Analgesia for cats (Proceedings)

Why should we treat pain?

Because we want to succeed! If we want to do the best medicine possible and give our patients the best chance to heal, then we have to treat pain. Pain initiates a fairly profound stress response and a sympathetic overdrive. Stress and autonomic imbalance are not benign and the cascade of side effects include gastrointestinal (GI) ileus, GI ulceration, clotting dysfunction, hypertension, tachycardia, tachyarrhythmias, and many others. Furthermore, stress and pain cause a fairly marked increase in cortisol release and a substantial increase in energy requirements, the latter of which may lead to a negative nitrogen balance and both of which impair healing. Clearly, pain compounds the negative effects of the initial disease, trauma or surgical condition, while alleviation of pain not only decreases side effects but also improves healing and sets us - and the patient - up for a successful outcome.

Principles of pain management

Regardless of which analgesic drugs are utilized in your practice, in order to maximize success, 3 basic tenets of pain management should be followed: 1) analgesic drugs should be administered preemptively; 2) multimodal analgesia should be used whenever pain is moderate to severe; and 3) analgesia should continue as long as pain is present.

What analgesic drugs are available for acute pain?

1. Opioids

     – Morphine, hydromorphone, fentanyl, butorphanol, buprenorphine (Buprenex®)

     – Opioids are THE MOST POTENT class of analgesic drugs available and should be utilized anytime that pain occurs – especially if pain is moderate to severe.

     – Advantages: Provide moderate to profound analgesia, safe, reversible, many are inexpensive, provide sedation, versatile (can be administered PO, IM, IV, SQ, in the epidural space, in the intra-articular space, etc...)

     – Disadvantages: may cause excitement in cats; may cause hyperthermia

     – NOTE: Opioid-induced respiratory depression is HIGHLY OVERRATED. In animals, respiratory depression is almost always directly related to degree of sedation - in which case, most sedatives are respiratory depressants.

          a. Full agonists (morphine, hydromorphone, fentanyl)

               • Most potent class of analgesic drugs

               • Should be considered any time that pain is moderate to severe

               • Excellent premedicants (morphine, hydromorphone)

               • Time to onset - < 5mins (< 1 min when administered IV)

               • Duration of action 2-6 hours

               • Uses: IV (morphine not generally bolused IV), IM, SQ, transdermal patch (fentanyl), CRI, epidural space, intra-articular space, etc...

               • Effects

                    o Excitement – use with a low-dose of a sedative

                    o Vomiting - beneficial effect when used pre-op, empties stomach

                    o Respiratory depression? Not a major concern like it is in human beings; directly related to degree of sedation.

                    o Cardiovascular depression? Very minor, opioids are extremely safe for patients with cardiovascular disease.

               • Recommendation: Don't be afraid to use a full opioid agonist in cats – just use a touch of acepromazine or medetomidine with the opioid.

               • Cat Dosages:

                    o Morphine 0.1-0.25 mg/kg IM

                    o Hydromorphone 0.1-0.2 mg/kg IM, IV, SQ

                    o Fentanyl 0.001-0.005 mg/kg IV (can be administered IM or SQ)

          b. Partial agonists (buprenorphine), agonist-antagonists (butorphanol)

               • Not as potent as the full agonist class

                    o Don't confuse binding potency with analgesic potency

               • Should be considered when pain is mild to moderate

               • May not be potent enough nor have a long enough duration (butorphanol) to be used alone as a premedicant for many of our surgical procedures. Use as part of a multimodal protocol.

               • Time to onset - < 5 mins (butorphanol); 10-20 mins (buprenorphine)

               • Duration of action - 45-90 mins (butorphanol); 6-12 hours (buprenorphine)

               • Uses: IV, IM, SQ, transmucosal (buprenorphine)

               • Effects

                    o Similar to the effects of full agonists but not as pronounced

                    o Butorphanol provides moderate sedation, buprenorphine generally provides mild to no sedation (can be sedating at higher dosages).

               • Recommendation: Use buprenorphine bucally in cats, both in-hospital and for at-home therapy. Use butorphanol as a sedative – use alone or with midazolam in old or debilitated patients or with an alpha-2 agonist in young, healthy patients.

               • Cat Dosages:

                    o Buprenorphine 0.01-0.03 mg/kg IM, IV, SQ, buccal (transmucosal)

                    o Butorphanol 0.2-0.4 mg/kg IM, IV, SQ

          c. Other Opioids – Tramadol

               • 'Opioid-like' drug – portion of analgesia is mediated through opioid pathway

                    o Other mechanisms of action include inhibition of serotonin re-uptake

               • Advantages: Not DEA controlled, excellent addition to NSAIDs

               • Disadvantages: Higher percentage of absorption & formation of active metabolite in cats than in most other veterinary species. Can cause dysphoria in cats but can cause sedation, decreased appetite and constipation (uncommon and generally only at higher dosages), may cause seizures in some veterinary species – not reported in the cat.

               • Recommendation: Use as part of multimodal therapy in most species

               • Cat Dosage: Not clear, 1-2 mg/kg PO BID?

2. Non-Steroidal Anti-inflammatory drugs

               • Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the few groups of drugs available that actually treats the source of the pain (inflammation) 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

                    o Most of the pain we treat involves some degree of inflammation (eg, surgery, trauma, osteoarthritis, cancer, etc...)

               • Advantages: Relatively long-lasting analgesia, easy to administer, anti-inflammatory, not controlled

               • Disadvantages: Not suitable for patients with some pre-existing diseases (eg, renal or hepatic disease, bleeding disorders).

               • Recommendation for cats: Antiinflammatory drugs should be used to treat pain of inflammation in cats. Both injectable Metacam® (approved in the US) and injectable Rimadyl® (approved in other countries but not the US) are used as a one-time injection to treat acute pain in cats.

               • Dosages: See label dosing for each NSAID for acute pain.

3. Local anesthetic drugs

               • Advantages: Inexpensive, easy to administer, extremely effective

               • Disadvantages: Almost none

               • Bupivacaine: 5 min onset, 4 hour duration; Lidocaine: 2 min onset, 60-90 min duration. Bupivacaine has a fairly long duration of action and should be used (either alone or with lidocaine) for all blocks.

               • NOTE: This class of drugs is grossly underutilized. USE LOCALS!

               • Cat Dosage: 1-1.5 mg/kg bupivacaine; 2-5 mg/kg lidocaine

4. Alpha-2 adrenergic agonists (medetomidine, dexmedetomidine)

               • Advantages: provide analgesia, effects are reversible, can provide anything from light to deep sedation

               • Disadvantages: cause cardiovascular changes that are acceptable in patients with healthy hearts but not appropriate for patients with cardiovascular disease.

               • NOTE: Alpha-2 agonists are synergistic with opioids for both sedation and analgesia, making alpha-2 agonists an excellent addition to a multimodal analgesic protocol.

               • Recommendation: Use alpha-2 agonists as premedicants, as part of a balanced anesthesia protocol, and in recovery when patients are having a rough recovery (these patients generally need analgesia AND sedation – and they need it fast)

               • Cat Dosages: (see dexmedetomidine label for FDA approved dose)

                    o Medetomidine 80-100 microg/kg IM as premed & for rough recovery

                    o Dexmedetomidine 20-30 microg/kg IM as premed & for rough recovery

5. NMDA receptor antagonists (ketamine)

               • Advantages: Prevent or treat 'wind-up', inexpensive

               • Disadvantages: Pharmacodynamics / pharmacokinetics not well-defined in all veterinary species. Ketamine must be administered by CRI.

               • NOTE: not true analgesic agents but analgesic adjuncts - must be administered with other agents (eg, NSAIDs and/or opioids)

                    o Dosage: Administer as CRI at 1-10 microg/kg min

What analgesic drugs are available for chronic pain?

1. Opioids: Buprenorphine (Buprenex®); Tramadol

               • Advantages: Provide moderate to profound analgesia, safe

               • Disadvantages: May cause sedation or excitement, anorexia and constipation (with long-term use)

                    o Buprenorphine: 0.01 mg/kg bucally SID-BID for chronic pain

                    o Tramadol: 1-2 mg/kg PO BID?

2. Non-Steroidal Anti-inflammatory drugs

               • Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the few groups of drugs available that actually treats the source of the pain (inflammation) 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

               • Most of the pain we treat involves some degree of inflammation (eg, surgery, trauma, osteoarthritis, cancer, etc...)

               • Advantages: Relatively long-lasting analgesia, easy to administer, anti-inflammatory, not controlled

               • Disadvantages: Not suitable for patients with some pre-existing diseases (eg, renal or hepatic disease, bleeding disorders).

               • Recommendation for cats: Antiinflammatory drugs should be used to treat pain of inflammation in cats. There are no oral NSAIDs approved for treatment of chronic pain in cats but meloxicam is widely used and should be considered for chronic inflammatory pain in NSAID-appropriate patients.

               • Dosages: 0.05-0.1 mg/kg PO SID q3-4 days

3. NMDA receptor antagonists (amantadine)

               • Advantages: Prevent or treat 'wind-up', inexpensive

               • Disadvantages: Pharmacodynamics / pharmacokinetics not well-defined in all veterinary species. Amantadine must be administered long-term (21 days or longer)

               • NOTE: not true analgesic agents but analgesic adjuncts - must be administered with other agents (eg, NSAIDs and/or opioids)

               • Dosage: Amantadine approx. 5 mg/kg PO SID x 21+ days

4. Gabapentin

               • Advantages: Moderately to highly effective for treatment of neuropathic pain (eg, pain associated with disc disease or nerve trauma)

               • Disadvantages: Pharmacodynamics / pharmacokinetics not well-defined in veterinary species.

               • NOTE: may or may not be true analgesic agent, recommend administering with other agents (eg, NSAIDs, opioids)

                    o Dosage: 1-10 mg/kg PO BID-TID (5 mg/kg BID) is a good place to start

5. Disease Modifying Agents

               • This group of agents includes nutraceuticals, special diets, glucosamine, chondroitin, poly-sulfated glycosaminoglycans, etc... Because these compounds are not potent pain relievers, they are generally best used alone only if pain is mild and are best used as part of multimodal therapy for moderate to severe pain. Great in cats! See individual products for dosages.