SURGERY—LAMENESS Review of Equine Analgesics and Pain Management Nora S. Matthews, DVM, Diplomate ACVA; and Gwendolyn L. Carroll, DVM, Diplomate ACVA Many drugs and administration techniques are now available to the veterinarian for the management of equine pain. Balancing the use of drugs that act at different locations or by different mechanisms in the pain pathway improves analgesia, minimizes cost, and lessens side effects. Providing good analgesia improves the patient’s recovery and shortens hospital stays, thus improving outcome. Au- thors’ address: Department of Veterinary Small Animal Clinical Sciences, Texas A&M University, 4474-TAMU, College Station, TX 77843-4474; e-mail: [email protected]. © 2007 AAEP. 1. Introduction action or that act on different receptor types; these Pain is very debilitating in the horse and may be primar- drugs are used to provide good analgesia with lower ily responsible for the result of euthanasia during certain dosages of each drug, which decreases possible side medical conditions (e.g., laminitis). Yet, adequate pain effects. The simplest (yet widely used) combination ␣ management may be expensive, difficult to evaluate, and of an 2-agonist (e.g., xylazine) for sedation, local may require frequent drug administration. Addition- anesthetic block, and an NSAID provides balanced ally, most commonly used analgesics (i.e., non-steroidal or “multimodal” analgesia. anti-inflammatory drugs [NSAIDs]) come with their own A multitude of such combinations may be formu- set of limiting side effects. lated depending on patient need and intended route Positive benefits of analgesia include mainte- of administration. Currently, many drugs may be nance of weight, shorter hospitalizations, and lower administered parenterally (e.g., IV, IM, or SC) as total patient bills.1 The use of analgesics in horses well as orally (PO). Regional local anesthetic grows as the complexity of surgical treatment in- blocks (e.g., intra-articular [IA], epidural, four- creases. Because equine pain management is a point, etc.), transdermal (TD), and transmucosal large topic, this review will focus on pain manage- (TM) are other routes that may be used. Constant- ment during the perioperative period. The drugs rate infusions (CRIs) of IV drugs allow for consistent and techniques used in perioperative pain manage- blood concentration with overall lower doses; thus, ment are also useful in chronic conditions. there are fewer side effects. 3. Methods of Administration 2. The Concept of Balanced Analgesia The usual routes of administration (IV, IM, SC, epi- The concept of balanced (or multimodal) analgesia is dural injections, and PO) are all very useful, but to use a variety of drugs that have different modes of newer analgesics can be administered transder- NOTES 240 2007 ր Vol. 53 ր AAEP PROCEEDINGS SURGERY—LAMENESS mally by patch or topical application. CRIs allow provided by butorphanol has been questioned, it has for the IV administration of lower doses (fewer side become widely used in equine medicine, particularly effects) to maintain consistent plasma concentra- before being scheduled. Nalbuphinel is another ag- tions, which produces analgesia with fewer peaks onist-antagonist opioid (much like butorphanol) that and troughs. Many drugs may be administered by currently has the advantage of not being a scheduled multiple methods depending on the method that is drug. Nalbuphine (0.3 mg/kg, IV) has been evalu- most practical for the patient. An analgesic regi- ated with detomidinem (0.01 mg/kg, IV) or men might combine different drugs given by differ- acepromazinen (0.05 mg/kg, IV), and it produced ent routes, which could help to reduce injection pain good sedation with both; however, the analgesic ef- or adverse gastrointestinal side effects and improve fect was not evaluated.2 Analgesia (dental dolo- owner compliance. rimetry model) was evaluated with nalbuphine (0.75 mg/kg, IV) and compared with morphine, butorpha- 4. NSAIDs nol, and xylazine.o3 No difference between groups Several different NSAIDs (phenylbutazone,a flunix- was seen. Nalbuphine is less potent and efficacious in,b and ketoprofenc) have been widely and effec- than butorphanol, but it has been used for analge- tively used for pain management in sia, especially in countries where other opioids are horses. However, all have the potential to produce not available. significant side effects, especially when used at high Buprenorphinep (0.004–0.006 mg/kg, IV, IM, or doses. Although not approved for use in horses in SC) has the advantage of a long duration of action the United States, the newer NSAIDs like meloxi- (6–8 h), but it is not approved for equine use (or any camd (0.6 mg/kg, IV) and carprofene (0.7 mg/kg, IV) veterinary use). Buprenorphine (q 8 h) has been may have fewer side effects with good efficacy. used in the multimodal analgesic management of Transdermal 1% diclofenacf may have the advan- laminitis. The TM or PO absorption of buprenor- tage of decreased side effects, because it can be used phine has not been reported in horses. In cats, TM on the specific site where analgesia is required. buprenorphine is 100% bioavailable. A transder- Because all are fairly similar, the choice of NSAID is mal form of buprenorphine is available in the United likely to depend on availability and cost. Indi- Kingdomq and Australia.r vidual patients may vary in their response to a par- Fentanyls is a short-acting, ␮-receptor opioid that ticular NSAID (much as occurs in humans), and this produces increased locomotor activity in horses, an may also affect the choice of drug to use for a par- effect that is similar to the earlier opioid studies that ticular patient. Although NSAIDs are very effec- were reported by Tobin et al.4,5 Transdermal fen- tive for pain reduction in horses, it is unlikely that tanylt (fentanyl patches are now generic) is not ap- they will produce sufficient analgesia for severely proved for use in horses but has been used for painful conditions; however, it should be a basic analgesia. Uptake of transdermal fentanyl is more “building block” of balanced analgesia. The veteri- rapid in the horse; blood levels consistent with an- narian must also remember that severe or chronic algesia are present within4hofapplication com- pain is very difficult to treat; it may be “refractory” pared with 12 h in humans and small animals.6 to analgesics that normally are quite effective. Two 100-mcg/h patches for a 450-kg horse are the Chronic pain requires aggressive and multimodal typical dose. The two patches may be applied to a analgesia for successful treatment. Reasonable clipped area of the skin and bandaged in place to outcome expectations for analgesia may need to in- insure good skin contact. Because it is easy to clude feed consumption and mobility rather than a place a bandage on the forearm or gaskin, these complete return to normal weight bearing. locations are easy sites to use. Although patches are supposed to provide analge- 5. Opioid Analgesics sia for 72 h in people, reapplication at 48 h should be Opioids have been a mainstay of pain relief in both considered depending on response and reevaluation the human and veterinary field. The usefulness of of pain. Systemic fentanyl (1–4 mcg/kg/h) has been opioids as single-agent analgesics in horses has been used in conjunction with inhalant anesthesia to re- tempered by the propensity for opioids to produce duce the vaporizer setting required. However, excitement when administered alone in non-painful when alfentanylu was used with halothane, no min- horses. Gastrointestinal stasis may also occur in imum alveolar concentration (MAC)-sparing effect some horses. Morphineg (0.1 mg/kg, IV or IM), me- was seen in horses, so further research is needed to peridineh (4.4 mg/kg, IV or IM), methadonei (0.22 determine if these drugs are beneficial when used mg/kg, IV), and oxymorphonej (0.033 mg/kg, IV) with inhalant anesthesia.7 Fentanyl is also a po- have all been used alone for analgesia and with tent respiratory depressant, and mechanical venti- sedatives to facilitate standing surgery. lation is required when it is used with inhalant Butorphanolk (schedule IV; 0.01–0.1 mg/kg, IV or anesthesia. IM), an agonist-antagonist opioid approved for use Tramadol,v a non-opiate ␮-agonist for the treat- in the horse in the United States, has also been ment of mild to moderate pain, has the advantage widely used for analgesia and sedation in conjuction that it is not currently a scheduled drug. In addi- ␣ with 2-agonists. Although the degree of analgesia tion to other drug activity, tramadol has analgesic AAEP PROCEEDINGS ր Vol. 53 ր 2007 241 SURGERY—LAMENESS activity similar to ␮-agonists; morphine is the gold used in a variety of ways: local infiltration, ana- standard for ␮-opioid activity). Tramadol is also a tomic nerve block, regional limb block or perfusion, serotonin-reuptake inhibitor, and it lowers the sei- epidural, and CRI. Although lidocainey and mepiv- zure threshold in people. Tramadol is not approved icainez produce a short duration of action, bupivic- for veterinary use, but it is used extensively to treat aineaa offers the advantage of lasting for 6–8 h. mild to moderate pain in dogs and cats. Although Although more toxic (dose should be limited to 2 the efficacy of tramadol has not been documented in mg/kg), bupivicaine may be used as a regional block horses, the pharmacokinetics of oral (10 mg/kg) and (e.g., pastern arthrodesis) intra-operatively and will IV (4 mg/kg) dosing have been reported in foals.8 last into the post-operative period. Local anes- Further investigation is needed for this promising thetic blocks (e.g., blocking the testicle during a drug, especially because the cost has decreased since castration or “splash blocking” ovarian pedicle dur- it became available in generic form.