Multimodal analgesia can be provided with combinations of local anesthetics, opioids, and alpha2 agonists.
In this article, we give an overview of drugs used for local and regional anesthesia and then discuss five anesthetic techniques—infiltration anesthesia, splash blocks, digital nerve blocks, intravenous regional anesthesia, and soaker-type catheters. We will discuss additional techniques—intra-articular stifle blocks, brachial plexus nerve blocks, intercostal nerve blocks, intrapleural nerve blocks, maxillary and mandibular nerve blocks, and epidural anesthesia and analgesia—in subsequent articles throughout this year. All of these techniques are easy to perform, do not require special equipment, and can greatly enhance the analgesic management of veterinary patients.
DRUGS USED FOR LOCAL AND REGIONAL ANALGESIA AND ANESTHESIA
Three general drug groups are used to produce regional anesthesia and analgesia in veterinary patients—local anesthetics, opioids, and alpha2 agonists.
Local anesthetic drugs
Structure and effects. Local anesthetic molecules consist of a lipophilic unsaturated aromatic ring and hydrophilic portion, usually a tertiary amine, separated by a connecting hydrocarbon chain. The lipophilic portion is essential for the anesthetic activity. Local anesthetics are categorized as amino esters or amino amides based on the chemical bond between the aromatic ring and the hydrocarbon chain of the molecule (Table 1). Although lidocaine (known as lignocaine in the United Kingdom) and bupivacaine are most commonly used in small-animal practice, a variety of local anesthetics are available, varying in their chemical structures, potency, onset of action, and duration of effect (Table 2).1,2
Systemic uptake. Local anesthetics are rapidly absorbed across mucosal, pleural, and peritoneal surfaces, with high bioavailability. Absorption from epidural and subcutaneous sites is slower, with lower bioavailability. The ultimate plasma concentration is determined by the rate of systemic uptake and the rate of drug clearance. The systemic absorption of a local anesthetic is determined by the dose administered (volume and concentration), the drug's protein binding and lipid solubility, the injection site's vascularity, and the use of a vasoconstrictor. Higher doses and increased injection site vascularity will increase systemic absorption.
Toxicity. Local anesthetics can cause severe toxic reactions after unintentional intravenous administration, vascular absorption of an excessive dose, or ingestion of topical local anesthetic preparations. Intravenous injection of bupivacaine is highly toxic to the cardiovascular system and central nervous system, resulting in agitation, muscular twitching, seizures, unconsciousness, coma, respiratory arrest, cardiac depression, dysrhythmias, hypotension, and death. Always aspirate the syringe before injecting any local anesthetic to avoid intravenous or intra-arterial injection.
Base dosage calculations on lean body weight, and always calculate the maximum safe dose to avoid toxicosis (Table 2). Animals with hepatic impairment or reduced hepatic blood flow (hypotension, cardiac failure), geriatric patients, and neonates are more prone to develop toxicosis with amide-linked local anesthetics, so reduce doses by 40% to 60%. In addition, cats should receive lower doses than dogs do since they are more likely to develop signs of toxicosis because they metabolize local anesthetics more slowly and, to a lesser extent, because of their decreased ability for glucuronidation.1-3
Relative or absolute overdosage of local anesthetics results in agitation, muscular twitching, seizures, unconsciousness, coma, respiratory arrest, cardiac depression, dysrhythmias, hypotension, and death.1,2 Some effects may be masked by general anesthesia, and dysrhythmias, hypotension, and respiratory arrest may be the only observable signs of toxicosis. Allergic reactions can occur but are uncommon. Benzocaine and prilocaine, and less commonly procaine and lidocaine, have been associated with the development of methemoglobinemia in dogs and cats.2 Cats are at increased risk for developing methemoglobinemia and Heinz-body anemia with benzocaine-containing products, including Cetacaine (a combination of benzocaine, butamben, and tetracaine), so these products should be avoided in cats.2
When given in high volumes epidurally or spinally, local anesthetics can cause excessive blockade of sympathetic neurons, resulting in hypotension, and excessive blockade of motor neurons, resulting in paralysis of intercostal muscles and the diaphragm.1,2
Opioids are sometimes added to local anesthetics to increase efficacy and extend the duration of the block. The efficacy of peripherally injected opioids is likely due to a combination of factors, including direct effects on opioid receptors in the periphery, anti-inflammatory effects, systemic absorption, and action at the spinal cord due to slow retrograde axonal transport along the nerve.4-6
Directly applying opioids to a peripheral nerve at high concentrations can produce analgesia that is not naloxone-reversible and is thought to be a nonspecific local anesthetic-like action.4 In addition, opioid mu and kappa receptors are present on the distant peripheral terminals of C fibers, and these receptors increase in number and become activated when there is inflammation at the site.4-6 Opioids attenuate the excitability of peripheral nociceptive terminals of primary afferent neurons during inflammation by inhibiting high-voltage activated calcium channels, which decreases the propagation of action potentials and the release of C fiber excitatory transmitters, such as substance P.4-6
Opioids may also mediate local analgesia through anti-inflammatory effects. Opioid receptors on immune cells and endogenous opioid peptides expressed in resident immune cells within peripheral inflamed tissue mediate lymphocyte function suppression and cytokine synthesis and release. Both mu and kappa opioid agonists have shown potent anti-inflammatory activity.5,6
Morphine is often used in intra-articular and epidural blocks, along with local anesthetics, and seems to provide additional analgesia in people and dogs.7-9 Buprenorphine has been shown to extend the duration of analgesia with brachial plexus and epidural blocks in people, compared with local anesthetic administration alone.10-13 Epidural morphine and buprenorphine have induced thermal nociception in cats, but morphine antinociception lasted longer and was more intense.14 The mechanism for the increased efficacy and duration of analgesia with peripherally administered opioids appears to be related to the lipophilicity of the opioid since the highly lipophilic buprenorphine provided a longer duration of satisfactory analgesia in people after a brachial plexus block than did the less lipophilic sufentanil.13 The anti-inflammatory effects of opioids likely also play a role in prolonging analgesia.5 Minimal adverse affects are associated with the peripheral administration of opioids because doses administered peripherally result in low plasma concentrations in most species.2,5
Alpha2 agonists, such as medetomidine, can be added to local anesthetic blocks to extend the duration and increase the efficacy of the block.15-18 Alpha2 agonists likely exert these effects through several mechanisms, including vasoconstriction, resulting in decreased systemic absorption of local anesthetics; facilitation of C fiber blockade by the local anesthetic; and action at the spinal cord due to slow retrograde axonal transport along the nerve.17 Norepinephrine is a principal neurotransmitter in the sympathetic nervous system that is also involved in nociception through alpha2-adrenergic receptors expressed on peripheral sensory neurons. In pathological pain states, such as neuropathic pain and inflammation, nociceptors develop increased sensitivity to norepinephrine, and peripheral antinociception is likely mediated through these peripheral alpha2-adrenergic receptors.17,18
Clonidine has been used for intra-articular, epidural, intrathecal, intravenous regional, and peripheral nerve blocks in people.17,18 Medetomidine provided effective analgesia when administered epidurally in goats, cows, dogs, and cats and extended the duration of radial nerve blockade with mepivacaine in dogs.15,19-22 Dexmedetomidine (Dexdomitor—Pfizer Animal Health) has potentiated and prolonged the effects of intrathecal and epidural local anesthetics in rats, sheep, guinea pigs, and people.23 Spinal administration of dexmedetomidine provided a powerful antinociceptive effect in dogs,24 and epidural dexmedetomidine was found to decrease the minimum alveolar concentration (MAC) of isoflurane in dogs.25 The addition of dexmedetomidine to the local anesthetic solution in intravenous regional anesthesia in people improved the quality of anesthesia and decreased analgesic requirements but had no effect on the sensory and motor blockade onset or duration.26 Sedation, bradycardia, and decreased cardiac output can occur from systemic absorption, so alpha2 agonists should not be used in hypovolemic patients or patients with impaired cardiovascular function.15,17,22,25
LOCAL AND REGIONAL BLOCKS
Strict adherence to sterile technique will prevent complications from infection. Always surgically prepare the skin, wear sterile gloves, and use only sterile needles, syringes, and catheters. Sterile skin preparation is not required for digital nerve blocks, but sterile needles and syringes should be used. To avoid complications from intravenous or intra-arterial injection of local anesthetics, always aspirate before injection. In addition, always calculate the maximum total dose for each patient, reducing the dose for debilitated, elderly, or neonatal patients.
Table 4 summarizes the indications, potential complications, drugs, dosages, and equipment required for each regional block technique described below.
A splash block refers to direct application of a local anesthetic to the site of interest, most commonly the body wall upon closure of the abdomen, the peritoneum intraoperatively, or the ovarian ligaments during an ovariohysterectomy. For this technique, 4 mg/kg of lidocaine or 2 mg/kg of bupivacaine is dripped from a syringe onto the area to be blocked, after flushing and suctioning the abdomen. These methods have been shown to reduce anesthetic requirements in some veterinary studies.28,29
Digital nerve blocks
These blocks are especially beneficial for onychectomies and will block the superficial branches of the radial nerve, the median nerve, and dorsal and palmar branches of the ulnar nerve, providing effective analgesia of a distal extremity.3,30 Because of its long duration of action, 0.5% bupivacaine is the drug of choice for this block, and it is often combined with lidocaine for immediate onset of the block. Do not use epinephrine because of the potential for ischemia in extremities.
Intravenous regional nerve blocks
Intravenous regional anesthesia, or a Bier block, is a rapid and reliable method for producing short-term (< 90 minutes) anesthesia and muscle relaxation of a distal extremity and can be performed in anesthetized or sedated animals.2,3,30 Because it requires restricted movement for a period of time, dogs often tolerate the procedure with moderate sedation, while cats often require heavy sedation. Sicker patients often tolerate this technique with minimal sedation, as they usually accept restraint for longer periods. This technique is indicated for mass removal, wound management, surgical biopsy, or fracture repair of a distal extremity.
Five to 10 minutes are required to achieve surgical anesthesia distal to the tourniquet, which will last up to 90 minutes. To avoid ischemic tissue damage, do not leave the tourniquet in place for more than 90 minutes.1,2 Sensation will return within five to 10 minutes of removing the tourniquet, and residual analgesia is minimal (20 to 30 minutes), so provide other analgesics postoperatively.2 This technique provides a blood-free surgical site and is also used with injectable antibiotics to obtain high tissue concentrations in a distal extremity.33,34 This technique is associated with few side effects as there is minimal systemic absorption of local anesthetic as long as the tourniquet remains in place and prevents blood flow to and venous return from the extremity.1,2 It is important to ensure that the tourniquet is not dislodged too early, as this will result in rapid plasma uptake of the anesthetic. Using lidocaine or mepivacaine doses below the toxic doses (Tables 2 & 4) will minimize the possibility of toxicosis should the tourniquet become dislodged.
The mechanism by which local anesthetics produce intravenous regional anesthesia is unknown but probably results from local diffusion of the anesthetic and the blockade of nerve endings and nerve trunks and from leakage under the cuff, resulting in systemic absorption.1 Some systemic absorption is also thought to occur from interosseous vessels.35
Soaker-type catheter placement
A soaker-type catheter, also referred to as a diffusion or wound catheter, is simply fenestrated tubing that is sterilely placed at a painful site for the continuous or intermittent administration of local anesthetics. Soaker-type catheters are easily placed during a surgical procedure, such as a limb amputation or large tumor resection, just before closure. In addition, they can be positioned nonsurgically at the site of a lesion that is painful but cannot be resected or when a course of palliative care has been chosen.
Efficacy and adverse effects. The veterinary literature regarding the use of soaker-type catheters is limited, but human medical experience is extensive and, for the most part, positive. A 2007 study demonstrated the viability of soaker-type catheters in postoperative pain management in dogs, cats, and goats.36 In another veterinary study, continuous infusion of bupivacaine into normal dogs' stifles for eight hours demonstrated plasma concentrations well below the toxic dose.37 Unfortunately, no studies have evaluated the efficacy of continuous infusion of local anesthetics in veterinary patients with surgical or traumatic wounds. Results from human trials are largely encouraging, with most showing an improvement in patient pain scores or a decrease in opioid requirements,38-46 whereas others have not found a benefit.47-50 Of great interest is the reduction in chronic pain in people a minimum of four years after bone graft harvesting with the use of continuous bupivacaine infusion at the graft site for 48 hours.51
Obtaining a catheter. Soaker-type catheters can be purchased commercially (Diffusion/Wound Catheter—MILA International; On-Q PainBuster Post-Op Relief System—I-Flow Corp) (Figure 4) or can be fashioned in a sterile manner from materials commonly found in the veterinary clinic. Commercial catheters are made of plastic tubing, often polyurethane, and typically range in length from 2.5 to 10 in. The fenestrated areas vary in length and are designed to spread local anesthetic over a predetermined area (5 to 22 cm).
Soaker-type catheter placement can be accomplished outside the operating room as well when a painful lesion is not to be surgically addressed. Commercially available catheters are advantageous in such situations because they have tear-away applicators that allow for minimal tissue trauma during placement. Homemade versions could also be placed in such a situation but would require some tissue dissection to appropriately localize the catheter. Tunneling the catheter some distance in the subcutaneous tissues before exiting the skin will help provide stability to the placement.
Elastomeric and electronic reservoirs that allow for continuous infusion of local anesthetic can be purchased from the same companies that supply commercial soaker-type catheters. Syringe pumps can also be used to provide continuous infusion. Lidocaine or mepivacaine are likely the safest choices for continuous infusion, and care should be taken to avoid toxic doses, especially in cats. Infusions of lidocaine or mepivacaine of 1 to 2 mg/kg/hr should be safe and effective in most cases. For intermittent administration, bupivacaine at 1 to 2 mg/kg is the best option because of its long duration of action (four to six hours). Catheters are typically left in place for one to three days, but can be left in longer if strict aseptic technique is followed.
The techniques described above are easy to perform and require simple materials and drugs available in most small-animal veterinary practices. By providing preemptive and multimodal analgesia, reducing the need for systemic analgesics and anesthetics and the attendant side effects, and decreasing the perioperative stress response through the use of local anesthetic techniques, you can improve the overall quality of the analgesic care in your patients. Look for subsequent articles in this series throughout the year covering additional helpful and easy-to-perform anesthetic techniques.
The authors wish to thank Gregory Hirshoren, Instructional Resources, College of Veterinary Medicine, The University of Tennessee, for the photos that accompany this article.
Christine Egger, DVM, MVSc, DACVA
Lydia Love, DVM
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
The University of Tennessee
Knoxville, TN 37996
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