Cats Are Not Small Dogs

 They demonstrate pain differently:

 Quiet/withdrawn

 Hide

 Don't misinterpret acquiescence for comfort

 Very dangerous and hard to control when scared

'Pain is an unpleasant sensory and emotional experience, associated with actual or potential tissue damage.'

A more animal-orientated definition is: 'an aversive sensory and emotional experience representing awareness by the animal of damage or threat to the integrity of its tissues... producing a change in physiology and behaviour directed to reduce or avoid the damage, reduce the likelihood of recurrence and promote recovery.'

Analgesics are used less frequently in cats than they are in dogs:

 There is a perception that morphine is contraindicated in cats because of their reported rage reaction.

 Cats can't metabolise non-steroidal antiinflammatory drugs (NSAIDs) as well as dogs and so, until recently, NSAIDs haven't been available.

 The small size of cats leaves them vulnerable to the toxic effects of local anaesthetics.

 Cats don't express pain and this acquiescence is often misinterpreted as comfort.

Good Analgesic Practice

 Use analgesics if you think the procedure would be painful if you were the patient .

 Use analgesics from different drug groups together.

 Use pre-emptive analgesia.

 Use pain-coring techniques to assess the need for analgesics and repeat them to measure the efficacy of drugs given.

 Balance the benefits of analgesia against the risks. Is it fair to deny an old cat with a fractured pelvis and mild chronic renal failure analgesia because of the risk of causing further kidney damage?

 Change your thought processes--instead of 'it's just a cat castrate' think 'what analgesia would be appropriate for this procedure?'

Analgesic Drugs

 NSAIDs

 Opioids

 N-methyl-D-aspartic acid (NMDA) receptor agonists

 Local analgesics

NSAIDS

These produce analgesia by blocking the conversion of arachidonic acid to prostaglandins by cyclooxygenase. Prostaglandins play a number of roles in the pain mechanism. They:

 Are inflammatory.

 Sensitise pain fibres to mechanical stimulation causing a normal mechanical event to produce pain--think of a small burn on your arm. Touching it with light finger pressure results in a lot of pain because of the prostaglandin-induced sensitization.

 Act within the spinal cord to up-regulate pain signals--in effect they allow more pain signals through resulting in a greater pain sensation.

By blocking prostaglandin production, NSAIDs reduce or inhibit these effects.

But, prostaglandins have other roles in the body. They:

 Maintain renal perfusion in the face of hypotension

 Have a role in the production of mucus in the stomach which helps prevent gastric ulceration

Hence, the side effects of NSAIDs include gastric ulceration and kidney damage if given to hypotensive or dehydrated patients.

There are two types of cyclo-oxygenase (COX). COX-1 produces 'good' prostaglandins, COX-2 produces prostaglandins which are inflammatory and produce peripheral sensitisation. NSAIDs should preferentially inhibit the COX-2 enzyme. This is why we talk about COX-2-specific or COX-2-selective NSAIDs.

NSAIDs are metabolised in the liver, and cats lack the enzyme that breaks NSAIDs down by glucuronidation. This means that NSAIDs have a very long duration of action in cats compared to other species; aspirin only needs to be given every 48-72 hours for instance.

The cat's inability to metabolise NSAIDs through glucuronidation also explains the high toxicity of paracetamol in cats; even in the smallest doses it causes fulminating liver failure. This occurs because paracetamol, unable to proceed down the normal metabolic pathway, is broken down into highly toxic metabolites via the cytochrome P450 pathway.

There are several NSAIDs licensed for use in cats but the product data sheets should be read carefully as some, not all, dog NSAIDs can be used in cats and there are some unexpected contraindications. Carprofen and meloxicam are the two most widely used in practice.

 Carprofen:

 Relatively COX-2 specific

 Licensed for use before general anaesthesia

 Onset <1 hour, duration 12-18 hours

 Analgesia comparable with pethidine

 Meloxicam:

 COX-2 selective

 Effective postoperative analgesic

 Not as potent as pure mu-agonist opioid

 Better than partial or mixed agonist opioid

 New cat licensed version

 According to the data sheet, oral meloxicam should not be used in cats after meloxicam injection

Opioids

These act on receptors in the spinal cord and the periphery. There are a variety of classifications but most people refer to mu (µ), kappa (κ) and delta (δ) also known as OP3, OP2 and OP1 receptors. Analgesia is, in broad terms, mediated through the mu and kappa receptors with the delta receptors being responsible for euphoria and addiction.

It seems odd that we would evolve receptors which suppress pain, but they exist as part of the mammalian pain perception mechanism. Endogenous opioids are produced by the body as part of the flight or fight response and they block pain perception when that pain could be detrimental. Think about an animal fighting for its life--it will sustain injuries but experiencing pain in the middle of the fight will only make it more likely to lose. Having a mechanism to suppress pain in these situations is useful and we are fortunate to have found chemicals that make use of this mechanism.

We talk about agonists, partial agonists, mixed agonist/antagonist, and antagonists and this can be confusing.

 Pure agonists are drugs that occupy the opioid receptor and activate it.

 Partial agonists occupy the receptor and activate it producing some analgesia but less than that seen with pure agonists.

 Mixed agonists/antagonists are drugs that act as agonists on one receptor and antagonists on another--butorphanol is agonist at the kappa receptor but antagonist at the mu receptor.

 Antagonists occupy the opioid receptor and don't activate them. Antagonists are used to reverse the deleterious effects of opioids in cases of overdose.

Should one use morphine after buprenorphine or buprenorphine after morphine? There is a concern that using a partial agonist or mixed agonist/antagonist after a pure agonist might expose the cat to pain. This is because the analgesically less potent partial or mixed agonist will displace the more potent pure agonist. Care should be exercised when giving buprenorphine after morphine but it is fine to switch a patient that has had morphine on to buprenorphine once the morphine starts to wear off. Conversely, you can give morphine at any time after buprenorphine. This situation often arises when a cat has been given buprenorphine as premedication but is in obvious pain on recovery from surgery. Morphine can be used to provide supplemental analgesia. Although theoretically the morphine should not work in these circumstances, clinically cats in this situation benefit.

 Morphine:

 The gold standard

 Pure mu agonist

 Dose is lower in cats than dogs

 Fear of rage reaction is unfounded at clinical doses

 Use with ketamine and lidocaine for postoperative analgesia infusion

 Rapid onset of action: 10 minutes if given by the intravenous route

 Reasonable duration of action: 4 hours

 Methadone:

 Like morphine but without the vomiting

 Slightly cumulative so first top-up after 4 hours, subsequent top-ups after 6-8 hours

 Pethidine:

 Good analgesic but very short acting

 Requires frequent re-administration

 Light sedation at 3-5 mg/kg

 Butorphanol:

 Butorphanol is not an analgesic

 Butorphanol is not an analgesic

 Butorphanol is not an analgesic

 Its duration of action is too short and it is not potent enough to be used as the sole means of analgesia in cats

 Buprenorphine:

 Good analgesic

 Long duration of action

 A great choice analgesic for moderately painful procedures

 Probably not sufficient for very painful procedures such as fracture repair

 Licensed dose 10-20 µg/kg but author often uses up to 40 µg/kg

 Bell-shaped dose-response curve not clinically very significant

NMDA Receptor Agonists

Ketamine acts on the NMDA receptor in the spinal cord. It is a very potent analgesic and can be very useful when given as an infusion to cats postoperatively. It is often combined with morphine ± lidocaine.

Local Analgesia

Local analgesics can be useful in cats but care must be taken not to give the animal a toxic dose. Doses in the order of 11 mg/kg of lidocaine can result in toxicity in cats. It is recommended that clinical doses don't exceed 7 mg/kg or 1 ml of 2% lidocaine to a 3 kg cat. If bupivacaine is used the same 3 kg cat shouldn't receive more than 1 ml of a 5% solution. One of the most useful local analgesic techniques in cats is epidural analgesia where lidocaine or bupivacaine is administered into the epidural space with or without morphine. In cats the spinal cord and meninges extend into the sacrum so more care is needed to prevent spinal cord trauma or intrathecal injection of anaesthetic drugs.

Morphine, Lidocaine and Ketamine

An infusion of morphine and ketamine with or without lidocaine produces profound analgesia in cats. It is very useful postoperatively.

 Morphine 0.05-0.2 mg/kg/hr

 Ketamine 0.002-0.06 mg/kg/hr

 ± lidocaine 0.015-3 mg/kg/hr. The use of lidocaine is controversial in cats and care must certainly be used to avoid toxicity.

Chemical Restraint

Chemical restraint is often needed in cats to facilitate examination, blood sampling, radiography, ultrasonography and minor surgical procedures. A well handled, friendly cat presenting for neutering might just need mild sedation to facilitate venipuncture whereas an aggressive entire male feral tom cat trapped by the local cat welfare group may well need rendering unconscious before it is even safe to remove it from the trap.

The choice of chemical restraint technique is based on:

 The degree of sedation required

 The animal's temperament

 Knowledge of the animal's condition (not always available). Some cats need heavy sedation just to get close enough to examine them.

 An assessment of the cat's anaesthetic risk

Chemical Restraint Techniques

 Opioid combinations

 Ketamine combinations

 Alpha-2 agonist combinations

Opioid Combinations

 Acepromazine (ACP) 30-50 μg/kg and buprenorphine 20-40 µg/kg (note doses higher than 20 µg/kg are not licensed for use in cats in the UK). This produces good conditions for venipuncture in cats and is the author's preferred premedication for most routine surgical procedures.

 ACP 30-50 μg/kg and morphine 0.1 mg/kg. Good sedation in malleable cats and excellent analgesia.

 High-dose morphine (0.6 mg/kg) and ACP (0.1 mg/kg) can be useful in fractious healthy cats.

Ketamine Combinations

Ketamine produces good sedation when combined with sedatives to counter the extensor rigidity and excitement that ketamine alone induces. Ketamine can be useful on its own in cats that are completely unapproachable. Combinations include:

 Ketamine 5 mg/kg with diazepam or midazolam at 0.25 mg/kg

 Ketamine at 5 mg/kg with ACP at 50 μg/kg

 Ketamine with an alpha-2 agonist--see below

 Ketamine on its own intraorally. Intraoral ketamine is very useful for very fractious cats. Ketamine is squirted into the open mouth of a hissing feral cat through the bars of its cage. Initially estimate a dose of 5 mg/kg but this might have to be repeated. Cover the cage between doses and carefully assess the ketamine's effect. Once the cat can be handled safely other drugs including propofol (intravenous), midazolam, diazepam or an alpha-2 agonist can be administered. Always make sure the needle is firmly attached to the syringe, as it is otherwise too easy to spear the cat's eye!

Alpha-2 Agonist Combinations

Alpha-2 agonist combinations produce profound sedation or general anaesthesia. Because of the profound cardiovascular effects of alpha-2 agonists these combinations should be used with care in patients with cardiovascular, hepatic or renal disease. Ideally they should be reserved for patients of American Society of Anesthesiologists grade 1 or occasionally grade 2. Combinations include:

 Medetomidine and butorphanol--sedation

 Medetomidine and buprenorphine--sedation

 Medetomidine and ketamine ± butorphanol--anaesthesia