Options for Analgesia in Dogs

Introduction

The field of pain management has profoundly evolved over the last 15 - 20 years. This change has been due to an increased understanding of the complex mechanisms of pain and the extensive negative impact of pathologic pain, as well as a drive by the pharmaceutical industry to identify and market unique drugs that reduce pain. Over this time one of the most clinically relevant discoveries has been the recognition of the "plasticity" of pain pathway and the fact that one or more extremely painful interventions (e.g. surgery, trauma) can influence the way pain, and possibly other sensory inputs (e.g. touch), are experienced later in a patient’s life [1]. Painful stimuli can cause changes in neurons in peripheral tissues and in the spinal cord that affect the way pain is perceived. The heightened intensity of sensation after a painful stimulation is called peripheral and central neuronal "sensitization". Inflammatory mediators released in response to tissue damage sensitize peripheral nerves. Glutamate acting at NMDA receptors is thought to be the primary neurotransmitter that mediates central neuronal changes after a painful stimulus. NMDA receptors in the spinal cord are activated after repeated stimulation by primary afferent nociceptive nerves. NMDA receptor antagonists such as ketamine and dextromethorphanblock these receptors and have been shown to prevent the hyperalgesia that occurs with central sensitization of dorsal horn neurons. Recent findings also suggest that prostaglandins produced through the action of cyclooxygenase 2 (COX-2) and nitric oxide produced by activation of nitric oxide synthase (NOS) also play a role in central sensitization [2]. The heightened efficiency of pain transmission with sensitization, if not effectively treated early on, will result in permanent changes in spinal nerves including neuronal and glial cell death as well as axonal sprouting and formation of new afferent synapses, all of which lead to the development of chronic pain.

Another factor critical to the evolution of pain management has been the realization that there are several "types" of pain and that the effectiveness of an analgesic is strongly influenced by the type of pain being treated. As an example, pain associated with inflammation is well managed with non-steroidal anti-inflammatory drugs (NSAIDs), but neuropathic pain is poorly responsive to these drugs and is much more effectively treated with NMDA receptor antagonists. Acute surgical pain tends to involve more than one type of pain, so although most analgesic drugs have been shown to be effective when given alone, the perioperative administration of more than one family of analgesic drugs is the most effective strategy for reducing postoperative pain.

Current Treatment Goals

Results of numerous studies on pain have provided support for two treatment concepts, both of which direct the administration of analgesics to reduce or eliminate pain-induced neural changes, reduce the amount of analgesic drug required (thereby reducing drug side effects) and improve the effectiveness of the analgesic drugs. These treatment approaches are described as follows:

Preemptive or Preventive Analgesia

It has been shown that administering analgesic drugs so that they are present prior to, during, and after a painful stimulus (surgery) reduces the dose of analgesics required to achieve effective pain relief, compared to that required if analgesics are only given after surgery [3-5]. This is true despite the fact that the patient is under a surgical plane of anesthesia and does not consciously perceive the painful stimulus. The best explanation for this observation is that a painful stimulus causes changes in pain pathways to alter the way pain is transmitted and experienced by the patient. When analgesics are not given prior to surgery, nerves in the pain pathway are repeatedly stimulated which increases the intensity of the pain transmission. Thus in recovery, although analgesics reduce the pain, they cannot reduce it to the level they would if the pain pathway had not been activated and up regulated. In contrast, when analgesics are given before the painful stimulus, pain transmission is reduced or blocked and the pain pathways remain as they were prior to surgery.

Multimodal Analgesia

There are many sites in the pain pathway where modification of pain transmission can occur. For instance, opioids act both centrally and peripherally to dampen pain transmission along afferent nerves and modulate neurotransmitter release across synapses in the dorsal horn of the spinal cord. In contrast, NSAIDs, although acting both peripherally and in the spinal cord, reduce the formation of prostaglandins, which are inflammatory mediators that increase the excitability of sensory and sympathetic nerve fibers, and sensitize peripheral nociceptors so that there is an increase in the response to painful stimulation (primary hyperalgesia). The combination of 2 or more analgesic drugs (multimodal analgesia) more effectively reduces painful transmission than one drug alone because different families of analgesics act through different receptors and at different sites along pain pathways. Analgesics administered together have an additive or synergistic effect with each other and allow the dose of each drug used to be reduced while still providing adequate analgesia. In addition to more effective analgesia, there is a reduction in drug side effects that are more common when higher doses are required.

Clinical Impact

Opioids, which have historically been viewed as the most effective analgesics, work by reducing neurotransmitter release from afferent pain nerves in the spinal cord. However, the longer opioids are used and the higher the dose that is used, the more likely they are to induce tolerance, which results in an increase in the required dose and a reduction in their effectiveness. Today the overall trend in acute pain management is to add non-opioid drugs to analgesic regimens, or use regional anesthesia/nerve blocks, or administer analgesics at the site of action as part of a treatment regimen to reduce the amount of opioid required and more effectively treat acute pain.

1. Non-opioid analgesics that are now routinely being included in veterinary analgesic regimens include ketamine, alpha-2 agonists, lidocaine and NSAIDs.

1. Although ketamine has been used for many years to induce or maintain anesthesia during surgery, it has only recently been shown to be a useful analgesic post-operatively. Administration of ketamine at subanesthetic doses (0.1 - 1.0 mg/kg IV, IM) can provide analgesia by functioning as an antagonist at the NMDA receptor. It potentiates the antinociceptive effects of both opioids and alpha-2 agonists, improving the analgesia achieved from the simultaneous administration of ketamine and either of these drugs, and is useful for reversing opioid tolerance due to chronic opioid administration [6]. At low doses ketamine has also been shown to have anticonvulsant properties and it is thought to be safe at these doses for relief of pain in seizure prone and head trauma patients [7,8]. When administering ketamine at low doses, usually as a constant rate infusion (CRI), it is important to taper off the infusion rate to prevent hypersensitivity that can occur if the infusion is suddenly stopped [7]. Ketamine is most effective when given concurrently with other analgesic drugs, especially opioids. Other medications that act at the same receptors as ketamine include dextromethorphan and amantadine, but they are administered orally.
2. Low doses of medetomidine (1 - 2 μg/kg) have also been shown to provide measurable analgesia with milder cardiovascular side effects than those commonly seen with higher doses [9,10]. As with ketamine, medetomidine is usually most effective when combined with opioids in the perioperative period. It may also be administered as a CRI for many hours, with other analgesics to reduce pain, stress and anxiety associated with hospitalization after trauma or surgery. Side effects of this technique (medetomidine at 1.5 μg/kg/hr) in healthy dogs include elevation of left atrial pressure, bradycardia, and a reduction in cardiac index and tissue oxygen delivery [10]. It is important that patients receiving a low dose medetomidine CRI be closely monitored for problems associated with these hemodynamic side effects.
3. Lidocaine administered systemically at antiarrhythmic doses (50 - 80 μg/kg/min) provides systemic analgesia, scavenges free radicals, and increases GI motility. Lidocaine administered to dogs as a CRI at doses of 50 and 200 μg/kg/min has been shown to reduce the minimum alveolar concentration (MAC) of isoflurane required to prevent purposeful movement in response to a noxious stimulus [11]. This effect is dose related and is thought to be due to its analgesic effects although the sedative effects of lidocaine may also reduce MAC. Lidocaine has also been shown to relieve neuropathic pain in humans at a dose of 5 mg/kg/hr but lower doses have not shown to be effective [12].
4. Perioperative administration of NSAIDs, specifically COX-2 inhibitors, reduces inflammation and pain associated with surgery and can be administered orally the night before surgery or by injection just prior to surgery since they do not have clinically significant effects on hemostasis. They should be continued through the postoperative period for 3 - 5 days to reduce the production of inflammatory mediators that play a role in the development of peripheral and central sensitization. Although there is clear indication for the preoperative use of NSAIDs, there are concerns about the effects of these drugs on kidney and liver function in the face of hypotension, which occurs in many patients during general anesthesia. Interestingly, there are several studies assessing the effects of COX-2 selective NSAIDs on the kidneys of healthy and compromised anesthetized patients and none of them demonstrated any adverse effect on renal function [13,14]. There are no studies assessing the effects on liver function in these same patient populations and until such data indicate otherwise, patients receiving preoperative NSAIDs should have blood pressure monitored, IV fluids administered, and hypotension treated with positive inotropes if volume replacement does not effectively treat hypotension.

2. The use of local anesthetics for nerve block or infiltrative regional analgesia was one of the first methods of surgical anesthesia and analgesia practiced in modern veterinary medicine. These techniques were also challenging and time consuming to perform in awake, small animal patients and were rapidly abandoned in favor of newer and safer methods of general anesthesia. We now know that the use of local nerve blocks and infiltrative analgesia in anesthetized patients are some of the most effective and least expensive ways to block pain transmission. These techniques also have few side effects if performed by an experienced clinician with a reasonable knowledge of anatomy. To this end, there is an excellent body of well-illustrated literature available that provides instruction for performing many specific nerve blocks in small animal patients [15-19]. One of the best ways to begin developing proficiency is to practice on cadavers using injections of food coloring or dye followed by dissection of tissues to assess placement of dye with respect to nerve location. Another method helpful in performing effective nerve blockade is the use of a "Nerve Locator". For more details on this technique, see the recent review by Campoy, 2006 [20]. A single injection of local anesthetic will last, depending on the drug injected, for 2 - 6 hours. The duration of nerve blockade or infiltrative regional analgesia can be extended by placement of a catheter designed to allow perineuronal or incisional infusion of local anesthetics over several days.
   When injection of local anesthetic is not feasible, there is a topical preparation [eutectic mixture of local anesthetics (EMLA® cream)] that can pass through intact skin to provide cutaneous analgesia for catheter placement and superficial surgery. There are also preparations such as lidocaine spray, gel and cream, which are most effective at providing analgesia for mucus membranes and skin that is not significantly cornified. Transdermal lidocaine patches (Lidoderm®) became available in 1999 and are approved for treatment of post herpetic neuralgia in humans. Although these patches have been prescribed for postoperative analgesia after orthopedic procedures, they have not been proven to be effective. The patches are designed to topically deliver lidocaine to damaged superficial nociceptors and cause analgesia without sensory blockade. There is no significant systemic uptake of lidocaine from the patch and as a result, the patch is considered safe if used as recommended by the manufacturer. Up to 3 patches may be applied to intact painful skin for 12 hours each day (12 hours on and 12 hours off).
3. Administering analgesics at the site of action can increase their effectiveness, reduce the required dose and reduce systemic side effects. Factors that determine the success of this technique include 1) specific characteristics of each drug such as lipid solubility, pH of the drug formulation, amount of protein binding and receptor affinity, and 2) characteristics of the tissue where the drug is being administered such as sites of expression of specific receptors and tissue pH. Techniques where the use of analgesics other than local anesthetic has been proven effective include epidural and intra-articular analgesia.

1. Epidural Route - Morphine and alpha-2 agonists have been shown to have advantages when administered epidurally either alone or in combination with local anesthetics. These drugs are able to cross from the epidural space to the spinal cord and act at the level of the dorsal horn to modify the release of pain neurotransmitters at doses lower than those required with systemic administration. It has been well established that the side effects associated with epidural morphine administration are significantly less and the duration of action is longer compared to systemic morphine administration. Also, there is no loss of motor function, which may make epidural morphine preferred over local anesthetics when assessment of post surgical motor function is required.
   Ketamine when administered epidurally has inconsistent effects, but appears to be most promising when the S (+) en antomer is used [21]. The ketamine that is used clinically is a racemic mixture of the R (-) and S (+) isomers, and it has not been shown to improve analgesia when administered epidurally.
2. Intra-articular Route - In addition to local anesthetics, intra-articular administration of morphine, steroids and alpha-2 agonists have been shown to be effective in providing acute and, in the case of steroids, chronic analgesia. Intra-articular alpha-2 agonists have been shown to produce analgesia when administered alone and act additively or synergistically when administered in combination with opioids and local anesthetics [22]. Intra-articular morphine has been shown to be effective when used alone or with local anesthetics, especially in situations where preexisting joint inflammation has caused an increase in the expression of opioid receptors on synovial membranes. Intra-articular morphine, administered post-operatively, has been reported to provide up to 18 hours of analgesia and it is recommended that after sterile injection, a tourniquet should be applied for 10 minutes just proximal to the joint to improve absorption into surrounding tissues [23].

Current Analgesic Regimens to Treat Acute Pain in Dogs

Preoperative Analgesics

Purpose: To reduce stress that worsens pain, reduce preexisting pain and inflammation, reduce amount of general anesthetics needed for intubation and patient preparation prior to surgery. More than one drug or technique should be used with each analgesic regimen.

IV/IM/SQ and Oral Drugs Administered

NSAIDs:

• COX-2 selective NSAIDs help prevent peripheral and central sensitization and are given routinely, in addition to an opioid, preoperatively to healthy patients. If intraoperative monitoring and cardiovascular support are not available, it may be preferable to administer these drugs post-surgically.
• Administer only COX-2 selective drugs (not COX-1 or non selective NSAIDs) prior to surgery, and when possible administer injectable preparations 1 - 2 hours prior to surgery and oral preparations 8 hours prior to surgery.
• Conservative opinion suggests that these drugs not be given to dogs that are dehydrated, have elevated liver enzymes, evidence of kidney disease, recent history of steroid or aspirin administration, or had a recent period (more than 2 days) of hospitalization or other sustained stressful experience.
• Drugs and dose:

• Carprofen (Rimadyl) 2 - 4 mg/kg SQ
• Meloxicam (Metacam) 0.2 mg/kg SQ
• Deracoxib (Deramaxx) 2 - 4 mg/kg PO
• Firocoxib (Previcox) 5 mg/kg PO

Opioids:

• Provide profound analgesia, sedation in patients with preexisting pain and are usually administered to every patient prior to surgery, with a tranquilizer such as acepromazine or diazepam to reduce anesthesia-associated dysphoria and vomiting commonly seen in healthy patients. Almost all opioids are easily reversed with naloxone if adverse effects require treatment (buprenorphine requires significantly higher doses of naloxone and only partial reversal can be achieved). Agonists can be given slowly IV to effect, or IM/SQ. Morphine causes histamine release and should only be given IM, SQ or very slowly IV. Dose should be reduced when administered concurrently with an alpha-2 agonist.
• May cause bradycardia and respiratory depression so patients should be monitored during anesthesia. Additional information on adverse effects can be found in several recent reviews [23,24].
• A fentanyl patch can be applied at least 12 hours preoperatively and may provide analgesia for up to 3 days post-operatively. Care should be taken to avoid placing the patch in contact with patient warming devices. If additional opioids are required intraoperatively, fentanyl should be administered and the patient closely monitored to prevent opioid overdose.
• Although butorphanol can provide analgesia, it is of short duration and other opioids are preferred in analgesic regimens. Butorphanol is however useful for reversal of opioid induced side effects at a dose of 0.1 mg/kg IV to effect.
• Drugs and dose:

• Morphine 0.5 - 1 mg/kg IM
• Oxymorphone 0.05 - 0.15 mg/kg IM
• Hydromorphone 0.05 - 0.2 mg/kg IM
• Fentanyl 0.005 - 0.01 mg/kg IM
• Methadone 0.2 - 0.3 mg/kg IM (may also have NMDA receptor activity)
• Buprenorphine 0.01 - 0.02 mg/kg IM

Alpha-2 Agonists:

• Cause vasoconstriction, systemic hypertension and bradycardia which is reasonably well tolerated in healthy patients. Concurrent administration of opioids results in more profound sedation and doses of both drugs should be reduced. Concurrent use of alpha-2 agonists and anticholinergics is not recommended, because it worsens hypertension and compromises cardiac function. Patients that have received alpha-2 agonists and have bradycardia and hypotension should preferentially be treated with atipamezol to reverse bradycardia.
• Monitoring patients that have received alpha-2 agonists is challenging since vasoconstriction adversely affects pulse oximetry and visual assessment of blanched, vasoconstricted mucus membranes makes it difficult to assess the cardiovascular status of the patient.
• Drugs and dose:

• Medetomidine 0.005 - 0.015 mg/kg IM, 0.001 - 0.010 mg/kg IV
• Xylazine 0.1 - 0.2 mg/kg IM

Ketamine:

• Can be administered IM or SQ at lower doses to control aggressive or painful patients without vascular access. An effective analgesic premedication without excessive sedation is a combination of ketamine with a tranquilizer such as acepromazine and an opioid.
• Lower doses of ketamine cause fewer unpleasant side effects (salivation, muscle rigidity, CNS stimulation) while still providing analgesia
• Drugs and dose:

• Ketamine 1 - 4 mg/kg IM
• Low dose ketamine 0.1 - 1 mg/kg IM or IV

More Common Local Nerve Blocks and Local Administration of Analgesics

Brachial Plexus Nerve Blocks:

• Indications for this block include any distal forelimb procedure such as fracture repair, orthoplasty for congenital malformations, digit amputation and extensive soft tissue surgery.
• Relatively simple technique to perform, more effective results are achieved when a nerve locater is used [20].
• The brachial plexus nerves can be blocked by administering bupivacaine into the axillary space at the level of the shoulder joint. A needle 1 - 6 cm, depending on patient size, is passed medial to the shoulder joint, parallel to the thoracic wall directing the needle tip toward a point approximately at the caudal aspect of the shoulder joint. The syringe is aspirated prior to injection and again any time the needle position is adjusted during the injection. A brachial plexus block performed using this technique, although helpful, appears to be inadequate for analgesia after front limb amputations. It only provides analgesia for procedures distal to the elbow.
• Another technique to perform a brachial plexus block has been described that extends analgesia proximal to the level of the shoulder [16] but is still not adequate for forelimb amputation.
• Longer acting local anesthetics such as bupivacaine tend to have a slower onset of action so lidocaine is added to bupivacaine to speed the onset of action.
• Drugs and dose:

• Bupivacaine 0.5 - 2 mg/kg
• Lidocaine 1.5 - 2 mg/kg

Epidural Analgesia:

• Complete anesthesia of the rear limbs can be achieved using epidural anesthesia with bupivacaine. Bupivacaine has a duration of action of about 4 hours and when given epidurally, causes complete motor and autonomic paralysis caudle to the L1 vertebra. Autonomic paralysis results in regional vasodilation of tissues that are affected by the block, which may result in hypotension. As a result, fluids should be administered when local anesthetics are administered epidurally and the anesthetist must be prepared to use a vasopressor such as ephedrine or dopamine, if hypotension is unresponsive to fluid therapy.
• If retention of normal motor function is desired, epidural analgesia can be provided for intra- and post-operative pain relief by including preservative-free morphine in the injection. This technique can provide analgesia during painful procedures involving the rear limbs and has the added advantage that it can provide some analgesia for thoracic surgery and surgical procedures involving the forelimbs. The epidural opioid selected for epidural administration should be more hydrophilic (less lipid soluble). Opioids with greater lipid solubility, such as fentanyl, enter the systemic circulation rapidly so they have a duration of action and side effect profile similar to that seen with systemic administration.
• Combinations of an opioid and local anesthetic provide more profound analgesia and longer duration of analgesia compared to morphine alone. Lowering the dose of local anesthetic administered with morphine has little effect on analgesia but motor function can be retained. Also, postoperative analgesia can be achieved for up to 6 hours after surgery and it is more effective than repeated doses of an opioid and a NSAID [25]. Using the combination of an alpha-2 agonist and morphine will prolong the analgesia after surgery compared to morphine alone, but systemic effects from the alpha-2 agonist are also seen and include bradycardia and peripheral vasoconstriction and hypertension.
• The epidural technique can be performed as either a single injection through a spinal needle inserted into the epidural space at the lumbosacral junction, or through a catheter inserted into the epidural space. The technique for epidural analgesia has been thoroughly described elsewhere [15-20,26]. Drugs that are administered epidurally should ideally be preservative-free. Any drug preserved with formaldehyde or its derivatives must be avoided.
• Preexisting diseases that preclude the use of epidural analgesia include coagulation disorders, septicemia, spinal trauma, rear limb neuropathies, and dermatitis from infection or trauma of the skin overlying the lumbosacral space.
• Drugs and dose: Drug volume injected should always be 0.1 - 0.2 ml/lkg and should be limited to 6 - 7 ml in all dogs.

• Bupivacaine 1 mg/kg
• Morphine 0.1 - 0.2 mg/kg
• Methadone 0.2 - 0.3 mg/kg
• Buprenorphine 0.004 - 0.01 mg/kg
• Morphine 0.1 mg/kg + bupivacaine 0.25 - 0.5 mg/kg
• Morphine 0.1 mg/kg + medetomidine 0.005 mg/kg

Intra-operative Analgesics:

Purpose: sustain effective levels of analgesia during painful surgery/procedures so as to reduce post-operative pain, reduce the concentration of inhalant anesthetic needed to maintain immobility, thereby reducing associated cardiovascular and respiratory depression.

Influence of Preoperative Analgesics: Local anesthetic techniques and drugs administered with a longer duration of action (e.g. fentanylpatch) will reduce the need for additional intraoperative drug administration, especially during short surgical procedures. Anesthetized patients should be closely monitored and maintenance anesthetic agents reduced to maintain cardiovascular variables within a normal physiologic range.

Analgesic Regimens:

CRI Fentanyl +/-NMDA Antagonists:

Fentanyl has been shown to be an effective intraoperative analgesic when administered at doses of 0.3 - 0.7 μg/kg/min. A recent study suggests that an even lower dose (0.15 μg/kg/min after a bolus of 10 μg/kg) will result in blood levels shown to provide effective analgesia in other species [27]. Fentanyl can also be combined with ketamine to reduce central sensitization that prolongs pain in the postoperative period. In a study by Wagner et al, ketamine at a dose of 0.6 mg/kg/hr was administered during forelimb amputation surgery in dogs premedicated with ketamine (0.5 mg/kg IV) and morphine (1 mg/kg SQ) [28]. The ketamine CRI was continued in the postoperative period for 18 hours at a rate of 0.12 mg/kg/hr with fentanyl at 1 - 5 μg/kg/hr. Compared to the control group that only received opioids for analgesia, the group that received opioids and ketamine had lower pain scores 12 and 18 hours after surgery and were significantly more active on day 3 after surgery.

Morphine-Lidocaine-Ketamine Combination (MLK)

In an analgesia regimen described by Muir et al. [29] drugs are added to a bag of maintenance fluids and administered over the surgery to maintain effective blood levels of each drug. To a 500 ml bag of fluids (LRS or equivalent) add morphine 12 mg, lidocaine 150 mg and ketamine 30 mg. The fluids are then administered at 10 ml/kg/hr for the duration of the surgery. From personal experience with this combination, we have found that it can be continued into the post-anesthetic period for patients with extremely painful conditions. To do this the fluid rate must be reduced to a maintenance fluid rate (2 ml/kg/hr) and the dose of drugs added to the bag (mg/ml) must be increased (e.g., a reduction to 2 ml/kg/hr means adding 5x the dose of drugs described above, or adding 60 mg morphine, 750 mg lidocaine and 150 mg ketamine to a 500 ml bag of fluids). Under some circumstances dogs may become excessively sedate on this combination during the recovery period. In this situation or if less postoperative pain is anticipated, the morphine dose should be reduced by half (to 30 mg in the example above).

Advantages: This technique provides effective analgesia for painful procedures without causing excessive respiratory depression. in addition, there is no requirement for specialized dosing equipment (calibrated pumps) to administer the drugs although the use of a fluid pump reduces the chance of errors in administration rate.

Disadvantages: Fluid boluses cannot be given unless a second bag of fluids without drugs is used. It is also very important to regularly monitor the volume administered to assure that the desired fluid rate is being administered. If the entire bag of MLK is not administered, it is difficult to know exactly how much drug the dog received which may complicate record keeping and recording discarded drug on the controlled substance log.

Intra-articular Analgesia:

Indications include arthroscopy, cruciate ligament repair and arthrotomy for removal of cartilage debris. One or more drugs are injected into the joint at the end of surgery, after closing the joint capsule. Drugs that have been shown to be effective include bupivacaine (2 mg/kg, 0.5% solution) and morphine (0.5 mg/kg).

Advantages: No or minimal systemic drug effect.

Disadvantages: Minimal analgesia for surrounding tissues affected during the surgical approach to the joint. Some systemic analgesia is still required.

Soaker Catheters:

These are ideal for limb amputations, ear canal ablations and any large invasive musculoskeletal surgery. Based on the concept of a soaker hose, soaker catheters are relatively large bore (6 - 12 French) blunt ended catheters with very tiny holes in the side that allow a uniform distribution of local anesthetic in the deepest tissues of a surgical site. They are placed just prior to closing a surgical incision and are secured to the skin at the end of the surgery. Catheters can be made from a red rubber catheter or purchased from a veterinary distributor (Mila International, Florence, KY, USA - www.milaint.com). A loading dose of lidocaine (2 mg/kg, 2% solution) or bupivacaine(1 - 2 mg/kg, 0.5% solution) is administered in the catheter at the end of the surgery and the patient is placed in recovery on either a constant rate infusion of lidocaine (2 mg/kg/hr, 1 - 2% solution), or an injection every 6 hours of bupivacaine (1 - 2 mg/kg, 0.5% solution) for the following 24 hours. Concurrent administration of low to moderate doses of systemic opioids (usually agonist opioids) are also given but can be reduced if excessive sedation is observed.

Advantages: The patient is alert, comfortable and can resume normal activities such as eating and walking outside without having to deal with the sedation associated with large doses of opioids.

Disadvantages: Possible contribution of local anesthetic to postoperative swelling and edema of surgical site. Although unlikely when proper sterile technique is used, it is possible to develop infections from contaminated drug solution or a contaminated catheter site.

Post-operative Analgesics:

Purpose: Reduce stress, pain and inflammation in the recovery period. Eliminate changes in the nervous system that could result in chronic pain. Include 2 or more analgesics from different drug groups and dose at low end of dose range.

Drugs Used During Recovery in Painful Hospitalized Patients:

• Acepromazine 0.02 - 0.05 mg/kg. This drug is not an analgesic but can reduce anxiety. (Anxiety contributes to the perception of pain.)
• Morphine-lidocaine-ketamine CRI (see description in intraoperative analgesic regimens above)
• Fentanyl  CRI at a rate of 2 - 10 μg/kg/hour. Administering drugs as a CRI reduces large fluctuations in blood levels, reducing side effects and periods of time where analgesia is inadequate.
• Morphine  CRI at 0.15 - 0.2 mg/kg/hr or intermittent dosing at 0.5 - 1 mg/kg IM every 4 hours or 0.5 mg/kg IV every 2 - 3 hours [30].
• Alpha-2 agonists: 1 - 2 μg/kg/hr. Avoid in patients unable to tolerate side effects described above.
• Ketamine  CRI at 0.1 - 0.3 mg/kg/hr administered for 18 hours post-operatively; has been shown to be effective at reducing pain post-operatively [27]. May be continued longer if needed.
• NSAIDs can be administered post-operatively if not already given prior to surgery. They reduce inflammation and sensitization of pain pathways. In addition to those previously mentioned, other NSAIDs that may be administered include. Ketoprofen 1 - 2 mg/kg SQ, SID and Etodolac 10 - 15 mg/kg PO SID.

Drugs Used to Treat Pain in Post surgical Patients at Home:

• NSAIDs: Continue NSAID initiated in hospital for 3 - 5 days after returning home.
• Opioids: More painful procedures may require the continued administration of opioids for 3 - 5 days post-operatively, either concurrently with NSAIDs or alone in patients where the use of NSAIDs is contraindicated. Of the options described below, only tramadol is not a scheduled drug. Options for non-injectable opioids include:

• Fentanyl patch: 3 μg/kg, change every 3 days
• Tramadol: 2 - 10 mg/kg PO (see reference [24] for drug description)
• Sustained release morphine sulfate: 1 mg/kg one to two times daily.
• Gabapentin: Patients with evidence of neuropathic pain after surgery may improve after early treatment with gabapentin (3 - 5 mg/kg) combined with an opioid and an NSAID.

Analgesics to Reduce Sustained Pain after Trauma/Surgery:

Purpose: Reduce sensitization of pain pathways, which if not treated, sustain pain in the recovery period. Consider possibility of nerve damage as cause of pain. Look for the presence of allodynia (painful response to non-painful stimuli) and hyperesthesia (heightened perceived intensity of painful stimuli) as signs of central sensitization. Effectiveness of analgesic regimens can be assessed using these signs. Treatment usually involves co-administering two or three analgesics from different drug groups.

Drugs that Treat Wind-up and Neuropathic Pain:

• NMDA Receptor Antagonists: Dextromethorphan 0.5 - 2 mg/kg PO and Amantadine: 3 - 5 mg/kg PO once daily
• Gabapentin: 3 - 5 mg/kg although can go higher (maximum of 50 mg/kg) incrementally as needed. Mechanism of analgesia not clearly defined. Shown to improve analgesia from opioids and/or an NSAID and reduce neuropathic pain. Wean gradually after longer period of administration to prevent rebound effect (seizures).
• Amitriptyline: 1 - 2 mg/kg PO one to two times daily. Reduces reuptake of serotonin and norepinephrine in CNS.
• Tramadol: 2 - 10 mg/kg PO one to two times daily. Acts both at opioid receptors (active metabolite) and to inhibit the reuptake of serotonin and norepinephrine (parent compound), so avoid concurrent use with amitriptyline.

Drugs that Reduce Inflammation:

• NSAIDs: Patients that present for pain and are on NSAIDs should have the NSAID changed after a 3 - 5 day withdrawal period. Any of the above mentioned NSAIDs may be used, or if these have been previously established to be ineffective, use one of the following:

• Acetaminophen 10 - 15 mg/kg PO two to three times daily. Mechanism of action unknown. Thought to inhibit COX-3 but recent data suggest there may be another site of action.
• Piroxicam 0.3 mg/kg. Very potent COX-2 selective NSAID used in human medicine.