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Pain Management in the Surgical Patient
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In spite of increased emphasis on pain management in small animals recently, veterinarians can be reluctant to administer appropriate analgesic agents to their patients. This reluctance appears to be based on the perception that pain free animals may damage surgical repairs, exhibit undesirable side effects from analgesic drugs, or that analgesic drugs may mask clinical signs of disease. It is known that untreated pain can produce detrimental physiologic effects that adversely affect the response to therapy. Transmission of painful stimuli to the central nervous system results in a marked neuroendocrine stress response. Increased levels of circulating catecholamines and catabolic hormones can lead to decreased immune system function, impaired wound healing, hypercoagulability, increased myocardial oxygen consumption, gastrointestinal stasis, and decreased pulmonary function.1 By designing and implementing appropriate analgesic protocols, veterinarians can decrease the neuroendocrine stress response and improve the postoperative recovery of surgical patients.
The Pain Pathway
In simple form, the pain pathway consists of three neurons. Specialized free nerve endings, or nociceptors, transduce mechanical, chemical, or thermal stimuli from the environment into electrical signals. These electrical signals are then transmitted by afferent sensory fibers to the dorsal horn of the spinal cord where modulation of the painful stimulus can occur. The signal ascends the spinal cord, and is then projected to the cerebral cortex where perception of pain occurs.2
Untreated pain can result in sensitization of both the central nervous system and peripheral receptor sites. Tissue damage and inflammation at the site of injury cause release of chemical mediators such as Substance P, prostaglandins, leukotrienes, and bradykinin. These mediators excite and increase the sensitivity of peripheral nociceptors to painful stimuli.3 The mechanism of central sensitization is complex and occurs at the level of the spinal cord and brain. Glutamate, appears to be the primary mediator and activator of N-methyl-D-aspartate (NMDA) receptors, which results in an increased responsiveness of spinal neurons to stimuli.4
The exact mechanisms responsible for the generation and maintenance of pain in animals are still being investigated. It is clear, however, that modulation and inhibition of painful stimuli serves to avoid or decrease the adverse consequences of the neuroendocrine response to untreated pain.
Recognition and Assessment of Pain
Recognition of pain in the small animal patient can be difficult. Several scoring systems have been developed or adapted from human medicine and general guidelines for recognizing painful behaviors in animals have been published. Traditionally, methods for scoring the intensity of pain in animals have included the visual analogue scale (VAS), the simple descriptive scale (SDS), and the numerical rating scale (NRS).5 However, a gold standard for pain recognition and assessment has not been established in veterinary medicine.
The visual analogue scale consists of a 10 cm line with the ends relating to extremes of pain intensity. The left end of the line is labeled as “no pain” while the right end of the line is labeled as “worst pain possible for this procedure”. An observer places a mark on this line that best corresponds with the intensity of the animal’s pain. The distance from the left end of the line to the intersecting mark is then measured and this number is the VAS pain score. The VAS has been used in several clinical studies to assess pain and although the VAS is easy to use, it does have limitations.6-8 First, this technique simply assigns a number to a subjective judgment, making the assessment one-dimensional. Significant observer variability has also been demonstrated, even when trained individuals view the same animal at the same time.8 These limitations must be recognized when using the VAS as a basis for designing analgesic protocols.
The simple descriptive scale is the most basic method for assessing pain in animals. The scale consists of four to five degrees of severity such as no pain, mild, moderate, and severe pain. An observer assigns the patient to a category based on their observations of that patient. The SDS is a broad classification and does not allow for small changes in pain response to be identified.5
Holton et al have shown that physiologic factors such as heart rate, respiratory rate, and pupil size are not useful indicators of pain in hospitalized dogs, however other investigators have shown that a combination of several physiologic and behavioral parameters considered together can be useful in assessing pain.9,10 The numerical rating scale, combines both physiologic and behavioral categories with numeric scores assigned to each category. The scores are then summed to yield an overall pain score and used as the basis for analgesic therapy (Table 9-1).
Recognizing Painful Behaviors
Characteristic changes in behavior have been associated with pain in both dogs and cats. It is important to observe the animal’s posture, temperament, locomotion, and vocalization for changes that may indicate untreated pain. In dogs, postural changes such as holding the tail between the legs, arching of the back, or drooping of the head have been associated with untreated pain. Additionally, a reluctance to move, nonweight-bearing lameness, attacking, biting, barking, and whimpering are also behaviors that have been associated with pain.11 Cats exhibit more subtle behavioral changes associated with pain such as escaping or avoidance, hiding, squinting of the eyes, reluctance to move, hissing or lack of interest in food or grooming.12 Assessments of animals for pain should occur frequently, at regular intervals, and be documented in the medical record. Especially important times for assessment are if there is onset of new pain, when previously identified pain changes in frequency or pattern, or when there has been a major therapeutic intervention. Changes in the analgesic plan should be made in response to these assessments.
The Analgesic Plan
Proactive planning and design of analgesic protocols should be performed for all small animals undergoing surgery. These plans should be individualized and should consider such factors as the type of surgery or procedure to be performed, the expected severity of pain, any underlying medical conditions, the risk/ benefit ratio of available analgesic techniques, and any previous clinical experiences with the animal. After considering these factors, a complete history should be gathered from the owner and a plan including preoperative, intraoperative, and postoperative analgesics should be constructed. Once the plan is enacted, the animal’s pain level and behavior should be assessed frequently and refinements in the treatment protocol should be made.
Preemptive and Multimodal Plans
Preemptive analgesia refers to the practice of administering analgesics to a patient before a painful stimulus occurs such as surgery. The preemptive administration of analgesics has been shown to decrease the intensity and duration of postoperative pain.13 Additionally, preemptive analgesics have been shown to decrease both peripheral and central nervous system sensitization.14,15 It is important to remember, however, that administration of analgesic drugs preemptively will not eliminate postoperative pain, but can reduce the severity and duration of that pain.
A simplified explanation of the pain pathway is described here however, it is important to recognize that clinical pain is the result of signals transmitted along a multitude of pathways throughout the peripheral and central nervous systems. These pathways involve many mechanisms and neurotransmitters so, it is unlikely that a single analgesic agent or technique will alleviate all pain. Construction of a multimodal analgesic plan that uses drugs of different classes, each acting at different sites along the pain pathway (e.g. NSAIDS, opioids, local anesthetics), will result in more effective pain relief. Additionally, the co-administration of drugs in various classes has additive or synergistic effects and individual drug doses can often be reduced.
The drugs commonly used to treat perioperative pain in companion animals consist of nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, alpha-2 agonists, local anesthetics, and adjunctive medications.
These are commonly used in the canine and less frequently in the cat for analgesia (Table 9-2). These drugs are used to treat pain in a variety of cases ranging from acute surgical pain to chronic pain. Analgesia, anti-inflammatory, and antipyretic effects are brought about by inhibition of the cyclooxygenase (COX) enzymes resulting in a decrease in the release of prostanoids and prostaglandin.16 It is known that NSAIDs act at the tissue injury site and there is evidence that NSAIDs also produce analgesia at the level of the central nervous system.17 NSAIDs are well absorbed after oral administration, or when given parenterally.18 Most are metabolized in the liver and the metabolites are then excreted in the urine and feces.19 NSAIDs are effective, relatively inexpensive, and long lasting analgesics, however side effects may occur. Gastrointestinal irritation ranging from mild gastritis and vomiting to intestinal ulceration, hemorrhage and death have been reported.20 Nephrotoxicity can also occur after NSAID administration due to decreases in renal blood flow.21 Hepatotoxicity has been reported (with Labrador Retrievers over represented) and is generally believed to be idiosyncratic.22 Serious complications have been associated with the use in dogs of NSAIDs intended for humans. NSAIDs should not be used in animals with existing renal or hepatic insufficiency, gastric ulceration, dehydration, hypotension, shock, or coagulopathies. Additionally, NSAIDs should not be administered concurrently with other nephrotoxic drugs, corti-costeroids, or other NSAIDs. Careful monitoring for gastrointestinal, renal, or hepatic toxicity is required when using NSAIDs, especially in animal’s at high risk. Renal and hepatic function should be evaluated before instituting NSAID therapy in dogs at risk for complications and during chronic NSAID therapy.
Opioids are the most consistently effective drugs used for the treatment of moderate to severe pain (Table 9-3). This class of drugs produces analgesia by acting on opioid receptors without the loss of proprioception or consciousness. Three opioid receptors (mu, kappa, and delta) have been identified and are found in varying numbers within the brain, dorsal horn of the spinal cord, and the periphery.23,24 Activation of opioid receptors results in inhibition of adenylate cyclase, a decrease in the opening of voltage-sensitive calcium channels, inhibition of the release of excitatory neurotransmitters, and activation of potassium channels resulting in membrane hyperpolarization.25 The overall effect of opioid receptor activation is a decrease in neurotransmission.26
Opioid analgesics are classified by their receptor selectivity and may be active at one or more receptors. Mu agonists include morphine, oxymorphone, hydromorphone, fentanyl, and meperidine. These agonists induce a maximal response, and can produce increasing levels of analgesia with increasing dosages. This is in contrast to the partial mu agonist, buprenorphine, which binds tightly to the mu receptor but does not induce a maximal response.27 Butorphanol has agonist activity at the kappa receptor and antagonist activity at the mu receptor.28 Increasing doses of butorphanol are associated with a ceiling effect, such that no improvement of analgesia occurs with increasing doses.
In addition to producing analgesia, the opioids also affect other organ systems. Opioid administration can result in respiratory depression due to a decrease in the respiratory center’s response to increasing levels of CO2.29 The respiratory rate and rhythm may also be altered. Some animals pant due to the drug’s effect on the thermoregulatory system. Respiratory depression is often cited as a reason for withholding opioid therapy but is rarely of clinical significance when proper dosing regimens are used.
The cardiovascular system may be affected by opioid administration. Bradycardia may result from inhibition of sympathetic tone to the heart.30 Opioid induced bradycardia is not life threatening and usually does not require treatment. Opioids have little effect on cardiac contractility. Some opioids, particularly morphine and meperidine, can produce hypotension due to histamine release.31,32 The degree of histamine release appears to be related to the overall dose and rate of administration, therefore small doses administered slowly should minimize this potential problem.
The propulsive activity of the gastrointestinal tract is decreased after opioid administration, which may result in constipation. Smooth muscle and sphincter tone tend to be increased, but intestinal peristalsis is decreased.33 Vomiting may occur after direct stimulation of the chemoreceptor trigger zone.34 Tone of the biliary sphincter is increased, which will increase biliary pressure. Contraction of the smooth muscle of the pancreatic ducts can increase plasma concentrations of lipase and amylase.
Alterations in mood and locomotion have been documented after opioid administration. Paradoxic excitement or dysphoria is possible in any species, although it appears that cats are more susceptible especially if excessive doses are given.37 Opioid induced dysphoria may be treated with sedatives such as acepromazine, or in severe cases an opioid antagonist such as naloxone. Antagonism of opioids should be performed cautiously in animals experiencing pain since the analgesic effect of the opioid will be reversed.
Opioids can produce additive or synergistic effects when used in combination with other analgesics such as NSAIDs, alpha-2 agonists, and local anesthetics. Commonly, the dosage of each drug can be reduced, thereby potentially reducing the severity of adverse effects of each class of drugs.
Local anesthetic drugs are tertiary amines connected to an aromatic ring by either an ester (procaine, tetracaine) or amide (lidocaine, mepivacaine, bupivacaine, ropivacaine) linkage (Table 9-4).18 Local anesthetics bind to voltage gated sodium channels within nerve membranes, preventing the influx of sodium ions.38 This prevents the conduction and propagation of nerve impulses and can produce complete analgesia. Local anesthetics with an ester linkage are hydrolyzed by pseudocholinesterases, while those with an amide linkage are metabolized by the liver.18
The use of local anesthetic drugs is relatively safe when administered correctly. However, if local anesthetic is injected intravenously or used in excessive doses, central nervous system and cardiotoxicty may occur. In the central nervous system, toxicity manifests as sedation, nausea, ataxia, nystagmus, and tremors, which can progress to convulsions, unconsciousness, coma, and eventually respiratory arrest.39 Blockade of sodium channels within the myocardium will depress the electrical conduction pathways and the mechanical function of the heart. This can result in sinus bradycardia and sinus arrest.40,41 The peripheral vasculature can also be affected by the administration of local anesthetics resulting in peripheral vasodilation and hypotension.42 Finally, local anesthetics can cause direct damage to the tissues injected, allergic reactions, and methemoglobinemia.43,44
Local anesthetics when used epidurally in conjunction with opioids will produce a more profound and longer lasting analgesia than either drug used individually.45 The use of local anesthetics also reduces the inhaled anesthetic requirements of animals thus reducing the dose dependant effects of inhaled anesthetics on the cardiopulmonary system.46 Specific analgesic techniques using local anesthetic drugs are discussed later in this chapter.
Alpha-2 receptor agonists (Table 9-5) bind to both pre and postsynaptic receptors throughout the central nervous system. Activation of these receptors results in neuronal hyperpolarization and a decrease in sympathetic nervous system activity.47 Alpha-2 receptors are closely located to structures involved in pain processing and activation is thought to interfere with sensory transmission and reduce the release of pain related neurotransmitters resulting in analgesia, sedation, and muscle relaxation.48
Alpha-2 agonists have profound effects on the cardiovascular system, commonly producing bradycardia and/or bradyarrhythmias, as well as decreases in contractile force, stroke volume, and cardiac output. After administration, blood pressure will transiently increase followed by a decrease in blood pressure from baseline values.49
Administration of Alpha-2 agonists will results in a dose dependent decrease in respiratory rate and tidal volume, which can result in significant respiratory acidosis and hypoxemia in some animals. Marked relaxation of the muscles of the upper airway also occurs; therefore, patency of the upper airway should be ensured and monitored.50
Vomiting and retching can occur after administration of an alpha-2 agonist, especially in cats.51 Gastrointestinal motility is decreased and urine output will increase.53 Hypoinsulinemia resulting in a transient hyperglycemia has also been reported in dogs after alpha-2 agonist administration.54
The usefulness of alpha-2 agonists as sole analgesic agents is limited by their short duration of action and dose dependant cardiopulmonary depression. However, alpha-2 agonists, when given in conjunction with other analgesics such as opioids, are extremely effective analgesic agents. Patient selection should be considered carefully and the use of alpha-2 agonists should be limited to animals without significant systemic disease or dysfunction. It is important to recognize that the sedative effects of alpha-2 agonists persist for a longer period of time than the analgesic effects.55 Therefore, adequate analgesia cannot be assumed based only on behavioral evaluation of the patient.
There are other classes of drugs that are not regarded as analgesics but may be helpful in the treatment of refractory pain states (Table 9-6). These drugs may enhance analgesia produced by traditional analgesic drugs by interacting with receptors within the pain pathway or altering nerve conduction pathways in pain modulating systems. It should be noted that while the drugs discussed here can play an important role in treating pain, especially in cases of refractory pain states, most produce little to no analgesia when used by themselves. They should be used in conjunction with known analgesics such as opioids.
Nociceptor activation and bombardment of the dorsal horn of the spinal cord leads to activation of N-methyl-D-aspartate (NMDA) receptors, which are thought to play a role in central sensitization. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist and is thought to produce analgesia and limit hyperalgesic states.56 It appears that ketamine is most effective when administered preemptively and its short duration of action suggests that administration via a constant rate infusion is beneficial.57 When administered as a constant rate infusion in dogs undergoing forelimb amputation, ketamine significantly reduced postoperative pain scores and increased animal activity three days postoperatively.58 Analgesic doses of ketamine are considerably lower than those used to produce anesthesia, but potential side effects include sympathetic stimulation of the cardiovascular system, respiratory depression, and stimulation of the central nervous system.
Amantadine is another NMDA receptor antagonist that has been used in humans for the treatment of neuropathic pain and in patients with opioid tolerance. The pharmacology of amantidine has not been well established in dogs and cats and behavioral effects can be seen at high doses.
The anticonvulsant, gabapentin, has been used in humans with chronic pain syndromes.60 The exact mechanism of action is unclear, although gabapentin is known to bind to receptors within the brain and may enhance the action of gamma-aminobutyric acid (GABA).61 There are no controlled studies involving the use of gabapentin to treat pain in dogs and cats however there are anecdotal reports of its use in animals.62 It appears that gabapentin may work synergistically with other drugs in producing analgesia and may inhibit the development of hyperalgesia due to injury. Gabapentin is metabolized by the liver and excreted by the kidneys. Side effects reported in humans include sleepiness, fatigue, and weight gain with long term administration.61
Tramadol is a centrally acting analgesic that has a low affinity for mu opioid receptors and is less potent than morphine.63 Tramadol inhibits norepinephrine uptake and facilitates serotonin release, which contributes to its analgesic effects.64 It has been shown that tramadol can be used safely to control pain after ovariohysterectomy and other soft tissue procedures in dogs.65 Tramadol is metabolized by the liver and side effects include nausea and vomiting and prolonged administration can result in constipation or diarrhea.66
Although glucocorticoids are not analgesic drugs, their use as potent anti-inflammatory agents may contribute to treating pain associated with inflammatory conditions such as otitis externa and osteoarthritis.68 Glucocorticoids inhibit and reduce inflammation by inhibiting phospholipase A2 and by stabilizing cellular membranes.68 Potential side effects of long-term glucocorticoid therapy include iatrogenic Cushing’s disease, while abrupt termination of glucocorticoid administration may lead to an Addisonian crisis. Glucocorticoids also affect the gastrointestinal mucosa, which may lead to ulceration and perforation.69 Immunosuppression and delayed wound healing may occur especially when higher doses are administered.
Tricyclic antidepressants can also play a role in pain management. Amitriptyline works in the central nervous system to block the reuptake of serotonin and norepinephrine.70 Amitriptyline has been shown in humans to be beneficial in the treatment of neuropathic and chronic pain states by enhancing the actions of opioids.71 There are no controlled studies using Amitryptilline in veterinary patients however it is thought that the tricyclic antidepressants would have similar analgesic effects in animals.
Finally, sedatives such as acepromazine and diazepam may be useful in potentiating or prolonging the effects of analgesic agents. If these sedatives are used, careful evaluation of the patient must continue as the central nervous system depression and sedation may mask signs of untreated pain.
Multimodal Analgesic Techniques
Systemic analgesic agents are often combined with local or regional anesthetic techniques to produce a balanced analgesic protocol that may maximize analgesic efficacy.
Local Anesthetic Techniques
Local anesthetic agents block transmission in all nerve fibers and are ideally suited for preemptive administration (Table 9-7). Local nerve block techniques are relatively easy to perform and have few complications. The benefits of performing these techniques include a significant reduction in inhaled anesthetic requirements and reduction in postoperative pain. Some of the techniques can be performed on conscious animals however most local techniques are easier to perform on sedated or anesthetized patients. The clinician should base their choice of which local anesthetic agent to use for a procedure on how quickly the local anesthetic is needed to work, the route of administration, and the expected duration of pain (Figure 9-1).
Topical local anesthetics can be used to desensitize cutaneous areas for minor, relatively noninvasive procedures. EMLA cream can be applied to the skin overlying a vessel before venepuncture, while 2% lidocaine jelly can be used to desensitize mucosal surfaces such as the urethra before catheterization.72 If local anesthetics are used on mucosal surfaces, doses should be calculated carefully, as these drugs are readily absorbed into the systemic circulation.
Most commonly, local anesthetics are infused around surgical sites allowing for procedures such as skin mass excision and repair of lacerations to be performed without general anesthesia although sedation is often required. After aseptically preparing the surgical site, local anesthetic should be infiltrated into all of the effected tissue planes. The needle is inserted into the skin and the plunger aspirated to prevent accidental intravenous injection. Total doses should be calculated carefully to avoid toxicity. If infiltration of lidocaine is being performed in a conscious patient, the lidocaine can be mixed with sodium bicarbonate (0.1 ml of 1mEq/ml NaHCO3 to 0.9 ml of 2% lidocaine) to reduce the discomfort felt by the animal on injection. Infiltration of local anesthetic into more invasive surgical sites can be continued over a period of time by using a fenestrated catheter attached to a reservoir. The catheter is placed in the surgical site and the reservoir is filled with local anesthetic. The reservoir can then be set to slowly deliver the local anesthetic to the surgical site over a period of days.
Local anesthetic infiltration into a surgical incision site either before the incision is made or just prior to closure is an effective analgesic technique. Infiltration of local anesthetic along the muscle of the abdominal wall of a celiotomy incision helps to control abdominal wall pain. If the block is performed before closure, a sterile syringe, needle, and local anesthetic agent are delivered to the surgeon aseptically. The musculature and subcutaneous tissues along both sides of the incision are then injected uniformly and wound closure proceeds normally.
Animals recovering from thoracotomy may benefit from blocking the intercostal nerves prior to incisional closure and/or the instillation of local anesthetics into the pleural space.74 If the patient has a thoracostomy tube, a local anesthetic such as 0.5% bupivacaine can be administered through the tube (1.5 mg/kg in the dog, flushing the tube with saline after administration). The animal is positioned to allow the local anesthetic solution to bathe the incision site (incision side down) for 10 to 20 minutes after instillation. If the animal does not have a thoracostomy tube in place, the local anesthetic can be instilled by aseptically placing an over the needle catheter into the pleural space. Complications of this procedure include infection and pneumothorax.75
Local anesthetics can also be infused into the peritoneal cavity using a similar technique. An over the needle catheter is aseptically placed into the abdomen at the level of the umbilicus. A mixture of local anesthetic and saline (total volume 10-20 mls) is then instilled. This technique may be helpful for those patients suffering from abdominal pain. Doses are calculated carefully, remembering that local anesthetic drug uptake will occur rapidly, particularly if the peritoneum is inflamed.76
Analgesia and/or anesthesia caudal to the diaphragm can be achieved with an epidural injection (Figure 9-2). The technique is relatively easy to perform and does not require specialized equipment. Injections are performed with the patient chemically restrained or anesthetized because the patient must remain still during the procedure. The hanging drop technique is described below. The animal is placed in sternal recumbency with the hind limbs extending cranially.The hair overlying the lumbosacral space is clipped and the skin is aseptically prepared. Sterile gloves are worn and the lumbosacral space is identified by placing the thumb and middle finger of the non-dominant hand on the cranial edges of the wings of the ilia. The index finger of the same hand then palpates the spinal process of the seventh lumbar vertebrae. The lumbosacral space is identified as a depression caudal to the spinous process. An appropriately sized spinal needle (20-22 gauge) is then introduced on midline at an angle that is perpendicular to the skin. Once the needle has passed through the skin, the stylet is removed and a small amount of sterile saline is placed into the hub of the needle. The needle is then slowly advanced through the overlying tissues until it passes through the ligamentum flavum. Commonly, a distinctive pop is felt and the saline in the hub of the needle is drawn into the space. If the needle encounters bone before puncturing the ligamentum flavum, it is withdrawn slightly and redirected. After the needle is directed into the epidural space, the hub of the needle is observed for the presence of blood or cerebral spinal fluid. If neither is present, the epidural injection is preformed. If blood is present, the needle is withdrawn and the process repeated. If cerebral spinal fluid is flowing from the needle, a decision to inject the analgesic into the subarachnoid space must be made. If it is decided to proceed with the injection, the dose of the analgesic must be reduced by at least 50%.77 After injection, the needle is completely withdrawn. If injecting a local anesthetic epidurally, the animal is placed with the affected side down for a period of 5 to 10 minutes.
Epidural injections can also be performed in lateral recumbency. The procedure is the same, with the area over the lumbosacral space clipped and aseptically prepared. The anatomic landmarks are identified, and the spinal needle is advanced through the skin. In this position, however, the stylet remains in place until the needle is thought to have penetrated the ligamentum flavum. Once the needle is in the epidural space, the stylet is removed and the hub of the needle is observed for blood or cerebrospinal fluid.
A test injection of a small amount of air can be performed to confirm the needle placement. If the needle is correctly placed, there should be little to no resistance to injection of air.78 The injection of drug is performed, the needle is withdrawn and the animal is placed with the affected area down if local anesthetic drug is administered. It should be noted that, in cats, the spinal cord usually ends at the first sacral vertebra making it more likely to puncture the dura during needle placement and obtain cerebrospinal fluid during epidural injection.77
If repeated injections or continuous administration of epidural analgesics is desired, placement of an epidural catheter should be considered. A Tuohy or Hustead needle is required to place an epidural catheter. These needles have a curve at the tip that aid in directing the catheter cranially when placed into the epidural space. There are a variety of epidural catheters available that are characterized by their size and material used to construct the catheter. Epidural catheters made of nylon or those with a wire spiral within the wall of the catheter are resistant to kinking, while others have a wire guide in the lumen of the catheter and are more flexible. Polyamide catheters are softer, more flexible and kink more easily.77 Prior to beginning the procedure, the clinician measures the animal to determine how much of the catheter needs to be inserted, making sure to account for the length of the Tuohy needle used for catheter placement. For a hind limb procedure, the catheter may only need to be inserted to the level of the fifth or sixth lumbar vertebrae, abdominal procedures require the catheter to be advanced to the second or third lumbar vertebrae, while for a thoracotomy the catheter should be advanced to the fifth or sixth thoracic vertebrae.
The animal is clipped and prepped using the anatomic landmarks for a epidural injection. A keyhole drape is placed over the lumbosacral space and the landmarks are palpated with sterile gloved hands. A small stab incision is made in the skin overlying the lumbosacral space using a sterile #11 blade to facilitate the passing of the Tuohy needle. The Tuohy needle is placed into the stab incision, and advanced through the overlying tissues until the ligamentum flavum is penetrated. Needle placement in the epidural space can be confirmed with a test injection of a small amount of air. The epidural catheter is then passed through the needle to the desired spinal segment. If the catheter has been advanced beyond the end of the Tuohy needle, no attempt should be made to withdraw it through the needle, as the catheter may be sheered off by the sharp edge of the needle. Once the catheter is in place, the wire stylet is removed if present, and an adapter is attached to the end of the catheter. A bacterial filter and injection cap primed with saline or analgesic are then connected to the catheter. The catheter should then be secured to skin at its exit site. A radiograph can be taken to confirm the placement of the catheter. Additionally, catheter placement can be guided by fluoroscopy, if available. If cleanliness and sterility are maintained, epidural catheters can remain in place for days to weeks.79
Complications of both single epidural injection and epidural catheter placement include infection, cranial spread of local anesthetic resulting in motor blockade of respiratory muscles, hypotension when using local anesthetics, and urine retention. Muscle spasms of the rear legs, pruritis, epidural hemorrhage, and spinal cord or nerve root trauma have also occurred. Contraindications for epidural injection include pyoderma at the site of injection, coagulopathy, and sepsis.77 Drugs commonly used in epidural injections and infusions are listed in Table 9-8. It is emphasized that preservative free formulations of these drugs should be used for epidural injection.
Transdermal Analgesic Administration
Transdermal administration of analgesics allows for delivery and maintenance of sustained concentrations of a drug avoiding the peaks and troughs associated with intermittent parenteral administration. Fentanyl and lidocaine are available in transdermal formulations and their use has been investigated in veterinary clinical patients.80-81
To apply a fentanyl patch, the hair of the animal is clipped and any gross debris is removed from the surface of the skin with water or saline. Alcohol should not be used as it will alter the lipids present on the epidermis, which will affect drug absorption. Once the area is completely dry, the patch is placed firmly onto the skin and held in place for one to two minutes. The patch should be placed in an area that will minimize patient removal and/or possible oral ingestion, as overdose may occur. Commonly, patches are placed on the dorsum of the neck or lateral thorax. A light bandage can then be placed over the patch. Transdermal patches should not be placed in direct contact with heating pads, as increases in cutaneous blood flow will increase drug absorption.82
Fentanyl patches are available in 25, 50, 75, and 100 mcg/hour concentrations. Clinicians should select a patch that will deliver a dose of 3-5 mcg/kg/hour in their patient. Once the patch has been placed, steady-state plasma concentrations are obtained in 18 to 24 hours in the dog while in the cat, 6 to 12 hours is required for steady plasma concentrations to be reached. Parenteral administration of opioids should be provided to animals when indicated to provide analgesia during the lag time until effective plasma concentrations are reached. The patch is designed to deliver fentanyl over a period of 72 hours, but they may be effective for longer periods. Studies have shown that there is significant inter and intra-individual variation in plasma fentanyl concentrations after patch application.83 For this reason, patients should be carefully monitored for signs of pain and/or side effects.
Complications associated with the use of fentanyl patches include respiratory depression, sedation, inadequate analgesia, skin irritation, failure of the patch to adhere to the skin, and human abuse. In cats, mydriasis, agitation, and dysphoria may be observed.83 If significant respiratory depression is observed, the patch should be removed and an opioid antagonist administered. Once a patch is removed, plasma levels decrease over a period of twelve hours. Patches should be disposed of carefully in the same manner as other controlled substances.
Lidocaine patches have been approved for use in humans for the treatment of peripheral neuropathies such as post-herpetic neuralgia and have generated interest in both human and veterinary pain management.84 It is thought that application of a lidocaine patch produces local tissue concentrations that are high enough to produce local analgesia, without complete sensory block, for periods up to 24 hours.85 The lidocaine patch is a 10 by 14 cm patch that contains 700 mg of 5% lidocaine. In human studies, once the patch is applied, up to 35 mg of lidocaine is absorbed topically, producing analgesia within 30 minutes,85 with a half-life of 6-8 hours.86 The amount of lidocaine absorbed is directly proportional to the area of skin that is covered and the length of time the patch is in contact with the area.85 In contrast to transdermal fentanyl, transdermally administered lidocaine has a very slow rate of systemic absorption, which makes systemic lidocaine toxicity unlikely.85 The pharmacokinetics of the lidocaine patch in dogs and cats are similar to those observed in human studies, showing significant tissue levels at the site of patch application, with peak plasma concentrations taking 10-36 hours to be achieved due to slow systemic absorption.87,88
To apply a lidocaine patch, the hair over the area should be clipped and the skin cleaned if needed. It is believed that the lidocaine patch acts by local nervous tissue penetration and not systemically like the fentanyl patch, thus the lidocaine patch must be placed close to or directly over the painful area. Unlike the fentanyl patch, the lidocaine patch can be cut to fit the patient or site of application without altering drug delivery. In surgical patients, the patch can be cut to the length of the incision and cut pieces should be placed on either side of the incision. Unused, cut portions of the patch can be saved for use at a later time. Seemingly, lidocaine patches can be left in place for three to five days with minimal side effects.88 Side effects of lidocaine patches in humans include skin irritation erythema, hives, and edema associated with the lidocaine patch. These complications typically resolved within hours of patch removal.89 In dogs, skin irritation/inflammation has been noted after patches have been in place for 72 hours.88 Although systemic toxicity is unlikely, animals should be monitored for signs of overdose that include bradycardia, hypotension, facial twitching, and seizures.
Fentanyl and lidocaine patches are useful as analgesic adjuncts but should not be used as the sole method of providing analgesia to animals with moderate to severe pain.
Constant Rate Drug Infusions (CRI)
Constant rate drug infusions administered intravenously through an indwelling catheter are used to manage pain effectively while limiting the peaks and troughs of intermittent analgesic administration. This technique has been found to be particularly effective in animals whose pain has been refractory to intermittent administration of analgesics. Typically, a loading dose of the analgesic is administered parenterally followed by a constant rate infusion of the analgesic. Analgesics may be delivered using a syringe pump, or added to the patient’s maintenance fluids. An example of the calculations used for constant rate infusions can be found in Table 9-9. Opioids, local anesthetics, and analgesic adjunct drugs have been used in constant rate infusions to treat pain in animals. Appropriate doses for these drugs are found in Table 9-10.
The clinician should be familiar with various analgesic drugs and drug delivery techniques available for administration of these agents. Use of combinations of drugs and techniques in a well-planned multimodal and balanced analgesic protocol will provide the safest and most effective clinical control of pain. The analgesic regimens described for the canine in Table 9-11 are examples of multimodal analgesic plans. All analgesic protocols should be designed to meet a specific patient’s needs and potentially modified in response to regular and frequent pain assessments.
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