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Veterinary surgery : VS2025; 55(1); 218-224; doi: 10.1111/vsu.70055

Liposomal bupivacaine caudal epidural in horses results in adverse effects without analgesia.

Abstract: To evaluate the analgesic properties and adverse effects of liposomal bupivacaine administered via caudal epidural in horses. Methods: Pharmacodynamic study. Methods: A total of 10 healthy adult horses. Methods: Liposomal bupivacaine (10 mL; 1.3%) was administered into the caudal epidural space via an indwelling epidural catheter inserted to a length of 15 cm. Mechanical nociceptive threshold (MNT) testing with pressure algometry was used to measure analgesia at four anatomic locations for 72 h following injection. Physical examinations (including rectal temperature, heart rate, respiratory rate, and ataxia scores) were performed every 4 h to monitor for adverse effects, and fecal and urine output were recorded. Results: There were no significant differences detected at any time point in rectal temperature, heart rate, respiratory rate, or MNT at any anatomic site compared to baseline. Ataxia scores were significantly elevated from 24 to 36 h following epidural injection. Adverse events included recumbency in two horses, urinary retention necessitating urinary catheter placement in three horses and decreased fecal output requiring manual manure removal from the rectum in six horses. Conclusions: Liposomal bupivacaine administered as a caudal epidural in horses resulted in ataxia and clinically relevant adverse effects but no detectable analgesia. Conclusions: Based on these findings, caudal epidural administration of liposomal bupivacaine in horses at the dose evaluated in this study is not recommended.
Publication Date: 2025-11-20 PubMed ID: 41261991DOI: 10.1111/vsu.70055Google Scholar: Lookup
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  • Journal Article

Summary

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Overview

  • This study investigated whether liposomal bupivacaine, when given as a caudal epidural injection in horses, provides pain relief (analgesia) and assessed its safety profile.
  • The findings showed no pain relief effects but significant adverse reactions, leading researchers to advise against this method in horses at the tested dose.

Introduction and Purpose

  • The research aimed to evaluate both the effectiveness (analgesic properties) and safety (adverse effects) of liposomal bupivacaine administered into the caudal epidural space of horses.
  • Liposomal bupivacaine is a long-acting local anesthetic, hypothesized to provide extended pain relief when given epidurally, but its effects via this route in horses had not been well studied.

Methods

  • Subjects: Ten healthy adult horses were enrolled in this pharmacodynamic study.
  • Administration: Liposomal bupivacaine was injected into the caudal epidural space by placing an indwelling catheter 15 cm into the epidural space, delivering a 10 mL dose at a 1.3% concentration.
  • Measurement of Analgesia: Mechanical nociceptive threshold (MNT) was assessed using pressure algometry—applying pressure to specific locations on the horses’ bodies to objectively measure pain sensitivity.
  • MNT was measured at four different anatomical points over a 72-hour period following the injection to assess potential pain relief.
  • Monitoring for Side Effects: Horses underwent physical exams every 4 hours, recording vital signs such as rectal temperature, heart rate, respiratory rate, and ataxia (loss of coordination) scores.
  • Additional monitoring noted fecal output and urine output to detect gastrointestinal or urinary side effects.

Results

  • Analgesia: There were no significant changes in pain threshold (no increased MNT) at any measured site or time point compared to each horse’s baseline, indicating a lack of detectable pain relief.
  • Vital Signs: Rectal temperature, heart rate, and respiratory rate remained stable and showed no significant change after epidural drug administration.
  • Ataxia: Horses exhibited significantly elevated ataxia scores from 24 to 36 hours post-injection, indicating impaired motor coordination during this period.
  • Adverse Effects:
    • Recumbency: Two horses became recumbent (unable to stand).
    • Urinary Retention: Three horses experienced urinary retention severe enough to require catheterization to empty their bladders.
    • Gastrointestinal Effects: Six horses showed decreased fecal output leading to constipation, which necessitated manual removal of manure from the rectum.

Conclusions

  • Liposomal bupivacaine administered via caudal epidural injection in horses at the studied dose did not provide analgesia throughout the 72-hour observation period.
  • The drug caused significant adverse clinical effects, including neurological impairment (ataxia), urinary retention, and constipation—all potentially harmful to the animals.
  • Given the absence of pain relief and presence of clinically relevant side effects, the study recommends against using caudal epidural liposomal bupivacaine at this dose in horses.

Implications for Practice and Future Research

  • Veterinarians should be cautious about employing liposomal bupivacaine epidurally in horses based on current evidence.
  • Further research may be needed to explore alternative dosages, administration techniques, or formulations to find safe and effective methods for prolonged analgesia in equine patients.
  • Understanding the mechanisms underlying adverse effects such as ataxia and urinary retention may help in designing safer analgesic protocols.

Cite This Article

APA
Stokes C, Natalini CC, Wills R, Eddy A, Mochal-King C, O'Shea C, Fontenot RL. (2025). Liposomal bupivacaine caudal epidural in horses results in adverse effects without analgesia. Vet Surg, 55(1), 218-224. https://doi.org/10.1111/vsu.70055

Publication

ISSN: 1532-950X
NlmUniqueID: 8113214
Country: United States
Language: English
Volume: 55
Issue: 1
Pages: 218-224

Researcher Affiliations

Stokes, Christopher
  • Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State, Mississippi, USA.
Natalini, Claudio Correa
  • Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State, Mississippi, USA.
Wills, Robert
  • Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State, Mississippi, USA.
Eddy, Alison
  • Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State, Mississippi, USA.
Mochal-King, Cathleen
  • Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State, Mississippi, USA.
O'Shea, Caitlin
  • Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State, Mississippi, USA.
Fontenot, Robin L
  • Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State, Mississippi, USA.

MeSH Terms

  • Animals
  • Bupivacaine / administration & dosage
  • Bupivacaine / adverse effects
  • Horses
  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / adverse effects
  • Liposomes
  • Male
  • Female
  • Injections, Epidural / veterinary
  • Analgesia, Epidural / veterinary
  • Ataxia / chemically induced
  • Ataxia / veterinary
  • Anesthesia, Caudal / veterinary
  • Anesthesia, Caudal / adverse effects

References

This article includes 35 references
  1. Skarda RT, Grosenbaugh DA, Muir WW. Caudal regional anaesthesia in horses. Equine Vet Educ 2005;15(SUPPL 7):108‐116.
  2. Natalini CC, Driessen B. Epidural and spinal anesthesia and analgesia in the equine. Clinical Techniques in Equine Practice 2007;6(2):145‐153.
  3. Valverde A, Little CB, Dyson DH, Motter CH. Use of epidural morphine to relieve pain in a horse. Can Vet J 1990;31:211‐212.
  4. Natalini C, Robinson E. Evaluation of the analgesic effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H in horses. Am J Vet Res 2000;61(12):1579‐1586.
    doi: 10.2460/ajvr.2000.61.1579google scholar: lookup
  5. Louro LF, Milner PI, Bardell D. Epidural administration of opioid analgesics improves quality of recovery in horses anaesthetised for treatment of hindlimb synovial sepsis. Equine Vet J 2021;53(4):682‐689.
    doi: 10.1111/evj.13338google scholar: lookup
  6. Rønnow Kjærulff LN, Lindegaard C. A narrative review of caudal epidural anaesthesia and analgesia in horses. Part 1: safety and efficacy of epidural drugs. Equine Vet Educ 2022;34(8):418‐431.
    doi: 10.1111/eve.13488google scholar: lookup
  7. Malinovsky JM, Le Corre P, Meunier JF. A dose‐response study of epidural liposomal bupivacaine in rabbits. J Control Release 1999;60(1):111‐119.
  8. Joshi GP, Patou G, Kharitonov V. The safety of liposome bupivacaine following various routes of administration in animals. J Pain Res 2015;8:781‐789.
    doi: 10.2147/jpr.s85424google scholar: lookup
  9. Dockery A, Beasley B, Goldberg M, Aguirre G, Moorman VJ. Dose effect and duration of action of liposomal bupivacaine administered as a perineural analgesic in a reversible and adjustable frog‐pressure model of equine lameness. Am J Vet Res 2023;85(1):1‐7.
    doi: 10.2460/ajvr.23.06.0122google scholar: lookup
  10. Le K, Caston S, Hossetter J, Hay Kraus B. 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.
  11. McCracken M, Schumacher J, Doherty T, Sun X, Nichols C, 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.
  12. Chahar P, Cummings KC. Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res 2012;5:257‐264.
    doi: 10.2147/jpr.s27894google scholar: lookup
  13. Lascelles BDX, Kirkby Shaw K. An extended release local anaesthetic: potential for future use in veterinary surgical patients?. Vet Med Sci 2016;2(4):229‐238.
    doi: 10.1002/vms3.43google scholar: lookup
  14. Gonzalez GA, Betbeze C, Wills R, Eddy A, Mochal-King C, Fontenot RL. Effects of subconjunctival ropivacaine, liposomal bupivacaine, and mepivacaine on corneal sensitivity in healthy horses. Vet Surg 2023;52(7):1041‐1049.
    doi: 10.1111/vsu.13980google scholar: lookup
  15. 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
  16. 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
  17. Boogaerts J, Lafont N, Declercq A. Epidural administration of liposome‐associated bupivacaine for the management of postsurgical pain ‐ a first study. J Clin Anesth 1994;6:315‐320.
  18. Viscusi ER, Candiotti KA, Onel E, Morren M, Ludbrook GL. The pharmacokinetics and pharmacodynamics of liposome bupivacaine administered via a single epidural injection to healthy volunteers. Regional Anesthesia Pain Medicine 2012;37(6):616‐622.
  19. Wolkowski D. How to place an epidural catheter for long‐term analgesia with morphine/Detomidine in horses. AAEP Proc 2018;64:291‐295.
  20. Hustace JL, Schlipf JJW, Acvim‐la D. How to place an epidural catheter easily and maximize its clinical effects. AAEP Proc 2009;55:401‐405.
  21. Reed S. Neurologic Exam. J Equine Vet Sci 2003;23(11):484‐492.
  22. Gardner RB. Evaluation and Management of the Recumbent Adult Horse. Vet Clin N Am Equine Pract 2011;27(3):527‐543.
  23. Faul F, Erdfelder E, Lang AG, Buchner A. G*power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007;39(2):175‐191.
    doi: 10.3758/bf03193146google scholar: lookup
  24. Douglas H, Midon M, Shroff K, Floriano D, Driessen B, Hopster K. Caudal epidural catheterization for pain management in 48 hospitalized horses: a descriptive study of demographics, complications, and outcomes. Front Vet Sci 2022;9:1‐12.
  25. Herperger LJ. Postoperative urinary retention in a dog following morphine with bupivacaine epidural analgesia. Can Vet J 1998;39:650‐652.
  26. Phillips L, McAbee K, Stephenson N, Stanke N, Booms M, Degner D. Evaluation of complications and feasibility of indwelling epidural catheter use for post‐operative pain control in dogs in the home environment. N Z Vet J 2015;63(2):86‐91.
  27. de Paula VB, Canola PA, Rivera GG. Intrabladder pressure as predictor of intra‐abdominal pressure in horses. PLoS One 2019;14:e0223705.
  28. Toribio RE. Essentials of equine renal and urinary tract physiology. Vet Clin N Am Equine Pract 2007;23(3):533‐561.
  29. Liu P, Chen G, Zhang J. A review of liposomes as a drug delivery system: current status of approved products, regulatory environments, and future perspectives. Molecules 2022;27(4):1372.
    doi: 10.3390/molecules27041372google scholar: lookup
  30. Campoy L, Martin‐Flores M, Gleed RD, Taylor LC, Yant JE, Pavlinac R. Block duration is substantially longer with a liposomal suspension of bupivacaine than with 0.5% bupivacaine HCl potentiated with dexmedetomidine following an ultrasound‐guided sciatic nerve block in beagles. Am J Vet Res 2022;83(8).
    doi: 10.2460/ajvr.22.01.0007google scholar: lookup
  31. Robinson EP, Natalini CC. Epidural anesthesia and analgesia in horses. Vet Clin N Am Equine Pract 2002;18(1):61‐82.
  32. Skarda RT, Muir WW, Hubbell JAE. Local anesthetic drugs and techniques. Equine Anesthesia: Monitoring and Emergency Therapy: Second Edition 2009:210‐242.
  33. Skarda R. Practical regional anesthesia. Equine Medicine & Surgery Vol 1. 1982:228‐249.
  34. Hendrickson DA, Southwood LL, Lopez MJ, Johnson R, Kruse-Elliott KT. Cranial migration of different volumes of new‐methylene blue after caudal epidural injection in the horse. Equine Practice 1998;20(2):12‐14.
  35. Natalini CC. Spinal anesthetics and analgesics in the horse. Vet Clin North Am Equine Pract 2010;26(3):551‐564.

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