opioids, α2 agonists,
opioids, α2 agonists,
Adapted from Figure 1-3, Pain Management for the Small Animal Practitioner, 2004.
A newer understanding of the physiological processes of pain has led to definitions that accurately reflect microprocesses operating within the periphery and the CNS. Pain is a very complex process, and the way we define and treat pain in our patients must reflect this complexity.
Adaptive pain versus maladaptive pain
In an adaptive pain state, the body’s central processes are operating normally. This type of pain serves a biological purpose—i.e., the body’s pain response warns the individual of impending or actual tissue damage and helps to prevent further trauma. It also results in tissue healing. Pain related to surgery or acute traumatic injury and pain that results from inflammation are examples of adaptive pain.
In a maladaptive pain state, the body’s central processing has gone awry. This is due to damage to the peripheral and/or central nervous system (neuropathic pain), or the CNS is not properly processing the pain. Spontaneous pain and hypersensitivity can occur. In this state, pain has actually become a disease process. Chronic pain, such as that related to osteoarthritis or cancer, is a good example of maladaptive pain.
Acute pain versus chronic pain
Acute pain is mild to severe pain that may be incapacitating. The degree of pain is related to the traumatic incident or procedure performed. Acute pain is relatively short-term (hours to days, up to a month) in duration and is generally adaptive in nature. Acute pain dissipates as the initial source of the pain (trauma, surgery, injury, etc.) resolves.
Chronic pain serves no biological purpose. Chronic pain may occur in the presence of a persistent stimulus (as with osteoarthritis), or there may be no stimulus at all (as happens when the pain has become maladaptive in nature).
Although it is not always possible to achieve, preemptive analgesia should be one of the primary goals when creating a pain management plan, especially during the perioperative period. Lower doses of analgesics are required to prevent and keep pain under control than are required to “rescue” an animal that has become painful. Preemptive analgesia can also help prevent windup and can help prevent acute pain from developing into chronic pain, or adaptive pain into maladaptive pain.
As in humans, pain in animals is an individual experience. Individuals may have very different responses to similar painful stimuli. Therefore, every pain management plan should be tailored to the individual, with periodic reassessments and modifications if necessary.
Providing preemptive and multimodal analgesia are goals in the management of both adaptive and maladaptive pain; however, the methods of doing so vary somewhat between the two.
Management of Adaptive Pain
Adaptive pain is the type most often associated with trauma and/or surgery. It is usually acute in nature, and it can be mild to severe. Most drugs administered for the management of this type of pain are administered on a relatively short-term basis, and the need for analgesic support should diminish as the initial source of pain resolves.
Nonsteroidal antiinflammatory drugs (NSAIDs)
NSAID administration is very common in small animal practices as a component of multimodal analgesia for the treatment of mild to moderate pain, both acute and chronic. Currently, six NSAIDs have FDA approval for use in dogs in the U.S.: etodolac, carprofen, deracoxib, tepoxalin, meloxicam, and firocoxib. Both carprofen and meloxicam are available in injectable formulations and can be given perioperatively. Deracoxib and carprofen are also approved for perioperative oral dosing for acute pain control. Injectable meloxicam is the only NSAID with FDA approval for use in cats.
The primary mechanism of action of NSAIDs is some preferential blockade of the cyclo-oxygenase-2 (COX-2) enzyme compared to the COX-1 enzyme (tepoxalin also inhibits the 5-lipoxygenase enzyme). The COX-2 enzyme converts arachadonic acid into prostaglandins. Some of these prostaglandins cause pain and inflammation, while others are crucial for the maintenance of GI mucosal integrity, renal blood flow, and proper platelet function during times of physiological stress (such as shock or dehydration). Because of the potential for blocking these beneficial prostaglandins, NSAID use should be avoided in patients with liver or kidney disease, those with a high likelihood of hemorrhage and/ or low blood pressure, and those with GI ulcerative disease. Although carprofen and deracoxib are approved for preoperative dosing, these authors do not recommend their use for preemptive analgesia unless the patient will receive IV fluids as well as blood pressure monitoring and rapid and appropriate treatment of low blood pressure throughout the perianesthetic period.
NSAIDs may be prescribed for several days postoperatively; however, because of the increased risk of GI ulceration when multiple NSAIDs are administered (or an NSAID is administered concurrently with corticosteroids), it is important to remember to never mix NSAIDs without a 4–10 day washout period. It is also recommended to treat with a GI protectant such as omeprazole or misoprostal.
No data exists that shows that one NSAID provides better analgesia than any other. However, similar to humans, there does appear to be some individual variability in the response to NSAID therapy. If a patient has an adverse response to one NSAID, it doesn’t mean that it will have an adverse effect from a different NSAID. Likewise, one NSAID may appear to provide better analgesia than another in the same patient.
The alpha-2 agonists dexmedetomidine and xylazine provide excellent short-term (20 minutes–2 hours) visceral analgesia, and they also provide excellent sedation pre-and postoperatively. However, they drastically decrease cardiac output as well as tissue perfusion and oxygenation. They should be avoided, if possible, in patients with cardiopulmonary or renal compromise. The effects of these drugs are dose-dependent.
Effective sedation and analgesia can be achieved at doses significantly lower than those listed on the bottles. Microdoses (e.g., 0.5–1 mcg / kg of dexmedetomidine) can be used pre-and postoperatively for added analgesia and increased sedation in patients receiving concurrent opioids.
Opioids, especially the mu agonists (morphine, methadone, hydromorphone, oxymorphone, fentanyl, and remifentanil) are the most efficacious analgesic drugs currently available. They are ideal as part of a presurgical protocol, providing outstanding preemptive analgesia. Opioids are discussed in detail in Chapter 14; however, some additional discussion is warranted.
The use of morphine in cats has recently come into question. Research has shown that it is the metabolite of morphine, morphine-6-glucuronide (M-6-G), that binds to the mu receptor and thereby produces analgesia. Since cats do not always metabolize drugs as effectively as dogs, it is unclear whether morphine produces the same level of analgesia in cats as it does in dogs. In research cats, M-6-G was detectable only after IV morphine dosing, and only in 50% of the cats studied. No M-6-G was detectable after IM morphine administration (Taylor et al. 2001).
Methadone, which has the same potency as morphine, has the lowest incidence of inducing vomiting in small animals. This makes methadone an excellent choice of premedication in patients where vomiting is contraindicated, such as those with gastric dilatation volvulus (GDV), laryngeal paralysis, or abdominal pain. Methadone also has NMDA receptor antagonist properties.
Remifentanil is an ultra–short-acting mu agonist. It requires no liver or kidney metabolism; rather, it is cleared by esterases that occur in blood and skeletal muscle (Gaynor and Muir 2009). It is best used as a constant rate infusion (CRI). There is only an 8–10 minute recovery time to normal after discontinuing the infusion, making it an ideal drug to use in trauma patients with a neurological component to their status and who require serial neurological exams. Remifentanil should be administered as a 4 mcg/ kg IV bolus followed by 6–20mcg/kg/hr.
Perianesthetic and postoperative opioids are best administered as CRIs. This ensures that a patient will have a steady state of plasma concentration of drug, decreasing the risk of the patient becoming painful. One study showed a clinically significant increase in the development of sepsis and DIC as well as death in infants who were treated with intermittent boluses of morphine for postoperative thoracotomy pain control as opposed to continuous fentanyl administration (Anand and Hickey 1992).
Intraoperative opioid CRIs can also reduce the amount of inhalant required to maintain an adequate plane of anesthesia.
Administering opioids continuously allows a practitioner to titrate the dose in order to effectively meet the patient’s need for more or less analgesia. CRIs can be administered via a syringe pump (Fig. 34.1), or they can be diluted and dripped into an intravenous line. To calculate a CRI, utilize the formula found in Table 34.2.
Tramadol is a synthetic, centrally acting analgesic and is useful for moderate to severe pain. Although tramadol is not a true opioid, its metabolites bind to mu receptors, causing opioidlike effects. Dosing in dogs and cats is generally 2–5 mg/kg 2–4 times daily. Tramadol is an excellent oral analgesic for mild-moderate post-surgical or chronic pain, especially in combination with an NSAID.
NMDA receptor antagonists
Ketamine is commonly used as an anesthetic induction agent, but it also plays a role in perioperative pain management as a potent NMDA receptor antagonist, especially for orthopedic trauma/surgery and for limb amputation. Animals should be given a 0.5 mg/kg IV loading dose followed by 10mcg/kg/min during the perianesthetic period (initiating prior to surgery), and then 2mcg/kg/min for the next 24–48 hours. It is unclear whether the higher dose of ketamine used for induction of anesthesia has the same NMDA receptor antagonist effects as a lower microdose administered as a constant rate infusion.