SPECIAL REPORT h ANESTHESIOLOGY/PAIN MANAGEMENT Alternatives to Opioids for Perianesthetic Analgesia Management Khursheed Mama, DVM, DACVAA Morgan Oakleaf, DVM Colorado State University The current opioid shortage Other options, including alprazolam administered so that tissue levels are 5 has resulted in challenges (0.01-0.02 mg/kg PO ), may be viable for reached, the more effective these medi- some animals. cations are likely to be for postopera- providing perioperative tive pain management. It is important analgesia to dogs and cats. Oral Analgesia to remember, however, that hypoten- Although direct substitution Although popular, tramadol (5-10 mg/kg sion under anesthesia may adversely PO) has not been consistently reported affect renal blood flow and compound is not appropriate for all to have good efficacy for pain manage- renal side effects.12 Grapiprant (2 mg/kg situations, many alternatives ment in dogs, as it has only weak opioid PO13) is a newer noncyclooxygenase are available. effects.6 However, it may provide a prostaglandin-receptor antagonist that sense of well-being based on its non- has been shown to have efficacy in opioid (serotonergic- and norepineph- treating osteoarthritis pain in dogs. Its To calm patients before and/or after rine-based) actions.7,8 A serotonin-like utility as a perioperative analgesic is anesthesia, gabapentin (5-10 mg/kg syndrome has not been reported in ani- not well studied, but an improved side PO1) or trazodone (3-5 mg/kg PO2) may mals but is theoretically possible when effect profile may prove advanta- be used in cats and dogs, respectively. this drug is combined with similar medi- geous.13 To the author’s knowledge, serotonin cations (eg, trazodone, fluoxetine) or syndrome has not been reported with certain opioids (most notably meperi- Injectable Analgesia trazodone use in veterinary medicine. dine).7 Many µ-opioid agonists (eg, morphine, hydromorphone, oxymorphone, meth- Oromucosal dexmedetomidine may Perioperative NSAIDs (eg, carprofen adone, fentanyl, alfentanil, remifent- also be considered for prearrival seda- [2.2-4.4 mg/kg PO or SC9], meloxicam anil, sufentanil) have been sporadically tion (125 µg/m2 oromucosal).3 Oral ace- [0.1-0.2 mg/kg PO or SC10], robenacoxib available. In addition to analgesia and promazine tends to have inconsistent [1-2 mg/kg PO or SC11]) may also be con- variable degrees of sedation, they pro- effects, but injectable acepromazine sidered in animals with no GI or renal vide anesthetic-sparing effects while (0.01-0.05 mg/kg IV, IM, or SC) is more disease and in the absence of steroid maintaining cardiovascular safety. For reliable and may be used in patients administration. The sooner in the premedication and intraoperative use that cannot receive oral medications.4 course of anesthesia they can be by infusion, these drugs are largely 48 cliniciansbrief.com July 2018 interchangeable, provided the clinician constant-rate infusion in healthy dogs Intravenous lidocaine (2%) may be a has knowledge of their relative potency, and cats; an initial maintenance dose cost-effective source of background onset and duration of action, and side of 1 µg/kg/hr IV has been suggested to analgesia and inhaled anesthetic dose effect profile.6 provide analgesia and anesthesia- reduction.22 Side effects include sei- sparing effects.17 zures but are rare if clinically appropri- Buprenorphine (20-30 µg/kg IV, IM, or ate doses are used. Nausea may also be buccal), a partial µ agonist, may be used Infusion Analgesia noticed at high doses in conscious alone or in combination with other Ketamine is an N-methyl-d-aspartate– patients. Anesthetic dose reduction medications as a substitute for other receptor antagonist that, at subanes- with 50 µg/kg/min CRI IV (low end of the µ agonists in dogs and cats for mildly- thetic doses, has been shown to antiarrhythmic dose range) has been to-moderately painful procedures.6,14 It mitigate or prevent spinal facilitation of reported in dogs19; however, the may also be used with other drugs for pain (ie, the wind-up effect). Although authors’ experience suggests that more complex and painful surgical pro- the drug is administered during anes- doses as low as 20-30 µg/kg/min IV are cedures to minimize pain. A dosing inter- thesia, the greatest benefit is thought to beneficial in clinical patients. Lidocaine val of approximately 6 to 8 hours has occur postoperatively.18 However, even is not routinely recommended for use in been suggested in the perioperative at low doses (eg, 10-20 µg/kg/min IV cats, as, despite a reduction in isoflu- period.14 Salivation, bradycardia, and after a loading dose of 0.5 mg/kg IV), rane dose, cardiovascular depression is respiratory depression may be observed ketamine can reduce anesthetic greater with a combination of lidocaine with use; drug effects are generally not requirements up to 25%.19 Higher doses and isoflurane than with an equivalent thought to be reversible. Sustained- in dogs and cats have been reported to dose of isoflurane alone.23 release or long-acting formulations of further reduce inhaled anesthesia buprenorphine for subcutaneous admin- requirements but exhibit a ceiling Combinations of an opioid, lidocaine, istration are available and are reported effect.20 Although reports of benefits and ketamine (opioid and ketamine for to provide between 24 and 72 hours of are largely anecdotal, ketamine infu- cats) may be used for their anesthesia- analgesia.15,16 sions may be continued into the post- sparing effects to provide analgesia and operative period in conscious animals. reduce spinal facilitation of pain in Butorphanol (0.1-0.5 mg/kg IV, IM, or Doses of 1-3 µg/kg/min IV have been dogs. When morphine, lidocaine, and SC), a k agonist and µ antagonist, is best suggested to minimize behavior ketamine are combined in dogs, the used as a sedative and analgesic for changes.18 In patients for which pre- isoflurane dose is reduced by approxi- presumed mildly painful procedures venting or reducing spinal facilitation is mately 45%.19 Respiratory depression is (eg, gastroduodenoscopy, colonoscopy, desirable but for which oral administra- generally less than with high doses of subcutaneous mass removal) or with tion is preferred, amantadine (3 mg/kg opioids alone. adjunct analgesic techniques (eg, as a PO q24h) may be considered.21 nerve block).6 Premedication with dexmedetomidine (3-10 µg/kg IM) can be considered in healthy dogs and cats to provide seda- tion and analgesia. Cardiovascular side Higher doses of ketamine in dogs and effects may occur and present chal- cats have been reported to further lenges with monitoring. If these effects are significant, partial reversal with ati- reduce inhaled anesthesia require- 20 pamezole can lessen them; however ments but exhibit a ceiling effect. alternative analgesia should be pro- vided prior to reversal. Dexmedetomi- dine may also be administered as a See page 19 for product information summary. July 2018 cliniciansbrief.com 49 SPECIAL REPORT h ANESTHESIOLOGY/PAIN MANAGEMENT Regional Anesthesia benefit. Targeted nerve blocks and Liposomal bupivacaine recently became Because of the shortage of drugs avail- intra-articular or epidural administra- available as another alternative for able for systemic administration, use of tion provide other options for localized long-acting pain relief following surgery regional techniques (eg, injecting lido- pain relief. Longer-acting local anes- when injected into tissues at the surgical caine [2%; up to 2 mg/kg] into the testi- thetics (eg, ropivacaine, bupivacaine) site.24 Label directions should be fol- cle prior to castration, providing a line may be used as warranted by the proce- lowed if this drug is being used with block to the abdominal wall during an dure and with consideration to duration other regionally or systemically adminis- ovariectomy/ovariohysterectomy) of motor effects and toxicity. tered local anesthetics. n when possible can be of significant References 1. van Haaften KA, Forsythe LRE, Stelow EA, Bain dogs undergoing ovariohysterectomy. and dexmedetomidine: a review of MJ. Effects of a single preappointment dose Vet Surg. 1998;27(6):568-582. cardiovascular effects and antinociceptive of gabapentin on signs of stress in cats during 10. Speranza C, Schmid V, Giraudel JM, Seeewald properties in the dog. Vet Anaesth Analg. transportation and veterinary examination. W, King JN. Robenacoxib versus meloxicam 2005;32(3): 117-127. J Am Vet Med Assoc. 2017;251(10):1175-1181. for the control of peri-operative pain and 18. Wagner AE, Walton JA, Hellyer PW, Gaynor 2. Gruen ME, Sherman BL. Use of trazadone as inflammation associated with orthopaedic JS, Mama KR. Use of low doses of ketamine an adjunctive agent in the treatment of canine surgery in cats: a randomised clinical trial. administered by constant rate infusion as an anxiety disorders: 56 cases (1995-2007). BMC Vet Res. 2015;11(1):79. adjunct for postoperative analgesia in dogs. J Am Vet Med Assoc. 2008;233(12):1902-1907. 11. Gruet P, Seewald W, King JN. Evaluation of J Am Vet Med Assoc. 2002;221(1):72-75. 3. Korpivaara M, Laapas K, Huhtinen M, Schöning subcutaneous and oral administration of 19. Muir WM III, Wiese AJ, March PA. Effects B, Overall K. Dexmedetomidine oromucosal robenacoxib and meloxicam for the treatment of morphine, lidocaine, ketamine, and gel for noise-associated acute anxiety and of acute pain and inflammation associated morphine-lidocaine-ketamine drug fear in dogs–a randomised, double-blind, with orthopedic surgery in dogs. Am J Vet Res. combination on minimum alveolar placebo-controlled clinical study. Vet Rec. 2011;72(2):184-193. concentration in dogs anesthetized with 2017;180(14):356. 12. Lascelles BD, McFarland JM, Swann H. isoflurane. Am J Vet Res. 2003;64(9):1155-1160. 4. Rankin DC. Sedatives and tranquilizers.