FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Equine veterinary journal2023; 56(5); 870-883; doi: 10.1111/evj.14027

Review of intra-articular local anaesthetic administration in horses: Clinical indications, cytotoxicity, and outcomes.

Abstract: Equine practitioners frequently inject local anaesthetics (LA) intra-articularly in both diagnosis of lameness and for pain management intra- or post-operatively with synovial endoscopy. Recent reviews of the human and veterinary literature support the concept that chondrotoxicity of LA on joint tissues depends on the type of drug, dose administered, and duration of exposure. The purpose of this review is to summarise the current literature describing intra-articular local anaesthetic use, including both in vitro and in vivo studies, and to draw some comparisons to literature from other species where potential toxicity and duration of effect have been evaluated with the goal of advancing the field's understanding of intra-articular local anaesthetic use in horses, and indicating future directions for the field. The aggregate data available from all species, while generally sparse for horses, indicate that LA are rapidly cleared from the synovial fluid after injection, often within 30 min. In vitro data strongly suggest that lidocaine and bupivacaine are likely more chondrotoxic than other LA, although to what extent is still unknown, and cytotoxicity of LA may be mitigated through concurrent injection with HA, PRP, and drug combinations including nonsteroidal anti-inflammatories and opioids. The current body of in vitro research is not reflective of the in vivo environment, and further in vitro work, if performed, should focus on mimicking the native joint environment, utilising PK data and joint/injection volumes to replicate the native environment more accurately within the joint and the expected exposures to LA.
© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Get Full Text
Publication Date: 2023-11-08 PubMed ID: 37940372DOI: 10.1111/evj.14027Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Review

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper reviews the current understanding of local anesthetic (LA) use in horses, with a particular focus on the issues of diagnosis, pain management, cytotoxicity, and outcomes.

Clinical Indications

Local anesthetics are often administered intra-articularly by equine practitioners for both diagnosing lameness and managing pain intra- or post-operatively with synovial endoscopy. In terms of clinical applications, the LA substances are seen as crucial tools.

  • They can reveal the source of lameness when used in diagnostic nerve blocks.
  • They serve as an essential part of pain management strategies for horses undergoing invasive procedures, such as synovial endoscopy.

Cytotoxicity

A significant part of the research focused on the potential cytotoxic effects of LA on joint tissues, an issue termed chondrotoxicity. It seems that several factors influence such cytotoxic effects.

  • The type of drug used is seen as an important determinant of the level of cytotoxicity.
  • The dose administered and the duration of exposure are other substantial factors.

The paper suggests that lidocaine and bupivacaine might be particularly chondrotoxic compared to other local anesthetics. However, the exact extent of this cytotoxicity is not yet fully known.

Potential Mitigation of Cytotoxicity

The research also delved into various methods to potentially mitigate the cytotoxic effects of LA. Some of these include the concurrent use of hyaluronic acid (HA), platelet-rich plasma (PRP), non-steroidal anti-inflammatories, and opioids with LA.

Comparison with Other Species

The study drew comparisons between horses and other species, especially regarding the potential toxicity, duration of effect, and effectiveness of local anesthetics. The researchers found out that these anesthetic substances are rapidly cleared from the synovial fluid after injection, typically within 30 minutes.

Future Direction

The authors identify areas of future study to help improve the understanding of LA use in horses. They call for more in vitro work that closely mimics the native joint environment to provide more accurate data. Their ultimate goal is to make the use of local anesthetic in horses safer and more effective.

Cite This Article

APA
Webster A, Pezzanite L, Hendrickson D, Griffenhagen G. (2023). Review of intra-articular local anaesthetic administration in horses: Clinical indications, cytotoxicity, and outcomes. Equine Vet J, 56(5), 870-883. https://doi.org/10.1111/evj.14027

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 56
Issue: 5
Pages: 870-883

Researcher Affiliations

Webster, Aaron
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Pezzanite, Lynn
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Hendrickson, Dean
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Griffenhagen, Gregg
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.

MeSH Terms

  • Horses
  • Animals
  • Anesthetics, Local / administration & dosage
  • Injections, Intra-Articular / veterinary
  • Horse Diseases / chemically induced
  • Horse Diseases / drug therapy

Grant Funding

  • Carolyn Quan and Porter Bennett
  • Colorado State University Department of Clinical Sciences
  • Colorado State University Veterinary Summer Scholars Program
  • Colorado State University Young Investigator Program in Companion Animal Studies

References

This article includes 114 references
  1. Schumacher J, Boone L. Local anaesthetics for regional and intra‐articular analgesia in the horse. Equine Vet Educ 2021;33(3):159–168.
    doi: 10.1111/eve.13235google scholar: lookup
  2. Schumacher J, Schramme M. Diagnostic and regional surgical anesthesia of the limbs and axial skeleton. Equine surgery St Louis, Missouri: Elsevier; 2019. p. 1220–1243.
    doi: 10.1016/b978-0-323-48420-6.00073-9google scholar: lookup
  3. Bromberg AL, Dennis JA, Gritsenko K. Exparel/peripheral catheter use in the ambulatory setting and use of peripheral catheters postoperatively in the home setting. Curr Pain Headache Rep 2017;21(3):13.
    doi: 10.1007/s11916-017-0605-0google scholar: lookup
  4. McIlwraith CW, Nixon AJ, Wright IM. Introduction. Diagnostic and surgical arthroscopy in the horse. Equine surgery St Louis, Missouri: Elsevier; 2015. p. 1–4.
    doi: 10.1016/b978-0-7234-3693-5.00001-1google scholar: lookup
  5. Goodwin RC, Amjadi F, Parker RD. Short‐term analgesic effects of intra‐articular injections after knee arthroscopy. Arthrosc J Arthrosc Relat Surg 2005;21(3):307–312.
    doi: 10.1016/j.arthro.2004.11.015google scholar: lookup
  6. Hube R, Tröger M, Rickerl F, Muench EO, von Eisenhart‐Rothe R, Hein W. Pre‐emptive intra‐articular administration of local anaesthetics/opiates versus postoperative local anaesthetics/opiates or local anaesthetics in arthroscopic surgery of the knee joint: a prospective randomized trial. Arch Orthop Trauma Surg 2009;129(3):343–348.
    doi: 10.1007/s00402-008-0614-xgoogle scholar: lookup
  7. Tuncer B, Babacan CA, Arslan M. The pre‐emptive analgesic effect of intra‐articular bupivacaine in arthroscopic knee surgery. Acta Anaesthesiol Scand 2005;49(9):1373–1377.
    doi: 10.1111/j.1399-6576.2005.00784.xgoogle scholar: lookup
  8. Rosseland L. No evidence for analgesic effect of intra‐articular morphine after knee arthroscopy: a qualitative systematic review. Reg Anesth Pain Med 2005;30(1):83–98.
    doi: 10.1016/j.rapm.2004.08.022google scholar: lookup
  9. Gaesser AM, Varner KM, Douglas HF, Barr CA, Hopster K, Levine DG. The effect of intra‐articular mepivacaine administration prior to carpal arthroscopy on anesthesia management and recovery characteristics in horses. Vet Surg 2020;49(7):1343–1349.
    doi: 10.1111/vsu.13501google scholar: lookup
  10. Bergese SD, Onel E, Portillo J. Evaluation of DepoFoam bupivacaine for the treatment of postsurgical pain. Pain Manag 2011;1(6):539–547.
    doi: 10.2217/pmt.11.62google scholar: lookup
  11. Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double‐blind, dose‐ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended‐release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee 2012;19(5):530–536.
    doi: 10.1016/j.knee.2011.12.004google scholar: lookup
  12. Joshi GP, Hawkins RJ, Frankle MA, Abrams JS. Best practices for periarticular infiltration with liposomal bupivacaine for the management of pain after shoulder surgery: consensus recommendation. J Surg Orthop Adv 2016;25(4):204–208.
  13. Malik O, Kaye AD, Kaye A, Belani K, Urman RD. Emerging roles of liposomal bupivacaine in anesthesia practice. J Anaesthesiol Clin Pharmacol 2017;33(2):151–156.
    doi: 10.4103/joacp.joacp_375_15google scholar: lookup
  14. Tong YCI, Kaye AD, Urman RD. Liposomal bupivacaine and clinical outcomes. Best Pract Res Clin Anaesthesiol 2014;28(1):15–27.
    doi: 10.1016/j.bpa.2014.02.001google scholar: lookup
  15. Vyas KS, Rajendran S, Morrison SD, Shakir A, Mardini S, Lemaine V. Systematic review of liposomal bupivacaine (exparel) for postoperative analgesia. Plast Reconstr Surg 2016;138(4):748e–756e.
    doi: 10.1097/prs.0000000000002547google scholar: lookup
  16. Knych HK, Mama KR, Moore CE, Hill AE, McKemie DS. Plasma and synovial fluid concentrations and cartilage toxicity of bupivacaine following intra‐articular administration of a liposomal formulation to horses. Equine Vet J 2019;51(3):408–414.
    doi: 10.1111/evj.13015google scholar: lookup
  17. Le KM, Caston SS, Hossetter JM, Hay Kraus BL. Comparison of analgesic and tissue effects of subcutaneous perineural injection of liposomal bupivacaine and bupivacaine hydrochloride in horses with forelimb lameness induced via circumferential clamp. Am J Vet Res 2020;81(7):551–556.
    doi: 10.2460/ajvr.81.7.551google scholar: lookup
  18. McCracken MJ, Schumacher J, Doherty TJ, Sun X, Nichols CL, Olivarez J. Efficacy and duration of effect for liposomal bupivacaine when administered perineurally to the palmar digital nerves of horses. Am J Vet Res 2020;81(5):400–405.
    doi: 10.2460/ajvr.81.5.400google scholar: lookup
  19. Moorman VJ, Pezzanite LM, Griffenhagen GM. Liposomal bupivacaine provides longer duration analgesia than bupivacaine hydrochloride in an adjustable sole‐pressure model of equine lameness. Am J Vet Res 2022;83(4):298–304.
    doi: 10.2460/ajvr.21.08.0132google scholar: lookup
  20. Pezzanite LM, Griffenhagen GM, Bass L, Okudaira M, Larson B, Hendrickson DA. Liposomal bupivacaine is both safe and effective when administered via local infiltration at surgical site and mesovarium for laparoscopic ovariectomy in mares. Equine Vet J 2023;55(5):755–764.
    doi: 10.1111/evj.13915google scholar: lookup
  21. Pérez‐Isidoro R, Sierra‐Valdez FJ, Ruiz‐Suárez JC. Anesthetic diffusion through lipid membranes depends on the protonation rate. Sci Rep 2014;4(1):7534.
    doi: 10.1038/srep07534google scholar: lookup
  22. Chernoff DM, Strichartz GR. Kinetics of local anesthetic inhibition of neuronal sodium currents. pH and hydrophobicity dependence. Biophys J 1990;58(1):69–81.
    doi: 10.1016/s0006-3495(90)82354-7google scholar: lookup
  23. Ueno T, Mizogami M, Takakura K, Tsuchiya H. Peroxynitrite affects lidocaine by acting on membrane‐constituting lipids. J Anesth 2008;22(4):475–478.
    doi: 10.1007/s00540-008-0664-9google scholar: lookup
  24. Taylor A, McLeod G. Basic pharmacology of local anaesthetics. BJA Educ 2020;20(2):34–41.
    doi: 10.1016/j.bjae.2019.10.002google scholar: lookup
  25. Salinas F, Malik K, Benzon H. Local anesthetics for regional anesthesia and pain management. In: Benzon H, Rathmell J, Wu CL, editors. Raj's practical management of pain. Philadelphia, PA: Mosby Elsevier; 2008. p. 811–838.
  26. Andreen D, Trumble T, Caron J, Decamp C, Hauptman J, Stick J. Onset and duration of intra‐articular mepivacaine in the horse. Proc Am Assoc Equine Pract 1994;40:151.
  27. Bassage I, Ross M. Diagnostic analgesia. In: Ross M, Dyson SJ, editors. Diagnosis and management of lameness in the horse. 2nd ed. St Louis, MO: Saunders Elsevier; 2011. p. 100–135.
  28. Bidwell LA, Brown KE, Cordier A, Mullineaux DR, Clayton HM. Mepivacaine local anaesthetic duration in equine palmar digital nerve blocks. Equine Vet J 2010;36(8):723–726.
    doi: 10.2746/0425164044848154google scholar: lookup
  29. Lamont LA. Local anesthetics. In: Doherty TJ, Valverde A, editors. Manual of equine anesthesia and analgesia. Ames, IA: Blackwell Publishing; 2006. p. 154–165.
  30. Silva GB, De La Côrte FD, Brass KE, Azevedo MS, Dou S, Ceni F. Duration and efficacy of different local anesthetics on the palmar digital nerve block in horses. J Equine Vet 2015;35(9):749–755.
    doi: 10.1016/j.jevs.2015.07.013google scholar: lookup
  31. Wyn‐Jones G. Equine lameness. Chicago, IL: Blackwell Scientific; 1988.
  32. Gulihar A, Robati S, Twaij H, Salih A, Taylor GJS. Articular cartilage and local anaesthetic: a systematic review of the current literature. J Orthop 2015;12:S200–S210.
    doi: 10.1016/j.jor.2015.10.005google scholar: lookup
  33. Jayaram P, Kennedy DJ, Yeh P, Dragoo J. Chondrotoxic effects of local anesthetics on human knee articular cartilage: a systematic review. PM R 2019;11(4):379–400.
    doi: 10.1002/pmrj.12007google scholar: lookup
  34. Piper SL, Kramer JD, Kim HT, Feeley BT. Effects of local anesthetics on articular cartilage. Am J Sports Med 2011;39(10):2245–2253.
    doi: 10.1177/0363546511402780google scholar: lookup
  35. Kreuz PC, Steinwachs M, Angele P. Single‐dose local anesthetics exhibit a type‐, dose‐, and time‐dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature. Knee Surg Sports Traumatol Arthrosc 2017;26(3):819–830.
    doi: 10.1007/s00167-017-4470-5google scholar: lookup
  36. Kohli S, Tandra V, Gulihar A. Effect of various factors on articular cartilage and their implications on arthroscopic procedures: a review of literature. J Clin Orthop Trauma 2020;11:S396–S401.
    doi: 10.1016/j.jcot.2019.06.017google scholar: lookup
  37. Barry SL, Martinez SA, Davies NM, Remsberg CM, Sayre CL, Bachelez A. Synovial fluid bupivacaine concentrations following single intra‐articular injection in normal and osteoarthritic canine stifles. J Vet Pharmacol Ther 2015;38(1):97–100.
    doi: 10.1111/jvp.12158google scholar: lookup
  38. Bubenik L, Hosgood G, Barker S, Hicks M, Serra V, Stout R. Estimated plasma bupivacaine concentration after single dose and eight‐hour continuous intra‐articular infusion of bupivacaine in normal dogs. Vet Surg 2007;36(8):783–791.
    doi: 10.1111/j.1532-950x.2007.00337.xgoogle scholar: lookup
  39. Debruyne D, Moulin MA, Carmes C, Beguin JA, Locker B. Monitoring serum bupivacaine levels during arthroscopy. Eur J Clin Pharmacol 1985;27(6):733–735.
    doi: 10.1007/bf00547058google scholar: lookup
  40. Kaeding CC, Hill JA, Katz J, Benson L. Bupivacaine use after knee arthroscopy: pharmacokinetics and pain control study. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc 1990;6(1):33–39.
    doi: 10.1016/0749-8063(90)90094-tgoogle scholar: lookup
  41. Sammarco JL, Conzemius MG, Perkowski SZ, Weinstein MJ, Gregor TP, Smith GK. Postoperative analgesia for stifle surgery: a comparison of intra‐articular bupivacaine, morphine, or saline. Vet Surg 1996;25(1):59–69.
    doi: 10.1111/j.1532-950x.1996.tb01377.xgoogle scholar: lookup
  42. Hoelzler MG, Harvey RC, Lidbetter DA, Millis DL. Comparison of perioperative analgesic protocols for dogs undergoing tibial plateau leveling osteotomy. Vet Surg 2005;34(4):337–344.
    doi: 10.1111/j.1532-950x.2005.00052.xgoogle scholar: lookup
  43. Møiniche S, Mikkelsen S, Wetterslev J, Dahl JB. A systematic review of intra‐articular local anesthesia for postoperative pain relief after arthroscopic knee surgery. Reg Anesth Pain Med 1999;24(5):430–437.
    doi: 10.1016/s1098-7339(99)90010-xgoogle scholar: lookup
  44. Park J, Sutradhar BC, Hong G, Choi SH, Kim G. Comparison of the cytotoxic effects of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes. Vet Anaesth Analg 2011;38(2):127–133.
    doi: 10.1111/j.1467-2995.2010.00590.xgoogle scholar: lookup
  45. Adler DMT, Frellesen JF, Karlsen CV, Jensen LD, Dahm ASQ, Berg LC. Evaluation of the in vitro effects of local anesthetics on equine chrondrocytes and fibroblast‐like synoviocytes. Am J Vet Res 2021;82(6):478–486.
  46. Rubio‐Martínez LM, Rioja E, Castro Martins M, Wipawee S, Clegg P, Peffers MJ. Local anaesthetics or their combination with morphine and/or magnesium sulphate are toxic for equine chondrocytes and synoviocytes in vitro. BMC Vet Res 2017;13(1):318.
    doi: 10.1186/s12917-017-1244-8google scholar: lookup
  47. Hussein K, Abdelbaset AE, Sadek AA, Noreldin A. In vitro and in vivo effects of a single dose of bupivacaine 5% on donkey chondrocytes. Front Vet Sci 2021;8:661426.
    doi: 10.3389/fvets.2021.661426google scholar: lookup
  48. Breu A, Rosenmeier K, Kujat R, Angele P, Zink W. The cytotoxicity of bupivacaine, ropivacaine, and mepivacaine on human chondrocytes and cartilage. Anesth Analg 2013;117(2):514–522.
    doi: 10.1213/ane.0b013e31829481edgoogle scholar: lookup
  49. Chu CR, Izzo NJ, Papas NE, Fu FH. In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthrosc J Arthrosc Relat Surg 2006;22(7):693–699.
    doi: 10.1016/j.arthro.2006.05.006google scholar: lookup
  50. Chu CR, Izzo NJ, Coyle CH, Papas NE, Logar A. The in vitro effects of bupivacaine on articular chondrocytes. J Bone Joint Surg Br 2008;90B(6):814–820.
    doi: 10.1302/0301-620x.90b6.20079google scholar: lookup
  51. Nole R, Munson NML, Fulkerson JP. Bupivacaine and saline effects on articular cartilage. Arthrosc J Arthrosc Relat Surg 1985;1(2):123–127.
    doi: 10.1016/s0749-8063(85)80042-6google scholar: lookup
  52. Hennig GS, Hosgood G, Bubenik‐Angapen LJ, Lauer SK, Morgan TW. Evaluation of chondrocyte death in canine osteochondral explants exposed to a 0.5% solution of bupivacaine. Am J Vet Res 2010;71(8):875–883.
    doi: 10.2460/ajvr.71.8.875google scholar: lookup
  53. Anz A, Smith MJ, Stoker A, Linville C, Markway H, Branson K. The effect of bupivacaine and morphine in a coculture model of diarthrodial joints. Arthrosc J Arthrosc Relat Surg 2009;25(3):225–231.
    doi: 10.1016/j.arthro.2008.12.003google scholar: lookup
  54. Lo IKY, Sciore P, Chung M, Liang S, Boorman RB, Thornton GM. Local anesthetics induce chondrocyte death in bovine articular cartilage disks in a dose‐ and duration‐dependent manner. YJARS 2009;25(7):707–715.
    doi: 10.1016/j.arthro.2009.03.019google scholar: lookup
  55. Karpie JC, Chu CR. Lidocaine exhibits dose‐ and time‐dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med 2007;35(10):1622–1627.
    doi: 10.1177/0363546507304719google scholar: lookup
  56. Bianchini E, Mancini F, Di Meo A, Stabile A, Buratta S, Moscati L. Protective effects of platelet‐rich plasma against lidocaine cytotoxicity on canine articular chondrocytes. Acta Vet Scand 2018;60(1):63.
    doi: 10.1186/s13028-018-0418-0google scholar: lookup
  57. Moser LB, Bauer C, Jeyakumar V, Niculescu‐Morzsa EP, Nehrer S. Hyaluronic acid as a carrier supports the effects of glucocorticoids and diminishes the cytotoxic effects of local anesthetics in human articular chondrocytes in vitro. Int J Mol Sci 2021;22(21):11503.
    doi: 10.3390/ijms222111503google scholar: lookup
  58. Shaw KA, Johnson PC, Zumbrun S, Chuang AH, Cameron CD. Chondrotoxicity of liposomal bupivacaine in articular chondrocytes: preliminary findings. Mil Med 2017;182(S1):185–188.
    doi: 10.7205/milmed-d-16-00079google scholar: lookup
  59. Rengert R, Snider D, Gilbert PJ. Effect of bupivacaine concentration and formulation on canine chondrocyte viability in vitro. Vet Surg 2021;50(3):633–640.
    doi: 10.1111/vsu.13590google scholar: lookup
  60. Dragoo JL, Korotkova T, Kim HJ, Jagadish A. Chondrotoxicity of low pH, epinephrine, and preservatives found in local anesthetics containing epinephrine. Am J Sports Med 2010;38(6):1154–1159.
    doi: 10.1177/0363546509359680google scholar: lookup
  61. Piat P, Richard H, Beauchamp G, Laverty S. In vivo effects of a single intra‐articular injection of 2% lidocaine or 0.5% bupivacaine on articular cartilage of normal horses: effects of local anesthetics on articular cartilage. Vet Surg 2012;41(8):1002–1010.
    doi: 10.1111/j.1532-950x.2012.01039.xgoogle scholar: lookup
  62. Adler DMT, Serteyn D, Franck T, Jørgensen E, Christophersen MT, Denwood M. Effects of intra‐articular administration of lidocaine, mepivacaine, and the preservative methyl parahydroxybenzoate on synovial fluid biomarkers of horses. Am J Vet Res 2020;81(6):479–487.
    doi: 10.2460/ajvr.81.6.479google scholar: lookup
  63. Fulkerson JP, Winters TF. Articular cartilage response to arthroscopic surgery: a review of current knowledge. Arthrosc J Arthrosc Relat Surg 1986;2(3):184–189.
    doi: 10.1016/s0749-8063(86)80065-2google scholar: lookup
  64. Gomoll AH, Kang RW, Williams JM, Bach BR, Cole BJ. Chondrolysis after continuous intra‐articular bupivacaine infusion: an experimental model investigating chondrotoxicity in the rabbit shoulder. Arthrosc J Arthrosc Relat Surg 2006;22(8):813–819.
    doi: 10.1016/j.arthro.2006.06.006google scholar: lookup
  65. Gomoll AH, Yanke AB, Kang RW, Chubinskaya S, Willliams JM, Bach BR. Long‐term effects of bupivacaine on cartilage in a rabbit shoulder model. Am J Sports Med 2009;37(1):72–77.
    doi: 10.1177/0363546508323748google scholar: lookup
  66. Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC. In vivo effects of single intra‐articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg‐Am 2010;92(3):599–608.
    doi: 10.2106/jbjs.i.00425google scholar: lookup
  67. Yazdi H, Nimavard BT, Shokrgozar M, Dehghan M, Moayedi RJ, Majidi M. An evaluation of the delayed effect of intra‐articular injections of lidocaine (2%) on articular cartilage: an experimental study in rabbits. Eur J Orthop Surg Traumatol 2014;24(8):1557–1561.
    doi: 10.1007/s00590-014-1437-9google scholar: lookup
  68. Sherman SL, James C, Stoker AM, Cook CR, Khazai RS, Flood DL. In vivo toxicity of local anesthetics and corticosteroids on chondrocyte and synoviocyte viability and metabolism. Cartilage 2015;6(2):106–112.
    doi: 10.1177/1947603515571001google scholar: lookup
  69. Shaw KA, Moreland C, Jacobs J, Hire JM, Topolski R, Hoyt N. Improved chondrotoxic profile of liposomal bupivacaine compared with standard bupivacaine after intra‐articular infiltration in a porcine model. Am J Sports Med 2018;46(1):66–71.
    doi: 10.1177/0363546517732558google scholar: lookup
  70. Pek YS, Pitukmanorom P, Ying JY. Sustained release of bupivacaine for post‐surgical pain relief using core–shell microspheres. J Mater Chem B 2014;2(46):8194–8200.
    doi: 10.1039/c4tb00948ggoogle scholar: lookup
  71. Sun QB, Liu SD, Meng QJ, Qu HZ, Zhang Z. Single administration of intra‐articular bupivacaine in arthroscopic knee surgery: a systematic review and meta‐analysis. BMC Musculoskelet Disord 2015;16:21.
    doi: 10.1186/s12891-015-0477-6google scholar: lookup
  72. Boden BP, Fassler S, Cooper S, Marchetto PA, Moyer RA. Analgesic effect of intraarticular morphine, bupivacaine, and morphine/bupivacaine after arthroscopic knee surgery. Arthrosc J Arthrosc Relat Surg 1994;10(1):104–107.
    doi: 10.1016/s0749-8063(05)80301-9google scholar: lookup
  73. Heard SO, Edwards WT, Ferrari D, Hanna D, Wong PD, Liland A. Analgesic effect of Intraarticular bupivacaine or morphine after arthroscopic knee surgery: a randomized, prospective, double‐blind study. Anesth Analg 1992;74:822–826.
  74. Marret E, Gentili M, Bonnet MP, Bonnet F. Intra‐articular ropivacaine 0.75% and bupivacaine 0.50% for analgesia after arthroscopic knee surgery: a randomized prospective study. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc 2005;21(3):313–316.
    doi: 10.1016/j.arthro.2004.11.005google scholar: lookup
  75. Mitra S, Kaushal H, Gupta RK. Evaluation of analgesic efficacy of intra‐articular bupivacaine, bupivacaine plus fentanyl, and bupivacaine plus tramadol after arthroscopic knee surgery. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc 2011;27(12):1637–1643.
    doi: 10.1016/j.arthro.2011.08.295google scholar: lookup
  76. Zeidan A, Kassem R, Nahleh N, Maaliki H, El‐Khatib M, Struys MMRF. Intraarticular tramadol‐bupivacaine combination prolongs the duration of postoperative analgesia after outpatient arthroscopic knee surgery. Anesth Analg 2008;107(1):292–299.
    doi: 10.1213/ane.0b013e31816ba364google scholar: lookup
  77. Zuniga JR, Ibanez C, Kozacko M. The analgesic efficacy and safety of intra‐articular morphine and mepivicaine following temporomandibular joint arthroplasty. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 2007;65(8):1477–1485.
    doi: 10.1016/j.joms.2007.04.001google scholar: lookup
  78. Neal J. Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: neurotoxicity and neural blood flow. Reg Anesth Pain Med 2003;28(2):124–134.
    doi: 10.1053/rapm.2003.50024google scholar: lookup
  79. Sinnott CJ, Cogswell LP, Johnson A, Strichartz GR. On the mechanism by which epinephrine potentiates lidocaine's peripheral nerve block. Anesthesiology 2003;98(1):181–188.
    doi: 10.1097/00000542-200301000-00028google scholar: lookup
  80. Saied NN, Gupta RK, Saffour L, Helwani MA. Dexamethasone and clonidine, but not epinephrine, prolong duration of ropivacaine brachial plexus blocks, cross‐sectional analysis in outpatient surgery setting. Pain Med 2017;18(10):2013–2026.
    doi: 10.1093/pm/pnw198google scholar: lookup
  81. Yang JH, Lee JJ, Hwang SM, Lim SY. The effect of fentanyl or epinephrine addition to ropivacaine in brachial plexus block. Korean J Anesthesiol 2004;47(5):655.
    doi: 10.4097/kjae.2004.47.5.655google scholar: lookup
  82. Schoenmakers KPW, Fenten MGE, Louwerens JW, Scheffer GJ, Stienstra R. The effects of adding epinephrine to ropivacaine for popliteal nerve block on the duration of postoperative analgesia: a randomized controlled trial. BMC Anesthesiol 2015;15(1):100.
    doi: 10.1186/s12871-015-0083-zgoogle scholar: lookup
  83. Krunic AL, Wang LC, Soltani K, Weitzul S, Taylor RS. Digital anesthesia with epinephrine: an old myth revisited. J Am Acad Dermatol 2004;51(5):755–759.
    doi: 10.1016/j.jaad.2004.05.028google scholar: lookup
  84. Lindegaard C, Thomsen MH, Larsen S, Andersen PH. Analgesic efficacy of intra‐articular morphine in experimentally induced radiocarpal synovitis in horses. Vet Anaesth Analg 2010;37(2):171–185.
    doi: 10.1111/j.1467-2995.2009.00521.xgoogle scholar: lookup
  85. Van Loon JPAM, De Grauw JC, Van Dierendonck M, L'Ami JJ, Back W, Van Weeren PR. Intra‐articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model: analgesic and anti‐inflammatory effects of intra‐articular opioids in equine synovitis. Equine Vet J 2010;42(5):412–419.
    doi: 10.1111/j.2042-3306.2010.00077.xgoogle scholar: lookup
  86. Santos LC, de Moraes AN, Saito ME. Effects of intraarticular ropivacaine and morphine on lipopolysaccharide‐induced synovitis in horses. Vet Anaesth Analg 2009;36(3):280–286.
    doi: 10.1111/j.1467-2995.2009.00452.xgoogle scholar: lookup
  87. Rasmussen S, Kramhøft M, Sperling K, Pedersen J. Increased flexion and reduced hospital stay with continuous intraarticular morphine and ropivacaine after primary total knee replacement: open intervention study of efficacy and safety in 154 patients. Acta Orthop Scand 2004;75(5):606–609.
    doi: 10.1080/00016470410001501google scholar: lookup
  88. Abrams GD, Chang W, Dragoo JL. In vitro chondrotoxicity of nonsteroidal anti‐inflammatory drugs and opioid medications. Am J Sports Med 2017;45(14):3345–3350.
    doi: 10.1177/0363546517724423google scholar: lookup
  89. Stueber T, Karsten J, Stoetzer C, Leffler A. Differential cytotoxic properties of drugs used for intra‐articular injection on human chondrocytes: an experimental in‐vitro study. Eur J Anaesthesiol 2014;31(11):640–645.
  90. Castro‐Cuellar G, Cremer J, Liu CC, Queiroz‐Williams P, Hampton C, Leise BS. Buprenorphine has a concentration‐dependent cytotoxic effect on equine chondrocytes in vitro. Am J Vet Res 2023;84(3):1–8.
    doi: 10.2460/ajvr.22.08.0143google scholar: lookup
  91. Bohlin AM, Kristoffersen M, Toft N. Infectious arthritis following intra‐articular injection in horses not receiving prophylactic antibiotics: a retrospective cohort study of 2833 medical records. Proc Am Assoc Equine Pract 2014;60:255–256.
  92. Zubrod CJ, Hague BA, Samuelson S, Blevins W, Major MD. Is intra‐articular mepivacaine, before intra‐articular administration of hyaluronan and/or cortisone, associated with joint sepsis?. Proc Am Assoc Equine Pract 2006;52:441–442.
  93. Baumann JR, Stoker AM, Bozynski CC, Sherman SL, Cook JL. An injectable containing morphine, ropivacaine, epinephrine, and ketorolac is not cytotoxic to articular cartilage explants from degenerative knees. Arthroscopy 2021;38(6):1980–1995.
    doi: 10.1016/j.arthro.2021.12.019google scholar: lookup
  94. Gough MR, Mayhew IG, Munroe GA. Diffusion of mepivacaine between adjacent synovial structures in the horse. Part 1: forelimb foot and carpus. Equine Vet J 2010;34(1):80–84.
    doi: 10.2746/042516402776181097google scholar: lookup
  95. Gough MR, Munroe GA, Mayhew IG. Diffusion of mepivacaine between adjacent synovial structures in the horse. Part 2: tarsus and stifle. Equine Vet J 2010;34(1):85–90.
    doi: 10.2746/042516402776181088google scholar: lookup
  96. Keegan KG, Dent EV, Wilson DA, Janicek J, Kramer J, Lacarrubba A. Repeatability of subjective evaluation of lameness in horses: repeatability of subjective evaluation of lameness in horses. Equine Vet J 2010;42(2):92–97.
    doi: 10.2746/042516409x479568google scholar: lookup
  97. Baxter GM. Manual of equine lameness. 2nd ed. Newark, NJ: Wiley‐Blackwell; 2022.
  98. Radtke A, Fortier LA, Regan S, Kraus S, Delco ML. Intra‐articular anaesthesia of the equine stifle improves foot lameness. Equine Vet J 2020;52(2):314–319.
    doi: 10.1111/evj.13135google scholar: lookup
  99. Pezzanite L, Contino E, Kawcak C. Lameness originating from the proximal metacarpus/tarsus: a review of local analgesic techniques and clinical diagnostic findings. Equine Vet Educ 2020;32(4):204–217.
    doi: 10.1111/eve.12904google scholar: lookup
  100. Dyson SJ, Romero JM. An investigation of injection techniques for local analgesia of the equine distal tarsus and proximal metatarsus. Equine Vet J 1993;25(1):30–35.
    doi: 10.1111/j.2042-3306.1993.tb02897.xgoogle scholar: lookup
  101. Jordana M, Martens A, Duchateau L, Vanderperren K, Saunders J, Oosterlinck M. Distal limb desensitisation following analgesia of the digital flexor tendon sheath in horses using four different techniques: distal limb desensitisation after analgesia of digital flexor tendon sheath. Equine Vet J 2014;46(4):488–493.
    doi: 10.1111/evj.12186google scholar: lookup
  102. Gillespie CC, Adams SB, Moore GE. Methods and variables associated with the risk of septic arthritis following intra‐articular injections in horses: a survey of veterinarians: risk factors for septic arthritis following intra‐articular injections in horses. Vet Surg 2016;45(8):1071–1076.
    doi: 10.1111/vsu.12563google scholar: lookup
  103. Steel C, Pannirselvam R, Anderson G. Risk of septic arthritis after intra‐articular medication: a study of 16,624 injections in thoroughbred racehorses. Aust Vet J 2013;91(7):268–273.
    doi: 10.1111/avj.12073google scholar: lookup
  104. Callahan ZM, Roberts AL, Christopher AN, Gadomski SP, Kuchta KM, Costanzo CM. The effect of commonly used local anesthetic on bacterial growth. J Surg Res 2022;274:16–22.
    doi: 10.1016/j.jss.2021.12.040google scholar: lookup
  105. Johnson SM, Saint John BE, Dine AP. Local anesthetics as antimicrobial agents: a review. Surg Infect (Larchmt) 2008;9(2):205–213.
    doi: 10.1089/sur.2007.036google scholar: lookup
  106. Kesici U, Demirci M, Kesici S. Antimicrobial effects of local anaesthetics. Int Wound J 2019;16(4):1029–1033.
    doi: 10.1111/iwj.13153google scholar: lookup
  107. Razavi BM, Fazly Bazzaz BS. A review and new insights to antimicrobial action of local anesthetics. Eur J Clin Microbiol Infect Dis 2019;38(6):991–1002.
    doi: 10.1007/s10096-018-03460-4google scholar: lookup
  108. Seshadri V, Coyle CH, Chu CR. Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthrosc J Arthrosc Relat Surg 2009;25(4):337–347.
    doi: 10.1016/j.arthro.2009.01.003google scholar: lookup
  109. Adams SB. How to avoid complications of intra‐synovial injections II: selection of drugs, injection of drugs, and recognition of treatment of sepsis. Proc Am Assoc Equine Pract 2012;58:476–482.
  110. Fürst AE. Diagnostic anesthesia. Equine surgery St Louis, MO: Elsevier; 2012. p. 998–1015.
    doi: 10.1016/b978-1-4377-0867-7.00072-7google scholar: lookup
  111. Adler DMT, Cornett C, Damborg P, Verwilghen DR. The stability and microbial contamination of bupivacaine, lidocaine and mepivacaine used for lameness diagnostics in horses. Vet J 2016;218:7–12.
    doi: 10.1016/j.tvjl.2016.10.008google scholar: lookup
  112. Colbath AC, Wittenburg LA, Gold JR, McIlwraith CW, Moorman VJ. The effects of mepivacaine hydrochloride on antimicrobial activity and mechanical nociceptive threshold during amikacin sulfate regional limb perfusion in the horse. Vet Surg 2016;45(6):798–803.
    doi: 10.1111/vsu.12515google scholar: lookup
  113. Mendez‐Angulo JL, Granados MM, Modesto R, Serrano‐Rodriguez JM, Funes FJ, Quiros S. Systemic and local effects of lidocaine or mepivacaine when used for intravenous regional anaesthesia of the distal limb in standing sedated horses. Equine Vet J 2020;52(5):743–751.
    doi: 10.1111/evj.13236google scholar: lookup
  114. Banh L, Cheung KK, Chan MWY, Young EWK, Viswanathan S. Advances in organ‐on‐a‐chip systems for modelling joint tissue and osteoarthritic diseases. Osteoarthr Cartil 2022;30(8):1050–1061.
    doi: 10.1016/j.joca.2022.03.012google scholar: lookup

Citations

This article has been cited 2 times.
  1. Nishikawa A, Tsunoda K, Hatano K, Tabuchi Y, Hirano T, Izumi R, Oshima S, Furusawa Y, Sakatoku A, Srivastav AK, Honda M, Matsubara H, Ogiso S, Takasu M, Hong CS, Hirayama J, Hattori A, Suzuki N. Acute toxicity of local anesthetics used for humans and other animals in the larvae of marine crustacean, red-clawed crab Chiromantes haematocheir. J Vet Med Sci 2025 Nov 1;87(11):1285-1294.
    doi: 10.1292/jvms.25-0273pubmed: 40930800google scholar: lookup
  2. Wójcik-Pastuszka D, Iwaszkiewicz R, Musiał W. The Effects of Synthetic Polymers on the Release Patterns of Bupivacaine Hydrochloride from Sodium Hyaluronate Hydrogels. Biomedicines 2024 Dec 27;13(1).
    doi: 10.3390/biomedicines13010039pubmed: 39857623google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.