www.ivis.org Proceeding of the SEVC Southern European Veterinary Conference Oct. 17-19, 2008 Barcelona, Spain http://www.sevc.info Reprinted in the IVIS website with the permission of the SEVC www.ivis.org
ORTHOPEDICS Pain Management in the Orthopedic Patient Sheilah A Robertson BVMS (Hons), PhD, DACVA, DECVA, MRCVS College of Veterinary Medicine, University of Florida, Gainesville, FL Introduction Pain is something we deal with every day in veterinary practice. It is essential that we know when pain may occur, its severity and duration, how to recognize it and how to utilize the available treatment options. Developing a logical treatment plan requires an understanding of the mechanisms involved in nociception and pain. The Physiology of Pain Firstly, what is pain? This has been described by the International Association for the Study (IASP) of pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. From this definition, pain is always subjective and always unpleasant therefore it is an emotional experience. The IASP also state the inability to communicate in no way negates the possibility that an individual is experiencing pain and is in need of appropriate pain relieving treatment. Thus, although we cannot measure pain in non-verbal humans and animals it is widely accepted that they can feel pain. The so-called pain experience can be considered under different headings; nociception which includes transduction, transmission and modulation, and perception of the unpleasant experience. Transduction is the process that involves translation of noxious stimuli into electrical activity at sensory nerve endings. Nociceptors respond to thermal, mechanical and chemical stimulation. Transmission is the process of sending the impulses throughout the sensory nervous system. Afferent signals from the periphery are relayed through the dorsal root ganglia to the dorsal horn of the spinal cord where sensory input can be modulated. Information then travels rostrally, finally reaching the cerebral cortex. Modulation is the modification of nociceptive transmission. The body can regulate and modify incoming impulses at the dorsal horn and this involves release of enkephalins, the body s natural opioids, and activation of serotonergic and noradrenergic pathways. The perception of pain can only occur in a conscious animal, and is a result of the interaction of transduction, transmission and modulation. The logical approach to the treatment of pain is based on manipulation of these processes. The concepts of peripheral and central sensitization explain a lot about an animal s response to an injury and also pave the way for better pain management. Surgery produces inflammation and a change in sensitivity to noxious stimuli. As the local area of tissue injury becomes more sensitive, the threshold for subsequent stimuli decreases; this is termed hyperalgesia. This hypersensitivity is not just localized to the original site of injury, it spreads to other parts of the body; this is termed secondary hyperalgesia. For example, following an ovariohysterectomy, there is not only a decrease in pain threshold at the incision site, but also at remote sites. Peripheral sensitization is a result of inflammatory mediators. When neurons in the dorsal horn are repeatedly stimulated, their rate of discharge dramatically increases with time; this is called central hypersensitisation. The barrage of signals that arrive in the spinal cord cause changes in the dorsal horn neurons, which become wound up. As a result of these changes, the response to subsequent incoming signals is dramatically changed.
The neurons are hypersensitive even after the noxious stimulus stops. This would be the case in a patient when surgery is performed under general anaesthesia using only agents with no recognized analgesic properties, for example propofol and isoflurane. The patient would not perceive pain during the procedure no matter how extensive the surgery, because they are unconscious (anesthetized), but the neural changes would be occurring in their spinal cord. On awaking, the pain is likely to be severe and prolonged. Specific receptors are involved in the process of wind up ; one is the N- methyl D-aspartate (NMDA) receptor in the spinal cord. Ketamine is a non-competitive NMDA antagonist and this has resulted in numerous studies on ketamine s ability to prevent, or treat pain.. Pre-emptive analgesia The term pre-emptive analgesia means institution of analgesic techniques before the painful stimulus occurs. It has been clearly demonstrated both in humans and in animals that pain is easier to prevent than treat, and that timing of treatment is important in preventing windup. In addition to timing, duration of treatment is important. Clinically, there are two phases associated with surgery; the first is the sensory input arising directly from the surgery itself and the second is from the resultant, more prolonged inflammatory reaction. Pre-emptive use of analgesic agents can prevent the development of sensitization, but cannot eliminate all post-operative pain. There is good evidence in veterinary medicine that pre-emptive analgesia is beneficial [1, 2]. Orthopaedic surgery is considered to be more painful and produce a longer inflammatory response than soft tissue surgery. It is essential that pain management is excellent so that animals will bear weight on their surgical limb (under controlled conditions) soon after surgery to prevent muscle atrophy or limb contracture secondary to disuse. Most orthopaedic pain can be managed with a combination of opioids, regional blocks and NSAIDs. Surgical technique In addition to carefully choosing the anaesthetic and analgesic techniques for orthopaedic patients, one should also consider the surgical technique. A study by Hoelzler and others [3] suggest that short-term postoperative morbidity may be reduced in dogs receiving arthroscopic joint surgery for stifle stabilization as compared with a traditional open arthrotomy technique. Opioids Opioids constitute the back bone of the acute peri-operative period. They have a good safety index [4] and are anaesthetic sparing. They are versatile and can be given systemically, as constant rate or target controlled infusions, intra-articularly, epidurally and transdermally. There are many opioids to choose from and the final choice will depend on personal choice and availability. Morphine, methadone, hydromorphone and buprenorphine are widely used in orthopaedic patients. Methadone may be especially useful as it also has an NMDA antagonist action which may help prevent central hypersensitisation. When dogs and cats are discharged treatment can be continued with tramadol which has opioid actions but is not a controlled substance. Non-steroidal anti-inflammatory drugs (NSAIDs) The use of NSAIDs in orthopaedic patients, especially those that have undergone fracture repair remains controversial because of the potential of these drugs to delay bone healing [5]. There are many NSAIDs available for use in dogs including carprofen, deracoxib, etodolac, firocoxib, ketoprofen, meloxicam, tepoxalin, tolfenamic acid, and vedaprofen. The list in cats is shorter but includes carprofen, ketoprofen, meloxicam and tolfenamic acid. It should be noted that each country has a different list of approved NSAIDs for dogs and cats and also some are labelled for perioperative, long-term use or both and a few are not specifically labelled as analgesic agents but as anti-fever agents (tolfenamic acid) therefore the reader should check with the authority overseeing the use of drugs in animals in their country for specific details. Carprofen or meloxicam have been used with equal success in dogs undergoing orthopaedic surgery [6] and are usually continued for several weeks after surgery.
Ketamine Because of ketamine s known interaction with the NMDA receptor it is now looked at as being more than a dissociative aesthetic agent [7]. Wagner et al [8], looked at the benefits of adding a ketamine infusion to an opioid based analgesic protocol in dogs undergoing forelimb amputation. The infusion protocol was as follows: 0.5 mg/kg bolus prior to surgery, 10 µg/kg/minute during surgery and 2 µg/kg/minute for 18 hours after surgery, a control group received saline infusion. Dogs that received ketamine had significantly lower pain scores 12 and 18 hours after surgery and were more active on the third recovery day [8]. Regional analgesia Regional analgesia is the most underutilized and under-rated technique in small animal surgery patients. There are excellent reviews of techniques for forelimb and hindlimb surgery [9, 10] and by Campoy 2008 (Fundamentals of regional anesthesia using nerve stimulation in the dog) at www.ivis.org. These techniques are well worth learning s they can provide excellent, long term pain relief with few systemic side effects. Epidural techniques Although many opioids have been administered epidurally in both dogs and cats, morphine, usually at a dose of 0.1 mg/kg with or without a local anaesthetic seems to have the greatest utility in both species [11]. The technique is well described by Jones [11]. In a clinical review epidural opioids were superior to systemically administered opioids and were anaesthetic sparing [12]. In patients undergoing tibial plateau levelling osteotomy, epidural morphine and bupivacaine was superior to systemic opioids alone [13].The duration of action may be as long as 24 hours and in a feline research model the duration of action of epidural morphine (0.1 mg/kg) was 16 hours [14]. A side-effect of epidural morphine is urinary retention and this was reported in approximately 3% of dogs and 9% of cats [12]. The combination of epidural morphine plus bupivacaine produced a significantly greater anaesthetic sparing effect and longer duration of postoperative analgesia than epidural morphine alone in a large scale clinical study of dogs undergoing various surgical procedures [12]. Multi-modal therapy As described, nociception and pain involves many steps and pathways so it seems obvious that one analgesic agent is unlikely to completely alleviate pain. An effective plan would include drugs of different classes, each of them acting at a different part of the pathway this is termed multimodal or balanced analgesia. For example an animal could be premedicated with an opioid, ketamine can be used as part of the induction protocol and a local anaesthetic block could be incorporated and an NSAID can also be added to the protocol. The combination of morphine, lidocaine and ketamine ( MLK ) is popular and may be used intraoperatively and continued into the post-operative period. These drugs are anaesthetic sparing [15] as shown by a significant reduction in the MAC (minimum alveolar concentration) of inhalant agents required to prevent movement in response to a noxious stimulus, however their effects on anaesthetic requirements are not additive and as yet there are no studies showing that the use of all three agents is superior to each individual agent. Rehabilitation medicine is a rapidly evolving specialty in veterinary medicine and techniques including therapeutic exercise, hot/cold therapy, ultrasound, laser and hydrotherapy are being used widely. Post-operative rehabilitation is beneficial in dogs after stifle surgery [16, 17]. References 1. Slingsby, L. and A. Waterman-Pearson, The post-operative analgesic effects of ketamine after canine ovariohysterectomy-- a comparison between pre- or post-operative administration. Res Vet Sci, 2000. 69(2): p. 147-52. 2. Lascelles, B., et al., Efficacy and kinetics of carprofen, administered preoperatively or postoperatively, for the prevention
of pain in dogs undergoing ovariohysterectomy. Vet Surg, 1998. 27(6): p. 568-82. 3. Hoelzler, M.G., et al., Results of arthroscopic versus open arthrotomy for surgical management of cranial cruciate ligament deficiency in dogs. Vet Surg, 2004. 33(2): p. 146-53. 4. Pascoe, P.J., Opioid analgesics. Vet Clin North Am Small Anim Pract, 2000. 30(4): p. 757-72. 5. Pountos, I., et al., Pharmacological agents and impairment of fracture healing: what is the evidence? Injury, 2008. 39(4): p. 384-94. 6. Laredo, F.G., et al., Comparison of the analgesic effects of meloxicam and carprofen administered preoperatively to dogs undergoing orthopaedic surgery. Vet Rec, 2004. 155(21): p. 667-71. 7. Kohrs, R. and M.E. Durieux, Ketamine: teaching an old drug new tricks. Anesth Analg, 1998. 87(5): p. 1186-93. 8. Wagner, A.E., et al., Use of low doses of ketamine administered by constant rate infusion as an adjunct for postoperative analgesia in dogs. J Am Vet Med Assoc, 2002. 221(1): p. 72-5. 9. Rasmussen, L.M., A.J. Lipowitz, and L.F. Graham, Development and verification of saphenous, tibial and common peroneal nerve block techniques for analgesia below the thigh in the nonchondrodystrophoid dog. Vet Anaesth Analg, 2006. 33(1): p. 36-48. 10. Mahler, S.P. and A.O. Adogwa, Anatomical and experimental studies of brachial plexus, sciatic, and femoral nervelocation using peripheral nerve stimulation in the dog. Vet Anaesth Analg, 2008. 35(1): p. 80-9. 11. Jones, R.S., Epidural analgesia in the dog and cat. Vet J, 2001. 161(2): p. 123-31. 12. Troncy, E., et al., Results of preemptive epidural administration of morphine with or without bupivacaine in dogs and cats undergoing surgery: 265 cases (1997-1999). J Am Vet Med Assoc, 2002. 221(5): p. 666-72. 13. Hoelzler, M.G., et al., Comparison of perioperative analgesic protocols for dogs undergoing tibial plateau leveling osteotomy. Vet Surg, 2005. 34(4): p. 337-44. 14. Pypendop, B.H., et al., Effects of epidural morphine or buprenorphine on the thermal threshold in cats. American Journal of Veterinary Research, 2008. En imprenta. 15. Muir, W.W., 3rd, A.J. Wiese, and P.A. March, Effects of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane. Am J Vet Res, 2003. 64(9): p. 1155-60. 16. Marsolais, G.S., G. Dvorak, and M.G. Conzemius, Effects of postoperative rehabilitation on limb function after cranial cruciate ligament repair in dogs. J Am Vet Med Assoc, 2002. 220(9): p. 1325-30. 17. Monk, M.L., C.A. Preston, and C.M. McGowan, Effects of early intensive postoperative physiotherapy on limb function after tibial plateau leveling osteotomy in dogs with deficiency of the cranial cruciate ligament. Am J Vet Res, 2006. 67(3): p. 529-36.