PAIN MANAGEMENT Alison Deputy, LVT

Transcription

1 VCA Veterinary Specialty Center of Seattle Continuing Education Seminar 2011 PAIN MANAGEMENT Alison Deputy, LVT The process in which the brain receives, interprets and reacts to pain is extremely complicated and involves multiple physiochemical reactions- the result being an unpleasant sensation. The unpleasant sensation can result from actual or perceived tissue damage. Our position as caretakers for veterinary patients places upon us the responsibility of correctly interpreting the signs of pain in animals and then treating that pain adequately. Sounds simple, right? Unfortunately, many of our veterinary patient's pain goes under-diagnosed and under-treated. My goal with this seminar is to equip Veterinary Technicians and Veterinary Assistants with the tools needed to understand the causes, signs and treatment options for pain in our patients. Why is controlling our patients pain so important? Studies have shown time and time again that pain has very negative affects on healing. Pain has been shown to increase metabolic demand, impair the immune system, increase wound healing times, increase the risk of sepsis and it has been shown in humans that untreated acute pain can lead to difficult to control chronic pain. Therefore, it is important that we control our patients pain early and effectively- it's easier to fix a dripping pipe that has only made a puddle, than it is to repair a ruptured pipe that has flooded your basement. Pre-medicate patients with appropriate analgesics to treat pain before it gets a foothold! Definitions: 1. Multimodal: acting in more than one aspect of the pain pathway. The benefits of which are increased efficacy across the pain pathways. 2. Synergistic: compounds work together to create an effect that is greater than if each were working alone. How painful stimuli are processed: Pathologic pain (acute and chronic) is defined as pain caused by tissue injury/ inflammation or damage of a portion of the nervous system. Pathologic pain can be broken down into four basic categories: 1. Nociceptive- injury sustained by the peripheral tissues (skin and nearby tissues). 2. Neuropathic- injury to or damage of peripheral nerves or spinal cord. 3. Visceral- injury to or damage of abdominal or thoracic visceral. 4. Somatic- injury to or damage of bones, joints, muscle. Nociception is defined as the processing of noxious stimuli being perceived by the brain as pain. This process is broken down into stages: 1. Transduction- the conversion of noxious stimuli (regardless of cause) into electrical energy. 2. Transmission- electrical energy is transmitted through the peripheral nervous system. 3. Modulation- electrical signal is passed from the peripheral nervous system to the spinal cord. 4. Perception- the response of the cerebral cortex to the pain signal. Transduction can be inhibited by opioids, NSAIDs and local anesthetics. Transmission involves different nerve fibers that transmit signal at different speeds. A-delta fibers transmit signals faster and are responsible for the initial sharp pain felt when an injury occurs. C fibers transmit more slowly and are responsible for the dull, throbbing pain felt after an injury occurs. A-beta fibers have a lower

2 threshold for stimulus and are responsible for quick actions taken (removing your hand from a hot pan) before more damage occurs. Alpha-2 agonists and local anesthetics can inhibit transmission. Local anesthetics, alpha-2 agonists, opioids, NSAID s, tricyclic antidepressants (TCA s) and serotoninselective re-uptake inhibitors (SSRIs) and NMDA receptor antagonists can all inhibit modulation. General anesthetics, opioids and alpha-2 agonists can inhibit perception. Wind up pain is a condition of increased sensitivity to noxious and innocuous stimuli. It is usually associated with chronic pain and occurs on both a peripheral and central level. On a peripheral level, chemical mediators are released which lead to a decrease in the noxious stimuli threshold (small or non-noxious stimuli are transmitted as more than they are.) On a central (spinal cord) level, spinal cord neurons are hyper-excited leading to an increase in modulation. Both the peripheral and central hypersensitivity lead to expanded pain receptor fields (areas feeling pain that are not exposed to noxious stimuli) and painful responses to normally innocuous stimuli. The result is an increase in the magnitude and duration of pain. Because of the complexity of the pain pathways and the multiple mechanisms that occur leading to perception of pain, it is VITAL that we understand that there is no one magic drug we can use to treat pain. We must use multiple tools in our arsenal to prevent and treat pain. Drug Classifications: Opioids- Because of their method of action on multiple parts of the pain pathway, opioids are our best defense of acute pain. They may not be as appropriate for chronic pain due to lessening effects and addiction potential, although for very painful terminal condition (such as malignancy) they can be effectively used. There are four types of opioid receptors: 1. Mu- these receptors, when activated, produce the most profound analgesia. They also can produce negative side effects such as bradycardia, respiratory depression, vomiting, defecation, constipation, urine retention and physical dependence. 2. Kappa- produce less of an analgesic response than mu receptors and may also cause dysphoria, miosis, and profound sedation. 3. Delta- these receptors modulate the activity of the mu receptors, meaning they can increase or decrease their activity. 4. Sigma- these receptors provide little to no analgesia and can cause significant negative side effects. Opioids act in three different ways: 1. Agonist- bind to and stimulate specific receptors. 2. Antagonist- bind to and block or inhibit specific receptors. 3. Mixed agonist/antagonist- binds to and stimulates some receptors, while blocking or inhibiting others. Pure mu agonists are the most effective at treating acute pain. That being said, they can also produce the most profound side effects including panting, vomiting, urination, urine retention, defecation and constipation. Commonly used pure mu agonists include morphine, hydromorphone, oxymorphone, fentanyl and codeine. Fentanyl patches can be used for constant drug delivery to patients at home. However, studies have shown that fentanyl patches provide widely varying plasma levels of the drug and there is the risk of accidental ingestion by the animal or children living at the home, and also the potential for the owner to use the patch. Because of its short duration of action, injectable fentanyl must be given as a CRI. Methadone is another pure mu agonist on the market for use- it's main advantage is that it is the least likely to cause vomiting and does not seem to cause as much panting as other mu agonists.

3 Partial mu agonists bind to the mu receptor, but only partially stimulate it. Buprenorphine is an example of this. Buprenorphine provides good analgesia, while not causing many negative side effects such as sedation or respiratory depression. Partial mu agonists have a ceiling affect meaning that increased dosages of the drug will increase its duration while not increasing its analgesia. This must be taken into account when using buprenorphine! Buprenorphine also has a very high affinity for mu receptors, meaning that they will block the action of other pure mu agonists. This can be a problem if the animal needs additional opioids to control their pain. Due to its cost, buprenorphine is most commonly used for moderate pain control in cats. A common protocol is to treat cats with a stronger opioid for intra and post-operative pain, and then change to oral buprenorphine- buprenorphine is well absorbed across oral mucous membranes in cats but mostly destroyed if actually ingested. It is not well absorbed transmucosally in the dog. Mixed agonist/antagonist opioids such as butorphanol, bind to kappa receptors while blocking mu receptors. This means they provide less than ideal analgesia while producing profound sedation. They will also block pure mu agonists from the mu receptor. Because of this, butorphanol should NOT be used as primary pain management! Do not confuse sedation with analgesia. Drug dosages: ** opioids are contraindicated in patients with head trauma or increased intracranial pressure. Should be used with caution in animals when vomiting is contraindicated, and in patients with severe renal insufficiency. Most opioids are synergistic with acepromazine- ace doses should be reduce when used with opioids. HYDROMORPHONE- Dogs: mg/kg IM/SQ/IV Cats: mg/kg IM/SQ/IV **vomiting is more common after IM administration. Onset minutes, duration 4-8 hours. OXYMORPHONE- Dogs: mg/kg IM/SQ/IV Cats: mg/kg IM/SQ/IV. Rapid onset, duration 4-6 hours. MORPHINE- Dogs: 0.5-1mg/kg IM/SQ/IV Cats: mg/kg IM/SQ/IV. Rapid onset, duration 4-6 hours. Potential to cause transient hypotension, often causes vomiting with IM or SQ use, and may cause histamine release with IV use. FENTANYL- Loading dose of 2-5 ug/kg followed by 2-45 ug/kg/hr IV CRI. Note- if animal is premedicated with another pure mu agonist, it may not be necessary to give a loading dose of the fentanyl. METHADONE- Dogs: 0.5 to 1.0 mg/kg IM/SQ/IV Cats: 0.25 to 0.5 mg/kg IM/SQ/ slow IV. Rapid onset, duration 4-6 hours. Least likely to cause vomiting. CODEINE 0.5-2mg/kg PO BID-QID. BUPRENORPHINE- Dogs: mg/kg IM/SQ/IV Cats: mg/kg IM/SQ/IV, buccal. Onset minutes, duration 4-12 hours depending on the dose. BUTORPHANOL mg/kg IM/SQ/IV. Rapid onset, duration 1-3 hours. Not recommended for somatic (orthopedic/joint/muscle) pain. NSAIDs- non-steroidal anti-inflammatory: NSAIDs work by blocking the production of prostaglandins by binding to cyclooxygenase. Prostaglandins are what produce inflammation. NSAIDs not only reduce inflammation, but they also reduce the sensitivity of peripheral nociceptors. Cyclooxygenase occurs in two isoforms: COX1 and COX2. COX1 is responsible for many functions in the body including GI mucosal protection, some blood clotting actions and renal blood flow. COX2 is responsible for inflammation mediation by the catabolism of prostaglandins. The NSAIDs used are those that are selective for COX2- providing antiinflammatory properties. That being said, NSAIDs will also bind with COX1 to a degree, causing negative side effects like GI ulcers. NSAIDs should never be used in animals with liver, kidney or intestinal dysfunction or coagulopathies. They should never be used in conjunction with steroids and

4 should be avoided or used with extreme caution in cats as they cannot break down the drug as effectively leading to prolonged drug half-lives and potential toxicity. Drug dosages: RIMADYL (Carprofen) Dogs only! 2.2mg/kg SQ/PO BID or 4.4mg/kg SQ/PO SID DERAMAXX (Deracoxib) Dogs only! 1-4mg/kg PO SID METACAM (Meloxicam) Dogs: 0.2mg/kg SQ/PO loading dose on day 1, then 0.1mg/kg PO SID. Cats: 0.1mg/kg SQ/PO loading dose on day 1, then 0.05mg/kg PO SID for up to 3 more days. Longer use is contraindicated. Should not be used in cats with renal or liver disease. Alpha-2 agonists: The most common alpha-2 agonists used are medetomidine and dexmedetomidine. Alpha-2 agonists work by inhibiting ascending transmission of pain signals to the brain. At low doses, their analgesic and sedative effects are dose dependent. As the dose is increased, a ceiling affect occurs (like buprenorphine) in which sedation is prolonged, but analgesia is not and there is an increased risk of negative side effects. For this reason, alpha-2's are best used at low doses in conjunction with other drugs, mainly opioids. There is also a synergistic effect when used with opioids. The most common side effect that we see with alpha-2s is bradycardia. This occurs because alpha-2's cause an initial peripheral vasoconstriction (noted by pale mm) and increase in blood pressure, which then causes a reflex bradycardia. After these effects diminish, hypotension occurs. These affects are mostly seen when higher (box label) doses of alpha-2's are given alone. For this reason, the box label dose of medetomidine and dexmedetomidine should not be used. The dose range I usually use is 2-5ug/kg along with an opioid. Alpha-2 agonists should only be used in healthy patients with good cardiac function. MEDETOMIDINE/ DEXMEDETOMIDINE: 2-10 ug/kg IV/IM/SQ (combined with an opioid is best) DEXMEDETOMIDINE CRI- 2 ug/kg loading dose, then 1-2 ug/kg/hr CRI. Tramadol: Tramadol works in two ways- it is a weak mu agonist and also a monamine re-uptake inhibitor. The two modes of action are synergistic and may provide pain control at the level of codeine. It also works well with neuropathic pain. Adding an oral opioid or NSAID will increase tramadol's efficacy by creating multimodal pain relief. Although tramadol does ask similar to an opioid, it is not a controlled substance and is not habit forming. Dogs: 3-5 mg/kg PO BID-QID Cats: 1-2mg/kg PO BID-QID NMDA receptor antagonists: By blocking the NMDA receptors, a reduction in CNS hyper-responsiveness occurs. In other words, these drugs work well for wind-up pain. They also allow for other analgesics to work more effectively, especially opioids, by increasing the sensitivity of opioid receptors which increases their effectiveness as well as reducing tolerance to them. Because of this action, NMDA antagonists are almost always used in conjunction with other drugs. Gabapentin and ketamine are examples of the most commonly used drugs. Gabapentin is used orally while ketamine is used as a CRI, most often in conjunction with an opioid and lidocaine. Ketamine is used at micro doses, and not the anesthetic induction doses most of us are used to. Gabapentin is particularly good for neuropathic pain and also has anti-convulsant properties. Oral ketamine has been shown to help control wind-up pain, but may take up to a week to take effect. KETAMINE (100 mg/ml) CRI - 2 to 20 ug/kg/minute (0.12 to 1.2 mg/kg/hr) after an initial loading

5 dose of mg/kg bolus. Failure to give a loading dose will result in a delay of achieving therapeutic blood levels. GABAPENTIN ORAL Dogs: 2-40 mgs/kg BID-TID Cats: 2-30 mgs/kg BID. Local anesthetics: Local anesthetics work by blocking the transmission of painful stimuli. Their drawbacks are relatively short duration of action and potential for toxicity. They are mostly used for nerve blocks for painful procedures such as dental blocks, ring blocks for de-claws, testicular blocks for cat neuters, brachial plexus blocks, intercostal blocks, and in the case of lidocaine, CRI analgesia. The most common local anesthetics used are lidocaine and Bupivacaine. Lidocaine has a short onset (5-10 minutes) but a short duration of action (1-2 hours). Bupivacaine has a longer onset time (20-30 minutes) but last for 3-5 hours. Overdoses of these drugs can cause CNS as well as cardiac toxicity so careful dose calculations must be performed. Lidocaine can be used IV, but Bupivacaine should not be used IV. IV lidocaine should be used with extreme caution in cats. LIDOCAINE- For local nerve blocks- 1-4mg/kg. Use caution in awake animals as lidocaine STINGS when injected. BUPIVACAINE (Marcaine)- For local nerve blocks- Dogs: generally 1.0 mg/kg up to a maximum dose of 2 mg/kg. Cats: maximum of 1.0 mg/kg. Combine with morphine (0.075mg/kg) or buprenorphine (0.003mg/kg) to increase duration of local blocks. CRI analgesia: Delivering a constant rate infusion of analgesics is an effective and flexible way to provide pain management. Drug levels can be tailored to each patient's pain level and tolerance. Common CRI protocols: Combination of Lidocaine/ketamine and opioids are used for perioperative and postoperative CRI s. Fentanyl is also commonly used by itself as a CRI. Dogs: LIDOCAINE (1mg/kg IV bolus followed by CRI of mg/kg/hr) and KETAMINE (0.5mg/kg bolus followed by CRI of mg/kg/hr). Add FENTANYL (2-5ug/kg loading dose followed by CRI of 2-45 ug/kg/hr), HYDROMORPHONE (0.1mg/kg loading dose followed by CRI of mg/kg/hr) or MORPHINE (0.5mg/kg slow IV loading dose followed by CRI of mg/kg/hr). Cats: Use lidocaine with caution in cats! Cats are very sensitive to the CNS effects of lidocaine. Decrease lidocaine bolus to mg/kg, then CRI of mg/kg/hr. If seizures occur, discontinue lidocaine and treat with diazepam. Epidural analgesia: Injecting preservative free opioids along with local analgesics into the epidural space is an effective and safe way to control lower body pain during and after surgical procedures. Performing epidurals requires specific skills and practice and should not be attempted by untrained individuals as damage to the spinal cord can occur with improper placement. Signs of pain: Gone are the days of statements like animals don't feel pain the same way humans do. Animals DO feel pain in the same way humans do, but they EXPRESS it differently. As Veterinary Technicians, it is imperative that we accurately assess and treat our patient's pain. Assessment of pain is the only area in which assumptions are acceptable. For example, an animal that presents with a fractured bone can be assumed to be in pain, even if they do not show traditional signs of pain. Other painful conditions that should be assumed to be painful and treated as such are intestinal foreign

6 bodies, pancreatitis, bladder obstructions, septic abdomen, malignancy, any post-surgical patients and patients that have experienced trauma. Some signs of pain in dogs: 1. Increase in vitals (HR, RR, temp, BP) 2. Behavior changes (sweet dog turned bitey dog) 3. Pacing, not wanting to lie down 4. Hunched posture (abdominal/back pain) 5. Lameness 6. Inappetence 7. Vocalization 8. Hiding Some signs of pain in cats: 1. Increase in vitals 2. Behavior changes 3. Aggression 4. Hiding 5. Lameness 6. Growling or absence of vocalization 7. Purring 8. Inappetence Unfortunately, signs of pain in many animals, especially cats, mimic many of the behaviors that animals exhibit while just being at the veterinary hospital. This makes it VITAL for Veterinary Technicians to be educated and astute in assessing patient pain. Methods for assessing pain should be standardized for use in the veterinary hospital. Pain should be assessed no less than four times within a 24 hour period.