematous; Found most commonly on abdomen and medial thighs; Single or multiple; often symmetrical; Associated with excessive licking; controversy exists as to which came first.

Diagnosis • History and physical examination • Histopathology: spongiosis, epidermal hyperplasia, intraepidermal microvesicles with eosinophils and perivascular or

diffuse dermal infiltration of eosinophils and mast cells. • Hemogram commonly shows eosinophilia. • In-vitro serum testing (ELISA tests) for allergen-specific IgE to aeroallergens and insects (not Intradermal testing),

hypoallergenic diet trials, response to antibiotics • FeLV and FIV tests, FIP titer • True plaque: associated with tissue and blood eosinophilia; not a true granuloma.

Treatment See eosinophilic ulcer.

Collagenolytic Granuloma – now called “Feline Eosinophilic Dermatoses (Linear Granuloma, Eosinophilic Granuloma) Etiology

• See eosinophilic ulcer • Has been associated with an insect bite hypersensitivity reaction (mosquitoes) on a seasonal basis • Food allergy associated

Clinical features – 3 forms 2 Cutaneous forms

• Bridge of nose and pinnae

- Has been associated with an insect bite hypersensitivity; Skin test positive for mosquito allergen; Responded to use of insect repellant Caudal or medial thigh most common

Oral form

- Can affect the lip, chin, foot pads; Etiology unknown; Linear, sharply demarcated, raised, firm plaques or nodules; “Linear Granuloma”; Yellowish-pink coloration; Non-pruritic and non-painful

Raised, firm, yellowish-pink focal nodule, plaque or cauliflower-like lesion (not linear); Usually seen on lower lip, tongue, gingiva and palate; Asymptomatic in that there is no licking, pain or excess salivation; Possible association with “Food Allergy”.

Diagnosis • History and physical examination • Histopathology: nodular to diffuse granulomatous inflammation with degeneration of collagen (collagenolysis, flame

figures) • In-vitro serum testing (ELISA tests) for allergen-specific IgE to aeroallergens and insects (not Intradermal testing),

hypoallergenic diet trials, response to antibiotics • FeLV tests, FIP titers

Treatment - see eosinophilic ulcer

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Feline Paraneoplastic Alopecia and Feline Thymoma-Associated Exfoliative Dermatitis

Edmund Rosser, DVM, DACVD Michigan State University

Lansing, MI

Feline paraneoplastic alopecia Introduction and etiology

Feline Paraneoplastic Alopecia is a relatively rare skin disease observed primarily in geriatric cats. The vast majority of affected cats have a pancreatic carcinoma of either acinar cell or pancreatic duct origin. It has also been reported in 2 cats with a bile duct adenocarcinoma.

Clinical presentation The first clinical sign is alopecia that occurs acutely with a rapid progression affecting the ventrum and legs in geriatric cats with the ears and periorbital regions occasionally affected as well. The hair is easily epilated and there are usually focal areas of erythema and scaling and the skin has a distinctly moist and shiny appearance. When the footpads are affected they appear shiny and smooth with scaling, crusts, and occasional fissures with lameness. A secondary Malassezia dermatitis may develop in some cases. In addition, affected cats are lethargic, anorectic, and have some weight loss.

Diagnosis Skin biopsies have characteristic changes as a marker for this systemic disease and include: telogen hair follicles with marked atrophy and miniaturization (so-called “faded follicles”); areas of predominantly hypokeratosis with focal areas of epidermal hyperplasia, and parakeratotic and orthokeratotic hyperkeratosis. Abdominal ultrasound and screening for metastasis (especially to the liver or lungs) should be performed as the prognosis for most cats with this disease is grave, with metastasis already present at the time of the initial diagnosis.

Management To date there are only 2 reported cases with a non-metastatic and localized pancreatic tumor that regrew hair and were doing well 10 weeks following a partial pancreatectomy, however one of these cats re-developed the alopecia 18 weeks later and metastasis was confirmed at necropsy. Feline thymoma-associated exfoliative dermatitis

Introduction and etiology Feline Thymoma-associated Exfoliative Dermatitis is a relatively rare skin disease observed primarily in middle-aged to older cats. All cases reported to date have a thymoma, and it is believed that this induces autoreactive T-cells that subsequently migrate to the skin, causing the skin lesions.

Clinical presentation Erythema, exfoliation, and marked scaling are followed by alopecia initially affecting the head, neck and pinnae. As the disease progresses, there are very large, adherent scales affecting most of the cat’s hair coat. In most cases, the skin lesions are the only clinical signs, however in advanced cases there may be coughing, dyspnea, anorexia, and lethargy.

Diagnosis Skin biopsies have characteristic changes suggestive of this systemic disease and include: hyperkeratosis with follicular and epidermal apoptotic cells; lymphocytic, hydropic, interface dermatitis extending to the isthmus of the hair follicles; pigmentary incontinence. Radiographs and/or ultrasound of the thorax reveals the presence of a mediastinal mass.

Management As most all thymomas in cats reported to date have been benign, early surgical excision can be curative. In one reported case in the cat, myasthenia gravis developed as a post-operative complication.

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Update on the Diagnosis and Long Term Management of Food Allergy in the Cat

Edmund Rosser, DVM, DACVD Michigan State University

Lansing, MI

Prospective clinical evaluation of food allergic cats • Previous recommendation of a 3 week elimination diet trial was empirical • Initial recommendation in this study was to feed a home-cooked restricted diet for 60 days • In several instances the results were equivocal after 60 days and the diet was fed an additional 30 days.

Data collected

• Time elapsed before maximal clinical response on diet • Time elapsed before return of initial clinical signs when fed previous diet • Age, breed, sex, clinical signs • Responsiveness to glucocorticoids • Concurrent disease conditions • Final treatment diets

Diets fed

• Formulated based on known past exposure • Avoided any previously consumed foods • Consisted of home cooked foods • Protein sources - rabbit, venison, lamb, duck, goose, ostrich, emu • Carbohydrate source - green peas, rarely

rice or potatoes

Results • Time elapsed before maximal clinical response • 1-3 weeks - 4 cats; 4-6 weeks - 7 cats; 7 weeks - 1 cat; 9 weeks - 1 cat; Recent date – diet trials x 12 weeks • Time elapsed before return of initial clinical signs • 15-30 minutes - 2 cats; 24 hours - 2 cats; 2-3 days - 4 cats; 6-8 days - 4 cats; 10 days - 1 cat; Recent data – feed previous

diet x 14 days “Why all the fuss about home-cooked elimination diets?” Rosser EJ: Food Allergy in the Cat: A Prospective Study of 13 Cats. Advances in Veterinary Dermatology, vol 2:33-39, 1993.

13 food allergic cats confirmed over a 4-year time while being fed a home-cooked elimination diet for 10 weeks 3 week trial only adequate for 30% of cats

Serologic test for food-specific IgE and/or intradermal testing for foods in cats? Belova S, et al: Factors Affecting Allergen-specific IgE Serum Levels in Cats. The Canadian Veterinary Journal, vol 76:45-51, 2012

Both false positives and false negatives occur! Ishida R, et al: Lymphocyte Blastogenic Responses to Food Antigens in Cats Showing Symptoms of Food Hypersensitivity.

Journal of Veterinary Medical Science, vol 74(6):821-825, 2012. Suggests a Delayed, Type IV Hypersensitivity Intradermal testing in cats Austel M, Hensel P, et al: Evaluation of three different histamine concentrations in intradermal testing of normal cats and attempted determination of “irritant” threshold concentrations for 48 allergens. Veterinary Dermatology, 17; 189-194, 2006.

“Irritant” reactive threshold was > 4000 PNU for most all aeroallergens > 10% of cats positive at 1000 PNU for D. farinae and D. pteronyssinus, False positive reactions!

Age at onset of clinical signs Range of 3 months to 11 years; <1 year old - 3 cats (23%); 1-2 years old - 3 cats (23%); 4 years old - 2 cats (15%); 6-11 years old - 5 cats (39%);

Compared to Atopic Dermatitis and Flea Allergy, this is older in general for the development of an allergic skin disease; New Record = 12 years of age

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Breeds affected Siamese, Domestic Shorthair, Domestic Longhair Clinical signs

• Non-seasonal pruritus; Most commonly affects the ear/pinnae, pre-aural region, neck, periorbital region and face; Miliary type lesions most common (“Miliary dermatitis”)

• Eosinophilic plaques, Rodent ulcers; Feline symmetrical alopecia • Severe excoriations can occur • Angioedema, urticaria, conjunctivitis

Response to glucocorticoids Complete cessation of pruritus - 64% of cases; Partial reduction in pruritus - 9% of cases; No reduction in pruritus - 27% of cases

Graham-Mize CA, Rosser EJ, Hauptman J: Absorption, bioavailability and activity of prednisone and prednisolone in cats. Adv Vet Derm, vol. 5: 152-158.

Greater than a 6-fold difference in Cmax of oral prednisolone (Cmax= 1400 ng/ml) vs. oral prednisone (Cmax= 220 ng/ml) Cmax of oral prednisolone after oral prednisone only 122 ng/ml Results indicate both a decreased gastrointestinal absorption of prednisone compared to prednisolone, and possible decreased

conversion of prednisone (inactive form) to prednisolone (active form) by the liver in cats = 12 fold difference

Concurrent primary pruritic skin diseases Flea Allergy Dermatitis; Atopic Dermatitis; Flea Allergy and Atopic Dermatitis; Flea Collar Hypersensitivity Diagnosis Treat suspected food allergy cases symptomatically for first 6-12 months before recommending an elimination diet trial

Rationale for initial symptomatic therapy for 6-12 months • 51 food allergic dogs followed for 3 years • Only 3 dogs re-developed pruritus; 2 dogs became flea allergic; 1 dog became atopic • None of the dogs became pruritic due to the new hypoallergenic treatment diet • All dogs had been eating the initial sensitizing diet for 6-12 months or longer

Dogs started on elimination diet prior to 6-12 months of pruritus 2 cases initially on beef/soy based diets; Placed on lamb based diets after 3 months; Pruritus controlled for 2 months; Pruritus re-developed and dogs found to be reacting to lamb

Dogs started on elimination diet prior to 6 months of pruritus 1 case initially on lamb/rice based diet; Placed on venison based diet after 2 months; Pruritus controlled for 3 months; Pruritus re-developed and dog found to be reacting to venison

Theory of an immunologic window Patient is genetically programmed to become sensitized to commonly exposed antigens in the diet after a certain age

At this age, sensitization begins over a 6-12 month time period? After this time period of programming, the sensitizing immunologic window closes Immunology of food allergy

• IgE mediated food allergy

• Rare in adults; False negative skin tests in adults

: Common in children - peaks at 1 yr.; Consider skin testing and in-vitro serum testing in kittens?

• Delayed hypersensitivity reactions to foods• More common in adults; Consider patch testing with foods

:

Elimination diet trial- minimum 8-12 weeks in duration

Protein hydrolysate formulated diets: • Reducing the Molecular Weight (Daltons) of a specific protein in the diet • Purina Veterinary Diets - HA Formula - Hydrolyzed soy (10,000 Daltons), rice starch, corn oil, canola oil, chicken liver,

hydrolyzed chicken • Hill’s Prescription Diets:

o Feline z/d (canned) - Hydrolyzed chicken liver (3,000 Daltons), corn starch, soybean oil o Feline z/d (dry) - Hydrolyzed chicken liver, rice, soybean oil o Feline Hypoallergenic Treats - Hydrolyzed chicken liver, rice, soybean oil

• Royal Canin Veterinary Diet (Waltham)

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o Hypoallergenic HP Feline – Hydrolyzed soy (10,000 Daltons), rice, chicken fat, beet pulp, anchovy oil, soya oil

o Ultamino Feline - Corn starch, hydrolyzed poultry by-products aggregate, coconut oil, vegetable oil, Home-cooked elimination diet trial

Restricted diet fed for up to 90 days; Formulate based on known past exposure; Avoid any previously consumed foods; “Nothing else is to pass the cat’s lips for the next 60 days”

Discontinue all Table scrapes; Cat treats; Chewable heartworm preventative; Chewable vitamin supplements; Essential fatty acid diet supplements Feline diets

Protein sources • Rabbit, lamb, venison, duck • Cook by boiling or broiling

Carbohydrate sources • Green peas • Often refuse rice or potatoes • Most often feed protein source alone

Treatment diets - feline

• Rabbit and rice based canned diets (Nature’s Recipe) • Venison, duck, or rabbit and green pea based canned and dry diets (d/d canned, Hill’s) • Lamb and barley based canned diet (Eukanuba Response Formula LB for Cats) • Lamb, venison, duck, or rabbit and green pea based canned and dry diets (Royal Canin/Waltham/Innovative Veterinary

Diets)

Home cooked treatment diets Protein source

Lamb, venison, rabbit, chicken, turkey, beef, duck, goose, ostrich, emu Carbohydrate source

• Green pea, rice, potato or sweet potatoes • • Derm Caps, EFA-Caps

Essential fatty acid dietary supplement

• Dicalcium phosphate • Non-flavored, additive free multiple vitamin and mineral supplement • Taurine for cats

Foods associated with exacerbation of clinical signs

• Any food items being prepared in the kitchen - “The Counter Cat” • Meats, cheeses, cooking oils, margarine, breads, odors from various cooked foods • Peoples favorite snack foods • Popcorn, pretzels, peanuts, cookies (Oreo), potato chips, corn chips, doughnuts, pizza, French fries

New dilemma

• Many patients with a possible food allergy that have already eaten and been exposed to “everything but the kitchen sink”

• Possible cross contamination of commercial diets during processing • Prescription and non-prescription hypoallergenic diets • Patients reacting to various ingredients used in the processing of commercial diets

Balalnced home-made elimination diet for cats ½ pound cooked green peas 1 pound cooked lamb, venison, ostrich, emu, rabbit1 teaspoon Dicalcium phosphate

, or duck

½ tablespoon Safflower Oil 2 teaspoons light salt 2 tablets of Nature Made® Multi Complete - Multiple Vitamin/Mineral Supplement with Iron

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350 mg Taurine Feeding guidelines

Broil, boil, or bake rabbit and grind or finely chop. Add salt to cooking water for green peas. Mix the safflower oil, Dicalcium phosphate, vitamin/mineral supplement, and taurine with the rice, potatoes, or green peas, and then add the mixture to the meat puree. Keep refrigerated and warm in microwave to increase palatability. Feed 2½ ounces/5 pounds of cat/day.

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What Causes Feline Military Dermatitis? Edmund Rosser, DVM, DACVD

Michigan State University Lansing, MI

Introduction A cutaneous reaction pattern, not

a specific disease entity.

Clinical presentation Signalment and history

Small focal to diffuse papular eruptions with small crusts. Usually pruritic and excoriations may occur. Flea allergy dermatitis

Affects the dorsal lumbo-sacral region, caudo-medial thighs, ventral abdomen, and flanks. May also affect the head and neck region, may become generalized. Warm weather seasonal or non-seasonal pruritus – geographic differences.

Cutaneous adverse food reactions - “food allergy” Affects the pre-aural region, pinnae, neck, periorbital region, face. Severe excoriations may occur. Non-seasonal pruritus, concurrent GI signs rare!

Atopic dermatitis (“catopy”) May mimic the distribution patterns of Flea Allergy or Food Allergy, or may also present with lesions of the forelegs, rear legs, ventral abdomen and chest. May be warm weather seasonal, present year round with exacerbations in warm weather, or non-seasonal.

Parasitic causes Presence of “miliary lesions” implies a hypersensitivity response.

• Cheyletiellosis •

(“Walking Dandruff”) - affects primarily the dorsal trunk, excess scaling a major sign. Notoedric Mange

(Feline Scabies) - affects the pinnae, face, periorbital region, neck (“Head Mange”) – heavy crusts/scales. May extend to the feet, perineum. Trombiculosis (“Chiggers”) - affects ground contact areas – legs, feet, ears

• , and ventrum with orange colored crusts.

Otoacariasis

(Ectopic Ear Mites) - may mimic the distribution patterns of Flea Allergy, Food Allergy, or Atopy. Usually has concurrent otitis externa. Demodicosis

- Demodex cati – long slender mite. Affects the periorbital region, head, and neck with concurrent ceruminous otitis externa. Pediculosis

• (Lice) - Felicola subrostrata. Affects primarily the dorsal trunk. Presence of “nits” on hair shafts.

Cat Fur Mite•

- Lynxacarus radovsky. Affects primarily the dorsal trunk. “Salt and pepper” like scale. Intestinal Parasite Hypersensitivity

Fungal causes

- roundworms, hookworms, whipworms, tapeworms, Coccidia. May mimic the distribution patterns of Flea Allergy, Food Allergy, or Atopy.

• Dermatophytosis

- may mimic the distribution patterns of Flea Allergy, Food Allergy, or Atopy. Additional areas of patchy alopecia, scales. History of other pets or humans in the household with skin lesions. Malassezia Dermatitis

Autoimmune causes - secondary complication.

• Pemphigus Foliaceus

- affects the nasal planum, periorbital region, and pinnae. May become generalized. May be systemically ill. Pemphigus Erythematosus

Immune mediated causes - lesions limited to the nasal planum, periorbital region, pinnae.

• Cutaneous Drug Reaction

- often mimics the distribution pattern of Food Allergy. Methimazole reported, Propranalol, Clopidogrel (Plavix), Hypereosinophilic Syndrome

Neoplastic causes

- multisystemic organ involvement. Anorexia, vomiting, diarrhea, weight loss. Generalized miliary lesions and pruritus.

• Cutaneous Mastocytosis

- most commonly affects the head and neck region, may be generalized. Geriatric Siamese cats predisposed. Gastrointestinal ulcers, coagulation disorder. Epitheliotropic Cutaneous Lymphoma

Viral causes (Mycosis Fungoides) - the “Great Imitator”.

• Feline Herpes Virus

- affects the nasal region and face. May have a history of previous upper respiratory infections. May have history of conjunctivitis and/or oral ulcers. FeLV and FIV Associated Skin Lesions

- chronic “miliary dermatitis” with concurrent systemic illness.

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Idiopathic causes • Idiopathic Sterile Granuloma and Pyogranuloma

- may mimic the distribution pattern of Food Allergy. Spontaneous remission may occur. Idiopathic “Miliary Dermatitis”

Diagnosis - relatively rare. A diagnosis of exclusion!

Flea allergy dermatitis Distribution pattern of lesions - posterior 1/3 of the body. Seasonal pruritus. Intradermal testing with flea antigen, in-vitro testing for flea. Response to intense flea treatment protocol.

Cutaneous adverse food reactions -“food allergy” Distribution pattern of lesions - anterior 1/3 of the body. Non-seasonal pruritus. Diagnosed using a home cooked, novel protein and carbohydrate elimination diet 8-12 weeks in duration. In cases where the owner will not cook a diet the following may be considered: Canin Veterinary Diets: Feline Hypoallergenic HP - hydrolyzed soy, chicken fat, rice, beet pulp, fish oil; Ultamino Feline - Corn starch, hydrolyzed poultry by-products aggregate, coconut oil, vegetable oil, Hill’s Prescription Diets: Feline z/d – hydrolyzed chicken and chicken liver, rice, vegetable oil; Purina Veterinary Diets - HA Formula

Atopic dermatitis (“catopy”)

- Hydrolyzed soy (10,000 Daltons), rice starch, corn oil, canola oil, chicken liver, hydrolyzed chicken.

Mimics Flea Allergy and Food Allergy. Seasonal or non-seasonal pruritus. Intradermal testing with aeroallergens or Aeroallergen specific IgE immunoassay.

Parasitic causes Distribution pattern of lesions. Skin scrapings, Scotch tape preparations, flea combing, fecal flotation, vacuum technique. Response to empirical parasiticidal treatments.

Dermatophytosis Areas of patchy alopecia, scales. History of other pets or humans in the household with skin lesions. Wood’s lamp examination, KOH prep, fungal cultures, skin biopsy.

Pemphigus foliaceus Affects the nasal planum, periorbital region, and pinnae. May become generalized, and systemically ill. Histopathology - subcorneal pustules with acantholytic cells.

Pemphigus erythematosus Lesions limited to the nasal planum, periorbital region, pinnae. Histopathology - subcorneal pustules with acantholytic cells.

Cutaneous drug reaction Distribution pattern of lesions - mimics Food Allergy. History of drug use and response to drug withdrawal. Histopathology – varied.

Hypereosinophilic syndrome Many organs involved, anorexia, vomiting, diarrhea, weight loss. Moderate to marked eosinophilia. Histopathology – superficial and deep perivascular to interstitial dermatitis with eosinophils.

Neoplastic causes • Cutaneous Mastocytosis•

- geriatric Siamese cats predisposed. Gastrointestinal ulcers, coagulation disorder. Epitheliotropic Cutaneous Lymphoma

Feline herpes virus (Mycosis Fungoides) - the “Great Imitator”.

Distribution pattern of lesions - affects the nasal region and face. History of previous upper respiratory infections, conjunctivitis, oral ulcers. Histopathology - epithelial cell intranuclear inclusion bodies. PCR for Feline Herpes virus 1.

Idiopathic sterile granuloma and pyogranuloma Distribution pattern of Food Allergy. Histopathology - Perifollicular pyogranulomatous dermatitis or; Preauricular xanthogranuloma – a diffuse granulomatous dermatitis with multinucleated giant cells. Chronic steroid or megestrol acetate use.

Idiopathic “miliary dermatitis” Histopathology - superficial perivascular dermatitis with neutrophils, eosinophils, plasma cells, mast cells.

Management Flea allergy dermatitis

Environmental treatment - pyrethroid + pyriproxifin; boric acid or sodium polyborate powder. Patient treatment - Imidacloprid – q14d + leufenuron – q30d; Fipronil + methoprene – q21d; Selamectin (Revolution) - Excellent for cats: Dr. Michael Dryden data – Kansas St. Univ.; CMAX = 63.7 x higher than in dogs; Bioavailability = 74% in cats, only 4.4 % in dogs; TMAX = 15 hrs in cats, 72 hrs in dogs. Aqueous hyposensitization with flea salivary antigen.

Cutaneous adverse food reactions – “food allergy” Commercial diet avoiding the known offending food source.

Rabbit and rice based canned diets (Nature’s Recipe); Venison, duck, or rabbit and green pea based canned and dry diets (d/d canned, Hill’s); Lamb and barley based canned diet (Eukanuba Response Formula LB for Cats); lamb, venison, duck, or rabbit and green pea based canned and dry diets (Royal Canin/Waltham/Innovative Veterinary Diets). Home-cooked Treatment Diets - “novel”

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protein and carbohydrate source, essential fatty acid dietary supplement, safflower oil, dicalcium phosphate, non-flavored, additive free vitamin and mineral supplement, and taurine for cats.

Atopic dermatitis (catopy) Allergen specific immunotherapy (ASIT). Prednisolone (not Prednisone) - 1 mg/kg q12h x 7 d, then q24h x 7 d, then q48h at lowest possible dose to control pruritus. Cyclosporine – 7 mg/kg q24h.

Parasitic diseases • Lime sulfur – q7d x 4 weeks - Cheyletiella, Notoedres, Trombicula, Lynxacarus, Demodex gatoi, Felicola subrostrata. • Selamectin – q14d x 3 treatments - Cheyletiella, Notoedres, Otodectes. • Fipronil spray – q30d - Cheyletiella, Notoedres, Felicola subrostrata. • Ivermectin - 200 ug/kg q7d x 4 weeks - Cheyletiella, Notoedres, Otodectes; 200-300 ug/kg q24h - Demodex cati. • Amitraz – 125 ppm q14d - Cheyletiella, Notoedres, Trombicula, Lynxacarus, Demodex gatoi, Demodex cati, Felicola

subrostrata. Dermatophytosis: Systemics

• Itraconazole capsules – 5-10 mg/kg SID with food • Itraconazole oral solution – 2 mg/kg SID with food; less hepatotoxic than ketoconazole • Fluconazole – 10 mg/kg SID with food • Terbinafine - 30 mg/kg q24h for 4-6 weeks. • Lufenuron - 60-100 mg/kg q30d x 2 treatments.

Dermatophytosis: Topicals • Lime sulfur - twice weekly for 4-6 weeks. • Enilconazole topical solution (10%) - twice weekly for 4-6 weeks. • Miconazole shampoo and leave on rinse 2% (ResiZole) - twice weekly for 4-6 weeks.

Pemphigus foliaceus and pemphigus erythematosus Prednisolone (not Prednisone) - Induction dosage - 2 mg/kg q12h; Maintenance dosage - gradually decrease the dosage every 2 weeks to prevent a relapse.

Chlorambucil - Induction dosage – 0.1 mg/kg q48h; Maintenance dosage – 0.05 mg/kg q48h. Drug eruption

Discontinue suspected drug. Avoid chemically related or similar drugs. Best advice: “Do no harm!” Hypereosinophilic syndrome

• Prednisolone (not Prednisone) - Induction dosage - 2 mg/kg q12h; Maintenance dosage - gradually decrease the dosage every 2 weeks to prevent a relapse.

• Lomustine – 60 mg/m2

• Alpha interferon - 30-60 IU orally q24h. • Poor prognosis.

Cutaneous mastocytosis Spontaneous remission may occur.

• Prednisolone (not Prednisone) - Induction dosage - 2 mg/kg q12h; Maintenance dosage - gradually decrease the dosage every 2 weeks.

• Chlorambucil - Induction dosage – 0.1 mg/kg q48h; Maintenance dosage – 0.05 mg/kg q48h. Epitheliotropic cutaneous lymphoma (mycosis fungoides)

• Prednisolone and Chlorambucil – as above. • Lomustine - 60 mg/m2 q21d.

Feline herpes virus • Pure lysine granules (78.8% lysine) - ¼ teaspoon (~570 mg) q12h for life. • L-lysine tablets (without propylene glycol) - 250-500 mg/cat for life. • Imiquimod 5% cream - 3 times weekly. • Alpha interferon - 30-1000 IU orally q24h. • Famciclovir (Famvir®) – 90 mg/kg TID x 21 days

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What Causes Feline Symmetrical Alopecia? Edmund Rosser, DVM, DACVD

Michigan State University Lansing, MI

A symptom of several possible underlying diseases. Is Not a specific disease entity and simply the result of excess symmetrical licking with the “barbs” of the tongue fracturing the hair shafts; Rarely

is the alopecia spontaneous.

Clinical presentation Signalment and history

A non-inflammatory, symmetrical alopecia that most commonly affects the ventral abdomen, inguinal region, perineum, dorsal lumbosacral region, medial and posterior thighs and may also affect the entire ventrum, anterior and medial forelegs. Additionally it may affect “anywhere the cat can lick”. Close inspection reveals diffuse thinning of hair rather than “total” alopecia. The owner is often unaware of excess grooming behavior as the cat may be a “secretive” or nocturnal groomer. There may also be a history of a problem with “hair balls”.

Flea allergy dermatitis Most commonly affects the dorsal lumbo-sacral region, caudo-medial thighs, ventral abdomen, and flanks. A warm weather seasonal or non-seasonal pruritus – geographic differences.

Cutaneous adverse food reactions - “food allergy” Often affects the ventral abdominal, inguinal regions. May also have “miliary lesions” in the pre-aural region, pinnae, neck, periorbital region, and face. Is a non-seasonal pruritus, with concurrent GI signs being rare!

Atopic dermatitis (“catopy”) Most commonly affects the medial thighs, entire ventrum, forelegs. It may mimic the distribution patterns of Flea Allergy or Food Allergy. Can be a warm weather seasonal problem, present year round with exacerbations in warm weather, or a non-seasonal problem.

Parasitic causes • Cheyletiellosis

(“Walking Dandruff”) - affects primarily the dorsal trunk with excess scaling a major sign. Symmetrical alopecia of the ventral abdomen. Demodicosis

• - Demodex gatoi – short stubby mite. Symmetrical alopecia of the ventral abdomen.

Otoacariasis

(Ectopic Ear Mites) - may mimic the distribution patterns of Flea Allergy, Food Allergy, or Atopy. Usually has concurrent otitis externa. Pediculosis

• (Lice) - Felicola subrostrata. Affects primarily the dorsal trunk. Presence of “nits” on hair shafts.

Cat Fur Mite•

- Lynxacarus radovsky. Affects primarily the dorsal trunk. “Salt and pepper” like scale. Intestinal Parasite Hypersensitivity

Fungal causes

- roundworms, hookworms, whipworms, tapeworms, Coccidia. May mimic the distribution patterns of Flea Allergy, Food Allergy, or Atopy.

• Dermatophytosis

- most commonly has areas of “patchy” alopecia, scales. History of other pets or humans in the household with skin lesions. Malassezia Dermatitis

Miscellaneous causes - secondary complication. Brownish discoloration to the skin.

• Hyperthyroidism•

- excess grooming from “hyperexcitable” behavior. Lower Urinary Tract Infections

• - affects the ventral abdomen.

Impacted anal glands Endocrine causes

(Anal sacculitis) - affects the perineal, perianal region.

• Hyperadrenocorticism

- spontaneous symmetrical, truncal alopecia, easily epilated hairs. May have concurrent “skin fragility”. Hypothyroidism

Neoplastic causes – extremely RARE.

Pancreatic Paraneoplastic Alopecia

Psychogenic causes

- geriatric cats. Alopecia most commonly on the ventrum and legs. Skin takes on a “shiny” appearance. Easily epilated hairs. Concurrent anorexia, lethargy.

Feline Psychogenic Alopecia

- an anxiety neurosis. Often due to a disturbing influence. New puppy or kitten, barking dogs, new baby, recent move, etc. Emotional breeds: Burmese, Siamese, Abyssinian. Sequela to previous pruritic skin disease. Most commonly affects the easiest areas to reach; medial thighs, ventral abdomen, medial forelegs. Darkened hair color in Siamese cats due to melanin pigment increase with cooler skin temperature.

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Diagnosis Spontaneous vs. post-traumatic alopecia

Physical exam - rarely is area completely alopecic, hairs do not easily epilate. Trichogram reveals anagen bulbs with broken distal ends vs. telogen bulbs with fine pointed ends.

Flea allergy dermatitis Distribution pattern of lesions - posterior 1/3 of the body, warm weather seasonal pruritus. Diagnosis supported via Intradermal testing with flea antigen or in-vitro testing for flea and subsequent response to an intense flea treatment protocol.

Cutaneous adverse food reactions -“food allergy” Often affects the ventral abdominal, inguinal regions and is a non-seasonal pruritic skin disease. Diagnosed using a home cooked, novel protein and carbohydrate elimination diet 8-12 weeks in duration. In cases where the owner will not cook a diet the following may be considered: Royal Canin Veterinary Diets: Feline Hypoallergenic HP - hydrolyzed soy, chicken fat, rice, beet pulp, fish oil; Ultamino Feline - Corn starch, hydrolyzed poultry by-products aggregate, coconut oil, vegetable oil, Hill’s Prescription Diets: Feline z/d – hydrolyzed chicken and chicken liver, rice, vegetable oil; Purina Veterinary Diets - HA Formula

Atopic dermatitis (“catopy”)

- Hydrolyzed soy (10,000 Daltons), rice starch, corn oil, canola oil, chicken liver, hydrolyzed chicken.

Most commonly affects the medial thighs, entire ventrum, and forelegs with either a seasonal or non-seasonal pruritus. Diagnosis is supported with the use of either Intradermal testing with aeroallergens or Aeroallergen specific IgE immunoassay.

Parasitic causes Most frequently Cheyletiellosis and Demodicosis and the following should be performed: skin scrapings, Scotch tape preparations, flea combing, fecal flotation, and the vacuum technique. Diagnosis is confirmed by the response to empirical parasiticidal treatments.

Dermatophytosis Most commonly have areas of “patchy” alopecia, scales. Look for a history of other pets or humans in the household with skin lesions. The following test should be performed: Wood’s lamp examination, KOH prep, fungal cultures, skin biopsy.

Hyperthyroidism Basal total serum thyroxine (T4).

Lower urinary tract infections Urine culture and susceptibility.

Impacted anal glands (anal sacculitis) Anal gland extirpation.

Hyperadrenocorticism Spontaneous symmetrical, truncal alopecia, easily epilated hairs. May have concurrent “skin fragility”. Dexamethasone suppression test - 0.1 mg/kg – baseline, 4 & 8 hours post dexamethasone. ACTH stimulation test - measure both cortisol and progesterone.

Pancreatic paraneoplastic alopecia Geriatric cats with alopecia most commonly on the ventrum, legs. Skin takes on a “shiny” appearance. Histopathology - marked follicular atrophy with a mild mononuclear perivascular dermatitis. Abdominal ultrasound and serum trypsin-like immonoreativity (TLI).

Feline psychogenic alopecia History of change in cat’s environment and is non-responsive to Prednisolone. Elizabethan collar response test. Histopathology - normal or very mild superficial perivascular dermatitis.

Management Flea allergy dermatitis

Environmental treatment - pyrethroid + pyriproxifin; boric acid or sodium polyborate powder. Patient treatment - Imidacloprid + Moxidectin (Advantage Multi) – q14d; Fipronil + methoprene (Frontline Plus) – q21d; Selamectin (Revolution) - Excellent for cats: Dr. Michael Dryden data – Kansas St. Univ.; CMAX = 63.7 x higher than in dogs; Bioavailability = 74% in cats, only 4.4 % in dogs; TMAX = 15 hrs in cats, 72 hrs in dogs; Fluralaner Topical (Bravecto) – q12weeks; Comfortis (Spinosad) Chewable Tablets – q30d; Cheristin (Spinetoram) for cats – q30d

Cutaneous adverse food reactions – “food allergy” Commercial diet avoiding the known offending food source. Rabbit and rice based canned diets (Nature’s Recipe); Venison, duck, or rabbit and green pea based canned and dry diets (d/d canned, Hill’s); Lamb and barley based canned diet (Eukanuba Response Formula LB for Cats); lamb, venison, duck, or rabbit and green pea based canned and dry diets (Royal Canin/Waltham/Innovative Veterinary Diets). Home-cooked Treatment Diets - “novel” protein and carbohydrate source, essential fatty acid dietary supplement, safflower oil, dicalcium phosphate, non-flavored, additive free vitamin and mineral supplement, and taurine for cats.

Atopic dermatitis (catopy) Allergen specific immunotherapy (ASIT). Prednisolone (not Prednisone) - 1 mg/kg q12h x 7 d, then q24h x 7 d, then q48h at lowest possible dose to control pruritus. Cyclosporine – 7 mg/kg q24h.

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Parasitic diseases • Lime sulfur (LimePlus™ Dip – Dechra) – q7d x 4 weeks - Cheyletiella, Notoedres, Trombicula, Lynxacarus, Demodex

gatoi, Felicola subrostrata. • Selamectin – q14d x 3 treatments - Cheyletiella, Notoedres, Otodectes. • Fipronil spray – q30d - Cheyletiella, Notoedres, Felicola subrostrata. • Ivermectin - 200 ug/kg q7d x 4 weeks - Cheyletiella, Notoedres, Otodectes; 200-300 ug/kg q24h - Demodex cati. • Amitraz – 125 ppm q14d - Cheyletiella, Notoedres, Trombicula, Lynxacarus, Demodex gatoi, Demodex cati, Felicola

subrostrata. Dermatophytosis: Systemics

• Itraconazole capsules – 5-10 mg/kg SID with food • Itraconazole oral solution – 2 mg/kg SID with food; less hepatotoxic than ketoconazole • Fluconazole – 10 mg/kg SID with food • Terbinafine - 30 mg/kg q24h for 4-6 weeks. • Lufenuron - 60-100 mg/kg q30d x 2 treatments.

Dermatophytosis: Topicals • Lime sulfur (LimePlus™ Dip – Dechra) - twice weekly for 4-6 weeks. • Enilconazole topical solution (10%) - twice weekly for 4-6 weeks. • Miconazole + Chlorhexidine and shampoo, rinse, and spray - MalaSeb® (DVM) - twice weekly for 4-6 weeks.

Hyperadrenocorticism • Unilateral/Bilateral adrenalectomy - Mineralocorticoid maintenance: Fludrocortisone acetate – 0.1-0.3 mg/cat or

Desoxycorticosterone pivalate – 2.2 mg/kg SQ once monthly. Glucocorticoid maintenance: Prednisolone – 1.25-2.5 mg/cat/day

• Metyrapone – 65 mg/kg q12h. • Trilostane (Vetoryl) – 1 mg/kg BID.

Pancreatic paraneoplastic alopecia Screen for evidence of metastasis. Radiographs and ultrasound - liver, diaphragm, lungs. Response to a partial pancreatectomy.

Feline psychogenic alopecia Correct or remove disturbing influence. Mood altering drugs: Clomipramine – 0.125 to 0.5 mg per pound (2.5-5 mg/cat/d).; Amitriptyline – 5 mg/cat q12h; Hydroxyzine – 10 mg/cat q12h; Paroxetine HCl – 2.5 mg/cat q24h. Feliway® Diffuser – feline facial pheromone; NurtureCALM Pheromone Collar for cats.

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Feline Aggression Towards People: Prevention and Management

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON

The feline species may generally be considered to be a solitary creature where social interactions are concerned, but domestication has allowed the adaptation to living in social communities with both humans and other cats. Domestic cats are well known to be able develop bonds with humans and other cats. The ability to socialize with other cats and humans will vary between individual cats as a function of their genetics, prenatal environment, early socialization and life experiences. Kittens that are handled by and interact with humans in their first few weeks of life are friendlier and less fearful of people. In contrast to this, some studies have suggested that hand-reared kittens tend to show more aggression. When available, understanding the cat’s socialization history may be beneficial in rooting out some of the underlying issues.

The causes of feline aggression towards humans can be multifold. These include play, territorial, fear and redirected aggression. Play aggression is a common concern amongst cat owners, and many times the predisposing factors can be identified through careful behavioral questioning at kitten examination visits. Hand play is probably one of the most common concerns the author identifies when discussing play aggression with clients. Many kittens and cats showing play aggression towards their owners actively engage in hand play, with encouragement from the owner. Use of toys, not hands and feet, and the avoidance of any hand ‘wrestling’ will help to some play aggression concerns. During every kitten visit, appropriate play should be discussed, with a firm recommendation to avoid any hand/feet play. Kittens and cats are not able to distinguish degrees of acceptable behavior. If the client makes hand play acceptable, then to the kitten, all body parts are ‘fair game’. Environmental enrichment and structured play times are beneficial in reducing play aggression.

Territorial aggression may be directed at new humans in the household, existing humans posing a threat to resources (this is rare) or may lead to redirected aggression where the human has become a new target during a territorial dispute. For example, cats may be anxious and feel territorial towards visible outdoor cats and turn this aggression inadvertently onto a human in the household.

Fear is a common reason for aggression towards humans. The cat may be fearful of the owner because of an incident that frightened the cat that was associated with the human in question. For example, a large item falling and crashing down causing a loud noise may have frightened the cat. The cat then associated the incident with the human that was nearby when the incident occurred. Unfortunately cats may experience abuse or aggressive treatment in their lifetime, either at the hands of a previous human or by the current owner. These experiences may leave the cat with a persistent fear against humans in general, the specific human causing the abuse, or humans with similar characteristics to the abuser (ex. men).

Redirected aggression is a complex problem that can occur for many reasons. The notable example is that described above under territorial aggression. In cases of redirected aggression, it can be doubly hard to identify the inciting cause or incident. These triggers must be identified, as avoiding them will be the mainstay to avoiding further episodes and increasing the chance of treatment success.

Behavioral questions should be a normal part of every feline visit from preventive care visits to sick cat visits to behavioral consultations. Clients will not always reveal their concerns unless asked. Even in cases where there are no concerns, the clinician might be able to identify potential triggers that may lead to future concerns (ex. hand play with kittens). When a client approaches the veterinary team for help with a behavioral problem, immediate and full support should be offered. The first step is to assess the cat or cats in question and ensure that no medical concerns exist. A full behavioral history should be obtained. The behavioral consultation can be conducted in clinic, or at the client household. The latter is a more favorable option, as it allows the clinician to directly observe the layout of the home and where incident(s) occur(red). It also allows the clinician to assess the environmental enrichment and determine the availability of appropriate resources. Goals for the behavioral interview and development of a treatment plan

1. Identify underlying motivation for the behavior 2. Identify triggers and formulate a plan on how to avoid these 3. Review enrichment and resource management. Correct any deficiencies. 4. Develop a treatment plan

Questions to ask during the behavioral interview Basic information should be gathered about the patient signalment, household members (people and animals), patient medical history and how/where the pet was acquired. The environment should be reviewed, including resource management and availability, litter box care, and household enrichment. The patient’s daily activities should be reviewed and in cases of house calls, traced throughout the house layout. Relationships with other pets in the house and with humans in the household should be reviewed. The stability of the human population should be assessed. For example, humans that work shift work hours may be home inconsistently, causing the

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patient’s environment to be inconsistent. Family children that attend college or university may come and go every 4 months, creating an unstable social circle.

The incident considered the initiating incident, as well as further incidents should be reviewed in detail. There should be an examination of the frequency, intensity and severity of the behavior(s) in question. The behavior of both the cat and the response by the human should be determined. Any attempts at treatment or punishment should be reviewed as these may negatively impact the prognosis. Points to consider with regards to the potential success of treatment Cases of aggression towards humans can be devastating to the human animal bond. A frank, open discussion is necessary with the client(s) in order to determine the prognosis for the patient. It is important to determine how weakened or broken the human-animal bond has become as a result of the behavioral issues. The clinician will need a frank admission by the client about how willing they are to implement the outlined treatment plan. The clients will need to be open about what options they are considering. Options may include following the prescribed treatment plan, drugs, relinquishment and/or euthanasia. Further, the clients’ expectations must be known. What are the clients’ goals and timeline? The clients may have unrealistic expectations, desiring complete resolution of the problem. Prognosis The ability to resolve a human-directed aggression is going to depend on many factors. First and foremost, it is going to depend on the points noted above, as to what client expectations are and whether they are willing to follow prescribed treatment plans. If this is not the case, then the chances of success diminish greatly. Secondly, the duration of the problem, and third, it’s severity, will impact the chance to implement change. Cats showing aggression towards a specific human may never achieve complete resolution of their issues, and a life long alteration of the household dynamics, as well as lifelong medications may become a necessity. Setting realistic expectations and realistic time frames for achieving goals early on in the consultation process is more likely to set the stage for success or at least partial resolution. Clients and clinicians should understand the limitations of the problem and what is reasonable to expect from treatment. Sample questionnaire for a home behavior consultation Patient ID: Patient Signalment:

Medical conditions 1. 2. 3.

Current medications 1. 2. 3.

What amount of day does cat spend in the following activities? Sleeping Resting Eating Grooming Hiding Playing Alone Playing with human How often does cat use litter box for BM? U?

Other pets? If Yes, details:

Environment Layout- rough drawings attached

Litter boxes Number Location Characteristics

Feeding stations Number Location Characteristics

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Feeding schedule Food Amount Timing

Private locations/Hidey spots Number Location Used?

Elevated locations/3D space availabilitynumber Location Used?

Windows Location Look out onto:

Other environmental enrichment Humans in household

Number Stability of residence Stability of employment hours: Relationship with Cat: Other regular visitors:

Potential external stressors noted outdoors Unique considerations (ex. flooring type, smoking, cleanliness, clutter, noise levels

Specific incidents reportsed Known Triggers of Aggression: Aggression directed towards: Client/Individual reaction to aggressive behavior: Any punishments used? Yelling, swatting, other Veterinarian Interactions with Cat during visit: References Bain, M and Stelow, E. Feline Aggression Toward Family Members: A Guide for Practitioners. Vet Clin North Am Small Anim Pract 2014: 44 (3): 581-597. Ellis, S and Sparkes, A. ISFM Guide Feline Stress and Health: Managing Negative Emotions to Improve Feline Health and Wellbeing. International Cat Care 2016.

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Feline Chronic Kidney Disease: A Practical Approach to IRIS Staging

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON Chronic renal disease & IRIS staging Decline in kidney function can result from a variety of causes including pyelonephritis, amyloidosis, polycystic kidney disease, neoplasia, nephrotoxicosis, hydronephrosis and chronic glomerulonephritis (Scherk, 2011). Although acute insult can lead to chronic kidney disease (CKD), age seems to be the only major, consistent risk factor associated with chronic renal insufficiency (White, 2011).

Mature cat visits ideally include a complete physical examination/consultation as well as data collection in the form of a minimum database (MDB) every 4 to 6 months. A minimum database for mature cats includes a full clinical chemistry, a total thyroid test (TT4), a complete blood count, a urinalysis and a blood pressure (BP) series. Blood urea nitrogen (BUN) and creatinine have traditionally been the go-to serum values for diagnosis of kidney disease. Early diagnosis can be challenging utilizing only these values, as azotemia does not develop until there is 75% loss of nephron function. The BUN can be influenced by factors other than renal disease, including dehydration, dietary protein content, gastrointestinal bleeding and hepatic insufficiency. Creatinine is a more reliable indicator of glomerular filtration rate (GFR). However, creatinine can be influenced by muscle wasting and by dehydration. Routine screening of these values can assist the clinician in documenting upward trends in these values.

Symmetrical dimethylarginine (SDMA) measures the methylated form of the amino acid arginine. This is a by-product of protein degradation excreted by the kidneys. SDMA increases with about 40% loss of kidney function. It can be impacted by dehydration. Symmetrical dimethylarginine is not a stand-alone test and should always be interpreted in light of patient status as well as other laboratory findings. Elevated SDMA in the absence of any other evidence of renal disease should be re-evaluated. Table 1 Urine specific gravity varies with age & diet (Scherk, 2011)

Age or condition Expected USG Comments 4-8 weeks of age 1.020-1.038 8+ weeks of age Up to 1.080 Denotes age at which full concentrating ability is

reached Dehydrates/normal renal function

>1.040 Diet dependent (wet vs dry)

Canned food only >1.025 Dry food only >1.035 Inability to concentrate urine

1.008-1.012 Nephrons no longer able to modify glomerular filtrate

Dehydrated/unknown renal function

1.007-1.039 Suggestive of renal insufficiency with or without azotemia

It is recommended that urine samples be collected by cystocentesis and tested immediately in the clinic laboratory. Urine testing should include chemistry testing using testing strips, measurement of urine specific gravity (USG) by refractometer and sediment analysis. Urine specific gravity can be impacted by age, diet and hydration status. Urine specific gravity varies throughout the day, such that a single low USG is not reliable evidence of a loss of concentrating ability (Scherk, 2011). Samples with a low urine specific gravity (USG; less than 1.035) should be submitted for culture. International renal interest society (IRIS) For cats that are diagnosed with CKD, it is critical for practitioners to develop and promote a relationship with clients that will allow continued monitoring of the disease, including disease staging. The application of human IRIS staging guidelines to the study of feline renal disease has dramatically advanced our ability to tailor our patient therapy, thereby improving quantity and quality of life. In addition to the MDB as discussed above, imaging is likely to be beneficial. Table 2. IRIS staging guidelines

Stage Renal Azotemia Creatinine Clinical signs 1 Non-azotemic <140 µmol/L Absent 2 Mild 140-249 µmol/L Mild or absent 3 Moderate 250-439 µmol/L Moderate 4 severe >440 µmol/L Severe

Adapted from AAFP 2015 Dru Forrester, DVM, MS, DACVIM & Jane Robertson, DVM, DACVIM Chronic Kidney Disease: Making the most of early diagnosis

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Table 3. Subclassifications of IRIS staging: Proteinuria Urine Protein:Creatinine Ratio (UPC) Substage

<0.2 Non-proteinuric (NP)

0.2-0.4 Borderline proteinuric (BP)

>0.4 Proteinuric (P)

Taken from AAFP 2015 Dru Forrester, DVM, MS, DACVIM & Jane Robertson, DVM, DACVIM Chronic Kidney Disease: Making the most of early diagnosis Table 4. Subclassifications of IRIS staging: Blood pressure

Systolic BP (mmHg) Diastolic BP (mmHg) Substage <150 <95 Minimal risk (N) 150-159 95-99 Low Risk (L) 160-179 100-119 Moderate Risk (M) >180 >120 High Risk (H)

Taken from AAFP 2015 Dru Forrester, DVM, MS, DACVIM & Jane Robertson, DVM, DACVIM Chronic Kidney Disease: Making the most of early diagnosis True proteinuria in cats is a known marker of poor prognosis in renal disease (Syme, H.M. et al, 2006; Syme, H.M., 2009). If proteinuria is established on the chemistry stick in the absence of active sediment, the sample will need to be submitted for a urine protein creatinine ratio (UPCR). The result should be used to direct therapy with medications to reduce the loss of protein into the urine. Ratios over 0.4 are significant and therapy is needed. If there is active sediment in the presence of proteinuria on the chemistry stick, and the UPCR is very high (>0.5), then the value may be significant and therapy may be indicated.

Blood pressure changes can be impacted by and/or impact the renal state of health (Brown, 2011). Sixty-five to 100% of cats with hypertension have evidence of reduced renal function (Jepson, 2011). The gold standard for blood pressure assessment in any species is central venous catheter assessment. Blood pressures can be measured non-invasively either by Doppler or oscillometric methods. Patient stress can be a limiting factor. Proper use of pain management in advance, as well as following cat friendly practice and handling guidelines will significantly reduce stress. References Brown, Scott. Chronic Kidney Disease and Hypertension in The Cat. Clinical Medicine and Management. Elsevier. 2011; 1120-1124. IRIS. www.iris-kidney.com: International Renal Interest Society, 2013 (accessed July 2015) Forrester, D, & Robertson, J., Chronic Kidney Disease: Making the most of early diagnosis. (2015). AAFP 3rd World Feline Congress, San Diego, CA. Roudebush, P, Polin, D.J., Ross, S. J., Towell, T. L., Adams, L.G. and Forrester, S.D. Therapy for Feline Chronic Kidney Disease. What is the evidence? JFMS (2009) 11, 195-210. Robertson, Sheilah A., and Lascelles, B. Duncan X. Long-Term Pain in Cats: How Much Do We Know about This Important Welfare Issue? Journal of Feline Medicine and Surgery 2010 12: 188 Scherk, M. Urinary Tract Disorders in The Cat. In Little, SE, The Cat. Clinical Medicine and Management. Elsevier Saunders Inc. 2011; 935-1013. Scherk, M. and Laflamme, DP. Controversies inVeterinary Nephrology:Renal Diets Are Indicated for Cats with International Renal Interest Society Chronic Kidney Disease Stages 2 to 4: The Con View. Vet Clin Small Anim 46 (2016) 1067–1094 Sparkes, A.H., Caney S., Chalhoub, S, Elliott, J., Finch, N., Gajanayake, I., Langston, C., Lefebvre, H.P., White, J., Quimby, J. ISFM Consensus Guidelines on the Diagnosis and Managemnt of Feline Chronic Kidney Disease. JFMS (2016) 18; 219-239. White, J.D., Malik, R., and Norris, J.M. Feline chronic kidney disease: Can we move from treatment to prevention? Vet. J. (2011) 190; 3: 317-322

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Feline Chronic Kidney Disease: Sound Therapeutic Goals

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON

With the utilization of IRIS staging, the clinician gains significant ground in combatting chronic renal disease in cats. The data collected for the purpose of IRIS staging allows a tailored, individual approach to patient therapy. Although the clinician will have a wide range of therapeutics available to improve quality and quantity of life in the CKD patient, the client and patient relationship must always be considered. In particular, the clinician should consider the client’s ability and willingness to medicate the patient with multiple drugs multiple times a day. Available and necessary therapeutics may need to be prioritized in order to maintain client quality of life and the client-patient relationship. Table 5: Survival time by IRIS stage

IRIS Stage 2b* 3 4 Median Survival (days) 1151 778 103 Range (days) 2-3107 22-2100 1-1920

*2b Creatinine of 203-249 µmol/L Taken from AAFP 2015 Dru Forrester, DVM, MS, DACVIM & Jane Robertson, DVM, DACVIM Chronic Kidney Disease: Making the most of early diagnosis Treatment for pain is essential. Medications such as gabapentin should be prescribed at a dosage of 15-20 mg/kg PO q12h. In debilitated cats, a dosage of 5-10 mg/kg POq12h is the initial chosen dosage. This medication is safe for use in all diseased states and the only initial side effect is sedation. After 1-2 weeks, any sedation will wear off and the cat will continue to be more comfortable. The dosage will need to be titrated up and down in order to meet the particular patient’s needs. Injectable products such as CartrophenTM or AdequanTM for degenerative joint disease (DJD) are also beneficial. Additional pain medications such as buprenorphine, amantadine and non-steroidal anti-inflammatory drugs (NSAIDs) may also require consideration. Elevated stages of CKD may preclude safe use of NSAIDs.

Dietary changes recommended for cats with renal disease should be considered. Many renal specific diets are formulated with reduced phosphorus; ideal, highly digestible protein sources; increased energy content; vitamins such as B12 and a range of other beneficial ingredients. The decision to commence renal diets and at what IRIS stage will vary from patient to patient. Increasing water intake may be a key factor in improving renal function and overall patient hydration status. Indirectly this can reduce pain from dehydration and constipation.

Identification of BP values over 160-180, with or without retinal changes indicate the need for BP-controlling drugs. Calcium channel blockers such as amlodipine are the most effective at controlling blood pressure in the feline species. Some patients will have partially or uncontrollable hypertension with amlodipine and may require additional medications. Benazepril (Fortekor) is not effective in the control of hypertension. The newly available drug telmisartran (Semintra) may be effective at controlling hypertension at higher doses, but has yet to be evaluated for further benefit to hypertension cats.

The indiscriminate use of antibiotics in the absence of evidence of urinary tract infection is not recommended. Antibiotics should be selected based on urine culture and sensitivity patterns. A repeat urine culture 7 days following cessation of therapy is critical. In cases where urine culture is negative, but a low USG exists in the face of renal disease, ultrasound is recommended.

Patients who exhibit even mild decreases in potassium levels in their serum require supplementation with potassium gluconate. The majority of body potassium is held in the intracellular or interstitial space. The serum potassium represents only 2% of body potassium. Therefore any decrease noted in the serum is significant of a major decrease in the overall body stores.

Elevated UPCR indicates abnormalities with the renin angiotensin aldosterone system (RAAS). These changes alter intra-glomerular pressures and result in protein loss into the filtrate/urine. The use of benazepril has been recommended in the past. However, this drug is not targeted to the particular pathway of RAAS that is affected and impacting the glomerulus. Over time, the RAAS can escape the control that benazepril exerts, resulting in resumed proteinuria. Telmisartan is a newer alternative that is more targeted and not likely to lead to escape mechanisms over time.

Improving hydration status in renal patients is generally considered to be beneficial to renal function and overall patient health. Addition of 20-40 mEq/L of potassium chloride to the fluids should be considered in the case of hypokalemia and/or where regular subcutaneous fluids will be administered.

Patients identified with elevated total calcium, elevated ionized calcium and/or elevated phosphorus may require phosphorus-binding agents to reduce phosphorus levels. The use of agents such as aluminum hydroxide can be challenging, as palatability is less than optimal. The use of phosphorus binding agents containing calcium should be minimized unless serial monitoring of ionized calcium can be pursued.

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Calcitriol is a drug that is recommended frequently in renal patients. It’s primary indication for use is following diagnosis of renal secondary hyperparathyroidism. In these cases, the use of calcitriol, with regulated serum phophporus levels, may benefit the patient in the short and long term. Low-dose calcitriol supplementation is recommended by some experts as a means of improving quality of life, however, more detailed studies on the benefits and risk of this approach are warranted (Sparkes et al, 2016).

Chronic kidney disease can lead to a reduced production of erythropoietin. The result is a reduced production of new red blood cells from the bone marrow. Some patients will also have iron deficiencies reducing production of new RBC. Evaluation of iron levels with consideration for supplementation is needed. These patients may also require injectable erythropoietin or darbopoietin to stimulate bone marrow production of RBC. References Forrester, D, & Robertson, J., Chronic Kidney Disease: Making the most of early diagnosis. (2015). AAFP 3rd World Feline Congress, San Diego, CA. Roudebush, P, Polin, D.J., Ross, S. J., Towell, T. L., Adams, L.G. and Forrester, S.D. Therapy for Feline Chronic Kidney Disease. What is the evidence? JFMS (2009) 11, 195-210. Robertson, Sheilah A., and Lascelles, B. Duncan X. Long-Term Pain in Cats: How Much Do We Know about This Important Welfare Issue? Journal of Feline Medicine and Surgery 2010 12: 188 Scherk, M. Urinary Tract Disorders in The Cat. In Little, SE, The Cat. Clinical Medicine and Management. Elsevier Saunders Inc. 2011; 935-1013. Scherk, M. and Laflamme, DP. Controversies inVeterinary Nephrology:Renal Diets Are Indicated for Cats with International Renal Interest Society Chronic Kidney Disease Stages 2 to 4: The Con View. Vet Clin Small Anim 46 (2016) 1067–1094 Sparkes, A.H., Caney S., Chalhoub, S, Elliott, J., Finch, N., Gajanayake, I., Langston, C., Lefebvre, H.P., White, J., Quimby, J. ISFM Consensus Guidelines on the Diagnosis and Managemnt of Feline Chronic Kidney Disease. JFMS (2016) 18; 219-239. White, J.D., Malik, R., and Norris, J.M. Feline chronic kidney disease: Can we move from treatment to prevention? Vet. J. (2011) 190; 3: 317-322

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Feline Diabetes Mellitus: Is Remission a Reasonable, Achievable Goal?

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON

Diabetes Mellitus (DM) is a common feline endocrinopathy. Most cases are primary and similar to type II diabetes in humans, which results from abnormal secretion of insulin from the pancreatic B cells and peripheral insulin resistance. The diagnosis of DM is made based on characteristic clinical signs of diabetes mellitus (polyuria, polydipsia, polyphagia, and weight loss), and documentation of hyperglycemia and glycosuria. In cats it may be complicated by the occurrence of stress hyperglycemia and sometimes stress glucosuria. When making a diagnosis of DM in cats, it is important not only to document persistent hyperglycemia and glucosuria, but also to rule out other diseases that may cause similar clinical signs. Measurement of fructosamine concentrations or urine glucose of samples collected in the home environment may allow the clinician to distinguish between stress induced hyperglycemia (and resultant glucosuria) and persistent hyperglycemia due to diabetes mellitus. Therapy for diabetes should be instituted as soon as possible after diagnosis.

The main goal of therapy is to achieve blood glucose levels within the normal range. The secondary goal is to achieve persistent normoglycemia with no further requirement for exogenous insulin. This latter goal is commonly termed diabetic remission. Diabetic remission is usually defined as the ability to maintain normal blood glucose without insulin treatment for 4 weeks without the reappearance of clinical signs. Clinicians need to accept that not all cats will achieve remission and in these patients the goal is to minimize the clinical signs without causing hypoglycaemia while avoiding excessive fluctuations of blood sugar above the normal range. The duration of remission is highly variable and unfortunately, at least 25% of cats that achieve remission subsequently become overtly diabetic and must receive insulin again. Tight glycemic control is required to achieve remission and as a result, there is an increased risk of at least one hypoglycaemic episode. This risk associated with tight glycemic control need to be discussed with the client. If this is not an approach the client is ready, willing or able to take, it may not be the ideal choice. Successful management of cats with DM includes minimizing clinical signs, improving quality of life, preventing complications such as DKA and preventing diabetic neuropathies and nephropathies. If the goal of diabetic remission is not an achievable target for the client, the clinician should continue to help them focus on the overall goals of DM management.

Administration of insulin and dietary modification are the principal therapies used for management of diabetic cats. A recent study showed that cats with newly diagnosed DM have a fair to good prognosis, with 46% living longer than 2 years.1 However, since 30 % of cats affected with DM are euthanized within their first year of treatment due to the emotional and financial burden of insulin treatment and the required veterinary care, achieving diabetic remission is the ideal goal for every feline patient faced with this disease. Intensive glycemic control after diagnosis has been shown in humans with DM type11 to improve long – term remission rates. It appears that the same holds true for our feline patients. Cats receiving treatment for diabetes within 6 months of diagnosis with twice daily insulin treatment aimed at euglycemia in conjunction with the cats been fed an ultra-low carbohydrate diet have the best chance of remission.

Which cat will go into remission??? Studies are suggestive that DM remission in the cat is likely to occur through reversal of glucose toxicity. As in humans, cats that have experienced more prolonged hyperglycemia will have experienced a greater deterioration of beta-cell function resulting in a lower chance of remission. There is no factor that consistently predicts diabetic remission in the cat but the shorter the duration of DM, the faster glycemic control is achieved and those patients with less severe hyperglycaemia when starting appear to be factors that are favourable. A retrospective cohort study showed that cats without hypercholesterolemia were more likely to achieve remission. In one study, diabetes as a potential result of recent corticosteroid treatment was associated with nearly 50 percent remission. A lack of diabetic neuropathy has also been associated with future remission, but neuropathy is a result of prolonged hyperglycaemia so this should not be a surprise. Early client recognition, early diagnosis, intensive treatment with twice daily insulin and ultra-low carbohydrate diet are key.

One of the challenges we face as veterinarians is the opportunity to diagnose this disease in the early stages. Cats are “masters of disguise” They also do not receive regular veterinary care. Often by the time we see the patient and diagnose the disease, the cat already has lost weight and muscle mass, has a poor hair coat, glucose toxicity of the beta cells, diabetic neuropathy and possibly DKA. Using every opportunity, a veterinary team has to teach cat owners the importance of early disease diagnosis through regular veterinary care. Teaching the subtle signs of sickness is critical. The author recommends using Cat Healthy as a resource to educate every client that comes through our doors. In addition, once diagnosed with diabetes, the Cat Healthy website http:/www.cathealthy.ca has a series of educational videos about diagnosis, treatment and outcome for the newly diagnosed diabetic cat family. The Cat Healthy Protocols contain a compliance section listing other useful resources for the family as they start the journey of insulin treatment and blood glucose monitoring for their cat. The earlier we diagnose and treat the disease, the better chance we have of remission.

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The use of an ultra-low carbohydrate (CHO) diet is an important part of DM therapy in the cat. Low carbohydrate diets reduce post-prandial hyperglycaemia in people. It seems a low carbohydrate diet in the cat is equally important. A study giving twice daily insulin showed a 12-week remission rate of 17% in cats fed diets with variable carbohydrate content and a 12-week remission rate of 40% in diabetic cats fed an ultra-low to low carbohydrate diet. The Bennett study reported a greater chance of remission in diabetic cats fed a low CHO diet than those fed a high fibre diet. Obesity is common in DM cats. If present, it should be addressed with a therapeutic weight-loss diet and an energy-restriction plan. Metabolic energy or resting energy requirements (MERs or RERs) should be calculated for each individual cat thus allowing determination of the actual food intake permitted for weight maintenance or weight loss (or in some cases, weight gain).

The clinician’s choice of insulin will vary depending on experience, training and current studies. Cats can theoretically achieve remission with the use of any insulin type. The type of insulin used for the best chance at achieving remission may be less important than factors such as the presence of concurrent diseases, initiating the treatment as soon as possible and the plan for close monitoring. Diseases such as Acromegaly and Cushings disease can be causes of a lack of response to insulin. Co-existing pancreatitis can also have an effect on the blood glucose levels and requirement for insulin. Clinicians should be familiar with at least two types of insulins that are appropriate for treating cats, as it is difficult to predict in advance which insulin is best for an individual cat. Glargine (LantusTM) has been proposed as the optimum insulin for diabetic cats based on the relatively high remission rate reported in some studies using this insulin, but this may be because it is the most frequently studied insulin. In a study assessing the influence of low CHO diets on remission rates, the insulin PZI (ProzincTM) achieved similar remission to a study examining twice daily glargine. Further studies are required to compare if there are different rates of remissions between the different insulins. Table 2. Comparison of insulin products for treatment of feline diabetes mellitus

Insulin Licensed in

cats Manufacturer Formulation Action Dose* ProZinc Yes Boehringer

Ingelheim U40 recombinant PZI Nadir 5–7 hours

Duration 8–9 hours Start 0.25–0.5 U/kg, BID Median maintenance dose 0.6 U/kg, BID

Vetsulin, Caninsulin

Yes Merck U40 Porcine zinc Nadir 4 hours Duration 8–12 hours

Start 0.25–0.5 U/kg, BID Median maintenance dose 0.5 U/kg, BID

Lantus No Sanofi Aventis U100 Insulin glargine (recombinant human analog)

Nadir and duration not determined in diabetic cats

Start 0.25–0.50 U/kg, BID Median maintenance dose 2.5 U/cat, BID

Levemir No Novo Nordisk U100 Insulin detemir (recombinant human analog)

Nadir and duration not determined in diabetic cats

Start 0.25–0.50 U/kg, BID Median maintenance dose 1.75 U/cat, BID

*Based on lean body weight Teaching our clients to be comfortable to take blood glucose levels at home is critical for remission. “In clinic” blood glucose curves are inaccurate and a diagnostic method of the past. Having a few team members on staff that can guide the clients through the early stages of diabetic monitoring and treatment is critical and will greatly improve the chance of remission. Commonly used protocols are to “Spot Check”, do home blood glucose curves or multiple daily monitoring. What protocol is needed will be determined by the client’s schedule and lifestyle and the individual patient’s needs. It appears that remission is likely only achieved in those cats that received long term glucose monitoring.

The earlier we diagnose DM in our feline patients and initiate treatment with twice daily insulin in conjunction with an ultra- low carbohydrate diet, the better chance we have of diabetic remission. Teaching clients to monitor blood glucose levels at home is a critical part of the plan as well. Remission in the diabetic cat is possible! References Callegari C, Mercuriali E, Hafner M, et al. Survival time and prognostic factors in cats with newly diagnosed diabetes mellitus: 114 cases (2000–2009). J Am Vet Med Assoc. 2013;243:91–95. Gostelow R, Forcada Y, Graves T, Church D, Niessen S Systemic review of feline diabetic remission:Seperating fact from opinion The Veterinary Journal 202 (2014) 208-221 These lecture notes and associated presentation were modified from a previous presentation by Dr. St. Dens and Dr. O’Brien at the Ontario Veterinary Medical Association 2017 conference & Trade Show.

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Feline Housesoiling: Medical, Behavioral, or Both?

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON

Identifying the underlying cause of house soiling can be problematic. House soiling often occurs as a result of multiple issues, which may include medical, environmental and/or anxiety-related issues. The main medical differential diagnoses for feline house soiling include feline idiopathic/interstital cystitis (FIC), urolithiasis, crystalluria, infection, constipation, dehydration and/or neoplasia. Environmental concerns may include insufficient availability of resources such as litter boxes, feeding stations and sleeping locations (to name a few). Poor litter box management such as covered boxes, infrequently cleaned or inconveniently located boxes, may also contribute. Anxiety may arise from a wide variety of problems including illness, inconsistent provision of daily care (feeding, play etc), insufficient resources, inter cat aggression, as well as territorial anxiety. Intact males or males neutered after puberty may be more prone to house soiling in the form of territorial urine marking.

When a cat is presented with house soiling, a detailed history including information about the cat’s age, home environment, census of other pets in the home, behaviour, diet (including treats), water intake and other concerns are critical. History is followed up with a thorough physical examination with attention to the palpation of the abdomen. Is their pain? Does palpation of the bladder illicit urination? Does the bladder feel soft, thickened, firm? Is there evidence of firm, small stool and/or evidence of constipation? Does the cat have a urinary obstruction which requires immediate resolution? All cats with house soiling require a basic urinalysis which includes visual assessment, specific gravity, dipstick analysis, and sediment microscopy. This includes cats with fecal house soiling, as some of these patients may have painful urination, leading them to defecate away from the pain-associated litter box. Blood work should be considered as an important part of the minimum data base required to rule out systemic disease. Depending on the findings, further investigations should then include radiographs of the abdomen and if needed ultrasound imaging of the bladder to identify evidence of constipation, urolithiasis or neoplasia. Urine culture and sensitivity should be carried out for any cat with an active sediment (WBC, bacteria), low urine specific gravity and/or glucosuria. Urine cultures should be obtained only by cystocentesis to prevent false positive results from contamination during a free-flow sample. Feline idiopathic cystitis (FIC) Feline idiopathic cystitis (FIC) is a complex disease process in cats that is not fully understood. The condition is often a diagnoses of exclusion, after all other potential medical causes have been ruled out. It is important to realize that FIC can occur as a result of contributing factors such as environmental mismanagement and anxiety. It is therefore difficult to tease out many factors related to FIC from factors associated with house soiling. The clinical signs of FIC may include pollakiuria, periuria, dysuria, hematuria and/or stanguria. Vocalization when urinating and hair loss on the ventral caudal abdomen may also occur. The severity of signs and the frequency with which they recur is variable. FIC can be obstructive or non-obstructive in its presentation. It is the most common cause of non-obstructive feline lower urinary disease.1 This disease is generally seen in younger and middle aged cats and is uncommonly diagnosed in cats greater than 10 years of age. In reported studies, excessive body weight, decreased activity, multiple cat households and indoor housing have been associated with increased of FIC. Affected cats can suffer recurrent episodes, which generally resolve without treatment over the course of 3–7 days. FIC can present as an acute episode or develop into a chronic re-occurring condition. While the condition of FIC currently remains, by definition, an idiopathic disorder, recent developments in the understanding of the neuro-hormonal abnormalities that exist in affected cats suggest that the signs develop from an inability to cope with chronic stress. This may manifest in a number of ways, including the development of bladder inflammation and pain.2 No cure is currently available for FIC, and treatment options are aimed at keeping the cat's clinical signs to a minimum, and increasing the disease-free interval. Clinical signs of acute FIC resolve spontaneously in as many as 85% of cats within 2-3 days, with or without treatment. Assessing the efficacy of any medical treatment for FIC is made difficult by the self-limiting nature of this disease. When a cat is diagnosed with FIC, analgesic therapy should be initiated for the acute management of the disease. These cats are painful and the pain needs to be treated in a multi-modal fashion with opioids, non-steroidal inflammatory drugs and other analgesics such as gabapentin. Prazosin hydrochloride may be helpful to relieve urethral spasm. It is important that the client appreciates that all current treatments for FIC are merely palliative and that without application of multi-modal environmental modification (MEMO) and measures to increase water intake, the FIC episodes will recur and will require continued management. A primary objective in managing FIC is to encourage the production of large volumes of dilute urine (SG < 1.035). Any measures which will increase the cat's water intake are likely to be helpful. Feeding canned food is particularly effective, as is offering the cat palatable fluids to drink (chicken or fish stock, water from tinned fish, etc.). Adding extra water to canned or dry foods works well. Monitoring of the success of the owner's attempts to increase water intake can be done via regular analysis of the urine samples collected at home or in the clinic. Aim is to keep the urine SG below 1.035.

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Environmental management Environmental modification is a key factor in the management of house soiling, since stress clearly plays an important part in the problem. Meeting the environmental needs of the cat and understanding the cat as a species is critical. Cats are not inherently social and in the wild are solitary hunters. They tend to be solitary and are territorial and although they are hunters, they are also prey. These traits make it challenging for cats to live in close proximity to other cats. 'Silent bullying' often goes unnoticed, but it is a major cause of chronic stress to the less dominant cat. When a cat is presented for house soiling, a questionnaire should be completed by the client to establish a thorough environmental history, followed by the recommendations for MEMO. For suggestions on developing a questionnaire, as well as a good client resource, the reader is referred to the following websites: http://www.indoorcat.org/ and http://www.cathealthy.ca.

Identifying and addressing environmental management issues in the affected households is a critical aspect in the reduction of house soiling. This applies to all causes of house soiling, but is of particular importance in cats with FIC. In one study, multi-modal environmental modification (MEMO) was evaluated in client-owned cats with FIC. Implementing MEMO as the sole management strategy with FIC was found to be successful in the majority of cats followed over a one year period of time.3 Dietary adjustments Diets such as Royal Canin Calm® or Royal Canin Urinary/Calm® and Hill’s Multicare C/D Stress® can be helpful in the long-term management of cats with house soiling issues, especially those with FIC. These type of diets reduce the frequency and intensity of recurring episodes of lower urinary tract signs. To achieve this aim, they need to be fed as the cat's sole source of nutrition and used consistently in the long term. Calming nutraceuticals such as Zylkene ® or Anxitane® may be helpful.

As cats that develop litter box issues, degnerative joint disease, and in particular FIC tend to be overweight, a weight loss program with a strict calorie counted amount of food fed per day is likely critical. Resource management To meet the needs of each cat within the house, each individual cat must have free access to its own key resources, ideally positioned out of sight of the other cats. Key resources include food and water bowls that are sited apart from each other; clean uncovered litter trays (one box per cat, plus one) in various locations around the home; resting places at different vertical heights with some that only fit one individual cat; and multiple scratching posts and scratching resources. Cats need mental and physical activity several times a day and cat families need to make time in their day to play with their cat as they would their dog. Putting the hunt back in meal-time using feeding toys is a good form of entertainment for the “predator” in the cat. Feline pheromones Although a statistically significant difference was not found when Feliway® was used in a home compared to placebo in cats with FIC, cats that had Feliway® used in the environment had a trend for fewer bouts of FIC and reduced negative behavioral traits. Pharmacologic interventions A variety of drugs have been tried in cats with housesoiling concerns, but their efficacy will vary with each cat in each separate situation. All medical, dietary, environmental and resource concerns must be addressed prior to or in conjunction with the use of pharmacologic agents in feline house soiling. Expectation that a drug may resolve house soiling on it’s own without these concerns being addressed is unrealistic and more likely to lead to treatment failure. Selection of drugs will be based on the identified areas of concern, whether these are anxiety based, or secondary to aggression or timidity in a multicat household. Urinary tract infection

Bacterial infections are rare and most likely seen in older female cats with a low urine specific gravity or cats with glucosuria. Cats presenting with house soiling and/or evidence of FIC should not be prescribed empirical antimicrobials. As the condition of FIC is waxing and waning, it may appear that the cat has responded to antimcirobials which will lead to a false diagnosis of infection. Rarely do cats have a bacterial infection, even when they have a urolith. The need for antibiotics should be based on a positive urine culture and treatment selected according to the sensitivity results. References 1. Buffington CAT. Idiopathic cystitis in domestic cats - beyond the lower urinary tract. J Vet Intern Med. 2011;25:784 2. Defauw PAM, et al. Risk factors and clinical presentation of cats with feline idiopathic cystitis. J Feline Med Surg. 2011;13:967–975. 3. Buffington CAT, et al. Clinical evaluation of multimodal environmental modification (MEMO) in the management of cats with idiopathic cystitis. J Feline Med Surg. 2006;8:261–268. 4. Wallius BM, Tidholm AE. Use of pentosan polysulphate in cats with idiopathic non-obstructive lower urinary tract disease: a double-blind randomised placebo-controlled trial. J Feline Med Surg. 2009;11:409–412. 5. Gunn-Moore DA, Shenoy CM. Oral glucosamine and the management of feline idiopathic cystitis. J Feline Med Surg. 2004;6:219–225.

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6. Kraijer M, et al. The short-term clinical efficiency of amitriptyline in the management of idiopathic feline lower urinary tract disease: a controlled clinical study. J Feline Med Surg. 2003;5:191–196. 7. Kruger JM, et al. Randomized controlled trial of the efficacy of short-term amitriptyline administration for treatment of acute, non-obstructive, idiopathic lower urinary tract disease in cats. J Am Vet Med Assoc. 2003;222:749–758. 8. Chew DJ, et al. Amitriptyline treatment for severe recurrent idiopathic cystitis in cats. J Am Vet Med Assoc. 1998;213:1282–1286. 9. Osborne CA, et al. Prednisolone therapy of idiopathic feline lower urinary tract disease: a double-blind clinical study. Vet Clin North Am Small Anim Pract. 1996;26:563–569. These lecture notes and associated presentation were modified from a previous presentation by Dr. St. Dens and Dr. O’Brien at the Ontario Veterinary Medical Association 2017 conference & Trade Show.

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Inter-Cat Aggression: I Love You, You Love Me

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON

The feline species may generally be considered to be a solitary creature where social interactions are concerned, but domestication has allowed the adaptation to living in social communities with both humans and other cats. Domestic cats are well known to be able develop bonds with humans and other cats. The ability to socialize with other cats and humans will vary between individual cats as a function of their genetics, prenatal environment, early socialization and life experiences. The acceptability of other cats within the household will in part depend on the history of the cats in question, including how and when introductions were made. One of the most common causes of inter-cat aggression issues is introduction of a new cat into a pre-existing social environment of a household with 1 cat or 1 or more pets. Other causes of inter-cat aggression include play aggression, territorial aggression, fear aggression and redirected aggression.

Cats that cohabitate are in many cases able to develop a social bond, or at least co-exist in the same environment. Cats that are bonded and not experiencing inter-cat anxiety will allogroom, allo-rub, allo-play, and sleep in close or direct physical proximity to one another. This is called affiliative behavior. Allogrooming and other cat-cat behaviors such as play should not end in physical or vocal violence. For example, cats that allogroom for a short duration followed by swatting and/or hissing and growling are not likely to be living in complete harmony with one another. Cats that cohabitate may not exhibit covert signs of aggression. Agonistic behavior can be subtle, and clients may not recognize the signs. Cats can exhibit signs of aggression simply through certain facial expressions and body positioning. Clients may not be aware of the subtle facial and body language that indicates an aggressor or defensor. Clients may not be aware of the moderately subtle signs such as physical blocking of access to resources, or passive blocking of access to resources (ex. staring). Clients may consider chasing to be a form of play when it is in fact the act of an aggressor towards a defensive cat. Normal play between cats should involved reciprocal chasing with minimal to no vocalization. Clients are more likely to be aware of agnostic behavior that is obvious, including biting and scratching and full physical fights.

When a client approaches the veterinary team for assistance with an inter-cat aggression problem, it is critical for the clinician to delve into the history of the cats in question. Affiliative and agnostic behaviors may be in their history, but the client may have always assumed the cats were affiliative. Teasing out a history of inter-cat anxiety is important to developing a treatment plan for the current aggression problem. As with aggression towards humans (see Feline Aggression Towards Humans- Prevention and management), the clinician will need to determine the forms of aggression that are being exhibited. This includes sorting out a history of play aggression, determining if there are territorial issues, whether there is fear and whether a redirected aggression episode occurred. The situation can be multifactorial. For example, two cohabiting cats may have always had territorial and fear aggression that was subtle. This subtle issue may suddenly become a major issue when a new cat is brought into the house or an outdoor stray presents itself at the window. In the case of a new household pet, the group dynamics must shift and in the case of outdoor cats, redirected aggression may worsen the situation. Goals for the behavioral interview and development of a treatment plan

1. Identify underlying motivation for the behavior 2. Identify pre-existing inter-cat issues (perhaps client was never aware) 3. Correctly identify the aggressor(s) and the defensor(s) 4. Identify triggers and formulate a plan on how to avoid these 5. Review enrichment and resource management. Correct any deficiencies. 6. Develop a treatment plan

Questions to ask during the behavioral interview1 Basic information should be gathered about the patient signalment, household members (people and animals), patient medical history and how/where the pet was acquired. The environment should be reviewed, including resource management and availability, litter box care, and household enrichment. The patient’s daily activities should be reviewed and in cases of house calls, traced throughout the house layout. Relationships with other pets in the house and with humans in the household should be reviewed. The stability of the human population should be assessed. For example, humans that work shift work hours may be home inconsistently, causing the patient’s environment to be inconsistent.

The incident considered the initiating incident, as well as further incidents should be reviewed in detail. There should be an examination of the frequency, intensity and severity of the behavior(s) in question. The behavior of all of the affected cats and subsequent responses should be determined. Videotaping of these incidents can be very helpful to the clinician, allowing direct

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visualization of body language rather than relying on the client’s memory. Any attempts at treatment or punishment should be reviewed as these may negatively impact the prognosis.

House calls are often the best approach to pursuing a behavior consultation, as the clinician can see first hand the environment that the cats live in, what resources are available and where incidents occurred. PLEASE NOTE: Where inter-cat aggression has become so severe that the cats cannot see each other without erupting into vocal and physical violence, they should be separated until such time as a treatment plan can be developed. During the home behavioral consultation, the cats should NOT be reintroduced to allow the veterinarian to see ‘what happens’. This can be potentially dangerous to cats and humans. The veterinarian must rely on the information gleaned during the interview as well as an video the client has. Points to consider with regards to the potential success of treatment Inter-cat aggression can disrupt animal bonds for life. The ability of two or more cats to live together again after the aggression has become severe may be limited. Reconciliation may be impossible. As with cat-human aggression, a frank, open discussion is necessary with the client(s) in order to determine the prognosis for the patient. It is important to determine how bad the aggression has become and whether this has also affected the human-animal bond. The clinician will need a frank admission by the client about how willing they are to implement the outlined treatment plan. The clients will need to be open about what options they are considering. Options may include following the prescribed treatment plan, drugs, relinquishment and/or euthanasia. Further, the clients’ expectations must be known. What are the clients’ goals and timeline? The clients may have unrealistic expectations, desiring complete resolution of the problem. Resource management: Critical in multi-pet environments Resource management in a multi-pet environment is critical to reducing territorial anxiety in cats. While litter box resources are often considered during house soiling consultations, these represent only one facet of household resources that are important to indoor cats:

• Litter boxes • Sleeping and resting areas • Food bowls • Water bowls • Toys • Perches • Scratch posts • Scratching surfaces

Litter boxes should be provided at a ratio of one litter box per cat, plus one additional box. The boxes should not be located in the same room, and not all on the same level of the house. Suitable box size, unscented clumping litter substrate and coverless boxes should be used. Regular, daily or twice daily scooping of the boxes is necessary. Sleeping and resting locations should be ample to accommodate all cats in a variety of locations. Most cats do not wish to sleep close to other cats, which means that sleeping and resting locations should be distributed widely throughout the household. Some of the scratch posts and perches should be located near windows, to allow the cat to visualize outdoor activities such as birds and squirrels, which is mentally stimulating for the cat. In cases where outdoor cats or animals are causing territorial anxiety, the yard view may need to be blocked temporarily. Other scratch surfaces should be located near sleeping spots, so that the cat who wishes to scratch and stretch after a nap has immediate access to an acceptable scratching surface. The client may choose to place scratching surfaces in both busy and quiet areas of the household, so that the cat has multiple locations to scratch.

For most cats, catnip and catnip spray help to encourage use of these articles. It is important to note that kittens under four months of age will not respond to catnip and some rare adult cats are actually non-responders.

Food can be a major source of anxiety in multi-cat households. Ideally, cats should be fed three-four meals a day, in separate rooms. Cats fed within visual, olfactory and/or auditory distance of each other may experience anxiety as they eat. This may not be obvious to the client, as signs can be subtle. Some cats may eat their food rapidly, others may move from bowl to bowl, sometimes pushing the other cat away. Some cats may eat and then move to another area of the household to mark territory in an expression of their anxiety. The client should ensure that one cat is not bullying the other cat away from its food. It is usually necessary to confine cats to separate rooms for feeding. Water bowls need to be distributed throughout the household.

Toys should be ample in number, with types of toys being rotated every week if at all possible. Dietary adjustments Diets such as Royal Canin Calm® or Royal Canin Urinary/Calm® and Hill’s Multicare C/D Stress® can be helpful in the long-term management of intercat anxieties. To achieve effect, they need to be fed as the cat's sole source of nutrition and used consistently in the long term. Calming nutraceuticals such as Zylkene ® or Anxitane® may be helpful.

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Medications Determining aggressor and defensor is a critical point in development of an appropriate treatment plan. This is most true when selecting potential behavior modifying drugs for each cat. For example, selection of a drug that will improve the confidence of a defensor, when the aggressor has been misidentified as the defensor can have disastrous consequences. The author refers the reader to the AAFP Behavior Guidelines booklet, which contains a thorough review of the available pharmaceuticals and the targeted individual for each of these drugs. Some of these drugs will be discussed during the lecture.

http://www.catvets.com/public/PDFs/PracticeGuidelines/FelineBehaviorGLS.pdf Prognosis The ability to resolve inter cat aggression is going to depend on many factors. First and foremost, it is going to depend on the points noted above, as to what client expectations are and whether they are willing to follow prescribed treatment plans. If this is not the case, then the chances of success diminish greatly. Secondly, the duration of the problem, and third, it’s severity, will impact the chance to implement change. Setting realistic expectations and realistic time frames for achieving goals early on in the consultation process is more likely to set the stage for success or at least partial resolution. Clients and clinicians should understand the limitations of the problem and what is reasonable to expect from treatment. Sample questionnaire for a home behavior consultation Patient ID: Patient Signalment: Medical Conditions: 1. 2. 3. Current Medications: 1. 2. 3. What amount of day does cat spend in the following activities? Sleeping Resting Eating Grooming Hiding Playing Alone Playing with human Playing with other cat How often does cat use litter box for BM? U? Other Pets 1. 2. 3. Environment: Layout- rough drawings attached- Y N

Environmental resources Litter boxes Number Location Characteristics Feeding Stations Number Location Characteristics Feeding Schedule Food Amount Timing Private Locations/Hidey spots Number Location Used?

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Elevated Locations/3D space AvailabilityNumber Location Used? Windows Location Look out onto: Other environmental enrichment: Toys: Directive play with client: Potential external stressors noted outdoors: Unique considerations (ex. flooring type, smoking, cleanliness, clutter, noise levels) Social Interactions Humans Number Stability of residence Stability of employment hours: Relationship with Cat: Other regular visitors: Dogs Cats How long have cats lived together? Do they groom each other? How often? Do they rest/sleep together? Do they stay in the same room together? Does one ever avoid the other? Does one cat ever block access to the food or resources? Do they play together? Describe the play Before the current incident have there ever been any incidents of concern? Has either cat ever shown any aggression towards people or other pets? Specific incidents reported Known Triggers of Aggression: Aggression directed towards: Client/Individual reaction to aggressive behavior: Any punishments used? Yelling, swatting, other Veterinarian Interactions with Cat during visit:

References Pachel, CL. Intercat Aggression: Restoring Harmony in the Home: A Guide for Practitioners. Vet Clin North Am Small Anim Pract 2014: 44 (3): 565-579. Bain, M and Stelow, E. Feline Aggression Toward Family Members: A Guide for Practitioners. Vet Clin North Am Small Anim Pract 2014: 44 (3): 581-597. Ellis, S and Sparkes, A. ISFM Guide Feline Stress and Health: Managing Negative Emotions to Improve Feline Health and Wellbeing. International Cat Care 2016.

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It’s Just a Hairball…or is it? Understanding the Vomiting Cat

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON

Clients and veterinarians often consider that vomiting in cats is a regular occurrence that is not significant of health problems. This is a particularly common assumption with regard to vomit containing hairballs. Cats spend approximately 25% of their waking hours grooming (Panaman et al, 1981). The majority of ingested hair passes through the cat’s digestive tract into the feces with no negative side effects (Panaman et al, 1981). Cats that vomit occasionally may not be considered to have any specific underlying gastrointestinal disease (GID). However, cats that are vomiting more often than every 2 weeks are significantly more likely to have some baseline underlying GID (Norsworthy et al, 2015).

During routine preventive care examinations, detailed questioning about diet, diet changes, vomiting and hairballs is essential. When clients are uncertain about vomiting and/or hairball frequency, a calendar recording system should be recommended. In addition to regular vomiting, the patient may be showing signs of nausea that are not obvious to the client. These signs might include a finicky appetite, occasional loss of appetite or periods of anorexia, licking of the lips, gagging, and/or ingestion of grass to stimulate vomiting.

A history of abnormal bowel movements should also be investigated. Diarrhea can occur in conjunction with upper GID, or as a manifestation of lower GID. The veterinarian should also carefully question the client to identify evidence of constipation. Conditions such as inflammatory bowel disease (IBD) can exist as a problem within the small intestine, combined small intestine/large intestine or solely the large intestine. Vomiting, diarrhea and/or constipation may manifest as a result.

A thorough physical examination of the vomiting cat will help elucidate signs of nausea. The patient should be observed for signs of lip licking and frequent swallowing. A thorough oral health examination may reveal foreign objects looped under the tongue, oral ulceration or other oral or dental disease that may impact appetite and vomiting.

Feline patient weights should be recorded on every visit to the clinic, as subtle weight loss can be one of the first signs of disease. The documentation of weight loss in a cat with frequent vomiting may be the only physical examination change noted. This change can be a hallmark of mild to significant GID.

The abdomen should be examined in quadrants and the patient carefully observed for evidence of nausea or pain during palpation of each quadrant. Evidence of pain during abdominal palpation may include very subtle changes. The patient’s face should be monitored closely for evidence of lip licking, wincing, blinking or other facial expression changes that could indicate pain. The patient may growl or hiss, although this is rare. Guarding of the abdomen during palpation of the painful quadrant(s) may also be observed. Abnormal findings during the palpation may include evidence of an enlarged liver, distended stomach, thickened/ropy intestines, abdominal fluid, masses and/or enlarged lymph nodes. Making a diagnosis The list of differential diagnoses in the adult and senior feline patient with chronic vomiting is long and complex. In all cases, a minimum database (MDB) plus a gastrointestinal (GI) profile is ideal for diagnostic testing. The GI profile should include cobalamin (B12), folate, feline specific pancreatic lipase (sfPL) & in many cases, trypsin-like immunoreactivity (TLI)

The patient’s feline leukemia virus (FelV) and feline immunodeficiency virus (FIV) status should be determined. Feline leukemia virus is a known cause of lymphoma in the feline patient. However, with the introduction of vaccination against FelV, there has been a shift in the types of intestinal lymphoma in cats (Cotter et al, 2011; Louwerens et al, 2005). This shift does not change the value of knowing the patient’s retroviral status, as disease management will be impacted by retrovirus infection.

Radiography is beneficial in elimination of some differential diagnoses in the vomiting cat. In older cats, the presence of neoplastic lesions within the thorax may be the only identifiable source of vomiting. Abdominal radiographs will be beneficial in identifying some foreign bodies, masses, intestinal accidents, and other changes. Evaluation of skeletal structures may indicate the presence of painful spondylosis, osteoarthritis and/or degenerative joint disease.

Ultrasonographic imaging is beneficial in identifying GI organ abnormalities (liver, gall bladder, spleen, pancreas) as well as the urinary tract. The intestines can be evaluated for abnormal gut motility, obstruction, or other intestinal accidents (ex. intussusception). The abdomen can be evaluated for a discrete mass or masses, including evidence of lymph node enlargement. Evaluation of intestinal wall thickness, as well as thickness and integrity of the four intestinal wall layers may help identify the presence of intramural disease such as IBD and lymphoma. Ultrasound changes associated with pancreatitis may be evident (Forman et al, 2004). The sensitivity of ultrasound in the diagnosis of pancreatitis is low (Cosford et al, 2010; Forman et al, 2004; Gerhardt et al, 2001).

Where clinical signs and laboratory studies are strongly indicative of disease such as IBD, lymphoma (diffuse neoplasia), discrete neoplasia, hepatitis, cholangitis, cholangiohepatitis and/or pancreatitis, biopsy is warranted. The decision to pursue endoscopy versus

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full abdominal exploratory may be impacted by the findings, the relative invasiveness of each procedure and cost. Exploratory surgery permits full visual assessment of all intra abdominal organs, biopsy of extra-intestinal tissues (liver, pancreas, lymph nodes etc) and full thickness intestinal biopsy (Kleinschmidt et al, 2010). Symptomatic, targeted and empirical therapies Dietary changes may be beneficial to the patient with GID. Changing dietary format, such as dry to canned food, may improve digestion. The use of veterinary formulations that are easy to digest such as Royal Canin Gastro, Hill’s i/d or PVD EN may reduce or in some cases eliminate active GID signs. The role of dietary allergens in IBD and other GID is difficult to confirm. Food-responsive enteropathy is characterized by signs similar to other GID, although large bowel signs are more often observed and cutaneous disease may also be present. (Jergens et al, 2012).

Anti-emetics such as maropitant (CereniaTM) may be beneficial to the vomiting patient. Drugs with pro-kinetic effects should be used with caution in case of obstruction. Gastric acid blockers such as ranitidine and omeprazole are less likely to play a beneficial role in feline patients with GID.

Appetite stimulants for loss of appetite or anorexia may be beneficial in improving intake, but in the presence of nausea and GI inflammation, these drugs are likely to be of little utility until underlying disease is addressed. Mirtazapine provides both appetite stimulant and anti-nausea activity, making it a beneficial option in certain cases of feline GID.

Patients with GID may be experiencing pain as a result of or concurrent to their GID. As the signs of pain in the feline patient can be subtle at best, any conditions identified as potentially painful should be treated as such. Gabapentin, buprenorphine and non-steroidal anti-inflammatories are all beneficial in pain management. Multimodal analgesic protocols are most effective over single drug therapy.

It has been recommended that all cats with signs of GID and a serum cobalamin of <300ng/L should receive parenteral supplementation of cobalamin (Ruaux et al, 2005). The current supplementation dosage recommendations from Texas A&M University (TAMU) are 250 micrograms cobalamin SQ once weekly for 6 weeks followed by 250 micrograms one month later. Thirty days following this injection, a repeat measurement of B12 is recommended http://vetmed.tamu.edu/gilab/research/cobalamin-information).

The empirical use of steroids is generally not recommended in any situation in feline medicine, however, this is a frequently used therapeutic in feline GID patients. Limitations of finances and client willingness to pursue diagnostic biopsy may impact the treatment selection process. Empirical steroid usage precludes or limits usefulness of ultrasound or biopsy, as the drugs will change the local inflammatory pattern, thus confounding diagnosis. Where steroids are to be employed, urine culture should be considered prior to drug initiation, in order to rule out occult UTI. Prednisolone or dexamethasone are the steroids of choice in cases of IBD or GI lymphoma. The author does not recommend the use of depot steroids such as methylprednisolone acetate. The usefulness of budesonide is questionable, although it may offer benefits as an adjunct therapy. Empirical use of cyclosporine or chlorambucil is not recommended. References Cosford KL, Shmon CL, Myers SL, et al. Prospective evaluation of laparoscopic pancreatic biopsies in 11 healthy cats. J Vet Intern Med 2010;24:104–113. Cotter, SM, Hardy, WD, and Essex, M. Association of feline leukemia virus with lymphosarcoma and other disorders in the cat. JAVMA 2011; 166: 449-454. Forman MA, Marks SL, De Cock HEV, et al. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis. J Vet Intern Med 2004;18:807–815. Gerhardt A, Steiner JM, Williams DA, et al. Comparison of the sensitivity of different diagnostic tests for pancreatitis in cats. J Vet Intern Med 2001;15:329–333 Jergens AE. Feline idiopathic inflammatory bowel disease: what we know and what remains to be unraveled. J Fel Med Surg 2012;14:445–458 Kleinschmidt S, Harder J, Nolte I, et al. Chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract in cats: diagnostic advantages of full-thickness intestinal and extraintestinal biopsies. J Feline Med Surg 2010;12:97–103. Louwerens M, London CA, Pedersen NC, et al. Feline lymphoma in the post-feline leukemia virus era. J Vet Intern Med 2005;19:329–335. Norsworthy, GD, Scot Estep, J, Kiupel, M, Olsen, JC, Gassler, LN. Diagnosis of chronic small bowel disease in cats: 100 cases (2008-2012). J Am Vet Med Assoc 2013: 243 (10): 1455-1461. Panaman, R. Behavior and ecology of free-ranging farm cats (Felis catus L). Z Tierpsychol 1981; 56: 59-73. 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.

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Think Like a Cat: How to be Feline Friendly at Home and in the Practice

Kelly St. Denis, DVM, DABVP Charing Cross Cat Clinic

Brantford, ON

Cats do not see or experience the world the way we do. Understanding natural cat instincts can help us improve environmental enrichment at home, as well as improving veterinary visits for cats. In a natural environment, cats are predators AND prey. We frequently think of cats as hunters but forget that they are also hunted. Cats must be on the alert even in their own homes, and particularly at the veterinary clinic. This is the baseline instinct that can lead to negative behaviors both at home and in the clinic. The cat’s unique senses The unique senses of the cat impact how they interact with their world. Cats communicate through olfactory, visual, tactile and auditory means. A cat’s sense of smell is significantly more sensitive than a human. They perceive their world in overlapping clouds of smell. This in itself can lead to a heightened sense of awareness in the examination room. Although we believe we thoroughly clean our hospitals, many scents remain behind to arouse our feline patients. This can lead to redirected aggression or fear in the examination room. Vision at night for cats may be good, thanks to the retinal tapetal reflective tissue. Since they primarily hunt at night, our feline friends have little need for colour vision. The feline range of vision is best at 2-6 metres. Close up, feline vision is less than ideal, thus impacting their stress levels when foreign items are close by (this includes cucumbers, which can completely traumatize the unsuspecting feline). The feline binocular vision which has a 98 degree overlap allows for accurate assessment and judgement of distance. Cats have amazing hearing, using their pinna to rotate and collect as many surrounding sounds as possible. The pinna can swivel almost 180 degrees and move independently of one another. This helps them to track and locate prey, but also to detect predators. Remote sounds from outside of the examination room can be frightening to the feline patient.

Tactile senses permit communication with fellow felines and other species, including the veterinarian. Their responses can include affiliate communication like rubbing, head bunting, nose touching, kneading, treading and allo-grooming. Negative or agonistic communication can include biting and scratching.

Cats are easily threatened. Their response to threats is to flee, freeze or fight. As veterinarians we have all experienced this range of reaction in our feline patients. Our patients communicate with us by many visual cues. Understanding these is critical to improving feline visits. We need to monitor their posture, examine their facial expressions and respond accordingly. Home environment As obligate carnivores and solitary hunters, cats tend to be territorial and find safety in predictability of their surrounding environment. As household members, most clients understand that their cats are schedule-oriented. Cats appreciate consistency, know when mealtime has arrived, and are stressed by disruptions in their regular routines as well as by additions to the family (humans and other pets alike). Provision of appropriate resources will also go a long way to maintaining health and normal behavior. Resource management in a multi-pet environment is critical for cats, particularly those in a multi-pet household, or where young children reside. While litter box resources are often considered during house soiling consultations, these represent only one facet of household resources that are important to indoor cats:

• Litter boxes • Sleeping and resting areas • Food bowls • Water bowls • Toys • Perches • Scratch posts • Scratching surfaces

Litter boxes should be provided at a ratio of one litter box per cat, plus one additional box. The boxes should not be located in the same room, and not all on the same level of the house. Suitable box size, unscented clumping litter substrate and coverless boxes should be used. Regular, daily or twice daily scooping of the boxes is necessary. Sleeping and resting locations should be ample to accommodate all cats in a variety of locations. Most cats do not wish to sleep close to other cats, which means that sleeping and resting locations should be distributed widely throughout the household. Some of the scratch posts and perches should be located near windows, to allow the cat to visualize outdoor activities such as birds and squirrels, which is mentally stimulating for the cat. In cases where outdoor cats or animals are causing territorial anxiety, the yard view may need to be blocked temporarily. Other scratch surfaces should be located near sleeping spots, so that the cat who wishes to scratch and stretch after a nap has immediate access to an

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acceptable scratching surface. The client may choose to place scratching surfaces in both busy and quiet areas of the household, so that the cat has multiple locations to scratch.

More information can be found in the following brochure: http://www.catvets.com/public/PDFs/ClientBrochures/Environmental%20GuidelinesEViewFinal.pdf and on the following

website: https://indoorpet.osu.edu/cats/basic-indoor-cat-needs Food can be a major source of anxiety in multi-cat households. Ideally, cats should be fed three-four meals a day, in separate

rooms. Cats fed within visual, olfactory and/or auditory distance of each other or other pets such as dogs, may experience anxiety as they eat. This may not be obvious to the client, as signs can be subtle. Some cats may eat their food rapidly, others may move from bowl to bowl, sometimes pushing the other cat away. Some cats may eat and then move to another area of the household to mark territory in an expression of their anxiety. Water bowls need to be distributed throughout the household. Toys should be ample in number, with types of toys being rotated every week if at all possible. The veterinary visit

Step 1: It starts at home Feline friendly handling starts when clients are scheduling the cat’s appointment. In advance of potential issues, asking the owner about their access to a good carrier, their ability to get the cat into the carrier and what experiences they have had in the past are important to addressing problems before they occur. A telephone script for all staff to use may be beneficial. Any previous issues should have been documented in the patient file for easy reference.

The provision of carrier-friendly resource materials and support is key. Many clinics provide information on the selection of the ideal carrier for cat transportation. In situations where clients may not own a carrier, or do not have a sufficiently secure or ideal carrier, clinics should offer a carrier on loan.

There are several pamphlets available that provide tips on travelling to the clinic with a cat. The American Association of Feline Practitioners (AAFP) pamphlet entitled ‘Getting your cat to the Veterinarian’ (Figure 1; http://www.catvets.com/cat-owners/brochures) is an excellent resource for clients. This type of literature should be provided well in advance of the veterinary visit.

Feline facial pheromones (Feliway) are frequently useful in the reduction of stress. In advance of travel, clients may wish to spray Feliway onto a cloth and place it in the carrier with the cat. Alternatively, clinics can provide the client with Feliway-infused cloth pieces, sealed into zip-lock bags. For some cats, a Feliway infused cloth will reduce agitation, vocalization and soiling during transport.

Step 2: Feline friendly waiting Calming the feline patient and the client is critical from the moment they enter the clinic. Minimizing loud noises and reducing visual and auditory exposure to dogs is ideal. The existence of a feline friendly waiting area or a separate waiting room can significantly reduce the stress for both patient and client. If a waiting room is too chaotic, the patient and client should be moved immediately to their examination room. Reduced or non-existent wait-times assist in avoiding a buildup of tension in the waiting feline patient. Some clinics offer feline exclusive appointment hours. Clinics may also choose to have feline exclusive examination rooms.

A cat friendly advocate should be appointed in each practice. This individual should be instrumental in helping the practice achieve an optimal feline friendly environment. The appointed staff member should mark a goal of achieving AAFP feline friendly practice status (http://www.catvets.com/cfp/veterinary-professionals).

Step 3: A feline friendly outpatient visit During the patient’s visit, the veterinary team must continue to strive to reduce stress. In advance of significant handling, the patient should be assessed for pain and treated appropriately. Sedatives should be employed where necessary. Physical restraint should be avoided.

The ambience in the consultation room is of critical consideration. Clinical settings can be harsh to the feline senses. Clinical settings often have strong odors of cleaning solutions, medicinal smells and the scents of other animals. The lighting may be bright and harsh. Examination surfaces are often hard and unforgiving. Stainless steel surfaces may give off disturbing reflections. Thin gauge stainless steel surfaces are known to shift, and as a result may make unsettling noises. Brushed stainless steel surfaces give off less reflection, which can reduce stress.

Soften it up Provision of soft, fuzzy blankets and table top cushioning are valuable for all cat age groups, but in particular for the old and sick. Infusion of blankets with Feliway can further improve relaxation.

Warm it up Cats prefer warmer ambient temperatures than humans. The relative warmth of the room air should be addressed. Warming blankets in a spa or medical towel warmer in advance of use can be very beneficial. Alternatively, heated oat bags can be used in a designated drawer to warm patient blankets (FIGURE 2)

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Darken it up Bright, overhead fluorescent lighting has an important role in the medical examination. However, it is not a necessity during the entire visit. Use of softer incandescent lighting for the majority of the appointment will be more appealing to the feline patient.

Keep it quiet The location of the feline examination room relative to other parts of the clinic may not be alterable. Still, consideration should be given to external noises that may frighten the feline patient. This includes barking dogs, delivery of supplies and loud veterinary equipment such as dental and laundry machines. If the examination room location cannot be altered, then the timing of feline examinations should be carefully planned to avoid these noises. Feline exclusive consultation hours can be beneficial in these scenarios.

Make is calming with feline facial pheromones A Feliway diffuser should be plugged into an outlet in the feline examination room more than 30 minutes prior to commencement of appointment hours (Figure 3).

Keep it scent free While the selection of cleaners for the examination is critical to reduce transmission of disease, it is best to select those with reduced odour. Cleaners should be used as far in advance as possible of the next appointment, in order to ensure that the majority of cleaner scent has dissipated. Soft towels used on surfaces can be removed for washing and will reduce the amount of surface cleaning required.

Soiling or spraying by other patients should be addressed well in advance of the next appointment. The affected areas should be cleaned. In some cases, Feliway spray at the location of soiling will reduce further anxiety in the next patient. Garbage cans containing either urine soaked towels or fecal matter should be emptied and cleaned. In extreme situations, it may be ideal to shift to an alternate examination room until offensive scents can be eliminated.

Let the cat own the room Prior to the physical examination, the consultation should begin with conversation between owner and veterinary team member. The cat carrier should be placed on the floor in the examination room and the patient allowed to enter or exit the carrier at will. The patient should not be forced from the carrier. While the conversation continues, the patient should be permitted to explore the consultation room. Familiarization with the room, including being permitted into and onto objects as well as facial marking, will serve to reduce the patient’s stress levels. When it is time to examine the patient, the lid should be removed from the carrier and reluctant participants gently lifted out.

The benefits of pain management Cats are masters at hiding illness. Concealing pain is no exception. For some painful cats, a defensive or offensive response to handling is a matter of apparent self-preservation. Predicting pain and understanding pain is critical to a feline friendly approach to handling.

Individual practices should establish or adopt a pain index within the veterinary practice. Colorado State University has developed a pain scale system that can be utilized in veterinary practices. (http://www.csuanimalcancercenter.org/assets/files/csu_acute_pain_scale_feline.pdf). All staff should be trained to use a pain index consistently. This allows for a standardized approach to the assessment of feline pain. Every patient should be evaluated prior to any other handling, including the physical examination. The mildest handling of a painful patient may provoke a negative response. Identification of the painful cat allows the clinician to employ pain management techniques prior to further handling.

Step 4: Inpatient care The stress of illness can reduce a cat’s tolerance for handling. Dehydration and the tissue trauma associated with illness can cause pain. Sources of stress and pain must be addressed in the intensive care unit (ICU) patient in order to improve recovery.

Patient housing should be at a distance from the noise and smell of canine patients, if at all possible. Other nearby noises should be minimized. Conversations should be kept quiet. Dimmed lighting should be considered.

Within the ICU, patients should be provided with a thick, warm layer of blankets (Figure 4). Soft or fuzzy surfaced blankets are generally preferred. The use of newsprint paper provides no comfort, is cold and unyielding. Warmed oat bags placed under the blankets will improve the ambient temperature of the ICU cage. Provision of boxes or make-shift tents allow the patient to conceal themselves within the ICU cage. A FeliwayTM infused cloth or warmed FeliwayTM-infused blankets can be placed within the ICU cage. The litter box provided to the ICU patient should be wide, low-walled with soft textured, unscented litter.

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Understanding the Aging Feline Kelly St. Denis, DVM, DABVP

Charing Cross Cat Clinic Brantford, ON

As cats reach their senior and geriatric years, our focus on their health needs to intensify. Cats age rapidly. The domestic cat reaches its prime by 3 to 6 years of age. At the age of 7 cats are experiencing biological changes related to senescence. Cats aged 7-10 are ‘mature’, cats aged 11-14 are ‘senior’ and after 15 years of age, cats are considered to be ‘geriatric’ (1). For the purpose of simplicity, this lecture will refer to all three age groups as ‘senior’.

By the time a cat reaches it’s senior years, it is hopeful that we have established a good working relationship with our client over the years of the patient’s life. Clients recognize that their pet is getting old. However they do not always understand exactly what changes are going to occur and which of those changes are normal and which are a sign of disease or pain.

Clients usually have a good awareness of their cat’s normal behaviors and activities. As cats age, clients should consider starting some form of journal or notebook to highlight the normal patterns of behavior of their particular cat. Timing of eating, elimination behaviors, sleep, and play, when documented, will act as an excellent resource when attempting to identify changes.

A key behavior that is often excused as a normal part of aging is sleep. Cats living in confinement (indoors) sleep up to 19 hours per day (2). Cats do not normally sleep more merely as a consequence of aging. Sleep patterns include hours spent sleeping or resting, choice of location, and timing of sleep in a 24-hour period. Any changes noted in the normal sleeping patterns should act as an alert to the caregiver that something is not normal. Changes in normal sleep patterns may occur as a result of pain, nutrition imbalances, disease or cognitive dysfunction. Knowledge of all of the cat’s normal behavior patterns is a basic foundation for knowing when changes occur. The subtle signs of sickness Cats are masters at hiding illness. We understand and seek to help our clients recognize what subtle changes can mean with regard to feline health. In addition to being a sign of disease, we also have to recognize these subtle changes as evidence of possible pain.

The 10 subtle signs of sickness 1. Inappropriate Elimination Behavior or Litter Box Use 2. Changes in Interaction 3. Changes in Activity 4. Changes in Sleeping Habits 5. Changes in Food and Water Consumption 6. Unexplained Weight Loss or Gain 7. Changes in Grooming 8. Signs of Stress 9. Changes in Vocalization 10. Bad Breath

Senior and geriatric patients are at increased risk of disease in general. Risks of conditions such as chronic renal disease and hyperthyroidism are known to increase with age. Older patients are also at increased risk of neoplasia, hypertension, cardiac disease, osteoarthritis (OA) and/or degenerative joint disease (DJD). Dental disease and dental pain are common. Observations of unexplained changes in body weight, behavior, appetite, drinking, elimination behavior and grooming need to be addressed by the client and clinician in a timely fashion. Pain If cats are masters at hiding illness, they are geniuses at hiding pain. Caregivers frequently expect to see obvious, outward displays that would indicate pain in their cat, thus leaving them unable to perceive subtle changes suggestive of pain. Some clients may excuse away any changes, citing age as a factor. Monitoring normal patterns of behavior will help detect changes that may be occurring as a result of pain. The caregiver should monitor the cat’s mobility pattern and willingness to jump up or down. Lameness or signs of stiffness after rest should be noted. Changes in litter box usage and/or elimination patterns may be observed in painful cats. For example, cats with painful DJD may no longer consider it necessary to travel to a litter box located in the basement. They may instead elect to use an inappropriate area on the main floor of the house. Increased sleeping hours can be a big indicator of pain, as the cat becomes reluctant to move. Some cats may howl and meow abnormally at odd times during the day, particularly at night. Any or all of these signs can be due to pain, but may also overlap with diseased conditions as well as cognitive dysfunction. Clients should be encouraged to actually make notes about their cat’s activities and behaviors, especially as they age. This way, subtle and gradual changes will not be missed. In many cases, the best way to ascertain whether a cat is truly experiencing pain is to administer a 2-4 week analgesic trial.

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Body & muscle condition changes As cats age, changes in body weight, body condition and/or muscle condition can be the earliest signs noted that disease is present. Assessment and recording of body weight, body condition scoring (BCS) as well as muscle condition scoring (MCS) at every single veterinary visit is necessary to detect subtle changes early. As cats age, body muscling naturally changes. Cats will undergo decreases in muscling, a natural process referred to as sarcopenia. This needs to be distinguished from the more negative and often more rapid change cachexia. Cachexia can indicate the presence of disease, insufficient dietary needs and in particular, insufficient dietary protein. In addition to senior biannual examinations with the veterinarian, regular weigh-ins and BCS/MCS assessments with a registered veterinary technician will assist in early detection of changes in any of these parameters. The client can be taught how to assess these parameters at home as well, making them more aware of changes should they occur. https://www.wsava.org/sites/default/files/Body%20condition%20score%20chart%20cats.pdf https://www.wsava.org/sites/default/files/Muscle%20condition%20score%20chart-Cats.pdf Dietary needs As cats age, appetite will often diminish. Changes that may impact the aging cat’s appetite include diminished taste, smell and vision, dental disease, painful arthritis and cognitive changes. Treatable conditions should be addressed and adjustments made to improve intake in the home setting. Dental surgery should not be avoided on the basis of age. Safe general anesthesia of senior patients is possible, with the right care and attention.

As cats age, their caloric and nutritional needs change (1). Early on in the aging process, up to 11 years of age, a cat’s energy needs will decrease by 3% per year. However, at the age of 12 and up, the energy needs actually increase. As cats age, they become less efficient at digesting food. In particular, the digestion of fats and proteins may be impaired. Senior and geriatric feline patients can be susceptible to weight loss. Dietary palatability is a major concern in this age group, including ensuring that the patient is consuming sufficient calories to meet their metabolic energy requirements (MERs).

Daily dietary intake needs to be quantified by the client in detail. Metabolic energy requirements (MERs) need to be calculated often by the clinician or veterinary technician. Quantifying daily intake for cats is a critical piece of knowledge for clients with senior and geriatric cats, particularly when unexplained weight loss has been detected.

Intake can be improved in the home setting by offering smaller, more frequent meals of highly palatable, age-appropriate food. Slight warming of the food either with warm water or briefly in the microwave, will improve the smell and taste of the food. The client should ensure that the cat has easy access to the food bowls and that competition from other household cats or dogs is completely eliminated. Cats may be experiencing some cervical pain as a result of arthritis, or have neck weakness associated with disease. Feeding platforms raised to a comfortable height will be beneficial for these cats. Age-appropriate diets from a reputable pet food company are best chosen during the senior and geriatric years. Many generic and over the counter foods do not contain age-appropriate content with regard to calories, protein, phosphorus and other nutrients. In these cases, it is best to rely on companies that have a good nutrition research program with an excellent track record of developing diets based on high-level evidence-based medicine. Cognitive changes Behavioral problems in the geriatric cat may be explained by the presence of disease and pain. Treatment of the disease, and/or treatment of pain will often resolve behavioral changes. Howling may be observed in some cases of hyperthyroidism, as well as patients with hypertension. Changes in elimination, including soiling outside of the litter box can occur with conditions such as arthritis, diabetes mellitus, renal disease, lower urinary tract disease, hyperthyroidism and neoplasia. Pain can lead to many changes in behavior including, but not limited to, elimination issues, irritability, increased sleeping, howling, decreased grooming and decreased mobility. Regular clinical testing as well as pain management will help identify disease and pain-related causes of behavior changes. Analgesic trials lasting 2-4 weeks will help identify pain-related behaviors. Cats that are over 6 years of age have evidence of DJD in at least one joint (3), and as a result many should be on daily analgesics and OA/DJD therapeutics.

In some cases, cognitive dysfunction (CD) may be the primary source behind the behavior changes noted (4). Although there are no specific diagnostic criteria for CD in cats, ruling out other causes and treating for pain will help the clinician form a presumptive diagnosis. Cognitive dysfunction signs in cats can include disorientation (time or space), altered learning and memory, house soiling, altered interactions with the client, activity changes, sleep pattern changes, alterations in appetite, and/or decreased grooming (4). Vocalization may also occur. Once other conditions have been treated and/or ruled out, CD becomes a more likely diagnosis. There are no specific medications that have been appropriately tested and shown to benefit cats with CD (1, 4), but adjustment for behavior and addressing environmental needs can go a long way to improving the patient. Mental stimulation is a key component in the aging cat and in particular the cat with CD (4). Regular play, feeding puzzles and other games will keep the mind active and engaged, reducing random CD behaviors.

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Unique environmental needs Senior and geriatric cats have unique environmental needs. This mainly stems from their likely reduced mobility secondary to arthritis, as well as weakness due to sarcopenia and/or disease. Particular consideration should be given to resource management. Litter boxes should be placed throughout the house, on more than one level, to reduce the travel time required for a senior cat to get to the box. Multiple litter boxes will also reduce competition issues in multi-cat households. A high walled litter box may be viewed as a painful challenge to be avoided. Use of low entry or low walled, uncovered litter boxes is recommended. Food and water bowls should be placed strategically throughout the house. Competition for food intake and potential safety threats at mealtime should be eliminated. This can be accomplished by feeding the senior cat in a confined environment away from other cats, dogs and young children. Food bowl preferences should be considered. Some cats will prefer bowls, but others may prefer flat, open edged plates. Raised feeding surfaces may reduce discomfort in those cats with cervical arthritis pain or weakness from disease. Assistance with access to higher furniture such as beds and windowsills can be accomplished with steps or platforms to reduce necessary jumping heights. Aging cats still need to play. Diminished play activity should be viewed as a potential sign of pain requiring an analgesic trial of 2-4 weeks duration. Favorite toys and play activities may vary from day to day. Caregivers should offer options as needed. Toys and feeding games that stimulate mental activity are beneficial. Electronic games on tablets such as Friskies App for cats offer alternatives for mental stimulation. Rather than placing it in a bowl, simply hiding kibble throughout the house at mealtime can provide a unique hunting experience for any age cat. End of life decision making It is the clinician and veterinary team’s role to help the caregiver understand what is normal for their cat and how this normal changes with advancing age. Encouraging the caregiver to record their cat’s daily behaviors will improve the ability to identify diminishing quality of life. Knowing the level of changes that have occurred in behavior patterns over time help the client to come to terms with end-of-life decisions. Regular contact with the caregiver and patient through 2-3 health checkups per year as well as frequent weigh ins can improve the bond and trust between the client and the veterinary team. This type of regular care opens channels of communication necessary as quality of life diminishes and euthanasia decisions need to be made. Quality of life discussions are difficult at best, but they will be made easier by open relationships based on trust and mutual respect. References Little, Susan E. The Cat. Clinical Medicine and Management. 2011. Elsevier Saunders Inc. Jongman, EC, Adaptation of domestic cats to confinement. J Vet Behav. 2007; 2: 193-196. Lascelles, B. Duncan X., et al. Cross-sectional study of the prevalence of radiographic degenerative joint disease in domesticated cats. Vet Surg. July 2010;39(5):535-44. Landsberg, G, Denenberg, S and Arauj, J. Cognitive Dysfunction in Cats. A syndrome we used to dismiss as ‘old age’. JFMS 2010; 12 (11): 837-848


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