Perioperative analgesia: surgery doesn't have to be a pain (Proceedings)

No matter what anesthetic protocol is chosen, the addition of adequate analgesia is imperative for safe anesthesia. 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. Thus, pain management isn't just the ethically 'right thing to do', it is also medically the 'right thing to do'.

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.

          • "From the recent research concerning the mechanisms of nociception, it is clear that it is better to prevent pain than to treat it. This is a somewhat novel idea when applied to treating pain, but the idea of prevention is clearly entrenched in other medical disciplines. Many animals are vaccinated to prevent them from suffering the pain related to particular disease even though the prevalence of many of these diseases is low. We know that every surgical procedure causes some pain to the patient and that some procedures are more painful than others. With the idea of prevention in mind, we must first do everything possible to reduce the factors that potentiate pain perception." Pascoe PJ. Perioperative Pain Management. In, Vet Clin NA, Small Ani Pract, KA Mathews, ed. 2000;30(4):917-932.

     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.

          • "The optimum duration of analgesic therapy after major surgery in companion animals is unknown. In an animal that is receiving analgesics, the apparent absence of pain or distress does not by itself justify discontinuation of therapy. This would be analogous to discontinuing antibiotic treatment the moment a patient's fever breaks." Bernie Hansen, Analgesic Therapy, The Compendium, July1994:868-875.

Sedative / analgesic drugs used preemptively

Opioids

          • Butorphanol, buprenorphine (Buprenex®)

          • Morphine, hydromorphone, oxymorphone, fentanyl, remifentanyl, methadone

          • 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), may provide more sedation than desired or may not provide adequate sedation when used alone in young, healthy patients, relatively short duration of action (when compared to the duration of surgically-induced pain)

               o 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.

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

               o Most potent class of analgesic drugs

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

               o 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)

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

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

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

               o Effects

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

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

                    • Minimal to moderate respiratory effects

                    • Minimal cardiovascular effects

               o 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.

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

               o Not as potent as the full agonist class

                    • Don't confuse binding potency with analgesic potency

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

                    • 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

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

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

               o Uses: IV, IM, SQ, transmucosal (TM; buprenorphine), CRI (not as effective as full agonist CRIs)

               o Effects

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

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

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

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

          • 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

Non-Steroidal Anti-inflammatory drugs

          • Advantages: Relatively long-lasting analgesia, easy to administer, anti-inflammatory

          • Disadvantages: Not suitable for patients with some pre-existing conditions (eg, renal dysfunction, clotting abnormalities, etc...). NSAID class side effects include the potential for GI upset (by far the most common side effect), GI ulceration, clotting disorders, hepatic dysfunction, renal damage.

Analgesic drugs/techniques used intra-operatively

Opioids

          • Repeat boluses of any of the opioids can be administered IV (or IM if slow onset is appropriate – give morphine SLOW IV or IM to prevent histamine release)

          • Opioids can also be used as CRIs

               o Morphine (0.05-0.2 mg/kg/hr)

               o Hydromorphone (0.01-0.05 mg/kg/hr)

               o Fentanyl (5-20 microg/kg/hr intraop and 2-5 microg/kg/hr postop)

               o Remifentanil (same as fentanyl)

               o NOTE: Opioids can be used alone as CRIs or with lidocaine or ketamine or both.

          • Opioids can also be used in the epidural space

Alpha-2 adrenergic agonists (medetomidine, dexmedetomidine)

          • Can be administered as repeat boluses

          • Can be administered as a CRI

          • Medetomidine 1-4 microg/kg/hr dogs and cats

          • Dexmedetomidine 0.5-1.0 (up to 4) microg/kg/hr dogs and cats

Local anesthetic blockade

          • Advantages: Inexpensive, easy to administer, very effective

          • 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

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

                    • Duration of action: 4 to 6 hours

                    • 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)

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

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

               o LIDOCAINE can be used as a constant rate infusion (CRI). NO OTHER local anesthetic can be administered IV.

                    • Dose for analgesia is 25-50 microg/kg/min in most species

                    • Controversial in cats – use 10 microg/kg/min or don't use at all

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.

Analgesic drugs used post-operatively

          • Repeat boluses or CRIs of opioids and/or alpha-2 agonists may be required in the immediate post-operative period, especially when surgical pain is judged to be moderate to severe.

          • NSAIDs should be considered (either alone or as part of multimodal therapy) for most cases of post-operative pain (which is primarily pain of inflammation).

          • Opioids are the most potent analgesic drugs available and should be added anytime that the NSAIDs are inadequate or inappropriate. Postoperative opioids can be administered transdermally (fentanyl patches), transmucosally (buprenorphine – primarily used in cats) and orally. Oral opioids include tramadol, codeine, codeine + acetaminophen and morphine. The most commonly used oral opioid is tramadol:

Sample perioperative analgesic protocols

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

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)

                    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

                         i. Opioid

                         ii. Lidocaine (omit in cat?)

                         iii. Ketamine

                         iv. Combo of any or all of these three drugs

                    c. Continue CRI post-operatively

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