Incorporating analgesia into anesthetic protocol (Proceedings)

A. No matter what anesthetic protocol is chosen, the addition of adequate analgesia is imperative for safe anesthesia and for enhanced patient outcome. Perioperative analgesia has two monumental advantages:

     1. Analgesia increases anesthetic safety by decreasing the necessary dosages of anesthetic drugs. Most anesthetic agents, including the anesthetic gases, block the brain's response to pain but don't actually block pain. If the pain is severe enough, the brain can still respond and make the animal appear to be inadequately anesthetized. The result is that the vaporizer is turned up and the brain ceases to respond, but the patient is now too deeply anesthetized and can be at a very dangerous physiologic plane. A more appropriate response would be to decrease the pain and maintain anesthesia at a light, safe depth of anesthesia.

     2. Analgesia improves our medical success rate because adequate analgesia improves healing and allows a decreased incidence of postoperative stress-related complications. 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.

Thus, pain management isn't just the ethically 'right thing to do', it is also medically beneficial.

B. When designing analgesic protocols, 3 basic tenets of pain management should always be followed: 1) analgesic drugs should be administered preemptively; 2) multimodal analgesia should be used (especially when pain is moderate to severe); and 3) analgesia should continue as long as pain is present or at least until pain can be reasonably tolerated.

     1. Analgesia provided prior to the pain stimulus ("pre-emptive analgesia") is more effective than analgesia provided once pain has occurred because it prevents or alleviates the hypersensitization of the pain pathways. Because animals try to hide pain when at all possible, it is likely that once an animal is exhibiting pain, the hypersensitization process has begun and pain will be more difficult to treat. Preempting pain will decrease the overall intensity of the pain sensation and will increase the effectiveness of analgesic drugs.

     2. Use of a variety of anesthetic drugs, techniques and routes of administration ("multimodal analgesia") capitalizes on the additive or synergistic effects of analgesic drugs and allows us to provide analgesia that is more intense and/or of longer duration than analgesia provided with any one drug used alone. For example, the use of an NSAID with an opioid typically provides greater analgesia than either an NSAID or opioid alone.

     3. Finally, pain must be addressed not only postoperatively but even after the patient has been discharged from the hospital. Many veterinarians feel that animals do not need analgesic drugs once they have left the hospital because the patients tend not to exhibit pain at home. However, we know that animals instinctively hide pain and that pain, even from elective procedures, does not just magically go away once the animal is no longer in the hospital. Instead, the pain dissipates gradually over a period of days to weeks (depending on the severity of the disease, injury or surgery) and the pain that the animal experiences in that time should be addressed. Even if the animal appears 'okay', as scientists, we know that we severed nerves, caused tissue trauma, and induced inflammation and that these sources of pain will undoubtedly cause some discomfort that does not cease as the patient exits our hospital door.

C. Analgesic Drugs

     a) Opioids

Morphine, hydromorphone, oxymorphone, fentanyl, butorphanol, buprenorphine

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

          • Disadvantages of opioid class: Controlled substances (as are many of the drugs we use for anesthesia), relatively short duration of action (when compared to the duration of surgically-induced pain)

          • NOTE: Opioid-induced respiratory depression is HIGHLY OVERRATED in veterinary patients. In animals, the opioid-induced respiratory depression is mild and tends to be related to degree of sedation - in which case, ALL sedatives could be respiratory depressants.

     a) Full agonists (morphine, hydromorphone, fentanyl, etc...)

     • Most potent class of analgesic drugs

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

     • Excellent premedicants since they provide analgesia and sedation (in dogs – in cats they may not be sedating so a small dose of a sedative is generally used with the opioid)

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

     • Duration of action 2-4 hours for morphine and hydromorphone

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

     • Effects

          o Sedation - good effect pre-op and often post-op in dogs

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

          o Minimal to moderate respiratory effects

          o Minimal cardiovascular effects

     • Recommendation: Use a full agonist opioid as the standard opioid, use other opioids in the instance when a full opioid isn't the best choice or the pain is only mild.

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

     • Not as potent as the full agonist class

          o Don't confuse binding potency with analgesic potency

          o May be appropriate when pain is mild to moderate or as part of a multimodal protocol

          o 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

     • 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 (TM; buprenorphine), CRI (not as effective as full agonist CRIs)

Effects

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

          o Butorphanol provides moderate sedation in both dogs and cats, buprenorphine provides mild to no sedation

     • Recommendation: Use buprenorphine transmucosally in cats, both in-hospital and for at-home therapy. Use butorphanol for sedation.

     c) Oral opioids that can be used perioperatively include tramadol, codeine, codeine + acetaminophen and morphine. The most commonly used oral opioid is tramadol:

     • Tramadol is called an 'opioid like' drug because only a portion of its effects are mediated through the opioid pathway.

     • Tramadol is an excellent 'add on' drug but its highly variable absorption (65±38% in the dog) and short duration of action (only lasts 4-6 hours) makes it inappropriate for use as a sole agent but an excellent inclusion in a multimodal protocol.

     • Tramadol is the most commonly used oral opioid primarily because it is currently not controlled by the DEA – NOT because it is the most effective or potent opioid.

     b) Local anesthetic drugs

Advantages: Inexpensive, easy to administer, very effective

          o Local anesthetic drugs are extremely effective, inexpensive and easy to use.

          o Local anesthetic drugs block pain impulses in the periphery and prevent the impulses from reaching the central nervous system.

          o This effect alleviates or even eliminates the sensation of pain for the duration of the block.

          o This effect also decreases the likelihood that 'wind-up' or hypersensitization will occur so the overall sensation of pain will be less than it might have been without the use of local blocks.

          o The analgesia allows the patient to be maintained under a lighter plane of anesthesia and this makes the anesthetic episode safer for the patient.

Disadvantages: Relatively short duration of action when compared to the duration of pain

Bupivicaine and lidocaine are the most commonly used local anesthetic drugs

          o Bupivacaine HCl

          o Onset of action: approximately 5-10 minutes after injection (up to 20 minutes)

          o Duration of action: 4 to 6 hours

          o Dose 1-2 mg/kg (use the lower end of the dose in cats)

          o Lidocaine

     • Onset of action: rapid (less than 5 minutes)

     • Duration of action: 90-120 minutes

     • Dose 2-4 mg/kg (use the lower end of the dose in cats)

     • LIDOCAINE can be used as a constant rate infusion (CRI). NO OTHER local anesthetic can be administered IV. Controversial in cats

     c) 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...)

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

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

          o Recommendation for dogs: Use injectable NSAIDs for perioperative pain and send patient home on oral version of SAME NSAID.

          o 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.

     d) Alpha-2 adrenergic agonists (medetomidine, dexmedetomidine)

     • Advantages: provide both sedation AND analgesia, effects are reversible, effects are 'titratable'

     • Disadvantages: cause cardiovascular changes that are well-tolerated in patients with healthy hearts but not appropriate for patients with cardiovascular disease

     e) NMDA receptor antagonists (ketamine)

     • Advantages: Prevent or treat wind-up, inexpensive

     • Disadvantages: Must be administered by CRI, may cause dysphoria if dose is too high, not a true analgesic drug

     • NOTE: Ketamine is used to eliminate or alleviate 'wind-up' (up regulation of the pain pathway) and is not a true analgesic drug, thus, it MUST be administered as part of multimodal therapy with analgesic drugs (eg, NSAIDs and/or opioids).

     f) Other drugs to consider include gabapentin for neuropathic pain.

D. Analgesic techniques

A discussion of pain management should not be limited to a discussion of drugs but should also include a discussion of ways to use the drugs and ways to provide analgesia that does not include drugs. Of course, bolus injections of drugs are commonly used. Other techniques include:

     a) Constant rate infusions (CRIs)

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

     • A more stable plane of analgesia with less incidence of break-through pain (which can be difficult to treat);

     • A lower drug dosage delivered at any given time, resulting in a lower incidence of dose-related side effects;

     • Greater control over drug administration (easy to change the dose);

     • Decreased need for stimulation of resting patients to administer drugs; and

     • Decreased cost (when compared to technician time, needles and syringes required for repeat injections).

Drugs that are useful for CRIs include fentanyl, hydromorphone, morphine, butorphanol, ketamine, lidocaine and a myriad of combinations of these drugs.

     b) Local and regional blockade

     • As previously discussed, this is an effective, easy and inexpensive way to make a profound impact on a patient's pain.

     • Commonly used local anesthetic blocks include: 'field' block, mandibular block, maxillary block, onychectomy block, intercostals block, brachial plexus block, etc...

     • Local anesthetics can also be used in the epidural and articular spaces

     • Regional blockade includes epidurals – opioids, like preservative free morphine, should be used for epidurals because of the long duration of action with minimal to no systemic effects or motor blockade.

     c Non-pharmacologic therapy can also be used to decrease post-operative pain. Therapies that could be considered as multimodal additions for treatment of surgical pain include:

     • Thermotherapy (heat or ice), acupuncture, physical therapy including light exercise (walking, swimming, etc...), transcutaneous electrical nerve stimulation (TENS), Etc...

E. Incorporating analgesic techniques

Anesthesia is divided into 4 separate and equally important phases (preanesthesia, induction, maintenance and recovery). Analgesia is not usually addressed during induction but should be addressed in the other 3 phases.

     1. Preanesthesia – use boluses of opioids, alpha-2 agonists and NSAIDs. Consider starting the CRI for patients with moderate to severe pain.

     2. Maintenance – can repeat boluses of opioids or alpha-2 agonists. Use local and regional blocks, use CRIs. Analgesia in the maintenance period improves anesthetic safety by allowing a decrease in the need for inhalant anesthetic drugs.

     3. Recovery – MUST ADDRESS PAIN. Can repeat boluses of opioids and/or alpha-2 agonists. May need to continue CRIs. Consider non-pharmacologic therapy. Prescribe drugs/techniques to be utilized after discharge from the hospital. NSAIDs, tramadol, other opioids like codeine and fentanyl patches are commonly used postoperatively. Post-operative techniques that the owners can do at home include icing incisions, simple flexion/extension exercises, controlled leash walking, etc...

F . Sample Perioperative Analgesic Protocols

     1. Routine OHE or neuter

          a) Preemptive hydromorphone (0.2 mg/kg IM) and carprofen (4 mg/kg SQ) ± 5-10 microg/kg dexmedetomidine

          b) Intraoperative field block of incision

          c) Postoperative assessment of comfort level and bolus of hydromorphone (0.1 mg/kg) or dexmedetomidine (1-5 microg/kg) if necessary

          d) Send home on 4 mg/kg carprofen PO SID x 4 days

          e) Exact same protocol for feline but use 0.2 mg/kg meloxicam (instead of carprofen) preemptively and do not repeat dose. Send home on 0.01-0.02 mg/kg TM buprenorphine BID x 4 days

     2. Cruciate repair

          a) Preemptive hydromorphone (0.2 mg/kg IM) and carprofen (4 mg/kg SQ) ± 5-10 microg/kg dexmedetomidine

          b) Intraoperative morphine epidural (0.1 mg/kg) ± bupivicaine (1 ml/4.5 kg); OR use one of the CRIs (like Morphine/Lidocaine/Ketamine – or MLK)

          c) Postoperative assessment of comfort level and bolus of hydromorphone (0.1 mg/kg) or dexmedetomidine (1-5 microg/kg) if necessary (most likely WILL BE NECESSARY); continue CRI for 12-24 hours if no epidural or if epidural ineffective (uncommon, but sometimes it just doesn't work)

          d) Send home on 4 mg/kg carprofen PO SID + 2-4 mg/kg tramadol PO BID x 7-10 days (or use a fentanyl patch or oral codeine in place of the tramadol); prescribe appropriate physical therapy for the patient.

          e) Exact same protocol for feline but use 0.2 mg/kg meloxicam (instead of carprofen) preemptively and do not repeat dose; change tramadol to 0.02 mg/kg buprenorphine TM BID x 7-10 days

Exploratory laparotomy – dog or cat

          a) Preemptive hydromorphone (0.1 mg/kg IM – dose is decreased because patient is compromised)

          b) Intraoperative CRI

          c) Opioid

          d) Lidocaine (omit in cat?)

          e) Ketamine

          f) Combo of any or all of these three drugs

          g) Continue CRI post-operatively

          h) Send home on opioids or NSAIDs (if appropriate – not appropriate if intestine is compromised) or both